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Sample records for anti-hiv agents

  1. Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Jing Li; Wen Long Huang; Hui Bin Zhang; Hai Qian; Yong Tang Zheng

    2011-01-01

    A series of Andro derivatives were described and evaluated for their anti-HIV activity in vitro. Compound 10 and 16b, of which TI were >10, had some anti-HTV-1 activity in vitro. Therein, compound 10 which was the best potent compound, could serve as a new lead for further development of anti-AIDS agents.

  2. Synthesis and bioevaluation of substituted chalcones, coumaranones and other flavonoids as anti-HIV agents.

    Science.gov (United States)

    Cole, Amy L; Hossain, Sandra; Cole, Alex M; Phanstiel, Otto

    2016-06-15

    A series of chalcone, flavone, coumaranone and other flavonoid compounds were screened for their anti HIV-1 activity in two cell culture models using TZM-bl and PM1 cells. Within the systems evaluated, the most promising compounds contained either an α- or β-hydroxy-carbonyl motif within their structure (e.g., 8 and 9). Efficacious substituents were identified and used to design new HIV inhibitors with increased potency and lower cytotoxicity. Of the scaffolds evaluated, specific chalcones were found to provide the best balance between anti-HIV potency and low host cell toxicity. Chalcone 8l was shown to inhibit different clinical isolates of HIV in a dose-dependent manner (e.g., IC50 typically⩽5μM). Inhibition of HIV infection experiments using TZM-bl cells demonstrated that chalcone 8l and flavonol 9c had IC50 values of 4.7μM and 10.4μM, respectively. These insights were used to design new chalcones 8o and 8p. Rewardingly, chalcones 8o and 8p (at 10μM) each gave >92% inhibition of viral propagation without impacting PM1 host cell viability. Inhibition of viral propagation significantly increased (60-90%) when PM1 cells were pre-incubated with chalcone 8o, but not with the related flavonol 9c. These results suggested that chalcone 8o may be of value as both a HIV prophylactic and therapy. In summary, O-benzyl-substituted chalcones were identified as promising anti-HIV agents for future investigation. PMID:27161874

  3. Topological estimation of cytotoxic activity of some anti-HIV agents: HEPT analogues

    Indian Academy of Sciences (India)

    Vijay K Agrawal; Kamlesh Mishra; Ruchi Sharma; P V Khadikar

    2004-03-01

    QSAR studies on anti-HIV cytotoxic activities of a series of HEPT(1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)-thymine) analogues have been discussed. The molecular descriptors used being van der Waals volume () and equalized electronegativity (eq). The in vitro cytotoxicities (50) were modelled using these parameters. It was observed that upon introduction of indicator parameters statistically excellent models are obtained. The predictive power of the models was examined using a cross-validation method.

  4. Approaches of Novel drug delivery systems for Anti-HIV agents

    OpenAIRE

    Vedha Hari B. N; Devendharan K,; Narayanan N

    2013-01-01

    The Human Immunodeficiency Virus (HIV) is a pandemic disease spreading very rapidly all over the world, causing approximately 15,000 or more new infections every day and the community acquiring sexually transmitted infections (STIs) is prone to easily acquire this HIV infections. The objective of the current review is to describe the comprehensiveness of the various advanced anti-HIV drug delivery systems and compounds that have been developed for targeting drugs to the macrophages, gastric m...

  5. Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND): A Brief Overview.

    Science.gov (United States)

    Kurapati, Kesava Rao V; Atluri, Venkata S; Samikkannu, Thangavel; Garcia, Gabriella; Nair, Madhavan P N

    2015-01-01

    As the threat of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART) provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS. Natural products such as plant-originated compounds and plant extracts have enormous potential to become drug leads with anti-HIV and neuroprotective activity. Accordingly, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action and for HIV-associated neurocognitive disorders (HAND). The basic challenge that still persists is to develop viral replication-targeted therapy using novel anti-HIV compounds with new mode of action, accepted toxicity and less resistance profile. Against this backdrop, the World Health Organization (WHO) suggested the need to evaluate ethno-medicines for the management of HIV/AIDS. Consequently, there is need to evaluate traditional medicine, particularly medicinal plants and other natural products that may yield effective and affordable therapeutic agents. Although there are a good number of reports on traditional uses of plants to treat various diseases, knowledge of herbal remedies used to manage HIV/AIDS and HAND are scanty, vague and not well documented. In this review, plant substances showing a promising action that is anti-HIV and HAND will be explored along with what they interact. Since some plant substances are also known to modulate several cellular

  6. Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND: A Brief Overview

    Directory of Open Access Journals (Sweden)

    Kesava Rao Venkata Kurapati

    2016-01-01

    Full Text Available As the threat of Human Immunodeficiency Virus (HIV/Acquired Immunodeficiency Syndrome (AIDS persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS. Natural products such as plant-originated compounds and plant extracts have enormous potential to become drug leads with anti-HIV and neuroprotective activity. Accordingly, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action and for HIV-associated neurocognitive disorders (HAND. The basic challenge that still persists is to develop viral replication-targeted therapy using novel anti-HIV compounds with new mode of action, accepted toxicity and less resistance profile. Against this backdrop, the World Health Organization (WHO suggested the need to evaluate ethno-medicines for the management of HIV/AIDS. Consequently, there is need to evaluate traditional medicine, particularly medicinal plants and other natural products that may yield effective and affordable therapeutic agents. Although there are a good number of reports on traditional uses of plants to treat various diseases, knowledge of herbal remedies used to manage HIV/AIDS and HAND are scanty, vague and not well documented. In this review, plant substances showing a promising action that is anti-HIV and HAND will be explored along with what they interact. Since some plant substances are also known to modulate

  7. HIV Integrase Inhibitors with Nucleobase Scaffolds: Discovery of a Highly Potent anti-HIV Agent

    OpenAIRE

    Nair, Vasu; Chi, Guochen; Ptak, Roger; Neamati, Nouri

    2006-01-01

    HIV integrase is essential for HIV replication. However, there are currently no integrase inhibitors in clinical use for AIDS. We have discovered a conceptually new β-diketo acid that is a powerful inhibitor of both the 3′-processing and strand transfer steps of HIV-1 integrase. The in vitro anti-HIV data of this inhibitor were remarkable as exemplified by its highly potent antiviral therapeutic efficacy against HIVTEKI and HIV-1NL4-3 replication in PBMC (TI >4,000 and >10,000, respectively).

  8. Inhibition of visna virus replication and cytopathic effect in sheep choroid plexus cell cultures by selected anti-HIV agents.

    Science.gov (United States)

    Thormar, H; Balzarini, J; Debyser, Z; Witvrouw, M; Desmyter, J; De Clercq, E

    1995-05-01

    Several anti-HIV agents were tested against visna virus replication and cytopathic effect (CPE) in sheep choroid plexus cell cultures. Sulphated polysaccharides (i.e., dextran sulphate, pentosan polysulphate and heparin) and plant lectins, which inhibit viral adsorption and fusion, were found to be 10- to 40-fold less active against visna virus than against HIV. Bicyclam derivatives were at least 250-fold less active against visna virus and the highly HIV-1 specific TIBO derivatives were without a significant inhibitory effect on visna virus at subtoxic concentrations. In contrast, several 2',3'-dideoxynucleosides and acyclic nucleoside phosphonate analogues, which inhibit reverse transcription, were found to be very effective inhibitors of visna virus replication and viral CPE in cell culture. PMID:7486958

  9. Approaches of Novel drug delivery systems for Anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Vedha Hari B. N

    2013-12-01

    Full Text Available The Human Immunodeficiency Virus (HIV is a pandemic disease spreading very rapidly all over the world, causing approximately 15,000 or more new infections every day and the community acquiring sexually transmitted infections (STIs is prone to easily acquire this HIV infections. The objective of the current review is to describe the comprehensiveness of the various advanced anti-HIV drug delivery systems and compounds that have been developed for targeting drugs to the macrophages, gastric mucosa and brain. Novel drug delivery system gives an opportunity to bypass the shortcomings related to the anti-retroviral treatment. It helps in addressing towards the complexity of dosage form development such as instability, insolubility and limited entrapment of the drugs. Several optional routes have been identified for the management of the ARV therapy which includes transdermal, mucosal (vaginal, rectal, buccal, etc. and also lymphatic delivery, with the application of novel systems like nanoparticles, vesicular systems (liposomes, niosomes, ethosomes, emulsomes, micellar assemblies, etc. This review spotlights the prospectives of novel drug release systems used in preventing the transmission and treatment of retroviral infections.

  10. Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2′,3′-seco-3′-nor DCP and DCK analogues

    Science.gov (United States)

    Chen, Ying; Cheng, Ming; Liu, Faqiang; Xia, Peng; Qian, Keduo; Yu, Donglei; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2011-01-01

    In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1′-O-, 1′-S-, 4′-O- and 4′-substituted-2′,3′-seco-3′-nor DCP and DCK analogues (8–37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1NL4-3 and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22–24, and 32) exhibited potent anti-HIV activity with EC50 values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1′-O-Isopropoxy-2′,3′-seco-3′-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC50 values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1NL4-3 and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates. PMID:21864952

  11. Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.

    Science.gov (United States)

    Chen, Ying; Cheng, Ming; Liu, Fa-Qiang; Xia, Peng; Qian, Keduo; Yu, Donglei; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2011-10-01

    In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates. PMID:21864952

  12. Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.

    Science.gov (United States)

    Chen, Ying; Cheng, Ming; Liu, Fa-Qiang; Xia, Peng; Qian, Keduo; Yu, Donglei; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2011-10-01

    In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates.

  13. High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents

    Science.gov (United States)

    Malik, Ruchi; Bunkar, Devendra; Choudhary, Bhanwar Singh; Srivastava, Shubham; Mehta, Pakhuri; Sharma, Manish

    2016-10-01

    Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses. Several endogenous peptides present in semen, including a 39-amino acid fragments of prostatic acid phosphatase (PAP248-286) assemble into amyloid fibrils named as semen-derived enhancer of viral infection (SEVI) that promote virion attachment to target cells which dramatically enhance HIV virus infection by up to 105-fold. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound, is the major catechin found in green tea which disaggregates existing SEVI fibers, and inhibits the formation of SEVI fibers. The aim of this study was to screen a number of relevant polyphenols to develop a rational approach for designing PAP248-286 aggregation inhibitors as potential anti-HIV agents. The molecular docking based virtual screening results showed that polyphenolic compounds 2-6 possessed good docking score and interacted well with the active site residues of PAP248-286. Amino acid residues of binding site namely; Lys255, Ser256, Leu258 and Asn265 are involved in binding of these compounds. In silico ADMET prediction studies on these hits were also found to be promising. Polyphenolic compounds 2-6 identified as hits may act as novel leads for inhibiting aggregation of PAP248-286 into SEVI.

  14. Metabolism of novel anti-HIV agent 3-cyanomethyl-4-methyl-DCK by human liver microsomes and recombinant CYP enzymes

    Institute of Scientific and Technical Information of China (English)

    Xiao-mei ZHUANG; Jing-ting DENG; Hua LI; Wei-li KONG; Jin-xiu RUAN; Lan XIE

    2011-01-01

    Aim:To investigate the metabolism of 3-cyanomethyl-4-methyl-DCK (CMDCK),a novel anti-HIV agent,by human liver microsomes (HLMs) and recombinant cytochrome P450 enzymes (CYPs).Methods:CMDCK was incubated with HLMs or a panel of recombinant cytochrome P450 enzymes including CYP1A2,2B6,2C8,2C9,2C19,2D6,3A4,and 3A5.LC-ion trap mass spectrometry was used to separate and identify CMDCK metabolites.In the experiments with recombinant cytochrome P450 enzymes,specific chemical inhibitors combined with CYP antibodies were used to identify the CYP isoforms involved in CMDCK metabolism.Results:CMDCK was rapidly and extensively metabolized by HLMs.Its intrinsic hepatic clearance estimated from the in vitro data was 19.4 mL.min-1·kg-1,which was comparable to the mean human hepatic blood flow rate (20.7 mL·min-1·kg-1).The major metabolic pathway of CMDCK was oxidation,and a total of 14 metabolites were detected.CYP3A4 and 3A5 were found to be the principal CYP enzymes responsible for CMDCK metabolism.Conclusion:CMDCK was metabolized rapidly and extensively in human hepatic microsomes to form a number of oxidative metabolites.CYP3A4 and 3A5 were the predominant enzymes responsible for the oxidation of CMDCK.

  15. Testing anti-HIV activity of antiretroviral agents in vitro using flow cytometry analysis of CEM-GFP cells infected with transfection-derived HIV-1 NL4-3.

    Science.gov (United States)

    Frezza, Caterina; Grelli, Sandro; Federico, Maurizio; Marino-Merlo, Francesca; Mastino, Antonio; Macchi, Beatrice

    2016-06-01

    An assay, specifically optimized to evaluate the anti-HIV activity of antiretrovirals by flow cytometry analysis, is described. As widely used anti-HIV agents, zidovudine (AZT), abacavir (ABC), 2',3'-dideoxyinosine (DDI), lamivudine (3TC), nevirapine (NVP), and efavirenz (EFV), and as drugs of recent approval raltegravir (RAL), etravirine (ETR), and rilpivirine (RPV), were utilized as reference drugs. HIV-1 NL4-3 virus was prepared by transfection of HEK293T cells with purified plasmid DNA and quantified by p24 antigen-capture assay. For infection, CEM-GFP cells were exposed to vehicle or to several concentrations of the drugs for 2 hr at 37 °C before HIV-1 NL4-3 was added to each sample. The adsorption was prolonged for 3 hr at 37 °C. After 72 hr of incubation, HIV-induced GFP expression in infected CEM-GFP cells was assessed by flow cytometry analysis and expressed as % positive cells. For comparison, p24 production in supernatants was assessed by a commercial ELISA kit. On the basis of IC50 values, the anti-HIV activity, as assayed by this method, was EFV > 3TC > AZT > NVP > DDI > ABC and ETR > RPV > RAL. The comparison between the IC50 values calculated through flow cytometry and p24 production revealed overlapping results, showing that the optimized protocol of CEM-GFP infection with HIV NL4-3 is a suitable method to perform quantitative, rapid and low-expensive screening tests to evaluate the in vitro effect of new candidate anti-HIV drugs. PMID:26519867

  16. Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.

    Science.gov (United States)

    Liu, Hong-Shan; Xu, Shi-Qing; Cheng, Ming; Chen, Ying; Xia, Peng; Qian, Keduo; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2011-10-01

    Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant inhibitory activity with an EC(50) of 128 nM and TI of 237.9.

  17. Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.

    Science.gov (United States)

    Liu, Hong-Shan; Xu, Shi-Qing; Cheng, Ming; Chen, Ying; Xia, Peng; Qian, Keduo; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2011-10-01

    Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant inhibitory activity with an EC(50) of 128 nM and TI of 237.9. PMID:21871800

  18. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-09-15

    In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 microM to 0.14 microM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 microM; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 microM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. PMID:20728367

  19. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2′,2′-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-01-01

    In a continued study, 23 3′R,4′R-di-O-(−)-camphanoyl-2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5–27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 μM to 0.14 μM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 μM; TI 310 and 200, respectively), and were two-fold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 μM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5–10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. PMID:20728367

  20. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-09-15

    In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 microM to 0.14 microM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 microM; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 microM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates.

  1. Anti-AIDS agents. 60. Substituted 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) analogues as potent anti-HIV agents.

    Science.gov (United States)

    Yu, Donglei; Chen, Chin-Ho; Brossi, Arnold; Lee, Kuo-Hsiung

    2004-07-29

    Synthesis of positional isomers is a commonly used technique in drug design. Accordingly, based on prior SAR studies of 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK, 1) analogues, a series of mono- and disubstituted chromone derivatives of 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP, 4) were designed and synthesized. Together with 1 and 4-methyl DCK (2), all newly synthesized DCP analogues (4-21) were screened for anti-HIV-1 activity against a non-drug-resistant strain in H9 lymphocytes and a multiple reverse transcriptase (RT) inhibitor-resistant strain in the MT4 cell line. Several DCP analogues (4, 5, 7, 8, 13, and 17) exhibited extremely high anti-HIV activity in the non-drug-resistant strain assay, with EC(50) values ranging from 0.00032 to 0.0057 microM and remarkable therapeutic indexes (TI) ranging from 5.6 x 10(3) to 1.16 x 10(5), which were similar to those of 2 (EC(50) 0.0059 microM, TI > 6.6 x 10(3)) and better than those of 1 (EC(50) 0.049 microM, TI > 328). Even more promisingly, some DCP analogues also showed activity against a multi-RT inhibitor-resistant strain, HIV-1 RTMDR1, whereas most DCK analogues did not. The most significant compound was 8, with an EC(50) value of 0.06 microM and TI of 718 against the multi-RT inhibitor-resistant HIV-1 strain. Compounds 9 and 10 also showed good activity with an EC(50) value of 0.14 microM, and TIs of 272 and >111, respectively. 2-Ethyl DCP (8) exhibited the best anti-HIV activity in both assays. Further development of 8-related compounds as clinical trial candidates is warranted.

  2. Anti-HIV-1 Activities of 4 Telomerase Restrictors

    Institute of Scientific and Technical Information of China (English)

    YU Xin; WANG Jinghui; de Giuli Morghen; Radaelli A; Zanotto C; Beggio P

    2007-01-01

    MTT Cell Proliferation Assay was used to optimize the concentration of Telomerase Restrictors(TRs) with minimum toxicity to the selected cells. FACSort flow cytometer and Innotest P24 HIV(Human immunodeficiency Virus) antigen mAb ELISA Kit were used to investigate the anti-HIV-1 activities of TRs. The results showed that TRs had low cytotoxicity to the PBMC (Peripheral Blood mononuclear cells) and CEM/GFP if the concentration of TRs was at 50 μmol/L or below, and the supernatant from PBMC pretreated with SHIV and TR1-001 /TR1-002 could not infect the PBMC, while can infect the C8166 with reduced infectivity, which suggested that the TRs may be one of the novel resources for screening anti-HIV-1 agents.

  3. Lectins with Anti-HIV Activity: A Review

    Directory of Open Access Journals (Sweden)

    Ouafae Akkouh

    2015-01-01

    Full Text Available Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin lectin, concanavalin A, Galanthus nivalis (snowdrop agglutinin-related lectins, Musa acuminata (banana lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus. The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

  4. Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity.

    Science.gov (United States)

    Li, Jizhen; Goto, Masuo; Yang, Xiaoming; Morris-Natschke, Susan L; Huang, Li; Chen, Chin-Ho; Lee, Kuo-Hsiung

    2016-01-01

    Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate other properties of 2-related compounds.

  5. In vitro anti-HIV-1 activity of fucoidan from Sargassum swartzii.

    Science.gov (United States)

    Dinesh, Subramaniam; Menon, Thangam; Hanna, Luke E; Suresh, V; Sathuvan, M; Manikannan, M

    2016-01-01

    Sargassum swartzii, a marine brown algae with wide range of biological properties belongs to the family Sargassaceae. Bioactive fucoidan fractions (CFF, FF1 and FF2) were isolated from S. swartzii and characterized by linear gradient anion-exchange chromatography and FT-IR. The characterized fucoidan fractions contained mainly sugars, sulfate and uronic acid. In the present study, anti-HIV-1 property of the fucoidan fractions was investigated. Fraction FF2 was found to exhibit significant anti-HIV-1 activity at concentrations of 1.56 and 6.25 μg/ml as observed by >50% reduction in HIV-1 p24 antigen levels and reverse transcriptase activity. Fucoidan fractions have no cytotoxic effects on PBMCs at the concentration range of 1.56-1000 μg/ml. These results suggest that fucoidan fractions could have inhibitory activity against HIV and has potential as an anti-HIV-1 agent. PMID:26472515

  6. A Review of Electroanalytical Techniques for Determination of Anti-HIV Drugs

    Directory of Open Access Journals (Sweden)

    Burçin Bozal

    2011-01-01

    Full Text Available Until now after the human immunodeficiency virus (HIV was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS, exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, lamivudine, abacavir, stavudine, and emtricitabine, nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir, nonnucleoside reverse transcriptase inhibitors (NNRTIs: efavirenz, nevirapine, delavirdine, and etravirine, protease inhibitors (PIs: ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir, fosamprenavir, atazanavir, tipranavir and darunavir, fusion inhibitors (FIs: enfuvirtide, coreceptor inhibitors (CRIs: maraviroc, and integrase inhibitors (INIs: raltegravir. The present paper submitted the use of various electroanalytical techniques for the determination of anti-HIV drugs. This paper covers the time period from 1990 to 2010 including voltammetric techniques that were reported. Presented application concerns analysis of anti-HIV drugs from pharmaceutical dosage forms and biological samples.

  7. Cyclotriazadisulfonamides: promising new CD4-targeted anti-HIV drugs.

    Science.gov (United States)

    Vermeire, Kurt; Schols, Dominique

    2005-08-01

    It is imperative to continue efforts to identify novel effective therapies that can assist in containing the spread of HIV. Recently acquired knowledge about the HIV entry process points to new strategies to block viral entry. For most HIV strains, the successful infection of their target cells is mainly dependent on the presence of the CD4 surface molecule, which serves as the primary virus receptor. The attachment of the viral envelope to this cellular CD4 receptor can be considered as an ideal target with multiple windows of opportunity for therapeutic intervention. Therefore, drugs that interfere with the CD4 receptor, and thus inhibit viral entry, may be promising agents for the treatment of AIDS. The CD4-targeted HIV entry inhibitors cyclotriazadisulfonamides represent a novel class of small molecule antiviral agents with a unique mode of action. The lead compound, CADA, specifically interacts with the cellular CD4 receptor and is active against a wide variety of HIV strains at submicromolar levels when evaluated in different cell-types such as T cells, monocytes and dendritic cells. Moreover, a strict correlation has been demonstrated between anti-HIV activity and CD4 interaction of about 20 different CADA analogues. In addition, CADA acted synergistically in combination with all other FDA-approved anti-HIV drugs as well as with compounds that target the main HIV co-receptors. In this article, the characteristics of cyclotriazadisulfonamide compounds are presented and the possible application of CADA as a microbicide is also discussed. PMID:15980096

  8. Lectins with Anti-HIV Activity: A Review

    OpenAIRE

    Ouafae Akkouh; Tzi Bun Ng; Senjam Sunil Singh; Cuiming Yin; Xiuli Dan; Yau Sang Chan; Wenliang Pan; Randy Chi Fai Cheung

    2015-01-01

    Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV al...

  9. [Anti-HIV drugs and drug delivery system].

    Science.gov (United States)

    Obaru, K; Mitsuya, H

    1998-03-01

    A number of candidate drugs for therapy of HIV-1 infection which show significant activity against the virus in vitro were reported; however, many of them have been dropped from drug development due to (i) insufficient intracellular activation in certain human target cells (particularly in case of nucleoside reverse transcriptase inhibitors), (ii) poor pharmacokinetic profiles, or (iii) intolerable in vitro and/or in vivo toxicities. To circumvent some of these problems, certain drug delivery systems have been applied and several candidate drugs including two novel nucleoside reverse transcriptase inhibitors, abacavir and adefovir, have acquired favorable properties in the clinical setting. This paper reviews several avenues for developing prodrugs of anti-HIV-1 agents to overcome their inherent limitations. PMID:9549371

  10. Anti - HIV-1 integrase activity of Thai Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Kingkan Bunluepuech

    2009-08-01

    Full Text Available For the purpose of discovering anti-HIV-1 agents from natural sources, the aqueous and EtOH extracts of eight Thaiplants including Clerodendron indicum (whole plant, Tiliacora triandra (stem, Capparis micracantha (wood, Harrissoniaperforata (wood, Ficus glomerata (wood, Diospyros decandra (wood, Dracaena loureiri (heartwood, and Tinospora crispa (stem were screened for their inhibitory activities against HIV-1 integrase (IN using the multiplate integration assay(MIA. Of the EtOH extracts, Ficus glomerata (wood was the most potent with an IC50 value of 7.8 g/ml; whereas the water extract of Harrisonia perforata (wood was the most potent aqueous extract with an IC50 value of 2.3 g/ml. The isolation of active principles against HIV-1 IN from Ficus glomerata is now actively pursued.

  11. A Review of Electroanalytical Techniques for Determination of Anti-HIV Drugs

    OpenAIRE

    Burçin Bozal; Bengi Uslu; Özkan, Sibel A.

    2011-01-01

    Until now after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, lamivudine, abacavir, stavudine, and emtricitabine), nucleotide reverse transcriptase inhibitors (NtRTIs: t...

  12. TARGETING OF ANTIVIRAL DRUGS TO LYMPHOCYTES-T4 - ANTI-HIV ACTIVITY OF NEOGLYCOPROTEIN AZTMP CONJUGATES INVITRO

    NARCIS (Netherlands)

    MOLEMA, G; JANSEN, RW; PAUWELS, R; DECLERCQ, E; MEIJER, DKF

    1990-01-01

    The delivery of the anti-HIV agent 3'-azido-3'-deoxythymidine (AZT), in its 5'-monophosphate form, (in)to human T-lymphocyte MT-4 cells in vitro through covalent coupling to neoglycoproteins was investigated. In vivo application of this drug targeting concept may lead to increased efficacy and/or di

  13. Anti-HIV drug development on the fast track

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ An international cooperation deal was made recently in Shanghai on developing a new anti-HIV drug based on the research results of CAS scientists and their preclinical studies,marking a breakthrough progress for China's research in the field.

  14. Clinical Evaluation on Several anti- HIV Diagnostic Reagents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective We Joined clinical evaluation on 6 anti - HIV diagnostic reagents which was organized by National Reference Laboratory of National Center for AIDS Prevention and Control. Method 100 sera of known result and 100 sera of unknown result were detected with 6 reagents according to test procedure of the reagents. Result The crude agreement (99.5 % ) of Organon Teknika and Determine reagents were higher than that of the other reagents. No anti - HIV positive serum was detected negative with Organon Teknika and Determine reagents. The sensitivity and specificity of Organon Teknika and Determine reagents were higher than those of the other reagents. The capacity of Organon Teknika reagent to detect the mild positive serum was greater than that of the other reagent. Conclusion Organon Teknika and Determine antiHIV diagnostic reagents were qualified for anti - HIV screening test while the other 4 reagents should be improved on sensitivity and specificity.

  15. GACPAT HIV 1 + 2: a simple, inexpensive assay to screen for, and discriminate between, anti-HIV 1 and anti-HIV 2.

    Science.gov (United States)

    Parry, J V; Connell, J A; Reinbott, P; Garcia, A B; Avillez, F; Mortimer, P P

    1995-01-01

    A simple and cheap assay suitable for screening for anti-HIV 1 and anti-HIV 2 and discriminating between them was evaluated. In it specimens are incubated in U-bottomed microplate wells coated with anti-human IgG for 30 min at room temperature. After washing, 100 microliters of a 1 in 50 dilution of HIV 1-coated gelatin particles (Serodia-HIV 1/2, Fujirebio) are added. Settling patterns are read on the second day: A positive reaction is indicated by adherence of the particles and a negative by a button. The HIV 1 particles are then washed away and HIV 2 particles added. Anti-HIV 2 reaction patterns are read on the third day. To assess the performance of the modified "GACPAT HIV 1 + 2" assay a panel of 1,621 serum/plasma specimens was used. It comprised validated anti-HIV 1 positive (n = 220), anti-HIV 2 positive (n = 214), dual anti-HIV 1/anti-HIV 2 positive (n = 11), and anti-HIV negative (n = 1,176) serum/plasma specimens. All 434 specimens that contained anti-HIV 1 or anti-HIV 2 reacted positively with the homologous particles. The 11 dually positive specimens reacted positively with both HIV 1 and HIV 2 particles. Five (2.3%) anti-HIV 1 and five (2.3%) anti-HIV 2 positive specimens gave positive reactions with both particle types, but none of the five cross-reactive anti-HIV 2 specimens were dually reactive when the order of particle addition was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Design, synthesis and anti-HIV activity of novel quinoxaline derivatives.

    Science.gov (United States)

    Patel, Saloni B; Patel, Bhumika D; Pannecouque, Christophe; Bhatt, Hardik G

    2016-07-19

    In order to design novel anti-HIV agents, pharmacophore modelling, virtual screening, 3D-QSAR and molecular docking studies were performed. Pharmacophore model was generated using 17 structurally diverse molecules using DISCOtech followed by refinement with GASP module of Sybyl X. The best model containing four features; two donor sites, one acceptor atom and one hydrophobic region; was used as a query for virtual screening in NCI database and 6 compounds with Qfit value ≥98 were retrieved. The quinoxaline ring which is the bio-isostere of pteridine ring, retrieved as a hit in virtual screening, was selected as a core moiety. 3D-QSAR was carried on thirty five 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide derivatives. Contour map analysis of best CoMFA and CoMSIA model suggested incorporation of hydrophobic, bulky and electronegative groups to increase potency of the designed compounds. 50 quinoxaline derivatives with different substitutions were designed on basis of both ligand based drug design approaches and were mapped on the best pharmacophore model. From this, best 32 quinoxaline derivatives were docked onto the active site of integrase enzyme and in-silico ADMET properties were also predicted. From this data, synthesis of top 7 quinoxaline derivatives was carried out and were characterized using Mass, (1)H-NMR and (13)C-NMR spectroscopy. Purity of compounds were checked using HPLC. These derivatives were evaluated for anti-HIV activity on III-B strain of HIV-1 and cytotoxicity studies were performed on VERO cell line. Two quinoxaline derivatives (7d and 7e) showed good results, which can be further explored to develop novel anti-HIV agents.

  17. 2'-Deoxythymidine Adducts from the Anti-HIV Drug Nevirapine

    Directory of Open Access Journals (Sweden)

    M. Matilde Marques

    2013-04-01

    Full Text Available Nevirapine (NVP is a non-nucleoside reverse transcriptase inhibitor (NNRTI used against HIV-1. Currently, NVP is the most widely used anti-HIV drug in developing countries, both in combination therapy and to prevent mother-to-child transmission of HIV. Despite its efficacy against HIV, NVP produces a variety of toxic responses, including hepatotoxicity and skin rash. It is also associated with increased incidences of hepatoneoplasias in rodents. In addition, epidemiological data suggest that NNRTI use is a risk factor for non-AIDS-defining cancers in HIV-positive patients. Current evidence supports the involvement of metabolic activation to reactive electrophiles in NVP toxicity. NVP metabolism includes oxidation to 12-hydroxy-NVP; subsequent Phase II sulfonation produces an electrophilic metabolite, 12-sulfoxy-NVP, capable of reacting with DNA to yield covalent adducts. Since 2’-deoxythymidine (dT adducts from several alkylating agents are regarded as having significant mutagenic/carcinogenic potential, we investigated the formation of NVP-dT adducts under biomimetic conditions. Toward this goal, we initially prepared and characterized synthetic NVP-dT adduct standards using a palladium-mediated Buchwald-Hartwig coupling strategy. The synthetic standards enabled the identification, by LC-ESI-MS, of 12-(2'-deoxythymidin-N3-yl-nevirapine (N3-NVP-dT in the enzymatic hydrolysate of salmon testis DNA reacted with 12-mesyloxy-NVP, a synthetic surrogate for 12-sulfoxy-NVP. N3-NVP-dT, a potentially cytotoxic and mutagenic DNA lesion, was also the only dT-specific adduct detected upon reaction of dT with 12-mesyloxy-NVP. Our data suggest that N3-NVP-dT may be formed in vivo and play a role in the hepatotoxicity and/or putative hepatocarcinogenicity of NVP.

  18. Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

    Directory of Open Access Journals (Sweden)

    Carolina Horta Andrade

    2011-06-01

    Full Text Available From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs, protease inhibitors (PIs, cell entry inhibitors or fusion inhibitors (FIs, co-receptor inhibitors (CRIs, and integrase inhibitors (INIs. Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR, inibidores nucleotídeos de transcriptase reversa (INtTR, inibidores não-nucleosídeos de transcriptase reversa (INNTR, inibidores de protease (IP, inibidores da entrada celular ou inibidores de fusão (IF, inibidores de co-receptores (ICR e inibidores de integrase (INI. O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A forma

  19. Enantioselective Synthesis of Protease Inhibitors and AntiHIV Agents

    Institute of Scientific and Technical Information of China (English)

    WANG Zhe

    2001-01-01

    @@ Part 1: A highly enantio-and diastereoselective Ireland-Claisen rearrangement of chiral C3(acyloxy)-vinyl silanes for the synthesis of anti-disubstituted succinic acid, an important intermediate for matrix metalloprotease inhibitors, has been developed (enantio-and anti/syn selectivities up to 95% and 38/1). The diastereoselectivity of this reaction was found to be sensitive to remote hydroxyl protecting groups, for example, with-OMOM group, the anti/syn ratio was 19/1, while with-OTBDMS, the ratio was 38/1. The resultant Ireland-Claisen rearrangement product was applied to the synthesis of macrocyclic MMP inhibitors, such as SL 422.

  20. Enantioselective Synthesis of Protease Inhibitors and AntiHIV Agents

    Institute of Scientific and Technical Information of China (English)

    WANG; Zhe

    2001-01-01

    Part 1: A highly enantio-and diastereoselective Ireland-Claisen rearrangement of chiral C3(acyloxy)-vinyl silanes for the synthesis of anti-disubstituted succinic acid, an important intermediate for matrix metalloprotease inhibitors, has been developed (enantio-and anti/syn selectivities up to 95% and 38/1). The diastereoselectivity of this reaction was found to be sensitive to remote hydroxyl protecting groups, for example, with-OMOM group, the anti/syn ratio was 19/1, while with-OTBDMS, the ratio was 38/1. The resultant Ireland-Claisen rearrangement product was applied to the synthesis of macrocyclic MMP inhibitors, such as SL 422.……

  1. Synthesis of zidovudine derivatives with anti-HIV-1 and antibacterial activities.

    Science.gov (United States)

    Senthilkumar, Palaniappan; Long, Jing; Swetha, Raparla; Shruthi, Vaidyanathan; Wang, Rui-Rui; Preethi, Srinivasan; Yogeeswari, Perumal; Zheng, Yong-Tang; Sriram, Dharmarajan

    2009-02-01

    Twelve novel zidovudine derivatives were prepared by modifying 5 '-hydroxyl group of sugar moiety (1-8) and 5-methyl group of thymidine nucleus (9-12) and characterized spectrally. The compounds were evaluated for anti-HIV-1, antitubercular and antibacterial activities. Compound (3-azido-tetrahydro-5- (3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)furan-2-yl)methyl 7-(4-(2-phenylacetoyloxy)-3,5- dimethylpiperazin-1-yl)-5-(2-phenylacetoyloxyamino)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (5) was found to be the most potent anti-HIV-1 agent with EC(50) of 0.0012 microM against HIV-1(IIIB) and CC(50) of 34.05 microM against MT-4 with selectivity index of 28,375. Compound 5 inhibited Mycobacterium tuberculosis with MIC of 1.72 microM and inhibited four pathogenic bacteria with MIC of less than 1 microM. PMID:19219739

  2. Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical trials.How to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for them.This article references the literature and the experience of reviewers,to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

  3. Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

    Institute of Scientific and Technical Information of China (English)

    LI YaJie; ZHAO Ming; ZHAO DeHeng

    2009-01-01

    Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical trials. How to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for them. This article references the literature and the experience of reviewers, to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

  4. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.

    Science.gov (United States)

    De Clercq, Erik

    2009-04-01

    In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co-receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs: raltegravir). These compounds should be used in drug combination regimens to achieve the highest possible benefit, tolerability and compliance and to diminish the risk of resistance development. PMID:19108994

  5. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.

    Science.gov (United States)

    De Clercq, Erik

    2009-04-01

    In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co-receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs: raltegravir). These compounds should be used in drug combination regimens to achieve the highest possible benefit, tolerability and compliance and to diminish the risk of resistance development.

  6. Nanomedicine in the development of anti-HIV microbicides.

    Science.gov (United States)

    das Neves, José; Nunes, Rute; Rodrigues, Francisca; Sarmento, Bruno

    2016-08-01

    Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. PMID:26829288

  7. The anti-HIV activities of photoactive terthiophenes

    International Nuclear Information System (INIS)

    Various synthetic analogues of naturally occurring terthiophene, α-terthienyl (αT), were evaluated for anti-human immunodeficiency virus (HIV) activity. The compounds were incubated individually with a known amount of virus, with or without UVA radiation (long-wavelength ultra violet) and residual virus was monitored for its ability to produce cytopathic effects in cell culture and the production of virus-specific protein. The basic terthiophene structure was essential for good anti-HIV activity, although various side chains, such as alcohols, bromo, methyl, thiomethyl and trimethylsilyl groups, permitted retention of maximum activity. Under optimum conditions, as little as 12 ng/mL of these compounds (i.e. approximately 3 x 10-8 M) could inactivate 103 infectious virions. None of the compounds however were more active than αT itself. In all cases, UVA radiation was essential. (Author)

  8. International award received recognizing anti-HIV spermicide.

    Science.gov (United States)

    1998-10-19

    Until recently, the only topical microbicide being considered for protection against sexually transmitted HIV infection contains nonoxynol-9 (N-9), a detergent ingredient widely used for more than 30 years in the form of gels, foams, aerosols, creams, sponges, suppositories, films, and foaming tablets. While N-9 has both spermicidal and antibacterial/antiviral properties against pathogens responsible for STDs, including HIV, recent clinical studies have found it to be ineffective in protecting against HIV and other STDs. Moreover, N-9 disrupts cell membranes, damages cervicovaginal epithelia, and causes an acute tissue inflammatory response, thus enhancing the likelihood of HIV infection. There is therefore an urgent need for new, effective, safe, and easy-to-use microbicides with anti-HIV activity lacking detergent-type membrane toxicity. Dr. Osmond D'Cruz et al. of the Hughes Institute in St. Paul, Minnesota, have developed an anti-HIV spermicide with the potential of becoming the active ingredient in many beneficial products. Its lead compound is 400 times more potent than N-9 against HIV and at least 10 times more potent than N-9 as a spermicide. These dual-function compounds are non-inflammatory by their nature. Hughes et al.'s discovery is expected to enter human clinical trials within 12 months. A clinical paper describing their achievement won the prestigious Prize Paper Award for the Plenary Session of the Conjoint 16th World Congress on Fertility and Sterility at the 54th Annual Meeting of the American Society of Reproductive Medicine, held in San Francisco, California, during October 4-9, 1998. PMID:12294481

  9. Drogas anti-VIH: passado, presente e perspectivas futuras Drugs anti-HIV: past, present and future perspectives

    Directory of Open Access Journals (Sweden)

    Marcus Vinícius Nora de Souza

    2003-05-01

    Full Text Available Currently available anti-HIV drugs can be classified into three categories: nucleoside analogue reverse transcriptase inhibitors (NRTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs and protease inhibitors (PIs. In addition to the reverse transcriptase (RT and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (1 viral adsorption, through binding to the viral envelope glycoprotein gp120; (2 viral entry, through blockage of the viral coreceptors CXCR4 and CCR5; (3 virus-cell fusion, through binding to the viral envelope glycoprotein gp 41; (4 viral assembly and disassembly through NCp7 zinc finger-targeted agents; (5 proviral DNA integration, through integrase inhibitors and (6 viral mRNA transcription, through inhibitors of the transcription (transactivation process. Also, various new NRTIs, NNRTIs and PIs have been developed, possessing different improved characteristics.

  10. Estratégias farmacológicas para a terapia anti-AIDS Pharmacological strategies for anti-HIV therapy

    Directory of Open Access Journals (Sweden)

    Emerson Poley Peçanha

    2002-12-01

    Full Text Available The replicative cycle of HIV presents several events. The proteins involved in these events can be anticipated as pharmacological targets, aiming to the development of anti viral agents. Presently, there are fifteen commercially available anti-HIV drugs, which act at substrate binding site of reverse transcriptase (zidovudine, didanosine, zalcitabine, stavudine, lamivudine and abacavir, at a non-substrate binding site of reverse transcriptase (nevirapine, delavirdine and efavirenz, or by inhibiting HIV protease activity (saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. The present review focus both on these established classes of drugs and on new classes of compounds acting on other virus specific steps.

  11. Current Status of Targets and Assays for Anti-HIV Drug Screening

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent, treat and to better understand the disease, it is one of the main causes of morbidity and mortality worldwide. Currently, there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects, price and drug resistance, it is essential to discover new targets, to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.

  12. Abo and Rh Blood Groups Distribution in Hemophilia and Anti Hiv Positive Individuals

    Directory of Open Access Journals (Sweden)

    D.D. FARHUD

    1987-07-01

    Full Text Available A group of Iranian patients suffering from Factor VIII deficiency (Hemophilia A and treated with contaminated coagulation factor (imported, became seropositive as determined by ELISA method. Sixty of these individuals, which were available, were studied for ABO distribution. The B blood group in anti HIV pos. individuals (13.33% shows a significant decrease in comparison with the total (1504 of factor VIII hemophilia (21.87%. Statistical analysis of ABO distribution in anti HIV Pos. compared with hemophilia A and the control group showed x2 values of 6.86(0.10 > p>0.05 and 10.21(0.02> P >0.01 respectively.

  13. Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum albumins in mice

    NARCIS (Netherlands)

    Kuipers, M.E; Swart, P.J; Schutten, M; Smit, C; Proost, Hans; Osterhaus, A.DME; Meijer, D.K F

    1997-01-01

    Negatively charged albumins (NCAs, with the prototypes succinylated human serum albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1) activity in vitro, were studied for their pharmacokinetic behaviour

  14. New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica

    DEFF Research Database (Denmark)

    Valsaraj, R; Pushpangadan, P; Smitt, U W;

    1997-01-01

    A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit rind led to the isolation of two new lignans named termilignan (1) and thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and anolignan B (4). All four compounds possessed demonstrable anti-HIV-1...

  15. Semi-synthesis of oxygenated dolabellane diterpenes with highly in vitro anti-HIV-1 activity.

    Science.gov (United States)

    Pardo-Vargas, Alonso; Ramos, Freddy A; Cirne-Santos, Claudio Cesar; Stephens, Paulo Roberto; Paixão, Izabel Christina Palmer; Teixeira, Valeria Laneuville; Castellanos, Leonardo

    2014-09-15

    Research on dolabellane diterpenes of brown algae Dictyota spp. has shown that these diterpenoids have strong anti-HIV-1 activity, but there are not data about antiviral activity of dolabellane diterpenes isolated from octocorals, which are antipodes of those isolated from the brown algae. Dolabellanes 13-keto-1(R),11(S)-dolabella-3(E),7(E),12(18)-triene (1) and β-Araneosene (2) were isolated from the Caribbean octocoral Eunicea laciniata, and both showed low anti-HIV-1 activity and low toxicity. Since it was shown that oxygenated dolabellanes from algae have better anti-HIV-1 activity, in this work some derivatives of the main dolabellane of E. laciniata1 were obtained by epoxidation (3), epoxide opening (4), and allylic oxidation (5). The derivatives showed significant improvement in the anti-HIV-1potency (100-fold), being compounds 3 and 5 the most active ones. Their high antiviral activities, along with their low cytotoxicity, make them promissory antiviral compounds; and it is worth noting that the absolute configuration at the ring junction in the dolabellane skeleton does not seem to be determinant in the antiviral potency of these diterpeneoids.

  16. 抗HIV巨噬细胞靶向给药系统的研究进展%Anti-HIV macrophage-targeted drug delivery systems:research advances

    Institute of Scientific and Technical Information of China (English)

    杜丽娜; 金义光

    2013-01-01

    巨噬细胞是人免疫缺陷病毒(HIV)的宿主,藏匿在巨噬细胞中的HIV能在适宜时机复制而导致艾滋病复发,因此,巨噬细胞可成为HIV的新传染源.目前大部分抗艾滋病药的细胞膜渗透性差、体内半衰期短,造成给药剂量大和次数频繁,并且难以在巨噬细胞内分布而清除残留HIV.因此抗HIV巨噬细胞靶向给药系统的研究很重要.本文综述了抗HIV药物的纳米给药系统及其巨噬细胞靶向作用,涉及纳米粒、脂质体、纳米混悬剂、自组装药物传递系统、纳米凝胶和纳米囊,为艾滋病治疗提供新思路.%Macrophages are the reservoir of human immunodeficiency virus (HIV). HIV hidden in the macrophages is replicated under appropriate conditions, leading to recurrence of AIDS. Macrophages are a new infection resource of HIV. Biomembrane penetration of current anti-HIV drugs is poor and the in vivo half life is short, resulting in high dose and frequent administration. Their distribution in macrophages is too little to eradicate the hidden HIV. Therefore, the development of anti-HIV macrophage-targeted delivery systems is very important. The review summarizes the nanoparticulate delivery systems of anti-HIV agents and their macrophage-targeted effects, involving nanoparticles, liposomes, nanosuspensions, self-assembled drug delivery systems, nanogels and nanocapsules, in order to provide a new strategy for the treatment of AIDS.

  17. Synthesis and Anti-HIV-1 Activity Evaluation for Novel 3a,6a-Dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-dione Derivatives

    Directory of Open Access Journals (Sweden)

    Guan-Nan Liu

    2016-09-01

    Full Text Available The search for new molecular constructs that resemble the critical two-metal binding pharmacophore and the halo-substituted phenyl functionality required for HIV-1 integrase (IN inhibition represents a vibrant area of research within drug discovery. As reported herein, we have modified our recently disclosed 1-[2-(4-fluorophenylethyl]-pyrrole-2,5-dione scaffolds to design 35 novel compounds with improved biological activities against HIV-1. These new compounds show single-digit micromolar antiviral potencies against HIV-1 and low toxicity. Among of them, compound 9g and 15i had potent anti-HIV-1 activities (EC50 < 5 μM and excellent therapeutic index (TI, CC50/EC50 > 100. These two compounds have potential as lead compounds for further optimization into clinical anti-HIV-1 agents.

  18. CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro

    OpenAIRE

    Vermeire, Kurt; Princen, Katrien; Hatse, Sigrid; De Clercq, Erik; Dey, Kaka; Bell, Thomas W.; Schols, Dominique

    2004-01-01

    OBJECTIVE: To evaluate the anti-HIV-1 activity of the cyclotriazadisulfonamide CADA against primary isolates in vitro and the combination of CADA with approved anti-HIV drugs for potential synergy. METHODS: Peripheral blood mononuclear cells (PBMC) were treated with CADA and infected with 16 different clinical isolates. After 8 days of infection, the median inhibitory concentration (IC50) was calculated from the p24 viral antigen content in the supernatant. MT-4 cells were infected with HIV-1...

  19. DNA Triplex-Based Complexes Display Anti-HIV-1-Cell Fusion Activity.

    Science.gov (United States)

    Xu, Liang; Zhang, Tao; Xu, Xiaoyu; Chong, Huihui; Lai, Wenqing; Jiang, Xifeng; Wang, Chao; He, Yuxian; Liu, Keliang

    2015-08-01

    DNA triplexes with hydrophobic modifications were designed and evaluated for their activity as inhibitors of the cell fusion of human immunodeficiency virus type 1 (HIV-1). Triplex inhibitors displayed low micromolar activities in the cell-cell fusion assay and nanomolar activities in the anti-HIV-1 pseudovirus test. Helix structure and the presence of sufficient numbers of hydrophobic regions were essential for the antifusion activity. Results from native polyacrylamide gel electrophoresis and a fluorescent resonance energy transfer-based inhibitory assay indicated that these triplexes may interact with the primary pocket at the glycoprotein 41 (gp41) N-heptad repeat, thereby inhibiting formation of the HIV-1 gp41 6-helical bundle. Triplex-based complexes may represent a novel category of HIV-1 inhibitors in anti-HIV-1 drug discovery. PMID:26192705

  20. Kan vericilerde HBsAg, anti-HCV, anti-HIV ve Sifilis seroprevalansı

    OpenAIRE

    Altındiş, Mustafa; Aslan, Savaş; Kalaycı, Raike

    2011-01-01

    Bu çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Kan Merkezi'ne başvuran donörlerde HBsAg, anti-HCV, anti-HIV 1/2 ve RPR seroprevalansının tespiti ve oranların yıllara ve cinsiyete göre dağılımının belirlenmesi amaçlanmıştır. Ocak'2001 ve Aralık'2010 tarihleri arasında Kan Merkezi'ne başvuran 37343 kan donörünün HBsAg, anti-HCV, anti-HIV ½ tarama testleri mikropartikül ELISA (Vitros, Ortho-Clinical Diagnostics) yöntemi ile Ortho-Clinical Diagnostics (HBsAg, HCV 3.jenerasyon, HIV 1/2) ki...

  1. Ab Initio Study on the Anti-HIV Activities of Hydroxyflavones

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu

    2005-01-01

    Flavone and 95 hydroxyflavones have been studied with ab initio method, and their total energies, atomic charges, dipole moments, multipole moments, molecular orbital compositions, orbital energies etc. were obtained. Among them the relationship between total atomic charges and activities against HIV is basically in accordance with the experimental results. The beneficial references are provided for the extraction and synthesis of strong active anti-HIV medicines.

  2. In vitro screening of traditional medicines for anti-HIV activity: memorandum from a WHO meeting.

    OpenAIRE

    1989-01-01

    Many plant products are being used by patients with acquired immunodeficiency syndrome (AIDS) in some countries without any scientific proof that they possess anti-HIV (human immunodeficiency virus) activity. Traditional healers are now offering their remedies for scientific evaluation, and a few studies provide information on the inhibitory activity against HIV of plants such as Viola yedoensis, Arctium lappa, Epimedium grandiflorum, Glycyrrhiza uralensis and Castanospermum australe. Natural...

  3. 7,8-secolignans from Schisandra neglecta and their anti-HIV-1 activities

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xuemei; Mu, Huaixue; Hu, Qiufen, E-mail: huqiufena@yahoo.com.cn [Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan University of Nationalities (China); Wang, Ruirui; Yang, Liumeng; Zheng, Yongtang [Kunming Institute of Zoology, Chinese Academy of Sciences (China); Sun, Handong; Xiao, Weilie, E-mail: xwl@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China)

    2012-10-15

    Four new 7,8-secolignans (neglectahenols A-D), together with two known 7,8-secolignans, were isolated from leaves and stems of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive one and two dimension NMR (nuclear magnetic resonance) techniques. 7,8-Secolignans and neglectahenols A-D were also tested for their anti-HIV-1 (human immunodeficiency virus type 1) activities, and all of them showed modest activities. (author)

  4. CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

    OpenAIRE

    Killian, M. Scott; Roop, Jeremy; Ng, Sharon; Frederick M Hecht; Levy, Jay A.

    2009-01-01

    CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. CD8+ lymphocytes from subjects with untreated primary HIV-1 in...

  5. In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds.

    Science.gov (United States)

    Forthal, Donald N; Phan, Tran B; Slepenkin, Anatoly V; Landucci, Gary; Chu, Hencelyn; Elofsson, Mikael; Peterson, Ellena

    2012-10-01

    Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. In this study, the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides were determined. Inhibitory activity was assessed using TZM-bl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Antiviral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the antibacterial activity of salicylidene acylhydrazides is reversible by Fe(2+), the ability of Fe(2+) and other cations to reverse the anti-HIV-1 activity of the compounds was determined. Real-time PCR was also employed to determine the stage affected in the HIV-1 replication cycle. Four compounds with 50% inhibitory concentrations against HIV-1 of 1-7 μM were identified. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether the target for virus replication was TZM-bl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe(2+), but not other cations, reversed the anti-HIV-1 effect. Finally, the inhibitory effect of the compounds occurred at a post-integration step. In conclusion, salicylidene acylhydrazides were identified with in vitro anti-HIV-1 activity in the micromolar range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide. PMID:22819150

  6. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  7. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

    Science.gov (United States)

    Li, Wan-Fei; Wang, Juan; Zhang, Jing-Jie; Song, Xun; Ku, Chuen-Fai; Zou, Juan; Li, Ji-Xin; Rong, Li-Jun; Pan, Lu-Tai; Zhang, Hong-Jie

    2015-01-01

    Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2). PMID:26610490

  8. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi

    Directory of Open Access Journals (Sweden)

    Wan-Fei Li

    2015-11-01

    Full Text Available Henrin A (1, a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D and two-dimensional (2D NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2.

  9. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

    Science.gov (United States)

    Li, Wan-Fei; Wang, Juan; Zhang, Jing-Jie; Song, Xun; Ku, Chuen-Fai; Zou, Juan; Li, Ji-Xin; Rong, Li-Jun; Pan, Lu-Tai; Zhang, Hong-Jie

    2015-11-24

    Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

  10. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes.

    Science.gov (United States)

    Dubey, Vaibhav; Mishra, Dinesh; Nahar, Manoj; Jain, Vikas; Jain, Narendra Kumar

    2010-08-01

    Indinavir, as a protease inhibitor with a short biological half life, variable pH-dependent oral absorption, and extensive first-pass metabolism, presents a challenge with respect to its oral administration. The current work aims to formulate and characterize indinavir-bearing ethanolic liposomes (ethosomes), and to investigate their enhanced transdermal delivery potential. The prepared ethanolic liposomes were characterized to be spherical, unilamellar structures having low polydispersity, nanometric size range, and improved entrapment efficiency over other delivery formulations. Permeation studies of indinavir across human cadaver skin resulted in enhanced transdermal flux from ethanolic liposomes that was significantly (P ethosomes), and investigate their enhanced transdermal delivery potential, demonstrating a potentially a suitable approach for transdermal delivery of this protease inhibitor for HIV treatment, which typically has been associated with limited bioavailability via the oral route. PMID:20093197

  11. Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity

    Directory of Open Access Journals (Sweden)

    Ana I. S. Esteves

    2011-01-01

    Full Text Available The extraction, fractionation and HIV-1 inhibition potential of polysaccharides extracted from three species of marine sponges, Erylus discophorus, Cliona celata and Stelletta sp., collected in the Northeastern Atlantic, is presented in this work. The anti-HIV activity of 23 polysaccharide pellets and three crude extracts was tested. Crude extracts prepared from Erylus discophorus specimens were all highly active against HIV-1 (90 to 95% inhibition. Cliona celata pellets showed low polysaccharide content (bellow 38.5% and almost no anti-HIV activity (<10% inhibition. Stelletta sp. pellets, although quite rich in polysaccharide (up to 97.3%, showed only modest bioactivity (<36% HIV-1 inhibition. Erylus discophorus pellets were among the richest in terms of polysaccharide content (up to 98% and the most active against HIV-1 (up to 95% inhibition. Chromatographic fractionation of the polysaccharide pellet obtained from a specimen of Erylus discophorus (B161 yielded only modestly active fractions. However, we could infer that the active molecule is most probably a high molecular weight sulfated polysaccharide (>2000 kDa, whose mechanism is possibly preventing viral attachment and entry (fusion inhibitor.

  12. Construction of Ru(II) Polypyridyl Based Macrocycles: Synthesis, Characterization, Electrochemical, Li+ Binding, Antitumour and Anti-HIV properties

    OpenAIRE

    Mishra, Lallan; Sinha, Ragini; Pandey, P. C.

    2001-01-01

    Some ruthenium (II) polypyridyl complexes with a bis-chalcone (obtained by the condensation of 3-methyl-thiophene-2-carboxaldehyde and 4-acetyl pyridine) have been synthesized and characterized spectroscopically (IR, NMR, UV/Vis), conductimetric, elemental analysis and FAB mass data. Their luminescent, redox and Li+ binding properties have been studied. The anti-HIV and antitumour activities have also been reported.

  13. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy

    Science.gov (United States)

    Lee, Sulggi A.; Bacchetti, Peter; Chomont, Nicolas; Fromentin, Remi; Lewin, Sharon R.; O’Doherty, Una; Palmer, Sarah; Richman, Douglas D.; Siliciano, Janet D.; Yukl, Steven A.; Deeks, Steven G.; Burbelo, Peter D.

    2016-01-01

    Background A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the “reservoir”). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART). Methods We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables. Results Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results. Conclusions Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV

  14. Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

    Directory of Open Access Journals (Sweden)

    Silvana Pasetto

    Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

  15. Ligand-Based Virtual Screening in a Search for Novel Anti-HIV-1 Chemotypes.

    Science.gov (United States)

    Kurczyk, Agata; Warszycki, Dawid; Musiol, Robert; Kafel, Rafał; Bojarski, Andrzej J; Polanski, Jaroslaw

    2015-10-26

    In a search for new anti-HIV-1 chemotypes, we developed a multistep ligand-based virtual screening (VS) protocol combining machine learning (ML) methods with the privileged structures (PS) concept. In its learning step, the VS protocol was based on HIV integrase (IN) inhibitors fetched from the ChEMBL database. The performances of various ML methods and PS weighting scheme were evaluated and applied as VS filtering criteria. Finally, a database of 1.5 million commercially available compounds was virtually screened using a multistep ligand-based cascade, and 13 selected unique structures were tested by measuring the inhibition of HIV replication in infected cells. This approach resulted in the discovery of two novel chemotypes with moderate antiretroviral activity, that, together with their topological diversity, make them good candidates as lead structures for future optimization.

  16. QSAR study for anti-HIV-1 activities of HEPT derivatives using MLR and PLS

    Directory of Open Access Journals (Sweden)

    Ivan Daniela

    2013-01-01

    Full Text Available A QSAR study using Multiple Linear Regression (MLR and a Partial Least Squares (PLS methodology was performed for a series of 127 derivatives of 1-(2-hydroxy-ethoxymethyl]-6-(phenylthio-timine (HEPT, a potent inhibitor of the of the human immunodeficiency virus type 1, HIV-1 reverse transcriptase (RT. To explore the relationship between a pool of HEPT derivative descriptors (as independent variables and anti-HIV-1 activity expressed as log (1/EC50, as dependent variable MLR and PLS methods have been employed. Using Dragon descriptors, the present study aims to develop a predictive and robust QSAR model for predicting anti-HIV activity of the HEPT derivatives for better understanding the molecular features of these compounds important for their biological activity. According to the squared correlation coefficients, which had values between 0.826 and 0.809 for the MLR and PLS methods, the results demonstrate almost identical qualities and good predictive ability for both MLR and PLS models. After dividing the dataset into training and test sets, the model predictability was tested by several parameters, including the Golbraikh-Tropsha external criteria and the goodness of fit tested with the Y-randomization test. [Acknowledgements. This project was financially supported by Project 1.1 and 1.2 of the Institute of Chemistry of the Romanian Academy. STATISTICA, MobyDigs and SIMCA-P+ acquisition was funded by Ministerul Educatiei, Cercetarii si Tineretului - Autoritatea Nationala pentru Cercetare Stiintifica (MedC-ANCS, contract grant number: 71GR/2006

  17. Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2006-10-01

    Full Text Available Abstract Background Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP, a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. Methods The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP, the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. Results The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate, cellulose sulfate, carrageenan, CAP (in soluble form and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold diminished in the presence of SP (33.3%. Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. Conclusion The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.

  18. Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2016-05-01

    Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy. PMID:26800572

  19. Aaptamine Derivatives with Antifungal and Anti-HIV-1 Activities from the South China Sea Sponge Aaptos aaptos

    Directory of Open Access Journals (Sweden)

    Hao-Bing Yu

    2014-12-01

    Full Text Available Five new alkaloids of aaptamine family, compounds (1–5 and three known derivatives (6–8, have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated by spectroscopic analyses, as well as by comparison with the literature data. Compounds 1–2 are characterized with triazapyrene lactam skeleton, whereas compounds 4–5 share an imidazole-fused aaptamine moiety. These compounds were evaluated in antifungal and anti-HIV-1 assays. Compounds 3, 7, and 8 showed antifungal activity against six fungi, with MIC values in the range of 4 to 64 μg/mL. Compounds 7–8 exhibited anti-HIV-1 activity, with inhibitory rates of 88.0% and 72.3%, respectively, at a concentration of 10 μM.

  20. [HPLC enantioseparation, absolute configuration determination and anti-HIV-1 activity of (±)-F18 enantiomers].

    Science.gov (United States)

    Zhang, Lei-lei; Xue, Hai; Li, Li; Lu, Xiao-fan; Chen, Zhi-wei; Lu, Gang

    2015-06-01

    Racemic (±)-F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide A), an analog of nature product (+)-calanolide A, is a new anti-HIV-1 nonnucleoside reverse transcript inhibitor (NNRTI). A successful enantioseparation of (±)-F18 offering (R)-F18 and (S)-F18 was achieved by a chiral stationary phase prepared HPLC. Their absolute configurations were determined by measurement of their electronic circular dichroisms combined with modem quantum-chemical calculations. Further investigation revealed that (R)-F18 and (S)-F18 shared a similar anti-HIV activities, however, (R)-F18 was more potent than (S)-F18 against wild-type virus, K101E mutation and P225H mutation pseudoviruses. PMID:26521445

  1. A new vinyl selenone-based domino approach to spirocyclopropyl oxindoles endowed with anti-HIV RT activity.

    Science.gov (United States)

    Palomba, M; Rossi, L; Sancineto, L; Tramontano, E; Corona, A; Bagnoli, L; Santi, C; Pannecouque, C; Tabarrini, O; Marini, F

    2016-02-14

    Herein, we disclose a general and flexible access to spirocyclopropyl oxindoles by a domino Michael/intramolecular nucleophilic substitution pathway with variously substituted vinyl selenones and enolizable oxindoles in aqueous sodium hydroxide solution. The spirocyclopropyl oxindole being a privileged scaffold, some of the synthesized compounds were selected for biological evaluation. Compound showed selective anti-HIV-1 activity thanks to its ability to inhibit the reverse transcriptase.

  2. The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC

    OpenAIRE

    Nicholas C. Obitte; Rohan, Lisa C; Adeyeye, Christianah M; Parniak, Michael A; Esimone, Charles O

    2013-01-01

    Background CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability. Objective The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity. Methods CSIC self-emulsifying oil formulations (SEFs)...

  3. Evaluation of HBsAg, anti-HCV, anti-HIV and VDRL test results in blood donors

    OpenAIRE

    Deveci, Özcan; Tekin, Alicem; Günbay, Seda Sibel; Kılıç, Dilek; KAYGUSUZ, Sedat; Ağalar, Canan; Özer, Türkan Toka

    2011-01-01

    Objectives: The most frequently encountered complication in the transfusion of blood and blood products are transmitted infections from these products. Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) remain the leading most important health problems in the transfusion of blood and blood products worldwide. Therefore, screening tests such as HBsAg, anti-HCV, anti-HIV, and RPR or VDRL for Treponema pallidum are mandatory tests to loo...

  4. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

    Science.gov (United States)

    Briz, Verónica; Sepúlveda-Crespo, Daniel; Diniz, Ana Rita; Borrego, Pedro; Rodes, Berta; de La Mata, Francisco Javier; Gómez, Rafael; Taveira, Nuno; Muñoz-Fernández, Mª Ángeles

    2015-08-01

    The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

  5. Fluorine Substituted 1,2,4-Triazinones as Potential Anti-HIV-1 and CDK2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Mohammed S. I. Makki

    2014-01-01

    Full Text Available Fluorine substituted 1,2,4-triazinones have been synthesized via alkylation, amination, and/or oxidation of 6-(2-amino-5-fluorophenyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H-one 1 and 4-fluoro-N-(4-fluoro-2-(5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-ylphenylbenzamide 5 as possible anti-HIV-1 and CDK2 inhibitors. Alkylation on positions 2 and 4 in 1,2,4-triazinone gave compounds 6–8. Further modification was performed by selective alkylation and amination on position 3 to form compounds 9–15. However oxidation of 5 yielded compounds 16–18. Structures of the target compounds have been established by spectral analysis data. Five compounds (5, 11, 14, 16, and 17 have shown very good anti-HIV activity in MT-4 cells. Similarly, five compounds (1, 3, and 14–16 have exhibited very significant CDK2 inhibition activity. Compounds 14 and 16 were found to have dual anti-HIV and anticancer activities.

  6. Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

    Directory of Open Access Journals (Sweden)

    Fabrizio Chiodo

    2014-06-01

    Full Text Available The therapeutic approach for the treatment of HIV infection is based on the highly active antiretroviral therapy (HAART, a cocktail of antiretroviral drugs. Notwithstanding HAART has shown different drawbacks like toxic side effects and the emergence of viral multidrug resistance. Nanotechnology offers new tools to improve HIV drug treatment and prevention. In this scenario, gold nanoparticles are an interesting chemical tool to design and prepare smart and efficient drug-delivery systems. Here we describe the preparation and antiviral activity of carbohydrate-coated gold nanoparticles loaded with anti-HIV prodrug candidates. The nucleoside reverse transcriptase inhibitors abacavir and lamivudine have been converted to the corresponding thiol-ending ester derivatives and then conjugated to ~3 nm glucose-coated gold nanoparticles by means of “thiol-for-thiol” ligand place exchange reactions. The drugs-containing glyconanoparticles were characterized and the pH-mediated release of the drug from the nanoparticle has been determined. The antiviral activity was tested by evaluating the replication of NL4-3 HIV in TZM-bl infected cells. The proof-of-principle presented in this work aims to introduce gold glyconanoparticles as a new multifunctional drug-delivery system in the therapy against HIV.

  7. Voltammetric determination of wedelolactone, an anti-HIV herbal drug, at boron-doped diamond electrode

    Indian Academy of Sciences (India)

    Sachin Saxena; Ratnanjali Shrivastava; Soami P Satsangee

    2015-05-01

    Boron-doped diamond electrode has been utilized for the study of electrochemical behaviour of an anti-HIV herbal drug wedelolactone in Britton-Robinson buffer (pH-2.5) by square-wave and cyclic voltammetry techniques. The response characteristics of cyclic voltammetry and square wave voltammetry showed a remarkable increase in the anodic peak current and electrochemical impedance spectroscopy revealed a lowering in charge transfer resistance at the boron-doped diamond electrode as compared to the glassy carbon electrode that can be attributed to the higher sensitivity of boron-doped diamond sensor. Cyclic voltammetry at the boron-doped diamond surface revealed the oxidation of wedelolactone with two oxidation peaks (P1 and P2) with Ep1 = 0.4V and Ep2 =1.00 V with scan rate varying from 10 - 220 mV/s and exhibits diffusion-controlled process. Based on the electrochemical measurements, a probable oxidation mechanism has been deduced and the electrode dynamics parameters have been evaluated. The effect of concentration on the peak currents of wedelolactone was found to have a linear relationship within the concentration range of 50–700 ng/mL. The LOD and LOQ were found to be 43.87 and 132.93 ng/mL respectively. The applicability of the proposed method was further scrutinized by the successful determination of wedelolactone in real plant samples.

  8. Transgenic Production of an Anti HIV Antibody in the Barley Endosperm.

    Directory of Open Access Journals (Sweden)

    Goetz Hensel

    Full Text Available Barley is an attractive vehicle for producing recombinant protein, since it is a readily transformable diploid crop species in which doubled haploids can be routinely generated. High amounts of protein are naturally accumulated in the grain, but optimal endosperm-specific promoters have yet to be perfected. Here, the oat GLOBULIN1 promoter was combined with the legumin B4 (LeB4 signal peptide and the endoplasmic reticulum (ER retention signal (SEKDEL. Transgenic barley grain accumulated up to 1.2 g/kg dry weight of recombinant protein (GFP, deposited in small roundish compartments assumed to be ER-derived protein bodies. The molecular farming potential of the system was tested by generating doubled haploid transgenic lines engineered to synthesize the anti-HIV-1 monoclonal antibody 2G12 with up to 160 μg recombinant protein per g grain. The recombinant protein was deposited at the periphery of protein bodies in the form of a mixture of various N-glycans (notably those lacking terminal N-acetylglucosamine residues, consistent with their vacuolar localization. Inspection of protein-A purified antibodies using surface plasmon resonance spectroscopy showed that their equilibrium and kinetic rate constants were comparable to those associated with recombinant 2G12 synthesized in Chinese hamster ovary cells.

  9. L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.

    Science.gov (United States)

    Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo; Zhang, Xiaoyan; Yan, Huimin

    2012-06-01

    A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens. PMID:22391529

  10. Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein.

    Science.gov (United States)

    Moghadam, Ali; Niazi, Ali; Afsharifar, Alireza; Taghavi, Seyed Mohsen

    2016-01-01

    In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents. PMID:27459300

  11. Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein

    Science.gov (United States)

    Moghadam, Ali; Niazi, Ali; Afsharifar, Alireza; Taghavi, Seyed Mohsen

    2016-01-01

    In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents. PMID:27459300

  12. Avaliação da testagem anti-HIV no pré-natal e na assistência ao parto no Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Daniela Marcondes Gomes

    2015-12-01

    Full Text Available Resumo Objetivos: avaliar a testagem anti-HIV durante a assistência pré-natal e ao parto no Sistema Único de Saúde. Métodos: estudo transversal conduzido em 2009 em 15 maternidades no Rio de Janeiro, sendo entrevistada amostra representativa de 835 parturientes e observados prontuários. Para avaliação da adequação da testagem anti-HIV foi elaborado um modelo lógico. Resultados: segundo informação das parturientes, 86,7% dispunham de sorologia não reagente do pré-natal e 55,7% foram submetidas ao teste rápido anti-HIV no hospital; em 49,9% dos casos o procedimento relativo ao teste rápido anti-HIV no hospital foi considerado adequado: mães com status ignorado de HIV do pré-natal submetidas ao teste rápido e mães com status conhecido não submetidas ao mesmo. Segundo dados do prontuário, 68,0% dispunham de sorologia não reagente e 79,6% foram submetidas ao teste rápido anti-HIV; em 50,9% dos casos o procedimento relativo ao teste rápido anti- HIV no hospital foi adequado. Conclusões: o protocolo de exames anti-HIV no pré-natal e na maternidade, vigentes em 2009, não foram cumpridos a contento, tanto por gerar procedimentos desnecessários quanto falhas na testagem da população alvo, ameaçando a instituição oportuna de medidas profiláticas de controle da transmissão vertical.

  13. In vitro and ex vivo inhibition of human telomerase by anti-HIV nucleoside reverse transcriptase inhibitors (NRTIs but not by non-NRTIs.

    Directory of Open Access Journals (Sweden)

    Kyle R Hukezalie

    Full Text Available Telomerase is a specialized reverse transcriptase responsible for the de novo synthesis of telomeric DNA repeats. In addition to its established reverse transcriptase and terminal transferase activities, recent reports have revealed unexpected cellular activities of telomerase, including RNA-dependent RNA polymerization. This telomerase characteristic, distinct from other reverse transcriptases, indicates that clinically relevant reverse transcriptase inhibitors might have unexpected telomerase inhibition profiles. This is particularly important for the newer generation of RT inhibitors designed for anti-HIV therapy, which have reported higher safety margins than older agents. Using an in vitro primer extension assay, we tested the effects of clinically relevant HIV reverse transcriptase inhibitors on cellular telomerase activity. We observed that all commonly used nucleoside reverse transcriptase inhibitors (NRTIs, including zidovudine, stavudine, tenofovir, didanosine and abacavir, inhibit telomerase effectively in vitro. Truncated telomere synthesis was consistent with the expected mode of inhibition by all tested NRTIs. Through dose-response experiments, we established relative inhibitory potencies of NRTIs on in vitro telomerase activity as compared to the inhibitory potencies of the corresponding dideoxynucleotide triphosphates. In contrast to NRTIs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs nevirapine and efavirenz did not inhibit the primer extension activity of telomerase, even at millimolar concentrations. Long-term, continuous treatment of human HT29 cells with select NRTIs resulted in an accelerated loss of telomere repeats. All tested NRTIs exhibited the same rank order of inhibitory potencies on telomerase and HIV RT, which, according to published data, were orders-of-magnitude more sensitive than other DNA polymerases, including the susceptible mitochondria-specific DNA polymerase gamma. We concluded that

  14. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity.

    Science.gov (United States)

    Dezzutti, Charlene S; Brown, Elizabeth R; Moncla, Bernard; Russo, Julie; Cost, Marilyn; Wang, Lin; Uranker, Kevin; Kunjara Na Ayudhya, Ratiya P; Pryke, Kara; Pickett, Jim; Leblanc, Marc-André; Rohan, Lisa C

    2012-01-01

    Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9), KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm. PMID:23144863

  15. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity.

    Science.gov (United States)

    Dezzutti, Charlene S; Brown, Elizabeth R; Moncla, Bernard; Russo, Julie; Cost, Marilyn; Wang, Lin; Uranker, Kevin; Kunjara Na Ayudhya, Ratiya P; Pryke, Kara; Pickett, Jim; Leblanc, Marc-André; Rohan, Lisa C

    2012-01-01

    Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9), KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm.

  16. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity.

    Directory of Open Access Journals (Sweden)

    Charlene S Dezzutti

    Full Text Available Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC aqueous- (n = 10, lipid- (n = 2, and silicone-based (n = 2 products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9, KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm.

  17. Conformational analysis on anti-HIV-1 peptide T22([Tyr5,12Lys7]-polyphemusinⅡ)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The conformational scan of anti-HIV peptide T22 ([Tyr5,12, Lys7]-polyphemusin Ⅱ) backbone on a deformed potential energy surface (PES) was performed using the potential smoothing searching (PSS) protocol. All located minima were then transferred to the original PES using undeformed optimized potentials for liquid simulations (OPLS) potential function, and minimized by multi-conformer minimization (MCM). For solution-phase calculations, the GB/SA continuum model for water was used. This application of PSS integrated with MCM is proved a feasible method for solving the multiple-minimum problem in the conformational analysis of flexible molecules with cyclic structure.

  18. Is Wetter Better? An Evaluation of Over-the-Counter Personal Lubricants for Safety and Anti-HIV-1 Activity

    OpenAIRE

    Dezzutti, Charlene S.; Brown, Elizabeth R.; Bernard Moncla; Julie Russo; Marilyn Cost; Lin Wang; Kevin Uranker; Kunjara Na Ayudhya, Ratiya P.; Kara Pryke; Jim Pickett; Marc-André Leblanc; Rohan, Lisa C.

    2012-01-01

    Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmo...

  19. In vitro anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca

    OpenAIRE

    Behbahani, M.; Sayedipour, S.; Pourazar, A.; Shanehsazzadeh, M.

    2014-01-01

    Previously, we reported that the kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca showed potent anti-HSV activity. In the present study the anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside are investigated at different concentrations (100, 50, 25 and 10 μg/ml) using HIV-1 p24 Antigen kit. Real-time Polymerase chain reaction (RT-PCR) assay was also used for quantification of full range of virus load observed in treated and untreated cells. According t...

  20. HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Olofsson, S; Nielsen, Jens Ole;

    1994-01-01

    on this infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/M phi s were highly susceptible to HIV-1 infection, in contrast to monocyte/M phi s cultured 4 weeks. The infection by virus isolated immediately...... to CD4 and that post binding events may be common to the infection of lymphocytes. Anti HIV-1 sera showed neutralizing activity against heterologous and even autologous escape virus. This finding, together with the observation that monocytes and M phi s are infected in vivo, suggests that protection...

  1. HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Olofsson, S; Nielsen, Jens Ole;

    1994-01-01

    To characterize the role of the humoral immune response on HIV-1 infection of monocytes and macrophages (M phi s) we examined the susceptibility of in vitro cultured monocyte/M phi s to various HIV-1 isolates and the influence of heterologous and particularly autologous anti HIV-1 sera...... on this infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/M phi s were highly susceptible to HIV-1 infection, in contrast to monocyte/M phi s cultured 4 weeks. The infection by virus isolated immediately...

  2. Semisynthetic analogues of PSC-RANTES, a potent anti-HIV protein.

    Science.gov (United States)

    Gaertner, Hubert; Offord, Robin; Botti, Paolo; Kuenzi, Gabriel; Hartley, Oliver

    2008-02-01

    New HIV prevention methods are needed, and among those currently being explored are "microbicides", substances applied topically to prevent HIV acquisition during sexual intercourse. The chemokine analogue PSC-RANTES (N(alpha)(n-nonanoyl)-des-Ser(1)-[ L-thioprolyl(2), L-cyclohexylglycyl(3)]-RANTES(4-68)) is a highly potent HIV entry inhibitor which has shown promising efficacy in its initial evaluation as a candidate microbicide. However, a way must be found to produce the molecule by cheaper means than total chemical synthesis. Since the only noncoded structures are located at the N-terminus, a possible solution would be to produce a protein fragment representing all but the N-terminal region using low-cost recombinant production methods and then to attach, site specifically, a short synthetic fragment containing the noncoded N-terminal structures. Here, we describe the evaluation of a range of different conjugation chemistries in order to identify those with potential for development as economical routes to production of a PSC-RANTES analogue with antiviral activity as close as possible to that of the parent protein. The strategies tested involved linkage through oxime, hydrazone/hydrazide, and Psi[CH2-NH] bonds, as well as through a peptide bond obtained either by a thiazolidine rearrangement or by direct alpha-amino acylation of a protein fragment in which 4 of the 5 lysine residues of the native sequence were replaced by arginine (the fifth lysine is essential for activity). Where conjugation involved replacement of one or more residues with a linker moiety, the point in the main chain at which the linker was introduced was varied. The resulting panel of 22 PSC-RANTES analogues was evaluated for anti-HIV activity in an entry inhibition assay. The [Arg (25,45,56,57)] PSC-RANTES analogue has comparable potency to PSC-RANTES, and one of the oxime linked analogues, 4L-57, has potency only 5-fold lower, with scope for improvement. Both represent promising leads for

  3. In vitro anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca.

    Science.gov (United States)

    Behbahani, M; Sayedipour, S; Pourazar, A; Shanehsazzadeh, M

    2014-01-01

    Previously, we reported that the kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca showed potent anti-HSV activity. In the present study the anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside are investigated at different concentrations (100, 50, 25 and 10 μg/ml) using HIV-1 p24 Antigen kit. Real-time Polymerase chain reaction (RT-PCR) assay was also used for quantification of full range of virus load observed in treated and untreated cells. According to the results of RT- PCR, tested compounds at a concentration of 100 μg/ml exerted potent inhibitory effect. Time of drug addition experiments demonstrated that these compounds exerted their inhibitory effects on the early stage of HIV infection. The results also showed potent anti-HIV-1 reverse transcriptase activity. Antiviral activity of kaempferol-7-O-glucoside was more pronounced than that of kaempferol. These findings demonstrate that kaempferol-7-O-glucoside could be considered as a new potential drug candidate for the treatment of HIV infection which requires further assessments. PMID:26339261

  4. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhang, Xiao-Liang; Song, Jia-Hao; Pang, Wei; Zheng, Yong-Tang

    2016-07-18

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  5. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina)

    Science.gov (United States)

    ZHANG, Xiao-Liang; SONG, Jia-Hao; PANG, Wei; ZHENG, Yong-Tang

    2016-01-01

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  6. HIV testing among pregnant women in Brazil: rates and predictors Prueba anti-HIV en mujeres embarazadas en Brasil: tasas y predictivos Testagem anti-HIV em mulheres grávidas no Brasil: taxas e preditores

    Directory of Open Access Journals (Sweden)

    Valdiléa G Veloso

    2008-10-01

    Full Text Available OBJECTIVE: To assess rates of offering and uptake of HIV testing and their predictors among women who attended prenatal care. METHODS: A population-based cross-sectional study was conducted among postpartum women (N=2,234 who attended at least one prenatal care visit in 12 cities. Independent and probabilistic samples were selected in the cities studied. Sociodemographic data, information about prenatal care and access to HIV prevention interventions during the current pregnancy were collected. Bivariate and multivariate analyses were carried out to assess independent effects of the covariates on offering and uptake of HIV testing. Data collection took place between November 1999 and April 2000. RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the current pregnancy. Offering of HIV testing was positively associated with: previous knowledge about prevention of mother-to-child transmission of HIV; higher number of prenatal care visits; higher level of education and being white. HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate that dissemination of information about prevention of mother-to-child transmission among women may contribute to increasing HIV testing coverage during pregnancy. Non-white women with lower level of education should be prioritized. Strategies to increase attendance of vulnerable women to prenatal care and to raise awareness among health care workers are of utmost importance.OBJETIVO: Estimar las tasas de oferta y realización de la prueba anti-HIV y sus predictivos entre mujeres que recibieron atención prenatal. MÉTODOS: Se realizó un estudio transversal, de base poblacional, con 2.234 puérperas en 12 ciudades de Brasil. Las muestras probabilísticas fueron seleccionadas independientemente por ciudad, entre puérperas que asistieron a por lo menos una visita prenatal. Se colectaron datos sociodemográficos, informaciones sobre cuidado prenatal y acceso a

  7. Particle agglutination test "Serodia HIV-1/2" as a novel anti-HIV-1/2 screening test: comparative study on 3311 serum samples.

    Science.gov (United States)

    Poljak, M; Zener, N; Seme, K; Kristancic, L

    1997-01-01

    Enzyme immunoassays are most widely used screening tests for antibodies to human immunodeficiency viruses (HIV). Nevertheless, the need of simpler, noninstrumented tests is evident in many parts of the world, where laboratory facilities and trained personnel are limited, and HIV incidence is high. A recently developed variant of gelatin-particle agglutination tests, Serodia HIV-1/2 (Fujirebio Inc., Tokyo, Japan), is one of such simple and noninstrumented tests. To evaluate its utility, 3311 serum samples (281 anti-HIV-1 positive, 8 anti-HIV-2 positive and 3022 anti-HIV-1/2 negative) obtained from 2632 individuals from Slovenia, other parts of former Yugoslavia and Senegal were investigated. No false-negative results and only one false-positive result were obtained during the procedures, giving overall sensitivity and specificity of the particle agglutination test of 100% and 99.97%, respectively. We have concluded that Serodia HIV-1/2 test is highly specific and sensitive for detection of anti-HIV-1/2 antibodies, suitable for small blood banks and for epidemiological surveys.

  8. Synthesis and Anti-HIV Activity of Trisubstituted (3'R, 4'R)-3',4'- Di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) Analogs

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To further explore the potential of DCK analogs as anti-HIV drug candidates, ten new tri-substituted (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives (4-13)were designed, synthesized, and evaluated against HIV replication in MT4 cells and H9 lymphocytes.

  9. 近红外光谱快速鉴别抗艾滋病药物%Near-infrared spectroscopic methods for rapid identification of anti-HIV drugs

    Institute of Scientific and Technical Information of China (English)

    周景岳; 尹利辉; 张学博; 高延甲; 卢京光; 金少鸿

    2012-01-01

    Objective:To develop near - infrared spectroscopic rapid methods for the anti - HIV drugs from different manufacturers. Method:The spectra of the samples collected by near - infrared spectrometer were selected to establish conformity test or correlation coefficient methods to identify the anti - HIV drugs. Results:The anti - HIV drugs from different manufacturers are well distinguished by the established near - infrared spectroscopic methods. Conclusion:The near - infrared spectroscopic methods can be used as an alternative method for the rapid identifica tion of the anti - HIV drugs from different manufacturers.%目的:建立鉴别不同厂家间抗艾滋病药物近红外快速检验方法.方法:采用近红外光谱仪采集样品光谱,建立一致性检验模型或相关系数模型,以区分不同厂家间的抗艾滋病药物.结果:对市场抽样的抗艾滋病药物样品,建立的近红外模型可以有效地区分.结论:所建立的近红外分析模型可以作为快速鉴别不同厂家间抗艾滋病药物的参考方法.

  10. Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm

    Directory of Open Access Journals (Sweden)

    Jones Maureen

    2010-07-01

    Full Text Available Abstract Background At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1 infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. Results Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC50 was ≤ 3.5 (0.8-3.5% and the TC50 ≤ 6.3 (1.0-6.3%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice

  11. A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    Full Text Available BACKGROUND: Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition. METHODS: 30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood. RESULTS: A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators. CONCLUSIONS: Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and

  12. Discovery of non-peptide small molecular CXCR4 antagonists as anti-HIV agents: Recent advances and future opportunities.

    Science.gov (United States)

    Zhang, Heng; Kang, Dongwei; Huang, Boshi; Liu, Na; Zhao, Fabao; Zhan, Peng; Liu, Xinyong

    2016-05-23

    CXCR4 plays vital roles in HIV-1 life cycle for it's essential in mediating the interaction of host and virus and completing the entry process in the lifecycle of HIV-1 infection. Compared with some traditional targets, CXCR4 provides a novel and less mutated drug target in the battle against AIDS. Its antagonists have no cross resistance with other antagonists. Great achievements have been made recent years and a number of small molecular CXCR4 antagonists with diversity scaffolds have been discovered. In this review, recent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists are described. Moreover, some classical medicinal chemistry strategies and novel methodologies are also introduced. PMID:26974376

  13. Inculcating safe sex attitudes in South African adolescents: a directive for the government's anti-HIV/AIDS policy.

    Science.gov (United States)

    D'Souza, Jayesh

    2010-01-01

    South Africa has one of the highest rates of HIV/AIDS in the world. Much blame for this has been laid on the apathy of the South African government and the cultural traits of South Africans. AIDS prevention research calls for early childhood education to raise awareness of the causes, dangers, and prevention of HIV/AIDS. This study involved surveys among a select sample of South African adolescents to determine their sexual attitudes before and after a cognitive-behavioral intervention. Overall, the results did not make a significant difference in their attitudes, suggesting pre-adolescent sex education might prove to be a more useful tool in anti-HIV/AIDS education. Risky sexual behavior, under the influence of alcohol, also serves as a warning to educate young consumers of alcohol. PMID:22192941

  14. A New Neolignan, and the Cytotoxic and Anti-HIV-1 Activities of Constituents from the Roots of Dasymaschalon sootepense.

    Science.gov (United States)

    Hongthong, Sakchai; Kuhakarn, Chutima; Jaipetch, Thaworn; Piyachaturawat, Pawinee; Jariyawat, Surawat; Suksen, Kanoknetr; Limthongkul, Jitra; Nuntasaen, Narong; Reutrakul, Vichai

    2016-06-01

    Bioassay-guided isolation from the ethyl acetate extract of Dasymaschalon sootepense roots led to the isolation of twelve compounds including a new dihydrobenzo-furan neolignan, (+)-(2S,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-methylbenzofuran-5-carbaldehyde (5), and eleven known compounds (1-4, and 6-12). The chemical structures and stereochemistry of all the isolated compounds were established by spectroscopic techniques. The known compounds 4 and 6 have been fully characterized spectroscopically, including their absolute configurations. Cytotoxic and anti-HIV-1 reverse transcriptase (RT) activities of compounds 1-3, 5 and 8-12 were determined. Among compounds screened, compounds 2, 3 and 10 displayed weak cytotoxic activity with ED50 values ranging from 9.6-47.5 μM and only compound 2 was found weakly active against HIV-1 RT with an IC50 value of 323.2 μM. PMID:27534123

  15. Inculcating safe sex attitudes in South African adolescents: a directive for the government's anti-HIV/AIDS policy.

    Science.gov (United States)

    D'Souza, Jayesh

    2010-01-01

    South Africa has one of the highest rates of HIV/AIDS in the world. Much blame for this has been laid on the apathy of the South African government and the cultural traits of South Africans. AIDS prevention research calls for early childhood education to raise awareness of the causes, dangers, and prevention of HIV/AIDS. This study involved surveys among a select sample of South African adolescents to determine their sexual attitudes before and after a cognitive-behavioral intervention. Overall, the results did not make a significant difference in their attitudes, suggesting pre-adolescent sex education might prove to be a more useful tool in anti-HIV/AIDS education. Risky sexual behavior, under the influence of alcohol, also serves as a warning to educate young consumers of alcohol.

  16. Anti-HIV-1 antibody-dependent cellular cytotoxicity mediated by hyperimmune bovine colostrum IgG.

    Science.gov (United States)

    Kramski, Marit; Lichtfuss, Gregor F; Navis, Marjon; Isitman, Gamze; Wren, Leia; Rawlin, Grant; Center, Rob J; Jaworowski, Anthony; Kent, Stephen J; Purcell, Damian F J

    2012-10-01

    Antibodies with antibody-dependent cellular cytotoxicity (ADCC) activity play an important role in protection against HIV-1 infection, but generating sufficient amounts of antibodies to study their protective efficacy is difficult. HIV-specific IgG can be easily and inexpensively produced in large quantities using bovine colostrum. We previously vaccinated cows with HIV-1 envelope gp140 and elicited high titers of anti-gp140-binding IgG in colostrum. In the present study, we determined whether bovine antibodies would also demonstrate specific cytotoxic activity. We found that bovine IgG bind to Fcγ-receptors (FcγRs) on human neutrophils, monocytes, and NK cells in a dose-dependent manner. Antibody-dependent killing was observed in the presence of anti-HIV-1 colostrum IgG but not nonimmune colostrum IgG. Killing was dependent on Fc and FcγR interaction since ADDC activity was not seen with F(ab')(2) fragments. ADCC activity was primarily mediated by CD14(+) monocytes with FcγRIIa (CD32a) as the major receptor responsible for monocyte-mediated ADCC in response to bovine IgG. In conclusion, we demonstrate that bovine anti-HIV colostrum IgG have robust HIV-1-specific ADCC activity and therefore offer a useful source of antibodies able to provide a rapid and potent response against HIV-1 infection. This could assist the development of novel Ab-mediated approaches for prevention of HIV-1 transmission. PMID:22730083

  17. Symmetrical 1-pyrrolidineacetamide showing anti-HIV activity through a new binding site on HIV-1 integrase

    Institute of Scientific and Technical Information of China (English)

    Li DU; Ya-xue ZHAO; Liu-meng YANG; Yong-tang ZHENG; Yun TANG; Xu SHEN; Hua-liang JIANG

    2008-01-01

    Aim:To characterize the functional and pharmacological features of a symmetrical 1-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene) bis-1-pyrrolidineacetamide,as a new anti-HIV compound which could competitively inhibit HIV-1 integrase (IN) binding to viral DNA.Methods:A surface plasma resonance (SPR)-based competitive assay was employed to determine the compound's inhibitory activity,and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell assay was used to qualify the antiviral activity.The potential binding sites were predicted by molecular modeling and determined by site-directed mutagenesis and a SPR binding assay.Results:l-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene) bis-1-pyrrolidineacetamide could competitively inhibit IN binding to viral DNA with a 50% inhibitory concentration (IC50) value of 7.29±0.68 μmol/L as investigated by SPR-based investigation.Another antiretroviral activity assay showed that this compound exhibited inhibition against HⅣ-Ⅰ(ⅢB) replication with a 50% effective concentration (EC50) value of 40.54 μmol/L in C8166 cells,and cytotoxicity with a cytotoxic concentration value of 173.84 μmol/L in mock-infected C8166 cells.Molecular docking predicted 3 potential residues as 1-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene)bis-1-pyrrolidineacetamide binding sites.The importance of 3 key amino acid residues (Lys103,Lys173,and Thr174) involved in the binding was further identified by site-directed mutagenesis and a SPR binding assay.Conclusion:This present work identified a new anti-HIV compound through a new IN-binding site which is expected to supply new potential drug-binding site information for HIV-1 integrase inhibitor discovery and development.

  18. Mapping the Vif-A3G interaction using peptide arrays: a basis for anti-HIV lead peptides.

    Science.gov (United States)

    Reingewertz, Tali H; Britan-Rosich, Elena; Rotem-Bamberger, Shahar; Viard, Mathias; Jacobs, Amy; Miller, Abigail; Lee, Ji Youn; Hwang, Jeeseong; Blumenthal, Robert; Kotler, Moshe; Friedler, Assaf

    2013-06-15

    Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3G (A3G) is a cytidine deaminase that restricts retroviruses, endogenous retro-elements and DNA viruses. A3G plays a key role in the anti-HIV-1 innate cellular immunity. The HIV-1 Vif protein counteracts A3G mainly by leading A3G towards the proteosomal machinery and by direct inhibition of its enzymatic activity. Both activities involve direct interaction between Vif and A3G. Disrupting the interaction between A3G and Vif may rescue A3G antiviral activity and inhibit HIV-1 propagation. Here, mapping the interaction sites between A3G and Vif by peptide array screening revealed distinct regions in Vif important for A3G binding, including the N-terminal domain (NTD), C-terminal domain (CTD) and residues 83-99. The Vif-binding sites in A3G included 12 different peptides that showed strong binding to either full-length Vif, Vif CTD or both. Sequence similarity was found between Vif-binding peptides from the A3G CTD and NTD. A3G peptides were synthesized and tested for their ability to counteract Vif action. A3G 211-225 inhibited HIV-1 replication in cell culture and impaired Vif dependent A3G degradation. In vivo co-localization of full-length Vif with A3G 211-225 was demonstrated by use of FRET. This peptide has the potential to serve as an anti-HIV-1 lead compound. Our results suggest a complex interaction between Vif and A3G that is mediated by discontinuous binding regions with different affinities.

  19. Studies on the Compounds of d4T Combined with Nitric Oxide Donors and Nitric Oxide Synthase Inhibitors and their Anti-HIV and AIDS Activity

    Institute of Scientific and Technical Information of China (English)

    KWALE MOLIME GUITREMBI Blaise(Central African); YAO Qi-zheng

    2004-01-01

    Stavudine, a potent anti-HIV and AiDS-related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5'-position on the sugar is an interesting template for the elaboration of new potent anti-HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.

  20. Anti-HIV-1 activities of the extracts from the medicinal plant Linum grandiflorum Desf

    DEFF Research Database (Denmark)

    Mohammed, Magdy M. D.; Christensen, Lars Porskjær; Ibrahim, Nabaweya A.;

    2009-01-01

    As part of our screening of anti-AIDS agents from natural sources e.g. Ixora undulata, Paulownia tomentosa, Fortunella margarita, Aegle marmelos and Erythrina abyssinica, the different organic and aqueous extracts of Linum grandiflorum leaves and seeds were evaluated in vitro by the microculture ...

  1. L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

    OpenAIRE

    Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo

    2012-01-01

    A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1...

  2. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo;

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate......, copper(I) iodide, and sodium tert-butoxide. Target compounds showed moderate activity against HIV-1....

  3. Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes.

    OpenAIRE

    Vandendriessche, T.; Chuah, M. K.; L. Chiang; Chang, H K; Ensoli, B; Morgan, R A

    1995-01-01

    Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4+ T lymphocytes. We therefore transduced CD4+ T lymphocytes from uninfected individuals with retroviral vect...

  4. Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

    OpenAIRE

    Chen Xi; Zhang Xiujuan; Lu Hong; Tan Suiyi; Lu Lu; Yang Jie; Qiao Pengyuan; Li Lin; Wu Shuguang; Jiang Shibo; Liu Shuwen

    2010-01-01

    Abstract Background Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbi...

  5. Highly potent HIV inhibition: engineering a key anti-HIV structure from PSC-RANTES into MIP-1 beta/CCL4.

    Science.gov (United States)

    Gaertner, Hubert; Lebeau, Olivier; Borlat, Irène; Cerini, Fabrice; Dufour, Brigitte; Kuenzi, Gabriel; Melotti, Astrid; Fish, Richard J; Offord, Robin; Springael, Jean-Yves; Parmentier, Marc; Hartley, Oliver

    2008-02-01

    The HIV coreceptor CCR5 is a validated target for both the prevention and therapy of HIV infection. PSC-RANTES, an N-terminally modified analogue of one of the natural chemokine ligands of CCR5 (RANTES/CCL5), is a potent inhibitor of HIV entry into target cells. Here, we set out to engineer the anti-HIV activity of PSC-RANTES into another natural CCR5 ligand (MIP-1beta/CCL4), by grafting into it the key N-terminal pharmacophore region from PSC-RANTES. We were able to identify MIP-1beta/CCL4 analogues that retain the receptor binding profile of MIP-1beta/CCL4, but acquire the very high anti-HIV potency and characteristic inhibitory mechanism of PSC-RANTES. Unexpectedly, we discovered that in addition to N-terminal structures from PSC-RANTES, the side chain of Lys33 is also necessary for full anti-HIV potency.

  6. 抗HIV活性木脂素类化合物研究进展%Advances in the Study on Anti-HIV Lignan Compounds

    Institute of Scientific and Technical Information of China (English)

    秦浩; 高丽; 郭军

    2012-01-01

    Lignan compounds have a variety of pharmacological activities. The mechanism of anti-HIV lig-nans is through affecting a particular aspect of HIV replication cycle, thus inhibiting viral replication and infection. Lignan is divided into four categories based on different anti-HIV detection methods. In this paper, we summarize the advance in the study on anti-HIV lignan compounds in last two decades.%木脂素类化合物具有多种药理活性,其抗HIV机制是通过影响HIV复制周期的某个环节,从而抑制病毒的复制和感染.按其抗HIV检测方法不同,将木脂素类化合物分成4类,本文对1990~2011年有关抗HIV活性木脂素类化合物研究文献进行综述.

  7. Amperometric sensing of anti-HIV drug zidovudine on Ag nanofilm-multiwalled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Rafati, Amir Abbas, E-mail: aa_rafati@basu.ac.ir; Afraz, Ahmadreza

    2014-06-01

    The zidovudine (ZDV) is the first drug approved for the treatment of HIV virus infection. The detection and determination of this drug are very importance in human serum because of its undesirable effects. A new ZDV sensor was fabricated on the basis of nanocomposite of silver nanofilm (Ag-NF) and multiwalled carbon nanotubes (MWCNTs) immobilized on glassy carbon electrode (GCE). The modified electrodes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry (CV), and linear sweep voltammetry (LSV) techniques. Results showed that the electrodeposited silver has a nanofilm structure and further electrochemical studies showed that the prepared nanocomposite has high electrocatalytic activity and is appropriate for using in sensors. The amperometric technique under optimal conditions is used for the determination of ZDV ranging from 0.1 to 400 ppm (0.37 μM–1.5 mM) with a low detection limit of 0.04 ppm (0.15 μM) (S/N = 3) and good sensitivity. The prepared sensor possessed accurate and rapid response to ZDV and shows an average recovery of 98.6% in real samples. - Highlights: • New anti-HIV drug sensor was fabricated on the basis of nanomaterials composite. • The GCE modified by prepared hydrophilic MWCNT silver nanoparticles. • Silver nanofilm electrodeposited on MWCNT/GCE and characterized by SEM, EDX, CV and LSV • Response of electrode to ZDV was thoroughly investigated by electrochemical techniques.

  8. Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

    Directory of Open Access Journals (Sweden)

    Min-Hsuan Lin

    Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

  9. Electrochemical studies of nevirapine, an anti-HIV drug, and its assay in tablets and biological samples

    Directory of Open Access Journals (Sweden)

    JALDAPPAGARI SEETHARAMAPPA

    2012-06-01

    Full Text Available The electrochemical oxidation of nevirapine, an anti-HIV drug, at a glassy carbon electrode has been studied by voltammetric techniques. Nevirapine showed one well defined irreversible oxidation peak with a potential of 0.749 V in phosphate buffer at pH 10. The effects of different electrolytes, pH and scan rate on the electrochemical behaviour of nevira¬pine were examined to determine the optimum reaction conditions. The oxidation peak current was found to vary linearly with the concentration of nevirapine in the range of 5.0 – 350 µM. The limit of detection and limit of quantification values were calculated and found to be 1.026 µM and 3.420 µM, respectively. The low relative standard deviation values of inter-day and intra-day assays highlighted the good reproducibility of the proposed m¬ethod for assay of nevirapine. Further, a sensitive and accurate differential pulse voltammetric method was developed for the determination of nevirapine concentrations in pharma¬ceutical formulations.

  10. Activation of the human nuclear xenobiotic receptor PXR by the reverse transcriptase-targeted anti-HIV drug PNU-142721

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yuan; Redinbo, Matthew R. (UNC)

    2012-10-09

    The human pregnane X receptor (PXR) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. PXR responds to a structurally diverse variety of endogenous and xenobiotic compounds, and coordinates the expression of genes central to the metabolism and excretion of potentially harmful chemicals, including human therapeutics. The reverse transcriptase inhibitor PNU-142721 has been designed to treat human immunodeficiency virus (HIV) infection. Although this compound has anti-HIV activity, it was established using cell-based assays that PNU-142721 is an efficacious PXR agonist. We present here the 2.8 {angstrom} resolution crystal structure of the human PXR ligand-binding domain in complex with PNU-142721. PXR employs one hydrogen bond and fourteen van der Waals contacts to interact with the ligand, but allows two loops adjacent to the ligand-binding pocket to remain disordered in the structure. These observations highlight the role structural flexibility plays in PXR's promiscuous responses to xenobiotics. The crystal structure also explains why PNU-173575, a thiomethyl metabolite of PNU-142721, exhibits enhanced PXR activation relative to the unmodified compound and why PNU-142721 can also activate rat PXR. Taken together, the results presented here elucidate the structural basis for PXR activation by PNU-142721 and related chemicals.

  11. Anti-HIV-1 protease- and HIV-1 integrase activities of Thai medicinal plants known as Hua-Khao-Yen.

    Science.gov (United States)

    Tewtrakul, Supinya; Itharat, Arunporn; Rattanasuwan, Pranee

    2006-04-21

    Ethanolic- and water extracts from five species of Thai medicinal plants known as Hua-Khao-Yen were tested for their inhibitory effects against HIV-1 protease (HIV-PR) and HIV-1 integrase (HIV-1 IN). The result revealed that the ethanolic (EtOH) extract of Smilax corbularia exhibited anti-HIV-1 IN activity with an IC50 value of 1.9 microg/ml, followed by the water extract of Dioscorea birmanica (IC50 = 4.5 microg/ml), the EtOH extract of Dioscorea birmanica (IC50 = 4.7 microg/ml), the water extract of Smilax corbularia (IC50 = 5.4 microg/ml), the EtOH extract of Smilax glabra (IC50 = 6.7 microg/ml) and the water extract of Smilax glabra (IC50 = 8.5 microg/ml). The extracts of Pygmaeopremna herbacea and Dioscorea membranacea were apparently inactive (IC50 > 100 microg/ml). Interestingly, only the EtOH extract of Dioscorea membranacea showed appreciable activity (IC50 = 48 microg/ml) against HIV-1 PR, while the other extracts possessed mild activity. This result strongly supported the basis for the use of Smilax corbularia and Dioscorea membranacea for AIDS treatment by Thai traditional doctors. PMID:16406414

  12. Synthesis of highly anti-HIV active sulfated poly- and oligo-saccharides and analysis of their action mechanisms by NMR [nuclear magnetic resonance] spectroscopy

    International Nuclear Information System (INIS)

    We have been synthesizing sulfated polysaccharides and oligosaccharides with highly anti-HIV (human immunodeficiency virus) activities. It has been known that sulfated polysaccharides such as dextran sulfate and pentosan polysulfate have biological activities such as anticoagulant activity and recently anti-HIV activity. Curdlan sulfate having 1,3-β-linked glucan backbone had high anti-HIV activity but low anticoagulant activity. Phase I/II test for the curdlan sulfate as an AIDS (acquired immunodeficiency syndrome) drug was carried out in the United States. In this study, regioselectivity sulfatec curdlan sulfates were prepared in order to study effects of sulfate groups and conformation of curdlan sulfates. In addition, action mechanisms of curdlan sulfate as anti-AIDS drug and of heparin as an anticoagulant were examined by means of NMR spectroscopy. 1. Structure dependence of anti-HIV and anticoagulant activities of sulfated polysaccharides. Curdlan with M n 9000 was regioselectively sulfated on its hydroxyl groups at 6, 4, and 2 positions. Those were a curdlan sulfate 62S in which 100% of 6-OH, and about 50% of 2-OH was sulfated, a curdlan sulfate 42S in which 4- and 2-OH's were sulfated, and a curdlan sulfate in which 6, 4, and 2-OH's were partially sulfated. All curdlan sulfates had very high anti-HIV activities exhibited by the drug concentration of 50% inhibition of infection, i.e., EC50 of 0.04 - 0.25 μg/mL. However, there was almost no difference in the activity among the samples. Therefore, it was revealed that the degree of sulfation and putative conformation of the curdlan sulfates but not the position of sulfate groups have large effects on the anti-HIV activity. On the other hand, the anticoagulant activity increased with increasing molecular weight of the curdlan sulfates. As a result, it is assumed that the size of reaction sites of the virus protein reacting with curdlan sulfate is different from that of the proteins related to anticoagulant. 2

  13. Synthesis and Anti-HIV-1 Evaluation of New Sonogashira-Modified Emivirine (MKC-442) Analogues

    DEFF Research Database (Denmark)

    Danel, Krzystof; Jørgensen, Per Trolle; La Colla, Paolo;

    2009-01-01

    with higher activity against HIV-1-resistant mutants. The syntheses involved Pd-catalyzed C,C-coupling reactions, addition of disulfides, and click chemistry on the terminal C C bond as well as addition of bromine to the so formed internal C C bonds. Sonogashira coupling were performed with silyl......The MKC-442 analogue 6-(3,5-dimethylbenzyl)-5-ethyluracil substituted with a (propargyloxo)methyl group at N(1) has previously been found highly active against HIV-1. The C C bond in the substituent at N(1) is here utilized in a series of chemical reactions in order to develop new agents...... effective compound against problematic HIV-1 mutants. The general observation in the present work is that a combination of alkyne and aryl in the substituent at N(1) leads to highly active compounds against HIV-1...

  14. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody.

    Directory of Open Access Journals (Sweden)

    Frank Sainsbury

    Full Text Available The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product.To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER. Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO cell-produced 2G12.Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for

  15. Identification of a Small Molecular Anti - HIV - 1 Compound that Interferes with Formation of the Fusion - active gp41 Core

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The human immunodeficiency virus type 1 (HIV - 1 ) envelope glycoprotein gp41 plays a critical role in the fusion of viral and target cell membranes. The gp41 extracellular domain, which contains fusion peptide (FP), N - and C - terminal hydrophobic heptad repeats (NHR and CHR, respectively). Peptides derived from NHR and CHR regions,designated N- and C- peptides, respectively, can interact with each other to form a six - stranded coiled - coil domain, representing the fusion-active gp41 core. Our previous studies demonstrated that the C- peptides have potent inhibitory activity against HIV- 1 infection.These peptides inhibit HIV- 1 -mediated membrane fusion by binding to NHR regions for preventing the formation of fusion- active gp41 core. One of the C - peptides, T - 20, which is in the phase Ⅲ clinical trails, is expected to become the first peptide HIV fusion inhibitory drug in the near future. However, this peptide HIV fusion inhibitor lacks oral availability and is sensitive to the proteolytic digestion.Therefore, it is essential to develop small molecular non -peptide HIV fusion inhibitors having similar mechanism of action as the C- peptides. We have established an ELISA- based screening assay using a unique monoclonal antibody, NC- 1, which can specifically bind to a conformational epitope on the gp41 core domain. Using this screening assay, we have identified a small molecular anti- HIV- 1 compound,named ADS-Jl, which inhibits HIV- 1- mediated membrane fusion by blocking the interaction between the NHR and CHR regions to form the fusion - active gp41 core. This compound will be used as a lead to design and develop novel HIV fusion inhibitors as new drugs for the treatment of HIV infection and/or AIDS.

  16. PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo.

    Science.gov (United States)

    Aravantinou, Meropi; Frank, Ines; Hallor, Magnus; Singer, Rachel; Tharinger, Hugo; Kenney, Jessica; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Salazar, Andres; Piatak, Michael; Lifson, Jeffrey D; Robbiani, Melissa; Derby, Nina

    2016-01-01

    Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of α4β7 and CD169, and induced type I IFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro- and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIVΔNef-infected animals, SIVΔNef viremia was higher, in line with the importance of DC and T cell activation in SIVΔNef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity. PMID:27603520

  17. Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2010-04-01

    Full Text Available Abstract Background Previous studies have shown that 3-hydroxyphthalic anhydride (HP-modified bovine milk protein, β-lactoglobulin (β-LG, is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission. Results Maleic anhydride (ML, succinic anhydride (SU and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low in vitro cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells. Conclusion ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.

  18. Regioselective synthesis and anti-HIV activity of the novel 2- and 4- substituted pyrazolo [4,5-e] [ 1,2,4]thiadiazines

    Institute of Scientific and Technical Information of China (English)

    Xin Yong Liu; Ren Zhang Yan; Nian Gen Chen; Wen Fang Xu

    2007-01-01

    The new regioisomer 7-methyl-pyrazolo[4,5-e] [1,2,4]thiadiazine nucleus (5) was synthesized, and its novel mono-N2- or N4-substituted pyrazolo[4,5-e][1,2,4]thiadiazines (6, 7) were regioselectively prepared by deprotonation of N2 or/and N4 atoms with different molar ratio of NaH and alkyl halides. Anti-HIV-1 screening tests showed some compounds to be potent as HIV-1 nonnucleoside reverse transcriptase inhibitors (HIV-1 NNRTIs).(C) 2006 Xin Yong Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  19. 抗 HIV 药物的研发现状及发展趋势分析%Research Status Quo and Development Trend of Anti - HIV Drugs

    Institute of Scientific and Technical Information of China (English)

    张婷; 贾晓峰; 安嘉璐

    2014-01-01

    近年来,艾滋病感染人数急剧增加,已成为威胁人类健康的重大疾病。为了解抗人类免疫缺陷病毒(HIV)药物的研究现状和发展趋势,对 Thomson Reuters Integrity 数据库中收录的抗 HIV 药物信息进行统计,从药物发展阶段、药物类型、作用靶点和天然来源类型等方面进行分析。研究发现,抗 HIV 药物大多处于生物测定阶段,生物制品在药物类型中占绝对优势,作用靶点大多数是针对 HIV 复制周期中的关键酶,抗 HIV 药物的天然来源以植物为主,天然产物是未来重要的发展方向。%( Research Institute of Medical Information . Medical Library,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China 100020) In recent years,the number of HIV infections increases sharply,which has become a major disease threatening the human health. In order to understand the research status quo and the development trend of anti - HIV drugs,the anti - HIV drugs information included in the Thomson Reuters Integrity database was performed the statistics for conducting the analysis on the aspects of the devel-opment stage of drugs,drug types,effect targets and natural source type. The study finds that most of the anti - HIV drugs are in the stage of biological testing;the biological products occupies the absolute superiority;the most effect targets aim at the key enzymes in the HIV replication cycle;natural sources of anti - HIV drugs are dominated by plants. The natural products are the important development direction in future.

  20. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  1. Zirconium phosphatidylcholine-based nanocapsules as an in vivo degradable drug delivery system of MAP30, a momordica anti-HIV protein.

    Science.gov (United States)

    Caizhen, Guo; Yan, Gao; Ronron, Chang; Lirong, Yang; Panpan, Chu; Xuemei, Hu; Yuanbiao, Qiao; Qingshan, Li

    2015-04-10

    An essential in vivo drug delivery system of a momordica anti-HIV protein, MAP30, was developed through encapsulating in chemically synthesized matrices of zirconium egg- and soy-phosphatidylcholines, abbreviated to Zr/EPC and Zr/SPC, respectively. Matrices were characterized by transmission electron microscopy and powder X-ray diffractometry studies. Zr/EPC granule at an approximate diameter of 69.43±7.78 nm was a less efficient encapsulator than the granule of Zr/SPC. Interlayer spacing of the matrices encapsulating MAP30 increased from 8.8 and 9.7 Å to 7.4 and 7.9 nm, respectively. In vivo kinetics on degradation and protein release was performed by analyzing the serum sampling of intravenously injected SPF chickens. The first order and biphasic variations were obtained for in vivo kinetics using equilibrium dialysis. Antimicrobial and anti-HIV assays yielded greatly decreased MIC50 and EC50 values of nanoformulated MAP30. An acute toxicity of MAP30 encapsulated in Zr/EPC occurred at a single intravenous dose above 14.24 mg/kg bw in NIH/KM/ICR mice. The folding of MAP30 from Zr/EPC sustained in vivo chickens for more than 8 days in high performance liquid chromatography assays. These matrices could protect MAP30 efficiently with strong structure retention, lowered toxicity and prolonged in vivo life.

  2. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Thiébaut, Rodolphe; Reiss, Peter;

    2010-01-01

    AIMS: HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We...... on Adverse Effects of Anti-HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score.The models included age, sex, systolic blood.......670-0.818) for coronary heart disease and 0.769 (0.695-0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. CONCLUSION: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters...

  3. A testagem anti-HIV nos serviços de ginecologia do município do Rio de Janeiro

    OpenAIRE

    Carla Luzia França Araújo; Priscila da Silva Aguiar; Gleice Kelly Araújo dos Santos; Maíra Guimarães Ponce de Oliveira; Lívia de Souza Câmara

    2014-01-01

    Esta pesquisa propõe um estudo sobre a oferta do teste anti-HIV em serviços da Atenção Básica de Saúde do município do Rio de Janeiro, na clínica de ginecologia. O objetivo desse estudo foi analisar os aspectos que envolvem a ampliação do acesso ao diagnóstico do HIV/AIDS nos serviços de Ginecologia da Atenção Básica no município do Rio de Janeiro. Métodos: Estudo qualitativo descritivo. Os dados foram obtidos por meio de entrevista semiestruturada, e, para a análise dos dados qualitativos, ...

  4. Suramin analogues with a 2-phenylbenzimidazole moiety as partial structure; potential anti HIV- and angiostatic drugs, 2: Sulfanilic acid-, benzenedisulfonic acid-, and naphthalenetrisulfonic acid analogues.

    Science.gov (United States)

    Kreimeyer, A; Müller, G; Kassack, M; Nickel, P; Gagliardi, A R

    1998-03-01

    The synthesis of suramin analogues bearing a 2-phenyl-benzimidazole moiety is described. Aminoarene sulfonic acids 2a-e are acylated with 3,4-dinitrobenzoyl chloride 3 yielding the amides 4a-e which are hydrogenated to the corresponding diamines 5a-e. These are treated with 3-nitrobenzaldehyde, yielding the azomethines 7a-e and their isomers 8a-e and 9a-e. Key step in the synthesis of the target compounds 12a-e is the oxidation of the azomethines with oxygen to the benzimidazoles 10a-e. These are hydrogenated to the amines 11a-e reacting with phosgene to yield the symmetric ureas 12a-e. Results of the anti-HIV, cytostatic, and antiangiogenic screening are presented.

  5. Assessment of activity of topical virucidal agents.

    Science.gov (United States)

    O' Connor, T

    2000-01-01

    There is currently considerable interest in the possibility of developing a potent, nontoxic anti-HIV agent that could be used intravaginally to reduce the risks of transmission of HIV. Worldwide up to 80% of HIV infections have been acquired heterosexually. Projections suggest that by the year 2000 approx 25 million individuals worldwide will have been infected by heterosexual transmission. This spread of infection is particularly rapid in parts of Africa, Asia, and Latin America. In the absence of a prophylactic vaccine, there is an urgent need to develop safe, effective, female-controlled, topical virucidal preparations to prevent sexual transmission of HIV and other sexually transmitted diseases (STDs). Many assays directed against the virus have had problems with removal of the presumptive agents, which in many cases are toxic to the cell culture system. Methods have includes dilution, centrifugation, and erythrocyte ghost preparations, but these have problems with virus dilution and an inability to examine the kinetics of inactivation. PMID:21331911

  6. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2015-11-01

    Full Text Available Olayide A Arodola, Mahmoud ES SolimanMolecular Modelling and Drug Design Lab, School of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South AfricaAbstract: Based on experimental data, the anticancer activity of nelfinavir (NFV, a US Food and Drug Administration (FDA-approved HIV-1 protease inhibitor (PI, was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90, a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 µM. Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively. Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602 played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding mechanism of the FDA-approved HIV PIs binding to human Hsp90. Information gained from this study should also provide a route map toward the design, optimization, and further experimental investigation of potential derivatives of PIs to treat HER2+ breast cancer.Keywords: binding free energy, loop docking, molecular dynamics, HIV-1 protease inhibitors, anticancer

  7. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Cele FN

    2016-04-01

    Full Text Available Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621 showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. Keywords: HIV-1, reverse transcriptase, GSK952, molecular dynamic simulations, pharmacophore model, molecular docking

  8. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents.

    Science.gov (United States)

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud Es

    2016-01-01

    A novel virtual screening approach is implemented herein, which is a further improvement of our previously published "target-bound pharmacophore modeling approach". The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD) simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621) showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  9. A Simplifed and Efficient Synthesis of 7-Hydroxymethyl-6,7- Dihydropyrro- [ 1,2- c ]-Pyrimidine-1,3-Dione as a Potent Anti- HIV-1 Agent

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-Wei; ZHANG Zhi-Li; HAN Peng; MA Xiao-Yan; LIU Jun-Yi

    2003-01-01

    @@ The reverse transcriptase of HIV provides a key target for the development of anti-AIDS drugs. The discovery of 1-[ 2-hydroxyethoxymethyl]-6-phenylthio-thymine (HEPT) as a compound with potent and selective in vivo activity against HIV-1[1] has led to the synthesis many new non-nucleoside reverse transcriptase inhibitors.[2

  10. Plasmids encoding therapeutic agents

    Science.gov (United States)

    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.

  11. Synthesis and anti-HIV evaluation of hybrid-type prodrugs conjugating HIV integrase inhibitors with d4t by self-cleavable spacers containing an amino acid residue.

    Science.gov (United States)

    Fossey, Christine; Huynh, Ngoc-Trinh; Vu, Anh-Hoang; Vidu, Anamaria; Zarafu, Irina; Laduree, Daniel; Schmidt, Sylvie; Laumond, Geraldine; Aubertin, Anne-Marie

    2007-10-01

    In an attempt to combine the anti-HIV inhibitory capacity of reverse transcriptase (RT) inhibitors (NRTIs) and integrase (IN) inhibitors (INIs), several heterodimer analogues of the previously reported [d4T]-PABC-[INI] and [d4T]-OABC-[INI] prototypes have been prepared. In these novel series, we wished to extend our results to conjugates which incorporated an enzymatically labile aminoacid unit (L-alanine) connected to d4T through a self-immolative para- or ortho-aminobenzyl carbonate (PABC or OABC) spacer. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable to that of the [L-708,906]-PABC-[d4T] Heterodimer A prototype. However, although the compounds proved inhibitory to HIV-1, they were less potent than the parent compounds from which they were derived. PMID:18035829

  12. Synthesis and anti-HIV evaluation of hybrid-type prodrugs conjugating HIV integrase inhibitors with d4t by self-cleavable spacers containing an amino acid residue.

    Science.gov (United States)

    Fossey, Christine; Huynh, Ngoc-Trinh; Vu, Anh-Hoang; Vidu, Anamaria; Zarafu, Irina; Laduree, Daniel; Schmidt, Sylvie; Laumond, Geraldine; Aubertin, Anne-Marie

    2007-10-01

    In an attempt to combine the anti-HIV inhibitory capacity of reverse transcriptase (RT) inhibitors (NRTIs) and integrase (IN) inhibitors (INIs), several heterodimer analogues of the previously reported [d4T]-PABC-[INI] and [d4T]-OABC-[INI] prototypes have been prepared. In these novel series, we wished to extend our results to conjugates which incorporated an enzymatically labile aminoacid unit (L-alanine) connected to d4T through a self-immolative para- or ortho-aminobenzyl carbonate (PABC or OABC) spacer. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable to that of the [L-708,906]-PABC-[d4T] Heterodimer A prototype. However, although the compounds proved inhibitory to HIV-1, they were less potent than the parent compounds from which they were derived.

  13. Synthesis and Anti-HIV-1 Activity of New MKC-442 Analogues with an Alkynyl-Substituted 6-Benzyl Group

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo;

    2007-01-01

    Synthesis and antiviral activities are reported of a series of 6-(3-alkynyl benzyl)-substituted analogues of MKC-442 (6-benzyl-1-(ethoxymethyl)-5-isopropyluracil), a highly potent agent against HIV. The 3-alkynyl group is assumed to give a better stacking of the substituted benzyl group to revers...

  14. Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120

    Energy Technology Data Exchange (ETDEWEB)

    Hoque, M. Mominul [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Rajshahi University, Rajshahi (Bangladesh); Suzuki, Kaoru [Iwaki Meisei University, Iwaki, Fukushima 970-8551 (Japan); Tsunoda, Masaru; Jiang, Jiandong; Zhang, Fang; Takahashi, Atsushi; Ohbayashi, Naomi; Zhang, Xiaoxue [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Tanaka, Haruo [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); KIIM Pharmaceutical Laboratories Inc., Fukushima 970-8551 (Japan); Ōmura, Satoshi [Kitasato University, Tokyo 108-8641 (Japan); Takénaka, Akio, E-mail: atakenak@sakura.email.ne.jp [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Tokyo Institute of Technology, Yokohama 226-8501 (Japan)

    2012-12-01

    X-ray analysis of anti-HIV actinohivin in complex with the target α(1-2)mannobiose moiety of high-mannose type glycans attached to HIV-1 gp120 reveals that the three rotamers generated with 120 rotations around the molecular pseudo-rotation axis are packed randomly in the unit cell according to the P2{sub 1}2{sub 1}2{sub 1} symmetry to exhibit an apparent space group P2{sub 1}3 as the statistical structure. However, the high-resolution X-ray structure shows the detailed interaction geometry for specific binding. Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1–2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C—H⋯O hydrogen bonds facilitated by the α(1–2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O{sup 3} and O{sup 4} atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O{sup 1} atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features

  15. The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications.

    Directory of Open Access Journals (Sweden)

    Geoffrey Férir

    Full Text Available Lantibiotics are peptides, produced by bacteria, that contain the noncanonical amino acid lanthionine and many of them exhibit antibacterial activities. The labyrinthopeptin A1 (LabyA1 is a prototype peptide of a novel class of carbacyclic lantibiotics. Here, we extensively evaluated its broad-spectrum activity against HIV and HSV in vitro, studied its mechanism of action and evaluated potential microbicidal applications. LabyA1 exhibited a consistent and broad anti-HIV activity (EC50s: 0.70-3.3 µM and anti-HSV activity (EC50s: 0.29-2.8 µM in cell cultures. LabyA1 also inhibited viral cell-cell transmission between persistently HIV-infected T cells and uninfected CD4(+ T cells (EC50∶2.5 µM and inhibited the transmission of HIV captured by DC-SIGN(+-cells to uninfected CD4(+ T cells (EC50∶4.1 µM. Time-of-drug addition studies revealed that LabyA1 acts as an entry inhibitor against HIV and HSV. Cellular and virus binding studies combined with SPR/FLIPR technology showed that LabyA1 interacted with the HIV envelope protein gp120, but not with the HIV cellular receptors. LabyA1 also demonstrated additive to synergistic effects in its anti-HIV-1 and anti-HSV-2 activity with anti(retroviral drugs in dual combinations such as tenofovir, acyclovir, saquinavir, raltegravir and enfuvirtide. LabyA1 can be considered as a novel lead peptide as it had profound antiviral activity against HIV and HSV. Pre-treatment of PBMCs with LabyA1 neither increased the expression of the activation markers CD69 and CD25, nor enhanced HIV replication, nor significantly induced various inflammatory cytokines/chemokines. LabyA1 also did not affect the growth of vaginal Lactobacilli populations. Based on the lack of toxicity on the vaginal Lactobacillus strains and its synergistic/additive profile in combination with clinically approved anti(retrovirals, it deserves further attention as a potential microbicide candidate in the prevention of sexual transmitted diseases.

  16. Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea mays strongly determine their eventual anti-HIV activity

    Directory of Open Access Journals (Sweden)

    Fouquaert Elke

    2011-02-01

    Full Text Available Abstract Background In a recent report, the carbohydrate-binding specificities of the plant lectins Galanthus nivalis (GNA and the closely related lectin from Zea mays (GNAmaize were determined by glycan array analysis and indicated that GNAmaize recognizes complex-type N-glycans whereas GNA has specificity towards high-mannose-type glycans. Both lectins are tetrameric proteins sharing 64% sequence similarity. Results GNAmaize appeared to be ~20- to 100-fold less inhibitory than GNA against HIV infection, syncytia formation between persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T-lymphocyte SupT1 cells, HIV-1 capture by DC-SIGN and subsequent transmission of DC-SIGN-captured virions to uninfected CD4+ T-lymphocyte cells. In contrast to GNA, which preferentially selects for virus strains with deleted high-mannose-type glycans on gp120, prolonged exposure of HIV-1 to dose-escalating concentrations of GNAmaize selected for mutant virus strains in which one complex-type glycan of gp120 was deleted. Surface Plasmon Resonance (SPR analysis revealed that GNA and GNAmaize interact with HIV IIIB gp120 with affinity constants (KD of 0.33 nM and 34 nM, respectively. Whereas immobilized GNA specifically binds mannose oligomers, GNAmaize selectively binds complex-type GlcNAcβ1,2Man oligomers. Also, epitope mapping experiments revealed that GNA and the mannose-specific mAb 2G12 can independently bind from GNAmaize to gp120, whereas GNAmaize cannot efficiently bind to gp120 that contained prebound PHA-E (GlcNAcβ1,2man specific or SNA (NeuAcα2,6X specific. Conclusion The markedly reduced anti-HIV activity of GNAmaize compared to GNA can be explained by the profound shift in glycan recognition and the disappearance of carbohydrate-binding sites in GNAmaize that have high affinity for mannose oligomers. These findings underscore the need for mannose oligomer recognition of therapeutics to be endowed with anti-HIV activity and that mannose, but

  17. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study

    OpenAIRE

    Kovari, Helen; Sabin, Caroline A.; Ledergerber, Bruno; Ryom, Lene; Reiss, Peter; Law, Matthew; Pradier, Christian; Dabis, Francois; D'Arminio Monforte, Antonella; Smith, Colette; De Wit, Stephane; Kirk, Ole; Lundgren, Jens D.; Weber, Rainer

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as fol...

  18. Study on Anti-HIV of Quercetin Derivants in Natural Products%天然产物中槲皮素类化合物的抗HIV作用研究

    Institute of Scientific and Technical Information of China (English)

    王晓建; 王珊; 黄胜阳

    2011-01-01

    Objective:To review the research about anti-HIV activity of quercetin derivants from natural products, and provide reference for clinical and further research. Method:Retrieve and inspect the literatures and monographs over the past decade about anti-HIV of quercetin derivants from natural products, and analyze and summary these paper by the different function of quercetin derivants. Result: Quercetin derivants have strong anti-HIV activity, and they are mainly inhibit HIV viral replication through the three key enzymes; protease, reverse transcriptase, integrase. Conclusion: Natural products in the anti-HIV compounds quercetin play an important role, there is great significance in-depth study of these compounds%目的:综述天然产物中槲皮素类化合物的抗HIV作用方面的研究进展,为进一步临床应用和研究提供参考.方法:全面检索、查阅国内外近10年来有关天然产物中槲皮素类化合物抗HIV作用的文献与著作,并按照槲皮素类化合物的不同作用对其进行分析总结.结果:槲皮素类化合物是天然产物中具有较强抗HIV活性的一类化合物,主要作用于HIV复制所需的三个关键酶——蛋白酶、逆转录酶、整合酶,从而抑制HIV在体内的复制.结论:天然产物中的槲皮素类化合物在抗HIV方面中有着重要的作用,深入研究该类化合物具有重大意义.

  19. A realização do teste anti-hiv no pré-natal: os significados para a gestante El establecimiento de la lucha contra la prueba del vih en pre-navidad: significados para el embarazo The establishment of anti-hiv test in pre-natal: meanings for pregnancy

    Directory of Open Access Journals (Sweden)

    Roberta Maria de Oliveira Silva

    2008-12-01

    Full Text Available O estudo teve por objetivo conhecer e analisar o significado da realização do teste anti-HIV no pré-natal para as gestantes. Trata-se de uma pesquisa com abordagem qualitativa e foi realizada em um Hospital Escola e em uma Maternidade do município do Rio de Janeiro. Como recurso técnico-metodológico utilizou-se o discurso do sujeito coletivo (DSC. Após a análise dos discursos verificamos que para as gestantes a realização do teste significa a possibilidade de prevenir a transmissão vertical do HIV e como parte da assistência pré-natal. O pré-natal foi considerado pelas gestantes uma excelente oportunidade para a realização do teste anti HIV, para o conhecimento da condição sorológica e início precoce do tratamento. Conclui-se que o teste, para a maioria das gestantes, representa a possibilidade de proteger o filho do HIV, além de fazer parte da construção do papel materno a partir de um cuidado concreto com a saúde do bebê.El estudio que tenía para que el objetivo sepa y analice el significado de la realización del anti-VIH de la prueba en el prenatal para las mujeres embarazadas. Uno está sobre una investigación con acercamiento cualitativo y fue ejecutado en una escuela del hospital y una maternidad de la ciudad de Rio de Janeiro. Como recurso técnico-metodológico el discurso del ciudadano colectivo fue utilizado (DSC. Después de que el análisis de los discursos, nosotros verificamos que para las mujeres embarazadas la realización de la prueba significa la posibilidad para prevenir la transmisión vertical del VIH y como parte de la ayuda prenatal. El prenatal era considerado por las mujeres embarazadas una ocasión excelente para la realización del anti VIH de la prueba, para el conocimiento de la condición sorological y del principio precoz del tratamiento. Se concluye que la prueba, para la mayoría de las mujeres embarazadas, representa la posibilidad para proteger al hijo del VIH, más allá de ser

  20. First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations.

    Science.gov (United States)

    Benjelloun, Fahd; Oruc, Zeliha; Thielens, Nicole; Verrier, Bernard; Champier, Gael; Vincent, Nadine; Rochereau, Nicolas; Girard, Alexandre; Jospin, Fabienne; Chanut, Blandine; Genin, Christian; Cogné, Michel; Paul, Stephane

    2016-09-01

    Mucosal HIV-1-specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir. PMID:27481846

  1. Formação, práticas e trajetórias de aconselhadores de centros de testagem anti-HIV do Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Claudia Mora

    2015-12-01

    Full Text Available Perante a importância do aconselhamento na testagem anti-HIV, analisamos as diretrizes institucionais, as competências privilegiadas no treinamento profissional e os saberes/práticas de aconselhadores. Trata-se de estudo qualitativo centrado na análise documental, observação e entrevista com aconselhadores de Centros de Testagem e Aconselhamento (CTA do estado do Rio de Janeiro. A análise foi orientada pela teoria de Pierre Bourdieu. Foi evidenciado que o habitus profissional dos aconselhadores resulta da articulação dos treinamentos, da graduação e de experiências e interesses pessoais. A operacionalização de competências, como a escuta ativa, é limitada pela rotina dos serviços e escassez de espaços de reflexão. Para incrementar a prática do aconselhamento, é importante desenvolver competências no treinamento, manter a educação continuada e fazer adequações na rotina do serviço. Tais ajustes podem fortalecer a passagem das diretrizes à ação e o aprimoramento da organização e gestão dos CTA.

  2. RD2-MolPack-Chim3, a packaging cell line for stable production of lentiviral vectors for anti-HIV gene therapy.

    Science.gov (United States)

    Stornaiuolo, Anna; Piovani, Bianca Maria; Bossi, Sergio; Zucchelli, Eleonora; Corna, Stefano; Salvatori, Francesca; Mavilio, Fulvio; Bordignon, Claudio; Rizzardi, Gian Paolo; Bovolenta, Chiara

    2013-08-01

    Over the last two decades, several attempts to generate packaging cells for lentiviral vectors (LV) have been made. Despite different technologies, no packaging clone is currently employed in clinical trials. We developed a new strategy for LV stable production based on the HEK-293T progenitor cells; the sequential insertion of the viral genes by integrating vectors; the constitutive expression of the viral components; and the RD114-TR envelope pseudotyping. We generated the intermediate clone PK-7 expressing constitutively gag/pol and rev genes and, by adding tat and rd114-tr genes, the stable packaging cell line RD2-MolPack, which can produce LV carrying any transfer vector (TV). Finally, we obtained the RD2-MolPack-Chim3 producer clone by transducing RD2-MolPack cells with the TV expressing the anti-HIV transgene Chim3. Remarkably, RD114-TR pseudovirions have much higher potency when produced by stable compared with transient technology. Most importantly, comparable transduction efficiency in hematopoietic stem cells (HSC) is obtained with 2-logs less physical particles respect to VSV-G pseudovirions produced by transient transfection. Altogether, RD2-MolPack technology should be considered a valid option for large-scale production of LV to be used in gene therapy protocols employing HSC, resulting in the possibility of downsizing the manufacturing scale by about 10-fold in respect to transient technology.

  3. 天然药物抗HIV机制的研究进展%Research Progress of the Mechanism of Anti-HIV Natural Medicines

    Institute of Scientific and Technical Information of China (English)

    赵梅; 周淑琴; 杨莉娅

    2012-01-01

    Acquired immunodeficiency syndrome (AIDS) is one of the most serious infectious diseases that severely threats the human health. Till now there are still no satisfactory therapeutic strategy against AIDS. Recent studies have shown that natural medicines possess various anti-AIDS pharmacological activities including immuno-regulation, inhibition of the enzymes in the process of HIV replication, and antioxidant function, etc. In this article, we overview the advances in the mechanism research of anti-HIV natural medicines.%艾滋病是威胁人类健康的重大传染性疾病,目前仍未有令人满意的治疗方法.近年来的研究发现,天然药物具有广泛的抗HIV药理学活性,如免疫调节、抑制HIV复制中相关功能酶、抗氧化等.本文就天然药物抗HIV的相关作用机制展开综述.

  4. Resultado do teste rápido anti-HIV após o parto: uma ameaça à amamentação ao nascimento Resultado de la prueba rápida anti-HIV posterior al parto: una amenaza al amamantamiento en el nacimiento Delivering rapid HIV tests results after delivery: a threat to breastfeeding at birth

    Directory of Open Access Journals (Sweden)

    Maria Inês Couto de Oliveira

    2010-02-01

    Full Text Available OBJETIVO: Analisar fatores associados à não-amamentação na primeira hora de vida, sobretudo a influência do momento do resultado do teste rápido anti-HIV. MÉTODOS: Estudo de coorte, sendo o ponto inicial a submissão ao teste rápido e o final a primeira mamada do bebê. A população estudada incluiu 944 parturientes submetidas ao teste rápido anti-HIV, com resultado negativo, em 2006, nos cinco hospitais amigos da criança do Sistema de Gestação de Alto Risco no município do Rio de Janeiro, RJ. Entrevistadoras treinadas obtiveram dados do laboratório e do prontuário e no pós-parto aplicaram questionário para entrevista às mães. O modelo multinível foi adotado para analisar a influência de características sociodemográficas, de assistência pré-natal e ao parto sobre a não-amamentação na primeira hora de vida. RESULTADOS: Dentre as participantes, apenas 15,6% receberam seu resultado antes do parto, 30,8% depois do parto e 53,6% ainda desconheciam o resultado ao ser entrevistada. A prevalência de não-amamentação na primeira hora de vida foi de 52,5% (IC 95%: 49,3;55,8. Após ajuste, o recebimento do resultado do teste rápido após o parto dobrou o risco da não-amamentação na primeira hora de vida (RR=2,06; IC 95%: 1,55;2,75. Outros fatores de risco foram: cor não branca, renda materna de um salário mínimo ou menos, parto cesáreo, mãe não querer amamentar o bebê ao nascimento e mãe referir que a equipe hospitalar não a escutava. O desconhecimento da realização do teste rápido anti-HIV pela mãe se mostrou como fator de proteção. CONCLUSÕES: O principal fator de risco para a não-amamentação na primeira hora de vida foi o recebimento do resultado do teste rápido após o parto. O teste anti-HIV deve ser amplamente disponibilizado no pré-natal e o teste rápido deve ser realizado sob indicação, na admissão, com busca ativa e pronta comunicação do resultado à mulher.OBJETIVO: Analizar factores

  5. 禹白附提取物抗HIV病毒的实验研究%Experimental study on anti-HIV activities with extract from tuber of Typhonium giganteum

    Institute of Scientific and Technical Information of China (English)

    温瑞兴; 马洪涛; 王晓艳; 王霞; 杨怡妹; 王小利

    2009-01-01

    Objective To study the effect of anti-HIV-1 virus with extracts from the tuber of Typhonium giganteum.so as to discover new and high efficient anti-HIV-1 leading compounds from natural prod-ucts and Chinese materia medica.Methods Extract from the tuber of T.giganteum was isolated and purifled by the way of phytochemistry,such as column chromatography.Then anti-HIV-1 activities of the extracts were assessed by in vitro method,MT4 cells and HIVⅢB virus were used for the experiment.The results were judged by cytopathic effect(CPE)method and p24 antigen assay method.Mechanism studies were carried out bv BIA techniques(BIACORE~(R)3000 molecule coupled equipment).Results The extracts of T. giganteum showed potential anti-HIV-1 activities.Two of them showed gp-41 transmembrance protein and Vif protein expression inhibition,respectively.Conclusion These extracts in the tuber of T.giganteum might rewardingly contribute to anti-HIV-1 activities,which could be developed to be more efficient and less toxic leading compounds in the further.%目的 研究白附子提取物抗HIV-1的作用,寻找新型高效的抗HIV-1中药先导化合物.方法 采用植物化学技术对禹白附进行提取分离,再通过细胞生物学方法 [细胞病变观察法(CPE)法和MTT法]检验提取物的抗HIV-1作用,并结合作用靶点的研究对提取物的作用机制进行探讨.结果 发现禹白附提取物具有很好的抗HIV-1作用,筛选出3个抗HIV-1作用显著的有效部位,其中两个有效部位的作用靶点分别为HIV-1的gp-41跨膜蛋白和Vif表达蛋白.结论 禹白附提取物具有很强的抗HIV-1作用,为进一步寻找高效低毒的抗HIV-1先导化合物奠定了基础,值得进行深入研究.

  6. Controlling drug efficiency by encapsulation into carbon nanotubes: A theoretical study of the antitumor Cisplatin and the anti-HIV TIBO molecules

    Science.gov (United States)

    Bessrour, R.; Belmiloud, Y.; Hosni, Z.; Tangour, B.

    2012-06-01

    From the beginning of last century, Paul Ehrlich, a specialist in the immune system and the Nobel Prize (1908) had raised the possibility of "magic bullets" can directly address, in an organism, drugs in a particular area of the body, sparing all other parts of side effects. Carbon nanotubes (CNTs) have particular property to cross cell membranes easily. In an effort to optimize the use of CNT as drug nanocarriers, we divided our study into two parts. In the first, our concern was to find the minimum diameter of a single wall CNT can encapsulate an anticancer drug that iscisplatin without altering its geometry in order conserve its therapeutic power. Behavior of one and two Cisplatin(Cp) molecules confined in capped and opened single-walled carbon nanotubes (CNTs) is studied by means of ab-initio calculations. Single molecule binding energies clearly exhibit encapsulation dependence on tube diameters that range from 6.26 Å to 12.04 Å. A weak stabilization energy of the Cp@(11,0) equal to -70 kcal.mol-1 has been obtained corresponding to a CNT's diameter of 8.5Å. We noticed that Cisplatin molecule changes shape when encapsulated into CNTs' whose diameters are less than 7.6 Å. In the presence of a second Cisplatin molecule in the (10,0) CNT, preferred position stays parallel to CNT's axis leading to a linear density of roughly 1588 molecules/μm of CNT's length corresponding to a linear density of 7.9 10-19 g/μm. The 195Pt chemical shift tensors are calculated using GIAO method. NMR calculations reveal that Platinum chemical shift is sensitive to CNT's diameter and is linearly correlated to confinement energy. 195Pt chemical shift measurement may be a direct method to access to the diameter of the encapsulating CNT's and to control the amount of drug molecule transported by this CNT. In the second part, the opposite has been sought is to say how the use of nanotubes with different diameters can control the change in a geometry of an anti-HIV drug that is TIBO

  7. [The management of dialysis patients seropositive for HBsAg, anti-HCV, or anti-HIV antibodies].

    Science.gov (United States)

    Fabrizi, Fabrizio; Messa, Piergiorgio

    2012-01-01

    Infections by hepatitis B or hepatitis C virus are still common among patients on maintenance dialysis in Western countries. The natural history of HBV and HCV in the dialysis population remains unclear; however, there is good evidence showing an adverse impact of an anti-HCV seropositive status on survival in dialysis patients. A recent meta-analysis of observational studies (n=7, 11,589 unique patients) reported that anti-HCV-positive patients on dialysis had a higher mortality rate than those who were anti-HCV negative (adjusted hazard ratio=1.35, 95% confidence interval, 1.13; 1.59, pdialysis. Standard precautions and specific procedures against the transmission of blood-borne agents have been recommended to control HCV infection within dialysis units. Isolation by dialysis machines, staff and rooms has been strongly recommended to control HBV. Vaccination is an important tool against transmission of HBV infection among patients on maintenance dialysis; however, the immune response towards the hepatitis B vaccine in uremic patients remains unsatisfactory. Monotherapy with lamivudine is currently used for dialysis patients with hepatitis B whereas combination antiviral therapy (pegylated interferon plus ribavirin) is the standard of care for hepatitis C in the dialysis population, even if various side effects have been observed.

  8. An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rγnull mice allows HIV replication and development of anti-HIV immune responses.

    Directory of Open Access Journals (Sweden)

    Maneesh Singh

    Full Text Available Cord blood hematopoietic progenitor cells (CB-HPCs transplanted immunodeficient NOD/LtsZ-scidIL2Rγ(null (NSG and NOD/SCID/IL2Rγ(null (NOG mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

  9. Anti-HIV Ⅰ/Ⅱ Activity and Molecular Cloning of a Novel Mannose/Sialic Acid-binding Lectin from Rhizome of Polygonatum cyrtonema Hua

    Institute of Scientific and Technical Information of China (English)

    Jie AN; Jin-Ku BAO; Jin-Zhi LIU; Chuan-Fang WU; Jian LI; Lei DAI; Els Van DAMME; Jan BALZARINI; Erik De CLERCQ; Fang CHEN

    2006-01-01

    The anti-human immunodeficiency virus (HIV) Ⅰ/Ⅱ activity of a mannose and sialic acid binding lectin isolated from rhizomes of Polygonatum cyrtonema Hua was elucidated by comparing its HIV infection inhibitory activity in MT-4 and CEM cells with that of other mannose-binding lectins (MBLs). The anti-HIV activity of Polygonatum cyrtonema Hua lectin (PCL) was 10- to 100-fold more potent than other tested MBLs, but without significant cytotoxicity towards MT-4 or CEM cells. To amplify cDNA of PCL by 3'/5'-rapid amplification of cDNA ends (RACE), the 30 amino acids of N-terminal were determined by sequencing and the degenerate oligonucleotide primers were designed. The full-length cDNA of PCL contained 693 bp with an open reading frame encoding a precursor protein of 160 amino acid residues, consisting of a 28-residue signal peptide, a 22-residue C-terminal cleavage peptide and a 110-residue mature polypeptide which contained three tandemly arranged subdomains with an obvious sequence homology to the monocot MBL. However, only one active mannose-binding site (QDNVY) was found in subdomain Ⅰ of PCL, that of subdomain Ⅱ and Ⅲ changed to HNNVY and PDNVY, respectively. There was no intron in PCL, which was in good agreement with other monocot MBLs. Molecular modeling of PCL indicated that its three-dimen-sional structure resembles that of the snowdrop agglutinin. By docking, an active sialic acid-binding site was found in PCL. The instabilization of translation initiation region (TIR) in mRNA of PCL benefits its high expression in rhizomes.

  10. Analysis on 37 cases Anti-HIV positive individuals from certain hospital of stomatology in Guangxi province%广西某口腔医院37例患者抗-HIV阳性结果分析

    Institute of Scientific and Technical Information of China (English)

    李润英; 陶人川; 陈桂英

    2013-01-01

    Objective:To analyze the anti-HIV positive individuals from Hospital of Stomatology affiliated to Guangxi Medical University (COSGXMU) in recent years,in order to improve the awareness of prevention from HIV infection for oral clinician,the early diagnosis of HIV infection as well. Method:Data and informations of the anti-HIV positive individuals in out-patients and in-patients of COSGXMU from January 2001 to June 2012 were collected and analyzed. Result:During this period,37 anti-HIV positive individuals were reported in total. From 2001 to 2006,only one case was reported every year,and more positive individuals since 2007,with a maximum of 8 in 2009. The age ranges from three months to seventy-nine years old,and 31-50 year age group was the largest. The anti-HIV positive individuals in out-patients were reported by the department of Periodontics and oral medicine with diagnosed of oral candidiasis,the remaining were reported through auxiliary examination due to trauma,tumor by Oral and Maxillofacial Surgery department. Conclusion:ln COSGXMU,the number of the anti-HIV positive patients was an upward trend recent years,however,because of the screening of non-census,only a small part of anti-HIV positive individuals were reported. It suggested that oral health care workers should raise awareness of the early oral manifestations of HIV,strengthen the HIV-test for patients,to make sure the HIV/AIDS to be diagnosed and treated earlier,as well as to reduce the risk of occupational exposure.%目的:收集广西医科大学附属口腔医院(简称口腔医院)近年就诊患者中抗-HIV阳性检出情况,以期提高口腔临床医生对HIV感染防范意识,促进HIV感染的早期诊断.方法:收集整理2001年1月~2012年6月,口腔医院门诊及住院患者中检出抗-HIV阳性者基本信息进行统计分析.结果:检出抗-HIV阳性患者37例,2007年前每年仅有1例报道,2007年后增多,其中2009年最多,为9例,年龄分布从3个月~79岁,以31

  11. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study)

    DEFF Research Database (Denmark)

    Worm, Signe W; De Wit, Stephane; Weber, Rainer;

    2009-01-01

    BACKGROUND: Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact...... of DM and preexisting CHD on the development of a new CHD episode among 33,347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). METHODS AND RESULTS: Over 159,971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV...

  12. 抗HIV融合多肽CP32M的制备工艺研究%Preparation Method of Anti-HIV Fusion Peptide CP32M

    Institute of Scientific and Technical Information of China (English)

    付超; 郭会芹; 王孝花; 胡洁; 戴秋云

    2011-01-01

    Objective: In order to provide a large quantity of CP32M, an anti-HIV-1 fusion peptide, for its pre-clinical trial, we probe its large scale of synthesis. Methods: CP32M was synthesized by using combined solid-liquid method, the crude peptide was purified by DEAE anion exchange chromatography and RP-HPLC. Results: Three optimized fragments which were easily synthesized and coupled were found, CP32M with purity more than 98% was obtained after the purification of DEAE anion exchange chromatography and RP-HPLC. Conclusion: The arrangement of three fragments (Ac-1-9-OH, Fmoc-10-21-OH, H-22-32-NH2) of CP32M could significantly elevate the yield of fragment syntheses and couplings, and DEAE anion exchange chromatography could efficiently isolate the impurities and increase the yield of the RP-HPLC purification in the second step.%目的:研究抗HIV融合多肽CP32M的制备工艺,为其临床前试验奠定基础.方法:采用固-液相混合策略规模合成目标肽,用离子交换色谱、反相高效液相色谱对粗肽进行纯化.结果:获得了利于提高合成及片段缩合效率的3条优选片段,CP32M粗品经DEAE离子交换色谱及C18反相纯化后纯度高于98%.结论:CP32M按3条片段(Ac-1-9-OH 、Fmoc- 10-21-OH 、H-22-32-NH2)划分,可显著提高片段合成及缩合效率,DEAE阴离子交换色谱能除去大部分杂质,提高了第二步C18反相色谱纯化效率.

  13. Assimetria nas relações internacionais, propriedade industrial e medicamentos anti-aids Asymmetry in international relations, industrial property rights and anti-HIV medication

    Directory of Open Access Journals (Sweden)

    Maria Helena Costa-Couto

    2008-12-01

    Full Text Available Este artigo analisa a assimetria nas relações internacionais entre países no que diz respeito ao reconhecimento da propriedade industrial no setor específico da indústria farmacêutica. O foco é o impacto destas relações no acesso a medicamentos anti-retrovirais (ARV, questão de interesse mundial em face da sua relação com o desenvolvimento das nações. A disputa de interesses no campo e o posicionamento de alguns países frente às leis patentárias, ao longo do tempo, apontam um cenário pouco favorável para acesso aos medicamentos anti-aids pelos países que não pertencem ao núcleo do sistema mundial. O sucesso do programa brasileiro de Doenças Sexualmente Transmissíveis (DSTs e Aids nas negociações dos preços dos ARV, ao contrário, aponta para novas possibilidades de enfrentamento desta realidade. A saída parece ser o fortalecimento interno dos Estados Nacionais e um papel ativo das Agências do Sistema das Nações Unidas na defesa dos interesses humanos coletivos.This paper analyzes the asymmetry in the international relations as refers to the recognition of industrial property rights in the pharmaceutical industry. It focuses on the impact of such relations upon the access to ARV medication, an issue of worldwide interest due to its connection with the development of the nations. Clashing interests and the position taken by some countries in their patent laws point to a scenario less favorable for the access of peripheral countries to anti-HIV/AIDS medication. On the other hand, it seems that the success of the Brazilian STD/AIDS program in negotiating ARV prices will open new possibilities. The solution may be the internal strengthening of the National States and the active role played by the Agencies of the United Nations System in defense of the collective human interests.

  14. HIV-1 tat promotes integrin-mediated HIV transmission to dendritic cells by binding Env spikes and competes neutralization by anti-HIV antibodies.

    Directory of Open Access Journals (Sweden)

    Paolo Monini

    Full Text Available Use of Env in HIV vaccine development has been disappointing. Here we show that, in the presence of a biologically active Tat subunit vaccine, a trimeric Env protein prevents in monkeys virus spread from the portal of entry to regional lymph nodes. This appears to be due to specific interactions between Tat and Env spikes that form a novel virus entry complex favoring R5 or X4 virus entry and productive infection of dendritic cells (DCs via an integrin-mediated pathway. These Tat effects do not require Tat-transactivation activity and are blocked by anti-integrin antibodies (Abs. Productive DC infection promoted by Tat is associated with a highly efficient virus transmission to T cells. In the Tat/Env complex the cysteine-rich region of Tat engages the Env V3 loop, whereas the Tat RGD sequence remains free and directs the virus to integrins present on DCs. V2 loop deletion, which unshields the CCR5 binding region of Env, increases Tat/Env complex stability. Of note, binding of Tat to Env abolishes neutralization of Env entry or infection of DCs by anti-HIV sera lacking anti-Tat Abs, which are seldom present in natural infection. This is reversed, and neutralization further enhanced, by HIV sera containing anti-Tat Abs such as those from asymptomatic or Tat-vaccinated patients, or by sera from the Tat/Env vaccinated monkeys. Thus, both anti-Tat and anti-Env Abs are required for efficient HIV neutralization. These data suggest that the Tat/Env interaction increases HIV acquisition and spreading, as a mechanism evolved by the virus to escape anti-Env neutralizing Abs. This may explain the low effectiveness of Env-based vaccines, which are also unlikely to elicit Abs against new Env epitopes exposed by the Tat/Env interaction. As Tat also binds Envs from different clades, new vaccine strategies should exploit the Tat/Env interaction for both preventative and therapeutic interventions.

  15. Assembling different antennas of the gp120 high mannose-type glycans on gold nanoparticles provides superior binding to the anti-HIV antibody 2G12 than the individual antennas.

    Science.gov (United States)

    Chiodo, Fabrizio; Enríquez-Navas, Pedro M; Angulo, Jesús; Marradi, Marco; Penadés, Soledad

    2015-03-20

    In order to re-build Man9GlcNAc2 clusters of the HIV gp120 glycoprotein, ∼2 nm gold glyconanoparticles (GNPs) were coated with the synthetic partial structures of Man9, the tetramannoside Manα1-2Manα1-2Manα1-3Manα1- and the pentamannoside Manα1-2Manα1-3[Manα1-2Manα1-6]Manα1-. Their interactions with the anti-HIV broadly neutralizing antibody 2G12 were studied by surface plasmon resonance (SPR)-based biosensors and saturation transfer difference (STD)-NMR spectroscopy. A synergistic effect of the tetra- and pentamannosides multimerized on a same GNP was observed. The assembly of these antennas of the gp120 high-mannose type glycan on GNPs provided superior binding to the anti-HIV antibody 2G12 with respect to GNPs carrying only the individual oligomannosides. The results presented in this work provide new molecular information on the interactions between clusters of oligomannosides and 2G12 that could help in the design of a carbohydrate-based vaccine against HIV.

  16. Rational design, synthesis, anti-HIV-1 RT and antimicrobial activity of novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propan-1-one derivatives.

    Science.gov (United States)

    Chander, Subhash; Wang, Ping; Ashok, Penta; Yang, Liu-Meng; Zheng, Yong-Tang; Murugesan, Sankaranarayanan

    2016-08-01

    In the present study, fifteen novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propan-1-one (6a-o) derivatives were designed as inhibitor of HIV-1 RT using ligand based drug design approach and in-silico evaluated for drug-likeness properties. Designed compounds were synthesized, characterized and in-vitro evaluated for RT inhibitory activity against wild HIV-1 RT strain. Among the tested compounds, four compounds (6a, 6b, 6j and 6o) exhibited significant inhibition of HIV-1 RT (IC50⩽10μg/ml). All synthesized compounds were also evaluated for anti-HIV-1 activity as well as cytotoxicity on T lymphocytes, in which compounds 6b and 6l exhibited significant anti-HIV activity (EC50 values 4.72 and 5.45μg/ml respectively) with good safety index. Four compounds (6a, 6b, 6j and 6o) found significantly active against HIV-1 RT in the in-vitro assay were in-silico evaluated against two mutant RT strains as well as one wild strain. Further, titled compounds were evaluated for in-vitro antibacterial (Escherichia coli, Pseudomonas putida, Staphylococcus aureus and Bacillus cereus) and antifungal (Candida albicans and Aspergillus niger) activities.

  17. Progress in clinical and basic researches on anti-HIV drug resistance%HIV耐药的临床和基础研究进展

    Institute of Scientific and Technical Information of China (English)

    孙丽君; 刘安

    2011-01-01

    The review focuses on the following topics: strategic study on sustaining survival ,storage and eradication of HIV-1 virus; study on resistance of HIV-1 entering anti-HIV drugs (including the determination of HIV-1 core acceptor sites by comparing the genotype and phenotype before using CCR5 inhibitors); study on resistance of reverse transcriptase inhibitor in polymerase ( including the resistance of hepatitis B and HIV-1 viruses to 3TC, and the mutation of HIV-1 B and C sub-types at K65Rw site); study on the resistance of reverse transcriptase inhibitor linking with RNase H( including role of mutation in response to EFV and etravirine ); study on resistance of hepatitis C virus and HIV-1 protease inhibitors; study of resistance of raltegravir, an integrase inhibitor; global resistance prevalence( including model of prediting resistance to second line ARV drugs in resource-limited areas); roles of a number of resistant mutation strains( including roles of mutation strains in PMTCT)%文章主要关注以下方面内容:艾滋病病毒Ⅰ型(HIV-1)持续存在、储存和消除等方面的策略研究;HIV-1侵入抑制剂的耐药研究(包括通过对比使用CCR5拈抗剂治疗前的基因型和表现型来确定HIV-1的核心接受位点);反转录酶抑制剂在聚合酶领域的耐药研究(包括乙型肝炎病毒和HIV-1对拉米夫定的耐药,HIV-1B和C亚型在K65Rw位点突变);反转录酶抑制剂在联结和RNase H领域的耐药研究[包括突变在对依非韦仑和etravirine(一种新药)应答方面的作用];对丙型肝炎病毒和HIV-1蛋白酶抑制剂的耐药研究;对整合酶抑制剂雷特格韦(Raltegravir)的耐药研究;全球耐药流行情况(包括对资源匮乏地区二线抗病毒药物耐药反应的预测模型);少数耐药变异株的作用(包括这些变异株在预防艾滋病母婴传播中的作用).

  18. Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kamata, Masakazu, E-mail: masa3k@ucla.edu [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Kim, Patrick Y. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ng, Hwee L. [Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O' Connor, Sean [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Yang, Otto O. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States); AIDS Healthcare Foundation, Los Angeles, CA (United States); Chen, Irvin S.Y. [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States)

    2015-07-31

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.

  19. Ectopic expression of anti-HIV-1 shRNAs protects CD8+ T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    International Nuclear Information System (INIS)

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8+ T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8+ T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8+ T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24Gag in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8+ T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8+ T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8+ T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8+ T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8+ T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8+ T cells from HIV-1 infection suppresses its cytopathic effect

  20. Anti-HIV-1 activity and structure-activity relationship of pyranocoumarin analogs%吡喃香豆素衍生物对HIV-1的抑制作用及其构效关系

    Institute of Scientific and Technical Information of China (English)

    董飚; 马涛; 章天; 周春梅; 刘刚; 王琳; 陶佩珍; 张兴权

    2011-01-01

    The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 μmol·L-1 of IC50 against HIV-1 PR/RT and 0.036 μmol·L-1 against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.%研究香豆素衍生物对人类免疫缺陷病毒l型逆转录酶(HIV-1 RT)、蛋白酶(HIV-1 PR)和细胞内复制的抑制作用及其构效关系.不同香豆素衍生物具有抑制HIV-1 RT、HIV-1 PR活性,且在细胞内显示出抑制HIV-1复制的作用已见报道.本课题根据国内传统药学的特点,考察以天然产物为先导化合物、结合HIV-1蛋白酶三维结构计算机辅助药物设计、合成的四环双吡喃香豆素及其类似物.以HIV-1 RT及HIV-1 PR以及细胞内病毒复制为靶点,利用酶学模型和细胞培养模型进行药物筛选及其构效关系研究,设计合成的7个化合物的药效学实验结果显示.部分化合物显示了不同程度的抗HIV-1活性.其中V0201作用最强,它对HIV-1 PR和HIV-1 RT的IC50分别为3.56和0.78 μmol·L-1;

  1. Disponibilidade de sorologia anti-HIV como um teste voluntário na rotina do atendimento pré-natal em unidades básicas de saúde

    OpenAIRE

    Fátima RAL Neves; Afonso DC Passos; Wagner L Gueleri

    1999-01-01

    São apresentadas, de forma sucinta, as principais etapas cumpridas para a implementação da sorologia anti-HIV no atendimento às gestantes em unidades básicas de saúde. A partir de agosto de 1996, a realização de testes sorológicos para detecção do HIV passou a ser ofertada às gestantes atendidas em unidades básicas de saúde de Ribeirão Preto, SP, integrada a um conjunto de atividades rotineiramente executadas no atendimento pré-natal. Até o final de 1998, o teste sorológico foi aplicado em 68...

  2. A Recent Perspective on Discovery and Development of Diverse Therapeutic Agents Inspired from Isatin Alkaloids.

    Science.gov (United States)

    Rane, Rajesh A; Karunanidhi, Sivanandhan; Jain, Kavita; Shaikh, Mahamadhanif; Hampannavar, Girish; Karpoormath, Rajshekhar

    2016-01-01

    Isatin as an alkaloidal framework have consistently attracted attention of medicinal chemist towards development of wide range of novel therapeutic agents. This review report has discussed significant isatin lead molecules and their derivatives which have shown promising biological potential in recent times. The substituted isatins showing a potent pharmacological activities such as antimicrobial, antitubercular, anticancer, antioxidant, anti-histaminic, anti-HIV, antiviral, anti-inflammatory, anti-Parkinson's and antidiabetic have been described in this review. The mechanism of action leading to therapeutic activity of the respective isatin derivation has also been recorded. This review reveals that the systematic and rational modifications on isatin motif exhibited significant bio-activities which can be exploited for the development of potent novel therapeutic agents in the future studies. Hence the quest to investigate more structural alterations on isatin scaffold should be continued. PMID:26369813

  3. Rescreening and confirmation of anti-HIV antibody positive serum in primary screening in Qingdao%青岛市HIV抗体初筛阳性标本的复检及确证结果分析

    Institute of Scientific and Technical Information of China (English)

    史晓燕; 张洪花; 赵国有; 弋英; 汪照国

    2013-01-01

    Objective To rescreen and confirm anti-HIV antibody positive serum in primary screening in Qingdao from 2009 to 2011 and to analyze the related data,so as to provide basis for prevention and control of AIDS in Qingdao.Methods Samples positive for anti-HIV antibody in primary screening test were re-screened with both Electroselenium method and ELISA.Then the positive samples in either re-screening test were further confirmed with Western Blot (WB).Results In 1348 positive samples from primary screening test,positive were found in 745 cases in re-screening test.By WB confirmation,563 cases were positive,95 cases were suspected and 87 cases were negative.In contrast to WB,positive coincidence rates of ELISA and Electroselenium method were 81.5% and 84.3% respectively.The sensitivity and specificity of ELISA were 100% and 93.6 % respectively,and those of Electroselenium method were 100% and 94.5% respectively.Flouting population accounted for 58.4% and MSM accounted for 40.1% of total HIV infection.Conclusion Anti-HIV antibody rescreening tests could exclude most false positive samples in primary screening test.However,there is still some false positive rate in either rescreening test.Flouting population and MSM are the high risk population of HIV infection in Qingdao city and intervention should be strengthened among those people.%目的 复检和确认HIV抗体初筛阳性血清并分析相关资料,为青岛市艾滋病防治工作提供依据.方法 对初筛阳性血清,用胶体硒和ELISA试验复检,任一复检试验阳性的血清再用WB试验确证并对确证阳性病例进行流行病学分析.结果 1348份初筛阳性血清经复检745份阳性,WB确证563份HIV-l抗体阳性,不确定95份,阴性87份.ELISA、胶体硒法与WB的阳性符合率分别为81.5%和84.3%,二者的敏感度均为100%,特异度分别为93.6%和94.5%,确证阳性人群中,外来人员占58.4%,男男性行为人群占40.1%.结论 ELISA和胶体硒

  4. In vitro anti-HIV-1 activities of resveratrol derivatives%白藜芦醇衍生物体外抗HIV-1活性的初步研究

    Institute of Scientific and Technical Information of China (English)

    黄宁; 杨柳萌; 王睿睿; 朱海亮; 郑永唐

    2012-01-01

    Objective; To study the in vitro anti-HIV-1 activities of resveratrol derivatives and the mechanisms. Methods; The cytotoxicities of compounds were tested by MTT assay. The anti-HIV activities of compounds in acute infection were evaluated by cytopathogenic effect (CPE) assay. The inhibition of HIV-lKm018 replication in PBMC was evaluated by p24 antigen expression. The fusion between of HIV-1 infected and uninfected cells was e-valuated by CPE. The inhibition of HIV-1 recombinant reverse transcriptase activity, HIV-1 recombinant protease activity and direct HIV-1 virus killing were used to determine the mechanism. Results; IFB-1 and IFB-9 from resveratrol derivatives markedly inhibited syncytium formation with selective indexes of 16. 16 and 230.27 , respectively. IFB-1 and IFB-9 suppressed HIV-1 p24 antigen production in acutely HIV-111IB-infected C8166 cells with EC50, of 14.57 and 0.23 μg·mL-1 , respectively. They also inhibited HIV-lKM018 replication in PBMC. IFB-1 and IFB-9 blocked the fusion between normal cells and chronically HIV-1-infected cells, but did not inhibit recombinant RT, PR activities and did not directly kill HIV-1. Conclusions; IFB-1 and IFB-9 show potential anti-HIV-1 activities and the mechanism might be associated with inhibition virus entry.%目的:检测白藜芦醇衍生物IFB-1和IFB-9的体外抗HIV-1活性,并对其进行抗HIV-1作用机制的初步研究.方法:采用MTT比色法检测白藜芦醇衍生物IFB-1和IFB-9的细胞毒性;细胞病变法检测化合物对HIV-1急性感染的抑制活性;采用HIV-1 p24抗原ELISA方法检测临床分离株HIV-1KM018在PBMC中复制的抑制实验;采用细胞病变法检测HIV-1感染和未感染细胞之间的融合;采用HIV-1重组逆转录酶活性抑制实验,HIV-1重组蛋白酶活性抑制实验以及直接杀病毒实验来研究化合物体外抗HIV-1机制.结果:白藜芦醇衍生物IFB-1和IFB-9对HIV-1 ⅢB诱导的合胞体形成抑制的选择指数分别为16

  5. Analysis of blood donors situation and anti-HIV antibody screening in a hospital of Madagascar%马达加斯加某医院献血员情况及 HIV 抗体筛查分析

    Institute of Scientific and Technical Information of China (English)

    张晓萍; 李勇

    2014-01-01

    Objective To understand the basic situation of blood donors and their anti-HIV antibody screening in a hospital of Madagascar during 2008- 2009 in order to provide the reference information for giving better medical aid and promoting the devel-opment of the clinical transfusion in Madagascar.Methods The blood doner′s personal informations were understood by inquiry and the anti-HIV antibody was detected by the rapid testing,the results were recorded,the constituent ratio of the data was calcu-lated and the chi-square test was performed.Results There were 2 298 blood donors including teenages less than 15 years old dur-ing 2008-2009,female doners were more than male donors,among them 366 cases were pregrant women.The blood donors from village were more than those from city,the education level was dominated by the middle school students,accounting for 51.65%. There were 22 tuberculosis patients in 2008,none in 2009.The detection rate of anti-HIV antibody was 0.04% for these 2 years. Conclusion The protection on the blood donors in Africa area is not optimistic.The phenomenon of pregrant women and teenages as the blood donors exists in Madagascar.%目的:了解马达加斯加某医院2008~2009年献血员的基本情况和艾滋病毒抗体筛查情况,为以后更好的医疗援助马达加斯加及促进其临床输血领域的发展提供参考信息。方法口头询问方式获取献血员的基本信息,采用快速法检测 HIV 抗体,记录结果,计算数据的构成比,并进行χ2检验。结果2008~2009年共2298名献血员,有15岁及以下的献血者,女性献血员多于男性,其中有366名是孕妇;农村多于城市,文化程度以中学为主,占51.65%。2008年有22名结核病患者,2009年为0。两年艾滋病毒抗体阳性检出率为0.04%。结论非洲地区对献血者的保护不容乐观,存在孕妇和青少年献血的现象。

  6. Aconselhamento na testagem anti-HIV no ciclo gravídico-puerperal: o olhar da integralidade Counseling in HIV testing in the pre and post labor periods: the look of the integrality

    Directory of Open Access Journals (Sweden)

    Ana Jaqueline Santiago Carneiro

    2010-06-01

    Full Text Available A sorologia para HIV em mulheres no pré-natal e os testes rápidos anti-HIV em maternidade devem ser realizados com aconselhamento pré e pós-teste. Na prática, observa-se que esse nem sempre é realizado, predominando o cumprimento de procedimentos técnicos destinados a prevenir a transmissão vertical. O objetivo deste estudo foi analisar o cuidado profissional a mulheres que tomaram conhecimento da positividade para o HIV durante o trabalho de parto ou puerpério. Trata-se de estudo exploratório de natureza qualitativa, utilizando como categorias analíticas gênero e integralidade. Participaram do estudo doze puérperas usuárias de um centro de referência para HIV/aids, em Salvador (BA. Foi recortado para este artigo o olhar das mulheres sobre o aconselhamento no processo de testagem para o HIV. Os resultados foram produzidos a partir de entrevista semiestruturada e analisados pela técnica de análise de discurso segundo Fiorin. A análise revelou que a testagem anti-HIV foi incorporada à prática clínica sem aconselhamento em nenhuma das etapas da atenção ao ciclo gravídico-puerperal, na realidade investigada. As relações entre profissionais e usuárias refletem mecanismos de poder que comprometem a autonomia das mulheres, distanciando o cuidado da perspectiva da integralidade.The sorology for HIV in woman and rapid HIV testing in maternity hospitals must be carried with pre and pos-test counseling. However, it has been observed that the counseling has not been accomplished by many health professionals, who give more importance to the prophylactic measures which intend to prevent vertical transmission. The objective of this qualitative study is to investigate how women evaluate the health care received during the HIV testing at pre and post-labor periods. For this paper the look of woman about counseling in the process of HIV testing was cut. We used gender and integrality as analytic categories. The technique used to collect

  7. SYNTHESIS OF NEW HETEROCYCLIC SCHIFF BASE, THIAZOLIDINONE AND AZETIDINONE COMPOUNDS AND THEIR ANTIBACTERIAL ACTIVITY AND ANTI –HIV ACTIVITIES Synthese neuer HETEROCYCLISCHE SCHIFF BASE, Thiazolidinon UND Azetidinonverbindungen UND IHRE antibakterielle Aktivität und ANTI-HIV AKTIVITÄTEN

    Directory of Open Access Journals (Sweden)

    RAJARSHI N. PATEL, P.V.PATEL , K.R. DESAI, P.Y. PUROHIT, K.S.NIMAVAT AND K.B. VYAS

    2012-01-01

    Full Text Available Thiazolidines and azetidinopnes have been prepared by the reaction of various Schiff bases with thioglycine acid chloroacetyl chloride respectively. The intermediate Schiff bases were synthesized by the condensation of 4-amino-2,4’-dichloro diphenyl ether with various aldehydes. The structures of the compounds have been confirmed by elemental analysis and spectral analysis. The antibacterial and anti HIV activities of the compounds have been also screened.

  8. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study.

    Science.gov (United States)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno; Ryom, Lene; Reiss, Peter; Law, Matthew; Pradier, Christian; Dabis, Francois; d'Arminio Monforte, Antonella; Smith, Colette; de Wit, Stephane; Kirk, Ole; Lundgren, Jens D; Weber, Rainer

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (2 years RR = 1.26, 95% CI, 1.13-1.41); stavudine (2 years RR = 1.17, 95% CI, 1.03-1.32), and tenofovir disoproxil fumarate (2 years RR = 1.18, 95% CI, 1.05-1.32), but only short-term exposure to nevirapine (abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE. Conclusions.  Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated. PMID:26925429

  9. In vitro anti-HIV-1 activities of Qishile, a Chinese medicine effective fraction formula%中药有效部位复方奇士乐体外抗HIV-1活性研究

    Institute of Scientific and Technical Information of China (English)

    杨柳萌; 王睿睿; 张高红; 张兴杰; 陈纪军; 郑永唐

    2011-01-01

    目的 评价有效部位复方奇士乐(QSL)的体外抗HIV-1药效学.方法 通过合胞体抑制、HIV-1感染细胞保护、HIV-1 p24抗原测定等方法检测急性感染中QSL对HIV-1实验株、临床分离株、耐药株的抑制作用和对慢性感染细胞中病毒复制的影响;通过ELISA方法和荧光法分别检测了QSL体外抑制HIV-1逆转录酶和蛋白酶活性作用.结果 有效部位复方制剂QSL能有效地抑制HIV-1ⅢB诱导淋巴细胞病变、保护HIV-1ⅢB感染MT-4细胞死亡、阻断HIV-1ⅢB慢性感染H9细胞与C8166细胞间融合的作用.QSL对HIV-1实验株HIV-1ⅢB、临床分离株HIV-1KM018、耐药株HIV-174V的病毒复制也有较好的抑制作用.QSL抑制HIV活性的作用机制可能为多靶点,主要是抑制HIV逆转录酶、蛋白酶和病毒进入细胞.结论 QSL是具有较好体外抗HIV-1活性的中药有效部位复方.%Aim To evaluate the anti-HIV-1 activities of Qishile ( QSL) in vitro , a Chinese medicine effective fraction formula. Methods The inhibition of syncytia formation induced by HIV -1 was determined under microscopy. The protection of HIV-1 induced MT-4 cell lytic effects was measured by MTT assay . The level of HIV-1 p24 antigen in acute and chronic HIV-1 infection was assayed by ELISA. HIV-1 reverse transcriptase and protease activites in vitro were tested by ELISA and FRET, respectively. Results QSL markedly inhibited syncytium formation induced by HIV-1 ⅢB , protected HIV-1 ⅢB induced MT-4 cell lytic effects and blocked cell-to-cell fusion. It also showed obviously inhibitory effect on the clinical strain HIV-1KM018 ancl drug resistant strain HIV-174V replication.QSL maybe inhibited HIV-I replication through multiple targets, including reverse transcriptase , protease and virus entry. Conclusion QSL is a Chinese medicine effective fraction formula with potent anti-HIV-1 activities.

  10. HIV感染者和艾滋病患者抗病毒疗效及耐药分析%Effect of anti-HIV treatment and drug-resistance HIV among infected persons and AIDS

    Institute of Scientific and Technical Information of China (English)

    张姝; 张佳峰; 高红; 焦素黎; 许国章

    2011-01-01

    目的 研究浙江省宁波市HIV感染者和艾滋病人(HIV/AIDS)抗病毒治疗(HAART)效果和发生耐药情况.方法 收集156例HIV-1型阳性病例血样,包括114例AIDS病人和42例未治疗感染者,检测CD4+T淋巴细胞数和HIV病毒载量,通过测序获得pol基因序列,经美国斯坦福大学HIV国际耐药数据库分析,获得毒株耐药情况.结果 成功获得42例病例的pol序列;在HIV感染者中,HIV毒株对蛋白酶抑制剂分别有8例潜在耐药和2例中度耐药;在艾滋病人中,病毒载量低于最低检测限(50 IU/mL)的有100例,占87.7%;HIV毒株对核苷类和非核苷类抑制剂分别有4例和5例高度耐药;该人群的CD4+T淋巴细胞绝对数为14~1 060个/μL,平均为(314±28)个/μL.结论 宁波市多数HIV感染者和艾滋病人对现有的抗病毒药物敏感,抗病毒治疗效果良好.%Objective To study the effect of anti-HTV treatment and status of drag-resistance among HTV /AIDS patients. Methods Whole blood samples were collected from HIV infected persons with or without anti-HIV treatment and AIDS patients. The absolute number of CD4 * T lymphocyte and virus load of the subjects were detected. The virus RNA was amplified with nested-PCR and then sequenced. The drug resistance of HIV-1 strains isolated were obtained by comparison with Stanford HIV Drug Resistance Database. Results Forty-two sequences of pol gene were obtained. Drug resistance to Pis was detected,including 8 potential resistance and 2 intermediate resistance,in HIV infected persons without treatment. Drug resistance to NRTIs was detected,including 4 high-level resistance,and to NNRTIs was detected,including 5 high-level resistance,in AIDS patients. The mean value of absolute number of CD4+ T lymphocyte was 314 ±28 /Μl.with the lowest of 14/μxL and the highest of 1 060/Μl. Conclusion Most of HIV/AIDS patients are susceptible to the anti-HIV drug at present and a good treatment effect is achieved.

  11. Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments

    Science.gov (United States)

    Ojha, R. P.; Dhingra, M. M.; Sarma, M. H.; Myer, Y. P.; Setlik, R. F.; Shibata, M.; Kazim, A. L.; Ornstein, R. L.; Rein, R.; Turner, C. J.; Sarma, R. H.

    1997-01-01

    The structure of an anti-HIV-1 ribozyme-DNA abortive substrate complex was investigated by 750 MHz NMR and computer modeling experiments. The ribozyme was a chimeric molecule with 30 residues-18 DNA nucleotides, and 12 RNA residues in the conserved core. The DNA substrate analog had 17 residues. The chimeric ribozyme and the DNA substrate formed a shortened ribozyme-abortive substrate complex of 47 nucleotides with two DNA stems (stems I and III) and a loop consisting of the conserved core residues. Circular dichroism spectra showed that the DNA stems assume A-family conformation at the NMR concentration and a temperature of 15 degrees C, contrary to the conventional wisdom that DNA duplexes in aqueous solution populate entirely in the B-form. It is proposed that the A-family RNA residues at the core expand the A-family initiated at the core into the DNA stems because of the large free energy requirement for the formation of A/B junctions. Assignments of the base H8/H6 protons and H1' of the 47 residues were made by a NOESY walk. In addition to the methyl groups of all T's, the imino resonances of stems I and III and AH2's were assigned from appropriate NOESY walks. The extracted NMR data along with available crystallographic data, were used to derive a structural model of the complex. Stems I and III of the final model displayed a remarkable similarity to the A form of DNA; in stem III, a GC base pair was found to be moving into the floor of the minor groove defined by flanking AT pairs; data suggest the formation of a buckled rhombic structure with the adjacent pair; in addition, the base pair at the interface of stem III and the loop region displayed deformed geometry. The loop with the catalytic core, and the immediate region of the stems displayed conformational multiplicity within the NMR time scale. A catalytic mechanism for ribozyme action based on the derived structure, and consistent with biochemical data in the literature, is proposed. The complex

  12. Development and identification of a novel anti-HIV-1 peptide derived by modification of the N-terminal domain of HIV-1 integrase

    Directory of Open Access Journals (Sweden)

    Marina eSala

    2016-06-01

    Full Text Available The viral enzyme integrase (IN is essential for the replication of human immunodeficiency virus type 1 (HIV-1 and represents an important target for the development of new antiretroviral drugs. In this study, we focused on the N-terminal domain (NTD, which is mainly involved into protein oligomerization process, for the development and synthesis of a library of overlapping peptide sequences, with specific length and specific offset covering the entire native protein sequence NTD IN 1-50. The most potent fragment, VVAKEIVAH (peptide 18, which includes a His residue instead of the natural Ser at position 39, inhibits the HIV-1 IN activity with an IC50 value of 4.5 M. Amino acid substitution analysis on this peptide revealed essential residues for activity and allowed us to identify two nonapeptides (peptides 24 and 25, that show a potency of inhibition similar to the one of peptide 18. Interestingly, peptide 18 does not interfere with the dynamic interplay between IN subunits, while peptides 24 and 25 modulated these interactions in different manners. In fact, peptide 24 inhibited the IN-IN dimerization, while peptide 25 promoted IN multimerization, with IC50 values of 32 and 4.8 µM, respectively. In addition, peptide 25 has shown to have selective anti-infective cell activity for HIV-1. These results confirmed peptide 25 as a hit for further development of new chemotherapeutic agents against HIV-1.

  13. Systematic evaluation of methyl ester bioisosteres in the context of developing alkenyldiarylmethanes (ADAMs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for anti-HIV-1 chemotherapy.

    Science.gov (United States)

    Hoshi, Ayako; Sakamoto, Takeshi; Takayama, Jun; Xuan, Meiyan; Okazaki, Mari; Hartman, Tracy L; Buckheit, Robert W; Pannecouque, Christophe; Cushman, Mark

    2016-07-01

    The alkenyldiarylmethanes (ADAMs) are a class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) targeting HIV-1. Four chemically and metabolically stabilized ADAMs incorporating N-methoxyimidoyl halide replacements of the methyl esters of the lead compound were previously reported. In this study, twenty-five new ADAMs were synthesized in order to investigate the biological consequences of installing nine different methyl ester bioisosteres at three different locations. Attempts to define a universal rank order of methyl ester bioisosteres and discover the 'best' one in terms of inhibitory activity versus HIV-1 reverse transcriptase (RT) led to the realization that the potencies are critically dependent on the surrounding structure at each location, and therefore the definition of universal rank order is impossible. This investigation produced several new non-nucleoside reverse transcriptase inhibitors in which all three of the three methyl esters of the lead compound were replaced by methyl ester bioisosteres, resulting in compounds that are more potent as HIV-1 RT inhibitors and antiviral agents than the lead compound itself and are expected to also be more metabolically stable than the lead compound. PMID:27234889

  14. Development and Identification of a Novel Anti-HIV-1 Peptide Derived by Modification of the N-Terminal Domain of HIV-1 Integrase

    Science.gov (United States)

    Sala, Marina; Spensiero, Antonia; Esposito, Francesca; Scala, Maria C.; Vernieri, Ermelinda; Bertamino, Alessia; Manfra, Michele; Carotenuto, Alfonso; Grieco, Paolo; Novellino, Ettore; Cadeddu, Marta; Tramontano, Enzo; Schols, Dominique; Campiglia, Pietro; Gomez-Monterrey, Isabel M.

    2016-01-01

    The viral enzyme integrase (IN) is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents an important target for the development of new antiretroviral drugs. In this study, we focused on the N-terminal domain (NTD), which is mainly involved into protein oligomerization process, for the development and synthesis of a library of overlapping peptide sequences, with specific length and specific offset covering the entire native protein sequence NTD IN 1–50. The most potent fragment, VVAKEIVAH (peptide 18), which includes a His residue instead of the natural Ser at position 39, inhibits the HIV-1 IN activity with an IC50 value of 4.5 μM. Amino acid substitution analysis on this peptide revealed essential residues for activity and allowed us to identify two nonapeptides (peptides 24 and 25), that show a potency of inhibition similar to the one of peptide 18. Interestingly, peptide 18 does not interfere with the dynamic interplay between IN subunits, while peptides 24 and 25 modulated these interactions in different manners. In fact, peptide 24 inhibited the IN-IN dimerization, while peptide 25 promoted IN multimerization, with IC50 values of 32 and 4.8 μM, respectively. In addition, peptide 25 has shown to have selective anti-infective cell activity for HIV-1. These results confirmed peptide 25 as a hit for further development of new chemotherapeutic agents against HIV-1. PMID:27375570

  15. Gnidimacrin, a Potent Anti-HIV Diterpene, Can Eliminate Latent HIV-1 Ex Vivo by Activation of Protein Kinase C β.

    Science.gov (United States)

    Lai, Weihong; Huang, Li; Zhu, Lei; Ferrari, Guido; Chan, Cliburn; Li, Wei; Lee, Kuo-Hsiung; Chen, Chin-Ho

    2015-11-12

    HIV-1-latency-reversing agents, such as histone deacetylase inhibitors (HDACIs), were ineffective in reducing latent HIV-1 reservoirs ex vivo using CD4 cells from patients as a model. This deficiency poses a challenge to current pharmacological approaches for HIV-1 eradication. The results of this study indicated that gnidimacrin (GM) was able to markedly reduce the latent HIV-1 DNA level and the frequency of latently infected cells in an ex vivo model using patients peripheral blood mononuclear cells. GM induced approximately 10-fold more HIV-1 production than the HDACI SAHA or romidepsin, which may be responsible for the effectiveness of GM in reducing latent HIV-1 levels. GM achieved these effects at low picomolar concentrations by selective activation of protein kinase C βI and βII. Notably, GM was able to reduce the frequency of HIV-1 latently infected cells at concentrations without global T cell activation or stimulating inflammatory cytokine production. GM merits further development as a clinical trial candidate for latent HIV-1 eradication.

  16. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    Directory of Open Access Journals (Sweden)

    Sandhya Boyapalle

    Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

  17. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    Science.gov (United States)

    Boyapalle, Sandhya; Xu, Weidong; Raulji, Payal; Mohapatra, Subhra; Mohapatra, Shyam S

    2015-01-01

    Human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and HIV-2) are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s) as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid) was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs) and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC) model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162) viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

  18. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation

    Science.gov (United States)

    Connell, Bridgette Janine; Chang, Sui-Yuan; Prakash, Ekambaranellore; Yousfi, Rahima; Mohan, Viswaraman; Posch, Wilfried; Wilflingseder, Doris; Moog, Christiane; Kodama, Eiichi N.; Clayette, Pascal; Lortat-Jacob, Hugues

    2016-01-01

    Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1–7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS) as well as to an antibody (mAb 17b) directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1. PMID:27788205

  19. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study

    Science.gov (United States)

    Kovari, Helen; Sabin, Caroline A.; Ledergerber, Bruno; Ryom, Lene; Reiss, Peter; Law, Matthew; Pradier, Christian; Dabis, Francois; d'Arminio Monforte, Antonella; Smith, Colette; de Wit, Stephane; Kirk, Ole; Lundgren, Jens D.; Weber, Rainer

    2016-01-01

    Background. Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (2 years RR = 1.26, 95% CI, 1.13–1.41); stavudine (2 years RR = 1.17, 95% CI, 1.03–1.32), and tenofovir disoproxil fumarate (2 years RR = 1.18, 95% CI, 1.05–1.32), but only short-term exposure to nevirapine (<2 years RR = 1.44, 95% CI, 1.29–1.61), efavirenz (<2 years RR = 1.14, 95% CI, 1.03–1.26), emtricitabine (<2 years RR = 1.18, 95% CI, 1.04–1.33), and atazanavir (<2 years RR = 1.20, 95% CI, 1.04–1.38). Chronic liver enzyme elevation was not associated with use of lamivudine, abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE. Conclusions. Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated. PMID:26925429

  20. Research Progress on the Interaction Between Herb Medicine and Anti-HIV Chemical Drugs%中草药与抗艾滋病病毒化学药物相互作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘晓茜; 孙涛; 张丽军

    2015-01-01

    目的 HIV感染者由于免疫力低下导致各种机会性感染,中草药和化学药物联合用药的现象十分普遍.但是中草药成分复杂,可能影响抗病毒化学药物的有效性、安全性,引起HIV耐药等问题.本研究综述中草药与抗艾滋病病毒化学药物相互作用的研究进展.方法 从百度(www.baidu.com)和Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/)中搜索有关"中草药(herb)、抗艾滋病病毒药物(anti-HIV drugs)、药物与药物相互作用(drug-drug interaction)"的文献,然后进行归纳整理.结果 综述了中草药与化学药物联合用药现状,中草药对抗病毒化学药物的药动学影响以及对CYP450代谢酶的作用.结论 系统地综述了中草药与抗艾滋病病毒化学药物的相互作用,为临床合理用药提供参考.

  1. Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge.

    Science.gov (United States)

    Sholukh, Anton M; Watkins, Jennifer D; Vyas, Hemant K; Gupta, Sandeep; Lakhashe, Samir K; Thorat, Swati; Zhou, Mingkui; Hemashettar, Girish; Bachler, Barbara C; Forthal, Donald N; Villinger, Francois; Sattentau, Quentin J; Weiss, Robin A; Agatic, Gloria; Corti, Davide; Lanzavecchia, Antonio; Heeney, Jonathan L; Ruprecht, Ruth M

    2015-04-21

    Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA2 used alone and the combination of the two neutralized the challenge virus equally well in vitro. All RMs given only i.v. HGN194 IgG1 became infected. In contrast, all RMs given HGN194 IgG1+dIgA2 were completely protected against high-dose i.r. SHIV-1157ipEL-p challenge. These data imply that combining suboptimal defenses at the mucosal and systemic levels can completely prevent virus acquisition. Consequently, active vaccination should focus on defense-in-depth, a strategy that seeks to build up defensive fall-back positions well behind the fortified frontline.

  2. 基于RNA的抗HIV-1基因治疗方法研究进展%Current Development on RNA-based Anti-HIV-1 Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    陈丰; 杨怡姝; 曾毅

    2012-01-01

    Acquired immune deficiency syndrome (AIDS) is a high-risk disease which spreads rapidly all over the world since it has been discovered. Although the highly active antiretroviral therapy (HAART) that are widely used in present can improve the quality of life of HIV-1 infected patient dramatically, treatment interruptions have often occurred because of the high cost, drug resistance and side effects. As a result, the new antiretroviral drugs and approaches are demanded for sustained antiretrovial effects. With the development of molecular biology, stem cell, nanotechnology and other related technology, gene therapy for HIV-1 infection has attracted considerable attention in recent years. RNA-based gene therapy for treatment of HIV-1 infection, including antisense RNA, ribozymes, RNA decoys and the RNA interference are focused on. These studies demonstrated that the RNA-based anti-HIV-1 gene therapy may serve as an effective adjuvant to traditional treatments.%艾滋病自发现以来在全球范围内迅速蔓延,危害性极高,目前广泛采用的高效抗逆转录病毒疗法(HAART)虽能够显著提高HIV-1感染者生活质量,但存在着价格昂贵,耐药和副作用的问题经常会导致HAART治疗的中断.要获得长期持续的抗病毒治疗效果还有待于研发新的抗病毒药物和治疗方法.近年来随着分子生物技术、干细胞研究、纳米技术等相关技术的发展,关于抗HIV-1基因治疗方法的研究受到了广泛关注.主要针对基于RNA的抗HIV-1基因治疗方法,包括反义RNA、核酶、RNA诱饵以及RNA干扰技术在抗HIV-1基因治疗方面进行综述.研究表明,以RNA为基础的抗HIV-1基因治疗方法有望成为传统治疗方法的一种有效辅助手段.

  3. Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D study

    Directory of Open Access Journals (Sweden)

    Kathy Petoumenos

    2012-10-01

    Full Text Available Introduction: HIV-positive patients receiving combination antiretroviral therapy (cART frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD and diabetes mellitus (DM. Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods: All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC curve and predicted DM events were determined. Results: Of 33,308 patients, 16,632 (50% patients were included, with 376 cases of new onset DM during 89,469 person-years (PY. Factors predictive of DM included higher glucose, body mass index (BMI and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940 and 0.877 (95% CI: 0.823, 0.932, respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower

  4. [Evaluation of the analytic performance of blood collection tubes (BD Vacutainer SST) for the screening of anti-HIV, anti-HTLV, anti-HCV, anti-HBc, anti-CMV antibodies, and of HBs, P24 HIV antigens, and of alanine aminotransferase].

    Science.gov (United States)

    Gobin, E; Desruelle, J M; Vigier, J P

    2001-02-01

    The Laboratory of Viral Diseases Immunology (Laboratoire d'Immunologie des Maladies Virales) of the Northern Region Blood Bank (Etablissement Français du Sang Nord de France) performs between 180.000 and 200.000 viral blood qualifications per year. The use of a serum gel separator evacuated tube should contribute to improve the quality of the pre-analytical phase. However, it must not impact negatively the analytical performances. We evaluated such tube within our specific environment and with the various reagents used in routine. The open study compared the BD Vacutainer plain tube (7 mL, non siliconised) with the BD Vacutainer SST tube (6 mL siliconised with serum gel separator) against the anti-HIV, anti-HTLV, anti-HCV, anti-HBc, anti-HBs, anti-CMV antibodies, the HBs, HIV P24 antigen and the alanine aminotransferase. The study objectives were to find potential gel interference; to verify the diagnostic sensitivity, reagents specificity, and reproducibility. The results analysis show: equivalent performances with the anti-HIV Ab (Anti HIV 1/2 recombinant--Biotest et Genscreen HIV 1/2--Sanofi), anti HIV WB Ab (New Lav Blot 1--Sanofi), anti-HBs Ab (Enzygnost anti-HBs micro--Behring), anti-HBc Ab (HBc Elisa Test System--Ortho), anti-CMV Ab (Enzygnost anti-CMV IgG + M--Behring) kits; lower performances with: The Vironostika HIV Uni Form II plus 0--Organon kit with a -3.5% signal decrease around the ratio R = 2.7 for positive anti-HIV Ab. The Elisa test System 3 Ag HBs-Ortho kit with an increase of the mean ratio of the negative Ag HBs samples; better performances with: the Vironostika HIV 1 Antigen--Organon kit with a +10% signal increase around the threshold ratio R = 1 for positive Ag HIV samples. This deserves further study to verify that the specificity is maintained. The HTLV Type 1 et 2 EIA--Ortho kit with +8% signal increase around the ratio R = 2 for positive anti-HTLV Ab samples without change of the specificity. The Ortho HCV 3.0 Elisa Test System and

  5. Dual anti-HIV mechanism of clofarabine

    OpenAIRE

    Daly, Michele B.; Roth, Megan E.; Bonnac, Laurent; Maldonado, José O.; Xie, Jiashu; Clouser, Christine L; Patterson, Steven E.; Kim, Baek; Louis M. Mansky

    2016-01-01

    Background HIV-1 replication kinetics inherently depends on the availability of cellular dNTPs for viral DNA synthesis. In activated CD4+ T cells and other rapidly dividing cells, the concentrations of dNTPs are high and HIV-1 reverse transcription occurs in an efficient manner. In contrast, nondividing cells such as macrophages have lower dNTP pools, which restricts efficient reverse transcription. Clofarabine is an FDA approved ribonucleotide reductase inhibitor, which has shown potent anti...

  6. Antibiotic Agents

    Science.gov (United States)

    ... either as public health or as non-public health antimicrobial agents. What is the difference between bacteriostats, sanitizers, disinfectants ... bacteria, however, there is considerable controversy surrounding their health benefits. The ... producing agents (Table of Antibacterials) have been used for many ...

  7. An important role for type Ⅲ interferon(IFN-lambda) in anti-HIV activity%新型干扰素——IFN-λ抗HIV-1感染

    Institute of Scientific and Technical Information of China (English)

    赵颖岚; 孙黎; 王旭; 侯炜; 霍文哲

    2009-01-01

    Objective To examine whether IFN-λ has the ability to inhibit HIV-1 infection of blood monocyte-derived macrophages and its mechanism(s). Methods Macrophages were pretreated with IFN-λ/ IFN-λ2 for 24 h before infected by HIV-1 R5 strains (Bal, Jago, and JRFL). And then the culture supernatants were detected HIV-1 reverse transcription (RT) activity and p24 protein expression by HIV-1 BT assay and ELISA. The expressions of IFN-λ receptor, CD4, CCRS, CXCR4 were evaluated by real-time PCR. Results Both IFN-λ1 and IFN-λ2, when added to macrophage cultures, inhibited HIV-1 infection and replication. This IFN-λ-mediated anti-HIV-I activity is broad, as IFN-λ could inhibit infection by both laboratory-adapted and clinical strains of HIV-1. Investigations of mechanism(s) responsible for the IFN-λ action showed that although IFN-λ had little effect on HIV-1 entry receptor CD4 and co-receptor CCR5 and CXCR4 expression, IFN-λ inhibited HIV-I infection of macrophages through connecting with IFN-λ recep-tor. Conclusion IFN-λ could inhibit HIV-I replication in macrophages. These findings indicate that IFN-λ may have a therapeutic value in the treatment of HIV-1 infection.%目的 研究干扰素λ(IFN-λ)是否对HIV-1感染人臣噬细胞有抑制作用,并对可能介导IFN-λ抗HIV-1作用的受体和辅助受体表达水平进行研究,初步探讨其抗HIV-1感染的机制.方法 HIV-1毒株感染人巨噬细胞前用IFN-λ处理细胞24 h,感染后第4天、第8天以及第12天分别检测感染细胞上清中HIV-1逆转录酶(RT)活性和p24蛋白水平,并用实时定量PCR检测细胞上IFN-λ受体、CD4、CCR5、CXCR4的表达.结果 IFN-λ对HIV-1感染人巨噬细胞具有明显抑制作用,且此作用与其剂量及作用时间呈正相关.但IFN-λ对CD4、CCR5、CXCR4的表达影响无统计学意义.结论 IFN-λ能有效抑制HIV-1感染人口噬细胞,并证实这一作用是通过其受体发挥功能的.但IFN-λ介导的抗HIV-1

  8. Mudanças no âmbito da testagem anti-HIV no Brasil entre 1998 e 2005 Changes in HIV testing in Brazil between 1998 and 2005

    Directory of Open Access Journals (Sweden)

    Ivan França Junior

    2008-06-01

    Full Text Available OBJETIVO: Analisar mudanças na realização de teste anti-HIV, as razões alegadas entre as pessoas que foram ou não testadas e o recebimento de aconselhamento. MÉTODOS: Estudos transversais conduzidos com homens e mulheres de 16 a 65 anos, com amostras representativas do Brasil urbano em 1998 (n=3.600 e 2005 (n=5.040. Características sociodemográficas, sexuais, reprodutivas e de experiências de vida e saúde foram consideradas na análise. A avaliação das possíveis diferenças nas distribuições das variáveis baseou-se nos testes qui-quadrado de Pearson e F design-based (±OBJECTIVE: To analize changes in HIV testing, reasons reported by those who were tested or not and received counseling. METHODS: Cross-sectional studies conducted in both men and women aged 16 to 65 years based on representative samples of urban Brazil in 1998 (n=3,600 and 2005 (n=5,040. Sociodemographic, sexual, reproductive characteristics, life experiences and health data were collected and analyzed. Potential differences in the distribution of variables was analyzed using Pearson's chi-square and design-based F test (±<5%. RESULTS: In 1998 and 2005, 20.2% and 33.6% of interviewees had been tested, respectively. A total of 60% women aged 25-34 years were tested, but those who reported sexual initiation before the age of 16 and four or more sexual partners in the fi ve years prior to the interview were less tested. There was no significant increase in testing among men, except among those aged 55-65 years, per capita income between 1-3 and 5-10 monthly minimum wages, retired, historical Protestant and followers of African-Brazilian religions, living in the North/Northeast region and who reported homosexual/bisexual partners or no sexual relationship in the five years prior to the interview. Testing rates did not increase in those who self-reported as high risk for HIV. Among women, prenatal testing rate increased while work-related testing decreased among men

  9. Agent, autonomous

    OpenAIRE

    Luciani, Annie

    2007-01-01

    The expression autonomous agents, widely used in virtual reality, computer graphics, artificial intelligence and artificial life, corresponds to the simulation of autonomous creatures, virtual (i.e. totally computed by a program), or embodied in a physical envelope, as done in autonomous robots.

  10. 蕨麻提取物的体外抗HIV-1活性及毒性研究%Study on the anti-HIV-1 activity and toxicity of the potentilla anserine L.extract

    Institute of Scientific and Technical Information of China (English)

    刘铁军; 黄洋; 徐维四; 孙坚萍; 刘玉磊; 李灵芝; 马丽英

    2012-01-01

    Objective To study the anti-HIV-1 activity and toxicity of the potenlilla anserine L. extract. Methods TZM-bl and MT-4 cell lines were infected with HIV-1 laboratory-adapted strain(SF33), two H1V-1 clinical i-solates(XJDC257,020100968)and four HIV-1 pseudotype viruses(9-14;18-36,74-2 and Z20-11). The activity of inhibiting replication of HIV-1 was observed respectively by using Luciferase assay system based on TZM bl cell line and P24 antigen expression detection based on MT-4 cell line.. The TZM-bl, MT-4 and PBMCs were co-cultured with polentilla anserine L. extract of different concentrations, then CCK-8 kit was used to detect the number of the living cells for evaluating the cytotoxicity of the extract. Results The IC50 and SI of the potentill anserine L. extract against SF33 was 6. 2 μg/mL. 26. 4 by using MT-4 cell line and 4. 7 μg/mL. 73. 5 by using TZM-bl cell line. The IC50 and TI of the extract against HIV-1 clinical isolates XJDC257 and 020100968 was 2.1 μg/mL. 70. 6 and 1. 9 μg/mL, 77. 6, respectively. The IC50 of the extract against the HIV-1 pseudotype viruses 9-14,18-36,74-2 and Z20-11 was 1. 8 μg/mL, 1. 0 μg/mL, 3. 4 μg/mL and 3. 5 μg/mL,respectively and therapeutic index(TI) was 81. 9, 147. 5,43. 4 and 42. 1, respectively. Conclusion: The potentilla anserine L. extract could inhibit the replication of HIV-1 in vitro.%目的 研究蕨麻提取物的抗艾滋病病毒Ⅰ型( HIV-1)活性及毒性.方法 用HIV-1实验室适应株SF33、临床分离株XJDC257和020100968、假病毒颗粒9-14,18-36,74-2和Z20-11分别感染TZM-b1、MT-4,利用基于TZM-b1细胞的荧光素酶检测体系和基于MT-4细胞的P24抗原检测方法,观察蕨麻提取物抑制HIV-1病毒复制的活性;用不同稀释度的蕨麻提取物与TZM-b1.MT-4.PBMCs共培养,使用Cell Counting Kit-8检测活细胞的数量,观察蕨麻提取物对相应细胞的毒性作用.结果 利用MT-4细胞和TZM-b1细胞测得蕨麻提取物对SF33的半数抑制浓度( IC50)

  11. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  12. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  13. An agent framework for dynamic agent retraining: Agent academy

    OpenAIRE

    Mitkas, P.; A. Symeonidis; Kechagias, D.; Athanasiadis, I.N.; Laleci, G.; KURT, G.; Kabak, Y.; Acar, A.; Dogac, A.

    2004-01-01

    Agent Academy (AA) aims to develop a multi-agent society that can train new agents for specific or general tasks, while constantly retraining existing agents in a recursive mode. The system is based on collecting information both from the environment and the behaviors of the acting agents and their related successes/failures to generate a body of data, stored in the Agent Use Repository, which is mined by the Data Miner module, in order to generate useful knowledge about the application domai...

  14. A Novel Class of HIV-1 Antiviral Agents Targeting HIV via a SUMOylation-Dependent Mechanism.

    Science.gov (United States)

    Madu, Ikenna G; Li, Shirley; Li, Baozong; Li, Haitang; Chang, Tammy; Li, Yi-Jia; Vega, Ramir; Rossi, John; Yee, Jiing-Kuan; Zaia, John; Chen, Yuan

    2015-12-08

    We have recently identified a chemotype of small ubiquitin-like modifier (SUMO)-specific protease (SENP) inhibitors. Prior to the discovery of their SENP inhibitory activity, these compounds were found to inhibit HIV replication, but with an unknown mechanism. In this study, we investigated the mechanism of how these compounds inhibit HIV-1. We found that they do not affect HIV-1 viral production, but significantly inhibited the infectivity of the virus. Interestingly, virions produced from cells treated with these compounds could gain entry and carry out reverse transcription, but could not efficiently integrate into the host genome. This phenotype is different from the virus produced from cells treated with the class of anti-HIV-1 agents that inhibit HIV protease. Upon removal of the SUMO modification sites in the HIV-1 integrase, the compound no longer alters viral infectivity, indicating that the effect is related to SUMOylation of the HIV integrase. This study identifies a novel mechanism for inhibiting HIV-1 integration and a new class of small molecules that inhibits HIV-1 via such mechanism that may contribute a new strategy for cure of HIV-1 by inhibiting the production of infectious virions upon activation from latency.

  15. Anti-HIV-1 activities of the extracts from the medicinal plant Linum grandiflorum Desf.:In Proceedings of 4th Conference on Research and Development of Pharmaceutical Industries (Current Challenges)

    OpenAIRE

    Mohammed, Magdy M. D.; Christensen, Lars Porskjær; Ibrahim, Nabaweya A.; Awad, Nagwa E.; Zeid, Ibrahim F.; Pedersen, Erik Bjerregaard; Jensen, Kenneth Bendix; Colla, Paolo L.

    2009-01-01

    As part of our screening of anti-AIDS agents from natural sources e.g. Ixora undulata, Paulownia tomentosa, Fortunella margarita, Aegle marmelos and Erythrina abyssinica, the different organic and aqueous extracts of Linum grandiflorum leaves and seeds were evaluated in vitro by the microculture tetrazolium (MTT) assay. The activity of the tested extracts against multiplication of HIV-1 wild type IIIB, N119, A17, and EFVR in acutely infected cells was based on inhibition of virus-induced cyto...

  16. Assessment on depressive status and the therapeutic effects of highly active antiretroviral therapy among anti-HIV-1 (+) population%高效抗反转录病毒治疗对HIV-1感染者抑郁情绪的影响及其评估

    Institute of Scientific and Technical Information of China (English)

    张俐; 杨涤; 赵红心; 韩宁; 肖江; 陈玉芳; 韩筑; 李彦媚; 魏凯

    2013-01-01

    Objective To assess the depressive status and its influence on Chinese HIV-1 (+) population,and how it was influenced by highly active antiretroviral therapy (HAART) and the CD4+ T cell count.Methods Anti-HIV-1 (+) patients (age between 18 and 65 years old) who had met the criteria to commence the anti-HIV treatment but had not yet started,were selected from the Beijing Ditan Hospital between March 2011 and June 2012.BDI-Ⅱ (Beck Depression Inventory) and a self-designed questionnaire were used to evaluate the baseline and the status of 48 weeks post the HAART treatment.Statistically,t test and the Wilcoxon rank sum test were used to compare the BDI scores under different conditions and before/after the HAART.Results (1) Of 100 subjects:male to female ratio was 99:1 ; the average age was 31.37 ± 5.58 years; the average education background was of 13.13 ± 3.51 years; the unemployed percentage was 4% ; time before being identified as anti-HIV-1 (+) was 5.0 (1.0-21.0)months; the percentage being infected through homosexual contact was 83%.The baseline BDI score was 6.0 (3-10.25).(2) There was no significant difference (P>0.05) in BDI score between those subjects having had education less or more than 12 years; the BDI score of patients whose anti-HIV-1 (+)was significantly higher (P<0.05) among those discovered within the past 6 months than those more than 6 months.The BDI score of patients whose baseline CD4+T cell count below 200 cells/μ1 was significantly higher (P<0.05) than those with baseline CD4+ T cell count greater than 200 cells/μl.The CD4+ T cell count was significantly high (P<0.001) after 48 weeks of anti-viral treatment,but the BDI score was not significantly different (P>0.05).There was no significant change (P> 0.05) in the proportion of patients with different degrees of BDI score before and after 48 weeks of antiviral treatment.Conclusion Depression in HIV patients was most overt in the first six months when they were aware of

  17. HIV-1逆转录酶抑制剂的合成及活性评价%Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

    Institute of Scientific and Technical Information of China (English)

    闫寒; 王孝伟; 郭盈; 张志丽; 刘俊义

    2011-01-01

    N-1-alkyl-5-halogeno-6-alkylamino uracils, which are novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)analogues, were synthesized as the selective and potent non-nucleoside human immunodeficiency virus(HIV)-1 reverse transcriptase inhibitors. Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase. For instance, compounds ld, lm and In exhibited potent anti-HIV-1 activity with the ICso values of 13.3, 11.7 and 3.15 gM, respectively,which are comparable to that of nevirapinc(IC5O 8.38 μM).%本研究以HIV-1逆转录酶为靶点,设计了一类具有HEPT类结构的化合物:1-乙氧基甲基/苄氧基甲基-5-卤代-6-脂肪胺尿嘧啶作为抑制剂,并对合成的目标化合物进行了生物活性测定,一些化合物显示出较强的抗HIV生物活性,与对照物奈韦拉平相比(IC50 8.30μM)化合物1d,1m和1n的IC50 值分别达到了13.3,11.7和3.15 μM.

  18. Agent Chameleons: Virtual Agents Real Intelligence

    OpenAIRE

    O'Hare, Gregory; Duffy, Brian; Schoen-Phelan, Bianca; Martin, Alan; Bradley, John

    2003-01-01

    Agent Chameleons provides virtual agents powered by real intelligence, delivering next generation autonomic entities that can seamlessly migrate, mutate and evolve on their journey between and within physical and digital information spaces.

  19. Interacting agents in finance

    NARCIS (Netherlands)

    C. Hommes

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response t

  20. AgentChess : An Agent Chess Approach

    OpenAIRE

    Fransson, Henric

    2003-01-01

    The game of chess has many times been discussed and used for test purpose by science departments of Artificial Intelligence (AI). Although the technique of agent and as well multi-agent systems is quite old, the use of these offspring of AI within chess is limited. This report describes the project performed applying the use of agents to a chess program. To measure the performance of the logic has tests between the developed program main parts been performed. Further tests against a tradition...

  1. Riot Control Agents

    Science.gov (United States)

    ... a person has been exposed to riot control agents. Long-term health effects of exposure to riot control agents Prolonged ... person is removed from exposure to riot control agents, long-term health effects are unlikely to occur. How you can ...

  2. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

    2008-01-01

    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in this f

  3. Agents modeling agents in information economies

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, J.M.; Durfee, E.H. [Univ. of Michigan, Ann Arbor, MI (United States)

    1996-12-31

    Our goal is to design and build agents that act intelligently when placed in an agent-based information economy, where agents buy and sell services (e.g. thesaurus, search, task planning services, etc.). The economy we are working in is the University of Michigan Digital Library (UMDL), a large scale multidisciplinary effort to build an infrastructure for the delivery of library services. In contrast with a typical economy, an information economy deals in goods and services that are often derived from unique sources (authors, analysts, etc.), so that many goods and services are not interchangeable. Also, the cost of replicating and transporting goods is usually negligible, and the quality of goods and services is difficult to measure objectively: even two sources with essentially the same information might appeal to different audiences. Thus, each agent has its own assessment of the quality of goods and services delivered.

  4. Evaluation Of Algorithms Of Anti- HIV Antibody Tests

    Directory of Open Access Journals (Sweden)

    Paranjape R.S

    1997-01-01

    Full Text Available Research question: Can alternate algorithms be used in place of conventional algorithm for epidemiological studies of HIV infection with less expenses? Objective: To compare the results of HIV sero- prevalence as determined by test algorithms combining three kits with conventional test algorithm. Study design: Cross â€" sectional. Participants: 282 truck drivers. Statistical analysis: Sensitivity and specificity analysis and predictive values. Results: Three different algorithms that do not include Western Blot (WB were compared with the conventional algorithm, in a truck driver population with 5.6% prevalence of HIV â€"I infection. Algorithms with one EIA (Genetic Systems or Biotest and a rapid test (immunocomb or with two EIAs showed 100% positive predictive value in relation to the conventional algorithm. Using an algorithm with EIA as screening test and a rapid test as a confirmatory test was 50 to 70% less expensive than the conventional algorithm per positive scrum sample. These algorithms obviate the interpretation of indeterminate results and also give differential diagnosis of HIV-2 infection. Alternate algorithms are ideally suited for community based control programme in developing countries. Application of these algorithms in population with low prevalence should also be studied in order to evaluate universal applicability.

  5. Clinical outcomes in clinical trials of anti-HIV treatment

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; J, Neaton;

    2007-01-01

    and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates...

  6. Development of HIV vectors for anti-HIV gene therapy.

    OpenAIRE

    Poeschla, E; Corbeau, P; Wong-Staal, F

    1996-01-01

    Current gene therapy protocols for HIV infection use transfection or murine retrovirus mediated transfer of antiviral genes into CD4+ T cells or CD34+ progenitor cells ex vivo, followed by infusion of the gene altered cells into autologous or syngeneic/allogeneic recipients. While these studies are essential for safety and feasibility testing, several limitations remain: long-term reconstitution of the immune system is not effected for lack of access to the macrophage reservoir or the pluripo...

  7. Criticality of timing for anti-HIV therapy initiation.

    Directory of Open Access Journals (Sweden)

    Filippo Castiglione

    Full Text Available The time of initiation of antiretroviral therapy in HIV-1 infected patients has a determinant effect on the viral dynamics. The question is, how far can the therapy be delayed? Is sooner always better? We resort to clinical data and to microsimulations to forecast the dynamics of the viral load at therapy interruption after prolonged antiretroviral treatment. A computational model previously evaluated, produces results that are statistically adherent to clinical data. In addition, it allows a finer grain analysis of the impact of the therapy initiation point to the disease course. We find a swift increase of the viral density as a function of the time of initiation of the therapy measured when the therapy is stopped. In particular there is a critical time delay with respect to the infection instant beyond which the therapy does not affect the viral rebound. Initiation of the treatment is beneficial because it can down-regulate the immune activation, hence limiting viral replication and spread.

  8. Clinical outcomes in clinical trials of anti-HIV treatment

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; J, Neaton;

    2007-01-01

    Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...

  9. THE INTEGRATED AGENT IN MULTI-AGENT SYSTEMS

    OpenAIRE

    Maleković, Mirko; Čubrilo, Mirko

    2000-01-01

    [n this paper, we characterize the integrated agent in multi-agent systems. The following result is proved: if a multi-agent system is reflexive (symmetric, transitive, Euclidean) then the integrated agent of the multi-agent system is reflexive (symmetric, transitive, Euclidean), respectively. We also prove that the analogous result does not hold for multi-agent system's serial ness. A knowledge relationship between the integrated agent and agents in a multiagent system is presented.

  10. Chemical crowd control agents.

    Science.gov (United States)

    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

  11. Decontamination Data - Blister Agents

    Data.gov (United States)

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions This dataset is associated with the following...

  12. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    A new technetium-based scintiscanning agent has been prepared comprising a water soluble sup(99m)Tc-methanehydroxydiphosphonate in combination with a reducing agent selected from stannous, ferrous, chromous and titanous salts. As an additional stabilizer salts and esters of gentisic or ascorbic acids have been used. (E.G.)

  13. Agent Development Toolkits

    CERN Document Server

    Singh, Aarti; Sharma, A K

    2011-01-01

    Development of agents as well as their wide usage requires good underlying infrastructure. Literature indicates scarcity of agent development tools in initial years of research which limited the exploitation of this beneficial technology. However, today a wide variety of tools are available, for developing robust infrastructure. This technical note provides a deep overview of such tools and contrasts features provided by them.

  14. Asimovian Adaptive Agents

    CERN Document Server

    Gordon, D F

    2011-01-01

    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  15. How do agents represent?

    Science.gov (United States)

    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.

  16. 2010-2012年新疆 HIV 感染产妇及其所生婴儿应用抗艾滋病病毒药物状况分析%Analysis on anti HIV drug Application among HIV positive mothers and their Children in Xinjiang,2010 -2012

    Institute of Scientific and Technical Information of China (English)

    沙吾力·艾力卡; 崔丹; 艾比拜·买买提明; 关灵灵; 王磊

    2013-01-01

    Objective To understand the anti-HIV drug application status and its trends among HIV-infected mothers and their children in Xinjiang.Methods Reports from Management system of HIV mother-to-child transmission pre-vention network were analyzed from 2010 to 2012,1303 cases of antiviral drugs application among HIV-infected mothers and their Children were carried out descriptive analysis.Results During 2010 -2012,among 1303 HIV positive lying-in women,there was 72.58%,77.40% and 79.55% of them used antiviral drugs with an increased trend by years (χ2 =6.30,P <0.05).There was an upward trend in the ratio of joint solution use beginning among HIV positive pregnant women before the 28th week of gestation (χ2 =13.81,P <0.01).The antiretroviral drugs application proportions among children of HIV-infected pregnant women were 77.63%,84.91%,84.09%,and the obvious increasing in 2011 than in 2010,declined slightly in 2012 than in 2011 (χ2 =8.82,P <0.01).Conclusion Antiviral drugs application proportions among HIV positive pregnant women and their infant increased year by years,but there were still a larger rising space.It is need to further improve antiviral drugs application proportion among them to reduce the risk of mother-to-child transmission.%目的了解新疆 HIV 感染产妇及其所生婴儿抗艾滋病病毒药物应用状况及变化趋势。方法对预防艾滋病母婴传播管理信息网络直报系统中报告的2010-2012年间分娩的1303例 HIV 感染产妇及其所生婴儿抗病毒药物应用情况进行描述性分析。结果1303例 HIV 感染产妇中,2010-2012年分别有72.58%,77.40%,79.55%的产妇应用了抗病毒药物,并呈逐年上升趋势(χ2=6.30,P <0.05),HIV 感染产妇孕28周及以前开始应用三联方案比例也呈逐年上升趋势(χ2=13.81,P <0.01);HIV 感染产妇所生婴儿抗逆转录病毒药物应用比例分别为77.63%,84.91%,84.09%,2011年比2010

  17. O aconselhamento e a testagem anti-HIV como estratégia preventiva: uma revisão da literatura internacional, 1999-2011 Counseling and testing for HIV as a prevention strategy: an international review of published research, 1999-2011

    Directory of Open Access Journals (Sweden)

    Priscilla da Silva Soares

    2012-12-01

    Full Text Available Com base em revisão bibliográfica discute-se a literatura produzida nos anos de 1999 a 2011, no campo da saúde coletiva, sobre uma importante estratégia de prevenção da transmissão do HIV: o aconselhamento e testagem anti-HIV. O artigo realiza um balanço da literatura internacional, analisando criticamente os aspectos mais assinalados pela comunidade científica, apontando divergências e convergências entre os estudos e identificando lacunas que possam estimular o desenvolvimento de novas pesquisas neste campo temático. Como resultado, evidenciou-se que os processos de decisão de realizar um teste e a experiência da testagem são discutidos na literatura com abordagens fragmentadas, sejam de ordem individual ou institucional. Para compreender diversas dimensões implicadas na adoção de uma prática preventiva como o teste HIV, é preciso contemplar indicadores sociais tais como gênero, religião, identidade sexual, raça/cor, e relacioná-los às políticas públicas e à operacionalização dos serviços de saúde. O uso expressivo do conceito de risco (aliado às categorias de grupo, comportamento, percepção e de escalas quantitativas para aferir a percepção individual do risco como uma barreira para a realização do teste ilustra o foco excessivo sobre uma dimensão individual e parcial do problema.Based in a bibliographical review, this paper discusses the literature produced between 1999 and 2011 in the field of Public Health over an important strategy of prevention of the transmission of HIV virus: the counseling and testing for HIV. The article critically analyzes the aspects highlighted by the literature, indicating divergences and convergences among the studies and identifying possible gaps that can stimulate new researches in this thematic field. The results of this work indicate a tendency of the literature in treating the processes of decision and the experience of taking a test under fragmented approaches at an

  18. Biological warfare agents

    Directory of Open Access Journals (Sweden)

    Duraipandian Thavaselvam

    2010-01-01

    Full Text Available 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.

  19. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  20. Users, Bystanders and Agents

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina

    2015-01-01

    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...... the construction of the agent’s identity, and (3) how HAI, as a mediated interaction, is framed by an asymmetric participation framework. The paper concludes by suggesting various participation roles, which may inform development of ECAs....

  1. Agent Standards Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation of the work herein proposed is the development of standards for software autonomous agents. These standards are essential to achieve software...

  2. Programming Service Oriented Agents

    OpenAIRE

    Hirsch, Benjamin; Konnerth, Thomas; Burkhardt, Michael; Albayrak, Sahin

    2010-01-01

    This paper introduces a programming language for service-oriented agents. JADL++ combines the ease of use of scripting-languages with a state-of-the-art service oriented approach which allows the seamless integration of web-services. Furthermore, the language includes OWL-based ontologies for semantic descriptions of data and services, thus allowing agents to make intelligent decisions about service calls.

  3. Biological Warfare Agents

    Directory of Open Access Journals (Sweden)

    Dev Vrat Kamboj

    2006-10-01

    Full Text Available There is a long historic record of use of biological warfare (BW agents by warring countriesagainst their enemies. However, the frequency of their use has increased since the beginningof the twentieth century. World war I witnessed the use of anthrax agent against human beingsand animals by Germans, followed by large-scale field trials by Japanese against war prisonersand Chinese population during world war II. Ironically, research and development in biologicalwarfare agents increased tremendously after the Geneva Protocol, signed in 1925, because ofits drawbacks which were overcome by Biological and Toxin Weapons Convention (BTWC in1972. Biological warfare programme took back seat after the 1972 convention but biologicalagents regained their importance after the bioterrorist attacks of anthrax powder in 2001. In thelight of these attacks, many of which turned out to be hoax, general awareness is required aboutbiological warfare agents that can be used against them. This review has been written highlightingimportant biological warfare agents, diseases caused by them, possible therapies and otherprotection measures.

  4. Agent Oriented Programming进展%Advances in Agent Oriented Programming

    Institute of Scientific and Technical Information of China (English)

    王一川; 石纯一

    2002-01-01

    Agent-oriented programming (AOP) is a framework to develop agents, and it aims to link the gap betweentheory and practical in agent research. The core of an AOP framework is its language and semantics. In this paper,we propose the necessary properties which agents should have, and then give a summary and analysis about differentAOP languages based on these properties.

  5. Developing Enculturated Agents

    DEFF Research Database (Denmark)

    Rehm, Matthias

    2010-01-01

    on our cultural profiles that provide us with heuristics of behavior and interpretation. Thus, integrating cultural aspects of communicative behaviors in virtual agents and thus enculturating such systems seems to be inevitable. But culture is a multi-defined domain and thus a number of pitfalls arise......Embodied Conversational Agents (ECAs) are complex multimodal systems with rich verbal and nonverbal repertoires. There human-like appearance raises severe expectations regarding natural communicative behaviors on the side of the user. But what is regarded as “natural” is to a large degree dependent...... that have to be avoided in the endeavor. This chapter presents some of the pitfalls for enculturating interactive systems and presents strategies on how to avoid these pitfalls in relation to the standard development process of Embodied Conversational Agents....

  6. Agents unleashed a public domain look at agent technology

    CERN Document Server

    Wayner, Peter

    1995-01-01

    Agents Unleashed: A Public Domain Look at Agent Technology covers details of building a secure agent realm. The book discusses the technology for creating seamlessly integrated networks that allow programs to move from machine to machine without leaving a trail of havoc; as well as the technical details of how an agent will move through the network, prove its identity, and execute its code without endangering the host. The text also describes the organization of the host's work processing an agent; error messages, bad agent expulsion, and errors in XLISP-agents; and the simulators of errors, f

  7. El agente encubierto

    OpenAIRE

    Anaya Marcos, María del Carmen

    2015-01-01

    [ES] El trabajo versa sobre la figura del agente encubierto. Debemos enmarcar tal medida de investigación dentro del ámbito de la criminalidad organizada. Actualmente, estamos asistiendo a una proliferación de la delincuencia organizada. La sociedad ha evolucionado, y con ella la delincuencia. Fruto de tal evolución fue necesario incluir en nuestra Ley de Enjuiciamiento Criminal medidas extraordinarias de investigación, y una de ellas es el agente encubierto. Se trata de una medida muy polémi...

  8. Programming multi-agent systems

    NARCIS (Netherlands)

    Dastani, Mehdi

    2015-01-01

    With the significant advances in the area of autonomous agents and multi-agent systems in the last decade, promising technologies for the development and engineering of multi-agent systems have emerged. The result is a variety of agent-oriented programming languages, development frameworks, executio

  9. Software Agent Techniques in Design

    DEFF Research Database (Denmark)

    Hartvig, Susanne C

    1998-01-01

    This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments.......This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments....

  10. Trading Agents for Roaming Users

    OpenAIRE

    Boman, Magnus; Bylund, Markus; Espinoza, Fredrik; Danielson, Mats; Lyback, David

    2002-01-01

    Some roaming users need services to manipulate autonomous processes. Trading agents running on agent trade servers are used as a case in point. We present a solution that provides the agent owners with means to upkeeping their desktop environment, and maintaining their agent trade server processes, via a briefcase service.

  11. Agents of Change

    DEFF Research Database (Denmark)

    Hansen, Jens Aage; Lehmann, Martin

    2004-01-01

    at large, it emphasises universities as key change agents and providers in new learning, including tools such as project based and problem oriented learning (PBL) as well as information and communication technology (ICT); as providers of competent and motivated graduates to fill key positions in society...

  12. Programming Agents with Emotions

    NARCIS (Netherlands)

    Dastani, Mehdi; Floor, Chr.; Meyer, John-Jules Charles

    2014-01-01

    In this paper we show how a cognitive agent programming language can be endowed with ways to program emotions. In particular we show how the programming language 2APL can be augmented so that it can work together with the computational emotion model ALMA to deal with appraisal, emotion/mood generati

  13. The need for agents

    DEFF Research Database (Denmark)

    Abolfazlian, Ali Reza Kian

    1996-01-01

    I denne artikel arbejder vi med begrebet Intelligent Software Agents (ISAs), som autonomous, social, reactive, proactive og subservient computer systemer. Baseret på socialt psykologiske argumenter viser jeg endvidere, hvordan både den menneskelige natur og det teknologiske stadium, som mennesket...

  14. SECOND BUYING AGENT

    CERN Multimedia

    SPL - SERVICES ACHATS

    2000-01-01

    Last year the buying agent LOGITRADE started operations on the CERN site, processing purchasing requests for well-defined families of products up to a certain value. It was planned from the outset that a second buying agent would be brought in to handle the remaining product families. So, according to that plan, the company CHARLES KENDALL will be commencing operations at CERN on 8 May 2000 in Building 73, 1st floor, offices 31 and 35 (phone and fax numbers to be announced).Each buying agent will have its own specific list of product families and will handle purchasing requests up to 10'000 CHF.Whenever possible they will provide the requested supplies at a price (including the cost of their own services) which must be equivalent to or lower than the price mentioned on the purchasing request, changing the supplier if necessary. If a lower price cannot be obtained, agents will provide the necessary administrative support free of charge.To ensure that all orders are processed in the best possible conditions, us...

  15. Build Autonomic Agents with ABLE

    Institute of Scientific and Technical Information of China (English)

    吴吉义

    2007-01-01

    The IBM Agent Building and Learning Environment(ABLE) provides a lightweight Java~(TM) agent frame- work,a comprehensive JavaBeansTM library of intelligent software components,a set of development and test tools, and an agent platform.After the introduction to ABLE,classes and interfaces in the ABLE agent framework were put forward.At last an autonomic agent that is an ABLE-based architecture for incrementally building autonomic systems was discussed.

  16. Perioperative allergy: uncommon agents.

    Science.gov (United States)

    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

  17. SAM : Semantic Agent Model for SWRL rule-based agents

    OpenAIRE

    Subercaze, Julien; Maret, Pierre

    2010-01-01

    International audience SemanticWeb technologies are part of multi-agent engineering, especially regarding knowledge base support. Recent advances in the field of logic for the semantic web enable a new range of applications. Among them, programming agents based on semantic rules is a promising field. In this paper we present a semantic agent model that allows SWRL programming of agents. Our approach, based on the extended finite state machine concept, results in a three layers architecture...

  18. Synthesis of carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases

    Science.gov (United States)

    Cho, Jong hyun; Coats, Steven J.; Schinazi, Raymond F.

    2015-01-01

    New carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases were synthesized and evaluated as potential anti-HIV and anti-HCV agents. Among the synthesized carbocyclic nucleoside analogs, the pyrazole amide 15f exhibited modest selective anti-HIV-1 activity (EC50 = 24 µM). PMID:26028788

  19. The Power Trading Agent Competition

    OpenAIRE

    Ketter, W.; Collins, J.; REDDY, P; Flath, C.

    2011-01-01

    This is the specification for the Power Trading Agent Competition for 2011 (Power TAC 2011). Agents are simulations of electrical power brokers, who must compete with each other for both power production and consumption, and manage their portfolios.

  20. Agents Play Mix-game

    CERN Document Server

    Gou, C

    2005-01-01

    In mix-game which is an extension of minority game, there are two groups of agents; group1 plays the majority game, but the group2 plays the minority game. This paper studies the change of the average winnings of agents and volatilities vs. the change of mixture of agents in mix-game model. It finds that the correlations between the average winnings of agents and the mean of local volatilities are different with different combinations of agent memory length when the proportion of agents in group 1 increases. This study result suggests that memory length of agents in group1 be smaller than that of agent in group2 when mix-game model is used to simulate the financial markets.

  1. The Power Trading Agent Competition

    NARCIS (Netherlands)

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph)

    2011-01-01

    textabstractThis is the specification for the Power Trading Agent Competition for 2011 (Power TAC 2011). Agents are simulations of electrical power brokers, who must compete with each other for both power production and consumption, and manage their portfolios.

  2. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset peripheral neuropathy is related to their exposure to Agent Orange or other herbicides during service when the disease ...

  3. Mediating Performance Through Virtual Agents

    OpenAIRE

    Giannachi, Gabriella; Gillies, Marco; Kaye, Nick; Swapp, David

    2009-01-01

    This paper presents the process of creation of virtual agents used in a virtual reality performance. The performance aimed to investigate how drama and performance could inform the creation of virtual agents and also how virtual reality could raise questions for drama and performance. The virtual agents were based on the performance of 2 actors. This paper describes the process of preparing the actors, capturing their performances and transferring them to the virtual agents. A second set of a...

  4. Cultural Differentiation of Negotiating Agents

    NARCIS (Netherlands)

    Hofstede, G.J.; Jonker, C.M.; Verwaart, D.

    2012-01-01

    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  5. Cultural differentiation of negotiating agents

    NARCIS (Netherlands)

    Hofstede, G.J.; Jonker, C.M.; Verwaart, T.

    2010-01-01

    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  6. Assigning agents to a line

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    2014-01-01

    We consider the problem of assigning agents to slots on a line, where only one agent can be served at a slot and each agent prefers to be served as close as possible to his target. Our focus is on aggregate gap minimizing methods, i.e., those that minimize the total gap between targets and assigned...

  7. Chemical warfare agents

    Directory of Open Access Journals (Sweden)

    Vijayaraghavan R

    2010-01-01

    Full Text Available 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.

  8. Secure Mobile Trade Agent

    Directory of Open Access Journals (Sweden)

    Musbah M. Aqe

    2007-01-01

    Full Text Available E-commerce on the internet has the ability to produce millions of transactions and a great number of merchants whose supply merchandise over the internet. As a result, it is difficult for entities to roam over every site on the internet and choose the best merchandise to trade. So, in this paper we introduced a mobile trade agent that visit the sites to gather and evaluate the information from merchant servers and decide to trade goods on behalf of the user. We observed that the combination of public key cryptosystem with distributed object technology make this proposed scheme more secure and efficient than the already existed schemes.

  9. Agentes de información Information Agents

    Directory of Open Access Journals (Sweden)

    Alfonso López Yepes

    2005-12-01

    Full Text Available Este artículo realiza un repaso sobre las tipologías de agentes de información y describe aspectos como movilidad, racionalidad y adaptatividad, y el ajuste final de estos conceptos a entornos distribuidos como Internet, donde este tipo de agentes tienen un amplio grado de aplicación. Asimismo, se propone una arquitectura de agentes para un sistema multiagente de recuperación de información donde se aplica un paradigma documental basado en el concepto de ciclo documental.This article summarizes the main information agent types reflecting on issues such as mobility, rationality, adaptability and the final adjustment of this concepts to distributed environments such as the Internet, where this kind of agents has wide range application. Likewise, an information agent architecture is proposed to create a multi-agent information retrieval system in which a documentary paradigm based on the documentary cycle is developed.

  10. Lipid-lowering agents.

    Science.gov (United States)

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented.

  11. Advances in antithrombotic agents.

    Science.gov (United States)

    Chakrabarti, Ranjan; Das, Saibal Kumar

    2007-07-01

    Thrombosis is the condition where an imbalance in the homeostatic mechanism results in unwanted intravascular thrombus formation. Imbalances in this highly regulated process of coagulation and anticoagulation can lead to a variety of pathophysiological conditions leading to stroke, pulmonary heart attack and other serious conditions. In the western world, thromboembolic diseases are the leading cause of morbidity and mortality. Remarkable progress has occurred over the last decade in the development of antithrombotic drugs, which can be classified into 3 major categories - Anticoagulants, Antiplatelets and thrombolytics. Increased understanding of the pathobiology of thrombotic and vascular disorders has helped researchers to target novel pathways involving the coagulation, thrombolytic, fibrinolytic and integrin systems. Traditionally aspirin and unfractionated heparin was used for myocardial infarction. Newer antiplatelet agents such as, clopidogrel, GP IIb/IIIa inhibitors, low molecular weight heparin, direct thrombin inhibitors and several improved thrombolytic agents have been introduced for clinical use. This review will discuss different important drugs, which have been launched in recent years and also some new targets pursued by different companies. PMID:17630943

  12. Holograms as Teaching Agents

    Science.gov (United States)

    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.

  13. Agent-oriented Software Engineering

    Institute of Scientific and Technical Information of China (English)

    GUAN Xu; CHENG Ming; LIU Bao

    2001-01-01

    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to design and build complex systems. Yet. todate, little effort had been devoted to discuss the advantages of agent-oriented approach as a mainstreamsoftware engineering paradigm. Here both of this issues and the relation between object-oriented and agent-oriented will be argued. we describe an agent-oriented methodology and provide a quote for designing anauction system.

  14. MORBIDITY AGENTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Shrivastava Neelesh

    2011-09-01

    Full Text Available This paper discuss on clinical representation of morbid jealousy which often termed delusional jealousy or ‘Othello Syndrome’ is a psychiatric condition where a lover believes against all reason and their beloved is being sexually unfaithful. Patients will be preoccupied with their partner’s perceived lack of sexual fidelity and will often behave in an unacceptable or extreme way as they endeavor to prove their ideas. Misuse of any psychomotor is an important association cause morbidity jealousy agents, like CNS stimulants that release the catecholamine, particularly dopamine, from pre synaptic terminals substance should be treated as a priority. Where higher levels of violence are reported Sildenafil may be useful as a diagnostic as well as therapeutic test in such cases .Many studies have shown an association between high alcohol consumption and developing morbid jealousy. Amphetamine-induced psychosis has been extensively studied because of its close resemblance to schizophrenia.

  15. Product and Agent

    DEFF Research Database (Denmark)

    Montecino, Alex; Valero, Paola

    2015-01-01

    In this paper we will explore how the “mathematics teacher” becomes a subject and, at the same time, is subjected as part of diverse dispositive of power. We argue that the mathematics teacher becomes both a product and a social agent, which has been set, within current societies, from the ideas...... of globalization, social progress, and competitive logic. For our approximation, we use the concepts societies of control, dispositive, and discourses from a Foucault–Deleuze toolbox. Our purpose is to cast light on the social and cultural constitution of the ways of thinking about the mathematics teacher. Hence......, our critical examination offers understandings about how mathematics teachers are part of the larger cultural politics of schooling and education....

  16. Mushrooms as therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sushila Rathee

    2012-04-01

    Full Text Available Mushrooms have been known for their nutritional and culinary values and used as medicines and tonics by humans for ages. In modern terms, they can be considered as functional foods which can provide health benefits beyond the traditional nutrients. There are monographs that cover the medicinal and healing properties of some individual traditional mushrooms. There has been a recent upsurge of interest in mushrooms not only as a health food which is rich in protein but also as a source of biologically active compounds of medicinal value which include complementary medicine/dietary supplements for anticancer, antiviral, hepatoprotective, immunopotentiating and hypocholesterolemic agents. However the mechanisms of the various health benefits of mushrooms to humans still require intensive investigation, especially given the emergence of new evidence of their health benefits. In the present paper the medicinal potential of mushrooms is being discussed.

  17. Newer Hemostatic Agents.

    Science.gov (United States)

    Franchini, Massimo; Favaloro, Emmanuel J; Lippi, Giuseppe

    2015-10-01

    The mainstay of treatment of inherited coagulation disorders is based on the infusion of the deficient clotting factor, when available. Significant advances have been made over the past two decades in the production and availability of factor replacement products. In spite of such progression, several issue are still unsolved, the most important being the need for frequent factor concentrate infusions and the development of inhibitory alloantibodies. To overcome these important limitations, several newer hemostatic agents with an extended half-life are at an advanced stage of clinical development. After a brief overview of hemostasis, this narrative review summarizes the current knowledge on the most promising novel products for hemostasis. The current status of gene therapy for hemophilia, the only therapeutic option to definitively cure this inherited bleeding disorder, is also concisely discussed. PMID:25893779

  18. Microencapsulation of chemotherapeutic agents

    International Nuclear Information System (INIS)

    Mixing various amounts of chemotherapeutic agents such as cisplatinum, 5-fluorouracil, mitomycin-C, and adriamycin with polymers such as poly-d, 1-lactide, ethylhydroxyethylcellulose, and polycaprolactone, several kinds of microcapsules were made. Among them, microcapsule made from ethylhydroxyethylcellulose showed best yield. Under light microscopy, the capsules were observed as particles with refractive properties. For the basic toxicity test, intraarterial administration of cisplatinum was done in 6 adult mongrel dogs. Follow-up angiography was accomplished in 2 wk intervals for 6 wks. Despite no significant difference in the histopathological examination between the embolized and normal kidneys, follow-up angiogram showed atrophy of renal cortex and diminished numbers of arterial branches in the embolized kidneys. In order to identify the structural properties of microcapsules, and to determine the drug content and the rate of release, further experiment is thought to be necessary. (Author)

  19. Hepatocytes as Immunological Agents.

    Science.gov (United States)

    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

  20. UTBot: A Virtual Agent Platform for Teaching Agent System Design

    Directory of Open Access Journals (Sweden)

    In-Cheol Kim

    2007-02-01

    Full Text Available We introduce UTBot, a virtual agent platform for teaching agent system design. UTBot implements a client for the Unreal Tournament game server and Gamebots system. It provides students with the basic functionality required to start developing their own intelligent virtual agents to play autonomously UT games. UTBot includes a generic agent architecture, CAA (Context-sensitive Agent Architecture, a domain-specific world model, a visualization tool, several basic strategies (represented by internal modes and internal behaviors, and skills (represented by external behaviors. The CAA architecture can support complex long-term behaviors as well as reactive short-term behaviors. It also realizes high context-sensitivity of behaviors. We also discuss our experience using UTBot as a pedagogical tool for teaching agent system design in undergraduate Artificial Intelligence course.

  1. Stability of Evolving Agent Populations

    CERN Document Server

    Briscoe, G

    2007-01-01

    Stability is perhaps the most desired feature in the systems that we design. It is important for us to be able to predict the response of a Multi-Agent System (MAS) to various environmental conditions prior to its actual deployment. The Chli-DeWilde agent stability measure views a MAS as a discrete time Markov chain with a potentially unknown transition probabilities. A MAS is considered to be stable when its state, a stochastic process, has converged to an equilibrium distribution. We investigate an extension of their agent stability definition to include MASs with evolutionary dynamics, focusing on evolving agent populations. Additionally, using our extended agent stability measure, we construct an entropy-based definition for the degree of instability. An example system, the Digital Ecosystem, is considered in detail to investigate the stability of an evolving agent population through simulations. The results are consistent with the original Chli-DeWilde measure.

  2. Agent-based enterprise integration

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Odor Classification using Agent Technology

    Directory of Open Access Journals (Sweden)

    Sigeru OMATU

    2014-03-01

    Full Text Available In order to measure and classify odors, Quartz Crystal Microbalance (QCM can be used. In the present study, seven QCM sensors and three different odors are used. The system has been developed as a virtual organization of agents using an agent platform called PANGEA (Platform for Automatic coNstruction of orGanizations of intElligent Agents. This is a platform for developing open multi-agent systems, specifically those including organizational aspects. The main reason for the use of agents is the scalability of the platform, i.e. the way in which it models the services. The system models functionalities as services inside the agents, or as Service Oriented Approach (SOA architecture compliant services using Web Services. This way the adaptation of the odor classification systems with new algorithms, tools and classification techniques is allowed.

  4. Agent 与Multi-Agent System 技术研究%The Research on Agent and Multi-Agent System

    Institute of Scientific and Technical Information of China (English)

    党建武; 韩泉叶; 崔文华

    2002-01-01

    分析了Multi-Agent System 涉及的相关问题,在普通的Multi-Agent System的组织结构的基础上提出了管理服务机构,中介服务机构和主控流动服务机构的Multi-Agent System,并对不同组织结构的Agent之间的协同进行了讨论.

  5. Mobile Agents for Digital Signage

    OpenAIRE

    SATOH, Ichiro

    2010-01-01

    International audience This paper presents an agent-based framework for building and operating context-aware multimedia content on digital signage in public/private spaces. It enables active and multimedia content to be composed from mobile agents, which can travel from computer to computer and provide multimedia content for advertising or user-assistant services to users. The framework automatically deploys their agents at computers near to their current positions to provide advertising o...

  6. An agent for ecological deliberation

    OpenAIRE

    Debenham, John; Sierra, Carles

    2010-01-01

    An agent architecture supports the two forms of deliberation used by human agents. Cartesian, constructivist rationalism leads to game theory, decision theory and logical models. Ecological rationalism leads to deliberative actions that are derived from agents’ prior interactions and are not designed; i.e., they are strictly emergent. This paper aims to address the scant attention paid by the agent community to the predominant form of deliberation used by mankind.

  7. Radioactive scanning agents with stabilizer

    International Nuclear Information System (INIS)

    Stable compositions useful as technetium 99-based scintigraphic agents comprise gentisyl alcohol or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

  8. Research on Negotiating Agent Development

    Institute of Scientific and Technical Information of China (English)

    WEI Ding-guo; PENG Hong

    2004-01-01

    The paper presents a flexible and effective method of development of negotiating agents.A strategy specification, which is specified by a state chart and defeasible rules, can be dynamically inserted into an agent shell incorporating a state chart interpreter and a defeasible logic inference engine, in order to yield a desirable agent.The set of desirable criteria and rules is required to be justified with different context of the application.

  9. Agent factory: towards social robots

    OpenAIRE

    O'Hare, G. M. P.; Duffy, Brian R.; Collier, Rem; Rooney, Colm, (Thesis); O'Donoghue, Ruadhan

    1999-01-01

    This paper advocates the application of multi-agent techniques in the realisation of social robotic behaviour. We present the Social Robot Architecture, which integrates the key elements of agent-hood and robotics in a coherent and systematic manner. This architecture seamlessly integrates, real world robots, multi-agent development tools, and VRML visualisation tools into a coherent whole. Using these elements, we deliver a development environment, which facilitates rapid prototyping of soci...

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

    Science.gov (United States)

    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.

  11. Agent Mediated Electronic Commerce: Designing Trading Agents and Mechanisms

    NARCIS (Netherlands)

    La Poutré, J.A.; Sadeh, N.M.; Janson, S.

    2006-01-01

    This book constitutes the thoroughly refereed post-proceedings of the 7th International Workshop on Agent-Mediated Electronic Commerce, AMEC VII 2005, held in Utrecht, Netherlands in July 2005, as part of AAMAS 2005, and the third Workshop on Trading Agent Design and Analysis, TADA 2005, held in Edi

  12. Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol

    Directory of Open Access Journals (Sweden)

    Meng Y

    2012-06-01

    virus-1. Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts.Conclusion/significance: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.Keywords: ribosome-inactivating proteins, alpha-momorcharin, momordica anti-HIV protein, antitumor, antivirus, (mPEG2-Lys-NHS (20 kDa, immunogenicity

  13. Deliberate evolution in multi-agent systems

    NARCIS (Netherlands)

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.

    1998-01-01

    This paper presents an architecture for an agent capable of deliberation about the creation of new agents, and of actually creating a new agent in the multi-agent system, on the basis of this deliberation. After its creation the new agent participates fully in the running multi-agent system. The age

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

    Science.gov (United States)

    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.

  15. Agent Roles in Human Teams

    OpenAIRE

    Lewis, M.; Sycara, K.; Payne, T.R.

    2003-01-01

    In this paper, we describe results of a series of experiments investigating the effects of agent aiding on human teams. The role an agent played, its task, and the ease with which it communicated with its human teammates all influenced team behavior. Team supporting tasks such as relaying and reminding seemed particularly effective.

  16. Implementing Lego Agents Using Jason

    CERN Document Server

    Jensen, Andreas Schmidt

    2010-01-01

    Since many of the currently available multi-agent frameworks are generally mostly intended for research, it can be difficult to built multi-agent systems using physical robots. In this report I describe a way to combine the multi-agent framework Jason, an extended version of the agent-oriented programming language AgentSpeak, with Lego robots to address this problem. By extending parts of the Jason reasoning cycle I show how Lego robots are able to complete tasks such as following lines on a floor and communicating to be able to avoid obstacles with minimal amount of coding. The final implementation is a functional extension that is able to built multi-agent systems using Lego agents, however there are some issues that have not been addressed. If the agents are highly dependent on percepts from their sensors, they are required to move quite slowly, because there currently is a high delay in the reasoning cycle, when it is combined with a robot. Overall the system is quite robust and can be used to make simple...

  17. Topical agents in burn care

    Directory of Open Access Journals (Sweden)

    Momčilović Dragan

    2002-01-01

    Full Text Available Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injured. It was not until the XX century, after the discovery of antibiotics, when this condition was fulfilled. In 1968, combining silver and sulfadiazine, fox made silver-sulfadiazine, which is a 1% hydro-soluble cream and a superior agent in topical treatment of burns today. Current topical agents None of the topical antimicrobial agents available today, alone or combined, have the characteristics of ideal prophylactic agents, but they eliminate colonization of burn wound, and invasive infections are infrequent. With an excellent spectrum of activity, low toxicity, and ease of application with minimal pain, silver-sulfadiazine is still the most frequently used topical agent. Conclusion The incidence of invasive infections and overall mortality have been significantly reduced after introduction of topical burn wound antimicrobial agents into practice. In most burn patients the drug of choice for prophylaxis is silver sulfadiazine. Other agents may be useful in certain clinical situations.

  18. Pharmacologic Agents for Chronic Diarrhea

    OpenAIRE

    Lee, Kwang Jae

    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 reductio...

  19. 2012 Survey of clothing agents

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Clothing agents take part in China International Clothing and Accessories Fairs ( CHIC ) year by year. In order to attracting investment, they compared with each other at improving their originality and service levels. At the exhibition brands manufacturers and agents had a face-to-face communication,

  20. Dialogue Games for Agent Argumentation

    Science.gov (United States)

    McBurney, Peter; Parsons, Simon

    The rise of the Internet and the growth of distributed computing have led to a major paradigm shift in software engineering and computer science. Until recently, the notion of computation has been variously construed as numerical calculation, as information processing, or as intelligent symbol analysis, but increasingly, it is now viewed as distributed cognition and interaction between intelligent entities [60]. This new view has major implications for the conceptualization, design, engineering and control of software systems, most profoundly expressed in the concept of systems of intelligent software agents, or multi-agent systems [99]. Agents are software entities with control over their own execution; the design of such agents, and of multi-agent systems of them, presents major research and software engineering challenges to computer scientists.

  1. Agent Communications using Distributed Metaobjects

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Mobile agent driven by aspect

    Directory of Open Access Journals (Sweden)

    Youssef Hannad

    2010-11-01

    Full Text Available Domain application of mobile agents is quite large. They are used for network management and the monitoring of complex architecture. Mobile agent is also essential into specific software architecture such that adaptable grid architecture. Even if the concept of mobile agent seems to be obvious, the development is always complex because it needs to understand network features but also security features and negotiation algorithms. We present a work about an application of aspects dedicated to mobile agent development over a local network. At this level, the underlying protocol is called jini and allows managing several essential concepts such that short transaction and permission management. Three subsets of aspects are defined in this work. A part is for the description of agent host and its security level, accessible resource, etc. A second part is about mobile agent and their collaboration. This means how they can operate on an agent host with the respect of the execution context. All the results are illustrated through a distributed monitoring application called DMA. Its main objective is the observation of component servers.

  3. Intelligent Farmer Agent for Multi-Agent Ecological Simulations Optimization

    OpenAIRE

    Filipe Cruz; António Pereira; Pedro Valente; Pedro Duarte; Luis Paulo Reis

    2007-01-01

    This paper presents the development of a bivalve farmer agent interacting with a realistic ecological simulation system. The purpose of the farmer agent is to determine the best combinations of bivalve seeding areas in a large region, maximizing the production without exceeding the total allowed seeding area. A system based on simulated annealing, tabu search, genetic algorithms and reinforcement learning, was developed to minimize the number of iterations required to unravel a semi-optimum s...

  4. MDE and Mobile Agents : another reflexion on the agent migration

    OpenAIRE

    Gherbi, Tahar; Borne, Isabelle; Meslati, Djamel

    2009-01-01

    International audience Model Driven Engineering (MDE) is a software development approach family based on the use of models in the software construction. It allows the exploitation of models to simulate, estimate, understand, communicate and produce code. Mobile agents are a very interesting technology to develop applications for mobile and distributed environments. A mobile agent is essentially a computer program that acts autonomously on behalf of a user and travels through a network of h...

  5. Agent Based Multiviews Requirements Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Based on the current researches of viewpoints oriented requirements engineering and intelligent agent, we present the concept of viewpoint agent and its abstract model based on a meta-language for multiviews requirements engineering. It provided a basis for consistency checking and integration of different viewpoint requirements, at the same time, these checking and integration works can automatically realized in virtue of intelligent agent's autonomy, proactiveness and social ability. Finally, we introduce the practical application of the model by the case study of data flow diagram.

  6. Antibacterial agents in the cinema.

    Science.gov (United States)

    García Sánchez, J E; García Sánchez, E; Merino Marcos, M L

    2006-12-01

    Numerous procedures used as antibacterial therapy are present in many films and include strategies ranging from different antimicrobial drugs to surgery and supporting measures. Films also explore the correct use and misuse of antimicrobial agents. Side effects and other aspects related to antibacterial therapy have also been reflected in some films. This article refers to the presence of antibacterial agents in different popular movies. There are movies in which antibacterial agents form part of the central plot, while in others it is merely an important part of the plot. In still others, its presence is isolated, and in these it plays an ambient or anecdotal role.

  7. Agent-oriented Software Engineering

    Institute of Scientific and Technical Information of China (English)

    MingCheng; XuGuan; BaoLiu

    2004-01-01

    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to designing and building complex systems. Yet, to date, little effort had been devoted to discussing the advantages of agent-oriented approach as a mainstream software engineering paradiam.Here both of this issues and the relation between object-oriented and agentoriented will be argued.We describe an agent-oriented methodology and provide a quote for designing a auction system.

  8. Deliberate Evolution in Multi-Agent Systems

    NARCIS (Netherlands)

    Brazier, F.M.T.; Jonker, C.M.; Treur, J.; Wijngaards, N.J.E.

    2000-01-01

    This paper presents an architecture for an agent capable of deliberation about the creation of new agents, and of actually creating a new agent in the multi-agent system, on the basis of this deliberation. The agent architecture is based on an existing

  9. Optimistic Agents are Asymptotically Optimal

    OpenAIRE

    Sunehag, Peter; Hutter, Marcus

    2012-01-01

    We use optimism to introduce generic asymptotically optimal reinforcement learning agents. They achieve, with an arbitrary finite or compact class of environments, asymptotically optimal behavior. Furthermore, in the finite deterministic case we provide finite error bounds.

  10. Agents containing chlorhexidine in dentistry

    OpenAIRE

    Lebedeva S.N.; Zemlyanichenko М.К.

    2011-01-01

    Aclinical definition of the efficacy of chlorhexidine-containing means for reducing the risk of dental caries and gingivitis with plastic caps. Chlorhexidine is an effective antimicrobial agent for the formation of individual programs for the prevention of dental caries

  11. Computational Environment of Software Agents

    Directory of Open Access Journals (Sweden)

    Martin Tomášek

    2008-05-01

    Full Text Available Presented process calculus for software agent communication and mobility canbe used to express distributed computational environment and mobile code applications ingeneral. Agents are abstraction of the functional part of the system architecture and theyare modeled as process terms. Agent actions model interactions within the distributedenvironment: local/remote communication and mobility. Places are abstraction of thesingle computational environment where the agents are evaluated and where interactionstake place. Distributed environment is modeled as a parallel composition of places whereeach place is evolving asynchronously. Operational semantics defines rules to describebehavior within the distributed environment and provides a guideline for implementations.Via a series of examples we show that mobile code applications can be naturally modeled.

  12. Epidemic Spreading with External Agents

    OpenAIRE

    Banerjee, Siddhartha; Gopalan, Aditya; Das, Abhik Kumar; Shakkottai, Sanjay

    2012-01-01

    We study epidemic spreading processes in large networks, when the spread is assisted by a small number of external agents: infection sources with bounded spreading power, but whose movement is unrestricted vis-\\`a-vis the underlying network topology. For networks which are `spatially constrained', we show that the spread of infection can be significantly speeded up even by a few such external agents infecting randomly. Moreover, for general networks, we derive upper-bounds on the order of the...

  13. Locating Agents in RFID Architectures

    OpenAIRE

    Abdel-Naby, Sameh; Giorgini, Paolo

    2006-01-01

    The use of software agents can create an “intelligent” interface between users’ preferences and the back‐end systems. Agents are now able to interact and communicate with each other, forming a virtual community and feeding back the user with suggestions. Innovative systems related to Asset Tracking, Inventory and Shelving architectures are more often involving advanced communication techniques (e.g., RFID); these systems are responsible for user authentication and objects verification. RFID s...

  14. Agents in E-learning

    OpenAIRE

    S. Mencke; Dumke, R

    2007-01-01

    This paper presents a framework to describe thecrossover domain of e-learning and agent technology.Furthermore it is used to classify existing work and possiblestarting points for the future development of agenttechniques and technologies order to enhance theperformance and the effectiveness of several aspects of elearningsystems. Agents are not a new concept but their usein the field of e-learning constitutes a basis for consequentialadvances.

  15. Handling of injectable antineoplastic agents.

    OpenAIRE

    Knowles, R S; Virden, J E

    1980-01-01

    Although the clinical toxicity of antineoplastic drugs has been well documented there is little or no information on the problems that may arise on the handling and mishandling of such agents. This paper attempts to highlight the importance of taking precautions to prevent adverse effects resulting from contact with cytotoxic drugs during handling and to suggest a practical guide for the handling of such agents.

  16. PENETRATION ENHANCEMENT OF MEDICINAL AGENTS

    OpenAIRE

    Sharma Ganesh N.; Sanadya Jyotsana; Kaushik Avinash; Dwivedi Abha

    2012-01-01

    Many current therapeutic agents like antibiotics, ionizable and peptide drugs are impermeable or do not possess the requisite physicochemical properties for efficient transport through outer tissue barrier to attain therapeutic blood level. For this reason the delivery of such drugs through barriers is currently one of the major interests in pharmaceutical research. Penetration enhancers or promoters are agents that have no therapeutic properties of their own but can transport the sorption of...

  17. Business Intelligence using Software Agents

    OpenAIRE

    Ana-Ramona BOLOGA; Razvan BOLOGA

    2011-01-01

    This paper presents some ideas about business intelligence today and the importance of developing real time business solutions. The authors make an exploration of links between business intelligence and artificial intelligence and focuses specifically on the implementation of software agents-based systems in business intelligence. There are briefly presented some of the few solutions proposed so far that use software agents properties for the benefit of business intelligence. The authors then...

  18. Antimicrobials for bacterial bioterrorism agents.

    Science.gov (United States)

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  19. Bacteriocins as potential anticancer agents

    OpenAIRE

    Sukhraj eKaur; Sumanpreet eKaur

    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 nonspecific toxicity towards 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 therapeu...

  20. Bacteriocins as Potential Anticancer Agents

    OpenAIRE

    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 therapeu...

  1. Natural products as antimitotic agents.

    Science.gov (United States)

    Dall'Acqua, Stefano

    2014-01-01

    Natural products still play an important role in the medicinal chemistry, especially in some therapeutic areas. As example more than 60% of currently-used anticancer agents are derives from natural sources including plants, marine organisms or micro-organism. Thus natural products (NP) are an high-impact source of new "lead compounds" or new potential therapeutic agents despite the large development of biotechnology and combinatorial chemistry in the drug discovery and development. Many examples of anticancer drugs as paclitaxel, combretastatin, bryostatin and discodermolide have shown the importance of NP in the anticancer chemotherapy through many years. Many organisms have been studied as sources of drugs namely plants, micro-organisms and marine organisms and the obtained NP can be considered a group of "privileged chemical structures" evolved in nature to interact with other organisms. For this reason NP are a good starting points for pharmaceutical research and also for library design. Tubulin and microtubules are one of the most studied targets for the search of anticancer compounds. Microtubule targeting agents (MTA) also named antimitotic agents are compounds that are able to perturb mitosis but are also able to arrest cell growing during interphase. The anticancer drugs, taxanes and vinca alkaloids have established tubulin as important target in cancer therapy. More recently the vascular disrupting agents (VDA) combretastatin analogues were studied for their antimitotics properties. This review will consider the anti mitotic NP and their potential impact in the development of new therapeutic agents.

  2. What makes virtual agents believable?

    Science.gov (United States)

    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.

  3. Geo-Agents: Design and Implement

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Geo-Agents, a multi-agent system that processes distr ib utedgeospatial information and geospatial service was presented. Firstly, the requirement for distributed geographical information process was discussed, and the architecture of Geo-Agents was introduced. Then in-depth discussions were r aised on agent system implementation, such as the basic agent, agent advertising , message passing, and collaborating. An example was also given to explain the p roblem solving process.

  4. Special issue about advances in Physical Agents

    OpenAIRE

    Cazorla Quevedo, Miguel Ángel; Matellán Olivera, Vicente

    2011-01-01

    Nowadays, there are a lot of Spanish groups which are doing research in areas related with physical agents: they use agent-based technologies concepts, especially industrial applications, robotics and domotics (physical agents) and applications related to the information society, (software agents) highlighting the similarities and synergies among physical and software agents. In this special issue we will show several works from those groups, focusing on the recent advances in Physical Agents.

  5. Colitis associated with biological agents

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2012-01-01

    In the past,there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity.Now,a variety of new biological monoclonal antibody agents,usually administered by infusion,have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents,adverse effects have been documented,including apparently new forms of immune-mediated inflammatory bowel disease.In some,only limited symptoms have been recorded,but in others,severe colitis with serious complications,such as bowel perforation has been recorded.In others,adverse effects may have a direct vascular or ischemic basis,while other intestinal effects may be related to a superimposed infection.Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases,or be responsible for disease exacerbation.Dramatic and well documented side effects have been observed with ipilimumab,a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4,a key negative feedback regulator of the T-cell anti-tumor response.This agent has frequently been used in the treatment of different malignancies,notably,malignant melanoma.Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated.One of these is a form of enterocolitis that may be severe,and occasionally,fatal.Other agents include rituximab (an antiCD20 monoclonal antibody),bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents,including infliximab,adalimumab and etanercept.

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

    Science.gov (United States)

    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.

  7. Relational agents in clinical psychiatry.

    Science.gov (United States)

    Bickmore, Timothy; Gruber, Amanda

    2010-01-01

    Relational agents are computational artifacts, such as animated, screen-based characters or social robots, that are designed to establish a sense of rapport, trust, and even therapeutic alliance with patients, using ideal therapeutic relationships between human counselors and patients as role models. We describe the development and evaluation of several such agents designed for health counseling and behavioral-change interventions, in which a therapeutic alliance is established with patients in order to enhance the efficacy of the intervention. We also discuss the promise of using such agents as adjuncts to clinical psychiatry, a range of possible applications, and some of the challenges and ethical issues in developing and fielding them in psychiatric interventions.

  8. Multi-Agent Software Engineering

    International Nuclear Information System (INIS)

    This paper proposed an alarm-monitoring system for people based on multi-agent using maps. The system monitors the users physical context using their mobile phone. The agents on the mobile phones are responsible for collecting, processing and sending data to the server. They can determine the parameters of their environment by sensors. The data are processed and sent to the server. On the other side, a set of agents on server can store this data and check the preconditions of the restrictions associated with the user, in order to trigger the appropriate alarms. These alarms are sent not only to the user who is alarmed to avoid the appeared restriction, but also to his supervisor. The proposed system is a general purpose alarm system that can be used in different critical application areas. It has been applied for monitoring the workers of radiation sites. However, these workers can do their activity tasks in the radiation environments safely

  9. Agent Based Individual Traffic Guidance

    DEFF Research Database (Denmark)

    Wanscher, Jørgen

    This thesis investigates the possibilities in applying Operations Research (OR) to autonomous vehicular traffic. The explicit difference to most other research today is that we presume that an agent is present in every vehicle - hence Agent Based Individual Traffic guidance (ABIT). The next...... evolutionary step for the in-vehicle route planners is the introduction of two-way communication. We presume that the agent is capable of exactly this. Based on this presumption we discuss the possibilities and define a taxonomy and use this to discuss the ABIT system. Based on a set of scenarios we conclude...... that the system can be divided into two separate constituents. The immediate dispersion, which is used for small areas and quick response, and the individual alleviation, which considers the longer distance decision support. Both of these require intrinsicate models and cost functions which at the beginning...

  10. Agent review phase one report.

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Dual Rationality and Deliberative Agents

    Science.gov (United States)

    Debenham, John; Sierra, Carles

    Human agents deliberate using models based on reason for only a minute proportion of the decisions that they make. In stark contrast, the deliberation of artificial agents is heavily dominated by formal models based on reason such as game theory, decision theory and logic—despite that fact that formal reasoning will not necessarily lead to superior real-world decisions. Further the Nobel Laureate Friedrich Hayek warns us of the ‘fatal conceit’ in controlling deliberative systems using models based on reason as the particular model chosen will then shape the system’s future and either impede, or eventually destroy, the subtle evolutionary processes that are an integral part of human systems and institutions, and are crucial to their evolution and long-term survival. We describe an architecture for artificial agents that is founded on Hayek’s two rationalities and supports the two forms of deliberation used by mankind.

  12. Agent communication and artificial institutions

    OpenAIRE

    Fornara, Nicoletta; Viganò, Francesco; Colombetti, Marco

    2011-01-01

    In this paper we propose an application-independent model for the definition of artificial institutions that can be used to define open multi-agent systems. Such a model of institutional reality makes us able also to define an objective and external semantics of a commitment-based Agent Communication Language (ACL). In particular we propose to regard an ACL as a set of conventions to act on a fragment of institutional reality, defined in the context of an artificial institution. Another c...

  13. Autonomous sensor manager agents (ASMA)

    Science.gov (United States)

    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.

  14. Raspberry Pi for secret agents

    CERN Document Server

    Sjogelid, Stefan

    2015-01-01

    This book is an easy-to-follow guide with practical examples in each chapter. Suitable for the novice and expert alike, each topic provides a fast and easy way to get started with exciting applications and also guides you through setting up the Raspberry Pi as a secret agent toolbox.

  15. SEM: A Cultural Change Agent

    Science.gov (United States)

    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…

  16. The Power Trading Agent Competition

    NARCIS (Netherlands)

    W. Ketter (Wolfgang); J. Collins (John); P. Reddy (Prashant); C. Flath (Christoph); M.M. Weerdt (Mathijs)

    2011-01-01

    textabstractThis is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff

  17. The Power Trading Agent Competition

    NARCIS (Netherlands)

    Ketter, W.; Collins, J.; Reddy, P.; Flath, C.; De Weerdt, M.M.

    2011-01-01

    This is the specification for the Power Trading Agent Competition for 2012 (Power TAC 2012). Power TAC is a competitive simulation that models a “liberalized” retail electrical energy market, where competing business entities or “brokers” offer energy services to customers through tariff contracts,

  18. Antibacterial activities of antineoplastic agents.

    OpenAIRE

    Bodet, C A; Jorgensen, J H; Drutz, D J

    1985-01-01

    Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens. Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities.

  19. Kriitikute lemmikfilm on "Agent Sinikael"

    Index Scriptorium Estoniae

    2003-01-01

    Eesti Filmiajakirjanike Ühing andis kümnendat korda välja auhinda Aasta film 2002. Parimaks filmiks tunnistati mängufilm "Agent Sinikael" : režissöör Marko Raat. Viimane sai preemiaks Neitsi Maali kuju ja 12 000 krooni

  20. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    A wide range of pharmaceuticals for labeling with Tc-99m, developed by the Soreq Radiopharmaceuticals Department, is described. Details of the production and quality control of 13 kits are given, as well as the range of results required for consistently high quality imaging agents

  1. Relational agents: A critical review

    DEFF Research Database (Denmark)

    Campbell, Robert H.; Grimshaw, Mark Nicholas; Green, Gill

    2009-01-01

    Relationships between people who meet in virtual worlds are common and these relationships can be long term, in some cases lasting a life-time. Although relationships formed in virtual worlds have invited a lot of recent interest, surprisingly little work has been done on developing computer agents...

  2. Direct Vasodilators and Sympatholytic Agents.

    Science.gov (United States)

    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

  3. Identity Management in Agent Systems

    NARCIS (Netherlands)

    Brazier, F.M.T.; Groot, de D.R.A.

    2006-01-01

    If agent-based applications are to be used in large scale, open environments, security is a main issue; digital identity management (DIDM) an essential element. DIDM is needed to be able to determine the rights and obligations of the four main

  4. Foodborne illness and microbial agents

    Science.gov (United States)

    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...

  5. Bridging humans via agent networks

    International Nuclear Information System (INIS)

    Recent drastic advance in telecommunication networks enabled the human organization of new class, teleorganization, which differ from any existing organization in that the organization which is easy to create by using telecommunication networks is virtual and remote, that people can join multiple organizations simultaneously, and that the organization can involve people who may not know each other. In order to enjoy the recent advance in telecommunication, the agent networks to help people organize themselves are needed. In this paper, an architecture of agent networks, in which each agent learns the preference or the utility functioin of the owner, and acts on behalf of the owner in maintaining the organization, is proposed. When an agent networks supports a human organization, the conventional human interface is divided into personal and social interfaces. The functionalities of the social interface in teleconferencing and telelearning were investigated. In both cases, the existence of B-ISDN is assumed, and the extension to the business meeting scheduling using personal handy phone (PHS) networks with personal digital assistant (PDA) terminals is expected. These circumstances are described. Mutual selection protocols (MSP) and their dynamic properties are explained. (K.I.)

  6. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Science.gov (United States)

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  7. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Science.gov (United States)

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Funding Leverage by Use of Sba-Guaranteed Trust Certificates (âtcsâ) § 107.1620... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  8. Multi-Agent Transport Planning

    NARCIS (Netherlands)

    Zutt, J.; Witteveen, C.

    2005-01-01

    We discuss a distributed transport planning problem with competitive autonomous actors that carry out time-constrained pick-up delivery orders from customers. The agents have to find conflict-free routes to execute a series of orders they have accepted. Hatzack and Nebel [2] were the first to sugges

  9. Using Agent to Coordinate Web Services

    CERN Document Server

    Liu, C H; Chen, Jason J Y

    2009-01-01

    Traditionally, agent and web service are two separate research areas. We figure that, through agent communication, agent is suitable to coordinate web services. However, there exist agent communication problems due to the lack of uniform, cross-platform vocabulary. Fortunately, ontology defines a vocabulary. We thus propose a new agent communication layer and present the web ontology language (OWL)-based operational ontologies that provides a declarative description. It can be accessed by various engines to facilitate agent communication. Further, in our operational ontologies, we define the mental attitudes of agents that can be shared among other agents. Our architecture enhanced the 3APL agent platform, and it is implemented as an agent communication framework. Finally, we extended the framework to be compatible with the web ontology language for service (OWL-S), and then develop a movie recommendation system with four OWL-S semantic web services on the framework. The benefits of this work are: 1) dynamic ...

  10. Anchor Toolkit - a secure mobile agent system

    OpenAIRE

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

    2008-01-01

    Mobile agent technology facilitates intelligent operation in software systems with less human interaction. Major challenge to deployment of mobile agents include secure transmission of agents and preventing unauthorized access to resources between interacting systems, as either hosts, or agents, or both can act maliciously. The Anchor toolkit, designed by LBNL, handles the transmission and secure management of mobile agents in a heterogeneous distributed computing environment. It provide...

  11. Halide test agent replacement study

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  12. Migration Dynamics in Artificial Agent Societies

    Directory of Open Access Journals (Sweden)

    Harjot Kaur

    2014-02-01

    Full Text Available An Artificial Agent Society can be defined as a collection of agents interacting with each other for some purpose and/or inhabiting a specific locality, possibly in accordance to some common norms/rules. These societies are analogous to human and ecological societies, and are an expanding and emerging field in research about social systems. Social networks, electronic markets and disaster management organizations can be viewed as such artificial (open agent societies and can be best understood as computational societies. Members of such artificial agent societies are heterogeneous intelligent software agents which are operating locally and cooperating and coordinating with each other in order to achieve goals of an agent society. These artificial agent societies have some kind of dynamics existing in them in terms of dynamics of Agent Migration, Role-Assignment, Norm- Emergence, Security and Agent-Interaction. In this paper, we have described the dynamics of agent migration process, starting from the various types of agent migration, causes or reasons for agent migration, consequences of agent migration, and an agent migration framework to model the its behavior for migration of agents between societies.

  13. Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes.

    Science.gov (United States)

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Chan, Wai Yee

    2015-12-01

    Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome, has claimed innumerable lives in the past. Many biomolecules which suppress HIV replication and also other biomolecules that inhibit enzymes essential to HIV replication have been reported. Proteins including a variety of milk proteins, ribosome-inactivating proteins, ribonucleases, antifungal proteins, and trypsin inhibitors; peptides comprising cathelicidins, defensins, synthetic peptides, and others; polysaccharides and polysaccharopeptides; nucleosides, nucleotides, and ribozymes, demonstrated anti-HIV activity. In many cases, the mechanism of anti-HIV action has been elucidated. Strategies have been devised to augment the anti-HIV potency of these compounds.

  14. CATS-based Agents That Err

    Science.gov (United States)

    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.

  15. Biological effects of mutagenic agents

    International Nuclear Information System (INIS)

    There is an increasing body of evidence that mutagenic agents (biological, chemical and physical) play an important role in the etiology of human diseases. Mutations may occur in the germinal as well as in the somatic cells. Mutations of the germ cells may result on infertility or fertilization of damaged cells, the later leading to abortion or birth of a malformed fetus. Somatic-cells mutations may have various biological effects, depending on the period of the human life at which the mutation occurs. If it occurs during the prenatal life, a teratogenic or carcinogenic effect will be observed. If the somatic cell is damaged during the postnatal life, this will lead to neoplastic transformation. Therefore it is extremely important to know the mutagenic, teratogenic and carcinogenic effects of various biological, chemical and physical agents in order to eliminate them from our environment. (author). 13 refs, 4 figs, 1 tab

  16. [Infectious agents and autoimmune diseases].

    Science.gov (United States)

    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

  17. Bacteriocins as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Sukhraj eKaur

    2015-11-01

    Full Text Available 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 nonspecific toxicity towards 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 towards 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.

  18. Oral agents in multiple sclerosis.

    Science.gov (United States)

    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

  19. [Pharmacology of bone anabolic agents].

    Science.gov (United States)

    Matsumoto, Toshio

    2015-10-01

    Bone is constantly remodeled to maintain its volume, structural integrity and strength Currently available bone anabolic agent is teriparatide. Teriparatide increases bone mass and strength via both remodeling-dependent and -independent mechanisms, although remodeling-dependent mechanism overweighs the other. Canonical Wnt signal plays an important role in enhancing osteoblast differentiation and bone formation, and its osteocyte-derived inhibitor, sclerostin, regulates bone formation via the regulation of Wnt signaling. Anti-sclerostin antibody stimulates Wnt signaling and enhances bone formation. Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment. The new modality of anabolic agents via remodeling-independent stimulation of bone formation may open up a new avenue for the treatment of osteoporosis.

  20. Design, synthesis and structural studies of meta-xylyl linked bis-benzimidazolium salts: potential anticancer agents against ‘human colon cancer’

    Directory of Open Access Journals (Sweden)

    Haque Rosenani A

    2012-07-01

    Full Text Available Abstract Background Benzimidazole derivatives are structurally bioisosteres of naturally occurring nucleotides, which makes them compatible with biopolymers of living systems. This property gives benzimidazole a biological and clinical importance. In the last decade, this class of compounds has been reported to possess anti-allergic, anti-diabatic, anti-HIV, anti-hypertensive, anti-inflammatory, anti-mycobacterial, anti-oxidant, anti-protozoal, and anti-viral properties. The researchers are now interested to explore their potential as anti-cancer agents. In the present study, an effort was made to further explore this area of research. Furthermore, in order to increase the solubility and efficacy of these heterocycles, the interest is now shifted to the salts of these compounds. With this background, we planned to synthesize a series of meta-xylyl linked bis-benzimidazolium salts to assess their anti-proliferation efficacy on human colon cancer cell line (HCT 116. Results A number of N-alkylbenzimidazoles were synthesized by reactions of benzimidazole with alkyl halides (i-PrBr, PrBr, EthBr, Pent-2-ylBr, BuBr, BenzCl, HeptBr. The subsequent treatment of the resulting N-alkylbenzimidazoles with 1,3-(bromomethylenebenzene afforded corresponding bis-benzimidazolium salts. All synthesized compounds were characterized by spectroscopic techniques (Additional file 1: NMR & FT-IR and microanalysis. Molecular structures of selected compounds were established through single crystal x-ray diffraction studies. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116. Results showed that the compounds exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 0.1 to 17.6 μM. The anti-proliferation activity of all compounds was more pronounced than that of standard reference drug 5-flourouracil (IC50 =19.2 μM. Conclusions All the synthesized bis-benzimidazolium salts

  1. Crimen organizado y agente encubierto

    OpenAIRE

    Herrero Reus, Ignacio

    2014-01-01

    Uno de los objetivos de la justicia penal actual es la lucha contra la criminalidad organizada, bien por su propia naturaleza de “crimen organizado”, bien porque presenta elementos trasnacionales que impiden su investigación a fondo. Todo ello exige la creación de recursos que permitan la investigación de dichos delitos, recursos como el de infiltración de los agentes policiales, objeto del trabajo.

  2. Antipsychotic agents and QT changes.

    OpenAIRE

    Welch, R.; Chue, P

    2000-01-01

    Recently, antipsychotic medications of the novel or atypical classes have received increased attention because of concerns with respect to potential lengthening of the QT interval, yet the currently available and commonly prescribed conventional antipsychotics are significantly more cardiotoxic, particularly agents in the butyrophenone and phenothiazine classes. Lengthening of the QT interval can be associated with a fatal paroxysmal ventricular arrhythmia known as torsades de pointes. The sp...

  3. Topical agents in burn care

    OpenAIRE

    Momčilović Dragan

    2002-01-01

    Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injure...

  4. Multi-agent autonomous system

    Science.gov (United States)

    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.

  5. An Agent Based Classification Model

    CERN Document Server

    Gu, Feng; Greensmith, Julie

    2009-01-01

    The major function of this model is to access the UCI Wisconsin Breast Can- cer data-set[1] and classify the data items into two categories, which are normal and anomalous. This kind of classifi cation can be referred as anomaly detection, which discriminates anomalous behaviour from normal behaviour in computer systems. One popular solution for anomaly detection is Artifi cial Immune Sys- tems (AIS). AIS are adaptive systems inspired by theoretical immunology and observed immune functions, principles and models which are applied to prob- lem solving. The Dendritic Cell Algorithm (DCA)[2] is an AIS algorithm that is developed specifi cally for anomaly detection. It has been successfully applied to intrusion detection in computer security. It is believed that agent-based mod- elling is an ideal approach for implementing AIS, as intelligent agents could be the perfect representations of immune entities in AIS. This model evaluates the feasibility of re-implementing the DCA in an agent-based simulation environ- ...

  6. Pharmacologic Agents for Chronic Diarrhea.

    Science.gov (United States)

    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.

  7. Pharmacologic Agents for Chronic Diarrhea.

    Science.gov (United States)

    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

  8. Preponderant agent, what is that?

    Directory of Open Access Journals (Sweden)

    Clara Luz Álvarez

    2015-05-01

    Full Text Available Purpose – Preponderant agent is a new instrument for preventing and reverting adverse impact in competition due to highly concentrated markets. Therefore, this paper's objective is to present and analyze the preponderant agent concept in Mexico with emphasis on the broadcast sector, the telecommunication regulator decisions and the courts' interpretation. Methodology/approach/design – The objectives were achieved by researching and analyzing the main legal documents, the Congress reports and debates, the regulator's decisions and other relevant regulator's documents, as well as final decisions by the courts in connection with broadcast sector. Findings – Among the findings are that certain topics were not duly addressed by the Mexican regulator, or by the Congress, whereas the courts were more willing to hold decisions in favor of public interest based on constitutional intent and deference to the regulator's decision. Originality/value – This paper will be valuable for persons interested in telecommunications, broadcast and antitrust. Although the preponderant agent concept created in Mexico is not necessarily a “best practice”, it does provide an alternative instrument in antitrust. Moreover, the courts decisions also provide criteria regarding regulatory deference for the regulator.

  9. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正

    2015-01-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic 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 agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  10. Agent planning in AgScala

    Science.gov (United States)

    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.

  11. Dimensions and Issues of Mobile Agent Technology

    Directory of Open Access Journals (Sweden)

    Yashpal Singh

    2012-09-01

    Full Text Available Mobile Agent is a type of software system which acts “intelligently” on one’s behalf with the feature of autonomy, learning ability and most importantly mobility. Now mobile agents are gaining interest in the research community. In this article mobile agents will be addressed as tools for mobile computing. Mobile agents have been used in applications ranging from network management to information management. We present mobile agent concept, characteristics, classification, need, applications and technical constraints in the mobile technology. We also provide a brief case study about how mobile agent is used for information retrieval.

  12. 14th International Conference on Practical Applications of Agents and Multi-Agent Systems : Special Sessions

    CERN Document Server

    Escalona, María; Corchuelo, Rafael; Mathieu, Philippe; Vale, Zita; Campbell, Andrew; Rossi, Silvia; Adam, Emmanuel; Jiménez-López, María; Navarro, Elena; Moreno, María

    2016-01-01

    PAAMS, the International Conference on Practical Applications of Agents and Multi-Agent Systems is an evolution of the International Workshop on Practical Applications of Agents and Multi-Agent Systems. PAAMS is an international yearly tribune to present, to discuss, and to disseminate the latest developments and the most important outcomes related to real-world applications. It provides a unique opportunity to bring multi-disciplinary experts, academics and practitioners together to exchange their experience in the development of Agents and Multi-Agent Systems. This volume presents the papers that have been accepted for the 2016 in the special sessions: Agents Behaviours and Artificial Markets (ABAM); Advances on Demand Response and Renewable Energy Sources in Agent Based Smart Grids (ADRESS); Agents and Mobile Devices (AM); Agent Methodologies for Intelligent Robotics Applications (AMIRA); Learning, Agents and Formal Languages (LAFLang); Multi-Agent Systems and Ambient Intelligence (MASMAI); Web Mining and ...

  13. Design, synthesis and structural studies of meta-xylyl linked bis-benzimidazolium salts: potential anticancer agents against ‘human colon cancer’

    OpenAIRE

    Haque Rosenani A; Iqbal Muhammad; Khadeer Ahamed Mohamed B; Majid AMS; Abdul Hameed Zena A

    2012-01-01

    Abstract Background Benzimidazole derivatives are structurally bioisosteres of naturally occurring nucleotides, which makes them compatible with biopolymers of living systems. This property gives benzimidazole a biological and clinical importance. In the last decade, this class of compounds has been reported to possess anti-allergic, anti-diabatic, anti-HIV, anti-hypertensive, anti-inflammatory, anti-mycobacterial, anti-oxidant, anti-protozoal, and anti-viral properties. The researchers are n...

  14. A framework for organization-aware agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia; Villadsen, Jørgen

    2016-01-01

    Open systems are characterized by the presence of a diversity of heterogeneous and autonomous agents that act according to private goals. Organizations, such as those used in real-life to structure human activities such as task allocation, coordination and supervision, can regulate the agents...... explicit coordination mechanisms within the agents. The organizational model is independent of that of the agents, and the approach is not tied to a specific organizational model, but uses an organizational metamodel. We show how AORTA helps agents work together in a system with an organization......’ behavior space and describe the expected behavior of the agents. Assuming an open environment, where agents are developed independently of the Organizational structures, agents need to be able to reason about the structure, so that they can deliberate about their actions and act within the expected...

  15. Analysis and Optimization for Mobile Agent Communication

    Institute of Scientific and Technical Information of China (English)

    YANGBo; LIUDayou

    2005-01-01

    Communication performance is one of the most important factors affecting the efficiency of mobile agent system. Only traditional optimization techniques for communication performance are not enough, especially in large-scale intelligent mobile agent system, so more intelligent optimization techniques are needed. In the background, the paper studies communication of mobile agent system from the viewpoint of performance. The paper makes qualitative and quantitative analysis of four important factors that will affect the communication performance of mobile agent system and presents the communication performance optimization model. The model hasthree primary functions. First, the model provides a formalism method to describe the communication task and process of mobile agent. Second, the model provides a means to make quantitative analysis of the performance of mobile agent system. Third, the model can plan out an optimal communication scheme for mobile agent to minimize the cost of whole communication. The model could thus be a building block for the optimization of the communication behavior of mobile agent.

  16. A Framework for Multi-Agent Planning

    NARCIS (Netherlands)

    Bos, A.; Tonino, J.F.M.; De Weerdt, M.M.; Witteveen, C.

    2000-01-01

    We introduce a computational framework, consisting of resources, skills, goals and services to represent the plans of individual agents and to develop models and algorithms for cooperation processes between a collection of agents.

  17. Agent Communication Channel Based on BACnet

    Institute of Scientific and Technical Information of China (English)

    Jiang Wen-bin; Zhou Man-li

    2004-01-01

    We analyze the common shortcoming in the existing agent MTPs (message transport protocols). With employing the File object and related service AtomicWriteFile of BACnet (a data communication protocol building automation and control networks), a new method of agent message transport is proposed and implemented. Every agent platform (AP) has one specified File object and agents in another AP can communicate with agents in the AP by using AtomicWriteFile service. Agent messages can be in a variety of formats. In implementation, BACnet/IP and Ethernet are applied as the BACnet data link layers respectively. The experiment results show that the BACnet can provide perfect support for agent communication like other conventional protocols such as hypertext transfer protocol(HTTP), remote method invocation (RMI) etc. and has broken through the restriction of TCP/IP. By this approach, the agent technology is introduced into the building automation control network system.

  18. Comparison of Communication Models for Mobile Agents

    Directory of Open Access Journals (Sweden)

    Xining Li

    2003-04-01

    Full Text Available An agent is a self-contained process being acting on behalf of a user. A Mobile Agent is an agent roaming the internet to access data and services, and carry out its assigned task remotely. This paper will focus on the communication models for Mobile Agents. Generally speaking, communication models concern with problems of how to name Mobile Agents, how to establish communication relationships, how to trace moving agents, and how to guarantee reliable communication. Some existing MA systems are purely based on RPC-style communication, whereas some adopts asynchronous message passing, or event registration/handling. Different communication concepts suitable for Mobile Agents are well discussed in [1]. However, we will investigate these concepts and existing models from a different point view: how to track down agents and deliver messages in a dynamic, changing world.

  19. Porphyria Cutanea Tarda and Agent Orange

    Science.gov (United States)

    ... ZIP code here Porphyria Cutanea Tarda and Agent Orange VA presumes porphyria cutanea tarda (PCT) is related to Veterans' exposure to Agent Orange or other herbicides during military service when the ...

  20. Soft Tissue Sarcomas and Agent Orange

    Science.gov (United States)

    ... ZIP code here Soft Tissue Sarcomas and Agent Orange VA presumes some soft tissue sarcomas in Veterans are related to their exposure to Agent Orange or other herbicides during military service. The soft ...

  1. Sports Agent Industry Emerges in China

    Institute of Scientific and Technical Information of China (English)

    HeiZiand; YiYou

    2003-01-01

    The agent profession is not new to Chinese. First appearing in the Western Zhou Dynasty, agents were called "Zhi Ren" then and "Ya Ren" from the Tang Dynasty onwards. In the Ming Dynasty, a certain amount of property and a license were required if one wanted to become an agent. In the late Qing Dynasty, Mai Ban (Chinese executives working in foreign firms), also a sort of agents, began to emerge in major cities of China.

  2. Mobile agents for distributed decision support systems

    OpenAIRE

    Blaz Rodič

    2011-01-01

    This article focuses on the performance of Java based mobile agents using format translation via an intermediary XML based format. Our goal was to develop and verify the performance of a lightweight, mobile agent based solution that would allow strong security, portability and access to heterogeneous data resources from a mobile platform to facilitate exchange of data between simulation models and data resources. We have developed two types of agents: a mobile agent that functions as a server...

  3. Security Issues in Mobile Agent Paradigm

    OpenAIRE

    Nitin Jain; Neeraj Singla

    2011-01-01

    A mobile Agent is a Software program that migrates from node tonode of a heterogeneous network. They are goal-oriented i.e. workautonomously towards a goal, capable of suspending their executionon one platform and moving to other where they can resumeexecution using resources of these nodes and they meet and interactwith other agents. Agents may be stationary, always resident at asingle platform or mobile, capable of moving among differentplatforms at different time. The mobile agent paradigm...

  4. Explaining Simulations Through Self Explaining Agents

    OpenAIRE

    Maaike Harbers; John-Jules Meyer; Karel Van den Bosch

    2010-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is more variable and harder to predict than reactive behavior, and therefore it might be harder to explain. However, the approach presented in this paper tries to make advantage of the agents' pro-active...

  5. ENZYMATIC DEINKING AGENTS FOR MIXED OFFICE WASTEPAPER

    Institute of Scientific and Technical Information of China (English)

    HuayuQiu; ChuanfuLiu; XiaokeMa; YingjuanFu

    2004-01-01

    This article focused on deinking agents for enzymatic deinking of MOW (mixed office wastepaper). The deinking performances of many series of surfactants were discussed at the experimental conditions, and finally some surfactants, which had good deinking effect, were selected. Then two-composed deinking agents were discussed. The deinkability of the deinking agents, e.g. deinking agents containing T-123 50% and P-10 50%, T-123 70% and O-15 30%, were better than that of the imported product.

  6. ENZYMATIC DEINKING AGENTS FOR MIXED OFFICE WASTEPAPER

    Institute of Scientific and Technical Information of China (English)

    Huayu Qiu; Chuanfu Liu; Xiaoke Ma; Yingjuan Fu

    2004-01-01

    This article focused on deinking agents for enzymatic deinking of MOW (mixed office wastepaper). The deinking performances of many series of surfactants were discussed at the experimental conditions, and finally, some surfactants, which had good deinking effect, were selected. Then two-composed deinking agents were discussed. The deinkability of the deinking agents, e.g. deinking agents containing T-123 50% and P-10 50%, T-123 70% and O-1530%, were better than that of the imported product.

  7. Virtual Knowledge Communities for Semantic Agents

    OpenAIRE

    Subercaze, Julien; Maret, Pierre

    2011-01-01

    International audience Virtual Knowledge Communities are a well suited paradigm for decentralized knowldege exchanges and they have been applied in several domains. In this paper we investigate the implementation of virtual knowledge communities with se- mantic agents. Using the SAM (Semantic Agent Modeling) approach, we show that agents can exchange community re- lated concepts (in OWL) and behavior (in SWRL). Agents can then learn and adapt new community-related behavior, which is useful...

  8. Topology and Social Behaviour of Agents

    OpenAIRE

    O. Hudak

    2003-01-01

    In a social group its members are caled here agents. Any two agents from the group may interact. The interaction consists of the exchange of information and it costs some energy. There exist subgroups of interacting agents which are nonreducibile. The structure, configuration of interactions between agents in the group, forms a macroscopic structure. The statistical equilibrium due to microreversibility is characterised by the maximum of entropy and by the minimum of energy, costs of informat...

  9. Integration of Agent System with Legacy Software

    Institute of Scientific and Technical Information of China (English)

    SHEN Qi; ZHAO Yan-hong; YIN Zhao-lin

    2003-01-01

    Agent technique is a new method that can analyze, design and realize a distributed open system. It has been used in almost every field. But if act for the real practical words in technique, it must integrate with legacy software, such as database system etc, and control them. This paper introduces the specification of agent software integration, ontology, instances database as implementing agent software integration with CORBA technique and takes XML, ACL as language communicating among agents.

  10. Bisimulation for Single-Agent Plausibility Models

    DEFF Research Database (Denmark)

    Andersen, Mikkel Birkegaard; Bolander, Thomas; van Ditmarsch, H.;

    2013-01-01

    Epistemic plausibility models are Kripke models agents use to reason about the knowledge and beliefs of themselves and each other. Restricting ourselves to the single-agent case, we determine when such models are indistinguishable in the logical language containing conditional belief, i.e., we......-agent epistemic plausibility models on a finite set of propositions. This gives decidability for single-agent epistemic plausibility planning....

  11. Self-Adapting Reactive Autonomous Agents

    Science.gov (United States)

    Andrecut, M.; Ali, M. K.

    This paper describes a new self-adapting control algorithm for reactive autonomous agents. The architecture of the autonomous agents integrates the reactive behavior with reinforcement learning. We show how these components perform on-line adaptation of the autonomous agents to various complex navigation situations by constructing an internal model of the environment. Also, a discussion on cooperation and coordination of teams of agents is presented.

  12. Pathogenic agents in freshwater resources

    Science.gov (United States)

    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.

  13. Honey - A Novel Antidiabetic Agent

    Directory of Open Access Journals (Sweden)

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

    2012-01-01

    Full Text Available 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.

  14. Embedded Automation in Human-Agent Environment

    CERN Document Server

    Tweedale, Jeffrey W

    2012-01-01

    This research book proposes a general conceptual framework for the development of automation in human-agents environments that will allow human- agent teams to work effectively and efficiently. We examine various schemes to implement artificial intelligence techniques in agents.  The text is directed to the scientists, application engineers, professors and students of all disciplines, interested in the agency methodology and applications.

  15. Preferences of Agents in Defeasible Logic

    NARCIS (Netherlands)

    Dastani, M.; Governatori, G.; Rotolo, A.; Torre, L.W.N. van der

    2005-01-01

    Defeasible Logic is extended to programming languages for cognitive agents with preferences and actions for planning. We define rule-based agent theories that contain preferences and actions, together with inference procedures. We discuss patterns of agent types in this setting. Finally, we illustra

  16. Cooperative heuristic multi-agent planning

    NARCIS (Netherlands)

    De Weerdt, M.M.; Tonino, J.F.M.; Witteveen, C.

    2001-01-01

    In this paper we will use the framework to study cooperative heuristic multi-agent planning. During the construction of their plans, the agents use a heuristic function inspired by the FF planner (l3l). At any time in the process of planning the agents may exchange available resources, or they may r

  17. Multi-Agent Planning with Planning Graph

    NARCIS (Netherlands)

    Bui, The Duy; Jamroga, Wojciech

    2003-01-01

    In this paper, we consider planning for multi-agents situations in STRIPS-like domains with planning graph. Three possible relationships between agents' goals are considered in order to evaluate plans: the agents may be collaborative, adversarial or indifferent entities. We propose algorithms to dea

  18. Explaining simulations through self explaining agents

    NARCIS (Netherlands)

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.

    2010-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is mor

  19. Explaining Simulations through Self Explaining Agents

    NARCIS (Netherlands)

    Harbers, M.; Dignum, F.; Bosch, K. van den; Meyer, J.J.C.

    2008-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is mor

  20. Stability of Evolving Multi-Agent Systems

    CERN Document Server

    De Wilde, Philippe; 10.1109/TSMCB.2011.2110642

    2011-01-01

    A Multi-Agent System is a distributed system where the agents or nodes perform complex functions that cannot be written down in analytic form. Multi-Agent Systems are highly connected, and the information they contain is mostly stored in the connections. When agents update their state, they take into account the state of the other agents, and they have access to those states via the connections. There is also external, user-generated input into the Multi-Agent System. As so much information is stored in the connections, agents are often memory-less. This memory-less property, together with the randomness of the external input, has allowed us to model Multi-Agent Systems using Markov chains. In this paper, we look at Multi-Agent Systems that evolve, i.e. the number of agents varies according to the fitness of the individual agents. We extend our Markov chain model, and define stability. This is the start of a methodology to control Multi-Agent Systems. We then build upon this to construct an entropy-based defi...

  1. The Ontogenesis of Agent: Linguistic Expression.

    Science.gov (United States)

    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)

  2. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    Science.gov (United States)

    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...

  3. Radioactive scanning agents with hydroquinone stabilizer

    International Nuclear Information System (INIS)

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise hydroquinone in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material which carries the radionuclide to bone, thus providing a skeletal imaging agent

  4. 7 CFR 1430.210 - MILC agents.

    Science.gov (United States)

    2010-01-01

    ... MILC agents. (a) MILC benefits may be disbursed by a dairy marketing cooperative that serves special... operation may authorize an agent of a dairy cooperative or milk handler affiliated with such cooperative to... 7 Agriculture 10 2010-01-01 2010-01-01 false MILC agents. 1430.210 Section 1430.210...

  5. Agents and Lattice-valued Logic

    Institute of Scientific and Technical Information of China (English)

    Germanno Resconi

    2006-01-01

    In fuzzy set theory, instead of the underlying membership set being a two -valued set it is a multi-valued set that generally has the structure of a lattice L with a minimal element O and the maximal element I. Furthermore if ∧, ∨, → and (「) are defined in the set L, then we can use these operations to define, as in the ordinary set theory, operations on fuzzy subsets. In this paper we give a model of the Lattice-Valued Logic with set of agents.Any agents know the logic value of a sentence p. The logic value is compatible with all of the accessible conceptual models or worlds of p inside the agent. Agent can be rational or irrational in the use of the logic operation.Every agent of n agents can have the same set of conceptual models for p and know the same logic for p in this case the agents form a consistent group of agents.When agents have different conceptual models for p,different subgroup of agents know different logic value for p. In this case the n agents are inconsistent in the expression of the logic value for p. The valuation structure of set of agents can be used as a semantic model for the Lattice-valued Logic and fuzzy logic.

  6. Improving Multi-Agent Systems Using Jason

    DEFF Research Database (Denmark)

    Vester, Steen; Boss, Niklas Skamriis; Jensen, Andreas Schmidt;

    2011-01-01

    We describe the approach used to develop the multi-agent system of herders that competed as the Jason-DTU team at the Multi-Agent Programming Contest 2010. We also participated in 2009 with a system developed in the agentoriented programming language Jason which is an extension of AgentSpeak. We ...

  7. Construction and Evaluation of Animated Teachable Agents

    Science.gov (United States)

    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.…

  8. Stigmergy in multi-agent reinforcement learning

    OpenAIRE

    Aras, Raghav; Dutech, Alain; Charpillet, François

    2004-01-01

    http://www.computer.org In this paper, we describe how certain aspects of the biological phenomena of stigmergy can be imported into multi-agent reinforcement learning (MARL), with the purpose of better enabling coordination of agent actions and speeding up learning. In particular, we detail how these stigmergic aspects can be used to define an inter-agent communication framework.

  9. Agent for roentgenocontrast examination of cavities

    International Nuclear Information System (INIS)

    The water-soluble agent, additionaly containing starch, agar, water, is suggested to increase accuracy of injured cavity diagnostics. The method for roentgenocontrast agent preparation on the base of starch-agar gel is described. Advantages of the agent suggested in comparison with those of roentgenologic cavity investigation used are shown

  10. On Programming Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt

    2013-01-01

    Since it is difficult (or even impossible) to assume anything about the agents’ behavior and goals in an open multi-agent system, it is often suggested that an organization is imposed upon the agents, whichhich, by abstracting away from the agents, specifies boundaries and objectives that the age...

  11. Properties of Ettringite Type Expansive Agent

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    By employing different forms and amounts of materials,many kinds of ettringite type expansive agents had been prepared.The relationship between the compositions and properties of expansive agents was analyzed.The design methods of expansive agent have been put forward according to the property requirement of expansive concrete.

  12. A theoretical framework for explaining agent behavior

    NARCIS (Netherlands)

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.

    2011-01-01

    To understand emergent processes in multi-agent-based simulations it is important to study the global processes in a simulation as well as the processes on the agent level. The behavior of individual agents is easier to understand when they are able to explain their own behavior. In this paper, a th

  13. Social Robots as Persuasive Agents

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2014-01-01

    Robots are more and more used in a social context, and in this paper we try to formulate a research agenda concerning ethical issues around social HRI in order to be prepared for future scenarios where robots may be a naturally integrated part of human society. We outline different paradigms...... to describe the role of social robots in communication processes with humans, and connect HRI with the topic of persuasive technology in health care, to critically reflect the potential benefits of using social robots as persuasive agents....

  14. Anticancer agents from marine sponges.

    Science.gov (United States)

    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

  15. Dopamine agents for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian;

    2014-01-01

    Hepato-Biliary Group Controlled Trials Register (January 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 12 of 12, 2013), MEDLINE (1946 to January 2014), EMBASE (1974 to January 2014), and Science Citation Index-Expanded (1900 to January 2014). Manual searches in reference...... therefore been assessed as a potential treatment for patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy. SEARCH METHODS: Trials were identified through the Cochrane...

  16. Mobile agent location in distributed environments

    Science.gov (United States)

    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.

  17. Camouflaging Agents for Vitiligo Patients.

    Science.gov (United States)

    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

  18. Surfactants as blackbird stressing agents

    Science.gov (United States)

    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.

  19. Anchor Toolkit - a secure mobile agent system

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. An Agent-Based Distributed Manufacturing System

    Institute of Scientific and Technical Information of China (English)

    J.Li; J.Y.H.Fuh; Y.F.Zhang; A.Y.C.Nee

    2006-01-01

    Agent theories have shown their promising capability in solving distributed complex system ever since its development. In this paper, one multi-agent based distributed product design and manufacturing planning system is presented. The objective of the research is to develop a distributed collaborative design environment for supporting cooperation among the existing engineering functions. In the system, the functional agents for design, manufacturability evaluation,process planning and scheduling are efficiently integrated with a facilitator agent. This paper firstly gives an introduction to the system structure, and the definitions for each executive agent are then described and a prototype of the proposed is also included at the end part.

  1. Cooperative planning in multi-agent systems

    OpenAIRE

    Torreño Lerma, Alejandro

    2016-01-01

    [EN] Automated planning is a centralized process in which a single planning entity, or agent, synthesizes a course of action, or plan, that satisfies a desired set of goals from an initial situation. A Multi-Agent System (MAS) is a distributed system where a group of autonomous agents pursue their own goals in a reactive, proactive and social way. Multi-Agent Planning (MAP) is a novel research field that emerges as the integration of automated planning in MAS. Agents are endowed with plan...

  2. A SURVEY OF THE PROPERTIES OF AGENTS

    Directory of Open Access Journals (Sweden)

    Kornelije Rabuzin

    2006-06-01

    Full Text Available In the past decade agent systems were considered to be as one of the major fields of study in Artificial Intelligence (AI field. Many different definitions of agents were presented and several different approaches describing agency can be distinguished. While some authors have tried to define “what” an agent really is, others have tried to identify agents by means of properties which they should possess. Most authors agree on these properties (at least basic set of properties which are intrinsic to agents. Since agent's definitions are not consistent, we are going to give an overview and list the properties intrinsic to an agent. Many different adjectives were attached to the term agent as well and many different kinds of agents and different architectures emerged too. The aim of this paper it go give an overview of what was going on in the field while taking into consideration main streams and projects. We will also present some guidelines important when modelling agent systems and say something about security issues. Also, some existing problems which restrict the wider usage of agents will be mentioned too.

  3. Introduction to Agent Mining Interaction and Integration

    Science.gov (United States)

    Cao, Longbing

    In recent years, more and more researchers have been involved in research on both agent technology and data mining. A clear disciplinary effort has been activated toward removing the boundary between them, that is the interaction and integration between agent technology and data mining. We refer this to agent mining as a new area. The marriage of agents and data mining is driven by challenges faced by both communities, and the need of developing more advanced intelligence, information processing and systems. This chapter presents an overall picture of agent mining from the perspective of positioning it as an emerging area. We summarize the main driving forces, complementary essence, disciplinary framework, applications, case studies, and trends and directions, as well as brief observation on agent-driven data mining, data mining-driven agents, and mutual issues in agent mining. Arguably, we draw the following conclusions: (1) agent mining emerges as a new area in the scientific family, (2) both agent technology and data mining can greatly benefit from agent mining, (3) it is very promising to result in additional advancement in intelligent information processing and systems. However, as a new open area, there are many issues waiting for research and development from theoretical, technological and practical perspectives.

  4. Mobile agents for distributed decision support systems

    Directory of Open Access Journals (Sweden)

    Blaz Rodič

    2011-03-01

    Full Text Available This article focuses on the performance of Java based mobile agents using format translation via an intermediary XML based format. Our goal was to develop and verify the performance of a lightweight, mobile agent based solution that would allow strong security, portability and access to heterogeneous data resources from a mobile platform to facilitate exchange of data between simulation models and data resources. We have developed two types of agents: a mobile agent that functions as a server for queries in SQL and converts the query results into XML documents and a stationary agent acting as a client for query forwarding and conversion of received documents into text files readable by a client application. We have tested the performance of the agents in a distributed simulation scenario and established that the agents can be used to connect heterogeneous simulation models and other applications, improving their connectivity and usability.

  5. Multi-agent for manufacturing systems optimization

    Science.gov (United States)

    Ciortea, E. M.; Tulbure, A.; Huţanu, C.-tin

    2016-08-01

    The paper is meant to be a dynamic approach to optimize manufacturing systems based on multi-agent systems. Multi-agent systems are semiautonomous decision makers and cooperate to optimize the manufacturing process. Increasing production the capacity is achieved by developing, implementing efficient and effective systems from control based on current manufacturing process. The model multi-agent proposed in this paper is based on communication between agents who, based on their mechanisms drive to autonomous decision making. Methods based on multi-agent programming are applied between flexible manufacturing processes and cooperation with agents. Based on multi-agent technology and architecture of intelligent manufacturing can lead to development of strategies for control and optimization of scheduled production resulting from the simulation.

  6. An Agent Framework of Tourism Recommender System

    Directory of Open Access Journals (Sweden)

    Jia Zhi Yang

    2016-01-01

    Full Text Available This paper proposes the development of an Agent framework for tourism recommender system. The recommender system can be featured as an online web application which is capable of generating a personalized list of preference attractions for tourists. Traditional technologies of classical recommender system application domains, such as collaborative filtering, content-based filtering and content-based filtering are effectively adopted in the framework. In the framework they are constructed as Agents that can generate recommendations respectively. Recommender Agent can generate recommender information by integrating the recommendations of Content-based Agent, collaborative filtering-based Agent and constraint-based Agent. In order to make the performance more effective, linear combination method of data fusion is applied. User interface is provided by the tourist Agent in form of webpages and mobile app.

  7. Knowledge Management in Role Based Agents

    Science.gov (United States)

    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.

  8. Model Based Testing for Agent Systems

    Science.gov (United States)

    Zhang, Zhiyong; Thangarajah, John; Padgham, Lin

    Although agent technology is gaining world wide popularity, a hindrance to its uptake is the lack of proper testing mechanisms for agent based systems. While many traditional software testing methods can be generalized to agent systems, there are many aspects that are different and which require an understanding of the underlying agent paradigm. In this paper we present certain aspects of a testing framework that we have developed for agent based systems. The testing framework is a model based approach using the design models of the Prometheus agent development methodology. In this paper we focus on model based unit testing and identify the appropriate units, present mechanisms for generating suitable test cases and for determining the order in which the units are to be tested, present a brief overview of the unit testing process and an example. Although we use the design artefacts from Prometheus the approach is suitable for any plan and event based agent system.

  9. Agent-Oriented Probabilistic Logic Programming

    Institute of Scientific and Technical Information of China (English)

    Jie Wang; Shi-Er Ju; Chun-Nian Liu

    2006-01-01

    Currently, agent-based computing is an active research area, and great efforts have been made towards the agent-oriented programming both from a theoretical and practical view. However, most of them assume that there is no uncertainty in agents' mental state and their environment. In other words, under this assumption agent developers are just allowed to specify how his agent acts when the agent is 100% sure about what is true/false. In this paper, this unrealistic assumption is removed and a new agent-oriented probabilistic logic programming language is proposed, which can deal with uncertain information about the world. The programming language is based on a combination of features of probabilistic logic programming and imperative programming.

  10. Unsupervised selection of informative descriptors in QSAR study of anti-HIV activities of HEPT derivatives

    DEFF Research Database (Denmark)

    Bagheri, Saeed; Omidikia, Nematollah; Kompany-Zareh, Mohsen

    2013-01-01

    features of HEPT derivatives. The aims of this procedure are generating a subset of descriptors from a data set with the relevant variables, eliminating redundancy, and reducing multicollinearity. The core of this methodology is based on jack-knife resampling method. In this paper, using jack-knife led...

  11. Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.

    Science.gov (United States)

    Escolano, Amelia; Steichen, Jon M; Dosenovic, Pia; Kulp, Daniel W; Golijanin, Jovana; Sok, Devin; Freund, Natalia T; Gitlin, Alexander D; Oliveira, Thiago; Araki, Tatsuya; Lowe, Sarina; Chen, Spencer T; Heinemann, Jennifer; Yao, Kai-Hui; Georgeson, Erik; Saye-Francisco, Karen L; Gazumyan, Anna; Adachi, Yumiko; Kubitz, Michael; Burton, Dennis R; Schief, William R; Nussenzweig, Michel C

    2016-09-01

    A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors. PMID:27610569

  12. Overcoming the Constraints of Anti-HIV/CD89 Bispecific Antibodies That Limit Viral Inhibition

    Directory of Open Access Journals (Sweden)

    Xiaocong Yu

    2016-01-01

    Full Text Available Innovative strategies are necessary to maximize the clinical application of HIV neutralizing antibodies. To this end, bispecific constructs of human antibody F240, reactive with well-conserved gp41 epitope and antibody 14A8, reactive with the IgA receptor (CD89 on effector cells, were constructed. A F240 × 14A8 bispecific single chain variable region (scFv molecule was constructed by linking two scFvs using a conventional GGGGS linker. Despite immunoreactivity with HIV gp41 and neutrophils, this bispecific scFv failed to inhibit HIV infection. This is in sharp contrast to viral inhibition using a chemical conjugate of the Fab of these two antibodies. Therefore, we constructed two novel Fab-like bispecific antibody molecules centered on fusion of the IgG1 CH1 domain or CH1-hinge domain to the C-terminus of F240scFv and fusion of the kappa chain CL domain to the C-terminus of 14A8scFv. Both Bi-Fab antibodies showed significant ADCVI activity for multiple clade B and clade C isolates by arming the neutrophils to inhibit HIV infection. The approach presented in this study is unique for HIV immunotherapy in that the impetus of neutralization is to arm and mobilize PMN to destroy HIV and HIV infected cells.

  13. Anti-HIV Drugs Decrease the Expression of Matrix Metalloproteinases in Astrocytes and Microglia

    Science.gov (United States)

    Liuzzi, G. M.; Mastroianni, C. M.; Latronico, T.; Mengoni, F.; Fasano, A.; Lichtner, M.; Vullo, V.; Riccio, P.

    2004-01-01

    The introduction of potent antiretroviral drugs for the treatment of patients with human immunodeficiency virus (HIV) infection has dramatically reduced the prevalence of HIV-associated neurological disorders. Such diseases can be mediated by proteolytic enzymes, i.e. matrix metalloproteinases (MMPs) and, in particular gelatinases, released from…

  14. A novel vaginal drug delivery system: anti-HIV bioadhesive film containing abacavir.

    Science.gov (United States)

    Ghosal, Kajal; Ranjan, Alok; Bhowmik, Benoy Brata

    2014-07-01

    Women are very much susceptible for acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases (STDs), mainly due to unprotected heterosexual vaginal intercourse and for some other social and economical disadvantages. Our aim was to formulate and optimize vaginal film of abacavir, a potent nucleoside reverse transcriptase inhibitor, for the treatment of AIDS and HIV. Abacavir films were prepared by solvent evaporation method using sodium alginate (Na-alginate) as the main polymer, Hydroxypropyl Methylcellulose E 15 (HPMC E 15) as the copolymer and glycerol as a humectant. Abacavir sulphate (ABC) was used here as a drug. Films were optimized for various physicochemical parameters such as tensile strength, % elongation at break, swelling capacity, drug content (mg/cm(2)), thickness, folding endurance, bioadhesion, pH, moisture content and SEM. Drug polymer interaction was studied by FTIR Spectra. The drug release study was accomplished in dissolution apparatus. In vivo study was also carried out. This newly formed film was one kind of sustain release type and can be considered as a novel drug carrier system for the treatment of AIDS and other STDs. It was suitable for local as well as systemic effect. The films showed good physicochemical property with good aesthetic appeal. PMID:24699799

  15. Overcoming the Constraints of Anti-HIV/CD89 Bispecific Antibodies That Limit Viral Inhibition.

    Science.gov (United States)

    Yu, Xiaocong; Duval, Mark; Gawron, Melissa; Posner, Marshall R; Cavacini, Lisa A

    2016-01-01

    Innovative strategies are necessary to maximize the clinical application of HIV neutralizing antibodies. To this end, bispecific constructs of human antibody F240, reactive with well-conserved gp41 epitope and antibody 14A8, reactive with the IgA receptor (CD89) on effector cells, were constructed. A F240 × 14A8 bispecific single chain variable region (scFv) molecule was constructed by linking two scFvs using a conventional GGGGS linker. Despite immunoreactivity with HIV gp41 and neutrophils, this bispecific scFv failed to inhibit HIV infection. This is in sharp contrast to viral inhibition using a chemical conjugate of the Fab of these two antibodies. Therefore, we constructed two novel Fab-like bispecific antibody molecules centered on fusion of the IgG1 CH1 domain or CH1-hinge domain to the C-terminus of F240scFv and fusion of the kappa chain CL domain to the C-terminus of 14A8scFv. Both Bi-Fab antibodies showed significant ADCVI activity for multiple clade B and clade C isolates by arming the neutrophils to inhibit HIV infection. The approach presented in this study is unique for HIV immunotherapy in that the impetus of neutralization is to arm and mobilize PMN to destroy HIV and HIV infected cells. PMID:27419146

  16. Integralidade do cuidado na testagem anti-HIV: o olhar das mulheres

    Directory of Open Access Journals (Sweden)

    Ana Jaqueline Santiago Carneiro

    2013-12-01

    Full Text Available A detecção da positividade para o HIV, durante o trabalho de parto, por meio dos testes rápidos, fragiliza as mulheres e gera demandas específicas de cuidados. Este estudo objetivou analisar o cuidado profissional a mulheres com teste rápido positivo para HIV a partir do olhar de mulheres que tomaram conhecimento da positividade durante o trabalho de parto ou puerpério. Trata-se de estudo do tipo exploratório, com abordagem qualitativa. Os dados foram coletados por meio de entrevista semiestruturada e analisados por meio da técnica de análise de discurso. Observou-se que as relações de cuidado às mulheres com teste rápido positivo para HIV se distanciam da integralidade, uma vez que se mantêm distantes e superficiais, sendo norteadas pelo modelo biomédico. A incorporação da perspectiva da integralidade nas ações de saúde exige reflexão por parte do(as profissionais, do(as gestore(as do sistema público de saúde, bem como a capacitação desse(as profissionais.

  17. Synthesis and Physicochemical Study of a Quinoxaline Derivative with Potencial Antineoplasic or Anti-HIV Activity

    Directory of Open Access Journals (Sweden)

    Gabriela A. Rodrigo

    2000-03-01

    Full Text Available Kinetics of the synthesis of 3-[3-quinoxaline(1H-one]propionic acid (I were performed. This compound was achieved from reaction between o-phenylenediamine and α-ketoglutaric acid under different experimental conditions, and it was sent to the National Cancer Institute (USA for its pharmacological evaluation.

  18. The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity.

    Directory of Open Access Journals (Sweden)

    Rui Jia

    Full Text Available The interferon-inducible transmembrane (IFITM proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1 strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3 is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117-125, which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117-125 mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117-125 to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117-125, mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.

  19. Discovery and Assesment of New Target Sites for Anti-HIV Therapies

    DEFF Research Database (Denmark)

    The HIV viruses infect cells by endocytosis and takes over parts of the cells reaction pathways in order to reproduce itself and spread the infection. One such pathway is the mammalian inflammatory signaling, which invoke NF-κB as the principal transcription factor. A treatment against HIV could ...

  20. Leptospirose em doentes com anticorpos anti-HIV: relato de dois casos

    Directory of Open Access Journals (Sweden)

    Marcos Vinícius da Silva

    1990-12-01

    Full Text Available Relata-se a concomitância de leptospirose e síndrome da imunodeficiência adquirida (SIDA em humanos. Nestes casos não foram observados aspectos clínicos diferentes que possam ser atribuídos à simultaneidade dessas patologias.Two patients with concomitant leptospirosis and the acquired immunodeficiency syndrome (AIDS are reported. In these cases different clinical aspects that can be attributed to simultaneity of these pathologies was not observed.

  1. Discrepancies Between Medical and Pharmacy Records for Patients on Anti-HIV Drugs

    NARCIS (Netherlands)

    de Maat, Monique M R; Frankfort, Suzanne V; Mathôt, Ron A A; Mulder, Jan W; Meenhorst, Pieter L; van Gorp, Eric C M; Koks, Cornelis H W; Hoetelmans, Richard M W; de Boer, Anthonius; Beijnen, Jos H

    2002-01-01

    OBJECTIVE: To compare and evaluate drug notations in outpatient medical records and in pharmacy records in a cohort of HIV-1-infected patients treated with antiretroviral drugs. METHODS: Data on 103 patients were obtained from January 1, 1998, through December 31, 1999, by medical chart review and c

  2. An alternative methodology for the prediction of adherence to anti HIV treatment

    Directory of Open Access Journals (Sweden)

    Denholm-Price James CW

    2009-06-01

    Full Text Available Abstract Background Successful treatment of HIV-positive patients is fundamental to controlling the progression to AIDS. Causes of treatment failure are either related to drug resistance and/or insufficient drug levels in the blood. Severe side effects, coupled with the intense nature of many regimens, can lead to treatment fatigue and consequently to periodic or permanent non-adherence. Although non-adherence is a recognised problem in HIV treatment, it is still poorly detected in both clinical practice and research and often based on unreliable information such as self-reports, or in a research setting, Medication Events Monitoring System caps or prescription refill rates. To meet the need for having objective information on adherence, we propose a method using viral load and HIV genome sequence data to identify non-adherence amongst patients. Presentation of the hypothesis With non-adherence operationally defined as a sharp increase in viral load in the absence of mutation, it is hypothesised that periods of non-adherence can be identified retrospectively based on the observed relationship between changes in viral load and mutation. Testing the hypothesis Spikes in the viral load (VL can be identified from time periods over which VL rises above the undetectable level to a point at which the VL decreases by a threshold amount. The presence of mutations can be established by comparing each sequence to a reference sequence and by comparing sequences in pairs taken sequentially in time, in order to identify changes within the sequences at or around 'treatment change events'. Observed spikes in VL measurements without mutation in the corresponding sequence data then serve as a proxy indicator of non-adherence. Implications of the hypothesis It is envisaged that the validation of the hypothesised approach will serve as a first step on the road to clinical practice. The information inferred from clinical data on adherence would be a crucially important feature of treatment prediction tools provided for practitioners to aid daily practice. In addition, distinct characteristics of biological markers routinely used to assess the state of the disease may be identified in the adherent and non-adherent groups. This latter approach would directly help clinicians to differentiate between non-responding and non-adherent patients.

  3. Protein adducts from the anti-HIV drug abacavir – possible biomarkers of drug toxicity

    OpenAIRE

    Grilo, Nádia Filipa Marques

    2012-01-01

    Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina While the benefits of combined antiretroviral therapy have revolutionized the life expectancy of patients infected with the human immunodeficiency virus, treatment-associated toxicity is frequently observed. Abacavir is a nucleoside reverse transcriptase inhibitor associated with acute toxic events,such as hypersensitivity reactions. In addition, its long-term use has increasingly been recognized as as...

  4. Human semen contains exosomes with potent anti-HIV-1 activity

    OpenAIRE

    Madison, Marisa N; Roller, Richard J.; Okeoma, Chioma M.

    2014-01-01

    Background Exosomes are membranous nanovesicles secreted into the extracellular milieu by diverse cell types. Exosomes facilitate intercellular communication, modulate cellular pheno/genotype, and regulate microbial pathogenesis. Although human semen contains exosomes, their role in regulating infection with viruses that are sexually transmitted remains unknown. In this study, we used semen exosomes purified from healthy human donors to evaluate the role of exosomes on the infectivity of diff...

  5. Transgenic Production of an Anti HIV Antibody in the Barley Endosperm

    OpenAIRE

    Goetz Hensel; Doreen M Floss; Elsa Arcalis; Markus Sack; Stanislav Melnik; Friedrich Altmann; Twan Rutten; Jochen Kumlehn; Eva Stoger; Udo Conrad

    2015-01-01

    Barley is an attractive vehicle for producing recombinant protein, since it is a readily transformable diploid crop species in which doubled haploids can be routinely generated. High amounts of protein are naturally accumulated in the grain, but optimal endosperm-specific promoters have yet to be perfected. Here, the oat GLOBULIN1 promoter was combined with the legumin B4 (LeB4) signal peptide and the endoplasmic reticulum (ER) retention signal (SE)KDEL. Transgenic barley grain accumulated up...

  6. Computational Investigation of the Anti-HIV Activity of Chinese Medicinal Formula Three-Huang Powder

    OpenAIRE

    Hu, Jack Z.; Bai, Li; Chen, Da-Gang; Xu, Qi-Tai; Southerland, William M.

    2010-01-01

    An essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1) is integration of the double-stranded retroviral DNA into the genome of the host cell. HIV-1 integrase, the enzyme that inserts the vital DNA into the host chromosome, is an attractive and rational target for anti-AIDS drug design because it is essential for HIV replication and there are no known counterparts in the host cell. Inhibitors of this enzyme have the great potential to complement the therapeutic use ...

  7. Agent-Based Modeling and Mapping of Manufacturing System

    Institute of Scientific and Technical Information of China (English)

    Z; Zhang

    2002-01-01

    Considering the agent-based modeling and mapping i n manufacturing system, some system models are described in this paper, which are included: Domain Based Hierarchical Structure (DBHS), Cascading Agent Structure (CAS), Proximity Relation Structure (PRS), and Bus-based Network Structure (BNS ). In DBHS, one sort of agents, called static agents, individually acts as Domai n Agents, Resources Agents, UserInterface Agents and Gateway Agents. And the oth ers, named mobile agents, are the brokers of task and ...

  8. 10th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Pérez, Javier; Golinska, Paulina; Giroux, Sylvain; Corchuelo, Rafael; Trends in Practical Applications of Agents and Multiagent Systems

    2012-01-01

    PAAMS, the International Conference on Practical Applications of Agents and Multi-Agent Systems is an evolution of the International Workshop on Practical Applications of Agents and Multi-Agent Systems. PAAMS is an international yearly tribune to present, to discuss, and to disseminate the latest developments and the most important outcomes related to real-world applications. It provides a unique opportunity to bring multi-disciplinary experts, academics and practitioners together to exchange their experience in the development of Agents and Multi-Agent Systems.   This volume presents the papers that have been accepted for the 2012 in the workshops: Workshop on Agents for Ambient Assisted Living, Workshop on Agent-Based Solutions for Manufacturing and Supply Chain and Workshop on Agents and Multi-agent systems for Enterprise Integration.

  9. Opinion evolution influenced by informed agents

    Science.gov (United States)

    Fan, Kangqi; Pedrycz, Witold

    2016-11-01

    Guiding public opinions toward a pre-set target by informed agents can be a strategy adopted in some practical applications. The informed agents are common agents who are employed or chosen to spread the pre-set opinion. In this work, we propose a social judgment based opinion (SJBO) dynamics model to explore the opinion evolution under the influence of informed agents. The SJBO model distinguishes between inner opinions and observable choices, and incorporates both the compromise between similar opinions and the repulsion between dissimilar opinions. Three choices (support, opposition, and remaining undecided) are considered in the SJBO model. Using the SJBO model, both the inner opinions and the observable choices can be tracked during the opinion evolution process. The simulation results indicate that if the exchanges of inner opinions among agents are not available, the effect of informed agents is mainly dependent on the characteristics of regular agents, including the assimilation threshold, decay threshold, and initial opinions. Increasing the assimilation threshold and decay threshold can improve the guiding effectiveness of informed agents. Moreover, if the initial opinions of regular agents are close to null, the full and unanimous consensus at the pre-set opinion can be realized, indicating that, to maximize the influence of informed agents, the guidance should be started when regular agents have little knowledge about a subject under consideration. If the regular agents have had clear opinions, the full and unanimous consensus at the pre-set opinion cannot be achieved. However, the introduction of informed agents can make the majority of agents choose the pre-set opinion.

  10. Interaction Protocols in Multi-Agent Systems based on Agent Petri Nets Model

    Directory of Open Access Journals (Sweden)

    Kamel Barkaoui

    2013-08-01

    Full Text Available This paper deals with the modeling of interaction between agents in Multi Agents System (MAS based on Agent Petri Nets (APN. Our models are created based on communicating agents. Indeed, an agent initiating a conversation with other can specify the interaction protocol wishes to follow. The combination of APN and FIPA Protocols schemes leads to a set of deployment formal rules for points where model interaction can be successfully implemented. We introduce some models FIPA standard protocols.

  11. Logical Theories for Agent Introspection

    DEFF Research Database (Denmark)

    Bolander, Thomas

    2004-01-01

    by self-reference. In the standard approach taken in artificial intelligence, the model that an agent has of its environment is represented as a set of beliefs. These beliefs are expressed as logical formulas within a formal, logical theory. When the logical theory is expressive enough to allow...... introspective reasoning, the presence of self-reference causes the theory to be prone to inconsistency. The challenge therefore becomes to construct logical theories supporting introspective reasoning while at the same time ensuring that consistency is retained. In the thesis, we meet this challenge by devising...... several such logical theories which we prove to be consistent. These theories are all based on first-order predicate logic. To prove our consistency results, we develop a general mathematical framework, suitable for proving a large number of consistency results concerning logical theories involving...

  12. Bioprotective agents in safety control

    Directory of Open Access Journals (Sweden)

    Dimitrijević-Branković Suzana I.

    2003-01-01

    Full Text Available Food poisoning is the one of the main health hazards even today. More than 200 known diseases are transmitted through food. The causes of foodborne illness include viruses, bacteria, parasites, toxins, metals, and prions and the symptoms of foodborne illness range from mild gastroenteritis to life-threatening neurological, hepatic and renal syndromes.The prevention of food poisonings represents very serious task for food manufacturers. Beside food control according to the concept "from the farm to the table" there is increased need for the development of new technology for longer shelf lifes of food. Food fermented by lactic acid bacteria (LAB and traditionally considered to be safe. There are many substances produced by LAB that affect the shelf life of fermented food, by active suppression of poisoning microorganisms growth. Because of that, the LAB is recently considered as bioprotective agents that have important role in food safety.

  13. Host modulation by therapeutic agents

    Directory of Open Access Journals (Sweden)

    Sugumari Elavarasu

    2012-01-01

    Full Text Available Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs, bisphosphonates, nitrous oxide (NO synthase inhibitors, recombinant human interleukin-11 (rhIL-11, omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA, mitogen-activated protein kinase (MAPK inhibitors, nuclear factor-kappa B (NF-kb inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α are some of the therapeutic agents that have host modulation properties.

  14. Fault Tolerance Mobile Agent System Using Witness Agent in 2-Dimensional Mesh Network

    Directory of Open Access Journals (Sweden)

    Ahmad Rostami

    2010-09-01

    Full Text Available Mobile agents are computer programs that act autonomously on behalf of a user or its owner and travel through a network of heterogeneous machines. Fault tolerance is important in their itinerary. In this paper, existent methods of fault tolerance in mobile agents are described which they are considered in linear network topology. In the methods three agents are used to fault tolerance by cooperating to each others for detecting and recovering server and agent failure. Three types of agents are: actual agent which performs programs for its owner, witness agent which monitors the actual agent and the witness agent after itself, probe which is sent for recovery the actual agent or the witness agent on the side of the witness agent. Communication mechanism in the methods is message passing between these agents. The methods are considered in linear network. We introduce our witness agent approach for fault tolerance mobile agent systems in Two Dimensional Mesh (2D-Mesh Network. Indeed Our approach minimizes Witness-Dependency in this network and then represents its algorithm.

  15. Agent Reward Shaping for Alleviating Traffic Congestion

    Science.gov (United States)

    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.

  16. Agent Grid技术研究初探%Initial Research on Agent Grid

    Institute of Scientific and Technical Information of China (English)

    张英朝; 张维明; 肖卫东; 沙基昌

    2003-01-01

    The term "Grid" is increasingly appearing in computer literature, generally referring to some form of system framework into which hardware, software, or information resources can be plugged, and which permits easy configuration and creation of new functionality from existing resources. In this article, first, we introduce the concepts of Grid and Agent Grid based on our own understanding. Then we compare Agent Grid with the traditional Multi-Agent System to make the concept and characters of Agent Grid much clearer. Next, the key techniques of Agent Grid, such as Agent Grid System Architecture, System Models, Intelligent Agents and Agent-Based System Resource Management, are thoroughly illustrated. Finally, we briefly discusse the future applications of Agent Grid.

  17. MATRIX-AGENT FRAMEWORK:A VIRTUAL PLATFORM FOR MULTI-AGENTS

    Institute of Scientific and Technical Information of China (English)

    Hao Lan ZHANG; Clement H.C. LEUNG; Gitesh K. RAIKUNDALIA

    2006-01-01

    Multi-agent technology has been applied extensively to many areas, including Decision Support Systems (DSS). However, the applications of multi-agent technology in DSS are still very preliminary.Most of the current agent frameworks, such as middle-agent-based or agent-facilitator-based frameworks, are basically agent-to-agent model. These agent-based frameworks often neglect the living environment for agents and they suffer from: (i) inability to adapt to the environment, (ii)inability to self-upgrade, and (iii) inefficiency in information acquisition. Here, we introduce a recently proposed multi-agent framework, namely Agent-based Open Connectivity for Decision Support Systems (AOCD). In this new framework, the communication and cooperation between agents are through a key component, the Matrix, which provides a virtual platform for agents. We use a unified Matrices framework to solve the bottleneck problem in the AOCD framework. Our experimental results based on different agent network topologies indicate that the hybrid topology presents superior performance compared with the centralised and decentralised topologies.

  18. Diuretic Agents in Treatment of Sudden Deafness

    Institute of Scientific and Technical Information of China (English)

    JI Chang-you; LI Hong-tao; ZHOU Ding-rong; CHEN Ji-chuan; WANG Yi-nan; GUAN Li-qian; ZHANG Min

    2008-01-01

    Objective To study the role of diuretic agents in treating sudden deafness (SD) and explore the possibility of endolymphatic hydrops as a potential cause of SD. Methods Twenty-eight SD cases were reviewed. In 23 cases, treatment was initiated with routine agents. Diuretic agents were later added in 8 of these cases that failed to respond to routine treatment agents. Diuretic agents were included in the initial treatment in the rest 5 cases. In total, 13 cases received diuretics in addition to routine treatment agents and 15 cases received conventional treatment only. Results In the 8 cases who received diuretics after failed conventional treatments, 4 showed hearing improvement, whereas all 5 cases in which diuretics were included in the initial treatment demonstrated hearing improvement. Conclusion These results suggest a possible role of endolymphatic hydrops in the pathophysiologic course of SD. Diuretics should be considered when clear indications exist with no conflicts to other medical conditions.

  19. Antagonistic formation motion of cooperative agents

    Science.gov (United States)

    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).

  20. Departments as Agents of Change

    Science.gov (United States)

    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

  1. Ultrasound contrast agents: bubbles, drops and particles

    OpenAIRE

    Lajoinie, Guillaume Pierre René

    2015-01-01

    The research on the medical use of microbubbles has coontinuously provided fascinating results for half a century. Investigating new agents or new uses of existing agents requires both innovative physics and ideas and extensive testing in-vitro and in vivo. The translation from the lab to the clinic is long and calls upon many specialties. In this dissertation, we have presented and studied various experimental agents for biomedical imaging and therapy, some in the early development phase and...

  2. Web-Based Computing Resource Agent Publishing

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Web-based Computing Resource Publishing is a efficient way to provide additional computing capacity for users who need more computing resources than that they themselves could afford by making use of idle computing resources in the Web.Extensibility and reliability are crucial for agent publishing. The parent-child agent framework and primary-slave agent framework were proposed respectively and discussed in detail.

  3. Intelligent Agents in E-Commerce

    Directory of Open Access Journals (Sweden)

    Valentin LITOIU

    2006-01-01

    Full Text Available This paper emphasizes the importance of intelligent agents in e-commerce, with a particular focus on the B2C and B2B context. From the consumer buying behaviour perspective, agents can be used to assist the following stages: need identification, product brokering, buyer coalition formation, merchant brokering and negotiation. Related to B2B commerce, intelligent agents are involved in partnership formation, brokering and negotiation.

  4. Massive Multi-Agent Systems Control

    Science.gov (United States)

    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.

  5. Applying Software Engineering to Agent Development

    OpenAIRE

    Cohen, Mark A.; Lock Haven University; RITTER, Frank E.; Haynes, Steven R

    2010-01-01

    Developing intelligent agents and cognitive models is a complex software engineering activity. This article shows how all intelligent agent creation tools can be improved by taking advantage of established software engineering principles such as high-level languages, maintenance-oriented development environments, and software reuse. We describe how these principles have been realized in the Herbal integrated development environment, a collection of tools that allows agent developers to exploi...

  6. Agent-based argumentation for ontology alignments

    OpenAIRE

    Laera, Loredana; Tamma, Valentina; Bench-Capon, Trevor; Euzenat, Jérôme

    2006-01-01

    laera2006a International audience When agents communicate they do not necessarily use the same vocabulary or ontology. For them to interact successfully they must find correspondences between the terms used in their ontologies. While many proposals for matching two agent ontologies have been presented in the literature, the resulting alignment may not be satisfactory to both agents and can become the object of further negotiation between them. This paper describes our work constructing ...

  7. NESTA: NASA Engineering Shuttle Telemetry Agent

    OpenAIRE

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

    2006-01-01

    The Electrical Systems Division at the 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 (NESTA), 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 crit...

  8. Decentralized network management based on mobile agent

    Institute of Scientific and Technical Information of China (English)

    李锋; 冯珊

    2004-01-01

    The mobile agent technology can be employed effectively for the decentralized management of complex networks. We show how the integration of mobile agent with legacy management protocol, such as simple network management protocol (SNMP), leads to decentralized management architecture. HostWatcher is a framework that allows mobile agents to roam network, collect and process data, and perform certain adaptive actions. A prototype system is built and a quantitative analysis underlines the benefits in respect to reducing network load.

  9. Glaucoma: role of neuroprotective agents

    Directory of Open Access Journals (Sweden)

    Achyut N. Pandey

    2014-10-01

    Full Text Available Glaucoma is an optic neuropathy, considered as the second leading cause of blindness worldwide. Glaucoma is characterized by selective death of retinal ganglion cells (RGC and a progressive loss of vision. Elevated intraocular pressure (IOP is one of the most important risk factors for developing glaucoma and hence we mainly focus on lowering IOP to arrest the progression of glaucoma. However, many patients continue to demonstrate a clinically downhill course despite the control of initially raised IOP. In fact, some patients develop what is called normal tension glaucoma, not associated to an increased IOP. This emphasizes that several pressure-independent mechanisms are responsible for the development and progression of glaucomatous neuropathy and that high IOP and vascular insufficiency in the optic nerve head are only risk factors for the development of glaucoma, and are not the only target for the treatment of glaucoma. The reason is that the process of RGC death is thought to be biphasic, and the primary injury is followed by a slower secondary degeneration related to a noxious environment surrounding the apoptotic cells. This environment is characterized by changes in the extra-cellular ionic concentrations, increased amounts of free radicals, neurotrophins (NT depletion and increased glutamate-induced excitotoxicity due to high extra-cellular glutamate levels, which binds to N-methyl-D-aspartate (NMDA receptors leading to an abnormally high intracellular Ca2+ concentration. Neuroprotection is a process that attempts to preserve the remaining cells that are still vulnerable to damage, and the main aim of neuroprotective therapy is to employ pharmacologic or other means to attenuate the hostility of the environment surrounding the degenerating cells, or to supply the cells with the tools to deal with this aggression, providing resilience to the insult. Several agents have been reported neuroprotective in glaucoma, both in clinical assays

  10. Agent fabrication and its implementation for agent-based electronic commerce

    OpenAIRE

    Guan, Su; Zhu, F.

    2002-01-01

    In the last decade, agent-based e-commerce has emerged as a potential role for the next generation of e-commerce. How to create agents for e-commerce applications has become a serious consideration in this field. This paper proposes a new scheme named agent fabrication and elaborates its implementation in multi-agent systems based on the SAFER (Secure Agent Fabrication, Evolution & Roaming) architecture. First, a conceptual structure is proposed for software agents carrying out e-commerce act...

  11. Multi-agent systems simulation and applications

    CERN Document Server

    Uhrmacher, Adelinde M

    2009-01-01

    Methodological Guidelines for Modeling and Developing MAS-Based SimulationsThe intersection of agents, modeling, simulation, and application domains has been the subject of active research for over two decades. Although agents and simulation have been used effectively in a variety of application domains, much of the supporting research remains scattered in the literature, too often leaving scientists to develop multi-agent system (MAS) models and simulations from scratch. Multi-Agent Systems: Simulation and Applications provides an overdue review of the wide ranging facets of MAS simulation, i

  12. Agent-Based Health Monitoring System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose combination of software intelligent agents to achieve decentralized reasoning, with fault detection and diagnosis using PCA, neural nets, and maximum...

  13. Integrating Interaction Framework for Agent Negotiation

    Institute of Scientific and Technical Information of China (English)

    肖正光; 王振杰; 徐良贤

    2003-01-01

    Agent negotiation has become increasingly important since the advent of electronic commerce.There are two kinds of interactions in the process of agent negotiation.One is the interaction between different agents,and the other is the interaction between the agent and the human user.In this paper,firstly,we introduce Q language,a scenario description language for designing interactions between agents and human users.Then we propose an integrating interaction framework for agent negotiation,in which both kinds of interactions are described by Q scenario.Our framework can make the interaction process open and easy to be understood by the users.Users can understand how the negotiation process goes and what is happening in the system including some erroneous or inappropriate actions caused by the negotiation agent.This gives the users a chance to terminate or change the behavior of negotiation agent in time to avoid unfavorable negotiation outcome.In addition,users can customize the agent's behaviors through visible interactions with it.

  14. Agent architecture for intelligent manufacturing systems

    Directory of Open Access Journals (Sweden)

    J. Madejski

    2008-08-01

    Full Text Available Purpose: Analysis is made of requirements posed by tasks of agents operating in the intelligent manufacturing systems and their resulting architecture is presented.Design/methodology/approach: Architecture of agent systems for industrial environment is presented, making it possible to generate the particular agents customised for the specific tasks, based on the automatic analysis of its required features.Findings: Extension of cellular automata approach underlying the conventional agent behaviour specification using the Fuzzy Cognitive Maps is presented in conjunction with the neural networks providing learning capability of the agents designed for the various levels of the manufacturing supervisory and execution systems. Adding reaction time specification to FCM makes it possible to analyse and design systems with the required behaviour.Research limitations/implications: Specific features of the designed agent architecture have been tested as separate mechanisms which can be merged into the final comprehensive at a later stage.Originality/value: Agent architecture is proposed for the industrial applications of single agents and their groups that can collaborate to achieve the individual and joint goals specified in reaction to changing environment conditions and into their agendas in XML format. Automatic generation of custom agent reactions models can be carried out based on a set of requirements that may be specified in the if-then rules form.

  15. TEST SUITE GENERATION PROCESS FOR AGENT TESTING

    Directory of Open Access Journals (Sweden)

    HOUHAMDI ZINA

    2011-04-01

    Full Text Available Software agents are a promising technology for today's complex, distributed systems. Methodologies and techniques that address testing and reliability of multi agent systems are increasingly demanded, in particular to support automated test case generation and execution. In this paper, we introduce a novel approach for goal-oriented software agent testing. It specifies a testing process that complements the goal oriented methodology Tropos and reinforces the mutual relationship between goal analysis and testing. Furthermore, it defines a structured and comprehensive agent test suite generation process by providing a systematic way of deriving test cases from goal analysis.

  16. Mobile Agents Principles of Operation and Applications

    CERN Document Server

    Genco, A

    2007-01-01

    Multi-agent systems are one of the most effective software design paradigms, and they are considered to be the most recent evolutionary step of object-oriented programming. Agents have several advantages when compared with objects. The most important among them is to be made of active code, which is capable of acting autonomously. Agents can be a suitable choice to exploit the Internet reality, since users can operate easily in a less compelling way and also reduce Internet connection time. Mobile agents thus make a PC an intelligent entity able to autonomously accomplish boring human tasks, s

  17. Potential use of rapamycin in HIV infection

    DEFF Research Database (Denmark)

    Donia, Marco; McCubrey, James A; Bendtzen, Klaus;

    2010-01-01

    The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies...... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...... replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood...

  18. Dronedarone: a new antiarrhythmic agent.

    Science.gov (United States)

    Oyetayo, Ola O; Rogers, Carrie E; Hofmann, Prudence O

    2010-09-01

    Dronedarone is an antiarrhythmic agent recently approved by the United States Food and Drug Administration for the reduction of cardiovascular-related hospitalizations in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. The drug is a derivative of amiodarone and has been modified to reduce the organ toxicities frequently encountered with amiodarone. Dronedarone exerts its antiarrhythmic effects through multichannel blockade of the sodium, potassium, and calcium channels and also possesses antiadrenergic activity, thereby exhibiting pharmacologic effects of all four Vaughan Williams classes of antiarrhythmics. The efficacy of dronedarone for the maintenance of sinus rhythm, ventricular rate control, and reduction in cardiovascular-related hospitalizations has been demonstrated in several randomized, placebo-controlled trials. Although a high rate of gastrointestinal events (e.g., nausea, vomiting, and diarrhea) has been associated with dronedarone, more serious adverse events such as thyroid, liver, or pulmonary toxicities have not been observed. Because of a possible increase in mortality, dronedarone should be avoided in patients with New York Heart Association class IV or II-III heart failure with a recent decompensation. Given the efficacy and safety data currently available, dronedarone represents a reasonable alternative for maintenance of sinus rhythm in appropriately selected patients.

  19. Copper complexes as therapeutic agents.

    Science.gov (United States)

    Duncan, Clare; White, Anthony R

    2012-02-01

    The importance of transition metals in biological processes has been well established. Copper (Cu) is a transition metal that can exist in oxidised and reduced states. This allows it to participate in redox and catalytic chemistry, making it a suitable cofactor for a diverse range of enzymes and molecules. Cu deficiency or toxicity is implicated in a variety of pathological conditions; therefore inorganic complexes of Cu have been investigated for their therapeutic and diagnostic potential. These Cu complexes have been shown to be effective in cancer treatment due to their cytotoxic action on tumour cells. Alternatively, Cu complexes can also modulate Cu homeostasis in the brain, resulting in protective effects in several models of neurodegeneration. In other diseases such as coronary heart disease and skin disease, the success of Cu complexes as potential therapeutics will most likely be due to their ability to increase SOD activity, leading to relief of oxidative stress. This review seeks to provide a broad insight into some of the diverse actions of Cu complexes and demonstrate the strong future for these compounds as potential therapeutic agents.

  20. Direct anti-HCV agents

    Directory of Open Access Journals (Sweden)

    Xingquan Zhang

    2016-01-01

    Full Text Available 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.

  1. Application Framework with Abstractions for Protocol and Agent Role

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun

    2016-01-01

    In multi-agent systems, agents interact by sending and receiving messages and the actual sequences of message form interaction structures between agents. Protocols and agents organized internally by agent roles support these interaction structures. Description and use of protocols based on agent...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Core Competencies Of A Call Centre AgentCore Competencies Of A Call Centre Agent

    OpenAIRE

    Christine White; Vera Roos

    2005-01-01

    Call centre agents are becoming increasingly important in the call centre context. They act as a contact point between the customer and the company. Call centre agents should have certain competencies to perform their duties sufficiently. Identifying competencies, required to be effective agents, will ease the task of training and recruitment. Due to the interrelatedness of the call centre agent, the management of a call centre and customers, all relevant role players’ perceptions were taken ...

  4. Your company's secret change agents.

    Science.gov (United States)

    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

  5. Designing Negotiating Agent for Automated Negotiations

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Traditional research in automated negotiation is focused on negotiation protocol and strategy.This paper studies automated negotiation from a new point of view, proposes a novel concept, namely negotiating agent, and discusses its significance in construction of automated negotiation system, with an abstract model formally described and the architecture designed, which supports both goal-directed reasoning and reactive response. A communication model was proposed to construct interaction mechanism used by negotiating agents, in which the negotiation language used by agents is defined.The communication model and the language are defined in a way general enough to support a wide variety of market mechanisms, thus being particularly suitable for flexible applications such as electronic business. The design and expression of the negotiation ontology is also discussed. On the base of the theoretical model of negotiating agent, negotiating agent architecture and negotiating agent communication model (NACM) are explicit and formal specifications for the agents negotiating in an E-business environment; especially, NACM defines the negotiation language template shared among all agents formally and explicitly. The novelty of the communication model is twofold.

  6. Modeling agents with a theory of mind

    NARCIS (Netherlands)

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.

    2009-01-01

    Training systems with intelligent virtual agents provide an effective means to train people for complex, dynamic tasks like crisis management or firefighting. Virtual agents provide more adequate behavior and explanations if they not only take their own goals and beliefs into account, but also the a

  7. Modeling of Agent Behavior Using Behavioral Specifications

    NARCIS (Netherlands)

    Sharpanskykh, A.; Treur, J.

    2006-01-01

    The behavioral dynamics of a cognitive agent can be considered both from an external and an internal perspective. From the external perspective, behavior is described by specifying (temporal) correlations between input and output states of the agent. From the internal perspective the agent’s dynamic

  8. 31 CFR 330.9 - Fiscal agents.

    Science.gov (United States)

    2010-07-01

    ... OF UNITED STATES SAVINGS BONDS AND UNITED STATES SAVINGS NOTES (FREEDOM SHARES) § 330.9 Fiscal agents. (a) The Federal Reserve Banks referred to below, as fiscal agents of the United States, are... Reserve Bank, Buffalo Branch, P.O. Box 961, Buffalo, NY 14240 New York, Boston CT, MA, ME, NH,...

  9. 31 CFR 342.9 - Fiscal agents.

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS NOTES § 342.9 Fiscal agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of the United States..., Buffalo, NY 14240 New York, Boston CT, MA, ME, NH, NJ (northern half), NY (City & State), RI, VT,...

  10. Transient Diversity in Multi-Agent Systems

    OpenAIRE

    Lyback, David

    2003-01-01

    Diversity is an important aspect of highly efficient multi-agent teams. We introduce the main factors that drive a multi-agent system in either direction along the diversity scale. A metric for diversity is described, and we speculate on the concept of transient diversity. Finally, an experiment on social entropy using a RoboCup simulated soccer team is presented.

  11. Semantics of Agent Communication: An Introduction

    NARCIS (Netherlands)

    Eijk, R.M. van

    2002-01-01

    Communication has been one of the salient issues in the research on concurrent and distributed systems. This holds no less for the research on multiagent systems. Over the last few years the study of agent communication, and in particular the semantics of agent communication, has attracted increased

  12. Agent-based simulation of animal behaviour

    NARCIS (Netherlands)

    Jonker, C.M.; Treur, J.

    1998-01-01

    In this paper it is shown how animal behaviour can be simulated in an agent-based manner. Different models are shown for different types of behaviour, varying from purely reactive behaviour to pro-active, social and adaptive behaviour. The compositional development method for multi-agent systems DES

  13. Assurance in Agent-Based Systems

    International Nuclear Information System (INIS)

    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

  14. Practice among Novice Change Agents in Schools

    Science.gov (United States)

    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…

  15. VIRAL GASTROENTERITIS AGENTS AND WATERBORNE DISEASE

    Science.gov (United States)

    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 ...

  16. Modelling cooperative agents in infrastructure networks

    NARCIS (Netherlands)

    Ligtvoet, A.; Chappin, E.J.L.; Stikkelman, R.M.

    2010-01-01

    This paper describes the translation of concepts of cooperation into an agent-based model of an industrial network. It first addresses the concept of cooperation and how this could be captured as heuristical rules within agents. Then it describes tests using these heuristics in an abstract model of

  17. Freeze conditioning agents ease winter railcar unloading

    Energy Technology Data Exchange (ETDEWEB)

    Olson, G.E.

    1982-02-01

    A US midwest utility's freeze control programme is described. All coal is treated with a glycol-based freeze control agent. Some rail wagons were treated with a side release agent which stops coal sticking to the metal wagon. The use of calcium chloride or heat to thaw frozen coal is also discussed.

  18. Explanation in human-agent teamwork

    NARCIS (Netherlands)

    Harbers, M.; Bradshaw, J.M.; Johnson, M.; Feltovich, P.; Bosch, K. van den; Meyer, J.J.C.

    2012-01-01

    There are several applications in which humans and agents jointly perform a task. If the task involves interdependence among the team members, coordination is required to achieve good team performance. This paper discusses the role of explanation in coordination in human-agent teams. Explanations ab

  19. Agent programming languages: programming with mental models

    NARCIS (Netherlands)

    Hindriks, K.V.

    2001-01-01

    Intelligent Agents are personal assistants which can provide proactive support to users by executing routine activities like searching on the Internet, the scheduling of meetings, etc. The concept of an Intelligent Agent has its roots in Artificial Intelligence and provides a basis for the con

  20. PU Sizing Agent Sector Starts Reform

    Institute of Scientific and Technical Information of China (English)

    Wang Lei

    2007-01-01

    @@ Polyurethane (PU) sizing agent is a thermoplastic PU elastomer extensively used in synthetic leather, artificial deerskin and electrostatic flocking sectors. The drastic production and demand increase of synthetic leather in China in recent years has promoted rapid consumption growth of PU sizing agent.