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Sample records for anti-hiv agents

  1. G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents.

    Science.gov (United States)

    Musumeci, Domenica; Riccardi, Claudia; Montesarchio, Daniela

    2015-09-22

    Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.

  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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Synthesis of new 2,3-diaryl-1,3-thiazolidin-4-ones as anti-HIV agents.

    Science.gov (United States)

    Rao, Angela; Balzarini, Jan; Carbone, Anna; Chimirri, Alba; De Clercq, Erik; Monforte, Anna Maria; Monforte, Pietro; Pannecouque, Christophe; Zappalà, Maria

    2004-01-01

    Several 2,3-diaryl-1,3-thiazolidin-4-ones were synthesized and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of HIV-1 replication at 30-50 nM concentrations with minimal cytotoxicity, thereby acting as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs).

  4. Structure-activity relationship study of phenylpyrazole derivatives as a novel class of anti-HIV agents.

    Science.gov (United States)

    Mizuhara, Tsukasa; Kato, Takayuki; Hirai, Atsushi; Kurihara, Hideki; Shimada, Yasuhiro; Taniguchi, Masahiko; Maeta, Hideki; Togami, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Okazaki, Shiho; Takeuchi, Tomoki; Ohno, Hiroaki; Oishi, Shinya; Fujii, Nobutaka

    2013-08-15

    The structure-activity relationship of phenylpyrazole derivative 1 was investigated for the development of novel anti-HIV agents. Initial efforts revealed that the diazenyl group can be replaced by an aminomethylene group. In addition, we synthesized various derivatives by the reductive amination of benzaldehydes with 5-aminopyrazoles and carried out parallel structural optimization on the benzyl group and the pyrazole ring. This optimization led to a six-fold more potent derivative 32j than the lead compound 1, and this derivative has a 3',4'-dichloro-(1,1'-biphenyl)-3-yl group. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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    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

  6. Diarylpyrimidine-dihydrobenzyloxopyrimidine hybrids: new, wide-spectrum anti-HIV-1 agents active at (sub)-nanomolar level.

    Science.gov (United States)

    Rotili, Dante; Tarantino, Domenico; Artico, Marino; Nawrozkij, Maxim B; Gonzalez-Ortega, Emmanuel; Clotet, Bonaventura; Samuele, Alberta; Esté, José A; Maga, Giovanni; Mai, Antonello

    2011-04-28

    Here, we describe a novel small series of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that combine peculiar structural features of diarylpyrimidines (DAPYs) and dihydro-alkoxy-benzyl-oxopyrimidines (DABOs). These DAPY-DABO hybrids (1-4) showed a characteristic SAR profile and a nanomolar anti-HIV-1 activity at both enzymatic and cellular level. In particular, the two compounds 4d and 2d, with a (sub)nanomolar activity against wild-type and clinically relevant HIV-1 mutant strains, were selected as lead compounds for next optimization studies.

  7. A novel class of anti-HIV agents with multiple copies of enfuvirtide enhances inhibition of viral replication and cellular transmission in vitro.

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    Chien-Hsing Chang

    Full Text Available We constructed novel HIV-1 fusion inhibitors that may overcome the current limitations of enfuvirtide, the first such therapeutic in this class. The three prototypes generated by the Dock-and-Lock (DNL technology to comprise four copies of enfuvirtide tethered site-specifically to the Fc end of different humanized monoclonal antibodies potently neutralize primary isolates (both R5-tropic and X4-tropic, as well as T-cell-adapted strains of HIV-1 in vitro. All three prototypes show EC(50 values in the subnanomolar range, which are 10- to 100-fold lower than enfuvirtide and attainable whether or not the constitutive antibody targets HIV-1. The potential of such conjugates to purge latently infected cells was also demonstrated in a cell-to-cell viral inhibition assay by measuring their efficacy to inhibit the spread of HIV-1(LAI from infected human peripheral blood mononuclear cells to Jurkat T cells over a period of 30 days following viral activation with 100 nM SAHA (suberoylanilide hydroxamic acid. The IgG-like half-life was not significantly different from that of the parental antibody, as shown by the mean serum concentration of one prototype in mice at 72 h. These encouraging results provide a rationale to develop further novel anti-HIV agents by coupling additional antibodies of interest with alternative HIV-inhibitors via recombinantly-produced, self-assembling, modules.

  8. Design, Synthesis, and Biological Evaluation of 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole Derivatives as Anti-HIV-1 Agents.

    Science.gov (United States)

    Ashok, Penta; Lu, Cui-Lin; Chander, Subhash; Zheng, Yong-Tang; Murugesan, Sankarnarayanan

    2015-06-01

    A novel series of 1-(thiophen-2-yl)-9H-pyrido [3,4-b]indole derivatives were synthesized using DL-tryptophan as starting material. All the compounds were characterized by spectral analysis such as (1) H NMR, Mass, IR, elemental analysis and evaluated for inhibitory potency against HIV-1 replication. Among the reported analogues, compound 7g exhibited significant anti-HIV activity with EC(50) 0.53 μm and selectivity index 483; compounds 7e, 7i, and 7o displayed moderate activity with EC(50) 3.8, 3.8, and 2.8 μm and selectivity index >105, >105, and 3.85, respectively. Interestingly, compound 7g inhibited p24 antigen expression in acute HIV-1(IIIB) infected cell line C8166 with EC50 1.1 μm. In this study, we also reported the Lipinski rule of 5 parameters, predicted toxicity profile, drug-likeness, and drug score of the synthesized analogues. © 2014 John Wiley & Sons A/S.

  9. Development of a Novel Anti-HIV-1 Agent from within: Effect of Chimeric Vpr-Containing Protease Cleavage Site Residues on Virus Replication

    Science.gov (United States)

    Serio, D.; Rizvi, T. A.; Cartas, M.; Kalyanaraman, V. S.; Weber, I. T.; Koprowski, H.; Srinivasan, A.

    1997-04-01

    Effective antiviral agents will be of great value in controlling virus replication and delaying the onset of HIV-1-related disease symptoms. Current therapy involves the use of antiviral agents that target the enzymatic functions of the virus, resulting in the emergence of resistant viruses to these agents, thus lowering their effectiveness. To overcome this problem, we have considered the idea of developing novel agents from within HIV-1 as inhibitors of virus replication. The specificity of the Vpr protein for the HIV-1 virus particle makes it an attractive molecule for the development of antiviral agents targeting the events associated with virus maturation. We have generated chimeric Vpr proteins containing HIV-1-specific sequences added to the C terminus of Vpr. These sequences correspond to nine cleavage sites of the Gag and Gag-Pol precursors of HIV-1. The chimeric Vpr constructs were introduced into HIV-1 proviral DNA to assess their effect on virus infectivity using single- and multiple-round replication assays. The virus particles generated exhibited a variable replication pattern depending on the protease cleavage site used as a fusion partner. Interestingly, the chimeric Vpr containing the cleavage sequences from the junction of p24 and p2, 24/2, completely abolished virus infectivity. These results show that chimeric proteins generated from within HIV-1 have the ability to suppress HIV-1 replication and make ideal agents for gene therapy or intracellular immunization to treat HIV-1 infection.

  10. Anti-HIV activity of extracts and compounds from marine algae.

    Science.gov (United States)

    Kim, Se-Kwon; Karadeniz, Fatih

    2011-01-01

    In recent years, elucidation of novel bioactive substances from different marine organisms is gaining importance rapidly not only from the research and publications but also from controlled clinical studies of natural product-derived substances. They offer important leads for the development of antiviral drugs against viral infections caused by human immunodeficiency virus type 1 (HIV-1). Regarding this issue, numerous anti-HIV-1 therapeutic agents from marine resources have been reported for their potential medicine/medical application as novel functional ingredients in anti-HIV therapy. In detail, marine macroalgae have attracted much of attention as a reliable source for potential anti-HIV compounds. Up to date, several types of compounds such as tannins, polysaccharides, lectins, and derivatives have been isolated, identified, and reported to possess significant anti-HIV-1 activity. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Science.gov (United States)

    Behbahani, Mandana

    2014-01-01

    Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs) used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR) assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50) values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  12. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Directory of Open Access Journals (Sweden)

    Mandana Behbahani

    Full Text Available Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50 values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  13. New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity.

    Science.gov (United States)

    Romanucci, Valeria; Zarrelli, Armando; Liekens, Sandra; Noppen, Sam; Pannecouque, Christophe; Di Fabio, Giovanni

    2018-02-10

    The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV agents has been extensively reported in the literature over the last years. In the light of our recent results regarding the slow G-quadruplex folding kinetics of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV screening to investigate the impact of the G-quadruplex folding on their anti-HIV activity. In particular, varying the single stranded concentrations of ODNs, it has been tested a pool of ODN sample solutions with different G-quadruplex concentrations. The anti-HIV assays have been designed favouring the limited kinetics involved in the tetramolecular G4-association based on the d(TGGGAG) sequence. Aiming to determine the stoichiometry of G-quadruplex structures in the same experimental conditions of the anti-HIV assays, a native gel electrophoresis was performed. The gel confirmed the G-quadruplex formation for almost all sample solutions while showing the formation of high order G4 structures for the more concentrated ODNs solutions. The most significant result is the discovery of a potent anti-HIV activity of the G-quadruplex formed by the natural d(TGGGAG) sequence (IC 50  = 14 nM) that, until now, has been reported to be completely inactive against HIV infection. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Lectins with Anti-HIV Activity: A Review

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    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.

  15. Isolation of anti-HIV-1 lignans from Larrea tridentata by counter-current chromatography.

    Science.gov (United States)

    Gnabre, J N; Ito, Y; Ma, Y; Huang, R C

    1996-01-08

    Several lignans, mostly new, were isolated from Larrea tridentata by assay-guided counter-current chromatography (CCC). Using the secreted alkaline phosphatase bioassay of HIV Tat transactivation and the two-phase hexane-ethyl acetate-methanol-water solvent system, two major components (Gr and Lo) were identified as anti-HIV active principles. The chemical structures of the constituents of Gr (G1-G4) and Lo (L1-L4) were determined by GC-MS and NMR. After optimization of isolation conditions, a large-scale isolation with the chloroform-methanol-water system yielded five constituents (FB1-FB5). The most predominant anti-HIV compound FB2 (denoted Malachi 4:5-6 or mal.4), which occurs in 0.23% yield, was separated from its FB1 isomer (0.13% yield). Compound FB4 and two tricyclic lignans (FB3 and FB5) were also isolated in a substantial amount for further testing of their anti-HIV activities. These compounds may represent a new class of anti-HIV agents with important clinical relevance.

  16. Quarter Century of Anti-HIV CAR T Cells.

    Science.gov (United States)

    Wagner, Thor A

    2018-04-01

    A therapy that might cure HIV is a very important goal for the 30-40 million people living with HIV. Chimeric antigen receptor T cells have recently had remarkable success against certain leukemias, and there are reasons to believe they could be successful for HIV. This manuscript summarizes the published research on HIV CAR T cells and reviews the current anti-HIV chimeric antigen receptor strategies. Research on anti-HIV chimeric antigen receptor T cells has been going on for at least the last 25 years. First- and second-generation anti-HIV chimeric antigen receptors have been developed. First-generation anti-HIV chimeric antigen receptors were studied in clinical trials more than 15 years ago, but did not have meaningful clinical efficacy. There are some reasons to be optimistic about second-generation anti-HIV chimeric antigen receptor T cells, but they have not yet been tested in vivo.

  17. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

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    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  18. Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7.

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    Yaoqing Chen

    Full Text Available For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1. In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC(50 value of 2.76 µg/ml (1.65 µM and showed low cytotoxicity to host cells with a selective index (SI of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.

  19. 2'-Deoxythymidine Adducts from the Anti-HIV Drug Nevirapine

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    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.

  20. Qualitative and quantitative intravaginal targeting: Key to anti-HIV-1 microbicide delivery from test tube to in vivo success

    CSIR Research Space (South Africa)

    Pillay, V

    2012-06-01

    Full Text Available MASHINGAIDZE,1 YAHYA E. CHOONARA,1 LISA C. DU TOIT,1 ECKHART BUCHMANN,2 VINESH MAHARAJ,3 VALENCE M. K. NDESENDO,4 PRADEEP KUMAR1 1Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, 2193..., Pretoria, South Africa 4School of Pharmacy and Pharmaceutical Sciences, St. John?s University of Tanzania, Dodoma, Tanzania ABSTRACT: The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint...

  1. Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5'-alpha-hydroxyphosphonates.

    Science.gov (United States)

    Szymańska, Agnieszka; Szymczak, Marzena; Boryski, Jerzy; Stawiński, Jacek; Kraszewski, Adam; Collu, Gabriella; Sanna, Giseppina; Giliberti, Gabriele; Loddo, Roberta; La Colla, Paolo

    2006-03-15

    Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosphonates 2 correlates well with the type and extent of their chemical or enzymatic degradation in culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides.

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

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    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

  3. Natural Products as Anti- HIV Agents | Adesegun | Nigerian ...

    African Journals Online (AJOL)

    The present report gives a concise account of the efforts of Traditional practitioners and herbal scientists or Pharmacognocists at unraveling promising natural products of terrestrial (plants) and marine origins with activity against the HIV. A wide range of plants and marine organism's families and origins, containing various ...

  4. AIDS: Anti-HIV Agents, Therapies, and Vaccines

    Science.gov (United States)

    1990-12-26

    M. GALLO, F. D. BOUDINOT, AND R. F. SCHINAZI " Department of Medicinal Chemistry and Pharmacognosy and Department oj Pharmaceutics College of... Pharmacognosy Purdue Universit v West Lafayette. Indiana 47907 Treatment of a mixture of salicylic acid and formaldehyde vith sulfuric acid and sodium...8217 STUART W. SN’YDER, AND S FEPHEN OROSZLAN’ hDepartinent of Medicinal Chemistry and Pharmacognosy Purdue University West Lafayette, Indiana 47907 "Laboro

  5. Characterization of Nanodiamond-based anti-HIV drug Delivery to the Brain.

    Science.gov (United States)

    Roy, Upal; Drozd, Vadym; Durygin, Andriy; Rodriguez, Jesse; Barber, Paul; Atluri, Venkata; Liu, Xiaohua; Voss, Thomas G; Saxena, Surendra; Nair, Madhavan

    2018-01-25

    Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the ineffective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature-making it a more efficient drug carrier than other carbon-based materials. Considering its potential and importance, we have characterized unmodified and surface-modified (-COOH and -NH 2 ) nanodiamond for its capacity to load the anti-HIV-1 drug efavirenz and cytotoxicity, in vitro. Overall, our study has established that unmodified nanodiamond conjugated drug formulation has significantly higher drug loading capacity than surface-modified nanodiamond with minimum toxicity. Further, this nanodrug formulation was characterized by its drug dissolution profile, transmigration through the BBB, and its therapeutic efficacy. The present biological characterizations provide a foundation for further study of in-vivo pharmacokinetics and pharmacodynamics of nanodiamond-based anti-HIV drugs.

  6. Testing of viscous anti-HIV microbicides using Lactobacillus

    OpenAIRE

    Moncla, B.J.; Pryke, K.; Rohan, L. C.; Yang, H.

    2011-01-01

    The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30 min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To...

  7. Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors

    Science.gov (United States)

    Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Santos, Fernanda da Costa; Batalha, Pedro Netto; Brozeguini, Leonardo; Seidl, Peter R.; de Alencastro, Ricardo Bicca; Cunha, Anna Cláudia; de Souza, Maria Cecília B. V.; Ferreira, Vitor F.; Giongo, Viveca A.; Cirne-Santos, Cláudio; Paixão, Izabel C. P.

    2014-09-01

    Although there are many antiviral drugs available for the treatment of herpes simplex virus (HSV) infections, still the synthesis of new anti-HSV candidates is an important strategy to be pursued, due to the emergency of resistant HSV strains mainly in human immunodeficiency virus (HIV) co-infected patients. Some 1,4-dihydro-4-oxoquinolines, such as PNU-183792 (1), show a broad spectrum antiviral activity against human herpes viruses, inhibiting the viral DNA polymerase (POL) without affecting the human POLs. Thus, on an ongoing antiviral research project, our group has synthesized ribonucleosides containing the 1,4-dihydro-4-oxoquinoline (quinolone) heterocyclic moiety, such as the 6-Cl derivative (2), which is a dual antiviral agent (HSV-1 and HIV-1). Molecular dynamics simulations of the complexes of 1 and 2 with the HSV-1 POL suggest that structural modifications of 2 should increase its experimental anti-HSV-1 activity, since its ribosyl and carboxyl groups are highly hydrophilic to interact with a hydrophobic pocket of this enzyme. Therefore, in this work, comparative molecular docking simulations of 1 and three new synthesized oxoquinoline-acylhydrazone HIV-1 inhibitors (3-5), which do not contain those hydrophilic groups, were carried out, in order to access these modifications in the proposition of new potential anti-HSV-1 agents, but maintaining the anti-HIV-1 activity. Among the docked compounds, the oxoquinoline-acylhydrazone 3 is the best candidate for an anti-HSV-1 agent, and, in addition, it showed anti-HIV-1 activity (EC50 = 3.4 ± 0.3 μM). Compounds 2 and 3 were used as templates in the design of four new oxoquinoline-acylhydrazones (6-9) as potential anti-HSV-1 agents to increase the antiviral activity of 2. Among the docked compounds, oxoquinoline-acylhydrazone 7 was selected as the best candidate for further development of dual anti-HIV/HSV activity.

  8. Evaluation of anti-HIV-1 activity of a new iridoid glycoside isolated from Avicenna marina, in vitro.

    Science.gov (United States)

    Behbahani, Mandana

    2014-11-01

    This study was carried out to check the efficacy of methanol seed extract of Avicenna marina and its column chromatographic fractions on Peripheral Blood Mono nuclear Cells (PBMCs) toxicity and HIV-1 replication. The anti-HIV-1 activities of crude methanol extract and its fractions were performed by use of real-time polymerase chain reaction (PCR) assay and HIV-1 p24 antigen kit. A time of drug addiction approach was also done to identify target of anti-HIV compound. The activity of the extracts on CD4, CD3, CD19 and CD45 expression in lymphocytes population was performed by use of flow cytometry. The most active anti-HIV agent was detected by spectroscopic analysis as 2'-O-(4-methoxycinnamoyl) mussaenosidic acid. The apparent effective concentrations for 50% virus replication (EC50) of methanol extract and iridoid glycoside were 45 and 0.1 μg/ml respectively. The iridoid glycoside also did not have any observable effect on the proportion of CD4, CD3, CD19 and CD45 cells or on the intensity of their expressions on PBMCs. In addition, the expression level of C-C chemokine receptor type 5 (CCR5) and chemokine receptor type 4 (CXCR4) on CD4(+) T cells were decreased in cells treated with this iridoid glycoside. The reduction of these two HIV coreceptors and the result of time of addition study demonstrated that this iridoid glycoside restricts HIV-1 replication on the early stage of HIV infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Screening inhibitory potential of anti-HIV RT RNA aptamers.

    Science.gov (United States)

    Lange, Margaret J; Burke, Donald H

    2014-01-01

    Aptamers targeted to HIV reverse transcriptase (RT) have been demonstrated to inhibit RT in biochemical assays and as in cell culture. However, methods employed to date to evaluate viral suppression utilize time-consuming serial passage of infectious HIV in aptamer-expressing stable cell lines. We have established a rapid, transfection-based assay system to effectively examine the inhibitory potential of anti-HIV RT aptamers expressed between two catalytically inactive hammerhead ribozymes. Our system can be altered and optimized for a variety of cloning schemes, and addition of sequences of interest to the cassette is simple and straightforward. When paired with methods to analyze aptamer RNA accumulation and localization in cells and as packaging into pseudotyped virions, the method has a very high level of success in predicting good inhibitors.

  10. Efavirenz Mannich bases: synthesis, anti-HIV and antitubercular activities.

    Science.gov (United States)

    Sriram, Dharmarajan; Banerjee, Debjani; Yogeeswari, Perumal

    2009-02-01

    A series of efavirenz Mannich bases has been synthesized by reacting efavirenz, formaldehyde, and various aryl substituted piperazines using microwave irradiation (yield 35-88%). The synthesized compounds were evaluated for in-vitro anti-HIV and antimycobacterial activities. The in-vitro antiretroviral activities indicated that compound 7-(4-((6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2-oxo-2H-benzo[d] [1,3]oxazin-1 (4H)-yl)methyl)-3-methylpiperazin-l -yl)-1-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (4i) was equipotent to efavirenz with EC(50) of 2.4 nM. Compound 4i also inhibited M. tuberculosis with minimum inhibitory concentration of 0.2 microg/mL.

  11. 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.

  12. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  13. [Retrospective evaluation of HBsAg, anti-HCV, anti-HIV and syphilis reagin antibody seropositivity in blood donors at the Trabzon Farabi Hospital].

    Science.gov (United States)

    Aydin, Faruk; Cubukçu, Kivanç; Yetişkul, Serpil; Yazici, Yelda; Kaklikkaya, Neşe

    2002-01-01

    Transfusion of blood and blood products is a widely used method for therapy in medicine, however it may result with the transmission of infectious agents from donor to recipient. In order to achieve safe blood transfusions and to minimize post-transfusion infections, several screening tests for infectious agents are routinely done all around the world as well as in our country. In this study, HBsAg, anti-HCV, anti-HIV and syphilis reagin antibody tests results have been retrospectively evaluated for 33.766 blood donors during January 1, 1997 to December 31, 2000 in Blood Center of Farabi Hospital, Black Sea Technical University. Testing for HBsAg, anti-HIV and anti-HCV has been done by using commercially available micro and/or macro enzyme immunoassays, and syphilis reagin antibody test by latex agglutination (RPR) method. The indeterminate results were confirmed by retesting of sera with microparticle enzyme immunoassay and Western blot methods. As a result, in 1331 (3.94%) subjects HBsAg, in 250 (0.74%) subjects anti-HCV, and in 161 (0.47%) subjects RPR were found positive. Twenty samples which have had the results in gray-zone for anti-HIV, have been found negative with the confirmation tests.

  14. Synthesis and evaluation of the anti-HIV activity of aza and deaza analogues of isoddA and their phosphates as prodrugs.

    Science.gov (United States)

    Franchetti, P; Cappellacci, L; Grifantini, M; Messini, L; abu Sheikha, G; Loi, A G; Tramontano, E; de Montis, A; Spiga, M G; La Colla, P

    1994-10-14

    Some aza and deaza analogues of the anti-HIV agent 2',3'-dideoxy-3'-oxoadenosine (isoddA) (8-aza-, 8-aza-1-deaza, 8-aza-3-deaza-, 1-deaza-, and 3-deaza-isoddA) were synthesized and found inactive against HIV in vitro. The hypothesis that the inactivity of these isonucleosides might be due to their poor affinity for cellular nucleoside kinases was checked by the synthesis of a series of 5'-[bis(2,2,2-trichloroethyl) phosphate] triesters and 5'-phenyl phosphoramidate derivatives which, acting as membrane soluble prodrugs, could release the free phosphate form inside the cell. The 5'-(phenylmethoxy)alaninyl phosphate derived from 8-aza-isoddA was found active against HIV-1 and HIV-2 with a potency similar to that of isoddA, while the anti-HIV potency of 5'-(phenylmethoxy)alaninyl phosphate of isoddA proved remarkably higher than that of isoddA, in particular against HIV-2, being similar to that of AZT. Further evidence that 8-aza-isoddA could behave as anti-HIV agent, provided that it is activated as phosphate, was obtained by the synthesis of its 5'-triphosphate derivative, which proved to be an active inhibitor of HIV-1 recombinant reverse transcriptase.

  15. Estimation of Anti-HIV Activity of HEPT Analogues Using MLR, ANN, and SVM Techniques.

    Science.gov (United States)

    Shaik, Basheerulla; Zafar, Tabassum; Agrawal, Vijay K

    2013-01-01

    The present study deals with the estimation of the anti-HIV activity (log1/C) of a large set of 107 HEPT analogues using molecular descriptors which are responsible for the anti-HIV activity. The study has been undertaken by three techniques MLR, ANN, and SVM. The MLR model fits the train set with R (2)=0.856 while in ANN and SVM with higher values of R (2) = 0.850, 0.874, respectively. SVM model shows improvement to estimate the anti-HIV activity of trained data, while in test set ANN have higher R (2) value than those of MLR and SVM techniques. R m (2) = metrics and ridge regression analysis indicated that the proposed four-variable model MATS5e, RDF080u, T(O⋯O), and MATS5m as correlating descriptors is the best for estimating the anti-HIV activity (log 1/C) present set of compounds.

  16. Testing of viscous anti-HIV microbicides using Lactobacillus.

    Science.gov (United States)

    Moncla, B J; Pryke, K; Rohan, L C; Yang, H

    2012-02-01

    The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To demonstrate the toxicity of formulated products a new assay was developed for use with viscous and non-viscous samples that we have termed the Lactobacillus toxicity test. We found that the vortex mixing of vaginal Lactobacillus species can lead to reductions in bacterial viability. Lactobacillus can survive briefly, about 2s, but viability declines with increased vortex mixing. The addition of heat inactivated serum or bovine serum albumin, but not glycerol, prevented the decrease in bacterial viability. Bacillus atrophaeus spores also demonstrated loss of viability upon extended mixing. We observed that many of the excipients used in film formulation and the films themselves also afford protection from the killing during vortex mixing. This method is of relevance for toxicity for cidal activities of viscous products. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Anti-HIV therapy with AZT prodrugs: AZT phosphonate derivatives, current state and prospects.

    Science.gov (United States)

    Khandazhinskaya, Anastasiya; Matyugina, Elena; Shirokova, Elena

    2010-06-01

    AIDS, a disease caused by human immunodeficiency virus, was called 'plague of the twentieth century'. 3'-Azido-3'-deoxythymidine (AZT), the first compound approved for the treatment of HIV, is still a mandatory component of treatment schemes. However, its toxicity stimulated a search for new agents. This review presents the history and current state of the design of AZT prodrugs based on its phosphonate derivatives. Although every effort was made to include as many AZT structures bearing phosphonate residues and demonstrate the variety they offer, we also concentrated on the studies performed in our laboratory. Special attention was also paid to AZT 5'-H-phosphonate (phosphazide, Nikavir) approved in the Russian Federation as a drug for the prevention and treatment of HIV infection. The prodrug strategy applied to AZT phosphonate derivatives enriched chemistry, biology and medicine not only with new knowledge, methods and structures, but also with a new anti-HIV drug Nikavir. Currently, study of another phosphonate, AZT 5'-aminocarbonylphosphonate, is underway. Slow release of AZT following oral administration and penetration into cells, decreased toxicity and the lack of cumulative properties make the compounds of this group promising as extended-release forms of AZT.

  18. 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.

  19. WHI-05, a novel bromo-methoxy substituted phenyl phosphate derivative of zidovudine, is a dual-action spermicide with potent anti-HIV activity.

    Science.gov (United States)

    D'Cruz, O J; Zhu, Z; Yiv, S H; Chen, C L; Waurzyniak, B; Uckun, F M

    1999-05-01

    potent anti-HIV agent that has spermicidal activity and is devoid of mucosal toxicity, WHI-05 shows a unique clinical potential to become the active ingredient for a vaginal contraceptive for women who are at high risk for acquiring HIV by heterosexual vaginal transmission.

  20. Synthesis of a Cholesteryl-HEG Phosphoramidite Derivative and Its Application to Lipid-conjugates of the Anti-HIV 5'TGGGAG3' Hotoda’s Sequence

    Directory of Open Access Journals (Sweden)

    Domenica Musumeci

    2012-10-01

    Full Text Available A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxycholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming 5'TGGGAG3' oligomer, known as the Hotoda’s sequence, to produce new potential anti-HIV agents.

  1. Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

    International Nuclear Information System (INIS)

    Shi Weiguo; Qi Zhi; Pan Chungen; Xue Na; Debnath, Asim K.; Qie Jiankun; Jiang Shibo; Liu Keliang

    2008-01-01

    The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins

  2. Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

    Science.gov (United States)

    Giri, Namita; Oh, Byeongtaek; Lee, Chi H.

    2016-05-01

    This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100® (ES100®), a pH-sensitive polymer. ES100® NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100® NPs. The morphology of the ES100® NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100® NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100® NPs had zeta potential in the range of -5 to -10 mV. In-vitro release studies displayed the potential benefits of ES100® NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100® NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100® NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100® NPs were taken by vaginal epithelial cells through the endocytosis

  3. Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

    Energy Technology Data Exchange (ETDEWEB)

    Giri, Namita; Oh, Byeongtaek; Lee, Chi H., E-mail: leech@umkc.edu [University of Missouri at Kansas City, Division of Pharmaceutical Sciences (United States)

    2016-05-15

    This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100{sup ®} (ES100{sup ®}), a pH-sensitive polymer. ES100{sup ®} NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100{sup ®} NPs. The morphology of the ES100{sup ®} NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100{sup ®} NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100{sup ®} NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100{sup ®} NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100{sup ®} NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100{sup ®} NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100{sup

  4. Stimuli-sensitive nanoparticles for multiple anti-HIV microbicides

    International Nuclear Information System (INIS)

    Giri, Namita; Oh, Byeongtaek; Lee, Chi H.

    2016-01-01

    This study is aimed to develop and evaluate an advanced intravaginal formulation for the delivery of multiple anti-HIV microbicides. Novel stimuli-sensitive nanoparticles (NPs) which protected the encapsulated drugs from being degraded in acidic pH conditions were made of Eudragit S-100 ® (ES100 ® ), a pH-sensitive polymer. ES100 ® NPs were prepared using the quasi-emulsion solvent diffusion technique and loaded with two microbicides namely Tenofovir (TNF) and Etravirine (ETV). The effects of various fabrication parameters on the formulation properties were evaluated for the optimization of ES100 ® NPs. The morphology of the ES100 ® NPs was examined by scanning electron microscopy. The cytotoxicity of NPs containing microbicides individually or in a combination was assessed using cell viability and trans-epithelial electrical resistance (TEER) measurements. The cellular uptake rates of the model microbicides by human vaginal epithelial cells, VK2 E6/E7 cells, were evaluated using confocal microscopy and florescence-assisted cell sorting technique. ES100 ® NPs had a spherical shape, smooth surface, and uniform texture with a little aggregation. The average particle size for NPs loaded with TNF ranged from 125 to 230 nm, whereas those for ETV-loaded NPs ranged from 160 to 280 nm. ES100 ® NPs had zeta potential in the range of −5 to −10 mV. In-vitro release studies displayed the potential benefits of ES100 ® NPs in retaining and protecting the loaded microbicides at vaginal pH (acidic), but immediately releasing them as the pH changes to neutral or 7.4 (physiological pH). Cell viability studies demonstrated that ES100 ® NPs did not exert any cytotoxicity individually or in a combination of both microbicides. TEER measurements confirmed that ES100 ® NPs loaded with TNF and ETV did not cause any changes in the barrier integrity of VK2 E6/E7 cell monolayer. The cellular uptake study revealed that ES100 ® NPs were taken by vaginal epithelial cells

  5. Anti-HIV-1 protease activities of crude extracts of some Garcinia ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-22

    Mar 22, 2010 ... indicated significant HIV-1 protease inhibition (Chen et al., 1996). Garcinia livingstoneii has been reported to produce gutifferone A, being an anti-HIV ..... Abe F, Estrada MJ, Soler C, Chilpa RR. (2004). HIV-1 inhibitory compounds from Calophyllum brasiliense leaves. Biol. Pharm. Bull. 27: 1471-1475.

  6. A Survey of Plants with Anti-HIV Active Compounds and their Modes ...

    African Journals Online (AJOL)

    Background: Several limitations of current antiretroviral therapy (ART) programmes will continue to push patients towards the use of plants to manage HIV/AIDS. However, evidence about the use of anti-HIV plants is anecdotal. Objectives: Search the literature for research articles that document plants with anti-HIV ...

  7. Effect of expressing an anti-HIV lectin, Griffithsin, in different plant cellular compartments

    CSIR Research Space (South Africa)

    Stark, T

    2010-08-01

    Full Text Available the Human Immunodeficiency Virus (HIV) in vitro in very low quantities. The molecular target of GRFT is the high mannose residues on the viral gp120 coat protein. Low cost production of GRFT and other anti-HIV drugs at minimal costs is crucial seeing...

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

    NARCIS (Netherlands)

    Kuipers, M E; Swart, P J; Schutten, Martin; Smit, C; Proost, J H; Osterhaus, A D; Meijer, D K

    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

  9. Synthesis and anti-HIV Activity of New 3'-O-Phosphonomethyl Nucleosides

    Czech Academy of Sciences Publication Activity Database

    Česnek, Michal; Herdewijn, P.

    2010-01-01

    Roč. 82, č. 1 (2010), s. 663-687 ISSN 0385-5414 Institutional research plan: CEZ:AV0Z40550506 Keywords : anti-HIV * 4-(S)-ethynyl nucleotides * PMDTT Subject RIV: CC - Organic Chemistry Impact factor: 1.093, year: 2010

  10. Photo-translocation of anti-HIV-1 drugs into TZM-bl cells

    CSIR Research Space (South Africa)

    Khanyile, T

    2013-04-01

    Full Text Available Targeted drug delivery into HIV-1 infected cells offers a reduction in toxicity and side effect. Using a femtosecond (fs) laser of different beam shapes anti-HIV-1 drugs are efficiently delivered into TZM-bl cells....

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

    DEFF Research Database (Denmark)

    Valsaraj, R.; Pushpangadan, P.; Wagner Smitt, U.

    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...

  12. Mechanism of anti-HIV activity of succinylated human serum albumin

    NARCIS (Netherlands)

    Kuipers, ME; Berg, HVD; Swart, PJ; Laman, Jon; Meijer, DKF; Kopelman, MHGM; Huisman, H

    1999-01-01

    In the present study, we described the interaction of succinylated human serum albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1 gp120 and in detail with the third variable domain of gp120 (V3 loop). To this end, different assay formats were tested in which gp120- and

  13. Structural and functional analysis of negatively charged milk proteins with anti-HIV activity

    NARCIS (Netherlands)

    Berkhout, B.; Derksen, G. C.; Back, N. K.; Klaver, B.; de Kruif, C. G.; Visser, S.

    1997-01-01

    Several polyanionic reagents such as dextran sulfates, heparin sulfates, and negatively charged proteins have been reported to exhibit anti-HIV activity in vitro. Particularly potent inhibition has been reported for the milk protein beta-lactoglobulin (betaLG) on modification by 3-hydroxyphthalic

  14. An improved microtiter assay for evaluating anti-HIV-1 neutralizing antibodies from sera or plasma

    Directory of Open Access Journals (Sweden)

    Chen Yunyun

    2003-12-01

    Full Text Available Abstract Background The anti-HIV-1 neutralizing antibody assay is widely used in AIDS vaccine research and other experimental and clinical studies. The vital dye staining method applied in the detection of anti-HIV-1 neutralizing antibody has been used in many laboratories. However, the unknown factor(s in sera or plasma affected cell growth and caused protection when the tested sera or plasma was continuously maintained in cell culture. In addition, the poor solubility of neutral red in medium (such as RPMI-1640 also limited the use of this assay. Methods In this study, human T cell line C8166 was used as host cells, and 3-(4,5-Dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT instead of neutral red was used as vital dye. In order to avoid the effect of the unknown factor(s, the tested sera or plasma was removed by a washout procedure after initial 3–6 h culture in the assay. Result This new assay eliminated the effect of the tested sera or plasma on cell growth, improved the reliability of detection of anti-HIV-1 neutralizing antibody, and showed excellent agreement with the p24 antigen method. Conclusion The results suggest that the improved assay is relatively simple, highly duplicable, cost-effective, and well reliable for evaluating anti-HIV-1 neutralizing antibodies from sera or plasma.

  15. Estimation of Anti-HIV Activity of HEPT Analogues Using MLR, ANN, and SVM Techniques

    Directory of Open Access Journals (Sweden)

    Basheerulla Shaik

    2013-01-01

    value than those of MLR and SVM techniques. Rm2= metrics and ridge regression analysis indicated that the proposed four-variable model MATS5e, RDF080u, T(O⋯O, and MATS5m as correlating descriptors is the best for estimating the anti-HIV activity (log 1/C present set of compounds.

  16. Anti-HIV Effect of Liposomes Bearing CXCR4 Receptor Antagonist ...

    African Journals Online (AJOL)

    Purpose: To evaluate lymphatic system targeting and inhibitory ability of N15P nano-liposomal preparation (naLipo-N15P) of CXCR4 receptor antagonist in HIV infection. Methods: Chemotactic and chemotaxic inhibition activity assays were used to analyze the biological activity of naLipo-N15P. The anti-HIV potential of ...

  17. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75

    International Nuclear Information System (INIS)

    Du Li; Zhao Yaxue; Chen, Jing; Yang Liumeng; Zheng Yongtang; Tang Yun; Shen Xu; Jiang Hualiang

    2008-01-01

    Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. Since LEDGF/p75 plays an important role in HIV integration, disruption of the LEDGF/p75 interaction with IN has provided a special interest for anti-HIV agent discovery. In this work, we reported that a benzoic acid derivative, 4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl) -1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)methyl]benzoic acid (D77) could potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution thus exhibiting antiretroviral activity. Molecular docking with site-directed mutagenesis analysis and surface plasmon resonance (SPR) binding assays has clarified possible binding mode of D77 against HIV-1 integrase. As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might supply useful structural information for further anti-HIV agent discovery

  18. Combinations against combinations: associations of anti-HIV 1 reverse transcriptase drugs challenged by constellations of drug resistance mutations.

    Science.gov (United States)

    Maga, Giovanni; Spadari, Silvio

    2002-02-01

    The reverse transcriptase inhibitors still represent the majority of the clinically used anti-HIV drugs and constitute the main backbone of currently employed combinatorial regimens. A major obstacle to successfull chemotherapic eradication of HIV is the emergence of viral strains resistant to the drugs in use. Counteracting the emergence of resistance necessitates alternating the panel of agents employed. In order to rationally design alternative drug combinations, physicians not only must know the genotype of the emerging viral strains, but should also be able to correlate it with its resistant phenotype. However, resistant viral strains usually carry multiple mutations, whose reciprocal influences on the overall level of resistance are largely unknown. Moreover, the choice of agents to be combined must take in account drug-drug interactions and adverse metabolic effects. This review will outline the main pharmacological and clinical features of the currently utilised anti-reverse transcriptase drugs, as well as the correspondent resistance profiles selected during therapy. A major focus will be on the reciprocal influence of drug associations on their own metabolism as well as on the interacting effects of the selected combinations of drug resistance mutations.

  19. Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of Garcinia hanburyi.

    Science.gov (United States)

    Reutrakul, Vichai; Anantachoke, Natthinee; Pohmakotr, Manat; Jaipetch, Thaworn; Sophasan, Samaisukh; Yoosook, Chalobon; Kasisit, Jittra; Napaswat, Chanita; Santisuk, Thawatchai; Tuchinda, Patoomratana

    2007-01-01

    Three new caged xanthones, 7-methoxydesoxymorellin (1), 2-isoprenylforbesione (2) and 8,8a-epoxymorellic acid (3), together with nine known caged xanthones were isolated from the EtOAc extracts of resin and fruits of Garcinia hanburyi. The structures were determined by spectroscopic methods. Most of the isolated compounds showed significant cytotoxicities against a panel of mammalian cancer cell lines. Compound 3, together with the known compounds desoxymorellin, morellic acid, gambogic acid, hanburin, forbesione and dihydroisomorellin, exhibited anti-HIV-1 activity in the reverse transcriptase (RT) assay while the known compounds desoxygambogenin and dihydroisomorellin were found moderately active in the syncytium assay. This work represents the first report on the anti-HIV-1 activities of caged xanthones.

  20. 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)

  1. Protein/peptide-based entry/fusion inhibitors as anti-HIV therapies: challenges and future direction.

    Science.gov (United States)

    Fumakia, Miral; Yang, Sidi; Gu, Jijin; Ho, Emmanuel A

    2016-01-01

    The failures of several first-generation and second-generation small molecule drug-based anti-HIV therapies in various stages of clinical trials are an indication that there is a need for a paradigm shift in the future designs of anti-HIV therapeutics. Over the past several decades, various anti-HIV drugs have been developed, among them, protein/peptide-based therapies. From the first peptide discovered (SJ2176) to the first peptide approved by the Food and Drug Administration (DP178/T20/enfuvirtide/Fuzeon®), anti-HIV proteins/peptides as fusion/entry inhibitors have been shown to provide potent effects and benefits. This review summarizes the past and current endeavors in this area, discusses the potential mechanisms of action for various anti-HIV proteins/peptides, compares the advantages and disadvantages between the different proteins/peptides, and finally, examines the future direction of the field, specifically, strategies that will enhance the therapeutic efficacy of fusion/entry inhibitor-based anti-HIV proteins/peptides. Although there are numerous reviews highlighting the general field of entry/fusion inhibitors, there is a lack of literature focused on protein/peptide-based entry/fusion inhibitors for HIV therapy, and as a result, this review is intended to fill this void by summarizing the past, current, and future development of these macromolecules. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Foamy virus vectors expressing anti-HIV transgenes efficiently block HIV-1 replication.

    Science.gov (United States)

    Taylor, Jason A; Vojtech, Lucia; Bahner, Ingrid; Kohn, Donald B; Laer, Dorothee Von; Russell, David W; Richard, Robert E

    2008-01-01

    Gene therapy has the potential to control human immunodeficiency virus (HIV) in patients who do not respond to traditional antiviral therapy. In this study, we tested foamy virus (FV) vectors expressing three anti-HIV transgenes, both individually and in a combination vector. The transgenes tested in this study are RevM10, a dominant negative version of the viral rev protein, Sh1, a short hairpin RNA directed against a conserved overlapping sequence of tat and rev, and membrane-associated C46 (maC46), a membrane-attached peptide that blocks HIV cell entry. FV vectors efficiently transduce hematopoietic stem cells and, unlike lentivirus (LV) vectors, do not share viral proteins with HIV. The titers of the FV vectors described in this study were not affected by anti-HIV transgenes. On a direct comparison of FV vectors expressing the individual transgenes, entry inhibition using the maC46 transgene was found to be the most effective at blocking HIV replication. A clinically relevant FV vector expressing three anti-HIV transgenes effectively blocked HIV infection in primary macrophages derived from transduced, peripheral blood CD34-selected cells and in a cell line used for propagating HIV, CEMx174. These results suggest that there are potential benefits of using FV vectors in HIV gene therapy.

  3. In vitro anti-HIV-1 activity of the aqueous extract of Asterina pectinifera.

    Science.gov (United States)

    Karadeniz, Fatih; Karagozlu, Mustafa Zafer; Kong, Chang-Suk; Kim, Se-Kwon

    2011-03-01

    An aqueous extract of starfish, Asterina pectinifera, was investigated for its anti-HIV-1 efficiency in vitro on human T-cell lines. A. pectinifera significantly maintained the viability of HIV-infected cells as much as 86% of the untreated infected control cells at the non-toxic concentrations (0.05~4 mg/mL) in CEM-SS cells. Anti-HIV-1 activity of A. pectinifera extract was further supported by quantification of syncytia formation, reverse transcriptase activity and Western blot analysis in C8166, CEM-SS and H9 cells, respectively. Current results demonstrated a notable inhibition of HIV-1 induced syncytia formation and HIV-1 reverse transcriptase activity assay with EC50 of 0.71 mg/mL and 0.65 mg/mL, respectively. Moreover, A. pectinifera extract treatment decreased the production of p24 protein and gene expression of HIV-1 viral infection factor in a dose-dependent manner according to immunoblot and reverse transcription polymerase chain reaction analysis. In the light of current study, it can be concluded that A. pectinifera contains highly potential anti-HIV-1 components and a further investigation for active compound isolation is urged.

  4. A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity

    Science.gov (United States)

    Ichiyama, Kozi; Yokoyama-Kumakura, Sei; Tanaka, Yuetsu; Tanaka, Reiko; Hirose, Kunitaka; Bannai, Kenji; Edamatsu, Takeo; Yanaka, Mikiro; Niitani, Yoshiaki; Miyano-Kurosaki, Naoko; Takaku, Hiroshi; Koyanagi, Yoshio; Yamamoto, Naoki

    2003-01-01

    A low molecular weight nonpeptide compound, KRH-1636, efficiently blocked replication of various T cell line-tropic (X4) HIV type 1 (HIV-1) in MT-4 cells and peripheral blood mononuclear cells through the inhibition of viral entry and membrane fusion via the CXC chemokine receptor (CXCR)4 coreceptor but not via CC chemokine receptor 5. It also inhibited binding of the CXC chemokine, stromal cell-derived factor 1α, to CXCR4 specifically and subsequent signal transduction. KRH-1636 prevented monoclonal antibodies from binding to CXCR4 without down-modulation of the coreceptor. The inhibitory effect against X4 viral replication by KRH-1636 was clearly reproduced in the human peripheral blood lymphocyte/severe combined immunodeficiency mouse system. Furthermore, this compound was absorbed into the blood after intraduodenal administration as judged by anti-HIV-1 activity and liquid chromatography MS in the plasma. Thus, KRH-1636 seems to be a promising agent for the treatment of HIV-1 infection. PMID:12642669

  5. Qualitative and quantitative intravaginal targeting: key to anti-HIV-1 microbicide delivery from test tube to in vivo success.

    Science.gov (United States)

    Pillay, Viness; Mashingaidze, Felix; Choonara, Yahya E; Du Toit, Lisa C; Buchmann, Eckhart; Maharaj, Vinesh; Ndesendo, Valence M K; Kumar, Pradeep

    2012-06-01

    The past decade has seen several effective anti-HIV-1 agent discoveries, yet microbicides continue to disappoint clinically. Our review expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal microenvironmental factors including pH should be maintained at HIV-1 prohibitive acidic levels simultaneously to ward off other sexually transmitted diseases, which compromise vaginal epithelial barrier properties. Furthermore, choice of receptors to target both on HIV-1 and on target cells is vital in deterring transmission. Appropriate modeling of virus-target cell interactions as well as targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could revolutionize microbicide research, ultimately delivering a female-controlled HIV-1 prevention modality appropriately. Copyright © 2012 Wiley Periodicals, Inc.

  6. Design, Conformation, and Crystallography of 2-Naphthyl Phenyl Ethers as Potent Anti-HIV Agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won-Gil; Chan, Albert H.; Spasov, Krasimir A.; Anderson, Karen S.; Jorgensen, William L.

    2016-12-08

    Catechol diethers that incorporate a 7-cyano-2-naphthyl substituent are reported as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Many of the compounds have 1–10 nM potencies toward wild-type HIV-1. An interesting conformational effect allows two unique conformers for the naphthyl group in complexes with HIV-RT. X-ray crystal structures for 4a and 4f illustrate the alternatives.

  7. Topological estimation of cytotoxic activity of some anti-HIV agents ...

    Indian Academy of Sciences (India)

    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 ...

  8. Mathematical modeling of tetrahydroimidazole benzodiazepine-1-one derivatives as an anti HIV agent

    Science.gov (United States)

    Ojha, Lokendra Kumar

    2017-07-01

    The goal of the present work is the study of drug receptor interaction via QSAR (Quantitative Structure-Activity Relationship) analysis for 89 set of TIBO (Tetrahydroimidazole Benzodiazepine-1-one) derivatives. MLR (Multiple Linear Regression) method is utilized to generate predictive models of quantitative structure-activity relationships between a set of molecular descriptors and biological activity (IC50). The best QSAR model was selected having a correlation coefficient (r) of 0.9299 and Standard Error of Estimation (SEE) of 0.5022, Fisher Ratio (F) of 159.822 and Quality factor (Q) of 1.852. This model is statistically significant and strongly favours the substitution of sulphur atom, IS i.e. indicator parameter for -Z position of the TIBO derivatives. Two other parameter logP (octanol-water partition coefficient) and SAG (Surface Area Grid) also played a vital role in the generation of best QSAR model. All three descriptor shows very good stability towards data variation in leave-one-out (LOO).

  9. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

    Science.gov (United States)

    Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

    2014-07-01

    Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

  10. Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

    Science.gov (United States)

    Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

    2015-01-01

    Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

  11. Two new compounds and anti-HIV active constituents from Illicium verum.

    Science.gov (United States)

    Song, Wen-Yong; Ma, Yun-Bao; Bai, Xue; Zhang, Xue-Mei; Gu, Qiong; Zheng, Yong-Tang; Zhou, Jun; Chen, Ji-Jun

    2007-04-01

    Two new compounds named illiverin A (1) and tashironin A (8) were isolated from the roots of Illicium verum, together with seven known compounds: 4-allyl-2-(3-methylbut-2-enyl)-1,6-methylenedioxybenzene-3-ol (2), illicinole (3), 3-hydroxy-4,5-methylenedioxyallyl-benzene (4), (-)-illicinone-A (5), 4-allyl-4-(3-methylbut-2-enyl)-1,2-methylenedioxycyclohexa-2,6-dien-5-one (6), 3,4-seco-(24 Z)- cycloart-4(28),24-diene-3,26-dioic acid, 26-methyl ester (7) and tashironin (9). Based on 1D- and 2D-NMR data (COSY, HMQC, HMBC), the structures of the new compounds were deduced to be (E)-1-[(3-methylbut-2-enyl)oxy]-2-methoxy-4-(prop-1-enyl)benzene (1) and 11-O-debenzoyl-11alpha-O-2-methylcyclopent-1-enecarboxyltashironin (8). Compounds 1-9 were screened for anti-HIV activity in vitro whereby compounds 5 and 7 possessed moderate anti-HIV activity with EC50 values of 16.0 and 5.1 microM with SI values of 18.2 and 15.6, respectively.

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

    Science.gov (United States)

    Esteves, Ana I. S.; Nicolai, Marisa; Humanes, Madalena; Goncalves, Joao

    2011-01-01

    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 (polysaccharide (up to 97.3%), showed only modest bioactivity (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). PMID:21339952

  13. 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.

  14. Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection.

    Science.gov (United States)

    Ramezani, Ali; Dubrovsky, Larisa; Pushkarsky, Tatiana; Sviridov, Dmitri; Karandish, Sara; Raj, Dominic S; Fitzgerald, Michael L; Bukrinsky, Michael

    2015-09-01

    Previous studies demonstrated that liver X receptor (LXR) agonists inhibit human immunodeficiency virus (HIV) replication by upregulating cholesterol transporter ATP-binding cassette A1 (ABCA1), suppressing HIV production, and reducing infectivity of produced virions. In this study, we extended these observations by analyzing the effect of the LXR agonist T0901317 [N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide] on the ongoing HIV infection and investigating the possibility of using LXR agonist for pre-exposure prophylaxis of HIV infection in a humanized mouse model. Pre-exposure of monocyte-derived macrophages to T0901317 reduced susceptibility of these cells to HIV infection in vitro. This protective effect lasted for up to 4 days after treatment termination and correlated with upregulated expression of ABCA1, reduced abundance of lipid rafts, and reduced fusion of the cells with HIV. Pre-exposure of peripheral blood leukocytes to T0901317 provided only a short-term protection against HIV infection. Treatment of HIV-exposed humanized mice with LXR agonist starting 2 weeks postinfection substantially reduced viral load. When eight humanized mice were pretreated with LXR agonist prior to HIV infection, five animals were protected from infection, two had viral load at the limit of detection, and one had viral load significantly reduced relative to mock-treated controls. T0901317 pretreatment also reduced HIV-induced dyslipidemia in infected mice. In conclusion, these results reveal a novel link between LXR stimulation and cell resistance to HIV infection and suggest that LXR agonists may be good candidates for development as anti-HIV agents, in particular for pre-exposure prophylaxis of HIV infection. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Anti-Human Immunodeficiency Virus (HIV) Agents | Okolie | Journal ...

    African Journals Online (AJOL)

    This article gives a brief review of anti-retroviral agents with activity against the Human Immunodeficiency Virus (HIV) the causative agen of Acquired Immunodeficiency Syndrome (AIDS). It also outlines the principles, mode of action of anti-HIV agents and their sites of therapeutic intervention. Zidovudine or Azidothymidine ...

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

    Directory of Open Access Journals (Sweden)

    Sulggi A Lee

    Full Text Available 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.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.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.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 during treatment.

  17. Anti-HIV-1 activity of combinations and covalent conjugates of negatively charged human serum albumins (NCAs) and AZT

    NARCIS (Netherlands)

    Kuipers, M.E; Swart, P.J; Witvrouw, M; Esté, J.A; Reymen, D; De Clercq, E; Meijer, D.K F

    1999-01-01

    Negatively charged albumins (NCAs, with the prototypes Suc-HSA and Aco-HSA), modified proteins with a potent anti-HIV-1 activity in the nanomolar concentration range, were studied for several aspects of their antiviral mechanism. In addition we investigated the antiviral activity of combinations and

  18. Synthesis and biological application of a new heterodinucleotide with both anti-HSV and anti-HIV activity.

    Science.gov (United States)

    Franchetti, P; Abu Sheikha, G; Cappellacci, L; Grifantini, M; Balestra, E; Perno, C F; Brandi, G; Rossi, L; Magnani, M

    1999-01-01

    A new antiviral drug with both anti-HSV and anti-HIV activity was synthesized by coupling Acyclovir and the acyclic nucleoside phosphonate (R)PMPA. The heterodinucleotide ACVpPMPA encapsulated into autologous erythrocytes was added to human macrophages providing an effective in vitro protection from HSV-1 and HIV-1 replication.

  19. Comparative pharmacokinetic, immunologic and hematologic studies on the anti-HIV-1/2 compounds aconitylated and succinylated HSA

    NARCIS (Netherlands)

    Swart, P. J.; Beljaars, E.; Smit, C.; Pasma, A.; Schuitemaker, H.; Meijer, D. K.

    1996-01-01

    Charge modification by succinylation or cis-aconitylation of the terminal epsilon NH2 functions of the amino acid lysine in human serum albumin, resulted in polyanionic compounds with an anti-HIV-1 activity in the low nanomolar concentration range. After iv injections in rats of the negatively

  20. The metabolic fate of the Anti-HIV active drug carrier succinylated human serum albumin after intravenous administration in rats

    NARCIS (Netherlands)

    Swart, P J; Kuipers, M E; Smit, C; Beljaars, L; Ter Wiel, J; Meijer, D K

    The pharmacokinetics and metabolic fate of the intrinsically active (anti-HIV) drug carrier succinylated human serum albumin (Suc-HSA) was studied in rats. Suc-HSA was prepared by derivatizing HSA with 1,4-[C-14]-succinic anhydride, a modification by which all available epsilonNH2-groups in HSA were

  1. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides

    NARCIS (Netherlands)

    Berkhout, Ben; van Wamel, Jeroen L. B.; Beljaars, Leonie; Meijer, Dirk K. F.; Visser, Servaas; Floris, René

    2002-01-01

    In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition

  2. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides

    NARCIS (Netherlands)

    Berkhout, B; van Wamel, JLB; Beljaars, L; Meijer, DKF; Visser, Servaas; Floris, R

    In a search for natural proteins with anti-HIV activity, we screened a large set of purified proteins from bovine milk and peptide fragments thereof. Because several charged proteins and peptides are known to inhibit the process of virus entry, we selected proteins with an unusual charge composition

  3. A Novel Method for Determining the Inhibitory Potential of Anti-HIV Drugs

    Science.gov (United States)

    Shen, Lin; Rabi, S. Alireza; Siliciano, Robert F.

    2009-01-01

    In the absence of a cure, most HIV-1-infected individuals will require life-long treatment. It is therefore essential to optimize highly active antiretroviral therapy. Recent research has shown that the slope parameter or Hill coefficient, which describes the steepness of a dose-response curve, is a critical missing dimension in the evaluation of antiviral drug activity. Based on this finding, the instantaneous inhibitory potential (IIP) has been derived as a new measure of antiviral drug activity. IIP incorporates the slope parameter and thus is a more accurate pharmacodynamic measure of antiviral activity than current measures such as IC50 and inhibitory quotient. However, it remains important to determine how to use IIP to predict the in vivo efficacy of anti-HIV-1 drugs. This article discusses recent advances in in vitro measures of antiviral activity and the therapeutic implications of the dose-response curve slope and IIP. PMID:19837466

  4. [Asymmetry in international relations, industrial property rights and anti-HIV medication].

    Science.gov (United States)

    Costa-Couto, Maria Helena; Nascimento, Alvaro César

    2008-01-01

    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.

  5. 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.

  6. Flazinamide, a novel β-carboline compound with anti-HIV actions

    International Nuclear Information System (INIS)

    Wang Yunhua; Tang Jianguo; Wang Ruirui; Yang Liumeng; Dong Zejun; Du Li; Shen Xu; Liu Jikai; Zheng Yongtang

    2007-01-01

    A β-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)-β-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38 μM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89 μM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77 μM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle

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

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    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.

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

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    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.

  9. Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study.

    Science.gov (United States)

    Chaniad, Prapaporn; Wattanapiromsakul, Chatchai; Pianwanit, Somsak; Tewtrakul, Supinya

    2016-01-01

    Dioscorea bulbifera L. (Dioscoreaceae) has been used in a traditional Thai longevity medicine preparation. Isolation of inhibitors from natural products is a potential source for continuous development of new HIV-1 integrase (IN) inhibitors. The objective of this study is to isolate the compounds and evaluate their anti-HIV-1 IN activity, as well as to predict the potential interactions of the compounds with an IN. The ethyl acetate and water fractions (1-100 μg/mL) of Dioscorea bulbifera bulbils were isolated and tested for their anti-HIV-1 IN activity using the multiplate integration assay (MIA). The interactions of the active compounds with IN were investigated using a molecular docking method. The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3',5'-tetrahydroxybibenzyl (2), and 5,7,4'-trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC50 value of 3.15 μM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC50 value= 14.20 μM), quercetin-3-O-β-D-glucopyranoside (6, IC50 value = 19.39 μM) and quercetin-3-O-β-D-galactopyranoside (7, IC50 value = 21.80 μM). Potential interactions of the active compounds (3, 4, 6, and 7) with the IN active site were additionally investigated. Compound 4 showed the best binding affinity to IN and formed strong interactions with various amino acid residues. These compounds interacted with Asp64, Thr66, His67, Glu92, Asp116, Gln148, Glu152, Asn155, and Lys159, which are involved in both the 3'-processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN.

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

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    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.

  11. Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids

    DEFF Research Database (Denmark)

    Pedersen, Erik Bjerregaard; Nielsen, Jakob Toudahl; Nielsen, Claus

    2011-01-01

    Two G-quadruplex forming sequences, 50-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1-pyrenylet......Two G-quadruplex forming sequences, 50-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4......-(1-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming...... of the antiviral QFOs in the present study formed more thermally stable G-quadruplexes and also high-order G-quadruplex structures which might be responsible for the increased antiviral activity observed....

  12. 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 in......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...... 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...

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

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    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.

  14. Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity

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    Carmela Saturnino

    2018-01-01

    Full Text Available Background: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human Immunodeficiency Virus prevention and sexual transmission and the development of new drugs to treat the chronic lifelong infection. Methods: Six chloro-1,4-dimethyl-9H-carbazoles (2a,b–4a,b have been prepared following opportunely modified known chemical procedures and tested in luciferase and Escherichia coli β-galactosidase expressing CD4+, CXCR4+, CCR5+ TZM-bl cells. Results and Conclusion: a preliminary biological investigation on the synthesized small series of chloro-1,4-dimethyl-9H-carbazoles has been carried out. Among all tested compounds, a nitro-derivative (3b showed the most interesting profile representing a suitable lead for the development of novel anti-HIV drugs.

  15. The anti-HIV activity of ADS-J1 targets the HIV-1 gp120

    International Nuclear Information System (INIS)

    Armand-Ugon, Mercedes; Clotet-Codina, Imma; Tintori, Cristina; Manetti, Fabrizio; Clotet, Bonaventura; Botta, Maurizio; Este, Jose A.

    2005-01-01

    Recent data suggest that heparin sulfates may bind to a CD4 induced epitope in the HIV-1 gp120 that constitutes the coreceptor binding site. We have studied the mechanism of action of ADS-J1, a non-peptidic compound selected by docking analysis to interact with gp41 and to interfere with the formation of N-36/C-34 complexes in sandwich ELISA experiments. We show that ADS-J1 blocked the binding of wild-type HIV-1 NL4-3 strain to MT-4 cells but not virus-cell binding of a polyanion-resistant virus. However, ADS-J1 blocked the replication of polyanion-resistant, T-20- and C34-resistant HIV-1, suggesting a second mechanism of action. Development of resistance to ADS-J1 on the polyanion-resistant HIV-1 led to mutations in gp120 coreceptor binding site and not in gp41. Time of addition experiments confirmed that ADS-J1, but not polyanions such as dextran sulfate or AR177, worked at a step that mimics the activity of an HIV coreceptor antagonist but prior to gp41-dependent fusion. We conclude that ADS-J1 may bind to the HIV coreceptor binding site as its mechanism of anti-HIV activity

  16. Anti-HIV-1 cycloartanes from leaves and twigs of Gardenia thailandica.

    Science.gov (United States)

    Tuchinda, Patoomratana; Saiai, Aroonchai; Pohmakotr, Manat; Yoosook, Chalobon; Kasisit, Jittra; Napaswat, Chanita; Santisuk, Thawatchai; Reutrakul, Vichai

    2004-04-01

    Thailandiol ( 1), gardenolic acid A ( 2), quadrangularic acid E ( 3) and 3beta-hydroxy-5alpha-cycloart-24(31)-en-28-oic acid ( 4) have been isolated from the leaves and twigs of Gardenia thailandica Tirveng (order: Rubiales; family: Rubiaceae). In addition, 5-hydroxy-7,2',3',4',5',6'-hexamethoxyflavone ( 5), 5,7-dihydroxy-2',3', 4',5',6'-pentamethoxyflavone ( 6), 5-hydroxy-7,2',3',4',5'-pentamethoxyflavone ( 7) and 5,7-dihydroxy-2',3',4',5'-tetramethoxyflavone ( 8) were also isolated from the same source. The structures were elucidated by spectroscopic methods. Crude extracts and compounds 1 - 4 displayed anti-HIV-1 activities as determined by using the (Delta)(Tat/Rev)MC99 virus and 1A2 cell line system. The EC (50) values determined by the syncytium assay ranged from < 7.8 to 110 microg/mL. They also exhibited moderate to high activities in reverse transcriptase (RT) assay; the IC (50) values of compounds 1 - 4, ranged from < 22.5 to 156.8 microg/mL.

  17. Synthesis, antibacterial, antifungal and anti-HIV activities of norfloxacin mannich bases.

    Science.gov (United States)

    Pandeya, S N; Sriram, D; Nath, G; De Clercq, E

    2000-02-01

    Mannich bases of norfloxacin were synthesized by reacting them with formaldehyde and several isatin derivatives. Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis. Investigation of in vitro antimicrobial activity of compounds was done by the agar dilution method against 28 pathogenic bacteria, eight pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. The in vivo antibacterial efficacy of selected derivatives was determined using a mouse infection model. All the synthesized compounds are more active than norfloxacin against the 13 bacteria tested. The compounds are also more active than the standard drug clotrimazole against Histoplasma capsulatum. Two compounds S-8 and S-9 have shown inhibition against HIV-1 (III B) with EC(50) values of 11.3 and 13.9 microgram/mL, respectively. In the mouse protection test, two compounds S-4 (ED(50): 1.25 mg/kg) and S-9 (ED(50): 1.62 mg/kg) are more active than norfloxacin (ED(50): 6mg/kg). Among the compounds tested, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7[[N(4)-[5'-bromo-3'-(4'-amino-5'-trimethoxybenzylpyr imidin-2'-yl]-imino-1'-isatinyl]methyl]N(1)-piperazinyl]-3-q uinoline carboxylicacid (S-9) showed promising activity in all the three tests.

  18. CXCR4-derived synthetic peptides inducing anti-HIV-1 antibodies.

    Science.gov (United States)

    Hashimoto, Chie; Nomura, Wataru; Narumi, Tetsuo; Fujino, Masayuki; Nakahara, Toru; Yamamoto, Naoki; Murakami, Tsutomu; Tamamura, Hirokazu

    2013-11-15

    Despite almost 30 years since the identification of the human immunodeficiency virus type I (HIV-1), development of effective AIDS vaccines has been hindered by the high mutability of HIV-1. The HIV-1 co-receptors CCR5 and CXCR4 are genetically stable, but viral proteins may mutate rapidly during the course of infection. CXCR4 is a seven transmembrane G protein-coupled receptor, possessing an N-terminal region (NT) and three extracellular loops (ECL1-3). Previous studies have shown that the CXCR4-ED-derived peptides inhibit the entry of HIV-1 by interacting with gp120, an HIV-1 envelope glycoprotein. In the present study, antigenicity of CXCR4-derived peptides has been investigated and the anti-HIV-1 effects of induced antisera have been assessed. It was found that CXCR4-ED-derived antigen molecules immunize mice, showing that the linear peptides have higher antigenicity than the cyclic peptides. The L1- and L2-induced antisera inhibited the HIV-1 entry significantly, while anti-N1 antibodies have no inhibitory activity. This study produced promising examples for the design of AIDS vaccines which target the human protein and can overcome mutability of HIV-1. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Anti-HIV activities of the compounds isolated from Polygonum cuspidatum and Polygonum multiflorum.

    Science.gov (United States)

    Lin, Hong-Wei; Sun, Ming-Xue; Wang, Yun-Hua; Yang, Liu-Meng; Yang, Ying-Ruo; Huang, Ning; Xuan, Li-Jiang; Xu, Ya-Ming; Bai, Dong-Lu; Zheng, Yong-Tang; Xiao, Kai

    2010-06-01

    The 70 % EtOH extract of Polygonum cuspidatum showed inhibitory action against HIV-1-induced syncytium formation at non-cytotoxic concentrations in vitro with a 50 % effective concentration (EC(50)) of 13.94 +/- 3.41 microg/mL. Through bioactivity-guided fractionation, 20 phenolic compounds, including eight stilbenoids, were isolated from the roots of Polygonum cuspidatum, and their anti-HIV-1 activities were evaluated. Results showed that compounds 1, 13, 14, and 16 demonstrated fairly strong antiviral activity against HIV-1-induced cytopathic effects in C8166 lymphocytes at non-cytotoxic concentrations, with EC (50) values of 4.37 +/- 1.96 microg/mL, 19.97 +/- 5.09, 14.4 +/- 1.34 microg/mL, and 11.29 +/- 6.26 microg/mL and therapeutic index (TI) values of 8.12, > 10.02, > 13.89, and > 17.71, respectively. Other compounds showed either weak or no effects. Compound 6 also showed weak inhibition (153.42 +/- 19.25 microg/mL); however, it possesses very good water solubility and showed almost no cytotoxicity (> 2000 microg/mL), therefore achieving a fairly good TI (13.04). The activities of the two compounds (3 and 18) from Polygonum multiflorum were also assayed. The relationship between molecular structures and their bioactivities was also discussed. Georg Thieme Verlag KG Stuttgart-New York.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Ali Moghadam

    Full Text Available 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.

  2. Medicinal chemistry discoveries among 1,3,5-triazines: recent advances (2000-2013) as antimicrobial, anti-TB, anti-HIV and antimalarials.

    Science.gov (United States)

    Patel, Rahul V; Keum, Young-Soo; Park, Se Won

    2014-01-01

    The chemistry and an extensive spectrum of biological activities of s-triazines have been examined since several decades and this heterocyclic core has received emerging consensus. This article aims to summarize recent advances (2000-2013) made towards the discovery of antimicrobial, antituberculosis, anti-HIV and antimalarial agents holding 1,3,5-triazine ring as a nucleus with the substitution of several types of nucleophiles. Molecular patterns associated with particular potency have been identified targeting several Gram-positive and Gram-negative bacteria and some fungal species, mycobacterium tuberculosis H37Rv, HIV type I and HIV type II, particularly, HIV-1I IIB and HIV- 1ROD strains as well as a variety of P. falciparum malarial strains as chloroquine-resistant K1, chloroquine-susceptible NF54, chloroquine-sensitive 3D7, P. falciparum (D6 clone), P. falciparum (W2 clone), cycloguanil-resistant FCR-3, chloroquine sensitive RKL2. The report will be of considerable interest to gain useful information for the furtherance of drug discovery with extended 1,3,5-triazine designs.

  3. Contribution of NK cell education to both direct and anti-HIV-1 antibody-dependent NK cell functions.

    Science.gov (United States)

    Kristensen, Anne B; Kent, Stephen J; Parsons, Matthew S

    2018-03-07

    Antibody Fc-dependent functions are linked to prevention and control of HIV-1 infection. Basic NK cell biology is likely key to understanding the contributions anti-HIV-1 antibody-dependent NK cell activation and cytolysis make to HIV-1 susceptibility and disease progression. The importance of NK cell education through inhibitory receptors specific for self-HLA-I in determining the potency of anti-HIV-1 antibody mediated NK cell activation and cytolysis is controversial. To address this issue more definitively we utilized HLA-I genotyping, flow cytometry staining panels and cytolysis assays to assess the functionality of educated and non-educated peripheral blood NK cells. We now demonstrate that educated NK cells are superior in terms of their capacity to become activated and/or mediate cytolysis following anti-HIV-1 antibody-dependent stimulation. The profiles of activation observed were similar to those observed upon direct stimulation of NK cells with HLA-I devoid target cells. Non-educated NK cells make significantly lower contributions to total NK cell activation than would be expected from their frequency within the total NK cell population (i.e., are hypofunctional) and educated NK cells make similar or higher contributions as their frequency in the total NK cell population. Finally, NK cells educated through at least one killer immunoglobulin-like receptor and NKG2A exhibited the most significant difference between actual and expected contribution to the total NK cell response, based on their frequency within the total NK cell population, suggesting summation of NK cell education through inhibitory receptors determines overall NK cell functionality. These observations have potential implications for understanding HIV-1 vaccine efficacy and disease progression. IMPORTANCE NK cells are major mediators of anti-HIV-1 antibody-dependent functions, including cytokine production and cytolysis. The mechanisms controlling the capacity of individual NK cells to

  4. 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

  5. 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

    2011-01-01

    Full Text Available 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.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.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.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 inexpensive bioassay may promote the development

  6. 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.

  7. Anti-HIV and immunomodulation activities of cacao mass lignin-carbohydrate complex.

    Science.gov (United States)

    Sakagami, Hiroshi; Kawano, Michiyo; Thet, May Maw; Hashimoto, Ken; Satoh, Kazue; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Haishima, Yuji; Maeda, Yuuichi; Sakurai, Koji

    2011-01-01

    Recently, a prominent antiviral and macrophage stimulatory activity of cacao lignin-carbohydrate complex (LCC) has been reported. However, the solubility and sterility of LCC have not been considered yet. In the present study, complete solubilisation and sterilisation was achieved by autoclaving under mild alkaline conditions and the previously reported biological activities were re-examined. LCCs were obtained by 1% NaOH extraction and acid precipitation, and a repeated extraction-precipitation cycle. Nitric oxide (NO) and cytokine productions were assayed by the Griess method and ELISA, respectively. Inducible NO synthase (iNOS) expression was determined by Western blot analysis. Superoxide anion, hydroxyl radical and nitric oxide radical-scavenging activity was determined by ESR spectroscopy. Cacao mass LCC showed reproducibly higher anti-HIV activity than cacao husk LCC. Cacao mass LCC, up to 62.5 μg/ml, did not stimulate mouse macrophage-like cells (RAW264.7 and J774.1) to produce NO, nor did it induce iNOS protein, in contrast to lipopolysaccharide (LPS). Cacao mass LCC and LPS synergistically stimulated iNOS protein expression, suggesting a different point of action. Cacao mass LCC induced tumour necrosis factor-α production markedly less than LPS, and did not induce interleukin-1β, interferon-α or interferon-γ. ESR spectroscopy showed that cacao mass LCC, but not LPS, scavenged NO produced from NOC-7. This study demonstrated several new biological activities of LCCs distinct from LPS and further confirmed the promising antiviral and immunomodulating activities of LCCs.

  8. Phase I/II trial of the anti-HIV activity of mifepristone in HIV-infected subjects ACTG 5200.

    Science.gov (United States)

    Para, Michael F; Schouten, Jeff; Rosenkranz, Susan L; Yu, Song; Weiner, David; Tebas, Pablo; White, C Jo; Reeds, Dominic; Lertora, Juan; Patterson, Kristine B; Daar, Eric S; Cavert, Winston; Brizz, Barbara

    2010-04-01

    Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug's safety and anti-HIV activity. A 28-day double-blind, placebo-controlled trial of mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in HIV+ persons with CD4+ lymphocyte counts >or=350 cells per cubic millimeter who had no recent antiretroviral therapy. Fifty-six male and 1 female subjects with a median entry CD4+ lymphocyte count of 555 cells per cubic millimeter and plasma HIV-1 RNA of 15,623 copies per milliliter were accrued. Forty-five subjects (78.9%) were available for endpoint analysis. In each arm, changes from baseline to day 28 in plasma HIV-1 RNA and CD4+ lymphocyte count were not significantly different from zero (no change). There was no relationship between mifepristone trough concentrations and plasma HIV-1 RNA. Day 28 morning plasma cortisol levels were significantly higher in the 150 mg and 225 mg arms compared with placebo, confirming biologic activity, and returned to baseline by day 56. Serum lipids did not change during the trial. Fasting blood sugar was 2.5 mg/dL higher on day 28 in the mifepristone arms, but the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) did not change. Three subjects (7.3%) receiving mifepristone developed a grade 2 rash. Mifepristone at doses of 75-225 mg daily was safe and well-tolerated, but did not show significant anti-HIV activity.

  9. 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...

  10. In vitro anti-HIV and antioxidant activity of Hoodia gordonii (Apocynaceae), a commercial plant product.

    Science.gov (United States)

    Kapewangolo, Petrina; Knott, Michael; Shithigona, Regina E K; Uusiku, Sylvia L; Kandawa-Schulz, Martha

    2016-10-24

    Hoodia gordonii products are widely commercialized for anti-obesity purposes; however, minimal research is available on the other health properties demonstrated by this popular herbal plant. H. gordonii crude extracts (ethanol and ethyl acetate) were assayed for in vitro anti-HIV-1 protease (PR), reverse transcriptase (RT) and integrase activity. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assays were used for the antioxidant analysis. In addition, qualitative and quantitative phytochemical analyses of the extracts were determined using standard methods. H. gordonii extract demonstrated good inhibition against HIV RT with IC 50 values of 73.55 ± 0.04 and 69.81 ± 9.45 μg/mL for ethanol and ethyl acetate extracts, respectively. Both extracts also demonstrated inhibitory activity against HIV PR with IC 50 values of 97.29 ± 0.01 and 63.76 ± 9.01 μg/mL for ethanol and ethyl acetate extracts. In addition, H. gordonii also showed good antioxidant activity with IC 50 values of 124.6 ± 11.3 and 126.2 ± 3.15 μg/mL obtained for ethanol and ethyl acetate extracts, respectively. The reducing power of H. gordonii extracts increased as the concentration increased which confirmed the presence of antioxidants (reductants) in the extracts. Phytochemical screening of H. gordonii revealed the presence of phenolics, alkaloids, terpenes, steroids, cardiac glycosides and tannins in the ethanolic extract, while the ethyl acetate extract only showed the presence of phenolics, cardiac glycosides and steroids. The total phenolic content was 420 ± 0.17 and 319.9 ± 0.2 mg GAE/g for the ethanol and ethyl acetate extracts, respectively. The ethanol extract, which revealed the presence of tannins, had a tannin content of 330 ± 0.2 mg TAE/g extract. This data suggests that H. gordonii has good in vitro inhibition against selected HIV-1 enzymes as well as antioxidant properties, suggesting new potential uses for this commercial

  11. Analysis of the CD8+T cell anti-HIV activity in heterologous cell co-cultures reveals the benefit of multiple HLA class I matches.

    Science.gov (United States)

    Killian, M Scott; Teque, Fernando; Sudhagoni, Ramu

    2018-02-01

    CD8 + T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4 + T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8 + T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4 + T cells. Altogether, CD8 + T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8 + T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21; p CD8 + T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8 + T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8 + T cell anti-HIV activity. Stimulated CD8 + T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8 + T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes.

  12. Computational analysis of anti-HIV-1 antibody neutralization panel data to identify potential functional epitope residues.

    Science.gov (United States)

    West, Anthony P; Scharf, Louise; Horwitz, Joshua; Klein, Florian; Nussenzweig, Michel C; Bjorkman, Pamela J

    2013-06-25

    Advances in single-cell antibody cloning methods have led to the identification of a variety of broadly neutralizing anti-HIV-1 antibodies. We developed a computational tool (Antibody Database) to help identify critical residues on the HIV-1 envelope protein whose natural variation affects antibody activity. Our simplifying assumption was that, for a given antibody, a significant portion of the dispersion of neutralization activity across a panel of HIV-1 strains is due to the amino acid identity or glycosylation state at a small number of specific sites, each acting independently. A model of an antibody's neutralization IC50 was developed in which each site contributes a term to the logarithm of the modeled IC50. The analysis program attempts to determine the set of rules that minimizes the sum of the residuals between observed and modeled IC50 values. The predictive quality of the identified rules may be assessed in part by whether there is support for rules within individual viral clades. As a test case, we analyzed antibody 8ANC195, an anti-glycoprotein gp120 antibody of unknown specificity. The model for this antibody indicated that several glycosylation sites were critical for neutralization. We evaluated this prediction by measuring neutralization potencies of 8ANC195 against HIV-1 in vitro and in an antibody therapy experiment in humanized mice. These experiments confirmed that 8ANC195 represents a distinct class of glycan-dependent anti-HIV-1 antibody and validated the utility of computational analysis of neutralization panel data.

  13. 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.

  14. 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

  15. Derivation of infectious HIV-1 molecular clones with LTR mutations: sensitivity to the CD8+ cell noncytotoxic anti-HIV response

    NARCIS (Netherlands)

    Bonneau, Kyle R.; Ng, Sharon; Foster, Hillary; Choi, Kelly B.; Berkhout, Ben; Rabson, Arnold; Mackewicz, Carl E.; Levy, Jay A.

    2008-01-01

    CD8(+) cells from healthy, asymptomatic HIV-1-infected individuals can inhibit HIV-1 replication in naturally or acutely infected CD4(+) cells in the absence of cell killing. This CD8(+) cell noncytotoxic anti-HIV response (CNAR) is mediated by a soluble CD8(+) cell antiviral factor (CAF). CNAR/CAF

  16. Detection of anti-HIV-1 IgG antibodies in whole saliva by GACELISA and Western blot assays.

    Science.gov (United States)

    Matee, M I; Lyamuya, E F; Simon, E; Mbena, E C; Kagoma, C; Samaranayake, L P; Scheutz, F

    1996-05-01

    The present study, based on 158 HIV seropositives and 167 HIV seronegatives, demonstrates that saliva collected with the Omni-SAL device and tested with GACELISA (an IgG antibody capture ELISA) is an effective non-invasive alternative to serum for anti-HIV IgG antibody screening. The study also shows that a conventional serum Western blot kit can be used, with slight modifications, for confirmatory testing of saliva specimens. Collecting saliva with the Omni-SAL device had a very good acceptance rate among Tanzanian subjects, and although this diagnostic method is not yet known by the general public, 65% of the study participants preferred to give saliva instead of blood for HIV testing.

  17. An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1

    International Nuclear Information System (INIS)

    Tan, Yee-Joo; Lim, S.-P.; Ting, Anthony E.; Goh, Phuay-Yee; Tan, Y.H.; Lim, Seng Gee; Hong Wanjin

    2003-01-01

    In this study, we used HIV-1 as a model to demonstrate a novel approach for receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120 antibody was engineered with endocytotic and transmembrane motifs from either the cation-independent mannose 6-phospate receptor or the low-density lipoprotein receptor. Flow cytometry and immunofluorescence studies showed that the chimeric antibodies were expressed on the cell surface and can undergo rapid internalization. Furthermore, one of the chimeric antibodies was able to bind and internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that internalized viruses could undergo replication. Therefore, we have demonstrated a proof-of-principle of a novel method that can be used to internalize virus into cells, without prior knowledge of the cellular receptor for the virus. We propose that this approach would be particularly useful for studying viruses whose cellular receptor(s) is not known

  18. Pure drug and polymer based nanotechnologies for the improved solubility, stability, bioavailability and targeting of anti-HIV drugs.

    Science.gov (United States)

    Sharma, Puneet; Garg, Sanjay

    2010-03-18

    The impact of human immunodeficiency virus (HIV) infection has been devastating with nearly 7400 new infections every day. Although, the advent of highly active antiretroviral therapy (HAART) has made a tremendous contribution in reducing the morbidity and mortality in developed countries, the situation in developing countries is still grim with millions of people being infected by this disease. The new advancements in the field of nanotechnology based drug delivery systems hold promise to improve the situation. These nanoscale systems have been successfully employed in other diseases such as cancer, and therefore, we now have a better understanding of the practicalities and technicalities associated with their clinical development. Nanotechnology based approaches offer some unique opportunities specifically for the improvement of water solubility, stability, bioavailability and targeting of antiretroviral drugs. This review presents discussion on the contribution of pure drug and polymer based nanotechnologies for the delivery anti-HIV drugs. Copyright 2009 Elsevier B.V. All rights reserved.

  19. Anti-HIV-1 activity and structure-activity-relationship study of a fucosylated glycosaminoglycan from an echinoderm by targeting the conserved CD4 induced epitope.

    Science.gov (United States)

    Lian, Wu; Wu, Mingyi; Huang, Ning; Gao, Na; Xiao, Chuang; Li, Zi; Zhang, Zhigang; Zheng, Yongtang; Peng, Wenlie; Zhao, Jinhua

    2013-10-01

    Fucosylated glycosaminoglycan (FG) is a novel glycosaminoglycan with a chondroitin sulfate-like backbone and fucose sulfate branches. The aim of this study is to investigate the mechanism and structure-activity relationships (SAR) of FG for combating HIV-1 infection. Anti-HIV activities of FGs were assessed by a cytopathic effect assay and an HIV-1 p24 detection assay. The biomolecule interactions were explored via biolayer interferometry technology. The SAR was established by comparing its anti-HIV-1 activities, conserved CD4 induced (CD4i) epitope-dependent interactions and anticoagulant activities. FG efficiently and selectively inhibited the X4- and R5X4-tropic HIV-1 infections in C8166 cells with little cytotoxicity against C8166 cells and PBMCs. Our data indicated that FG bound to gp120 with nanomolar affinity and may interact with CD4i of gp120. Additionally, the CD4i binding affinity of FG was higher than that of dextran sulfate. SAR studies suggested that the unique sulfated fucose branches account for the anti-HIV-1 activity. The molecular size and present carboxyl groups of FG may also play important roles in various activities. Notably, several FG derivatives showed higher anti-HIV-1 activities and much lower anticoagulant activities than those of heparin. FG exhibits strong activity against X4- and R5X4-tropic HIV-1 infections. The mechanism may be related to targeting CD4i of gp120, which results in inhibition of HIV-1 entry. The carboxyl group substituted derivatives of FG (8.5-12.8kDa), might display high anti-HIV-1 activity and low anticoagulant activity. Our data supports further the investigation of FG derivatives as novel HIV-1 entry inhibitors targeting CD4i. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Immune biomarkers and anti-HIV activity in the reproductive tract of sexually active and sexually inactive adolescent girls.

    Science.gov (United States)

    Ghosh, Mimi; Jais, Mariel; Biswas, Roshni; Jarin, Jason; Daniels, Jason; Joy, Christopher; Juzumaite, Monika; Emmanuel, Vanessa; Gomez-Lobo, Veronica

    2018-03-13

    Adolescent girls are disproportionately affected by the HIV/AIDS pandemic, accounting for 22% of all new HIV infections globally. Yet little is known regarding the immune microenvironment of the adolescent female reproductive tract, especially regarding differences among sexually active and inactive girls, a critical parameter to evaluate HIV susceptibility associated with young age and sexual debut. Cervico-vaginal lavage (CVL) was collected from sexually active (10) and inactive (8) girls aged 11-19 years and analyzed by ELISA for inflammation-associated biomarkers IL-6, IL-8, TNF-α, MIP-3α, IL-1α, IL-1β, matrix metalloproteinases (MMP) 1, 2, 7, 8, and 9, as well as anti-HIV mediators, Elafin, SLPI, human beta-defensin 2, and tissue inhibitor of matrix metalloproteinases (TIMP) 1 and 2. Cervical ectopy was analyzed using Volocity. Anti-HIV activity was determined by TZM-bl assay. Statistical analyses were performed using GraphPad Prism and R. Sexually inactive girls had significantly higher levels of TNF-α (P = .029) in CVL compared to sexually active girls. In contrast, sexually active girls showed a trend toward higher levels of IL-1α (P = .051) compared to the sexually inactive girls. Heat-map correlations between cervical ectopy and immune biomarkers were also distinct between the 2 populations with significant positive associations between % ectopy and inflammation-associated biomarkers IL-6, IL-1β, IL-8, MIP-3α, MMP-8, and MMP-9 observed in the sexually inactive but not sexually active group. Higher pro-inflammatory biomarker TNF-α, as well as a distinct inflammation-associated immune clustering in sexually inactive girls, can potentially increase risk for infections including HIV upon sexual debut. Future studies with larger sample sizes are needed to characterize the immune parameters associated with sexual activity. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy.

    Science.gov (United States)

    Tung, Frank Y; Tung, Jack K; Pallikkuth, Suresh; Pahwa, Savita; Fischl, Margaret A

    2016-04-27

    HIV-1 specific cellular immunity plays an important role in controlling viral replication. In this first-in-human therapeutic vaccination study, a replication-defective HIV-1 vaccine (HIVAX) was tested in HIV-1 infected participants undergoing highly active antiretroviral therapy (HAART) to enhance anti-HIV immunity (Clinicaltrials.gov, identifier NCT01428596). A010 was a randomized, placebo-controlled trial to evaluate the safety and the immunogenicity of a replication defective HIV-1 vaccine (HIVAX) given as a subcutaneous injection to HIV-1 infected participants who were receiving HAART with HIV-1 viral load 500 cells/mm(3). HIV-1 specific immune responses were monitored by INF-γ enzyme linked immunospot (Elispot) and intracellular cytokine staining (ICS) assay after vaccination. Following the randomized placebo-controlled vaccination phase, subjects who received HIVAX vaccine and who met eligibility underwent a 12-week analytical antiretroviral treatment interruption (ATI). Viral load was monitored throughout the study. HIVAX was well tolerated in trial participants. Transient grade 1 to 2 (mild to moderate) injection site reactions occurred in 8 of 10 vaccinated participants. HIVAX was immunogenic in all vaccinated participants. The functionality of T cells was significantly enhanced after vaccination. Median viral load (3.45 log10 copies/ml, range of 96-12,830 copies/ml) at the end of the 12-week treatment interruption in HIVAX vaccinated group was significantly lower than the pre-treatment levels. Three vaccinated participants extended ATI for up to 2 years with stable CD4 cells and low viral loads. HIVAX vaccine is generally safe, elicits strong anti-HIV-1 immune responses, and may play an important role in controlling viral load during treatment interruption in HIV-1 infected participants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Preparation and characterization of anti-HIV nanodrug targeted to microfold cell of gut-associated lymphoid tissue.

    Science.gov (United States)

    Roy, Upal; Ding, Hong; Pilakka-Kanthikeel, Sudheesh; Raymond, Andrea D; Atluri, Venkata; Yndart, Adriana; Kaftanovskaya, Elena M; Batrakova, Elena; Agudelo, Marisela; Nair, Madhavan

    2015-01-01

    The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host-pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz (EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the GALT. In this work, we have exploited this paracellular transport property of M-cells for targeted delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell-specific antibodies to the GALT (nanodrug). Preliminary characterization showed that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index, and the zeta potential of the particles was -19.38±2.2 mV. Further, drug dissolution study has shown a significantly improved sustained release over free drugs. Binding potential of nanodrug with M-cell was also confirmed with fluorescence microscopy and in vitro uptake and release studies. The anti-HIV activity of the nanodrug was also significantly higher compared to that of free drug. This novel formulation was able to show sustained release of EFV and inhibit the HIV-1 infection in the GALT compared to the free drug. The present study has potential for our in vivo targeted nanodrug delivery system by combining traditional enteric-coated capsule technique via oral administration.

  3. A model of transluminal flow of an anti-HIV microbicide vehicle: Combined elastic squeezing and gravitational sliding.

    Science.gov (United States)

    Szeri, Andrew J; Park, Su Chan; Verguet, Stéphane; Weiss, Aaron; Katz, David F

    2008-08-01

    ELASTOHYDRODYNAMIC LUBRICATION OVER SOFT SUBSTRATES IS OF IMPORTANCE IN A NUMBER OF BIOMEDICAL PROBLEMS: From lubrication of the eye surface by the tear film, to lubrication of joints by synovial fluid, to lubrication between the pleural surfaces that protect the lungs and other organs. Such flows are also important for the drug delivery functions of vehicles for anti-HIV topical microbicides. These are intended to inhibit transmission into vulnerable mucosa, e.g., in the vagina. First generation prototype microbicides have gel vehicles, which spread after insertion and coat luminal surfaces. Effectiveness derives from potency of the active ingredients and completeness and durability of coating. Delivery vehicle rheology, luminal biomechanical properties, and the force due to gravity influence the coating mechanics. We develop a framework for understanding the relative importance of boundary squeezing and body forces on the extent and speed of the coating that results. A single dimensionless number, independent of viscosity, characterizes the relative influences of squeezing and gravitational acceleration on the shape of spreading in the Newtonian case. A second scale, involving viscosity, determines the spreading rate. In the case of a shear-thinning fluid, the Carreau number also plays a role. Numerical solutions were developed for a range of the dimensionless parameter and compared well with asymptotic theory in the limited case where such results can be obtained. Results were interpreted with respect to trade-offs between wall elasticity, longitudinal forces, bolus viscosity, and bolus volume. These provide initial insights of practical value for formulators of gel delivery vehicles for anti-HIV microbicidal formulations.

  4. 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 ...

  5. Glycosyl-Phosphatidylinositol-Anchored Anti-HIV Env Single-Chain Variable Fragments Interfere with HIV-1 Env Processing and Viral Infectivity.

    Science.gov (United States)

    Misra, Anisha; Gleeson, Emile; Wang, Weiming; Ye, Chaobaihui; Zhou, Paul; Kimata, Jason T

    2018-04-01

    In previous studies, we demonstrated that single-chain variable fragments (scFvs) from anti-human immunodeficiency virus (HIV) Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphatidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with the infectivity of newly produced virions. Here, we show that expression of the anti-HIV Env GPI-scFvs in virus-producing cells reduced the release of HIV from cells 5- to 22-fold, and infectivity of the virions that were released was inhibited by 74% to 99%. Additionally, anti-HIV Env GPI-scFv X5 inhibited virion production and infectivity after latency reactivation and blocked transmitter/founder virus production and infectivity in primary CD4 + T cells. In contrast, simian immunodeficiency virus (SIV) production and infectivity were not affected by the anti-HIV Env GPI-scFvs. Loss of infectivity of HIV was associated with a reduction in the amount of virion-associated Env gp120. Interestingly, an analysis of Env expression in cell lysates demonstrated that the anti-Env GPI-scFvs interfered with processing of Env gp160 precursors in cells. These data indicate that GPI-scFvs can inhibit Env processing and function, thereby restricting production and infectivity of newly synthesized HIV. Anti-Env GPI-scFvs therefore appear to be unique anti-HIV molecules as they derive their potent inhibitory activity by interfering with both early (receptor binding/entry) and late (Env processing and incorporation into virions) stages of the HIV life cycle. IMPORTANCE The restoration of immune function and persistence of CD4 + T cells in HIV-1-infected individuals without antiretroviral therapy requires a way to increase resistance of CD4 + T cells to

  6. Synthesis and anti-HIV activity of novel phenyl branched cyclopropyl nucleosides.

    Science.gov (United States)

    Wu, Ying; Hong, Joon Hee

    2005-09-01

    Novel phenyl branched cyclopropyl nucleoside analogues were designed and synthesized as potential antiviral agents. Cyclopropanation was performed via classical Simmons-Smith reaction using Zn(Et)2 and CH2I2. Coupling of the mesylates 11 and 12 with natural bases (A,C,T,U) and desilylation afforded a series of novel cyclopropyl nucleosides 21-28. The synthesized compounds were evaluated for their antiviral and antitumor activity against various viruses such as HIV, HSV-1, HSV-2 and HCMV.

  7. Challenges in integrating component level technology and system level information from Ayurveda: Insights from NMR phytometabolomics and anti-HIV potential of select Ayurvedic medicinal plants.

    Science.gov (United States)

    Jayasundar, Rama; Ghatak, Somenath; Makhdoomi, Muzamil Ashraf; Luthra, Kalpana; Singh, Aruna; Velpandian, Thirumurthy

    2018-01-03

    Information from Ayurveda meeting the analytical challenges of modern technology is an area of immense relevance. Apart from the cerebral task of bringing together two different viewpoints, the question at the pragmatic level remains 'who benefits whom'. The aim is to highlight the challenges in integration of information (Ayurvedic) and technology using test examples of Nuclear Magnetic Resonance (NMR) metabolomics and anti-HIV-1 potential of select Ayurvedic medicinal plants. The other value added objective is implications and relevance of such work for Ayurveda. Six medicinal plants (Azadirachta indica, Tinospora cordifolia, Swertia chirata, Terminalia bellerica, Zingiber officinale and Symplocos racemosa) were studied using high resolution proton NMR spectroscopy based metabolomics and also evaluated for anti-HIV-1 activity on three pseudoviruses (ZM53 M.PB12, ZM109F.PB4, RHPA 4259.7). Of the six plants, T.bellerica and Z.officinale showed minimum cell cytotoxicity and maximum anti-HIV-1 potential. T.bellerica was effective against all the three HIV-1 pseudoviruses. Untargeted NMR profiling and multivariate analyses demonstrated that the six plants, all of which had different Ayurvedic pharmacological properties, showed maximum differences in the aromatic region of the spectra. The work adds onto the list of potential plants for anti-HIV-1 drug molecules. At the same time, it has drawn attention to the different perspectives of Ayurveda and Western medicine underscoring the inherent limitations of conceptual bilinguism between the two systems, especially in the context of medicinal plants. The study has also highlighted the potential of NMR metabolomics in study of plant extracts as used in Ayurveda. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  8. ANN multiscale model of anti-HIV drugs activity vs AIDS prevalence in the US at county level based on information indices of molecular graphs and social networks.

    Science.gov (United States)

    González-Díaz, Humberto; Herrera-Ibatá, Diana María; Duardo-Sánchez, Aliuska; Munteanu, Cristian R; Orbegozo-Medina, Ricardo Alfredo; Pazos, Alejandro

    2014-03-24

    This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration the social determinants and activity/structure of anti-HIV drugs in preclinical assays. We trained different Artificial Neural Networks (ANNs) using as input information indices of social networks and molecular graphs. We used a Shannon information index based on the Gini coefficient to quantify the effect of income inequality in the social network. We obtained the data on AIDS prevalence and the Gini coefficient from the AIDSVu database of Emory University. We also used the Balaban information indices to quantify changes in the chemical structure of anti-HIV drugs. We obtained the data on anti-HIV drug activity and structure (SMILE codes) from the ChEMBL database. Last, we used Box-Jenkins moving average operators to quantify information about the deviations of drugs with respect to data subsets of reference (targets, organisms, experimental parameters, protocols). The best model found was a Linear Neural Network (LNN) with values of Accuracy, Specificity, and Sensitivity above 0.76 and AUROC > 0.80 in training and external validation series. This model generates a complex network of AIDS prevalence in the US at county level with respect to the preclinical activity of anti-HIV drugs in preclinical assays. To train/validate the model and predict the complex network we needed to analyze 43,249 data points including values of AIDS prevalence in 2,310 counties in the US vs ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4,856 protocols, and 10 possible experimental measures.

  9. Attitudes toward Shock Advertising of Western-European and Serbian University Students With Regard To Public Health Context (Anti-Smoking and Anti-HIV/AIDS Campaigns)

    OpenAIRE

    Krstic, Tamara

    2007-01-01

    The main objective of this dissertation is to examine attitudes toward shock advertising of western-European and Serbian university students with regard to public health context (anti-smoking and anti-HIV/AIDS campaigns). Although the use of shock advertising is widely adopted in practice, there has not been extensive research with regard to this topic. Public health context is of special interest in this dissertation as there is an urge for social marketing on Serbian market. The results of ...

  10. 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

    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...... 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...

  11. DNA topoisomerase IIα inhibitory and anti-HIV-1 flavones from leaves and twigs of Gardenia carinata.

    Science.gov (United States)

    Kongkum, Naowarat; Tuchinda, Patoomratana; Pohmakotr, Manat; Reutrakul, Vichai; Piyachaturawat, Pawinee; Jariyawat, Surawat; Suksen, Kanoknetr; Yoosook, Chalobon; Kasisit, Jitra; Napaswad, Chanita

    2012-03-01

    Four new flavones, 5,2'-dihydroxy-7,3',4',5'-tetramethoxyflavone (1), 5,2',5'-trihydroxy-7,3',4'-trimethoxyflavone (2), 5,7,2',5'-tetrahydroxy-6,3',4'-trimethoxyflavone (3) and 5,2',5'-trihydroxy-6,7,3',4'-tetramethoxyflavone (4), along with the known 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (5), 5,7,3',5'-tetrahydroxy-6,4'-dimethoxyflavone (6), syringaldehyde, vanillic acid and scopoletin were isolated from the leaves and twigs of Gardenia carinata (Rubiaceae). Their structures were determined by spectroscopic methods. Flavone 2 exhibited cytotoxic activity against P-388 and MCF-7 cell lines, while 3, 5 and 6 were active only in P-388 cell line. All active compounds were found to inhibit DNA topoisomerase IIα activity, which may be responsible for the observed cytotoxicity. Flavones 1-3, 5 and 6 also exhibited anti-HIV-1 activity in the anti-syncytium assay using (∆Tat/rev)MC99 virus and 1A2 cell line system; 2 was most potent. Only flavones 1 and 6 showed considerably activity against HIV-1 reverse transcriptase. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. 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.

  13. 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.

  14. A novel dual-luciferase assay for anti-HIV drug screening based on the CCR5/CXCR4 promoters.

    Science.gov (United States)

    Feng, Long; Lu, Wuhao; Ma, Yunyun; Guo, Wentao; Wang, Yuanyuan; Sun, Qianqian; Wu, Jianbo; Zhao, Guoqiang; Zhang, Xiaoli

    2018-02-23

    Acquired immunodeficiency syndrome (AIDS) is a serious worldwide disease caused by infection with the human immunodeficiency virus (HIV). C-C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 4 (CXCR4) are important coreceptors mediating HIV-1 cell entry. Many new anti-HIV drugs are currently in preclinical and clinical trials; however, drug development has proceeded slowly partly because of the lack of a high-throughput system to screen these drugs. Here, we describe the development of a novel dual-luciferase assay using a CCR5/CXCR4 promoter-driven firefly and Renilla luciferase vector (pGL4.10-RLUC-CCR5 /CXCR4). Drugs were screened for the ability to regulate CCR5 and CXCR4 promoter activities. The CCR5 and CXCR4 promoters were inserted separately into the recombinant vector and transfected into the acute T lymphocyte leukemia cell line H9. Treatment of stable transfected cells with four traditional Chinese medicine compounds resulted in the dose-dependent inhibition of the CXCR4 and CCR5 promoter activities. The dual-luciferase reporter assay provides a rapid and direct method to screen anti-AIDS/HIV drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. 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.

  16. Solubilization and preformulation studies on PG-300995 (an anti-HIV drug).

    Science.gov (United States)

    Ran, Yingqing; Jain, Akash; Yalkowsky, Samuel H

    2005-02-01

    This study investigates the solubilization of a potential anti-human immunodeficiency virus agent [PG-300995 or 2-(2-thiophenyl)-4-azabenzoimidazole] for oral administration. The intrinsic solubility of PG-300995 is 51 microg/mL. Multiple approaches including combinations of pH control and cosolvency, micellization, or complexation were used to improve the solubility of PG-300995. The combined techniques increased the solubility of both the unionized and ionized species. The solubility of the drug increased from 20 to 200 times depending on the pH and concentration of solubilization agents. The following formulations which contain the desired doses of 5 and 10 mg/mL were developed for oral administration. Formulation A: 10 mg/mL PG-300995 in 20% sulfobutyl ether-beta-cyclodextrin at pH 2; formulations B: 5 mg/mL PG-300995 in 10% sulfobutyl ether-beta-cyclodextrin at pH 2; formulation C: 5 mg/mL PG-300995 in 10% ethanol + 40% propylene glycol at pH 2. No precipitation was observed after series dilution of these three formulations with water or pH 2 buffers. These formulations are stable for at least 6 months after storing at room temperature and 37 degrees C. Copyright 2004 Wiley-Liss, Inc.

  17. Combined molecular docking, molecular dynamics simulation and quantitative structure-activity relationship study of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives as potent anti-HIV drugs

    Science.gov (United States)

    Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun; Li, Peizhen; Tian, Yueli; Zhai, Honglin; Li, Yang

    2014-06-01

    3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine is an antiretroviral agent, which can act against human immunodeficiency virus (HIV) infection, but the mechanism of action of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives remained ambiguous. In this study, multiple linear regression (MLR) was applied to establish a quite reliable model with the squared correlation coefficient (R2) of 0.8079. We also used chemical information descriptors based on the simplified molecular input line entry system (SMILES) to get a better model with R2 of 0.9086 for the training set, and R2 of 0.8031 for the test set. Molecular docking was utilized to provide more useful information between pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives and HIV-1 protease, such as active site, binding mode and important residues. Molecular dynamics simulation was employed to further validate the docking results. This work may lead to a better understanding of the mechanism of action and aid to design novel and more potent anti-HIV drugs.

  18. Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.

    Science.gov (United States)

    Dosenovic, Pia; Kara, Ervin E; Pettersson, Anna-Klara; McGuire, Andrew T; Gray, Matthew; Hartweger, Harald; Thientosapol, Eddy S; Stamatatos, Leonidas; Nussenzweig, Michel C

    2018-04-16

    The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.

  19. 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

    2010-11-01

    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

  20. 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)

    Uryu, Toshiyuki

    1998-01-01

    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., EC 50 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

  1. Bitter gourd (Momordica charantia) is a cornucopia of health: a review of its credited antidiabetic, anti-HIV, and antitumor properties.

    Science.gov (United States)

    Fang, E F; Ng, T B

    2011-07-01

    Bitter gourd (Momordica charantia, BG) is both a nutritious and healthy food with a distinctive bitter flavor, and it is also widely exploited in folklore medicine. This review focuses on the efficacies and molecular mechanisms of BG-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty active components. The intent of this review is to provide comprehensive and valuable information for medicinal researchers, drug investigators, clinicians, and even patients with an interest in BG. In conclusion, BG is a cornucopia of health and it deserves in-depth investigations for clinical application in the future.

  2. Herb-drug interaction between an anti-HIV Chinese herbal SH formula and atazanavir in vitro and in vivo.

    Science.gov (United States)

    Cheng, Bao-Hui; Zhou, Xuelin; Wang, Yan; Chan, Judy Yuet-Wa; Lin, Huang-Quan; Or, Penelope M Y; Wan, David Chi-Cheong; Leung, Ping-Chung; Fung, Kwok-Pui; Wang, Yi-Fen; Lau, Clara Bik-San

    2015-03-13

    affect the metabolism of ATV in rats. Our study demonstrated for the first time that there is no metabolism-based herb-drug interaction between SH formula and ATV in rats, but this combination enhances the inhibition potentials against HIV protease activity. This observation may support the combinational use of anti-HIV treatment in human. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. A quantitative comparison of anti-HIV gene therapy delivered to hematopoietic stem cells versus CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Borislav Savkovic

    2014-06-01

    Full Text Available Gene therapy represents an alternative and promising anti-HIV modality to highly active antiretroviral therapy. It involves the introduction of a protective gene into a cell, thereby conferring protection against HIV. While clinical trials to date have delivered gene therapy to CD4+T cells or to CD34+ hematopoietic stem cells (HSC, the relative benefits of each of these two cellular targets have not been conclusively determined. In the present analysis, we investigated the relative merits of delivering a dual construct (CCR5 entry inhibitor + C46 fusion inhibitor to either CD4+T cells or to CD34+ HSC. Using mathematical modelling, we determined the impact of each scenario in terms of total CD4+T cell counts over a 10 year period, and also in terms of inhibition of CCR5 and CXCR4 tropic virus. Our modelling determined that therapy delivery to CD34+ HSC generally resulted in better outcomes than delivery to CD4+T cells. An early one-off therapy delivery to CD34+ HSC, assuming that 20% of CD34+ HSC in the bone marrow were gene-modified (G+, resulted in total CD4+T cell counts ≥ 180 cells/ µL in peripheral blood after 10 years. If the uninfected G+ CD4+T cells (in addition to exhibiting lower likelihood of becoming productively infected also exhibited reduced levels of bystander apoptosis (92.5% reduction over non gene-modified (G- CD4+T cells, then total CD4+T cell counts of ≥ 350 cells/ µL were observed after 10 years, even if initially only 10% of CD34+ HSC in the bone marrow received the protective gene. Taken together our results indicate that: 1. therapy delivery to CD34+ HSC will result in better outcomes than delivery to CD4+T cells, and 2. a greater impact of gene therapy will be observed if G+ CD4+T cells exhibit reduced levels of bystander apoptosis over G- CD4+T cells.

  4. The distribution of the anti-HIV drug, tenofovir (PMPA, into the brain, CSF and choroid plexuses

    Directory of Open Access Journals (Sweden)

    Gibbs Julie E

    2006-01-01

    Full Text Available Abstract Background Tenofovir disoproxil fumarate, a prodrug of the nucleotide reverse transcriptase inhibitor, tenofovir (9-[9(R-2-(phosphonomethoxypropyl]adenine; PMPA, was recently approved for use in the combination therapy of human immunodeficiency virus (HIV-1 infection. This study was undertaken to understand PMPA distribution to the virus sanctuary sites located in the brain, CSF and choroid plexuses and to clarify its possible role in reducing the neurological problems associated with HIV infection. Methods The methods used included an established bilateral carotid artery perfusion of [3H]PMPA and a vascular marker, D-[14C]mannitol, in anaesthetised guinea-pigs followed by scintillation counting, HPLC and capillary depletion analyses. Movement of [3H]PMPA into the brain, cisternal CSF and lateral ventricle choroid plexus was also examined in the absence and presence of additional anti-HIV drugs and a transport inhibitor. Control and test groups were compared by ANOVA or Student's t-test, as appropriate. Results The distribution of [3H]PMPA in the cerebrum, cerebellum, pituitary gland and cerebral capillary endothelial cells was not significantly different to that measured for D-[14C]mannitol. However, [3H]PMPA accumulation was significantly higher than that of D-[14C]mannitol in the choroid plexus and CSF. Further experiments revealed no cross-competition for transport of [3H]PMPA by probenecid, a non-specific inhibitor of organic anion transport, or the nucleoside reverse transcriptase inhibitors into any of the CNS regions studied. The octanol-saline partition coefficient measurement for [3H]PMPA was 0.0134 ± 0.00003, which is higher that the 0.002 ± 0.0004 measured for D-[14C]mannitol in an earlier study. Conclusion There is negligible transport of [3H]PMPA across the blood-brain barrier, but it can cross the blood-CSF barrier. This is a reflection of the differing physiological and functional characteristics of the blood

  5. 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.

  6. Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody

    Science.gov (United States)

    Sainsbury, Frank; Sack, Markus; Stadlmann, Johannes; Quendler, Heribert; Fischer, Rainer; Lomonossoff, George P.

    2010-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions 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

  7. FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

    Science.gov (United States)

    Alcolea Palafox, M.; Kattan, D.; Afseth, N. K.

    2018-04-01

    A theoretical and experimental vibrational study of the anti-HIV d4T (stavudine or Zerit) nucleoside analogue was carried out. The predicted spectra in the three most stable conformers in the biological active anti-form of the isolated state were compared. Comparison of the conformers with those of the natural nucleoside thymidine was carried out. The calculated spectra were scaled by using different scaling procedures and three DFT methods. The TLSE procedure leads to the lowest error and is thus recommended for scaling. With the population of these conformers the IR gas-phase spectra were predicted. The crystal unit cell of the different polymorphism forms of d4T were simulated through dimer forms by using DFT methods. The scaled spectra of these dimer forms were compared. The FT-IR spectrum was recorded in the solid state in the 400-4000 cm-1 range. The respective vibrational bands were analyzed and assigned to different normal modes of vibration by comparison with the scaled vibrational values of the different dimer forms. Through this comparison, the polymorphous form of the solid state sample was identified. The study indicates that d4T exist only in the ketonic form in the solid state. The results obtained were in agreement with those determined in related anti-HIV nucleoside analogues.

  8. The offer of the anti-HIV test to the users of the health basic net units: different aproaches of professionals

    Directory of Open Access Journals (Sweden)

    Sergio Corrêa Marques

    2015-01-01

    Full Text Available Objetivos: identificar e descrever as condutas dos profissionais de saúde na oferta do teste anti-HIV; analisar as práticas dos profissionais a partir dos relatos das usuárias dos serviços da rede básica de saúde. Método: é um estudo descritivo, qualitativo, com 40 mulheres assistidas em 08 Centros Municipais de Saúde. Resultados: a produção discursiva das entrevistas foi submetida ao programa Alceste, constituindo duas categorias de análise. A primeira contempla as abordagens no atendimento individual na rede de CMS do Rio de Janeiro descrevendo os três modos de conduta dos profissionais de saúde durante a oferta de teste anti-HIV. A segunda categoria refere-se às abordagens no atendimento coletivo, onde se observa que as atividades de aconselhamento não ocorrem de maneira uniforme. Conclusão: que os resultados apontam para uma prática que se desvirtua do que vem sendo preconizado pelos Programas oficiais em relação ao Aconselhamento.

  9. One-by-one imprinting in two eccentric layers of hollow core-shells: Sequential electroanalysis of anti-HIV drugs.

    Science.gov (United States)

    Singh, Kislay; Jaiswal, Swadha; Singh, Richa; Fatma, Sana; Prasad, Bhim Bali

    2018-07-15

    Double layered one-by-one imprinted hollow core-shells@ pencil graphite electrode was fabricated for sequential sensing of anti-HIV drugs. For this, two eccentric layers were developed on the surface of vinylated silica nanospheres to obtain double layered one-by-one imprinted solid core-shells. This yielded hollow core-shells on treatment with hydrofluoric acid. The modified hollow core-shells (single layered dual imprinted) evolved competitive diffusion of probe/analyte molecules. However, the corresponding double layered one-by-one imprinted hollow core-shells (outer layer imprinted with Zidovudine, and inner layer with Lamivudine) were found relatively better owing to their bilateral diffusions into molecular cavities, without any competition. The entire work is based on differential pulse anodic stripping voltammetry at double layered one-by-one imprinted hollow core-shells. This resulted in indirect detection of electro inactive targets with limits of detection as low as 0.91 and 0.12 (aqueous sample), 0.94 and 0.13 (blood serum), and 0.99 and 0.20 ng mL -1 (pharmaceutics) for lamivudine and zidovudine, respectively in anti-HIV drug combination. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Slaying the Trojan horse: natural killer cells exhibit robust anti-HIV-1 antibody-dependent activation and cytolysis against allogeneic T cells.

    Science.gov (United States)

    Gooneratne, Shayarana L; Richard, Jonathan; Lee, Wen Shi; Finzi, Andrés; Kent, Stephen J; Parsons, Matthew S

    2015-01-01

    Many attempts to design prophylactic human immunodeficiency virus type 1 (HIV-1) vaccines have focused on the induction of neutralizing antibodies (Abs) that block infection by free virions. Despite the focus on viral particles, virus-infected cells, which can be found within mucosal secretions, are more infectious than free virus both in vitro and in vivo. Furthermore, assessment of human transmission couples suggests infected seminal lymphocytes might be responsible for a proportion of HIV-1 transmissions. Although vaccines that induce neutralizing Abs are sought, only some broadly neutralizing Abs efficiently block cell-to-cell transmission of HIV-1. As HIV-1 vaccines need to elicit immune responses capable of controlling both free and cell-associated virus, we evaluated the potential of natural killer (NK) cells to respond in an Ab-dependent manner to allogeneic T cells bearing HIV-1 antigens. This study presents data measuring Ab-dependent anti-HIV-1 NK cell responses to primary and transformed allogeneic T-cell targets. We found that NK cells are robustly activated in an anti-HIV-1 Ab-dependent manner against allogeneic targets and that tested target cells are subject to Ab-dependent cytolysis. Furthermore, the educated KIR3DL1(+) NK cell subset from HLA-Bw4(+) individuals exhibits an activation advantage over the KIR3DL1(-) subset that contains both NK cells educated through other receptor/ligand combinations and uneducated NK cells. These results are intriguing and important for understanding the regulation of Ab-dependent NK cell responses and are potentially valuable for designing Ab-dependent therapies and/or vaccines. NK cell-mediated anti-HIV-1 antibody-dependent functions have been associated with protection from infection and disease progression; however, their role in protecting from infection with allogeneic cells infected with HIV-1 is unknown. We found that HIV-1-specific ADCC antibodies bound to allogeneic cells infected with HIV-1 or coated

  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

    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. PHARMACOKINETIC ANALYSIS AND CELLULAR-DISTRIBUTION OF THE ANTI-HIV COMPOUND SUCCINYLATED HUMAN SERUM-ALBUMIN (SUC-HSA) IN-VIVO AND IN THE ISOLATED-PERFUSED RAT-LIVER

    NARCIS (Netherlands)

    JANSEN, RW; OLINGA, P; HARMS, G; MEIJER, DKF

    1993-01-01

    After intravenous injection of a low dose (25 mug/kg) in rats, the anti HIV-1 compound succinylated human serum albumin (Suc-HSA) is taken up mainly in the liver and spleen and is proteolytically degraded. Ten minutes after injection of I-125-Suc-HSA, 72 and 14% of the dose were found in the liver

  13. Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells.

    Science.gov (United States)

    Sahu, Gautam K; Sango, Kaori; Selliah, Nithianandan; Ma, Qiangzhong; Skowron, Gail; Junghans, Richard P

    2013-11-01

    The current antiretroviral therapy (ART) can effectively reduce plasma HIV loads to undetectable levels, but cannot eliminate latently infected resting memory CD4 T cells that persist for the lifetime of infected patients. Therefore, designing new therapeutic approaches to eliminate these latently infected cells or the cells that produce HIV upon reactivation from latency is a priority in the ART era in order to progress to a cure of HIV. Here, we show that "designer" T cells expressing chimeric antigen receptor (CAR), CD4-CD28-CD3ζ, can target and kill HIV Env-expressing cells. Further, they secrete effector cytokines upon contact with HIV Env+ target cells that can reactivate latent HIV in a cell line model, thereby exposing those cells to recognition and killing by anti-HIV CAR+ T cells. Taken to the limit, this process could form the basis for an eventual functional or sterilizing cure for HIV in patients. © 2013 Elsevier Inc. All rights reserved.

  14. 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

  15. 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

  16. 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

  17. 5-Modified-2'-dU and 2'-dC as mutagenic anti HIV-1 proliferation agents: synthesis and activity.

    Science.gov (United States)

    El Safadi, Yazan; Paillart, Jean-Christophe; Laumond, Géraldine; Aubertin, Anne-Marie; Burger, Alain; Marquet, Roland; Vivet-Boudou, Valérie

    2010-02-25

    With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified on the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds plus two additional ones (5-carbamoyl-2'-dU (1a) and 5-carbamoylmethyl-2'-dU (1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.

  18. How to easily replace the independent atom model - the example of bergenin, a potential anti-HIV agent of traditional Asian medicine.

    Science.gov (United States)

    Dittrich, Birger; Weber, Manuela; Kalinowski, Roman; Grabowsky, Simon; Hübschle, Christian B; Luger, Peter

    2009-12-01

    Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu Kalpha room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree-Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research.

  19. Crystal structure of ammonium 3′-azido-3′-deoxythymidine-5′-aminocarbonylphosphonate hemihydrate: an anti-HIV agent

    Directory of Open Access Journals (Sweden)

    Maxim V. Jasko

    2014-11-01

    Full Text Available The asymmetric unit of the title compound, NH4+·C11H14N6O7P−·0.5H2O, contains one 3′-azido-3′-deoxythymidine-5′aminocarbonylphosphonate (ACP–AZT anion, half of an NH4+ cation lying on a twofold rotation axis and in another position, occupied with equal probabilities of 0.5, an NH4+ cation and a water molecule. The amide group of the ACP–AZT anion is disordered (occupancy ratio 0.5:0.5, with one part forming an N—H...O (involving C=O...H4N+ hydrogen bond and the other an O—H...N (involving C—NH2...OH2 hydrogen bond with the components of the split NH4+/H2O position. The pseudorotation parameters of ACP–AZT set it apart from previously studied AZT and thymidine. In the crystal, the various components are linked by N—H...O, O—H...O, N—H...N, C—H...O and C—H...N hydrogen bonds, forming a three-dimensional framework.

  20. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

    DEFF Research Database (Denmark)

    Worm, Signe Westring; Sabin, Caroline; Weber, Rainer

    2010-01-01

    BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients......% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI...

  1. Uso rotineiro do teste anti-HIV entre homens que fazem sexo com homens: do risco à prevenção

    Directory of Open Access Journals (Sweden)

    Bruna Robba Lara Redoschi

    Full Text Available Resumo: Desenvolvemos uma revisão crítica da literatura sobre o uso recorrente do teste anti-HIV entre homens que fazem sexo com homens (HSH. Procedemos a uma revisão narrativa da literatura, em que analisamos as diversas concepções sobre testagem frequente ao longo do tempo, suas implicações para os programas de saúde e os principais marcadores sociais que influenciam a incorporação do teste anti-HIV como rotina de cuidado. Embora exista desde os anos 1990, a testagem recorrente entre HSH era frequentemente interpretada como exposição aumentada ao HIV em razão da ausência de uso do preservativo e, consequentemente, uma testagem “desnecessária”. A partir dos anos 2000, a testagem periódica passou a ser uma recomendação programática e, sua realização, interpretada como meta a ser atingida. A percepção dos indivíduos sobre o uso que faziam do teste foi raramente considerada para caracterizar este uso como rotina de cuidado. No plano social e cultural, aspectos individuais associados ao teste recente ou de rotina estiveram inscritos em contextos de normas favoráveis ao teste e de menor estigma da AIDS. Diferenças geracionais, de escolarização e relacionadas ao tipo de parceria afetivo-sexual desempenham importantes papéis para o teste. Tais diferenças realçam que a categoria epidemiológica “homens que fazem sexo com homens” abrange diversas relações, identidades e práticas que resultam em usos específicos do teste como estratégia de prevenção. Assim, o diálogo entre programas, profissionais de saúde e as pessoas mais afetadas pela epidemia é central à construção de respostas com efetivo potencial de enfrentamento à epidemia de HIV, e pautadas no respeito aos direitos humanos.

  2. 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

  3. 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

  4. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  5. 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

  6. 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 reverse...... transcriptase (RT) and this was believed to improve antiviral activity against HIV-1. The bromo derivatives, 5-alkyl-6-(3-bromo-benzyl)-1-ethoxymethyl derivatives 7a, b and 5-alkyl-6-(3-bromobenzyl)-1-allyloxymethyl derivatives 9a, b, showed activity against HIV on the same level as their corresponding...

  7. Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization.

    Science.gov (United States)

    Liu, Zhaoqiang; Chen, Wenmin; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

    2014-11-24

    Through a structure-based molecular hybridization approach, a novel series of diarylnicotinamide derivatives (DANAs) targeting the entrance channel of HIV-1 NNRTIs binding pocket (NNIBP) were rationally designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells together with the inhibition against the reverse transcriptase (RT) in an enzymatic assay. Encouragingly, most of the new DANAs were found to be active against wild-type HIV-1 with an EC50 in the range of 0.027-4.54 μM. Among them, compound 6b11 (EC50 = 0.027 μM, SI > 12518) and 6b5 (EC50 = 0.029 μM, SI = 2471) were identified as the most potent inhibitors, which were more potent than the reference drugs nevirapine (EC50 = 0.31 μM) and delavirdine (EC50 = 0.66 μM). Some DANAs were also active at micromolar concentrations against the K103N + Y181C resistant mutant. Compound 6b11 exhibited the highest enzymatic inhibition activity (IC50 = 20 nM), which is equal to that of efavirenz (EC50 = 20 nM) and 31 times higher than that of nevirapine (EC50 = 0.62 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new DANAs have been discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Genome-wide expression profiling analysis to identify key genes in the anti-HIV mechanism of CD4+and CD8+T cells.

    Science.gov (United States)

    Gao, Lijie; Wang, Yunqi; Li, Yi; Dong, Ya; Yang, Aimin; Zhang, Jie; Li, Fengying; Zhang, Rongqiang

    2018-03-06

    Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 + and CD8 + T cells. The numbers of CD4 + and CD8 + T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 + and CD8 + T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 + and CD8 + T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 + T cells counts and ratio of CD4 + /CD8 + T cells decreased while CD8 + T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 + and CD8 + T cells at acute and chronic stage with the criterial of P-value CD8 + T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells. © 2018 Wiley Periodicals, Inc.

  9. 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.

  10. Aconselhamento pós-teste anti-HIV: análise à luz de uma teoria humanística de Enfermagem Consejería pós test Anti-HIV: análisis a luz de una teoría humanistica de enfermería Anti-HIV after-test counselling: analysis at a light of a Nursing humanistic theory

    Directory of Open Access Journals (Sweden)

    Maria Alix Leite Araújo

    2006-12-01

    Full Text Available Este trabalho analisa o aconselhamento pós-teste anti-HIV em Unidades Básicas de Saúde. Trata-se de um estudo qualitativo desenvolvido em Unidades Básicas de Saúde da Família de Fortaleza (UBASF. O trabalho de campo ocorreu pela observação do atendimento de 12 enfermeiros em consultas de pré-natal. O referencial teórico de análise foi a Teoria Humanística de Enfermagem de Paterson e Zderad visto que a Enfermagem, segundo a teoria, implica um tipo especial de encontro entre seres humanos. A análise baseou-se no conceito de diálogo, tendo como variáveis seus elementos estruturais: o encontro, o relacionamento, a presença e o chamado, e a resposta. Observou-se que a assistência às gestantes não atingiu o relacionamento EU-TU, ou seja, o relacionamento sujeito-sujeito, com a presença do diálogo genuíno. Prevaleceu o relacionamento EU-ISSO, sujeito-objeto. As consultas eram rápidas e puramente mecânicas, levando esses profissionais, em certos momentos, a fugirem de uma assistência humanizada.Este trabajo analiza el pos test de consejería anti-HIV en las Unidades Básicas de Salud. Es un estudio cualitativo desarrollado en las Unidades Básicas de Salud de la Familia en la ciudad de Fortaleza (UBASF. El trabajo de campo sucedió por la observación de la asistencia de 12 enfermeros en las consultas de pré-natal. El referencial teórico de análisis fué la Teoría Humanistica de Paterson y Zderad de Enfermería, visto en la enfermería, según la teoría, implica en un tipo especial de encuentro entre los seres humanos. El análisis era basado en el concepto de diálogo, teniendo como las variables sus elementos estructurales: el encuentro, la relación, la presencia y el llamamiento y la respuesta. Fue observado que la ayuda a la embarazada no alcanzó la relación YO-USTED, en otros términos, el sujeto-sujeto de la relación, con la presencia del diálogo auténtico. La relación que prevaleció era el YO-AQUEL, sujeto

  11. Desenvolvimento de formulações e tecnologia de obtenção de comprimidos revestidos de efavirenz: terapia anti-HIV Development of formulations and technology of efavirenz coated tablets obtention: anti-HIV therapy

    Directory of Open Access Journals (Sweden)

    Osnir de Sá Viana

    2006-12-01

    Full Text Available O efavirenz é uma das mais recentes classes de agentes anti-retrovirais aplicados no tratamento de infecções por HIV. Está entre os medicamentos de primeira escolha no tratamento da AIDS. Como o efavirenz possui característica hidrofóbica, baixa densidade e oferece grande resistência ao escoamento, a escolha de uma formulação adequada deste fármaco é essencial no desenvolvimento dos comprimidos e para garantir melhor disponibilização no trato gastrointestinal, de forma a alcançar a biodisponibilidade e o efeito terapêutico desejados. Neste trabalho, apresentamos, de forma lógica, o desenvolvimento tecnológico de comprimidos revestidos de efavirenz, levando em consideração suas características físicas e físico-químicas. Os núcleos (comprimidos de efavirenz foram obtidos utilizando-se a técnica de granulação por via úmida. No revestimento por película utilizou-se Opadry® Y-1-7000 em sistema aquoso. Os parâmetros adotados para avaliação física dos comprimidos seguiram as especificações farmacopéicas oficiais e a determinação quantitativa foi realizada mediante método analítico desenvolvido e validado.Efavirenz is one of the most recent classes of anti-retroviral drugs used in the treatment of HIV infections. It is the first choice therapy for AIDS treatment. As efavirenz detains hydrofobic characteristic, low density and offers great resistance to draining, it has been essential to choose an adequated formulation for it, in order to guarantee drug's availability in gastro-intestinal tract, achieving bioavailability and expected therapeutical effects. This work presents efavirez coated tablets thecnological development, considering the physics and physico-chemical characteristics of this drug. The efavirez nucleus (tablets has been obtained employing granulation technics by humid via. In the coating by film, Opadry Y-1-7000 in aquous system was used. The adopted parameters to tablet phisics evaluation

  12. 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

  13. Developing a community-level anti-HIV/AIDS stigma and homophobia intervention in new York city: The project CHHANGE model.

    Science.gov (United States)

    Frye, Victoria; Paige, Mark Q; Gordon, Steven; Matthews, David; Musgrave, Geneva; Kornegay, Mark; Greene, Emily; Phelan, Jo C; Koblin, Beryl A; Taylor-Akutagawa, Vaughn

    2017-08-01

    HIV/AIDS stigma and homophobia are associated with significant negative health and social outcomes among people living with HIV/AIDS (PLWHA) and those at risk of infection. Interventions to decrease HIV stigma have focused on providing information and education, changing attitudes and values, and increasing contact with people living with HIV/AIDS (PLWHA), activities that act to reduce stereotyped beliefs and prejudice, as well as acts of discrimination. Most anti-homophobia interventions have focused on bullying reduction and have been implemented at the secondary and post-secondary education levels. Few interventions address HIV stigma and homophobia and operate at the community level. Project CHHANGE, Challenge HIV Stigma and Homophobia and Gain Empowerment, was a community-level, multi-component anti-HIV/AIDS stigma and homophobia intervention designed to reduce HIV stigma and homophobia thus increasing access to HIV prevention and treatment access. The theory-based intervention included three primary components: workshops and trainings with local residents, businesses and community-based organizations (CBO); space-based events at a CBO-partner drop-in storefront and "pop-up" street-based events and outreach; and a bus shelter ad campaign. This paper describes the intervention design process, resultant intervention and the study team's experiences working with the community. We conclude that CHHANGE was feasible and acceptable to the community. Promoting the labeling of gay and/or HIV-related "space" as a non-stigmatized, community resource, as well as providing opportunities for residents to have contact with targeted groups and to understand how HIV stigma and homophobia relate to HIV/AIDS prevalence in their neighborhood may be crucial components of successful anti-stigma and discrimination programming. Copyright © 2017. Published by Elsevier Ltd.

  14. Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma.

    Science.gov (United States)

    Kraft, John C; McConnachie, Lisa A; Koehn, Josefin; Kinman, Loren; Collins, Carol; Shen, Danny D; Collier, Ann C; Ho, Rodney J Y

    2017-03-27

    The aim of the present study was to determine whether a combination of anti-HIV drugs - tenofovir (TFV), lopinavir (LPV) and ritonavir (RTV) - in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma. Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analysed using a validated combination LC-MS/MS assay. For the two active drugs (TFV, LPV), plasma and PBMC intracellular drug levels persisted for over 2 weeks; PBMC drug exposures were three- to four-fold higher than those in plasma. Apparent terminal half-lives (t1/2) of TFV and LPV were 65.3 and 476.9 h in plasma, and 169.1 and 151.2 h in PBMCs. At 24 and 192 h, TFV and LPV drug levels in LNMCs were up to 79-fold higher than those in PBMCs. Analysis of PBMC intracellular TFV and its active metabolite TFV-diphosphate (TFV-DP) indicated that intracellular exposures of total TFV and TFV-DP were markedly higher and persisted longer than in humans and macaques dosed with oral TFV prodrugs, tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). A simple, scalable three-drug combination, lipid-stabilized nanosuspension exhibited persistent drug levels in cells of lymph nodes and the blood (HIV host cells) and in plasma. With appropriate dose adjustment, TLC-ART101 may be a useful HIV treatment with a potential to impact residual virus in lymph nodes.

  15. 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.

  16. Anti-HIV I/II activity and molecular cloning of a novel mannose/sialic acid-binding lectin from rhizome of Polygonatum cyrtonema Hua.

    Science.gov (United States)

    An, Jie; Liu, Jin-Zhi; Wu, Chuan-Fang; Li, Jian; Dai, Lei; Van Damme, Els; Balzarini, Jan; De Clercq, Erik; Chen, Fang; Bao, Jin-Ku

    2006-02-01

    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-dimensional 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.

  17. Expression of deoxynucleotide carrier is not associated with the mitochondrial DNA depletion caused by anti-HIV dideoxynucleoside analogs and mitochondrial dNTP uptake.

    Science.gov (United States)

    Lam, Wing; Chen, ChinShing; Ruan, Shuolun; Leung, Chung-Hang; Cheng, Yung-Chi

    2005-02-01

    Our previous studies suggested that the dNTP/dNDP transporter systems that exist in mitochondria for transporting dNTP/dNDP from the cytoplasm to the mitochondria for mitochondrial DNA (mtDNA) synthesis play a critical role in delayed cytotoxicity of anti-human immunodeficiency virus (HIV) dideoxynucleoside analogs in mitochondria. A protein, termed mitochondrial deoxynucleotide carrier (DNC), based on its ability to transport dNTPs in reconstituted proteoliposomes, was recently isolated. Lacking cellular information to substantiate DNC's involvement in the delayed cytotoxicity of dideoxynucleoside analogs, we expressed DNC and reconstituted it into proteoliposomes. The K(m) values for dNTPs uptake by reconstituted DNC were in the millimolar range, which is a thousandfold higher than that of the physiological level. Furthermore, we found that overexpressing DNC (wt and G177A-mutated DNC) in RKO cells did not sensitize the cells to the mtDNA depletion caused by beta-d-2',3'-dideoxycytidine (ddC), 2',3'-didehydro-2',3'-dideoxythymidine, and 2',3'-dideoxyinosine or affect the mtDNA recovery rate after ddC treatment. Mitochondria isolated from DNC-overexpressing cells did not significantly differ from that isolated from RKO cells in terms of the rate of uptake or the incorporation of dTTP into mitochondria DNA. Down-regulation of DNC expression by small interfering RNA was also ineffective in changing the action of dideoxynucleoside analogs on the mtDNA depletion and the rate of dTTP uptake into isolated mitochondria. Down-regulation of both DNC and thymidine kinase-2 also did not cause mtDNA depletion. We conclude that DNC does not play an important role in the delayed cytotoxicity (mtDNA depletion) of anti-HIV dideoxynucleoside analogs and dNTPs uptake into mitochondria.

  18. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

    DEFF Research Database (Denmark)

    De Wit, Stephane; Sabin, Caroline A; Weber, Rainer

    2008-01-01

    OBJECTIVE: The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated...... with the onset of diabetes, and to identify possible mechanisms for any relationships found. RESEARCH DESIGN AND METHODS: D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes...

  19. 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.

  20. First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration of its safety and enhancement of anti-HIV antibody responses.

    Science.gov (United States)

    Choi, Eunsil; Michalski, Chad J; Choo, Seung Ho; Kim, Gyoung Nyoun; Banasikowska, Elizabeth; Lee, Sangkyun; Wu, Kunyu; An, Hwa-Yong; Mills, Anthony; Schneider, Stefan; Bredeek, U Fritz; Coulston, Daniel R; Ding, Shilei; Finzi, Andrés; Tian, Meijuan; Klein, Katja; Arts, Eric J; Mann, Jamie F S; Gao, Yong; Kang, C Yong

    2016-11-28

    Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus. This genetically modified virus (gmHIV-1 NL4-3 ) was inactivated and formulated as a killed whole-HIV vaccine, and then used for a Phase I human clinical trial (Trial Registration: Clinical Trials NCT01546818). The gmHIV-1 NL4-3 was propagated in the A3.01 human T cell line followed by virus purification and inactivation with aldrithiol-2 and γ-irradiation. Thirty-three HIV-1 positive volunteers receiving cART were recruited for this observer-blinded, placebo-controlled Phase I human clinical trial to assess the safety and immunogenicity. Genetically modified and killed whole-HIV-1 vaccine, SAV001, was well tolerated with no serious adverse events. HIV-1 NL4-3 -specific PCR showed neither evidence of vaccine virus replication in the vaccine virus-infected human T lymphocytes in vitro nor in the participating volunteers receiving SAV001 vaccine. Furthermore, SAV001 with adjuvant significantly increased the pre-existing antibody response to HIV-1 proteins. Antibodies in the plasma of vaccinees were also found to recognize HIV-1 envelope protein on the surface of infected cells as well as showing an enhancement of broadly neutralizing antibodies inhibiting tier I and II of HIV-1 B, D, and A subtypes. The killed whole-HIV vaccine, SAV001, is safe and triggers anti-HIV immune responses. It remains to be determined through an appropriate trial whether this immune response prevents

  1. 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.

  2. Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity

    Directory of Open Access Journals (Sweden)

    McKnight Áine

    2010-03-01

    Full Text Available Abstract Background Previous reports have shown that peptides derived from the apolipoprotein E receptor binding region and the amphipathic α-helical domains of apolipoprotein AI have broad anti-infective activity and antiviral activity respectively. Lipoproteins and viruses share a similar cell biological niche, being of overlapping size and displaying similar interactions with mammalian cells and receptors, which may have led to other antiviral sequences arising within apolipoproteins, in addition to those previously reported. We therefore designed a series of peptides based around either apolipoprotein receptor binding regions, or amphipathic α-helical domains, and tested these for antiviral and antibacterial activity. Results Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170 - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367 dp (apoBdp, the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W. Conclusions These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of

  3. HIV-1 Tat Promotes Integrin-Mediated HIV Transmission to Dendritic Cells by Binding Env Spikes and Competes Neutralization by Anti-HIV Antibodies

    Science.gov (United States)

    Monini, Paolo; Cafaro, Aurelio; Srivastava, Indresh K.; Moretti, Sonia; Sharma, Victoria A.; Andreini, Claudia; Chiozzini, Chiara; Ferrantelli, Flavia; Cossut, Maria R. Pavone.; Tripiciano, Antonella; Nappi, Filomena; Longo, Olimpia; Bellino, Stefania; Picconi, Orietta; Fanales-Belasio, Emanuele; Borsetti, Alessandra; Toschi, Elena; Schiavoni, Ilaria; Bacigalupo, Ilaria; Kan, Elaine; Sernicola, Leonardo; Maggiorella, Maria T.; Montin, Katy; Porcu, Marco; Leone, Patrizia; Leone, Pasqualina; Collacchi, Barbara; Palladino, Clelia; Ridolfi, Barbara; Falchi, Mario; Macchia, Iole; Ulmer, Jeffrey B.; Buttò, Stefano; Sgadari, Cecilia; Magnani, Mauro; Federico, Maurizio P. M.; Titti, Fausto; Banci, Lucia; Dallocchio, Franco; Rappuoli, Rino; Ensoli, Fabrizio; Barnett, Susan W.; Garaci, Enrico; Ensoli, Barbara

    2012-01-01

    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. PMID:23152803

  4. Aconselhamento em DST/Aids às gestantes que realizaram o teste anti-HIV na admissão para o parto: os sentidos de uma prática

    Directory of Open Access Journals (Sweden)

    Patrícia de Lima Fonseca

    2012-06-01

    Full Text Available Foram analisadas as práticas e os sentidos do aconselhamento para gestantes submetidas ao teste anti-HIV na admissão para o parto, e para profissionais de saúde que atuam na assistência à maternidade em Salvador, Brasil. Foi realizado um estudo qualitativo em uma maternidade, com observação participante e entrevistas semiestruturadas com 13 puérperas sem diagnóstico prévio para o HIV e sete profissionais de saúde. Observou-se que o exame anti-HIV é realizado de forma compulsória, sem considerar a autonomia da gestante, e que o aconselhamento se limita a informar o diagnóstico e dar orientações no pós-teste somente àquelas cujos resultados foram positivos. Os sentidos que permeiam o exame, assim como o entendimento da experiência e os significados construídos pelas puérperas, sobretudo quando se descobrem positivas para o HIV, não são abordados pelos profissionais, que não se sentem capacitados para acolherem a subjetividade das pacientes.

  5. Aconselhamento em DST/Aids às gestantes que realizaram o teste anti-HIV na admissão para o parto: os sentidos de uma prática

    Directory of Open Access Journals (Sweden)

    Patrícia de Lima Fonseca

    Full Text Available Foram analisadas as práticas e os sentidos do aconselhamento para gestantes submetidas ao teste anti-HIV na admissão para o parto, e para profissionais de saúde que atuam na assistência à maternidade em Salvador, Brasil. Foi realizado um estudo qualitativo em uma maternidade, com observação participante e entrevistas semiestruturadas com 13 puérperas sem diagnóstico prévio para o HIV e sete profissionais de saúde. Observou-se que o exame anti-HIV é realizado de forma compulsória, sem considerar a autonomia da gestante, e que o aconselhamento se limita a informar o diagnóstico e dar orientações no pós-teste somente àquelas cujos resultados foram positivos. Os sentidos que permeiam o exame, assim como o entendimento da experiência e os significados construídos pelas puérperas, sobretudo quando se descobrem positivas para o HIV, não são abordados pelos profissionais, que não se sentem capacitados para acolherem a subjetividade das pacientes.

  6. Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S; Nogueira, Lilian; Schoofs, Till; Krassnig, Lisa; Butler, Allison; Millard, Katrina; Fitzsimons, Tomas; Daniell, Xiaoju; Dizon, Juan P; Shimeliovich, Irina; Montefiori, David C; Caskey, Marina; Nussenzweig, Michel C

    2018-03-01

    HIV-1 epidemic. Antibodies with exceptional neutralizing activity against HIV-1 may provide several advantages to traditional HIV drugs, including an improved side-effect profile, a reduced dosing frequency, and immune enhancement. The activity of these antibodies has been established in vitro by utilizing HIV-1 Env-pseudotyped viruses derived from circulating viruses but produced in 293T cells by pairing Env proteins with a backbone vector. We tested PBMC-produced circulating viruses against five anti-HIV-1 antibodies currently in clinical development. We found that the activity of these antibodies against PBMC isolates is significantly less than that against 293T Env-pseudotyped viruses. This decline varied among the antibodies tested, with some demonstrating moderate reductions in activity and others showing an almost 100-fold reduction. As the development of these antibodies progresses, it will be critical to determine how the results of different in vitro tests correspond to performance in the clinic. Copyright © 2018 Cohen et al.

  7. 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.

  8. 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)

    Kamata, Masakazu; Kim, Patrick Y.; Ng, Hwee L.; Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O'Connor, Sean; Yang, Otto O.; Chen, Irvin S.Y.

    2015-01-01

    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 p24 Gag 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

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

    Directory of Open Access Journals (Sweden)

    Neves Fátima RAL

    1999-01-01

    Full Text Available 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 68,3% das 17.589 mulheres atendidas em pré-natal, resultando numa positividade de 0,76%.

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

    Directory of Open Access Journals (Sweden)

    Fátima RAL Neves

    1999-12-01

    Full Text Available 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 68,3% das 17.589 mulheres atendidas em pré-natal, resultando numa positividade de 0,76%.

  11. 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.

  12. 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.; hide

    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

  13. 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.

    Directory of Open Access Journals (Sweden)

    Bridgette Janine Connell

    Full Text Available 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.

  14. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  15. Disponibilidade de sorologia anti-HIV como um teste voluntário na rotina do atendimento pré-natal em unidades básicas de saúde Availability of voluntary prenatal HIV screening in primary health centers

    Directory of Open Access Journals (Sweden)

    Fátima RAL Neves

    1999-12-01

    Full Text Available 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 68,3% das 17.589 mulheres atendidas em pré-natal, resultando numa positividade de 0,76%.A summary of the main steps towards the implementation of anti-HIV testing for pregnant women in the city is presented. Starting from August 1996, voluntary HIV testing became available to pregnant women seen at primary health centers in Ribeirão Preto, SP (Brazil, as part of the Prenatal Care Program. By the end of 1998, 68.3% of the 17,589 women seeking prenatal care had been tested, resulting in a positivity rate of 0.76%.

  16. 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

  17. Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial.

    Science.gov (United States)

    Mayer, Kenneth H; Seaton, Kelly E; Huang, Yunda; Grunenberg, Nicole; Isaacs, Abby; Allen, Mary; Ledgerwood, Julie E; Frank, Ian; Sobieszczyk, Magdalena E; Baden, Lindsey R; Rodriguez, Benigno; Van Tieu, Hong; Tomaras, Georgia D; Deal, Aaron; Goodman, Derrick; Bailer, Robert T; Ferrari, Guido; Jensen, Ryan; Hural, John; Graham, Barney S; Mascola, John R; Corey, Lawrence; Montefiori, David C

    2017-11-01

    , nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. VRC01 administered as either an IV infusion (10-40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants' sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials. Clinical Trials Registration: NCT02165267.

  18. Anti-V3/Glycan and Anti-MPER Neutralizing Antibodies, but Not Anti-V2/Glycan Site Antibodies, Are Strongly Associated with Greater Anti-HIV-1 Neutralization Breadth and Potency.

    Science.gov (United States)

    Jacob, Rajesh Abraham; Moyo, Thandeka; Schomaker, Michael; Abrahams, Fatima; Grau Pujol, Berta; Dorfman, Jeffrey R

    2015-05-01

    The membrane-proximal external region (MPER), the V2/glycan site (initially defined by PG9 and PG16 antibodies), and the V3/glycans (initially defined by PGT121-128 antibodies) are targets of broadly neutralizing antibodies and potential targets for anti-HIV-1 antibody-based vaccines. Recent evidence shows that antibodies with moderate neutralization breadth are frequently attainable, with 50% of sera from chronically infected individuals neutralizing ≥ 50% of a large, diverse set of viruses. Nonetheless, there is little systematic information addressing which specificities are preferentially targeted among such commonly found, moderately broadly neutralizing sera. We explored associations between neutralization breadth and potency and the presence of neutralizing antibodies targeting the MPER, V2/glycan site, and V3/glycans in sera from 177 antiretroviral-naive HIV-1-infected (>1 year) individuals. Recognition of both MPER and V3/glycans was associated with increased breadth and potency. MPER-recognizing sera neutralized 4.62 more panel viruses than MPER-negative sera (95% prediction interval [95% PI], 4.41 to 5.20), and V3/glycan-recognizing sera neutralized 3.24 more panel viruses than V3/glycan-negative sera (95% PI, 3.15 to 3.52). In contrast, V2/glycan site-recognizing sera neutralized only 0.38 more panel viruses (95% PI, 0.20 to 0.45) than V2/glycan site-negative sera and no association between V2/glycan site recognition and breadth or potency was observed. Despite autoreactivity of many neutralizing antibodies recognizing MPER and V3/glycans, antibodies to these sites are major contributors to neutralization breadth and potency in this cohort. It may therefore be appropriate to focus on developing immunogens based upon the MPER and V3/glycans. Previous candidate HIV vaccines have failed either to induce wide-coverage neutralizing antibodies or to substantially protect vaccinees. Therefore, current efforts focus on novel approaches never before

  19. 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

  20. 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.

  1. Sorologia anti-HIV e aconselhamento pré-teste em gestantes na região noroeste do Paraná, Brasil HIV serology and pretest counseling among pregnant women in the northwest region of Paraná State, Brazil

    Directory of Open Access Journals (Sweden)

    Norico Miyagui Misuta

    2008-03-01

    Full Text Available OBJETIVOS: analisar a cobertura do aconselhamento e do teste anti-HIV, e identificar fatores associados à sua realização no pré-natal. MÉTODOS: estudo transversal, com mulheres de cinco municípios do Noroeste do Paraná, Brasil, com partos entre janeiro e março de 2003, identificadas a partir dos sistemas de informação. Os dados foram obtidos em entrevistas domiciliares. Considerou-se teste realizado quando havia registro do resultado do exame para HIV no cartão de gestante ou no laboratório de referência. As análises estatísticas foram feitas utilizando o teste do χ2 e exato de Fisher (α=0,05. RESULTADOS: das 435 mulheres entrevistadas, todas foram acompanhadas no pré-natal, com cobertura do teste anti-HIV de 89,6% - [IC95%: 86,8-92,4]. Não foram evidenciadas associações significativas entre a realização do teste e as variáveis sócio-demográficas, de vulnerabilidade e da assistência pré-natal. Embora a maioria tenha sido testada, apenas 13,6% relataram ter recebido aconselhamento pré-teste. CONCLUSÕES: a cobertura do teste anti-HIV durante a gestação foi satisfatória. A não-associação entre a realização do teste e as variáveis estudadas sugere que a sua solicitação se dá indistintamente, conforme recomendação do Ministério da Saúde. Porém, a baixa freqüência do aconselhamento e o atraso no recebimento do resultado dos exames são indicativos de problemas na atenção pré-natal.OBJECTIVES: to analyze the coverage of counseling and anti-HIV testing, and to identify factors associated with testing during antenatal care. METHODS: cross-sectional study, with women identified through the information systems in five municipalities in the Northwestern Paraná, Brazil, with deliveries between January to March, 2003. Data was collected during home interviews and an HIV test was considered performed if it could be confirmed in the maternity card or in the reference laboratory records. The χ2 and Fisher

  2. Agent Building Software

    Science.gov (United States)

    2000-01-01

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

  3. Competing agents in agent-mediated institutions

    OpenAIRE

    Plaza, Enric; Arcos, Josep Ll.; Noriega, Pablo; Sierra, Carles

    1998-01-01

    Social processes and agent interaction always take place in a specific context. A school of thought in social studies analyses them in the framework of institutions. We present in this paper the notion of agentmediated institutions and show how it is relevant for multi-agent systems (MAS) in general and, more specifically, for MAS that include human agents and software agents involved in socioeconomic interactions. We show how the social interactions of human and software agents taking place ...

  4. RNA glycosidase and other agents target Tat to inhibit HIV-1 transcription.

    Science.gov (United States)

    Harrich, David; Jin, Hongping

    2018-03-20

    The HIV-1 tat gene encodes a small 86-104 amino acid protein depending on the HIV-1 strain. Tat is essential for HIV-1 replication through interactions with numerous cellular transcription factors. The interaction between Tat and P-TEFb, which is a cellular protein complex composed of cyclin T1 and CDK9, delivers P-TEFb to the newly transcribed viral mRNAs where phosphorylation of RNA polymerase II by CDK9 leads to highly efficient mRNA transcription. It has long been recognized that Tat is a potential anti-HIV-1 target and possibly a viral Achilles' heel. However, specifically targeting Tat without affecting normal host cell functions has been challenging. Means to inactivate Tat have been reported that includes small compounds, transdominant negative Tat proteins, and by plant-derived antivirals. Investigations of these agents have reported encouraging outcomes that inform and may hopefully affect strategies for a functional HIV-1 cure. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Agility: Agent - Ility Architecture

    National Research Council Canada - National Science Library

    Thompson, Craig

    2002-01-01

    ...., object and web technologies). The objective of the Agility project is to develop an open agent grid architecture populated with scalable, deployable, industrial strength agent grid components, targeting the theme 'agents for the masses...

  6. Mobile Agent Security

    National Research Council Canada - National Science Library

    Jansen, Wayne

    1998-01-01

    Mobile agent technology offers a new computing paradigm in which a program, in the form of a software agent, can suspend its execution on a host computer, transfer itself to another agent-enabled host...

  7. Interacting agents in finance

    NARCIS (Netherlands)

    Hommes, C.; Durlauf, S.N.; Blume, L.E.

    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

  8. Radiopharmaceutical scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    This invention is directed to dispersions useful in preparing radiopharmaceutical scanning agents, to technetium labelled dispersions, to methods for preparing such dispersions and to their use as scanning agents

  9. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

    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

  10. Asymptotically Optimal Agents

    OpenAIRE

    Lattimore, Tor; Hutter, Marcus

    2011-01-01

    Artificial general intelligence aims to create agents capable of learning to solve arbitrary interesting problems. We define two versions of asymptotic optimality and prove that no agent can satisfy the strong version while in some cases, depending on discounting, there does exist a non-computable weak asymptotically optimal agent.

  11. DEVELOPMENT OF ANTIVIRAL AGENTS

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. DEVELOPMENT OF ANTIVIRAL AGENTS. Chandipura virus can be regarded as a model system to design and develop antiviral agents. These agents could be small molecules or RNA/PNA aptamers or Antisense RNA to speicific gene sequence in the viral genome.

  12. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Bevan, J.A.

    1983-01-01

    This invention relates to radiodiagnostic agents and more particularly to a composition and method for preparing a highly effective technetium-99m-based bone scanning agent. One deficiency of x-ray examination is the inability of that technique to detect skeletal metastases in their incipient stages. It has been discovered that the methanehydroxydiphosphonate bone mineral-seeking agent is unique in that it provides the dual benefits of sharp radiographic imaging and excellent lesion detection when used with technetium-99m. This agent can also be used with technetium-99m for detecting soft tissue calcification in the manner of the inorganic phosphate radiodiagnostic agents

  13. Agente adaptable y aprendizaje

    Directory of Open Access Journals (Sweden)

    Arturo Angel Lara Rivero

    2013-05-01

    Full Text Available En este trabajo se contrasta el concepto de agente programado con el de agente complejo adaptable, se presenta una nueva visión ligada al aprendizaje y la estructura del agente. La imagen del agente se analiza considerando los modelos internos, la práctica, el concepto de rutina y la influencia en su comportamiento, y la importancia del aprendizaje ex ante y ex post. Por último se muestra que la resolución de problemas está sujeta a restricciones del agente y se describen las formas de explorar el espacio de soluciones mediante tres tipos de exploración: exhaustiva, aleatoria y selectiva.

  14. Arylazolyl(azinyl)thioacetanilide. Part 9: Synthesis and biological investigation of thiazolylthioacetamides derivatives as a novel class of potential antiviral agents.

    Science.gov (United States)

    Zhan, Peng; Wang, Liu; Liu, Hong; Chen, Xuwang; Li, Xiao; Jiang, Xin; Zhang, Qiangqiang; Liu, Xinyong; Pannecouque, Christophe; Naesens, Lieve; De Clercq, Erik; Liu, Ailin; Du, Guanhua

    2012-06-01

    In continuation of our endeavor to develop new, potent, selective and less toxic antiviral agents, a novel series of 2-(2-amino/chloro-4-(2,4-dibromophenyl) thiazol-5-ylthio)acetamide derivatives was synthesized via an expeditious route and evaluated for their anti-HIV activities against wild-type virus and clinically relevant mutant strains, and for their anti-influenza virus activities against influenza A (H1N1 and H3N2) and influenza B in cellular assays. The selected active compounds were also assayed for their enzymic inhibitory activities. The results showed that some 2-chloro substituted thiazolylthioacetamide derivatives possessed potent activity against wild type HIV-1 and several key mutant strains (E138K, K103N, L100I) of HIV-1 in MT-4 cells with EC(50) values in micromolar range. Two 2-amino substituted thiazole derivatives 8a7 and 8a8 displayed significant potency against influenza A/H1N1 in MDCK cells with EC(50) values much lower than that of oseltamivir carboxylate, ribavirin, amantadine and rimantadine. Though the mechanism of actions is still unclear, these novel thiazolylthioacetamides might serve as original leads for further pharmacological investigations as potential therapeutic agents against HIV-1 or influenza virus.

  15. Agent Programming Languages and Logics in Agent-Based Simulation

    DEFF Research Database (Denmark)

    Larsen, John

    2018-01-01

    and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI......Research in multi-agent systems has resulted in agent programming languages and logics that are used as a foundation for engineering multi-agent systems. Research includes reusable agent programming platforms for engineering agent systems with environments, agent behavior, communication protocols...... paradigm, and work that combines agent-based simulation platforms with agent programming platforms. This paper analyzes and evaluates benefits of using agent programming languages and logics for agent-based simulation. In particular, the paper considers the use of agent programming languages and logics...

  16. Moral actor, selfish agent.

    Science.gov (United States)

    Frimer, Jeremy A; Schaefer, Nicola K; Oakes, Harrison

    2014-05-01

    People are motivated to behave selfishly while appearing moral. This tension gives rise to 2 divergently motivated selves. The actor-the watched self-tends to be moral; the agent-the self as executor-tends to be selfish. Three studies present direct evidence of the actor's and agent's distinct motives. To recruit the self-as-actor, we asked people to rate the importance of various goals. To recruit the self-as-agent, we asked people to describe their goals verbally. In Study 1, actors claimed their goals were equally about helping the self and others (viz., moral); agents claimed their goals were primarily about helping the self (viz., selfish). This disparity was evident in both individualist and collectivist cultures, attesting to the universality of the selfish agent. Study 2 compared actors' and agents' motives to those of people role-playing highly prosocial or selfish exemplars. In content (Study 2a) and in the impressions they made on an outside observer (Study 2b), actors' motives were similar to those of the prosocial role-players, whereas agents' motives were similar to those of the selfish role-players. Study 3 accounted for the difference between the actor and agent: Participants claimed that their agent's motives were the more realistic and that their actor's motives were the more idealistic. The selfish agent/moral actor duality may account for why implicit and explicit measures of the same construct diverge, and why feeling watched brings out the better angels of human nature.

  17. Stabilized radiographic scanning agents

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1982-01-01

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise gentisic acid 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

  18. 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...

  19. Empathic Agent Technology (EAT)

    NARCIS (Netherlands)

    Johnson, L.; van den Broek, Egon; Richards, D.; Sklar, E.; Wilensky, U.

    2005-01-01

    A new view on empathic agents is introduced, named: Empathic Agent Technology (EAT). It incorporates a speech analysis, which provides an indication for the amount of tension present in people. It is founded on an indirect physiological measure for the amount of experienced stress, defined as the

  20. Agents in domestic environments

    NARCIS (Netherlands)

    Daniël Telgen; John-Jules Meyer; Glenn Meerstra; Franc Pape; Ing. Erik Puik; Leo van Moergestel; Niels van Nieuwenburg; Wouter Langerak

    2013-01-01

    Athor supplied : "This paper describes an agent-based architecture for domotics. This architecture is based on requirements about expandability and hardware independence. The heart of the system is a multi-agent system. This system is distributed over several platforms to open the possibility to

  1. Change Agent Survival Guide

    Science.gov (United States)

    Dunbar, Folwell L.

    2011-01-01

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

  2. Travel Agent Course Outline.

    Science.gov (United States)

    British Columbia Dept. of Education, Victoria.

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

  3. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  4. 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile.

    Science.gov (United States)

    Nawrozkij, Maxim B; Rotili, Dante; Tarantino, Domenico; Botta, Giorgia; Eremiychuk, Alexandre S; Musmuca, Ira; Ragno, Rino; Samuele, Alberta; Zanoli, Samantha; Armand-Ugón, Mercedes; Clotet-Codina, Imma; Novakov, Ivan A; Orlinson, Boris S; Maga, Giovanni; Esté, José A; Artico, Marino; Mai, Antonello

    2008-08-14

    A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl- S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  5. 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.

  6. Cardiovascular risk prediction in HIV-infected patients: comparing the Framingham, atherosclerotic cardiovascular disease risk score (ASCVD), Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk prediction models.

    Science.gov (United States)

    Krikke, M; Hoogeveen, R C; Hoepelman, A I M; Visseren, F L J; Arends, J E

    2016-04-01

    The aim of the study was to compare the predictions of five popular cardiovascular disease (CVD) risk prediction models, namely the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, the Framingham Heart Study (FHS) coronary heart disease (FHS-CHD) and general CVD (FHS-CVD) models, the American Heart Association (AHA) atherosclerotic cardiovascular disease risk score (ASCVD) model and the Systematic Coronary Risk Evaluation for the Netherlands (SCORE-NL) model. A cross-sectional design was used to compare the cumulative CVD risk predictions of the models. Furthermore, the predictions of the general CVD models were compared with those of the HIV-specific D:A:D model using three categories ( 20%) to categorize the risk and to determine the degree to which patients were categorized similarly or in a higher/lower category. A total of 997 HIV-infected patients were included in the study: 81% were male and they had a median age of 46 [interquartile range (IQR) 40-52] years, a known duration of HIV infection of 6.8 (IQR 3.7-10.9) years, and a median time on ART of 6.4 (IQR 3.0-11.5) years. The D:A:D, ASCVD and SCORE-NL models gave a lower cumulative CVD risk, compared with that of the FHS-CVD and FHS-CHD models. Comparing the general CVD models with the D:A:D model, the FHS-CVD and FHS-CHD models only classified 65% and 79% of patients, respectively, in the same category as did the D:A:D model. However, for the ASCVD and SCORE-NL models, this percentage was 89% and 87%, respectively. Furthermore, FHS-CVD and FHS-CHD attributed a higher CVD risk to 33% and 16% of patients, respectively, while this percentage was D:A:D, ASCVD and SCORE-NL models. This could have consequences regarding overtreatment, drug-related adverse events and drug-drug interactions. © 2015 British HIV Association.

  7. Evaluation of enzyme-linked immunosorbent and alternative assays for detection of HIV antibodies using panels of Brasilian sera Avaliação de testes sorológicos para a detecção de anticorpos anti-HIV em painéis de soros de brasileiros

    Directory of Open Access Journals (Sweden)

    Jairo Ivo-Dos-Santos

    1990-04-01

    Full Text Available Sera from 472 Brazilian subjects, confirmed to be either positive or negative for HIV antibodies and comprising the total clinical spectrum of HIV infection, were utilized in the evaluation of six commercially available enzyme-linked immunosorbent assays (ELISA, as well as of four alternative assays, namely indirect immunofluorescence (IIF, passive hemagglutination (PHA, dot blot and Karpas AIDS cell test. The sensitivities ranged from 100% (Abbott and Roche ELISA to 84.2% (PHA and the specificities ranged from 99.3% (IIF to 80.2% (PHA. The sensitivity and specificity of the PHA and the sensitivity of the Karpas cell test were significantly lower than those of the other tests. Although the IFF and dot blot had good sensitivities and specificities, the six ELISA were more attractive than those tests when other parameters such as ease of reading and duration of assay were considered.Os soros de 472 brasileiros, confirmados como sendo positivos ou negativos em relação à presença de anticorpos anti-HIV e compreendendo todo o espectro clínico da infecção, foram utilizados na avaliação de seis ensaios imunoenzimáticos comerciais (ELISA, bem como de quatro testes alternativos tais como imunofluorescência indireta (IFI, hemaglutinação passiva (HP, dot blot e Karpas AIDS cell test. As sensibilidades variaram de 100% (ELISA Abbott e Roche a 84,2% (HP e as especificidades variaram de 99,3% (IFI a 80,2% (HP. A sensibilidade e especificidade da HP e a sensibilidade do Karpas AIDS cell test foram significativamente menores que os outros ensaios. Embora a IFI e o dot blot tivessem apresentado uma boa sensibilidade e especificidade, os ensaios imunoenzimáticos (ELISA foram mais adequados para serem utilizados em triagem quando outros parâmetros tais como facilidade de leitura e interpretação dos resultados e duração dos ensaios foram considerados.

  8. 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...

  9. Health care agents

    Science.gov (United States)

    ... do not want these treatments. Order sterilization or abortion. Choosing Your Health Care Agent Choose a person ... working well. A health care proxy is a legal paper that you fill out. You can get ...

  10. Robust Agent-Based Systems Incorporating Teams of Communicating Agents

    National Research Council Canada - National Science Library

    Cohen, Philip

    2004-01-01

    ... (AgentTalk). The A3 architecture supports human participation as agents, dynamic formation of agent teams, reorganization of teams based on network loads, and offers libraries for legacy code to be able...

  11. Agent amplified communication

    Energy Technology Data Exchange (ETDEWEB)

    Kautz, H.; Selman, B.; Milewski, A. [AT& T Laboratories, Murray Hill, NJ (United States)

    1996-12-31

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

  12. Monitoring volatile anaesthetic agents

    International Nuclear Information System (INIS)

    Russell, W.J.

    2000-01-01

    Full text: The methods that have been used for monitoring volatile anaesthetic agents depend on some physical property such as Density, Refractometry, Mass, Solubility, Raman scattering, or Infra-red absorption. Today, refractometry and infra-red techniques are the most common. Refractometry is used for the calibration of vaporizers. All anaesthetic agents increase the refractive index of the carrier gas. Provided the mixture is known then the refractive change measures the concentration of the volatile anaesthetic agent. Raman Scattering is when energy hits a molecule a very small fraction of the energy is absorbed and re-emitted at one or more lower frequencies. The shift in frequency is a function of the chemical bonds and is a fingerprint of the substance irradiated. Electromagnetic (Infra-red) has been the commonest method of detection of volatile agents. Most systems use a subtractive system, i.e. the agent in the sampling cell absorbed some of the infrared energy and the photo-detector therefore received less energy. A different approach is where the absorbed energy is converted into a pressure change and detected as sound (Acoustic monitor). This gives a more stable zero reference. More recently, the detector systems have used multiple narrow-band wavelengths in the infrared bands and by shape matching or matrix computing specific agent identification is achieved and the concentration calculated. In the early Datex AS3 monitors, a spectral sweep across the 3 micron infrared band was used to create spectral fingerprints. The recently released AS3 monitors use a different system with five very narrow band filters in the 8-10 micron region. The transmission through each of these filters is a value in a matrix which is solved by a micro computer to identify the agent and its concentration. These monitors can assist in improving the safety and efficiency of our anaesthetics but do not ensure that the patient is completely anaesthetized. Copyright (2000

  13. The anti-HIV-1 effect of scutellarin

    International Nuclear Information System (INIS)

    Zhang Gaohong; Wang Qian; Chen Jijun; Zhang Xuemei; Tam, S.-C.; Zheng Yongtang

    2005-01-01

    Scutellarin was purified from the plant Erigeron breviscapus (Vant.) Hand.-Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-1 IIIB ), drug-resistant virus (HIV-1 74V ), and low-passage clinical isolated virus (HIV-1 KM018 ). From syncytia inhibition study, the EC 50 of scutellarin against HIV-1 IIIB direct infection in C8166 cells was 26 μM with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC 50 reduced to 15 μM. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-1 74V (EC 50 253 μM) and HIV-1 KM018 (EC 50 136 μM) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433 μM, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54 μM. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication

  14. 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...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

  15. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

  16. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    Science.gov (United States)

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-02

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Cytotoxicity and anti-HIV evaluations of some new synthesized ...

    Indian Academy of Sciences (India)

    Chemistry Department, Faculty of Science, El-Azhar University, Cairo 11787, Egypt; Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt; Research Unit, ...

  18. Cytotoxicity and anti-HIV evaluations of some new synthesized ...

    Indian Academy of Sciences (India)

    (FBS), 2mM L-glutamine, and non-essential amino acids. Stable Huh-7 cells containing the self-replicating, sub-genomic HCV replicon, which was identical in sequence to the I377neo/NS3-3 /wt replicon described by Lohmann et al.23 were selected and maintained in the presence of 0.25 mg/ml G418 (Invitrogen, Carlsbad,.

  19. 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.

  20. Contribution of the anti HIV/AIDS community conversation programs ...

    African Journals Online (AJOL)

    Opportunities for 'experience sharing', 'members' cohesiveness', and 'self- disclosure' were amongst the major factors for the success of the CC programs. However, evidences also suggested that a number of technical, professional and budgetary constraints were affecting the implementation of these programs.

  1. Plant made anti-HIV microbicides: a field of opportunity

    CSIR Research Space (South Africa)

    Lotter-Stark, HCT

    2012-11-01

    Full Text Available (Armbruster et al., 2002). Clinical trials with 2G12 produced in transgenic tobacco have commenced in 2009 (Paul and Ma, 2011). MAb 2G12 is unique in its structure in that it naturally forms a single Fab region via domain swapping between the variable...

  2. Contribution of the anti HIV/AIDS community conversation programs ...

    African Journals Online (AJOL)

    admin

    investigations (11, 18-20) also suggest that CC appears to make important contributions in preventing and controlling HIV/AIDS. It was reported that CC has a significant role in expanding services and improving accessibility, raising community awareness (21), improving members' perceptions of their own concerns.

  3. 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......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...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

  4. Voltammetric determination of wedelolactone, an anti-HIV herbal ...

    Indian Academy of Sciences (India)

    USIC, Dayalbagh Educational Institute, Dayalbagh, Agra 282 005, India e-mail: ... wedelolactone was found to have a linear relationship within the concentration range of 50–700 ng/mL. The. LOD and LOQ ... method was further scrutinized by the successful determination of wedelolactone in real plant samples. Keywords.

  5. Teaching tourism change agents

    DEFF Research Database (Denmark)

    Blichfeldt, Bodil Stilling; Kvistgaard, Hans-Peter; Hird, John

    2017-01-01

    This article discuss es know ledge, competencies and skills Master’s students should obtain during their academic studies and particularly, the differences between teaching about a topic and teaching to do. This is ex emplified by experiential learning theory and the case of a change management...... course that is part of a Tourism Master’s program, where a major challenge is not only to teach students about change and change agents, but to teach them how change feels and ho w to become change agents. The c hange management course contains an experiment inspired by experiential teaching literature...... and methods. The experiment seeks to make students not only hear/learn about change agency and management, but to make them feel cha nge, hereby enabling them to develop the skills and competencies necessary for them to take on the role as change agent s and thus enable them to play key role s in implementing...

  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. 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...... 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....

  8. Teaching Tourism Change Agents

    DEFF Research Database (Denmark)

    Stilling Blichfeldt, Bodil; Kvistgaard, Hans-Peter; Hird, John

    2017-01-01

    This article discuss es know ledge, competencies and skills Master’s students should obtain during their academic studies and particularly, the differences between teaching about a topic and teaching to do. This is ex emplified by experiential learning theory and the case of a change management...... course that is part of a Tourism Master’s program, where a major challenge is not only to teach students about change and change agents, but to teach them how change feels and ho w to become change agents. The c hange management course contains an experiment inspired by experiential teaching literature...

  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. Agent Persuasion Mechanism of Acquaintance

    Science.gov (United States)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

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

  11. 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...

  12. Fluoroquinolone antimicrobial agents.

    OpenAIRE

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The dr...

  13. Socially Intelligent Tutor Agents

    NARCIS (Netherlands)

    Heylen, Dirk K.J.; Nijholt, Antinus; op den Akker, Hendrikus J.A.; Vissers, M.; Aylett, R.; Ballin, D.; Rist, T.

    2003-01-01

    Emotions and personality have received quite a lot of attention the last few years in research on embodied conversational agents. Attention is also increasingly being paid to matters of social psychology and interpersonal aspects, for work of our group). Given the nature of an embodied

  14. Cell control with agents

    NARCIS (Netherlands)

    Ir Peter Boots; Ir. Dick van Schenk Brill

    2000-01-01

    A software system is described that uses the agent concept in the Cell Control layer. Important design goals are: the system continues as good as possible after a process crash, crashed processes are recreated whenever possible, and equivalent workstations are allocated dynamically. This project is

  15. 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...

  16. Multimodal training between agents

    DEFF Research Database (Denmark)

    Rehm, Matthias

    2003-01-01

    In the system Locator1, agents are treated as individual and autonomous subjects that are able to adapt to heterogenous user groups. Applying multimodal information from their surroundings (visual and linguistic), they acquire the necessary concepts for a successful interaction. This approach has...

  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. Towards Soft Computing Agents

    Czech Academy of Sciences Publication Activity Database

    Neruda, Roman; Krušina, Pavel; Petrová, Zuzana

    2000-01-01

    Roč. 10, č. 5 (2000), s. 859-868 ISSN 1210-0552. [SOFSEM 2000 Works hop on Soft Computing. Milovy, 27.11.2000-28.11.2000] R&D Projects: GA ČR GA201/00/1489; GA ČR GA201/99/P057 Institutional research plan: AV0Z1030915 Keywords : hybrid systems * intelligent agents Subject RIV: BA - General Mathematics

  19. Amphoteric surface active agents

    OpenAIRE

    Eissa, A.M. F.

    1995-01-01

    2-[trimethyl ammonium, triethyl ammonium, pyridinium and 2-amino pyridinium] alkanoates, four series of surface active agents containing carbon chain C12, C14, C16 and C18carbon atoms, were prepared. Their structures were characterized by microanalysis, infrared (IR) and nuclear magnetic resonance (NMR). Surface and interfacial tension, Krafft point, wetting time, emulsification power, foaming height a...

  20. 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.

  1. Constructing Secure Mobile Agent Systems Using the Agent Operating System

    NARCIS (Netherlands)

    van t Noordende, G.J.; Overeinder, B.J.; Timmer, R.J.; Brazier, F.M.; Tanenbaum, A.S.

    2009-01-01

    Designing a secure and reliable mobile agent system is a difficult task. The agent operating system (AOS) is a building block that simplifies this task. AOS provides common primitives required by most mobile agent middleware systems, such as primitives for secure communication, secure and

  2. Logics for Intelligent Agents and Multi-Agent Systems

    NARCIS (Netherlands)

    Meyer, John-Jules Charles

    2014-01-01

    This chapter presents the history of the application of logic in a quite popular paradigm in contemporary computer science and artificial intelligence, viz. the area of intelligent agents and multi-agent systems. In particular we discuss the logics that have been used to specify single agents, the

  3. Holonic multi-agent systems

    OpenAIRE

    Gerber, Christian; Siekmann, Jörg; Vierke, Gero

    1999-01-01

    A holonic multi-agent paradigm is proposed, where agents give up parts of their autonomy and merge into a super-agent"(a holon), that acts - when seen from the outside - just as a single agent again. We explore the spectrum of this new paradigm, ranging from definitorial issues over classification of possible application domains, an algebraic characterization of the merge operation, to implementational aspects: We propose algorithms for holon formation and on-line re-configuration. Based on s...

  4. Respiratory agents: irritant gases, riot control agents, incapacitants, and caustics.

    Science.gov (United States)

    Warden, Craig R

    2005-10-01

    There are many chemical respiratory agents suitable for use by terrorists. They are the oldest chemical agents used and have caused the most casualties throughout the 20th century. Many are available in large quantities for industrial use and are susceptible to potential sabotage. This paper will concentrate on respiratory agents that are readily available and have the potential to cause a large number of casualties and panic. These agents have a lower rate of lethality when compared to other chemical agents but could produce many casualties that may overwhelm the emergency medical system.

  5. 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.

  6. Toxorhynchites as biocontrol agents.

    Science.gov (United States)

    Focks, Dana A

    2007-01-01

    Toxorhynchites is an unusual and interesting genus of large, non-biting mosquitoes. In spite of their size, they are--like many species of mosquitoes--completely harmless to man. The larvae are predaceous on other mosquitoes and aquatic organisms that inhabit both natural and artificial containers. Because this habitat is the source of several medically important species of mosquitoes, there is warrant for evaluating the potential of Toxorhynchites as a biological control agent under various conditions. Toxorhynchites is not seen as a panacea for the control of all container-inhabiting mosquitoes. However, it has demonstrated practical potential in certain restricted but important situations.

  7. 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...

  8. Motivating agents in software tutorials

    NARCIS (Netherlands)

    van der Meij, Hans

    2013-01-01

    Pedagogical agents can provide important support for the user in human–computer interaction systems. This paper examines whether a supplementary, motivating agent in a print tutorial can enhance student motivation and learning in software training. The agent served the role of motivator, attending

  9. 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.

  10. [New agents for hypercholesterolemia].

    Science.gov (United States)

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  11. Amphoteric surface active agents

    Directory of Open Access Journals (Sweden)

    Eissa, A.M. F.

    1995-10-01

    Full Text Available 2-[trimethyl ammonium, triethyl ammonium, pyridinium and 2-amino pyridinium] alkanoates, four series of surface active agents containing carbon chain C12, C14, C16 and C18carbon atoms, were prepared. Their structures were characterized by microanalysis, infrared (IR and nuclear magnetic resonance (NMR. Surface and interfacial tension, Krafft point, wetting time, emulsification power, foaming height and critical micelle concentration (cmc were determined and a comparative study was made between their chemical structure and surface active properties. Antimicrobial activity of these surfactants was also determined.

    Se prepararon cuatro series de agentes tensioactivos del tipo 2-[trimetil amonio, trietil amonio, piridinio y 2-amino piridinio] alcanoatos, que contienen cadenas carbonadas con C12, C14, C16 y C18 átomos de carbono.
    Se determinaron la tensión superficial e interfacial, el punto de Krafft, el tiempo humectante, el poder de emulsionamiento, la altura espumante y la concentración critica de miscela (cmc y se hizo un estudio comparativo entre la estructura química y sus propiedades tensioactivas. Se determinó también la actividad antimicrobiana de estos tensioactivos. Estas estructuras se caracterizaron por microanálisis, infrarrojo (IR y resonancia magnética nuclear (RMN.

  12. Flexible, secure agent development framework

    Science.gov (United States)

    Goldsmith,; Steven, Y [Rochester, MN

    2009-04-07

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

  13. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer's disease.

    Science.gov (United States)

    Tommonaro, Giuseppina; García-Font, Nuria; Vitale, Rosa Maria; Pejin, Boris; Iodice, Carmine; Cañadas, Sixta; Marco-Contelles, José; Oset-Gasque, María Jesús

    2016-10-21

    Avarol is a marine sesquiterpenoid hydroquinone, previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida), with antiinflammatory, antitumor, antioxidant, antiplatelet, anti-HIV, and antipsoriatic effects. Recent findings indicate that some thio-avarol derivatives exhibit acetylcholinesterase (AChE) inhibitory activity. The multiple pharmacological properties of avarol, thio-avarol and/or their derivatives prompted us to continue the in vitro screening, focusing on their AChE inhibitory and neuroprotective effects. Due to the complex nature of Alzheimer's disease (AD), there is a renewed search for new, non hepatotoxic anticholinesterasic compounds. This paper describes the synthesis and in vitro biological evaluation of avarol-3'-thiosalicylate (TAVA) and thiosalycil-prenyl-hydroquinones (TPHs), as non hepatotoxic anticholinesterasic agents, showing a good neuroprotective effect on the decreased viability of SHSY5Y human neuroblastoma cells induced by oligomycin A/rotenone and okadaic acid. A molecular modeling study was also undertaken on the most promising molecules within the series to elucidate their AChE binding modes and in particular the role played by the carboxylate group in enzyme inhibition. Among them, TPH4, bearing a geranylgeraniol substituent, is the most significant Electrophorus electricus AChE (EeAChE) inhibitor (IC50 = 6.77 ± 0.24 μM), also endowed with a moderate serum horse butyrylcholinesterase (eqBuChE) inhibitory activity, being also the least hepatotoxic and the best neuroprotective compound of the series. Thus, TPHs represents a new family of synthetic compounds, chemically related to the natural compound avarol, which has been discovered for the potential treatment of AD. Findings prove the relevance of TPHs as a new possible generation of competitive AChE inhibitors pointing out the importance of the salycilic substituents on the hydroquinone ring. Since these compounds do not belong to the class of

  14. 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.

  15. Microencapsulation of chemotherapeutic agents

    International Nuclear Information System (INIS)

    Byun, Hong Sik

    1993-01-01

    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)

  16. New MR contrast agent

    International Nuclear Information System (INIS)

    Grossman, C.D.; Subramanian, G.; Schneider, R.; Szeverenyi, N.E.; Rosenbaum, A.M.; Gagne, G.; Tillapaugh-Fay, G.; Berlin, R.; Ritter-Hrncirik, C.; Yu, S.

    1990-01-01

    This paper evaluates an MR contrast agent-meglumine tris-(2,6-dicarboxypyridine) gadolinium (III) or gadolinium dipicolinate (Gd-DPC)-produced in-house. Rats were anesthetized with pentobarbital. For renal imaging, bowel motion artifact was minimized with glucagon (0.014 mg/kg, intravenous (IV)). Enhanced images were generated on a 2-T chemical shift imaging system with a 31-cm horizontal bore magnet after IV injection of Gd-DPC (100 μM/kg). Coronal sections of the kidneys and sagittal sections of the brain, 2 mm thick, were made. Six to eight excitations and 128 or 356 phase-encoding steps were used for each image. Control animals were injected with equivalent doses of gadopentetate dimeglumine

  17. A Composite Agent Architecture for Multi-Agent Simulations

    OpenAIRE

    VanPutte, Michael; Osborn, Brian; Hiles, John

    2002-01-01

    CGF Computer Generated Forces and Behavioral Representation The MOVES Institute’s Computer-Generated Autonomy Group has focused on a research goal of modeling complex and adaptive behavior while at the same time making the behavior easier to create and control. This research has led to several techniques for agent construction, that includes a social and organization relationship management engine, a composite agent architecture, an agent goal apparatus, a structure for capturi...

  18. 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.

  19. 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.

  20. Radioactive scanning agents with stabilizer

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1982-01-01

    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

  1. Believable Social and Emotional Agents.

    Science.gov (United States)

    1996-05-01

    generation). Our agent is now also capable of talking about its emo- tions. Emotions might also affect how the agent speaks, such as stuttering when the...he will eventually tell the teacher and get the user in trouble1. Sluggo goes into the trade with an impatient and aggressive attitude and quickly...personality resulted in a more interesting character. 1. There is no teacher agent in the simulation, but the simulation can end with a message to the user

  2. Towards Information-Seeking Agents

    OpenAIRE

    Bachman, Philip; Sordoni, Alessandro; Trischler, Adam

    2016-01-01

    We develop a general problem setting for training and testing the ability of agents to gather information efficiently. Specifically, we present a collection of tasks in which success requires searching through a partially-observed environment, for fragments of information which can be pieced together to accomplish various goals. We combine deep architectures with techniques from reinforcement learning to develop agents that solve our tasks. We shape the behavior of these agents by combining e...

  3. Choice a real estate agent

    OpenAIRE

    Pantelic, Marija

    2014-01-01

    Every year a hundreds of new Estate agents is examined, and new agency comes to, which increase the competition for estate agents. Property sellers have the option to choose the estate agent which they think is the best one that will best mediate their property at a flexible and a correct way. It has been common that property sellers choose and compare estate agents in the city, the competition is today equal outside the city as in the city. Possibly, these are other criteria that values high...

  4. Judicial supervision of enforcement agents

    Directory of Open Access Journals (Sweden)

    Bodiroga Nikola

    2015-01-01

    Full Text Available The main focus of this paper is the supervision of enforcement agents conducted by enforcement courts. Law on Enforcement and Security recognizes three levels of control of enforcement agents. Certain monitoring powers are delegated to the Ministry of Justice and to Chamber of Enforcement Agents. However, for parties and other participants to enforcement proceedings control of enforcement agents implemented by enforcement courts seems to be the most important one. The strongest powers of enforcement agents are related to the special procedure for collection of claims for utilities and other similar services (exclusive competence of enforcement agents and for carrying out the enforcement (if enforcement creditor has requested it. When it comes to special procedure for collection of claims for utilities and other similar services objection can be used in order to control legality of decisions rendered by enforcements agents. However, many procedural issues related to the objection procedure remain unsolved. Motion for correction of irregularities is the only legal remedy that can be used when enforcement is being carried out by enforcement agents. This legal remedy cannot be considered an effective one in the sense of Article 13 European Convention for Protection of Human Rights and Fundamental Liberties. The new proposed Law on Enforcement and Security expected to come into force on July 1, 2016, will delegate the exclusive competence for carrying out the enforcement to enforcement agents (except cases related to family relations and reinstatement, but it will not improve the court supervision of their work.

  5. GOAL Agents Instantiate Intention Logic

    OpenAIRE

    Hindriks, Koen; van der Hoek, Wiebe

    2008-01-01

    It is commonly believed there is a big gap between agent logics and computational agent frameworks. In this paper, we show that this gap is not as big as believed by showing that GOAL agents instantiate Intention Logic of Cohen and Levesque. That is, we show that GOAL agent programs can be formally related to Intention Logic.We do so by proving that the GOAL Verification Logic can be embedded into Intention Logic. It follows that (a fragment of) Intention Logic can be used t...

  6. Business Intelligence using Software Agents

    Directory of Open Access Journals (Sweden)

    Ana-Ramona BOLOGA

    2011-12-01

    Full Text Available 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 propose some basic ideas for developing real-time agent-based software system for business intelligence in supply chain management, using Case Base Reasoning Agents.

  7. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  8. Gastrointestinal scanning agent

    International Nuclear Information System (INIS)

    Francis, M.D.

    1980-01-01

    An easily prepared radiolabeled gastrointestinal scanning agent is described. Technetium-99m has ideal characteristics for imaging the upper and lower GI tract and determining stomach emptying and intestinal transit time when used with an insoluble particulate material. For example, crystalline and amorphous calcium phosphate particles can be effectively labeled in a one-step process using sup(99m)TcO 4 and SnCl 2 . These labeled particles have insignificant mass and when administered orally pass through the GI tract unchanged, without affecting the handling and density of the intestinal contents. Visualization of the esophageal entry into the stomach, the greater and lesser curvatures of the stomach, ejection into the duodenum, and rates of passage through the upper and lower GI tract are obtained. The slurry of sup(99m)TC particulate can be given rectally by enema. Good images of the cecum and the ascending, transverse, and descending colon are obtained. Mucosal folds and the splenic and hepatic flexures are visualized. The resilience of the large intestine is also readily visualized by pneumocolonographic techniques. (author)

  9. 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.

  10. The Agent of Change: The Agent of Conflict.

    Science.gov (United States)

    Hatfield, C. R., Jr.

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

  11. 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.

  12. Players' agents worldwide: legal aspects

    NARCIS (Netherlands)

    Siekmann, R.C.R.; Parrish, R.; Branco Martins, R.; Soek, J.W.

    2007-01-01

    Publicly, at least, there appears to be a strong collective will within football to clean up the game, to make the work of players’ agents more transparent and to allow a greater share of the game’s profits to stay within the game. Privately, there seems to be unease that current agent regulation is

  13. Overview of shoreline cleaning agents

    International Nuclear Information System (INIS)

    Clayton, J.

    1992-01-01

    Chemical cleaning agents may be used to promote release of stranded oil from shorelines for reasons including biological sensitivity of indigenous fauna and flora to the oil, amenity considerations of the shoreline, or concern about refloating of the oil and subsequent stranding on adjacent shorelines. While use of chemical cleaning agents may be appropriate under proper toxic responses in circumstances, certain limitations should be recognized. The potential for toxic responses in indigenous fauna and flora to the cleaning agents must be considered. Enhanced penetration of oil into permeable shorelines following treatment with chemical cleaning agents also is not desirable. However, if conditions related to toxicity and substrate permeability are determined to be acceptable, the use of chemical cleaning agents for treatment of stranded oil can be considered. Chemical agents for cleaning oiled shorelines can be grouped into three categories: (1) non-surfactant-based solvents, (2) chemical dispersants, and (3) formulations especially designed to release stranded oil from shoreline substrates (i.e., shoreline-cleaning-agents). Depending on the specific circumstances present on an oiled shoreline, it is generally desirable that chemical agents used for cleaning will release oil from shoreline substrate(s) to surface waters. Recovery of the oil can then be accomplished by mechanical procedures such as booming and skimming operations

  14. 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.

  15. A Verification Logic for GOAL Agents

    Science.gov (United States)

    Hindriks, K. V.

    Although there has been a growing body of literature on verification of agents programs, it has been difficult to design a verification logic for agent programs that fully characterizes such programs and to connect agent programs to agent theory. The challenge is to define an agent programming language that defines a computational framework but also allows for a logical characterization useful for verification. The agent programming language GOAL has been originally designed to connect agent programming to agent theory and we present additional results here that GOAL agents can be fully represented by a logical theory. GOAL agents can thus be said to execute the corresponding logical theory.

  16. New agents for cancer chemoprevention.

    Science.gov (United States)

    Kelloff, G J; Boone, C W; Crowell, J A; Steele, V E; Lubet, R A; Doody, L A; Malone, W F; Hawk, E T; Sigman, C C

    1996-01-01

    Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, Beta carotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D3 analogs. Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin

  17. Smart Agents and Sentiment in the Heterogeneous Agent Model

    Czech Academy of Sciences Publication Activity Database

    Vácha, Lukáš; Baruník, Jozef; Vošvrda, Miloslav

    2009-01-01

    Roč. 18, č. 3 (2009), s. 209-219 ISSN 1210-0455 R&D Projects: GA MŠk(CZ) LC06075; GA ČR GP402/08/P207; GA ČR(CZ) GA402/09/0965 Institutional research plan: CEZ:AV0Z10750506 Keywords : heterogeneous agent model * market structure * smart traders * Hurst exponent Subject RIV: AH - Economics http://library.utia.cas.cz/separaty/2009/E/vacha- smart agents and sentiment in the heterogeneous agent model.pdf

  18. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Topological estimation of cytotoxic activity of some anti-HIV agents: HEPT analogues · Vijay K Agrawal Kamlesh Mishra Ruchi Sharma P V Khadikar · More Details Abstract Fulltext PDF. QSAR studies on anti-HIV cytotoxic activities of a series of HEPT(1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)-thymine) analogues have ...

  19. Immunological effects of hypomethylating agents.

    Science.gov (United States)

    Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

    2017-08-01

    Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

  20. Complex responses to alkylating agents

    International Nuclear Information System (INIS)

    Samson, L.D.

    2003-01-01

    Using Affymetrix oligonucleotide GeneChip analysis, we previously found that, upon exposure to the simple alkylating agent methylmethane sulfonate, the transcript levels for about one third of the Saccharomyces cerevisiae genome (∼2,000 transcripts) are induced or repressed during the first hour or two after exposure. In order to determine whether the responsiveness of these genes has any relevance to the protection of cells against alkylating agents we have undertaken several follow-up studies. First, we explored the specificity of this global transcriptional response to MMS by measuring the global response of S. cerevisiae to a broad range of agents that are known to induce DNA damage. We found that each agent produced a very different mRNA transcript profile, even though the exposure doses produced similar levels of toxicity. We also found that the selection of genes that respond to MMS is highly dependent upon what cell cycle phase the cells are in at the time of exposure. Computational clustering analysis of the dataset derived from a large number of exposures identified several promoter motifs that are likely to control some of the regulons that comprise this large set of genes that are responsive to DNA damaging agents. However, it should be noted that these agents damage cellular components other than DNA, and that the responsiveness of each gene need not be in response to DNA damage per se. We have also begun to study the response of other organisms to alkylating agents, and these include E. coli, cultured mouse and human cells, and mice. Finally, we have developed a high throughput phenotypic screening method to interrogate the role of all non-essential S. cerevisiae genes (about 4,800) in protecting S. cerevisiae against the deleterious effects of alkylating agents; we have termed this analysis 'genomic phenotyping'. This study has uncovered a plethora of new pathways that play a role in the recovery of eukaryotic cells after exposure to toxic

  1. Industrial Agents: Emerging Applications of Software Agents in Industry

    OpenAIRE

    Leitão P.; Leitão, Paulo; Karnouskos, Stamatis

    2015-01-01

    The objective of this book is to address both industry practitioners and academia, providing the vision, on-going efforts, example applications, assessments, and roadmaps associated with industrial agents used in multiple industries. Such a book provides an introduction to the “industrial agents” domain by discussing up-to-date examples of their applications in industry, and it offers a view of future challenges with an accompanying roadmap. Part I introduces industrial agents,...

  2. Nuclear magnetic resonance contrast agents

    Science.gov (United States)

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

    1997-12-30

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

  3. Cytotoxicity of dentin bonding agents.

    Science.gov (United States)

    Cal, Ebru; Guneri, Pelin; Atay, Ayse; Cetintas, Vildan Bozok

    2014-01-01

    This study sought to evaluate the cytotoxicity of 5 dentin bonding agents (Admira Bond, Adper Single Bond Plus, Clearfil SE Bond, Clearfil S3 Bond, and Heliobond) by XTT assay using human gingival fibroblast cells. Samples of dentin bonding agents were prepared on a black 96-well microplate, and the cytotoxicity of each bonding material was measured every 24 hours for 7 days, then on Days 14, 21, and 28. One-way ANOVA and Bonferroni post hoc tests were used for statistical analyses. All 5 materials were evaluated as severely cytotoxic (P agents showed severe cytotoxicity with viability results exception of Adper Single Bond Plus, toxicity continued to Day 28 for all compounds. The utmost care must be considered during the clinical utilization of dentin bonding agents to keep them within the area of restoration and prevent their contact with adjacent tissues.

  4. Chemical Agents: Facts about Evacuation

    Science.gov (United States)

    ... What CDC is Doing Blog: Public Health Matters Chemical Agents: Facts About Evacuation Format: Select one PDF [ ... on Facebook Tweet Share Compartir Some kinds of chemical accidents or attacks, such as a train derailment ...

  5. 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 agen...... but remain few and far between. This review critically assesses the progress of relational agent development and research since their inception in 2005, proposes new areas of research and considers the potential for their exploitation in virtual worlds....... and non-player characters that can actively participate in such relationships. The focus of this review is relational agents, agents that can build long term socioemotional relationships with users. In virtual worlds, such agents are just starting to emerge; they are more common in other environments...

  6. Antisense Treatments for Biothreat Agents

    National Research Council Canada - National Science Library

    Warfield, Kelly L; Panchal, Rekha G; Aman, M J; Bavari, Sina

    2006-01-01

    ... a variety of pathogens in cell culture studies and nonhuman primate models of infection. For these reasons, antisense technologies are being pursued as treatments against biothreat agents such as Ebola virus, dengue virus and Bacillus anthracis...

  7. 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...

  8. Mobile Objects and Agents (MOA)

    Science.gov (United States)

    Milojicic, Dejan S.; LaForge, William; Chauhan, Deepika

    1998-12-01

    This paper describes the design and implementation of the Mobile Objects and Agents (MOA) project at the Open Group Research Institute. MOA was designed to support migration, communication and control of agents. It was implemented on top of the Java Virtual Machine, without any modifications to it. The initial project goals were to support communication across agent migration, as a means for collaborative work; and to provide extensive resource control, as a basic support for countering denial of service attacks. In the course of the project we added two further goals: compliance with the Java Beans component model, which provides for additional configurability and customization of agent system and agent applications; and interoperability, which allows cooperation with other agent systems. This paper analyses the architecture of MOA, in particular the support for mobility, naming and locating, communication, and resource management. Object and component models of MOA are discussed and some implementation details described. We summarize the lessons learned while developing and implementing MOA and compare it with related work.

  9. Oral hypoglycemic agents in pregnancy.

    Science.gov (United States)

    Tran, Nam D; Hunter, Stephen K; Yankowitz, Jerome

    2004-06-01

    Pregnancies in diabetic women are associated with increased risk of spontaneous abortion, congenital malformations, preeclampsia, preterm labor, macrosomia, shoulder dystocia, and cesarean section. Advances in antepartum cares and strict adherence to dietary and insulin regimens have been shown to significantly reduce the rate of maternal morbidity as well as perinatal morbidity and mortality. Historically, reports of potential fetal teratogenicity and hypoglycemic effects on the fetus contraindicated the use of oral hypoglycemic agents in pregnancies complicated with either type II diabetes mellitus (DM) or gestational diabetes mellitus (GDM). Recently, physicians increasingly prescribe newer generations of oral hypoglycemic agents to treat GDM and type II DM to pregnant patients. This review addresses the safety, current recommendations, and controversies surrounding use of the available oral hypoglycemic agents during pregnancy. Obstetricians & Gynecologists, Family Physicians After completion of this article, the reader should be able to describe the mechanisms of actions of the various oral hypoglycemic agents, to list the known side effects of these agents, and to summarize the data on the use of these agents during pregnancy.

  10. 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

  11. 13 CFR 120.952 - Fiscal agent.

    Science.gov (United States)

    2010-01-01

    ... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of...

  12. Homeostatic Agent for General Environment

    Science.gov (United States)

    Yoshida, Naoto

    2018-03-01

    One of the essential aspect in biological agents is dynamic stability. This aspect, called homeostasis, is widely discussed in ethology, neuroscience and during the early stages of artificial intelligence. Ashby's homeostats are general-purpose learning machines for stabilizing essential variables of the agent in the face of general environments. However, despite their generality, the original homeostats couldn't be scaled because they searched their parameters randomly. In this paper, first we re-define the objective of homeostats as the maximization of a multi-step survival probability from the view point of sequential decision theory and probabilistic theory. Then we show that this optimization problem can be treated by using reinforcement learning algorithms with special agent architectures and theoretically-derived intrinsic reward functions. Finally we empirically demonstrate that agents with our architecture automatically learn to survive in a given environment, including environments with visual stimuli. Our survival agents can learn to eat food, avoid poison and stabilize essential variables through theoretically-derived single intrinsic reward formulations.

  13. 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...

  14. 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.

  15. 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.

  16. Monitoring presence of chemical agents

    International Nuclear Information System (INIS)

    Preston, J.M.

    1984-01-01

    The specification describes a case for use with a hand-portable chemical agent detector for continuously monitoring an atmosphere for the presence of predetermined chemical agents. The detector having means for ionizing air samples and providing at an output terminal electrical signals representative of the mobility spectrum of ionized chemical vapours produced by the ionizing means. The case comprises means for defining a chamber in the case for supporting and removably enclosing the detector, means for communicating ambient atmosphere to the chamber, electrical circuit means in the case, the circuit means being adapted to be detachably connected to the detector output terminal when the detector is positioned in the chamber and being responsive to the electrical signals for producing an alarm signal when the signals detect a chemical agent concentration in the atmosphere exceeding a predetermined concentration level, and alarm means responsive to the alarm signal. (author)

  17. Solidifying agent for radioactive waste

    International Nuclear Information System (INIS)

    Kida, Tsutomu; Sakai, Etsuro.

    1988-01-01

    Purpose: To increase the processing performance even when the iodine content is great and obtain solidification products of excellent durability. Constitution: The solidifying agent mainly comprises waterhardenable material, calcium aluminate (CA), gypsum, ultrafine powder and high performance water reducer. As the water hardenable material, mixed cement incorporated with portland cement, for example, is used. CA with CAO/Al 2 O 3 molar ratio of about 1.5 - 4 is used. Gypsum dihydrate is used as the gypsum in an amount of about 2 to 19 parts by weight based on 29 to 93 parts by weight of water-hardenable materials. The average grain size of the ultrafine powder is lower by about one digit than that of water-hardenable material, CA and gypsum and, for example, silica dust is used. The high performance water reducing agent is a surface active agent, for example, mainly comprising naphthalene sulfonate, etc. (Yoshio, Y.)

  18. Thyroid Dysfunction from Antineoplastic Agents

    Science.gov (United States)

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

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

  19. Intelligent agent software for medicine.

    Science.gov (United States)

    Lieberman, Henry; Mason, Cindy

    2002-01-01

    An important trend for the future of health technology will be the increasing use of intelligent agent software for medical applications. As the complexity of situations faced by both patients and health care providers grows, conventional interfaces that rely on users to manually transfer data and manually perform each problem-solving step, won't be able to keep up. This article describes how software agents that incorporate learning, personalization, proactivity, context-sensitivity and collaboration will lead to a new generation of medical applications that will streamline user interfaces and enable more sophisticated communication and problem-solving.

  20. 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.

  1. Transdominant Rev and Protease Mutant Proteins of HIV-SIV as Potential Antiviral Agents in Vitro and in Vivo (AIDS)

    Science.gov (United States)

    1993-10-30

    1577- 1580. 7. Sarver, N., E.M. Cantin , P.S. Chang, J.A. Zaia, P.A. Landne, D.A. Stephens, and J.J Rossi. 1990. Ribozymes as potential anti-HIV-1...activities. Nature (London) 334: 585-591. 16 Chang, P.S., E.M. Cantin , J.A. Zaia, P.A. Landne, D.A. Stephens, N. Sarver, and J.J. Rossi. 1990. Clinical

  2. Clustering recommendations to compute agent reputation

    Science.gov (United States)

    Bedi, Punam; Kaur, Harmeet

    2005-03-01

    Traditional centralized approaches to security are difficult to apply to multi-agent systems which are used nowadays in e-commerce applications. Developing a notion of trust that is based on the reputation of an agent can provide a softer notion of security that is sufficient for many multi-agent applications. Our paper proposes a mechanism for computing reputation of the trustee agent for use by the trustier agent. The trustier agent computes the reputation based on its own experience as well as the experience the peer agents have with the trustee agents. The trustier agents intentionally interact with the peer agents to get their experience information in the form of recommendations. We have also considered the case of unintentional encounters between the referee agents and the trustee agent, which can be directly between them or indirectly through a set of interacting agents. The clustering is done to filter off the noise in the recommendations in the form of outliers. The trustier agent clusters the recommendations received from referee agents on the basis of the distances between recommendations using the hierarchical agglomerative method. The dendogram hence obtained is cut at the required similarity level which restricts the maximum distance between any two recommendations within a cluster. The cluster with maximum number of elements denotes the views of the majority of recommenders. The center of this cluster represents the reputation of the trustee agent which can be computed using c-means algorithm.

  3. 2APL: a practical agent programming language

    NARCIS (Netherlands)

    Dastani, M.M.

    2008-01-01

    This article presents a BDI-based agent-oriented programming language, called 2APL (A Practical Agent Programming Language). This programming language facilitates the implementation ofmulti-agent systems consisting of individual agents thatmay share and access external environments. It realizes

  4. Fundamental studies of oral contrast agents for MR. Comparison of manganese agent and iron agent

    International Nuclear Information System (INIS)

    Fujita, Osamu; Hiraishi, Kumiko; Suginobu, Yoshito; Takeuchi, Masayasu; Narabayashi, Isamu

    1996-01-01

    We investigated and compared signal intensity and the effect of imaging the upper abdomen with blueberry juice (B.J.), a Mn agent utilizing the properties of paramagnetic metals, and FerriSeltz (F.S.), an iron agent. Since the relaxation effect was much stronger with B.J. than with F.S., the signal intensity required of a peroral contrast agent was able to be obtained at a much lower concentration of B.J. In imaging the upper abdomen, B.J. had a positive effect on imaging in T1-weighted images, and a negative effect in T2-weighted images. F.S. had a positive imaging effect in both, and because it showed extremely high signals in T2-weighted images, motion artifact arose. (author)

  5. Dopamine agents for hepatic encephalopathy

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have...

  6. Agent Supported Serious Game Environment

    Science.gov (United States)

    Terzidou, Theodouli; Tsiatsos, Thrasyvoulos; Miliou, Christina; Sourvinou, Athanasia

    2016-01-01

    This study proposes and applies a novel concept for an AI enhanced serious game collaborative environment as a supplementary learning tool in tertiary education. It is based on previous research that investigated pedagogical agents for a serious game in the OpenSim environment. The proposed AI features to support the serious game are the…

  7. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Science.gov (United States)

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA Financial Assistance for NMVC Companies (Leverage) Funding Leverage by Use of Sba Guaranteed Trust Certificates (âtcsâ... Debenture, SBA may cause each NMVC Company to appoint a Selling Agent to perform functions that include, but...

  8. Design of Collaborative Information Agents

    NARCIS (Netherlands)

    Jonker, C.M.; Klusch, M.; Treur, J.; Klusch, M.; Kerschberg, L.

    2000-01-01

    Effective development of nontrivial systems of collaborative information agents requires that an in-depth analysis is made resulting in (1) specification of requirements at different levels of the system, (2) specification of design structures, and (3) a systematic verification. To support a

  9. 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.

  10. Voice in the Agentic Assemblage

    Science.gov (United States)

    Mazzei, Lisa A.; Jackson, Alecia Y.

    2017-01-01

    In this article, we explore how a posthumanist stance has enabled us to work a different consideration of the way in which "voice" is constituted and constituting in educational inquiry; that is, we position voice in a posthuman ontology that is understood as attributable to a complex network of human and nonhuman agents that exceed the…

  11. Strategic management of biotechnology agents.

    Science.gov (United States)

    Huber, S L

    1993-07-01

    The use of biologic response modifiers to demonstrate a value-driven approach to strategic management by pharmacists is described. To participate in decisions on the use of technology in their institutions, pharmacists must practice strategic management. This process includes environmental scanning, analysis of clinical and pharmacoeconomic data, and development of clinical management approaches. It is ideal for analyzing biologic response modifiers such as filgrastim and sargramostim. Emphasis must be placed on maximizing the fit among the products, the institution, and the health care environment. Pharmacists will find plentiful opportunities for clinical management with biotechnology agents. Practitioners who specialize in determining the total cost of care by using pharmacoeconomic methods are needed, as are practitioners trained to monitor the complicated biotechnology agents. Also, the institution needs to forecast accurately the impact of emerging biotechnology agents. If pharmacists can develop and control clinical, pharmacoeconomic, and reimbursement information databases for biotechnology agents, the pharmacy profession will be in a strong position to meet the challenges of biotechnology and realize the inherent opportunities.

  12. Bridging humans via agent networks

    International Nuclear Information System (INIS)

    Ishida, Toru

    1994-01-01

    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.)

  13. Hyperthermia as a teratogenic agent

    Science.gov (United States)

    Poswillo, David; Nunnerley, Heather; Sopher, Dinah; Keith, John

    1974-01-01

    The common cotton-eared marmoset, a nonhuman primate with a narrow zone of thermoneutrality, was used in an experiment to assess the effects of hyperthermia as a teratogenic agent. Mild heat stress conditions were used. The results of this preliminary study justify further investigation of the effect of hyperthermia on the primate embryo during morphogenesis. Imagesp173-a PMID:4214348

  14. Real Estate Agent Commission Disputes

    Directory of Open Access Journals (Sweden)

    Anida Duarte

    2015-06-01

    Full Text Available The purpose of this study was to examine the relationship among Procuring Cause Law, real estate agent years of experience, and real estate commission disputes. A pilot survey was conducted in the southwestern United States among real estate agents, realtor(s, and brokers. After testing the hypothesis, the decision was made to fail to reject the hypothesis and conclude that real estate agent experience and not Procuring Cause Law produced favorable outcomes in disputes. As a result, the following recommendations were made: (a Agency seller and buyer’s agreements should be used in each transaction to avoid disputes, (b proper expectations and guidelines should be reviewed prior to starting any real estate transaction, (c a checklist may assist in the assurance that all valuable information is reviewed, (d agents could benefit from fully understanding Procuring Cause Law and sharing this information with their clients, (e state and national regulatory requirements of the law could be modified for easier understanding and use, and (f consumers who willfully violate the law could be subject to monetary penalties.

  15. The DARPA agent markup language

    NARCIS (Netherlands)

    Lassila, O; van Harmelen, F; Horrocks, I.; Hendler, J.; McGuinness, DL

    2000-01-01

    The DARPA Agent Markup Language (DAML) program is a United States government sponsored endeavor aimed at providing the foundation for the next web evolution – the semantic web. The program is funding critical research to develop languages, tools and techniques for making considerably more of the

  16. 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

  17. Biocontrol agents in signalling resistance

    NARCIS (Netherlands)

    Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    The mechanisms by which biological control agents suppress disease comprise competition for nutrients, notably iron, production of antibiotics, and secretion of lytic enzymes, as well as inducing resistance in the plant. The former three mechanisms act primarily on the pathogen by decreasing its

  18. The Power Trading Agent Competition

    NARCIS (Netherlands)

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

  19. 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,

  20. Agents containing chlorhexidine in dentistry

    Directory of Open Access Journals (Sweden)

    Lebedeva S.N.

    2011-03-01

    Full Text Available 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

  1. Humor and Embodied Conversational Agents

    NARCIS (Netherlands)

    Nijholt, Antinus

    This report surveys the role of humor in human-to-human interaction and the possible role of humor in human-computer interaction. The aim is to see whether it is useful for embodied conversational agents to integrate humor capabilities in their internal model of intelligence, emotions and

  2. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    Weininger, J.; Trumper, J.

    1984-01-01

    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

  3. Travel Agent. Occupational Simulation Kit.

    Science.gov (United States)

    Peterson, Wayne

    This career exploration instructional booklet on the travel agent's occupation is one of several resulting from the rural southwestern Colorado CEPAC Project (Career Education Process of Attitude Change). Based on a job analysis and utilizing a programed instructional format, the following content is included: A brief description of what a travel…

  4. 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…

  5. 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.

  6. Limonene and tetrahydrofurfurly alcohol cleaning agent

    Science.gov (United States)

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

    1997-10-21

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

  7. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    Science.gov (United States)

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

    1996-05-07

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

  8. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    Science.gov (United States)

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

    1997-10-21

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

  9. Innovative agents in cancer prevention.

    Science.gov (United States)

    Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

    2005-01-01

    There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

  10. Does an Agent Matter? The Effects of Animated Pedagogical Agents on Multimedia Environments.

    Science.gov (United States)

    Craig, Scotty D.; Gholson, Barry

    Data are presented on the effects of Animated Agents on multimedia learning environments with specific concerns of split attention and modality effects. The study was a 3 (agent properties: agent only, agent with gestures, no agent) x 3 (picture features: static picture, sudden onset, animation) factorial design with outcome measures of mental…

  11. 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.

  12. Software agents in molecular computational biology.

    Science.gov (United States)

    Keele, John W; Wray, James E

    2005-12-01

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

  13. Children as digital rights agents

    DEFF Research Database (Denmark)

    Stald, Gitte Bang

    2016-01-01

    the role of the “adult world” is. We need to focus more on the active role that children and adolescents play, according to age, skills and various capacities, in identifying, reflecting upon and acting according to opportunities and challenges in relation to digital media and digital rights (Hartman et al...... 2007). The paper presents a model for analyzing the intersecting levels of children as agents in relation to digital risks and rights: Children as peer-to-peer agents. Children provide mutual practical guidance; experience sharing; advice. re. to risk and harm. Children as advocates/ politicians....... Children participate in youth parliaments; media councils; Safer Internet day; IGF; NGOs, Children as informants. Children contribute to research; media coverage; content providers; reporters (of negative content/ behavior The model is primarily supported by empirical data from the Net Children Go Mobile...

  14. Extension agents and conflict narratives

    DEFF Research Database (Denmark)

    Bond, Jennifer Lauren

    2016-01-01

    conflict. Originality: This work contributes to a growing body of literature interested in the role of extension agents in conflict management. By applying Q methodology, this work has shown that while extension agents are involved in conflict management, their perceptions of these conflicts are subjective......Purpose: This work investigated the narratives of development extensionists in relation to natural resource conflict, in order to understand the competing discourses surrounding the wicked problems of natural resource management in Laikipia County, Kenya. Methodology: Q methodology was used...... to elicit the conflict narratives present among extension professionals. A concourse of 221 statements were devised from interviews and group discussions with key informants and a final sample of 49 statements was used for the sorting. Thirteen Q-sorts were undertaken with among rural extension...

  15. Logical Theories for Agent Introspection

    DEFF Research Database (Denmark)

    Bolander, Thomas

    2004-01-01

    Artificial intelligence systems (agents) generally have models of the environments they inhabit which they use for representing facts, for reasoning about these facts and for planning actions. Much intelligent behaviour seems to involve an ability to model not only one's external environment...... 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...... by developments within semantics for logic programming within computational logic and formal theories of truth within philosophical logic. The thesis provides a number of examples showing how the developed theories can be used as reasoning frameworks for agents with introspective abilities. In Danish...

  16. Solidifying agent for radioactive waste

    International Nuclear Information System (INIS)

    Sakai, Etsuro; Kida, Tsutomu; Sasagawa, Yukio.

    1988-01-01

    Purpose: To apply solidifying treatment to boron-containing radioactive wastes while improving the durability, rapid hardening property and processing performance, as well as reducing the leaching property. Constitution: A solidifying agent comprising calcium aluminate having CaO and Al 2 O 3 at 1.5 - 4 molar ratio, super fine powder and high performance moderator is used. As the super fine powder, those having a grain size smaller by 1 - 2 orders than that of the calcium aluminate are preferred. Specifically, there can be used silica dust, calcium carbonate, silica gel, titanium oxide, aluminum oxide, etc. As the moderator, there are used those surface active agents of great dispersing performance not causing excess delay for coagulation or excess air entrainment when added in a great amount to cements. Specifically, there can be mentioned those mainly composed of salts of naphthalene sulfonic acid-formaldehyde condensates, salts of melamine sulfonic acid formaldehyde condensates, etc. (Ikeda, J.)

  17. Strategic Design of Mobile Agents

    OpenAIRE

    Vulkan, Nir

    2002-01-01

    Much of the economic value of electronic commerce comes from the automation of interactions between businesses and individuals. Game theory is a useful set of tools that can be used by designers of electronic-commerce applications in analyzing and engineering of automated agents and communication protocols. The central theoretical concept used in game theory is the Nash equilibrium. In this article, I show how the outcomes supported by a Nash equilibrium can positively be enlarged using autom...

  18. Needs, Pains, and Motivations in Autonomous Agents.

    Science.gov (United States)

    Starzyk, Janusz A; Graham, James; Puzio, Leszek

    This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.

  19. 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.

  20. Solidification agent for radioactive waste

    International Nuclear Information System (INIS)

    Sakai, Etsuro; Shibayama, Yukio.

    1986-01-01

    Purpose: In low and medium level radioactive waste processing, to obtain superior solidified blocks by mixing cement, super-fine dusts and high-performance water-reducing agent and water to radioactive waste materials for solidification. Constitution: The various types of portland cements available are used for solidification. Silica dust is used as the super-fine dust and has an average article size of one order smaller than that of the cement used for solidification. Napthalene, sulfonic acid formalydehyde condensation salts etc. are used as the water-reducing agents. For example, for hundred units, by weight, of cement and super-fine dust 10 units (by solid content) are added. Furthermore, smaller quantities of water are desirable. By mixing the radioactive wastes with cement, super-fine dust, water-reducing agents, and water, the solidified material shows superior chemical resistance and durability. The processing capacity is also increased. Furthermore, a more leach resistant solid can be obtained for storage. (Takahashi, M.)

  1. Overprescribing of lipid lowering agents.

    Science.gov (United States)

    Smith, M A; Cox, E D; Bartell, J M

    2006-08-01

    Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. 2034 physicians were surveyed twice: baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?" During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors.

  2. Commission of the commercial agent

    Directory of Open Access Journals (Sweden)

    Radović Mirjana

    2015-01-01

    Full Text Available In this paper the author analyses the commercial agent's commission as the most important type of remuneration for commercial agency. In the European Union the issue of commercial agent's commission is regulated in the Directive 86/653/EEC on self-employed commercial agents, whereas the Serbian Law on Obligations has still not been harmonised with those rules. Such state of law would change if and when the new Serbian Civil Code is enacted, since its latest Draft contains numerous new solutions, which were inspired by the Directive. The first part of the paper is dedicated to defining the term 'commission' and its distinguishing from the wider term 'remuneration'. Thereafter, the main types of commission are explained. The following part investigates whether the commission or its specific type constitutes essentialia or naturalia negotii of the contract on commercial agency. Finally, the last part of the paper deals with the amount and the extent of covering costs by the commission, in the absence of any agreement on that matter.

  3. 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 ...

  4. Borrelioses, agentes e vetores Borrelioses, agents and vectors: a review

    Directory of Open Access Journals (Sweden)

    Cleber O. Soares

    2000-03-01

    Full Text Available As borrelioses são enfermidades infecciosas determinadas por espiroquetas do gênero Borrelia, agentes transmissíveis, principalmente, por carrapatos aos animais e/ou ao homem. Nesta revisão são apresentadas e discutidas as enfermidades determinadas por borrélias, bem como as características gerais das espiroquetas, os aspectos relacionados a transmissão por artrópodes, as enfermidades nos animais domésticos e silvestres, quanto aos aspectos biológicos e patológicos, a doença de Lyme como principal zoonose do grupo, a associação de borrélia com outros agentes hematozoários e os métodos diagnósticos e a epidemiologia comparativa entre dados obtidos no Brasil com os de outros países. Estas borrelioses possuem características patológicas, clínicas e epidemiológicas variadas de acordo à região fisiográfica, devido à existência de distintas espécies, genoespécies e cepas; estes aspectos variam ainda em função dos artrópodes vetores, da interação vetor-patógeno e dos ecossistemas distintos.Borrelioses are infectous diseases caused by spirochaetes of the genus Borrelia. They are born mainly through ticks at animals and/or human beings. In this review are shown and discussed five groups of diseases determined by borrelia, general characteristics of the spirochaetes, aspects related to transmission by arthropods, biological and pathological aspects of the diseases in domestic and wild animals, Lyme disease as an important zoonosis, the association of borrelia with other hematozoa agents, the diagnostic methods and the comparative epidemiology with data obtained from Brazil and other countries. The borrelioses have pathological, clinical and epidemiological characteristics which vary according to physiographic regions due to the existence of different species, genospecies and strains of borrelia, of arthropod vectors, vector-agent relationship and of different ecocystems.

  5. 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.

  6. Validation of Agent Based Distillation Movement Algorithms

    National Research Council Canada - National Science Library

    Gill, Andrew

    2003-01-01

    Agent based distillations (ABD) are low-resolution abstract models, which can be used to explore questions associated with land combat operations in a short period of time Movement of agents within the EINSTein and MANA ABDs...

  7. Surface modification agents for lithium batteries

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonghai; Amine, Khalil; Belharouak, Ilias

    2017-11-21

    An active material for an electrochemical device wherein a surface of the active material is modified by a surface modification agent, wherein the surface modification agent is an organometallic compound.

  8. Dendritic cells used in anti-HIV immunotherapy showed different modulation in anti-HIV genes expression: New concept for the improvement of patients' selection criteria

    Directory of Open Access Journals (Sweden)

    Alessandra Pontillo

    2016-11-01

    Conclusions: These results suggest that the actual selection of HIV+ individual for immunotherapy, based on clinical features, did not ensure the same DC product, and that less “activated/exhausted” DC could positively affect the outcome of immunotherapy.

  9. 2APL: a practical agent programming language

    OpenAIRE

    Dastani, M.M.

    2008-01-01

    This article presents a BDI-based agent-oriented programming language, called 2APL (A Practical Agent Programming Language). This programming language facilitates the implementation ofmulti-agent systems consisting of individual agents thatmay share and access external environments. It realizes an effective integration of declarative and imperative style programming by introducing and integrating declarative beliefs and goals with events and plans. It also provides practical programming const...

  10. An overview of agents in knowledge management

    OpenAIRE

    Dignum, M.V.

    2006-01-01

    Current developments in Knowledge Management concern the sharing and usage of knowledge in dynamic environments. The need for systems that both react to and anticipate the needs and expectations of users calls for flexible and adaptable development and implementation frameworks. These are exactly the characteristics that identify software agents and agent societies, which make natural the application of the agent paradigm in KM. This paper attempts to identify both the advantages of agents fo...

  11. Honey - A Novel Antidiabetic Agent

    Science.gov (United States)

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

    2012-01-01

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

  12. Agent based energy management systems

    Energy Technology Data Exchange (ETDEWEB)

    Wolter, Martin

    2012-07-01

    In liberalized, regulated energy markets, the different participants - namely producers and consumers of energy, transmission and distribution system operators as well as regulatory authorities - have partly divergent and partly convergent interests. Loads, power plants and grid operators try to maximize their own benefit in this highly complex environment accepting to act detrimentally to others. Although the relationship between the participants is mostly competitive, there are some fundamental shared interests, e.g. voltage stability, a constant system frequency or efficient energy production, transmission and distribution, which are endangered e.g. by increased injection of volatile sources in low and medium voltage grids, displacement of stabilizing bulk generation and the slowly progressing extension of the electric grid. There is a global consensus, that the resulting challenges can efficiently be faced using information and communication technologies to coordinate grid utilization and operation. The basic idea is to benefit from unused reserves by participating in deployment of system services e.g. reactive power supply to keep the voltage within certain bounds. The coordination can best be done by the grid operator. All activities of that kind are summarized under the umbrella term ''Smart Grid''. To simultaneously model the behavior and interests of different types of market participants and their convergent and divergent interests, multi-agent systems are used. They offer a perfectly fitting framework for this sort of game theory and can easily be adapted to all kinds of new challenges of electricity markets. In this work, multi-agent systems are used to either cooperatively or competitively solve problems in distribution and transmission systems. Therefore, conventional algorithms have to be modified to converge into multiple local optima using only small pieces of the entire system information. It is clearly stated, that personal

  13. 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.

  14. 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 d...... 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....

  15. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  16. Multi agent gathering waste system

    Directory of Open Access Journals (Sweden)

    Álvaro LOZANO MURCIEGO

    2016-07-01

    Full Text Available Along this paper, we present a new multi agent-based system to gather waste on cities and villages. We have developed a low cost wireless sensor prototype to measure the volume level of the containers. Furthermore a route system is developed to optimize the routes of the trucks and a mobile application has been developed to help drivers in their working days. In order to evaluate and validate the proposed system a practical case study in a real city environment is modeled using open data available and with the purpose of identifying limitations of the system.

  17. Diarrhea caused by circulating agents.

    Science.gov (United States)

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. A principal-agent Model of corruption

    NARCIS (Netherlands)

    Groenendijk, Nico

    1997-01-01

    One of the new avenues in the study of political corruption is that of neo-institutional economics, of which the principal-agent theory is a part. In this article a principal-agent model of corruption is presented, in which there are two principals (one of which is corrupting), and one agent (who is

  19. Do pedagogical agents enhance software training?

    NARCIS (Netherlands)

    van der Meij, Hans

    2013-01-01

    This study investigates whether a tutorial for software training can be enhanced by adding a pedagogical agent, and whether the type of agent matters (i.e., cognitive, motivational, or mixed). The cognitive agent was designed to stimulate students to process their experiences actively. The

  20. Animated BDP agents in virtual environments

    NARCIS (Netherlands)

    Nijholt, Antinus; Egges, A.; op den Akker, Hendrikus J.A.; Zwiers, Jakob; Krose, B.; de Rijke, M.; Schreiber, G.; van Someren, M.

    2001-01-01

    We introduce a Believes, Desires and Plans (BDP) agent that acts in a virtual environment using multi-modal interaction with the user. The environment is our virtual theatre environment. In this environment different agents have been introduced. In order to obtain a more uniform framework for agent

  1. Group Formation Among Decentralized Autonomous Agents

    NARCIS (Netherlands)

    Ogston, E.F.Y.L.; van Steen, M.R.; Brazier, F.M.

    2004-01-01

    This paper examines a method of clustering within a fully decentralized multi-agent system. Our goal is to group agents with similar objectives or data, as is done in traditional clustering. However, we add the additional constraint that agents must remain in place on a network, instead of first

  2. Individualism and Collectivism in Trade Agents

    NARCIS (Netherlands)

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

    2008-01-01

    Agent-Based Modeling can contribute to the understanding of international trade processes. Models for the effects of culture and cultural differences on agent behavior are required for realistic agent-based simulation of international trade. This paper makes a step toward modeling of culture in

  3. A Framework for Organization-Aware Agents

    DEFF Research Database (Denmark)

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

    2016-01-01

    This short paper introduces and summarizes the AORTA reasoning framework that can be integrated into BDI-agents to enable organizational decision-making. This work has recently been published in the Journal of Autonomous Agents and Multi-Agent Systems (JAAMAS), as [3]....

  4. Radioactive scanning agents with hydroquinone stabilizer

    International Nuclear Information System (INIS)

    Whitehouse, H.S.

    1982-01-01

    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

  5. 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...

  6. 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

  7. IRANIAN MEDICINAL PLANTS AS ANTIMICROBIAL AGENTS

    OpenAIRE

    Mohaddese Mahboubi

    2013-01-01

    Resistance of human and food spoilage pathogens to antimicrobial agents and the side effects of chemical agents or preservative for human is caused for finding natural new antimicrobial agents, especially among the medicinal plants. This review introduces the methods that are used for antimicrobial evaluations and synergistic activities and the antimicrobial potential of some Iranian medicinal plants.

  8. 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.

  9. Mobile Agents in Networking and Distributed Computing

    CERN Document Server

    Cao, Jiannong

    2012-01-01

    The book focuses on mobile agents, which are computer programs that can autonomously migrate between network sites. This text introduces the concepts and principles of mobile agents, provides an overview of mobile agent technology, and focuses on applications in networking and distributed computing.

  10. Agent modelling in METATEM and DESIRE

    NARCIS (Netherlands)

    Mulder, Marco; Treur, Jan; Fisher, Michael

    1998-01-01

    In spite of the rapid spread of agent technology, there is, as yet, little evidence of an engineering approach to the development of multi-agent systems. For example, both development methods and verification techniques for multi-agent systems are rare. In this paper, we describe a case study aimed

  11. Using Intelligent Agents To Assist Educators.

    Science.gov (United States)

    Knode, Steve; Knode, Jon-David W.

    This paper begins with background on intelligent agents (software programs built to perform certain specific tasks for the user). A taxonomy that categorizes intelligent agents by the degree of intelligence embedded in the software is presented. Applications of today's intelligent agents are discussed, including specific examples of the following:…

  12. Information brokering agents in intelligent Websites

    NARCIS (Netherlands)

    Jonker, Catholijn M.; Treur, J.

    1999-01-01

    In this paper a generic information broker agent for intelligent Websites is introduced. The agent architecture has been designed using the compositional development method for multi-agent systems Desire. The use of the architecture is illustrated in an Electronic Commerce application for a

  13. Modelling an Agent's Mind and Matter

    NARCIS (Netherlands)

    Jonker, C.M.; Treur, J.; Boman, M.

    1997-01-01

    In agent models often it is assumed that the agent maintains internal representations of the material world (e.g., its beliefs). An overall model of the agent and the material world necessarily incorporates sub-models for physical simulation and symbolic simulation, and a formalisation of the

  14. Making Agents Gaze Naturally. Does it work?

    NARCIS (Netherlands)

    van Es, Ivo; De Marsico, M.; Levialdi, S.; Heylen, Dirk K.J.; Panizzi, E.; van Dijk, Elisabeth M.A.G.; Nijholt, Antinus

    2002-01-01

    We investigated the effects of varying eye gaze behavior of an embodied conversational agent on the quality of human-agent dialogues. In an experiment we compared three versions of an agent: one with gaze behavior that is typically found to occur in human-human dialogues, one with gaze that is fixed

  15. Effectiveness testing of spill-treating agents

    International Nuclear Information System (INIS)

    Fingas, M.F.; Stoodley, R.; Laroche, N.

    1990-01-01

    Laboratory effectiveness tests are described for four classes of spill-treating agents: solidifiers, demulsifying agents, surface-washing agents and dispersants. Many treating agents in these four categories have been tested for effectiveness and the results are presented. Solidifiers or gelling agents solidify oil, requiring a large amount of agent to solidify oil-ranging between 16% by weight, to over 200%. Emulsion breakers prevent or reverse the formation of water-in-oil emulsions. A newly-developed effectiveness test shows that only one product is highly effective; however, many products will work, but require large amounts of spill-treating agent. Surfactant--containing materials are of two types, surface-washing agents and dispersants. Testing has shown that an agent that is a good dispersant is conversely a poor surface-washing agent, and vice versa. Tests of surface-washing agents show that only a few agents have effectiveness of 25-40%, where this effectiveness is the percentage of heavy oil removed from a test surface. Results using the 'swirling flask' test for dispersant effectiveness are reported. Heavy oils show effectiveness values of about 1%, medium crudes of about 10%, light crude oils of about 30% and very light oils of about 90%. (author)

  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. Nonsteroid anti-inflammatory agents.

    Science.gov (United States)

    Paulus, H E; Whitehouse, M W

    1973-01-01

    Nonsteroidal antiinflammatory agents (NSAID) are reviewed. Aspirin, indomethacin, and salicylate have all been shown to interfere or prevent the synthesis of prostaglandins (PGs), a main tissue inflammatory substance. However, an exception to the correlation of PG-synthetase inhibition with antiinflammatory activity has been noted with certain arylacetic acids. Studies on the role of lysosomes in the inflammation are criticized in this review, mainly because of improper understanding of the role of lysosomes in a physiological system. Since lysosomes are not a specific body, but an activator, attempts to isolate lysosomes to study functions are doomed to failure; i.e., a lysosome has no definition without the rest of its self-regulating system. NSAIDs work in 2 main ways; either via antiaggregation or antiinflammation. This may result in drug interactions between various types of NSAIDs. For example, simultaneous administration of aspirin with indomethacine did not produce an additive effect; rather they produced no effect in the rat paw edema test dissimilar to the action of either drug separately. However, hydrocortisone combined with another NSAID enhanced its antiinflammatory effects. Albumin binding theories of NSAID mechanism of action state that drugs are active only when albumin-bound because it has displaced tryptophane, or urate, or some other normally bound substance. The only way to discover an efficient antiinflammatory agent is to obviate the need for it by discovering the actual mechanism of inflammation, for when specific anti-etiologic therapy is developed, the need for treatment with NSAIDs is irrelevant.

  18. A Review of Luting Agents

    Directory of Open Access Journals (Sweden)

    Cornelis H. Pameijer

    2012-01-01

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

  19. Animal venoms as antimicrobial agents.

    Science.gov (United States)

    Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

    2017-06-15

    Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Ruthenium complexes as antimicrobial agents.

    Science.gov (United States)

    Li, Fangfei; Collins, J Grant; Keene, F Richard

    2015-04-21

    One of the major advances in medical science has been the development of antimicrobials; however, a consequence of their widespread use has been the emergence of drug-resistant populations of microorganisms. There is clearly a need for the development of new antimicrobials--but more importantly, there is the need for the development of new classes of antimicrobials, rather than drugs based upon analogues of known scaffolds. Due to the success of the platinum anticancer agents, there has been considerable interest in the development of therapeutic agents based upon other transition metals--and in particular ruthenium(II/III) complexes, due to their well known interaction with DNA. There have been many studies of the anticancer properties and cellular localisation of a range of ruthenium complexes in eukaryotic cells over the last decade. However, only very recently has there been significant interest in their antimicrobial properties. This review highlights the types of ruthenium complexes that have exhibited significant antimicrobial activity and discusses the relationship between chemical structure and biological processing--including site(s) of intracellular accumulation--of the ruthenium complexes in both bacterial and eukaryotic cells.

  1. 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.

  2. Building Multi-Agent Systems Using Jason

    DEFF Research Database (Denmark)

    Boss, Niklas Skamriis; Jensen, Andreas Schmidt; Villadsen, Jørgen

    2010-01-01

    We provide a detailed description of the Jason-DTU system, including the used methodology, tools as well as team strategy. We also discuss the experience gathered in the contest. In spring 2009 the course “Artificial Intelligence and Multi- Agent Systems” was held for the first time...... on the Technical University of Denmark (DTU). A part of this course was a short introduction to the multi-agent framework Jason, which is an interpreter for AgentSpeak, an agent-oriented programming language. As the final project in this course a solution to the Multi-Agent Programming Contest from 2007, the Gold...

  3. Reversal agents in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Nibedita Pani

    2015-01-01

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

  4. Variations on agent-oriented programming

    Directory of Open Access Journals (Sweden)

    Dalia Baziukė

    2017-12-01

    Full Text Available Occurrence of the agent paradigm and its further applications have stimulated the emergence of new concepts and methodologies in computer science. Today terms like multi-agent system, agent-oriented methodology, and agent-oriented programming (AOP are widely used. The aim of this paper is to clarify the validity of usage of the terms AOP and AOP language. This is disclosed in two phases of an analysis process. Determining to which concepts, terms like agent, programming, object-oriented analysis and design, object-oriented programming, and agent-oriented analysis and design correspond is accomplished in the first phase. Analysis of several known agent system engineering methodologies in terms of key concepts used, final resulting artifacts, and their relationship with known programming paradigms and modern tools for agent system development is performed in the second phase. The research shows that in most cases in the final phase of agent system design and in the coding stage, the main artifact is an object, defined according to the rules of the object-oriented paradigm. Hence, we say that the computing society still does not have AOP owing to the lack of an AOP language. Thus, the term AOP is very often incorrectly assigned to agent system development frameworks that in most cases, transform agents into objects.DOI: 10.15181/csat.v5i1.1361

  5. 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.

  6. 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.

  7. A Framework for Organization-Aware Agents

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...... boundaries and work towards the objectives of the organization. In this paper, we present the AORTA reasoning framework and show how it can be integrated into typical BDI-agents. We provide operational semantics that enables agents to make organizational decisions in order to coordinate and cooperate without...... 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...

  8. 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.

  9. 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.

  10. 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.

  11. Survey of agent for intelligent information retrieval; Chiteki kensaku no tame no agent no chosa

    Energy Technology Data Exchange (ETDEWEB)

    Yazawa, T. [Central Research Institute of Electric Power Industry, Tokyo (Japan)

    1996-09-01

    Development of agent systems has been surveyed, to classify and arrange characteristic functions of the agents, and to grasp the realization situation of these agents in their development. In addition, prospective functions of information retrieval systems using the agents at maximum and functions to be developed among these in the future are clarified. The agents are characterized by the expression function, communication function, planning function, adaptive function, and learning function. The agents are desired to be classified into interface agents whose works are to respond to individual workers, coordinator agents which conduct works with high pervasion, such as assignment of works and their control, and task agents which conduct specialized works for individual examples. Thus, design and configuration of the agent system, and improvement and expansion of system functions can be effectively and easily conducted. 52 refs., 5 figs., 3 tabs.

  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.

    Science.gov (United States)

    Meng, Yao; Liu, Shuangfeng; Li, Juan; Meng, Yanfa; Zhao, Xiaojun

    2012-01-01

    Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG)(2)-Lys-NHS (20 kDa). In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex 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. 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

  13. 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.

  14. Il libro agente della socializzazione

    Directory of Open Access Journals (Sweden)

    Daniela Sideri

    2017-06-01

    Full Text Available Il saggio indaga il ruolo del libro come agente di socializzazione, con particolare riferimento al pubblico dei lettori ragazzi e bambini e alle specifiche funzioni formative della “lettura della letteratura” in età pre-scolare e scolare fino ai 14 anni. La ricerca di matrice socio-culturale si è occupata per lo più del libro in qualità di prodotto eminentemente sociale (sociologia della letteratura, contenitore di testi significanti (semiotica, e bene di consumo dell’industria culturale (cultural studies: lo studio proposto richiama le conclusioni fondamentali di decenni di studi intorno al libro, con l’intento di rintracciare i criteri adeguati (tema, target, identità visiva, funzione pratica e utopica a guidare una classificazione dei generi 0-14 che evidenzi il valore socializzante di ciascuno, proponendo così una originale tipologia, che giustifica l’inserimento del libro tra quelle definite “agenzie testuali” della socializzazione.

  15. 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.

  16. DNA minor groove alkylating agents.

    Science.gov (United States)

    Denny, W A

    2001-04-01

    Recent work on a number of different classes of anticancer agents that alkylate DNA in the minor groove is reviewed. There has been much work with nitrogen mustards, where attachment of the mustard unit to carrier molecules can change the normal patterns of both regio- and sequence-selectivity, from reaction primarily at most guanine N7 sites in the major groove to a few adenine N3 sites at the 3'-end of poly(A/T) sequences in the minor groove. Carrier molecules discussed for mustards are intercalators, polypyrroles, polyimidazoles, bis(benzimidazoles), polybenzamides and anilinoquinolinium salts. In contrast, similar targeting of pyrrolizidine alkylators by a variety of carriers has little effect of their patterns of alkylation (at the 2-amino group of guanine). Recent work on the pyrrolobenzodiazepine and cyclopropaindolone classes of natural product minor groove binders is also reviewed.

  17. Blasting agents and initiation systems

    Energy Technology Data Exchange (ETDEWEB)

    Fiscor, S.

    2000-01-01

    Although blasting differs between and within each industry, as a whole, the mines and quarries are making a shift from a purely ammonium nitrate/fuel oil (ANFO) mixture to a blend of emulsion and ANFO on a straight emulsion. Non-electric (shock tube) initiation systems have provided a viable alternative to the electric detonator (blasting cap). Explosives manufacturers are seeing their roles changes to being blasting contractors or consultants rather than just suppliers. The article discusses these trends and gives examples of typical blasting techniques and amounts of blasting agent used at large USA surface coal mines. Electric caps are still used in blasting underground coal. The Ensign Bickford Co. (EBCo) is developing electronic detonators and has been field testing an electronic initiator, the DIGIDET detonator, for the last four years. When commercially available, electronic detonators will be accurate but will come with a hefty price tag. 2 photos.

  18. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull 2007; 6(6.000: 491-500

  19. An Important Chemical Weapon Group: Nerve Agents

    Directory of Open Access Journals (Sweden)

    Hakan Yaren

    2007-12-01

    Full Text Available As a result of developing modern chemistry, nerve agents, which are one of the most important group of efficient chemical warfare agents, were developed just before Second World War. They generate toxic and clinical effects via inhibiting acetylcholinesterase irreversibly and causing excessive amounts of acetylcholine at cholinergic synapses in the body. Clinical symptoms are occurred as a result of affected muscarinic (stimulation of secretuar glands, miosis, breathing problems etc., nicotinic (stimulation of skeletal muscles, paralyse, tremors etc. and central nerve system (convulsions, loss of consciousness, coma etc. areas. In case of a nerve agent exposure, treatment includes the steps of ventilation, decontamination, antidotal treatment (atropine, oximes, diazepam and pyridostigmine bromide and supportive theraphy. Because of arising possibility of using chemical warfare agents due to current conjuncture of the world, medical staff should know about nerve agents, their effects and how to treat the casualties exposured to nerve agents. [TAF Prev Med Bull. 2007; 6(6: 491-500

  20. Supporting a Learner Community with Software Agents

    Directory of Open Access Journals (Sweden)

    Pierre Tchounikine

    2004-04-01

    Full Text Available This paper describes a multi- agent approach that aims at supporting learners involved in a collective activity. We consider pedagogical situations where students have to explicitly define the articulation of their collective work and then achieve the different tasks they have defined. Our objective is to support these students by taking some of these tasks in charge whilst making them work out such organisation features. For this purpose, we propose to consider that the group of students forms a multi- agent system and to introduce software agents that can achieve some of the tasks within this group. This conducts students to tackle the problem in terms of human and software agent coordination. We present how this approach can be conceptualized and modelled using Engeström’s triangle, how task delegation can be used as a means to enable students to define the software agents’ behaviour and the multi-agent implementation we propose.

  1. Persuasive Conversational Agent with Persuasion Tactics

    Science.gov (United States)

    Narita, Tatsuya; Kitamura, Yasuhiko

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

  2. Radioiodine: the classic theranostic agent.

    Science.gov (United States)

    Silberstein, Edward B

    2012-05-01

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

  3. Inaccessibility in Multi-Agent Systems

    Science.gov (United States)

    2004-03-08

    Mař́ık, D. McFarlane, and P. Valckenaers (eds.): Holonic and Multi-Agent Systems for Manufacturing , No. 2744 in LNAI. Springer-Verlag, Heidelberg. 17...in Multi-Agent Systems 5c. PROGRAM ELEMENT NUMBER 5d. PROJECT NUMBER 5d. TASK NUMBER 6. AUTHOR(S) Professor Vladimir Marik 5e. WORK UNIT NUMBER...short term inaccessibility, (3) long term inaccessibility, and (4) testing and validation. 15. SUBJECT TERMS EOARD, Multi Agent Systems , Behavior

  4. Different Views of Software Agent Paradigm

    OpenAIRE

    Anand Kumar Pandey; Rashmi Pandey

    2012-01-01

    Agent modelling in software engineering is a relatively young area, and there are, as yet, no standard methodologies, development tools, or software architectures. Although our work is emphasized on to represent the agent specifications using different views, they are not oriented for software engineering in terms of providing a modeling notation that directly supports software development. There are, however, some software frameworks using different views of software agents, that are beginni...

  5. Running agent-based simulations. Unternehmensmodell / Computersimulation.

    OpenAIRE

    Meyer, David; Karatzoglou, Alexandros; Buchta, Christian; Leisch, Friedrich; Hornik, Kurt

    2001-01-01

    When running agent-based simulations using ready-made components, one usually faces heterogenity problems both for the agents' implementation and for the underlying platform. To circumvent these kind of hindrances, we introduce a wrapper technique for mapping the functionality of agents living in an interpreter-based environment to a standardized CORBA interface, thus facilitating the task for any control mechanism (like a simulation manager) which just will need to handle one set of commands...

  6. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  7. Rule Value Reinforcement Learning for Cognitive Agents

    OpenAIRE

    Child, C. H. T.; Stathis, K.

    2006-01-01

    RVRL (Rule Value Reinforcement Learning) is a new algorithm which extends an existing learning framework that models the environment of a situated agent using a probabilistic rule representation. The algorithm attaches values to learned rules by adapting reinforcement learning. Structure captured by the rules is used to form a policy. The resulting rule values represent the utility of taking an action if the rule`s conditions are present in the agent`s current percept. Advantages of the new f...

  8. 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.

  9. Conversational Agents in E-Learning

    Science.gov (United States)

    Kerry, Alice; Ellis, Richard; Bull, Susan

    This paper discusses the use of natural language or 'conversational' agents in e-learning environments. We describe and contrast the various applications of conversational agent technology represented in the e-learning literature, including tutors, learning companions, language practice and systems to encourage reflection. We offer two more detailed examples of conversational agents, one which provides learning support, and the other support for self-assessment. Issues and challenges for developers of conversational agent systems for e-learning are identified and discussed.

  10. Multi-agent and complex systems

    CERN Document Server

    Ren, Fenghui; Fujita, Katsuhide; Zhang, Minjie; Ito, Takayuki

    2017-01-01

    This book provides a description of advanced multi-agent and artificial intelligence technologies for the modeling and simulation of complex systems, as well as an overview of the latest scientific efforts in this field. A complex system features a large number of interacting components, whose aggregate activities are nonlinear and self-organized. A multi-agent system is a group or society of agents which interact with others cooperatively and/or competitively in order to reach their individual or common goals. Multi-agent systems are suitable for modeling and simulation of complex systems, which is difficult to accomplish using traditional computational approaches.

  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 Negotiation in Uncertain Environments

    Science.gov (United States)

    Debenham, John; Sierra, Carles

    An agent aims to secure his projected needs by attempting to build a set of (business) relationships with other agents. A relationship is built by exchanging private information, and is characterised by its intimacy — degree of closeness — and balance — degree of fairness. Each argumentative interaction between two agents then has two goals: to satisfy some immediate need, and to do so in a way that develops the relationship in a desired direction. An agent's desire to develop each relationship in a particular way then places constraints on the argumentative utterances. The form of negotiation described is argumentative interaction constrained by a desire to develop such relationships.

  13. Toddlers Selectively Help Fair Agents

    Directory of Open Access Journals (Sweden)

    Luca Surian

    2017-06-01

    Full Text Available Previous research showed that infants and toddlers are inclined to help prosocial agents and assign a positive valence to fair distributions. Also, they expect that positive and negative actions directed toward distributors will conform to reciprocity principles. This study investigates whether toddlers are selective in helping others, as a function of others’ previous distributive actions. Toddlers were presented with real-life events in which two actresses distributed resources either equally or unequally between two puppets. Then, they played together with a ball that accidentally fell to the ground and asked participants to help them to retrieve it. Participants preferred to help the actress who performed equal distributions. This finding suggests that by the second year children’s prosocial actions are modulated by their emerging sense of fairness.HighlightsToddlers (mean age = 25 months are selective in helping distributors.Toddlers prefer helping a fair rather than an unfair distributor.Toddlers’ selective helping provides evidence for an early sense of fairness.

  14. Viruses: agents of coral disease?

    Science.gov (United States)

    Davy, S K; Burchett, S G; Dale, A L; Davies, P; Davy, J E; Muncke, C; Hoegh-Guldberg, O; Wilson, W H

    2006-03-23

    The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.

  15. Novel Methylselenoesters as Antiproliferative Agents.

    Science.gov (United States)

    Díaz-Argelich, Nuria; Encío, Ignacio; Plano, Daniel; Fernandes, Aristi P; Palop, Juan Antonio; Sanmartín, Carmen

    2017-08-02

    Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH₃SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH₃SeH. The fifteen compounds follow Lipinski's Rule of Five and with exception of compounds 1 and 14 , present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI 50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G₂/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.

  16. Novel Methylselenoesters as Antiproliferative Agents

    Directory of Open Access Journals (Sweden)

    Nuria Díaz-Argelich

    2017-08-01

    Full Text Available Selenium (Se compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia and two non-malignant (lung and mammary epithelial cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase.

  17. 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.

  18. 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

  19. Novel infectious agents causing uveitis.

    Science.gov (United States)

    Khairallah, Moncef; Chee, Soon Phaik; Rathinam, Sivakumar R; Attia, Sonia; Nadella, Venu

    2010-10-01

    In any patient with uveitis, an infectious cause should be ruled out first. The differential diagnosis includes multiple well-known diseases including herpes, syphilis, toxoplasmosis, tuberculosis, bartonellosis, Lyme disease, and others. However, clinician should be aware of emerging infectious agents as potential causes of systemic illness and also intraocular inflammation. Air travel, immigration, and globalization of business have overturned traditional pattern of geographic distribution of infectious diseases, and therefore one should work locally but think globally. This review recapitulates the systemic and ocular manifestations of several emergent infectious diseases relevant to the ophthalmologist including Rickettsioses, West Nile virus infection, Rift valley fever, Dengue fever, and Chikungunya. Retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement have been associated with these emergent infectious diseases. The diagnosis of any of these infections is usually based on pattern of uveitis, systemic symptoms and signs, and specific epidemiological data and confirmed by detection of specific antibody in serum. A systematic ocular examination, showing fairly typical fundus findings, may help establish an early clinical diagnosis, which allows prompt, appropriate management.

  20. 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 ...... roles are supported by a simple and expressive application framework....

  1. Ultrasound contrast agents: An overview

    International Nuclear Information System (INIS)

    Cosgrove, David

    2006-01-01

    With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI < 0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating

  2. Ultrasound contrast agents: an overview.

    Science.gov (United States)

    Cosgrove, David

    2006-12-01

    With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI<0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating

  3. Evolution of hemostatic agents in surgical practice

    Directory of Open Access Journals (Sweden)

    Chandru P Sundaram

    2010-01-01

    Conclusions : A review of the evolution of topical hemostatic agents highlights opportunities for potential novel research. Fibrin sealants may have the most opportunity for advancement, and understanding the history of these products is useful. With the drive in urology for minimally invasive surgical techniques, adaptation of topical hemostatic agents to this surgical approach would be valuable and offers an opportunity for novel contributions.

  4. Computational Intelligence Agent-Oriented Modelling

    Czech Academy of Sciences Publication Activity Database

    Neruda, Roman

    2006-01-01

    Roč. 5, č. 2 (2006), s. 430-433 ISSN 1109-2777 R&D Projects: GA MŠk 1M0567 Institutional research plan: CEZ:AV0Z10300504 Keywords : multi-agent systems * adaptive agents * computational intelligence Subject RIV: IN - Informatics, Computer Science

  5. Agent Based Reasoning in Multilevel Flow Modeling

    DEFF Research Database (Denmark)

    Lind, Morten; Zhang, Xinxin

    2012-01-01

    to launch the MFM Workbench into an agent based environment, which can complement disadvantages of the original software. The agent-based MFM Workbench is centered on a concept called “Blackboard System” and use an event based mechanism to arrange the reasoning tasks. This design will support the new...

  6. Anonymity and Software Agents: An Interdiscplinary Challenge

    NARCIS (Netherlands)

    Brazier, F.M.; Oskamp, A.; Prins, J.M.; Schellekens, M.H.M.; Wijngaards, N.J.E.

    2004-01-01

    Software agents that play a role in E-commerce and E-government applications involving the Internet often contain information about the identity of their human user such as credit cards and bank accounts. This paper discusses whether this is necessary: whether human users and software agents are

  7. Anonymity and Software Agents: An Interdisciplinary Challenge

    NARCIS (Netherlands)

    Oskamp, A.; Brazier, F.M.; Prins, J.E.J.; Schellekens, M.H.M.; Wijngaards, N.J.E.

    2004-01-01

    Software agents that play a role in E-commerce and E-government applications involving the Internet often contain information about the identity of their human user such as credit cards and bank accounts. This paper discusses whether this is necessary: whether human users and software agents are

  8. Dynamics of three-agent games

    International Nuclear Information System (INIS)

    Mungan, Muhittin; Rador, Tonguc

    2008-01-01

    We study the dynamics and resulting score distribution of three-agent games where after each competition a single agent wins and scores a point. A single competition is described by a triplet of numbers p, t and q denoting the probabilities that the team with the highest, middle or lowest accumulated score wins. The three-agent game can be regarded as a social model where a player can be favored or disfavored for advancement, based on his/her accumulated score. We study the full family of solutions in the regime, where the number of agents and competitions is large, which can be regarded as a hydrodynamic limit. Depending on the parameter values (p, q, t), we find six qualitatively different asymptotic score distributions and we provide a qualitative explanation of these results. We also compare our analytical results against numerical simulations of the microscopic model and find these to be in excellent agreement. It is possible to decide the outcome of a three-agent game through a mini-tournament of two-agent competitions among the participating players and it turns out that the resulting possible score distributions are a subset of those obtained for the general three-agent games. We discuss how one can add a steady and democratic decline rate to the model and present a simple geometric construction that allows one to obtain the score evolution equations for n-agent games

  9. On conversational agents with mental states

    NARCIS (Netherlands)

    Bosse, T.; Provoost, S.

    2015-01-01

    Embodied conversational agents (ECAs) have been put forward as a promising means for the training of social skills. The traditional approach to drive the behaviour of ECAs during human-agent dialogues is to use conversation trees. Although this approach is easy to use and very transparent, an

  10. 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

  11. assessment of extension agents' communication methods

    African Journals Online (AJOL)

    USER

    ABSTRACT. The need to improve aquaculture production through enhanced technology transfer necessitated this study to assess extension agents' use of communication methods and its impact on linkage. A structured questionnaire was administered to 44 extension agents who were randomly selected from Lagos State ...

  12. Mansion, A Distributed Multi-Agent System

    NARCIS (Netherlands)

    van t Noordende, G.; Brazier, F.M.; Tanenbaum, A.S.

    2001-01-01

    In this position summary we present work in progress on a worldwide, scalable multi-agent system, based on a paradigm of hyperlinked rooms. The framework offers facilities for managing distribution, security and mobility aspects for both active elements (agents) and passive elements (objects) in the

  13. Some Pitfalls for Developing Enculturated Conversational Agents

    DEFF Research Database (Denmark)

    Rehm, Matthias; André, Elisabeth; Nakano, Yukiko

    2009-01-01

    A review of current agent-based systems exemplifies that a Western perspective is predominant in the field. But as conversational agents focus on rich multimodal interactive behaviors that underlie face-to-face encounters, it is indispensable to incorporate cultural heuristics of such behaviors...

  14. Security of Mobile Agents on the Internet.

    Science.gov (United States)

    Corradi, Antonio; Montanari, Rebecca; Stefanelli, Cesare

    2001-01-01

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

  15. Inhabited interfaces : Attentive conversational agents that help

    NARCIS (Netherlands)

    Nijholt, Antinus; Heylen, Dirk K.J.; Vertegaal, R.P.H.; Sharkey, P.; Cesarani, A.; Pugnetti, L.; Rizzo, A.

    2000-01-01

    We discuss the role of attentive agents in virtual reality interfaces. This discussion is guided by experiences and experiments with a virtual reality environment we designed and implemented. In this environment we have introduced agents, sometimes embodied, with which the users can communicate

  16. Biomonitoring of exposure to chemical warfare agents

    NARCIS (Netherlands)

    Noort, D.; Schans, M.J. van der; Benschop, H.P.

    2006-01-01

    An overview is presented of the major methods that are presently available for biomonitoring of exposure to chemical warfare agents, i.e., nerve agents and sulfur mustard. These methods can be applied for a variety of purposes such as diagnosis and dosimetry of exposure of casualties, verification

  17. Deliberate Evolution in Multi-Agent Systems

    NARCIS (Netherlands)

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

    2001-01-01

    Evolution in societies of agents is a challenging phenomenon, both from a fundamental perspective and from an applied perspective. In the literature often genetic programming approaches are used and relatively simple agents are considered, which have no deliberate influence on the direction of the

  18. AGENT: Awareness Game Environment for Natural Training

    NARCIS (Netherlands)

    Linssen, Johannes Maria; de Groot, Thomas

    We propose AGENT, the Awareness Game Environment for Natural Training, as a virtual environment in which serious games can be enacted. AGENT combines research on interactive storytelling, game design, turn-taking and social signal processing with a multi-modal UI in a modular fashion. Current work

  19. Assurance in Agent-Based Systems

    Energy Technology Data Exchange (ETDEWEB)

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-05-10

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

  20. Assurance in Agent-Based Systems

    International Nuclear Information System (INIS)

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-01-01

    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

  1. Giving advice to agents with hidden goals

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2014-05-01

    Full Text Available on an approximation of the trade-off in utility between potential benefits to the exploring agent and the costs incurred in giving this advice. This model is evaluated on a maze world domain by providing advice to different types of agents, and we show that this leads...

  2. Sanguinarine: A Novel Agent Against Prostate Cancer

    National Research Council Canada - National Science Library

    Ahmad, Nihal

    2005-01-01

    .... Therefore, the search for novel agents and approaches for the treatment of CaP continues. Natural plant-based products have shown promise as anticancer agents. Sanguinarine (13-methyl[ 1,3]benzodioxolo[5,6-c]- 1,3-dioxolo[4,5-i]phenanthridinium...

  3. Marine Natural Products as Prototype Agrochemical Agents

    Science.gov (United States)

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

    2016-01-01

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

  4. 21 CFR 181.28 - Release agents.

    Science.gov (United States)

    2010-04-01

    ... Release agents. Substances classified as release agents, when migrating from food-packaging material shall...). Linoleamide (linoleic acid amide). Oleamide (oleic acid amide). Palmitamide (palmitic acid amide). Stearamide (stearic acid amide). [42 FR 14638, Mar. 15, 1977; 42 FR 56728, Oct. 28, 1977] ...

  5. BOA: A cognitive tactical picture compilation agent

    NARCIS (Netherlands)

    Heuvelink, A.; Both, F.

    2007-01-01

    Simulation-based training in complex decision-making can be made more effective by using intelligent software agents to play key roles, such as teammates, opponents and instructors. This paper presents a cognitive software agent that is capable of compiling a tactical picture in the domain of Naval

  6. Cognitive agent programming : A semantic approach

    NARCIS (Netherlands)

    Riemsdijk, M.B. van

    2006-01-01

    In this thesis we are concerned with the design and investigation of dedicated programming languages for programming agents. We focus in particular on programming languages for rational agents, i.e., flexibly behaving computing entities that are able to make "good" decisions about what to do. An

  7. Mechanisms of bacterial resistance to antimicrobial agents.

    NARCIS (Netherlands)

    van Duijkeren, Engeline; Schink, Anne-Kathrin; Roberts, Marilyn C; Wang, Yang; Schwarz, Stefan

    During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either

  8. Moral conflicts between groups of agents

    NARCIS (Netherlands)

    Kooi, Barteld; Tamminga, A.

    Two groups of agents, G1 and G2, face a *moral conflict* if G1 has a moral obligation and G2 has a moral obligation, such that these obligations cannot both be fulfilled. We study moral conflicts using a multi-agent deontic logic devised to represent reasoning about sentences like 'In the interest

  9. 7 CFR 983.86 - Agents.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 983.86 Section 983.86 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... NEW MEXICO Miscellaneous Provisions § 983.86 Agents. The Secretary may, by a designation in writing...

  10. Econophysics of agent-based models

    CERN Document Server

    Aoyama, Hideaki; Chakrabarti, Bikas; Chakraborti, Anirban; Ghosh, Asim

    2014-01-01

    The primary goal of this book is to present the research findings and conclusions of physicists, economists, mathematicians and financial engineers working in the field of "Econophysics" who have undertaken agent-based modelling, comparison with empirical studies and related investigations. Most standard economic models assume the existence of the representative agent, who is “perfectly rational” and applies the utility maximization principle when taking action. One reason for this is the desire to keep models mathematically tractable: no tools are available to economists for solving non-linear models of heterogeneous adaptive agents without explicit optimization. In contrast, multi-agent models, which originated from statistical physics considerations, allow us to go beyond the prototype theories of traditional economics involving the representative agent. This book is based on the Econophys-Kolkata VII Workshop, at which many such modelling efforts were presented. In the book, leading researchers in the...

  11. Agent-based models of cellular systems.

    Science.gov (United States)

    Cannata, Nicola; Corradini, Flavio; Merelli, Emanuela; Tesei, Luca

    2013-01-01

    Software agents are particularly suitable for engineering models and simulations of cellular systems. In a very natural and intuitive manner, individual software components are therein delegated to reproduce "in silico" the behavior of individual components of alive systems at a given level of resolution. Individuals' actions and interactions among individuals allow complex collective behavior to emerge. In this chapter we first introduce the readers to software agents and multi-agent systems, reviewing the evolution of agent-based modeling of biomolecular systems in the last decade. We then describe the main tools, platforms, and methodologies available for programming societies of agents, possibly profiting also of toolkits that do not require advanced programming skills.

  12. Fault Reconnaissance Agent for Sensor Networks

    Directory of Open Access Journals (Sweden)

    Elhadi M. Shakshuki

    2010-01-01

    Full Text Available One of the key prerequisite for a scalable, effective and efficient sensor network is the utilization of low-cost, low-overhead and high-resilient fault-inference techniques. To this end, we propose an intelligent agent system with a problem solving capability to address the issue of fault inference in sensor network environments. The intelligent agent system is designed and implemented at base-station side. The core of the agent system – problem solver – implements a fault-detection inference engine which harnesses Expectation Maximization (EM algorithm to estimate fault probabilities of sensor nodes. To validate the correctness and effectiveness of the intelligent agent system, a set of experiments in a wireless sensor testbed are conducted. The experimental results show that our intelligent agent system is able to precisely estimate the fault probability of sensor nodes.

  13. Advances on Practical Applications of Agents and Multi-Agent Systems 10th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Müller, Jörg; Rodríguez, Juan; Pérez, Javier

    2012-01-01

    Research on Agents and Multi-Agent Systems has matured during the last decade and many effective applications of this technology are now deployed. PAAMS provides an international forum to present and discuss the latest scientific developments and their effective applications, to assess the impact of the approach, and to facilitate technology transfer. PAAMS started as a local initiative, but has since grown to become THE international yearly platform 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 and deployment of Agents and Multi-Agent Systems. PAAMS intends to bring together researchers and developers from industry and the academic world to report on the latest scientific and technical advances on the application of multi-agent systems, to discuss and debate the major ...

  14. Highlights on Practical Applications of Agents and Multi-Agent Systems 10th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Sánchez, Miguel; Mathieu, Philippe; Rodríguez, Juan; Adam, Emmanuel; Ortega, Alfonso; Moreno, María; Navarro, Elena; Hirsch, Benjamin; Lopes-Cardoso, Henrique; Julián, Vicente

    2012-01-01

    Research on Agents and Multi-Agent Systems has matured during the last decade and many effective applications of this technology are now deployed. PAAMS provides an international forum to present and discuss the latest scientific developments and their effective applications, to assess the impact of the approach, and to facilitate technology transfer. PAAMS started as a local initiative, but has since grown to become THE international yearly platform 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 and deployment of Agents and Multi-Agent Systems. PAAMS intends to bring together researchers and developers from industry and the academic world to report on the latest scientific and technical advances on the application of multi-agent systems, to discuss and debate the major ...

  15. In vitro testing of plaque control agents.

    Science.gov (United States)

    Coburn, R A

    1979-12-01

    The development of a number of in vitro techniques for the evaluation of antiplaque effects of test agents has followed the characterization and culturing of plaque-forming microorganisms. Studies of the mechanism of action of chlorhexidine and clinical observations have assisted in defining critical aspects of these in vitro techniques. Such assays may play an increasingly important role in screening potential new agents as well as in the optimization of properties by chemical modification of new lead agents. In addition, data generated in the in vitro assay may assist the design of in vivo evaluations of new agents. Proper selection of in vitro techniques for these various functions in the pre-clinical development process may reduce the time and cost involved in the development of new antiplaque agents.

  16. Biological agents in polyarticular juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Amarilyo, Gil; Tarp, Simon; Foeldvari, Ivan

    2016-01-01

    (nearly all exceptions were in agreement with the original study data). Serious AEs occurred very infrequently (0-8%) and an analysis was not possible. There were no differences for AEs when compared among biological agents or to placebo. CONCLUSION: There were no statistical differences among biological......BACKGROUND AND OBJECTIVE: Although various biological agents are in use for polyarticular juvenile idiopathic arthritis (pJIA), head-to-head trials comparing the efficacy and safety among them are lacking. We aimed to compare the efficacy and safety of biological agents in pJIA using all currently...... available randomized withdrawal trials (wRCTs). METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov was performed. Eligible wRCTs: patients with pJIA where a biological agent was compared with another biological agent or placebo. Efficacy was evaluated using disease flare...

  17. CEST and PARACEST MR contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Hancu, Ileana; Dixon, W. Thomas (GE Global Research Center, Niskayuna, NY (United States)); Woods, Mark; Sherry, A. Dean (Univ. of Texas at Dallas, Dallas, TX (United States)); Vinogradov, Elena; Lenkinski, Robert E. (Beth Israel Deaconess Medical Center, Boston, MA (United States)), e-mail: rlenkins@bidmc.harvard.edu

    2010-10-15

    In this review we describe the status of development for a new class of magnetic resonance (MR) contrast agents, based on chemical exchange saturation transfer (CEST). The mathematics and physics relevant to the description of the CEST effect in MR are presented in an appendix published in the online version only. We discuss the issues arising when translating in vitro results obtained with CEST agents to using these MR agents in in vivo model studies and in humans. Examples are given on how these agents are imaged in vivo. We summarize the status of development of these CEST agents, and speculate about the next steps that may be taken towards the demonstration of CEST MR imaging in clinical applications

  18. The agent-relative/agent-neutral distinction: my two sense(s) | Lerm ...

    African Journals Online (AJOL)

    -relative in the dependence sense but agent-neutral in the homogeneous sense, and – perhaps surprisingly – of Utilitarianism, according to which reasons are agent-neutral in the independence sense but agent-relative in the heterogeneous ...

  19. Human-agent experience sharing : Creating social agents for elderly people with dementia

    NARCIS (Netherlands)

    Peeters, M.M.M.; Neerincx, M.A.

    2016-01-01

    As intelligent technology steadily becomes a part of modern societies, people collaborate with agents more frequently, and so agents need to be socially intelligent, i.e. personalised and context-sensitive. This paper introduces a context-sensitive personalisation framework for social agents that

  20. 9th KES Conference on Agent and Multi-Agent Systems : Technologies and Applications

    CERN Document Server

    Howlett, Robert; Jain, Lakhmi

    2015-01-01

    Agents and multi-agent systems are related to a modern software paradigm which has long been recognized as a promising technology for constructing autonomous, complex and intelligent systems. The topics covered in this volume include agent-oriented software engineering, agent co-operation, co-ordination, negotiation, organization and communication, distributed problem solving, specification of agent communication languages, agent privacy, safety and security, formalization of ontologies and conversational agents. The volume highlights new trends and challenges in agent and multi-agent research and includes 38 papers classified in the following specific topics: learning paradigms, agent-based modeling and simulation, business model innovation and disruptive technologies, anthropic-oriented computing, serious games and business intelligence, design and implementation of intelligent agents and multi-agent systems, digital economy, and advances in networked virtual enterprises. Published p...

  1. For whom will the Bayesian agents vote?

    Science.gov (United States)

    Caticha, Nestor; Cesar, Jonatas; Vicente, Renato

    2015-04-01

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

  2. For whom will the Bayesian agents vote?

    Directory of Open Access Journals (Sweden)

    Nestor eCaticha

    2015-04-01

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

  3. Multi-Agent Systems for E-Commerce

    OpenAIRE

    Solodukha, T. V.; Sosnovskiy, O. A.; Zhelezko, B. A.

    2009-01-01

    The article focuses on multi-agent systems (MAS) and domains that can benefit from multi-agent technology. In the last few years, the agent based modeling (ABM) community has developed several practical agent based modeling toolkits that enable individuals to develop agent-based applications. The comparison of agent-based modeling toolkits is given. Multi-agent systems are designed to handle changing and dynamic business processes. Any organization with complex and distributed busine...

  4. Chemical Warfare Agent Decontaminant Solution Using Quaternary Ammonium Complexes

    Science.gov (United States)

    1997-12-11

    warfare agents, which include a variety of organophosphorus and organosulfur compounds, are known in the art. 15 However, these known methods use...chemical warfare agents, and works particularly well for neutralization of organosulfur agents such as mustard gas (HD), and organophosphorus agents such...detoxifying/neutralizing a variety of chemical warfare agents, including organosulfur agents such as mustard gas (HD), and organophosphorus agents such as

  5. Traitement de l'hétérogénéité sémantique dans les interactions humain-agent et agent-agent

    OpenAIRE

    Mazuel , Laurent

    2008-01-01

    The main purpose of this thesis is the management of semantic heterogeneity in human-agent and agent-agent interaction. We especially focus on the situation where a software agent, supplied with a knowledge representation model, has to understand requests coming from different interlocutors; either it is a human user or another software agent.Most work in this domain either focus on human-agent interaction or agent-agent interaction. On the contrary, we suggest that it is possible to use a co...

  6. Human butyrylcholinesterase efficacy against nerve agent exposure.

    Science.gov (United States)

    Reed, Beth A; Sabourin, Carol L; Lenz, David E

    2017-05-01

    Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems. HuBChE was effective when used as both a pre-treatment and as a post-exposure therapy. HuBChE has potential for use in both military settings and to protect civilian first responders in situations where nerve agent usage is suspected. We reviewed various animal models studies evaluating the efficacy of HuBChE against nerve agent exposure, pursuant to its submission for approval under the FDA Animal Rule. © 2017 Wiley Periodicals, Inc.

  7. Persistent agents in Axelrod's social dynamics model

    Science.gov (United States)

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

    2016-01-01

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

  8. Agent-Supported Mission Operations Teamwork

    Science.gov (United States)

    Malin, Jane T.

    2003-01-01

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

  9. Continuum deformation of multi-agent systems

    CERN Document Server

    Rastgoftar, Hossein

    2016-01-01

    This monograph presents new algorithms for formation control of multi-agent systems (MAS) based on principles of continuum mechanics. Beginning with an overview of traditional methods, the author then introduces an innovative new approach whereby agents of an MAS are considered as particles in a continuum evolving in ℝn whose desired configuration is required to satisfy an admissible deformation function. The necessary theory and its validation on a mobile-agent-based swarm test bed are considered for two primary tasks: homogeneous transformation of the MAS and deployment of a random distribution of agents on a desired configuration. The framework for this model is based on homogeneous transformations for the evolution of an MAS under no inter-agent communication, local inter-agent communication, and intelligent perception by agents. Different communication protocols for MAS evolution, the robustness of tracking of a desired motion by an MAS evolving in ℝn, and the effect of communication delays in an MAS...

  10. Relay tracking control for second-order multi-agent systems with damaged agents.

    Science.gov (United States)

    Dong, Lijing; Li, Jing; Liu, Qin

    2017-11-01

    This paper investigates a situation where smart agents capable of sensory and mobility are deployed to monitor a designated area. A preset number of agents start tracking when a target intrudes this area. Some of the tracking agents are possible to be out of order over the tracking course. Thus, we propose a cooperative relay tracking strategy to ensure the successful tracking with existence of damaged agents. Relay means that, when a tracking agent quits tracking due to malfunction, one of the near deployed agents replaces it to continue the tracking task. This results in jump of tracking errors and dynamic switching of topology of the multi-agent system. Switched system technique is employed to solve this specific problem. Finally, the effectiveness of proposed tracking strategy and validity of the theoretical results are verified by conducting a numerical simulation. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Agent and multi-Agent systems in distributed systems digital economy and e-commerce

    CERN Document Server

    Hartung, Ronald

    2013-01-01

    Information and communication technology, in particular artificial intelligence, can be used to support economy and commerce using digital means. This book is about agents and multi-agent distributed systems applied to digital economy and e-commerce to meet, improve, and overcome challenges in the digital economy and e-commerce sphere. Agent and multi-agent solutions are applied in implementing real-life, exciting developments associated with the need to eliminate problems of distributed systems.   The book presents solutions for both technology and applications, illustrating the possible uses of agents in the enterprise domain, covering design and analytic methods, needed to provide a solid foundation required for practical systems. More specifically, the book provides solutions for the digital economy, e-sourcing clusters in network economy, and knowledge exchange between agents applicable to online trading agents, and security solutions to both digital economy and e-commerce. Furthermore, it offers soluti...

  12. Multi-Agent Pathfinding with n Agents on Graphs with n Vertices

    DEFF Research Database (Denmark)

    Förster, Klaus-Tycho; Groner, Linus; Hoefler, Torsten

    2017-01-01

    We investigate the multi-agent pathfinding (MAPF) problem with $n$ agents on graphs with $n$ vertices: Each agent has a unique start and goal vertex, with the objective of moving all agents in parallel movements to their goal s.t.~each vertex and each edge may only be used by one agent at a time....... We give a combinatorial classification of all graphs where this problem is solvable in general, including cases where the solvability depends on the initial agent placement. Furthermore, we present an algorithm solving the MAPF problem in our setting, requiring O(n²) rounds, or O(n³) moves...... of individual agents. Complementing these results, we show that there are graphs where Omega(n²) rounds and Omega(n³) moves are required for any algorithm....

  13. Cytotoxic and anti-HIV activities of some Tanzanian Garcinia species

    African Journals Online (AJOL)

    Among the tested extracts, the fruit extracts of G. livingstoneii and G. semseii showed moderate to mild cytotoxic activities against A549, DU145, KB and Kbivin human cell lines with 50 % cytotoxic (CC50) values ranging from 5.7-20.0 µg/ml. Furthermore, only fruit extracts of G. livingstonei and G. semseii showed significant ...

  14. A Multi-targeted Drug Candidate with Dual Anti-HIV and Anti-HSV Activity

    Czech Academy of Sciences Publication Activity Database

    Balzarini, J.; Andrei, G.; Balestra, E.; Huskens, D.; Vanpouille, C.; Introini, A.; Zicari, S.; Liekens, S.; Snoeck, R.; Holý, Antonín; Perno, C. F.; Margolis, L.; Schols, D.

    2013-01-01

    Roč. 9, č. 7 (2013), e1003456 E-ISSN 1553-7374 Institutional support: RVO:61388963 Keywords : herpes simplex virus * phosphonylmethoxyalkyl derivatives * nucleoside phosphonates * antiviral activity Subject RIV: EE - Microbiology, Virology Impact factor: 8.057, year: 2013 http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003456

  15. Anti-HIV Effect of Liposomes Bearing CXCR4 Receptor Antagonist ...

    African Journals Online (AJOL)

    Human PBMCs were separated from whole blood by centrifugation using Ficoll density gradient centrifugation. Lymphocyte separation medium was purchased from Sigma (USA). The recombinant human chemokine SDF-1a was lyophilized and dissolved as 1 or 2.5 μg/μL stock solutions in sterile phosphate-buffered saline.

  16. 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 ...

  17. Anti-HIV-1 activity of anionic polymers: a comparative study of candidate microbicides

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2002-11-01

    Full Text Available Abstract Background Cellulose acetate phthalate (CAP in soluble form blocks coreceptor binding sites on the virus envelope glycoprotein gp120 and elicits gp41 six-helix bundle formation, processes involved in virus inactivation. CAP is not soluble at pH Methods Enzyme linked immunosorbent assays (ELISA were used to (1 study HIV-1 IIIB and BaL binding to micronized CAP; (2 detect virus disintegration; and (3 measure gp41 six-helix bundle formation. Cells containing integrated HIV-1 LTR linked to the β-gal gene and expressing CD4 and coreceptors CXCR4 or CCR5 were used to measure virus infectivity. Results 1 HIV-1 IIIB and BaL, respectively, effectively bound to micronized CAP. 2 The interaction between HIV-1 and micronized CAP led to: (a gp41 six-helix bundle formation; (b virus disintegration and shedding of envelope glycoproteins; and (c rapid loss of infectivity. Polymers other than CAP, except Carbomer 974P, elicited gp41 six-helix bundle formation in HIV-1 IIIB but only poly(napthalene sulfonate, in addition to CAP, had this effect on HIV-1 BaL. These polymers differed with respect to their virucidal activities, the differences being more pronounced for HIV-1 BaL. Conclusions Micronized CAP is the only candidate topical microbicide with the capacity to remove rapidly by adsorption from physiological fluids HIV-1 of both the X4 and R5 biotypes and is likely to prevent virus contact with target cells. The interaction between micronized CAP and HIV-1 leads to rapid virus inactivation. Among other anionic polymers, cellulose sulfate, BufferGel and aryl sulfonates appear most effective in this respect.

  18. 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.

  19. 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.

  20. A Survey of Plants with Anti-HIV Active Compounds and their Modes ...

    African Journals Online (AJOL)

    Administrator

    jacalin-related lectin that binds to glycosylated viral envelopes blocked HIV-1 entry into cells , and. Phytolacca americana pokeweed antiviral protein (PAP), a 29 KDa ribosome-inactivating protein that. 46 removes adenine from rRNA was found to be a potent microbicide . Table 1: Plants with active compounds and modes ...