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Sample records for antineoplastic agents phytogenic

  1. Occupational rhinosinusitis due to etoposide, an antineoplastic agent

    DEFF Research Database (Denmark)

    Meyer, Harald W; Skov, Per Stahl

    2010-01-01

    This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent.......This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent....

  2. Infiltrative Lung Diseases: Complications of Novel Antineoplastic Agents in Patients with Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Bobbak Vahid

    2008-01-01

    Full Text Available Infiltrative lung disease is a well-known complication of antineoplastic agents in patients with hematological malignancies. Novel agents are constantly being added to available treatments. The present review discusses different pulmonary syndromes, pathogenesis and management of these novel agents.

  3. Clinical effect of Cystenosine on leukocytopenia at the time of therapy with radiation and antineoplastic agents

    International Nuclear Information System (INIS)

    Sato, Kazuhide; Usui, Ryu; Inoue, Hiroshi; Mihashi, Norio; Niibe, Hideo.

    1977-01-01

    Out of 62 cases, 25 cases received only radiotherapy, 11 cases received both radiotherapy and antineoplastic agents, and 26 cases received only antineoplastic agents. Total dose of x-ray ranges from 3000 to 6200 rad in 18 of 36 cases of the former two groups, and 2600 to 6260 rad of 60 Co dose were irradiated to 18 cases of the rest. This agent was administered 9 tablets per a day (one tablet contains 200 mg of inosine and 20 mg of cystine) for 19 to 142 days. Its effects on leukocytopenia showed marked effectiveness in 9 out of 25 cases treated with only radiation, effectiveness in 8 cases, and ineffectiveness in 3 cases. Its effective rate was 72.8%. The effective rate was 65.4% in the cases treated with only antineoplastic agents, and was 67.7% in all cases. A certain relationship between dose and the effective rate was not recognized. Radiation sickness, such as loss of appetite general fatigue and mausea, decreased gradually by using this agent. Side effect was not recognized particularly. (Kanao. N.)

  4. QSPR modeling of octanol/water partition coefficient of antineoplastic agents by balance of correlations.

    Science.gov (United States)

    Toropov, Andrey A; Toropova, Alla P; Raska, Ivan; Benfenati, Emilio

    2010-04-01

    Three different splits into the subtraining set (n = 22), the set of calibration (n = 21), and the test set (n = 12) of 55 antineoplastic agents have been examined. By the correlation balance of SMILES-based optimal descriptors quite satisfactory models for the octanol/water partition coefficient have been obtained on all three splits. The correlation balance is the optimization of a one-variable model with a target function that provides both the maximal values of the correlation coefficient for the subtraining and calibration set and the minimum of the difference between the above-mentioned correlation coefficients. Thus, the calibration set is a preliminary test set. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  5. Kinetics of micronucleus induction and cytotoxicity caused by distinct antineoplastics and alkylating agents in vivo.

    Science.gov (United States)

    Morales-Ramírez, Pedro; Vallarino-Kelly, Teresita; Cruz-Vallejo, Virginia

    2014-01-30

    This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  7. The emerging role of antineoplastic agents in the treatment of keloids and hypertrophic scars: a review.

    Science.gov (United States)

    Shridharani, Sachin M; Magarakis, Michael; Manson, Paul N; Singh, Navin K; Basdag, Basak; Rosson, Gedge D

    2010-03-01

    The management of keloids and hypertrophic scars continues to challenge health-care providers. Though both forms of pathologic scarring are distinct entities at the macro and microscopic level, their etiologies and treatment are often similar. Potential treatment approaches are progressing, and combinations of treatment options have been proposed in the literature with promising outcomes. The treatment evolution has reached a level where molecular therapeutic modalities are being investigated. Currently, no gold standard treatment exists. Overall success rates and patient satisfaction seem to be slowly climbing, but additional investigational studies must continue to be performed. Several studies have investigated antineoplastic agents, and there seems to be a marked improvement in rates of recurrence, patient satisfaction, and overall quality of scar when these agents are used. Intralesional injection and/or wound irrigation with interferon-a2b, interferon-g, mitomycin-C, bleomycin, or 5-fluorouracil seems to have a positive effect on the reduction of pathologic scars. There is mounting evidence that these drugs used alone or in combination therapy, have the potential to be an integral part of the treatment paradigm for hypertrophic scars and keloids.

  8. Effect of corticosteroids on phlebitis induced by intravenous infusion of antineoplastic agents in rabbits.

    Science.gov (United States)

    Kohno, Emiko; Murase, Saori; Matsuyama, Kenji; Okamura, Noboru

    2009-08-06

    Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL. VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL. The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked. The present findings suggested that pre-treatment with DEX may be a useful method for preventing

  9. Oral antineoplastic agent interactions with medicinal plants and food: an issue to take into account.

    Science.gov (United States)

    Collado-Borrell, Roberto; Escudero-Vilaplana, Vicente; Romero-Jiménez, Rosa; Iglesias-Peinado, Irene; Herranz-Alonso, Ana; Sanjurjo-Sáez, María

    2016-11-01

    To review interactions between oral antineoplastic agents (OAAs) for the treatment of solid and hematological tumors and common food and medicinal plants. All potential interactions between OAAs, medicinal plants and food were reviewed. OAAs were considered to be drugs for oral administration that have direct antitumor activity and were approved by the European Medicines Agency in April 2015. We performed the literature search in Pubmed(®) considering only medicinal plants and food. In addition, available data were analyzed from each OAA in secondary data sources taken from Thomson Micromedex(®) and Lexi-comp(®), as well as in the summary of product characteristics. Fifty-eight OAAs were analyzed. We found interactions in 60.3 % of OAAs. Those with most interactions described were: imatinib and procarbazine (4 interactions) and erlotinib, vemurafenib, pomalidomide, medroxyprogesterone and methotrexate (3 interactions). We found 39 interactions (74.4 % important). St. John's wort was the medicinal plant with most interactions (92.6 % were considered important). The rest were: important (ginseng-imatinib, methotrexate-cola and tobacco-erlotinib and tobacco-pomalidomide) and moderate (caffeine-vemurafenib/medroxyprogesterone, medroxyprogesterone-ruxolitinib/St. John's wort, garlic-anagrelide and ginseng-procarbazine). Twenty-six interactions (61.5 % important). Grapefruit had most interactions (82.4 % were considered important). The rest were: important (alcohol-procarbazine) and moderate (dairy-estramustine, methotrexate-ethanol, procarbazine-tyramine, vitamin A-tretinoin/bexarotene and grapefruit-bexarotene/etoposide/sunitinib). A review of interactions of medicinal plants and food should be taken into account in the management of OAAs, since more than half have interactions with MPs and food, of which 70.3 % are considered important. The most relevant are HSJ, grapefruit, ginseng and tobacco. This review is intended to serve as a support to all healthcare

  10. Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

    Science.gov (United States)

    Madrigal-Burgaleta, R; Berges-Gimeno, M P; Angel-Pereira, D; Ferreiro-Monteagudo, R; Guillen-Ponce, C; Pueyo, C; Gomez de Salazar, E; Alvarez-Cuesta, E

    2013-07-01

    Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization.

    Science.gov (United States)

    Alvarez-Cuesta, E; Madrigal-Burgaleta, R; Angel-Pereira, D; Ureña-Tavera, A; Zamora-Verduga, M; Lopez-Gonzalez, P; Berges-Gimeno, M P

    2015-07-01

    Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization). Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables. A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5. These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans. © 2015 John Wiley & Sons A/S. Published by

  12. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    International Nuclear Information System (INIS)

    Price, Paul S.; Keenan, Russell E.; Swartout, Jeffrey C.

    2008-01-01

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals

  13. Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

    Science.gov (United States)

    Alehashem, Maryam; Baniasadi, Shadi

    2018-01-01

    A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

  14. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  15. Accelerator mass spectrometry analysis of 14C-oxaliplatin concentrations in biological samples and 14C contents in biological samples and antineoplastic agents

    Science.gov (United States)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-10-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the 14C concentration in 14C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) - AMS system. The calibration curves of 14C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a 14C content of water in three vacuum blood collection tubes and a syringe were measured. 14C was not detected from water in these devices. The mean 14C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of 14C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, 14C contents of the antineoplastic agents were quantitated. 14C contents were different among 10 antineoplastic agents; 14C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  16. Accelerator mass spectrometry analysis of "1"4C-oxaliplatin concentrations in biological samples and "1"4C contents in biological samples and antineoplastic agents

    International Nuclear Information System (INIS)

    Toyoguchi, Teiko; Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi; Kato, Kazuhiro; Tokanai, Fuyuki

    2015-01-01

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the "1"4C concentration in "1"4C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of "1"4C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a "1"4C content of water in three vacuum blood collection tubes and a syringe were measured. "1"4C was not detected from water in these devices. The mean "1"4C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of "1"4C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, "1"4C contents of the antineoplastic agents were quantitated. "1"4C contents were different among 10 antineoplastic agents; "1"4C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  17. Accelerator mass spectrometry analysis of {sup 14}C-oxaliplatin concentrations in biological samples and {sup 14}C contents in biological samples and antineoplastic agents

    Energy Technology Data Exchange (ETDEWEB)

    Toyoguchi, Teiko, E-mail: tteiko@med.id.yamagata-u.ac.jp [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kobayashi, Takeshi; Konno, Noboru; Shiraishi, Tadashi [Department of Pharmacy, Yamagata University Hospital, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata 990-9585 (Japan); Kato, Kazuhiro; Tokanai, Fuyuki [Department of Physics, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa-machi, Yamagata-shi, Yamagata 990-8560 (Japan)

    2015-10-15

    Accelerator mass spectrometry (AMS) is expected to play an important role in microdose trials. In this study, we measured the {sup 14}C concentration in {sup 14}C-oxaliplatin-spiked serum, urine and supernatant of fecal homogenate samples in our Yamagata University (YU) – AMS system. The calibration curves of {sup 14}C concentration in serum, urine and supernatant of fecal homogenate were linear (the correlation coefficients were ⩾0.9893), and the precision and accuracy was within the acceptance criteria. To examine a {sup 14}C content of water in three vacuum blood collection tubes and a syringe were measured. {sup 14}C was not detected from water in these devices. The mean {sup 14}C content in urine samples of 6 healthy Japanese volunteers was 0.144 dpm/mL, and the intra-day fluctuation of {sup 14}C content in urine from a volunteer was little. The antineoplastic agents are administered to the patients in combination. Then, {sup 14}C contents of the antineoplastic agents were quantitated. {sup 14}C contents were different among 10 antineoplastic agents; {sup 14}C contents of paclitaxel injection and docetaxel hydrate injection were higher than those of the other injections. These results indicate that our quantitation method using YU-AMS system is suited for microdosing studies and that measurement of baseline and co-administered drugs might be necessary for the studies in low concentrations.

  18. Curcumin: An age-old anti-inflammatory and anti-neoplastic agent

    Directory of Open Access Journals (Sweden)

    Matthew C. Fadus

    2017-07-01

    Full Text Available Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to systematically analyze the wealth of information regarding the medical use of curcumin, the “curry spice”, and to understand the existent gaps which have prevented its widespread application in the medical community.

  19. Effects of antineoplastic agents and ionizing irradiation on a human testicular cancer xenograft

    International Nuclear Information System (INIS)

    Osieka, R.; Pfeiffer, R.; Glatte, P.; Schmidt, C.G.; Bamberg, M.; Scherer, E.

    1985-01-01

    Chemotherapy has afforded a high percentage of definitive cures in advanced testicular cancer. Nevertheless some patients with large tumor burden still succumb to chemorefractory disease. Therefore preclinical and clinical evaluation of new drugs and agents not primarily used against this type of disease are still mandatory. For preclinical drug screening purposes heterotransplantation of specific human tumors yields a model with high validity for tumor markers and drug response. Heterotransplantation of a human embryonal testicular cancer was used for simultaneous testing of established agents such as cisplatin, melphalan, bleomycin, vinblastine, etoposide and adriamycin and some newer derivatives such as PHM or mafosfamide. Furthermore agents such as procarbazine, dacarbazine and methyl-CCNU that cross the blood-brain-barrier displayed some interesting activity. The results hint at a unique chemosensitivity pattern of the xenograft line, with some accordance between clinical response to vinblastine and bleomycin and good response of the xenografts to bleomycin but not to vinblastine. Radiotherapy was also effective against this tumor line, but there was not much difference in response when the schedule of fractionation was changed. It is concluded that a combined modality approach might salvage patients with residual, chemorefractory disease. (orig.) [de

  20. The antineoplastic agent α-bisabolol promotes cell death by inducing pores in mitochondria and lysosomes.

    Science.gov (United States)

    Rigo, Antonella; Vinante, Fabrizio

    2016-08-01

    The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis. The study focuses on the relevant steps in the cytotoxic cascade triggered by α-BSB: (1) the lipid rafts through which α-BSB enters the cells, (2) the opening of pores in the mitochondria and lysosomes, (3) the activation of both caspase-dependent and caspase-independent cell death pathways, (4) the induction of autophagy and (5) apoptosis. The effectiveness of α-BSB as an agent against tumor cells is grounded on its capability to act on different layers of cell regulation to elicit different concurrent death signals, thereby neutralizing a variety of aberrant survival mechanisms leading to treatment resistance in neoplastic cell.

  1. A rationale for the use of proton pump inhibitors as antineoplastic agents.

    Science.gov (United States)

    De Milito, Angelo; Marino, Maria Lucia; Fais, Stefano

    2012-01-01

    It is becoming increasingly acknowledged that tumorigenesis is not simply characterized by the accumulation of rapidly proliferating, genetically mutated cells. Microenvironmental biophysical factors like hypoxia and acidity dramatically condition cancer cells and act as selective forces for malignant cells, adapting through metabolic reprogramming towards aerobic glycolysis. Avoiding intracellular accumulation of lactic acid and protons, otherwise detrimental to cell survival is crucial for malignant cells to maintain cellular pH homeostasis. As a consequence of the upregulated expression and/or function of several pH-regulating systems, cancer cells display an alkaline intracellular pH (pHi) and an acidic extracellular pH (pHe). Among the pH-regulating proteins, proton pumps play an important role in both drug-resistance and metastatic spread, thus representing a suitable therapeutic target. Proton pump inhibitors (PPI) have been reported as cytotoxic drugs active against several human tumor cells and preclinical data have prompted the investigation of PPI as anticancer agents in humans. This review will update the current knowledge on the antitumor activities of PPI and their potential applications.

  2. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    Science.gov (United States)

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment.

  3. Inhibition of RecBCD enzyme by antineoplastic DNA alkylating agents.

    Science.gov (United States)

    Dziegielewska, Barbara; Beerman, Terry A; Bianco, Piero R

    2006-09-01

    To understand how bulky adducts might perturb DNA helicase function, three distinct DNA-binding agents were used to determine the effects of DNA alkylation on a DNA helicase. Adozelesin, ecteinascidin 743 (Et743) and hedamycin each possess unique structures and sequence selectivity. They bind to double-stranded DNA and alkylate one strand of the duplex in cis, adding adducts that alter the structure of DNA significantly. The results show that Et743 was the most potent inhibitor of DNA unwinding, followed by adozelesin and hedamycin. Et743 significantly inhibited unwinding, enhanced degradation of DNA, and completely eliminated the ability of the translocating RecBCD enzyme to recognize and respond to the recombination hotspot chi. Unwinding of adozelesin-modified DNA was accompanied by the appearance of unwinding intermediates, consistent with enzyme entrapment or stalling. Further, adozelesin also induced "apparent" chi fragment formation. The combination of enzyme sequestering and pseudo-chi modification of RecBCD, results in biphasic time-courses of DNA unwinding. Hedamycin also reduced RecBCD activity, albeit at increased concentrations of drug relative to either adozelesin or Et743. Remarkably, the hedamycin modification resulted in constitutive activation of the bottom-strand nuclease activity of the enzyme, while leaving the ability of the translocating enzyme to recognize and respond to chi largely intact. Finally, the results show that DNA alkylation does not significantly perturb the allosteric interaction that activates the enzyme for ATP hydrolysis, as the efficiency of ATP utilization for DNA unwinding is affected only marginally. These results taken together present a unique response of RecBCD enzyme to bulky DNA adducts. We correlate these effects with the recently determined crystal structure of the RecBCD holoenzyme bound to DNA.

  4. Evaluation of real-time data obtained from gravimetric preparation of antineoplastic agents shows medication errors with possible critical therapeutic impact: Results of a large-scale, multicentre, multinational, retrospective study.

    Science.gov (United States)

    Terkola, R; Czejka, M; Bérubé, J

    2017-08-01

    Medication errors are a significant cause of morbidity and mortality especially with antineoplastic drugs, owing to their narrow therapeutic index. Gravimetric workflow software systems have the potential to reduce volumetric errors during intravenous antineoplastic drug preparation which may occur when verification is reliant on visual inspection. Our aim was to detect medication errors with possible critical therapeutic impact as determined by the rate of prevented medication errors in chemotherapy compounding after implementation of gravimetric measurement. A large-scale, retrospective analysis of data was carried out, related to medication errors identified during preparation of antineoplastic drugs in 10 pharmacy services ("centres") in five European countries following the introduction of an intravenous workflow software gravimetric system. Errors were defined as errors in dose volumes outside tolerance levels, identified during weighing stages of preparation of chemotherapy solutions which would not otherwise have been detected by conventional visual inspection. The gravimetric system detected that 7.89% of the 759 060 doses of antineoplastic drugs prepared at participating centres between July 2011 and October 2015 had error levels outside the accepted tolerance range set by individual centres, and prevented these doses from reaching patients. The proportion of antineoplastic preparations with deviations >10% ranged from 0.49% to 5.04% across sites, with a mean of 2.25%. The proportion of preparations with deviations >20% ranged from 0.21% to 1.27% across sites, with a mean of 0.71%. There was considerable variation in error levels for different antineoplastic agents. Introduction of a gravimetric preparation system for antineoplastic agents detected and prevented dosing errors which would not have been recognized with traditional methods and could have resulted in toxicity or suboptimal therapeutic outcomes for patients undergoing anticancer treatment.

  5. Effect of alpha-interferon alone and combined with other antineoplastic agents on renal cell carcinoma determined by the tetrazolium microculture assay.

    Science.gov (United States)

    Homma, Y; Aso, Y

    1994-01-01

    The antiproliferative effect of various alpha-interferons (alpha-IFNs), alone or combined with other agents, on a renal cell carcinoma cell line was evaluated by the tetrazolium microculture assay to examine the rationale for combination therapies. Cells incubated in 96-week microculture plates at 5 x 10(3)/well were exposed to various agents for 3 days. There were no obvious differences in the growth inhibition caused by the 5 kinds of alpha-IFN examined as single agents. The combination of alpha-IFN with the following agents was also assessed: 5-fluorouracil (5FU), methotrexate (MTX), mitomycin C, bleomycin, cis-diaminedichloroplatinum (CDDP), vinblastine, etoposide (ETOP), alpha-IFN, tumor necrosis factor-alpha (TNF), and alpha-difluoromethylornithine. Synergism was observed for the combination of alpha-IFN+TNF, while the other combinations had additive or subadditive effects. No interference or antagonism was found. Trimodal combinations of alpha-IFN+MTX with either 5FU, ETOP, or CDDP all showed subadditive effects. These results indicated that an increased antiproliferative effect, although not necessarily synergistic, was obtained by the combination of alpha-IFN with a variety of antineoplastic agents, providing a rationale to seek for combination therapies including alpha-IFN for treating renal cell carcinoma.

  6. Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

    Czech Academy of Sciences Publication Activity Database

    Weber, T.; Lu, M.; Anděra, Ladislav; Lahm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, A.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neuzil, J.

    2002-01-01

    Roč. 8, - (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA ČR GA312/99/0348 Institutional research plan: CEZ:AV0Z5052915 Keywords : Vitamin E, Antineoplastic Agent, Tumor Necrosis Factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

  7. Prevention of disease progression in a patient with a gastric cancer-re-recurrence. Outcome after intravenous treatment with the novel antineoplastic agent taurolidine. Report of a case

    Directory of Open Access Journals (Sweden)

    Menenakos Charalambos

    2006-06-01

    Full Text Available Abstract Background Taurolidine (TRD is a novel agent with multimodal antineoplastic effects. We present the case of a tumor remission after intravenous administration of taurolidine in a patient with gastric cancer re-recurrence. Case presentation A 58 years old male patient suffering from a gastric adenocarcinoma was submitted to partial gastrectomy and partial liver resection (pT2, pN1, pM1L (liver segment 2, N0, V0. 24 months later a local recurrence was diagnosed and the patient was reoperated. Postoperatively the patient underwent a palliative chemotherapy with eloxatin, FU, and leucovorin. A subsequent CT-revealed a liver metastasis and a recurrence adjacent to the hepatic artery. After successful radiofrequency ablation of the liver metastasis the patient was intravenously treated with 2% taurolidine. The patient endured the therapy well and no toxicity was observed. CT-scans revealed a stable disease without a tumor progression or metastatic spread. After 39 cycles the patient was submitted to left nephrectomy due to primary urothelial carcinoma and died 2 days later due to myocardial infarction. Postmortem histology of the esophageal-jejunal anastomosis and liver revealed complete remission of the known metastasized gastric adenocarcinoma. Conclusion The intravenous treatment with 2% taurolidine led to a histological remission of the tumor growth without any toxicity for the patient.

  8. Bringing Radiotracing to Titanium-Based Antineoplastics: Solid Phase Radiosynthesis, PET and ex Vivo Evaluation of Antitumor Agent [45Ti](salan)Ti(dipic)

    DEFF Research Database (Denmark)

    Severin, Gregory; Nielsen, Carsten H.; Jensen, Andreas Tue Ingemann

    2015-01-01

    We present a novel solid-phase based 45Ti radiolabeling methodology and the implementation of 45Ti-PET in titanium-based antineoplastics using the showcase compound [45Ti](salan)Ti(dipic). This development is intended to allow elucidation of the biodistribution and pharmacokinetics of promising new...

  9. Effects of arginine and phytogenic additive supplementation on performance and health of brown-egg layers

    Directory of Open Access Journals (Sweden)

    Vitor Barbosa Fascina

    Full Text Available ABSTRACT This study was performed to evaluate the effects of the association of different digestible arginine and phytogenic additive dietary levels on performance and health status of brown-egg layers. In this study, a total of 504 33-week-old Hisex Brown layers were distributed into a completely randomized experimental design to a 4 × 3 factorial arrangement (dietary digestible arginine levels: 880, 968, 1056, or 1144 mg/kg of feed × phytogenic additive levels: 0, 100, and 200 mg/kg of feed with six replicate cages of seven birds per cage. The phytogenic additive was composed of extracts of Baccharis dracunculifolia (40%, Astragalus membranaceus lipopolysaccharides (20%, cinnamon, and grape seed (20%. Feed intake was reduced when diets containing 1056 mg of arginine were supplemented with 100 or 200 mg phytogenic additive per kg. Feed conversion ratio was improved when diets were supplemented with 100 mg of phytogenic additive or with 1056 mg of arginine per kg of feed. Egg mass was increased when diets were supplemented with 1056 mg arginine per kg of feed. Arginine supplementation quadratically increased albumen percentage and reduced yolk percentage. Higher arginine and phytogenic additive levels reduced heterophyl:lymphocyte ratio and blood uric acid, total cholesterol, very-low density lipoprotein, and triglyceride levels. Dietary supplementation of 100 mg of phytogenic additive associated with high arginine levels increased nitric oxide production by peritoneal macrophages and 1056 mg of arginine increased antibodies titers against Newcastle disease virus. Blood and intestinal malonaldehyde levels were reduced when 200 mg of the phytogenic additive was added. Dietary supplementation of 968 mg of arginine or 100 mg of a phytogenic additive (40% Baccharis dracunculifolia, 20% Astragalus membranaceus, 20% cinnamon, and 20% grape seed extracts per kilogram of diet improves the feed conversion ratio and associated inclusion of 1144 mg of

  10. Antineoplastic treatment of patients with renal insufficiency

    International Nuclear Information System (INIS)

    Rajec, J.; Mego, M.; Rajec, J.

    2011-01-01

    Kidneys are the main route of elimination for many antineoplastic drugs and their metabolites. The kidney dysfunction may lead to the drug cumulation in organism with the resulting increased systemic toxicity. A lot of used cytostatics requires a dose modification at different levels of renal insufficiency. Due to the lack of data from clinical trials, the limiting of systemic toxicity is difficult especially in patients with severe renal impairment or patients undergoing chronic hemodialysis. The following article is focused on the preventive strategies dealing with recommended dosing modification of various antineoplastic agents in patients with renal insufficiency. (author)

  11. Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays. General considerations, the nitrosoureas and alkylating agents.

    Science.gov (United States)

    Bosanquet, A G

    1985-01-01

    In vitro drug sensitivity of tumour biopsies is currently being determined using a variety of methods. For these chemosensitivity assays many drugs are required at short notice, and this in turn means that the drugs must generally be stored in solution. There are, however, a number of potential problems associated with dissolving and storing drugs for in vitro use, which include (a) drug adsorption; (b) effects of freezing; (c) drug stability under the normal conditions of dilution and setting up of an in vitro assay; and (d) insolubility of drugs in normal saline (NS) or phosphate-buffered saline (PBS). These problems are considered in general, and some recommendations for use of solutions of drugs in in vitro assays are suggested. The nitrosoureas and alkylating agents are also investigated in greater detail in this respect. The nitrosoureas are found to be very labile in PBS at pH 7, with 5% degradation (t0.95) occurring in 10-50 min at room temperature. These values are increased about 10-fold on refrigeration and about 5- to 10-fold on reduction of the pH of the medium to pH 4-5. At pH 7 and room temperature, t0.95 is observed in under 1 h with the alkylating agents nitrogen mustard, chlorambucil, melphalan, 2,5-diaziridinyl-3,6-bis(2-hydroxyethylamino)-1,4-benzoquinone (BZQ), dibromodulcitol, dibromomannitol, treosulphan, and procarbazine. Of the other alkylating agents, 4-hydroperoxycylophosphamide (sometimes used in vitro in place of cyclophosphamide), busulphan, dianhydrogalactitol, aziridinylbenzoquinone (AZQ), and dacarbazine have a t0.95 of between 2 and 24 h, while ifosfamide and pentamethylmelamine are both stable in aqueous solution for greater than 7 days. About half the drugs studied in detail have been stored frozen in solution for in vitro use, although very little is known about their stability under these conditions.

  12. Phytogenic Compounds as Alternatives to In-Feed Antibiotics: Potentials and Challenges in Application

    Directory of Open Access Journals (Sweden)

    Chengbo Yang

    2015-03-01

    Full Text Available This article summarizes current experimental knowledge on the efficacy, possible mechanisms and feasibility in the application of phytogenic products as feed additives for food-producing animals. Phytogenic compounds comprise a wide range of plant-derived natural bioactive compounds and essential oils are a major group. Numerous studies have demonstrated that phytogenic compounds have a variety of functions, including antimicrobial/antiviral, antioxidative and anti-inflammation effects and improvement in the palatability of feed and gut development/health. However, the mechanisms underlying their functions are still largely unclear. In the past, there has been a lack of consistency in the results from both laboratory and field studies, largely due to the varied composition of products, dosages, purities and growing conditions of animals used. The minimal inhibitory concentration (MIC of phytogenic compounds required for controlling enteric pathogens may not guarantee the best feed intake, balanced immunity of animals and cost-effectiveness in animal production. The lipophilic nature of photogenic compounds also presents a challenge in effective delivery to the animal gut and this can partially be resolved by microencapsulation and combination with other compounds (synergistic effect. Interestingly, the effects of photogenic compounds on anti-inflammation, gut chemosensing and possible disruption of bacterial quorum sensing could explain a certain number of studies with different animal species for the better production performance of animals that have received phytogenic feed additives. It is obvious that phytogenic compounds have good potential as an alternative to antibiotics in feed for food animal production and the combination of different phytogenic compounds appears to be an approach to improve the efficacy and safety of phytogenic compounds in the application. It is our expectation that the recent development of high-throughput and

  13. Turmeric (Curcuma Longa: An Underutilized Phytogenic Additive in Poultry Nutrition

    Directory of Open Access Journals (Sweden)

    Olumuyiwa Joseph Olarotimi

    2018-02-01

    Full Text Available The aim of this review paper is to explore the available information from research findings on the use of Turmeric (Curcuma longa as a reliable phytogenic antibiotic for poultry production in the tropics especially in Nigeria and other countries. A wide range of phytogenic additives has found a growing interest in fortification of poultry diets. Supplementation of natural alternatives to antibiotic growth promoters in order to maintain both birds’ performance and health in the tropics will be a welcome development. Turmeric has reportedly been widely supplemented in poultry diets as natural alternative antibiotics in several studies with outstanding performances. The nutritional, medicinal, haematological and phyto-toxicological effects of turmeric were reviewed in this paper. Hence, turmeric supplementation at recommended inclusion rate in poultry feeds without posing any deleterious effects to the birds’ performances as well as the consumers of the products, and ultimately, leading to better profitability on the part of the farmers, will be a nutritional breakthrough for the farmers in the tropics.

  14. The effect of garlic and ginger phytogenics on the shelf life and ...

    African Journals Online (AJOL)

    The effect of garlic and ginger phytogenics on the shelf life and microbial contents ... The preservative effects of garlic and ginger was compared with that of sodium ... reduced health risks of infection and/or intoxication from their consumption.

  15. Catalytic and recyclability properties of phytogenic copper oxide nanoparticles derived from Aglaia elaeagnoidea flower extract

    Directory of Open Access Journals (Sweden)

    G. Manjari

    2017-07-01

    Full Text Available The phytogenic synthesis method to highly active, recoverable and recyclable heterogeneous copper oxide nanocatalyst and encapsulated within biomaterial that acts as a nontoxic and renewable source of reducing and stabilizing agent. The biosynthesized CuO NPs were characterized using UV–Vis absorption spectroscopy, X-ray diffraction (XRD, field emission scanning electron microscopy (FESEM, energy dispersive X-ray spectroscopy (EDX, transmission electron microscopy (TEM and thermo gravimetric analysis-differential scanning calorimetry (TGA–DSC, techniques. The formation of CuO NPs with the size 20–45 nm range is shown in TEM image. Significantly, in aqueous phase CuO NPs have high catalytic activity for the reduction of Congo red (CR, methylene blue (MB and 4-nitrophenol (4-NP in the presence of the sodium borohydride (NaBH4 at room temperature. In addition, CuO NPs catalyst can be easily recovered by centrifugation and reused for 6 cycles with more than 90% conversion efficiency. CuO nanocatalyst, leaching after catalytic application was investigated by ICPAES (Inductively coupled plasma atomic emission spectroscopy. CuO NPs possess great prospects in reduction of pernicious dyes and nitro organic pollutants in water.

  16. Steroid compounds of phytogenic origin: scientometric research data of scientific and practical literature

    Directory of Open Access Journals (Sweden)

    Sukhanov А.Е.

    2017-03-01

    Full Text Available Steroid compounds of phytogenic origin are important in clinical medicine rendering anti-inflammatory, anti-prolifer-ative and antithrombotic actions. However, steroid compounds of phytogenic origin, in particular, steroid saponins are insufficiently studied from an identification position in tissues of vegetable organisms and methods of their physical and chemical analysis. The scientometric analysis of research data (abstract documents containing an analytical array of scientific publications concerning isolation, selection, cleaning, identification and the quantitative definition of steroid saponins in tissues of the higher vascular plants in the abstract bibliographic database SciVerse Scopus (Elsevier publishing house with use of criteria "key word" and "the key phrase" is provided in the article.

  17. EFFECT OF PHYTOGENIC ADDITIVES ON OXIDATION STABILITY OF FROZEN CHICKEN MEAT

    Directory of Open Access Journals (Sweden)

    Marek Bobko

    2016-10-01

    Full Text Available In this study, oxidative stability of frozen chicken breast and thigh muscle after application of feed mixtures enriched by phytogenic additives was investigated. The 150 pieces one-day-old chicks of Cobb 500 hybrid combination were divided into three groups: C - control group, G1 – experimental group with addition 1000 mg kg-1 Biostrong 510 + FortiBac and G2 – experimental group with addition 1000 mg kg-1 Agolin Acid.  The broiler chickens were fed during 42 days by ad libitum. Samples of chicken breast and thigh muscle were analysed in the 1st day and after 1st, 2nd, 3rd, 4th, 5th and 6th month of frozen storage at -18 °C. During testing period we recorded positive influence of phytogenic additives on oxidative stability of chicken meat in experimental groups (G1, G2. After 6th month of frozen storage, we found higher malondialdehyde (MDA values and lower oxidative stability of breast muscle in control group (0.167 mg.kg-1 compared to experimental groups G1 (0.149 mg.kg-1 and G2 (0.145 mg.kg-1. Similar tendency of oxidative changes as in the breast muscle was recorded in the thigh muscle. At the end of frozen storage MDA average values of thigh muscle were higher in control group (0.181 mg.kg-1 compared to experimental groups (G1 - 0.163 mg.kg-1 and G2 - 0.160 mg.kg-1.  Based on the obtained results we can stated, that phytogenic additives applied in chicken nutrition had positive influence of, namely on oxidation stability of fatty substances.

  18. Effect of different phytogenic additives on oxidation stability of chicken meat

    Directory of Open Access Journals (Sweden)

    Marek Bobko

    2016-05-01

    Full Text Available The aim of the study was to evaluate the oxidative stability (TBARS method of breast and thigh muscle after application of feed mixtures enriched by phytogenic additives. The experiment started with 150 pieces one-day-old chicks of Cobb 500 hybrid combination. They were divided into one control (C and two experimental groups (1st EG and 2nd EG. Each group included 50 chicks. In experimental groups, feed additives were applied as followed: 100 mg.kg-1 Agolin Poultry (in the 1st EG and 500 mg.kg-1 Agolin Tannin Plus (in the 2nd EG. Experimental broiler chickens were fed during 42 days by ad libitum. Chicken meat samples of breast and thigh muscle were analysed in the 1st day, 1st, 2nd, 3rd, 4th, 5th and 6th month of storage in frozen storage at -18 °C. We recorded positive influence on chicken meat oxidative stability in all experimental groups with application of phytogenic feed additives. Obtained results showed that applied phytogenic additives had positive influence on oxidative stability of breast and thigh muscles. At the end of frozen storage (in 6th month, we found higher malondialdehyde (MDA values and lower oxidative stability (p <0.05 of breast muscle in control group (0.167 mg.kg-1 compared to experimental groups (from 0.150 mg.kg-1 in 1. EG to 0.155 mg.kg-1 in 2. EG. In the thigh muscle, we found similar tendency of oxidative changes as in the breast muscle. At the end of frozen storage (in the 6th month, MDA average values of thigh muscle were higher (p <0.05 in control group (0.181 mg.kg-1 compared to experimental groups (1. EG 0.164 mg.kg-1 and 2. EG 0.169 mg.kg-1. Significant differences (p <0.05 between the control and experimental groups were found from the 5th month of storage in thigh and breast muscle. Obtained results indicate positive influence of phytogenic additives applied in chicken nutrition, namely on stabilization of fatty substance to degradation processes. Normal 0 21 false false false SK X-NONE X-NONE Normal 0

  19. Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.

    Science.gov (United States)

    Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

    2017-11-23

    Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

  20. OXIDATIVE STABILITY OF CHICKEN MEAT AFTER APPLICATION PHYTOGENIC ADDITIVES IN THEIR DIET

    Directory of Open Access Journals (Sweden)

    Marek Bobko

    2015-02-01

    Full Text Available The aim of the study was to evaluate the oxidative stability (TBARS method of breast and thigh muscle after application of feed mixtures enriched by phytogenic additives. The experiment started with 250 pieces one-day-old chicks of Cobb 500 hybrid combination. They were divided into one control (C and four experimental groups (1st EG, 2nd EG, 3rd EG, 4th EG. Each group included 50 chicks. In experimental groups, feed additives were applied as followed: 100 mg kg-1 Agolin Poultry (in the 1st EG, 500 mg kg-1 Agolin Tannin Plus (in the 2nd EG, 1000 mg kg-1 Biostrong 510 + FortiBac (in the 3rd EG and 1000 mg kg-1 Agolin Acid (in the 4th EG. We recorded positive influence on chicken meat oxidative stability in all experimental groups with application of plant feed additives. Experimental broiler chickens were fed during 42 days by ad libitum. Chicken meat samples of breast and thigh muscle were analyzed in the 1st, 3rd, 5th and 7th day of storage in cold conditions at 4 °C. Obtained results showed that applied phytogenic additives had positive influence on oxidative stability of breast and thigh muscles. At the end of cold store (in 7th day, we found higher malondialdehyde (MDA values and lower oxidative stability (P<0.05 of breast muscle in control group (0.157 mg kg-1 compared to experimental groups (from 0.124 mg kg-1 in the 3rd EG to 0.133 mg kg-1 in the 1st EG. In the thigh muscle, we found similar tendency of oxidative changes as in the breast muscle. At the end of cold store (in the 7th day, MDA average values of thigh muscle were higher (P<0.05 in control group (0.179 mg kg-1 compared to experimental groups (from 0.136 mg kg-1 in the 4th EG to 0.141 mg kg-1 in the 1st EG. Significant differences (P<0.05 between the control and experimental groups were found from the 5th day of storage in thigh muscle in contrast to breast muscle. Obtained results indicate positive influence of phytogenic additives applied in chicken nutrition, namely on

  1. Flavonoids from Heliotropium subulatum exudate and their evaluation for antioxidant, antineoplastic and cytotoxic activities II.

    Science.gov (United States)

    Singh, Bharat; Sahu, Pooran M; Sharma, Ram A

    2017-02-01

    The flavonoids are the largest group of phenolic compounds isolated from a wide range of higher plants. These compounds work as antimicrobials, anti-insect agents and protect plants from other types of biotic and abiotic stresses. Various researchers have suggested that flavonoids possessed antioxidant, antineoplastic and cytotoxic activities. The main objective of this study was to test dichloromethane fraction of resinous exudate of Heliotropium subulatum for their antioxidant, antineoplastic and cytotoxic activities, as well as to search new antioxidant and antineoplastic agents for pharmaceutical formulations. Five flavonoids were isolated from resinous exudate of this plant species and screened for their in vitro and in vivo antioxidant models (DPPH radical scavenging, reducing power, superoxide anion scavenging, metal chelating scavenging systems, catalase and lipid peroxidation), antineoplastic (Sarcoma 180), and cytotoxic (Chinese hamster V79 cells) activities. Tricetin demonstrated maximum antioxidant activity against both in vitro and in vivo experimental systems while galangin exhibited maximum inhibition (78.35%) at a dose of 10 µg/kg/day against Sarcoma 180. Similarly, it was found that galangin also showed highest activity (21.1 ± 0.15%) at a concentration of 70 µg/ml to Chinese hamster V79 cells. The observed results suggest that tricetin has a potential to scavenge free radicals in both in vitro and in vivo models while the galangin could be considered as antitumor and cytotoxic agent.

  2. Antineoplastic drugs: Occupational exposure and health risks

    NARCIS (Netherlands)

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used.

  3. Relation between selected nutrients in the chicken meat depending on phytogenic feed additives

    Directory of Open Access Journals (Sweden)

    Mária Angelovičová

    2016-05-01

    Full Text Available The aim of study was to evaluate the relation between selected nutrients in the breast and thigh muscles after the application of different phytogenic additives in the diet of broiler chickens and between same indicators of meat disregarding additive and parts of carcass, from which muscles originate. We realized an in vivo experiment on the Zámostie Company poultry test station with deep litter breeding system. The experiment included 100 pcs of one-day-old hybrid chickens Cobb 500 divided into 2 groups (n = 50: the 1st experimental group with an application of feed additive from chestnut tree and lemon fruit extracts and the 2nd experimental group with an application of feed additive from citrus fruits extract. We used a cereal and soybean basal diet and we divided the fattening period into four phases: starter (1 - 10 days, grower I (11 - 20 days, grower II (21 - 28 days and finisher (29 - 42 days. We applied a powder form feed mixtures. Nutritive value of feed mixtures was the same in each experimental group during the whole experiment and in accordance with the physiological needs of broiler chickens. We fed the 1st experimental group with a basal diet enriched by feed additive from chestnut tree and lemon fruit extracts (50 g/100 kg. As for the 2nd experimental group, we applied feed additive from citrus fruits extracts through the drinking water (100 mL/100 L. In the 2nd part of our experiment, we compared results obtained from two experimental groups with other four groups of diet. We applied other phytogenic additives to these four groups and we did not take into account the origin of the meat sample. We measured indicators of the chemical composition of protein, fat, water and cholesterol on a sample (50 g of breast and thigh muscle without skin by the method of FT IR by use of the apparatus Nicolet 6700. Detected relations between nutrients of breast and thigh muscles were defined by correlation coefficient of -0.6 ≤ r ≥ +0

  4. Antineoplastic drugs: Occupational exposure and health risks

    OpenAIRE

    Fransman, W.

    2006-01-01

    Antineoplastic drugs are pharmaceuticals commonly used to treat cancer (and some non-neoplastic diseases), which are generally referred to as 'chemotherapy'. Oncology nurses are exposed to these drugs via the skin of hands during daily nursing activities, even when protective gloves are being used. Results of tests on bulk and surface contamination samples confirmed that patients intravenously treated with cyclophosphamide excrete the unmetabolized drug. The introduction of new guidelines and...

  5. Glycaemic adverse drug reactions from anti-neoplastics used in ...

    African Journals Online (AJOL)

    235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

  6. [Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature].

    Science.gov (United States)

    Pérez Huertas, Pablo; Cueto Sola, Margarita; Escobar Cava, Paloma; Borrell García, Carmela; Albert Marí, Asunción; López Briz, Eduardo; Poveda Andrés, José Luis

    2015-07-01

    The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  7. Applying dose banding to the production of antineoplastic drugs: a narrative review of the literature

    Directory of Open Access Journals (Sweden)

    Pablo Pérez Huertas

    2015-07-01

    Full Text Available The dosage of antineoplastic drugs has historically been based on individualized prescription and preparation according to body surface area or patient´s weight. Lack of resources and increased assistance workload in the areas where chemotherapy is made, are leading to the development of new systems to optimize the processing without reducing safety. One of the strategies that has been proposed is the elaboration by dose banding. This new approach standardizes the antineoplastic agents doses by making ranges or bands accepting a percentage of maximum variation. It aims to reduce processing time with the consequent reduction in waiting time for patients; to reduce errors in the manufacturing process and to promote the rational drug use. In conclusion, dose banding is a suitable method for optimizing the development of anticancer drugs, obtaining reductions in oncologic patients waiting time but without actually causing a favorable impact on direct or indirect costs.

  8. Tumor targeting using liposomal antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Jörg Huwyler

    2008-03-01

    Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

  9. Does applying technology throughout the medication use process improve patient safety with antineoplastics?

    Science.gov (United States)

    Bubalo, Joseph; Warden, Bruce A; Wiegel, Joshua J; Nishida, Tess; Handel, Evelyn; Svoboda, Leanne M; Nguyen, Lam; Edillo, P Neil

    2014-12-01

    Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors. This article will review both the pros and cons of today's technologies and their ability to simplify the medication use process, reduce medication errors, improve documentation, improve healthcare costs and increase provider efficiency as relates to the use of antineoplastic therapy throughout the medication use process. Several technologies, mainly computerized provider order entry (CPOE), barcode medication administration (BCMA), smart pumps, electronic medication administration record (eMAR), and telepharmacy, have been well described and proven to reduce medication errors, improve adherence to quality metrics, and/or improve healthcare costs in a broad scope of patients. The utilization of these technologies during antineoplastic therapy is weak at best and lacking for most. Specific to the antineoplastic medication use system, the only technology with data to adequately support a claim of reduced medication errors is CPOE. In addition to the benefits these technologies can provide, it is also important to recognize their potential to induce new types of errors and inefficiencies which can negatively impact patient care. The utilization of technology reduces but does not eliminate the potential for error. The evidence base to support technology in preventing medication errors is limited in general but even more deficient in the realm of antineoplastic therapy. Though CPOE has the best evidence to support its use in the

  10. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

    Directory of Open Access Journals (Sweden)

    Zbynek Heger

    2013-10-01

    Full Text Available Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine. An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05. This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.

  11. Dental anomalies in children submitted to antineoplastic therapy.

    Science.gov (United States)

    Carrillo, Camila Merida; Corrêa, Fernanda Nahás Pires; Lopes, Nilza Nelly Fontana; Fava, Marcelo; Odone Filho, Vicente

    2014-06-01

    Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  12. Dental anomalies in children submitted to antineoplastic therapy

    Directory of Open Access Journals (Sweden)

    Camila Merida Carrillo

    2014-06-01

    Full Text Available Cancer is the third most frequent cause of death in children in Brazil. Early diagnosis and medical advances have significantly improved treatment outcomes, which has resulted in higher survival rates and the management of late side effects has become increasingly important in caring for these patients. Dental abnormalities are commonly observed as late effects of antineoplastic therapy in the oral cavity. The incidence and severity of the dental abnormalities depend on the child's age at diagnosis and the type of chemotherapeutic agent used, as well as the irradiation dose and area. The treatment duration and aggressivity should also be considered. Disturbances in dental development are characterized by changes in shape, number and root development. Enamel anomalies, such as discoloration, opacities and hypoplasia are also observed in these patients. When severe, these abnormalities can cause functional and esthetic sequelae that have an impact on the children's and adolescents' quality of life. General dentists and pediatric dentists should understand these dental abnormalities and how to identify them aiming for early diagnosis and appropriate treatment.

  13. Antineoplastic drugs and radiation: comparison of the phenomena determining the effectiveness of fractionated treatments

    International Nuclear Information System (INIS)

    Mauro, F.; Briganti, G.; Nervi, C.

    1983-01-01

    In the last ten years the criteria for effective radiotherapy regimens have been rediscussed by analyzing the dependence of radiation response upon the radiobiological phenomena affecting the results of fractionated treatments. In the original definition of H.R. Withers, these phenomena have been referred to as the four R's of radiotherapy, and today we suspect that their number may be higher than that. By analogy, and in spite of the fact that chemical cytotoxic agents are seldom radiomimetic in the strict sense of the word, a similar general analysis could be used to discuss the effectiveness of fractionated administrations of anti-neoplastic drugs. However, information is only available for the cell-cycle age-dependence of lethal and kinetic effects and the repair from potentially lethal damage induced by these agents. In the present work, an attempt is made to discuss some of the neglected R's of chemotherapy, with the aim of establishing (not exclusively empirical) criteria for drug scheduling and of clarifying some of the observations on interaction between agents. In particular, with regard to antineoplastic drugs, published and unpublished information is available not only for the well-known phenomenon of reassortment, but also for the shape of the survival curve, recovery (or potentiation) between dose fraction, and recruitment. Some advantages (and pitfalls) can be evidenced when applying this kind of radiobiological approach to chemotherapy

  14. Exposure to antineoplastic drugs outside the hospital environment.

    Science.gov (United States)

    Meijster, T; Fransman, W; Veldhof, R; Kromhout, H

    2006-10-01

    The objectives were (i) to identify occupational populations outside hospitals working with antineoplastic drugs, (ii) to determine the size of the populations 'at risk', (iii) to identify major determinants and routes of exposure outside hospitals and (iv) to estimate exposure levels and frequencies relative to levels found in hospitals. The survey consisted of two phases; (i) identification of activities with potential exposure to antineoplastic drugs by literature review, interviews, questionnaires and workplace visits, (ii) exploratory measurements of exposure and surface contamination in selected sectors. Eight sectors were identified with potential exposure to antineoplastic drugs: pharmaceutical industry, pharmacies, universities, veterinary medicine, nursing homes, home care, laundry facilities, and waste treatment. Four sectors were of primary concern: veterinary medicine, home care, nursing homes and industrial laundries. The populations potentially exposed in these sectors vary considerably (from several tens to thousands of workers), as do their levels of exposure. Exposure measurements collected in the veterinary medicine sector showed that workers are indeed exposed to antineoplastic drugs and, in some cases (on gloves after administration), levels were 15 times higher than levels measured during administration in hospitals. Workers sorting contaminated hospital laundry in industrial laundry facilities were exposed to antineoplastic drugs through inhalation. For the home care and nursing homes sectors the highest exposure levels were found when cleaning toilets and washing treated patients. These two sectors are expected to have the largest exposed population (5,000-10,000 individuals). This study has resulted in a comprehensive overview of populations with potential exposure to antineoplastic drugs. Exposure levels can potentially be high compared with the hospital environment, because exposure routes are complex and awareness of the hazard (and

  15. Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

    Science.gov (United States)

    Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman

    2011-01-01

    In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

  16. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  17. New solid state forms of antineoplastic 5-fluorouracil with anthelmintic piperazine

    Science.gov (United States)

    Moisescu-Goia, C.; Muresan-Pop, M.; Simon, V.

    2017-12-01

    The aim of the present study was to asses the formation of solid forms between the 5-fluorouracil chemotherapy drug and the anthelmintic piperazine. Two new solid forms of antineoplastic agent 5-fluorouracil with anthelmintic piperazine were obtained by liquid assisted ball milling and slurry crystallization methods. The Nsbnd H hydrogen bonding donors and C = O hydrogen bonding acceptors of 5-fluorouracil allow to form co-crystals with other drugs delivering improved properties for medical applications, as proved for other compounds of pharmaceutical interest. Both new solid forms were investigated using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. The XRD results show that by both methods were successfully synthesized new solid forms of 5-fluorouracil with piperazine. According to FTIR results the form prepared by lichid assisted grinding process was obtained as co-crystal and the other one, prepared by slurry method, resulted as a salt.

  18. The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2016-03-01

    Full Text Available Taurine (2-aminoethane sulfonic acid is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 μM, 100 μM and 1000 μM of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5 Fluorouracil, Doxorubicin and Dacarbazine via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+. Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug treated livers. It was found that taurine (5 and 10 mM and glycine (5 and 10 mM administration significantly mitigated the biomarkers of liver injury and attenuated drug induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

  19. Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review.

    Science.gov (United States)

    Gérard, S; Bréchemier, D; Lefort, A; Lozano, S; Abellan Van Kan, G; Filleron, T; Mourey, L; Bernard-Marty, C; Rougé-Bugat, M E; Soler, V; Vellas, B; Cesari, M; Rolland, Y; Balardy, L

    2016-01-01

    The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

  20. Impact of Robotic Antineoplastic Preparation on Safety, Workflow, and Costs

    Science.gov (United States)

    Seger, Andrew C.; Churchill, William W.; Keohane, Carol A.; Belisle, Caryn D.; Wong, Stephanie T.; Sylvester, Katelyn W.; Chesnick, Megan A.; Burdick, Elisabeth; Wien, Matt F.; Cotugno, Michael C.; Bates, David W.; Rothschild, Jeffrey M.

    2012-01-01

    Purpose: Antineoplastic preparation presents unique safety concerns and consumes significant pharmacy staff time and costs. Robotic antineoplastic and adjuvant medication compounding may provide incremental safety and efficiency advantages compared with standard pharmacy practices. Methods: We conducted a direct observation trial in an academic medical center pharmacy to compare the effects of usual/manual antineoplastic and adjuvant drug preparation (baseline period) with robotic preparation (intervention period). The primary outcomes were serious medication errors and staff safety events with the potential for harm of patients and staff, respectively. Secondary outcomes included medication accuracy determined by gravimetric techniques, medication preparation time, and the costs of both ancillary materials used during drug preparation and personnel time. Results: Among 1,421 and 972 observed medication preparations, we found nine (0.7%) and seven (0.7%) serious medication errors (P = .8) and 73 (5.1%) and 28 (2.9%) staff safety events (P = .007) in the baseline and intervention periods, respectively. Drugs failed accuracy measurements in 12.5% (23 of 184) and 0.9% (one of 110) of preparations in the baseline and intervention periods, respectively (P < .001). Mean drug preparation time increased by 47% when using the robot (P = .009). Labor costs were similar in both study periods, although the ancillary material costs decreased by 56% in the intervention period (P < .001). Conclusion: Although robotically prepared antineoplastic and adjuvant medications did not reduce serious medication errors, both staff safety and accuracy of medication preparation were improved significantly. Future studies are necessary to address the overall cost effectiveness of these robotic implementations. PMID:23598843

  1. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  2. Investigation of antineoplastic activity of chewing tablets based on dry oat extract and quercetin

    Directory of Open Access Journals (Sweden)

    Ярослав Ростиславович Андрійчук

    2015-07-01

    Full Text Available One of the main goals of domestic pharmaceutical science is development of new medicines. Thus, new tablet drug was created based on dry oat extract and quercetin. Investigation of antineoplastic activity was performed. Antineoplastic activity of investigational drug based on dry oat extract and quercetin was experimentally proved.

  3. 77 FR 38297 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-06-27

    ... removed 15 drugs from the 2012 list because they did not meet the NIOSH definition, were no longer... NIOSH-033-A] Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in... of the following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in...

  4. 75 FR 57044 - NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010

    Science.gov (United States)

    2010-09-17

    ... identified 24 drugs that fit the NIOSH definition of hazardous drugs. The second draft list also proposed... Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2010 AGENCY: National Institute for Occupational... publication of the following document entitled ``NIOSH List of Antineoplastic and Other Hazardous Drugs in...

  5. Prophylaxis and management of antineoplastic drug induced nausea and vomiting in children with cancer

    Directory of Open Access Journals (Sweden)

    Sidharth Totadri

    2016-10-01

    Full Text Available Antineoplastic drug induced nausea and vomiting (AINV is a major adverse event which deeply impacts the quality of life of children with cancer. It additionally causes distress to parents and negatively impacts compliance to therapy. A robust AINV prophylaxis regimen is essential to achieve complete control; and prevent anticipatory, breakthrough and refractory AINV. With a wide array of available anti-emetics, standard guidelines for their use are crucial to ensure uniform and optimum prophylaxis. Chemotherapeutic agents are classified as having high, moderate, low or minimal emetic risk based on their potential to cause emesis in the absence of prophylaxis. Three drug regimen with aprepitant, ondansetron/granisetron and dexamethasone is recommended for protocols with high emetic risk. Although approved in children ≥12 years, there is mounting evidence for the use of aprepitant in younger children too. In protocols with moderate and low emetic risk, combination of ondansetron/granisetron and dexamethasone; and single agent ondansetron/granisetron are recommended, respectively. Metoclopramide is an alternative when steroids are contraindicated. Olanzapine and lorazepam are useful drugs for breakthrough AINV and anticipatory AINV. Knowledge of pediatric dosage, salient adverse events, drug interactions as well as cost of drugs is essential to prescribe anti-emetics accurately and safely in resource constrained settings. Non pharmacological interventions such as hypnosis, acupressure and psychological interventions can benefit a sub-group of patients without significant risk of adverse events.

  6. Phytogenic additive on diet of dairy heifers: Performance and behavior parameters Desempenho produtivo e comportamento de novilhas submetidas a dietas com aditivo fitogênico

    Directory of Open Access Journals (Sweden)

    Fernando Reimann Skonieski

    2009-12-01

    Full Text Available This experiment evaluated the effects in the performance and behavior parameters of Jersey dairy heifers supplemented with herbal extracts. The experiment was conducted in Boapaba Ranch, Silveira Martins (RS, from July to September, 2004, utilizing 12 Jersey’s heifers. The animals were separated in two groups, with the same number of replications, considered a Control group (without addition of phytogenic additive and a Treatment group (with inclusion of 500 grams of phytogenic additive per ton. of concentrate. The phytogenic additive utilized was a commercial blend of essential oils, flavonoids and mucilage. The animals received daily, divided in two feeding, 2 kg. of concentrate and, 3 kg. of alfalfa hay and 10 kg. of chopped fresh black oat and ryegrass. The performance parameters evaluated were initial weight, final weight, and daily average daily weight gain and feed conversion and behavior parameters analyzed were feeding behavior, time of intake for concentrate and roughage, rectal temperature, and cardiac frequency. There were not significantly differences (P > 0.05 between treatments for performance parameters in general analysis of data, but occurred significantly differences between treatments when analyzed the periods (P< 0.05. Significant differences could be observed in feeding behavior (P < 0.05, cardiac frequency (P < 0.05, and time of intake for concentrate (P < 0.002,. The authors leading to the conclusion that the herbal extract influence on the performance and behavior parameters of dairy heifers receiving this supplement.Este experimento avaliou os efeitos no desempenho e no comportamento de novilhas leiteiras suplementadas com extratos herbais. O experimento foi conduzido na Granja Boapaba, no município de Silveira Martins (RS, de julho a setembro de 2004, com a utilização de 12 novilhas da raça Jersey. Os animais foram separados em dois grupos, com o mesmo número de indivíduos, considerados como grupo-controle (sem

  7. Preliminary screening of some traditional Zulu medicinal plants for antineoplastic activities versus the HepG2 cell line.

    Science.gov (United States)

    Opoku, A R; Geheeb-Keller, M; Lin, J; Terblanche, S E; Hutchings, A; Chuturgoon, A; Pillay, D

    2000-11-01

    Aqueous and methanol extracts of nine traditional Zulu medicinal plants, Cissus quandrangularis L., Cyphostemma flaviflorum (Sprague) Descoings, Cyphostemma lanigerum (Harv.) Descoings ex Wild & Drum, Cyphostemma natalitium (Szyszyl.) J. v. d. Merwe, Cyphostemma sp., Rhoicissus digitata (L. F.) Gilg & Brandt, Rhoicissus rhomboidea (E. Mey. Ex harv.) Planch, Rhoicissus tomentosa (Lam.) Wild & Drum, R. tridentata (L. F.) Wild & Drum and Rhoicissus tridentata (L. F.) Wild & Drum subsp. cuneifolia (Eckl. & Zeyh.) N. R. Urton, all belonging to the Vitaceae family, were evaluated to determine their therapeutic potentials as antineoplastic agents. The antiproliferative activity in vitro against HepG2 cells was determined. Twenty-two of the twenty-seven crude plant extracts showed activities ranging from 25% to 97% inhibition of proliferation when compared with the control which showed no inhibitory activity. Higher degrees of growth inhibition were found in aqueous root extracts in comparison with the methanol extracts of the same plant parts. The results show potential antineoplastic activity, indicating some scientific validation for traditional usage. Copyright 2000 John Wiley & Sons, Ltd.

  8. 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

  9. Spatially explicit prioritization of human antibiotics and antineoplastics in Europe.

    Science.gov (United States)

    Oldenkamp, Rik; Huijbregts, Mark A J; Hollander, Anne; Versporten, Ann; Goossens, Herman; Ragas, Ad M J

    2013-01-01

    This paper presents a screening tool for the location-specific prioritization of human pharmaceutical emissions in Europe, based on risk quotients for the aquatic environment and human health. The tool provides direction towards either monitoring activities or additional research. Its application is illustrated for a set of 11 human antibiotics and 7 antineoplastics. Risk quotients for the aquatic environment were highest for levofloxacin, doxycycline and ciprofloxacin, located in Northern Italy (Milan region; particularly levofloxacin) and other densely populated areas in Europe (e.g. London, Krakow and the Ruhr area). Risk quotients for human health not only depend on pharmaceutical and location, but also on behavioral characteristics, such as consumption patterns. Infants in eastern Spain that consume locally produced food and conventionally treated drinking water were predicted to run the highest risks. A limited comparison with measured concentrations in surface water showed that predicted and measured concentrations are approximately within one order of magnitude. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Molecular biomonitoring of a population of nurses handling antineoplastic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Cornetta, Tommaso [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy); ' Don Carlo Gnocchi' Foundation, Rome (Italy); Padua, Luca [' Don Carlo Gnocchi' Foundation, Rome (Italy); Department of Neuroscience, Neurology Institute, Catholic University, Rome (Italy); Testa, Antonella; Ievoli, Elena [Toxicology and Biomedical Sciences Section, ENEA Research Center, Casaccia (Rome) (Italy); Festa, Fabiola [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy); Tranfo, Giovanna [Department of Occupational Hygiene, Italian Institute for Occupational Prevention and Safety, Monteporzio Catone (Rome) (Italy); Baccelliere, Luigi [S. Martino Hospital, Genova (Italy); Cozzi, Renata [Department of Biology, ' Roma Tre' University, Viale Guglielmo Marconi, 446-00146 Rome (Italy)], E-mail: cozzi@bio.uniroma3.it

    2008-02-01

    Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.

  11. Molecular biomonitoring of a population of nurses handling antineoplastic drugs

    International Nuclear Information System (INIS)

    Cornetta, Tommaso; Padua, Luca; Testa, Antonella; Ievoli, Elena; Festa, Fabiola; Tranfo, Giovanna; Baccelliere, Luigi; Cozzi, Renata

    2008-01-01

    Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances

  12. Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

    Science.gov (United States)

    Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi

    2015-05-01

    Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

  13. BEL β-trefoil: a novel lectin with antineoplastic properties in king bolete (Boletus edulis) mushrooms.

    Science.gov (United States)

    Bovi, Michele; Cenci, Lucia; Perduca, Massimiliano; Capaldi, Stefano; Carrizo, Maria E; Civiero, Laura; Chiarelli, Laurent R; Galliano, Monica; Monaco, Hugo L

    2013-05-01

    A novel lectin was purified from the fruiting bodies of king bolete mushrooms (Boletus edulis, also called porcino, cep or penny bun). The lectin was structurally characterized i.e its amino acid sequence and three-dimensional structure were determined. The new protein is a homodimer and each protomer folds as β-trefoil domain and therefore we propose the name Boletus edulis lectin (BEL) β-trefoil to distinguish it from the other lectin that has been described in these mushrooms. The lectin has potent anti-proliferative effects on human cancer cells, which confers to it an interesting therapeutic potential as an antineoplastic agent. Several crystal forms of the apoprotein and of complexes with different carbohydrates were studied by X-ray diffraction. The structure of the apoprotein was solved at 1.12 Å resolution. The interaction of the lectin with lactose, galactose, N-acetylgalactosamine and T-antigen disaccharide, Galβ1-3GalNAc, was examined in detail. All the three potential binding sites present in the β-trefoil fold are occupied in at least one crystal form and are described in detail in this paper. No important conformational changes are observed in the lectin when comparing its co-crystals with carbohydrates with those of the ligand-free protein.

  14. Sesquiterpene lactones: Mechanism of antineoplastic activity; relationship of cellular glutathione to cytotoxicity; and disposition

    International Nuclear Information System (INIS)

    Grippo, A.A.

    1987-01-01

    Helenalin, a sesquiterpene lactone, inhibited the growth of P388 lymphocytic and L1210 lymphoid leukemia, and Ehrlich ascites and KB carcinoma cells. The L1210 leukemia cells were most sensitive to the cytotoxic effects of helenalin. Helenalin's antineoplastic effects were due to inhibition of DNA synthesis by suppressing the activities of enzymes involved in this biosynthetic pathway; i.e., IMP dehydrogenase, ribonucleoside diphosphate reductase, thioredoxin complex, GSH disulfide oxidoreductase and DNA polymerase α activities. The relationship of reduced glutathione (GSH) to the cytotoxic effects of helanalin was evaluated. L1210 cells, which were more sensitive to helenalin's toxicity, contained lower basal concentrations of GSH. Helenalin decreased the concentration of reduced glutathione in both L1210 and P388 leukemia cells. Concurrent administration of helanalin with agents reported to raise GSH concentrations did not substantially effect GSH levels, nor were survival times of tumor-bearing mice enhanced. Following intraperitoneal administration of 3 H-plenolin, no radioactive drug and/or metabolite was sequestered in the organs of BDF 1 mice. Approximately 50% of 3 H-plenolin and/or its metabolites were eliminated via urine while lesser amounts of radioactive drug and/or metabolites were eliminated in the feces

  15. Near-infrared fluorescence imaging and photodynamic therapy with indocyanine green lactosome has antineoplastic effects for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Takumi Tsuda

    Full Text Available Anticancer agents and operating procedures have been developed for hepatocellular carcinoma (HCC patients, but their prognosis remains poor. It is necessary to develop novel diagnostic and therapeutic strategies for HCC to improve its prognosis. Lactosome is a core-shell-type polymeric micelle, and enclosing labeling or anticancer agents into this micelle enables drug delivery. In this study, we investigated the diagnostic and therapeutic efficacies of indocyanine green (ICG-loaded lactosome for near-infrared fluorescence (NIF imaging and photodynamic therapy (PDT for HCC.The human HCC cell line HuH-7 was treated with ICG or ICG-lactosome, followed by PDT, and the cell viabilities were measured (in vitro PDT efficiency. For NIF imaging, HuH-7 cells were subcutaneously transplanted into BALB/c nude mice, followed by intravenous administration of ICG or ICG-lactosome. The transplanted animals were treated with PDT, and the antineoplastic effects were analyzed (in vivo PDT efficiency.PDT had toxic effects on HuH-7 cells treated with ICG-lactosome, but not ICG alone. NIF imaging revealed that the fluorescence of tumor areas in ICG-lactosome-treated animals was higher than that of contralateral regions at 24 h after injection and thereafter. PDT exerted immediate and continuous phototoxic effects in the transplanted mice treated with ICG-lactosome.Our results demonstrate that ICG-lactosome accumulated in xenograft tumors, and that PDT had antineoplastic effects on these malignant implants. NIF imaging and PDT with ICG-lactosome could be useful diagnostic and/or therapeutic strategies for HCC.

  16. Evidence for tankyrases as antineoplastic targets in lung cancer

    International Nuclear Information System (INIS)

    Busch, Alexander M; Johnson, Kevin C; Stan, Radu V; Sanglikar, Aarti; Ahmed, Yashi; Dmitrovsky, Ethan; Freemantle, Sarah J

    2013-01-01

    New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common cause of cancer death for men and women. This study identified one such target. This is the canonical Wnt signaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or β-catenin mutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1 and TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the β-catenin phosphorylation complex. This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine transgenic and human lung cancers, relative to normal lung. Antineoplastic consequences of genetic and pharmacologic targeting of TNKS in murine and human lung cancer cell lines were explored, and validated in vivo in mice by implantation of murine transgenic lung cancer cells engineered with reduced TNKS expression relative to controls. Microarray analyses comparing Wnt pathway members in malignant versus normal tissues of a murine transgenic cyclin E lung cancer model revealed deregulation of Wnt pathway components, including TNKS1 and TNKS2. Real-time PCR assays independently confirmed these results in paired normal-malignant murine and human lung tissues. Individual treatments of a panel of human and murine lung cancer cell lines with the TNKS inhibitors XAV939 and IWR-1 dose-dependently repressed cell growth and increased cellular axin 1 and tankyrase levels. These inhibitors also repressed expression of a Wnt-responsive luciferase construct, implicating the Wnt pathway in conferring these antineoplastic effects. Individual or combined knockdown of TNKS1 and TNKS2 with siRNAs or shRNAs reduced lung cancer cell growth, stabilized axin, and repressed tumor formation in murine xenograft and syngeneic lung cancer models. Findings reported here uncovered deregulation of specific components of the Wnt pathway in both

  17. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Science.gov (United States)

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  18. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  19. Injectable-antineoplastic-drug practices in Michigan hospitals.

    Science.gov (United States)

    Cohen, I A; Newland, S J; Kirking, D M

    1987-05-01

    Practices related to parenteral (injectable) antineoplastic drugs (PADs) in Michigan hospitals were surveyed. All hospitals in Michigan were surveyed to assess compliance with American Society of Hospital Pharmacists (ASHP) and Occupational Safety and Health Administration (OSHA) recommendations related to PADs. Other PAD-related practice issues not covered within those guidelines were also studied. Surveys were mailed to the pharmacy directors of the state's 192 acute-care hospitals. Included were questions concerning policies and procedures for ordering, storing, preparing, handling, labeling, transporting, administering, and disposing of PADs. Questions concerning staff education, spill cleanup, and personnel issues were also included. A total of 169 questionnaires were returned, yielding a response rate of 88%. Of those respondents, 132 indicated that they prepare PAD doses for inpatients. Adherence rates were high for several of the PAD-preparation recommendations, including handwashing (97%) and gloving (98.5%). Rates for gowning (71.2%), labeling of PAD doses as biohazards (chemical hazards) (73.5%), and use of Class II biological-safety cabinets (71.2%) were less favorable. Practice areas with relatively poor adherence rates included use of plastic-backed absorbent pads under PAD preparation areas (53.8%), storing PADs separately from other drugs (48.5%), informing prospective employees of potential risks of handling PADs (36.4%), availability of spill kits (36.4%), and attaching and priming i.v. tubing before adding PADs to i.v. containers (5.4%). Many pharmacy departments in Michigan hospitals can substantially improve their adherence to ASHP and OSHA recommendations related to PADs.

  20. [Blending powdered antineoplastic medicine in disposable ointment container].

    Science.gov (United States)

    Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

    2014-01-01

    On dispensing powdered antineoplastic medicines, it is important to prevent cross-contamination and environmental exposure. Recently, we developed a method for blending powdered medicine in a disposable ointment container using a planetary centrifugal mixer. The disposable container prevents cross-contamination. In addition, environmental exposure associated with washing the apparatus does not arise because no blending blade is used. In this study, we aimed to confirm the uniformity of the mixture and weight loss of medicine in the blending procedure. We blended colored lactose powder with Leukerin(®) or Mablin(®) powders using the new method and the ordinary pestle and mortar method. Then, the blending state was monitored using image analysis. Blending variables, such as the blending ratio (1:9-9:1), container size (35-125 mL), and charging rate (20-50%) in the container were also investigated under the operational conditions of 500 rpm and 50 s. At a 20% charging rate in a 35 mL container, the blending precision of the mixtures was not influenced by the blending ratio, and was less than 6.08%, indicating homogeneity. With an increase in the charging rate, however, the blending precision decreased. The possible amount of both mixtures rose to about 17 g with a 20% charging rate in a 125 mL container. Furthermore, weight loss of medicines with this method was smaller than that with the pestle and mortar method, suggesting that this method is safer for pharmacists. In conclusion, we have established a precise and safe method for blending powdered medicines in pharmacies.

  1. Comparison of new nitrosoureas esters with modified steroidal nucleus for cytogenetic and antineoplastic activity.

    Science.gov (United States)

    Hussein, A; Mioglou-Kalouptsi, E; Papageorgiou, A; Karapidaki, I; Iakovidou-Kritsi, Z; Lialiaris, T; Xrysogelou, E; Camoutsis, C; Mourelatos, D

    2007-01-01

    Nitrosourea is decomposed under physiological conditions to react with biological macromolecules by two mechanisms: alkylation (with proteins and nucleic acids) and carbamoylation (with proteins but not nucleic acids). It has been suggested that the alkylating action is responsible for the therapeutic effects of nitrosoureas, and that the carbamoylation activity leads to toxicity effects. In order to reduce systemic toxicity and improve specificity and distribution for cancer therapy, 2-haloethyl nitrosourea has been esterified with modified steroids, which are used as biological platforms for transporting the alkylating agent to the tumor site in a specific manner. The cytogenetic and antineoplastic effect were studied of seven newly synthesized esters of N,N-bis(2-chloroethyl)alanyl carboxyl derivatives with a modified steroidal nucleus (compounds 1-7). As a very sensitive indicator of genotoxicity the Sister Chromatid Exchange (SCE) assay was used and as a valuable marker of cytostatic activity the cell Proliferation Rate Index (PRI) in cultures of normal human lymphocytes was used. The order of magnitude of the cytogenetic activity on a molar basis (15, 30, 120 microM) of the compounds was 7>6>3>5>2>4>1. The most active compound 7 has an enlarged (seven carbon atoms) A ring modified with a lactam group (-NHCO-) with the nitrosourea moiety esterified at position 17 In the group of seven substances a correlation was observed between the magnitude of SCE response and the depression in PRI (r=-O, 65, p6>2>5>4>3>1 and on lympocytic P388 leukemia cells is 7>2>6>5>4>3>1. The present results are in agreement with previous suggestions that the effectiveness in cytogenetic activity may well be correlated with antitumor effects [T/C: 248% for the compound 7 in 250 mg/kg b.w.; T/C: mean survival time of drug-treated animals (T) (excluding long term survivals) vs. corn-oil-treated controls (C)].

  2. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan.

    Science.gov (United States)

    Yoshida, Jin; Koda, Shigeki; Nishida, Shozo; Yoshida, Toshiaki; Miyajima, Keiko; Kumagai, Shinji

    2011-03-01

    The aim of the present study was to evaluate the measurement of contamination by antineoplastic drugs for safer handling of such drugs by medical workers. We investigated the relationship between the contamination level of antineoplastic drugs and the conditions of their handling. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A-E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the antineoplastic drugs were analyzed for CPA and Pt. Pt was detected from air samples inside BSC in hospital B. Antineoplastic drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of the air-conditioner filter in hospital A, and CPA was detected from that in hospital D. Cyclophosphamide was detected from urine samples of workers in hospitals B, D, and E. The contamination level of antineoplastic drugs was suggested to be related with the amount of drugs handled, cleaning methods of the equipment, and the skill level of the technique of maintaining negative pressure inside a vial. In order to reduce the contamination and exposure to antineoplastic drugs in the hospital work environment very close to zero, comprehensive safety precautions, including adequate mixing and cleaning methods was required in addition to BSC and closed system device.

  3. Histone deacetylase inhibitors: can we consider potent anti-neoplastic agents for the treatment of asthma?

    Science.gov (United States)

    Royce, Simon G; Ververis, Katherine; Karagiannis, Tom C

    2012-01-01

    Histone deacetylase inhibitors have emerged as a new class of anti-cancer therapeutics due to their potent anti-proliferative and apoptotic effects in malignant cells. Accumulating evidence is indicating that histone deacetylase inhibitors may also have potential clinical utility in non-oncological applications, including asthma. However, the potential of histone deacetylase inhibitors in asthma remains controversial. For example, the mechanisms of action of the broad-spectrum histone deacetylase inhibitor, Trichostatin A, in animal models of allergic airways disease are conflicting. Further, there is evidence suggesting potential problems associated with histone deacetylase 2 inhibition and conventional glucocorticosteroid therapy. Similarly, disparate findings are emerging following modulation of the class III, sirtuin 1 enzyme. Indeed, it is becoming apparent that the mechanism of action may not be related to histone deacetylase inhibition activity per se. Further, there is only limited evidence that these compounds possess anti-inflammatory effects in models of asthma. In this review, we provide an overview of the biology of the metal-dependent and sirtuin deacetylases in the context of asthma. The controversies surrounding the potential use of histone deacetylase inhibitors in asthma are discussed and future directions involving the investigation of more specific analogues are explored.

  4. 77 FR 41190 - Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare...

    Science.gov (United States)

    2012-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number NIOSH-190] Revised Document Posted: NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012, Correction AGENCY: National Institute for Occupational Safety and Health (NIOSH) of the...

  5. Comet assay as a human biomonitoring tool: application in occupational exposure to antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-05-01

    Occupational exposure to antineoplastic drugs is associated with genotoxic effects, although comet assay analyzed parameters were higher in exposed comparing with controls, were not significant. Also the study of the susceptibility biomarkers did not show statistical significant differences, the small size of our sample hampered the finding of a possible association, let alone a causality relationship.

  6. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy.

    Science.gov (United States)

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; Almeida, Ana Maria de; Gozzo, Thais de Oliveira

    2016-10-10

    to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. identificar os fatores relacionados ao diagnóstico de enfermagem náusea entre pacientes oncológicos durante o tratamento quimioterápico. revisão integrativa de quatro bases eletrônicas de dados (PUBMED, EMBASE, CINAHL e LILACS) com as palavras-chaves neoplasia, agentes antineoplásicos e náusea. dos 1258 artigos identificados, somente 30 atenderam aos critérios de inclusão. Os fatores relacionados mais frequentes foram: idade abaixo de 50 anos, doença do movimento, sexo feminino, potencial emético do quimioterápico, ansiedade, estímulo condicionado e expectativa de náuseas depois do tratamento. diante dos resultados encontrados e da incidência de náusea entre os pacientes oncológicos em tratamento quimioterápico, observa-se diferença importante entre as evidências encontradas e as utilizadas pela NANDA International, Inc. Apesar da definição estar adequada entre os fatores relacionados, não há menção à quimioterapia mesmo com inúmeros estudos, com diferentes delineamentos

  7. Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

    Science.gov (United States)

    Connor, Thomas H.; Lawson, Christina C.; Polovich, Martha; McDiarmid, Melissa A.

    2015-01-01

    Objectives Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods A structured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results While effect sizes varied with study size and population, occupational exposure to antineoplastic drugs appears to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time-to-pregnancy also suggested an increased risk for sub-fertility. Conclusions Antineoplastic drugs are highly toxic in patients receiving treatment and adverse reproductive effects have been well documented in these patients. Healthcare workers with chronic, low level occupational exposure to these drugs also appear to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered. PMID:25153300

  8. A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

    Directory of Open Access Journals (Sweden)

    Fangping Li

    2018-03-01

    Full Text Available Sepia ink polysaccharide (SIP isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami, cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.

  9. Dental root agenesis following radiation and antineoplastic therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Abdul Hafiz

    2016-01-01

    Full Text Available The survival rates of patients suffering from various childhood neoplasms have improved dramatically with the advent of chemo-radiation therapy. The harmful effects of chemo-radiation therapy in the oro-facial region such as root agenesis, short roots, impaired amelogenesis, dentinogenesis, radiation caries, and other soft tissue pathologies are well recognized. In spite of these documented risks, the antineoplastic treatment modalities continue to serve the patient for overall improvement in survival and quality of life. However, a thorough understanding of the growth and development process and its relation with the complex antineoplastic treatment is very important for all clinicians. Such awareness could significantly improve the status of patients in the posttreatment period with the implementation of proper preventive and interceptive measures. This article intends to document a case of root agenesis that developed secondary to chemo-radiation therapy in a 12-year-old girl.

  10. Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon

    Directory of Open Access Journals (Sweden)

    Astha Varma

    2011-01-01

    Full Text Available Plant-derived natural products occupy an important position in the area of cancer chemotherapy. Molecules such as vincristine, vinblastine, paclitaxel, camptothecin derivatives, epipodophyllotoxin, and so forth, are invaluable contributions of nature to modern medicine. However, the quest to find out novel therapeutic compounds for cancer treatment and management is a never-ending venture; and diverse plant species are persistently being studied for identification of prospective anticancer agents. In this regard, Andrographis paniculata Nees, a well-known plant of Indian and Chinese traditional system of medicines, has drawn attention of researchers in recent times. Andrographolide, the principal bioactive chemical constituent of the plant has shown credible anticancer potential in various investigations around the globe. In vitro studies demonstrate the capability of the compound of inducing cell-cycle arrest and apoptosis in a variety of cancer cells at different concentrations. Andrographolide also shows potent immunomodulatory and anti-angiogenic activities in tumorous tissues. Synthetic analogues of the compound have also been created and analyzed, which have also shown similar activities. Although it is too early to predict its future in cancer chemotherapy, the prologue strongly recommends further research on this molecule to assess its potential as a prospective anticancer agent.

  11. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  12. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde

    Czech Academy of Sciences Publication Activity Database

    Mušák, L.; Šmerhovský, Z.; Halásová, E.; Osina, O.; Letková, L.; Vodičková, Ludmila; Poláková, Veronika; Buchancová, J.; Hemminki, K.; Vodička, Pavel

    2013-01-01

    Roč. 39, č. 6 (2013), s. 618-630 ISSN 0355-3140 Grant - others:MŠVV(SK) 26220220111; UK(SK) 1/0576/10 VEGA; MZd(SK) 2007/48-UK-13; GA MŠMT(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 Keywords : anesthesiologist * antineoplastic drug * chromosomal aberration Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.095, year: 2013

  13. Toxicity classification and evaluation of four pharmaceuticals classes: antibiotics, antineoplastics, cardiovascular, and sex hormones

    International Nuclear Information System (INIS)

    Sanderson, Hans; Brain, Richard A.; Johnson, David J.; Wilson, Christian J.; Solomon, Keith R.

    2004-01-01

    Four different classes of environmental concern are quantitatively and qualitatively assessed for environmental hazards; antibiotics (n = 226), antineoplastics (n = 81), cardiovascular (n = 272), and sex hormones (n 92). These along with an ECOSAR scan of all pharmaceuticals (n = 2848) were then classified according to the OECD aquatic toxicity classification system. The predicted species susceptibility is: daphnid > fish > algae, and the predicted rank order of relative toxicity: sex hormones > cardiovascular antibiotics > antineoplastics (Table 1). Generally, a relatively large proportion (1/3) of all pharmaceuticals are potentially very toxic to aquatic organisms (Table 2). The qualitative risk assessment ranking relative to probability and potential severity for human and environmental health effects is: antibiotics > sex hormones > cardiovascular > antineoplastics. (Q)SARs and pharmacodynamic information should be used to prioritize and steer experimental risk assessments of pharmaceuticals, and potentially, also be used in new drug discovery optimizing efficacy and in minimising environmental hazards of new products. Nuclear receptors are relatively well conserved in evolution. Currently, antibacterial resistance represents the most significant human health hazard, and potentially the largest non-target organism hazard is sex hormones acting as endocrine modulators in wildlife. Data for the individual compounds are accessible via http://www.uoguelph.ca/~hsander/

  14. Cardiotoxicity of copper-based antineoplastic drugs casiopeinas is related to inhibition of energy metabolism

    International Nuclear Information System (INIS)

    Hernandez-Esquivel, Luz; Marin-Hernandez, Alvaro; Pavon, Natalia; Carvajal, Karla; Moreno-Sanchez, Rafael

    2006-01-01

    Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based antineoplastic drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O 2 consumption with half-maximal inhibitory concentrations (IC 5 ) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC 5 = 2.6 μM), a well-known potent cardiotoxic and antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new antineoplastic drugs with milder secondary toxic effects than proven drugs such as adriamycin

  15. Changes in the chemical composition of mineralised teeth in children after antineoplastic treatment.

    Science.gov (United States)

    Krasuska-Sławińska, Ewa; Dembowska-Bagińska, Bożenna; Brożyna, Agnieszka; Olczak-Kowalczyk, Dorota; Czarnowska, Elżbieta; Sowińska, Agnieszka

    2018-01-01

    Chemotherapy, neoplasms, and their complications linked to malabsorption, malnutrition, and metabolic disorders may lead to improper tooth development and frequent severe caries in patients during/after antineoplastic treatment and to a more frequent improper tooth development in patients undergoing chemotherapy during odontogenesis. However, the causes of these abnormalities remain unknown; there are no studies on the impact of antineoplastic treatment and its complications on the chemical composition of mineralised teeth. To compare the chemical composition of mineralised teeth extracted due to complicated caries in children after chemotherapy, and of teeth extracted due to orthodontic treatment in generally healthy children. The treatment group included five teeth extracted due to complicated caries in children after antineoplastic treatment. The control group included five teeth extracted due to orthodontic treatment in generally healthy children. The chemical composition of enamel, dentine, cementum, interior of the canal, and enamel abnormalities in teeth extracted from patients after chemotherapy and in generally healthy patients were assessed with energy-dispersive X-ray spectroscopy. Results were analysed statistically. The magnesium (Mg) and zinc (Zn) mass contents in the enamel of patients after chemotherapy increased and so did the calcium (Ca) to phosphorus (P) ratio when compared to controls. Areas with abnormal enamel in patients after chemotherapy had lower concentrations of Ca and P, and higher concentrations of trace elements (Mg, Cl, and Na). The levels of the assessed elements in dentine, cementum, and inside the canal were similar in both groups of teeth.

  16. Comparative efficacy of a phytogenic feed additive and an antibiotic growth promoter on production performance, caecal microbial population and humoral immune response of broiler chickens inoculated with enteric pathogens

    Directory of Open Access Journals (Sweden)

    Toshi Wati

    2015-09-01

    Full Text Available The aim of this work was to compare the efficacy of a commercially available phytogenic feed additive (PFA and an antibiotic growth promoter, which was bacitracin methylene disalicylate (BMD, on performance, nutrient retention, caecal colonization of bacteria and humoral immune responses against Newcastle disease in broiler chickens challenged orally with Salmonella enteritidis and Escherichia coli. One-day-old male Cobb 400 broiler chicks (n = 120 were fed with 1 a negative control (NC diet, which is the basal diet without any added growth promoter, 2 a positive control (PC diet, the basal diet supplemented with BMD, 500 mg/kg and 3 a diet supplemented with PFA (150 mg/kg for 39 days and the birds were inoculated with S. enteritidis and E. coli on d 28. Supplementation of PFA improved body weight, feed conversion ratio, retention of N and crude fiber, increased fecal moisture content and decreased digesta transit time as compared with the NC and PC groups (P < 0.01. Both the PC and the PFA was found to be equally effective in controlling the surge in numbers of Salmonella and E. coli following oral inoculation of these bacteria as compared with the NC group (P < 0.05 at 24 h past inoculation. Caecal content analysis on d 39 indicated lower numbers of Salmonella, E. coli and Clostridium in the PC and PFA groups as compared with the NC group (P < 0.05. The number of Lactobacillus in the PFA group was higher than those in the NC and PC groups (P < 0.05. Humoral immune response, measured as hemagglutination inhibition titer against Newcastle disease, was better in the PC and PFA groups compared with the NC group (P < 0.05 at d 21 but the difference did not last till d 39. The heterophil to lymphocyte ratio was narrower (P < 0.001 and alkaline phosphatase activity was higher (P < 0.01 in the PFA group as compared with the NC and PC groups on d 39. It was concluded that the PFA, which is animal, environment and consumer friendly, may be used as an

  17. Extraction and Isolation of Antineoplastic Pristimerin from Mortonia greggii (Celastraceae).

    Science.gov (United States)

    Mejia-Manzano, Luis Alberto; Barba-Dávila, Bertha A; Gutierrez-Uribe, Janet A; Escalante-Vázquez, Edgardo J; Serna-Saldivar, Sergio O

    2015-11-01

    The aim of this research was to identify, extract and isolate pristimerin in leaves, stems and roots of the Mexican plant Mortonia greggii (Celastraceae). The principal objective was to determine the best laboratory experimental conditions for the extraction and isolation of this powerful natural anticancer agent from the root tissue. Six experimental factors in solid-liquid pristimerin extraction were analyzed: solvent systems, number of extractions, ratio of plant weight (g)/solvent volume (mL) used, time of extraction, temperature and agitation. A mathematical model was generated for pristimerin purity and yield. Ethanol, first extraction, 0.5 ratio of plant weight/solvent volume (g/mL), 0.5 h, 200 rpm and 49.7°C were optimal conditions for the extraction of this phytochemical. The degree of purification of pristimerin root extract was studied by size-exclusion chromatography (SEC) using Sephadex LH-20 reaching fractions with purification indexes (PI) greater than 2 and recoveries of 28.3%. When fractions with purification indices higher than 1 and less than 2 were accumulated, the recovery of pristimerin increased by about 73.6%. By combining the optimum extracts and SEC purification protocols, an enriched fraction containing 245.6 mg pristimerin was obtained from 100 g of root bark, representing about 14.4%, w/w, pristimerin from the total solids presented in the fraction.

  18. 90Y Colchicine: an attempt to prepare a tumor radiotherapeutic agent

    International Nuclear Information System (INIS)

    Korde, Aruna; Satpati, Drishty; Pandey, Usha; Banerjee, Sharmila; Venkatesh, Meera

    2006-01-01

    Colchicine, an alkaloid occurring in the seeds of the plant Colchicum autumnale has been used for the treatment of acute gout. Colchicine binds to microtubules and exhibits antimitotic action in dividing cells. Various structural modifications of colchicine moiety have been studied with an aim to identify an antineoplastic agent with reduced toxicity

  19. Evaluation of respiration of mitochondria in cancer cells exposed to mitochondria-targeted agents.

    Czech Academy of Sciences Publication Activity Database

    Klučková, Katarína; Dong, L. F.; Bajziková, Martina; Rohlena, Jakub; Neužil, Jiří

    2015-01-01

    Roč. 1265, 07 Oct 2015 (2015), s. 181-194 ISSN 1940-6029 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Animals * Antineoplastic Agents * drug effects * *pharmacology Subject RIV: EB - Genetics ; Molecular Biology

  20. Stability of allopurinol and of five antineoplastics in suspension.

    Science.gov (United States)

    Dressman, J B; Poust, R I

    1983-04-01

    The stability of allopurinol, azathioprine, chlorambucil, melphalan, mercaptopurine, and thioguanine each in an extemporaneously prepared suspension was studied. Tablets of each drug were crushed, mixed with a suspending agent, and brought to a final volume of 10, 15, or 20 ml with a 2:1 mixture of simple syrup and wild cherry syrup. Suspensions were prepared in the following concentrations: allopurinol (20 mg/ml), azathioprine (50 mg/ml), chlorambucil (2 mg/ml), melphalan (2 mg/ml), mercaptopurine (50 mg/ml), and thioguanine (40 mg/ml). Using high-performance liquid chromatography or ultraviolet scans, duplicate assays were performed on each suspension periodically during storage for up to 84 days at ambient room temperature or 5 degrees C. The time required for the suspensions to drop below 90% of labeled strength was used as an indicator of drug stability. Allopurinol and azathioprine were stable for at least 56 days at room temperature and at 5 degrees C. Chlorambucil decomposed rapidly at room temperature but was stable for seven days when stored at 5 degrees C. Melphalan suspensions did not meet the stated criteria for stability even at the time of initial assay. Mercaptopurine and thioguanine were stable for 14 and 84 days, respectively, at room temperature; at 5 degrees C, assay values dropped below those obtained at room temperature. In the suspension formulation tested, allopurinol, azathioprine, mercaptopurine, and thioguanine are stable for at least 14 days at room temperature; chlorambucil suspensions should be refrigerated and discarded after seven days. Melphalan decomposes too rapidly to make this suspension formulation feasible for extemporaneous compounding.

  1. [Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service].

    Science.gov (United States)

    Pacheco Ramos, María de la Paz; Arenaza Peña, Ainhoa Elisa; Santiago Pérez, Alejandro; Bilbao Gómez-Martino, Cristina; Zamora Barrios, María Dolores; Arias Fernández, María Lourdes

    2015-05-01

    To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months). 2- Usage period (22 months). On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation's errors. 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133) of the errors were identified by the robot and therefore didn't reach the patient (negative desviation - 4%). These errors were corrected manually. The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. Implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service

    Directory of Open Access Journals (Sweden)

    María de la Paz Pacheco Ramos

    2015-01-01

    Full Text Available Objective: To describe the implementation of a robot for the preparation of antineoplastic drugs in the Pharmacy Service and to be able to analyze the added value to pharmacotherapy. Methods: The implementation was carried out in June 2012 at a tertiary level Hospital, taking place in two periods: 1- test period with the installation of the robot, with technical configuration of the equipment and validation of 29 active ingredients and the integration of electronic prescribing software with the robot application (9 months. 2- Usage period (22 months. On the other hand, training was given to pharmacists and nurses. The robot uses image recognition, barcode identification and gravimetric controls for proper operation. These checks provide information about the error ratio in the preparation, with a margin of ± 10%, which after a pilot study was restricted to a range of ±4%. The robot was programmed to recognize bags, infusion pumps, syringes and vials. The added value was assessed for 31 months by identifying preparation´s errors. Results: 11,865 preparations were made by the robot, which meant approximately 40% of all antineoplastic prepared from 29 different active ingredients. 1.12% (n=133 of the errors were identified by the robot and therefore didn´t reach the patient (negative desviation - 4%. These errors were corrected manually. Conclusion: The implementation of a robot in the preparation of antineoplastic drugs allows to identify errors therefore preventing them to arrive to the patient. This promotes safety and quality of the process, reducing the exposure to cytotoxic drugs from the manipulator

  3. New approaches to wipe sampling methods for antineoplastic and other hazardous drugs in healthcare settings.

    Science.gov (United States)

    Connor, Thomas H; Smith, Jerome P

    2016-09-01

    At the present time, the method of choice to determine surface contamination of the workplace with antineoplastic and other hazardous drugs is surface wipe sampling and subsequent sample analysis with a variety of analytical techniques. The purpose of this article is to review current methodology for determining the level of surface contamination with hazardous drugs in healthcare settings and to discuss recent advances in this area. In addition it will provide some guidance for conducting surface wipe sampling and sample analysis for these drugs in healthcare settings. Published studies on the use of wipe sampling to measure hazardous drugs on surfaces in healthcare settings drugs were reviewed. These studies include the use of well-documented chromatographic techniques for sample analysis in addition to newly evolving technology that provides rapid analysis of specific antineoplastic. Methodology for the analysis of surface wipe samples for hazardous drugs are reviewed, including the purposes, technical factors, sampling strategy, materials required, and limitations. The use of lateral flow immunoassay (LFIA) and fluorescence covalent microbead immunosorbent assay (FCMIA) for surface wipe sample evaluation is also discussed. Current recommendations are that all healthc a re settings where antineoplastic and other hazardous drugs are handled include surface wipe sampling as part of a comprehensive hazardous drug-safe handling program. Surface wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. New technology, although currently limited in scope, may make wipe sampling for hazardous drugs more routine, less costly, and provide a shorter response time than classical analytical techniques now in use.

  4. Toxic agents causing cerebellar ataxias.

    Science.gov (United States)

    Manto, Mario

    2012-01-01

    The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening. 2012 Elsevier B.V. All rights reserved.

  5. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  6. Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

    Directory of Open Access Journals (Sweden)

    Coppola C

    2016-11-01

    Full Text Available Carmela Coppola,1 Gennaro Riccio,1 Antonio Barbieri,2 Maria Gaia Monti,3 Giovanna Piscopo,1 Domenica Rea,2 Claudio Arra,2 Carlo Maurea,1 Claudia De Lorenzo,4,5 Nicola Maurea1 1Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 2Animal Facility Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, IRCCS, Naples, Italy; 3Department of Translational Medical Sciences, University Federico II, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy; 5CEINGE Biotecnologie Avanzate, Naples, Italy Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage.Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response.Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01. Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional

  7. Aryl sulfonate based anticancer alkylating agents.

    Science.gov (United States)

    Sheikh, Hamdullah Khadim; Arshad, Tanzila; Kanwal, Ghazala

    2018-05-01

    This research work revolves around synthesis of antineoplastic alkylating sulfonate esters with dual alkylating sites for crosslinking of the DNA strands. These molecules were evaluated as potential antineoplastic cross linking alkylating agents by reaction with the nucleoside of Guanine DNA nucleobase at both ends of the synthesized molecule. Synthesis of the alkylating molecules and the crosslinking with the guanosine nucleoside was monitored by MALDITOF mass spectroscopy. The synthesized molecule's crosslinking or adduct forming rate with the nucleoside was compared with that of 1,4 butane disulfonate (busulfan), in form of time taken for the appearance of [M+H] + . It was found that aryl sulfonate leaving group was causing higher rate of nucleophilic attack by the Lewis basic site of the nucleobase. Furthermore, the rate was also found to be a function of electron withdrawing or donating nature of the substituent on the aryl ring. Compound with strong electron withdrawing substituent on the para position of the ring reacted fastest. Hence, new alkylating agents were synthesized with optimized or desired reactivity.

  8. Treatment of mice with a novel antineoplastic agent taxol before irradiation increases the frequency of micronuclei in the bone marrow

    International Nuclear Information System (INIS)

    Jagetia, Ganesh Chandra; Nayak, Vijayashree

    1995-01-01

    The frequency of micronucleated polychromatic erythrocytes (MPCE) and the normochromatic erythrocytes (MNCE) and polychromatic and normochromatic erythrocyte ratio (P/N ratio) was studied at 12, 24 and 36 h postirradiation in the bone marrow of male mice treated or not with taxol before exposure to 0-4 Gy of 60 Co gamma radiation. The frequency of MPCE increased with the increase in radiation dose in a dose-related manner in the irradiated control group. A peak frequency of MPCE was observed at 24 h postirradiation in irradiated control group. The pattern of increase in MNCE was similar to that of MPCE except that a highest number of MNCE was scored at 36 h postirradiation. Taxol administration to animals before irradiation resulted in a significant elevation in the frequency of MPCE and MNCE at all the postirradiation time periods studied. This increase was dose related as observed in the irradiated control group. Irradiation resulted in a dose-dependent decline in the P/N ratio at all the postirradiation time periods studied. The P/N ratio was significantly lower in the taxol+irradiated group compared to the irradiated control group at all postirradiation time periods. A maximum decline in P/N ratio was observed at 36 h postirradiation for both irradiated control and taxol+irradiated groups. The dose response for MPCE, MNCE and P/N ratio was linear quadratic for both the irradiated and taxol+irradiated groups

  9. Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models.

    Science.gov (United States)

    Pal, Shipra; Sadhu, Arpita Sengupta; Patra, Swarup; Mukherjea, Kalyan K

    2008-11-12

    Cisplatin, a platinum based anticancer drug has played a vital role in the treatment of cancers by chemical agents, but in view of the serious toxicity including nephrotoxicity of cisplatin, various other platinum based drugs have been synthesized and screened to overcome its toxicity. A Pt-ATP compound was prepared in our laboratory hoping to have reduced or no toxicity along with the potentiality of reducing neoplasm growth. A Pt-ATP compound was prepared. It was first screened for its antineoplastic efficacy. Confirming that, subsequent experiments were carried on to test its toxicity on animals, viz. Albino Swiss mice. The animals were randomly divided into four sets--Set I: Erhlich Ascites Carcinoma (EAC) challenged mice; Set II: Normal mice; Set III: Drug treated mice, Set IVA Cisplatin (CDDP) treated mice, Set IV B EAC challenged Cisplatin treated mice. Set I was used to test antineoplasticity of the drug, Set II and Set III for studying drug toxicity and Set IV was treated with CDDP. Set II was used as a control. Animals were sacrificed after 5 days, 10 days 15 days and 20 days of drug administration on the 6th, 11th, 16th and 21st days respectively for Set I, II and III. Set IVA was sacrificed only on the 16th day and Set IV B on 6th and 11th days. For Set I only tumor cell count and packed cell volume (PCV) of tumor cells were recorded. For Set II and III, aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. For cytotoxicity assessment liver, spleen and kidney tissues were collected and subjected to scanning electron microscopy (SEM) after extensive treatment. Set IV A was only studied for the biochemical parameters viz. aspartate aminotransferase (AST), alanine aminotransferase (ALT) assays were done using serum while blood creatinine and creatine were assayed from blood filtrate. Set IV B was studied for tumor cell count after treatment with

  10. Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

    Science.gov (United States)

    Dranitsaris, G; Altmayer, C; Quirt, I

    1997-06-01

    Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

  11. French Health Technology Assessment of Antineoplastic Drugs Indicated in the Treatment of Solid Tumours: Perspective for Future Trends.

    Science.gov (United States)

    Chouaid, Christos; Borget, Isabelle; Braun, Eric; Bazil, Marie-Laure; Schaetz, Dominique; Rémuzat, Cécile; Toumi, Mondher

    2016-08-01

    France is one of the European countries that spend the most on oncology drugs. To keep pharmaceutical expenditure under control, Health Authorities highly scrutinize market access of costly medicines. To assess current and future trends in French health technology assessment (HTA) of antineoplastic drugs indicated in the treatment of solid tumours. A review of the SMR and ASMR drivers of the Transparency Committee (CT) opinions issued for antineoplastic drugs indicated in the treatment of solid tumours and approved between 2009 and 2014 was performed to assess current trends in French health technology assessment (HTA), complemented by an expert board consultation to capture the critical issues on the future of antineoplastic drugs HTA. Thirty-one drugs indicated for the treatment of solid tumours were identified (77 % targeted therapies). Initial CT assessments were available for 26 drugs. Four key items in the CT assessment were identified: 1) Clinical trial methodology; 2) Acceptance of progression-free survival (PFS) as a valuable endpoint; 3) Transferability of clinical trials in clinical practice; 4) Unpredictability of CT decisions. Experts raised the important development of personalised medicines in oncology and key challenges for oncology products to generate information expected from HTA perspective. The French system remains committed to its values and philosophy (access of all innovations for everybody) which are threatened by the increasing launch of innovative therapies and budget constraint. Both HTA decision framework evolution and revision of the current pricing process should be considered in France to cope with these new challenges.

  12. Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone

    Directory of Open Access Journals (Sweden)

    М. R. Fil

    2014-12-01

    Full Text Available Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, “hybrid” 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM. It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

  13. Use of oral antineoplastic in special situations in a third level hospital: real life results

    Directory of Open Access Journals (Sweden)

    José Miguel Ferrari-Piquero

    2018-01-01

    Full Text Available Objective: To analyse the effectiveness and safety of oral antineoplastic drugs (ANEOs that are authorized in special situations in a third-level hospital and to compare the results obtained with the clinical evidence used for this authorization. Method: Descriptive observational and retrospective study. We included all adult patients who started treatment with ANEO in special situations during the year 2016. We collected demographic, treatment-related and clinical variables (overall survival (OS, progression-free survival (PFS. Adverse reactions and detected interactions were collected. An unadjusted comparison was made between the results of the available evidence and those of the study patients. Results: 34 patients were treated, 50% were men, the median age was 58 years (38-80 and they presented ECOG 1 in 64.7%. Most of the treated patients were diagnosed with advanced colorectal cancer, treated with trifluridine-tipiracil, followed by palbociclib in breast cancer, obtaining results similar to those of the evidence. The median PFS was 2.8 months (95% CI 0.8- 4.8 and the 8-month SG (95% CI 3.4-12.5 for all patients. 26% of patients required dose reduction because of treatment toxicity. We found 13 interactions, which affected 15 patients, only two of category X. Conclusions: The effectiveness of ANEO in special situations in our center is similar to that of available evidence. The impact on survival is low and adverse effects are common.

  14. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    International Nuclear Information System (INIS)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua; Pollak, Michael; Gotlieb, Walter H.

    2011-01-01

    Highlights: ► siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. ► Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. ► Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. ► Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  15. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides

    Energy Technology Data Exchange (ETDEWEB)

    Segal, Eric D.; Yasmeen, Amber; Beauchamp, Marie-Claude; Rosenblatt, Joshua [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Pollak, Michael [Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada); Gotlieb, Walter H., E-mail: walter.gotlieb@mcgill.ca [Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Segal Cancer Center, Lady Davis Institute of Medical Research, McGill University, Montreal, Quebec (Canada); Department of Oncology, McGill University, Montreal, Quebec (Canada)

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer siRNA knockdown of OCT1 reduced sensitivity of EOC cells to metformin, but not to another biguanide, phenformin. Black-Right-Pointing-Pointer Suppression of OCT1 also affects the activation of AMP kinase in response to metformin, but not to phenformin. Black-Right-Pointing-Pointer Direct actions of metformin may be limited by low OCT1 expression in EOC tumors. Black-Right-Pointing-Pointer Phenformin could be used as an alternative biguanide. -- Abstract: Epidemiologic and laboratory data suggesting that metformin has antineoplastic activity have led to ongoing clinical trials. However, pharmacokinetic issues that may influence metformin activity have not been studied in detail. The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. We observed that there is heterogeneity between primary human tumors with respect to OCT1 expression. These results suggest that there may be settings where drug uptake limits direct action of metformin on neoplastic cells, raising the possibility that metformin may not be the optimal biguanide for clinical investigation.

  16. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  17. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    Grau, C.

    1994-01-01

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

  18. Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients

    International Nuclear Information System (INIS)

    Monroy-Cisneros, Karina; Esparza-Romero, Julián; Valencia, Mauro E.; Guevara-Torres, Alfonso G.; Méndez-Estrada, Rosa O.; Anduro-Corona, Iván; Astiazarán-García, Humberto

    2016-01-01

    Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm 2 in femoral neck and 0.063 g/cm 2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm 2 in femoral neck and 0.035 g/cm 2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm 2 (p = 0.003). The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status

  19. The husk fiber of Cocos nucifera L. (Palmae) is a source of anti-neoplastic activity.

    Science.gov (United States)

    Koschek, P R; Alviano, D S; Alviano, C S; Gattass, C R

    2007-10-01

    In the present study, we investigated the in vitro anti-tumoral activities of fractions from aqueous extracts of the husk fiber of the typical A and common varieties of Cocos nucifera (Palmae). Cytotoxicity against leukemia cells was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cells (2 x 10(4)/well) were incubated with 0, 5, 50 or 500 microg/mL high- or low-molecular weight fractions for 48 h, treated with MTT and absorbance was measured with an ELISA reader. The results showed that both varieties have almost similar antitumoral activity against the leukemia cell line K562 (60.1 +/- 8.5 and 47.5 +/- 11.9% for the typical A and common varieties, respectively). Separation of the crude extracts with Amicon membranes yielded fractions with molecular weights ranging in size from 1-3 kDa (fraction A) to 3-10 kDa (fraction B) and to more than 10 kDa (fraction C). Cells were treated with 500 microg/mL of these fractions and cytotoxicity was evaluated by MTT. Fractions ranging in molecular weight from 1-10 kDa had higher cytotoxicity. Interestingly, C. nucifera extracts were also active against Lucena 1, a multidrug-resistant leukemia cell line. Their cytotoxicity against this cell line was about 50% (51.9 +/- 3.2 and 56.3 +/- 2.9 for varieties typical A and common, respectively). Since the common C. nucifera variety is extensively cultured in Brazil and the husk fiber is its industrial by-product, the results obtained in the present study suggest that it might be a very inexpensive source of new antineoplastic and anti-multidrug resistant drugs that warrants further investigation.

  20. Use of oral antineoplastic in special situations in a third level hospital: real life results.

    Science.gov (United States)

    Garcia-Muñoz, Carmen; Rodriguez-Quesada, Pedro Pablo; Ferrari-Piquero, José Miguel

    2018-01-01

    To analyse the effectiveness and safety of oral antineoplastic drugs  (ANEOs) that are authorized in special situations in a third-level hospital and to  compare the results obtained with the clinical evidence used for this  authorization. Descriptive observational and retrospective study. We included all  adult patients who started treatment with ANEO in special situations during the  year 2016. We collected demographic, treatment-related and clinical variables  (overall survival (OS), progression-free survival (PFS)). Adverse reactions and  detected interactions were collected. An unadjusted comparison was made  between the results of the available evidence and those of the study patients. 34 patients were treated, 50% were men, the median age was 58  years (38-80) and they presented ECOG 1 in 64.7%. Most of the treated  patients were diagnosed with advanced colorectal cancer, treated with  trifluridine-tipiracil, followed by palbociclib in breast cancer, obtaining results  similar to those of the evidence. The median PFS was 2.8 months (95% CI 0.8- 4.8) and the 8-month SG (95% CI 3.4-12.5) for all patients. 26% of patients  required dose reduction because of treatment toxicity. We found 13 interactions,  which affected 15 patients, only two of category X. The effectiveness of ANEO in special situations in our center is  similar to that of available evidence. The impact on survival is low and adverse  effects are common. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

    Science.gov (United States)

    Bontempo, P; Doto, A; Miceli, M; Mita, L; Benedetti, R; Nebbioso, A; Veglione, M; Rigano, D; Cioffi, M; Sica, V; Molinari, A M; Altucci, L

    2012-02-01

    Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation. © 2011 Blackwell Publishing Ltd.

  2. The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.

    Science.gov (United States)

    Ehrhardt, Michael; Craveiro, Rogerio B; Velz, Julia; Olschewski, Martin; Casati, Anna; Schönberger, Stefan; Pietsch, Torsten; Dilloo, Dagmar

    2018-04-01

    Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi-kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment. Indeed, our results delineate anti-neoplastic activity of Axitinib in medulloblastoma cell lines modelling the most aggressive c-myc-amplified Non-WNT/Non-SHH and SHH-TP53-mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in marked inhibition of proliferation and profound induction of cell death. The differential efficacy of Axitinib is in line with target expression of medulloblastoma cells identifying VEGFR 1/2, PDGFR α/β and c-kit as potential markers for drug application. The high specificity of Axitinib and the consequential low impact on the haematopoietic and immune system render this drug ideal multi-modal treatment approaches. In this context, we demonstrate that the clinically available PI3K inhibitor GDC-0941 enhances the anti-neoplastic efficacy of Axitinib against c-myc-amplified medulloblastoma. Our findings provide a rational to further evaluate Axitinib alone and in combination with other therapeutic agents for the treatment of most aggressive medulloblastoma subtypes. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture

    OpenAIRE

    Deng, Liting; Ng, Lindsay; Ozawa, Tatsuya; Stella, Nephi

    2017-01-01

    Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mo...

  4. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  5. Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2017-03-01

    One molecular-based approach that increases potency and reduces dose-limited sequela is the implementation of selective 'targeted' delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine-monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine-reactive gemcitabine-(5'-phosphorylimidazolide) intermediate. Monoclonal anti-IGF-1R immunoglobulin was combined with gemcitabine-(5'-phosphorylimidazolide) resulting in the synthetic formation of gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]. The gemcitabine molar incorporation index for gemcitabine-(5'-phosphoramidate)-[anti-IGF-R1] was 2.67:1. Cytotoxicity Analysis - dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine-equivalent concentrations of 10 -9  M and 10 -7  M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine-reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non-dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

  6. To Take or Not to Take With Meals? Unraveling Issues Related to Food Effects Labeling for Oral Antineoplastic Drugs.

    Science.gov (United States)

    Deng, Jiexin; Brar, Satjit S; Lesko, Lawrence J

    2017-12-02

    There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models. In 2000-2009, 80% (4 out of 5) of all approved oral antineoplastics with increased bioavailability in the fed state were labeled as "take on empty stomach." In contrast, we found that in 2010-2016 there is a greater diversity in food recommendations for drugs with increased bioavailability in the fed state. Currently, many oral oncology drugs are given with food to maximize their bioavailability; however, as seen from our case study of sonidegib, failure to fully adhere to label recommendations to either take with food or not could lead to adverse consequences in terms of safety and efficacy. © 2017, The American College of Clinical Pharmacology.

  7. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  8. Antineoplastic Activities of MT81 and Its Structural Analogue in Ehrlich Ascites Carcinoma-Bearing Swiss Albino Mice

    Directory of Open Access Journals (Sweden)

    Sujata Maiti Choudhury

    2010-01-01

    Full Text Available Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin, a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p. at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST, increased life span (ILS, tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA and reduced glutathione (GSH content, and by the activity of superoxide dismutase (SOD and catalase (CA T. MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

  9. Oncogenic targets, magnitude of benefit, and market pricing of antineoplastic drugs.

    Science.gov (United States)

    Amir, Eitan; Seruga, Bostjan; Martinez-Lopez, Joaquin; Kwong, Ryan; Pandiella, Atanasio; Tannock, Ian F; Ocaña, Alberto

    2011-06-20

    The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the U.S. Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.

  10. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  11. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

    Directory of Open Access Journals (Sweden)

    Gelatti Umberto

    2011-03-01

    Full Text Available Abstract Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes and on the exposed nurses' clothes (pads. The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases will also be analysed. Using standardized questionnaires

  12. Chemical Agents

    Science.gov (United States)

    ... CR) see Riot Control Agents Digitalis Distilled mustard (HD) see Sulfur mustard E Ethylene glycol F Fentanyls and other opioids H Hydrazine Hydrofluoric acid (hydrogen fluoride) Hydrogen chloride Hydrogen cyanide (AC) Hydrogen ...

  13. Podophyllotoxin: a novel potential natural anticancer agent

    Directory of Open Access Journals (Sweden)

    Hamidreza Ardalani

    2017-06-01

    Full Text Available Objective: The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes. Materials and Methods: Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016. Results: PTOX is an important plant-derived natural product, has derivatives such as etoposide and teniposide, which have been used as therapies for cancers and venereal wart. PTOX structure is closely related to the aryltetralin lactone lignans that have antineoplastic and antiviral activities. Podophyllum emodi Wall. (syn. P. hexandrum and Podophyllum peltatum L. (Berberidaceae are the major sources of PTOX. It has been shown that ferulic acid and methylenedioxy substituted cinnamic acid are the enzymes involved in PTOX synthesis. PTOX prevents cell growth via polymerization of tubulin, leading to cell cycle arrest and suppression of the formation of the mitotic-spindles microtubules.   Conclusion: Several investigations have been performed in biosynthesis of PTOX such as cultivation of these plants, though they were unsuccessful. Thus, it is important to find alternative sources to satisfy the pharmaceutical demand for PTOX. Moreover, further preclinical studies are warranted to explore the molecular mechanisms of these agents in treatment of cancer and their possible potential to overcome chemoresistance of tumor cells.

  14. Podophyllotoxin: a novel potential natural anticancer agent

    Science.gov (United States)

    Ardalani, Hamidreza; Avan, Amir; Ghayour-Mobarhan, Majid

    2017-01-01

    Objective: The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX) as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes. Materials and Methods: Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016. Results: PTOX is an important plant-derived natural product, has derivatives such as etoposide and teniposide, which have been used as therapies for cancers and venereal wart. PTOX structure is closely related to the aryltetralin lactone lignans that have antineoplastic and antiviral activities. Podophyllum emodi Wall. (syn. P. hexandrum) and Podophyllum peltatum L. (Berberidaceae) are the major sources of PTOX. It has been shown that ferulic acid and methylenedioxy substituted cinnamic acid are the enzymes involved in PTOX synthesis. PTOX prevents cell growth via polymerization of tubulin, leading to cell cycle arrest and suppression of the formation of the mitotic-spindles microtubules. Conclusion: Several investigations have been performed in biosynthesis of PTOX such as cultivation of these plants, though they were unsuccessful. Thus, it is important to find alternative sources to satisfy the pharmaceutical demand for PTOX. Moreover, further preclinical studies are warranted to explore the molecular mechanisms of these agents in treatment of cancer and their possible potential to overcome chemoresistance of tumor cells. PMID:28884079

  15. Inciting and etiologic agents of colitis.

    Science.gov (United States)

    Silva, J; Fekety, R; Werk, C; Ebright, J; Cudmore, M; Batts, D; Syrjamaki, C; Lukens, J

    1984-01-01

    Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 ml per day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxic drugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

  16. Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

    OpenAIRE

    Maree, M. David; Neuse, Eberhard W.; Erasmus, Elizabeth; Swarts, Jannie C.

    2007-01-01

    The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymer...

  17. Interactions of radiation repair systems in escherichia colt with antineoplastic anthracyclines

    International Nuclear Information System (INIS)

    Kacinski, B.M.; Rupp, W.D.

    1984-01-01

    The authors have studied the interactions of several anthracylines with the UVR DN*a repair system of E. coli. The authors found that doxorubicin is quite toxic for uvr- but not for uvr+strains. They also found that exposure of cells carrying a multicopy plasmid to this agent yielded plasmid DNA molecules with lesions which were recognized and cleaved by purified E. coli UVRABC DNA repair endonuclease. A derivative of doxorubicin was not measurably toxic for either uvr+ or uvr- strains but nevertheless produced lesions which were substrates for the UVRABC endonuclease. The authors propose that anthracycline toxicity in uvr- E. coli may correlate with clinical toxicity while anthracylcine antineopolastic activity may correlate with their ability to produce UVRABC endonuclease-sensitive DNA damage

  18. Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

    Science.gov (United States)

    Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

    2016-01-01

    Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

  19. Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy.

    Science.gov (United States)

    Leite Cavalcanti, Alessandro; José de Macêdo, Dário; Suely Barros Dantas, Fernanda; Dos Santos Menezes, Karla; Filipe Bezerra Silva, Diego; Alves de Melo Junior, William; Fabia Cabral Cavalcanti, Alidianne

    2018-04-24

    Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%). Acute lymphoid leukemia was the most frequent neoplasm (37.3%). Regarding the maximum oral mucositis, grade 2 (41.2%) was predominant, with jugal mucosa (29.9%) and tongue (17.7%) being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%). Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

  20. Evaluation of Oral Mucositis Occurrence in Oncologic Patients under Antineoplastic Therapy Submitted to the Low-Level Laser Coadjuvant Therapy

    Directory of Open Access Journals (Sweden)

    Alessandro Leite Cavalcanti

    2018-04-01

    Full Text Available Low-level laser therapy has been widely used in treating many conditions, including oral mucositis. The purpose of this study was to evaluate the occurrence of oral mucositis in patients undergoing antineoplastic therapy submitted to preventive and therapeutic treatment with low-level laser therapy. This cross-sectional study was carried out with 51 children and adolescents of both sexes with malignant neoplasias who developed oral mucositis and underwent low-level laser therapy. Data were collected on sex, age, type and degree of neoplasia, region affected, and remission time. 64.7% of the patients were male and were between 3 and 6 years of age (39.2%. Acute lymphoid leukemia was the most frequent neoplasm (37.3%. Regarding the maximum oral mucositis, grade 2 (41.2% was predominant, with jugal mucosa (29.9% and tongue (17.7% being the most affected regions. The majority of cases presented lesion remission time between 4 and 7 days (44.0%. Most patients were young, male, and diagnosed with acute lymphoid leukemia. Predominance of grade 2 oral mucositis was observed, with jugal mucosa and tongue being the most affected regions, with the majority of cases presenting lesion remission time between 4 and 7 days. Low-level laser therapy has been shown to be an essential therapy in the prevention and treatment of these lesions, since it is a non-invasive and low-cost method.

  1. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

    Science.gov (United States)

    Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

    2012-01-01

    DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

  2. Organotypic Culture of Breast Tumor Explants as a Multicellular System for the Screening of Natural Compounds with Antineoplastic Potential

    Directory of Open Access Journals (Sweden)

    Irma Edith Carranza-Torres

    2015-01-01

    Full Text Available Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of ​​intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control decreased significantly (P<0.05; however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.

  3. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  4. PEGylated DX-1000: Pharmacokinetics and Antineoplastic Activity of a Specific Plasmin Inhibitor

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2007-11-01

    Full Text Available Novel inhibitors of the urokinase-mediated plasminogen (plg activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pin (Ki = 99 pM. When tested in vitro, DX-1000 blocks plasminmediated pro-matrix metal loproteinase-9 (proMMP-9 activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor (~ 7 kDa exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogenactivated protein kinase (MAPK in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

  5. Brain tumor chemo-radiotherapy: a study of direct intratumoral perfusion with antineoplastic drugs

    International Nuclear Information System (INIS)

    Rousseau, J.

    2007-10-01

    High grade gliomas are aggressive tumors for which current treatments remain palliative. Radiotherapy efficacy is restricted by the surrounding brain tissue tolerance. One method based on the concomitant use of chemotherapeutic drugs and external photon irradiation has been proposed to improve the treatment outcome. The systemic administration of drugs is not effective in achieving the therapeutic level of drug needed for brain tumor treatment. This is due to the blood brain barrier (BBB) that prevents molecules passing through the vascular endothelium. Recent methods have been developed to circumvent the BBB. Among them, convection-enhanced delivery (CED) relies on the continuous infusion of a fluid containing a therapeutic agent, under a pressure gradient. It permits a homogeneous and controlled drug distribution. The aims of this study were to characterise the CED method, and then to utilize it for glioma treatment in preclinical studies. Several drugs were tested: cisplatin, carbo-platin, oxaliplatin, and iodo-deoxyuridine. Two radiation modalities were evaluated: synchrotron stereotactic radiotherapy (monochromatic beam < 100 keV) and high energy irradiation (6 MV) obtained with a conventional medical linear accelerator. The results obtained reveal that the effectiveness of the combined treatment (platinated drug plus photon irradiation) is highly related to that of the chemotherapy. The data, obtained with the platinated chemotherapy, also show that high-energy X-ray irradiation (6 MV) is as effective as synchrotron X-ray irradiation. The results broaden the applicability of this chemotherapeutic approach to clinical trials. (author)

  6. Long-term cytogenetic effects of antineoplastic treatment in relation to secondary leukemia

    International Nuclear Information System (INIS)

    Genuardi, M.; Zollino, M.; Serra, A.; Leone, G.; Mancini, R.; Mango, G.; Neri, G.

    1988-01-01

    Chromosome translocations are consistently present in leukemias and lymphomas and are likely to represent primary events in the development of these neoplasias. A study of conditions that predispose to leukemia could shed some light on the origin of these translocations and therefore help in clarifying their exact role in the process of neoplastic transformation. Based on this assumption, we studied a group of individuals treated with radiochemotherapy for previous lymphoma and who were at increased risk of developing a secondary leukemia. The group comprised 14 Hodgkin's disease patients, 11 non-Hodgkin's lymphoma patients, and 13 controls. The patients were in remission and had been off therapy for at least 6 months. Chromosomes were studied from phytohemagglutinin (PHA)-stimulated peripheral lymphocytes and from bone marrow cells by the direct method and after short-term cultures (72 hours). The latter were also exposed to 5-bromodeoxyuridine (BrdU). Metaphases were scored for chromosome breaks, gaps, and other rearrangements. The percentage of gaps and breaks was significantly higher in patients than in controls. The difference was induced by BrdU and was apparent in bone marrow cells, but not in peripheral lymphocytes. We conclude that individuals exposed to the action of mutagenic agents (radiochemotherapy) have an increased chromosome instability that could be related to their increased risk of developing a secondary leukemia

  7. Synthesis of novel amides based on acridone scaffold with interesting antineoplastic activity.

    Science.gov (United States)

    Mahajan, Anand A; Rane, Rajesh A; Amritkar, Anish A; Naphade, Shital S; Miniyar, Pankaj B; Bangalore, Pavan Kumar; Karpoormath, Rajshekhar

    2015-01-01

    In search of novel cytotoxic agents based on acridone scaffold, twenty five derivatives of acridone-2- carboxamide were synthesized and evaluated against a panel of eleven cancer cell lines by using MTT assay. Amides, A5 and A8 (IC50 = 0.3 µM) exhibited good cytotoxicity against MCF7. Compound A22 (IC50 = 4.3 µM) was found to be selectively cytotoxic against cancer cell line MCF7 and KB403. Particularly, promising cytotoxic activities were shown by amides A6 (IC50 = 0.7 µM), A16 (IC50 = 6.3 µM), A8 (IC50 = 0.9 µM ), A21 (IC50 = 1.3 µM), A5 (IC50 = 2.9 µM), A8 (IC50 = 2.8 µM), A14 (IC50 = 0.8 µM), A9 (IC50 = 0.8 µM) and A8 (IC50 = 0.4 µM) against cell lines; PA1, WRL68, CaCO2, TK-10, K-562, PC-3, HOP-92, ECV-304 and UACC-257, respectively. The favorable cytotoxic profile and non-toxicity towards normal human cells displayed by the derivative revealed their potential for further anticancer drug developments.

  8. Mitochondria play a central role in apoptosis induced by alpha-tocopheryl succinate, an agent with antineoplastic activity: comparison with receptor-mediated pro-apoptotic signaling

    Czech Academy of Sciences Publication Activity Database

    Weber, T. D.; Dalen, H.; Anděra, Ladislav; Negre-Salvayre, A.; Auge, N.; Sticha, M.; Lloret, A.; Terman, A.; Witting, P. K.; Higuchi, M.; Plasilova, M.; Zivny, J.; Gellert, N.; Weber, C.; Neuzil, J.

    2003-01-01

    Roč. 42, č. 14 (2003), s. 4277-91 ISSN 0006-2960 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : apoptosis, TRAIL, TOS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.922, year: 2003

  9. Cell-based laboratory evaluation of coagulation activation by antineoplastic drugs for the treatment of lymphoid tumors

    Directory of Open Access Journals (Sweden)

    Misae Tsunaka

    2016-07-01

    Full Text Available Objectives: Combining vorinostat, L-asparaginase, and doxorubicin (Dox led to improved response rates in the treatment of lymphoid tumors. However, deep-vein thrombosis has been noted as one of the most serious side effects with these drugs, and how these regimens cause deep-vein thrombosis is unclear. Methods: We investigated the procoagulant effects of vorinostat, L-asparaginase, and doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine, and antithrombin. The human vascular endothelial cell line EAhy926 as well as the lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma, Molt4 (acute T-lymphoblastic leukemia, and Ramos (Burkitt lymphoma were employed to investigate these procoagulant effects. Results: Vorinostat, L-asparaginase, and doxorubicin induced exposure of phosphatidylserine and procoagulant activity on the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells. Expression of tissue factor antigen was induced by doxorubicin on the surface of each type of cells, whereas expression of tissue factor mRNA was unchanged. Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase. Conclusion: These data suggest that vorinostat and doxorubicin may induce procoagulant activity in vessels through apoptosis of tumor cells and through phosphatidylserine exposure and/or tissue factor expression on vascular endothelial cells. L-asparaginase may induce a thrombophilic state by reducing the secretion of anticoagulant proteins such as antithrombin. The laboratory methods described here could be useful to evaluate the procoagulant effects of antineoplastic drugs.

  10. Multicenter evaluation of a new closed system drug-transfer device in reducing surface contamination by antineoplastic hazardous drugs.

    Science.gov (United States)

    Bartel, Sylvia B; Tyler, Timothy G; Power, Luci A

    2018-02-15

    Results of a study to evaluate the effectiveness of a recently introduced closed system drug-transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil). Stainless steel templates were placed over the 6 previously sampled surfaces, and the marker drugs were compounded and infused per a specific protocol using all components of the CSTD. Wipe samples were collected from the templates after completion of tasks and analyzed for both marker AHDs. Aggregated results of wipe sampling to detect preexisting contamination at the 13 study sites showed that overall, 66.7% of samples (104 of 156) had detectable levels of at least 1 marker AHD; subsequent testing after CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156 samples). In the administration areas alone, the rate of preexisting contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of use, with 100% indicating that they were satisfied or extremely satisfied. A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  11. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    International Nuclear Information System (INIS)

    Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

    2011-01-01

    Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

  12. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  13. Marketed nonsteroidal anti-inflammatory agents, antihypertensives, and human immunodeficiency virus protease inhibitors: as-yet-unused weapons of the oncologists’ arsenal

    Directory of Open Access Journals (Sweden)

    Papanagnou P

    2015-05-01

    Full Text Available Panagiota Papanagnou,1 Panagiotis Baltopoulos,2 Maria Tsironi1 1Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, 2Department of Sports Medicine and Biology of Physical Activity, Faculty of Physical Education and Sport Science, National and Kapodistrian University of Athens, Athens, Greece Abstract: Experimental data indicate that several pharmacological agents that have long been used for the management of various diseases unrelated to cancer exhibit profound in vitro and in vivo anticancer activity. This is of major clinical importance, since it would possibly aid in reassessing the therapeutic use of currently used agents for which clinicians already have experience. Further, this would obviate the time-consuming process required for the development and the approval of novel antineoplastic drugs. Herein, both pre-clinical and clinical data concerning the antineoplastic function of distinct commercially available pharmacological agents that are not currently used in the field of oncology, ie, nonsteroidal anti-inflammatory drugs, antihypertensive agents, and anti-human immunodeficiency virus agents inhibiting viral protease, are reviewed. The aim is to provide integrated information regarding not only the molecular basis of the antitumor function of these agents but also the applicability of the reevaluation of their therapeutic range in the clinical setting. Keywords: repositioning, tumorigenesis, pleiotropy, exploitation

  14. [Biological agents].

    Science.gov (United States)

    Amano, Koichi

    2009-03-01

    There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

  15. Revisiting the structure of the anti-neoplastic glucans of Mycobacterium bovis Bacille Calmette-Guerin. Structural analysis of the extracellular and boiling water extract-derived glucans of the vaccine substrains.

    Science.gov (United States)

    Dinadayala, Premkumar; Lemassu, Anne; Granovski, Pierre; Cérantola, Stéphane; Winter, Nathalie; Daffé, Mamadou

    2004-03-26

    The attenuated strain of Mycobacterium bovis Bacille Calmette-Guérin (BCG), used worldwide to prevent tuberculosis and leprosy, is also clinically used as an immunotherapeutic agent against superficial bladder cancer. An anti-tumor polysaccharide has been isolated from the boiling water extract of the Tice substrain of BCG and tentatively characterized as consisting primarily of repeating units of 6-linked-glucosyl residues. Mycobacterium tuberculosis and other mycobacterial species produce a glycogen-like alpha-glucan composed of repeating units of 4-linked glucosyl residues substituted at some 6 positions by short oligoglucosyl units that also exhibits an anti-tumor activity. Therefore, the impression prevails that mycobacteria synthesize different types of anti-neoplastic glucans or, alternatively, the BCG substrains are singular in producing a unique type of glucan that may confer to them their immunotherapeutic property. The present study addresses this question through the comparative analysis of alpha-glucans purified from the extracellular materials and boiling water extracts of three vaccine substrains. The polysaccharides were purified, and their structural features were established by mono- and two-dimensional NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of the enzymatic and chemical degradation products of the purified compounds. The glucans isolated by the two methods from the three substrains of BCG were shown to exhibit identical structural features shared with the glycogen-like alpha-glucan of M. tuberculosis and other mycobacteria. Incidentally, we observed an occasional release of dextrans from Sephadex columns that may explain the reported occurrence of 6-substituted alpha-glucans in mycobacteria.

  16. 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

  17. ET-09DECOY OLIGONUCLEOTIDE DERIVED FROM MGMT ENHANCER HAS AN ANTINEOPLASTIC ACTIVITY IN-VITRO AND IN-VIVO

    Science.gov (United States)

    Canello, Tamar; Ovadia, Haim; Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    INTRODUCTION: Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, correlates with a better therapeutic response and with increased survival. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through binding of p65/NF-kappaB homodimers to the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer. METHODS AND RESULTS: In an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to MGMT enhancer, the potential of the MGMT-kB1-LODN to enhance cell killing was studied in vitro in two glioma cell lines (T98G and U87) and a melanoma cell line (A375P). All three cell lines manifested a significant enhanced cell killing effect following exposure to temozolomide (TMZ) when first transfected with MGMT-kb1-LODN, and also induced a significant cell killing when administered as monotherapy. These results were confirmed also in-vivo on A375P Melanoma xenografts. Intratumoral (Intralesional - IL) injection of MGMT-kB1-LODN with or without IP injection of TMZ induced significant tumor growth inhibition either as a monotherapy or in combination with TMZ. The long-term effect of MGMT-kB1-LODN monotherapy was evaluated using a repetitive IL injection every 4 to 5 days for 55 days with either MGMT-κB1 LODN or control ODN or vehicle. A significant difference (p < 0.01) in tumor volume was obtained by MGMT-κB1-LODN compared to both control groups. Moreover, two out of the seven mice treated with MGMT-κB1-LODN demonstrated tumor regression by day 55 and no tumor recurrence was observed five months later. CONCLUSION: The results of these experiments show that the MGMT-kB1-LODN has a substantial antineoplastic effect when used either in combination with

  18. 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.

  19. The anti-neoplastic activity of Vandetanib against high-risk medulloblastoma variants is profoundly enhanced by additional PI3K inhibition.

    Science.gov (United States)

    Craveiro, Rogerio B; Ehrhardt, Michael; Velz, Julia; Olschewski, Martin; Goetz, Barbara; Pietsch, Torsten; Dilloo, Dagmar

    2017-07-18

    Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches. In this context our investigation documents that Vandetanib in combination with the clinically available PI3K inhibitor GDC-0941 leads to enhanced cytotoxicity against MYC-amplified and SHH-TP53-mutated medulloblastoma. In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT. Furthermore, we document that Vandetanib and the standard chemotherapeutic Etoposide display additive anti-neoplastic efficacy in the investigated medulloblastoma cell lines that could be further enhanced by PI3K inhibition. Of note, the combination of Vandetanib, GDC-0941 and Etoposide results in MYC-amplified and SHH-TP53-mutated cell lines in complete loss of cell viability. Our findings therefore provide a rational to further evaluate Vandetanib in combination with PI3K inhibitors as well as standard chemotherapeutics in vivo for the treatment of most aggressive medulloblastoma variants.

  20. Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.

    Science.gov (United States)

    Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while

  1. The Antineoplastic Effect of Nitric Oxide-Donating Acetylsalicylic Acid (NO-ASA) in Chronic Lymphocytic Leukemia (CLL) Cells is Highly Dependent on its Positional Isomerism.

    Science.gov (United States)

    Gehrke, Iris; Razavi, Regina; Poll-Wolbeck, Simon Jonas; Berkessel, Albrecht; Hallek, Michael; Kreuzer, Karl-Anton

    2011-10-01

    Chronic Lymphocytic Leukemia (CLL) is not curable in patients that are not eligible for allogeneic stem cell transplantation. Therefore, new treatment options are highly desirable. Chemically modified nonsteroidal anti-inflammatory drugs (NSAIDs), such as nitric-oxide-donating acetylsalicylic acid (NO-ASA), have been described to possess antineoplastic capacity. Recently, we could demonstrate a potent apoptosis induction in primary CLL cells in vitro and tumor growth inhibition by para-NO-ASA in a xenograft mouse model. However, little is known about the impact of positional isomerism of NO-ASA on its antineoplastic capacity in CLL. Primary CLL cells were treated with the meta-or para-isomer of NO-ASA at varying concentrations and durations. Viability was assessed flow cytometrically by annexin V-FITC/PI staining and by CellTiter-Glo luminescence cell viability assay. Caspase and PARP cleavage as well as involvement of β-catenin/Lef-1 signaling was determined by immunoblotting. For caspase inhibition, BD™ ApoBlock was used. Nude mice were xenografted with JVM3 cells and treated with meta-NO-ASA, para-NO-ASA or vehicle control. The meta-isomer was entirely ineffective in inducing CLL cell apoptosis in concentrations up to 100 μM, while para-NO-ASA acted in the low micromolar range. meta-NO-ASA, in contrast to para-NO-ASA, did not alter caspase activity. While para-NO-ASA action involved inhibition of β-catenin/Lef-1 signaling, meta-NO-ASA did not show any impact on this signaling pathway. Further, meta-NO-ASA did not significantly reduce tumor growth in a CLL xenograft mouse model, while para-NO-ASA was highly potent. We conclude that positional isomerism is crucial for the antineoplastic effect of NO-ASA in CLL. It can be suggested that the para-isomer, but not the meta-isomer, generates a chemical structure which is essential for the neoplastic effect of NO-ASA.

  2. Biological activity of some novel synthesized 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives: In vitro and in vivo antineoplastic activity

    Directory of Open Access Journals (Sweden)

    Satyajit Dutta

    2014-12-01

    Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives and the basic compound 2-(4-methylphenylsulfonamidopentanedioic acid have been synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ovarian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female swiss albino mice against Ehrlich ascites carcinoma (EAC. Among the synthesized compounds, ureide, anilide, p-nitoanilide and o-bromoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid bis amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

  3. Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

    Directory of Open Access Journals (Sweden)

    Arturo Alejandro Dreifuss

    Full Text Available This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT brute hydroethanolic (BHE extract with those of two fractions derived from it. These fractions are choroformic (CHCl3 and n-butanolic (BuOH, rich in pentacyclic oxindole alkaloids (POA and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1 or its fractions (as per the yield of the fractioning process or vehicle (Control was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

  4. Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments.

    Science.gov (United States)

    Rubino, F M; Floridia, L; Pietropaolo, A M; Tavazzani, M; Colombi, A

    1999-01-01

    Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.

  5. 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

  6. Riot Control Agents

    Science.gov (United States)

    ... Submit What's this? Submit Button Facts About Riot Control Agents Interim document Recommend on Facebook Tweet Share Compartir What riot control agents are Riot control agents (sometimes referred to ...

  7. Reasoning about emotional agents

    OpenAIRE

    Meyer, J.-J.

    2004-01-01

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

  8. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ye J

    2016-08-01

    Full Text Available Jun Ye,1,2 Xuejun Xia,1,2 Wujun Dong,1,2 Huazhen Hao,1,2 Luhua Meng,1,2 Yanfang Yang,1,2 Renyun Wang,1,2 Yuanfeng Lyu,3 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: There is no effective clinical therapy for triple-negative breast cancers (TNBCs, which have high low-density lipoprotein (LDL requirements and express relatively high levels of LDL receptors (LDLRs on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231 and non-TNBC (MCF7 cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native

  9. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

    Science.gov (United States)

    Aggarwal, Abhishek; Höbaus, Julia; Tennakoon, Samawansha; Prinz-Wohlgenannt, Maximilian; Graça, João; Price, Sally A; Heffeter, Petra; Berger, Walter; Baumgartner-Parzer, Sabina; Kállay, Enikö

    2016-01-01

    Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R-568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced differentiation and apoptosis only in cells with a functional CaSR, which were further enhanced in the presence of NPS R-568, a positive allosteric modulator of CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3 suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part, mediated by the CaSR. Taken together, our data provides molecular evidence to support the epidemiological observation that both, vitamin D and calcium are needed for protection against malignant transformation of the colon and that their effect is modulated by the presence of a functional CaSR. This article is part of a Special Issue

  10. Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).

    Science.gov (United States)

    Coyne, Cody P; Narayanan, Lakshmi

    2016-01-01

    Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10(-9) M and 10(-5) M. Rapid increases in

  11. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K

    2013-02-01

    advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.Keywords: chromatin modifications, histone acetylation, histone deacetylase inhibitor, suberoylanilide hydroxamic acid, depsipeptide, entinostat

  12. Chemical warfare agents.

    Science.gov (United States)

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  13. Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.

    Science.gov (United States)

    Stipp, Maria Carolina; Bezerra, Iglesias de Lacerda; Corso, Claudia Rita; Dos Reis Livero, Francislaine A; Lomba, Luiz Alexandre; Caillot, Adriana Rute Cordeiro; Zampronio, Aleksander Roberto; Queiroz-Telles, José Ederaldo; Klassen, Giseli; Ramos, Edneia A S; Sassaki, Guilherme Lanzi; Acco, Alexandra

    2017-03-15

    Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  15. Applicability of the comet assay in evaluation of DNA damage in healthcare providers' working with antineoplastic drugs: a systematic review and meta-analysis.

    Science.gov (United States)

    Zare Sakhvidi, Mohammad Javad; Hajaghazadeh, Mohammad; Mostaghaci, Mehrdad; Mehrparvar, Amir Houshang; Zare Sakhvidi, Fariba; Naghshineh, Elham

    2016-01-01

    Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by genotoxic biomarkers. To evaluate the obstacles to obtaining conclusive results from a comet assay test to determine DNA damage among AND exposed healthcare workers. We systematically reviewed studies that used alkaline comet assay to determine the magnitude and significance of DNA damage among health care workers with potential AND exposure. Fifteen studies were eligible for review and 14 studies were used in the meta-analysis. Under random effect assumption, the estimated standardized mean difference (SMD) in the DNA damage of health care workers was 1.93 (95% CI: 1.15-2.71, p comet moment, I2 test results, as a measure of heterogeneity, dropped to zero. Heterogeneity analysis showed that date of study publication was a possible source of heterogeneity (B = -0.14; p comet assay methodological variables, and exposure characteristics may be responsible for heterogenic data from comet assay studies and interfere with obtaining conclusive results. Lack of quantitative environmental exposure measures and variation in comet assay protocols across studies are important obstacles in generalization of results.

  16. Applicability of the comet assay in evaluation of DNA damage in healthcare providers’ working with antineoplastic drugs: a systematic review and meta-analysis

    Science.gov (United States)

    Zare Sakhvidi, Mohammad Javad; Hajaghazadeh, Mohammad; Mostaghaci, Mehrdad; Mehrparvar, Amir houshang; Zare Sakhvidi, Fariba; Naghshineh, Elham

    2016-01-01

    Background Unintended occupational exposure to antineoplastic drugs (ANDs) may occur in medical personnel. Some ANDs are known human carcinogens and exposure can be monitored by genotoxic biomarkers. Objective To evaluate the obstacles to obtaining conclusive results from a comet assay test to determine DNA damage among AND exposed healthcare workers. Methods We systematically reviewed studies that used alkaline comet assay to determine the magnitude and significance of DNA damage among health care workers with potential AND exposure. Fifteen studies were eligible for review and 14 studies were used in the meta-analysis. Results Under random effect assumption, the estimated standardized mean difference (SMD) in the DNA damage of health care workers was 1.93 (95% CI: 1.15–2.71, p comet moment, I2 test results, as a measure of heterogeneity, dropped to zero. Heterogeneity analysis showed that date of study publication was a possible source of heterogeneity (B = −0.14; p comet assay methodological variables, and exposure characteristics may be responsible for heterogenic data from comet assay studies and interfere with obtaining conclusive results. Lack of quantitative environmental exposure measures and variation in comet assay protocols across studies are important obstacles in generalization of results. PMID:27110842

  17. Photo-Fenton and Fenton-like processes for the treatment of the antineoplastic drug 5-fluorouracil under simulated solar radiation.

    Science.gov (United States)

    Koltsakidou, Α; Antonopoulou, M; Sykiotou, M; Εvgenidou, Ε; Konstantinou, I; Lambropoulou, D A

    2017-02-01

    In the present study, photo-Fenton and Fenton-like processes were investigated for the degradation and mineralization of the antineoplastic drug 5-fluorouracil (5-FU). For the optimization of photo-Fenton treatment under simulated solar light (SSL) radiation, the effects of several operating parameters (i.e., 5-FU concentration, Fe 3+ , and oxidant concentration) on the treatment efficiency were studied. According to the results, SSL/[Fe(C 2 Ο 4 ) 3 ] 3- /Η 2 Ο 2 process was the most efficient, since faster degradation of 5-FU and higher mineralization percentages were achieved. All the applied processes followed quite similar transformation routes which include defluorination-hydroxylation as well as pyrimidine ring opening, as demonstrated by the transformation products identified by high resolution mass spectrometry analysis. The toxicity of the treated solutions was evaluated using the Microtox assay. In general, low toxicity was recorded for the initial solution and the solution at the end of the photocatalytic treatment, while an increase in the overall toxicity was observed only at the first stages of SSL/Fe 3+ /Η 2 Ο 2 and SSL/Fe 3+ /S 2 O 8 2- processes.

  18. 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

  19. Taskable Reactive Agent Communities

    National Research Council Canada - National Science Library

    Myers, Karen

    2002-01-01

    The focus of Taskable Reactive Agent Communities (TRAC) project was to develop mixed-initiative technology to enable humans to supervise and manage teams of agents as they perform tasks in dynamic environments...

  20. Users, Bystanders and Agents

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina

    2015-01-01

    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution

    International Nuclear Information System (INIS)

    Nishi, Yoshisuke; Miyanaga, Kumiko; Sato, Sei-ichi; Inui, Naomichi

    1990-01-01

    The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with 60 Co γ-rays also induced DNA strand breaks. The elution profiles for γ-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than γ-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice. (Author)

  6. DNA damage induced in mouse peritoneal exudate cells after in vivo administration of chemical and physical agents as determined by alkaline elution

    Energy Technology Data Exchange (ETDEWEB)

    Nishi, Yoshisuke (Japan Tobacco Inc., Yokohama (Japan). Central Research Inst.); Miyanaga, Kumiko; Sato, Sei-ichi (Japan Tobacco Inc., Hatano, Kanagawa (Japan). Toxicology Research Lab.); Inui, Naomichi (Japan Tobacco Inc., Yokohama, Kanagawa (Japan). Pharmaceutical Research Labs.)

    1990-01-01

    The alkaline elution technique for detecting DNA strand breaks has been applied to the study of DNA damage in mouse peritoneal exudate cells resulting from the in vivo administration of chemical and physical agents. The direct methylating agents methyl methanesulphonate and N-methyl-N-nitrosourea induced extensive breakage in samples taken 2 h after administration. The direct ethylating agents ethyl methanesulphonate and N-ethyl-N-nitrosourea also induced DNA strand breaks, but to a lesser extent than the methylating agents. The indirect methylating agent dimethylnitrosamine showed hardly any effect in this system. A weak but positive response was observed upon treatment with the anti-neoplastic alkylating agent procarbazine hydrochloride. The whole-body irradiation of mice with {sup 60}Co {gamma}-rays also induced DNA strand breaks. The elution profiles for {gamma}-ray irradiation were different from those of alkylating agents, and indicate that alkylating agents produce many more secondary lesions leading to DNA strand breaks than {gamma}-rays. N-methyl-N-nitrosourea produced slightly more DNA strand breaks in mutagen-sensitive mice, which are derived from the CD-1 strain, than in ICR mice. (Author).

  7. 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.

  8. Dexamethasone-(C21-phosphoramide-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549

    Directory of Open Access Journals (Sweden)

    Coyne CP

    2016-08-01

    did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10-9 M and 10-5 M. Rapid increases in antineoplastic cytotoxicity were observed at and between the dexamethasone equivalent concentrations of 10-9 M and 10-7 M where cancer cell death increased from 7.7% to a maximum of 64.9% (92.3%–35.1% residual survival, respectively, which closely paralleled values for “free” noncovalently bound dexamethasone. Discussion: Organic chemistry reaction regimens were optimized to develop a multiphase synthesis regimen for dexamethasone-(C21-phosphoramide-[anti-EGFR]. Attributes of dexamethasone-(C21-phosphoramide-[anti-EGFR] include a high dexamethasone molar incorporation-index, lack of extraneous chemical group introduction, retained EGFR-binding avidity (“targeted” delivery properties, and potential to enhance long-term pharmaceutical moiety effectiveness. Keywords: dexamethasone, anti-EGFR, organic chemistry reactions, synthesis, selective “targeted” delivery, covalent immunopharmaceuticals, EGFR 

  9. Design of novel antitumor DNA alkylating agents: the benzacronycine series.

    Science.gov (United States)

    David-Cordonnier, Marie-Hélène; Laine, William; Gaslonde, Thomas; Michel, Sylvie; Tillequin, Francois; Koch, Michel; Léonce, Stéphane; Pierré, Alain; Bailly, Christian

    2004-03-01

    Acronycine, a natural alkaloid originally extracted from the bark of the Australian ash scrub Acronychia baueri, has shown a significant antitumor activity in animal models. Acronycine has been tested against human cancers in the early 1980s, but the clinical trials showed modest therapeutic effects and its development was rapidly discontinued. In order to optimize the antineoplastic effect, different benzoacronycine derivatives were synthesized. Among those, the di-acetate compound S23906-1 was recently identified as a promising anticancer drug candidate and a novel alkylating agent specifically reacting with the exocylic 2-NH2 group of guanines in DNA. The study of DNA bonding capacity of acronycine derivatives leads to the identification of the structural requirements for DNA alkylation. In nearly all cases, the potent alkylating agents, such as S23906-1, were found to be much more cytotoxic than the unreactive analogs such as acronycine itself or diol derivatives. Alkylation of DNA by the monoacetate derivative S28687-1, which is a highly reactive hydrolysis metabolite of S23906-1, occurs with a marked preference for the N2 position of guanine. Other bionucleophiles can react with S23906-1. The benzacronycine derivatives, which efficiently alkylate DNA, also covalently bind to the tripeptide glutathione (GSH) but not to the oxidized product glutathione disulfide. Here we review the reactivity of S23906-1 and some derivatives toward DNA and GSH. The structure-activity relationships in the benzacronycine series validate the reaction mechanism implicating DNA as the main molecular target. S23906-1 stands as the most promising lead of a medicinal chemistry program aimed at discovering novel antitumor drugs based on the acronycine skeleton.

  10. Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

    Science.gov (United States)

    Katragadda, L; Shahid, Z; Restrepo, A; Muzaffar, J; Alapat, D; Anaissie, E

    2013-08-01

    Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B

  11. Population pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients.

    Science.gov (United States)

    Nassar, Ala F; Wisnewski, Adam V; King, Ivan

    2017-05-01

    1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity. 2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide. Of these, 104 patients were included in the final NONMEM analysis. 3. The population estimates for total clearance (CL) and volume of distribution of the central compartment (V 1 ) were 96.3 L/h and 45.9 L, associated with high inter-patient variability of 52.9% and 79.8% and inter-occasion variability of 26.7% and 49.3%, respectively. The population estimates for Q and V 2 were 73.2 L/h and 29.9 L, and inter-patient variability in V 2 was 63.1%, respectively. 4. The estimate of V ss (75.8 L) exceeds total body water, indicating that laromustine is distributed to tissues. The half-life is short, less than 1 h, reflecting rapid clearance. Population PK analysis showed laromustine pharmacokinetics to be independent of dose and organ function with no effect on subsequent dosing cycles.

  12. Apoptosis by antitumor agents and other factors in relation to cell cycle checkpoints

    International Nuclear Information System (INIS)

    Kondo, Sohei

    1995-01-01

    More than a cancer patients died in 1993 after treatment with antineoplastic derivatives of 5-fluorouracil and the antiherpes drug Sorivudine. This paper gives a short review of previous reports showing that killing of cells by 5-fluorouracil and other antitumor agents, including radiation at high doses, results from activation of apoptosis in the G2 phase. On the other hand, apoptosis of lymphocytes by radiation at low doses and treatment with other agents is known to occur in the G1 phase. The cells dying in the G1 or G2 phase could share the same final self-killing steps. For these common steps, I assume a mitotic catastrophe model, in which commitment to self-killing results from premature activation of the mitosis machinery, and propose a concept of a 'G1/G2 death circuit' for cells dying in the G1/G2 phase by short circuit to the M phase. Based on this model, reported modes of cell death, spontaneously occurring or after treatment with various agents, are classified by the phase of dying cells. The associations of incomplete apoptosis with production of chromosomal aberrations and prevention of tumorigenesis by complete apoptosis of carcinogen-treated cells are discussed. A presumptive rule for differentiation of G1 apoptosis and G2 apoptosis is proposed. (author)

  13. Agent Architectures for Compliance

    Science.gov (United States)

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

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

  14. 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

  15. Contrast agents for MRI

    International Nuclear Information System (INIS)

    Bonnemain, B.

    1994-01-01

    Contrast agents MRI (Magnetic Resonance Imaging) have been developed to improve the diagnostic information obtained by this technic. They mainly interact on T1 and T2 parameters and increase consequently normal to abnormal tissues contrast. The paramagnetic agents which mainly act on longitudinal relaxation rate (T1) are gadolinium complexes for which stability is the main parameter to avoid any release of free gadolinium. The superparamagnetic agents that decrease signal intensity by an effect on transversal relaxation rate (T2) are developed for liver, digestive and lymph node imaging. Many area of research are now opened for optimal use of present and future contrast agents in MRI. (author). 28 refs., 4 tabs

  16. 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...

  17. The impact of religiosity and individual prayer activities on advanced cancer patients' health: is there any difference in function of whether or not receiving palliative anti-neoplastic therapy?

    Science.gov (United States)

    Paiva, Carlos Eduardo; Paiva, Bianca Sakamoto Ribeiro; Yennurajalingam, Sriram; Hui, David

    2014-12-01

    Consecutive patients (n = 221) presenting for initial consultation at a palliative care outpatient clinic were prospectively interviewed and then followed until death. Individual prayer activity (IPA) and global religion scores were associated with quality of life, symptoms, inflammatory markers, and survival. Analyses were adjusted for whether patients were still receiving anti-neoplastic therapies (ANTs) or not. Higher religion scores were associated with lower levels of inflammation in advanced cancer patients still undergoing ANTs. Additionally, higher IPA was an independent good prognostic factor in patients on active ANTs. Further studies are necessary to confirm these findings and to investigate possible biological mechanisms involved.

  18. 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…

  19. Teaching Tourism Change Agents

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...... change in tourism in the future....

  20. 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…

  1. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    Bevan, J.A.

    1979-01-01

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

  2. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    A stable radiographic scanning agent on a sup(99m)Tc basis has been developed. The substance contains a pertechnetate reduction agent, tin(II)-chloride, chromium(II)-chloride, or iron(II)-sulphate, as well as an organospecific carrier and ascorbic acid or a pharmacologically admissible salt or ester of ascorbic acid. (VJ) [de

  3. Stable radiographic scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    Stable compositions which are useful in the preparation of Technetium-99m-based scintigraphic agents are discussed. They are comprised of ascorbic acid or a pharmaceutically acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in oxidized pertechnetate-99m (sup(99m)TcO 4 - ) solution

  4. Investigation of the interaction of radiation and cardiotoxic anticancer agents using a fetal mouse heart organ culture system

    International Nuclear Information System (INIS)

    Kimler, B.F.; Rethorst, R.D.; Cox, G.G.

    1985-01-01

    The fetal mouse heart organ culture was utilized in an attempt to predict the cardiotoxic effects of combinations of radiation, Adriamycin (ADR), and Dihydroxyanthraquinone (DHAQ), antineoplastic agents which have been shown to produce clinical cardiomyopathy. Seventeen-day fetal hearts were removed and placed in a culture system of micro-titer plates. A single heart was placed in each well on a piece of aluminum mesh to keep the heart above the culture medium but bathed by capillary action. The plates were then placed in a 100% oxygen environment at 37 0 C. Treatments were performed on day 1 after culture: radiation doses (Cs-137) of 10, 20, or 40 Gy; drug treatment with 10, 30, or 100 μg/ml of ADR; 5, 20, or 50 μg/ml of DHAQ; and combinations and sequences of drug and radiation. Hearts were checked every day for functional activity as evidenced by a continuous heart beat. Untreated hearts beat rhythmically for up to 9 days; treated hearts stopped beating earlier. Using an endpoint of functional retention time, dose response curves were obtained for all individual agents and for combinations of agents. This system may help to predict the cardiotoxic effects that result from the use of these drugs and radiation. It may also aid in the development of new anthracycline chemotherapeutic agents that lack cardiotoxicity

  5. 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...

  6. Biological warfare agents

    Directory of Open Access Journals (Sweden)

    Duraipandian Thavaselvam

    2010-01-01

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

  7. Biological warfare agents

    Science.gov (United States)

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

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

  8. Culturally Aware Agent Communication

    DEFF Research Database (Denmark)

    Rehm, Matthias; Nakano, Yukiko; Koda, Tomoko

    2012-01-01

    Agent based interaction in the form of Embodied Conversational Agents (ECAs) has matured over the last decade and agents have become more and more sophisticated in terms of their verbal and nonverbal behavior like facial expressions or gestures. Having such “natural” communication channels...... available for expressing not only task-relevant but also socially and psychologically relevant information makes it necessary to take influences into account that are not readily implemented like emotions or cultural heuristics. These influences have a huge impact on the success of an interaction...

  9. 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.

  10. Mobile Agent Data Integrity Using Multi-Agent Architecture

    National Research Council Canada - National Science Library

    McDonald, Jeffrey

    2004-01-01

    .... Security issues for mobile agents continue to produce research interest, particularly in developing mechanisms that guarantee protection of agent data and agent computations in the presence of malicious hosts...

  11. Delta agent (Hepatitis D)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000216.htm Hepatitis D (Delta agent) To use the sharing features on this page, please enable JavaScript. Hepatitis D is a viral infection caused by the ...

  12. Agents Within our Midst

    Science.gov (United States)

    2012-03-14

    agents; and the development of bio -monitoring protocols for civilian and service personnel during a chemical attack. These efforts have resulted in greater...produced by staphylococcal bacteria that is and is classified as a CDC select agent which has the potential to be used as a biological weapon .1...NMR chemical shift perturbation titrations with Fab (fragment, antigen binding regions) domains of 20B1, 14G8, and 6D3 using deuterated (2H) SEB

  13. Adrenal imaging agents

    International Nuclear Information System (INIS)

    Davis, M.A.; Hanson, R.N.; Holman, B.L.

    1980-01-01

    The goals of this proposal are the development of selenium-containing analogs of the aromatic amino acids as imaging agents for the pancreas and of the adrenal cortex enzyme inhibitors as imaging agents for adrenal pathology. The objects for this year include (a) the synthesis of methylseleno derivatives of phenylalanine and tryptophan, and (b) the preparation and evaluation of radiolabeled iodobenzoyl derivatives of the selenazole and thiazole analogs of metyrapone and SU-9055

  14. 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

  15. Monitoring volatile anaesthetic agents

    Energy Technology Data Exchange (ETDEWEB)

    Russell, W J [Royal Adelaide Hospital, SA (Australia). Department of Anaesthesia and Intensive Care

    2000-12-01

    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

  16. Agent independent task planning

    Science.gov (United States)

    Davis, William S.

    1990-01-01

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

  17. [Supramolecular Agents for Theranostics].

    Science.gov (United States)

    Deyev, S M; Lebedenko, E N

    2015-01-01

    This mini-review summarizes recent data obtained in the process of creation of a versatile module platform suitable for construction of supramolecular theranostic agents. As an example, we consider multifunctional hybrid agents for imaging and elimination of cancer cells. The use of an adapter protein system barnase:barstar for producing targeted multifunctional hybrid structures on the basis of highly specific peptides and mini-antibodies as addressing modules and recombinant proteins and/or nanoparticles of different nature (quantum dots, nanogold, magnetic nanoparticles, nanodiamonds, upconverting nanophosphores, polymer nanoparticles) as agents visualizing and damaging cancer cells is described. New perspectives for creation of selective and highly effective compounds for theranostics and personified medicine are contemplated.

  18. 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...

  19. Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo

    Czech Academy of Sciences Publication Activity Database

    Weber, T.; Lu, M.; Anděra, Ladislav; Lanm, H.; Gellert, N.; Fariss, M. W.; Kořínek, Vladimír; Sattler, W.; Ucker, D. S.; Terman, A.; Schroder, B.; Erl, W.; Brunk, U. T.; Coffey, R. J.; Weber, C.; Neužil, J.

    2002-01-01

    Roč. 8, č. 3 (2002), s. 863-869 ISSN 1078-0432 R&D Projects: GA AV ČR IAA5052001; GA ČR GA301/99/0350 Keywords : Vitamin E * TRAIL * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.991, year: 2002

  20. Interacción de los antineoplásicos orales con los alimentos: revisión sistemática Antineoplastic oral agents and drug-nutrient interactions: a sistematic review

    OpenAIRE

    N. V. Jiménez Torres; I. Romero Crespo; M. Ballester Solaz; A. Albert Marí; V. Jiménez Arenas

    2009-01-01

    Introducción: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA). Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los aliment...

  1. 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

  2. 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.

  3. 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...

  4. 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

  5. Alternative inerting agents

    CSIR Research Space (South Africa)

    Du

    1997-08-01

    Full Text Available Final Project Report ALTERNATIVE INERTING AGENTS Author/s: J J L DU PLESSIS Research Agency: OSIR MINING TECHNOLOGY Project No: Date: 3 2 7 2 COL 443 APRIL 1999 N’ ) ( G~6~ I Title: 9 / The results show...

  6. 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...

  7. Stabilized radiographic scanning agent

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1979-01-01

    A stable composition useful in preparation of technetium-99m-based radiographic scanning agents has been developed. The composition contains a stabilizing amount of gentisate stabilizer selected from gentisic acid and its soluble pharmaceutically-acceptable salts and esthers. (E.G.)

  8. A waterproofing agent

    Energy Technology Data Exchange (ETDEWEB)

    Shchipanov, A.I.; Bass, U.M.; Belousov, E.D.; Chernova, S.P.; Gioev, K.A.; Perlin, L.M.; Shapiro, B.O.; Silantev, U.R.

    1979-12-25

    A waterproofing agent is proposed with improved physiomechanical properties. The agent contains (by parts): bitumens: 100; emulsifier: .6-5; polyvinylpyrrolidone: .4-8; synthetic latex: 5.24; a corrosion inhibitor: .2-10; SPL methyl methacrylate with chloroprene: 2.24; hydrochlorinated amine of adduct diethylene triamine with diglycidyl diamine: 2-10, water: 118-220. The agent is prepared using either periodic or continuous action in emulsifying dispersion machines. The bitumen is dispersed in the machine in an aqueous emulsifying solution in which polyvinylpyrrolidone and the corrosion inihibitor are first introduced. Then a synthetic latex solution is introduced into the bitumen emulsion while being mixed in rotor-type turbulent mixers; a solution and a hydrochlorinated amine of adduct diethylene triamine with diglycidyl diamine solution until a homogeneous mixture is obtained. Example: a waterproofing agent is obtained in parts: bitumen 100, emulsifyer (oxidized petrolatum): .6; polyvinylpyrrolidone: .4; synthetic latex (nitrile): 5; corrosion inhibitor (guanidine chromate): .2, SPL:2; and water 118. The properties of the proposed composition are better than the properties of the composition currently used.

  9. 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...

  10. E-Learning Agents

    Science.gov (United States)

    Gregg, Dawn G.

    2007-01-01

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

  11. Applying ligands profiling using multiple extended electron distribution based field templates and feature trees similarity searching in the discovery of new generation of urea-based antineoplastic kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Eman M Dokla

    Full Text Available This study provides a comprehensive computational procedure for the discovery of novel urea-based antineoplastic kinase inhibitors while focusing on diversification of both chemotype and selectivity pattern. It presents a systematic structural analysis of the different binding motifs of urea-based kinase inhibitors and the corresponding configurations of the kinase enzymes. The computational model depends on simultaneous application of two protocols. The first protocol applies multiple consecutive validated virtual screening filters including SMARTS, support vector-machine model (ROC = 0.98, Bayesian model (ROC = 0.86 and structure-based pharmacophore filters based on urea-based kinase inhibitors complexes retrieved from literature. This is followed by hits profiling against different extended electron distribution (XED based field templates representing different kinase targets. The second protocol enables cancericidal activity verification by using the algorithm of feature trees (Ftrees similarity searching against NCI database. Being a proof-of-concept study, this combined procedure was experimentally validated by its utilization in developing a novel series of urea-based derivatives of strong anticancer activity. This new series is based on 3-benzylbenzo[d]thiazol-2(3H-one scaffold which has interesting chemical feasibility and wide diversification capability. Antineoplastic activity of this series was assayed in vitro against NCI 60 tumor-cell lines showing very strong inhibition of GI(50 as low as 0.9 uM. Additionally, its mechanism was unleashed using KINEX™ protein kinase microarray-based small molecule inhibitor profiling platform and cell cycle analysis showing a peculiar selectivity pattern against Zap70, c-src, Mink1, csk and MeKK2 kinases. Interestingly, it showed activity on syk kinase confirming the recent studies finding of the high activity of diphenyl urea containing compounds against this kinase. Allover, the new series

  12. Topical antifungal agents: an update.

    Science.gov (United States)

    Diehl, K B

    1996-10-01

    So many topical antifungal agents have been introduced that it has become very difficult to select the proper agent for a given infection. Nonspecific agents have been available for many years, and they are still effective in many situations. These agents include Whitfield's ointment, Castellani paint, gentian violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific antifungal agents include, among others, the polyenes (nystatin, amphotericin B), the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine, naftifine). Although the choice of an antifungal agent should be based on an accurate diagnosis, many clinicians believe that topical miconazole is a relatively effective agent for the treatment of most mycotic infections. Terbinafine and other newer drugs have primary fungicidal effects. Compared with older antifungal agents, these newer drugs can be used in lower concentrations and shorter therapeutic courses. Studies are needed to evaluate the clinical efficacies and cost advantages of both newer and traditional agents.

  13. Halon firefighting agents

    International Nuclear Information System (INIS)

    Pope, P.R.; Dalzell, G.A.

    1991-01-01

    This paper examines the current state of the International agreements on the use of halons and the subsequent National and industry approaches to the subject. It examines the definition of Essential Use and gives particular examples to clarify its interpretation. Alternative methods of loss control are reviewed. It does not address alternative active firefighting agents but examines the need for protection in particular areas. It addresses reduction of the hazards and consequences so that the need for protection can be minimized. Practical measures to minimize the installed quantities of halon are described. This covers specifications for new, essential, systems and the short term reduction of inventories in existing systems. The causes of leakage and accidental releases are studied and preventive measures are proposed. The paper concludes with an overview of the current research into replacement agents and the future outlook

  14. Blasting agent package

    Energy Technology Data Exchange (ETDEWEB)

    Fox, R.

    1971-03-17

    A protected preassembled package for blasting agents susceptible to desensitization by water consists of, in combination: (1) an inner rigid and self-supporting tube, the upper end of which is suited to be connected, or attached, to the discharge end of a loading hose for a blasting agent and the lower end of which is open; and (2) a flexible tubular liner made of water-resistant film, having a diameter greater than that of the inner tube and a length at least equal to the desired depth of its insertion into the borehole, the liner being sleeved over the length of the inner tube, the upper end of the liner being attached to the inner tube and the lower end of the liner being closed so as to prevent substantial discharge of the explosive mixture therefrom when the latter is pumped into it. (24 claims)

  15. Quantitative Analyses of Synergistic Responses between Cannabidiol and DNA-Damaging Agents on the Proliferation and Viability of Glioblastoma and Neural Progenitor Cells in Culture.

    Science.gov (United States)

    Deng, Liting; Ng, Lindsay; Ozawa, Tatsuya; Stella, Nephi

    2017-01-01

    Evidence suggests that the nonpsychotropic cannabis-derived compound, cannabidiol (CBD), has antineoplastic activity in multiple types of cancers, including glioblastoma multiforme (GBM). DNA-damaging agents remain the main standard of care treatment available for patients diagnosed with GBM. Here we studied the antiproliferative and cell-killing activity of CBD alone and in combination with DNA-damaging agents (temozolomide, carmustine, or cisplatin) in several human GBM cell lines and in mouse primary GBM cells in cultures. This activity was also studied in mouse neural progenitor cells (NPCs) in culture to assess for potential central nervous system toxicity. We found that CBD induced a dose-dependent reduction of both proliferation and viability of all cells with similar potencies, suggesting no preferential activity for cancer cells. Hill plot analysis indicates an allosteric mechanism of action triggered by CBD in all cells. Cotreatment regimens combining CBD and DNA-damaging agents produced synergistic antiproliferating and cell-killing responses over a limited range of concentrations in all human GBM cell lines and mouse GBM cells as well as in mouse NPCs. Remarkably, antagonistic responses occurred at low concentrations in select human GBM cell lines and in mouse GBM cells. Our study suggests limited synergistic activity when combining CBD and DNA-damaging agents in treating GBM cells, along with little to no therapeutic window when considering NPCs. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. 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

  17. 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

  18. Organizations as Socially Constructed Agents in the Agent Oriented Paradigm

    NARCIS (Netherlands)

    G. Boella (Guido); L.W.N. van der Torre (Leon)

    2005-01-01

    htmlabstractIn this paper we propose a new role for the agent metaphor in the definition of the organizational structure of multiagent systems. The agent metaphor is extended to consider as agents also social entities like organizations, groups and normative systems, so that mental attitudes can

  19. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents

    KAUST Repository

    Xü , Ying; Kersten, Roland D.; Nam, Sang Jip; Lu, Liang; Al-Suwailem, Abdulaziz M.; Zheng, Huajun; Fenical, William H.; Dorrestein, Pieter C.; Moore, Bradley S.; Qian, Peiyuan

    2012-01-01

    The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B's development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-proteobacteria Tistrella mobilis and Tistrella bauzanensis via a unique post-assembly line maturation process. Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020-065 with its five circular replicons revealed the putative didemnin biosynthetic gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a 13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme complex organized in a collinear arrangement for the synthesis of the fatty acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured the time-dependent extracellular conversion of the didemnin X and Y precursors to didemnin B, in support of an unusual post-synthetase activation mechanism. Significantly, the discovery of the didemnin biosynthetic gene cluster may provide a long-term solution to the supply problem that presently hinders this group of marine natural products and pave the way for the genetic engineering of new didemnin congeners. © 2012 American Chemical Society.

  20. Three-agent Peer Evaluation

    OpenAIRE

    Vicki Knoblauch

    2008-01-01

    I show that every rule for dividing a dollar among three agents impartially (so that each agent's share depends only on her evaluation by her associates) underpays some agent by at least one-third of a dollar for some consistent profile of evaluations. I then produce an impartial division rule that never underpays or overpays any agent by more than one-third of a dollar, and for most consistent evaluation profiles does much better.

  1. Agent control of cooperating satellites

    OpenAIRE

    Lincoln, N.K.; Veres, S.M.; Dennis, Louise; Fisher, Michael; Lisitsa, Alexei

    2011-01-01

    A novel, hybrid, agent architecture for (small)swarms of satellites has been developed. The software architecture for each satellite comprises ahigh-level rational agent linked to a low-level control system. The rational agent forms dynamicgoals, decides how to tackle them and passes theactual implementation of these plans to the control layer. The rational agent also has access to aMatLabmodel of the satellite dynamics, thus allowing it to carry out selective hypothetical reasoningabout pote...

  2. Believable Social and Emotional Agents.

    Science.gov (United States)

    1996-05-01

    While building tools to support the creation of believable emotional agents, I had to make a number of important design decisions . Before describing...processing systems, it is difficult to give an artist direct control over the emotion - al aspects of the character. By making these decisions explicit, I hope...Woody on “Cheers”). Believable Agents BELIEVABLE SOCIAL AND EMOTIONAL AGENTS 11 Lesson: We don’t want agent architectures that enforce rationality and

  3. 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.

  4. Chemical warfare agents

    Science.gov (United States)

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

    2010-01-01

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

  5. Synergistic Effects of Secretory Phospholipase A2 from the Venom of Agkistrodon piscivorus piscivorus with Cancer Chemotherapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jennifer Nelson

    2013-01-01

    Full Text Available Healthy cells typically resist hydrolysis catalyzed by snake venom secretory phospholipase A2. However, during various forms of programmed cell death, they become vulnerable to attack by the enzyme. This observation raises the question of whether the specificity of the enzyme for dying cells could be used as a strategy to eliminate tumor cells that have been intoxicated but not directly killed by chemotherapeutic agents. This idea was tested with S49 lymphoma cells and a broad range of antineoplastic drugs: methotrexate, daunorubicin, actinomycin D, and paclitaxel. In each case, a substantial population of treated cells was still alive yet vulnerable to attack by the enzyme. Induction of cell death by these agents also perturbed the biophysical properties of the membrane as detected by merocyanine 540 and trimethylammonium-diphenylhexatriene. These results suggest that exposure of lymphoma cells to these drugs universally causes changes to the cell membrane that render it susceptible to enzymatic attack. The data also argue that the snake venom enzyme is not only capable of clearing cell corpses but can aid in the demise of tumor cells that have initiated but not yet completed the death process.

  6. The search for novel anticancer agents: a differentiation-based assay and analysis of a folklore product.

    Science.gov (United States)

    Dinnen, R D; Ebisuzaki, K

    1997-01-01

    One alternative approach to the current use of cytotoxic anticancer drugs involves the use of differentiation-inducing agents. However, a wider application of this strategy would require the development of assays to search for new differentiation-inducing agents. In this report we describe an in vitro assay using the murine erythroleukemia (clone 3-1) cells. Tests for the efficacy of this assay for the analysis of antineoplastic activity in natural products led to studies on pau d'arco, a South American folklore product used in the treatment of cancer. Purification of the activity in aqueous extracts by solvent partition and thin layer chromatography (TLC) indicated the presence of two activities, one of which was identified as lapachol. The activity in the pau d'arco extracts and of lapachol was inhibited by vitamin K1. As a vitamin K antagonist, lapachol might target such vitamin K-dependent reactions as the activation of a ligand for the Axl receptor tyrosine kinase.

  7. 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.

  8. 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.

  9. [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.

  10. 2-[(aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Coγ-ray irradiation

    International Nuclear Information System (INIS)

    Hill, C.K.; Nagy, B.; Peraino, C.; Grdina, D.

    1986-01-01

    The effect of 2[(aminopropyl)amino]ethanethiol (WR1065) has been studied on the induction of neoplastic transformation using 10T1/2 cells and on mutation of the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using Chinese hamster V79 cells. The first observations that treatment of 10T1/2 cells with 1 mM WR1065 for a total of 35 min during irradiation with 60 C γ-rays significantly reduces the incidence of neoplastic transformation while having no effect on cell viability are reported. In a similar experiment with V79 cells in which 4mM WR1065 was used, a significant reduction in mutation frequency at the HGPRT locus and significant protection against cell killing was found. These results suggest that WR1965 acts to modulate both acute damage and sub-lethal processes that lead to mutation and neoplastic transformation. Beyond the purely mechanistic approach of these studies, the potential application of these agents to minimizing the long-term neoplastic effects of radiation or chemotherapeutic agents currently in use for treating potentially curable cancer patients should be further investigated. (author)

  11. 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)

  12. 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

  13. 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...

  14. Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

    Science.gov (United States)

    Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

    2018-08-01

    In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

  15. Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Kirsi Ketola

    Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram

  16. 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.

  17. 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.

  18. 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

  19. Principals, agents and research programmes

    OpenAIRE

    Elizabeth Shove

    2003-01-01

    Research programmes appear to represent one of the more powerful instruments through which research funders (principals) steer and shape what researchers (agents) do. The fact that agents navigate between different sources and styles of programme funding and that they use programmes to their own ends is readily accommodated within principal-agent theory with the help of concepts such as shirking and defection. Taking a different route, I use three examples of research programming (by the UK, ...

  20. 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.

  1. 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...

  2. Aspects of agents for safeguards

    International Nuclear Information System (INIS)

    Kotte, U.

    1999-01-01

    With the development of the Internet and the WWW, information treatment has gained a new dimension. (Intelligent) software agents are one of the means expected to relieve human staff of the burden of information overload, and in the future to contribute to safeguards data acquisition, data evaluation and decision-making. An overview is given for the categories of Internet, intranet and desktop agents. Aspects of the potential application of agents are described in three fields: information access and delivery, collaboration and workflow management, adaptive interfaces and learning assistants. Routine application of agents is not yet in sight, but the scientific and technical progress seems to be encouraging. (author)

  3. 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

  4. 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.

  5. 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…

  6. 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)

  7. 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.

  8. Influence of Alternative Tubulin Inhibitors on the Potency of a Epirubicin-Immunochemotherapeutic Synthesized with an Ultra Violet Light-Activated Intermediate: Influence of incorporating an internal/integral disulfide bond structure and Alternative Tubulin/Microtubule Inhibitors on the Cytotoxic Anti-Neoplastic Potency of Epirubicin-(C3-amide)-Anti-HER2/neu Synthesized Utilizing a UV-Photoactivated Anthracycline Intermediate.

    Science.gov (United States)

    Coyne, C P; Jones, Toni; Bear, Ryan

    2012-11-01

    Immunochemotherapeutics, epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] with an internal disulfide bond, and epirubicin-(C 3 - amide )-[anti-HER2/ neu ] were synthesized utilizing succinimidyl 2-[(4,4'-azipentanamido) ethyl]-1,3'-dithioproprionate or succinimidyl 4,4-azipentanoate respectively. Western blot analysis was used to determine the presence of any immunoglobulin fragmentation or IgG-IgG polymerization. Retained HER2/ neu binding characteristics of epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] were validated by cell-ELISA using a mammary adenocarcinoma (SKBr-3) population that highly over-expresses trophic HER2/ neu receptor complexes. Cytotoxic anti-neoplastic potency of epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] between epirubicin-equivalent concentrations of 10 -10 M and 10 -6 M was determined by measuring the vitality/proliferation of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3 cell type). Cytotoxic anti-neoplastic potency of benzimidazoles (albendazole, flubendazole, membendazole) and griseofulvin were assessed between 0-to-2 μg/ml and 0-to-100 μg/ml respectively while mebendazole and griseofulvin were analyzed at fixed concentrations of 0.35 μg/ml and 35 g/ml respectively in dual combination with gradient concentrations of epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ]. Cytotoxic anti-neoplastic potency for epirubicin-(C 3 - amide )-[anti-HER2/ neu ] and epirubicin-(C 3 - amide )-SS-[anti-HER2/ neu ] against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) was nearly identical at epirubicin-equivalent concentrations of 10 -10 M and 10 -6 M. The benzimadazoles also possessed cytotoxic anti-neoplastic activity with flubendazole and albendazole being the most and least potent respectively. Similarly, griseofulvin had cytotoxic anti-neoplastic activity and was more potent than

  9. Artificial agents learning human fairness

    NARCIS (Netherlands)

    Jong, de S.; Tuyls, K.P.; Verbeeck, K.; Padgham, xx; Parkes, xx

    2008-01-01

    Recent advances in technology allow multi-agent systems to be deployed in cooperation with or as a service for humans. Typically, those systems are designed assuming individually rational agents, according to the principles of classical game theory. However, research in the field of behavioral

  10. 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

  11. Reactive agents and perceptual ambiguity

    NARCIS (Netherlands)

    Dartel, M. van; Sprinkhuizen-Kuyper, I.G.; Postma, E.O.; Herik, H.J. van den

    2005-01-01

    Reactive agents are generally believed to be incapable of coping with perceptual ambiguity (i.e., identical sensory states that require different responses). However, a recent finding suggests that reactive agents can cope with perceptual ambiguity in a simple model (Nolfi, 2002). This paper

  12. Radiopharmaceutical agents for skeletal scanning

    International Nuclear Information System (INIS)

    Jansen, S.E.; Van Aswegen, A.; Loetter, M.G.; Minnaar, P.C.; Otto, A.C.; Goedhals, L.; Dedekind, P.S.

    1987-01-01

    The quality of bone scan images obtained with a locally produced and with an imported radiopharmaceutical bone agent, methylene diphosphonate (MDP), was compared visually. Standard skeletal imaging was carried out on 10 patients using both agents, with a period of 2 to 7 days between studies with alternate agents. Equal amounts of activity were administered for both agents. All images were acquired on Polaroid film for subsequent evaluation. The acquisition time for standard amount of counts per study was recorded. Three physicians with applicable experience evaluated image quality (on a 4 point scale) and detectability of metastasis (on a 3 point scale). There was no statistically significant difference (p 0,05) between the two agents by paired t-test of Hotelling's T 2 analysis. It is concluded that the imaging properties of the locally produced and the imported MDP are similar

  13. 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.

  14. 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 agent s and sentiment in the heterogeneous agent model.pdf

  15. Contrast agents for cardiac angiography: effects of a nonionic agent vs. a standard ionic agent

    International Nuclear Information System (INIS)

    Bettmann, M.A.; Bourdillon, P.D.; Barry, W.H.; Brush, K.A.; Levin, D.C.

    1984-01-01

    The effects on cardiac hemodynamics and of a standard contrast agent, sodium methylglucamine diatrizoate [Renografin 76] were compared with the effects of a new nonionic agent (iohexol) in a double-blind study in 51 patietns undergoing coronary angiography and left ventriculography. No significant alteration in measured blood parameters occurred with either contrast agent. Hemodynamic changes occurred with both, but were significantly greater with the standard renografin than with the low-osmolality, nonionic iohexol. After left ventriculography, heart rate increased and peripheral arterial pressure fell with both agents, but less with iohexol. It is concluded that iohexol causes less alteration in cardiac function than does the agent currently most widely used. Nonionic contrast material is likely to improve the safety of coronary angiography, particularly in those patients at greatest risk

  16. Agents Play Mix-game

    Science.gov (United States)

    Gou, Chengling

    In recent years, economics and finance see the shift of paradigm from representative agent models to heterogeneous agent models [1, 2]. More and more economists and physicists made efforts in research on heterogeneous agent models for financial markets. Minority game (MG) proposed by D. Challet, and Y. C. Zhang [3] is an example among such efforts. Challet and Zhang's MG model, together with the original bar model of Arthur, attracts a lot of following studies [4-6]. Given MG's richness and yet underlying simplicity, MG has also received much attention as a financial market model [4]. MG comprises an odd number of agents choosing repeatedly between the options of buying (1) and selling (0) a quantity of a risky asset. The agents continually try to make the minority decision, i.e. buy assets when the majority of other agents are selling, and sell when the majority of other agents are buying. Neil F. Johnson [4, 5] and coworkers extended MG by allowing a variable number of active traders at each timestep— they called their modified game as the Grand Canonical Minority Game (GCMG). GCMG, and to a lesser extent the basic MG itself, can reproduce the stylized facts of financial markets, such as volatility clustering and fat-tail distributions.

  17. Agent Communications using Distributed Metaobjects

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

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

  18. 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.

  19. 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

  20. Requirements Modeling with Agent Programming

    Science.gov (United States)

    Dasgupta, Aniruddha; Krishna, Aneesh; Ghose, Aditya K.

    Agent-oriented conceptual modeling notations are highly effective in representing requirements from an intentional stance and answering questions such as what goals exist, how key actors depend on each other, and what alternatives must be considered. In this chapter, we review an approach to executing i* models by translating these into set of interacting agents implemented in the CASO language and suggest how we can perform reasoning with requirements modeled (both functional and non-functional) using i* models. In this chapter we particularly incorporate deliberation into the agent design. This allows us to benefit from the complementary representational capabilities of the two frameworks.

  1. Dynamics of Three Agent Games

    OpenAIRE

    Rador, Tonguc; Mungan, Muhittin

    2007-01-01

    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. 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 parame...

  2. Noncontraceptive use of contraceptive agents.

    Science.gov (United States)

    Nickles, Monique Collier; Alderman, Elizabeth

    2014-06-01

    • On the basis of strong research evidence, there are many noncontraceptive advantages to use of hormonal contraceptive agents in adolescent girls. (3) (4)(5)(7)(10)(11)(12)(13)(14). • On the basis of research evidence and consensus, most of these agents are safe with minor adverse effects. (2)(3)(4)(5)(7)(10)(11)(12)(13)(14). • On the basis of research evidence and consensus, through application of evidence-based approaches and proper counseling, pediatricians can use various contraceptive agents to treat several medical conditions and to help alleviate many of the undesired symptoms and complications associated with menstrual periods. (2)(3)(4)(5)(7)(10)(11)(12)(13) (14). • On the basis of research evidence and consensus, these agents may be used in sexually active adolescents to simultaneously help prevent unintended adolescent pregnancies. (2)(3)(4)(5)(7)(10)(11)(12)(13)(14).

  3. 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 ...

  4. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  5. 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...

  6. Macroeconomic Policies and Agent Heterogeneity

    OpenAIRE

    GOTTLIEB, Charles

    2012-01-01

    Defence date: 24 February 2012 Examining Board: Giancarlo Corsetti, Arpad Abraham, Juan Carlos Conesa, Jonathan Heathcote. This thesis contributes to the understanding of macroeconomic policies’ impact on the distribution of wealth. It belongs to the strand of literature that departs from the representative agent assumption and perceives agent heterogeneity and the induced disparities in wealth accumulation, as an important dimension of economic policy-making. Within such economic envir...

  7. Agents in E-learning

    Directory of Open Access Journals (Sweden)

    S. Mencke

    2007-12-01

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

  8. Building Agents to Serve Customers

    OpenAIRE

    Barbuceanu, Mihai; Fox, Mark S.; Hong, Lei; Lallement, Yannick; Zhang, Zhongdong

    2004-01-01

    AI agents combining natural language interaction, task planning, and business ontologies can help companies provide better-quality and more costeffective customer service. Our customer-service agents use natural language to interact with customers, enabling customers to state their intentions directly instead of searching for the places on the Web site that may address their concern. We use planning methods to search systematically for the solution to the customer's problem, ensuring that a r...

  9. 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...

  10. What makes virtual agents believable?

    Science.gov (United States)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

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

  11. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents

    KAUST Repository

    Xü, Ying

    2012-05-23

    The anti-neoplastic agent didemnin B from the Caribbean tunicate Trididemnum solidum was the first marine drug to be clinically tested in humans. Because of its limited supply and its complex cyclic depsipeptide structure, considerable challenges were encountered during didemnin B\\'s development that continue to limit aplidine (dehydrodidemnin B), which is currently being evaluated in numerous clinical trials. Herein we show that the didemnins are bacterial products produced by the marine α-proteobacteria Tistrella mobilis and Tistrella bauzanensis via a unique post-assembly line maturation process. Complete genome sequence analysis of the 6,513,401 bp T. mobilis strain KA081020-065 with its five circular replicons revealed the putative didemnin biosynthetic gene cluster (did) on the 1,126,962 bp megaplasmid pTM3. The did locus encodes a 13-module hybrid non-ribosomal peptide synthetase-polyketide synthase enzyme complex organized in a collinear arrangement for the synthesis of the fatty acylglutamine ester derivatives didemnins X and Y rather than didemnin B as first anticipated. Imaging mass spectrometry of T. mobilis bacterial colonies captured the time-dependent extracellular conversion of the didemnin X and Y precursors to didemnin B, in support of an unusual post-synthetase activation mechanism. Significantly, the discovery of the didemnin biosynthetic gene cluster may provide a long-term solution to the supply problem that presently hinders this group of marine natural products and pave the way for the genetic engineering of new didemnin congeners. © 2012 American Chemical Society.

  12. Interactions of ionic and nonionic contrast agents with thrombolytic agents

    International Nuclear Information System (INIS)

    Fareed, J.; Moncada, R.; Scanlon, P.; Hoppensteadt, D.; Huan, X.; Walenga, J.M.

    1987-01-01

    Both the ionic and nonionic intravascular contrast media have been used before and after the administration of thrombolytic agents to evaluate clot lysis during angioplasty and the treatment of myocardial infarction. In experimental animal models, the authors found that the clot lytic efficacy of streptokinase, streptokinase-plasminogen complex, and tissue plasminogen activator (t-PA) is markedly augmented if these agents are administered within 1 hour after the angiographic producers. Furthermore, contrast agents injected after the administration of t-Pa exhibit a synergistic action. In stimulated models administration of one ionic contrast medium (Angiovist, Berlex, Wayne, NJ) and two nonionic contrast agents (Isovue-370, Squibb Diagnostics, New Brunswick, NJ; Omnipaque-350, Winthrop, NY) 15 minutes before the administration of t-PA resulted in marked enhancement of the lytic activity. Although the mechanism of this interaction is unknown at this time, it should be taken into consideration in the treatment of patients with myocardial infarction, in whom contrast agents are continually used to evaluate the therapeutic lysis. Furthermore, this interaction may be partly related to the therapeutic efficacy and/or hemorrhagic actions observed

  13. Smart Agents and Sentiment in the Heterogeneous Agent Model

    Czech Academy of Sciences Publication Activity Database

    Vácha, Lukáš; Baruník, Jozef; Vošvrda, Miloslav

    -, č. 81 (2010), s. 39-40 ISSN 0926-4981 R&D Projects: GA ČR(CZ) GA402/09/0965; GA ČR GP402/08/P207 Grant - others:GAUK(CZ) GAUK 46108 Institutional research plan: CEZ:AV0Z10750506 Keywords : Smart traders * price movements * smart traders concept Subject RIV: AH - Economics http://library.utia.cas.cz/separaty/2010/E/vacha- smart agent s and sentiment in the heterogeneous agent model.pdf

  14. 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.

  15. Multi-Agent Software Engineering

    International Nuclear Information System (INIS)

    Mohamed, A.H.

    2014-01-01

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

  16. 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.

  17. 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)

  18. Alkylating agents for Waldenstrom's macroglobulinaemia.

    Science.gov (United States)

    Yang, Kun; Tan, Jianlong; Wu, Taixiang

    2009-01-21

    Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management. To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM). We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008. Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia. Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This

  19. 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.

  20. Imprecise Beliefs in a Principal Agent Model

    NARCIS (Netherlands)

    Rigotti, L.

    1998-01-01

    This paper presents a principal-agent model where the agent has multiple, or imprecise, beliefs. We model this situation formally by assuming the agent's preferences are incomplete. One can interpret this multiplicity as an agent's limited knowledge of the surrounding environment. In this setting,

  1. 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

  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. 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)

  4. Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH2 -vitamina D3 Vitamin D and cancer: antineoplastic effects of 1α,25(OH2-vitamin D3

    Directory of Open Access Journals (Sweden)

    Verónica González Pardo

    2012-04-01

    Full Text Available La forma hormonalmente activa de la vitamina D, 1α,25(OH2-vitamina D3 (1α,25(OH2D3, además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.The hormonal form of vitamin D, 1α,25(OH2-vitamin D3 (1α,25(OH2D3, in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

  5. 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.

  6. 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.

  7. Ultrasound Contrast Agent Microbubble Dynamics

    NARCIS (Netherlands)

    Overvelde, M.L.J.; Vos, Henk; de Jong, N.; Versluis, Michel; Paradossi, Gaio; Pellegretti, Paolo; Trucco, Andrea

    2010-01-01

    Ultrasound contrast agents are traditionally used in ultrasound-assisted organ perfusion imaging. Recently the use of coated microbubbles has been proposed for molecular imaging applications where the bubbles are covered with a layer of targeting ligands to bind specifically to their target cells.

  8. 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…

  9. Why Do Extension Agents Resign?

    Science.gov (United States)

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

    1985-01-01

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

  10. 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,

  11. 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

  12. 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

  13. FACT : forgiving agent comfort technology

    NARCIS (Netherlands)

    Zeiler, W.; Wortel, W.; Kamphuis, I.G.; Akkermans, Hans; Jelsma, J.; Bakker, L.

    2005-01-01

    To further reduce energy consumption of office buildings, a new control technology is needed in which the end-user behaviour is integrated. Improvement of the energy consumption is offered by agent-based systems for energy management in buildings, as well as possibilities for enhancing the comfort

  14. 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

  15. 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

  16. 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…

  17. 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…

  18. Sophisticated Players and Sophisticated Agents

    NARCIS (Netherlands)

    Rustichini, A.

    1998-01-01

    A sophisticated player is an individual who takes the action of the opponents, in a strategic situation, as determined by decision of rational opponents, and acts accordingly. A sophisticated agent is rational in the choice of his action, but ignores the fact that he is part of a strategic

  19. 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

  20. 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.)

  1. Security Infrastructure and Applicationsfor Mobile Agents

    OpenAIRE

    Shibli, Awais

    2010-01-01

    Research areas of this dissertation are security for mobile agents, for applications based on mobile agents, and for distributed network environments in which mobile agents execute. Mobile agents paradigm has captured researchers’ and industry’s interests long time ago because of its innovative capabilities and attractive applications. The ability of mobile agents to autonomously migrate from host to host, transferring their code and internal state, enables them to accomplish tasks in network...

  2. From SMART to agent systems development

    OpenAIRE

    Ashri, R; Luck, M; d'Inverno, M

    2005-01-01

    In order for agent-oriented software engineering to prove effective it must use principled notions of agents and enabling specification and reasoning, while still considering routes to practical implementation. This paper deals with the issue of individual agent specification and construction, departing from the conceptual basis provided by the smart agent framework. smart offers a descriptive specification of an agent architecture but omits consideration of issues relating to\\ud construction...

  3. 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.

  4. 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.

  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. 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

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

    Science.gov (United States)

    Andrews, R. J.

    1999-01-01

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

  8. 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...... by self-reference. In the standard approach taken in artificial intelligence, the model that an agent has of its environment is represented as a set of beliefs. These beliefs are expressed as logical formulas within a formal, logical theory. When the logical theory is expressive enough to allow...... introspective reasoning, the presence of self-reference causes the theory to be prone to inconsistency. The challenge therefore becomes to construct logical theories supporting introspective reasoning while at the same time ensuring that consistency is retained. In the thesis, we meet this challenge by devising...

  9. Injectable agents affecting subcutaneous fats.

    Science.gov (United States)

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

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.

  10. Diagnostic agent for radioimmunological determinations

    International Nuclear Information System (INIS)

    Updike, S.J.

    1978-01-01

    The invention concerns a diagnostic agent for radioimmunological determinations. According to the invention, a binding protein (protein globulins, antibodies) of an aqueous solution specific for the substance to be determined is incorporated in gel particles of a strongly hydrophilic insoluble gel of controlled pore size. After subsequent drying of the system, a radioactively labelled form of the substance to be determined from a non-aqueous medium is included. The mixture is dried again. The diagnostic agent forred can be well stored and is very stable. There is no loss of activity of the specific bonding protein when drying according to the invented method. The described reagent can be effectively applied to the determination of many antigens and haptens: The gel is rehydrated by the sample to be investigated; as a result of this, the non-bonded tracer is set free and competes with the non-labelled substance for the bonding position. (VJ) [de

  11. 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...... therefore been assessed as a potential treatment for patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy. SEARCH METHODS: Trials were identified through the Cochrane...... hepatic encephalopathy that were published during 1979 to 1982 were included. Three trials assessed levodopa, and two trials assessed bromocriptine. The mean daily dose was 4 grams for levodopa and 15 grams for bromocriptine. The median duration of treatment was 14 days (range seven to 56 days). None...

  12. Behavior acquisition in artificial agents

    OpenAIRE

    Thurau, Christian

    2006-01-01

    Computational skill acquisition in robots and simulated agents has been a topic of increasing popularity throughout the last years. Despite impressive progress, autonomous behavior at a level of animals and humans are not yet replicated by machines. Especially when a complex environment demands versatile, goal-oriented behavior, current artificial systems show shortcomings. Consider for instance modern 3D computer games. Despite their key role for more emersive game experience, surprisingly l...

  13. Belief Change in Reasoning Agents

    OpenAIRE

    Jin, Yi

    2007-01-01

    The capability of changing beliefs upon new information in a rational and efficient way is crucial for an intelligent agent. Belief change therefore is one of the central research fields in Artificial Intelligence (AI) for over two decades. In the AI literature, two different kinds of belief change operations have been intensively investigated: belief update, which deal with situations where the new information describes changes of the world; and belief revision, which assumes the world is st...

  14. 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.

  15. Biochemical toxicology of environmental agents

    International Nuclear Information System (INIS)

    Bruin, A. de

    1976-01-01

    A thorough and up-to-date account of the molecular-biological aspects of harmful agents - both chemical and physical - is given. This current treatise is principally intended to serve as an informative reference work for researchers in various areas of the field. In the pursuit of this aim, a devision of the entire field into 42 chapters has been made. Each chapter starts with a short introductory account dealing with the biochemical essentials of the particular subject. Radiation effects are discussed briefly at the end of each treatise. In order to make the treatise useful as a source book, a substantial collection of pertinent literature references is provided which are numbered in order of citation in the text. Initial chapters are devoted to the metabolic fate of the major classes of xenobiotic compounds. Peripheral topics, closely related to metabolism and dealing with modification of xenobiotic-metabolizing ability, as well as interaction phenomena follow (chs. 5-8). Subjects that draw heavily on the practical field of occupational hygiene are dealt with in chapters 9 and 10. The systematic treatment of how chemical and physical agents interact with the various biochemical and enzymatic systems they encounter during their passage through the organism occupies quantitatively the main part of the book (chs. 11-36). Finally, radiation biochemistry is discussed from the viewpoint of its high degree of scientific advancement, and secondly because the type of biochemical changes produced in vivo by X-rays closely parallel those evoked by chemical agents

  16. Agent planning in AgScala

    Science.gov (United States)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

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

  17. 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].......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]....

  18. 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 ...

  19. 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...

  20. Security Measures to Protect Mobile Agents

    Science.gov (United States)

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

    2010-11-01

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

  1. Prostate Activated Prodrugs and Imaging Agents

    National Research Council Canada - National Science Library

    Jones, Graham B

    2004-01-01

    .... The substrate chosen was a 3 component system composed of a peptide sequence with affinity for PSA, an imaging agent and a deactivating bridge-linker, which electronically incapacitates the imaging agent...

  2. 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.

  3. Protecting mobile agents from external replay attacks

    OpenAIRE

    Garrigues Olivella, Carles; Migas, Nikos; Buchanan, William; Robles, Sergi; Borrell Viader, Joan

    2014-01-01

    Peer-reviewed This paper presents a protocol for the protection of mobile agents against external replay attacks. This kind of attacks are performed by malicious platforms when dispatching an agent multiple times to a remote host, thus making it reexecute part of its itinerary. Current proposals aiming to address this problem are based on storing agent identifiers, or trip markers, inside agent platforms, so that future reexecutions can be detected and prevented. The problem of these solut...

  4. Extinguishing agent for combustible metal fires

    Science.gov (United States)

    Riley, John F.; Stauffer, Edgar Eugene

    1976-10-12

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

  5. 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

  6. Pathogenic agents in freshwater resources

    Science.gov (United States)

    Geldreich, Edwin E.

    1996-02-01

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

  7. 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.

  8. 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...

  9. 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

  10. Switching dynamics of multi-agent learning

    NARCIS (Netherlands)

    Vrancx, P.; Tuyls, K.P.; Westra, R.

    2008-01-01

    This paper presents the dynamics of multi-agent reinforcement learning in multiple state problems. We extend previous work that formally modelled the relation between reinforcement learning agents and replicator dynamics in stateless multi-agent games. More precisely, in this work we use a

  11. 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

  12. 21 CFR 178.3860 - Release agents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Release agents. 178.3860 Section 178.3860 Food and... and Production Aids § 178.3860 Release agents. Substances listed in paragraph (b) of this section may be safely used as release agents in petroleum wax complying with § 178.3710 and in polymeric resins...

  13. 21 CFR 181.28 - Release agents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Release agents. Substances classified as release agents, when migrating from food-packaging material shall...

  14. 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

  15. Fairness in multi-agent systems

    NARCIS (Netherlands)

    Jong, de S.; Tuyls, K.P.; Verbeeck, K.

    2008-01-01

    Multi-agent systems are complex systems in which multiple autonomous entities, called agents, cooperate in order to achieve a common or personal goal. These entities may be computer software, robots, and also humans. In fact, many multi-agent systems are intended to operate in cooperation with or as

  16. 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

  17. 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)

  18. 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

  19. 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

  20. Modeling culture in intelligent virtual agents

    NARCIS (Netherlands)

    Mascarenhas, S.; Degens, N.; Paiva, A.; Prada, R.; Hofstede, G.J.; Beulens, A.J.M.; Aylett, R.

    2016-01-01

    This work addresses the challenge of creating virtual agents that are able to portray culturally appropriate behavior when interacting with other agents or humans. Because culture influences how people perceive their social reality it is important to have agent models that explicitly consider social

  1. 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.

  2. [Antiangiogenic agents in ARMD treatment].

    Science.gov (United States)

    Coroi, Mihaela-Cristiana; Demea, Sorina; Todor, Meda; Apopei, Emmanuela

    2012-01-01

    The aim of antiangiogenic agents in the treatment of age related senile macular degeneration is to destroy coroidian neoformation vessels by minimally affecting the central vision. We present a case of important central vision recovery after 3 intravitreal injections of Avastin. The therapeutic decision and patient monitoring have been made using imaging studies, such as OCT and AFG. A modern therapeutic approach of neovascular forms of age related macular degeneration, backed up by AFG and OCT is a modern treatment method of this disabling illness which brings patients optimal functional and structural improvement.

  3. 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....

  4. 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

  5. Agent Based Individual Traffic guidance

    DEFF Research Database (Denmark)

    Wanscher, Jørgen Bundgaard

    2004-01-01

    When working with traffic planning or guidance it is common practice to view the vehicles as a combined mass. >From this models are employed to specify the vehicle supply and demand for each region. As the models are complex and the calculations are equally demanding the regions and the detail...... of the road network is aggregated. As a result the calculations reveal only what the mass of vehicles are doing and not what a single vehicle is doing. This is the crucial difference to ABIT (Agent Based Individual Trafficguidance). ABIT is based on the fact that information on the destination of each vehicle...

  6. 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.

  7. 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.

  8. 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.

  9. Sustained release of radioprotective agents

    International Nuclear Information System (INIS)

    Shani, J.

    1980-11-01

    New pharmaceutical formulations for the sustained release into the G.I. tract of radioprotective agents have been developed by the authors. The experimental method initially consisted in the production of methylcellulose microcapsules. This method failed apparently because of the premature ''explosion'' of the microcapsules and the consequent premature release of massive amounts of the drug. A new method has been developed which consists in drying and pulverising cysteamine and cysteine preparations, mixing them in various proportions with stearic acid and ethylcellulose as carriers. The mixture is then compressed into cylindrical tablets at several pressure values and the leaching rate of the radioprotective agents is then measured by spectrophotometry. The relation between the concentration of the active drug and its rate of release, and the effect on the release rate of the pressure applied to the tablet during its formation were also investigated. Results indicating that the release rate was linearly related to the square root of ''t'' seem to be in agreement with what is predictable, according to Higuchi's equation, save for the very initial and terminal phases. A clear correlation was also established between the stearic acid/ethylcellulose ratios and the release of 20% cysteine, namely a marked decrease in the rate of cysteine release was observed with increasing concentrations of stearic acid. Finally, it was observed that a higher formation pressure results in quicker release of the drug

  10. Preemptive mobile code protection using spy agents

    OpenAIRE

    Kalogridis, Georgios

    2011-01-01

    This thesis introduces 'spy agents' as a new security paradigm for evaluating trust in remote hosts in mobile code scenarios. In this security paradigm, a spy agent, i.e. a mobile agent which circulates amongst a number of remote hosts, can employ a variety of techniques in order to both appear 'normal' and suggest to a malicious host that it can 'misuse' the agent's data or code without being held accountable. A framework for the operation and deployment of such spy agents is described. ...

  11. 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.

  12. 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...

  13. A Framework for Organization-Aware Agents

    DEFF Research Database (Denmark)

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

    2017-01-01

    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......’ behavior space and describe the expected behavior of the agents. Assuming an open environment, where agents are developed independently of the Organizational structures, agents need to be able to reason about the structure, so that they can deliberate about their actions and act within the expected...

  14. 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

  15. 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.

  16. Knowledge Management in Role Based Agents

    Science.gov (United States)

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

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

  17. 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.

  18. 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.

  19. Metabolism and disposition of a novel antineoplastic JS-38 (Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl)) in rats.

    Science.gov (United States)

    Zhang, Hong; Liu, Quanhai; Fan, Tingting; Fang, Yu; Li, Ying; Wang, Guoping

    2012-03-01

    The metabolism and catabolism of a novel antineoplastic (ID code JS-38),Benzamide, N-[4-(2,4-dimethoxyphenyl)-4,5-dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl]-3,5-bis (trifluoromethyl)-(9Cl), were investigated in Wistar rats (3 female, 3 male). LC/UV, LC/MS, LC/MS/MS, NMR and acid hydrolysis methods showed that the metabolic process of JS-38 consists of a series of acetylation and glucoronation that form a metabolic product with a unique pharmacologic property of accelerating bone-marrow cell formation, and also showed a novel metabolic pathway of being acetylated and glucuronated in series.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Children as digital rights agents

    DEFF Research Database (Denmark)

    Stald, Gitte Bang

    2016-01-01

    This paper looks at children’s involvement and contribution to internet safety policy. In many respects, the research perspective on children and young people has also seen a shift towards the child as agent, as citizen (Livingstone 2002, 2009; Dahlgren 2007). With increasing attention given...... to children’s communication rights there is an acknowledgement that children’s voices should be heard in all matters that affect them (Hamelink 2008). We still, however, primarily discuss how adults could and should take responsibility in guarding children and young people from risk and harm, and what...... 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...

  5. Sustainable Society Formed by Unselfish Agents

    Science.gov (United States)

    Kikuchi, Toshiko

    It has been pointed out that if the social configuration of the three relations (market, communal and obligatory relations) is not balanced, a market based society as a total system fails. Using multi-agent simulations, this paper shows that a sustainable society is formed when all three relations are integrated and function respectively. When agent trades are based on the market mechanism (i.e., agents act in their own interest and thus only market relations exist), weak agents who cannot perform transactions die. If a compulsory tax is imposed to enable all weak agents to survive (i.e., obligatory relations exist), then the fiscal deficit increases. On the other hand, if agents who have excess income undertake the unselfish action of distributing their surplus to the weak agents (i.e., communal relations exist), then trade volume increases. It is shown that the existence of unselfish agents is necessary for the realization of a sustainable society. However, the survival of all agents is difficult in a communal society. In an artificial society, for all agents survive and fiscal balance to be maintained, all three social relations need to be fully integrated. These results show that adjusting the balance of the three social relations well lead to the realization of a sustainable society.

  6. Effects of cytochalasin congeners, microtubule-directed agents, and doxorubicin alone or in combination against human ovarian carcinoma cell lines in vitro

    International Nuclear Information System (INIS)

    Trendowski, Matthew; Christen, Timothy D.; Acquafondata, Christopher; Fondy, Thomas P.

    2015-01-01

    Although the actin cytoskeleton is vital for carcinogenesis and subsequent pathology, no microfilament-directed agent has been approved for cancer chemotherapy. One of the most studied classes of microfilament-directed agents has been the cytochalasins, mycotoxins known to disrupt the formation of actin polymers. In the present study, we sought to determine the effects of cytochalasin congeners toward human drug sensitive and multidrug resistant cell lines. SKOV3 human ovarian carcinoma and several multidrug resistant derivatives were tested for sensitivity against a panel of nine cytochalasin congeners, as well as three clinically approved chemotherapeutic agents (doxorubicin, paclitaxel, and vinblastine). In addition, verapamil, a calcium ion channel blocker known to reverse P-glycoprotein (P-gp) mediated drug resistance, was used in combination with multiple cytochalasin congeners to determine whether drug sensitivity could be increased. While multidrug resistant SKVLB1 had increased drug tolerance (was more resistant) to most cytochalasin congeners in comparison to drug sensitive SKOV3, the level of resistance was 10 to 1000-fold less for the cytochalasins than for any of the clinically approved agents. While cytochalasins did not appear to alter the expression of ATP binding cassette (ABC) transporters, several cytochalasins appeared to inhibit the activity of ABC transporter-mediated efflux of rhodamine 123 (Rh123), suggesting that these congeners do have affinity for drug efflux pumps. Cytochalasins also appeared to significantly decrease the F/G-actin ratio in both drug sensitive and drug resistant cells, indicative of marked microfilament inhibition. The cytotoxicity of most cytochalasin congeners could be increased with the addition of verapamil, and the drug sensitivity of resistant SKVLB1 to the clinically approved antineoplastic agents could be increased with the addition of cytochalasins. As assessed by isobolographic analysis and Chou

  7. Process for preparation of MR contrast agents

    DEFF Research Database (Denmark)

    2002-01-01

    The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution...... in droplet form into a chamber containing hydrogen gas (H2) enriched in para-hydrogen (p-1H2) and/or ortho-deuterium (o-2H2) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below...... earth's ambient field strength; iv) optionally dissolving said imaging agent in an aqueous medium; v) optionally separating said catalyst from the solution of said imaging agent in said aqueous medium; vi) optionally separating said solvent from the solution of said imaging agent in said aqueous medium...

  8. 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

  9. 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

  10. 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.

  11. Pinning synchronization of a mobile agent network

    International Nuclear Information System (INIS)

    Wang, Lei; Sun, You-xian

    2009-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  13. Modeling culture in intelligent virtual agents

    OpenAIRE

    Mascarenhas, S.; Degens, N.; Paiva, A.; Prada, R.; Hofstede, G.J.; Beulens, A.J.M.; Aylett, R.

    2016-01-01

    This work addresses the challenge of creating virtual agents that are able to portray culturally appropriate behavior when interacting with other agents or humans. Because culture influences how people perceive their social reality it is important to have agent models that explicitly consider social elements, such as existing relational factors. We addressed this necessity by integrating culture into a novel model for simulating human social behavior. With this model, we operationalized a par...

  14. 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...

  15. Emotional Storytelling using Virtual and Robotic Agents

    OpenAIRE

    Costa, Sandra; Brunete, Alberto; Bae, Byung-Chull; Mavridis, Nikolaos

    2016-01-01

    In order to create effective storytelling agents three fundamental questions must be answered: first, is a physically embodied agent preferable to a virtual agent or a voice-only narration? Second, does a human voice have an advantage over a synthesised voice? Third, how should the emotional trajectory of the different characters in a story be related to a storyteller's facial expressions during storytelling time, and how does this correlate with the apparent emotions on the faces of the list...

  16. 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.

  17. Intelligent Agents in E-Commerce

    OpenAIRE

    Valentin LITOIU; Amelia BADICA; Cristian ETEGAN

    2006-01-01

    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.

  18. Three essays in agent-based macroeconomics

    OpenAIRE

    Canzian, Giulia

    2009-01-01

    The dissertation is aimed at offering an insight into the agent-based methodology and its possible application to the macroeconomic analysis. Relying on this methodology, I deal with three different issues concerning heterogeneity of economic agents, bounded rationality and interaction. Specifically, the first chapter is devoted to describe the distinctive characteristics of agent-based economics and its advantages-disadvantages. In the second chapter I propose a credit market framework c...

  19. 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 (MIdeveloped 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 vasospasm after subarachnoid haemorrhage). An important situation where demonstrating tissue devitalisation is important is in interstitial ablation of focal liver lesions: using microbubble contrast agents at the end of a procedure allows immediate evaluation of the

  20. A Multi-Agent Environment for Negotiation

    Science.gov (United States)

    Hindriks, Koen V.; Jonker, Catholijn M.; Tykhonov, Dmytro

    In this chapter we introduce the System for Analysis of Multi-Issue Negotiation (SAMIN). SAMIN offers a negotiation environment that supports and facilitates the setup of various negotiation setups. The environment has been designed to analyse negotiation processes between human negotiators, between human and software agents, and between software agents. It offers a range of different agents, different domains, and other options useful to define a negotiation setup. The environment has been used to test and evaluate a range of negotiation strategies in various domains playing against other negotiating agents as well as humans. We discuss some of the results obtained by means of these experiments.

  1. 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.

  2. Story telling engine based on agent interaction

    OpenAIRE

    Porcel, Juan Carlos

    2008-01-01

    Comics have been used as a programming tool for agents, giving them instructions on how to act. In this thesis I do this in reverse, I use comics to describe the actions of agents already interacting with each other to create a storytelling engine that dynamically generate stories, based on the interaction of said agents. The model for the agent behaviours is based on the improvisational puppets model of Barbara Hayes-Roth. This model is chosen due to the nature of comics themselves. Comics ...

  3. Improving Multi-Agent Systems Using Jason

    DEFF Research Database (Denmark)

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

    2011-01-01

    We describe the approach used to develop the multi-agent system of herders that competed as the Jason-DTU team at the Multi-Agent Programming Contest 2010. We also participated in 2009 with a system developed in the agentoriented programming language Jason which is an extension of AgentSpeak. We ...... used the implementation from 2009 as a foundation and therefore much of the work done this year was on improving that implementation. We present a description which includes design and analysis of the system as well as the main features of our agent team strategy. In addition we discuss...

  4. 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.

  5. Characterization of chemical agent transport in paints.

    Science.gov (United States)

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

    2013-09-15

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

  6. 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

  7. 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.

  8. 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.

  9. Cutting agents for special metals

    International Nuclear Information System (INIS)

    Sugito, Seiji; Sakakibara, Fumi

    1979-01-01

    The quantity of use of special metals has increased year after year in the Plasma Research Institute, Nagoya University, with the development of researches on plasma and nuclear fusion. Most of these special metals are hard to cut, and in order to secure the surface smoothness and dimensional accuracy, considerable efforts are required. The method of experiment is as follows: cutting agents salt water and acetone, rape-seed oil, sulfide and chloride oil and water soluble cutting oil W grade 3; metals to be cut niobium, molybdenum, tantalum, titanium and tungsten; cutting conditions cutting speed 4.7 to 90 m/min, feed 0.07 to 0.2 mm/rev, depth of cut 0.1 to 0.4 mm, tool cemented carbide bit. Chemicals such as tetrachloromethane and trichloroethane give excellent cutting performance, but the toxicity is intense and the stimulative odor exists, accordingly they are hard to use practically. Cutting was easier when the salt water added with acetone was used than the case of rape-seed oil, but salt water is corrosive. Recently, the machining of molybdenum has been often carried out, and the water soluble cutting oil was the best. It is also good for cutting stainless steel, and its lubricating property is improved by adding some additives such as sulfur, chlorine, phosphorus and molybdenum disulfide. However after cutting with it, washing is required. (Kako, I.)

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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....

  15. 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

  16. A Secure Protocol Based on a Sedentary Agent for Mobile Agent Environments

    OpenAIRE

    Abdelmorhit E. Rhazi; Samuel Pierre; Hanifa Boucheneb

    2007-01-01

    The main challenge when deploying mobile agent environments pertains to security issues concerning mobile agents and their executive platform. This paper proposes a secure protocol which protects mobile agents against attacks from malicious hosts in these environments. Protection is based on the perfect cooperation of a sedentary agent running inside a trusted third host. Results show that the protocol detects several attacks, such as denial of service, incorrect execution and re-execution of...

  17. 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

  18. 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

  19. Prophylaxis and Therapy Against Chemical Agents

    Science.gov (United States)

    2009-11-01

    Hematopoietic Consequences F. Dorandeu 5) pH Dependent Toxicity of Sulphur Mustard In Vitro J. Mikler Nerve Agents / Scavengers 1) Mutagenesis...symptoms such as salivation or shortness of breath and lower level exposures could be rendered inconsequential. B.2 CURRENT THERAPY FOR NERVE AGENT

  20. Modeling agents with a theory of mind

    NARCIS (Netherlands)

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

    2009-01-01

    Training systems with intelligent virtual agents provide an effective means to train people for complex, dynamic tasks like crisis management or firefighting. Virtual agents provide more adequate behavior and explanations if they not only take their own goals and beliefs into account, but also the

  1. 13 CFR 120.952 - Fiscal agent.

    Science.gov (United States)

    2010-01-01

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

  2. Biological agents in polyarticular juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Amarilyo, Gil; Tarp, Simon; Foeldvari, Ivan

    2016-01-01

    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...

  3. 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.

  4. 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

  5. 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

  6. Deliberate normative agents : principles and architecture

    NARCIS (Netherlands)

    Dignum, F.P.M.; Castelfranchi, C.; Jonker, C.; Treur, J.; Jennings, N.R.; Lespérance, Y.

    2000-01-01

    In this paper norms are assumed to be useful in agent societies. It is claimed that not only following norms, but also the possibility of ‘intelligent’ norm violation can be useful. Principles for agents that are able to behave deliberatively on the basis of explicitly represented norms are

  7. 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

  8. 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...

  9. Stock market dynamics created by interacting agents

    Directory of Open Access Journals (Sweden)

    Mohamed Riad Remita

    2006-01-01

    Full Text Available We study a stock market model, consisting in a large number of agents, going eventually to infinity, and evaluate the stock price under the influence of opinions of different agents. Next we study the behavior of prices when the market is very nervous; there appear discontinuities (phase transitions which can be interpreted as stock market crashes.

  10. 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

  11. 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.

  12. 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

  13. Vivid agents : theory, architecture, and applications

    NARCIS (Netherlands)

    Schroeder, M.; Wagner, G.R.

    2000-01-01

    Vivid agents (Wagner, 1996) are software-controlled systems whose state comprises the mental components of knowledge, perceptions, tasks, and intentions, and whose behavior is represented by means of action and reaction rules. An execution model for vivid agents is presented, which is based on an

  14. 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

  15. Practice among Novice Change Agents in Schools

    Science.gov (United States)

    Blossing, Ulf

    2016-01-01

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

  16. 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

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

    Science.gov (United States)

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

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

  18. Process for encapsulating active agents in gels

    NARCIS (Netherlands)

    Yilmaz, G.; Jongboom, R.O.J.; Oosterhaven, J.

    2001-01-01

    The present invention relates to a process for encapsulating an active agent in a biopolymer in the form of a gel, comprising the steps of: a) forming a dispersion or solution of the biopolymer in water; and b) adding the active agent to the dispersion or solution obtained in step a); wherein the

  19. 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

  20. 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

  1. Dynamics of three-agent games

    Science.gov (United States)

    Mungan, Muhittin; Rador, Tonguç

    2008-02-01

    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.

  2. Improving Disability Awareness among Extension Agents

    Science.gov (United States)

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

    2014-01-01

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

  3. Your company's secret change agents.

    Science.gov (United States)

    Pascale, Richard Tanner; Sternin, Jerry

    2005-05-01

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

  4. Agent-Based Models in Social Physics

    Science.gov (United States)

    Quang, Le Anh; Jung, Nam; Cho, Eun Sung; Choi, Jae Han; Lee, Jae Woo

    2018-06-01

    We review the agent-based models (ABM) on social physics including econophysics. The ABM consists of agent, system space, and external environment. The agent is autonomous and decides his/her behavior by interacting with the neighbors or the external environment with the rules of behavior. Agents are irrational because they have only limited information when they make decisions. They adapt using learning from past memories. Agents have various attributes and are heterogeneous. ABM is a non-equilibrium complex system that exhibits various emergence phenomena. The social complexity ABM describes human behavioral characteristics. In ABMs of econophysics, we introduce the Sugarscape model and the artificial market models. We review minority games and majority games in ABMs of game theory. Social flow ABM introduces crowding, evacuation, traffic congestion, and pedestrian dynamics. We also review ABM for opinion dynamics and voter model. We discuss features and advantages and disadvantages of Netlogo, Repast, Swarm, and Mason, which are representative platforms for implementing ABM.

  5. CEST and PARACEST MR contrast agents

    International Nuclear Information System (INIS)

    Hancu, Ileana; Dixon, W. Thomas; Woods, Mark; Sherry, A. Dean; Vinogradov, Elena; Lenkinski, Robert E.

    2010-01-01

    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

  6. 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 ...

  7. 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 ...

  8. 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.

  9. 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...

  10. 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...

  11. Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope

    Science.gov (United States)

    Cremolini, Chiara; Aprile, Giuseppe; Lonardi, Sara; Orlandi, Armando; Mennitto, Alessia; Berenato, Rosa; Antoniotti, Carlotta; Casagrande, Mariaelena; Marsico, Valentina; Marmorino, Federica; Cardellino, Giovanni Gerardo; Bergamo, Francesca; Tomasello, Gianluca; Formica, Vincenzo; Longarini, Raffaella; Giommoni, Elisa; Caporale, Marta; Di Bartolomeo, Maria; Loupakis, Fotios; de Braud, Filippo

    2015-01-01

    Background. No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in “frail” elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. Materials and Methods. Forty elderly patients (aged ≥75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results. The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9–8 months) and 14.3 months (95% CI: 10.9–17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. Conclusion. Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. Implications for Practice: Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could

  12. Study of Crossling Agent and Couplink Agent Synergism on Mechanical Properties of HDPE-Cu Composites

    International Nuclear Information System (INIS)

    Mashuri; Sujud, A.A.; Karo Karo, Aloma

    2001-01-01

    The effects of crosslink agents, coupling agents and synergism on mechanical properties of HDPE-Cu composites materials has been investigated. The crosslink was made with dicumyl peroxide as crosslink agents of 2% concentration, so the interface adhesion of matrix-filler was made with 3-amino propyl triethoxysilane as coupling agents of 0.5% concentration. The results of research's showed, that the crosslink and interface adhesion of matrix-filler can increase tensile strength and elongation at break of HDPE-Cu composites. The synergism of two agents can increase tensile strength to 20% and elongation at break to 23% of HDPE-Cu composites materials

  13. 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 business pro...

  14. 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...

  15. [Decorporation agents for internal radioactive contamination].

    Science.gov (United States)

    Ohmachi, Yasushi

    2015-01-01

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

  16. 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.

  17. Metareasoning and Social Evaluations in Cognitive Agents

    Science.gov (United States)

    Pinyol, Isaac; Sabater-Mir, Jordi

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

  18. New antithrombotic agents in the ambulatory setting.

    Science.gov (United States)

    Gibbs, Neville M; Weightman, William M; Watts, Stephen A

    2014-12-01

    Many patients presenting for surgical or other procedures in an ambulatory setting are taking new antiplatelet or anticoagulant agents. This review assesses how the novel features of these new agents affect the management of antithrombotic therapy in the ambulatory setting. There have been very few studies investigating the relative risks of continuing or ceasing new antithrombotic agents. Recent reviews indicate that the new antithrombotic agents offer greater efficacy or ease of administration but are more difficult to monitor or reverse. They emphasize the importance of assessing the bleeding risk of the procedure, the thrombotic risk if the agent is ceased, and patient factors that increase the likelihood of bleeding. The timing of cessation of the agent, if required, depends on its pharmacokinetics and patients' bleeding risks. Patients at high risk of thrombotic complications may require bridging therapy. Once agreed upon, the perioperative plan should be made clear to all involved. As there are few clinical studies to guide management, clinicians must make rational decisions in relation to continuing or ceasing new antithrombotic agents. This requires knowledge of their pharmacokinetics, and a careful multidisciplinary assessment of the relative thrombotic and bleeding risks in individual patients.

  19. 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.

  20. 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...

  1. 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.

  2. 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...

  3. 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....

  4. Mechanisms of resistance to alkylating agents

    OpenAIRE

    Damia, G.; D‘Incalci, M.

    1998-01-01

    Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...

  5. AORTA: Adding Organizational Reasoning to Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Dignum, Virginia

    2014-01-01

    the expected behavior of the agents. Agents need to be able to reason about the regulations, so that they can act within the expected boundaries and work towards the objectives of the organization. This extended abstract introduces AORTA, a component that can be integrated into agents’ reasoning mechanism......, allowing them to reason about (and act upon) regulations specified by an organizational model using simple reasoning rules. The added value is that the organizational model is independent of that of the agents, and that the approach is not tied to a specific organizational model....

  6. Automatic Generation of Agents using Reusable Soft Computing Code Libraries to develop Multi Agent System for Healthcare

    OpenAIRE

    Priti Srinivas Sajja

    2015-01-01

    This paper illustrates architecture for a multi agent system in healthcare domain. The architecture is generic and designed in form of multiple layers. One of the layers of the architecture contains many proactive, co-operative and intelligent agents such as resource management agent, query agent, pattern detection agent and patient management agent. Another layer of the architecture is a collection of libraries to auto-generate code for agents using soft computing techni...

  7. Francisella tularensis - potential biological agent

    International Nuclear Information System (INIS)

    Taleski, V.

    2009-01-01

    Francisella tularensis is a small, nonmotile, aerobic, gram-negative coccobacillus capable of surviving for weeks at low temperatures in water, moist soil, hay, straw, or decaying animal carcasses. F. tularensis is the causative of the zoonotic disease tularemia. This bacterium was first identified in ground squirrels in Tulare County, California (1912). The human disease was recognized and described by Edward Francis (1922) as tularemia, and the agent was renamed Francisella tularensis in his honor. F. tularensis is one of the most infectious bacterial pathogens known, as few as 10-50 organisms can cause disease. Humans can become incidentally infected through diverse environmental exposures: bites by infected arthropods; handling infectious animal tissues or fluids; direct contact with or ingestion of contaminated food, water, or soil and inhalation of infective aerosols. Humans can develop severe and sometimes fatal illness, but do not transmit the disease to others. F. tularensis have few subspecies: 1) F. tularensis subsp. tularensis (type A), highly virulent, found only in North America. The bacterium is transmitted among animals and from animals to humans by ticks, occasionally deerfly, or by aerosols; 2) F. tularensis subsp. holarctica (type B), moderately virulent, occurs in Euroasia and North America, mainly associated with streams, lakes, ponds, rivers and semi-aquatic animals such as muskrats and beavers (water-borne disease). Type B tularemia has been observed during war times (during Second World War 100 000 cases occurred each year, in Kosovo in 2000 and 2003 over 300 cases each year); 3) F. tularensis subsp. mediasiatica, rarely reported, isolated only in Kazahstan and Turkmenistan; 4) F. tularensis subsp. novicida is of low virulence, isolated in USA, Canada, Spain and Australia; 5) F. tularensis subsp. philomiragia, is of low virulence, associated with salt water (Atlantic, Mediterranean). Tularemia is very rear in Macedonia, but in 1996 an

  8. Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

    Science.gov (United States)

    Daryaei, Iman; Pagel, Mark D

    2015-01-01

    Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

  9. Modelling User Preferences and Mediating Agents in Electronic Commerce

    NARCIS (Netherlands)

    Dastani, M.M.; Jacobs, N.; Jonker, C.M.; Treur, J.

    2005-01-01

    An important ingredient in agent-mediated electronic commerce is the presence of intelligent mediating agents that assist electronic commerce participants (e.g. individual users, other agents, organisations). These mediating agents are in principle autonomous agents that interact with their

  10. Modeling User Preferences and Mediating Agents in Electronic Commerce

    NARCIS (Netherlands)

    Dastani, M.M.; Jacobs, N.; Jonker, C.M.; Treur, J.; Dignum, F.; Sierra, C.

    2001-01-01

    An important ingredient in agent-mediated Electronic Commerce is the presence of intelligent mediating agents that assist Electronic Commerce participants (e.g., individual users, other agents, organisations). These mediating agents are in principle autonomous agents that will interact with their

  11. Towards Culturally-Aware Virtual Agent Systems

    DEFF Research Database (Denmark)

    Endrass, Birgit; André, Elisabeth; Rehm, Matthias

    2010-01-01

    Globalization leads to an increase in intercultural encounters with a risk of misunderstandings due to different patterns of behavior and understanding. Learning applications have been proposed that employ virtual agents as their primary tool. Through their embodiment, learning can be done...... in a game-like environment in a more interesting way than for example learning with a textbook. The authors support the idea that virtual agents are a great opportunity for teaching cultural awareness. Realizing this, the concept of culture needs to be translated into computational models and the advantages...... of different systems using virtual agents need to be considered. Therefore, the authors reflect in this chapter on how virtual agents can help to learn about culture, scan definitions of culture from the social sciences, give an overview on how multiagent systems developed over time and classify the state...

  12. Agent-based modeling of sustainable behaviors

    CERN Document Server

    Sánchez-Maroño, Noelia; Fontenla-Romero, Oscar; Polhill, J; Craig, Tony; Bajo, Javier; Corchado, Juan

    2017-01-01

    Using the O.D.D. (Overview, Design concepts, Detail) protocol, this title explores the role of agent-based modeling in predicting the feasibility of various approaches to sustainability. The chapters incorporated in this volume consist of real case studies to illustrate the utility of agent-based modeling and complexity theory in discovering a path to more efficient and sustainable lifestyles. The topics covered within include: households' attitudes toward recycling, designing decision trees for representing sustainable behaviors, negotiation-based parking allocation, auction-based traffic signal control, and others. This selection of papers will be of interest to social scientists who wish to learn more about agent-based modeling as well as experts in the field of agent-based modeling.

  13. Veterans and agent orange: update 2000

    National Research Council Canada - National Science Library

    Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Third Biennial Update), Division of Health Promotion and Disease Prevention

    2001-01-01

    Veterans and Agent Orange: Update 2000 examines the state of the scientific evidence regarding associations between diseases and exposure to dioxin and other chemical compounds in herbicides used in Vietnam...

  14. Ontology-based multi-agent systems

    Energy Technology Data Exchange (ETDEWEB)

    Hadzic, Maja; Wongthongtham, Pornpit; Dillon, Tharam; Chang, Elizabeth [Digital Ecosystems and Business Intelligence Institute, Perth, WA (Australia)

    2009-07-01

    The Semantic web has given a great deal of impetus to the development of ontologies and multi-agent systems. Several books have appeared which discuss the development of ontologies or of multi-agent systems separately on their own. The growing interaction between agents and ontologies has highlighted the need for integrated development of these. This book is unique in being the first to provide an integrated treatment of the modeling, design and implementation of such combined ontology/multi-agent systems. It provides clear exposition of this integrated modeling and design methodology. It further illustrates this with two detailed case studies in (a) the biomedical area and (b) the software engineering area. The book is, therefore, of interest to researchers, graduate students and practitioners in the semantic web and web science area. (orig.)

  15. Penetratin and derivatives acting as antifungal agents

    NARCIS (Netherlands)

    Masman, Marcelo F.; Rodriguez, Ana M.; Raimondi, Marcela; Zacchino, Susana A.; Luiten, Paul G. M.; Somlai, Csaba; Kortvelyesi, Tamas; Penke, Botond; Enriz, Ricardo D.

    The synthesis, in vitro evaluation, and conformational study of RQIKTWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC

  16. Ulipristal acetate as an emergency contraceptive agent.

    Science.gov (United States)

    Martinez, Alan M; Thomas, Michael A

    2012-09-01

    Emergency contraceptive agents play a crucial role in preventing unplanned pregnancy. These agents and devices have been studied since the 1960s and have had varied results in terms of side effects and efficacy. A new oral tablet for emergency contraception (EC), ulipristal acetate (UPA) , is a selective progesterone receptor modulator and can be used up to 120 h following unprotected intercourse, without an increase in adverse effects or a decrease in efficacy. This article reviews studies that evaluate the pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile of UPA as an emergency contraceptive agent. UPA, a selective progesterone receptor modulator, is administered as a single 30 mg dose for EC. This agent provides a comparable, if not better, efficacy and side effect profile than seen with levonorgestrel or mifepristone. Because it has both agonistic and antagonistic effects on the progesterone receptor, ongoing clinical trials are documenting UPA's use for patients with endometriosis and as an extended use contraceptive.

  17. Competing intelligent search agents in global optimization

    Energy Technology Data Exchange (ETDEWEB)

    Streltsov, S.; Vakili, P. [Boston Univ., MA (United States); Muchnik, I. [Rutgers Univ., Piscataway, NJ (United States)

    1996-12-31

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

  18. Putative neuroprotective agents in neuropsychiatric disorders.

    Science.gov (United States)

    Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael

    2013-04-05

    In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Agentes de software móviles

    Directory of Open Access Journals (Sweden)

    Crisman Martínez Barrera

    2001-10-01

    Full Text Available Los agentes móviles son programas de software inteligentes que realizan un objetivo que involucran desarrollos soportados en técnicas de Inteligencia Artificial, los cuales pretenden facilitar la interoperabilidad de sistemas. Este artículo define las disciplinas, plataformas y herramientas necesarias para el desarrollo de agentes móviles, sus características principales y las arquitecturas predominantes de éstas; presenta además una evaluación de sus perspectivas futuras.Mobile agents are intelligent software programs that can obtain an objective that involucrates developments supported in Artificial Intelligence techniques. These pretend to facilitate the interoperability of systems. This article defines disciplines, platforms and tools necessary for the development of mobile agents, their principal characteristics and the predominant architectures of these. A final evaluation and future perspectives are offered.

  20. Mandatory Compensation to Commercial Agents upon Termination ...

    African Journals Online (AJOL)

    Kamil Abdu Oumer

    the compensation due to the agent upon the termination of the commercial .... Virginia School of Law Legal Studies Working Papers Series, Working Paper No. ..... grant up to a one year commission if they find the circumstances equitable.67 In.

  1. Chemical Agents: Facts about Sheltering in Place

    Science.gov (United States)

    ... What CDC is Doing Blog: Public Health Matters Chemical Agents: Facts About Sheltering in Place Format: Select ... What “sheltering in place” means Some kinds of chemical accidents or attacks may make going outdoors dangerous. ...

  2. Nominaliseeritud protsessi agent meediauudistes / Reet Kasik

    Index Scriptorium Estoniae

    Kasik, Reet, 1946-

    2006-01-01

    Ajalehe "Postimees" 2005. aasta materjalile toetudes vaadeldakse, mis tüüpi on nominalisatsioonides representeeritavad protsessid ja mis kujul on esitatud protsessi agent ehk tegija. Aluseks on võetud funktsionaalse grammatika põhimõtted.

  3. Argumentation and Multi-Agent Decision Making

    OpenAIRE

    Parsons, S.; Jennings, N. R.

    1998-01-01

    This paper summarises our on-going work on mixed- initiative decision making which extends both classical decision theory and a symbolic theory of decision making based on argumentation to a multi-agent domain.

  4. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... cancer cells for cancer diagnosis in MRI. F127-Folate coated SPION were stable in various types of suspension medium for over six months. They could specifically target folate receptor of cancer cells in vitro and in vivo thus enhancing the contrast in MRI T2/T2* weighted images. These are preliminary...

  5. Production of Antimicrobial Agent by Streptomyces violachromogenes

    International Nuclear Information System (INIS)

    Ahmed, Arwa A.

    2007-01-01

    The isolation of antibiotics from microorganisms improved the discovery of novel antibiotics, which is relatively easy as compared to chemical synthesis of antimicrobial agents. This study starts from isolation and purification of the antimicrobial producing Sterptomycetes obtained from soil habitat of Yemen. The good antimicrobial producing Sterptomycetes isolate was selected from a batch of Sterptomycetes isolates then identified. This isolate has bioactivity against some G+ve and G-ve bacteria. The antimicrobial agent isolated from Streptomyces violachromogenes (isolate no.YA118) was extracted with ethyl acetate at pH 3. The residue was applied to a silica gel column chromatography and eluted stepwise with many solvent systems. The active fractions were tested with B. subtilis NCTC10400. The purification of the antibiotic has been carried out by thin layer chromatography then the physical and chemical properties were studied to identify the antimicrobial agent. The isolated antimicrobial agent is an antibiotic belonging to the neomycin group. (author)

  6. Intelligent agents in data-intensive computing

    CERN Document Server

    Correia, Luís; Molina, José

    2016-01-01

    This book presents new approaches that advance research in all aspects of agent-based models, technologies, simulations and implementations for data intensive applications. The nine chapters contain a review of recent cross-disciplinary approaches in cloud environments and multi-agent systems, and important formulations of data intensive problems in distributed computational environments together with the presentation of new agent-based tools to handle those problems and Big Data in general. This volume can serve as a reference for students, researchers and industry practitioners working in or interested in joining interdisciplinary work in the areas of data intensive computing and Big Data systems using emergent large-scale distributed computing paradigms. It will also allow newcomers to grasp key concepts and potential solutions on advanced topics of theory, models, technologies, system architectures and implementation of applications in Multi-Agent systems and data intensive computing. .

  7. Enzymatic Decontamination of Chemical Warfare Agents

    National Research Council Canada - National Science Library

    Raushel, Frank

    2000-01-01

    The primary objective of this research program is the development of a versatile enzyme-based system that is fully optimized for the decontamination, destruction, and detection of know chemical warfare agents...

  8. Behavioural domain knowledge transfer for autonomous agents

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2014-11-01

    Full Text Available , and Behavior Transfer in Autonomous Robots, AAAI 2014 Fall Symposium Series, 13-15 November 2014 Behavioural Domain Knowledge Transfer for Autonomous Agents Benjamin Rosman Mobile Intelligent Autonomous Systems Modelling and Digital Science Council...

  9. Multi-agent sequential hypothesis testing

    KAUST Repository

    Kim, Kwang-Ki K.; Shamma, Jeff S.

    2014-01-01

    incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well

  10. Spions as nano-theranostics agents

    CERN Document Server

    Zarepour, Atefeh; Khosravi, Arezoo

    2017-01-01

    This Brief introduces SuperParamagnetic Iron Oxide Nanoparticles (SPIONs), the different synthesis approaches, their applications in the field of diagnostics and treatment and finally as theranostic agents in cancer.

  11. inventory management, VMI, software agents, MDV model

    Directory of Open Access Journals (Sweden)

    Waldemar Wieczerzycki

    2012-03-01

    Full Text Available Background: As it is well know, the implementation of instruments of logistics management is only possible with the use of the latest information technology. So-called agent technology is one of the most promising solutions in this area. Its essence consists in an entirely new way of software distribution on the computer network platform, in which computer exchange among themselves not only data, but also software modules, called just agents. The first aim is to propose the alternative method of the implementation of the concept of the inventory management by the supplier with the use of intelligent software agents, which are able not only to transfer the information but also to make the autonomous decisions based on the privileges given to them. The second aim of this research was to propose a new model of a software agent, which will be both of a high mobility and a high intelligence. Methods: After a brief discussion of the nature of agent technology, the most important benefits of using it to build platforms to support business are given. Then the original model of polymorphic software agent, called Multi-Dimensionally Versioned Software Agent (MDV is presented, which is oriented on the specificity of IT applications in business. MDV agent is polymorphic, which allows the transmission through the network only the most relevant parts of its code, and only when necessary. Consequently, the network nodes exchange small amounts of software code, which ensures high mobility of software agents, and thus highly efficient operation of IT platforms built on the proposed model. Next, the adaptation of MDV software agents to implementation of well-known logistics management instrument - VMI (Vendor Managed Inventory is illustrated. Results: The key benefits of this approach are identified, among which one can distinguish: reduced costs, higher flexibility and efficiency, new functionality - especially addressed to business negotiation, full automation

  12. Agent-Based Computing: Promise and Perils

    OpenAIRE

    Jennings, N. R.

    1999-01-01

    Agent-based computing represents an exciting new synthesis both for Artificial Intelligence (AI) and, more genrally, Computer Science. It has the potential to significantly improve the theory and practice of modelling, designing and implementing complex systems. Yet, to date, there has been little systematic analysis of what makes an agent such an appealing and powerful conceptual model. Moreover, even less effort has been devoted to exploring the inherent disadvantages that stem from adoptin...

  13. Institutions, Behavior of Agents and Efficiency

    Directory of Open Access Journals (Sweden)

    Sukharev Oleg, S.

    2016-03-01

    Full Text Available We study the efficiency criterion, describing the behavior and choices of agents, the influence of moral norms on the model of behavior, as well as the criterion of efficiency as an institution to assess the behavior and development of the economic system. Curve proposed institutional compromise that allows to determine the possibility of changes in the welfare of interacting agents and their compliance with ethical standards when welfare increases due to violation or compliance with these standards. For the purposes of this demonstration of the influence of the model of chart-based dilemmas Holmes-Moriarty. Incentives in determining the agents behaviors play a key role in their formation due to the moral principles of behavior. However, in economics there are situations when moral principles are derived certain behaviors or interactions agents. Holmes and Moriarty there is an alternative interaction, which they can not take advantage of, and there is a full range of alternatives that actually programs the strategic outcomes of interactions that reflect the curves of "institutional compromise." Choosing an agent of moral standards as a potential model determines its behavior and, most importantly, interaction with other agents, adhering to certain moral principles. Assess the condition and the possibility of using a static criterion of Pareto efficiency for the analysis of situations where it is important to measure the economic efficiency. Showing institutional aspects that must be considered in the application or formulation of new performance criteria. It is proved that there is a connection microeconomic efficiency / inefficiency and parameters of behavior of agents that actualizes the need to impact on the behavior of agents incentives to solve the task of changing the structure.

  14. Maintaining the Identify of Dynamically Embodied Agents

    OpenAIRE

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

    2005-01-01

    Virtual agents are traditionally constrained in their embod- iment, as they are restricted to one form of body. We propose allowing them to change their embodiment in order to expand their capabili- ties. This presents users with a number of di±culties in maintaining the identity of the agents, but these can be overcome by using identity cues, certain features that remain constant across embodiment forms. This pa- per outlines an experiment that examines these identity cues, and shows that th...

  15. Executive Compensation and Principal-Agent Theory.

    OpenAIRE

    Garen, John E

    1994-01-01

    The empirical literature on executive compensation generally fails to specify a model of executive pay on which to base hypotheses regarding its determinants. In contrast, this paper analyzes a simple principal-agent model to determine how well it explains variations in CEO incentive pay and salaries. Many findings are consistent with the basic intuition of principle-agent models that compensation is structured to trade off incentives with insurance. However, statistical significance for some...

  16. Quality of service agents in the internet

    OpenAIRE

    Schelén, Olov

    1998-01-01

    The Internet is a multi-purpose communication network supporting users and applications with different service demands. To meet these demands, mechanisms for service differentiation in the network are proposed. This thesis presents an admission control architecture where clients can make resource reservations through agents. For each domain in the network there is an agent responsible for admission control. The architecture provides scalable resource reservations for virtual leased lines. Res...

  17. Bisimulation for Single-Agent Plausibility Models

    DEFF Research Database (Denmark)

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

    2013-01-01

    define a proper notion of bisimulation, and prove that bisimulation corresponds to logical equivalence on image-finite models. We relate our results to other epistemic notions, such as safe belief and degrees of belief. Our results imply that there are only finitely many non-bisimilar single......-agent epistemic plausibility models on a finite set of propositions. This gives decidability for single-agent epistemic plausibility planning....

  18. Non-toxic brominated perfluorocarbons radiopaque agents

    International Nuclear Information System (INIS)

    Long, D.M. Jr.

    1976-01-01

    Non-toxic bromofluorocarbon radiopaque agents are disclosed. Certain monobrominated acyclic fluorocarbons, e.g., CF 3 (CF 2 ) 6 CF 2 Br, are improved non-toxic radiopaque agents useful in diagnostic roentgenology, for example in visualizing the gastrointestinal tract, the tracheobronchial tree, the alveolar spaces or parenchyma of the lung, the spleen, the urinary bladder and ureters, the common bile duct and its radicals, the pancreatic ducts, the blood vessels, etc. 13 claims, no drawings

  19. Antimicrobial Agents Used in Endodontic Treatment

    Directory of Open Access Journals (Sweden)

    Marina George Kudiyirickal

    2008-01-01

    Full Text Available Biomechanical preparation alone does not completely eradicate microorganisms from the root canal, hence the next logical step is to perform root canal procedures in conjunction with antimicrobials. The use of an antimicrobial agent improves the efficacy and prognosis of endodontic treatment. This review enumerates the most widely used antimicrobial agents, their mechanism of action and their potential use in reducing the microbial load.

  20. Contrast agent incompatibility with intravascular medications

    International Nuclear Information System (INIS)

    Irving, H.D.; Burbridge, B.E.

    1988-01-01

    In vitro and in vivo precipitation of iodinated contrast agents with commonly used medications have been reported. The intent of this in vitro study is to verify these reports and investigate other medications not previously tested. Contrast agents and medications were analyzed with a light spectrometer and observed for visible precipitates for up to 120 minutes. Previously reported incompatibilities were verified, and several new incompatibilities were discovered