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Sample records for differentiation-inducing agents mycophenolic

  1. Mycophenolic acid agents: is enteric coating the answer?

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    Manitpisitkul W

    2011-03-01

    Full Text Available Wana Manitpisitkul1, Sabrina Lee2, Matthew Cooper31Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA; 2Solid Organ Transplant Program, University of Utah Health Care, Salt Lake City, UT, USA; 3Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Addition of mycophenolate mofetil (MMF to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological and gastrointestinal (GI side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium (EC-MPS was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.Keywords: enteric-coated mycophenolate sodium, mycophenolate mofetil, kidney transplant, efficacy, gastrointestinal tolerability

  2. Enteric-coated mycophenolate sodium.

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    Gabardi, Steven; Tran, Jennifer L; Clarkson, Michael R

    2003-11-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis. All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects. Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia. Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.

  3. Properties of a non-bioactive fluorescent derivative of differentiation-inducing factor-3, an anti-tumor agent found in Dictyostelium discoideum

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    Yuzuru Kubohara

    2014-03-01

    Full Text Available Differentiation-inducing factor-3 (DIF-3, found in the cellular slime mold Dictyostelium discoideum, and its derivatives, such as butoxy-DIF-3 (Bu-DIF-3, are potent anti-tumor agents. To investigate the activity of DIF-like molecules in tumor cells, we recently synthesized a green fluorescent DIF-3 derivative, BODIPY-DIF-3G, and analyzed its bioactivity and cellular localization. In this study, we synthesized a red (orange fluorescent DIF-3 derivative, BODIPY-DIF-3R, and compared the cellular localization and bioactivities of the two BODIPY-DIF-3s in HeLa human cervical cancer cells. Both fluorescent compounds penetrated the extracellular membrane within 0.5 h and localized mainly to the mitochondria. In formalin-fixed cells, the two BODIPY-DIF-3s also localized to the mitochondria, indicating that the BODIPY-DIF-3s were incorporated into mitochondria independently of the mitochondrial membrane potential. After treatment for 3 days, BODIPY-DIF-3G, but not BODIPY-DIF-3R, induced mitochondrial swelling and suppressed cell proliferation. Interestingly, the swollen mitochondria were stainable with BODIPY-DIF-3G but not with BODIPY-DIF-3R. When added to isolated mitochondria in vitro, BODIPY-DIF-3G increased dose-dependently the rate of O2 consumption, but BODIPY-DIF-3R did not. These results suggest that the bioactive BODIPY-DIF-3G suppresses cell proliferation, at least in part, by altering mitochondrial activity, whereas the non-bioactive BODIPY-DIF-3R localizes to the mitochondria but does not affect mitochondrial activity or cell proliferation.

  4. Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].

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    Yuzuru Kubohara

    Full Text Available Differentiation-inducing factor-3 (DIF-3, found in the cellular slime mold Dictyostelium discoideum, and its derivatives such as butoxy-DIF-3 (Bu-DIF-3 are potent anti-tumor agents. However, the precise mechanisms underlying the actions of DIF-3 remain to be elucidated. In this study, we synthesized a green fluorescent derivative of DIF-3, BODIPY-DIF-3, and a control fluorescent compound, Bu-BODIPY (butyl-BODIPY, and investigated how DIF-like molecules behave in human cervical cancer HeLa cells by using both fluorescence and electron microscopy. BODIPY-DIF-3 at 5-20 µ M suppressed cell growth in a dose-dependent manner, whereas Bu-BODIPY had minimal effect on cell growth. When cells were incubated with BODIPY-DIF-3 at 20 µM, it penetrated cell membranes within 0.5 h and localized mainly in mitochondria, while Bu-BODIPY did not stain the cells. Exposure of cells for 1-3 days to DIF-3, Bu-DIF-3, BODIPY-DIF-3, or CCCP (a mitochondrial uncoupler induced substantial mitochondrial swelling, suppressing cell growth. When added to isolated mitochondria, DIF-3, Bu-DIF-3, and BOIDPY-DIF-3, like CCCP, dose-dependently promoted the rate of oxygen consumption, but Bu-BODIPY did not. Our results suggest that these bioactive DIF-like molecules suppress cell growth, at least in part, by disturbing mitochondrial activity. This is the first report showing the cellular localization and behavior of DIF-like molecules in mammalian tumor cells.

  5. [Duodenal villous atrophy associated with Mycophenolate mofetil: report of one case].

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    Tapia, Oscar; Villaseca, Miguel; Sierralta, Armando; Roa, Juan Carlos

    2010-05-01

    Mycophenolate mofetil (MMF) is an immunosupressor agent frequently used in patients after bone marrow or solid organ transplants. The most common adverse reactions of the drug are gastrointestinal, specially diarrhea and vomiting. We report a 53-year-old male, that received a heart transplant receiving immunosuppression with cyclosporine, mycophenolate mofetil and prednisone. Six months after the transplant, the patient started with diarrhea, anorexia and weight loss. A duodenal biopsy showed villous atrophy. Celiac disease and the presence of parasites were discarded. Mycophenolate mofetil was discontinued and one week later, diarrhea subsided. Two months later the patient was asymptomatic and recovered weight. A new duodenal biopsy showed absence of villous atrophy.

  6. Exposure to Mycophenolate and Fatherhood.

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    Midtvedt, Karsten; Bergan, Stein; Reisæter, Anna Varberg; Vikse, Bjørn Egil; Åsberg, Anders

    2017-07-01

    Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium, and it is widely used after organ transplantation. In women, taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by men exposed to MPA. We compared outcomes in pregnancies fathered by renal transplant men per whether they had been exposed to MPA or not at time of conception. A nationwide population-based retrospective cohort study was performed. Data from the Norwegian Renal Registry with all renal transplanted men alive between January 1, 1995 and December 31, 2015 were included, and relevant outcome data were extracted from the Medical Birth Registry of Norway. During the given time, 230 immunosuppressed renal transplanted men fathered 350 children (155 on MPA/195 not on MPA). There were no significant increased risks of malformation (3.9% vs. 2.6%, P = 0.49) in MPA exposed versus unexposed cohorts of children. The average dose (±SD) of mycophenolate was 1.42 ± 0.3 g/day and the individual median MPA trough concentration in the time period of anticipated conception and pregnancy was 2.8 ± 1.6 mg/L. Birth weight was similar in exposed and unexposed cohorts of children; 3381 ± 681 g vs. 3429 ± 714 g (P = 0.53). Paternal exposure to MPA did not increase the risk of adverse birth outcomes in children fathered by male kidney transplanted patients. These results are reassuring and support the continuation of paternal MPA treatment before, during, and after conception.

  7. Determination of the oxygen enhancement ratio (OER) of human colon tumor cells in vitro after chronic exposure to the differentiation-inducing agents n-methylformamide (NMF) and sodium butyrate (NAB)

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    Hallows, K.; Bliven, S.; Leith, J.T.

    1987-01-01

    The authors previously showed that both rodent and human tumor cells in either exponentially growing or plateau phase cultures can be sensitized to X-irradiation by chronic exposure to NMF or NAB. This effect is particularly evident in the low dose region of the survival curve as noted by a significant increase in the term of the linear-quadratic equation or by a significant decrease in the D/sub q/ value using single-hit, multitarget nomenclature. However, these agents are operationally distinct, as these changes are accompanied by inhibition of sublethal damage recovery (SLDR) after NAB treatment, while no effect on SLDR is seen with NMF treatment. As they think that the use of differentiation-inducing agent such as NMF or NAB may be useful in combining modality therapy of solid tumors, the authors extended their previous studies to note if any change in the OER accompanying this observed radiosensitization of oxic cells could be found. Tumor cells were grown in either 170mM NMF or 2 mM NAB and were irradiated with 250 kVp x-rays. Data is presented

  8. Mycophenolate

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    ... your muscles; confusion or difficulty thinking clearly; unsteadiness; memory loss; difficulty speaking or understanding what others say; ... is important to keep all medication out of sight and reach of children as many containers (such ...

  9. Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

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    Gabardi, Steven; Olyaei, Ali

    2012-01-01

    To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity

  10. Transcriptional activation of cyclin-dependent kinase inhibitor, p21waf1 gene by treatment with a differentiation inducing agent, vesnarinone in a human salivary gland cancer cell line.

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    Omotehara, F; Nakashiro, K; Uchida, D; Hino, S; Fujimori, T; Kawamata, H

    2003-03-01

    Recently, a new concept for cancer therapy termed "tumor dormancy therapy" has been proposed. The concept of this therapy is to prolong the survival time of cancer patients while maintaining their quality of life. We have been developing a differentiation-inducing therapy, which is included in the tumor dormancy therapy, for salivary gland cancer. In this study, we examined the effect of a differentiation-inducing drug, Vesnarinone on the growth of several cancer cells, and examined the molecular mechanism by which Vesnarinone induces the cyclin dependent kinase inhibitor, p21waf1 in the cancer cells. Vesnarinone significantly suppressed the growth of TYS (salivary gland cancer cells), PC3 (prostate cancer cells), and A431 (squamous cell cancer cells). Furthermore, Vesnarinone dose-dependently enhanced the expression of p21waf1 mRNA in TYS cells. Using the luciferase reporter assay it was found that the enhancement of p21waf1 mRNA expression by Vesnarinone was through direct transcriptional activation of the p21waf1 promoter. Thus, analyzing the molecular mechanisms of differentiation inducing drugs may lead to the development of a new therapeutic strategy for several human malignancies, including salivary gland cancer.

  11. Mycophenolate fetal toxicity and risk evaluation and mitigation strategies.

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    Kim, M; Rostas, S; Gabardi, S

    2013-06-01

    The mycophenolic acid (MPA) preparations are one of the most commonly used immunosuppressants in the United States. However, these agents carry a black box warning regarding their use during pregnancy due to an association with increased risk of miscarriage and congenital defects. To ensure that the benefits of MPA outweigh the risks, the Food and Drug Administration (FDA) required all manufacturers of MPA products to propose risk evaluation and mitigation strategies (REMS). Four years after initially calling for proposals, the FDA approved a single shared REMS system in September 2012. The elements of the MPA REMS include a medication guide and elements to assure safe use (ETASU). The medication guide, which was previously FDA-approved in 2008, should continue to be distributed to patients, and the ETASU requires physicians to complete training and obtain patient signatures on the "Patient-Prescriber Acknowledgement Form." A single, national, voluntary pregnancy registry is available, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA products among patients and possibly practitioners. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. USE OF MYCOPHENOLATE MOPHETYL IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS

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    S.I. Valiyeva,

    2006-01-01

    Full Text Available The article reports a case of highly active SLE and lupusbnephritis in a 15 years old boy, who was treated with mycophenolate mophetyl the case was notable for high activity and aggressive course of the disease with rapid development of renal unsufficiency, polyorganic unsufficiency and antiphospholipid syndrome. Although the patient received an appropriate active therapy, including synchronized therapy (consisting of timebrelated plasmopherresis and infusions of cyclophosphamide and metyl prednisolone, glucocorticoides, preparations improving blood circulation (pentoxyphillin, dipiridamol, heparine, intravenous immunoglobulins, the disease activity control was unsufficient. The administration of mycophenolate mophetyl has led to diminuition of the disease activity, which was registered at the end of the second week of treatment, and finally has reached a level of clinical and laboratoty remission of the disease.Key words: systemic lupus erythematosus, mycophenolate mophetyl, children, treatment.

  13. Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.

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    Deen, Kristyn; McMeniman, Erin

    2015-03-01

    Erosive genital lichen planus is a disabling, inflammatory mucocutaneous condition that can cause significant patient morbidity and loss of function. Treatment initially involves topical corticosteroids but some patients can have severe treatment-resistant courses requiring systemic immunosuppression. With potentially unfavorable adverse effect profiles and subsequent intolerance of these agents by patients, erosive lichen planus can ultimately be a challenging condition to treat effectively. We present a case of a 66-year-old woman with treatment-resistant erosive genital lichen planus who was successfully managed with mycophenolate mofetil. Although there is only weak evidence for this agent in this condition, its role in dermatology is growing due to its efficacy and advantageous adverse effect profile and should therefore be considered in patients with treatment-resistant erosive genital lichen planus. © 2015 Japanese Dermatological Association.

  14. Pharmacokinetic study of mycophenolic acid in Iranian kidney transplant patients

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    Saeed Rezaee

    2013-02-01

    Full Text Available Background: The purpose of this study was to characterize the pharmacokinetic parameters of mycophenolic acid (MPA in Iranian kidney transplant patients. Methods: Plasma MPA concentration of mycophenolate mofetile (MMF 1 gram two times a day was measured in 21 Iranian kidney transplant recipients receiving treatment. Patients who entered the study had been transplanted for more than 3 months and their drug level was supposed to be at steady state. MMF concentration was measured with high-performance liquid chromatography (HPLC. Results: The plasma MPA concentration-time curve was characterized by an early sharp peak at about 1 hour postdose. The mean Area Under Curve (AUC, Cmax and Tmax were 47.0±18.3 µg.h/ml, 18.6±8.5 µg/ml and 1.0±0.5 hours respectively. Conclusion: The plasma MPA concentration-time curve pattern of Iranian patients was similar and consistent with previously reported profiles in other populations taking the same dose. Keywords: Mycophenolate mofetil, Mycophenolic acid, Pharmacokinetics, Area Under Curve, Kidney transplantation

  15. Risk evaluation and mitigation strategies: a focus on the mycophenolic acid preparations.

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    Rostas, Sara; Kim, Miae; Gabardi, Steven

    2014-03-01

    To review risks associated with mycophenolic acid (MPA) preparations and evaluate their required risk evaluation and mitigation strategies (REMS) elements. Articles were identified through a non-date-limited MEDLINE and EMBASE search using the terms fetal toxicity, teratogenicity, risk evaluation and mitigation strategies, REMS, MPA, mycophenolate mofetil, entericcoated MPA, and organ transplant. Information from the Food and Drug Administration (FDA) and the manufacturers of the MPA preparations was also evaluated. The MPA preparations are associated with several potential risks, including gastrointestinal disturbances and myelosuppression; however, their impact on the fetus in pregnant patients taking 1 of these agents poses the greatest risk. The FDA approved REMS programs for all MPA products, both innovator and generic preparations, in September 2012. With evidence of increased risk of miscarriage and birth defects associated with MPA use, the FDA instituted a REMS program that contains both a medication guide and elements to assure safe use (ETASU). The medication guides for the MPA products, which were previously FDA approved, should continue to be distributed to patients who get either an initial prescription filled or a refill. The ETASU requires prescribers to complete training and obtain patient signatures on the Patient-Prescriber Acknowledgment Form. A single, national, voluntary pregnancy registry specific to this medication has been established, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA.

  16. Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation.

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    Ma, Xiaoli; He, Jiawei; Yan, Jin; Wang, Qing; Li, Hui

    2016-03-25

    Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Limited sampling strategies drawn within 3 hours postdose poorly predict mycophenolic acid area-under-the-curve after enteric-coated mycophenolate sodium.

    NARCIS (Netherlands)

    Winter, B.C. de; Gelder, T. van; Mathôt, R.A.A.; Glander, P.; Tedesco-Silva, H.; Hilbrands, L.B.; Budde, K.; Hest, R.M. van

    2009-01-01

    Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of

  18. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    International Nuclear Information System (INIS)

    Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-01-01

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

  19. Anti-Rhodotorula activity of mycophenolic acid enhanced in the presence of polyene antibiotic nystatin.

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    Kinoshita, H; Wongsuntornpoj, S; Ihara, F; Nihira, T

    2017-02-01

    Rhodotorula species are opportunistic pathogens, which cause not only systemic fungaemia but also other localized infections. Despite serious side effects such as nephrotoxicity and hypokalemia, amphotericin B (a polyene antifungal) has been commonly prescribed for Rhodotorula infection because Rhodotorula species are resistant against a candin family of antifungal agents. In this study, novel active compounds against Rhodotorula species were screened from the extracts of entomopathogenic fungi based on the synergistic effect of polyene nystatin (NYS), which causes efficient targeting of compounds due to increased permeability through the fungal cell membrane. Around 37% of culture extracts from 31 entomopathogenic fungal strains showed anti-Rhodotorula activity in the synergistic bioassay system, suggesting that the coexistence assay with NYS enhanced the discovery of anti-Rhodotorula compounds. Judging from various physicochemical data, the active component from strain HF763 was identified as an immunosuppressant drug, mycophenolic acid (MPA). The minimum inhibitory concentration of MPA against three pathogenic Rhodotorula strains was determined, focusing on the synergistic effect with NYS. The results revealed that the values decreased by at least 87% in the presence of NYS, indicating that MPA showed a synergistic effect with NYS. This study aimed to screen active compounds against Rhodotorula species that are resistant to a candin family of antifungal agents, from entomopathogenic fungi. Assuming that most of the latent antifungal compounds do not exert their activity due to their inability to penetrate the membrane, we took advantage of polyene nystatin in the screening to increase permeability through the fungal cell membrane. The result of the screening revealed hidden antifungal activity of mycophenolic acid, demonstrating that the method applied in this study unlocks the potentials of bioresources, and proposes a new remedy for mycosis. © 2016 The

  20. Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

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    Tellier, Stéphanie; Dallocchio, Aymeric; Guigonis, Vincent; Saint-Marcoux, Frank; Llanas, Brigitte; Ichay, Lydia; Bandin, Flavio; Godron, Astrid; Morin, Denis; Brochard, Karine; Gandia, Peggy; Bouchet, Stéphane; Marquet, Pierre; Decramer, Stéphane

    2016-01-01

    Background and objectives Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid–dependent nephrotic syndrome. Design, setting, participants, & measurements This was a retrospective multicenter study including 95 children with steroid–dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. Results In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30–60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). Conclusions Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid–dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population. PMID:27445161

  1. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease

    NARCIS (Netherlands)

    de Winter, Brenda C. M.; Neumann, Irmgard; van Hest, Reinier M.; van Gelder, Teun; Mathot, Ron A. A.

    2009-01-01

    Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the

  2. Predicting the usefulness of therapeutic drug monitoring of mycophenolic acid: a computer simulation

    NARCIS (Netherlands)

    van Hest, Reinier; Mathot, Ron; Vulto, Arnold; Weimar, Willem; van Gelder, Teun

    2005-01-01

    The usefulness of therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) was investigated with a computer simulation model. For a fixed-dose (FD) and a concentration-controlled (CC) MMF dosing regimen exposure to mycophenolic acid (MPA) was compared. A nonlinear mixed-effects model

  3. Pharmacodynamic Monitoring of Inosine Monophosphate Dehydrogenase Activity: A Basis For Optimized and Individualized Mycophenolate Mofetil Therapy

    NARCIS (Netherlands)

    F. Sombogaard (Ferdi)

    2010-01-01

    textabstractIn 1896 Gosic isolated for the first time mycophenolic acid (MPA) from Penicillium glaucum.It was subsequently isolated from Penicillium stoloniferum Thom (synonym P. brevi-compactum Dierckx) by Alsberg and Black in 1913 who gave the acid phenolic substance its name mycophenolic acid

  4. A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins.

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    Vendrell-Criado, Victoria; González-Bello, Concepción; Miranda, Miguel A; Jiménez, M Consuelo

    2018-06-15

    Binding of the immunosuppressive agent mycophenolate mofetil (MMP) and its pharmacologically active metabolite mycophenolic acid (MPA) to human serum albumin (HSA) and α 1 -acid glycoprotein (HAAG) has been investigated by means of an integrated approach involving selective excitation of the drug fluorophore, following their UV-A triggered fluorescence and docking studies. The formation of the protein/ligand complexes was evidenced by a dramatic enhancement of the fluorescence intensity and a hypsochromic shift of the emission band. In HSA, competitive studies using oleic acid as site I probe revealed site I as the main binding site of the ligands. Binding constants revealed that the affinity of the active metabolite by HSA is four-fold higher than its proactive form. Moreover, the affinity of MMP by HSA is three-fold higher than by HAAG. Docking studies revealed significant molecular binding differences in the binding of MMP and MPA to sub-domain IIA of HSA (site 1). For MPA, the aromatic moiety would be in close contact to Trp214 with the flexible chain pointing to the other end of the sub-domain; on the contrary, for MMP, the carboxylate group of the chain would be fixed nearby Trp214 through electrostatic interactions with residues Arg218 and Arg222. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms.

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    Pithukpakorn, Manop; Tiwawanwong, Tiwat; Lalerd, Yupaporn; Assawamakin, Anunchai; Premasathian, Nalinee; Tasanarong, Adis; Thongnoppakhun, Wanna; Vongwiwatana, Attapong

    2014-01-01

    Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population. Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis. A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39-89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC. Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.

  6. Enteric-coated mycophenolate sodium experience in liver transplant patients.

    Science.gov (United States)

    Cantisani, G P C; Zanotelli, M L; Gleisner, A L M; de Mello Brandão, A; Marroni, C A

    2006-04-01

    Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

  7. Future immunosuppressive agents in solid-organ transplantation.

    Science.gov (United States)

    Gabardi, Steven; Cerio, Jeffrey

    2004-06-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.

  8. The necrotic signal induced by mycophenolic acid overcomes apoptosis-resistance in tumor cells.

    Directory of Open Access Journals (Sweden)

    Gwendaline Guidicelli

    Full Text Available BACKGROUND: The amount of inosine monophosphate dehydrogenase (IMPDH, a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP, is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA-mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL-overexpressing cells. All tested cells remained sensitive to MPA-mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers. CONCLUSIONS/SIGNIFICANCE: These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells.

  9. Esophageal Cicatricial Pemphigoid as an Isolated Involvement Treated with Mycophenolate Mofetil

    Directory of Open Access Journals (Sweden)

    Sandra Sánchez Prudencio

    2015-01-01

    Full Text Available Cicatricial pemphigoid (CP is a rare blistering autoimmune disease. Esophageal involvement occurs in widespread disease and rarely appears as the only affected organ. We report a 67-year-old Caucasian female with esophageal dysphagia and weight loss. Several oral panendoscopies showed multiple exudative ulcerations with fibrin and webs in mid- and proximal esophagus and a peeling mucosa. There were no lesions in other organs. We established the diagnosis performing a direct immunofluorescence (DIF, demonstrating IgG3 and complement deposition along the basement membrane. As initial treatment the patient received prednisone 60 mg and 1 gr twice daily of mycophenolate mofetil (MMF as a steroid-sparing agent due to its lower toxicity and its selective mechanism of action. Six months later there was a significant clinical improvement and the esophageal ulcerations had disappeared, developing cicatricial fibrous rings, although no stenosis was present. Four years later, the patient remains asymptomatic with a low maintenance dose of MMF.

  10. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome.

    Science.gov (United States)

    Perez-Aytes, Antonio; Marin-Reina, Purificacion; Boso, Virginia; Ledo, Ana; Carey, John C; Vento, Maximo

    2017-01-01

    Mycophenolate mofetil (MMF) is probably the most common employed immunosuppressant drug in recipients of solid organ transplant and in many autoimmune diseases. In vitro studies, a significant number of single clinical observations and a recent study from a group of different European teratogen information services, have provided very consistent data supporting the existence of a specific MMF embryopathy. The typical malformative pattern of MMF embryopathy includes external ear anomalies ranging from hypoplastic pinna (microtia) to complete absence of pinna (anotia); cleft lip, with or without cleft palate, and ocular anomalies as iris or chorioretinal coloboma and anophthalmia/microphthalmia. Other less frequent features are congenital heart defects, distal limbs anomalies, esophageal atresia, vertebral malformations, diaphragmatic hernia, and kidney and central nervous system anomalies. Neurodevelopmental outcome seems favorable in the small number of patients where information about this issue is available, but neurological deficits have been documented. Physicians in charge of women under MMF therapy should be aware of the potential risk of this drug to cause a specific embryopathy and the need of interrupting the treatment at least six weeks before becoming pregnant. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Mycophenolate mofetil in pediatric renal transplantation: A single center experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-01

    Raheem OA, Kamel MH, Daly PJ, Mohan P, Little DM, Awan A, Hickey DP. Mycophenolate mofetil in pediatric renal transplantation: A single center experience. Pediatr Transplantation 2011: 15:240-244. © 2009 John Wiley & Sons A\\/S. Abstract:  We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p < 0.0001). In conclusion, the use of MMF in pediatric renal transplantation was not associated with a lower rejection rate or immunological graft loss. It did, however, result in a significantly higher rate of viral infections.

  12. Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

    Science.gov (United States)

    Doycheva, Deshka; Zierhut, Manfred; Blumenstock, Gunnar; Sobolewska, Bianka; Voykov, Bogomil; Hohmann, Johanna; Spitzer, Martin S; Deuter, Christoph

    2016-08-01

    To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

    Science.gov (United States)

    Segovia, Javier; Gerosa, Gino; Almenar, Luis; Livi, Ugolino; Viganò, Mario; Arizón, Jose Maria; Yonan, Nizar; Di Salvo, Thomas G; Renlund, Dale G; Kobashigawa, Jon A

    2008-01-01

    Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

  14. Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis.

    LENUS (Irish Health Repository)

    Moore, Jason

    2009-02-27

    Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.

  15. Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation.

    Science.gov (United States)

    Patel, Gopal; Patil, Mahesh D; Soni, Surbhi; Chisti, Yusuf; Banerjee, Uttam Chand

    2017-05-01

    Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KH 2 PO 4 8.0, MgSO4⋅7H 2 O 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.

  16. Simultaneous determination of ochratoxin A, mycophenolic acid and fumonisin B-2 in meat products

    DEFF Research Database (Denmark)

    Sørensen, Louise Marie; Mogensen, Jesper; Nielsen, Kristian Fog

    2010-01-01

    Here we present a method for simultaneous determination of the fungal metabolites mycophenolic acid, ochratoxin A (OTA) and fumonisin B-2 (FB2) in meat products. Extraction was performed with water-acetonitrile, followed by acetone-induced precipitation of salts and proteins. Purification...

  17. Mycophenolate mofetil in renal transplantation : 3-year results from the placebo-controlled trial

    NARCIS (Netherlands)

    Behrend, M; Grinyo, J; Vanrenterghem, Y; Rodicio, J; Albrechtsen, D; Sadek, S; Soulillou, JP; van Son, W; Groth, C; Mjornstedt, L; Wiesel, M; Neumayer, HH; Tufveson, G; Ekberg, H; Tarantino, A; Thiel, G; Hene, R; Morgan, A; Ramos, E; Rees, M

    1999-01-01

    Background. The European double-blind, placebo (PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of

  18. Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

    NARCIS (Netherlands)

    Mertens, Jorre S.; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

    2016-01-01

    To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events

  19. Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation

    NARCIS (Netherlands)

    D. Kuypers (Dirk); Y. le Meur (Yann); M. Cantarovich (Marcelo); M.J. Tredger (Michael); S.E. Tett (Susan); D. Cattaneo (Dario); B. Tönshoff (Burkhard); D.W. Holt (David); J. Chapman (Jeremy); T. van Gelder (Teun)

    2010-01-01

    textabstractWith the increasing use of mycophenolic acid (MPA) in solid organ transplantation, the need for more accurate drug dosing has become evident. Personalized immunosuppressive therapy requires better strategies for avoidance of drug-related toxicity while maintaining efficacy. Few studies

  20. Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy: A Case Series.

    Science.gov (United States)

    Avasare, Rupali S; Canetta, Pietro A; Bomback, Andrew S; Marasa, Maddalena; Caliskan, Yasar; Ozluk, Yasemin; Li, Yifu; Gharavi, Ali G; Appel, Gerald B

    2018-03-07

    C3 glomerulopathy is a form of complement-mediated GN. Immunosuppressive therapy may be beneficial in the treatment of C3 glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its role in the treatment of other complement-mediated diseases and the results of the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study the outcomes of patients with C3 glomerulopathy treated with steroids and mycophenolate mofetil. We conducted a retrospective chart review of patients in the C3 glomerulopathy registry at Columbia University and identified patients treated with mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We studied clinical, histologic, and genetic data for the whole group and compared data for those who achieved complete or partial remission (responders) with those who did not achieve remission (nonresponders). We compared remission with mycophenolate mofetil with remission with other immunosuppressive regimens. We identified 30 patients who met inclusion criteria. Median age was 25 years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine (interquartile range, 1720-6759). The median follow-up time was 32 months (interquartile range, 21-68). Twenty (67%) patients were classified as responders. There were no significant differences in baseline characteristics between responders and nonresponders, although initial proteinuria was lower (median 2468 mg/g creatinine) in responders compared with nonresponders (median 5000 mg/g creatinine) and soluble membrane attack complex levels were higher in responders compared with nonresponders. For those tapered off mycophenolate mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done, and in 12 patients, we found 18 variants predicted to be damaging. None of these variants were previously reported to be pathogenic. Mycophenolate

  1. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis.

    Science.gov (United States)

    Sobrin, Lucia; Christen, William; Foster, C Stephen

    2008-08-01

    To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. Retrospective noncomparative case series. Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

  2. A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Non-Infectious Uveitis

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne TA; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-01-01

    Objective To compare the relative effectiveness of methotrexate and mycophenolate mofetil for non-infectious intermediate uveitis, posterior uveitis, or panuveitis. Design Multicenter, block-randomized, observer-masked clinical trial Participants Eighty patients with non-infectious intermediate, posterior or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Intervention Patients were randomized to receive 25mg weekly oral methotrexate or 1g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Main Outcome Measures Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤ 10 mg of prednisone and ≤ 2 drops of prednisolone acetate 1% a day and (3) no declaration of treatment failure due to intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Results Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (p=0.09). Treatment failure due to adverse events or tolerability was not significantly different by treatment arm (p=0.99). There were no statistically significant differences between treatment groups in time to corticosteroid-sparing control of inflammation (p=0.44), change in best spectacle-corrected visual acuity (p=0.68), and resolution of macular

  3. A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne T A; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-10-01

    To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of

  4. Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

    Science.gov (United States)

    Lv, Qing-Kang; Liu, Ju-Xiong; Li, Su-Nan; Gao, Ying-Jie; Lv, Yan; Xu, Zi-Peng; Huang, Bing-Xu; Xu, Shi-Yao; Yang, Dong-Xue; Zeng, Ya-Long; Liu, Dian-Feng; Wang, Wei

    2015-11-06

    Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

  5. Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

    Science.gov (United States)

    Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

    2017-09-01

    Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

  6. Simultaneous determination of mycophenolate mofetil and its active metabolite, mycophenolic acid, by differential pulse voltammetry using multi-walled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Madrakian, Tayyebeh, E-mail: madrakian@basu.ac.ir; Soleimani, Mohammad; Afkhami, Abbas

    2014-09-01

    A highly sensitive electrochemical sensor for the simultaneous determination of mycophenolate mofetil (MPM) and mycophenolic acid (MPA) was fabricated by multi-walled carbon nanotubes modified glassy carbon electrode (MWCNTs/GCE). The electrochemical behavior of these two drugs was studied at the modified electrode using cyclic voltammetry and adsorptive differential pulse voltammetry. MPM and MPA were oxidized at the GCE during an irreversible process. DPV analysis showed two oxidation peaks at 0.87 V and 1.1 V vs. Ag/AgCl for MPM and an oxidation peak at 0.87 V vs. Ag/AgCl for MPA in phosphate buffer solution of pH 5.0. The MWCNTs/GCE displayed excellent electrochemical activities toward oxidation of MPM and MPA relative to the bare GCE. The experimental design algorithm was used for optimization of DPV parameters. The electrode represents linear responses in the range 5.0 × 10{sup −6} to 1.6 × 10{sup −4} mol L{sup −1} and 2.5 × 10{sup −6} mol L{sup −1} to 6.0 × 10{sup −5} mol L{sup −1} for MPM and MPA, respectively. The detection limit was found to be 9.0 × 10{sup −7} mol L{sup −1} and 4.0 × 10{sup −7} mol L{sup −1} for MPM and MPA, respectively. The modified electrode showed a good sensitivity and stability. It was successfully applied to the simultaneous determination of MPM and MPA in plasma and urine samples. - Highlights: • A new modified electrochemical sensor was constructed and used. • Multiwalled carbon nanotubes were used as the modifiers. • MPM and MPA were measured simultaneously at the low levels. • The sensor was used to the determination of MPA and MPM in real samples.

  7. Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

    Science.gov (United States)

    Lemaitre, Florian; Ben Ali, Zeineb; Tron, Camille; Jezequel, Caroline; Boglione-Kerrien, Christelle; Verdier, Marie-Clémence; Guyader, Dominique; Bellissant, Eric

    2017-08-01

    No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

  8. Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

    Science.gov (United States)

    Paul, Christina; Lin-Shaw, Ammy; Joseph, Mariamma; Kwan, Keith; Sergiacomi, Gianluigi; Mura, Marco

    2016-01-01

    Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored. © 2016 S. Karger AG, Basel.

  9. Effectiveness of cyclosporine and mycophenolate mofetil in a child with refractory evans syndrome

    Directory of Open Access Journals (Sweden)

    Piero Farruggia

    2011-05-01

    Full Text Available Evans Syndrome is a rare autoimmune disease consisting of hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. Its course can be extremely serious and, rarely, even life-threatening; thus it represents a excellent treatment challenge for the pediatric hematologist. First line treatment consists of steroids and/or immunoglobulin; further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We describe a baby with refractory Evans Syndrome that was cured by prolonged administration of mycophenolate mofetil and remained disease-free for 4 years after the discontinuation of treatment.

  10. Isolation of furocoumarins from bergamot fruits as HL-60 differentiation-inducing compounds.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

    1999-10-01

    The HL-60 differentiation-inducing compounds in bergamot fruits were isolated with column chromatography and identified as bergamottin, bergapten, and citropten by (1)H and (13)C NMR. Their HL-60 differentiation-inducing activity was measured by examining nitro blue tetrazolium (NBT) reducing, nonspecific acid esterase (NSE), specific esterase (SE), and phagocytic activities, and bergamottin showed the strongest activity among the coumarins isolated from bergamot fruits. The structure-activity relationship obtained from HL-60 differentiation assay suggests that hydrophobicity of furocoumarins is correlated with their activity.

  11. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways.

    Directory of Open Access Journals (Sweden)

    Boying Dun

    Full Text Available Mycophenolic acid (MPA is the metabolized product and active element of mycophenolate mofetil (MMF that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, we demonstrated for the first time MPA's antimigratory and anti-invasion abilities of MPA-sensitive AGS (gastric cancer cells. Genome-wide expression analyses using Illumina whole genome microarrays identified 50 genes with ≥2 fold changes and 15 genes with > 4 fold alterations and multiple molecular pathways implicated in cell migration. Real-time RT-PCR analyses of selected genes also confirmed the expression differences. Furthermore, targeted proteomic analyses identified several proteins altered by MPA treatment. Our results indicate that MPA modulates gastric cancer cell migration through down-regulation of a large number of genes (PRKCA, DOCK1, INF2, HSPA5, LRP8 and PDGFRA and proteins (PRKCA, AKT, SRC, CD147 and MMP1 with promigratory functions as well as up-regulation of a number of genes with antimigratory functions (ATF3, SMAD3, CITED2 and CEAMCAM1. However, a few genes that may promote migration (CYR61 and NOS3 were up-regulated. Therefore, MPA's overall antimigratory role on cancer cells reflects a balance between promigratory and antimigratory signals influenced by MPA treatment.

  12. Do cytostatic drugs reach drinking water? The case of mycophenolic acid

    International Nuclear Information System (INIS)

    Franquet-Griell, Helena; Ventura, Francesc; Boleda, M.Rosa; Lacorte, Silvia

    2016-01-01

    Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17–56.2 ng L"−"1). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. - Highlights: • MPA, a cytostatic drug, has been identified as a new river water contaminant. • MPA is eliminated during dioxychlorination in a drinking water treatment plant. • No residues of MPA were detected in finished drinking water. • Isotope dilution LC-MS/MS permitted the trace quantification of MPA in water. - Mycophenolic acid, a cytostatic drug, has been identified as a new river water contaminant and it is removed during purification in a Drinking Water Treatment Plant.

  13. PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

    NARCIS (Netherlands)

    GRINYO, J; GROTH, C; PICHLMAYR, R; SADEK, SA; VANRENTERGHEM, Y; BEHREND, M; LUCK, R; MORESO, F; PEETERS, J; RODICIO, J; MORALES, J; ALBRECHTSEN, D; FAUCHALD, P; SADEK, S; LODGE, J; SOULILLOU, JP; CANTAROVICH, D; van Son, W; Tegzess, Adam; WAGNER, K; ERHARD, J; BRATTSTROM, C; MJORNSTEDT, L; WIESEL, M; CARL, S; NEUMAYER, HH; HAUSER, [No Value; LANG, P; BOURGEON, B; TUFVESON, G; GANNEDAHL, G; EKBERG, H; PERSSON, N; TARANTINO, A; CAMPISE, M; THIEL, G; ZEILER, M; HENE, R; LIGTENBERG, G; MORGAN, A; RIGG, K; HOOFTMAN, L; HUTCHINSON, K

    1995-01-01

    Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with

  14. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  15. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  16. Do cytostatic drugs reach drinking water? The case of mycophenolic acid.

    Science.gov (United States)

    Franquet-Griell, Helena; Ventura, Francesc; Boleda, M Rosa; Lacorte, Silvia

    2016-01-01

    Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17-56.2 ng L(-1)). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Proteomic analysis of PC12 cell differentiation induced by ionizing radiation

    International Nuclear Information System (INIS)

    Zhang Junquan; Gao Ronglian; Chen Xiaohua; Wang Zhidong; Dong Bo; Rao Yalan; Hou Lili; Zhang Hao; Mao Bingzhi

    2005-01-01

    Objective: To explore the molecular mechanism of PC12 cell differentiation induced by ionizing radiation and screen the molecular target of nervous system injured by irradiation. Methods: PC12 cells were irradiated with 16 Gy 60 Co γ ray. Total proteins of normal and irradiated cells were prepared 48 hours after irradiation and separated with two dimensional gel electrophoresis. Some differential expressed proteins were characterized with mass spectrometry. Results: 876 differential expressed proteins were observed. Up-regulated expression of ubiquitin carboxyl-terminal hydratase L1 was found. Down-regulated expression of new protein similar to HP1α was found. Conclusion: The characterization of some differential expressed proteins through proteomic analysis would benefit the research of molecular mechanism of PC12 cell differentiation induced by ionizing radiation. (authors)

  18. Inosine monophosphate dehydrogenase messenger RNA expression is correlated to clinical outcomes in mycophenolate mofetil-treated kidney transplant patients, whereas inosine monophosphate dehydrogenase activity is not

    NARCIS (Netherlands)

    Sombogaard, Ferdi; Peeters, Annemiek M. A.; Baan, Carla C.; Mathot, Ron A. A.; Quaedackers, Monique E.; Vulto, Arnold G.; Weimar, Willem; van Gelder, Teun

    2009-01-01

    Measurement of the pharmacodynamic biomarker inosine monophosphate dehydrogenase (IMPDH) activity in renal transplant recipients has been proposed to reflect the biological effect better than using pharmacokinetic parameters to monitor mycophenolate mofetil therapy. The IMPDH assays are however

  19. Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Hyeyoung Kim

    2014-09-01

    Full Text Available Background/AimsThe dose of mycophenolate mofetil (MMF has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT.MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12 for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter, with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day, and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

  20. "Determination of mycophenolic acid in human plasma by high-performance liquid chromatography"

    Directory of Open Access Journals (Sweden)

    "Mehdi Ahadi Barzoki

    2005-05-01

    Full Text Available A simple, sensitive and reproducible HPLC method is presented for determination of mycophenolic acid(MPA in human plasma. Samples were prepared after precipitation of the plasma protein by addition of acetonitrile and naproxen was used as internal standard (I.S.. Separation was performed by reversedphase HPLC, using a Hamilton PRP-C18 Column, 51% acetonitrile and 49% potassium phosphate buffer (20 mM at pH 3.0 as mobile phase, flow rate of 1.0 ml/min, and UV detection at 215 nm. MPA and I.S. had retention times of 7.5 and 11.35 min, respectively. The method showed an acceptable linearity in the range of 0.1µg/ml-40µg/ml with r2 of .9992. The concentration of 0.1µg/ml was determined as quantification limit. Mean absolute recovery was 94.8%. The mean intra- and inter-day reproducibility of method was 4.6 and 11.4% respectively.

  1. Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis.

    Science.gov (United States)

    Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik

    2017-06-01

    To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

  2. Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

    Directory of Open Access Journals (Sweden)

    Einollahi Behzad

    2015-04-01

    Full Text Available Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF was prescribed to control chronic allograft nephropathy. He presented with complaints of severe abdominal pain, vomiting, loss of appetite and fever requiring hospital admission twelve days later. Acute pancreatitis was diagnosed on the basis of laboratory data and imaging findings during hospital admission. There was no history of alcohol consumption in our patient. Unfortunately he died one week later and autopsy findings demonstrated acute necrotizing pancreatitis. The bladder drainage of this patients was normal. Laboratory findings in this patient did not endorse infections and other possibilities regarding the etiology of acute pancreatitis in this patient. Therefore, we concluded that acute pancreatitis in near the patient was induced by drugs and basis on our evidence, MMF is the most important suspect. This study suggests that acute pancreatitis can be considered as a side effect of MMF.

  3. Mycophenolic acid suppresses human pterygium and normal tenon fibroblast proliferation in vitro.

    Science.gov (United States)

    Amer, Radgonde; Rabinowich, Liane; Maftsir, Genia; Puxeddu, Ilaria; Levi-Schaffer, Francesca; Solomon, Abraham

    2010-10-01

    To investigate whether mycophenolic acid (MPA) exerts antifibrotic effects on pterygium fibroblasts (PFB) with and without stimulation with fibrogenic cytokines, and to compare the efficacy of MPA with mitomycin (MMC) and dexamethasone (DXM) on PFB and tenon fibroblasts (TFB). TFB and PFB were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts ± basic fibroblast growth factor (bFGF) (10 ng/ml) was assessed by using the (3H) thymidine-incorporation assay. Cell cultures were incubated with MPA, MMC or DXM. Apoptosis was evaluated by quantifying Annexin V and propidium iodide positive cells with flow cytometry. MPA showed a concentration-dependent inhibition of proliferation of PFB ± bFGF as well as TFB ± bFGF. The antiproliferative effect of MPA was comparable with that of MMC and DXM. Short exposure of PFB to MPA under profibrogenic conditions was significantly inhibitory. No apoptotic effect was found on TFB. MPA suppressed tenon and pterygium fibroblast proliferation in vitro under basal and profibrogenic conditions. It was comparable with MMC under long-term exposure, but MMC was more suppressive under short-term exposure. MPA may be safer than MMC due to a more specific mechanism of action and lack of cytotoxicity. Further investigation is warranted regarding MPA concentrations that will lead to a potent antiproliferative effect in vivo.

  4. Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

    Science.gov (United States)

    Phillips, Karen; Reddy, Prabashni; Gabardi, Steven

    2017-02-01

    The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

  5. Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kubohara, Yuzuru, E-mail: ykuboha@juntendo.ac.jp [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Health Science, Juntendo University Graduate School of Health and Sports Science, Inzai 270-1695 (Japan); Komachi, Mayumi [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Homma, Yoshimi [Department of Biomolecular Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295 (Japan); Kikuchi, Haruhisa; Oshima, Yoshiteru [Laboratory of Natural Product Chemistry, Tohoku University Graduate School of Pharmaceutical Sciences, Aoba-yama, Aoba-ku, Sendai 980-8578 (Japan)

    2015-08-07

    Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.

  6. Validated, Ultra Violet Spectroscopy method for the Dissolution study of Mycophenolate mofetil immediate release 500mg tablets

    OpenAIRE

    Surajpal P. Verma; Ozair Alam; Pooja Mullick; Nadeem Siddiqui; Suroor A. Khan

    2008-01-01

    A simple, selective and precise dissolution method was developed and validated for the Mycophenolate mofetil immediate release tablets. The method employed dissolution medium 0.1N HCl (pH1.2) and volume 900ml with USP-II apparatus (Paddle). Detection was made by measuring the absorbance on UV at the [lambda]~max~ 250nm. The method show the linearity in the range of conc. 5[micro]g/ml to 40[micro]g/ml with r^2^=0.999. The method is also validated as per International Conference of Harmonizatio...

  7. De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression

    Directory of Open Access Journals (Sweden)

    F. Friedersdorff

    2010-04-01

    Full Text Available Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient’s current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

  8. Determination of Mycophenolic acid in the vitreous humor using the HPLC-ESI-MS/MS method: application of intraocular pharmacokinetics study in rabbit eyes with ophthalmic implantable device.

    Science.gov (United States)

    Martins Duarte Byrro, Ricardo; de Oliveira Fulgêncio, Gustavo; Rocha Chellini, Paula; da Silva Cunha, Armando; Pianetti, Gerson Antônio

    2013-10-01

    Mycophenolic acid (MPA) is an immunosuppressive agent widely used in the treatment of solid organ transplant rejection. The success of MPA in the treatment of inflammatory intraocular diseases has been reported in recent literature. The treatment of inflammatory eye diseases in the posterior chamber is a challenge due to the anatomy of the eye, which presents certain barriers to drug access. Thus, the bioavailability of drugs in the eye is quite low, and successful drug delivery may well represent a key limiting factor to attaining a successful therapeutic strategy. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions. Thus, a novel delivery system based on a biodegradable polymeric device, which can be implanted inside the eye and deliver MPA directly to the target, is being developed. Specific analytical methods to determine the use of effective drugs within the eye are needed to characterize this device. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantitation of MPA in the vitreous humor of rabbits was developed and validated. The vitreous was collected from rabbits, extracted by a protein precipitation extraction procedure and then separated on a C18 column with a mobile phase comprised of 0.15% aqueous acetic acid and methanol (60:40, v/v). The calibration curve was constructed within the range of 3-10,000 ng/mL for MPA. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the MPA concentration in the vitreous humor of rabbits treated with an ocular implantable device. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Differentiation-inducing effects of small fruit juices on HL-60 leukemic cells.

    Science.gov (United States)

    Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Murofushi, N; Nishimura, H

    2000-08-01

    Epidemiological studies indicate that high intakes of fruits and vegetables are associated with a reduced risk of cancer, and several plant-derived drugs have been developed in medical oncology. Since only a small part of the flora has been tested for any kind of bioactivity, we chose small fruits as sources of differentiation-inducing activity against HL-60 leukemic cells. We have prepared juices from various small fruits that grow mainly in the northern part of Japan. Screening of 43 samples indicated that juices of Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray, and Sorbus sambucifolia Roem. strongly induced differentiation of HL-60 cells to monocyte/macrophage characteristics in a concentration-dependent manner as indicated by histochemical and biochemical examinations.

  10. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

    Directory of Open Access Journals (Sweden)

    Hidekazu Kuwayama

    Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

  11. Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

    Science.gov (United States)

    Li, Pengmei; Shuker, Nauras; Hesselink, Dennis A; van Schaik, Ron H N; Zhang, Xianglin; van Gelder, Teun

    2014-10-01

    Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20-46% lower in Asian transplant recipients than in Caucasian or African American patients. © 2014 Steunstichting ESOT.

  12. Differential proteome analysis of human embryonic kidney cell line (HEK-293 following mycophenolic acid treatment

    Directory of Open Access Journals (Sweden)

    Rahman Hazir

    2011-09-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as a post transplantation medicine to prevent acute organ rejection. In the present study we used proteomics approach to identify proteome alterations in human embryonic kidney cells (HEK-293 after treatment with therapeutic dose of MPA. Following 72 hours MPA treatment, total protein lysates were prepared, resolved by two dimensional gel electrophoresis and differentially expressed proteins were identified by QTOF-MS/MS analysis. Expressional regulations of selected proteins were further validated by real time PCR and Western blotting. Results The proliferation assay demonstrated that therapeutic MPA concentration causes a dose dependent inhibition of HEK-293 cell proliferation. A significant apoptosis was observed after MPA treatment, as revealed by caspase 3 activity. Proteome analysis showed a total of 12 protein spots exhibiting differential expression after incubation with MPA, of which 7 proteins (complement component 1 Q subcomponent-binding protein, electron transfer flavoprotein subunit beta, cytochrome b-c1 complex subunit, peroxiredoxin 1, thioredoxin domain-containing protein 12, myosin regulatory light chain 2, and profilin 1 showed significant increase in their expression. The expression of 5 proteins (protein SET, stathmin, 40S ribosomal protein S12, histone H2B type 1 A, and histone H2B type 1-C/E/F/G/I were down-regulated. MPA mainly altered the proteins associated with the cytoskeleton (26%, chromatin structure/dynamics (17% and energy production/conversion (17%. Both real time PCR and Western blotting confirmed the regulation of myosin regulatory light chain 2 and peroxiredoxin 1 by MPA treatment. Furthermore, HT-29 cells treated with MPA and total kidney cell lysate from MMF treated rats showed similar increased expression of myosin regulatory light chain 2. Conclusion The emerging use of MPA in diverse pathophysiological conditions demands in-depth studies to

  13. Mycophenolate pharmacokinetics and pharmacodynamics in belatacept treated renal allograft recipients – a pilot study

    Directory of Open Access Journals (Sweden)

    Stenstrøm Jean

    2009-07-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as part of immunosuppressive regimens following allograft transplantation. The large pharmacokinetic (PK and pharmacodynamic (PD variability and narrow therapeutic range of MPA provide a potential for therapeutic drug monitoring. The objective of this pilot study was to investigate the MPA PK and PD relation in combination with belatacept (2nd generation CTLA4-Ig or cyclosporine (CsA. Methods Seven renal allograft recipients were randomized to either belatacept (n = 4 or cyclosporine (n = 3 based immunosuppression. Samples for MPA PK and PD evaluations were collected predose and at 1, 2 and 13 weeks posttransplant. Plasma concentrations of MPA were determined by HPLC-UV. Activity of inosine monophosphate dehydrogenase (IMPDH and the expressions of two IMPDH isoforms were measured in CD4+ cells by HPLC-UV and real-time reverse-transcription PCR, respectively. Subsets of T cells were characterized by flow cytometry. Results The MPA exposure tended to be higher among belatacept patients than in CsA patients at week 1 (P = 0.057. Further, MPA concentrations (AUC0–9 h and C0 increased with time in both groups and were higher at week 13 than at week 2 (P = 0.031, n = 6. In contrast to the postdose reductions of IMPDH activity observed early posttransplant, IMPDH activity within both treatment groups was elevated throughout the dosing interval at week 13. Transient postdose increments were also observed for IMPDH1 expression, starting at week 1. Higher MPA exposure was associated with larger elevations of IMPDH1 (r = 0.81, P = 0.023, n = 7 for MPA and IMPDH1 AUC0–9 h at week 1. The maximum IMPDH1 expression was 52 (13–177% higher at week 13 compared to week 1 (P = 0.031, n = 6. One patient showed lower MPA exposure with time and did neither display elevations of IMPDH activity nor IMPDH1 expression. No difference was observed in T cell subsets between treatment groups. Conclusion The

  14. Determination of mycophenolic acid in mest products using mixed mode reversed phase-anion exchange clean-up and liquid chromatography-high-resolution mass spectrometry

    DEFF Research Database (Denmark)

    Sørensen, Louise Marie; Nielsen, Kristian Fog; Jacobsen, Thomas

    2008-01-01

    A method for determination of mycophenolic acid (MPA) in dry-cured ham, fermented sausage and liver pate is described. MPA was extracted from meat with bicarbonate-acetonitrile, further cleaned-up by mixed mode reversed phase-anion exchange and detected using a LC-MS system with electrospray...

  15. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-01-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the an...

  16. Differentiation-inducing factor-1 suppresses gene expression of cyclin D1 in tumor cells

    International Nuclear Information System (INIS)

    Yasmin, Tania; Takahashi-Yanaga, Fumi; Mori, Jun; Miwa, Yoshikazu; Hirata, Masato; Watanabe, Yutaka; Morimoto, Sachio; Sasaguri, Toshiyuki

    2005-01-01

    To determine the mechanism by which differentiation-inducing factor-1 (DIF-1), a morphogen of Dictyostelium discoideum, inhibits tumor cell proliferation, we examined the effect of DIF-1 on the gene expression of cyclin D1. DIF-1 strongly reduced the expression of cyclin D1 mRNA and correspondingly decreased the amount of β-catenin in HeLa cells and squamous cell carcinoma cells. DIF-1 activated glycogen synthase kinase-3β (GSK-3β) and inhibition of GSK-3β attenuated the DIF-1-induced β-catenin degradation, indicating the involvement of GSK-3β in this effect. Moreover, DIF-1 reduced the activities of T-cell factor (TCF)/lymphoid enhancer factor (LEF) reporter plasmid and a reporter gene driven by the human cyclin D1 promoter. Eliminating the TCF/LEF consensus site from the cyclin D1 promoter diminished the effect of DIF-1. These results suggest that DIF-1 inhibits Wnt/β-catenin signaling, resulting in the suppression of cyclin D1 promoter activity

  17. Diagnostic efficiency of truncated area under the curve from 0 to 2 h (AUC₀₋₂) of mycophenolic acid in kidney transplant recipients receiving mycophenolate mofetil and concomitant tacrolimus.

    Science.gov (United States)

    Lampón, Natalia; Tutor-Crespo, María J; Romero, Rafael; Tutor, José C

    2011-07-01

    Recently, the use of the truncated area under the curve from 0 to 2 h (AUC(0-2)) of mycophenolic acid (MPA) has been proposed for therapeutic monitoring in liver transplant recipients. The aim of our study was the evaluation of the clinical usefulness of truncated AUC(0-2) in kidney transplant patients. Plasma MPA was measured in samples taken before the morning dose of mycophenolate mofetil, and one-half and 2 h post-dose, completing 63 MPA concentration-time profiles from 40 adult kidney transplant recipients. The AUC from 0 to 12 h (AUC(0-12)) was calculated using the validated algorithm of Pawinski et al. The truncated AUC(0-2) was calculated using the linear trapezoidal rule, and extrapolated to 0-12 h (trapezoidal extrapolated AUC(0-12)) as previously described. Algorithm calculated and trapezoidal extrapolated AUC(0-12) values showed high correlation (r=0.995) and acceptable dispersion (ma68=0.71 μg·h/mL), median prediction error (6.6%) and median absolute prediction error (12.6%). The truncated AUC(0-2) had acceptable diagnostic efficiency (87%) in the classification of subtherapeutic, therapeutic or supratherapeutic values with respect to AUC(0-12). However, due to the high inter-individual variation of the drug absorption-rate, the dispersion between both pharmacokinetic variables (ma68=6.9 μg·h/mL) was unacceptable. The substantial dispersion between truncated AUC(0-2) and AUC(0-12) values may be a serious objection for the routine use of MPA AUC(0-2) in clinical practice.

  18. The impact of everolimus versus mycophenolate on blood and lymphocyte cyclosporine exposure in heart-transplant recipients

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Barth, David; Delgado, Diego H

    2009-01-01

    CsA C2 levels and blood CsA AUC(0-12) in groups of patients treated with MMF or everolimus (R(2) 0.93 and 0.96, respectively; P 2) = 0.98), there was poor correlation...... between whole-blood C2 and lymphocyte AUC(0-12) in patients treated with everolimus (R(2) = 0.24). CONCLUSION: Standard blood CsA levels accurately predict intralymphocytic exposure to CsA in patients concomitantly treated with MMF but not in patients treated with everolimus........ METHODS: Twelve-hour pharmacokinetic studies of whole-blood and intralymphocytic CsA concentrations were conducted in long-term heart-transplant recipients treated with mycophenolate mofetil (MMF) + CsA (n = 8) and everolimus + CsA (n = 9). RESULTS: There was a highly significant correlation between blood...

  19. Comparison of 3 estimation methods of mycophenolic acid AUC based on a limited sampling strategy in renal transplant patients.

    Science.gov (United States)

    Hulin, Anne; Blanchet, Benoît; Audard, Vincent; Barau, Caroline; Furlan, Valérie; Durrbach, Antoine; Taïeb, Fabrice; Lang, Philippe; Grimbert, Philippe; Tod, Michel

    2009-04-01

    A significant relationship between mycophenolic acid (MPA) area under the plasma concentration-time curve (AUC) and the risk for rejection has been reported. Based on 3 concentration measurements, 3 approaches have been proposed for the estimation of MPA AUC, involving either a multilinear regression approach model (MLRA) or a Bayesian estimation using either gamma absorption or zero-order absorption population models. The aim of the study was to compare the 3 approaches for the estimation of MPA AUC in 150 renal transplant patients treated with mycophenolate mofetil and tacrolimus. The population parameters were determined in 77 patients (learning study). The AUC estimation methods were compared in the learning population and in 73 patients from another center (validation study). In the latter study, the reference AUCs were estimated by the trapezoidal rule on 8 measurements. MPA concentrations were measured by liquid chromatography. The gamma absorption model gave the best fit. In the learning study, the AUCs estimated by both Bayesian methods were very similar, whereas the multilinear approach was highly correlated but yielded estimates about 20% lower than Bayesian methods. This resulted in dosing recommendations differing by 250 mg/12 h or more in 27% of cases. In the validation study, AUC estimates based on the Bayesian method with gamma absorption model and multilinear regression approach model were, respectively, 12% higher and 7% lower than the reference values. To conclude, the bicompartmental model with gamma absorption rate gave the best fit. The 3 AUC estimation methods are highly correlated but not concordant. For a given patient, the same estimation method should always be used.

  20. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  1. A flavin-dependent halogenase catalyzes the chlorination step in the biosynthesis of Dictyostelium differentiation-inducing factor 1

    OpenAIRE

    Neumann, Christopher S.; Walsh, Christopher T.; Kay, Robert R.

    2010-01-01

    Differentiation-inducing factor 1 (DIF-1) is a polyketide-derived morphogen which drives stalk cell formation in the developmental cycle of Dictyostelium discoideum. Previous experiments demonstrated that the biosynthetic pathway proceeds via dichlorination of the precursor molecule THPH, but the enzyme responsible for this transformation has eluded characterization. Our recent studies on prokaryotic flavin-dependent halogenases and insights from the sequenced Dd genome led us to a candidate ...

  2. A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent

    Directory of Open Access Journals (Sweden)

    Fleming D

    2006-01-01

    Full Text Available Background : Therapeutic drug monitoring for mycophenolic acid (MPA is increasingly being advocated. Thepresent therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC.However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this samplingperiod? Aim : To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. Settings and Design : Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paireddata. Materials and Methods : Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept ® wereevaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the timeafter transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factorapplied. These two AUCs were then compared. Statistical Analysis : Linear regression, intra-class correlations (ICC and a two-tailed paired t-test were appliedto the data. Results : Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2 were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. Nobias was seen with a Bland Altman plot or by calculation. Conclusion : For patients on Cellcept ® with prednisolone ± cyclosporine the 6-hour corrected is an accuratemeasure of the full 12-hour AUC.

  3. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  4. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  5. Differential Sensitivities of Fast- and Slow-Cycling Cancer Cells to Inosine Monophosphate Dehydrogenase 2 Inhibition by Mycophenolic Acid

    Science.gov (United States)

    Chen, Kan; Cao, Wanlu; Li, Juan; Sprengers, Dave; Hernanda, Pratika Y; Kong, Xiangdong; van der Laan, Luc JW; Man, Kwan; Kwekkeboom, Jaap; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2015-01-01

    As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA. PMID:26467706

  6. Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

    Directory of Open Access Journals (Sweden)

    Mahesh Jonnalagadda

    Full Text Available Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX and mycophenolate mofetil (MMF in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS; L22F, F31S and inosine monophosphate dehydrogenase II (IMPDH2(IY; T333I, S351Y conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA. Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+DHFR(FS+IMPDH2(IY+ T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold, MMF alone (2.9-fold, or combined MTX and MMF (4.9-fold. These findings demonstrate the utility of both DHFR(FS/MTX and IMPDH2(IY/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

  7. Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

    Science.gov (United States)

    Jonnalagadda, Mahesh; Brown, Christine E; Chang, Wen-Chung; Ostberg, Julie R; Forman, Stephen J; Jensen, Michael C

    2013-01-01

    Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX) and mycophenolate mofetil (MMF) in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS); L22F, F31S) and inosine monophosphate dehydrogenase II (IMPDH2(IY); T333I, S351Y) conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA). Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+)DHFR(FS+)IMPDH2(IY+) T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold), MMF alone (2.9-fold), or combined MTX and MMF (4.9-fold). These findings demonstrate the utility of both DHFR(FS)/MTX and IMPDH2(IY)/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

  8. 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. ...

  9. Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat.

    Science.gov (United States)

    Ugrasbul, Figen; Moore, Wayne V; Tong, Pei Ying; Kover, Karen L

    2008-12-01

    Anti-CD25 and mycophenolate mofetil (MMF) treatment of patients with new-onset diabetes is currently being tested as one of the trials in TrialNet. We tested the effectiveness of MMF and anti-CD25 in preventing autoimmune diabetes in the diabetes-resistant biobreeding (DRBB) rat. Autoimmune diabetes in the DRBB rat was induced with a Treg cell depletion regimen starting at 24-26 d of age. Treatment was started on the first day of the depletion regimen in the following groups: (i) control (vehicle); (ii) MMF 25 mg/kg/d intramuscularly daily for 8 wk; (iii) anti-CD25 0.8 mg/kg/d intraperitoneally 5 d/wk for 3 wk; and (iv) combination of MMF and anti-CD25. In a second set of experiments, treatments were started on day 5 of the depletion regimen (delayed treatment) with groups 1, 3, and 4. Rats that had diabetes-free survival for at least 30 d after the treatment was stopped underwent a second Treg depletion (redepletion). In each of the three treatment groups (n = 10/group), onset of diabetes was delayed or prevented in 20, 40 and 80% in groups 2, 3, and 4, respectively. After redepletion, diabetes-free survival was unchanged in group 2 and decreased to 10 and 30% in groups 3 and 4, respectively. With delayed treatment, groups 3 and 4 had 33 and 50% diabetes-free survival that decreased to 0 and 33% after redepletion. MMF and anti-CD25 alone or in combination are effective in delaying and preventing diabetes in the DRBB rat especially if treatment is started before stimulation and expansion of the autoreactive T cells.

  10. The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients.

    Science.gov (United States)

    Flechner, S M; Glyda, M; Cockfield, S; Grinyó, J; Legendre, Ch; Russ, G; Steinberg, S; Wissing, K M; Tai, S S

    2011-08-01

    Safety and efficacy of two sirolimus (SRL)-based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF). Renal transplantation recipients were randomized to Group 1 (SRL+TAC; week 13 TAC elimination [n = 152]), Group 2 (SRL + MMF [n = 152]) or Group 3 (TAC + MMF [n = 139]). Group 2, with higher-than-expected biopsy-confirmed acute rejections (BCARs), was sponsor-terminated; therefore, Group 2 two-year data were limited. At 1 and 2 years, respectively, graft (Group 1: 92.8%, 88.5%; Group 2: 90.6%, 89.9%; Group 3: 96.2%, 95.4%) and patient (Group 1: 97.3%, 94.4%; Group 2: 95.2%, 94.5%; Group 3: 97.0%, 97.0%) survival rates were similar. One- and 2-year BCAR incidence was: Group 1, 15.2%, 17.4%; Group 2, 31.3%, 32.8%; Group 3, 8.2%, 12.3% (Group 2 vs. 3, p < 0.001). Mean 1- and 2-year modified intent-to-treat glomerular filtration rates (mL/min) were similar. Primary reason for discontinuation was adverse events (Group 1, 34.2%; Group 2, 33.6%; Group 3, 22.3%; p < 0.05). In Groups 1 and 2, delayed wound healing and hyperlipidemia were more frequent. One-year post hoc analysis of new-onset diabetes posttransplantation was greater in TAC recipients (Groups 1 and 3 vs. 2, 17% vs. 6%; p = 0.004). Between-group malignancy rates were similar. The SRL-based regimens were not associated with improved outcomes for kidney transplantation patients. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. A new class of IMP dehydrogenase with a role in self-resistance of mycophenolic acid producing fungi

    Directory of Open Access Journals (Sweden)

    Mortensen Uffe H

    2011-09-01

    Full Text Available Abstract Background Many secondary metabolites produced by filamentous fungi have potent biological activities, to which the producer organism must be resistant. An example of pharmaceutical interest is mycophenolic acid (MPA, an immunosuppressant molecule produced by several Penicillium species. The target of MPA is inosine-5'-monophosphate dehydrogenase (IMPDH, which catalyses the rate limiting step in the synthesis of guanine nucleotides. The recent discovery of the MPA biosynthetic gene cluster from Penicillium brevicompactum revealed an extra copy of the IMPDH-encoding gene (mpaF embedded within the cluster. This finding suggests that the key component of MPA self resistance is likely based on the IMPDH encoded by mpaF. Results In accordance with our hypothesis, heterologous expression of mpaF dramatically increased MPA resistance in a model fungus, Aspergillus nidulans, which does not produce MPA. The growth of an A. nidulans strain expressing mpaF was only marginally affected by MPA at concentrations as high as 200 μg/ml. To further substantiate the role of mpaF in MPA resistance, we searched for mpaF orthologs in six MPA producer/non-producer strains from Penicillium subgenus Penicillium. All six strains were found to hold two copies of IMPDH. A cladistic analysis based on the corresponding cDNA sequences revealed a novel group constituting mpaF homologs. Interestingly, a conserved tyrosine residue in the original class of IMPDHs is replaced by a phenylalanine residue in the new IMPDH class. Conclusions We identified a novel variant of the IMPDH-encoding gene in six different strains from Penicillium subgenus Penicillium. The novel IMPDH variant from MPA producer P. brevicompactum was shown to confer a high degree of MPA resistance when expressed in a non-producer fungus. Our study provides a basis for understanding the molecular mechanism of MPA resistance and has relevance for biotechnological and pharmaceutical applications.

  12. FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.

    Science.gov (United States)

    Tedesco-Silva, Helio; Szakaly, Peter; Shoker, Ahmed; Sommerer, Claudia; Yoshimura, Norio; Schena, Francesco Paolo; Cremer, Malika; Hmissi, Abdel; Mayer, Hartmut; Lang, Philippe

    2007-10-15

    FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC). This multicenter, double-blind, Phase IIb, randomized study evaluated the safety and efficacy of 5 mg FTY720 (n=87; Group 1) vs. 2.5 mg FTY720 (n=90; Group 2) vs. mycophenolate mofetil (MMF; n=94; Group 3) in de novo renal transplant patients receiving FDC and prednisone. The primary efficacy endpoint was the occurrence of treated biopsy-proven acute rejection, graft loss, death, or premature study discontinuation (composite endpoint) within 6 months. The primary endpoint was superior in Group 1 (24%) and statistically noninferior in Group 2 compared to Group 3 (24.1% vs. 29.2% vs. 39.4%; P=0.025 and 0.0039, respectively). FTY720 plus FDC was generally well tolerated, with a similar incidence of adverse events across all groups. FTY720 was associated with higher incidence of bradycardia (Group 1: 26.4%, P=0.0002 and Group 2: 15.6%, P=0.046, vs. Group 3: 6.4%), respiratory disorders (Group 1: 40.2%, not significant [P=NS] and Group 2: 34.4%, P=NS vs. Group 3: 28.7%). One macular edema occurred in Group 2. Lower creatinine clearances were observed with FTY720 versus MMF (Group 1: 52.4 ml/min, P=NS and Group 2: 51.7 ml/min, P=0.039 vs. Group 3: 62.5 ml/min). Although FTY720 with FDC provided adequate protection from acute rejection the safety profile was less favorable for adverse events than current standard immunosuppression in de novo renal transplant patients.

  13. A flavin-dependent halogenase catalyzes the chlorination step in the biosynthesis of Dictyostelium differentiation-inducing factor 1.

    Science.gov (United States)

    Neumann, Christopher S; Walsh, Christopher T; Kay, Robert R

    2010-03-30

    Differentiation-inducing factor 1 (DIF-1) is a polyketide-derived morphogen which drives stalk cell formation in the developmental cycle of Dictyostelium discoideum. Previous experiments demonstrated that the biosynthetic pathway proceeds via dichlorination of the precursor molecule THPH, but the enzyme responsible for this transformation has eluded characterization. Our recent studies on prokaryotic flavin-dependent halogenases and insights from the sequenced Dd genome led us to a candidate gene for this transformation. In this work, we present in vivo and in vitro evidence that chlA from Dd encodes a flavin-dependent halogenase capable of catalyzing both chlorinations in the biosynthesis of DIF-1. The results provide in vitro characterization of a eukaryotic oxygen-dependent halogenase and demonstrate a broad reach in biology for this molecular tailoring strategy, notably its involvement in the differentiation program of a social amoeba.

  14. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    International Nuclear Information System (INIS)

    Engl, Tobias; Makarević, Jasmina; Relja, Borna; Natsheh, Iyad; Müller, Iris; Beecken, Wolf-Dietrich; Jonas, Dietger; Blaheta, Roman A

    2005-01-01

    Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype

  15. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    Directory of Open Access Journals (Sweden)

    Beecken Wolf-Dietrich

    2005-01-01

    Full Text Available Abstract Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a, alpha2beta1 (CD49b, alpha3beta1 (CD49c, alpha4beta1 (CD49d, alpha5beta1 (CD49e, and alpha6beta1 (CD49f receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.

  16. [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.

  17. Evaluation of Multiple Linear Regression-Based Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Brooks, Emily K; Tett, Susan E; Isbel, Nicole M; McWhinney, Brett; Staatz, Christine E

    2018-04-01

    Although multiple linear regression-based limited sampling strategies (LSSs) have been published for enteric-coated mycophenolate sodium, none have been evaluated for the prediction of subsequent mycophenolic acid (MPA) exposure. This study aimed to examine the predictive performance of the published LSS for the estimation of future MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12) in renal transplant recipients. Total MPA plasma concentrations were measured in 20 adult renal transplant patients on 2 occasions a week apart. All subjects received concomitant tacrolimus and were approximately 1 month after transplant. Samples were taken at 0, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours and 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and 12 hours after dose on the first and second sampling occasion, respectively. Predicted MPA AUC0-12 was calculated using 19 published LSSs and data from the first or second sampling occasion for each patient and compared with the second occasion full MPA AUC0-12 calculated using the linear trapezoidal rule. Bias (median percentage prediction error) and imprecision (median absolute prediction error) were determined. Median percentage prediction error and median absolute prediction error for the prediction of full MPA AUC0-12 were multiple linear regression-based LSS was not possible without concentrations up to at least 8 hours after the dose.

  18. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

    Directory of Open Access Journals (Sweden)

    Cron Randy Q

    2011-01-01

    Full Text Available Abstract Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology.

  19. Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma

    International Nuclear Information System (INIS)

    Mori, Jun; Takahashi-Yanaga, Fumi; Miwa, Yoshikazu; Watanabe, Yutaka; Hirata, Masato; Morimoto, Sachio; Shirasuna, Kanemitsu; Sasaguri, Toshiyuki

    2005-01-01

    Differentiation-inducing factors (DIFs) are morphogens which induce cell differentiation in Dictyostelium. We reported that DIF-1 and DIF-3 inhibit proliferation and induce differentiation in mammalian cells. In this study, we investigated the effect of DIF-1 on oral squamous cell carcinoma cell lines NA and SAS, well differentiated and poorly differentiated cell lines, respectively. Although DIF-1 did not induce the expression of cell differentiation makers in these cell lines, it inhibited the proliferation of NA and SAS in a dose-dependent manner by restricting the cell cycle in the G 0 /G 1 phase. DIF-1 induced cyclin D1 degradation, but this effect was prevented by treatment with lithium chloride and SB216763, the inhibitors of glycogen synthase kinase-3β (GSK-3β). Depletion of endogenous GSK-3β by RNA interference also attenuated the effect of DIF-1 on cyclin D1 degradation. Therefore, we investigated the effect of DIF-1 on GSK-3β and found that DIF-1 dephosphorylated GSK-3β on Ser 9 and induced the nuclear translocation of GSK-3β, suggesting that DIF-1 activated GSK-3β. Then, we examined the effect of DIF-1 on cyclin D1 mutants (Thr286Ala, Thr288Ala, and Thr286/288Ala). We revealed that Thr286Ala and Thr286/288Ala mutants were highly resistant to DIF-1-induced degradation compared with wild-type cyclin D1, indicating that the phosphorylation of Thr 286 was critical for cyclin D1 degradation induced by DIF-1. These results suggest that DIF-1 induces degradation of cyclin D1 through the GSK-3β-mediated phosphorylation of Thr 286

  20. Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1.

    Science.gov (United States)

    Myre, Michael A; Washicosky, Kevin; Moir, Robert D; Tesco, Giuseppina; Tanzi, Rudolph E; Wasco, Wilma

    2009-04-01

    The detection of cell cycle proteins in Alzheimer's disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Abeta properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid beta-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Abeta40 and Abeta42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Abeta42 to Abeta40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Abeta. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a gamma-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668.

  1. Reduced amyloidogenic processing of the amyloid β-protein precursor by the small-molecule Differentiation Inducing Factor-1

    Science.gov (United States)

    Myre, Michael A.; Washicosky, Kevin; Moir, Robert D.; Tesco, Giuseppina; Tanzi, Rudolph E.; Wasco, Wilma

    2013-01-01

    The detection of cell cycle proteins in Alzheimer’s disease (AD) brains may represent an early event leading to neurodegeneration. To identify cell cycle modifiers with anti-Aβ properties, we assessed the effect of Differentiation-Inducing Factor-1 (DIF-1), a unique, small-molecule from Dictyostelium discoideum, on the proteolysis of the amyloid β-protein precursor (APP) in a variety of different cell types. We show that DIF-1 slows cell cycle progression through G0/G1 that correlates with a reduction in cyclin D1 protein levels. Western blot analysis of DIF-treated cells and conditioned medium revealed decreases in the levels of secreted APP, mature APP, and C-terminal fragments. Assessment of conditioned media by sandwich ELISA showed reduced levels of Aβ40 and Aβ42, also demonstrating that treatment with DIF-1 effectively decreases the ratio of Aβ42 to Aβ40. In addition, DIF-1 significantly diminished APP phosphorylation at residue T668. Interestingly, site-directed mutagenesis of APP residue Thr668 to alanine or glutamic acid abolished the effect of DIF-1 on APP proteolysis and restored secreted levels of Aβ. Finally, DIF-1 prevented the accumulation of APP C-terminal fragments induced by the proteasome inhibitor lactacystin, and calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN). Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a γ-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668. PMID:19154786

  2. 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 ...

  3. [Activation of endoplasmic reticulum stress and its effect on osteogenic differentiation induced by micropit/nanotube topography].

    Science.gov (United States)

    Shi, M Q; Song, W; Han, T X; Chang, B; Zhang, Y M

    2017-02-09

    Objective: To explore the activation of endoplasmic reticulum stress (ERS) in bone marrow mesenchymal stem cell (BMMSC) and its effect on osteogenic differentiation induced by micropit/nanotube topography (MNT), so as to provide guidance for the topography design of biomaterials. Methods: Four sample groups were fabricated: polishing control group (polished titanium, PT, no treatment), thapsigargin treatment (TG, 0.1 μmol/L TG treated for 9 h), MNT5 and MNT20 (anodized at 5 V and 20 V after acid etching). Scanning electron microscope (SEM) was used to observe the topography of Ti samples. The alkaline phosphatase (ALP) production, collagen secretion and extracellular matrix (ECM) mineralization of BMMSC (osteogenic induced for 7, 14 and 21 d) on Ti samples were detected to evaluate the osteogenic differentiation. After 12 h incubation, the shape and size of ER was examined using a transmission electron microscope (TEM), and ERS-related genes including immunoglobulin heavy chain binding protein (BiP), protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) were detected by quantitative real-time PCR (qRT-PCR). Results: After 7, 14 and 21 d of induction, the ALP production, collagen secretion and ECM mineralization in TG and MNT20 all significantly increased compared to PT ( P< 0.05). The cells grown on TG, MNT5 and MNT20 surfaces displayed gross distortions of the ER. Compared to PT, BiP, PERK, ATF4 mRNA expression in TG was respectively 1.87±0.10, 2.24±0.35, 1.85±0.14; BiP, ATF4 mRNA expression in MNT5 were respectively 1.27±0.09, 1.25±0.04; BiP, PERK, ATF4 mRNA expression in MNT20 were respectively 1.44±0.09, 2.40±0.60, 1.48±0.05 ( P< 0.05). Conclusions: MNT triggered different degree of ERS, and the activated ERS may promote MNT-induced osteogenic differentiation.

  4. Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

    Science.gov (United States)

    Staatz, Christine E; Tett, Susan E

    2011-12-01

    This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared

  5. A possible simplification for the estimation of area under the curve (AUC₀₋₁₂) of enteric-coated mycophenolate sodium in renal transplant patients receiving tacrolimus.

    Science.gov (United States)

    Fleming, Denise H; Mathew, Binu S; Prasanna, Samuel; Annapandian, Vellaichamy M; John, George T

    2011-04-01

    Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplantation. With a delayed absorption profile, it has not been possible to develop limited sampling strategies to estimate area under the curve (mycophenolic acid [MPA] AUC₀₋₁₂), which have limited time points and are completed in 2 hours. We developed and validated simplified strategies to estimate MPA AUC₀₋₁₂ in an Indian renal transplant population prescribed EC-MPS together with prednisolone and tacrolimus. Intensive pharmacokinetic sampling (17 samples each) was performed in 18 patients to measure MPA AUC₀₋₁₂. The profiles at 1 month were used to develop the simplified strategies and those at 5.5 months used for validation. We followed two approaches. In one, the AUC was calculated using the trapezoidal rule with fewer time points followed by an extrapolation. In the second approach, by stepwise multiple regression analysis, models with different time points were identified and linear regression analysis performed. Using the trapezoidal rule, two equations were developed with six time points and sampling to 6 or 8 hours (8hrAUC[₀₋₁₂exp]) after the EC-MPS dose. On validation, the 8hrAUC(₀₋₁₂exp) compared with total measured AUC₀₋₁₂ had a coefficient of correlation (r²) of 0.872 with a bias and precision (95% confidence interval) of 0.54% (-6.07-7.15) and 9.73% (5.37-14.09), respectively. Second, limited sampling strategies were developed with four, five, six, seven, and eight time points and completion within 2 hours, 4 hours, 6 hours, and 8 hours after the EC-MPS dose. On validation, six, seven, and eight time point equations, all with sampling to 8 hours, had an acceptable r with the total measured MPA AUC₀₋₁₂ (0.817-0.927). In the six, seven, and eight time points, the bias (95% confidence interval) was 3.00% (-4.59 to 10.59), 0.29% (-5.4 to 5.97), and -0.72% (-5.34 to 3.89) and the precision (95% confidence interval) was 10

  6. A novel freeze-dried storage and preparation method for the determination of mycophenolic acid in plasma by high-performance liquid chromatography.

    Science.gov (United States)

    Wang, Lei; Qiang, Wei; Li, Ying; Cheng, Zeneng; Xie, Mengmeng

    2017-09-01

    Plasma samples were conventionally stored at freezing conditions until the time of detection. Such a technique, when carried out over an extended period, is energy consuming; in addition, preparation and transportation of stored samples is inconvenient. In this study, a freeze-dried storage and preparation method was proposed to determine the presence of mycophenolic acid (MPA) in plasma. Fresh plasma samples were freeze-dried using a device, and then stored at ambient temperature. After the stored samples were soaked with methanol spiked with the internal standard, high-performance liquid chromatography was conducted to detect MPA. The proposed method was demonstrated to be precise and accurate over the linear range of 0.5-50 μg mL -1 , with both intra- and inter-day precision being plasma concentration, time point of maximum plasma concentration and elimination half-life, among others, were consistent with the results in the published study. This proposed technique was proved to be simple, reproducible and energy saving. This approach could also simplify the storage and analysis of samples in clinical and scientific drug research. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new- onset type 1 diabetes.

    Science.gov (United States)

    Gottlieb, Peter A; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J; Wilson, Darrell M; Rodriguez, Henry; Schatz, Desmond A; Moran, Antoinette M; Lachin, John M; Skyler, Jay S

    2010-04-01

    This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing beta-cells in subjects with new-onset type 1 diabetes. A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process.

  8. Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes

    Science.gov (United States)

    Gottlieb, Peter A.; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J.; Wilson, Darrell M.; Rodriguez, Henry; Schatz, Desmond A.; Moran, Antoinette M.; Lachin, John M.; Skyler, Jay S.

    2010-01-01

    OBJECTIVE This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. RESULTS One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. CONCLUSIONS Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process. PMID:20067954

  9. Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a five-year randomized prospective study.

    Science.gov (United States)

    Boillot, Olivier; Seket, Belhassen; Dumortier, Jérôme; Pittau, Gabriella; Boucaud, Catherine; Bouffard, Yves; Scoazec, Jean-Yves

    2009-11-01

    This randomized, comparative study assessed the long-term efficacy and tolerability of thymoglobulin (TMG) induction in 93 liver transplant patients with an initial regimen of tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids. Forty-four patients were randomly allocated to the TMG+ group, and 49 patients were randomly allocated to the TMG- group. In both groups, Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily, and MMF was given at the initial daily dose of 2 g/day. Steroid withdrawal was planned at 3 months after liver transplantation. The results were evaluated with respect to acute rejection incidence, patient and graft survival, graft function, and medical complications until 5 years or death for all patients. No significant differences were found between groups for the incidence of acute rejection at 5 years (11.4% versus 14.3%), 5-year patient survival (77.3% versus 87.8%), graft function, or postoperative renal function. One patient in the TMG- group underwent retransplantation. There was no difference between groups with respect to the incidence of medical complications, excepted for a higher rate of leukopenia in the TMG+ group, during the 5-year follow-up. In conclusion, the results of this prospective randomized study suggest that the addition of TMG to a triple immunosuppressive regimen (Tac, MMF, and steroids) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates.

  10. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids.

    Science.gov (United States)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-05-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the analysis of MPA alone or with MPAG/AcMPAG in various biological specimens including plasma/serum, urine, ultrafiltrate, saliva, PBMC, dried blood spots, tissue extract, tumor biopsies and vitreous humor. Based on the need for experimental work, a proper choice of the assay and internal standard may be made using the choices in the literature. While the chemical methods involving high-performance liquid chromatography (HPLC) or LC coupled with triple quadrupole mass spectrometry (LC-MS/MS) are popular, enzymatic assays, in spite of their higher bias, have been used for the routine drug monitoring of MPA. The objectives of the present review are: (a) to provide a focused systematic compilation of the HPLC or LC-MS/MS methods for MPA, MPAG and/or AcMPAG published in the last decade (2005 to current) to enable visual comparison of the methods; (b) to compare and contrast a few enzymatic assays with those of the chemical methods; and (c) to discuss relevant issues/limitations and perspectives on select assays under various subheadings. Copyright © 2016 John Wiley & Sons, Ltd.

  11. [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.

  12. Anti-proliferative and differentiation-inducing activities of the green tea catechin epigallocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line.

    Science.gov (United States)

    Lung, H L; Ip, W K; Wong, C K; Mak, N K; Chen, Z Y; Leung, K N

    2002-12-06

    A novel approach for the treatment of leukemia is the differentiation therapy in which immature leukemia cells are induced to attain a mature phenotype when exposed to differentiation inducers, either alone or in combinations with other chemotherapeutic or chemopreventive drugs. Over the past decade, numerous studies indicated that green tea catechins (GTC) could suppress the growth and induce apoptosis on a number of human cancer cell lines. However, the differentiation-inducing activity of GTC on human tumors remains poorly understood. In the present study, the effect of the major GTC epigallocatechin-3-gallate (EGCG) on the proliferation and differentiation of a human eosinophilc leukemic cell line, EoL-1, was examined. Our results showed that EGCG suppressed the proliferation of the EoL-1 cells in a dose-dependent manner, with an estimated IC(50) value of 31.5 microM. On the other hand, EGCG at a concentration of 40 microM could trigger the EoL-1 cells to undergo morphological differentiation into mature eosinophil-like cells. Using RT-PCR and flow cytometry, it was found that EGCG upregulated the gene and protein expression of two eosinophil-specific granule proteins, the major basic protein (MBP) and eosinophil peroxidase (EPO), in EoL-1 cells. Taken together, our findings suggest that EGCG can exhibit anti-leukemic activity on a human eosinophilic cell line EoL-1 by suppressing the proliferation and by inducing the differentiation of the leukemia cells.

  13. 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

  14. Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

    Science.gov (United States)

    Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

    2017-08-01

    Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Three-Year Outcomes in Kidney Transplant Patients Randomized to Steroid-Free Immunosuppression or Steroid Withdrawal, with Enteric-Coated Mycophenolate Sodium and Cyclosporine: The Infinity Study

    Directory of Open Access Journals (Sweden)

    A. Thierry

    2014-01-01

    Full Text Available In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter, and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal. The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR graft loss, death, or loss to follow-up occurred in 21.4% (95% CI 11.8–31.0% of steroid avoidance patients and 16.4% (95% CI 7.1–25.7% of steroid withdrawal patients by month 36 (P=0.46. BPAR had occurred in 20.0% and 11.5%, respectively (P=0.19. The incidence of adverse events with a suspected relation to steroids during months 6–36 was 22.9% versus 37.1% (P=0.062. By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months.

  16. Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

    Science.gov (United States)

    Nieto, Yago; Patton, Nigel; Hawkins, Timothy; Spearing, Ruth; Bearman, Scott I; Jones, Roy B; Shpall, Elizabeth J; Rabinovitch, Rachel; Zeng, Chan; Barón, Anna; McSweeney, Peter A

    2006-02-01

    We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.

  17. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

    Science.gov (United States)

    Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

    2018-04-19

    We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

    Science.gov (United States)

    Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

    2017-03-01

    Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  19. 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.

  20. 器官移植患者的霉酚酸酯治疗药物监测%Therapeutic drug monitoring of mycophenolate mofetil in patients undergoing organ transplantation

    Institute of Scientific and Technical Information of China (English)

    崔学艳; 施孝金

    2009-01-01

    麦考酚酸酯(霉酚酸酯,mycophenlate mofetil,MMF)是麦考酚酸(霉酚酸,mycophenolic acid,MPA)的一种酯类衍生物。MMF无生物活性,口服后迅速水解为具活性的MPA。MMF是近年来发现的一种新型免疫抑制剂,临床上主要用于预防和治疗器官移植排斥反应。

  1. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    International Nuclear Information System (INIS)

    Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

    2011-01-01

    Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  2. Control of proliferating potential of myeloid leukemia cells during long-term treatment with vitamin D3 analogues and other differentiation inducers in combination with antileukemic drugs: in vitro and in vivo studies.

    Science.gov (United States)

    Kasukabe, T; Honma, Y; Hozumi, M; Suda, T; Nishii, Y

    1987-01-15

    Growth inhibition of murine and human myeloid leukemia cells by differentiation inducers during long-term culture was examined to improve the strategy for therapy of myeloid leukemia by differentiation inducers. When the effect of 1 alpha,25-dihydroxyvitamin D3, a typical differentiation inducer, on proliferation of mouse myeloid leukemia M1 cells was examined at a constant product of time and concentration (480 nM in 20 days), the continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3 was the most effective for inhibition of cell proliferation. After 20 days, the cumulative cell number was reduced about 3 X 10(5) times by continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. Similar results were obtained when M1 cells were treated continuously with dexamethasone. M1 cells resistant to 1 alpha,25-dihydroxyvitamin D3 appeared about 25 days after the start of continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. On the other hand, when M1 cells were treated continuously with 1 alpha,25-dihydroxyvitamin D3 and noncytotoxic doses of antileukemic drugs such as 1-beta-D-arabinofuranosylcytosine and daunomycin, resistant cells did not appear for at least 35 days. A similar effect of 1 alpha,25-dihydroxyvitamin D3 and antileukemic drugs on cell proliferation was observed with the human monoblast-like cell line U937. The survival of syngeneic SL mice inoculated with M1 cells was prolonged more by treatment with both 1 alpha-hydroxyvitamin D3 and daunomycin than by treatment with either drug alone. These results suggest that continuous treatment with both differentiation inducers and certain antileukemic drugs may be more effective therapeutically than treatment with a differentiation inducer alone.

  3. 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

  4. 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 ...

  5. 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.

  6. Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial.

    Science.gov (United States)

    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Nohr-Westphal, Constanze; Brockmann, Jens; Andrassy, Joachim; Reinke, Petra; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Pascher, Andreas; Illner, Wolf-Dieter; Banas, Bernhard; Jauch, Karl-Walter

    2010-07-27

    De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%). Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

  7. 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.

  8. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

    Science.gov (United States)

    Pasadhika, Sirichai; Rosenbaum, James T

    2014-01-01

    Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

  9. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

    Directory of Open Access Journals (Sweden)

    Pasadhika S

    2014-02-01

    Full Text Available Sirichai Pasadhika,1 James T Rosenbaum2 1Department of Ophthalmology, Southern Arizona Veterans Administration Health Care System, Tucson, AZ, USA; 2Legacy Devers Eye Institute, Portland, OR, USA Abstract: Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet's disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet's disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present

  10. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    Science.gov (United States)

    Mika, Adriana; Stepnowski, Piotr

    2016-08-05

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 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

  12. 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...

  13. 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...

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying...... or reactivated EBV infection (PREBV) was correlated to acute rejection (treated with OKT3; Pdisease is included); (2) aciclovir protected against PREBV (P

  19. 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.

  20. 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.

  1. 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

  2. Metformin inhibition of neuroblastoma cell proliferation is differently modulated by cell differentiation induced by retinoic acid or overexpression of NDM29 non-coding RNA

    OpenAIRE

    Costa, Delfina; Gigoni, Arianna; Würth, Roberto; Cancedda, Ranieri; Florio, Tullio; Pagano, Aldo

    2014-01-01

    Background Metformin is a widely used oral hypoglycemizing agent recently proposed as potential anti-cancer drug. In this study we report the antiproliferative effect of metformin treatment in a high risk neuroblastoma cell model, focusing on possible effects associated to different levels of differentiation and/or tumor initiating potential. Methods Antiproliferative and cytotoxic effects of metformin were tested in human SKNBE2 and SH-SY5Y neuroblastoma cell lines and in SKNBE2 cells in whi...

  3. 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

  4. 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...

  5. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  6. Dermatose por IgA e IgG linear: relato de caso com boa resposta terapêutica à dapsona e ao micofenolato mofetil Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil

    Directory of Open Access Journals (Sweden)

    Leny Passos

    2011-08-01

    Full Text Available Relata-se o caso de paciente feminina, de 21 anos, com dermatose por IgA e IgG linear. Inicialmente, a resposta clínica foi favorável à dapsona. Após a interrupção desta medicação, por crise de anemia sintomática, precipitada por malária, houve piora da doença, apesar da utilização da prednisona e pulsoterapia com metilprednisolona. A reintrodução da dapsona, associada ao micofenolato mofetil, possibilitou o controle da enfermidadeA 21-year-old female presenting linear IgA and IgG disease initially responded well to dapsone therapy. However, the treatment with dapsone was withdrawn due to severe anemia induced by malaria, which led to worsening of the clinical picture. Although prednisone and methylprednisolone were tried, the patient responded only to the association of dapsone and mycophenolate mofetil

  7. 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…

  8. 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....

  9. 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…

  10. 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.)

  11. 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

  12. 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

  13. 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

  14. 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.

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

    DEFF Research Database (Denmark)

    Larsen, John

    2018-01-01

    and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI...

  16. 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.

  17. 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

  18. 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...

  19. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

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

  20. 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...

  1. 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 ...

  2. 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

  3. 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

  4. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

    Science.gov (United States)

    Abu El-Asrar, Ahmed M; Dosari, Mona; Hemachandran, Suhail; Gikandi, Priscilla W; Al-Muammar, Abdulrahman

    2017-02-01

    To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. 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

  6. 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

  7. 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.

  8. [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.

  9. 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...

  10. 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

  11. 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.

  12. 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...

  13. Socially Intelligent Tutor Agents

    NARCIS (Netherlands)

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

    2003-01-01

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

  14. 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...

  15. 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...

  16. 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.)

  17. 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.

  18. 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...

  19. 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…

  20. 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.

  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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...

  8. 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

  9. Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound.

    Science.gov (United States)

    Viggiano, Davide; Gigliotti, Giuseppe; Vallone, Gianfranco; Giammarino, Anna; Nigro, Michelangelo; Capasso, Giovambattista

    2018-01-01

    Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels. © 2018 The Author(s). Published by S. Karger AG, Basel.

  10. Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound

    Directory of Open Access Journals (Sweden)

    Davide Viggiano

    2018-04-01

    Full Text Available Current urate-lowering therapy (ULT includes three direct acting drugs (allopurinol, febuxostat, Rasburicase and at least four ‘indirect’ drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer. Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis, the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels.

  11. Improved Survival and Initiation of Differentiation of Human Induced Pluripotent Stem Cells to Hepatocyte-Like Cells upon Culture in William's E Medium followed by Hepatocyte Differentiation Inducer Treatment.

    Directory of Open Access Journals (Sweden)

    Minoru Tomizawa

    Full Text Available Hepatocyte differentiation inducer (HDI lacks both glucose and arginine, but is supplemented with galactose and ornithine, and is added together with other reagents such as apoptosis inhibitor and oncostatin M. Although human induced pluripotent stem (iPS cells initiate hepatocyte differentiation, most die within 7 days. In this study, we investigated both HDI and conventional media for their potential to improve cell survival.201B7 iPS cells were cultured in conventional media. This consisted of three cycles of 5-day culture in William's E (WE medium, followed by a 2-day culture in HDI.Expression levels of α-feto protein (AFP were higher in cells cultured in WE and in Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DF12. 201B7 cells expressed the highest AFP and albumin (ALB when cultured in HDI for 2 days following 7-day culture in WE. After three cycles of 5-day culture in WE followed by 2 days in HDI, 201B7 cells expressed AFP and ALB 54 ± 2.3 (average ± standard deviation and 73 ± 15.1 times higher, respectively, than those cultured in ReproFF (feeder-free condition.201B7 cells survived culture in WE for 7 days followed HDI for 2 days. After three cycles of culture under these conditions, hepatocyte differentiation was enhanced, as evidenced by increased AFP and ALB expression.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. [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.

  17. 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)

  18. 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

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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, ...

  4. 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.

  5. GOAL Agents Instantiate Intention Logic

    OpenAIRE

    Hindriks, Koen; van der Hoek, Wiebe

    2008-01-01

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

  6. 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)

  7. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

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

  8. 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.

  9. 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…

  10. 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)

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

    Science.gov (United States)

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

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

  12. 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

  13. Overview of shoreline cleaning agents

    International Nuclear Information System (INIS)

    Clayton, J.

    1992-01-01

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

  14. 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

  15. 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

  16. 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.

  17. Smart Agents and Sentiment in the Heterogeneous Agent Model

    Czech Academy of Sciences Publication Activity Database

    Vácha, Lukáš; Baruník, Jozef; Vošvrda, Miloslav

    2009-01-01

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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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...

  5. 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).

  6. 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 ...

  7. 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 ...

  8. 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...

  9. 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...

  10. 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.

  11. 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...

  12. 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...

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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)

  20. 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

  1. Prevalence of premature ovarian failure in systemic lupus erythematosus patients treated with immunosuppressive agents in Thailand.

    Science.gov (United States)

    Akawatcharangura, P; Taechakraichana, N; Osiri, M

    2016-04-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries. To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy. Women aged 18-40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L. Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95% CI 1.96-147.72, p = 0.01). From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients. © The Author(s) 2015.

  2. 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.

  3. 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,

  4. 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

  5. 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.

  6. 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)

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. 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)

  12. 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,

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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…

  19. 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…

  20. 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

  1. Humor and Embodied Conversational Agents

    NARCIS (Netherlands)

    Nijholt, Antinus

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

  2. 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.)

  3. 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...

  4. 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...

  5. 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.

  6. Limonene and tetrahydrofurfurly alcohol cleaning agent

    Science.gov (United States)

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

    1997-10-21

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

  7. 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.

  8. 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

  9. 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

  10. 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...

  11. 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.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  17. 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

  18. 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.

  19. 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]....

  20. 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 ...

  1. 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...

  2. 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.

  3. 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...

  4. 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.

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. Mobile Agents in Networking and Distributed Computing

    CERN Document Server

    Cao, Jiannong

    2012-01-01

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

  10. On Programming Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt

    2013-01-01

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

  11. 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

  12. 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

  13. 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

  14. 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...

  15. 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...

  16. Cooperative heuristic multi-agent planning

    NARCIS (Netherlands)

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

    2001-01-01

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

  17. 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

  18. 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

  19. 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)

  20. 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

  1. 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

  2. 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

  3. 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.

  4. [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.

  5. 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....

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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. ...

  13. 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.

  14. 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...

  15. 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...

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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. 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.

  6. 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...

  7. 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.

  8. 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...

  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(6.000: 491-500

  10. 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

  11. 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.

  12. 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

  13. 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…

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. 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.

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. 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 ...

  4. 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...

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.)

  11. 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

  12. 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.

  13. Toddlers Selectively Help Fair Agents

    Directory of Open Access Journals (Sweden)

    Luca Surian

    2017-06-01

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

  14. Viruses: agents of coral disease?

    Science.gov (United States)

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

    2006-03-23

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

  15. 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....

  16. Micofenolato mofetil na síndrome de Sjögren primária: uma opção para o tratamento da agranulocitose Mycophenolate mofetil in primary Sjögren's syndrome: a treatment option for agranulocytosis

    Directory of Open Access Journals (Sweden)

    Sonia Cristina de Magalhães Souza Fialho

    2012-04-01

    Full Text Available A síndrome de Sjögren (SS é uma doença autoimune caracterizada pela presença de infiltrado linfocítico nas glândulas salivares e lacrimais. Manifestações hematológicas da síndrome de Sjögren primária (SSp geralmente consistem em anemia leve, trombocitopenia, neutropenia moderada e linfopenia. Agranulocitose é raramente descrita e, em geral, responde bem ao tratamento de imunossupressão. Neste trabalho, descrevemos o caso de uma paciente portadora de SSp que apresentou quadro de agranulocitose refratária ao tratamento. A biópsia de medula revelou medula óssea hipocelular com maturação normal da série granulocítica. A paciente foi sucessivamente tratada com prednisona em altas doses, fator estimulador de colônia de macrófagos e ciclosporina, todos sem resposta hematológica. Micofenolato mofetil (MMF foi iniciado, e após dois meses houve aumento na contagem das células brancas. Após um ano de seguimento a paciente não apresentou novos episódios de neutropenia, nem complicações infecciosas. Concluímos que, na agranulocitose refratária associada à SSp, o tratamento com MMF pode ser uma opção eficaz e bem tolerada.The Sjögren's syndrome (SS is an autoimmune disease characterized by a lymphocytic infiltration of salivary and lacrimal glands. Hematological manifestations of primary SS (pSS usually consist of mild anemia, thrombocytopenia, moderate neutropenia, and lymphopenia. Agranulocytosis is rarely reported and usually responds to immunosuppression. We report the case of a pSS patient who presented with refractory agranulocytosis. Bone marrow biopsy disclosed a hypocellular bone marrow with normal maturation of the granulocytic series. The patient was successively treated with high-dose prednisone, granulocyte-macrophage colony stimulation factor, and cyclosporine, with no hematological response. Mycophenolate mofetil (MMF was initiated and after two months there was a rise on the white blood cell count. After

  17. 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

  18. 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...

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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...

  4. 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...

  5. 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.

  6. Anonymity and Software Agents: An Interdiscplinary Challenge

    NARCIS (Netherlands)

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

    2004-01-01

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

  7. Anonymity and Software Agents: An Interdisciplinary Challenge

    NARCIS (Netherlands)

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

    2004-01-01

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

  8. 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

  9. 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

  10. 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...

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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…

  18. 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

  19. 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…

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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…

  5. 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.

  6. 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.

  7. 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

  8. 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 ...

  9. 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 ...

  10. 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.

  11. 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...

  12. 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...

  13. 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

  14. 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...

  15. 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...

  16. [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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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...

  4. 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....

  5. 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...

  6. 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....

  7. 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...

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Mycophenolate mofetil in pediatric renal transplantation: a single center experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p < 0.0001). In conclusion, the use of MMF in pediatric renal transplantation was not associated with a lower rejection rate or immunological graft loss. It did, however, result in a significantly higher rate of viral infections.

  13. 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...

  14. 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.

  15. 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...

  16. 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.)

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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. ...

  4. 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.

  5. 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.

  6. 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...

  7. 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)

  8. 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. .

  9. 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...

  10. 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...

  11. 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

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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....

  20. 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

  1. 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.

  2. 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

  3. New Safety rule for Chemical Agents

    CERN Multimedia

    Safety Commission

    2010-01-01

    The following Safety rule has been issued on 08-01-2010: Safety Regulation SR-C Chemical Agents This document applies to all persons under the Director General’s authority. It sets out the minimal requirements for the protection of persons from risks to their safety and health arising, or likely to arise, from the effects of hazardous chemical agents used in any CERN activity. All Safety rules are available on the web pages.

  4. Using Cognitive Agents to Train Negotiation Skills

    Directory of Open Access Journals (Sweden)

    Christopher A. Stevens

    2018-02-01

    Full Text Available Training negotiation is difficult because it is a complex, dynamic activity that involves multiple parties. It is often not clear how to create situations in which students can practice negotiation or how to measure students' progress. Some have begun to address these issues by creating artificial software agents with which students can train. These agents have the advantage that they can be “reset,” and played against multiple times. This allows students to learn from their mistakes and try different strategies. However, these agents are often based on normative theories of how negotiators should conduct themselves, not necessarily how people actually behave in negotiations. Here, we take a step toward addressing this gap by developing an agent grounded in a cognitive architecture, ACT-R. This agent contains a model of theory-of-mind, the ability of humans to reason about the mental states of others. It uses this model to try to infer the strategy of the opponent and respond accordingly. In a series of experiments, we show that this agent replicates some aspects of human performance, is plausible to human negotiators, and can lead to learning gains in a small-scale negotiation task.

  5. Using Cognitive Agents to Train Negotiation Skills.

    Science.gov (United States)

    Stevens, Christopher A; Daamen, Jeroen; Gaudrain, Emma; Renkema, Tom; Top, Jakob Dirk; Cnossen, Fokie; Taatgen, Niels A

    2018-01-01

    Training negotiation is difficult because it is a complex, dynamic activity that involves multiple parties. It is often not clear how to create situations in which students can practice negotiation or how to measure students' progress. Some have begun to address these issues by creating artificial software agents with which students can train. These agents have the advantage that they can be "reset," and played against multiple times. This allows students to learn from their mistakes and try different strategies. However, these agents are often based on normative theories of how negotiators should conduct themselves, not necessarily how people actually behave in negotiations. Here, we take a step toward addressing this gap by developing an agent grounded in a cognitive architecture, ACT-R. This agent contains a model of theory-of-mind, the ability of humans to reason about the mental states of others. It uses this model to try to infer the strategy of the opponent and respond accordingly. In a series of experiments, we show that this agent replicates some aspects of human performance, is plausible to human negotiators, and can lead to learning gains in a small-scale negotiation task.

  6. Agent-based modeling and network dynamics

    CERN Document Server

    Namatame, Akira

    2016-01-01

    The book integrates agent-based modeling and network science. It is divided into three parts, namely, foundations, primary dynamics on and of social networks, and applications. The book begins with the network origin of agent-based models, known as cellular automata, and introduce a number of classic models, such as Schelling’s segregation model and Axelrod’s spatial game. The essence of the foundation part is the network-based agent-based models in which agents follow network-based decision rules. Under the influence of the substantial progress in network science in late 1990s, these models have been extended from using lattices into using small-world networks, scale-free networks, etc. The book also shows that the modern network science mainly driven by game-theorists and sociophysicists has inspired agent-based social scientists to develop alternative formation algorithms, known as agent-based social networks. The book reviews a number of pioneering and representative models in this family. Upon the gi...

  7. Transfection Agent Induced Nanoparticle Cell Loading

    Directory of Open Access Journals (Sweden)

    Karin Montet-Abou

    2005-07-01

    Full Text Available Loading cells with magnetic nanoparticles, and tracking their fate in vivo by high resolution MRI, is an attractive approach for enhancing the efficacy of cell-based therapies including those utilizing hematopoietic stem cells, neuroprogenitor cells, and T cells. The transfection agent (internalization agent assisted loading with the Feridex IV® nanoparticle is an attractive method of loading because of the low cost of materials, and possible low regulatory barriers for eventual clinical use. We therefore explored the interaction between Feridex IV® and three internalization agents protamine (PRO, polylysine (PLL, and lipofectamine (LFA. Feridex reacted with internalization agents to form aggregates, except when either the internalization agent or Feridex was present in large excess. When Jurkat T cells were incubated with Feridex/LFA or Feridex/PRO mixtures, and washed by centrifugation, nanoparticle aggregates co-purified with cells. With C17.2 cells large iron oxide particles adhered to the cell surface. At 30 μg/mL Feridex and 3 μg/mL LFA, internalization was largely mediated by LFA and was largely cytoplasmic. However, we found that the conditions used to label cells with Feridex and transfection agents need to be carefully selected to avoid the problems of surface adsorption and nanoparticle precipitation.

  8. Intelligent agents for e-commerce applications

    Science.gov (United States)

    Vuppala, Krishna

    1999-12-01

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

  9. CHI: A General Agent Communication Framework

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-17

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

  10. Reaching High Interactive Levels with Situated Agents

    Directory of Open Access Journals (Sweden)

    Guzmán-Obando J.

    2013-01-01

    Full Text Available El documento presenta un proceso coordinado a través del cual los agentes situados son capaces de trabajar en forma conjunta con el conocimiento de sus habilidades para interactuar con otras entidades similares. Una buena coordinación se deriva de que cada agente situado es capaz de representar sus tasas de idoneidad para llevar a cabo cualquier acción de una manera eficaz. Además de utilizar dichas tasas, un agente puede coordinar sus acciones con otros agentes. En este sentido, cada agente situado trata de seleccionar y realizar sólo las acciones con los mayores índices de ejecución. Algunos experimentos en un verdadero fútbol robótico banco de pruebas están diseñadas para poner en práctica el enfoque coordinado propuesto. Observaciones finales concluir la eficacia y las ventajas de la obra presentada con el fin de aumentar el rendimiento de un equipo integrado por agentes situados cuando tienen que resolver tareas complejas en un escenario dinámico, competitivo e impredecible.

  11. Unibot, a Universal Agent Architecture for Robots

    Directory of Open Access Journals (Sweden)

    Saša Mladenović

    2017-01-01

    Full Text Available Today there are numerous robots in different applications domains despite the fact that they still have limitations in perception, actuation and decision process. Consequently, robots usually have limited autonomy, they are domain specific or have difficulty to adapt on new environments. Learning is the property that makes an agent intelligent and the crucial property that a robot should have to proliferate into the human society. Embedding the learning ability into the robot may simplify the development of the robot control mechanism. The motivation for this research is to develop the agent architecture of the universal robot – Unibot. In our approach the agent is the robot i.e. Unibot that acts in the physical world and is capable of learning. The Unibot conducts several simultaneous simulations of a problem of interest like path-finding. The novelty in our approach is the Multi-Agent Decision Support System which is developed and integrated into the Unibot agent architecture in order to execute simultaneous simulations. Furthermore, the Unibot calculates and evaluates between multiple solutions, decides which action should be performed and performs the action. The prototype of the Unibot agent architecture is described and evaluated in the experiment supported by the Lego Mindstorms robot and the NetLogo.

  12. History of chemical and biological warfare agents

    International Nuclear Information System (INIS)

    Szinicz, L.

    2005-01-01

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

  13. History of chemical and biological warfare agents.

    Science.gov (United States)

    Szinicz, L

    2005-10-30

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

  14. [Community health agents: profile and education].

    Science.gov (United States)

    Marzari, Carla Kowalski; Junges, José Roque; Selli, Lucilda

    2011-01-01

    This research discusses the profile and education of the community health agents. There is no clarity about the kind of professional needed and the appropriate training to the fulfillment of the function. The research is a case study with exploratory methodology and qualitative approach. The data was collected with a focused group, formed by ten agents, intentional selected from those with more time in service in Family Health Strategy teams from the municipality of Santa Maria, Rio Grande do Sul State. The discussions were recorded and transcribed by the researcher. The data was interpreted by content analysis. The results pointed to some important questions concerning the identity of the community health agents: integration on the health team, insertion in the community, profile and education. The profile which emerges from the research, is not different from the one proposed by the Ministry of Health. However, the difference is the professionalization, an initiative assumed by the agent, guided by reality, which he faces in his activity. The gaps, perceived in his formation, cause the agent to construct his professional identity, determined more by the technical aspect of the scientific knowledge than by his social competence as a community agent.

  15. Optimization of extinguishing agents for nuclear power plants

    International Nuclear Information System (INIS)

    Boleman, M.; Lipar, M.; Balog, K.

    1998-01-01

    Focus is placed on use of extinguishing agents in nuclear power plants. The advantages and disadvantages of these agents are compared. Further perspectives for using particular extinguishing agents in nuclear power plants are outlined. (author)

  16. Newer agents for the management of overactive bladder | Epstein ...

    African Journals Online (AJOL)

    Newer agents for the management of overactive bladder. ... that these newer agents decrease the frequency of incontinence episodes, the number ... for selection of an appropriate agent based on individual factors such as cost and tolerability.

  17. A Novel Security Approach in Mobile Agent Using Encryption

    OpenAIRE

    Nidhi Gupta; Dr. Anurag Dixit

    2012-01-01

    The appearance of software agents has given rise too much discussion of what such an agent is and how it differs from programs in general. An agent is anything that can be viewed as perceiving its environment through sensors & acting upon that environment through actuators. The existing systems can be classified in the context of singleagent systems and multi-agent systems. Mobile agents cantransport themselves from one host to another. Mobile agents have been developed as an extension to and...

  18. Environmental Agents Service (EAS) Registry System of Records

    Data.gov (United States)

    Department of Veterans Affairs — The Environmental Agent Service (EAS) Registries is the information system encompassing the Ionizing Radiation Registry (IRR), the Agent Orange Registry (AOR), and...

  19. In vitro penetration of bleaching agents into the pulp chamber

    DEFF Research Database (Denmark)

    Benetti, Ana Raquel; Valera, M C; Mancini, M N G

    2004-01-01

    To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures.......To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures....

  20. 2015 Special Sessions of the 13th International Conference on Practical Applications of Agents and Multi-Agent Systems

    CERN Document Server

    Hernández, Josefa; Mathieu, Philippe; Campbell, Andrew; Fernández-Caballero, Antonio; Moreno, María; Julián, Vicente; Alonso-Betanzos, Amparo; Jiménez-López, María; Botti, Vicente; Trends in Practical Applications of Agents, Multi-Agent Systems and Sustainability : the PAAMS Collection

    2015-01-01

    This volume presents the papers that have been accepted for the 2015 special sessions of the 13th International Conference on Practical Applications of Agents and Multi-Agent Systems, held at University of Salamanca, Spain, at 3rd-5th June, 2015: Agents Behaviours and Artificial Markets (ABAM); Agents and Mobile Devices (AM); Multi-Agent Systems and Ambient Intelligence (MASMAI); Web Mining and Recommender systems (WebMiRes); Learning, Agents and Formal Languages (LAFLang); Agent-based Modeling of Sustainable Behavior and Green Economies (AMSBGE); Emotional Software Agents (SSESA) and Intelligent Educational Systems (SSIES). The volume also includes the paper accepted for the Doctoral Consortium in PAAMS 2015. 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 develo...

  1. Agent Based Modeling Applications for Geosciences

    Science.gov (United States)

    Stein, J. S.

    2004-12-01

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

  2. Effects of the differentiating agents sodium butyrate and N-methylformamide on the oxygen enhancement ratio of human colon tumor cells

    International Nuclear Information System (INIS)

    Hallows, K.R.; Bliven, S.F.; Leith, J.T.

    1988-01-01

    We have previously shown that chronic adaptation of human tumor cells to the differentiation-inducing agents N-methylformamide (NMF) and sodium butyrate (NAB) increases the sensitivity of oxic cells to graded single doses of X rays. These studies were carried out to define the sensitivity of hypoxic cells after adaptation. Clone A colon tumor cells were grown for three passages in medium containing 170 mM NMF or 2 mM NAB and irradiated in suspension culture, after gassing with either oxygen (60 min) or ultrapure nitrogen (90 min), and complete survival curves were generated. Using the linear-quadratic equation to describe the data, it was found that NMF and NAB produced increased X-ray killing of hypoxic cells. At the 10% level of survival, the dose-modifying factors were about 1.20 and 1.25 for NMF- and NAB-adapted hypoxic cells, respectively, as compared to hypoxic control cells. However, since both oxic and hypoxic cells exhibited increased sensitivity after NMF and NAB adaptation, there was no major change in the oxygen enhancement ratio

  3. Liposomes as carriers of imaging agents

    International Nuclear Information System (INIS)

    Caride, V.J.

    1985-01-01

    This review discusses the utilization of liposomes as imaging agents or as vehicles for contrast materials. The initial approach was the use of radiolabeled liposomes for scintigraphy. To this end liposomes were either labeled in the lipid membrane or aqueous radiotracers were incorporated inside the lipid vesicles. The lipid labeling provides a more stable association of the radioactive tracer and the lipid vesicles, while the use of water-soluble radiotracers provides a wider selection of compounds. Early attempts at selective tumor imaging using radiolabeled liposomes were unsuccessful. The use of monoclonal antibodies attached to liposomes offers new hopes. Several strategies have been proposed in this respect and several others can be envisioned. The use of liposomes permits the use of several administration routes for imaging agents. Of particular interest is the subcutaneous administration for lymph node visualization. Liposomes offer clear advantages over most radiocontrast agents for prolonged hepatosplenic contrast enhancement. This is particularly relevant in the diagnostic evaluation of the abdomen with computed tomography. Important research efforts are being conducted in this area. Two different approaches have been advanced: the incorporation of contrast agents into liposomes and the preparation of radiopaque liposomes from radiodense lipids. Nuclear magnetic resonance imaging can also benefit from contrast agents. Several centers are investigating this exciting field using liposomes loaded with paramagnetic elements.152 references

  4. Constructing Agent Model for Virtual Training Systems

    Science.gov (United States)

    Murakami, Yohei; Sugimoto, Yuki; Ishida, Toru

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

  5. Contrast agent choice for intravenous coronary angiography

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  6. Use of contrast agents for liver MRI

    International Nuclear Information System (INIS)

    Ward, Janice

    2007-01-01

    Contrast-enhanced MRI is recognised as one of the most accurate imaging methods for investigating diseases of the liver. Uniquely several different types of contrast agents are available for liver MRI. They can be divided into non-specific extracellular fluid space (ECF), hepatocyte specific and reticulo-endothelial system (RES) specific agents. They are used to improve the detection of focal liver lesions by increasing normal-abnormal tissue contrast and to assist in lesion characterisation by demonstrating tissue perfusion and cellular function. ECF-gadolinium (Gd) chelates have been widely used in abdominal MRI for many years. They provide valuable information regarding the vascularisation and perfusion characteristics of lesions and assist in lesion detection, particularly of hypervascular lesions. The hepatocyte and RES-specific agents further improve lesion detection, provide important functional information and allow the distinction between hepatocellular and non-hepatocellular tumours. This article describes the different MR contrast agents and discusses their current status for diagnosing focal liver lesions. The importance of optimised technique and appropriate selection of contrast agent is emphasised

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

    Science.gov (United States)

    Seto, Yasuo

    2009-01-01

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

  8. Electrospun biodegradable polymers loaded with bactericide agents

    Directory of Open Access Journals (Sweden)

    Ramaz Katsarava

    2016-03-01

    Full Text Available Development of materials with an antimicrobial activity is fundamental for different sectors, including medicine and health care, water and air treatment, and food packaging. Electrospinning is a versatile and economic technique that allows the incorporation of different natural, industrial, and clinical agents into a wide variety of polymers and blends in the form of micro/nanofibers. Furthermore, the technique is versatile since different constructs (e.g. those derived from single electrospinning, co-electrospinning, coaxial electrospinning, and miniemulsion electrospinning can be obtained to influence the ability to load agents with different characteristics and stability and to modify the release behaviour. Furthermore, antimicrobial agents can be loaded during the electrospinning process or by a subsequent coating process. In order to the mitigate burst release effect, it is possible to encapsulate the selected drug into inorganic nanotubes and nanoparticles, as well as in organic cyclodextrine polysaccharides. In the same way, processes that involve covalent linkage of bactericide agents during surface treatment of electrospun samples may also be considered. The present review is focused on more recent works concerning the electrospinning of antimicrobial polymers. These include chitosan and common biodegradable polymers with activity caused by the specific load of agents such as metal and metal oxide particles, quaternary ammonium compounds, hydantoin compounds, antibiotics, common organic bactericides, and bacteriophages.

  9. Quantum Speedup for Active Learning Agents

    Directory of Open Access Journals (Sweden)

    Giuseppe Davide Paparo

    2014-07-01

    Full Text Available Can quantum mechanics help us build intelligent learning agents? A defining signature of intelligent behavior is the capacity to learn from experience. However, a major bottleneck for agents to learn in real-life situations is the size and complexity of the corresponding task environment. Even in a moderately realistic environment, it may simply take too long to rationally respond to a given situation. If the environment is impatient, allowing only a certain time for a response, an agent may then be unable to cope with the situation and to learn at all. Here, we show that quantum physics can help and provide a quadratic speedup for active learning as a genuine problem of artificial intelligence. This result will be particularly relevant for applications involving complex task environments.

  10. ECONOMÍA COMPUTACIONAL BASADA EN AGENTES

    Directory of Open Access Journals (Sweden)

    FABIÁN ANDRÉS GIRALDO GIRALDO

    2012-12-01

    Full Text Available El artículo tiene como objetivo mostrarvarios trabajos de investigación sobre un enfoque desimulación denominado Economía computacional basadaen agentes, el cual rechaza las asunciones delos enfoques de estudio tradicionales que indican quela economía es un sistema cerrado que eventualmentelogra un estado de equilibrio, en el que deben realizarsesupuestos de racionalidad perfecta e inversioneshomogéneas para que los modelos sean tratadosanalíticamente. En su lugar, ve a la economía comoun sistema complejo, adaptativo y dinámico. Estenuevo enfoque permite usar la simulación basada enagentes para comprender que varios agentes económicos(firmas, grupos económicos con sus propiasreglas y objetivos, son capaces de interactuar entresí y con su entorno para obtener comportamientosemergentes que no son explicables directamente delas propiedades de los agentes individuales.

  11. Microbial biofilms: biosurfactants as antibiofilm agents.

    Science.gov (United States)

    Banat, Ibrahim M; De Rienzo, Mayri A Díaz; Quinn, Gerry A

    2014-12-01

    Current microbial inhibition strategies based on planktonic bacterial physiology have been known to have limited efficacy on the growth of biofilm communities. This problem can be exacerbated by the emergence of increasingly resistant clinical strains. All aspects of biofilm measurement, monitoring, dispersal, control, and inhibition are becoming issues of increasing importance. Biosurfactants have merited renewed interest in both clinical and hygienic sectors due to their potential to disperse microbial biofilms in addition to many other advantages. The dispersal properties of biosurfactants have been shown to rival those of conventional inhibitory agents against bacterial and yeast biofilms. This makes them suitable candidates for use in new generations of microbial dispersal agents and for use as adjuvants for existing microbial suppression or eradication strategies. In this review, we explore aspects of biofilm characteristics and examine the contribution of biologically derived surface-active agents (biosurfactants) to the disruption or inhibition of microbial biofilms.

  12. Network Management using Multi-Agents System

    Directory of Open Access Journals (Sweden)

    Nestor DUQUE

    2013-07-01

    Full Text Available This paper aims to present a multiagent system for network management. The models developed for the proposed system defines certain intelligent agents interact to achieve the objectives and requirements of the multiagent organization.These agents have the property of being adaptive, acquire knowledge and skills to make decisions according to the actual state of the network that is represented in the information base, MIB, SNMP devices. The ideal state of the network policy is defined by the end user entered, which contain the value that should have performance variables and other parameters such as the frequency with which these variables should be monitored.. An agent based architecture increase the integration, adaptability, cooperation, autonomy and the efficient operation in heterogeneous environment in the network supervision. 

  13. Network Management using Multi-Agents System

    Directory of Open Access Journals (Sweden)

    Gustavo ISAZA

    2012-12-01

    Full Text Available This paper aims to present a multiagent system for network management. The models developed for the proposed system defines certain intelligent agents interact to achieve the objectives and requirements of the multiagent organization.These agents have the property of being adaptive, acquire knowledge and skills to make decisions according to the actual state of the network that is represented in the information base, MIB, SNMP devices. The ideal state of the network policy is defined by the end user entered, which contain the value that should have performance variables and other parameters such as the frequency with which these variables should be monitored.. An agent based architecture increase the integration, adaptability, cooperation, autonomy and the efficient operation in heterogeneous environment in the network supervision. 

  14. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  15. Anti-Infectious Agents against MRSA

    Directory of Open Access Journals (Sweden)

    Nobuhiro Koyama

    2012-12-01

    Full Text Available Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652 targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described.

  16. Autonomous Formations of Multi-Agent Systems

    Science.gov (United States)

    Dhali, Sanjana; Joshi, Suresh M.

    2013-01-01

    Autonomous formation control of multi-agent dynamic systems has a number of applications that include ground-based and aerial robots and satellite formations. For air vehicles, formation flight ("flocking") has the potential to significantly increase airspace utilization as well as fuel efficiency. This presentation addresses two main problems in multi-agent formations: optimal role assignment to minimize the total cost (e.g., combined distance traveled by all agents); and maintaining formation geometry during flock motion. The Kuhn-Munkres ("Hungarian") algorithm is used for optimal assignment, and consensus-based leader-follower type control architecture is used to maintain formation shape despite the leader s independent movements. The methods are demonstrated by animated simulations.

  17. Agents That Negotiate Proficiently with People

    Science.gov (United States)

    Kraus, Sarit

    Negotiation is a process by which interested parties confer with the aim of reaching agreements. The dissemination of technologies such as the Internet has created opportunities for computer agents to negotiate with people, despite being distributed geographically and in time. The inclusion of people presents novel problems for the design of autonomous agent negotiation strategies. People do not adhere to the optimal, monolithic strategies that can be derived analytically, as is the case in settings comprising computer agents alone. Their negotiation behavior is affected by a multitude of social and psychological factors, such as social attributes that influence negotiation deals (e.g., social welfare, inequity aversion) and traits of individual negotiators (e.g., altruism, trustworthiness, helpfulness). Furthermore, culture plays an important role in their decision making and people of varying cultures differ in the way they make offers and fulfill their commitments in negotiation.

  18. Using Mobile Agents to Implement Workflow System

    Institute of Scientific and Technical Information of China (English)

    LI Jie; LIU Xian-xing; GUO Zheng-wei

    2004-01-01

    Current workflow management systems usually adopt the existing technologies such as TCP/IP-based Web technologies and CORBA as well to fulfill the bottom communications.Very often it has been considered only from a theoretical point of view, mainly for the lack of concrete possibilities to execute with elasticity.MAT (Mobile Agent Technology) represents a very attractive approach to the distributed control of computer networks and a valid alternative to the implementation of strategies for workflow system.This paper mainly focuses on improving the performance of workflow system by using MAT.Firstly, the performances of workflow systems based on both CORBA and mobile agent are summarized and analyzed; Secondly, the performance contrast is presented by introducing the mathematic model of each kind of data interaction process respectively.Last, a mobile agent-based workflow system named MAWMS is presented and described in detail.

  19. Chromosome analyses of nurses handling cytostatic agents

    International Nuclear Information System (INIS)

    Waksvik, H.; Klepp, O.; Brogger, A.

    1981-01-01

    A cytogenetic study of ten nurses handling cytostatic agents (average exposure, 2150 hours) and ten female hospital clerks revealed an increased frequency of chromosome gaps and a slight increase in sister chromatid exchange frequency among the nurses. The increase may be due to exposure to cytostatic drugs and points to these agents as a possible occupational health hazard. A second group of 11 nurses handling cytostatic agents for a shorter period of time (average exposure, 1078 hours), and three other groups (eight nurses engaged in therapeutic and diagnostic radiology, nine nurses engaged in anesthesiology, and seven nurses in postoperative ward) did not differ from the office personnel, except for an increased frequency of chromosome gaps in the radiology group

  20. FIPA agent based network distributed control system

    Energy Technology Data Exchange (ETDEWEB)

    D. Abbott; V. Gyurjyan; G. Heyes; E. Jastrzembski; C. Timmer; E. Wolin

    2003-03-01

    A control system with the capabilities to combine heterogeneous control systems or processes into a uniform homogeneous environment is discussed. This dynamically extensible system is an example of the software system at the agent level of abstraction. This level of abstraction considers agents as atomic entities that communicate to implement the functionality of the control system. Agents' engineering aspects are addressed by adopting the domain independent software standard, formulated by FIPA. Jade core Java classes are used as a FIPA specification implementation. A special, lightweight, XML RDFS based, control oriented, ontology markup language is developed to standardize the description of the arbitrary control system data processor. Control processes, described in this language, are integrated into the global system at runtime, without actual programming. Fault tolerance and recovery issues are also addressed.

  1. Planning of Autonomous Multi-agent Intersection

    Directory of Open Access Journals (Sweden)

    Viksnin Ilya I.

    2016-01-01

    Full Text Available In this paper, we propose a traffic management system with agents acting on behalf autonomous vehicle at the crossroads. Alternatively to existing solutions based on usage of semiautonomous control systems with the control unit, proposed in this paper algorithm apply the principles of decentralized multi-agent control. Agents during their collaboration generate intersection plan and determinate the optimal order of road intersection for a given criterion based on the exchange of information about them and their environment. The paper contains optimization criteria for possible routes selection and experiments that perform in order to estimate the proposed model. Experiment results show that this model can significantly reduce traffic density compared to the traditional traffic management systems. Moreover, the proposed algorithm efficiency increases with road traffic density. Furthermore, the availability of control unit in the system significantly reduces the negative impact of possible failures and hacker attacks.

  2. FIPA agent based network distributed control system

    International Nuclear Information System (INIS)

    Abbott, D.; Gyurjyan, V.; Heyes, G.; Jastrzembski, E.; Timmer, C.; Wolin, E.

    2003-01-01

    A control system with the capabilities to combine heterogeneous control systems or processes into a uniform homogeneous environment is discussed. This dynamically extensible system is an example of the software system at the agent level of abstraction. This level of abstraction considers agents as atomic entities that communicate to implement the functionality of the control system. Agents' engineering aspects are addressed by adopting the domain independent software standard, formulated by FIPA. Jade core Java classes are used as a FIPA specification implementation. A special, lightweight, XML RDFS based, control oriented, ontology markup language is developed to standardize the description of the arbitrary control system data processor. Control processes, described in this language, are integrated into the global system at runtime, without actual programming. Fault tolerance and recovery issues are also addressed

  3. Non-radiological contrast agents (MRI)

    International Nuclear Information System (INIS)

    Bonnemain, B.; Lautrou, J.; Meyer, D.; Doucet, D.

    1987-01-01

    Over the past few years, extensive research has been carried out in an attempt to develop contrast agents that could help improve both the performance (acquisition times) and the diagnostic efficacy of Magnetic Resonance Imaging (MRI) techniques. On the basis of physicochemical and pharmacological criteria discussed in this presentation, a few efficacious, well-tolerated compounds could be developed. Two of them, the gadolinium complexes Gd-DOTA and Gd-DTPA, are currently being tried in man. This first generation of contrast agents, which are aspecific markers of the intravascular space, has been shown to have good diagnostic potential in conventional MRI procedures. The diagnostic contribution of these contrast agents will probably be a most essential factor in new MRI techniques using low field strengh or fast imaging sequences [fr

  4. DIRAC - Distributed Infrastructure with Remote Agent Control

    CERN Document Server

    Tsaregorodtsev, A; Closier, J; Frank, M; Gaspar, C; van Herwijnen, E; Loverre, F; Ponce, S; Graciani Diaz, R.; Galli, D; Marconi, U; Vagnoni, V; Brook, N; Buckley, A; Harrison, K; Schmelling, M; Egede, U; Bogdanchikov, A; Korolko, I; Washbrook, A; Palacios, J P; Klous, S; Saborido, J J; Khan, A; Pickford, A; Soroko, A; Romanovski, V; Patrick, G N; Kuznetsov, G; Gandelman, M

    2003-01-01

    This paper describes DIRAC, the LHCb Monte Carlo production system. DIRAC has a client/server architecture based on: Compute elements distributed among the collaborating institutes; Databases for production management, bookkeeping (the metadata catalogue) and software configuration; Monitoring and cataloguing services for updating and accessing the databases. Locally installed software agents implemented in Python monitor the local batch queue, interrogate the production database for any outstanding production requests using the XML-RPC protocol and initiate the job submission. The agent checks and, if necessary, installs any required software automatically. After the job has processed the events, the agent transfers the output data and updates the metadata catalogue. DIRAC has been successfully installed at 18 collaborating institutes, including the DataGRID, and has been used in recent Physics Data Challenges. In the near to medium term future we must use a mixed environment with different types of grid mid...

  5. Nondestructive Intervention to Multi-Agent Systems through an Intelligent Agent

    Science.gov (United States)

    Han, Jing; Wang, Lin

    2013-01-01

    For a given multi-agent system where the local interaction rule of the existing agents can not be re-designed, one way to intervene the collective behavior of the system is to add one or a few special agents into the group which are still treated as normal agents by the existing ones. We study how to lead a Vicsek-like flocking model to reach synchronization by adding special agents. A popular method is to add some simple leaders (fixed-headings agents). However, we add one intelligent agent, called ‘shill’, which uses online feedback information of the group to decide the shill's moving direction at each step. A novel strategy for the shill to coordinate the group is proposed. It is strictly proved that a shill with this strategy and a limited speed can synchronize every agent in the group. The computer simulations show the effectiveness of this strategy in different scenarios, including different group sizes, shill speed, and with or without noise. Compared to the method of adding some fixed-heading leaders, our method can guarantee synchronization for any initial configuration in the deterministic scenario and improve the synchronization level significantly in low density groups, or model with noise. This suggests the advantage and power of feedback information in intervention of collective behavior. PMID:23658695

  6. Agent-based land markets: Heterogeneous agents, land proces and urban land use change

    NARCIS (Netherlands)

    Filatova, Tatiana; Parker, Dawn C.; van der Veen, A.; Amblard, F.

    2007-01-01

    We construct a spatially explicit agent-based model of a bilateral land market. Heterogeneous agents form their bid and ask prices for land based on the utility that they obtain from a certain location (houte/land) and base on the state of the market (an excess of demand or supply). We underline the

  7. An Interactive Tool for Creating Multi-Agent Systems and Interactive Agent-based Games

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Pagliarini, Luigi

    2011-01-01

    Utilizing principles from parallel and distributed processing combined with inspiration from modular robotics, we developed the modular interactive tiles. As an educational tool, the modular interactive tiles facilitate the learning of multi-agent systems and interactive agent-based games...

  8. A Comparison of Organization-Centered and Agent-Centered Multi-Agent Systems

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Villadsen, Jørgen

    2013-01-01

    Whereas most classical multi-agent systems have the agent in center, there has recently been a development towards focusing more on the organization of the system, thereby allowing the designer to focus on what the system goals are, without considering how the goals should be fulfilled. We have d...

  9. Nondestructive intervention to multi-agent systems through an intelligent agent.

    Directory of Open Access Journals (Sweden)

    Jing Han

    Full Text Available For a given multi-agent system where the local interaction rule of the existing agents can not be re-designed, one way to intervene the collective behavior of the system is to add one or a few special agents into the group which are still treated as normal agents by the existing ones. We study how to lead a Vicsek-like flocking model to reach synchronization by adding special agents. A popular method is to add some simple leaders (fixed-headings agents. However, we add one intelligent agent, called 'shill', which uses online feedback information of the group to decide the shill's moving direction at each step. A novel strategy for the shill to coordinate the group is proposed. It is strictly proved that a shill with this strategy and a limited speed can synchronize every agent in the group. The computer simulations show the effectiveness of this strategy in different scenarios, including different group sizes, shill speed, and with or without noise. Compared to the method of adding some fixed-heading leaders, our method can guarantee synchronization for any initial configuration in the deterministic scenario and improve the synchronization level significantly in low density groups, or model with noise. This suggests the advantage and power of feedback information in intervention of collective behavior.

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

    African Journals Online (AJOL)

    Careful analysis of various metaethics supports that there are these two senses – analysis, in particular, of a neo-Kantian metaethic, according to which reasons are agent-relative in the dependence sense but agent-neutral in the homogeneous sense, and – perhaps surprisingly – of Utilitarianism, according to which ...

  11. 31 CFR 10.4 - Eligibility for enrollment as enrolled agent or enrolled retirement plan agent.

    Science.gov (United States)

    2010-07-01

    ...) Enrollment as an enrolled agent upon examination. The Director of the Office of Professional Responsibility may grant enrollment as an enrolled agent to an applicant who demonstrates special competence in tax... the Office of Professional Responsibility and who has not engaged in any conduct that would justify...

  12. Contrast agent choice for intravenous coronary angiography

    International Nuclear Information System (INIS)

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

    1990-01-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. (orig./HSI)

  13. 10th KES Conference on Agent and Multi-Agent Systems : Technologies and Applications

    CERN Document Server

    Chen-Burger, Yun-Heh; Howlett, Robert; Jain, Lakhmi

    2016-01-01

    The modern economy is driven by technologies and knowledge. Digital technologies can free, shift and multiply choices, often intruding on the space of other industries, by providing new ways of conducting business operations and creating values for customers and companies. The topics covered in this volume include software agents, multi-agent systems, agent modelling, mobile and cloud computing, big data analysis, business intelligence, artificial intelligence, social systems, computer embedded systems and nature inspired manufacturing, etc. that contribute to the modern Digital Economy. This volume highlights new trends and challenges in agent, new digital and knowledge economy research and includes 28 papers classified in the following specific topics: business process management, agent-based modeling and simulation, anthropic-oriented computing, learning paradigms, business informatics and gaming, digital economy, and advances in networked virtual enterprises. Published papers were selected for presentatio...

  14. Developing Agent-Oriented Video Surveillance System through Agent-Oriented Methodology (AOM

    Directory of Open Access Journals (Sweden)

    Cheah Wai Shiang

    2016-12-01

    Full Text Available Agent-oriented methodology (AOM is a comprehensive and unified agent methodology for agent-oriented software development. Although AOM is claimed to be able to cope with a complex system development, it is still not yet determined up to what extent this may be true. Therefore, it is vital to conduct an investigation to validate this methodology. This paper presents the adoption of AOM in developing an agent-oriented video surveillance system (VSS. An intruder handling scenario is designed and implemented through AOM. AOM provides an alternative method to engineer a distributed security system in a systematic manner. It presents the security system at a holistic view; provides a better conceptualization of agent-oriented security system and supports rapid prototyping as well as simulation of video surveillance system.

  15. Organophosphate Nerve Agent Detection with Europium Complexes

    Directory of Open Access Journals (Sweden)

    Jake R. Schwierking

    2004-01-01

    Full Text Available We explore the detection of paraoxon, a model compound for nonvolatile organophosphate nerve agents such as VX. The detection utilizes europium complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing ligands. Both europium luminescence quenching and luminescence enhancement modalities are involved in the detection, which is simple, rapid, and sensitive. It is adaptable as well to the more volatile fluorophosphate nerve agents. It involves nothing more than visual luminescence observation under sample illumination by an ordinary hand-held ultraviolet lamp.

  16. Organic Colouring Agents in the Pharmaceutical Industry

    Directory of Open Access Journals (Sweden)

    Šuleková M.

    2017-09-01

    Full Text Available Food dyes are largely used in the process of manufacturing pharmaceutical products. The aim of such a procedure is not only to increase the attractiveness of products, but also to help patients distinguish between pharmaceuticals. Various dyes, especially organic colouring agents, may in some cases have a negative impact on the human body. They are incorporated into pharmaceutical products including tablets, hard gelatine capsules or soft gelatine capsules, lozenges, syrups, etc. This article provides an overview of the most widely used colouring agents in pharmaceuticals, their characteristics and the EU legislation which regulates their use.

  17. Limit values for exposure to physical agents

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    The limit values for exposure to thermal environments adopted by the French AFNOR and by the ISO Working Group (AFNOR Standard X 35-201 and ISO Standard 7243, and AFNOR Standard X 35-204). The limit values for exposure to other physical agents established by the American ACGIH for 1982. The following agents are covered: - laser radiation (ocular and skin exposure); - ultraviolet radiation; - visible and near-infrared radiation (retinal thermal and photochemical injury); - airborne and upper sonic and ultrasonic acoustic radiation; - radiofrequency radiation [fr

  18. Quitina y carboximetilquitosana como agentes desintegrantes

    OpenAIRE

    Sol A Fernández Monagas; María D Rodríguez Albadalejo; Ofelia Bilbao Revoredo; Olga M Nieto Acosta

    1998-01-01

    Se realizó un estudio comparativo de la quitina y la carboximetilquitosana como agentes desintegrantes, y se evaluó la influencia ejercida por el método empleado en la elaboración de las tabletas sobre la actividad desintegrante de ambos polímeros. La quitina presentó buenas características como agente desintegrante independientemente del método utilizado en la elaboración de las tabletas, mientras que la actividad desintegrante de la carboximetilquitosana fue afectada por el proceso de granu...

  19. Psoriatic arthritis: treatment strategies using biologic agents

    Directory of Open Access Journals (Sweden)

    C. Palazzi

    2012-06-01

    Full Text Available The traditional management of psoriatic arthritis (PsA includes NSAIDs, corticosteroids and DMARDs. Advancement in the knowledge of the immunopathogenesis of PsA has been associated with the development of biologic agents which have revolutionized the management of the disease. Among biologics drugs, there are the 4 currently availablee anti-TNFα blocking agents (etanercept, infliximab, adalimumab and golimumab which are more effective than traditional DMARDs on symptoms/signs of inflammation, quality of life, function, and in inhibiting the progression of the structural joint damage. Despite of the high cost, TNF inhibitors are costeffective on both the musculoskeletal and skin manifestations of psoriatic disease.

  20. Agentes Comunitários de Saúde e os sentidos de "ser agente" Community Health Agents and the meanings of "being an agent"

    Directory of Open Access Journals (Sweden)

    Viviane Milan Pupin

    2008-08-01

    Full Text Available O Programa Saúde da Família constitui-se enquanto estratégia de mudança do modelo assistencial. O artigo apresenta os resultados de uma pesquisa qualitativa sobre os sentidos de "ser agente" produzidos, por meio de entrevistas abertas, com Agentes Comunitários de Saúde que trabalham nos cinco Núcleos de Saúde da Família da cidade de Ribeirão Preto - São Paulo, vinculados à Faculdade de Medicina de Ribeirão Preto - USP. As entrevistas foram gravadas e transcritas na íntegra e analisadas segundo princípios da análise de conteúdo. A análise permitiu a descrição de sentidos acerca de ser agente subdivididos em: Sentidos produzidos na relação com a comunidade e Sentidos produzidos na relação com a equipe. A análise dos sentidos de ser agente possibilitou construir um diálogo sobre as tensões relacionadas a um fazer em saúde ora permeado por concepções atreladas ao modelo biomédico, ora atrelado aos novos paradigmas em saúde.The Family Health Program consists of a strategy to change the health care model. This article presents the results from a qualitative study about the meanings of "being an agent" obtained through open interviews with Community Health Agents who work in five Family Health Centers of the Ribeirão Preto School of Medicine (University of São Paulo, located in Ribeirão Preto, São Paulo. Interviews were tape recorded, fully transcribed, and then content analyzed. The analysis allowed for descriptions of meanings toward "being an agent", subdivided into: Meanings produced by relationships with the community, and Meanings produced by relationships with the team. Analyzing the meanings of being an agent provided the establishment of a dialogue about the tensions related to a health practice that is at times influenced by conceptions associated with the biomedical method, and at other times with the new health paradigm.