21 CFR 341.14 - Antitussive active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antitussive active ingredients. 341.14 Section 341.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE...

21 CFR 341.74 - Labeling of antitussive drug products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of antitussive drug products. 341.74 Section 341.74 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... years of age. Drug interaction precaution. “Do not use in a child who is taking a prescription monoamine...

21 CFR 341.74 - Labeling of antitussive drug products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of antitussive drug products. 341.74 Section 341.74 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... years of age. Drug interaction precaution. “Do not use in a child who is taking a prescription monoamine...

Antitussive arabinogalactan of Andrographis paniculata demonstrates synergistic effect with andrographolide.

PubMed

Nosáľová, Gabriela; Majee, Sujay Kumar; Ghosh, Kanika; Raja, Washim; Chatterjee, Udipta Ranjan; Jureček, Ludovít; Ray, Bimalendu

2014-08-01

Traditional Indian medicines have been used in humans for thousands of years. While the link to a particular indication has been established in man, the active principle of the formulations often remains unknown. In this study, we aim to investigate the structural features and antitussive activity of fractions from Andrographis paniculata leaves. In vivo investigations of water extract (WE), and both ethanol-soluble (WES) and precipitated (WEP) fractions from WE on the citric-acid induced cough efforts and airways smooth muscle reactivity in guinea pigs were performed. Chemical, chromatographic and spectroscopic analysis revealed the existence of a highly branched pectic arabinogalactan (109kDa) in WEP and andrographolide in WES. WEP showed significant antitussive activity while the potencies of WE and WES are even higher. Neither WE nor WES significantly alter specific airway smooth muscle reactivity. Remarkably, the antitussive activity of arabinogalactan could be increased by synergistic action with andrographolide. Finally, traditional aqueous extraction method provides an arabinogalactan from A. paniculata, which stimulate biological response but without addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.

PubMed

Posod, A; Pinzer, K; Urbanek, M; Wegleiter, K; Keller, M; Kiechl-Kohlendorfer, U; Griesmaier, E

2014-08-22

Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Antitussive, expectorant, and anti-inflammatory activities of four caffeoylquinic acids isolated from Tussilago farfara.

PubMed

Wu, Qi-Zhen; Zhao, Dong-Xia; Xiang, Juan; Zhang, Mian; Zhang, Chao-Feng; Xu, Xiang-Hong

2016-07-01

The flower bud of Tussilago farfara L. (Compositae) (FTF) is one of the traditional Chinese medicinal herbs used to treat cough, phlegm, bronchitic, and asthmatic conditions. The objective of this study is to isolate four caffeoylquinic acids from the ethyl acetate extract (EtE) of FTF and to evaluate their antitussive, expectorant, and anti-inflammatory activities. The structures of compounds 1-4 isolated from EtE were determined by spectral analysis. Mice were orally treated with these compounds and their mixture (in a ratio of 5:28:41:26 as in EtE) at doses of 10 and 20 mg/kg once daily for 3 d. The antitussive and expectorant activities were evaluated separately with the ammonia liquor-induced model and the phenol red secretion model. The anti-inflammation activity was evaluated using leukocyte count in the bronchoalveolar lavage fluid after ammonia liquor-induced acute airway inflammation. The four compounds were identified as chlorogenic acid (1), 3,5-dicaffeoylquinic acid (2), 3,4-dicaffeoylquinic acid (3), and 4,5-dicaffeoylquinic acid (4). All compounds, especially compound 4 (58.0% inhibition in cough frequency), showed a significant antitussive effect. However, the mixture was the most effective to inhibit the cough frequency by 61.7%. All compounds also showed a significant expectorant effect, while compound 2 was the most potent to enhance the phenol red secretion by 35.7%. All compounds significantly alleviated inflammation, but compound 4 showed the strongest effect to inhibit the leukocytosis by 49.7%. The caffeoylquinic acids and their mixture, exhibiting significant antitussive, expectorant, and anti-inflammatory effects, could be considered as the main effective ingredients of FTF, and they may act in a collective and synergistic way.

Antitussive activity of Althaea officinalis L. polysaccharide rhamnogalacturonan and its changes in guinea pigs with ovalbumine-induced airways inflammation.

PubMed

Sutovska, M; Capek, P; Franova, S; Joskova, M; Sutovsky, J; Marcinek, J; Kalman, M

2011-01-01

The presented studies were aimed on experimental confirmation of Althaea officinalis polysaccharide rhamnogalacturonan antitussive effect and its changes in conditions of allergic inflammation. We have tested whether rhamnogalacturonan inhibits cough reflex and modulates airways reactivity of guinea pigs in vivo. The cough in guinea pigs was induced by 0.3 M citric acid (CA) aerosol for 3 min interval, in which total number of cough efforts (sudden enhancement of expiratory flow accompanied by cough movement and sound) was counted. Specific airway resistance and its changes induced by citric acid aerosol were considered as an indicator of the in vivo reactivity changes. 1) Althaea officinalis polysaccharide rhamnogalacturonan dose- dependently inhibits cough reflex in unsensitized guinea pigs. Simultaneously, plant polysaccharide shortened the duration of antitussive effect when it was been tested in inflammatory conditions. 2) Rhamnogalacturonan did not influence airways reactivity in vivo conditions expressed as specific resistance values neither sensitized nor unsensitized groups of animals. 3) The antitussive activity of codeine (dose 10 mg.kg(-1) b.w. orally) tested under the same condition was comparable to higher dose of rhamnogalacturonan in unsensitized animals. 4) The characteristic cellular pattern of allergic airways inflammation was confirmed by histopathological investigations. Rhamnogalacturonan isolated from Althaea officinalis mucilage possesses very high cough suppressive effect in guinea pigs test system, which is shortened in conditions of experimentally induced airways allergic inflammation (Tab. 1, Fig. 4, Ref. 25). Full Text in free PDF www.bmj.sk.

Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigs.

PubMed

Laude, E A; Bee, D; Crambes, O; Howard, P

1995-10-01

Fenspiride is a nonsteroidal anti-inflammatory agent, which we have previously shown to have an in vivo antibronchoconstrictor action in guinea pigs. We have currently studied this action using the constrictors Substance P, neurokinin A, citric acid and capsaicin in anaesthetized guinea-pigs. Fenspiride has also been reported to produce a subjective improvement in cough in patients. We have used a conscious guinea-pig model of cough as a more definitive method to study the effect of fenspiride on capsaicin- and citric acid-induced cough. Aerosolized fenspiride (1 mg.mL-1) caused a 58% reversal of capsaicin-induced bronchoconstriction; and i.v. fenspiride (1mg.kg-1) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A-induced bronchoconstriction were unaffected by 1 mg.kg-1 i.v. fenspiride. Aerosolized fenspiride (1, 3 and 10 mg.mL-1) administered for 4 min reduced citric acid (300 mM) induced cough, but 0.1 mg.mL-1 was without effect. Pretreatment with aerosolized fenspiride (10 mg.mL-1) caused a shift in the citric acid dose response curve to the right. For citric acid-induced cough, the duration of action of aerosolized fenspiride (10 mg.mL-1) was found to be 5 and 15 min post-treatment. Aerosolized capsaicin (30 microM) induced cough was also reduced by 3 and 10 mg.mL-1 aerosolized fenspiride, but no significant effect was found with 1 mg.mL-1. We conclude that aerosolized fenspiride reduces capsaicin- and citric acid-induced bronchoconstriction as well as induced cough in guinea-pigs in vivo. Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established. We postulate that fenspiride, acting as an antitussive and antibronchoconstrictor agent, would be beneficial in the clinical situation for those patients with hyperresponsive airways.

Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs

PubMed Central

Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico

2016-01-01

Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID:26837703

Olodaterol Attenuates Citric Acid-Induced Cough in Naïve and Ovalbumin-Sensitized and Challenged Guinea Pigs

PubMed Central

Wex, Eva; Bouyssou, Thierry

2015-01-01

Excessive coughing is a common feature of airway diseases. Different G-protein coupled receptors, including β2-adrenergic receptors (β2-AR), have been implicated in the molecular mechanisms underlying the cough reflex. However, the potential antitussive property of β2-AR agonists in patients with respiratory disease is a matter of ongoing debate. The aim of our study was to test the efficacy of the long-acting β2-AR agonist olodaterol with regard to its antitussive property in a pre-clinical model of citric acid-induced cough in guinea pigs and to compare the results to different clinically relevant β2-AR agonists. In our study β2-AR agonists were intratracheally administered, as dry powder, into the lungs of naïve or ovalbumin-sensitized guinea pigs 15 minutes prior to induction of cough by exposure to citric acid. Cough events were counted over 15 minutes during the citric acid exposure. Olodaterol dose-dependently inhibited the number of cough events in naïve and even more potently and with a greater maximal efficacy in ovalbumin-sensitized guinea pigs (p < 0.01). Formoterol and salmeterol showed a trend towards reducing cough. On the contrary, indacaterol demonstrated pro-tussive properties as it significantly increased the number of coughs, both in naïve and ovalbumin-sensitized animals (p < 0.001). In conclusion, olodaterol, at doses eliciting bronchodilation, showed antitussive properties in a model of citric acid-induced cough in naïve and ovalbumin-sensitized guinea pigs. This is in agreement with pre-clinical and clinical studies showing antitussive efficacy of β2-AR agonists. Indacaterol increased the number of coughs in this model, which concurs with clinical data where a transient cough has been observed after indacaterol inhalation. While the antitussive properties of β2-AR agonists can be explained by their ability to lead to the cAMP-induced hyperpolarization of the neuron membrane thereby inhibiting sensory nerve activation and the cough reflex, the mechanism underlying the pro-tussive property of indacaterol is not known. PMID:25781609

Observational study on the dispensing of cough syrups to children with acute cough by community pharmacists in France.

PubMed

Allaert, François-André; Villet, Stéphanie; Vincent, Stéphane; Sauve, Laurent

2018-04-01

Over-the-counter medicines may be proposed by pharmacists for children with acute cough. Study objectives were to describe the sociodemographic profile of children who were proposed a cough syrup by a pharmacist, the nature of the cough and type(s) of cough syrup proposed and to assess the evolution of the cough, tolerance and satisfaction with treatment. Observational, prospective, longitudinal, multicentre study with 157 pharmacies in France. Children who were proposed a cough syrup by a pharmacist were recruited. Questionnaires were completed by the pharmacists and/or parents at inclusion and by the parents after 5 days of treatment. Four hundred fourteen children were included (mean age: 6.0±2.9 years); 45.9% had a dry and 43.3% a productive cough. 30.4% were proposed an allopathic antitussive syrup, 28.3% an allopathic expectorant syrup and 23.7% a homeopathic syrup. Children with a dry cough were more likely to be given an allopathic antitussive (55.2%) or homeopathic (28.2%) syrup. Children with a productive cough or cough of several days duration were more likely to be given an allopathic expectorant syrup (70.1%). Cough disappearance was more frequent with homeopathic syrups compared to allopathic expectorants (P=0.002), or allopathic antitussives (P=0.042). Adverse events were most common with allopathic antitussive syrups (18.7%) (P<0.001). Two-thirds of parents were satisfied with the treatment their child received. Pharmacists play an important role in the management of acute cough in children. Homeopathic cough syrups may have an interest in terms of public health.

Metabolomic profiling of the flower bud and rachis of Tussilago farfara with antitussive and expectorant effects on mice.

PubMed

Li, Zhen-Yu; Zhi, Hai-Juan; Xue, Shui-Yu; Sun, Hai-Feng; Zhang, Fu-Sheng; Jia, Jin-Ping; Xing, Jie; Zhang, Li-Zeng; Qin, Xue-Mei

2012-03-06

Flower bud of Tussilago farfara L. is widely used for the treatment of cough, bronchitis and asthmatic disorders in the Traditional Chinese Medicine. However, due to the increasing demands, adulteration with rachis is frequently encountered in the marketplace. No report demonstrated the chemical and pharmacological differences between flower bud and rachis before. The water extracts were orally administrated to mice. Ammonia induced mice coughing model was used to evaluate the antitussive activity. The expectorant activity was evaluated by volume of phenol red in mice's tracheas. Metabolites were identified directly from the crude extracts through 1D- and 2D-NMR spectra. A metabolic profiling carried out by (1)H NMR spectroscopy and multivariate data analysis was applied to crude extracts from flower bud and rachis. Flower bud significantly lengthened the latent period of cough, decreased cough frequency caused by ammonia and enhanced tracheal phenol red output in expectorant evaluation. Principal component analysis (PCA) yielded good separation between flower bud and rachis, and corresponding loading plot showed that the phenolic compounds, organic acid, sugar, amino acid, terpene and sterol contributed to the discrimination. These findings provide pharmacological and chemical evidence that only flower bud can be used as the antitussive and expectorant herbal drug. The high concentration of chlorogenic acid, 3,5-dicaffeoylquinic acid, rutin in flower buds may be related with the antitussive and expectorant effects of Flos Farfara. To guarantee the clinical effect, rachis should be picked out before use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Saffron as an antidote or a protective agent against natural or chemical toxicities.

PubMed

Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2015-05-01

Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine throughout the world. The wide spectrum of saffron pharmacological activities is related to its major constituents including crocin, crocetin and safranal. Based on several studies, saffron and its active ingredients have been used as an antioxidant, antiinflammatory and antinociceptive, antidepressant, antitussive, anticonvulsant, memory enhancer, hypotensive and anticancer. According to the literatures, saffron has remarkable therapeutic effects. The protective effects of saffron and its main constituents in different tissues including brain, heart, liver, kidney and lung have been reported against some toxic materials either natural or chemical toxins in animal studies.In this review article, we have summarized different in vitro and animal studies in scientific databases which investigate the antidotal and protective effects of saffron and its major components against natural toxins and chemical-induced toxicities. Due to the lake of human studies, further investigations are required to ascertain the efficacy of saffron as an antidote or a protective agent in human intoxication.

[The use of opium in Roman society and the dependence of Princeps Marcus Aurelius].

PubMed

Trancas, Bruno; Borja Santos, Nuno; Patrício, Luís D

2008-01-01

Opium was known and frequently used in Roman society. Medical practice recognized its usefulness as an analgesic, soporific, anti-tussic or anti-diarrheic agent, as well as other currently unsupported uses with quasi-magical properties. It was additionally used as an ingredient in antidotes, panaceas and poisons. The authors present a non-exhaustive compilation of opium use according to medical doctors, writers and encyclopaedists of the time. Mythological and literary representations of the opium poppy reflected its diverse roles, being associated with prosperity and fertility, sleep, death and the underworld and with the art of medicine. Despite its free and routine use, there is no solid evidence of addiction, except the putative case of emperor Marcus Aurelius, consistently reported as one of the most likely cases of addiction to opium.

Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities

PubMed Central

Tavakkoli, Alireza; Ahmadi, Ali; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2017-01-01

Nigella sativa (N. sativa), which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. N. sativa seeds and oil have been used in the treatment of different diseases. Various studies on N. sativa have been carried out and a broad spectrum of its pharmacological actions have been established which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator. This is also indicated that the majority of the therapeutic effects of N. sativa are due to the presence of thymoquinone (TQ) that is the main bioactive constituent of the essential oil. According to several lines of evidence, the protective effects of this plant and its main constituent in different tissues including brain, heart, liver, kidney, and lung have been proved against some toxic agents either natural or chemical toxins in animal studies. In this review article, several in-vitro and animal studies in scientific databases which investigate the antidotal and protective effects of N. sativa and its main constituents against natural and chemical induced toxicities are introduced. Because human reports are rare, further studies are required to determine the efficacy of this plant as an antidote or protective agent in human intoxication. PMID:29844772

21 CFR 341.74 - Labeling of antitussive drug products.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2... oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson...

21 CFR 341.74 - Labeling of antitussive drug products.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2... oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson...

21 CFR 341.74 - Labeling of antitussive drug products.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2... oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson...

Cough: impact, beliefs, and expectations from a national survey.

PubMed

Dal Negro, Roberto W; Mazzolini, Massimiliano; Turco, Paola; Zanasi, Alessandro

2016-01-01

Cough is one of the most common discomforts affecting general population, which can disrupt subjects' quality of life due to its physical, social, and psychological effects. Aim of the study was to investigate the impact of cough and related beliefs of general population. A cross-sectional telephone survey was carried out by means of a specific, validated questionnaire on a representative sample of Italian general population. All the interviews were carried out according to the Computer Assisted Telephone Interview (CATI) methodology by expert, professional interviewers. Distributions of all answers were calculated in the overall sample. A total of 1,251 subjects (mean age: 49 years; females 44.2 %) completed the interviews. The overall number of telephone calls was 5362, and the corresponding redemption rate was 1/4.3 (23.%). The sample was representative of national population in terms of geographical distribution, age, gender, and smoking habit. The majority of respondents was convinced that cough is merely a symptom of several different diseases, but 46.4 % of respondents affirmed that cough should be regarded as "a disease" per se. Only 29.1 % of subjects say that they usually do not complain of any cough over the year, while 18.4 % reported ≥ 3 episodes of cough/year. These episodes have a duration ranging 10-30 days in 19.9 % of subjects, and > 30 days in 6.9 % of subjects. The majority of respondents is worried about their cough only after 1 week, but 76.9 % of subjects is much more worried if cough affects a child. After a few days of cough, 23.1 % of subjects use domestic remedies; 20.9 % ask their pharmacist, and 33.4 % their doctor, being GPs (69.6 %) and lung physicians (16.2 %) the most asked professionals. The occurrence of bronchitis, pneumonia, upper airway infections, and allergic troubles are the most feared events. The majority of respondents are convinced that antibiotics and steroids should not be regarded as the gold standard for treating persistent cough (61.2 and 58.2 %, respectively), while anti-tussive drugs and aerosols in general are regarded as the most effective strategies (69.1 and 74.1 %, respectively). Moreover, 33.8 % of the sample is in favour of homeopathic drugs, while 23.2 % had already used an homeopathic anti-tussive syrup, and 27.6 % of subjects are really interested in using the homeopathic approach. The willingness to pay for an effective anti-tussive remedy was: 46.3 % up to 10 €; 27.8 % up to 20 €, and 13.3 % more than 20 €. Cough confirms its high impact in Italy, and a substantial proportion of individuals regards cough as "a disease". Only one out of three Italians refers to their doctor, but when cough is already persistent. Cough in children is much more feared than in adults. The majority of Italians have a proper and conservative position versus both antibiotic and the systemic steroid uses against cough. The Italian attitude to aerosol therapy confirms very high. Differently from the cough guidelines, anti-tussive drugs are highly valued among Italian people. The attitude and the interest to homeopathic anti-tussive remedies proves high. Finally, the willingness to pay for an effective anti-tussive remedy is quite high in Italy.

Kappa Opioid Receptor Agonist and Brain Ischemia

PubMed Central

Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

2014-01-01

Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

Aspergillus tracheobronchitis in a mild immunocompromised host.

PubMed

Cho, Byung Ha; Oh, Youngmin; Kang, Eun Seok; Hong, Yong Joo; Jeong, Hye Won; Lee, Ok-Jun; Chang, You-Jin; Choe, Kang Hyeon; Lee, Ki Man; An, Jin-Young

2014-11-01

Aspergillus tracheobronchitis is a form of invasive pulmonary aspergillosis in which the Aspergillus infection is limited predominantly to the tracheobronchial tree. It occurs primarily in severely immunocompromised patients such as lung transplant recipients. Here, we report a case of Aspergillus tracheobronchitis in a 42-year-old man with diabetes mellitus, who presented with intractable cough, lack of expectoration of sputum, and chest discomfort. The patient did not respond to conventional treatment with antibiotics and antitussive agents, and he underwent bronchoscopy that showed multiple, discrete, gelatinous whitish plaques mainly involving the trachea and the left bronchus. On the basis of the bronchoscopic and microbiologic findings, we made the diagnosis of Aspergillus tracheobronchitis and initiated antifungal therapy. He showed gradual improvement in his symptoms and continued taking oral itraconazole for 6 months. Physicians should consider Aspergillus tracheobronchitis as a probable diagnosis in immunocompromised patients presenting with atypical respiratory symptoms and should try to establish a prompt diagnosis.

Cough Medicine: Understanding Your OTC Options

MedlinePlus

... and expectorants. A common antitussive is dextromethorphan (some brand names: Triaminic Cold and Cough, Robitussin Cough, Vicks ... expectorant available in OTC products is guaifenesin (2 brand names: Mucinex, Robitussin Chest Congestion). How do OTC ...

Analysis of the impact of removing mucolytics and expectorants from the list of reimbursable drugs on prescription rates: a time-series analysis for France 1998-2010.

PubMed

Pichetti, Sylvain; Sorasith, Christine; Sermet, Catherine

2011-10-01

After a comprehensive review of the therapeutic advantage of all drugs reimbursed by the French Public Health Insurance, a large number of drugs were removed from the list of reimbursable drugs, among them mucolytics and expectorants (ATC Class R05C) in March 2006. The aim of this study is to evaluate the impact of this measure on the mucolytic and expectorant class, on the prescription of possible substitute drugs (other bronchodilators, antitussives and antibacterials) and on the costs for Public Health Insurance. Prescription data were taken from a 850 French physicians sample surveyed by the IMS-Health Permanent Survey on Medical Prescription from 1998 to 2010. We performed linear segmented regression to determine changes in the level and slope of the prescription rates and to estimate the budget impact. Following their removal from the list of reimbursable drugs, the prescription rate for mucolytics declined significantly and we recorded an increase in the prescription rates for antitussives and bronchodilators. The medically unexpected increase in antitussives can be viewed as a negative side-effect of the policy. Four years after the reform, total savings for Public Health Insurance were estimated at EUR 32.1 million. Further removals from the list of reimbursable drugs should take into account the possibility of negative impact on public health and potential savings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Dextromethorphan abuse leading to assault, suicide, or homicide.

PubMed

Logan, Barry K; Yeakel, Jillian K; Goldfogel, Gary; Frost, Michael P; Sandstrom, Greg; Wickham, Dennis J

2012-09-01

Dextromethorphan is a commonly encountered antitussive medication which has found additional therapeutic use in the treatment of pseudobulbar disorder and as an adjunct to opiate use in pain management. Dextromethorphan at high doses has phencyclidine-like effects on the NMDA receptor system; recreational use of high doses has been found to cause mania and hallucinations. The toxicology and pharmacology of the drug in abuse are reviewed, and the historical literature of adverse psychiatric outcomes is assessed. Five new cases of dextromethorphan intoxication that resulted in assault, suicide, and homicide are reported, together with the corresponding toxicology results. Blood concentrations ranged from 300 to 19,000 μg/L. These results are compared with typical concentrations reported in therapeutic use and impaired driving cases. Based on these findings, dextromethorphan should be considered as a potential causative agent in subjects presenting with mania, psychosis, or hallucinations, and abusers are at risk for violent and self-destructive acts. © 2012 American Academy of Forensic Sciences.

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2011 CFR

2011-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2010 CFR

2010-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2014 CFR

2014-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2012 CFR

2012-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

21 CFR 341.70 - Labeling of OTC drug products containing ingredients that are used for treating concurrent...

Code of Federal Regulations, 2013 CFR

2013-04-01

... name of the drug, if any, and identifies the product as a “cough suppressant/oral anesthetic” or “antitussive (cough suppressant)/oral anesthetic.” The indications shall be combined from § 341.74(b) and part...

MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.

PubMed

Thomas, David M; Kuhn, Donald M

2005-07-19

Methamphetamine causes long-term toxicity to dopamine nerve endings of the striatum. Evidence is emerging that microglia can contribute to the neuronal damage associated with disease, injury, or inflammation, but their role in methamphetamine-induced neurotoxicity has received relatively little attention. Lipopolysaccharide (LPS) and the neurotoxic HIV Tat protein, which cause dopamine neuronal toxicity after direct infusion into brain, cause activation of cultured mouse microglial cells as evidenced by increased expression of intracellular cyclooxygenase-2 and elevated secretion of tumor necrosis factor-alpha. MK-801, a non-competitive NMDA receptor antagonist that is known to protect against methamphetamine neurotoxicity, prevents microglial activation by LPS and HIV Tat. Dextromethorphan, an antitussive agent with NMDA receptor blocking properties, also prevents microglial activation. In vivo, MK-801 and dextromethorphan reduce methamphetamine-induced activation of microglia in striatum and they protect dopamine nerve endings against drug-induced nerve terminal damage. The present results indicate that the ability of MK-801 and dextromethorphan to protect against methamphetamine neurotoxicity is related to their common property as blockers of microglial activation.

The Treatment of the Behavioral Sequelae of Autism with Dextromethorphan: A Case Report

ERIC Educational Resources Information Center

Woodard, Cooper; Groden, June; Goodwin, Matthew; Shanower, Cori; Bianco, Joanne

2005-01-01

Dextromethorphan is the d-isomer of levorphenol, and an ingredient in antitussive preparations. A 10 year-old male diagnosed with Autistic Disorder, Pervasive Developmental Disorder, and Generalized Anxiety Disorder was administered this medication initially to treat a medical condition. This became a quasi-experimental ABAB design (A = baseline,…

Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves.

PubMed

Hernández, Jehison Jiménez; Ragone, María Inés; Bonazzola, Patricia; Bandoni, Arnaldo L; Consolini, Alicia E

2018-01-10

Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca 2+ ) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC 50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca 2+ -CRC, with IC 50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a maximal relaxation that was 1.9 times higher than that of papaverine. In the isolated heart, EO-Bs induced a poor negative inotropic response, and did not improve the contractile and energetic recovery after ischemia and reperfusion. In the mouse cough model, EO-Bs (90mg/Kg) was as effective as codeine (30mg/Kg) in reducing cough frequency. The results indicate that the preparations from Blepharocalyx salicifolius leaves were effective as central antitussive, bronchodilating and antispasmodic agents, suggestive of a mechanism associated with the inhibition of Ca 2+ influx into smooth muscle. The EO-Bs displayed only a poor ability to reduce cardiac inotropism, and was devoid of any cardioprotective properties. Thus, the present study validates the traditional use of this South American plant for asthma, cough and bronchospasm, shedding new light into its potency and putative mechanism of action. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

[Prescription of systemic cold and cough drugs to children 0-13 years old. An unresolved problem].

PubMed

Cano Garcinuño, A; Casares Alonso, I; Rodríguez Barbero, J; Pérez García, I; Blanco Quirós, A

2013-01-01

Upper respiratory tract infections are the most common cause of paediatric consultation, generating a high volume of prescriptions of drugs with unfavourable risk-benefit ratio. The aim of this study is to describe the prescription of systemic cough and cold medicines to children under 14 years of age in Castilla y León and analyse its variability. A count was made of the prescriptions for the R05 therapeutic subgroup (antitussives and mucolytics) and the R01B pharmacological therapeutic subgroup (nasal decongestants for systemic use), prescribed for children under the age of 14 in the Public Health System between 2005-2010. The number of prescriptions was analysed as crude and age-adjusted rates, as well as a a multivariate analysis (Poisson regression) of the variability associated with health area, the urban/rural environment, age, and year of prescription. There were 806,785 prescriptions for systemic cough and cold drugs given to an exposed population of 1,580,229 person-years. Prescription rates (per 100 person-years) were 20.7 (antitussives), 7.0 (sympathomimetic) and 23.4 (mucolytics). These drugs were employed more often in children <4 years. The prescription of mucolytics and sympathomimetics was highest at age of 1 year (rates=41.9 and 18.7, respectively) and of antitussives at 3 years (35.7). Multivariate analysis showed that in rural areas the prescription was higher than in urban areas, and that there were also significant differences between health areas. Between 2005 and 2010 there was a high prescription of systemic cough and cold medicines, especially in children under 2 years old, and often outside the recommended conditions of use, and there was a high geographic variabilty. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier España. All rights reserved.

[Parental representations of children's cough and expectations on its management].

PubMed

Ventaja, G; Steyer, E; Machu, J-L; Boivin, J-M

2016-04-01

Providing medications for the management of acute cough in infants less than 24 months, a frequent reason for medical consultation, has recently been reduced by the contraindication of various antitussive specialties in France. The objective of this study was to assess the expectations and fears of coughing infants' parents, to determine their representations of coughing, and to quantify the use of self-medication and the risk of a deferral requests to prescribe other drug classes. An opinion and cross-survey was carried out with parents of infants under 24 months of age. A multiple-choice questionnaire was proposed to them in day care centers and Mother and Infant Welfare centers. The data collected were analyzed descriptively and using the Chi(2) test. Logistic regression enabled us to interpret some of the results. Sixty-four percent of parents expect an antitussive treatment from the doctor. For most parents, lifestyle modifications are well integrated (nasal irrigation, considered effective cough relief, hydration, smoking cessation). For 33 % of parents, corticosteroids are an alternative therapy to stop cough. Nearly half (43 %) of parents have sought treatment from their doctor, usually nasal suspensions, corticosteroids, and saline irrigation. Regarding self-medication, 30 % of parents have already given cough syrup or an antitussive suppository without a prescription, in order to stop the cough rapidly for 66 % of them. These parents seem more worried by coughing than other parents (P=0.0110, CI: 0.217; 1.751) as did those who had only one child (P=0.0029, CI: 0.120; 0.582). This study suggests that a large majority of parents understand and accept the new recommendations. But one-third of parents are still worried, not knowing what to do without prescribed medications, which led them to give nonprescription cough syrups and ask for inappropriate treatments. It seems essential to inform parents about the natural history of infant coughing and educate them on lifestyle rules to reduce the risk of deferral prescription. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.

PubMed

Kawaura, Kazuaki; Ogata, Yukino; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

2016-04-01

We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline α2 receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. These results suggest that tipepidine exerts an antidepressant-like effect in the forced swimming test in ACTH-treated rats, and that the effect of tipepidine is mediated by the stimulation of dopamine D1 receptors and adrenaline α2 receptors. The results also suggest that an increase in the extracellular dopamine level in the NAc may be involved in the antidepressant-like effect of tipepidine in ACTH-treated rats. Copyright © 2016. Published by Elsevier B.V.

Dextromethorphan Analogs: Receptor Binding and Pharmacological Profile of Novel Anticonvulsant/Neuroprotectant Drugs

DTIC Science & Technology

1993-05-13

AD-POO8 801 Dextromethorphan Analogs: Receptor Binding and Pharmacological Profile of Novel Anticonvulsant/Neuroprotective Drugs F.C. Tortella, L...Baltimore, MD 21224 CD ABSTRACT A series of 3-substituted 17-methylmorphinan analogs of dextromethorphan (DM) have open developed which are...nTTrTTn) INTRODUCTION The antitussives dextromethorphan (DM), caramiphen and carbetapentane have distinguished themselves as anticonvulsant drugs (1

Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma.

PubMed

Jiao, Hao-yan; Su, Wei-wei; Li, Pei-bo; Liao, Yan; Zhou, Qian; Zhu, Na; He, Li-li

2015-08-01

Naringin, a well known component isolated from Exocarpium Citri Grandis, has significant antitussive effects. Recently, Naringin exhibited novel anti-inflammatory effect in chronic inflammatory diseases. In this work, we firstly evaluated the effects of naringin on enhanced cough, airway hyper-responsiveness (AHR), and airway inflammation in an ovalbumin-induced experimental cough-variant asthma (CVA) model in guinea pigs. We investigated the effect of naringin (18.4 mg/kg, per os, single dose or consecutively) on cough to inhaled capsaicin after challenge with an aerosolized antigen in actively sensitized guinea pigs. The effect of naringin on AHR to inhaled methacholine was evaluated 24 h after cough determination. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cytology and lung histopathology. Naringin, given consecutively, significantly reduced ovalbumin-induced enhanced cough and AHR, inhibited the increases in the leukocytes, interleukin-4 (IL-4), IL-5, and IL-13 in BALF compared with the model group. Moreover, the pathologic changes in lung tissues were clearly ameliorated by naringin treatment. These results suggest that naringin may be a beneficial agent for CVA treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antimicrobial Activity and Chemical Composition of Essential Oils from Verbenaceae Species Growing in South America.

PubMed

Pérez Zamora, Cristina M; Torres, Carola A; Nuñez, María B

2018-03-01

The Verbenaceae family includes 2600 species grouped into 100 genera with a pantropical distribution. Many of them are important elements of the floras of warm-temperature and tropical regions of America. This family is known in folk medicine, and its species are used as digestive, carminative, antipyretic, antitussive, antiseptic, and healing agents. This review aims to collect information about the essential oils from the most reported species of the Verbenaceae family growing in South America, focusing on their chemical composition, antimicrobial activity, and synergism with commercial antimicrobials. The information gathered comprises the last twenty years of research within the South American region and is summarized taking into consideration the most representative species in terms of their essential oils. These species belong to Aloysia , Lantana , Lippia , Phyla , and Stachytarpheta genera, and the main essential oils they contain are monoterpenes and sesquiterpenes, such as β-caryophyllene, thymol, citral, 1,8-cineole, carvone, and limonene. These compounds have been found to possess antimicrobial activities. The synergism of these essential oils with antibiotics is being studied by several research groups. It constitutes a resource of interest for the potential use of combinations of essential oils and antibiotics in infection treatments.

Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V)

NASA Astrophysics Data System (ADS)

El-Shiekh, Ragaa; Zahran, Faten; El-Fetouh Gouda, Ayman Abou

2007-04-01

Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of anti-tussive drugs, e.g., dextromethorphan hydrobromide (DEX) and pipazethate hydrochloride (PiCl) and anti-spasmodic drugs, e.g., drotaverine hydrochloride (DvCl) and trimebutine maleate (TM) in bulk and in their pharmaceutical formulations. The proposed methods depend upon the reaction of cobalt(II)-thiocyanate (method A) and molybdenum(V)-thiocyanate ions (method B) with the cited drugs to form stable ion-pair complexes which extractable with an n-butnol-dichloromethane solvent mixture (3.5:6.5) and methylene chloride for methods A and B, respectively. The blue and orange red color complexes are determined either colorimetrically at λmax 625 nm (using method A) and 467 or 470 nm for (DEX and PiCl) or (DvCl and TM), respectively (using method B). The concentration range is 20-400 and 2.5-50 μg mL -1 for methods A and B, respectively. The proposed method was successfully applied for the determination of the studied drugs in pure and in pharmaceutical formulations applying the standard additions technique and the results obtained in good agreement well with those obtained by the official method.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

PubMed

Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

2013-07-15

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves

PubMed Central

Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

2015-01-01

The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis. PMID:26576193

In Vivo Evaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of Three Elaeagnus Leaves.

PubMed

Ge, Yuebin; Zhang, Fei; Qin, Qin; Shang, Yingying; Wan, Dingrong

2015-01-01

The leaf of Elaeagnus lanceolata and Elaeagnus henryi as well as Elaeagnus pungens has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional clinical medicine. This study was aimed at evaluating the antiasthmatic, antitussive, and expectorant activities of the water extracts from the three plants in vivo and analyzing their chemical components by HPLC-DAD. At the medium and high doses, the water extracts of three Elaeagnus leaves significantly prolonged the preconvulsive time (P < 0.01) in guinea pigs, lengthened the latent period of cough (P < 0.01) and decreased the cough frequency caused by aqueous ammonia in mice (P < 0.01), and enhanced tracheal phenol red output in mice (P < 0.01). There were no significant differences in the pharmacological actions between the three Elaeagnus leaves. Moreover, there was more similarity on overlap peaks in the range of retention time from 10 to 40 min by HPLC and many peaks that belonged to flavonoids compounds. It suggested that the main constituents of the three Elaeagnus leaves were flavonoid for the pharmacological activities. These effects were the important evidence for the traditional use of E. henryi leaf and E. lanceolata leaf as well as E. pungens to treat asthma and chronic bronchitis.

A fatal case of potential chronic overdoses of prescribed and proprietary remedies.

PubMed

Takase, Izumi; Yamamoto, Yoshio; Nakagawa, Tokiko; Nishi, Katsuji

2010-08-01

A 33-year-old man was found in a state of cardiopulmonary arrest. He was transported to an emergency hospital but was pronounced dead. He had suffered from depression for about 8 years and had attempted suicide repeatedly. A search by the police found 645 empty Press Through Package (PTP) sheets. They had included neuroleptics, antidepressants, hypnotics, proprietary antitussives containing caffeine, proprietary cold remedies containing caffeine, and other unidentified drugs. An autopsy showed higher rectal temperature (38 degrees C), severe pulmonary edema (left: 681 g, right: 821 g), and a large amount of urine in the bladder (about 760 mL). Toxicological analyses using gas chromatography-mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC) demonstrated that doses of clomipramine hydrochloride (a tricyclic antidepressant), chlorpromazine (a phenothiazine), and caffeine (a methylxanthine derivative) were within the toxic range (0.68, 0.64, and 34.24 [microg/mL], respectively). Histological examination showed centrilobular necrosis of the liver with small fat droplets. We concluded that he had died of pulmonary edema due to combined drug intoxication including proprietary antitussives and cold remedies. Furthermore, there was a strong possibility that he had habitually taken overdoses of those drugs. Herein, the risk of misuse of prescribed and proprietary drugs, especially for people with psychological problems, should be reemphasized.

The Effect of Pre-Emptive Administration of Dextromethorphan on Postoperative Pain in Patients Undergoing Interval Laparoscopic Tubal Sterilization

DTIC Science & Technology

2001-10-01

requirements following surgery. Dextromethorphan , a readily available nonopioid antitussive in clinical use for more than 40 years, is one such NMDA...receptor Anticosti. This prospective, randomized, double blind pilot study compared the effects over time when patients received dextromethorphan versus...groups. Group I received 60 mg of dextromethorphan orally, and Group II received an oral placebo. Postoperative pain was assessed using an 11 point

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

In this report—the fourth of a series on codeine and its alternates for pain and cough relief—an attempt is made to evaluate, on the basis of experimental and clinical data, and wherever possible in comparison with codeine, the effectiveness of a number of antitussive substances currently in clinical use. In the discussion of the undesired side-effects particular attention is paid to the risk of dependence and abuse. PMID:4390406

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

PubMed Central

Ramsay, James; Wright, Caroline; Thompson, Rachel; Hull, David; Morice, Alyn H

2008-01-01

AIMS Using an established model of smokers cough we measured the antitussive effects of dextromethorphan compared with placebo. METHODS The study was a randomized, double-blind placebo controlled, crossover comparison of 22 mg 0.8 ml−1 dextromethorphan delivered pregastrically with matched placebo. Objective and subjective measurements of cough were recorded. Subjective measures included a daily diary record of cough symptoms and the Leicester quality of life questionnaire. Cough frequency was recorded using a manual cough counter. The objective measure of cough reflex sensitivity was the citric acid, dose–response cough challenge. RESULTS Dextromethorphan was significantly associated with an increase in the concentration of citric acid eliciting an average of two coughs/inhalation (C2) when compared with placebo, 1 h post dose by 0.49 mM (95% CI 0.05, 0.45, geometric mean 3.09) compared with placebo 0.24 mM (geometric mean 1.74) P < 0.05 and at 2 h 0.57 mM (95% CI 0.01, 0.43, geometric mean 3.75) compared with placebo 0.34 mM (geometric mean 2.19) P < 0.05). There was a highly significant improvement in the subjective data when compared with baseline. However, there was no significant difference between placebo and active treatment. No correlation was seen between cough sensitivity to citric acid and recorded cough counts or symptoms. When both subjective and objective data were compared with screening data there was evidence of a marked ‘placebo’ effect. CONCLUSIONS The objective measure of cough sensitivity demonstrates dextromethorphan effectively diminishes the cough reflex sensitivity. However, subjective measures do not support this. Other studies support these findings, which may represent a profound sensitivity of the cough reflex to higher influences. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Dextromethorphan is widely used as a cough suppressant in over the counter medications. Its efficacy in altering cough reflex sensitivity has been shown in healthy volunteers. In contrast evidence for an effect on clinically important cough is poor. WHAT THIS STUDY ADDS A significant decrease in evoked cough was seen with dextromethorphan compared with placebo. However, both placebo and active treatment improved subjective data to a similar degree. We doubt the validity of currently used objective tests in the investigation of antitussives. PMID:18279476

Effect of guaifenesin on cough reflex sensitivity.

PubMed

Dicpinigaitis, Peter V; Gayle, Yvonne E

2003-12-01

Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Academic medical center. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells.

PubMed

Basar, Norazah; Oridupa, Olayinka Ayotunde; Ritchie, Kenneth J; Nahar, Lutfun; Osman, Nashwa Mostafa M; Stafford, Angela; Kushiev, Habibjon; Kan, Asuman; Sarker, Satyajit D

2015-06-01

Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G. glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G. glabra. Copyright © 2015 John Wiley & Sons, Ltd.

Effects of four antitussives on airway neurogenic inflammation in a guinea pig model of chronic cough induced by cigarette smoke exposure.

PubMed

Luo, Yu-long; Li, Pei-bo; Zhang, Chen-chen; Zheng, Yan-fang; Wang, Sheng; Nie, Yi-chu; Zhang, Ke-jian; Su, Wei-wei

2013-12-01

The effects of four antitussives, including codeine phosphate (CP), moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic inflammation and enhanced cough were investigated in guinea pig model of chronic cough. Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24 mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin challenge were recorded. The substance P (SP) content, NK-1 receptor expression and neutral endopeptidase (NEP) activity in lung were determined. Chronic CS exposure induced a bi-phase time course of cough responsiveness to capsaicin. Eight weeks of CS exposure significantly enhanced the airway neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS-exposure enhanced cough. Only naringin exerted significant effect on inhibiting Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the declining of NEP activity in lung. Chronic CS-exposed guinea pig is suitable for studying chronic pathological cough, in which naringin is effective on inhibiting both airway neurogenic inflammation and enhanced cough.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol

PubMed Central

Plevkova, J.; Kollarik, M.; Poliacek, I.; Brozmanova, M.; Surdenikova, L.; Tatar, M.; Mori, N.

2013-01-01

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (−)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose. PMID:23640596

The research of the possible mechanism and the treatment for capsaicin-induced cough.

PubMed

Zhang, Li; Sun, Tieying; Liu, Longteng; Wang, Lifang

2018-04-01

Unexplained chronic cough (UCC) affects millions of patients worldwide. New therapeutic approaches to this condition are urgently needed, since current treatment options provide only symptomatic relief. Cough reflex hypersensitivity has been shown to play an important role in the pathogenesis of UCC. The transient receptor potential vanilloid type 1 (TRPV1) is present on peripheral terminals of airway sensory nerves and modulation of its activity represents a potential target for the pharmacological treatment of UCC. The aim of this study was to explore the efficacy and the possible mechanism of SB705498, a TRPV1 antagonist, for cough in a capsaicin-induced cough animal model (i.e. guinea pigs). Induction of cough by capsaicin was successfully implemented in the guinea pigs, and the animals that met the inclusion criteria were randomly divided into four treatment groups: (1) Saline inhalation group (NSInh group, N = 10, negative control group), (2) Codeine phosphate intraperitoneal injection group (CPInp group, N = 10, positive control group), (3) SB705498 inhalation group (SBInh group, N = 10), (4) SB705498 intragastric administration group (SBIng group, N = 10). After treatment with above compounds, the capsaicin-induced cough experiment was performed again. The cough numbers and the cough incubation periods were recorded to evaluate the antitussive effect of SB705498. Enzyme-linked immunosorbent assay (ELISA) testing and Immunohistochemistry (IHC) staining for substance P (SP), calcitonin gene related peptide (CGRP) and neurokinin A (NKA) expression in lung and brain tissues were performed as an indication of neurogenic inflammation. Hematoxylin-Eosin (H&E) staining was used to observe the pathology morphology of lung and brain tissues. When the CPInp, SBInh and SBIng groups were compared to the NSInh group, the cough numbers were significantly reduced (p < .001), while the cough incubation periods were significantly prolonged (P < .001). In addition, the expression of SP, CGRP and NKA in lung and brain tissue was reduced (P < .05). None of the animals in the four groups exhibited lung and brain parenchymal inflammation. The results from this study showed that SB705498 had a significant antitussive effect, could reduce the neurogenic inflammation by reducing the expression of SP, CGRP and NKA in a capsaicin-induced cough model of guinea pigs. The results further indicated that TRPV1 played an important role in UCC and SB705498 might be a promising therapeutic agent for UCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transient Receptor Potential Ankyrin 1 Receptor Activation In Vitro and In Vivo by Pro-tussive Agents: GRC 17536 as a Promising Anti-Tussive Therapeutic

PubMed Central

Mukhopadhyay, Indranil; Kulkarni, Abhay; Aranake, Sarika; Karnik, Pallavi; Shetty, Mahesh; Thorat, Sandeep; Ghosh, Indraneel; Wale, Dinesh; Bhosale, Vikram; Khairatkar-Joshi, Neelima

2014-01-01

Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1) is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca+2 influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1. PMID:24819048

An Analysis of Prescription Claims for Medications from Retail Pharmacies in TRICARE Region 2

DTIC Science & Technology

2000-05-01

RECOMMENDATIONS 34 REFERENCES 36 APPENDIX A APPENDIX B APPENDIX C Retail Pharmacy Prescription Analysis 5 List of Tables Table 1. Pharmacy Beneficiary Categories...All claims data used in this analysis was obtained from the Region 2 Managed Care Support Contractor (MCSC), Anthem Alliance Health Insurance Company ...66,297.76 $17,084,273.96 92.73% $39.04 PROGESTINS 3148 454684 85.78% $60,831.60 $17,145,105.56 93.06% $86.92 ANTITUSSIVES 8324 463008 87.35% $60,616.97

Inhibition of cough-reflex sensitivity by benzonatate and guaifenesin in acute viral cough.

PubMed

Dicpinigaitis, Peter V; Gayle, Yvonne E; Solomon, Gail; Gilbert, Richard D

2009-06-01

Acute cough due to viral upper respiratory tract infection (URI) is the most common form of cough and accounts for tremendous expenditure on prescription and non-prescription cough products worldwide. However, few agents have been shown in properly conducted clinical trials to be effective for cough due to URI. The present study evaluated the effect of benzonatate 200mg (B), guaifenesin 600 mg (G), their combination (B+G), and placebo (P) on capsaicin-induced cough in 30 adult nonsmokers with acute URI. On 3 separate days within a 7-day period, 1h after ingesting randomly assigned study drug in a double-blind fashion, subjects underwent capsaicin cough challenge testing, which involved inhalation of incremental doubling concentrations of capsaicin until the concentration of capsaicin inducing 5 or more coughs (C(5)) was attained. Each subject received 3 of 4 possible study drugs. G (p=0.01) but not B (p=NS) inhibited cough-reflex sensitivity (log C(5)) relative to P. The combination of B+G suppressed capsaicin-induced cough to a greater degree than B alone (p<0.001) or G alone (p=0.008). The mechanism by which the combination of B+G causes a potentiation of antitussive effect remains to be elucidated. Our results suggest that B+G may be an effective therapy for acute cough due to the common cold (URI).

Synthetic substances with morphine-like effect

PubMed Central

Eddy, Nathan B.; Halbach, H.; Braenden, Olav J.

1957-01-01

A review of effects in man of morphine-like drugs which have been brought under international narcotics control is presented in the form of individual monographs. These are based on controlled observations with quantitative data and significant reports of results obtained in medical practice. In a summarizing section, the drugs are compared with respect to effectiveness, side-effects and addiction liability. Morphine-like drugs of natural and synthetic origin now cover a wide range of potency (analgesic, antitussive), not necessarily paralleled by incidence of side-effects or addiction liability. PMID:13511135

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

This chapter concludes the survey of experimental and clinical data on the analgesic and antitussive properties of codeine and its potential therapeutic alternates. From an evaluation of their effectiveness on the one hand and the side-effects, including tolerance, dependence and abuse liability on the other, it would appear that the therapeutic goals of codeine could be achieved by other substances, except perhaps where analgesia, cough relief, and sedation are required simultaneously. The use of these other substances would, however, result in no particular gain and probably no particular loss. PMID:4898386

[The antitussive effect of theophylline].

PubMed

Nemceková, E; Nosál'ová, G; Rybár, A

1994-08-01

Theophylline belongs to a group of medicaments used in asthma therapy. It yields an antiinflammatory effect, reduces allergic reactions, and in respiratory airways it improves the mucociliary clearance and eminently dilates smooth muscles. Therefore, the main aim of our interest is its effect on the cough reflex. Cough was evoked by mechanical irritation of the airways in cats with chronic tracheal cannula. It has been discovered that theophylline, when dosed 10 mg per kg of body weight i.p. achieved a more intensive effect than dextromethorphane, namely in evaluation of cough parameters, but it had a lower suppressive effect than codeine. (Fig. 3, Ref. 13.)

Unclear loss of consciousness after clobutinol intake.

PubMed

Kirschbaum, Katrin M; Musshoff, Frank; Madea, Burkhard

2009-08-10

The case of a 13-month-old boy with a diagnosis of unclear unconsciousness is reported on. As the physical examination did not lead to any explanation of his condition, the administration of drugs in the context of Munchausen syndrome by proxy was suspected. Complex forensic-toxicological analyses using HPLC/UV, LC/MS/MS, and GC/MS identified ambroxol and clobutinol, two drugs that are indicated for acute respiratory diseases. No other central active compounds were detected. The accusation of intentional bodily injury raised against the parents could be rebutted, since the boy's unconsciousness could be explained with a rare but harmful side effect of the antitussive clobutinol.

A biologically active fructan from the roots of Arctium lappa L., var. Herkules.

PubMed

Kardosová, A; Ebringerová, A; Alföldi, J; Nosál'ová, G; Franová, S; Hríbalová, V

2003-11-01

From the roots of Arctium lappa L., var. Herkules a low-molecular-weight fructofuranan of the inulin-type has been isolated by water extraction and ethanol precipitation, followed by ion-exchange chromatography and gel filtration of the crude precipitate. The methods employed in structural determination were methylation analysis and 1H and 13C NMR spectral measurements. In tests for antitussive activity in cats the fructan was found to be equally active as some non-narcotic, synthetic preparations used in clinical practice to treat coughing, and in mitogenic and comitogenic tests its biological response was comparable to that of the commercial Zymosan immunomodulator.

Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents.

PubMed

Andrè, E; Gatti, R; Trevisani, M; Preti, D; Baraldi, P G; Patacchini, R; Geppetti, P

2009-11-01

The transient receptor potential ankyrin receptor 1 (TRPA1) is a cation channel, co-expressed with the pro-tussive transient receptor potential vanilloid type 1 (TRPV1) channel in primary sensory neurons. TRPA1 is activated by a series of irritant exogenous and endogenous alpha,beta-unsaturated aldehydes which seem to play a role in airway diseases. We investigated whether TRPA1 agonists provoke cough in guinea pigs and whether TRPA1 antagonists inhibit this response. Animals were placed in a Perspex box, and cough sounds were recorded and counted by observers unaware of the treatment used. Inhalation of two selective TRPA1 agonists, allyl isothiocyanate and cinnamaldehyde, dose-dependently caused cough in control guinea pigs, but not in those with airway sensory nerves desensitized by capsaicin. Coughs elicited by TRPA1 agonists were reduced by non-selective (camphor and gentamicin) and selective (HC-030031) TRPA1 antagonists, whereas they were unaffected by the TRPV1 antagonist, capsazepine. Acrolein and crotonaldehyde, two alpha,beta-unsaturated aldehydes recently identified as TRPA1 stimulants and contained in cigarette smoke, air pollution or produced endogenously by oxidative stress, caused a remarkable tussive effect, a response that was selectively inhibited by HC-030031. Part of the cough response induced by cigarette smoke inhalation was inhibited by HC-030031, suggesting the involvement of TRPA1. A novel pro-tussive pathway involves the TRPA1 channel, expressed by capsaicin-sensitive airway sensory nerves and is activated by a series of exogenous (cigarette smoke) and endogenous irritants. These results suggest TRPA1 may be a novel target for anti-tussive medicines.

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters

PubMed Central

2013-01-01

Background Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. Methods A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling’s method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. Results All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). Conclusion The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies’ strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public about the risks from the consumption of medicines potentially harmful to dental tissues. PMID:24325544

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters.

PubMed

Xavier, Alidianne Fábia C; Moura, Eline F F; Azevedo, Waldeneide F; Vieira, Fernando F; Abreu, Mauro H N G; Cavalcanti, Alessandro L

2013-12-10

Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling's method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies' strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public about the risks from the consumption of medicines potentially harmful to dental tissues.

Method for analysis of psychopharmaceuticals in real industrial wastewater and groundwater with suspended organic particulate matter using solid phase extraction disks extraction and ultra-high performance liquid chromatography/time-of-flight mass spectrometry.

PubMed

Křesinová, Zdena; Linhartová, Lucie; Petrů, Klára; Krejčová, Lucie; Šrédlová, Kamila; Lhotský, Ondřej; Kameník, Zdeněk; Cajthaml, Tomáš

2016-04-01

A rapid and reliable analytical method was developed for the quantitative determination of psychopharmaceuticals, their precursors and by-products in real contaminated samples from a pharmaceutical company in Olomouc (Czech Republic), based on SPE disk extraction and detection by ultra performance liquid chromatography, combined with time-of-flight mass spectrometry. The target compounds were quantified in the real whole-water samples (water including suspended particles), both in the presence of suspended particulate matter (SPM) and high concentrations of other organic pollutants. A total of nine compounds were analyzed which consisted of three commonly used antidepressants (tricyclic antidepressants and antipsychotics), one antitussive agent and five by-products or precursors. At first, the SPE disk method was developed for the extraction of water samples (dissolved analytes, recovery 84-104%) and pressurised liquid extraction technique was verified for solid matrices (sludge samples, recovery 81-95%). In order to evaluate the SPE disk technique for whole water samples containing SPM, non contaminated groundwater samples were also loaded with different amounts (100 and 300mgL(-1)) of real contaminated sludge originating from the same locality. The recoveries from the whole-water samples obtained by SPE disk method ranged between 67 and 119% after the addition of the most contaminated sludge. The final method was applied to several real groundwater (whole-water) samples from the industrial area and high concentrations (up to 10(3)μgL(-1)) of the target compounds were detected. The results of this study document and indicate the feasibility of the SPE disk method for analysis of groundwater. Copyright © 2016 Elsevier B.V. All rights reserved.

LC-MS/MS determination and pharmacokinetic study of bergenin, the main bioactive component of Bergenia purpurascens after oral administration in rats.

PubMed

Li, Bao-Hong; Wu, Jin-Dong; Li, Xiang-Lu

2013-08-01

Bergenin, a C -glucoside of 4-O-methyl gallic acid from Bergenia purpurascens , is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of the active component-bergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil ® C 18 column (150 mm×4.6 mm, 5 μm) with isocratic elution using a mobile phase consisting of water-methanol (30:70, v/v ) at a flow rate of 0.6 mL/min. The detection was accomplished by a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring (MRM) scanning via an electrospray ionization (ESI) source operating in the negative mode. The optimized mass transition ion-pairs ( m/z ) for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5 min between injections. The calibration curve exhibited good linearity ( r 2 >0.99) over a range of 1.00-2000 ng/mL for bergenin. The lower limit of quantitation (LLOQ) was 1.00 ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors (RE) were within the range of 0.0-4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats.

The utility of the combination of dextromethorphan and quinidine in the treatment of bipolar II and bipolar NOS.

PubMed

Kelly, Tammas Frederick; Lieberman, Daniel Z

2014-01-01

Dextromethorphan is an over-the-counter antitussive agent that may be a rapidly acting treatment for bipolar depression. Like ketamine, it is an NMDA receptor antagonist. We conducted a retrospective chart review of depressed patients with treatment resistant bipolar II or bipolar NOS disorder who were treated with the combination of dextromethorphan 20 mg and quinidine 10 mg (DMQ). One pill of DMQ taken once or twice a day was added to participants׳ drug regimen. No changes were made to the pre-existing drug regimen during the course of treatment with DMQ. The primary outcome measure was the Clinical Global Impression-Improvement (CGI-I) score after 90 days of treatment. Seventy-seven participants met the inclusion criteria. All had been experiencing depressive symptoms for at least two years, and the mean number of failed medication trials was 21.2. The average CGI-I score at day 90 was 1.66 (1=slightly improved, 2=much improved). Some patients reported improvement within 1-2 days of starting DMQ. Nineteen patients discontinued treatment due to adverse effects, chiefly nausea. Because this was a retrospective chart review with no control group, conclusions about causation cannot be made. Nevertheless, the duration of depressive symptoms prior to starting DMQ makes spontaneous recovery less likely. DMQ, an NMDA antagonist, may be effective in the treatment of bipolar depression. Because its putative mechanism does not depend on the monoaminergic system, it may be appropriate for patients who have not responded to other medications. Unlike ketamine, DMQ does not require i.v. administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Yi; Zhang, Qing; Shen, Yi

Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts hasmore » been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.« less

Honey in otorhinolaryngology: when, why and how?

PubMed

Werner, A; Laccourreye, O

2011-06-01

In this review of the literature devoted to the use of honey, the authors analyse the composition, indications, benefits and adverse effects of this product in otorhinolaryngology and head and neck surgery. Published data indicate that honey applied topically to skin and mucosal wounds and/or burns and administered orally as antitussive medication (after the first year of life) is highly effective with no adverse effects. The physiological action of honey is the result of various mechanisms (osmotic, detersion, bactericidal action). Various medicinal honeys are available worldwide, but only one has Food and Drug Administration approval for the treatment of wounds. After the first year of life, the use of food honey appears to be as effective as medicinal honey, while decreasing the overall cost of treatment. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats.

PubMed

Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Kim, Won Ki; Lee, Jae-Chul; Jeong, Ji Hoon; Wie, Myung Bok; Jang, Choon-Gon; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2016-10-01

Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders.

PubMed

Nguyen, Linda; Thomas, Kelan L; Lucke-Wold, Brandon P; Cavendish, John Z; Crowe, Molly S; Matsumoto, Rae R

2016-03-01

Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Plant germination and production of callus from the yellow hornpoppy (Glaucium flavum): the first stage of micropropagation.

PubMed

Mohamed, M E; Arafa, A M; Soliman, S S; Eldahmy, S I

2014-09-01

The yellow hornpoppy, Glaucium flavum Cr. (Fam. Papaveraceae) is a perennial herb, distributed in the Mediterranean region, including Egypt. The plant contains many benzyl isoquinoline alkaloids from the aporphine type such as glaucine, isoboldine, 1-chelidonine, 1-norchelidonine and 3-O-methylarterenol, making it to display various medicinal activities including antitussive, anticancer, antioxidant, antimicrobial, antiviral, hypoglycemic, analgesic, antipyretic, bronchodilator and anti-inflammatory effects. The plant is now rare and endangered in the Egyptian flora due to urban sprawl. The present study looks into Glaucium flavum seeds' in vitro germination as well as the ability of the explants taken from the growing seedlings to form stable callus lines in order to enable micropropagation as a way to save the rare plant. The study also scans the production of different medicinally valuable alkaloids, particularly glaucine, in produced callus.

Interesting asian plants: their compounds and effects on electrophysiology and behaviour.

PubMed

Abdullah, Jafri Malin

2011-10-01

There have been numerous non-scientific reports on the behavioural effects of Asian plants in humans who consumed these plants wholly or part thereof. Knowledge passed from generation to generation informs us of plants that increase effort and stamina, such as during paddy planting after the ingestion of Mitragyna speciosa Korth (ketum) as a tea supplement. Centella asiatica and Myristica fragrans are used as herbs to improve memory and to treat epilepsy, respectively. Zizyphus mauritiana is used to treat headache and burn pain, acts as an antitussive, and reduces rigor mortis immediately after death. These plants, which have been identified to exhibit analgaesic, muscle-relaxing, and nootropic effects, may contain important bio-compounds for medicinal chemistry and pharmaceutical research in Malaysia. The electrophysiology properties of these plants and their effects on epilepsy, behaviour, and pain will lead Malaysia to future new drug discoveries.

Acute renal failure after ingestion of guaifenesin and dextromethorphan.

PubMed

Small, Evan; Sandefur, Benjamin J

2014-07-01

Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells.

PubMed

Song, Jin-Ho; Yeh, Jay Z

2012-05-10

Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC(50) value of 51.7 μM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Inhibition of artificially induced cough in man by bronchodilators.

PubMed Central

Lowry, R; Higenbottam, T; Johnson, T; Godden, D

1987-01-01

1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 micrograms; 14 volunteers) both significantly reduced couch compared with placebo (P less than 0.01). Oral salbutamol sulphate (4 mg; 11 volunteers) and oral pirenzepine hydrochloride (50 mg; 14 volunteers) had lesser effects. 4. Cough inhibition correlated with a small but statistically significant degree of bronchodilatation as measured by specific airway conductance (sGaw) and forced expiratory volume in one second (FEV1) in six normal subjects studied with each treatment in a placebo controlled, double blind study (r = 0.67, P less than 0.001). 5. Small reductions in airway tone are associated with a reduced cough response elicited by inhaled ultrasonically nebulized distilled water. PMID:3689630

Cognitive deterioration from long-term abuse of dextromethorphan: a case report.

PubMed Central

Hinsberger, A; Sharma, V; Mazmanian, D

1994-01-01

Dextromethorphan (DM), the dextrorotatory isomer of 3-hydroxy-N-methylmorphinan, is the main ingredient in a number of widely available, over-the-counter antitussives. Initial studies (Bornstein 1968) showed that it possessed no respiratory suppressant effects and no addiction liability. Subsequently, however, several articles reporting abuse of this drug have appeared in the literature. The drug is known to cause a variety of acute toxic effects, ranging from nausea, restlessness, insomnia, ataxia, slurred speech and nystagmus to mood changes, perceptual alterations, inattention, disorientation and aggressive behavior (Rammer et al 1988; Katona and Watson 1986; Isbell and Fraser 1953; Devlin et al 1985; McCarthy 1971; Dodds and Revai 1967; Degkwitz 1964; Hildebrand et al 1989). There have also been two reported fatalities from DM overdoses (Fleming 1986). However, there are no reports describing the effects of chronic abuse. This report describes a case of cognitive deterioration resulting from prolonged use of DM. PMID:7803371

[Two cases of suspected Munchausen by proxy syndrome: the importance of forensic toxicological analyses in handling suspicions and producing evidence].

PubMed

Musshoff, Frank; Kirschbaum, Katrin M; Madea, Burkhard

2008-01-01

The authors report on two cases of suspected Munchausen by proxy syndrome. In a 3-year-old boy, clinical toxicological analyses produced suspicious clues that an antidepressant had been administered, which could not be verified by forensic toxicological investigations. In a 13-month-old boy, the mother was also suspected of having poisoned the child. Initial clinical toxicological examinations failed to explain the observed symptoms (unclear unconsciousness, narrowed pupils). While in the first case, the incorrect interpretation of findings by a laboratory without forensic experience resulted in suspicions against the mother, the cause for the observed symptoms in the second case could be proved by complex analyses not performed before and the suspicion that the clinical picture had been intentionally brought about could be cleared up (use of an antitussive containing clobutinol). The two reports show that especially in cases with a potential forensic background, adequately qualified forensic laboratories with a broad spectrum of analytical methods should be involved.

Dextromethorphan Addiction Mediated Through the NMDA System: Common Pathways With Alcohol?

PubMed

Roy, A Kenison; Hsieh, Chenen; Crapanzano, Kathleen

2015-01-01

Dextromethorphan, an antitussive (cough suppressant) drug of the morphinan class with sedative and dissociative properties found in cough syrup and other over-the-counter products, is also a substance of abuse, seen primarily in young adults all over the world. A case of dextromethorphan use disorder is presented in a 45-year-old women. Her repeated attempts at abstinence were unsuccessful secondary to continued intense cravings. Treatment with topiramate resulted in complete resolution of her cravings. Topiramate was chosen empirically because of a common action with dextromethorphan in the NMDA system. Genetic testing was obtained and the patient was found to be a carrier of the GRIK1 rs2832407(C:C) allele. The (C:C) allele has been associated with an increased risk of alcohol use disorder and a treatment response of patients with heavy drinking to topiramate. This case provides an opportunity to discuss personalized medicine (treatment options aided by the use of genetic testing) and the possible shared genetic susceptibility for dependence in 2 substances of abuse.

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1968-01-01

This report—the first of a series on codeine and its alternates for pain and cough relief—presents a detailed evaluation of experimental and clinical data concerning the analgesic action of codeine (the antitussive action will be assessed separately). The authors discuss the pharmacology of the drug, including side-effects and toxicity; effects on the respiratory, circulatory, digestive and urinary systems; tolerance, dependence and liability to abuse; metabolic effects; and mechanism of action. Though codeine is generally more toxic than morphine to animals on account of its convulsant action, it is less toxic to man, possibly because it produces less respiratory depression. Again, tolerance to its analgesic effects has been demonstrated in several animal species, but dependence in man is observed far less frequently than it is with morphine, and the abstinence syndrome is less intense. From their extensive review of the evidence available, the authors conclude that codeine is a good analgesic and that little risk to public health is likely to arise from its clinical use to relieve pain. PMID:4972938

Structural Elements and Cough Suppressing Activity of Polysaccharides from Zingiber officinale Rhizome.

PubMed

Bera, K; Nosalova, G; Sivova, V; Ray, B

2016-01-01

Zingiber officinale is used for the management of fever, bronchial asthma and cough for thousands of years. While the link to a particular indication has been established in human, the active principle of the formulation remains unknown. Herein, we have investigated a water extracted polysaccharides (WEP) containing fraction from its rhizome. Utilizing a traditional aqueous extraction protocol and using chemical, chromatographic and spectroscopic methods a fraction containing a branched glucan and polygalaturonan in a ratio of 59:1 was characterized. This glucan, which has a molecular mass of 36 kDa, is made up of terminal-, (1,4)- and (1,4,6)-linked α-Glcp residues. Oral administration of WEP in doses of 25 and 50 mg/kg body weight significantly inhibited the number of citric acid-induced cough efforts in guinea pigs. It does not alter the specific airway smooth muscle reactivity significantly. Thus, traditional aqueous extraction method provides molecular entities, which induces antitussive activity without addiction. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of the effects of food on levodropropizine controlled-release tablet and its pharmacokinetic profile in comparison to that of immediate-release tablet.

PubMed

Lee, Soyoung; Nam, Kyu-Yeol; Oh, Jaeseong; Lee, SeungHwan; Cho, Sang-Min; Choi, Youn-Woong; Cho, Joo-Youn; Lee, Beom-Jin; Hong, Jang Hee

2018-01-01

Levodropropizine is a non-opioid antitussive agent that inhibits cough reflex by reducing the release of sensory peptide in the peripheral region. To improve patients' compliance, a controlled-release (CR) tablet is under development. The aim of this study was to compare the pharmacokinetic (PK) profiles of the CR and immediate-release (IR) tablets of levodropropizine. In addition, the effect of food on the PK properties of levodropropizine CR tablet in healthy subjects was evaluated. A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence, crossover study was conducted on 47 healthy subjects. All subjects were randomly assigned to one of the six sequences, which involve combinations of the following three treatments: levodropropizine IR 60 mg three times in the fasted state (R), levodropropizine CR 90 mg two times in the fasted state (T), and levodropropizine CR 90 mg two times in the fed state (TF). Serial blood samples were collected up to 24 h after the first dose. Tolerability was assessed based on the vital signs, adverse events (AEs), and clinical laboratory tests. Levodropropizine CR showed lower maximum drug concentration ( C max ) and similar total exposure compared to levodropropizine IR. The geometric mean ratios (GMRs) (90% confidence intervals [CIs]) of T to R for the C max and area under the concentration-time curve from the 0 to 24 h time points (AUC 0-24h ) were 0.80 (0.75-0.85) and 0.89 (0.86-0.93), respectively. In the fed group, levodropropizine CR showed exposure similar to that in the fasted group. The GMRs (90% CIs) of TF to T for the C max and AUC 0-24h were 0.90 (0.85-0.97) and 1.10 (1.05-1.14), respectively. No serious AEs occurred with both levodropropizine CR and IR tablets. Total systemic exposure for levodropropizine was similar in subjects receiving the CR and IR formulations in terms of the AUC. Although food delayed the absorption of levodropropizine CR, systemic exposure was not affected.

Methods of recording and analysing cough sounds.

PubMed

Subburaj, S; Parvez, L; Rajagopalan, T G

1996-01-01

Efforts have been directed to evolve a computerized system for acquisition and multi-dimensional analysis of the cough sound. The system consists of a PC-AT486 computer with an ADC board having 12 bit resolution. The audio cough sound is acquired using a sensitive miniature microphone at a sampling rate of 8 kHz in the computer and simultaneously recorded in real time using a digital audio tape recorder which also serves as a back up. Analysis of the cough sound is done in time and frequency domains using the digitized data which provide numerical values for key parameters like cough counts, bouts, their intensity and latency. In addition, the duration of each event and cough patterns provide a unique tool which allows objective evaluation of antitussive and expectorant drugs. Both on-line and off-line checks ensure error-free performance over long periods of time. The entire system has been evaluated for sensitivity, accuracy, precision and reliability. Successful use of this system in clinical studies has established what perhaps is the first integrated approach for the objective evaluation of cough.

Fluorescent bovine serum albumin interacting with the antitussive quencher dextromethorphan: a spectroscopic insight.

PubMed

Durgannavar, Amar K; Patgar, Manjanath B; Nandibewoor, Sharanappa T; Chimatadar, Shivamurti A

2016-05-01

The interaction of dextromethorphan hydrobromide (DXM) with bovine serum albumin (BSA) is studied by using fluorescence spectra, UV-vis absorption, synchronous fluorescence spectra (SFS), 3D fluorescence spectra, Fourier transform infrared (FTIR) spectroscopy and circular dichroism under simulated physiological conditions. DXM effectively quenched the intrinsic fluorescence of BSA. Values of the binding constant, K(A), are 7.159 × 10(3), 9.398 × 10(3) and 16.101 × 10(3)  L/mol; the number of binding sites, n, and the corresponding thermodynamic parameters ΔG°, ΔH° and ΔS° between DXM and BSA were calculated at different temperatures. The interaction between DXM and BSA occurs through dynamic quenching and the effect of DXM on the conformation of BSA was analyzed using SFS. The average binding distance, r, between the donor (BSA) and acceptor (DXM) was determined based on Förster's theory. The results of fluorescence spectra, UV-vis absorption spectra and SFS show that the secondary structure of the protein has been changed in the presence of DXM. Copyright © 2015 John Wiley & Sons, Ltd.

Ephedrine- and guaifenesin-induced nephrolithiasis.

PubMed

Bennett, Stephen; Hoffman, Nathan; Monga, Manoj

2004-12-01

Ephedrine and guaifenesin are herbal supplements that have experienced increased use over the past decade. Ephedrine has been used as a stimulant and weight-loss product, guaifenesin as an expectorant and cough suppressant; both are found in combination in many antitussives and expectorants. This paper reviews the reported cases of ephedrine- and guaifenesin-induced nephrolithiasis, as well as the diagnostic techniques and treatments that have been successfully used for these stones. A systematic review of the literature pertaining to nephrolithiasis and the compounds ephedrine and guaifenesin was conducted. Ephedrine and guaifenesin use results in over 35% of urinary stones that are related to pharmaceutical metabolites, and collectively are present in 0.1% of all urinary stones. These calculi are radiolucent, requiring the use of computerized tomography (CT scan) for diagnosis. Alkalinization therapy offers an alternative to surgical intervention and may have a role in prevention of recurrence. Ephedrine and guaifenesin have been shown to cause nephrolithiasis in cases of abuse when taken individually or in combination. It is important for the clinician to be aware of the potential for these compounds to cause nephrolithiasis.

Anti-inflammatory properties of drugs from saffron crocus.

PubMed

Poma, Anna; Fontecchio, Gabriella; Carlucci, Giuseppe; Chichiriccò, Giuseppe

2012-01-01

The medicinal uses of saffron (Crocus sativus Linnaeus) have a long history beginning in Asian countries since the Late Bronze Age. Recent studies have validated its potential to lower the risk of several diseases. Some metabolites derived from saffron stigmas exert numerous therapeutic effects due to hypolipidemic, antitussive, antioxidant, antidiabetic activities and many others. Water and ethanol extracts of Crocus sativus L. are cardioprotective and counteract neurodegenerative disorders. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. Botany, worldwide spreading of cultivars, biochemical pathways, active constituents and chemical detection methods are reviewed. Therapeutic uses of saffron principles with particular regard to those exhibiting antioxidant and thus anti-inflammatory features are discussed. To date, very few adverse health effects of saffron have been demonstrated. At high doses (more than 5 g/die day), it should be avoided in pregnancy owing to its uterine stimulation activity.

Quercetin, kaempferol and isorhamnetin in Elaeagnus pungens Thunb. leaf: pharmacological activities and quantitative determination studies.

PubMed

Zhu, Ji-Xiao; Wen, Le; Zhong, Wei-Jin; Xiong, Li; Liang, Jian; Wang, Hong-Ling

2018-05-26

Elaeagnus pungens (E. pungens) leaf was documented to be very effective to treat asthma and chronic bronchitis both as traditional Chinese medicine and minority traditional medicine; yet the actual effective components still remain unknown. This work is to investigate the anti-inflammatory, antalgic and antitussive activities of E. pungens leaf, quercetin and kaempferol, and their contents in E. pungens leaf. Pharmacological experiments showed they could considerably reduce ear-swelling of mouse and relieve writhing reaction of mouse; they could also prevent mouse from coughing, significantly. These findings suggested quercetin and kaempferol are major effective components treating asthma and chronic bronchitis. Quantitative analysis results indicated the levels of quercetin, kaempferol and isorhamnetin varied greatly in different species of Elaeagnus and in different plant parts: E. pungens leaf is more similar to Elaeagnus umbellate leaf chemically; quercetin level is exceptionally high in Elaeagnus oldhami leaf; E. pungens leaf is a better medical part for treating asthma and chronic bronchitis in comparison with other parts. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cough in children.

PubMed

Lamas, Adelaida; Ruiz de Valbuena, Marta; Máiz, Luis

2014-07-01

Cough during childhood is very common, and is one of the most frequent reasons for consultation in daily pediatric practice. The causes differ from those in adults, and specific pediatric guidelines should be followed for correct diagnosis and treatment. The most common cause of cough in children is viral infection producing "normal cough", but all children with persistent cough, i.e. a cough lasting more than 4-8weeks or "chronic cough", must be carefully evaluated in other to rule out specific causes that may include the entire pediatric pulmonology spectrum. The treatment of cough should be based on the etiology. Around 80% of cases can be diagnosed using an optimal approach, and treatment will be effective in 90% of them. In some cases of "nonspecific chronic cough", in which no underlying condition can be found, empirical treatment based on the cough characteristics may be useful. There is no scientific evidence to justify the use of over-the-counter cough remedies (anti-tussives, mucolytics and/or antihistamines), as they could have potentially serious side effects, and thus should not be prescribed in children. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Mechanical Stimulation by Postnasal Drip Evokes Cough

PubMed Central

Iwata, Toshiyuki; Ito, Isao; Niimi, Akio; Ikegami, Koji; Marumo, Satoshi; Tanabe, Naoya; Nakaji, Hitoshi; Kanemitsu, Yoshihiro; Matsumoto, Hisako; Kamei, Junzo; Setou, Mitsutoshi; Mishima, Michiaki

2015-01-01

Cough affects all individuals at different times, and its economic burden is substantial. Despite these widespread adverse effects, cough research relies on animal models, which hampers our understanding of the fundamental cause of cough. Postnasal drip is speculated to be one of the most frequent causes of chronic cough; however, this is a matter of debate. Here we show that mechanical stimuli by postnasal drip cause chronic cough. We distinguished human cough from sneezes and expiration reflexes by airflow patterns. Cough and sneeze exhibited one-peak and two-peak patterns, respectively, in expiratory airflow, which were also confirmed by animal models of cough and sneeze. Transgenic mice with ciliary dyskinesia coughed substantially and showed postnasal drip in the pharynx; furthermore, their cough was completely inhibited by nasal airway blockade of postnasal drip. We successfully reproduced cough observed in these mice by injecting artificial postnasal drip in wild-type mice. These results demonstrated that mechanical stimulation by postnasal drip evoked cough. The findings of our study can therefore be used to develop new antitussive drugs that prevent the root cause of cough. PMID:26581078

Possible mechanisms of dose-dependent cough suppressive effect of Althaea officinalis rhamnogalacturonan in guinea pigs test system.

PubMed

Sutovská, M; Nosálová, G; Sutovský, J; Franová, S; Prisenznáková, L; Capek, P

2009-07-01

The rhamnogalacturonan, isolated from the roots of medicinal plant Althaea officinalis L., showed various biological effects on the citric acid-induced cough reflex and reactivity of airways smooth muscle in vitro and in vivo conditions. It possessed dose-dependent cough suppression effect comparable with opioid agonist codeine. However, reactivity of the airways smooth muscle, measured in vitro as well as in vivo conditions was not significantly affected by rhamnogalacturonan and thus bronchodilatory activity did not participate in the cough suppression effect of polysaccharide tested. Moreover, the cough suppression effect of the polymer was not significantly modified by pretreatment of K(+)(ATP) ion channels with selective antagonist and therefore activation of this type of ion channels is not involved in the mechanism of rhamnogalacturonan cough suppressive ability. On the contrary, pretreatment of animals with selective 5-HT(2) receptors antagonist significantly decreased rhamnogalacturonan antitussive efficacy. From this point of view it seems that the cough suppression effect of the polymer is associated with the serotonergic 5-HT(2) receptor's function.

Standardization of the manufacturing procedure for Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine.

PubMed

Su, Tao; Zhang, Wei-Wei; Zhang, Ya-Ming; Cheng, Brian Chi-Yan; Fu, Xiu-Qiong; Li, Ting; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Cao, Hui; Yu, Zhi-Ling

2016-12-04

Pinelliae Rhizoma (PR), the dried tuber of Pinellia ternata (Thunb.) Breit., is a traditional Chinese medicinal herb. It is commonly used for treating cancer, cough and phlegm. To treat cancer, Chinese medicine practitioners often use raw PR; while to treat cough and phlegm, they usually use Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRZA, raw PR processed with ginger juice and alumen as adjuvant materials). Currently, the producing protocol of PRZA varies greatly among different places in China. This study aims to standardize the manufacturing procedure for PRZA. We also evaluated the impact of processing on the bioactivities and chemical profile of raw PR. We used the orthogonal design to optimize the manufacturing procedure of PRZA at bench scale, and validated the optimized procedure in pilot-scale production. The MTT assay was used to compare the cytotoxicities of raw PR and PRZA in hepatocellular carcinoma HepG2 cells. Animal models (ammonia liquor-induced cough model and phenol red secretion model) were used to compare the antitussive and expectorant effects of raw PR and PRZA, respectively. The chemical profiles of raw PR and PRZA samples were compared using a newly developed ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method. The standardized manufacturing procedure for PRZA is as follows: soak raw PR in water until the center of the cut surface is devoid of a dry core, after that, boil the herb in water (for each 100kg raw PR, 12.5kg alumen and 25L freshly squeezed ginger juice are added) for 6h, and then take out and dry them. The cytotoxicity of PRZA was less potent than that of raw PR. Intragastric administration of raw PR or PRZA demonstrated antitussive and expectorant effects in mice. These effects of PRZA were more potent than that of raw PR at the dose of 3g/kg. By comparing the chemical profiles, we found that six peaks were lower, while nine other peaks were higher in PRZA than in raw PR. Six compounds corresponding to six individual changed peaks were tentatively identified by matching with empirical molecular formulae and mass fragments. The manufacturing procedure for PRZA was standardized. This protocol can be used for PRZA industrial production. The bioactivity assay results of raw PR and PRZA (produced using the standardized protocol) support the common practice for the clinical applications of these two decoction pieces. Moreover, raw PR and PRZA showed different chemical profiles. Further studies are warranted to establish the relationship between the alteration of chemical profiles and the changes of medicinal properties caused by processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Morella serrata (Lam.) Killick stabilizes biomembrane and rejuvenates sexual competence in male Wistar rats.

PubMed

Sabiu, S; Ashafa, A O T

2017-06-09

Morella serrata L. is an indigenous medicinal plant to South and southern Africa with folkloric applications as aphrodisiac, laxative, antimicrobial, anti-inflammatory, analgesic, anti-hypertensive, antitussive and antidiabetic agent. This study evaluated the membrane stabilization and aphrodisiac potentials of its aqueous root extract in male Wistar rats. While the membrane stabilization of the extract was investigated against bovine erythrocytes (BE), the male rats for the aphrodisiac study were randomized into five groups with animals in group 1 given sterile placebo and served as control. The rats in group 2 were treated with 7.14mg/kg body weight of PowMaxM, while animals in groups 3, 4 and 5 were administered with the extract (100, 200 and 400mg/kg, respectively). All treatments (1mL) were done once daily for 4 weeks via oral gavaging and their mating behavioural, testicular, spermatogenetic and antioxidant parameters were evaluated. With the exception of the mount, intromission and post ejaculatory latencies that were dose-dependently reduced by the extract, other mating parameters were significantly improved when compared with the control. Similar patterns of significant improvement were also observed on the testes-body weight ratio, quality and viability of sperm cells as well as testicular concentrations of proteins, cholesterol, glycogen, testosterone, follicle stimulating hormone, leuitenizing hormone and glutathione (reduced) subsequent to treatment with the extract. Although, administration of M. serrata had no significant (p>0.05) effect on the testicular activity of gamma glutamyl transferase, those of lactate dehydrogenase, phosphatases (alkaline and acid), superoxide dismutase and catalase were significantly (p<0.05) induced in the treated animals. The extract also conferred respective significant (p<0.05) membrane stabilization potential of 66.02% and 60.87% on the BE against hypotonic solution and heat-induced hemolysis relative to 62.14% and 40.19% for ibuprofen. The effect elicited by the extract at the tested doses could partly be attributed to its antioxidant and adaptogenic constituents. The data presented in this study have enriched biochemical information on the root extract of M. serrata as a viable source of phytonutrients that could be potentially useful for the development of aphrodisiac drugs, and thus lending scientific credence to its much touted sex enhancing attributes by the Basothos of the eastern Free State Province of South Africa. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Patterns and Perceptions of Dextromethorphan Use in Adult Members of an Online Dextromethorphan Community.

PubMed

Pringle, George; McDonald, Michael P; Gabriel, Kara I

2015-01-01

Dextromethorphan (DXM) is a widely available antitussive that has, at elevated dose levels, euphoric and dissociative effects. This article presents the reported patterns and preferences of DXM use, and perceptions of DXM use among adult members of an online DXM community. Analyses were conducted of quantitative and qualitative responses from nine female and 43 male individuals, aged 18-63 years old. All respondents reported illegal and DXM drug use, beginning, on average, at 15.7 and 17.1 years of age, respectively. The majority of respondents first heard about DXM online or from a friend, preferred to use DXM alone, ingested substances concurrently with DXM to modify its effects, had not been to an emergency room or arrested because of their DXM use, and used DXM for its dissociative and mind-altering effects. DXM was perceived as safe and in no need of further regulation with only 14% of respondents mentioning DXM's addictive qualities. Findings from this sample of adult DXM users reveal a sophisticated subculture in which users report using DXM specifically to induce changes to their mental state and use a variety of substances to modify or enhance DXM's effects.

Potential transducers based man-tailored biomimetic sensors for selective recognition of dextromethorphan as an antitussive drug.

PubMed

El-Naby, Eman H; Kamel, Ayman H

2015-09-01

A biomimetic potentiometric sensor for specific recognition of dextromethorphan (DXM), a drug classified according to the Drug Enforcement Administration (DEA) as a "drug of concern", is designed and characterized. A molecularly imprinted polymer (MIP), with special molecular recognition properties of DXM, was prepared by thermal polymerization in which DXM acted as template molecule, methacrylic acid (MAA) and acrylonitrile (AN) acted as functional monomers in the presence of ethylene glycol dimethacrylate (EGDMA) as crosslinker. The sensors showed a high selectivity and a sensitive response to the template in aqueous system. Electrochemical evaluation of these sensors revealed near-Nernstian response with slopes of 49.6±0.5 and 53.4±0.5 mV decade(-1) with a detection limit of 1.9×10(-6), and 1.0×10(-6) mol L(-1) DXM with MIP/MAA and MIP/AN membrane based sensors, respectively. Significantly improved accuracy, precision, response time, stability, selectivity and sensitivity were offered by these simple and cost-effective potentiometric sensors compared with other standard techniques. The method has the requisite accuracy, sensitivity and precision to assay DXM in pharmaceutical products. Copyright © 2015 Elsevier B.V. All rights reserved.

Plantago major in Traditional Persian Medicine and modern phytotherapy: a narrative review.

PubMed

Najafian, Younes; Hamedi, Shokouh Sadat; Farshchi, Masoumeh Kaboli; Feyzabadi, Zohre

2018-02-01

Plantago major has been used widely since ancient times, to manage a wide range of diseases including constipation, coughs and wounds. The aim of this study is to review the traditional application, botanical characterization, pharmacological activities, phytochemistry effects and toxicity of Plantago major. In this review study, medicinal properties of Plantago major are collected from credible pharmacopeias, textbooks of traditional Persian medicine (TPM) belonging to the 10-18th century AD, such as "The Canon of Medicine", "Makhzan-Al- Advia" and so on. Moreover, electronic databases including Scopus, Medline and Web of science were explored for this purpose. Plantago major has been prescribed in various forms such as roasted seeds, decoction, syrup, liniment, gargle, rectal enema, vaginal suppository, eye and nasal drop for each illness by TPM scholars. Some of its traditional properties including wound healing, antipyretic, antitussive, anti-infective, anti-hemorrhagic, anti-inflammatory, diuretic, laxative, astringent and hemostatic have been confirmed in recent researches. Phytochemical investigations showed that Plantago major contains volatile compounds, triterpenoids, phenolic acids and flavonoids. Modern pharmacological studies have proven some of the traditional applications of Plantago major. Nevertheless, more investigations are required on this plant, because it has the potential to be used to produce various natural medications.

[Rapid determination of illicit beta2-agonist additives in health foods and traditional Chinese patent medicines with DCBI-MS/MS method].

PubMed

Hou, Yu-Lan; Wu, Shuang; Wang, Hua; Zhao, Yong; Liao, Peng; Tian, Qing-Qing; Sun, Wen-Jian; Chen, Bo

2013-01-01

A novel rapid method for detection of the illicit beta2-agonist additives in health foods and traditional Chinese patent medicines was developed with the desorption corona beam ionization mass spectrometry (DCBI-MS) technique. The DCBI conditions including temperature and sample volume were optimized according to the resulting mass spectra intensity. Matrix effect on 9 beta2-agonists additives was not significant in the proposed rapid determination procedure. All of the 9 target molecules were detected within 1 min. Quantification was achieved based on the typical fragment ion in MS2 spectra of each analyte. The method showed good linear coefficients in the range of 1-100 mg x L(-1) for all analytes. The relative deviation values were between 14.29% and 25.13%. Ten claimed antitussive and antiasthmatic health foods and traditional Chinese patent medicines from local pharmacies were analyzed. All of them were negative with the proposed DCBI-MS method. Without tedious sample pretreatments, the developed DCBI-MS is simple, rapid and sensitive for rapid qualification and semi-quantification of the illicit beta2-agonist additives in health foods and traditional Chinese patent medicines.

Plantago major in Traditional Persian Medicine and modern phytotherapy: a narrative review

PubMed Central

Najafian, Younes; Hamedi, Shokouh Sadat; Farshchi, Masoumeh Kaboli

2018-01-01

Plantago major has been used widely since ancient times, to manage a wide range of diseases including constipation, coughs and wounds. The aim of this study is to review the traditional application, botanical characterization, pharmacological activities, phytochemistry effects and toxicity of Plantago major. In this review study, medicinal properties of Plantago major are collected from credible pharmacopeias, textbooks of traditional Persian medicine (TPM) belonging to the 10–18th century AD, such as “The Canon of Medicine”, “Makhzan-Al- Advia” and so on. Moreover, electronic databases including Scopus, Medline and Web of science were explored for this purpose. Plantago major has been prescribed in various forms such as roasted seeds, decoction, syrup, liniment, gargle, rectal enema, vaginal suppository, eye and nasal drop for each illness by TPM scholars. Some of its traditional properties including wound healing, antipyretic, antitussive, anti-infective, anti-hemorrhagic, anti-inflammatory, diuretic, laxative, astringent and hemostatic have been confirmed in recent researches. Phytochemical investigations showed that Plantago major contains volatile compounds, triterpenoids, phenolic acids and flavonoids. Modern pharmacological studies have proven some of the traditional applications of Plantago major. Nevertheless, more investigations are required on this plant, because it has the potential to be used to produce various natural medications. PMID:29629064

Evaluation of antinociceptive activity of aqueous extract of bark of psidium guajava in albino rats and albino mice.

PubMed

Sekhar, N Chandra; Jayasree, T; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-09-01

Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. AEPG antinociceptive activity involves activation of the peripheral and central mechanisms.

Symptomatic Treatment of Cough Among Adult Patients With Lung Cancer: CHEST Guideline and Expert Panel Report.

PubMed

Molassiotis, Alex; Smith, Jaclyn A; Mazzone, Peter; Blackhall, Fiona; Irwin, Richard S

2017-04-01

Cough among patients with lung cancer is a common but often undertreated symptom. We used a 2015 Cochrane systematic review, among other sources of evidence, to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. The CHEST methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on data from the Cochrane systematic review on the topic, uncontrolled studies, case studies, and the clinical context. Final grading was reached by consensus according to the Delphi method. The Cochrane systematic review identified 17 trials of primarily low-quality evidence. Such evidence was related to both nonpharmacologic (cough suppression) and pharmacologic (demulcents, opioids, peripherally acting antitussives, or local anesthetics) treatments, as well as endobronchial brachytherapy. Compared with the 2006 CHEST Cough Guideline, the current recommendations and suggestions are more specific and follow a step-up approach to the management of cough among patients with lung cancer, acknowledging the low-quality evidence in the field and the urgent need to develop more effective, evidence-based interventions through high-quality research. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Cough reflex hypersensitivity: A role for neurotrophins.

PubMed

El-Hashim, Ahmed Z; Jaffal, Sahar M

2017-03-01

Cough is one of the most common complaints for which sufferers seek medical assistance. However, currently available drugs are not very effective in treating cough, particularly that which follows an upper respiratory tract infection. Nonetheless, there has been a significant increase in our understanding of the mechanisms and pathways of the defensive cough as well as the hypersensitive/pathophysiological cough, both at airway and central nervous system (CNS) levels. Numerous molecules and signaling pathways have been identified as potential targets for antitussive drugs, including neurotrophins (NTs). NTs belong to a family of trophic factors and are critical for the development and maintenance of neurons in the central and peripheral nervous system including sympathetic efferents, sensory neuron afferents, and immune cells. Nerve growth factor (NGF) was the first member of the NT family to be discovered, with wide ranging actions associated with synapse formation, survival, proliferation, apoptosis, axonal and dendritic outgrowth, expression and activity of functionally important proteins such as ion channels, receptors, and neurotransmitters. In addition, NGF has been implicated in several disease states particularly neuropathic pain and most recently in the sensitization of the cough reflex. This review will briefly address the peripheral and central sensitization mechanisms of airway neurons and will then focus on NGF signaling and its role in cough hypersensitivity.

Care of Patients at the End of Life: Management of Nonpain Symptoms.

PubMed

Baralatei, Florence T; Ackermann, Richard J

2016-08-01

Management of nonpain symptoms can improve quality of life for patients at the end of life and their family members. Constipation is the most common nonpain symptom. It can be related to opioid therapy and/or medical conditions. After abdominal examination to detect masses or evidence of bowel obstruction and rectal examination to exclude fecal impaction, constipation should be managed with a stimulant laxative (eg, senna) or an osmotic laxative (eg, sorbitol). Dyspnea also is common, and often improves with use of a fan to blow air into the face, as well with breathing and relaxation exercises. However, many patients require titrated doses of opioids to address respiratory depression, and anxiolytics such as haloperidol may be needed to manage dyspnea-related anxiety. Oxygen typically is not effective in dyspnea management in nonhypoxemic patients at the end of life. Cough is managed with antitussives. Nausea and vomiting occur in 70% of patients in palliative care units. If no reversible etiology can be identified, dopamine antagonists and motility-enhancing drugs can be used. There are no clearly effective treatments to manage noisy respiratory secretions, but position change, decrease in fluid intake, and drugs such as scopolamine or glycopyrrolate may be effective. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Systematic chemical profiling of Citrus grandis 'Tomentosa' by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Li, Pan-lin; Liu, Meng-hua; Hu, Jie-hui; Su, Wei-wei

2014-03-01

Citrus grandis 'Tomentosa', as the original plant of the traditional Chinese medicine "Huajuhong", has been used as antitussive and expectorant in clinic for thousands of years. The fruit epicarp and whole fruit of this plant were both literarily recorded and commonly used. In the present study, an ultra-fast liquid chromatography coupled with diode-array detection and quadrupole/time-of-flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) based chemical profiling method was developed for rapid holistic quality evaluation of C. grandis 'Tomentosa', which laid basis for chemical comparison of two medicinal parts. As a result, forty-eight constituents, mainly belonging to flavonoids and coumarins, were unambiguously identified by comparison with reference standards and/or tentatively characterized by elucidating UV spectra, quasi-molecular ions and fragment ions referring to information available in literature. Both of the epicarp and whole fruit samples were rich in flavonoids and coumarins, but major flavonoids contents in whole fruit were significantly higher than in epicarp (P<0.5). The proposed method could be useful in quality control and standardization of C. grandis 'Tomentosa' raw materials and its products. Results obtained in this study will provide a basis for quality assessment and further study in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of Antinociceptive Activity of Aqueous Extract of Bark of Psidium Guajava in Albino Rats and Albino Mice

PubMed Central

Jayasree, T.; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-01-01

Background: Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. Aim: To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Materials and Methods: Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. Results: The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. Conclusion: AEPG antinociceptive activity involves activation of the peripheral and central mechanisms. PMID:25386462

Adverse events associated with pediatric exposures to dextromethorphan.

PubMed

Paul, Ian M; Reynolds, Kate M; Kauffman, Ralph E; Banner, William; Bond, G Randall; Palmer, Robert B; Burnham, Randy I; Green, Jody L

2017-01-01

Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children <12 years old from a surveillance program of OTC cough/cold medication exposures. This is a retrospective case series of oral exposures to dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure. 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children <4 years old. No deaths or pathologic dysrhythmias occurred. Central nervous system [e.g., ataxia (N = 420)] and autonomic symptoms [e.g., tachycardia (N = 224)] were the most common adverse events. Flushing and/or urticarial rash occurred in 18.1% of patients. Dystonia occurred in 5.4%. No fatalities were identified in this multifaceted surveillance program following a dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.

The effect of long-term administered CRAC channels blocker on the functions of respiratory epithelium in guinea pig allergic asthma model.

PubMed

Sutovska, Martina; Kocmalova, Michaela; Joskova, Marta; Adamkov, Marian; Franova, Sona

2015-04-01

Previously, therapeutic potency of CRAC channels blocker was evidenced as a significant decrease in airway smooth muscle hyperreactivity, antitussive and anti-inflammatory effects. The major role of the respiratory epithelium in asthma pathogenesis was highlighted only recently and CRAC channels were proposed as the most significant route of Ca2+ entry into epithelial cells. The aim of the study was to analyse the impact of long-term administered CRAC channels blocker on airway epithelium, e.g. cytokine production and ciliary beat frequency (CBF) using an animal model of allergic asthma. Ovalbumin-induced allergic airway inflammation of guinea pigs was followed by long-term (14 days lasted) therapy by CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA). The influence of long-term therapy on cytokines (IL-4, IL-5 and IL-13) in BALF and in plasma, immunohistochemical staining of pulmonary tissue (c-Fos positivity) and CBF in vitro were used for analysis. Decrease in cytokine levels and in c-Fos positivity confirmed an anti-inflammatory effect of long-term administered FPCA. Cytokine levels in BALF and distribution of c-Fos positivity suggested that FPCA was a more potent inhibitor of respiratory epithelium secretory functions than budesonide. FPCA and budesonide reduced CBF only insignificantly. All findings supported CRAC channels as promising target in the new strategy of antiasthmatic treatment.

Identifying mechanism-of-action targets for drugs and probes

PubMed Central

Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A.; Irwin, John J.; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L.; Shoichet, Brian K.

2012-01-01

Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to “de-orphanize” drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration—approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801

Encoding of the cough reflex in anesthetized guinea pigs

PubMed Central

Mori, Nanako

2011-01-01

We have previously described the physiological and morphological properties of the cough receptors and their sites of termination in the airways and centrally in the nucleus tractus solitarius (nTS). In the present study, we have addressed the hypothesis that the primary central synapses of the cough receptors subserve an essential role in the encoding of cough. We found that cough requires sustained, high-frequency (≥8-Hz) afferent nerve activation. We also found evidence for processes that both facilitate (summation, sensitization) and inhibit the initiation of cough. Sensitization of cough occurs with repetitive subthreshold activation of the cough receptors or by coincident activation of C-fibers and/or nTS neurokinin receptor activation. Desensitization of cough evoked by repetitive and/or continuous afferent nerve activation has a rapid onset (<60 s) and does not differentiate between tussive stimuli, suggesting a central nervous system-dependent process. The cough reflex can also be actively inhibited upon activation of other airway afferent nerve subtypes, including slowly adapting receptors and pulmonary C-fibers. The sensitization and desensitization of cough are likely attributable to the prominent, primary, and unique role of N-methyl-d-aspartate receptor-dependent signaling at the central synapses of the cough receptors. These attributes may have direct relevance to the presentation of cough in disease and for the effectiveness of antitussive therapies. PMID:20926760

Involvement of AMPA receptors in the antidepressant-like effects of dextromethorphan in mice.

PubMed

Nguyen, Linda; Matsumoto, Rae R

2015-12-15

Dextromethorphan (DM) is an antitussive with rapid acting antidepressant potential based on pharmacodynamic similarities to ketamine. Building upon our previous finding that DM produces antidepressant-like effects in the mouse forced swim test (FST), the present study aimed to establish the antidepressant-like actions of DM in the tail suspension test (TST), another well-established model predictive of antidepressant efficacy. Additionally, using the TST and FST, we investigated the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in the antidepressant-like properties of DM because accumulating evidence suggests that AMPA receptors play an important role in the pathophysiology of depression and may contribute to the efficacy of antidepressant medications, including that of ketamine. We found that DM displays antidepressant-like effects in the TST similar to the conventional and fast acting antidepressants characterized by imipramine and ketamine, respectively. Moreover, decreasing the first-pass metabolism of DM by concomitant administration of quinidine (CYP2D6 inhibitor) potentiated antidepressant-like actions, implying DM itself has antidepressant efficacy. Finally, in both the TST and FST, pretreatment with the AMPA receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide) significantly attenuated the antidepressant-like behavior elicited by DM. Together, the data show that DM exerts antidepressant-like actions through AMPA receptors, further suggesting DM may act as a safe and effective fast acting antidepressant drug. Copyright © 2015 Elsevier B.V. All rights reserved.

MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor.

PubMed

Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2017-11-01

Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1

Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-fungus-associated chronic cough (FACC).

PubMed

Ogawa, Haruhiko; Fujimura, Masaki; Takeuchi, Yasuo; Makimura, Koichi

2009-05-01

This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi. Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging. The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p < 0.001) when compared with that of the placebo. Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

PubMed

Zur, Moran; Hanson, Allison S; Dahan, Arik

2014-09-30

While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

PubMed

Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

2016-08-01

Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Highly sensitive on-site detection of drugs adulterated in botanical dietary supplements using thin layer chromatography combined with dynamic surface enhanced Raman spectroscopy.

PubMed

Fang, Fang; Qi, Yunpeng; Lu, Feng; Yang, Liangbao

2016-01-01

The phenomenon of botanical dietary supplements (BDS) doped with illegal adulterants has become a serious problem all over the world, which could cause great threat to human's health. Therefore, it is of great value to identify BDS. Herein, we put forward a highly sensitive method for on-site detection of antitussive and antiasthmatic drugs adulterated in BDS using thin layer chromatography (TLC) combined with dynamic surface enhanced Raman spectroscopy (DSERS). Adulterants in BDS were separated on a TLC plate and located under UV illumination. Then DSERS detection was performed using a portable Raman spectrometer with 50% glycerol silver colloid serving as DSERS active substrate. Here, the effects of different solvents on detection efficacy were evaluated using phenformin hydrochloride (PHE) as a probe. It was shown that 50% glycerol resulted in higher SERS enhancement and relatively higher stability. Moreover, practical application of this novel TLC-DSERS method was demonstrated with rapid analysis of real BDS samples and one sample adulterated with benproperine phosphate (BEN) was found. Furthermore, the obtained result was verified by ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF/MS). The sensitivity of the TLC-DSERS technique is 1-2 orders of magnitude higher than that of TLC-SERS technique. The results turned out that this combined method would have good prospects for on-site and sensitive detection of adulterated BDS. Copyright © 2015 Elsevier B.V. All rights reserved.

Inappropriate prescription of cough remedies among children hospitalised with respiratory illness over the period 2002-2015 in Kenya.

PubMed

Maina, Michuki; Akech, Samuel; Mwaniki, Paul; Gachau, Susan; Ogero, Morris; Julius, Thomas; Ayieko, Phillip; Irimu, Grace; English, Mike

2017-03-01

To examine trends in prescription of cough medicines over the period 2002-2015 in children aged 1 month to 12 years admitted to Kenyan hospitals with cough, difficulty breathing or diagnosed with a respiratory tract infection. We reviewed hospitalisation records of children included in four studies providing cross-sectional prevalence estimates from government hospitals for six time periods between 2002 and 2015. Children with an atopic illness were excluded. Amongst eligible children, we determined the proportion prescribed any adjuvant medication for cough. Active ingredients in these medicines were often multiple and were classified into five categories: antihistamines, antitussives, mucolytics/expectorants, decongestants and bronchodilators. From late 2006, guidelines discouraging cough medicine use have been widely disseminated and in 2009 national directives to decrease cough medicine use were issued. Across the studies, 17 963 children were eligible. Their median age and length of hospital stay were comparable. The proportion of children who received cough medicines shrank across the surveys: approximately 6% [95% CI: 5.4, 6.6] of children had a prescription in 2015 vs. 40% [95% CI: 35.5, 45.6] in 2002. The most common active ingredients were antihistamines and bronchodilators. The relative proportion that included antihistamines has increased over time. There has been an overall decline in the use of cough medicines among hospitalised children over time. This decline has been associated with educational, policy and mass media interventions. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

[Potential of antiinflammatory therapy in patients with chronic obstructive lung disease].

PubMed

Fedorova, T A; Ekkert, N V; Chernekhovskaia, N E; Roĭtman, A P; Makarova, O V; Zhidkova, N V

2005-01-01

The aim of the study was to investigate the effects of erespal (fenspirid) on the clinical manifestations and parameters of inflammation in patients with chronic obstructive lung disease (COLD). The two stages of the study included 3-weak treatment during exacerbation periods and a 3-month outpatient follow-up during clinical remission periods. Erespal was administered twice a day in a total dose of 160 mg/day. The study included evaluation of clinical symptoms, respiratory function, bronchoscopic data, laboratory indices of inflammation, antioxydative status, life quality (LQ), as well as cytological and cytochemical analysis of induced sputum (IS). During exacerbation periods of COLD the researchers observed early and noticeable antitussive and mucolytic action of erespal, which were associated with lessening of bronchial obstruction and inflammation, significant fall of C-reactive protein level, cytosis in IS, proportion of neutrophiles (p < 0.01), elevation of lysosomal cation proteins in neutrophiles (p < 0.01), increase of total oxidant serum level (in 46.2% of the patients vs. 26.3% of the patients in the conventional therapy group). Long term (3 months) treatment with erespal led to further positive dynamics of clinical and laboratory indices of inflammation, and improved the results of cytological and cytochemical study of IS. The results of the study demonstrate that inclusion of erespal in complex therapy of COLD increases efficacy of treatment, due to its anti-inflammatory action during the periods of exacerbation and relative remission, prevents augmenting of bronchial obstruction, and improves patients' LQ.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.

PubMed

Ahmad, Zulfiqar; Hassan, Sherif S; Azim, Sofiya

2017-11-20

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phytochemicals is based on tradition or word of mouth with few evidence-based studies. Moreover, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become pertinent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of dietary phytochemicals are known to inhibit ATP synthase. Structural modifications of phytochemicals have been shown to increase the inhibitory potency and extent of inhibition. Sitedirected mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can result in selective binding and inhibition of microbial ATP synthase. In this review, the therapeutic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective targeting of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase

PubMed Central

Ahmad, Zulfiqar; Hassan, Sherif S.; Azim, Sofiya

2017-01-01

For centuries, phytochemicals have been used to prevent and cure multiple health ailments. Phytochemicals have been reported to have antioxidant, antidiabetic, antitussive, antiparasitic, anticancer, and antimicrobial properties. Generally, the therapeutic use of phy-tochemicals is based on tradition or word of mouth with few evidence-based studies. Moreo-ver, molecular level interactions or molecular targets for the majority of phytochemicals are unknown. In recent years, antibiotic resistance by microbes has become a major healthcare concern. As such, the use of phytochemicals with antimicrobial properties has become perti-nent. Natural compounds from plants, vegetables, herbs, and spices with strong antimicrobial properties present an excellent opportunity for preventing and combating antibiotic resistant microbial infections. ATP synthase is the fundamental means of cellular energy. Inhibition of ATP synthase may deprive cells of required energy leading to cell death, and a variety of die-tary phytochemicals are known to inhibit ATP synthase. Structural modifications of phyto-chemicals have been shown to increase the inhibitory potency and extent of inhibition. Site-directed mutagenic analysis has elucidated the binding site(s) for some phytochemicals on ATP synthase. Amino acid variations in and around the phytochemical binding sites can re-sult in selective binding and inhibition of microbial ATP synthase. In this review, the therapeu-tic connection between dietary phytochemicals and ATP synthase is summarized based on the inhibition of ATP synthase by dietary phytochemicals. Research suggests selective target-ing of ATP synthase is a valuable alternative molecular level approach to combat antibiotic resistant microbial infections. PMID:28831918

The epidemiology of childhood poisonings in Cyprus.

PubMed

Koliou, Maria; Ioannou, Chrystalla; Andreou, Kyriaki; Petridou, Alexandra; Soteriades, Elpidoforos Soterakis

2010-07-01

Information on childhood poisonings in Cyprus is limited. Our objective was to examine the epidemiology of poisonings among children in Cyprus. All children up to 15 years of age admitted for poisoning to the Archbishop Makarios Hospital in Nicosia, Cyprus between 2005 and 2008 were included in our study. All hospital poisoning records were reviewed. A total of 257 children were admitted for poisoning. The mean age of children was 3.1 years, of which 83.7% were below the age of 5 years old, while 53% were boys. The poisoning hospitalizations accounted for about 3% of all admissions to the pediatric department during the study period (4 years). The annual cumulative incidence of childhood poisoning hospitalizations was 116 per 100,000 children. Medications accounted for 46.1% of all poisonings, the most frequent cause being paracetamol (9.8%), cardiovascular medications (5.3%), antitussive medications (4.5%), and other painkillers (4.1%). Another 37.6% of hospitalizations involved household products such as household cleaning products (11.8%), petroleum products (11.0%), and rodenticides (5.7%). Among children who ingested petroleum distillates, 55.6% developed clinical symptomatology. The vast majority of cases were accidental (93.8%). Suicidal cases involved children 8-14 years old, mainly girls, and the most frequent poisoning ingested was paracetamol (46.7%). Poisoning hospitalizations represent an important cause of morbidity among children in Cyprus. Preventive strategies should include the education of caregivers on the handling of medications and household products as well as legislation requiring child-resistant packaging for all medications and household products including petroleum distillates.

Determination of Dextromethorphan in Oral Fluid by LC-MS-MS.

PubMed

Amaratunga, Piyadarsha; Clothier, Morgan; Lorenz Lemberg, Bridget; Lemberg, Dave

2016-06-01

Dextromethorphan (DXM) is an antitussive drug found in commonly used nonprescription cold and cough medications. At low doses, DXM is a safe drug that does not produce adverse reactions. However, abuse of DXM has been reported among adolescents and young adults using the drug at higher doses. DXM is not a scheduled drug in the USA, and the primary reason for its abuse is the ease of availability. DXM is available to purchase in the form of over-the-counter cough medications, such as Robitussin(®) and Coricidin(®), or it can be purchased over the Internet in the form of a powder. In this research work, we developed an LC-MS-MS method that can quantify DXM and dextrorphan (DXO) in oral fluid in a high-throughput toxicology laboratory setting. The developed method was validated according to the Scientific Working Group for Forensic Toxicology guidelines. The linear dynamic range was 5-100 ng/mL with a lowest limit of quantitation (LLOQ) of 5.0 ng/mL for DXM and DXO. Overall, the results of the accuracy and the precision values were within the acceptance criteria for both drugs. In addition, selectivity, matrix effect and recovery were calculated for the LC-MS-MS method. Authentic samples (n = 59) were tested to evaluate the applicability of the method. Thirty samples were found to be positive for DXM and DXO and two samples were found to be positive for DXM only. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pharmacokinetic profile of dextromethorphan hydrobromide in a syrup formulation in children and adolescents.

PubMed

Guenin, Eric; Armogida, Marianna; Riff, Dennis

2014-09-01

Dextromethorphan hydrobromide (DM) is a widely used antitussive. This study determined, for the first time, the basic pharmacokinetic profile of DM and its active metabolite, dextrorphan (DP) in children and adolescents. Thirty-eight male and female subjects at risk for developing an upper respiratory tract infection (URTI), or symptomatic with cough due to URTI, were enrolled in this single-dose, open-label study: ages 2-5 years (Group A, n = 8), 6-11 years (Group B, n = 17), 12-17 years (Group C, n = 13). Subjects were genotyped for cytochrome P450 (CYP) 2D6 polymorphisms and characterized as poor (PM) or non-poor metabolizers (non-PM). Groups A and B were dosed using an age-weight dosing schedule (DM range 7.5-24.75 mg); a 30-mg dose was used for Group C. Average exposures to total DP increased as age group increased, and average exposure to DM was highest in the adolescent group. One subject in that group was a PM. The terminal half-life (t ½) values were longer in the adolescent group due in part to the single PM subject. No relationship between body weight and pharmacokinetic parameters was noted. This is the first evaluation of the pharmacokinetic characteristics of DM in children and adolescents. A single dose of DM in this population was safe, and well tolerated at all doses tested. The data are used to model and compare pediatric DM exposures with those of adults.

Successful management of enzyme replacement therapy in related fabry disease patients with severe adverse events by switching from agalsidase Beta (fabrazyme(®)) to agalsidase alfa (replagal (®)).

PubMed

Tsuboi, Kazuya; Yamamoto, Hiroshi; Somura, Fuji; Goto, Hiromi

2015-01-01

Enzyme replacement therapy (ERT) is the only approved therapy for Fabry disease. In June 2009, there was a worldwide shortage of agalsidase beta, necessitating dose reductions or switching to agalsidase alfa in some patients. We present two cases of Fabry disease (a parent and a child) who received agalsidase beta for 27 months at the licensed dose and 10 months at a reduced dose, followed by a switch to agalsidase alfa for 28 months. Case 1, a 26-year-old male had severe coughing and fatigue during ERT with agalsidase beta requiring antitussive and asthmatic drug therapy. After switching to agalsidase alfa, the coughing gradually resolved completely. Case 2, a 62-year-old female had advanced cardiac manifestations at the time of diagnosis. Despite receiving ERT with the approved dose of agalsidase beta, she experienced aggravation of congestive heart failure and was hospitalized. After switching to agalsidase alfa with standard care in heart disease, BNP level, echocardiographic parameters, eGFR rate and lyso-Gb3 levels were improved or stabilized. We report on two Fabry disease patients who experienced severe adverse events while on approved and/or reduced doses of agalsidase beta. Switching to agalsidase alfa associated with standard care in heart disease led to resolution or improvement in the cardiorespiratory status. And reduction in dose associated with standard care in respiratory disease was useful for decrease in cough and fatigue. Plasma BNP level was useful for monitoring heart failure and the effects of ERT.

Development of a capillary electrophoresis method for the determination of the chiral purity of dextromethorphan by a dual selector system using quality by design methodology.

PubMed

Krait, Sulaiman; Heuermann, Matthias; Scriba, Gerhard K E

2018-03-01

Dextromethorphan is a centrally acting antitussive drug, while its enantiomer levomethorphan is an illicit drug with opioid analgesic effects. As capillary electrophoresis has been proven as an ideal technique for enantiomer analysis, the present study was conducted in order to develop a capillary electrophoresis-based limit test for levomethorphan. The analytical target profile was defined as a method that should be able to determine levomethorphan with acceptable precision and accuracy at the 0.1 % level. From initial scouting experiments, a dual selector system consisting of sulfated β-cyclodextrin and methyl-α-cyclodextrin was identified. The critical process parameters were evaluated in a fractional factorial resolution IV design followed by a central composite face-centered design and Monte Carlo simulations for defining the design space of the method. The selected working conditions consisted of a 30/40.2 cm, 50 μm id fused-silica capillary, 30 mM sodium phosphate buffer, pH 6.5, 16 mg/mL sulfated β-cyclodextrin, and 14 mg/mL methyl-α-cyclodextrin at 20°C and 20 kV. The method was validated according to ICH guideline Q2(R1) and applied to the analysis of a capsule formulation. Furthermore, the apparent binding constants between the enantiomers and the cyclodextrins as well as complex mobilities were determined to understand the migration behavior of the analytes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[6]-Shogaol inhibits the production of proinflammatory cytokines via regulation of NF-κB and phosphorylation of JNK in HMC-1 cells.

PubMed

Sohn, Youngjoo; Han, Na-Young; Lee, Min Jung; Cho, Hyun-Joo; Jung, Hyuk-Sang

2013-08-01

[6]-Shogaol is a major bioactive component of Zingiber officinale. Although [6]-shogaol has a number of pharmacological activities including antipyretic, analgesic, antitussive and anti-inflammatory effects, the specific mechanisms of its anti-allergic effects have not been studied. In this study, we present the effects of [6]-shogaol on mast cell-mediated allergic reactions in vivo and in vitro. Sprague-Dawley rats received intradermal injections of anti-DNP IgE was injected into dorsal skin sites. After 48 h, [6]-shogaol was administered orally 1 h prior to challenge with DNP-HSA in saline containing 4% Evans blue through the dorsal vein of the penis. In addition, rat peritoneal mast cells (RPMCs) were cultured and purified to investigate histamine release. In vitro, we evaluated the regulatory effects of [6]-shogaol on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionomycin A23187-stimulated human mast cells (HMC-1). [6]-Shogaol reduced the passive cutaneous anaphylaxis reaction compared to the control group, and histamine release decreased significantly following the treatment of RPMCs with [6]-shogaol. In HMC-1 cells, [6]-shogaol inhibited the production of TNF-α, IL-6 and IL-8, as well as the activation of nuclear factor-κB (NF-κB) and phosphorylation of JNK in compound 48/80-induced HMC-1 cells. [6]-shogaol inhibited mast cell-mediated allergic reactions by inhibiting the release of histamine and the production of proinflammatory cytokines with the involvement of regulation of NF-κB and phosphorylation of JNK.

Low doses of dextromethorphan attenuate morphine-induced rewarding via the sigma-1 receptor at ventral tegmental area in rats.

PubMed

Chen, Shiou-Lan; Hsu, Kuei-Ying; Huang, Eagle Yi-Kung; Lu, Ru-Band; Tao, Pao-Luh

2011-09-01

Chronic use of morphine causes rewarding and behavioral sensitization, which may lead to the development of psychological craving. In our previous study, we found that a widely used antitussive dextromethorphan (known as a low affinity NMDA receptor antagonist), at doses of 10-20 mg/kg (i.p.), effectively decreased morphine rewarding in rats. In this study, we further investigated the effects and mechanisms of low doses of DM (μg/kg range) on morphine rewarding and behavioral sensitization. A conditioned place preference test was used to determine the rewarding and a locomotor activity test was used to determine the behavioral sensitization induced by the drug(s) in rats. When a low dose of DM (3 or 10 μg/kg, i.p.) was co-administered with morphine (5 mg/kg, s.c.), the rewarding effect, but not behavioral sensitization, induced by morphine was inhibited. The inhibiting effect of DM could be blocked by systemically administering a sigma-1 receptor antagonist, BD1047 (3 mg/kg, i.p.). When BD1047 (5 nmole/site) was locally given at the VTA, it also blocked the effects of a low dose of DM in inhibiting morphine rewarding. Our findings suggest that the activation of the sigma-1 receptor at the VTA may be involved in the mechanism of low doses of DM in inhibiting the morphine rewarding effect and the possibility of using extremely low doses of DM in treatment of opioid addiction in clinics. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Stereoselective pharmacokinetics of moguisteine metabolites in healthy subjects.

PubMed

Bernareggi, A; Crema, A; Carlesi, R M; Castoldi, D; Ratti, E; Renoldi, M I; Ratti, D; Ceserani, R; Tognella, S

1995-01-01

We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral antitussive drug, in 12 healthy male subjects after a single oral administration of 200 mg. The unchanged drug was absent in plasma and urine of all subjects. Moguisteine was immediately and completely hydrolyzed to its main active metabolite, the free carboxylic acid M1. Therefore, we evaluated the kinetic profiles of M1, of its enantiomers R(+)-M1 and S(-)-M1, and of M1 sulfoxide optical isomers M2/I and M2/II by conventional and stereospecific HPLC. Maximum plasma concentrations for M1 (2.83 mg/l), M2/I (0.26 mg/l) and M2/II (0.40 mg/l), were respectively reached at 1.3, 1.6 and 1.5 h after moguisteine administration. Plasma concentrations declined after the peak with mean apparent terminal half-lives of 0.65 h (M1), 0.88 h (M2/I) and 0.84 h (M2/II). Most of the administered dose was recovered in urine within 6 h from moguisteine treatment. The systemic and renal clearance values indicated high renal extraction ratio for all moguisteine metabolites, and particularly for M1 sulfoxide optical isomers. Plasma concentration-time profiles and urinary excretion patterns for M1 enantiomers R(+)-M1 and S(-)-M1 were quite similar. Thus, for later moguisteine pharmacokinetic evaluations the investigation of the plasma concentration-time curve and the urinary excretion of the sole racemic M1 through non-stereospecific analytical methods may suffice in most cases.

Translating Cough Mechanisms Into Better Cough Suppressants.

PubMed

Keller, Jennifer A; McGovern, Alice E; Mazzone, Stuart B

2017-10-01

Chronic cough is a significant problem, and in many patients cough remains refractive to both disease-specific therapies and current cough-suppressing medicines, creating a need for improved antitussive therapies. Most patients with chronic cough also display heightened sensitivity so that they experience a persistent sense of the need to cough, and often innocuous stimuli can trigger their coughing. This hypersensitivity underpins the newly described concept of cough hypersensitivity syndrome (CHS), a term that encapsulates the notion of common underlying mechanisms producing neuronal activation, sensitization and/or dysfunction, which are at the core of excessive coughing. Understanding these mechanisms has been a focus of recent research efforts in the field in the hope that new therapies can be developed to selectively target sensitized unproductive cough while maintaining the reflexive cough essential for airway protection. However, efforts to achieve this have been slower than expected, in part because of some significant challenges and limitations translating current cough models. In this review, we summarize recent advances in our understanding of the sensory circuits innervating the respiratory system that are important for cough, how cough sensory pathways become hypersensitive, and some of the recently described neural targets under development for treating chronic cough. We present the case that better use of current cough models or the development of new models, or both, is ultimately needed to advance our efforts to translate the discovery of basic cough mechanisms into effective medicines for treating patients with chronic cough. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

PubMed

Miceli Sopo, S; Greco, M; Monaco, S; Varrasi, G; Di Lorenzo, G; Simeone, G

2015-01-01

Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

The role of excitatory amino acids and substance P in the mediation of the cough reflex within the nucleus tractus solitarii of the rabbit.

PubMed

Mutolo, Donatella; Bongianni, Fulvia; Fontana, Giovanni A; Pantaleo, Tito

2007-09-28

We hypothesized that cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit is primarily mediated by glutamatergic neurotransmission at the level of the caudal portions of the medial subnucleus of the nucleus tractus solitarii (NTS) and the lateral commissural NTS where cough-related afferents terminate, and that this reflex is potentiated by local release of substance P. To test our hypothesis, we performed bilateral microinjections (30-50 nl) of ionotropic glutamate receptor antagonists or substance P into these locations in pentobarbitone anaesthetized, spontaneously breathing rabbits. Blockade of NMDA and non-NMDA receptors by 50mM kynurenic acid abolished the cough reflex without affecting the Breuer-Hering inflation reflex or the pulmonary chemoreflex. Blockade of non-NMDA receptors using 10mM CNQX or 5mM NBQX caused identical effects. Blockade of NMDA receptors by 10mM D-AP5 strongly reduced, but did not abolish cough responses. Microinjections of 1mM substance P increased peak and rate of rise of abdominal muscle activity as well as cough number. These results are the first to provide evidence that ionotropic glutamate receptors, especially non-NMDA receptors, located within specific regions of NTS are primarily involved in the mediation of cough evoked by mechanical stimulation of the tracheobronchial tree in the rabbit. Present findings on substance P cough-enhancing effects extend previous observations and are relevant to the tachykinin-mediated central sensitization of the cough reflex. They also may provide hints for further studies on centrally acting antitussive drugs.

Fast determination of diphenhydramine hydrochloride in reconstitutable syrups by CWT, PLS AND PCR methods.

PubMed

Devrim, Burcu; Dinç, Erdal; Bozkir, Asuman

2014-01-01

Diphenhydramine hydrochloride (DPH), a histamine H1-receptor antagonist, is widely used as antiallergic, antiemetic and antitussive drug found in many pharmaceutical preparations. In this study, a new reconstitutable syrup formulation of DPH was prepared because it is more stable in solid form than that in liquid form. The quantitative estimation of the DPH content of a reconstitutable syrup formulation in the presence of pharmaceutical excipients, D-sorbitol, sodium citrate, sodium benzoate and sodium EDTA is not possible by the direct absorbance measurement. Therefore, a signal processing approach based on continuous wavelet transform was used to determine the DPH in the reconstitutable syrup formulations and to eliminate the effect of excipients on the analysis. The absorption spectra of DPH in the range of 5.0-40.0 μg/mL were recorded between 200-300 nm. Various wavelet families were tested and Biorthogonal1.1 continuous wavelet transform (BIOR1.1-CWT) was found to be optimal signal processing family to get fast and desirable determination results and to overcome excipient interference effects. For a comparison of the experimental results obtained by partial least squares (PLS) and principal component regression (PCR) methods were applied to the quantitative prediction of DPH in the mentioned samples. The validity of the proposed BIOR1.1-CWT, PLS and PCR methods were achieved analyzing the prepared samples containing the mentioned excipients and using standard addition technique. It was observed that the proposed graphical and numerical approaches are suitable for the quantitative analysis of DPH in samples including excipients.

A portable automatic cough analyser in the ambulatory assessment of cough.

PubMed

Krajnik, Malgorzata; Damps-Konstanska, Iwona; Gorska, Lucyna; Jassem, Ewa

2010-03-14

Cough is one of the main symptoms of advanced lung disease. However, the efficacy of currently available treatment remains unsatisfactory. Research into the new antitussives requires an objective assessment of cough. The aim of the study was to test the feasibility of a new automatic portable cough analyser and assess the correlation between subjective and objective evaluations of cough in 13 patients with chronic cough. The patients' individual histories, a cough symptom score and a numeric cough scale (1-10) were used as a subjective evaluation of cough and a computerized audio-timed recorder was used to measure the frequency of coughing. The pre-clinical validation has shown that an automated cough analyser is an accurate and reliable tool for the ambulatory assessment of chronic cough. In the clinical part of the experiment for the daytime, subjective cough scoring correlated with the number of all cough incidents recorded by the cough analyser (r = 0.63; p = 0.022) and the number of cough incidents per hour (r = 0.60; p = 0.03). However, there was no relation between cough score and the time spent coughing per hour (r = 0.48; p = 0.1). As assessed for the night-time period, no correlation was found between subjective cough scoring and the number of incidents per hour (r = 0.29; p = 0.34) or time spent coughing (r = 0.26; p = 0.4). An automated cough analyser seems to be a feasible tool for the ambulatory monitoring of cough. There is a moderate correlation between subjective and objective assessments of cough during the daytime, whereas the discrepancy in the evaluation of night-time coughing might suggest that subjective analysis is unreliable.

Survey of Spanish general practitioners' attitudes toward management of sore throat: an internet-based questionnaire study.

PubMed

Llor, Carl; Vilaseca, Isabel; Lehrer-Coriat, Eduardo; Boleda, Xavier; Cañada, José L; Moragas, Ana; Cots, Josep M

2017-02-14

The management of sore throat varies widely in Europe. The objective of this study was to gain insight into clinicians' perceptions on the current management of sore throat in Spain. Cross-sectional, internet-based questionnaire study answered from July to September 2013. General practitioners (GPs) affiliated with the two largest scientific societies of primary care were invited to participate in the study. Questions were asked about physician knowledge, the use of current national guidelines for sore throat management, and management in two clinical scenarios, depicting a young adult with sore throat and: 1. cough, coriza with or without fever, and 2. fever without cough and coriza. The questionnaire was completed by 1476 GPs (5%) and 12.7% declared using rapid antigen detection tests. Antibiotics were considered by 18.8% of the GPs in the first scenario and by 32% in the second scenario (p < 0.001). The antibiotics most commonly mentioned by GPs were amoxicillin and amoxicillin + clavulanate (52.7 and 31.2%, respectively) whereas penicillin V was only prescribed in 11.9% of the cases. The drugs most commonly considered in both scenarios were analgesics and anti-inflammatory drugs. Antitussives, decongestants and expectorants were more commonly prescribed in cases of suspected viral infection (p < 0.001). GPs have misconceptions as to the indications for using rapid antigen detection tests and prescribing drugs in the management of sore throat. These results suggest that guidelines are seldom followed since one in five GPs declared giving antibiotics for patients with a suspected viral infection and the use of second-choice antibiotics seems considerable.

Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan.

PubMed

Nguyen, Linda; Robson, Matthew J; Healy, Jason R; Scandinaro, Anna L; Matsumoto, Rae R

2014-01-01

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3)H](+)-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.

Dextromethorphan differentially affects opioid antinociception in rats

PubMed Central

Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh

2005-01-01

Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510

Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

PubMed

Corado, Carley R; McKemie, Daniel S; Knych, Heather K

2017-06-01

Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Involvement of Sigma-1 Receptors in the Antidepressant-like Effects of Dextromethorphan

PubMed Central

Nguyen, Linda; Robson, Matthew J.; Healy, Jason R.; Scandinaro, Anna L.; Matsumoto, Rae R.

2014-01-01

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [3H](+)-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors. PMID:24587167

Simultaneous quantification of six alkaloid components from commercial stemonae radix by solid phase extraction-high-performance liquid chromatography coupled with evaporative light scattering detector

PubMed Central

Zhang, Rong-Rong; Lu, Dan-Yi; Yang, Zhen-Ya; Zhao, Wen; But, Paul Pui-Hay; Shaw, Pang-Chui; Jiang, Ren-Wang; Ma, Zhi-Guo

2015-01-01

Background: Stemonae radix has been applied in traditional Chinese medicine for centuries. Alkaloids are the main active ingredient in stemonae radix, so their composition and concentration levels are directly linked to clinic effects. Objective: The objective was to develop an analytical method with multiple markers for quality survey of commercial stemonae radix. Materials and Methods: A method for simultaneous determination of six compounds in commercial stemonae radix was performed using solid-phase extraction and high-performance liquid chromatography coupled with evaporative light scattering detector. The separation was carried out on an Agilent TC-C18 column with 0.1% acetonitrile solution of triethylamine aqueous solution and acetonitrile as the mobile phase under gradient elution within 70 min. The hierarchical clustering analysis (HCA) was successfully used to classify the samples in accordance with their chemical constituents. Results: Linearity (R2 > 0.9990), intra- and inter-day precision (relative standard deviations <4%), limit of detection (0.011–0.086 μg/mL), limit of quantification (0.033–0.259 μg/mL) of the six alkaloids were determined, and the recoveries were between 96.6% and 103.7%. The method was successfully applied to analysis 36 batches of commercial stemonae radix. All the samples could be classified into five clusters by HCA. Conclusion: This article provides an accurate and simple analytical method for quality survey of commercial stemonae radix. Because of the significant chemical variations, careful selection of Stemona sources with obvious antitussive value but devoid of croomine followed by good agricultural practice and good manufacturing practice process is suggested. PMID:25829776

Benzonatate inhibition of voltage-gated sodium currents.

PubMed

Evans, M Steven; Maglinger, G Benton; Fletcher, Anita M; Johnson, Stephen R

2016-02-01

Benzonatate was FDA-approved in 1958 as an antitussive. Its mechanism of action is thought to be anesthesia of vagal sensory nerve fibers that mediate cough. Vagal sensory neurons highly express the Nav1.7 subtype of voltage-gated sodium channels, and inhibition of this channel inhibits the cough reflex. Local anesthetics inhibit voltage-gated sodium channels, but there are no reports of whether benzonatate affects these channels. Our hypothesis is that benzonatate inhibits Nav1.7 voltage-gated sodium channels. We used whole cell voltage clamp recording to test the effects of benzonatate on voltage-gated sodium (Na(+)) currents in two murine cell lines, catecholamine A differentiated (CAD) cells, which express primarily Nav1.7, and N1E-115, which express primarily Nav1.3. We found that, like local anesthetics, benzonatate strongly and reversibly inhibits voltage-gated Na(+) channels. Benzonatate causes both tonic and phasic inhibition. It has greater effects on channel inactivation than on activation, and its potency is much greater at depolarized potentials, indicating inactivated-state-specific effects. Na(+) currents in CAD cells and N1E-115 cells are similarly affected, indicating that benzonatate is not Na(+) channel subtype-specific. Benzonatate is a mixture of polyethoxy esters of 4-(butylamino) benzoic acid having varying degrees of hydrophobicity. We found that Na(+) currents are inhibited most potently by a benzonatate fraction containing the 9-ethoxy component. Detectable effects of benzonatate occur at concentrations as low as 0.3 μM, which has been reported in humans. We conclude that benzonatate has local anesthetic-like effects on voltage-gated sodium channels, including Nav1.7, which is a possible mechanism for cough suppression by the drug. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Cough induction by high-frequency chest percussion in healthy volunteers and patients with common cold].

PubMed

Lee, P C L; Eccles, R

2004-08-01

In patients with chronic obstructive pulmonary disease, chest percussion is often used to facilitate the drainage of respiratory secretions which may be removed from the airway by coughing. The cough reflex is believed to be mediated by mechanically sensitive rapidly adapting receptors (RARs). Chest percussion stimulation may stimulate RAR cough receptors, but there is no evidence that mechanical airway stimulation in man induces cough. The aim of this study was to determine if cough can be induced by high-frequency chest percussion in healthy subjects and in patients with acute upper respiratory tract infection (URTI). Two groups were studied: 15 healthy subjects and 29 subjects with URTI, mean age 22 years. Percussion stimulation (70 Hz) was applied to the chest. Cough frequency and latency were recorded. All subjects were asked to complete a questionnaire about how they felt after the chest percussion by questionnaires. The results demonstrate that high-frequency chest percussion causes cough in human subjects with a recent history of URTI, but induces relatively little cough in healthy subjects. In URTI subjects there was a significant increase in the number of coughs after three periods of airway vibration, whereas in healthy subjects there was no change in cough. Furthermore, analysis of the questionnaires showed that more of the subjects with URTI felt an urge to cough compared to the healthy subjects in the subjective questionnaires. This study demonstrates that cough can be induced in subjects with URTI by chest percussion. This method of inducing cough in subjects with URTI may be useful for studies on the mechanism of cough and for studies on antitussive medicines.

Downregulation of the cough reflex by aclidinium and tiotropium in awake and anesthetized rabbits.

PubMed

Mutolo, Donatella; Cinelli, Elenia; Iovino, Ludovica; Pantaleo, Tito; Bongianni, Fulvia

2016-06-01

Long-acting muscarinic receptor antagonists (LAMAs) have been reported to attenuate cough in preclinical and clinical studies. The present study was performed on rabbits to compare aclidinium and tiotropium efficacy in the downregulation of the cough reflex. This reflex was evoked by citric acid inhalation in unanesthetized animals and by both citric acid inhalation and mechanical stimulation of the tracheobronchial tree in anesthetized animals 90 min following the inhalation of each drug (nebulizer output always at 1 mL/min). Aclidinium 4 mg/mL and tiotropium 200 μg/mL inhaled in 1 min proved to have similar protective effect on methacholine-induced bronchoconstriction in anesthetized animals. The total dosage employed for aclidinium and tiotropium was 4 mg and 200 μg, respectively. In awake animals, similar reductions in the cough number were observed following 10-min inhalation of each drug with a slight, not significant tendency to higher antitussive effects for aclidinium. In anesthetized animals, 1-min inhalation of each drug caused similar depressant effects on cough responses induced by both mechanical and chemical stimulation. A complete suppression of cough responses to mechanical stimuli was seen in some preparations. The results strongly suggest that the LAMA-induced downregulation of cough may be mediated not only by transient receptor potential vanilloid type 1 channels, as already reported, but also by acid-sensing ion channels and mechanoreceptors. The route of administration along with the more rapid hydrolysis of aclidinium into inactive metabolites minimize potential systemic side effects and give to this drug a very favorable safety profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

GABAA- and glycine-mediated inhibitory modulation of the cough reflex in the caudal nucleus tractus solitarii of the rabbit.

PubMed

Cinelli, Elenia; Iovino, Ludovica; Bongianni, Fulvia; Pantaleo, Tito; Mutolo, Donatella

2016-09-01

Cough-related sensory inputs from rapidly adapting receptors (RARs) and C fibers are processed by second-order neurons mainly located in the caudal nucleus tractus solitarii (NTS). Both GABAA and glycine receptors have been proven to be involved in the inhibitory control of second-order cells receiving RAR projections. We investigated the role of these receptors within the caudal NTS in the modulation of the cough reflex induced by either mechanical or chemical stimulation of the tracheobronchial tree in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nl) of the receptor antagonists bicuculline and strychnine as well as of the receptor agonists muscimol and glycine were performed. Bicuculline (0.1 mM) and strychnine (1 mM) caused decreases in peak abdominal activity and marked increases in respiratory frequency due to decreases in both inspiratory time (Ti) and expiratory time (Te), without concomitant changes in arterial blood pressure. Noticeably, these microinjections induced potentiation of the cough reflex consisting of increases in the cough number associated with decreases either in cough-related Ti after bicuculline or in both cough-related Ti and Te after strychnine. The effects caused by muscimol (0.1 mM) and glycine (10 mM) were in the opposite direction to those produced by the corresponding antagonists. The results show that both GABAA and glycine receptors within the caudal NTS mediate a potent inhibitory modulation of the pattern of breathing and cough reflex responses. They strongly suggest that disinhibition is one important mechanism underlying cough regulation and possibly provide new hints for novel effective antitussive strategies. Copyright © 2016 the American Physiological Society.

Effects of a novel sodium channel blocker, GSK2339345, in patients with refractory chronic cough
.

PubMed

Smith, Jaclyn A; McGarvey, Lorcan P A; Badri, Huda; Satia, Imran; Warren, Francis; Siederer, Sarah; Liefaard, Lia; Murdoch, Robert D; Povey, Kathryn; Marks-Konczalik, Joanna

2017-09-01

Voltage-gated sodium channels (VGSC) are important in the initiation and propagation of action potentials in afferent sensory nerve fibers responsible for evoking cough. This study investigated the efficacy of GSK2339345, a VGSC inhibitor, in the treatment of refractory chronic cough (RCC). A three-part randomized, double-blind, placebo-controlled, cross-over study was conducted in the UK. In part A, patients with RCC received two inhaled doses of either GSK2339345 or placebo, 4 hours apart during three study periods. Patients were monitored for cough for 8 hours post-first dose using the VitaloJAK, ambulatory cough monitor. In parts B and C, patients underwent full dose-response cough challenges with capsaicin and citric acid respectively following single doses of randomly assigned GSK2339345 or placebo (4 study days). Part A was analyzed using a mixed effects model and parts B and C using population non-linear mixed effects models. Of 16 enrolled patients, 11 completed the study. 8-hour cough counts increased following GSK2339345 treatment compared with placebo (GSK2339345/placebo ratio of adjusted geometric means: 1.26 (90% credible interval 1.10, 1.44), associated with GSK2339345-evoked coughing, recorded during the 2 minutes post-dose. This was not observed with placebo. The effect of GSK2339345 on cough responses during cough challenges was inconclusive. GSK2339345 was well tolerated. While these data could not determine if GSK2339345 reached the target VGSC, they strongly suggest that GSK2339345 has no anti-tussive effect despite reaching airway sensory nerves as evidenced by the evoked transient cough.
.

Quantitative determination of mogroside V in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

PubMed

Yan, Huiyu; Tao, Lina; Qu, Xiaoyu; Zhou, Liting; Zhang, Sixi

2018-05-01

Mogroside V is the most abundant (approximately 0.50%) cucurbitane-type triterpene glycoside in Siraitia grosvenorii and exhibits significant antitussive, expectorant, anti-carcinogenic, and anti-inflammatory effects. A sensitive, robust and selective liquid chromatography tandem with mass spectrometry (LC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of mogroside V in rat plasma. Samples were prepared through an one-step deproteinization procedure with 250 µL of methanol to a 75-µL plasma sample. Plasma samples were effectively separated on a Shiseido Capcell Pak UG120 C18 column (2.0 × 50mm, 3.0µm) using a mobile phase consisting of methanol: water (60:40, v/v) with an isocratic elution program. The running time for each sample was 7.0 min and the elution times of mogroside V and IS were 2.0 and 4.8 min, respectively. The detection relied on a triple-quadrupole tandem with mass spectrometer equipped with negative-ion electrospray ionization interface by selected-reaction monitoring (SRM) of the transitions at m/z 1285.6 → 1123.7 for mogroside V and m/z 1089.6 → 649.6 for IS. The calibration curve was linear over the range of 96.0-96000ng/mL with a limit of quantitation (LOQ) of 96.0ng/mL. Intra-day and inter-day precisions were both <10.1%. Mean recovery and matrix effect of mogroside V in plasma were in the range of 91.3-95.7% and 98.2-105.0%, respectively. This method was successfully applied in the pharmacokinetic study of mogroside V after intravenous or intraperitoneal administration of 1.12mg/kg mogroside V in rats.

High-speed countercurrent chromatographic recovery and off-line electrospray ionization mass spectrometry profiling of bisdesmodic saponins from Saponaria officinalis possessing synergistic toxicity enhancing properties on targeted antitumor toxins.

PubMed

Thakur, Mayank; Jerz, Gerold; Tuwalska, Dorota; Gilabert-Oriol, Roger; Wybraniec, Sławomir; Winterhalter, Peter; Fuchs, Hendrik; Weng, Alexander

2014-04-01

Saponaria officinalis L. (Caryophyllaceae), also known as fuller's herb or soapwort is a medicinal plant, which grows from Europe to Central Asia. Medicinal properties attributed to this plant include its antitussive and galactogogue properties. Recently, bisdesmodic saponins with very specific structural features from S. officinalis have been shown to strongly enhance the efficacy of specific targeted toxins (anti-tumor antibodies connected to protein toxins) in-vitro and in-vivo in a synergistic manner. In the presently reported novel approach we used preparative all-liquid high-speed countercurrent chromatography (HSCCC) to recover a total of 22 fractions using biphasic solvent system tert-butylmethylether/n-butanol/acetonitrile/water 1:3:1:5 (v/v/v/v) from a complex precipitated crude saponin mixture. Out of these 22 fractions, 3 fractions had the enhancer effect on anti-tumor toxins out of which one fraction (F7) was further tested elaborately in different cell lines. The molecular weight distribution and compound profiles of separated saponins were monitored by off-line injections of the sequentially collected fractions to an electrospray ion-trap mass-spectrometry system (ESI-IT-MS). The functional saponin fractions were mainly bisdesmosidc and contained saponin m/z 1861 amongst other. Using the bio-assay guided monitoring, the highly active fractions containing 2 to 3 bisdesmodic saponins (5μg/mL) were screened for their effectiveness in enhancing the anti-tumor activity of targeted toxin Sap3-EGF, which was determined using the impedance based real-time cell cytotoxicity evaluation. This novel combination of HSCCC fractionation, MS-target-guided profiling procedure and bio-assay guided fractionation yielded 100mg of functional saponins from a 60g crude drug powder in a rapid and convenient manner. Copyright © 2014 Elsevier B.V. All rights reserved.

Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

PubMed Central

Sasaki, Tsuyoshi; Hashimoto, Kenji; Tachibana, Masumi; Kurata, Tsutomu; Okawada, Keiko; Ishikawa, Maki; Kimura, Hiroshi; Komatsu, Hideki; Ishikawa, Masatomo; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shiraishi, Tetsuya; Iyo, Masaomi

2014-01-01

Background Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK)-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD) symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD. Subjects and methods This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0) received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS), Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS), Japanese version. Results A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores) improved significantly (P<0.001). Furthermore, a comparison of baseline DN-CAS total scores and 4-week end-point scores showed a mild trend of improvement (P=0.093). Tipepidine was well tolerated, with no patients discontinuing medication because of side effects. Conclusion Our pilot study suggests that tipepidine therapy may prove to be an effective alternative treatment for pediatric patients with ADHD. Nonetheless, more detailed randomized, double-blind trials are needed to confirm tipepidine’s efficacy. PMID:24493927

Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice.

PubMed

Nguyen, Linda; Scandinaro, Anna L; Matsumoto, Rae R

2017-10-01

The over-the-counter antitussive dextromethorphan (DM) may have rapid antidepressant actions based on its overlapping pharmacology with ketamine, which has shown fast antidepressant effects but whose widespread use remains limited by problematic side effects. We have previously shown that DM produces antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST) that are mediated in part through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic (AMPA) and sigma-1 receptors, two protein targets associated with a faster onset of antidepressant efficacy. To utilize DM clinically, however, a major challenge that must be addressed is its rapid first-pass metabolism. Two strategies to inhibit metabolism of DM and maintain stable therapeutic blood levels are 1) chemically modifying DM and 2) adding quinidine, an inhibitor of the primary metabolizer of DM, the cytochrome P450 (CYP) 2D6 enzyme. The purpose of this study was to determine if modified DM (deuterated (d6)-DM) elicits antidepressant-like effects and if AMPA and sigma-1 receptors are involved. Furthermore, d6-DM was tested in conjunction with quinidine to determine if further slowing the metabolism of d6-DM affects its antidepressant-like actions. In the FST and TST, d6-DM produced antidepressant-like effects. Upon further investigation in the FST, the most validated animal model for predicting antidepressant efficacy, d6-DM produced antidepressant-like effects both in the absence and presence of quinidine. However, pretreatment with neither an AMPA receptor antagonist (NBQX) nor sigma-1 receptor antagonists (BD1063, BD1047) significantly attenuated the antidepressant-like effects. The data suggest d6-DM has antidepressant-like effects, though it may be recruiting different molecular targets and/or acting through a different mix or ratio of metabolites from regular DM. Copyright © 2017 Elsevier Inc. All rights reserved.

Cough induced by mechanical stimulation of the upper airway in humans.

PubMed

Lee, Patrick; Eccles, Ronald

2004-08-01

Cough has previously been induced in animals by means of mechanical stimulation of the upper airway but this method has not previously been applied to humans. The aims of this study were to determine if cough could be induced in humans on mechanical stimulation of the upper airway and to see if this mechanically induced cough was reproducible. We also wished to investigate if there was any difference in cough sensitivity between healthy subjects and those with acute upper respiratory tract infection (URTI). In the first investigation, 2 groups were studied: 15 healthy subjects and 30 subjects with URTI with a mean age of 20 years. Cough was induced by vibration of the airway at the level of the trachea using a modified men's shaver. In the second investigation to determine the reproducibility of this mechanically induced cough, two groups from a different population were studied: 15 healthy subjects and 29 subjects with URTI with a mean age of 20.3 years. Cough was induced by airway vibration before and after a 90-min rest period. In the first investigation it was demonstrated that cough can be induced within 2 s of vibration; subjects with URTI are more sensitive to cough induction and cough approximately five times more than healthy subjects; cough increases with repeated stimulation and reaches a maximum after three periods of vibration; the cough response may be mediated by rapidly adapting airway sensory receptors. In the second investigation there was no significant difference in mean cough counts before and after a 90-min rest period in both groups, which demonstrates that the mechanically induced cough is reproducible. This is the first study to elicit cough in humans by mechanical stimulation of the upper airway. This new method of inducing cough in subjects with URTI may be useful for studying both the mechanism of cough and the effects of antitussive medicines.

Effect of e-Cigarette Use on Cough Reflex Sensitivity.

PubMed

Dicpinigaitis, Peter V; Lee Chang, Alfredo; Dicpinigaitis, Alis J; Negassa, Abdissa

2016-01-01

E-cigarettes (e-cigs) have attained widespread popularity, yet knowledge of their physiologic effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on cough reflex sensitivity. Thirty healthy nonsmokers underwent cough reflex sensitivity measurement using capsaicin cough challenge at baseline, 15 min, and 24 h after e-cig exposure (30 puffs 30 s apart). The end point of cough challenge is the concentration of capsaicin inducing five or more coughs (C5). The number of coughs induced by each e-cig inhalation was counted. A subgroup of subjects (n = 8) subsequently underwent an identical protocol with a non-nicotine-containing e-cig. Cough reflex sensitivity was significantly inhibited (C5 increased) 15 min after e-cig use (?0.29; 95% CI, ?0.43 to ?0.15; P < .0001); 24 h later, C5 returned to baseline (0.24; 95% CI, 0.10-0.38; P = .0002 vs post-15-min value). A subgroup of eight subjects demonstrating the largest degree of cough reflex inhibition had no suppression after exposure to a non-nicotine-containing e-cig (P = .0078 for comparison of ?C5 after nicotine vs non-nicotine device). Furthermore, more coughing was induced by the nicotine-containing vs non-nicotine-containing device (P = .0156). A single session of e-cig use, approximating nicotine exposure of one tobacco cigarette, induces significant inhibition of cough reflex sensitivity. Exploratory analysis of a subgroup of subjects suggests that nicotine is responsible for this observation. Our data, consistent with previous studies of nicotine effect, suggest a dual action of nicotine: an immediate, peripheral protussive effect and a delayed central antitussive effect. ClinicalTrials.gov; No.: NCT02203162; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Perceived health properties of wild and cultivated food plants in local and popular traditions of Italy: A review.

PubMed

Guarrera, P M; Savo, V

2013-04-19

Many wild and cultivated plants are rich in mineral elements and bioactive compounds and are consumed for health purposes. Studies have demonstrated the curative properties of many of these food plants. In this paper, we discuss the properties of several plants with potential health benefits that have previously received little attention. This review provides an overview and critical discussion of food plants perceived by informants (emic view) as healthy or used as 'food medicine' in Italy. Pharmacological activity of these plants is explored, based upon published scientific research (etic view). Preparation methods, taste perception, toxicity and various potentialities of some food plants are also discussed. The present review includes literature available from 1877 to 2012. The information was collected from books, scientific papers, and abstracts that reported any plants used as food medicine in Italy. The perceived health properties were analyzed in the framework of recent international phytochemical and phytopharmacological literature. A total of 67 edible wild plants and 18 cultivated vegetables, distributed into 20 families, were reported by informants (in literature). Several plants were highly cited (e.g., Taraxacum officinale Webb., Crepis vesicaria L., Allium cepa L., Allium sativum L.). The most frequent health properties attributed to edible plants by the informants were: laxative (22 species), diuretic (15), digestive (11), galactagogue (8), antitussive (cough) (8), hypotensive (7), tonic (7), sedative (7), hypoglycemic (6). Some edible plants are promising for their potential health properties, such as Crepis vesicaria L., Sanguisorba minor Scop. and Sonchus oleraceus L. Several wild species were perceived by informants to maintain health but have never been studied from a phytochemical or pharmacological point of view: e.g., Asparagus albus L., Crepis leontodontoides All., Hyoseris radiata L. subsp. radiata, Phyteuma spicatum L. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

40 CFR 300.910 - Authorization of use.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dispersants, surface washing agents, surface collecting agents, bioremediation agents, or miscellaneous oil... agents, surface collecting agents, bioremediation agents, or miscellaneous oil spill control agents on..., bioremediation agent, or miscellaneous oil spill control agent, including products not listed on the NCP Product...

40 CFR 300.910 - Authorization of use.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dispersants, surface washing agents, surface collecting agents, bioremediation agents, or miscellaneous oil... agents, surface collecting agents, bioremediation agents, or miscellaneous oil spill control agents on..., bioremediation agent, or miscellaneous oil spill control agent, including products not listed on the NCP Product...

40 CFR 300.910 - Authorization of use.

Code of Federal Regulations, 2014 CFR

2014-07-01

... dispersants, surface washing agents, surface collecting agents, bioremediation agents, or miscellaneous oil... agents, surface collecting agents, bioremediation agents, or miscellaneous oil spill control agents on..., bioremediation agent, or miscellaneous oil spill control agent, including products not listed on the NCP Product...

40 CFR 300.910 - Authorization of use.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dispersants, surface washing agents, surface collecting agents, bioremediation agents, or miscellaneous oil... agents, surface collecting agents, bioremediation agents, or miscellaneous oil spill control agents on..., bioremediation agent, or miscellaneous oil spill control agent, including products not listed on the NCP Product...

78 FR 22256 - Proposed Information Collection Request; Comment Request; The National Oil and Hazardous...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... Chemicals''). The use of bioremediation agents, dispersants, surface washing agents, surface collecting... basic categories: dispersants, surface washing agents, surface collecting agents, bioremediation agents..., manufacturers of bioremediation agents, dispersants, surface collecting agents, surface washing agents...

Emergency management of chemical weapons injuries.

PubMed

Anderson, Peter D

2012-02-01

The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia.

40 CFR 300.920 - Addition of products to Schedule.

Code of Federal Regulations, 2011 CFR

2011-07-01

... manufacturer of his decision in writing. (b) Surface washing agents, surface collecting agents, bioremediation... collecting agent, bioremediation agent, or miscellaneous oil spill control agent to the NCP Product Schedule... collecting agent, bioremediation agent, or miscellaneous oil spill control agent. On the basis of this data...

40 CFR 300.920 - Addition of products to Schedule.

Code of Federal Regulations, 2014 CFR

2014-07-01

... manufacturer of his decision in writing. (b) Surface washing agents, surface collecting agents, bioremediation... collecting agent, bioremediation agent, or miscellaneous oil spill control agent to the NCP Product Schedule... collecting agent, bioremediation agent, or miscellaneous oil spill control agent. On the basis of this data...

40 CFR 300.920 - Addition of products to Schedule.

Code of Federal Regulations, 2012 CFR

2012-07-01

... manufacturer of his decision in writing. (b) Surface washing agents, surface collecting agents, bioremediation... collecting agent, bioremediation agent, or miscellaneous oil spill control agent to the NCP Product Schedule... collecting agent, bioremediation agent, or miscellaneous oil spill control agent. On the basis of this data...

40 CFR 300.920 - Addition of products to Schedule.

Code of Federal Regulations, 2013 CFR

2013-07-01

... manufacturer of his decision in writing. (b) Surface washing agents, surface collecting agents, bioremediation... collecting agent, bioremediation agent, or miscellaneous oil spill control agent to the NCP Product Schedule... collecting agent, bioremediation agent, or miscellaneous oil spill control agent. On the basis of this data...

40 CFR 300.920 - Addition of products to Schedule.

Code of Federal Regulations, 2010 CFR

2010-07-01

... manufacturer of his decision in writing. (b) Surface washing agents, surface collecting agents, bioremediation... collecting agent, bioremediation agent, or miscellaneous oil spill control agent to the NCP Product Schedule... collecting agent, bioremediation agent, or miscellaneous oil spill control agent. On the basis of this data...

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.

PubMed

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.

Chiral analyses of dextromethorphan/levomethorphan and their metabolites in rat and human samples using LC-MS/MS.

PubMed

Kikura-Hanajiri, Ruri; Kawamura, Maiko; Miyajima, Atsuko; Sunouchi, Momoko; Goda, Yukihiro

2011-04-01

In order to develop an analytical method for the discrimination of dextromethorphan (an antitussive medicine) from its enantiomer, levomethorphan (a narcotic) in biological samples, chiral analyses of these drugs and their O-demethyl and/or N-demethyl metabolites in rat plasma, urine, and hair were carried out using LC-MS/MS. After the i.p. administration of dextromethorphan or levomethorphan to pigmented hairy male DA rats (5 mg/kg/day, 10 days), the parent compounds and their three metabolites in plasma, urine and hair were determined using LC-MS/MS. Complete chiral separation was achieved in 12 min on a Chiral CD-Ph column in 0.1% formic acid-acetonitrile by a linear gradient program. Most of the metabolites were detected as being the corresponding O-demethyl and N, O-didemethyl metabolites in the rat plasma and urine after the hydrolysis of O-glucuronides, although obvious differences in the amounts of these metabolites were found between the dextro and levo forms. No racemation was observed through O- and/or N-demethylation. In the rat hair samples collected 4 weeks after the first administration, those differences were more clearly detected and the concentrations of the parent compounds, their O-demethyl, N-demethyl, and N, O-didemethyl metabolites were 63.4, 2.7, 25.1, and 0.7 ng/mg for the dextro forms and 24.5, 24.6, 2.6, and 0.5 ng/mg for the levo forms, respectively. In order to fully investigate the differences of their metabolic properties between dextromethorphan and levomethorphan, DA rat and human liver microsomes were studied. The results suggested that there might be an enantioselective metabolism of levomethorphan, especially with regard to the O-demethylation, not only in DA rat but human liver microsomes as well. The proposed chiral analyses might be applied to human samples and could be useful for discriminating dextromethorphan use from levomethorphan use in the field of forensic toxicology, although further studies should be carried out using authentic human samples.

Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae

Highlights: {yields} Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. {yields} PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. {yields} PRPA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} PRPAs attenuate HFD-induced obesity by activating AMPK and PPAR{delta}, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remainsmore » unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor {delta} (PPAR{delta}) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPAR{delta} protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. Consistent with the in vitro results, PRPA activated AMPK signaling and altered the expression of lipid metabolism-related proteins in liver and skeletal muscle. Taken together, these findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK and PPAR{delta}, and regulate lipid metabolism, suggesting their potential anti-obesity effects.« less

Influence of ethnic group on asthma treatment in children in 1990-1: national cross sectional study.

PubMed Central

Duran-Tauleria, E.; Rona, R. J.; Chinn, S.; Burney, P.

1996-01-01

OBJECTIVE--To examine the extent to which the prescription of drugs for asthma adhered to recommended guidelines in 1990-1 and to assess the influence of ethnic group on prescription. DESIGN--Cross sectional. SETTING--Primary schools in England and Scotland in 1990-1. SUBJECTS--Children aged mainly 5-11 years. The representative samples included 10628 children. The inner city sample included 7049 children, 4866 (69%) from ethnic minority groups. For the prevalence estimation 14490 children were included in the analysis (82% of the eligible children). For the treatment analysis a subgroup of 5494 children with respiratory symptoms was selected. MAIN OUTCOME MEASURES--Prevalence of respiratory symptoms and drugs commonly prescribed for asthma, method of administration, inappropriate treatment, and odds ratios to assess the effect of ethnic group on rate of prescription and method of administration. RESULTS--Children with respiratory symptoms in the inner city sample were less likely to be diagnosed as having asthma. Of children with reported asthma attacks, those in inner city areas had a higher risk of not having been prescribed any drug for asthma (odds ratio 1.87 (95% confidence interval 1.26 to 2.77). Overall, 773 (75%) of these children had received a beta 2 agonist, 259 (25%) had received steroids, 148 (14%) had received sodium cromoglycate, and 194 (19%) had received no drug treatment in the previous year. When prescribed, beta 2 agonists were inhaled in 534 (69%) of cases, and this percentage was even lower in ethnic minority groups. Children of Afro-Caribbean and Indian subcontinent origin who had asthma were less likely to receive beta 2 agonists, and those from the Indian subcontinent were less likely to receive anti-inflammatory drugs. Antibiotics were less prescribed and antitussives more prescribed in children from ethnic minority groups than in white children. CONCLUSION--In 1990-1 the risk of underdiagnosis and undertreatment of asthma was higher in children from ethnic minority groups. The implementation of indicators and targets to monitor inequalities in the treatment of asthma in ethnic groups could improve equity and effectiveness in the NHS. PMID:8688777

Technological Evaluation of Emulsions Containing The Volatile Oil from Leaves of Plectranthus Amboinicus Lour

PubMed Central

Lopes, Pablo Queiroz; Carneiro, Fabíola Bernardo; de Sousa, Ana Letícia Braz; Santos, Sócrates Golziodo; Oliveira, Elquio Eleamen; Soares, Luiz Alberto Lira

2017-01-01

Background: Plectranthus amboinicus Lour is a species which is widespread throughout tropical countries where it is widely used against respiratory tract disorders such as bronchodilator, antitussive, and expectorant conditions. Objective: This study aims to characterize the essential oil of P. amboinicus (PaEO) and produce and evaluate emulsions containing PaEO. Materials and Methods: The essential oil was characterized by physical-chemical analyses for density, refractive index, 90% ethanol solubility, color, appearance, and identification by gas chromatography coupled to mass spectrometry detection. The emulsions were prepared following a hydrophile-lipophile balance [HLB] spreadsheet design from two nonionic surfactants (Span 80® and Tween 20®) producing HLB values ranging from 4.3 to 16.7. The products were stored at room temperature at 5°C. The emulsion stabilities were tested both in the long and short-term. Results: The PaEO was obtained by steam distillation and the total extraction was reached after 3 hours yielding of 0.2% (w/w). This essential oil was characterized by physicochemical analyses for density [1.5 g.ml-1], refraction index [0.9167], ethanol 90% solubility [1:2], color, and appearance (yellow/clear). Nineteen components were identified in the oil, among them the sesquiterpenes: carvacrol [33.50%], p-cymene [28.20%] and γ-terpinene [14.77%]. The emulsions obtained successfully showed, for the first time, HLB values for essential oils from Plectranthus amboinicus [15.7]. Conclusion: The experimental data shows a relationship between HLB values of the surfactant mixtures contributing to the emulsified systems production containing phytopharmaceuticals. Such an approach is of great importance to the development of lipid carriers for therapeutic drugs. SUMMARY The essential oil from leaves of Plectranthus amboinicus was extracted by steam distillation and characterized.The emulsions containing essential oil were produced and the stability was performed in the short and long term.The critical hydrophilic-lipophilic balance (HLB) of the essential oil was 15.7 and was achieved by the combination of surfactants (Tween 80® and Span 20®). Abbreviations used: PaEO: essential oil of P. amboinicus, HLB: hydrophilic-lipophilic balance, CI: Creaming Index, MET: micro-emultocrit technique PMID:28216901

Mechanical induction of cough in Idiopathic Pulmonary Fibrosis

PubMed Central

2011-01-01

Background Patients with idiopathic pulmonary fibrosis (IPF) frequently develop a dry, irritating cough which often proves refractory to anti-tussive therapies. The precise pathogenetic mechanisms responsible for this cough are unknown. We hypothesised that changes in nerves modulating mechanical sensitivity in areas of interstitial fibrosis might lead to enhanced cough response to mechanical stimulation of the chest in IPF. Methods We studied 27 non-smoking subjects with IPF (63% male), mean (SD) age 71.7 (7) years and 30 healthy non-smokers. Quality of life (Leicester Cough Questionnaire), cough symptom scores and cough severity scores (visual analog scales) were recorded. Percussion stimulation was applied over the posterior lung base, upper anterior chest and manubrium sternum at sequential frequencies (20 Hertz (Hz), 40 Hz and 60 Hz) for up to 60 seconds and repeated twice at two minute intervals. The number of subjects achieving two and five-cough responses, total cough counts and cough latency were recorded. In separate experiments, the effect of mechanical stimulation on the pattern of breathing was determined in eight IPF subjects and five control subjects. Results In patients with IPF, we demonstrated strong correlations between subjective cough measurements, particularly the cough symptom score and Leicester Cough Questionnaire (r = -0.86; p < 0.001). Mechanical percussion induced a true cough reflex in 23/27 (85%) IPF subjects, but only 5/30 (17%) controls (p < 0.001). More patients with IPF reached the two-cough response at a lower frequency (20 Hz) posteriorly than at other positions. Highest mean cough totals were seen with stimulation at or above 40 Hz. Mechanical stimulation had no effect on respiratory rate but increased tidal volume in four (50%) subjects with IPF, particularly at higher frequencies. It was associated with increased urge to cough followed by a true cough reflex. Conclusions This study demonstrates that patients with IPF show enhanced cough reflex sensitivity to mechanical stimulation of the chest wall whilst normal individuals show little or no response. The observation that low frequency stimulation over the lung base, where fibrosis is most extensive, induces cough in more patients than at other sites supports the hypothesis that lung distortion contributes to the pathogenesis of cough in IPF. PMID:21477349

Bergenin, Acting as an Agonist of PPARγ, Ameliorates Experimental Colitis in Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-κB-Mediated Macrophage Activation.

PubMed

Wang, Kai; Li, Yun-Fan; Lv, Qi; Li, Xi-Ming; Dai, Yue; Wei, Zhi-Feng

2017-01-01

Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao), has anti-inflammatory, antitussive and wound healing activities. The aim of the present study was to identify the effect of bergenin on experimental colitis, and explored the related mechanisms. Our results showed that oral administration of bergenin remarkably alleviated disease symptoms of mice with dextran sulfate sodium (DSS)-induced colitis, evidenced by reduced DAI scores, shortening of colon length, MPO activity and pathologic abnormalities in colons. Bergenin obviously inhibited the mRNA and protein expressions of IL-6 and TNF-α in colon tissues, but not that of mucosal barrier-associated proteins occludin, E -cadherin and MUC-2. In vitro , bergenin significantly inhibited the expressions of IL-6 and TNF-α as well as nuclear translocation and DNA binding activity of NF-κB-p65 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and RAW264.7 cells, which was almost reversed by addition of PPARγ antagonist GW9662 and siPPARγ. Subsequently, bergenin was identified as a PPARγ agonist. It could enter into macrophages, bind with PPARγ, promote nuclear translocation and transcriptional activity of PPARγ, and increase mRNA expressions of CD36, LPL and ap2. In addition, bergenin significantly up-regulated expression of SIRT1, inhibited acetylation of NF-κB-p65 and increased association NF-κB-p65 and IκBα. Finally, the correlation between activation of PPARγ and attenuation of colitis, inhibition of IL-6 and TNF-α expressions, NF-κB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could ameliorate colitis in mice through inhibiting the activation of macrophages via regulating PPARγ/SIRT1/NF-κB-p65 pathway. The findings can provide evidence for the further development of bergenin as an anti-UC drug, and offer a paradigm for the recognization of anti-UC mechanisms of compound with similar structure occurring in traditional Chinese medicines.

Petri Nets as Modeling Tool for Emergent Agents

NASA Technical Reports Server (NTRS)

Bergman, Marto

2004-01-01

Emergent agents, those agents whose local interactions can cause unexpected global results, require a method of modeling that is both dynamic and structured Petri Nets, a modeling tool developed for dynamic discrete event system of mainly functional agents, provide this, and have the benefit of being an established tool. We present here the details of the modeling method here and discuss how to implement its use for modeling agent-based systems. Petri Nets have been used extensively in the modeling of functional agents, those agents who have defined purposes and whose actions should result in a know outcome. However, emergent agents, those agents who have a defined structure but whose interaction causes outcomes that are unpredictable, have not yet found a modeling style that suits them. A problem with formally modeling emergent agents that any formal modeling style usually expects to show the results of a problem and the results of problems studied using emergent agents are not apparent from the initial construction. However, the study of emergent agents still requires a method to analyze the agents themselves, and have sensible conversation about the differences and similarities between types of emergent agents. We attempt to correct this problem by applying Petri Nets to the characterization of emergent agents. In doing so, the emergent properties of these agents can be highlighted, and conversation about the nature and compatibility of the differing methods of agent creation can begin.

Clustering recommendations to compute agent reputation

NASA Astrophysics Data System (ADS)

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.

Forest Service special agents, assistant special agents in charge, senior special agents, and supervisory special agents report: nationwide study

Treesearch

Deborah J. Chavez; Joanne F. Tynon

2007-01-01

This is the fourth in a series of studies to evaluate perceptions of U.S. Department of Agriculture Forest Service law enforcement personnel of the roles, responsibilities, and issues related to their jobs. An e-mail survey was administered to the 89 Forest Service special agents, assistant special agents in charge, senior special agents, and supervisory special agents...

Chemical warfare agents.

PubMed

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.

Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

PubMed Central

Sinharay, Sanhita; Pagel, Mark D.

2016-01-01

Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

Needs, Pains, and Motivations in Autonomous Agents.

PubMed

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

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

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

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

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 T2-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 T1 and T2 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. PMID:27747191

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

ERIC Educational Resources Information Center

Baker, Lauri M.; Hadley, Gregg

2014-01-01

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

Burnout among Extension Agents in the Ohio Cooperative Extension Service.

ERIC Educational Resources Information Center

Igodan, O. Chris; Newcomb, L. H.

A study examined the extent and causes of burnout among extension agents in Ohio. From the 241 extension agents working in the 88 counties of Ohio, researchers selected a random sample of 101 agents. Included in the sample were 34 agriculture agents, 33 home economics agents. Included in the sample agents were asked to complete a survey…

CATS-based Agents That Err

NASA Technical Reports Server (NTRS)

Callantine, Todd J.

2002-01-01

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

Resilient Distributed Estimation Through Adversary Detection

NASA Astrophysics Data System (ADS)

Chen, Yuan; Kar, Soummya; Moura, Jose M. F.

2018-05-01

This paper studies resilient multi-agent distributed estimation of an unknown vector parameter when a subset of the agents is adversarial. We present and analyze a Flag Raising Distributed Estimator ($\\mathcal{FRDE}$) that allows the agents under attack to perform accurate parameter estimation and detect the adversarial agents. The $\\mathcal{FRDE}$ algorithm is a consensus+innovations estimator in which agents combine estimates of neighboring agents (consensus) with local sensing information (innovations). We establish that, under $\\mathcal{FRDE}$, either the uncompromised agents' estimates are almost surely consistent or the uncompromised agents detect compromised agents if and only if the network of uncompromised agents is connected and globally observable. Numerical examples illustrate the performance of $\\mathcal{FRDE}$.

System for reactivating catalysts

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Anderson, Raymond P.

2010-03-02

A method of reactivating a catalyst, such as a solid catalyst or a liquid catalyst is provided. The method comprises providing a catalyst that is at least partially deactivated by fouling agents. The catalyst is contacted with a fluid reactivating agent that is at or above a critical point of the fluid reactivating agent and is of sufficient density to dissolve impurities. The fluid reactivating agent reacts with at least one fouling agent, releasing the at least one fouling agent from the catalyst. The at least one fouling agent becomes dissolved in the fluid reactivating agent and is subsequently separated or removed from the fluid reactivating agent so that the fluid reactivating agent may be reused. A system for reactivating a catalyst is also disclosed.

Design and Simulation of Material-Integrated Distributed Sensor Processing with a Code-Based Agent Platform and Mobile Multi-Agent Systems

PubMed Central

Bosse, Stefan

2015-01-01

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques. PMID:25690550

Design and simulation of material-integrated distributed sensor processing with a code-based agent platform and mobile multi-agent systems.

PubMed

Bosse, Stefan

2015-02-16

Multi-agent systems (MAS) can be used for decentralized and self-organizing data processing in a distributed system, like a resource-constrained sensor network, enabling distributed information extraction, for example, based on pattern recognition and self-organization, by decomposing complex tasks in simpler cooperative agents. Reliable MAS-based data processing approaches can aid the material-integration of structural-monitoring applications, with agent processing platforms scaled to the microchip level. The agent behavior, based on a dynamic activity-transition graph (ATG) model, is implemented with program code storing the control and the data state of an agent, which is novel. The program code can be modified by the agent itself using code morphing techniques and is capable of migrating in the network between nodes. The program code is a self-contained unit (a container) and embeds the agent data, the initialization instructions and the ATG behavior implementation. The microchip agent processing platform used for the execution of the agent code is a standalone multi-core stack machine with a zero-operand instruction format, leading to a small-sized agent program code, low system complexity and high system performance. The agent processing is token-queue-based, similar to Petri-nets. The agent platform can be implemented in software, too, offering compatibility at the operational and code level, supporting agent processing in strong heterogeneous networks. In this work, the agent platform embedded in a large-scale distributed sensor network is simulated at the architectural level by using agent-based simulation techniques.

BSL-3 laboratory practices in the United States: comparison of select agent and non-select agent facilities.

PubMed

Richards, Stephanie L; Pompei, Victoria C; Anderson, Alice

2014-01-01

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non-select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non-select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non-select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non-select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non-select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non-select agent laboratories to improve occupational health and safety.

BSL-3 Laboratory Practices in the United States: Comparison of Select Agent and Non–Select Agent Facilities

PubMed Central

Pompei, Victoria C.; Anderson, Alice

2014-01-01

New construction of biosafety level 3 (BSL-3) laboratories in the United States has increased in the past decade to facilitate research on potential bioterrorism agents. The Centers for Disease Control and Prevention inspect BSL-3 facilities and review commissioning documentation, but no single agency has oversight over all BSL-3 facilities. This article explores the extent to which standard operating procedures in US BSL-3 facilities vary between laboratories with select agent or non–select agent status. Comparisons are made for the following variables: personnel training, decontamination, personal protective equipment (PPE), medical surveillance, security access, laboratory structure and maintenance, funding, and pest management. Facilities working with select agents had more complex training programs and decontamination procedures than non–select agent facilities. Personnel working in select agent laboratories were likely to use powered air purifying respirators, while non–select agent laboratories primarily used N95 respirators. More rigorous medical surveillance was carried out in select agent workers (although not required by the select agent program) and a higher level of restrictive access to laboratories was found. Most select agent and non–select agent laboratories reported adequate structural integrity in facilities; however, differences were observed in personnel perception of funding for repairs. Pest management was carried out by select agent personnel more frequently than non–select agent personnel. Our findings support the need to promote high quality biosafety training and standard operating procedures in both select agent and non–select agent laboratories to improve occupational health and safety. PMID:24552359

Multi-Agent Patrolling under Uncertainty and Threats.

PubMed

Chen, Shaofei; Wu, Feng; Shen, Lincheng; Chen, Jing; Ramchurn, Sarvapali D

2015-01-01

We investigate a multi-agent patrolling problem where information is distributed alongside threats in environments with uncertainties. Specifically, the information and threat at each location are independently modelled as multi-state Markov chains, whose states are not observed until the location is visited by an agent. While agents will obtain information at a location, they may also suffer damage from the threat at that location. Therefore, the goal of the agents is to gather as much information as possible while mitigating the damage incurred. To address this challenge, we formulate the single-agent patrolling problem as a Partially Observable Markov Decision Process (POMDP) and propose a computationally efficient algorithm to solve this model. Building upon this, to compute patrols for multiple agents, the single-agent algorithm is extended for each agent with the aim of maximising its marginal contribution to the team. We empirically evaluate our algorithm on problems of multi-agent patrolling and show that it outperforms a baseline algorithm up to 44% for 10 agents and by 21% for 15 agents in large domains.

Prediction, events, and the advantage of agents: the processing of semantic roles in visual narrative.

PubMed

Cohn, Neil; Paczynski, Martin

2013-11-01

Agents consistently appear prior to Patients in sentences, manual signs, and drawings, and Agents are responded to faster when presented in visual depictions of events. We hypothesized that this "Agent advantage" reflects Agents' role in event structure. We investigated this question by manipulating the depictions of Agents and Patients in preparatory actions in wordless visual narratives. We found that Agents elicited a greater degree of predictions regarding upcoming events than Patients, that Agents are viewed longer than Patients, independent of serial order, and that visual depictions of actions are processed more quickly following the presentation of an Agent vs. a Patient. Taken together these findings support the notion that Agents initiate the building of event representation. We suggest that Agent First orders facilitate the interpretation of events as they unfold and that the saliency of Agents within visual representations of events is driven by anticipation of upcoming events. Copyright © 2013 Elsevier Inc. All rights reserved.

Distributed Planning in a Mixed-Initiative Environment

DTIC Science & Technology

2008-06-01

Knowledge Sources Control Remote Blackboard Remote Knowledge Sources Remot e Data Remot e Data Java Distributed Blackboard Figure 3 - Distributed...an interface agent or planning agent and the second type is a critic agent. Agents in the DEEP architecture extend and use the Java Agent...chosen because it is fully implemented in Java , and supports these requirements. 2.3.3 Interface Agents Interface agents are the interfaces through

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

NASA Technical Reports Server (NTRS)

Tumer, Kagan

2005-01-01

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

Prediction, events, and the advantage of Agents: The processing of semantic roles in visual narrative

PubMed Central

Cohn, Neil; Paczynski, Martin

2013-01-01

Agents consistently appear prior to Patients in sentences, manual signs, and drawings, and Agents are responded to faster when presented in visual depictions of events. We hypothesized that this “Agent advantage” reflects Agents’ role in event structure. We investigated this question by manipulating the depictions of Agents and Patients in preparatory actions in a wordless visual narrative. We found that Agents elicited a greater degree of predictions regarding upcoming events than Patients, that Agents are viewed longer than Patients, independent of serial order, and that visual depictions of actions are processed more quickly following the presentation of an Agent versus a Patient. Taken together these findings support the notion that Agents initiate the building of event representation. We suggest that Agent First orders facilitate the interpretation of events as they unfold and that the saliency of Agents within visual representations of events is driven by anticipation of upcoming events. PMID:23959023

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

22 CFR 51.22 - Passport agents and passport acceptance agents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

Method of predicting a change in an economy

DOEpatents

Pryor, Richard J [Albuquerque, NM; Basu, Nipa [Albany, NY

2006-01-10

An economy whose activity is to be predicted comprises a plurality of decision makers. Decision makers include, for example, households, government, industry, and banks. The decision makers are represented by agents, where an agent can represent one or more decision makers. Each agent has decision rules that determine the agent's actions. Each agent can affect the economy by affecting variable conditions characteristic of the economy or the internal state of other agents. Agents can communicate actions through messages. On a multiprocessor computer, the agents can be assigned to processing elements.

Method for reactivating catalysts and a method for recycling supercritical fluids used to reactivate the catalysts

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Anderson, Raymond P.

2008-08-05

A method of reactivating a catalyst, such as a solid catalyst or a liquid catalyst. The method comprises providing a catalyst that is at least partially deactivated by fouling agents. The catalyst is contacted with a fluid reactivating agent that is at or above a critical point of the fluid reactivating agent and is of sufficient density to dissolve impurities. The fluid reactivating agent reacts with at least one fouling agent, releasing the at least one fouling agent from the catalyst. The at least one fouling agent becomes dissolved in the fluid reactivating agent and is subsequently separated or removed from the fluid reactivating agent so that the fluid reactivating agent may be reused. A system for reactivating a catalyst is also disclosed.

Multi-agent planning and scheduling, execution monitoring and incremental rescheduling: Application to motorway traffic

NASA Technical Reports Server (NTRS)

Mourou, Pascal; Fade, Bernard

1992-01-01

This article describes a planning method applicable to agents with great perception and decision-making capabilities and the ability to communicate with other agents. Each agent has a task to fulfill allowing for the actions of other agents in its vicinity. Certain simultaneous actions may cause conflicts because they require the same resource. The agent plans each of its actions and simultaneously transmits these to its neighbors. In a similar way, it receives plans from the other agents and must take account of these plans. The planning method allows us to build a distributed scheduling system. Here, these agents are robot vehicles on a highway communicating by radio. In this environment, conflicts between agents concern the allocation of space in time and are connected with the inertia of the vehicles. Each vehicle made a temporal, spatial, and situated reasoning in order to drive without collision. The flexibility and reactivity of the method presented here allows the agent to generate its plan based on assumptions concerning the other agents and then check these assumptions progressively as plans are received from the other agents. A multi-agent execution monitoring of these plans can be done, using data generated during planning and the multi-agent decision-making algorithm described here. A selective backtrack allows us to perform incremental rescheduling.

Construction of a Learning Agent Handling Its Rewards According to Environmental Situations

NASA Astrophysics Data System (ADS)

Moriyama, Koichi; Numao, Masayuki

The authors aim at constructing an agent which learns appropriate actions in a Multi-Agent environment with and without social dilemmas. For this aim, the agent must have nonrationality that makes it give up its own profit when it should do that. Since there are many studies on rational learning that brings more and more profit, it is desirable to utilize them for constructing the agent. Therefore, we use a reward-handling manner that makes internal evaluation from the agent's rewards, and then the agent learns actions by a rational learning method with the internal evaluation. If the agent has only a fixed manner, however, it does not act well in the environment with and without dilemmas. Thus, the authors equip the agent with several reward-handling manners and criteria for selecting an effective one for the environmental situation. In the case of humans, what generates the internal evaluation is usually called emotion. Hence, this study also aims at throwing light on emotional activities of humans from a constructive view. In this paper, we divide a Multi-Agent environment into three situations and construct an agent having the reward-handling manners and the criteria. We observe that the agent acts well in all the three Multi-Agent situations composed of homogeneous agents.

The highly intelligent virtual agents for modeling financial markets

NASA Astrophysics Data System (ADS)

Yang, G.; Chen, Y.; Huang, J. P.

2016-02-01

Researchers have borrowed many theories from statistical physics, like ensemble, Ising model, etc., to study complex adaptive systems through agent-based modeling. However, one fundamental difference between entities (such as spins) in physics and micro-units in complex adaptive systems is that the latter are usually with high intelligence, such as investors in financial markets. Although highly intelligent virtual agents are essential for agent-based modeling to play a full role in the study of complex adaptive systems, how to create such agents is still an open question. Hence, we propose three principles for designing high artificial intelligence in financial markets and then build a specific class of agents called iAgents based on these three principles. Finally, we evaluate the intelligence of iAgents through virtual index trading in two different stock markets. For comparison, we also include three other types of agents in this contest, namely, random traders, agents from the wealth game (modified on the famous minority game), and agents from an upgraded wealth game. As a result, iAgents perform the best, which gives a well support for the three principles. This work offers a general framework for the further development of agent-based modeling for various kinds of complex adaptive systems.

Computation of the target state and feedback controls for time optimal consensus in multi-agent systems

NASA Astrophysics Data System (ADS)

Mulla, Ameer K.; Patil, Deepak U.; Chakraborty, Debraj

2018-02-01

N identical agents with bounded inputs aim to reach a common target state (consensus) in the minimum possible time. Algorithms for computing this time-optimal consensus point, the control law to be used by each agent and the time taken for the consensus to occur, are proposed. Two types of multi-agent systems are considered, namely (1) coupled single-integrator agents on a plane and, (2) double-integrator agents on a line. At the initial time instant, each agent is assumed to have access to the state information of all the other agents. An algorithm, using convexity of attainable sets and Helly's theorem, is proposed, to compute the final consensus target state and the minimum time to achieve this consensus. Further, parts of the computation are parallelised amongst the agents such that each agent has to perform computations of O(N2) run time complexity. Finally, local feedback time-optimal control laws are synthesised to drive each agent to the target point in minimum time. During this part of the operation, the controller for each agent uses measurements of only its own states and does not need to communicate with any neighbouring agents.

Security patterns and a weighting scheme for mobile agents

NASA Astrophysics Data System (ADS)

Walker, Jessie J.

The notion of mobility has always been a prime factor in human endeavor and achievement. This need to migrate by humans has been distilled into software entities, which are their representatives on distant environments. Software agents are developed to act on behalf of a user. Mobile agents were born from the understanding that many times it was much more useful to move the code (program) to where the resources are located, instead of connecting remotely. Within the mobile agent research community, security has traditionally been the most defining issue facing the community and preventing the paradigm from gaining wide acceptance. There are still numerous difficult problems being addressed with very few practical solutions, such as the malicious host and agent problems. These problems are some of the most active areas of research within the mobile agent community. The major principles, facets, fundamental concepts, techniques and architectures of the field are well understood within the community. This is evident by the many mobile agent systems developed in the last decade that share common core components such as agent management, communication facilities, and mobility services. In other words new mobile agent systems and frameworks do not provide any new insights into agent system architecture or mobility services, agent coordination, communication that could be useful to the agent research community, although these new mobile agent systems do in many instances validate, refine, demonstrate the reuse of many previously proposed and discussed mobile agent research elements. Since mobile agent research for the last decade has been defined by security and related issues, our research into security patterns are within this narrow arena of mobile agent research. The research presented in this thesis examines the issue of mobile agent security from the standpoint of security pattern documented from the universe of mobile agent systems. In addition, we explore how these documented security patterns can be quantitatively compared based on a unique weighting scheme. The scheme is formalized into a theory that can be used improve the development of secure mobile agents and agent-based systems.

Security Measures to Protect Mobile Agents

NASA Astrophysics Data System (ADS)

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

2010-11-01

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

Liposome encapsulation of chelating agents

DOEpatents

Rahman, Yueh Erh

1976-01-13

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

Mobile agent location in distributed environments

NASA Astrophysics Data System (ADS)

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

2012-12-01

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

A Systematic Review of Pedagogical Agents' Persona, Motivation, and Cognitive Load Implications for Learners

ERIC Educational Resources Information Center

Schroeder, Noah L.; Adesope, Olusola O.

2014-01-01

After more than a decade of pedagogical agent research, this review synthesizes the affective implications of learning with pedagogical agents. The review investigates different affective measures within 99 pedagogical agent outcome measures. The results suggest that learners may prefer pedagogical agents compared to non-agent control conditions,…

76 FR 2617 - User Fees Relating to Enrolled Agents and Enrolled Retirement Plan Agents; Hearing Cancellation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

... User Fees Relating to Enrolled Agents and Enrolled Retirement Plan Agents; Hearing Cancellation AGENCY... regulations relating to the imposition of user fees for enrolled agents and enrolled retirement plan agents... FURTHER INFORMATION CONTACT: Richard A. Hurst of the Publications and Regulations Branch, Legal Processing...

The agent-based spatial information semantic grid

NASA Astrophysics Data System (ADS)

Cui, Wei; Zhu, YaQiong; Zhou, Yong; Li, Deren

2006-10-01

Analyzing the characteristic of multi-Agent and geographic Ontology, The concept of the Agent-based Spatial Information Semantic Grid (ASISG) is defined and the architecture of the ASISG is advanced. ASISG is composed with Multi-Agents and geographic Ontology. The Multi-Agent Systems are composed with User Agents, General Ontology Agent, Geo-Agents, Broker Agents, Resource Agents, Spatial Data Analysis Agents, Spatial Data Access Agents, Task Execution Agent and Monitor Agent. The architecture of ASISG have three layers, they are the fabric layer, the grid management layer and the application layer. The fabric layer what is composed with Data Access Agent, Resource Agent and Geo-Agent encapsulates the data of spatial information system so that exhibits a conceptual interface for the Grid management layer. The Grid management layer, which is composed with General Ontology Agent, Task Execution Agent and Monitor Agent and Data Analysis Agent, used a hybrid method to manage all resources that were registered in a General Ontology Agent that is described by a General Ontology System. The hybrid method is assembled by resource dissemination and resource discovery. The resource dissemination push resource from Local Ontology Agent to General Ontology Agent and the resource discovery pull resource from the General Ontology Agent to Local Ontology Agents. The Local Ontology Agent is derived from special domain and describes the semantic information of local GIS. The nature of the Local Ontology Agents can be filtrated to construct a virtual organization what could provides a global scheme. The virtual organization lightens the burdens of guests because they need not search information site by site manually. The application layer what is composed with User Agent, Geo-Agent and Task Execution Agent can apply a corresponding interface to a domain user. The functions that ASISG should provide are: 1) It integrates different spatial information systems on the semantic The Grid management layer establishes a virtual environment that integrates seamlessly all GIS notes. 2) When the resource management system searches data on different spatial information systems, it transfers the meaning of different Local Ontology Agents rather than access data directly. So the ability of search and query can be said to be on the semantic level. 3) The data access procedure is transparent to guests, that is, they could access the information from remote site as current disk because the General Ontology Agent could automatically link data by the Data Agents that link the Ontology concept to GIS data. 4) The capability of processing massive spatial data. Storing, accessing and managing massive spatial data from TB to PB; efficiently analyzing and processing spatial data to produce model, information and knowledge; and providing 3D and multimedia visualization services. 5) The capability of high performance computing and processing on spatial information. Solving spatial problems with high precision, high quality, and on a large scale; and process spatial information in real time or on time, with high-speed and high efficiency. 6) The capability of sharing spatial resources. The distributed heterogeneous spatial information resources are Shared and realizing integrated and inter-operated on semantic level, so as to make best use of spatial information resources,such as computing resources, storage devices, spatial data (integrating from GIS, RS and GPS), spatial applications and services, GIS platforms, 7) The capability of integrating legacy GIS system. A ASISG can not only be used to construct new advanced spatial application systems, but also integrate legacy GIS system, so as to keep extensibility and inheritance and guarantee investment of users. 8) The capability of collaboration. Large-scale spatial information applications and services always involve different departments in different geographic places, so remote and uniform services are needed. 9) The capability of supporting integration of heterogeneous systems. Large-scale spatial information systems are always synthetically applications, so ASISG should provide interoperation and consistency through adopting open and applied technology standards. 10) The capability of adapting dynamic changes. Business requirements, application patterns, management strategies, and IT products always change endlessly for any departments, so ASISG should be self-adaptive. Two examples are provided in this paper, those examples provide a detailed way on how you design your semantic grid based on Multi-Agent systems and Ontology. In conclusion, the semantic grid of spatial information system could improve the ability of the integration and interoperability of spatial information grid.

Applications of Multi-Agent Technology to Power Systems

NASA Astrophysics Data System (ADS)

Nagata, Takeshi

Currently, agents are focus of intense on many sub-fields of computer science and artificial intelligence. Agents are being used in an increasingly wide variety of applications. Many important computing applications such as planning, process control, communication networks and concurrent systems will benefit from using multi-agent system approach. A multi-agent system is a structure given by an environment together with a set of artificial agents capable to act on this environment. Multi-agent models are oriented towards interactions, collaborative phenomena, and autonomy. This article presents the applications of multi-agent technology to the power systems.

DYNACLIPS (DYNAmic CLIPS): A dynamic knowledge exchange tool for intelligent agents

NASA Technical Reports Server (NTRS)

Cengeloglu, Yilmaz; Khajenoori, Soheil; Linton, Darrell

1994-01-01

In a dynamic environment, intelligent agents must be responsive to unanticipated conditions. When such conditions occur, an intelligent agent may have to stop a previously planned and scheduled course of actions and replan, reschedule, start new activities and initiate a new problem solving process to successfully respond to the new conditions. Problems occur when an intelligent agent does not have enough knowledge to properly respond to the new situation. DYNACLIPS is an implementation of a framework for dynamic knowledge exchange among intelligent agents. Each intelligent agent is a CLIPS shell and runs a separate process under SunOS operating system. Intelligent agents can exchange facts, rules, and CLIPS commands at run time. Knowledge exchange among intelligent agents at run times does not effect execution of either sender and receiver intelligent agent. Intelligent agents can keep the knowledge temporarily or permanently. In other words, knowledge exchange among intelligent agents would allow for a form of learning to be accomplished.

Social Dynamics in Web Page through Inter-Agent Interaction

NASA Astrophysics Data System (ADS)

Takeuchi, Yugo; Katagiri, Yasuhiro

Social persuasion abounds in human-human interactions. Attitudes and behaviors of people are invariably influenced by the attitudes and behaviors of other people as well as our social roles/relationships toward them. In the pedagogic scene, the relationship between teacher and learner produces one of the most typical interactions, in which the teacher makes the learner spontaneously study what he/she teaches. This study is an attempt to elucidate the nature and effectiveness of social persuasion in human-computer interaction environments. We focus on the social dynamics of multi-party interactions that involve both human-agent and inter-agent interactions. An experiment is conducted in a virtual web-instruction setting employing two types of agents: conductor agents who accompany and guide each learner throughout his/her learning sessions, and domain-expert agents who provide explanations and instructions for each stage of the instructional materials. In this experiment, subjects are assigned two experimental conditions: the authorized condition, in which an agent respectfully interacts with another agent, and the non-authorized condition, in which an agent carelessly interacts with another agent. The results indicate performance improvements in the authorized condition of inter-agent interactions. An analysis is given from the perspective of the transfer of authority from inter-agent to human-agent interactions based on social conformity. We argue for pedagogic advantages of social dynamics created by multiple animated character agents.

Agent-Based Crowd Simulation Considering Emotion Contagion for Emergency Evacuation Problem

NASA Astrophysics Data System (ADS)

Faroqi, H.; Mesgari, M.-S.

2015-12-01

During emergencies, emotions greatly affect human behaviour. For more realistic multi-agent systems in simulations of emergency evacuations, it is important to incorporate emotions and their effects on the agents. In few words, emotional contagion is a process in which a person or group influences the emotions or behavior of another person or group through the conscious or unconscious induction of emotion states and behavioral attitudes. In this study, we simulate an emergency situation in an open square area with three exits considering Adults and Children agents with different behavior. Also, Security agents are considered in order to guide Adults and Children for finding the exits and be calm. Six levels of emotion levels are considered for each agent in different scenarios and situations. The agent-based simulated model initialize with the random scattering of agent populations and then when an alarm occurs, each agent react to the situation based on its and neighbors current circumstances. The main goal of each agent is firstly to find the exit, and then help other agents to find their ways. Numbers of exited agents along with their emotion levels and damaged agents are compared in different scenarios with different initialization in order to evaluate the achieved results of the simulated model. NetLogo 5.2 is used as the multi-agent simulation framework with R language as the developing language.

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

PubMed

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

Intelligent Agent Architectures: Reactive Planning Testbed

NASA Technical Reports Server (NTRS)

Rosenschein, Stanley J.; Kahn, Philip

1993-01-01

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

Modeling of a production system using the multi-agent approach

NASA Astrophysics Data System (ADS)

Gwiazda, A.; Sękala, A.; Banaś, W.

2017-08-01

The method that allows for the analysis of complex systems is a multi-agent simulation. The multi-agent simulation (Agent-based modeling and simulation - ABMS) is modeling of complex systems consisting of independent agents. In the case of the model of the production system agents may be manufactured pieces set apart from other types of agents like machine tools, conveyors or replacements stands. Agents are magazines and buffers. More generally speaking, the agents in the model can be single individuals, but you can also be defined as agents of collective entities. They are allowed hierarchical structures. It means that a single agent could belong to a certain class. Depending on the needs of the agent may also be a natural or physical resource. From a technical point of view, the agent is a bundle of data and rules describing its behavior in different situations. Agents can be autonomous or non-autonomous in making the decision about the types of classes of agents, class sizes and types of connections between elements of the system. Multi-agent modeling is a very flexible technique for modeling and model creating in the convention that could be adapted to any research problem analyzed from different points of views. One of the major problems associated with the organization of production is the spatial organization of the production process. Secondly, it is important to include the optimal scheduling. For this purpose use can approach multi-purposeful. In this regard, the model of the production process will refer to the design and scheduling of production space for four different elements. The program system was developed in the environment NetLogo. It was also used elements of artificial intelligence. The main agent represents the manufactured pieces that, according to previously assumed rules, generate the technological route and allow preprint the schedule of that line. Machine lines, reorientation stands, conveyors and transport devices also represent the other type of agent that are utilized in the described simulation. The article presents the idea of an integrated program approach and shows the resulting production layout as a virtual model. This model was developed in the NetLogo multi-agent program environment.

Using an agent-based model to analyze the dynamic communication network of the immune response

PubMed Central

2011-01-01

Background The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. Results Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. Conclusions An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies. PMID:21247471

Nanoparticles as potential new generation broad spectrum antimicrobial agents.

PubMed

Yah, Clarence S; Simate, Geoffrey S

2015-09-02

The rapid emergence of antimicrobial resistant strains to conventional antimicrobial agents has complicated and prolonged infection treatment and increased mortality risk globally. Furthermore, some of the conventional antimicrobial agents are unable to cross certain cell membranes thus, restricting treatment of intracellular pathogens. Therefore, the disease-causing-organisms tend to persist in these cells. However, the emergence of nanoparticle (NP) technology has come with the promising broad spectrum NP-antimicrobial agents due to their vast physiochemical and functionalization properties. In fact, NP-antimicrobial agents are able to unlock the restrictions experienced by conventional antimicrobial agents. This review discusses the status quo of NP-antimicrobial agents as potent broad spectrum antimicrobial agents, sterilization and wound healing agents, and sustained inhibitors of intracellular pathogens. Indeed, the perspective of developing potent NP-antimicrobial agents that carry multiple-functionality will revolutionize clinical medicine and play a significant role in alleviating disease burden.

An Agent-Based Data Mining System for Ontology Evolution

NASA Astrophysics Data System (ADS)

Hadzic, Maja; Dillon, Darshan

We have developed an evidence-based mental health ontological model that represents mental health in multiple dimensions. The ongoing addition of new mental health knowledge requires a continual update of the Mental Health Ontology. In this paper, we describe how the ontology evolution can be realized using a multi-agent system in combination with data mining algorithms. We use the TICSA methodology to design this multi-agent system which is composed of four different types of agents: Information agent, Data Warehouse agent, Data Mining agents and Ontology agent. We use UML 2.1 sequence diagrams to model the collaborative nature of the agents and a UML 2.1 composite structure diagram to model the structure of individual agents. The Mental Heath Ontology has the potential to underpin various mental health research experiments of a collaborative nature which are greatly needed in times of increasing mental distress and illness.

Topical antifungal agents: an update.

PubMed

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.

Effects of competition and cooperation interaction between agents on networks in the presence of a market capacity

NASA Astrophysics Data System (ADS)

Sonubi, A.; Arcagni, A.; Stefani, S.; Ausloos, M.

2016-08-01

A network effect is introduced taking into account competition, cooperation, and mixed-type interaction among agents along a generalized Verhulst-Lotka-Volterra model. It is also argued that the presence of a market capacity undoubtedly enforces a definite limit on the agent's size growth. The state stability of triadic agents, i.e., the most basic network plaquette, is investigated analytically for possible scenarios, through a fixed-point analysis. It is discovered that: (i) market demand is only satisfied for full competition when one agent monopolizes the market; (ii) growth of agent size is encouraged in full cooperation; (iii) collaboration among agents to compete against one single agent may result in the disappearance of this single agent out of the market; and (iv) cooperating with two rivals may become a growth strategy for an intelligent agent.

Effects of competition and cooperation interaction between agents on networks in the presence of a market capacity.

PubMed

Sonubi, A; Arcagni, A; Stefani, S; Ausloos, M

2016-08-01

A network effect is introduced taking into account competition, cooperation, and mixed-type interaction among agents along a generalized Verhulst-Lotka-Volterra model. It is also argued that the presence of a market capacity undoubtedly enforces a definite limit on the agent's size growth. The state stability of triadic agents, i.e., the most basic network plaquette, is investigated analytically for possible scenarios, through a fixed-point analysis. It is discovered that: (i) market demand is only satisfied for full competition when one agent monopolizes the market; (ii) growth of agent size is encouraged in full cooperation; (iii) collaboration among agents to compete against one single agent may result in the disappearance of this single agent out of the market; and (iv) cooperating with two rivals may become a growth strategy for an intelligent agent.

Department of Defense Chemical, Biological, Defense Program, Annual Report to Congress, March 2005

DTIC Science & Technology

2005-03-01

nerve agents ( GA , GB, GD, and GF), V type nerve agents , and H (mustard) type blister agents . M8 paper can identify agents through...The M21 RSCAAL is an automatic scanning, passive infrared sensor that detects nerve ( GA , GB, and GD) and blister (H and L) agent vapor clouds...Chief of Staff for Programs GA – tabun, a nerve agent GAO – General Accounting Office GB – sarin, a nerve agent GD – soman, a nerve

Contrast enhanced spectroscopic optical coherence tomography

NASA Technical Reports Server (NTRS)

Xu, Chenyang (Inventor); Boppart, Stephen A. (Inventor)

2010-01-01

A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately.

Opinion evolution influenced by informed agents

NASA Astrophysics Data System (ADS)

Fan, Kangqi; Pedrycz, Witold

2016-11-01

Guiding public opinions toward a pre-set target by informed agents can be a strategy adopted in some practical applications. The informed agents are common agents who are employed or chosen to spread the pre-set opinion. In this work, we propose a social judgment based opinion (SJBO) dynamics model to explore the opinion evolution under the influence of informed agents. The SJBO model distinguishes between inner opinions and observable choices, and incorporates both the compromise between similar opinions and the repulsion between dissimilar opinions. Three choices (support, opposition, and remaining undecided) are considered in the SJBO model. Using the SJBO model, both the inner opinions and the observable choices can be tracked during the opinion evolution process. The simulation results indicate that if the exchanges of inner opinions among agents are not available, the effect of informed agents is mainly dependent on the characteristics of regular agents, including the assimilation threshold, decay threshold, and initial opinions. Increasing the assimilation threshold and decay threshold can improve the guiding effectiveness of informed agents. Moreover, if the initial opinions of regular agents are close to null, the full and unanimous consensus at the pre-set opinion can be realized, indicating that, to maximize the influence of informed agents, the guidance should be started when regular agents have little knowledge about a subject under consideration. If the regular agents have had clear opinions, the full and unanimous consensus at the pre-set opinion cannot be achieved. However, the introduction of informed agents can make the majority of agents choose the pre-set opinion.

Computational memory architectures for autobiographic agents interacting in a complex virtual environment: a working model

NASA Astrophysics Data System (ADS)

Ho, Wan Ching; Dautenhahn, Kerstin; Nehaniv, Chrystopher

2008-03-01

In this paper, we discuss the concept of autobiographic agent and how memory may extend an agent's temporal horizon and increase its adaptability. These concepts are applied to an implementation of a scenario where agents are interacting in a complex virtual artificial life environment. We present computational memory architectures for autobiographic virtual agents that enable agents to retrieve meaningful information from their dynamic memories which increases their adaptation and survival in the environment. The design of the memory architectures, the agents, and the virtual environment are described in detail. Next, a series of experimental studies and their results are presented which show the adaptive advantage of autobiographic memory, i.e. from remembering significant experiences. Also, in a multi-agent scenario where agents can communicate via stories based on their autobiographic memory, it is found that new adaptive behaviours can emerge from an individual's reinterpretation of experiences received from other agents whereby higher communication frequency yields better group performance. An interface is described that visualises the memory contents of an agent. From an observer perspective, the agents' behaviours can be understood as individually structured, and temporally grounded, and, with the communication of experience, can be seen to rely on emergent mixed narrative reconstructions combining the experiences of several agents. This research leads to insights into how bottom-up story-telling and autobiographic reconstruction in autonomous, adaptive agents allow temporally grounded behaviour to emerge. The article concludes with a discussion of possible implications of this research direction for future autobiographic, narrative agents.

Multi-Agent Information Classification Using Dynamic Acquaintance Lists.

ERIC Educational Resources Information Center

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

2003-01-01

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

The Effects of Peer-Like and Expert-Like Pedagogical Agents on Learners' Agent Perceptions, Task-Related Attitudes, and Learning Achievement

ERIC Educational Resources Information Center

Liew, Tze Wei; Tan, Su-Mae; Jayothisa, Chandrika

2013-01-01

The present study examined the impact of peer-like and expert-like agent stereotypes, as operationalized by agent's image and voice, on learners' agent perceptions, task-related attitudes, and learning achievement. 56 university freshmen (23 males and 33 females) interacted with either the peer-like agent (female college student) or the…

Introduction to Agent Mining Interaction and Integration

NASA Astrophysics Data System (ADS)

Cao, Longbing

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

Hybrid evolutionary computing model for mobile agents of wireless Internet multimedia

NASA Astrophysics Data System (ADS)

Hortos, William S.

2001-03-01

The ecosystem is used as an evolutionary paradigm of natural laws for the distributed information retrieval via mobile agents to allow the computational load to be added to server nodes of wireless networks, while reducing the traffic on communication links. Based on the Food Web model, a set of computational rules of natural balance form the outer stage to control the evolution of mobile agents providing multimedia services with a wireless Internet protocol WIP. The evolutionary model shows how mobile agents should behave with the WIP, in particular, how mobile agents can cooperate, compete and learn from each other, based on an underlying competition for radio network resources to establish the wireless connections to support the quality of service QoS of user requests. Mobile agents are also allowed to clone themselves, propagate and communicate with other agents. A two-layer model is proposed for agent evolution: the outer layer is based on the law of natural balancing, the inner layer is based on a discrete version of a Kohonen self-organizing feature map SOFM to distribute network resources to meet QoS requirements. The former is embedded in the higher OSI layers of the WIP, while the latter is used in the resource management procedures of Layer 2 and 3 of the protocol. Algorithms for the distributed computation of mobile agent evolutionary behavior are developed by adding a learning state to the agent evolution state diagram. When an agent is in an indeterminate state, it can communicate to other agents. Computing models can be replicated from other agents. Then the agents transitions to the mutating state to wait for a new information-retrieval goal. When a wireless terminal or station lacks a network resource, an agent in the suspending state can change its policy to submit to the environment before it transitions to the searching state. The agents learn the facts of agent state information entered into an external database. In the cloning process, two agents on a host station sharing a common goal can be merged or married to compose a new agent. Application of the two-layer set of algorithms for mobile agent evolution, performed in a distributed processing environment, is made to the QoS management functions of the IP multimedia IM sub-network of the third generation 3G Wideband Code-division Multiple Access W-CDMA wireless network.

Detection of Alkylating Agents using Electrical and Mechanical Means

NASA Astrophysics Data System (ADS)

Gerchikov, Yulia; Borzin, Elena; Gannot, Yair; Shemesh, Ariel; Meltzman, Shai; Hertzog-Ronen, Carmit; Tal, Shay; Stolyarova, Sara; Nemirovsky, Yael; Tessler, Nir; Eichen, Yoav

2011-08-01

Alkylating agents are reactive molecules having at least one polar bond between a carbon atom and a good leaving group. These often simple molecules are frequently used in organic synthesis, as sterilizing agents in agriculture and even as anticancer agents in medicine. Unfortunately, for over a century, some of the highly reactive alkylating agents are also being used as blister chemical warfare agents. Being relatively simple to make, the risk is that these will be applied by terrorists as poor people warfare agents. The detection and identification of such alkylating agents is not a simple task because of their high reactivity and simple structure of the reactive site. Here we report on new approaches to the detection and identification of such alkylating agents using electrical (organic field effect transistors) and mechanical (microcantilevers) means.

Consensus pursuit of heterogeneous multi-agent systems under a directed acyclic graph

NASA Astrophysics Data System (ADS)

Yan, Jing; Guan, Xin-Ping; Luo, Xiao-Yuan

2011-04-01

This paper is concerned with the cooperative target pursuit problem by multiple agents based on directed acyclic graph. The target appears at a random location and moves only when sensed by the agents, and agents will pursue the target once they detect its existence. Since the ability of each agent may be different, we consider the heterogeneous multi-agent systems. According to the topology of the multi-agent systems, a novel consensus-based control law is proposed, where the target and agents are modeled as a leader and followers, respectively. Based on Mason's rule and signal flow graph analysis, the convergence conditions are provided to show that the agents can catch the target in a finite time. Finally, simulation studies are provided to verify the effectiveness of the proposed approach.

Hierarchical Controlled Remote State Preparation by Using a Four-Qubit Cluster State

NASA Astrophysics Data System (ADS)

Ma, Peng-Cheng; Chen, Gui-Bin; Li, Xiao-Wei; Zhan, You-Bang

2018-06-01

We propose a scheme for hierarchical controlled remote preparation of an arbitrary single-qubit state via a four-qubit cluster state as the quantum channel. In this scheme, a sender wishes to help three agents to remotely prepare a quantum state, respectively. The three agents are divided into two grades, that is, an agent is in the upper grade and other two agents are in the lower grade. In this process of remote state preparation, the agent of the upper grade only needs the assistance of any one of the other two agents for recovering the sender's original state, while an agent of the lower grade needs the collaboration of all the other two agents. In other words, the agents of two grades have different authorities to reconstruct sender's original state.

Method and apparatus to characterize ultrasonically reflective contrast agents

NASA Technical Reports Server (NTRS)

Pretlow, Robert A., III (Inventor)

1993-01-01

A method and apparatus for characterizing the time and frequency response of an ultrasonically reflective contrast agent is disclosed. An ultrasonically reflective contrast agent is injected, under constant pressure, into a fluid flowing through a pump flow circuit. The fluid and the ultrasonically reflective contrast agent are uniformly mixed in a mixing chamber, and the uniform mixture is passed through a contrast agent chamber. The contrast agent chamber is acoustically and axially interposed between an ultrasonic transducer chamber and an acoustic isolation chamber. A pulse of ultrasonic energy is transmitted into the contrast agent chamber from the ultrasonic transducer chamber. An echo waveform is received from the ultrasonically reflective contrast agent, and it is analyzed to determine the time and frequency response of the ultrasonically reflective contrast agent.

Modelling of robotic work cells using agent based-approach

NASA Astrophysics Data System (ADS)

Sękala, A.; Banaś, W.; Gwiazda, A.; Monica, Z.; Kost, G.; Hryniewicz, P.

2016-08-01

In the case of modern manufacturing systems the requirements, both according the scope and according characteristics of technical procedures are dynamically changing. This results in production system organization inability to keep up with changes in a market demand. Accordingly, there is a need for new design methods, characterized, on the one hand with a high efficiency and on the other with the adequate level of the generated organizational solutions. One of the tools that could be used for this purpose is the concept of agent systems. These systems are the tools of artificial intelligence. They allow assigning to agents the proper domains of procedures and knowledge so that they represent in a self-organizing system of an agent environment, components of a real system. The agent-based system for modelling robotic work cell should be designed taking into consideration many limitations considered with the characteristic of this production unit. It is possible to distinguish some grouped of structural components that constitute such a system. This confirms the structural complexity of a work cell as a specific production system. So it is necessary to develop agents depicting various aspects of the work cell structure. The main groups of agents that are used to model a robotic work cell should at least include next pattern representatives: machine tool agents, auxiliary equipment agents, robots agents, transport equipment agents, organizational agents as well as data and knowledge bases agents. In this way it is possible to create the holarchy of the agent-based system.

Agent Reward Shaping for Alleviating Traffic Congestion

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian

2006-01-01

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

Polydopamine-coated capsules

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Scott R.; Sottos, Nancy R.; Kang, Sen

One aspect of the invention is a polymer material comprising a capsule coated with PDA. In certain embodiments, the capsule encapsulates a functional agent. The encapsulated functional agent may be an indicating agent, healing agent, protecting agent, pharmaceutical drug, food additive, or a combination thereof.

40 CFR 300.915 - Data requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... this section. (d) Bioremediation Agents. (1) Name, brand, or trademark, if any, under which the agent...) Bioremediation Agent Effectiveness. Use bioremediation agent effectiveness test methods described in appendix C to part 300. (8) Bioremediation Agent Toxicity [Reserved]. (9) Biological additives. (i) For...

[Utilization of polymeric micelle magnetic resonance imaging (MRI) contrast agent for theranostic system].

PubMed

Shiraishi, Kouichi

2013-01-01

We applied a polymeric micelle carrier system for the targeting of a magnetic resonance imaging (MRI) contrast agent. Prepared polymeric micelle MRI contrast agent exhibited a long circulation characteristic in blood, and considerable amount of the contrast agent was found to accumulate in colon 26 solid tumor by the EPR effect. The signal intensities of tumor area showed 2-folds increase in T1-weighted images at 24 h after i.v. injection. To observe enhancement of the EPR effect by Cderiv pretreatment on tumor targeting, we used the contrast agent for the evaluation by means of MRI. Cderiv pretreatment significantly enhanced tumor accumulation of the contrast agent. Interestingly, very high signal intensity in tumor region was found at 24 h after the contrast agent injection in Cderiv pretreated mice. The contrast agent visualized a microenvironmental change in tumor. These results indicate that the contrast agent exhibits potential use for tumor diagnostic agent. To combine with a polymeric micelle carrier system for therapeutic agent, the usage of the combination makes a new concept of "theranostic" for a better cancer treatment.

United States Army Biomedical Research and Development Laboratory Annual Progress Report FY90

DTIC Science & Technology

1991-01-01

pesticide . Parallel and follow-on studies will include hydrolysis products of nerve agents , vesicants, and agents of...Division FO Fog oil FORSCOM U.S. Army Forces Command FY Fiscal year 249 GA The nerve agent tabun GB The nerve agent soman GD The nerve agent sarin GLP... Nerve Agents , Industrial Hygiene Sampling, Microbiology, Combustion Products, Liquid Gun Propellant, Organic Chemistry, Inorganic

A Systems Approach to Depaint Chemistry

DTIC Science & Technology

2009-02-01

continuous colored film by curing through solvent evaporation, oxidation, catylization or other means. – Vehicle: Film former, binder, resin or polymer...impart large changes in properties. – Suspending agents – Driers – Anti-Skinning Agents – Wetting Agents – Anti- Foaming Agents – Coalescing Agents ...volatile stripper inside the coating. Paint Release Agent Coating Removal Mechanism Zone1: PRA Layer Zone2: PRA Initial Permeation into coating system Epoxy

GC-MS and LC-MS analysis of nerve agents in body fluids: intra-laboratory verification test using spiked plasma and urine samples.

PubMed

Koller, Marianne; Becker, Christian; Thiermann, Horst; Worek, Franz

2010-05-15

The purpose of this study was to check the applicability of different analytical methods for the identification of unknown nerve agents in human body fluids. Plasma and urine samples were spiked with nerve agents (plasma) or with their metabolites (urine) or were left blank. Seven random samples (35% of all samples) were selected for the verification test. Plasma was worked up for unchanged nerve agents and for regenerated nerve agents after fluoride-induced reactivation of nerve agent-inhibited butyrylcholinesterase. Both extracts were analysed by GC-MS. Metabolites were extracted from plasma and urine, respectively, and were analysed by LC-MS. The urinary metabolites and two blank samples could be identified without further measurements, plasma metabolites and blanks were identified in six of seven samples. The analysis of unchanged nerve agent provided five agents/blanks and the sixth agent after further investigation. The determination of the regenerated agents also provided only five clear findings during the first screening because of a rather noisy baseline. Therefore, the sample preparation was extended by a size exclusion step performed before addition of fluoride which visibly reduced baseline noise and thus improved identification of the two missing agents. The test clearly showed that verification should be performed by analysing more than one biomarker to ensure identification of the agent(s). Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical Action of Halogenated Agents in Fire Extinguishing

NASA Technical Reports Server (NTRS)

Belles, Frank E.

1955-01-01

The action of halogenated agents in preventing flame propagation in fuel-air mixtures in laboratory tests is discussed in terms of a possible chemical mechanism. The mechanism chosen is that of chain-breaking reactions between agent and active particles (hydrogen and oxygen atoms and hydroxyl radicsls). Data from the literature on the flammability peaks of n-heptane agent-air mixtures are treated. Ratings of agent effectiveness in terms of the fuel equivalent of the agent, based on both fuel and agent concentrations at the peak, are proposed as preferable to ratings in terms of agent concentration alone. These fuel-equivalent ratings are roughly correlated by reactivities assigned to halogen and hydrogen atoms in the agent molecules. It is concluded that the presence of hydrogen in agent need not reduce its fire-fighting ability, provided there is enough halogen to make the agent nonflammable. A method is presented for estimating from quenching-distance data a rate constant for the reaction of agent with active particles. A quantitative result is obtained for methyl bromide. This rate constant predicts the observed peak concentration of methyl bromide quite well. However, more data are needed to prove the validity of the method. The assumption that hal.ogenatedagents act mainly by chain-bresking reactions with active particles is consistent with the experimental facts and should help guide the selection of agents for further tests.

Casuist BDI-Agent: A New Extended BDI Architecture with the Capability of Ethical Reasoning

NASA Astrophysics Data System (ADS)

Honarvar, Ali Reza; Ghasem-Aghaee, Nasser

Since the intelligent agent is developed to be cleverer, more complex, and yet uncontrollable, a number of problems have been recognized. The capability of agents to make moral decisions has become an important question, when intelligent agents have developed more autonomous and human-like. We propose Casuist BDI-Agent architecture which extends the power of BDI architecture. Casuist BDI-Agent architecture combines CBR method in AI and bottom up casuist approach in ethics in order to add capability of ethical reasoning to BDI-Agent.

Method of encapsulating polyaminopolycarboxylic acid chelating agents in liposomes

DOEpatents

Rahman, Yueh Erh

1977-11-10

A method is provided for transferring a polyaminopolycarboxylic acid chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. The chelating agent is encapsulated within liposomes by drying a lipid mixture to form a thin film and wetting the lipid film with a solution containing the chelating agent. Mixing then results in the formation of a suspension of liposomes encapsulating the chelating agent, which liposomes can then be separated.

Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

PubMed

Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

2008-12-01

Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

Knowledge Management in Role Based Agents

NASA Astrophysics Data System (ADS)

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

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

Flexible, secure agent development framework

DOEpatents

Goldsmith,; Steven, Y [Rochester, MN

2009-04-07

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

Learning other agents` preferences in multiagent negotiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Hierarchically controlled remote preparation of an arbitrary single-qubit state by using a four-qubit |χ > entangled state

NASA Astrophysics Data System (ADS)

Ma, Peng-Cheng; Chen, Gui-Bin; Li, Xiao-Wei; Zhan, You-Bang

2018-05-01

In this paper, we present a scheme for Hierarchically controlled remote preparation of an arbitrary single-qubit state via a four-qubit |χ > state as the quantum channel. In this scheme, a sender wishes to help three agents to remotely prepare a quantum state, respectively. The three agents are divided into two grades, that is, an agent is in the upper grade and other two agents are in the lower grade. It is shown that the agent of the upper grade only needs the assistance of any one of the other two agents for recovering the sender's original state, while an agent of the lower grade needs the collaboration of all the other two agents. In other words, the agents of two grades have different authorities to recover sender's original state.

Method for tracking the location of mobile agents using stand-off detection technique

DOEpatents

Schmitt, Randal L [Tijeras, NM; Bender, Susan Fae Ann [Tijeras, NM; Rodacy, Philip J [Albuquerque, NM; Hargis, Jr., Philip J.; Johnson, Mark S [Albuquerque, NM

2006-12-26

A method for tracking the movement and position of mobile agents using light detection and ranging (LIDAR) as a stand-off optical detection technique. The positions of the agents are tracked by analyzing the time-history of a series of optical measurements made over the field of view of the optical system. This provides a (time+3-D) or (time+2-D) mapping of the location of the mobile agents. Repeated pulses of a laser beam impinge on a mobile agent, such as a bee, and are backscattered from the agent into a LIDAR detection system. Alternatively, the incident laser pulses excite fluorescence or phosphorescence from the agent, which is detected using a LIDAR system. Analysis of the spatial location of signals from the agents produced by repeated pulses generates a multidimensional map of agent location.

Agent-based method for distributed clustering of textual information

DOEpatents

Potok, Thomas E [Oak Ridge, TN; Reed, Joel W [Knoxville, TN; Elmore, Mark T [Oak Ridge, TN; Treadwell, Jim N [Louisville, TN

2010-09-28

A computer method and system for storing, retrieving and displaying information has a multiplexing agent (20) that calculates a new document vector (25) for a new document (21) to be added to the system and transmits the new document vector (25) to master cluster agents (22) and cluster agents (23) for evaluation. These agents (22, 23) perform the evaluation and return values upstream to the multiplexing agent (20) based on the similarity of the document to documents stored under their control. The multiplexing agent (20) then sends the document (21) and the document vector (25) to the master cluster agent (22), which then forwards it to a cluster agent (23) or creates a new cluster agent (23) to manage the document (21). The system also searches for stored documents according to a search query having at least one term and identifying the documents found in the search, and displays the documents in a clustering display (80) of similarity so as to indicate similarity of the documents to each other.

Agents in bioinformatics, computational and systems biology.

PubMed

Merelli, Emanuela; Armano, Giuliano; Cannata, Nicola; Corradini, Flavio; d'Inverno, Mark; Doms, Andreas; Lord, Phillip; Martin, Andrew; Milanesi, Luciano; Möller, Steffen; Schroeder, Michael; Luck, Michael

2007-01-01

The adoption of agent technologies and multi-agent systems constitutes an emerging area in bioinformatics. In this article, we report on the activity of the Working Group on Agents in Bioinformatics (BIOAGENTS) founded during the first AgentLink III Technical Forum meeting on the 2nd of July, 2004, in Rome. The meeting provided an opportunity for seeding collaborations between the agent and bioinformatics communities to develop a different (agent-based) approach of computational frameworks both for data analysis and management in bioinformatics and for systems modelling and simulation in computational and systems biology. The collaborations gave rise to applications and integrated tools that we summarize and discuss in context of the state of the art in this area. We investigate on future challenges and argue that the field should still be explored from many perspectives ranging from bio-conceptual languages for agent-based simulation, to the definition of bio-ontology-based declarative languages to be used by information agents, and to the adoption of agents for computational grids.

Method For Reactivating Solid Catalysts Used For Alklation Reactions

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

2005-05-03

A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

Method for reactivating solid catalysts used in alkylation reactions

DOEpatents

Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

2003-06-17

A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

Incorporating BDI Agents into Human-Agent Decision Making Research

NASA Astrophysics Data System (ADS)

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

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

Spacecraft sanitation agent development

NASA Technical Reports Server (NTRS)

1972-01-01

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

Drilling fluids and thinners therefor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allison, G.M. III

1986-10-21

This patent describes an aqueous drilling fluid comprising water, finely divided solids and a first agent and a second agent. The first agent comprises a sulfoalkylated tannin containing no complexing heavy metal. The second agent comprises at least one at least partly water-soluble metal compound comprising tin. The weight ratio of the first agent to the second agent is in the range from about 100;1 to about 1:1.

Learning Sequences of Actions in Collectives of Autonomous Agents

NASA Technical Reports Server (NTRS)

Turner, Kagan; Agogino, Adrian K.; Wolpert, David H.; Clancy, Daniel (Technical Monitor)

2001-01-01

In this paper we focus on the problem of designing a collective of autonomous agents that individually learn sequences of actions such that the resultant sequence of joint actions achieves a predetermined global objective. We are particularly interested in instances of this problem where centralized control is either impossible or impractical. For single agent systems in similar domains, machine learning methods (e.g., reinforcement learners) have been successfully used. However, applying such solutions directly to multi-agent systems often proves problematic, as agents may work at cross-purposes, or have difficulty in evaluating their contribution to achievement of the global objective, or both. Accordingly, the crucial design step in multiagent systems centers on determining the private objectives of each agent so that as the agents strive for those objectives, the system reaches a good global solution. In this work we consider a version of this problem involving multiple autonomous agents in a grid world. We use concepts from collective intelligence to design goals for the agents that are 'aligned' with the global goal, and are 'learnable' in that agents can readily see how their behavior affects their utility. We show that reinforcement learning agents using those goals outperform both 'natural' extensions of single agent algorithms and global reinforcement, learning solutions based on 'team games'.

Adaptivity in Agent-Based Routing for Data Networks

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Kirshner, Sergey; Merz, Chris J.; Turner, Kagan

2000-01-01

Adaptivity, both of the individual agents and of the interaction structure among the agents, seems indispensable for scaling up multi-agent systems (MAS s) in noisy environments. One important consideration in designing adaptive agents is choosing their action spaces to be as amenable as possible to machine learning techniques, especially to reinforcement learning (RL) techniques. One important way to have the interaction structure connecting agents itself be adaptive is to have the intentions and/or actions of the agents be in the input spaces of the other agents, much as in Stackelberg games. We consider both kinds of adaptivity in the design of a MAS to control network packet routing. We demonstrate on the OPNET event-driven network simulator the perhaps surprising fact that simply changing the action space of the agents to be better suited to RL can result in very large improvements in their potential performance: at their best settings, our learning-amenable router agents achieve throughputs up to three and one half times better than that of the standard Bellman-Ford routing algorithm, even when the Bellman-Ford protocol traffic is maintained. We then demonstrate that much of that potential improvement can be realized by having the agents learn their settings when the agent interaction structure is itself adaptive.

Agent tracking: a psycho-historical theory of the identification of living and social agents.

PubMed

Bullot, Nicolas J

To explain agent-identification behaviours, universalist theories in the biological and cognitive sciences have posited mental mechanisms thought to be universal to all humans, such as agent detection and face recognition mechanisms. These universalist theories have paid little attention to how particular sociocultural or historical contexts interact with the psychobiological processes of agent-identification. In contrast to universalist theories, contextualist theories appeal to particular historical and sociocultural contexts for explaining agent-identification. Contextualist theories tend to adopt idiographic methods aimed at recording the heterogeneity of human behaviours across history, space, and cultures. Defenders of the universalist approach tend to criticise idiographic methods because such methods can lead to relativism or may lack generality. To overcome explanatory limitations of proposals that adopt either universalist or contextualist approaches in isolation, I propose a philosophical model that integrates contributions from both traditions: the psycho-historical theory of agent-identification. This theory investigates how the tracking processes that humans use for identifying agents interact with the unique socio-historical contexts that support agent-identification practices. In integrating hypotheses about the history of agents with psychological and epistemological principles regarding agent-identification, the theory can generate novel hypotheses regarding the distinction between recognition-based, heuristic-based, and explanation-based agent-identification.

Efficient Evaluation Functions for Multi-Rover Systems

NASA Technical Reports Server (NTRS)

Agogino, Adrian; Tumer, Kagan

2004-01-01

Evolutionary computation can be a powerful tool in cresting a control policy for a single agent receiving local continuous input. This paper extends single-agent evolutionary computation to multi-agent systems, where a collection of agents strives to maximize a global fitness evaluation function that rates the performance of the entire system. This problem is solved in a distributed manner, where each agent evolves its own population of neural networks that are used as the control policies for the agent. Each agent evolves its population using its own agent-specific fitness evaluation function. We propose to create these agent-specific evaluation functions using the theory of collectives to avoid the coordination problem where each agent evolves a population that maximizes its own fitness function, yet the system has a whole achieves low values of the global fitness function. Instead we will ensure that each fitness evaluation function is both "aligned" with the global evaluation function and is "learnable," i.e., the agents can readily see how their behavior affects their evaluation function. We then show how these agent-specific evaluation functions outperform global evaluation methods by up to 600% in a domain where a set of rovers attempt to maximize the amount of information observed while navigating through a simulated environment.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Use of positive oral contrast agents in abdominopelvic computed tomography for blunt abdominal injury: meta-analysis and systematic review.

PubMed

Lee, Chau Hung; Haaland, Benjamin; Earnest, Arul; Tan, Cher Heng

2013-09-01

To determine whether positive oral contrast agents improve accuracy of abdominopelvic CT compared with no, neutral or negative oral contrast agent. Literature was searched for studies evaluating the diagnostic performance of abdominopelvic CT with positive oral contrast agents against imaging with no, neutral or negative oral contrast agent. Meta-analysis reviewed studies correlating CT findings of blunt abdominal injury with positive and without oral contrast agents against surgical, autopsy or clinical outcome allowing derivation of pooled sensitivity and specificity. Systematic review was performed on studies with common design and reference standard. Thirty-two studies were divided into two groups. Group 1 comprised 15 studies comparing CT with positive and without oral contrast agents. Meta-analysis of five studies from group 1 provided no difference in sensitivity or specificity between CT with positive or without oral contrast agents. Group 2 comprised 17 studies comparing CT with positive and neutral or negative oral contrast agents. Systematic review of 12 studies from group 2 indicated that neutral or negative oral contrasts were as effective as positive oral contrast agents for bowel visualisation. There is no difference in accuracy between CT performed with positive oral contrast agents or with no, neutral or negative oral contrast agent. • There is no difference in the accuracy of CT with or without oral contrast agent. • There is no difference in the accuracy of CT with Gastrografin or water. • Omission of oral contrast, utilising neutral or negative oral contrast agent saves time, costs and decreases risk of aspiration.

Autonomous Mission Operations for Sensor Webs

NASA Astrophysics Data System (ADS)

Underbrink, A.; Witt, K.; Stanley, J.; Mandl, D.

2008-12-01

We present interim results of a 2005 ROSES AIST project entitled, "Using Intelligent Agents to Form a Sensor Web for Autonomous Mission Operations", or SWAMO. The goal of the SWAMO project is to shift the control of spacecraft missions from a ground-based, centrally controlled architecture to a collaborative, distributed set of intelligent agents. The network of intelligent agents intends to reduce management requirements by utilizing model-based system prediction and autonomic model/agent collaboration. SWAMO agents are distributed throughout the Sensor Web environment, which may include multiple spacecraft, aircraft, ground systems, and ocean systems, as well as manned operations centers. The agents monitor and manage sensor platforms, Earth sensing systems, and Earth sensing models and processes. The SWAMO agents form a Sensor Web of agents via peer-to-peer coordination. Some of the intelligent agents are mobile and able to traverse between on-orbit and ground-based systems. Other agents in the network are responsible for encapsulating system models to perform prediction of future behavior of the modeled subsystems and components to which they are assigned. The software agents use semantic web technologies to enable improved information sharing among the operational entities of the Sensor Web. The semantics include ontological conceptualizations of the Sensor Web environment, plus conceptualizations of the SWAMO agents themselves. By conceptualizations of the agents, we mean knowledge of their state, operational capabilities, current operational capacities, Web Service search and discovery results, agent collaboration rules, etc. The need for ontological conceptualizations over the agents is to enable autonomous and autonomic operations of the Sensor Web. The SWAMO ontology enables automated decision making and responses to the dynamic Sensor Web environment and to end user science requests. The current ontology is compatible with Open Geospatial Consortium (OGC) Sensor Web Enablement (SWE) Sensor Model Language (SensorML) concepts and structures. The agents are currently deployed on the U.S. Naval Academy MidSTAR-1 satellite and are actively managing the power subsystem on-orbit without the need for human intervention.

Using Synchronous Boolean Networks to Model Several Phenomena of Collective Behavior

PubMed Central

Kochemazov, Stepan; Semenov, Alexander

2014-01-01

In this paper, we propose an approach for modeling and analysis of a number of phenomena of collective behavior. By collectives we mean multi-agent systems that transition from one state to another at discrete moments of time. The behavior of a member of a collective (agent) is called conforming if the opinion of this agent at current time moment conforms to the opinion of some other agents at the previous time moment. We presume that at each moment of time every agent makes a decision by choosing from the set (where 1-decision corresponds to action and 0-decision corresponds to inaction). In our approach we model collective behavior with synchronous Boolean networks. We presume that in a network there can be agents that act at every moment of time. Such agents are called instigators. Also there can be agents that never act. Such agents are called loyalists. Agents that are neither instigators nor loyalists are called simple agents. We study two combinatorial problems. The first problem is to find a disposition of instigators that in several time moments transforms a network from a state where the majority of simple agents are inactive to a state with the majority of active agents. The second problem is to find a disposition of loyalists that returns the network to a state with the majority of inactive agents. Similar problems are studied for networks in which simple agents demonstrate the contrary to conforming behavior that we call anticonforming. We obtained several theoretical results regarding the behavior of collectives of agents with conforming or anticonforming behavior. In computational experiments we solved the described problems for randomly generated networks with several hundred vertices. We reduced corresponding combinatorial problems to the Boolean satisfiability problem (SAT) and used modern SAT solvers to solve the instances obtained. PMID:25526612

Riot Control Agents

MedlinePlus

... 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 ...

Agility: Agent - Ility Architecture

DTIC Science & Technology

2002-10-01

existing and emerging standards (e.g., distributed objects, email, web, search engines , XML, Java, Jini). Three agent system components resulted from...agents and other Internet resources and operate over the web (AgentGram), a yellow pages service that uses Internet search engines to locate XML ads for agents and other Internet resources (WebTrader).

42 CFR 73.11 - Security.

Code of Federal Regulations, 2010 CFR

2010-10-01

... select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan must be... activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of... of select agents or toxins, (iv) Any release of a select agent or toxin, and (v) Any sign that...

9 CFR 121.11 - Security.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the select agent or toxin against unauthorized access, theft, loss, or release. (b) The security plan... activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of... of select agents or toxins; (iv) Any release of a select agent or toxin; and (v) Any sign that...

Preparing Change Agents for Change Agent Roles.

ERIC Educational Resources Information Center

Sedlacek, James R.

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

77 FR 71702 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... of Select Agents and Toxins; Biennial Review AGENCY: Centers for Disease Control and Prevention (CDC... designated certain select agents and toxins as Tier 1 agents. DATES: Effective Date: Effective December 4, 2012. FOR FURTHER INFORMATION CONTACT: Robbin Weyant, Director, Division of Select Agents and Toxins...

Using Physiological Measures to Assess the Effects of Animated Pedagogical Agents in Multimedia Instruction

ERIC Educational Resources Information Center

Romero-Hall, Enilda; Watson, Ginger; Papelis, Yiannnis

2014-01-01

To examine the visual attention, emotional responses, learning, perceptions and attitudes of learners interacting with an animated pedagogical agent, this study compared a multimedia learning environment with an emotionally-expressive animated pedagogical agent, with a non-expressive animated pedagogical agent, and without an agent. Visual…

Intelligent Agents for the Digital Battlefield

DTIC Science & Technology

1998-11-01

specific outcome of our long term research will be the development of a collaborative agent technology system, CATS , that will provide the underlying...software infrastructure needed to build large, heterogeneous, distributed agent applications. CATS will provide a software environment through which multiple...intelligent agents may interact with other agents, both human and computational. In addition, CATS will contain a number of intelligent agent components that will be useful for a wide variety of applications.

Agent planning in AgScala

NASA Astrophysics Data System (ADS)

Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

2013-10-01

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

Mining Temporal Patterns to Improve Agents Behavior: Two Case Studies

NASA Astrophysics Data System (ADS)

Fournier-Viger, Philippe; Nkambou, Roger; Faghihi, Usef; Nguifo, Engelbert Mephu

We propose two mechanisms for agent learning based on the idea of mining temporal patterns from agent behavior. The first one consists of extracting temporal patterns from the perceived behavior of other agents accomplishing a task, to learn the task. The second learning mechanism consists in extracting temporal patterns from an agent's own behavior. In this case, the agent then reuses patterns that brought self-satisfaction. In both cases, no assumption is made on how the observed agents' behavior is internally generated. A case study with a real application is presented to illustrate each learning mechanism.

Learning to cooperate in solving the traveling salesman problem.

PubMed

Qi, Dehu; Sun, Ron

2005-01-01

A cooperative team of agents may perform many tasks better than single agents. The question is how cooperation among self-interested agents should be achieved. It is important that, while we encourage cooperation among agents in a team, we maintain autonomy of individual agents as much as possible, so as to maintain flexibility and generality. This paper presents an approach based on bidding utilizing reinforcement values acquired through reinforcement learning. We tested and analyzed this approach and demonstrated that a team indeed performed better than the best single agent as well as the average of single agents.

Epoxy foams using multiple resins and curing agents

DOEpatents

Russick, Edward M.; Rand, Peter B.

2000-01-01

An epoxy foam comprising a plurality of resins, a plurality of curing agents, at least one blowing agent, at least one surfactant and optionally at least one filler and the process for making. Preferred is an epoxy foam comprising two resins of different reactivities, two curing agents, a blowing agent, a surfactant, and a filler. According to the present invention, an epoxy foam is prepared with tailorable reactivity, exotherm, and pore size by a process of admixing a plurality of resins with a plurality of curing agents, a surfactant and blowing agent, whereby a foamable mixture is formed and heating said foamable mixture at a temperature greater than the boiling temperature of the blowing agent whereby said mixture is foamed and cured.

A Novel Network Attack Audit System based on Multi-Agent Technology

NASA Astrophysics Data System (ADS)

Jianping, Wang; Min, Chen; Xianwen, Wu

A network attack audit system which includes network attack audit Agent, host audit Agent and management control center audit Agent is proposed. And the improved multi-agent technology is carried out in the network attack audit Agent which has achieved satisfactory audit results. The audit system in terms of network attack is just in-depth, and with the function improvement of network attack audit Agent, different attack will be better analyzed and audit. In addition, the management control center Agent should manage and analyze audit results from AA (or HA) and audit data on time. And the history files of network packets and host log data should also be audit to find deeper violations that cannot be found in real time.

Formal Consistency Verification of Deliberative Agents with Respect to Communication Protocols

NASA Technical Reports Server (NTRS)

Ramirez, Jaime; deAntonio, Angelica

2004-01-01

The aim of this paper is to show a method that is able to detect inconsistencies in the reasoning carried out by a deliberative agent. The agent is supposed to be provided with a hybrid Knowledge Base expressed in a language called CCR-2, based on production rules and hierarchies of frames, which permits the representation of non-monotonic reasoning, uncertain reasoning and arithmetic constraints in the rules. The method can give a specification of the scenarios in which the agent would deduce an inconsistency. We define a scenario to be a description of the initial agent s state (in the agent life cycle), a deductive tree of rule firings, and a partially ordered set of messages and/or stimuli that the agent must receive from other agents and/or the environment. Moreover, the method will make sure that the scenarios will be valid w.r.t. the communication protocols in which the agent is involved.

Children's understanding of the costs and rewards underlying rational action.

PubMed

Jara-Ettinger, Julian; Gweon, Hyowon; Tenenbaum, Joshua B; Schulz, Laura E

2015-07-01

Humans explain and predict other agents' behavior using mental state concepts, such as beliefs and desires. Computational and developmental evidence suggest that such inferences are enabled by a principle of rational action: the expectation that agents act efficiently, within situational constraints, to achieve their goals. Here we propose that the expectation of rational action is instantiated by a naïve utility calculus sensitive to both agent-constant and agent-specific aspects of costs and rewards associated with actions. In four experiments, we show that, given an agent's choices, children (range: 5-6 year olds; N=96) can infer unobservable aspects of costs (differences in agents' competence) from information about subjective differences in rewards (differences in agents' preferences) and vice versa. Moreover, children can design informative experiments on both objects and agents to infer unobservable constraints on agents' actions. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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.

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

PubMed

Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

2005-02-01

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

A Measure of Real-Time Intelligence

NASA Astrophysics Data System (ADS)

Gavane, Vaibhav

2013-03-01

We propose a new measure of intelligence for general reinforcement learning agents, based on the notion that an agent's environment can change at any step of execution of the agent. That is, an agent is considered to be interacting with its environment in real-time. In this sense, the resulting intelligence measure is more general than the universal intelligence measure (Legg and Hutter, 2007) and the anytime universal intelligence test (Hernández-Orallo and Dowe, 2010). A major advantage of the measure is that an agent's computational complexity is factored into the measure in a natural manner. We show that there exist agents with intelligence arbitrarily close to the theoretical maximum, and that the intelligence of agents depends on their parallel processing capability. We thus believe that the measure can provide a better evaluation of agents and guidance for building practical agents with high intelligence.

Propagation of the state change induced by external forces in local interactions

NASA Astrophysics Data System (ADS)

Lu, Jianjun; Tokinaga, Shozo

2016-10-01

This paper analyses the propagation of the state changes of agents that are induced by external forces applied to a plane. In addition, we propose two models for the behavior of the agents placed on a lattice plane, both of which are affected by local interactions. We first assume that agents are allowed to move to another site to maximise their satisfaction. Second, we utilise a model in which the agents choose activities on each site. The results show that the migration (activity) patterns of agents in both models achieve stability without any external forces. However, when we apply an impulsive external force to the state of the agents, we then observe the propagation of the changes in the agents' states. Using simulation studies, we show the conditions for the propagation of the state changes of the agents. We also show the propagation of the state changes of the agents allocated in scale-free networks and discuss the estimation of the agents' decisions in real state changes. Finally, we discuss the estimation of the agents' decisions in real state temporal changes using economic and social data from Japan and the United States.

Exchanging large data object in multi-agent systems

NASA Astrophysics Data System (ADS)

Al-Yaseen, Wathiq Laftah; Othman, Zulaiha Ali; Nazri, Mohd Zakree Ahmad

2016-08-01

One of the Business Intelligent solutions that is currently in use is the Multi-Agent System (MAS). Communication is one of the most important elements in MAS, especially for exchanging large low level data between distributed agents (physically). The Agent Communication Language in JADE has been offered as a secure method for sending data, whereby the data is defined as an object. However, the object cannot be used to send data to another agent in a different location. Therefore, the aim of this paper was to propose a method for the exchange of large low level data as an object by creating a proxy agent known as a Delivery Agent, which temporarily imitates the Receiver Agent. The results showed that the proposed method is able to send large-sized data. The experiments were conducted using 16 datasets ranging from 100,000 to 7 million instances. However, for the proposed method, the RAM and the CPU machine had to be slightly increased for the Receiver Agent, but the latency time was not significantly different compared to the use of the Java Socket method (non-agent and less secure). With such results, it was concluded that the proposed method can be used to securely send large data between agents.

Application of Toxic Chinese Medicine in Chinese Pharmacopoeia

NASA Astrophysics Data System (ADS)

Zhao, Hui; Feng, Yu; Mao, Mingsan

2018-01-01

Objective: Explore the application characteristics of proprietary Chinese medicine prescriptions containing toxic herbs in pharmacopoeia. Methods: In this paper, according to the clinical application of pharmacopoeia proprietary Chinese medicine is divided into table agent, Qushu agent, diarrhea agent, heat agent, Wen Li agent, cough and asthma agents, resuscitation agent, Gutian agent, Fuzheng agent, Anshen agent, hemostatic agent, The traditional Chinese medicine prescription and the clinical application of the Chinese herbal medicine containing the toxic Chinese medicine were analyzed and sorted out., Summed up the compatibility of toxic herbs and application characteristics. Results: Toxic Chinese herbal medicine in the cure of traditional Chinese medicine to play a long-standing role, through the overall thinking, dialectical thinking, and thinking of toxic Chinese medicine in the analysis of Chinese medicine that [2], toxic Chinese medicine in the application of proprietary Chinese medicine can not lack. Conclusion: Pharmacopoeia included proprietary Chinese medicine not only in the clinical treatment of good, but also the application of its toxic traditional Chinese medicine and its understanding of the enrichment of the toxic characteristics of traditional Chinese medicine and treatment-related disease pathology between the points of contact for patients with clinical applications Based on and theoretical guidance of Chinese medicine [3].

Unifying Temporal and Structural Credit Assignment Problems

NASA Technical Reports Server (NTRS)

Agogino, Adrian K.; Tumer, Kagan

2004-01-01

Single-agent reinforcement learners in time-extended domains and multi-agent systems share a common dilemma known as the credit assignment problem. Multi-agent systems have the structural credit assignment problem of determining the contributions of a particular agent to a common task. Instead, time-extended single-agent systems have the temporal credit assignment problem of determining the contribution of a particular action to the quality of the full sequence of actions. Traditionally these two problems are considered different and are handled in separate ways. In this article we show how these two forms of the credit assignment problem are equivalent. In this unified frame-work, a single-agent Markov decision process can be broken down into a single-time-step multi-agent process. Furthermore we show that Monte-Carlo estimation or Q-learning (depending on whether the values of resulting actions in the episode are known at the time of learning) are equivalent to different agent utility functions in a multi-agent system. This equivalence shows how an often neglected issue in multi-agent systems is equivalent to a well-known deficiency in multi-time-step learning and lays the basis for solving time-extended multi-agent problems, where both credit assignment problems are present.

Infectious causes of reproductive disorders in cattle.

PubMed

Yoo, Han Sang

2010-01-01

The incidences of reproductive disorders in bovine are increasing over years. This scenario is further aggravating due to more emphasis on selection and rearing of animal for specific commercial purposes which compromises livestock reproduction. Reproductive disorders like infertility and abortions in cattle are major problems in the bovine industry. The reproductive disorders might be caused by several different agents such as physical agents, chemical agents, biological agents, etc. Also, the causative agent and pathogenesis of reproductive disorders are influenced by various factors including environmental factor. The exact causes may not be evident and are often complicated with multiple causative agents. Thus, there is a need for multi-faceted approach to understand correlation of various factors with reproductive performance. Of the agents, infectious biological agents are significant cause of reproductive disorder and are of high priority in the bovine industry. These factors are not only related to the prosperity of bovine industry but are also important from public health point of view because of their zoonotic potentials. Several infectious agents like bacterial, viral, protozoon, chlamydial and fungal agents are known to have direct impact on reproductive health of cattle. These diseases can be arranged and discussed in different groups based on the causative agents.

Toward Shared Working Space of Human and Robotic Agents Through Dipole Flow Field for Dependable Path Planning.

PubMed

Trinh, Lan Anh; Ekström, Mikael; Cürüklü, Baran

2018-01-01

Recent industrial developments in autonomous systems, or agents, which assume that humans and the agents share the same space or even work in close proximity, open for new challenges in robotics, especially in motion planning and control. In these settings, the control system should be able to provide these agents a reliable path following control when they are working in a group or in collaboration with one or several humans in complex and dynamic environments. In such scenarios, these agents are not only moving to reach their goals, i.e., locations, they are also aware of the movements of other entities to find a collision-free path. Thus, this paper proposes a dependable, i.e., safe, reliable and effective, path planning algorithm for a group of agents that share their working space with humans. Firstly, the method employs the Theta * algorithm to initialize the paths from a starting point to a goal for a set of agents. As Theta * algorithm is computationally heavy, it only reruns when there is a significant change of the environment. To deal with the movements of the agents, a static flow field along the configured path is defined. This field is used by the agents to navigate and reach their goals even if the planned trajectories are changed. Secondly, a dipole field is calculated to avoid the collision of agents with other agents and human subjects. In this approach, each agent is assumed to be a source of a magnetic dipole field in which the magnetic moment is aligned with the moving direction of the agent. The magnetic dipole-dipole interactions between these agents generate repulsive forces to help them to avoid collision. The effectiveness of the proposed approach has been evaluated with extensive simulations. The results show that the static flow field is able to drive agents to the goals with a small number of requirements to update the path of agents. Meanwhile, the dipole flow field plays an important role to prevent collisions. The combination of these two fields results in a safe path planning algorithm, with a deterministic outcome, to navigate agents to their desired goals.

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

PubMed

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Carboxylate-containing chelating agent interactions with amorphous chromium hydroxide: Adsorption and dissolution

NASA Astrophysics Data System (ADS)

Carbonaro, Richard F.; Gray, Benjamin N.; Whitehead, Charles F.; Stone, Alan T.

2008-07-01

Anthropogenic chelating agents and biological chelating agents produced by indigenous organisms may dissolve Cr III (hydr)oxides in soils and sediments. The resulting dissolved Cr III-chelating agent complexes are more readily transported through porous media, thereby spreading contamination. With this work, we examine chelating agent-assisted dissolution of amorphous chromium hydroxide (ACH) by the (amino)carboxylate chelating agents iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), tricarballylic acid (TCA), citric acid (CIT), ethylenediaminetetraacetic acid (EDTA), trans-1,2-cyclohexanediaminetetraacetic acid (CDTA), and trimethylenediaminetetraacetic acid (TMDTA). The extent of chelating agent adsorption onto ACH increased quickly over the first few hours, and then increased more gradually until a constant extent was attained. The extent of chelating agent adsorption versus pH followed "ligand-like" behavior. All chelating agents with the exception of TCA and IDA effectively dissolved significant amounts of ACH within 10 days from pH 4.0 to 9.4. IDA dissolved ACH below pH 6.5 and above pH 7.5. Rates of ACH dissolution normalized to the extent of chelating agent adsorption were pH dependent. IDA, NTA, CIT, and CDTA exhibited an increase in normalized dissolution rate with decreasing pH. EDTA and TMDTA exhibited a maximum in normalized dissolution rate near pH 8.5. Use of acetic acid as a pH buffer in experiments decreased the extent of chelating agent adsorption for IDA, NTA, and CIT but increased normalized rates of chelating agent-assisted dissolution for all chelating agents except EDTA. The results from this study provide the necessary information to calculate the extents and time scales of ACH dissolution in the presence of (amino)carboxylate chelating agents.

Symposium on Toxic Substance Control: Decontamination, April 22 - 24, 1980, Columbus, Ohio.

DTIC Science & Technology

1981-06-01

standard decontaminants is used. TABLE 1. Standard Chemical Decontaminants Decontaminant Agents Used On STB Blister and nerve agents DS-2 All chemical... agents M258 Kit Sodium Hydroxide, Ethanol, G-Series nerve agents Phenol, Water Chloramine B, ZnCI2, Blister ana V-Series Ethanol, Water nerve agents A...is a point source alarm that actively samples ambient air and reacts to low concentrations of nerve agents . The M-8 alarm detector also detects several

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujimura, Kikuo.

1990-01-01

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

Limonene and tetrahydrofurfurly alcohol cleaning agent

DOEpatents

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.

Limonene and tetrahydrofurfuryl alcohol cleaning agent

DOEpatents

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

1997-10-21

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

Benzamide Derivatives as Protective Agents against the Action of Xenotoxic Agents on Human Cells.

DTIC Science & Technology

1984-05-31

4D-AlI45 396 BENZAMIDE DERIVATIVES AS PROTECTIVE AGENTS AGAINST THE I/i ACTION OF XENOTOXI..(U) OHIO STATE UNIV RESEARCH I FOUNDATION COLUMBUS G E...AS PROTECTIVE AGENTS AGAINST THE ACTION OF XENOTOXIC AGENTS ON HUMAN CELLS CD George E. Milo * Department of Physiological Chemistry and...TITLE (and Subtitle) S. .YPE OF REPORT & PERIOD COVERED Benzamide Derivatives as Protective Agents Annual Scientific Report 5 Against the Action of

Home Energy Management System - VOLTTRON Integration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zandi, Helia

In most Home Energy Management Systems (HEMS) available in the market, different devices running different communication protocols cannot interact with each other and exchange information. As a result of this integration, the information about different devices running different communication protocol can be accessible by other agents and devices running on VOLTTRON platform. The integration process can be used by any HEMS available in the market regardless of the programming language they use. If the existing HEMS provides an Application Programming Interface (API) based on the RESTFul architecture, that API can be used for integration. Our candidate HEMS in this projectmore » is home-assistant (Hass). An agent is implemented which can communicate with the Hass API and receives information about the devices loaded on the API. The agent publishes the information it receives on the VOLTTRON message bus so other agents can have access to this information. On the other side, for each type of devices, an agent is implemented such as Climate Agent, Lock Agent, Switch Agent, Light Agent, etc. Each of these agents is subscribed to the messages published on the message bus about their associated devices. These agents can also change the status of the devices by sending appropriate service calls to the API. Other agents and services on the platform can also access this information and coordinate their decision-making process based on this information.« less

Adaptive Neuro-Fuzzy Determination of the Effect of Experimental Parameters on Vehicle Agent Speed Relative to Vehicle Intruder.

PubMed

Shamshirband, Shahaboddin; Banjanovic-Mehmedovic, Lejla; Bosankic, Ivan; Kasapovic, Suad; Abdul Wahab, Ainuddin Wahid Bin

2016-01-01

Intelligent Transportation Systems rely on understanding, predicting and affecting the interactions between vehicles. The goal of this paper is to choose a small subset from the larger set so that the resulting regression model is simple, yet have good predictive ability for Vehicle agent speed relative to Vehicle intruder. The method of ANFIS (adaptive neuro fuzzy inference system) was applied to the data resulting from these measurements. The ANFIS process for variable selection was implemented in order to detect the predominant variables affecting the prediction of agent speed relative to intruder. This process includes several ways to discover a subset of the total set of recorded parameters, showing good predictive capability. The ANFIS network was used to perform a variable search. Then, it was used to determine how 9 parameters (Intruder Front sensors active (boolean), Intruder Rear sensors active (boolean), Agent Front sensors active (boolean), Agent Rear sensors active (boolean), RSSI signal intensity/strength (integer), Elapsed time (in seconds), Distance between Agent and Intruder (m), Angle of Agent relative to Intruder (angle between vehicles °), Altitude difference between Agent and Intruder (m)) influence prediction of agent speed relative to intruder. The results indicated that distance between Vehicle agent and Vehicle intruder (m) and angle of Vehicle agent relative to Vehicle Intruder (angle between vehicles °) is the most influential parameters to Vehicle agent speed relative to Vehicle intruder.

The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents

PubMed Central

Manuelidis, Laura; Chakrabarty, Trisha; Miyazawa, Kohtaro; Nduom, Nana-Aba; Emmerling, Kaitlin

2009-01-01

Human sporadic Creutzfeldt–Jakob disease (sCJD), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K. BSE agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agents is critical, particularly because infected humans do not develop disease for many years. As with viruses, transmissible spongiform encephalopathy (TSE) agents can adapt to new species and become more virulent yet maintain fundamentally unique and stable identities. To make agent differences manifest, one must keep the host genotype constant. Many TSE agents have revealed their independent identities in normal mice. We transmitted primate kuru, a TSE once epidemic in New Guinea, to mice expressing normal and ≈8-fold higher levels of murine prion protein (PrP). High levels of murine PrP did not prevent infection but instead shortened incubation time, as would be expected for a viral receptor. Sporadic CJD and BSE agents and representative scrapie agents were clearly different from kuru in incubation time, brain neuropathology, and lymphoreticular involvement. Many TSE agents can infect monotypic cultured GT1 cells, and unlike sporadic CJD isolates, kuru rapidly and stably infected these cells. The geographic independence of the kuru agent provides additional reasons to explore causal environmental pathogens in these infectious neurodegenerative diseases. PMID:19633190

Can Moral Hazard Be Resolved by Common-Knowledge in S4n-Knowledge?

NASA Astrophysics Data System (ADS)

Matsuhisa, Takashi

This article investigates the relationship between common-knowledge and agreement in multi-agent system, and to apply the agreement result by common-knowledge to the principal-agent model under non-partition information. We treat the two problems: (1) how we capture the fact that the agents agree on an event or they get consensus on it from epistemic point of view, and (2) how the agreement theorem will be able to make progress to settle a moral hazard problem in the principal-agents model under non-partition information. We shall propose a solution program for the moral hazard in the principal-agents model under non-partition information by common-knowledge. Let us start that the agents have the knowledge structure induced from a reflexive and transitive relation associated with the multi-modal logic S4n. Each agent obtains the membership value of an event under his/her private information, so he/she considers the event as fuzzy set. Specifically consider the situation that the agents commonly know all membership values of the other agents. In this circumstance we shall show the agreement theorem that consensus on the membership values among all agents can still be guaranteed. Furthermore, under certain assumptions we shall show that the moral hazard can be resolved in the principal-agent model when all the expected marginal costs are common-knowledge among the principal and agents.

Mother ship and physical agents collaboration

NASA Astrophysics Data System (ADS)

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

1999-07-01

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

Cooperation and Coordination Between Fuzzy Reinforcement Learning Agents in Continuous State Partially Observable Markov Decision Processes

NASA Technical Reports Server (NTRS)

Berenji, Hamid R.; Vengerov, David

1999-01-01

Successful operations of future multi-agent intelligent systems require efficient cooperation schemes between agents sharing learning experiences. We consider a pseudo-realistic world in which one or more opportunities appear and disappear in random locations. Agents use fuzzy reinforcement learning to learn which opportunities are most worthy of pursuing based on their promise rewards, expected lifetimes, path lengths and expected path costs. We show that this world is partially observable because the history of an agent influences the distribution of its future states. We consider a cooperation mechanism in which agents share experience by using and-updating one joint behavior policy. We also implement a coordination mechanism for allocating opportunities to different agents in the same world. Our results demonstrate that K cooperative agents each learning in a separate world over N time steps outperform K independent agents each learning in a separate world over K*N time steps, with this result becoming more pronounced as the degree of partial observability in the environment increases. We also show that cooperation between agents learning in the same world decreases performance with respect to independent agents. Since cooperation reduces diversity between agents, we conclude that diversity is a key parameter in the trade off between maximizing utility from cooperation when diversity is low and maximizing utility from competitive coordination when diversity is high.

Multiagent data warehousing and multiagent data mining for cerebrum/cerebellum modeling

NASA Astrophysics Data System (ADS)

Zhang, Wen-Ran

2002-03-01

An algorithm named Neighbor-Miner is outlined for multiagent data warehousing and multiagent data mining. The algorithm is defined in an evolving dynamic environment with autonomous or semiautonomous agents. Instead of mining frequent itemsets from customer transactions, the new algorithm discovers new agents and mining agent associations in first-order logic from agent attributes and actions. While the Apriori algorithm uses frequency as a priory threshold, the new algorithm uses agent similarity as priory knowledge. The concept of agent similarity leads to the notions of agent cuboid, orthogonal multiagent data warehousing (MADWH), and multiagent data mining (MADM). Based on agent similarities and action similarities, Neighbor-Miner is proposed and illustrated in a MADWH/MADM approach to cerebrum/cerebellum modeling. It is shown that (1) semiautonomous neurofuzzy agents can be identified for uniped locomotion and gymnastic training based on attribute relevance analysis; (2) new agents can be discovered and agent cuboids can be dynamically constructed in an orthogonal MADWH, which resembles an evolving cerebrum/cerebellum system; and (3) dynamic motion laws can be discovered as association rules in first order logic. Although examples in legged robot gymnastics are used to illustrate the basic ideas, the new approach is generally suitable for a broad category of data mining tasks where knowledge can be discovered collectively by a set of agents from a geographically or geometrically distributed but relevant environment, especially in scientific and engineering data environments.

Remote Agent Demonstration

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

76 FR 62412 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... for Registration, (2) Request to Transfer Select Agent or Toxin, (3) Report of Theft, Loss, or Release..., or Release of Select Agent and Toxin, (4) Report of Identification of Select Agent or Toxin. There... Release of Select Agent or Toxin; (4) Report of Identification of Select Agent or Toxin; and (5) Request...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2010 CFR

2010-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2011 CFR

2011-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2012 CFR

2012-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2013 CFR

2013-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2014 CFR

2014-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

The Effect of Pacing on Learners' Perceptions of Pedagogical Agents

ERIC Educational Resources Information Center

Schroeder, Noah L.; Craig, Scotty D.

2017-01-01

This study examined the influence of three levels of learner control on learners' perceptions when learning with a pedagogical agent. Pedagogical agents have shown promise for improving learning and connections with learning materials within video-based instruction, and research has shown that agent design choices can influence how agents are…

29 CFR 1926.905 - Loading of explosives or blasting agents.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 8 2010-07-01 2010-07-01 false Loading of explosives or blasting agents. 1926.905 Section... Explosives § 1926.905 Loading of explosives or blasting agents. (a) Procedures that permit safe and efficient... have contained explosives or blasting agents. (g) No explosives or blasting agents shall be left...

78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-23

...-toxic macromolecular MRI contrast agents such as chelated Gd(III). These macromolecular imaging agents... Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent With a Surrogate Tracer for... Enhanced Delivery of Therapeutic Agents'', U.S. Provisional Patent Application 60/413,673 (filed September...

17 CFR 240.17Ad-10 - Prompt posting of certificate detail to master securityholder files, maintenance of accurate...

Code of Federal Regulations, 2014 CFR

2014-04-01

... between co-transfer agents and recordkeeping transfer agents, maintenance of current control book...-transfer agents and recordkeeping transfer agents, maintenance of current control book, retention of certificate detail and “buy-in” of physical over-issuance. (a)(1) Every recordkeeping transfer agent shall...

EMOTION RECOGNITION OF VIRTUAL AGENTS FACIAL EXPRESSIONS: THE EFFECTS OF AGE AND EMOTION INTENSITY

PubMed Central

Beer, Jenay M.; Fisk, Arthur D.; Rogers, Wendy A.

2014-01-01

People make determinations about the social characteristics of an agent (e.g., robot or virtual agent) by interpreting social cues displayed by the agent, such as facial expressions. Although a considerable amount of research has been conducted investigating age-related differences in emotion recognition of human faces (e.g., Sullivan, & Ruffman, 2004), the effect of age on emotion identification of virtual agent facial expressions has been largely unexplored. Age-related differences in emotion recognition of facial expressions are an important factor to consider in the design of agents that may assist older adults in a recreational or healthcare setting. The purpose of the current research was to investigate whether age-related differences in facial emotion recognition can extend to emotion-expressive virtual agents. Younger and older adults performed a recognition task with a virtual agent expressing six basic emotions. Larger age-related differences were expected for virtual agents displaying negative emotions, such as anger, sadness, and fear. In fact, the results indicated that older adults showed a decrease in emotion recognition accuracy for a virtual agent's emotions of anger, fear, and happiness. PMID:25552896

Learning comunication strategies for distributed artificial intelligence

NASA Astrophysics Data System (ADS)

Kinney, Michael; Tsatsoulis, Costas

1992-08-01

We present a methodology that allows collections of intelligent system to automatically learn communication strategies, so that they can exchange information and coordinate their problem solving activity. In our methodology communication between agents is determined by the agents themselves, which consider the progress of their individual problem solving activities compared to the communication needs of their surrounding agents. Through learning, communication lines between agents might be established or disconnected, communication frequencies modified, and the system can also react to dynamic changes in the environment that might force agents to cease to exist or to be added. We have established dynamic, quantitative measures of the usefulness of a fact, the cost of a fact, the work load of an agent, and the selfishness of an agent (a measure indicating an agent's preference between transmitting information versus performing individual problem solving), and use these values to adapt the communication between intelligent agents. In this paper we present the theoretical foundations of our work together with experimental results and performance statistics of networks of agents involved in cooperative problem solving activities.

[Alkylating agents].

PubMed

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.

Influences of Agents with a Self-Reputation Awareness Component in an Evolutionary Spatial IPD Game

PubMed Central

Huang, Chung-Yuan; Lee, Chun-Liang

2014-01-01

Iterated prisoner’s dilemma (IPD) researchers have shown that strong positive reputations plus an efficient reputation evaluation system encourages both sides to pursue long-term collaboration and to avoid falling into mutual defection cycles. In agent-based environments with reliable reputation rating systems, agents interested in maximizing their private interests must show concern for other agents as well as their own self-reputations–an important capability that standard IPD game agents lack. Here we present a novel learning agent model possessing self-reputation awareness. Agents in our proposed model are capable of evaluating self-behaviors based on a mix of public and private interest considerations, and of testing various solutions aimed at meeting social standards. Simulation results indicate multiple outcomes from the addition of a small percentage of self-reputation awareness agents: faster cooperation, faster movement toward stability in an agent society, a higher level of public interest in the agent society, the resolution of common conflicts between public and private interests, and a lower potential for rational individual behavior to transform into irrational group behavior. PMID:24945966

Distributed Evaluation Functions for Fault Tolerant Multi-Rover Systems

NASA Technical Reports Server (NTRS)

Agogino, Adrian; Turner, Kagan

2005-01-01

The ability to evolve fault tolerant control strategies for large collections of agents is critical to the successful application of evolutionary strategies to domains where failures are common. Furthermore, while evolutionary algorithms have been highly successful in discovering single-agent control strategies, extending such algorithms to multiagent domains has proven to be difficult. In this paper we present a method for shaping evaluation functions for agents that provide control strategies that both are tolerant to different types of failures and lead to coordinated behavior in a multi-agent setting. This method neither relies of a centralized strategy (susceptible to single point of failures) nor a distributed strategy where each agent uses a system wide evaluation function (severe credit assignment problem). In a multi-rover problem, we show that agents using our agent-specific evaluation perform up to 500% better than agents using the system evaluation. In addition we show that agents are still able to maintain a high level of performance when up to 60% of the agents fail due to actuator, communication or controller faults.

Biological Agents

MedlinePlus

... 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. ...

Persuasive Conversational Agent with Persuasion Tactics

NASA Astrophysics Data System (ADS)

Narita, Tatsuya; Kitamura, Yasuhiko

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

Agent Architectures for Compliance

NASA Astrophysics Data System (ADS)

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

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

Use of topical hemostatic agents in gynecologic surgery.

PubMed

Wysham, Weiya Z; Roque, Dario R; Soper, John T

2014-09-01

Sutures, hemoclips, and electrocautery are the primary mechanisms used to achieve hemostasis during gynecologic surgery, but in situations in which these are inadequate or not feasible, an array of hemostatic agents are available to help achieve hemostasis. These agents include physical agents such as cellulose, collagen, or gelatin products as well as biologic agents such as thrombin and fibrin products. Limited data are available on many of these agents, although their use is increasing, sometimes at high costs. In gynecologic surgery, hemostatic agents are likely most effective when used in areas of oozing or slow bleeding and as an adjunct to conventional surgical methods of hemostasis.

Knowledge focus via software agents

NASA Astrophysics Data System (ADS)

Henager, Donald E.

2001-09-01

The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be able to communicate to receive and disseminate information and provide the decision-maker with assistance via focused knowledge. THe agent must also be able to monitor the state of its own environment and make decisions necessary to carry out its delegated tasks. Agents bring three elements to the C2 domain that offer to improve decision-making. First, they provide higher-quality feedback and provide it more often. In doing so, the feedback loop becomes nearly continuous, reducing or eliminating delays in situation updates to decision-makers. Working with the most current information possible improves the control process, thus enabling effects based operations. Second, the agents accept delegation of actions and perform those actions following an established process. Agents' consistent actions reduce the variability of human input and stabilize the control process. Third, through the delegation of actions, agents ensure 100 percent consideration of plan details.

Preapproval and postapproval availability of published comparative efficacy research on biological agents.

PubMed

Thomas, Rachel Hutchins; Freeman, Maisha Kelly; Hughes, Peter J

2013-07-15

Preapproval and postapproval availability of published comparative efficacy studies on biological agents approved between 2000 and 2010 was investigated. Approval packages published on the Food and Drug Administration (FDA) website were examined for all biological agents approved between 2000 and 2010 to determine if comparative efficacy studies were available at the time of FDA approval. The availability of comparative efficacy studies published subsequent to approval was determined by searching PubMed for randomized, active-controlled experimental or observational study designs that measured efficacy as the primary endpoint and were relevant to the original FDA-approved indication. From 2000 to 2010, 107 biological agents were approved by FDA. Of the biological agents with alternative treatments, 54.6% had comparative efficacy data available at the time of approval. Although standard-reviewed biological agents were more likely to have comparative efficacy trials included in the FDA approval packages than priority-reviewed biological agents, statistically significant differences are unlikely. Subsequent to approval, 58.1% of biological agents had at least one published comparative efficacy trial, representing a 3.5% absolute increase in the availability of comparative efficacy studies since the time of approval. Vaccines and biological agents in the hematologic diseases, oncology, and miscellaneous diseases classes had fewer published postapproval comparative efficacy studies per agent compared with the overall group of biological agents. Nearly half of all biological agents approved for marketing between 2000 and 2010 lacked publicly accessible, active-controlled efficacy studies at the time of drug approval; a slightly greater proportion of biological agents had comparative efficacy data published subsequent to their approval.

Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

PubMed Central

Herrmann, Kelsey; Johansen, Mette L.; Craig, Sonya E.; Vincent, Jason; Howell, Michael; Gao, Ying; Lu, Lan; Erokwu, Bernadette; Agnes, Richard S.; Lu, Zheng-Rong; Pokorski, Jonathan K.; Basilion, James; Gulani, Vikas; Griswold, Mark; Flask, Chris; Brady-Kalnay, Susann M.

2015-01-01

Magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM) with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA)3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA)3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA)3 agent, a scrambled-Tris-(Gd-DOTA)3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA)3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA)3 agent over time compared to the non-specific contrast agent currently in clinical use. PMID:26435847

The balance between adaptation to catalysts and competition radius shapes the total wealth, time variability and inequality

NASA Astrophysics Data System (ADS)

Davidovich, Hadar; Louzoun, Yoram

2013-05-01

The globalization of modern markets has led to the emergence of competition between producers in ever growing distances. This opens the interesting question in population dynamics of the effect of long-range competition. We here study a model of non-local competition to test the effect of the competition radius on the wealth distribution, using the framework of a stochastic birth-death process, with non-local interactions. We show that this model leads to non-trivial dynamics that can have implications in other domains of physics. Competition is studied in the context of the catalyst induced growth of autocatalytic agents, representing the growth of capital in the presence of investment opportunities. These agents are competing with all other agents in a given radius on growth possibilities. We show that a large scale competition leads to an extreme localization of the agents, where typically a single aggregate of agents can survive within a given competition radius. The survival of these aggregates is determined by the diffusion rates of the agents and the catalysts. For high and low agent diffusion rates, the agent population is always annihilated, while for intermediate diffusion rates, a finite agent population persists. Increasing the catalyst diffusion rate always leads to a decrease in the average agent population density. The extreme localization of the agents leads to the emergence of intermittent fluctuations, when a large aggregate of agents disappear. As the competition radius increases, so does the average agent density and its spatial variance as well as the volatility.

Cooperation in Human-Agent Systems to Support Resilience: A Microworld Experiment.

PubMed

Chiou, Erin K; Lee, John D

2016-09-01

This study uses a dyadic approach to understand human-agent cooperation and system resilience. Increasingly capable technology fundamentally changes human-machine relationships. Rather than reliance on or compliance with more or less reliable automation, we investigate interaction strategies with more or less cooperative agents. A joint-task microworld scenario was developed to explore the effects of agent cooperation on participant cooperation and system resilience. To assess the effects of agent cooperation on participant cooperation, 36 people coordinated with a more or less cooperative agent by requesting resources and responding to requests for resources in a dynamic task environment. Another 36 people were recruited to assess effects following a perturbation in their own hospital. Experiment 1 shows people reciprocated the cooperative behaviors of the agents; a low-cooperation agent led to less effective interactions and less resource sharing, whereas a high-cooperation agent led to more effective interactions and greater resource sharing. Experiment 2 shows that an initial fast-tempo perturbation undermined proactive cooperation-people tended to not request resources. However, the initial fast tempo had little effect on reactive cooperation-people tended to accept resource requests according to cooperation level. This study complements the supervisory control perspective of human-automation interaction by considering interdependence and cooperation rather than the more common focus on reliability and reliance. The cooperativeness of automated agents can influence the cooperativeness of human agents. Design and evaluation for resilience in teams involving increasingly autonomous agents should consider the cooperative behaviors of these agents. © 2016, Human Factors and Ergonomics Society.

Replication and spread of CJD, kuru and scrapie agents in vivo and in cell culture

PubMed Central

Miyazawa, Kohtaro; Emmerling, Kaitlin

2011-01-01

Transmissible Spongiform Encephalopathy (TSE) agents are defined by their virulence for particular species, their spread in the population, their incubation time to cause disease, and their neuropathological sequelae. Murine adapted human agents, including sporadic CJD (sCJD), New Guinea kuru, and Japanese CJD agents, display particularly distinct incubation times and maximal infectious brain titers. They also induce agent-specific patterns of neurodegeneration. When these TSE agents are transmitted to cultured hypothalamic GT1 cells they maintain their unique identities. Nevertheless, the human kuru (kCJD) and Japanese FU-CJD agents, as well as the sheep 22L and 263K scrapie agents display doubling times that are 8× to 33× faster in cells than in brain, indicating release from complex innate immune responses. These data are most consistent with a foreign viral structure, rather than an infectious form of host prion protein (PrP-res). Profound agent-specific inhibitory effects are also apparent in GT1 cells, and maximal titer plateau in kCJD and FU-CJD differed by 1,000-fold in a cell-based assay. Remarkably, the lower titer kCJD agent rapidly induced de novo PrP-res in GT1 cells, whereas the high titer FU-CJD agent replicated silently for multiple passages. Although PrP-res is often considered to be toxic, PrP-res instead may be part of a primal defense and/or clearance mechanism against TSE environmental agents. Limited spread of particular TSE agents through nanotubes and cell-to-cell contacts probably underlies the long peripheral phase of human CJD. PMID:21527829

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2013-10-01

Carcinoma Stage IIB N N .149 1 8 .132 1 8 .092 1 No - Quit Smoking 50 AR Agent Orange , Nuclear weapons, Second-hand smoke Agent Orange , Nuclear weapons...Smoking 30 None Agent Orange , Asbestos, Second-hand smoke Agent Orange , Asbestos, Second-hand smoke S0159 Squamous Cell Carcinoma Stage IIB Y N...2.560 100 80 25 6 7 0.670 4 4 0.370 1 No - Quit Smoking 30 NV Agent Orange , Asbestos, Nuclear weapons, Second- hand smoke Agent Orange , Asbestos

Limonene and tetrahydrofurfuryl alcohol cleaning agent

DOEpatents

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

1996-05-07

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

The Resurrection of Malthus: space as the final escape from the law of diminishing returns

NASA Astrophysics Data System (ADS)

Sommers, J.; Beldavs, V.

2017-09-01

If there is a self-sustaining space economy, which is the goal of the International Lunar Decade, then it is a subject of economic analysis. The immediate challenge of space economics then is to conceptually demonstrate how a space economy could emerge and work where markets do not exist and few human agents may be involved, in fact where human agents may transact with either human agents or robotic agents or robotic agents may transact with other robotic agents.

Quicker Q-Learning in Multi-Agent Systems

NASA Technical Reports Server (NTRS)

Agogino, Adrian K.; Tumer, Kagan

2005-01-01

Multi-agent learning in Markov Decisions Problems is challenging because of the presence ot two credit assignment problems: 1) How to credit an action taken at time step t for rewards received at t' greater than t; and 2) How to credit an action taken by agent i considering the system reward is a function of the actions of all the agents. The first credit assignment problem is typically addressed with temporal difference methods such as Q-learning OK TD(lambda) The second credit assi,onment problem is typically addressed either by hand-crafting reward functions that assign proper credit to an agent, or by making certain independence assumptions about an agent's state-space and reward function. To address both credit assignment problems simultaneously, we propose the Q Updates with Immediate Counterfactual Rewards-learning (QUICR-learning) designed to improve both the convergence properties and performance of Q-learning in large multi-agent problems. Instead of assuming that an agent s value function can be made independent of other agents, this method suppresses the impact of other agents using counterfactual rewards. Results on multi-agent grid-world problems over multiple topologies show that QUICR-learning can achieve up to thirty fold improvements in performance over both conventional and local Q-learning in the largest tested systems.

An agent-based method for simulating porous fluid-saturated structures with indistinguishable components

NASA Astrophysics Data System (ADS)

Kashani, Jamal; Pettet, Graeme John; Gu, YuanTong; Zhang, Lihai; Oloyede, Adekunle

2017-10-01

Single-phase porous materials contain multiple components that intermingle up to the ultramicroscopic level. Although the structures of the porous materials have been simulated with agent-based methods, the results of the available methods continue to provide patterns of distinguishable solid and fluid agents which do not represent materials with indistinguishable phases. This paper introduces a new agent (hybrid agent) and category of rules (intra-agent rule) that can be used to create emergent structures that would more accurately represent single-phase structures and materials. The novel hybrid agent carries the characteristics of system's elements and it is capable of changing within itself, while also responding to its neighbours as they also change. As an example, the hybrid agent under one-dimensional cellular automata formalism in a two-dimensional domain is used to generate patterns that demonstrate the striking morphological and characteristic similarities with the porous saturated single-phase structures where each agent of the ;structure; carries semi-permeability property and consists of both fluid and solid in space and at all times. We conclude that the ability of the hybrid agent to change locally provides an enhanced protocol to simulate complex porous structures such as biological tissues which could facilitate models for agent-based techniques and numerical methods.

Sustainable Society Formed by Unselfish Agents

NASA Astrophysics Data System (ADS)

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.

An embodiment effect in computer-based learning with animated pedagogical agents.

PubMed

Mayer, Richard E; DaPra, C Scott

2012-09-01

How do social cues such as gesturing, facial expression, eye gaze, and human-like movement affect multimedia learning with onscreen agents? To help address this question, students were asked to twice view a 4-min narrated presentation on how solar cells work in which the screen showed an animated pedagogical agent standing to the left of 11 successive slides. Across three experiments, learners performed better on a transfer test when a human-voiced agent displayed human-like gestures, facial expression, eye gaze, and body movement than when the agent did not, yielding an embodiment effect. In Experiment 2 the embodiment effect was found when the agent spoke in a human voice but not in a machine voice. In Experiment 3, the embodiment effect was found both when students were told the onscreen agent was consistent with their choice of agent characteristics and when inconsistent. Students who viewed a highly embodied agent also rated the social attributes of the agent more positively than did students who viewed a nongesturing agent. The results are explained by social agency theory, in which social cues in a multimedia message prime a feeling of social partnership in the learner, which leads to deeper cognitive processing during learning, and results in a more meaningful learning outcome as reflected in transfer test performance.

Schools as Agents of Social Exclusion and Inclusion

ERIC Educational Resources Information Center

Razer, Michal; Friedman, Victor J.; Warshofsky, Boaz

2013-01-01

Although schools are usually regarded as important agents for social inclusion, research has shown that they may also function as agents of exclusion itself. The goal of this paper is to deepen our understanding of how schools function as agents of exclusion and how they can become more effective agents of inclusion. It is based on action research…

Agent Persuasion Mechanism of Acquaintance

NASA Astrophysics Data System (ADS)

Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

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

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

9 CFR 121.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... select agent or toxin to APHIS or CDC. (i) The seizure of any of the following overlap select agents and.... This report must be followed by submission of APHIS/CDC Form 4 within 7 calendar days after seizure of the overlap select agent or toxin. (ii) For all other overlap select agents or toxins, APHIS/CDC Form...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

13 CFR 120.950 - SBA and CDC must appoint agents.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...

PCBs Alter Dopamine Mediated Function in Aging Workers

DTIC Science & Technology

2010-01-01

sympathomimetic agents, beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, COX-2 inhibitors, other non - steroidal anti - inflammatory ...other non - steroidal anti - inflammatory agents, opiate agonists, miscellaneous analgesics and antipyretics, thyroid agents and antithyroid agents. ⁎ p...fold from peak values during occupational PCB use but remain elevated (two-fold) compared to a similar-aged non -occupationally exposed population

Automated monitoring of medical protocols: a secure and distributed architecture.

PubMed

Alsinet, T; Ansótegui, C; Béjar, R; Fernández, C; Manyà, F

2003-03-01

The control of the right application of medical protocols is a key issue in hospital environments. For the automated monitoring of medical protocols, we need a domain-independent language for their representation and a fully, or semi, autonomous system that understands the protocols and supervises their application. In this paper we describe a specification language and a multi-agent system architecture for monitoring medical protocols. We model medical services in hospital environments as specialized domain agents and interpret a medical protocol as a negotiation process between agents. A medical service can be involved in multiple medical protocols, and so specialized domain agents are independent of negotiation processes and autonomous system agents perform monitoring tasks. We present the detailed architecture of the system agents and of an important domain agent, the database broker agent, that is responsible of obtaining relevant information about the clinical history of patients. We also describe how we tackle the problems of privacy, integrity and authentication during the process of exchanging information between agents.

Autonomous Decentralized Voltage Profile Control of Super Distributed Energy System using Multi-agent Technology

NASA Astrophysics Data System (ADS)

Tsuji, Takao; Hara, Ryoichi; Oyama, Tsutomu; Yasuda, Keiichiro

A super distributed energy system is a future energy system in which the large part of its demand is fed by a huge number of distributed generators. At one time some nodes in the super distributed energy system behave as load, however, at other times they behave as generator - the characteristic of each node depends on the customers' decision. In such situation, it is very difficult to regulate voltage profile over the system due to the complexity of power flows. This paper proposes a novel control method of distributed generators that can achieve the autonomous decentralized voltage profile regulation by using multi-agent technology. The proposed multi-agent system employs two types of agent; a control agent and a mobile agent. Control agents generate or consume reactive power to regulate the voltage profile of neighboring nodes and mobile agents transmit the information necessary for VQ-control among the control agents. The proposed control method is tested through numerical simulations.

Emergence of trend trading and its effects in minority game

NASA Astrophysics Data System (ADS)

Liu, Xing-Hua; Liang, Xiao-Bei; Wang, Nai-Jing

2006-09-01

In this paper, we extended Minority Game (MG) by equipping agents with both value and trend strategies. In the new model, agents (we call them strong-adaptation agents) can autonomically select to act as trend trader or value trader when they game and learn in system. So the new model not only can reproduce stylized factors but also has the potential to investigate into the process of some problems of securities market. We investigated the dynamics of trend trading and its impacts on securities market based on the new model. Our research found that trend trading is inevitable when strong-adaptation agents make decisions by inductive reasoning. Trend trading (of strong-adaptation agents) is not irrational behavior but shows agent's strong-adaptation intelligence, because strong-adaptation agents can take advantage of the pure value agents when they game together in hybrid system. We also found that strong-adaptation agents do better in real environment. The results of our research are different with those of behavior finance researches.

Interaction and Communication of Agents in Networks and Language Complexity Estimates

NASA Technical Reports Server (NTRS)

Smid, Jan; Obitko, Marek; Fisher, David; Truszkowski, Walt

2004-01-01

Knowledge acquisition and sharing are arguably the most critical activities of communicating agents. We report about our on-going project featuring knowledge acquisition and sharing among communicating agents embedded in a network. The applications we target range from hardware robots to virtual entities such as internet agents. Agent experiments can be simulated using a convenient simulation language. We analyzed the complexity of communicating agent simulations using Java and Easel. Scenarios we have studied are listed below. The communication among agents can range from declarative queries to sub-natural language queries. 1) A set of agents monitoring an object are asked to build activity profiles based on exchanging elementary observations; 2) A set of car drivers form a line, where every car is following its predecessor. An unsafe distance cm create a strong wave in the line. Individual agents are asked to incorporate and apply directions how to avoid the wave. 3) A set of micro-vehicles form a grid and are asked to propagate information and concepts to a central server.

Can human-like Bots control collective mood: agent-based simulations of online chats

NASA Astrophysics Data System (ADS)

Tadić, Bosiljka; Šuvakov, Milovan

2013-10-01

Using an agent-based modeling approach, in this paper, we study self-organized dynamics of interacting agents in the presence of chat Bots. Different Bots with tunable ‘human-like’ attributes, which exchange emotional messages with agents, are considered, and the collective emotional behavior of agents is quantitatively analyzed. In particular, using detrended fractal analysis we determine persistent fluctuations and temporal correlations in time series of agent activity and statistics of avalanches carrying emotional messages of agents when Bots favoring positive/negative affects are active. We determine the impact of Bots and identify parameters that can modulate that impact. Our analysis suggests that, by these measures, the emotional Bots induce collective emotion among interacting agents by suitably altering the fractal characteristics of the underlying stochastic process. Positive emotion Bots are slightly more effective than negative emotion Bots. Moreover, Bots which periodically alternate between positive and negative emotion can enhance fluctuations in the system, leading to avalanches of agent messages that are reminiscent of self-organized critical states.

Effects of Manipulation on Attributions of Causation, Free Will, and Moral Responsibility.

PubMed

Murray, Dylan; Lombrozo, Tania

2017-03-01

If someone brings about an outcome without intending to, is she causally and morally responsible for it? What if she acts intentionally, but as the result of manipulation by another agent? Previous research has shown that an agent's mental states can affect attributions of causal and moral responsibility to that agent, but little is known about what effect one agent's mental states can have on attributions to another agent. In Experiment 1, we replicate findings that manipulation lowers attributions of responsibility to manipulated agents. Experiments 2-7 isolate which features of manipulation drive this effect, a crucial issue for both philosophical debates about free will and attributions of responsibility in situations involving social influence more generally. Our results suggest that "bypassing" a manipulated agent's mental states generates the greatest reduction in responsibility, and we explain our results in terms of the effects that one agent's mental states can have on the counterfactual relations between another agent and an outcome. Copyright © 2016 Cognitive Science Society, Inc.

A development framework for distributed artificial intelligence

NASA Technical Reports Server (NTRS)

Adler, Richard M.; Cottman, Bruce H.

1989-01-01

The authors describe distributed artificial intelligence (DAI) applications in which multiple organizations of agents solve multiple domain problems. They then describe work in progress on a DAI system development environment, called SOCIAL, which consists of three primary language-based components. The Knowledge Object Language defines models of knowledge representation and reasoning. The metaCourier language supplies the underlying functionality for interprocess communication and control access across heterogeneous computing environments. The metaAgents language defines models for agent organization coordination, control, and resource management. Application agents and agent organizations will be constructed by combining metaAgents and metaCourier building blocks with task-specific functionality such as diagnostic or planning reasoning. This architecture hides implementation details of communications, control, and integration in distributed processing environments, enabling application developers to concentrate on the design and functionality of the intelligent agents and agent networks themselves.

Agent oriented programming: An overview of the framework and summary of recent research

NASA Technical Reports Server (NTRS)

Shoham, Yoav

1993-01-01

This is a short overview of the agent-oriented programming (AOP) framework. AOP can be viewed as an specialization of object-oriented programming. The state of an agent consists of components called beliefs, choices, capabilities, commitments, and possibly others; for this reason the state of an agent is called its mental state. The mental state of agents is captured formally in an extension of standard epistemic logics: beside temporalizing the knowledge and belief operators, AOP introduces operators for commitment, choice and capability. Agents are controlled by agent programs, which include primitives for communicating with other agents. In the spirit of speech-act theory, each communication primitive is of a certain type: informing, requesting, offering, etc. This document describes these features in more detail and summarizes recent results and ongoing AOP-related work.

Hydrolysis of Synthetic Esters by the Antibacterial Agent in Serum

PubMed Central

Yotis, William W.

1966-01-01

Yotis, William W. (Loyola University, Chicago, Ill.). Hydrolysis of synthetic esters by the antibacterial agent in serum. J. Bacteriol. 91:488–493. 1966.—An antistaphylococcal serum agent was assayed colorimetrically, manometrically, and titrimetrically for esterase activity. p-Nitrophenol acetate, triacetin, l-lysine methyl and ethyl ester, and norleucine methyl ester were hydrolyzed by the antistaphylococcal agent. Acetylcholine and benzoylcholine esters, triolein, tristearin, and p-tosylarginine methyl ester were not attacked by this agent. With p-nitrophenol acetate as substrate, optimal activity occurred at pH 7.4. Incubation at 60 C for 30 min reduced drastically the esterase activity of the antistaphylococcal agent, and incubation at 75 C for 30 min abolished the esterase activity of this agent. Almost complete inhibition of esterase activity was observed with 0.001 m HgCl2, ZnSO4, and ethylenediaminetetraacetic acid (EDTA). EDTA inhibition could be reversed by the addition of CaCl2, but not MgCl2. Cysteine reversed the inhibition of HgCl2. NaF, atoxyl, diisopropyl fluorophosphate, quinine, and physostigmine did not influence the esterase activity of the antibacterial agent. The demonstration of esterase activity of both the antistaphylococcal agent and coagulase may shed further light on the reported ability of coagulase to neutralize the antistaphylococcal activity of this agent, or the prevention of absorption of the agent on the staphylococcal cell surface. In addition, the colorimetric procedure described in this report may be a convenient tool in assaying the potency of the antistaphylococcal agent. Images PMID:4956776

Consentaneous Agent-Based and Stochastic Model of the Financial Markets

PubMed Central

Gontis, Vygintas; Kononovicius, Aleksejus

2014-01-01

We are looking for the agent-based treatment of the financial markets considering necessity to build bridges between microscopic, agent based, and macroscopic, phenomenological modeling. The acknowledgment that agent-based modeling framework, which may provide qualitative and quantitative understanding of the financial markets, is very ambiguous emphasizes the exceptional value of well defined analytically tractable agent systems. Herding as one of the behavior peculiarities considered in the behavioral finance is the main property of the agent interactions we deal with in this contribution. Looking for the consentaneous agent-based and macroscopic approach we combine two origins of the noise: exogenous one, related to the information flow, and endogenous one, arising form the complex stochastic dynamics of agents. As a result we propose a three state agent-based herding model of the financial markets. From this agent-based model we derive a set of stochastic differential equations, which describes underlying macroscopic dynamics of agent population and log price in the financial markets. The obtained solution is then subjected to the exogenous noise, which shapes instantaneous return fluctuations. We test both Gaussian and q-Gaussian noise as a source of the short term fluctuations. The resulting model of the return in the financial markets with the same set of parameters reproduces empirical probability and spectral densities of absolute return observed in New York, Warsaw and NASDAQ OMX Vilnius Stock Exchanges. Our result confirms the prevalent idea in behavioral finance that herding interactions may be dominant over agent rationality and contribute towards bubble formation. PMID:25029364

Technological advancements for the detection of and protection against biological and chemical warfare agents.

PubMed

Eubanks, Lisa M; Dickerson, Tobin J; Janda, Kim D

2007-03-01

There is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. In this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. In particular, nerve agents are described as a typical chemical warfare agent, and the two potent biothreat agents, anthrax and botulinum neurotoxin, are used as illustrative examples of potent weapons for which countermeasures are urgently needed.

Promoting motivation with virtual agents and avatars: role of visual presence and appearance.

PubMed

Baylor, Amy L

2009-12-12

Anthropomorphic virtual agents can serve as powerful technological mediators to impact motivational outcomes such as self-efficacy and attitude change. Such anthropomorphic agents can be designed as simulated social models in the Bandurian sense, providing social influence as virtual 'role models'. Of particular value is the capacity for designing such agents as optimized social models for a target audience and context. Importantly, the visual presence and appearance of such agents can have a major impact on motivation and affect regardless of the underlying technical sophistication. Empirical results of different instantiations of agent presence and appearance are reviewed for both autonomous virtual agents and avatars that represent a user.

Collaborating Fuzzy Reinforcement Learning Agents

NASA Technical Reports Server (NTRS)

Berenji, Hamid R.

1997-01-01

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

Multi-Agent Design and Implementation for an Online Peer Help System

ERIC Educational Resources Information Center

Meng, Anbo

2014-01-01

With the rapid advance of e-learning, the online peer help is playing increasingly important role. This paper explores the application of MAS to an online peer help system (MAPS). In the design phase, the architecture of MAPS is proposed, which consists of a set of agents including the personal agent, the course agent, the diagnosis agent, the DF…

A STUDY OF NORTH CAROLINA AGRICULTURAL EXTENSION AGENTS' PERCEPTION OF THE ROLE OF FERTILIZER DEALERS IN EXTENSION PROGRAMMING.

ERIC Educational Resources Information Center

WOODARD, BRUCE H.

A QUESTIONNAIRE MAILED TO 98 AGRICULTURAL EXTENSION AGENTS IN NORTH CAROLINA WITH PRIMARY RESPONSIBILITY IN AGRONOMY IN THEIR COUNTIES WAS USED TO COLLECT DATA ON THE AGENTS' PERCEPTION OF THE NATURE AND FREQUENCY OF PERFORMANCE BY DEALERS IN SOIL FERTILITY PROGRAMS, AGENTS' FEELINGS ABOUT DEALER PARTICIPATION, AND THE ASSOCIATION BETWEEN AGENTS'…

KODAMA and VPC based Framework for Ubiquitous Systems and its Experiment

NASA Astrophysics Data System (ADS)

Takahashi, Kenichi; Amamiya, Satoshi; Iwao, Tadashige; Zhong, Guoqiang; Kainuma, Tatsuya; Amamiya, Makoto

Recently, agent technologies have attracted a lot of interest as an emerging programming paradigm. With such agent technologies, services are provided through collaboration among agents. At the same time, the spread of mobile technologies and communication infrastructures has made it possible to access the network anytime and from anywhere. Using agents and mobile technologies to realize ubiquitous computing systems, we propose a new framework based on KODAMA and VPC. KODAMA provides distributed management mechanisms by using the concept of community and communication infrastructure to deliver messages among agents without agents being aware of the physical network. VPC provides a method of defining peer-to-peer services based on agent communication with policy packages. By merging the characteristics of both KODAMA and VPC functions, we propose a new framework for ubiquitous computing environments. It provides distributed management functions according to the concept of agent communities, agent communications which are abstracted from the physical environment, and agent collaboration with policy packages. Using our new framework, we conducted a large-scale experiment in shopping malls in Nagoya, which sent advertisement e-mails to users' cellular phones according to user location and attributes. The empirical results showed that our new framework worked effectively for sales in shopping malls.

A distributed agent architecture for real-time knowledge-based systems: Real-time expert systems project, phase 1

NASA Technical Reports Server (NTRS)

Lee, S. Daniel

1990-01-01

We propose a distributed agent architecture (DAA) that can support a variety of paradigms based on both traditional real-time computing and artificial intelligence. DAA consists of distributed agents that are classified into two categories: reactive and cognitive. Reactive agents can be implemented directly in Ada to meet hard real-time requirements and be deployed on on-board embedded processors. A traditional real-time computing methodology under consideration is the rate monotonic theory that can guarantee schedulability based on analytical methods. AI techniques under consideration for reactive agents are approximate or anytime reasoning that can be implemented using Bayesian belief networks as in Guardian. Cognitive agents are traditional expert systems that can be implemented in ART-Ada to meet soft real-time requirements. During the initial design of cognitive agents, it is critical to consider the migration path that would allow initial deployment on ground-based workstations with eventual deployment on on-board processors. ART-Ada technology enables this migration while Lisp-based technologies make it difficult if not impossible. In addition to reactive and cognitive agents, a meta-level agent would be needed to coordinate multiple agents and to provide meta-level control.

Efficient Agent-Based Cluster Ensembles

NASA Technical Reports Server (NTRS)

Agogino, Adrian; Tumer, Kagan

2006-01-01

Numerous domains ranging from distributed data acquisition to knowledge reuse need to solve the cluster ensemble problem of combining multiple clusterings into a single unified clustering. Unfortunately current non-agent-based cluster combining methods do not work in a distributed environment, are not robust to corrupted clusterings and require centralized access to all original clusterings. Overcoming these issues will allow cluster ensembles to be used in fundamentally distributed and failure-prone domains such as data acquisition from satellite constellations, in addition to domains demanding confidentiality such as combining clusterings of user profiles. This paper proposes an efficient, distributed, agent-based clustering ensemble method that addresses these issues. In this approach each agent is assigned a small subset of the data and votes on which final cluster its data points should belong to. The final clustering is then evaluated by a global utility, computed in a distributed way. This clustering is also evaluated using an agent-specific utility that is shown to be easier for the agents to maximize. Results show that agents using the agent-specific utility can achieve better performance than traditional non-agent based methods and are effective even when up to 50% of the agents fail.

The influence of retraction agents on cytoskeleton reorganization and oxidative stress in primary human gingival fibroblasts (HGFs).

PubMed

Nowakowska, Danuta; Saczko, Jolanta; Bieżuńska-Kusiak, Katarzyna; Choromańska, Anna; Dubińska-Magiera, Magda; Ziętek, Marek; Kulbacka, Julita

2014-03-01

Contemporary gingival retraction chemicals are not without disagreeable side-effects; there appears to be no best gingival retraction agent. The aim of this research was to select the most biocompatible retraction agents based on examination of the parameters of oxidative stress in fibroblasts derived from human primary cell culture. In this in vitro study we evaluated parameters of oxidative stress after treatment with retraction agents. Visine, Afrin, Neosynephrin, Strazolin and Adrenaline were the commercial products studied as gingival retraction agents. Additionally we examined three experimental agents. We determined lipid peroxidation and protein damage and monitored changes in cellular cytoskeleton proteins. Proliferative and survival efficiency were also evaluated. Oxidative changes included by evaluated retraction agents were at the lowest level in the case of the experimental gels. Also cytoskeleton observations suggest that the experimental agents did not degrade the cellular structure of human gingival fibroblasts (HGFs). The current study was performed because of a need to project new nontoxic and save retraction agents for peridontological therapeutic usage. We suggest that the new investigational gels are most biocompatible with periodontal tissues and can be applied as new vasoconstrictor chemical retraction agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Exposure to biological agents used in Polish enterprises: analysis of data derived from the National Register of Biological Agent].

PubMed

Kozajda, Anna; Szadkowska-Stańczyk, Irena

2011-01-01

The National Register of Biological Agents at Work and the National Information Centre for Biological Agents Present at Workplaces were established in the Nofer Institute of Occupational Medicine in 2005. The National Information Centre carries out consultation and education activities concerning occupational exposure and risk assessment, development and implementation of preventive programs and accurate registration of reliable information about the use of biological agents. Educational materials on biological exposure are published on the website. The National Register of Biological Agents (database) collects and periodically analyzes the information obtained from employers about the use of biological agents for research, diagnostic or industrial purposes. As of 10 December 2010 there were 240 notifications from companies, which use biological agents for the following purposes: research--69, industrial--30 and diagnostic--321. Near 75% of all notifications were obtained from different diagnostic laboratories (public and private). In total, 3226 workers, including 2967 (92%) women and 256 (8%) men were exposed to biological agents. In general, occupational exposure to 209 biological agents (186 of risk group 2 and 23 of risk group 3, of which 16 are additionally marked by 3**) were registered in the data base.

Adaptive behaviors in multi-agent source localization using passive sensing.

PubMed

Shaukat, Mansoor; Chitre, Mandar

2016-12-01

In this paper, the role of adaptive group cohesion in a cooperative multi-agent source localization problem is investigated. A distributed source localization algorithm is presented for a homogeneous team of simple agents. An agent uses a single sensor to sense the gradient and two sensors to sense its neighbors. The algorithm is a set of individualistic and social behaviors where the individualistic behavior is as simple as an agent keeping its previous heading and is not self-sufficient in localizing the source. Source localization is achieved as an emergent property through agent's adaptive interactions with the neighbors and the environment. Given a single agent is incapable of localizing the source, maintaining team connectivity at all times is crucial. Two simple temporal sampling behaviors, intensity-based-adaptation and connectivity-based-adaptation, ensure an efficient localization strategy with minimal agent breakaways. The agent behaviors are simultaneously optimized using a two phase evolutionary optimization process. The optimized behaviors are estimated with analytical models and the resulting collective behavior is validated against the agent's sensor and actuator noise, strong multi-path interference due to environment variability, initialization distance sensitivity and loss of source signal.

A Scalable and Robust Multi-Agent Approach to Distributed Optimization

NASA Technical Reports Server (NTRS)

Tumer, Kagan

2005-01-01

Modularizing a large optimization problem so that the solutions to the subproblems provide a good overall solution is a challenging problem. In this paper we present a multi-agent approach to this problem based on aligning the agent objectives with the system objectives, obviating the need to impose external mechanisms to achieve collaboration among the agents. This approach naturally addresses scaling and robustness issues by ensuring that the agents do not rely on the reliable operation of other agents We test this approach in the difficult distributed optimization problem of imperfect device subset selection [Challet and Johnson, 2002]. In this problem, there are n devices, each of which has a "distortion", and the task is to find the subset of those n devices that minimizes the average distortion. Our results show that in large systems (1000 agents) the proposed approach provides improvements of over an order of magnitude over both traditional optimization methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents fail midway through the simulation) the system remains coordinated and still outperforms a failure-free and centralized optimization algorithm.

Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

NASA Astrophysics Data System (ADS)

Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

2017-09-01

Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

Chemical terrorism for the intensivist.

PubMed

Chalela, Julio A; Burnett, Thomas

2012-05-01

The use of chemical agents for terrorist attacks or military warfare is a major concern at the present time. Chemical agents can cause significant morbidity, are relatively inexpensive, and are easy to store and use. Weaponization of chemical agents is only limited by the physicochemical properties of some agents. Recent incidents involving toxic industrial chemicals and chemical terrorist attacks indicate that critical care services are frequently utilized. For obvious reasons, the critical care literature on chemical terrorism is scarce. This article reviews the clinical aspects of diagnosing and treating victims of chemical terrorism while emphasizing the critical care management. The intensivist needs to be familiar with the chemical agents that could be used in a terrorist attack. The military classification divides agents into lung agents, blood agents, vesicants, and nerve agents. Supportive critical care is the cornerstone of treatment for most casualties, and dramatic recovery can occur in many cases. Specific antidotes are available for some agents, but even without the antidote, aggressive intensive care support can lead to favorable outcome in many cases. Critical care and emergency services can be overwhelmed by a terrorist attack as many exposed but not ill will seek care.

Embodied artificial agents for understanding human social cognition.

PubMed

Wykowska, Agnieszka; Chaminade, Thierry; Cheng, Gordon

2016-05-05

In this paper, we propose that experimental protocols involving artificial agents, in particular the embodied humanoid robots, provide insightful information regarding social cognitive mechanisms in the human brain. Using artificial agents allows for manipulation and control of various parameters of behaviour, appearance and expressiveness in one of the interaction partners (the artificial agent), and for examining effect of these parameters on the other interaction partner (the human). At the same time, using artificial agents means introducing the presence of artificial, yet human-like, systems into the human social sphere. This allows for testing in a controlled, but ecologically valid, manner human fundamental mechanisms of social cognition both at the behavioural and at the neural level. This paper will review existing literature that reports studies in which artificial embodied agents have been used to study social cognition and will address the question of whether various mechanisms of social cognition (ranging from lower- to higher-order cognitive processes) are evoked by artificial agents to the same extent as by natural agents, humans in particular. Increasing the understanding of how behavioural and neural mechanisms of social cognition respond to artificial anthropomorphic agents provides empirical answers to the conundrum 'What is a social agent?' © 2016 The Authors.

Muriel Driver Memorial Lecture 2013: Embracing our role as change agents.

PubMed

Finlayson, Marcia L

2013-10-01

Given the nature of occupational therapy philosophy and practice, it is not surprising that "change agent" has been identified as one of the seven professional roles that occupational therapists fulfill. This Muriel Driver lecture examines the change agent role, what it means, and what knowledge, skills, and personal qualities are necessary to be effective. Overall, relatively little has been written about the change agent role in the occupational therapy literature. Much of what does exist is implicit and often embedded in related topics, such as advocacy. An examination of literature from outside of occupational therapy uncovered four major themes about this role: (a) Change agents are insightful, reflective, and disciplined; (b) Charnge agents are visionary leaders and mobilizers; (c) Change agents are knowledge integrators and translators; and (d) Change agents are diplomatic interventionists who produce meaningful outcomes. These themes point to several areas of silence in the occupational therapy literature. Overcoming these areas of silence and moving forward will require open, challenging, and scholarly debates; reconsideration of change agent role competencies; and clear messaging that we all have the capacity to be competent and effective change agents regardless of our title or setting.

Agent autonomy approach to probabilistic physics-of-failure modeling of complex dynamic systems with interacting failure mechanisms

NASA Astrophysics Data System (ADS)

Gromek, Katherine Emily

A novel computational and inference framework of the physics-of-failure (PoF) reliability modeling for complex dynamic systems has been established in this research. The PoF-based reliability models are used to perform a real time simulation of system failure processes, so that the system level reliability modeling would constitute inferences from checking the status of component level reliability at any given time. The "agent autonomy" concept is applied as a solution method for the system-level probabilistic PoF-based (i.e. PPoF-based) modeling. This concept originated from artificial intelligence (AI) as a leading intelligent computational inference in modeling of multi agents systems (MAS). The concept of agent autonomy in the context of reliability modeling was first proposed by M. Azarkhail [1], where a fundamentally new idea of system representation by autonomous intelligent agents for the purpose of reliability modeling was introduced. Contribution of the current work lies in the further development of the agent anatomy concept, particularly the refined agent classification within the scope of the PoF-based system reliability modeling, new approaches to the learning and the autonomy properties of the intelligent agents, and modeling interacting failure mechanisms within the dynamic engineering system. The autonomous property of intelligent agents is defined as agent's ability to self-activate, deactivate or completely redefine their role in the analysis. This property of agents and the ability to model interacting failure mechanisms of the system elements makes the agent autonomy fundamentally different from all existing methods of probabilistic PoF-based reliability modeling. 1. Azarkhail, M., "Agent Autonomy Approach to Physics-Based Reliability Modeling of Structures and Mechanical Systems", PhD thesis, University of Maryland, College Park, 2007.

Joint chemical agent detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.

2003-08-01

The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Cognitive, cultural, and linguistic sources of a handshape distinction expressing agentivity.

PubMed

Brentari, Diane; Di Renzo, Alessio; Keane, Jonathan; Volterra, Virginia

2015-01-01

In this paper the cognitive, cultural, and linguistic bases for a pattern of conventionalization of two types of iconic handshapes are described. Work on sign languages has shown that handling handshapes (H-HSs: those that represent how objects are handled or manipulated) and object handshapes (O-HSs: those that represent the class, size, or shape of objects) express an agentive/non-agentive semantic distinction in many sign languages. H-HSs are used in agentive event descriptions and O-HSs are used in non-agentive event descriptions. In this work, American Sign Language (ASL) and Italian Sign Language (LIS) productions are compared (adults and children) as well as the corresponding groups of gesturers in each country using "silent gesture." While the gesture groups, in general, did not employ an H-HS/O-HS distinction, all participants (signers and gesturers) used iconic handshapes (H-HSs and O-HSs together) more often in agentive than in no-agent event descriptions; moreover, none of the subjects produced an opposite pattern than the expected one (i.e., H-HSs associated with no-agent descriptions and O-HSs associated with agentive ones). These effects are argued to be grounded in cognition. In addition, some individual gesturers were observed to produce the H-HS/O-HS opposition for agentive and non-agentive event descriptions-that is, more Italian than American adult gesturers. This effect is argued to be grounded in culture. Finally, the agentive/non-agentive handshape opposition is confirmed for signers of ASL and LIS, but previously unreported cross-linguistic differences were also found across both adult and child sign groups. It is, therefore, concluded that cognitive, cultural, and linguistic factors contribute to the conventionalization of this distinction of handshape type. Copyright © 2014 Cognitive Science Society, Inc.

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

PubMed

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

2016-01-01

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

Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Shan, Liang; Gu, Xinbin; Wang, Paul

2013-09-01

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

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

Code of Federal Regulations, 2010 CFR

2010-07-01

... agent empowered to fulfill your obligations under the Act, the lease, or the regulations in this part... agent empowered to receive notices and submit requests, applications, notices, or supplemental...

How gestures affect students: A comparative experiment using class presentations conducted by an anthropomorphic agent

NASA Astrophysics Data System (ADS)

Shirakawa, Tomohiro; Sato, Hiroshi; Imao, Tomoya

2017-07-01

Recently, a variety of user interfaces have been developed based on human-robot and human-agent interaction, and anthropomorphic agents are used as one type of interface. However, the use of anthropomorphic agents is applied mainly to the medical and cognitive sciences, and there are few studies of their application to other fields. Therefore, we used an anthropomorphic agent of MMD in a virtual lecture to analyze the effect of gestures on students and search for ways to apply anthropomorphic agents to the field of educational technology.

Exhaustive search system and method using space-filling curves

DOEpatents

Spires, Shannon V.

2003-10-21

A search system and method for one agent or for multiple agents using a space-filling curve provides a way to control one or more agents to cover an area of any space of any dimensionality using an exhaustive search pattern. An example of the space-filling curve is a Hilbert curve. The search area can be a physical geography, a cyberspace search area, or an area searchable by computing resources. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace.

MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

PubMed

Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

2016-09-30

Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

MIDAS: A Practical Bayesian Design for Platform Trials with Molecularly Targeted Agents

PubMed Central

Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

2016-01-01

Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time, and thus not efficient for this task. We propose a Bayesian phase II platform design, the Multi-candidate Iterative Design with Adaptive Selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and “graduate” the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. PMID:27112322

Product Categories under the National Contingency Plan Subpart J

EPA Pesticide Factsheets

There are five types authorized for use in oil spill cleanups, defined in 40 CFR 300.5. They are bioremediation agents, dispersants, sorbents, surface collecting agents, surface washing agents, and miscellaneous oil spill control agents.

30 CFR 550.145 - How do I designate an agent or a local agent?

Code of Federal Regulations, 2012 CFR

2012-07-01

... designate an agent empowered to fulfill your obligations under the Act, the lease, or the regulations in... local agent empowered to receive notices and submit requests, applications, notices, or supplemental...

30 CFR 550.145 - How do I designate an agent or a local agent?

Code of Federal Regulations, 2013 CFR

2013-07-01

... designate an agent empowered to fulfill your obligations under the Act, the lease, or the regulations in... local agent empowered to receive notices and submit requests, applications, notices, or supplemental...

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

Code of Federal Regulations, 2011 CFR

2011-07-01

... Director may require you to designate an agent empowered to fulfill your obligations under the Act, the... Regional Supervisor's approval a local agent empowered to receive notices and submit requests, applications...

30 CFR 550.145 - How do I designate an agent or a local agent?

Code of Federal Regulations, 2014 CFR

2014-07-01

... designate an agent empowered to fulfill your obligations under the Act, the lease, or the regulations in... local agent empowered to receive notices and submit requests, applications, notices, or supplemental...

Antithrombogenic Polymer Coating.

DOEpatents

Huang, Zhi Heng; McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

2003-01-21

An article having a non-thrombogenic surface and a process for making the article are disclosed. The article is formed by (i) coating a polymeric substrate with a crosslinked chemical combination of a polymer having at least two amino substituted side chains, a crosslinking agent containing at least two crosslinking functional groups which react with amino groups on the polymer, and a linking agent containing a first functional group which reacts with a third functional group of the crosslinking agent, and (ii) contacting the coating on the substrate with an antithrombogenic agent which covalently bonds to a second functional group of the linking agent. In one example embodiment, the polymer is a polyamide having amino substituted alkyl chains on one side of the polyamide backbone, the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl, the linking agent is a polyhydrazide and the antithrombogenic agent is heparin.

Emotional Multiagent Reinforcement Learning in Spatial Social Dilemmas.

PubMed

Yu, Chao; Zhang, Minjie; Ren, Fenghui; Tan, Guozhen

2015-12-01

Social dilemmas have attracted extensive interest in the research of multiagent systems in order to study the emergence of cooperative behaviors among selfish agents. Understanding how agents can achieve cooperation in social dilemmas through learning from local experience is a critical problem that has motivated researchers for decades. This paper investigates the possibility of exploiting emotions in agent learning in order to facilitate the emergence of cooperation in social dilemmas. In particular, the spatial version of social dilemmas is considered to study the impact of local interactions on the emergence of cooperation in the whole system. A double-layered emotional multiagent reinforcement learning framework is proposed to endow agents with internal cognitive and emotional capabilities that can drive these agents to learn cooperative behaviors. Experimental results reveal that various network topologies and agent heterogeneities have significant impacts on agent learning behaviors in the proposed framework, and under certain circumstances, high levels of cooperation can be achieved among the agents.

Demeter, persephone, and the search for emergence in agent-based models.

DOE Office of Scientific and Technical Information (OSTI.GOV)

North, M. J.; Howe, T. R.; Collier, N. T.

2006-01-01

In Greek mythology, the earth goddess Demeter was unable to find her daughter Persephone after Persephone was abducted by Hades, the god of the underworld. Demeter is said to have embarked on a long and frustrating, but ultimately successful, search to find her daughter. Unfortunately, long and frustrating searches are not confined to Greek mythology. In modern times, agent-based modelers often face similar troubles when searching for agents that are to be to be connected to one another and when seeking appropriate target agents while defining agent behaviors. The result is a 'search for emergence' in that many emergent ormore » potentially emergent behaviors in agent-based models of complex adaptive systems either implicitly or explicitly require search functions. This paper considers a new nested querying approach to simplifying such agent-based modeling and multi-agent simulation search problems.« less

Fluid extraction using carbon dioxide and organophosphorus chelating agents

DOEpatents

Smart, N.G.; Wai, C.M.; Lin, Y.; Kwang, Y.H.

1998-11-24

Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO{sub 2}, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO{sub 2} and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process. 1 fig.

Fluid extraction using carbon dioxide and organophosphorus chelating agents

DOEpatents

Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

1998-01-01

Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

How to justify enforcing a Ulysses contract when Ulysses is competent to refuse.

PubMed

Davis, John K

2008-03-01

Sometimes the mentally ill have sufficient mental capacity to refuse treatment competently, and others have a moral duty to respect their refusal. However, those with episodic mental disorders may wish to precommit themselves to treatment, using Ulysses contracts known as "mental health advance directives." How can health care providers justify enforcing such contracts over an agent's current, competent refusal? I argue that providers respect an agent's autonomy not retrospectively--by reference to his or her past wishes-and not merely synchronically--so that the agent gets what he or she wants right now-but diachronically and prospectively, acting so that the agent can shape his or her circumstances as the agent wishes over time, for the agent will experience the consequences of providers' actions over time. Mental health directives accomplish this, so they are a way of respecting the agent's autonomy even when providers override the agent's current competent refusal.

Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

Cachard, Christian; Basset, Olivier

While the use of contrast agents in other imaging modalities (X ray, MRI, PET, …) has been routinely accepted for many years, the development and commercialization of contrast agents designed specifically for ultrasound imaging has occurred only very recently. As in the other imaging modalities, the injection of contrast agents during an ultrasound examination is intended to facilitate the detection and diagnosis of specific pathologies. Contrast agents efficiency is based on the backscattering of ultrasound by microbubbles. These microparticules are intravenously injected in the blood flow. After an introduction and generalities on ultrasound contrast agents (UCA) the microbubble physics in an acoustic field will be developed. Second, physics characteristics of contrast agents will be compared (bubbles with or without shell, gas nature, size distribution). Influence of acoustic pressure on the behaviour of the microparticules (linear, non linear and destruction) will be discussed. Finally, a review of specific imaging adapted to contrast agent properties as harmonic imaging, pulse inversion imaging will be presented.

Daphnia swarms: from single agent dynamics to collective vortex formation

NASA Astrophysics Data System (ADS)

Ordemann, Anke; Balazsi, Gabor; Caspari, Elizabeth; Moss, Frank

2003-05-01

Swarm theories have become fashionable in theoretical physics over the last decade. They span the range of interactions from individual agents moving in a mean field to coherent collective motions of large agent populations, such as vortex-swarming. But controlled laboratory tests of these theories using real biological agents have been problematic due primarily to poorly known agent-agent interactions (in the case of e.g. bacteria and slime molds) or the large swarm size (e.g. for flocks of birds and schools of fish). Moreover, the entire range of behaviors from single agent interactions to collective vortex motions of the swarm have here-to-fore not been observed with a single animal. We present the results of well defined experiments with the zooplankton Daphnia in light fields showing this range of behaviors. We interpret our results with a theory of the motions of self-propelled agents in a field.

Manipulating Scrip Systems: Sybils and Collusion

NASA Astrophysics Data System (ADS)

Kash, Ian A.; Friedman, Eric J.; Halpern, Joseph Y.

Game-theoretic analyses of distributed and peer-to-peer systems typically use the Nash equilibrium solution concept, but this explicitly excludes the possibility of strategic behavior involving more than one agent. We examine the effects of two types of strategic behavior involving more than one agent, sybils and collusion, in the context of scrip systems where agents provide each other with service in exchange for scrip. Sybils make an agent more likely to be chosen to provide service, which generally makes it harder for agents without sybils to earn money and decreases social welfare. Surprisingly, in certain circumstances it is possible for sybils to make all agents better off. While collusion is generally bad, in the context of scrip systems it actually tends to make all agents better off, not merely those who collude. These results also provide insight into the effects of allowing agents to advertise and loan money.

Social Cognition Unbound: Insights Into Anthropomorphism and Dehumanization.

PubMed

Waytz, Adam; Epley, Nicholas; Cacioppo, John T

2010-02-01

People conceive of wrathful gods, fickle computers, and selfish genes, attributing human characteristics to a variety of supernatural, technological, and biological agents. This tendency to anthropomorphize nonhuman agents figures prominently in domains ranging from religion to marketing to computer science. Perceiving an agent to be humanlike has important implications for whether the agent is capable of social influence, accountable for its actions, and worthy of moral care and consideration. Three primary factors-elicited agent knowledge, sociality motivation, and effectance motivation-appear to account for a significant amount of variability in anthropomorphism. Identifying these factors that lead people to see nonhuman agents as humanlike also sheds light on the inverse process of dehumanization, whereby people treat human agents as animals or objects. Understanding anthropomorphism can contribute to a more expansive view of social cognition that applies social psychological theory to a wide variety of both human and nonhuman agents.

Social Cognition Unbound: Insights Into Anthropomorphism and Dehumanization

PubMed Central

Waytz, Adam; Epley, Nicholas; Cacioppo, John T.

2014-01-01

People conceive of wrathful gods, fickle computers, and selfish genes, attributing human characteristics to a variety of supernatural, technological, and biological agents. This tendency to anthropomorphize nonhuman agents figures prominently in domains ranging from religion to marketing to computer science. Perceiving an agent to be humanlike has important implications for whether the agent is capable of social influence, accountable for its actions, and worthy of moral care and consideration. Three primary factors—elicited agent knowledge, sociality motivation, and effectance motivation—appear to account for a significant amount of variability in anthropomorphism. Identifying these factors that lead people to see nonhuman agents as humanlike also sheds light on the inverse process of dehumanization, whereby people treat human agents as animals or objects. Understanding anthropomorphism can contribute to a more expansive view of social cognition that applies social psychological theory to a wide variety of both human and nonhuman agents. PMID:24839358

Multi-agent Reinforcement Learning Model for Effective Action Selection

NASA Astrophysics Data System (ADS)

Youk, Sang Jo; Lee, Bong Keun

Reinforcement learning is a sub area of machine learning concerned with how an agent ought to take actions in an environment so as to maximize some notion of long-term reward. In the case of multi-agent, especially, which state space and action space gets very enormous in compared to single agent, so it needs to take most effective measure available select the action strategy for effective reinforcement learning. This paper proposes a multi-agent reinforcement learning model based on fuzzy inference system in order to improve learning collect speed and select an effective action in multi-agent. This paper verifies an effective action select strategy through evaluation tests based on Robocop Keep away which is one of useful test-beds for multi-agent. Our proposed model can apply to evaluate efficiency of the various intelligent multi-agents and also can apply to strategy and tactics of robot soccer system.

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents.

PubMed

Anderson, Christian E; Donnola, Shannon B; Jiang, Yun; Batesole, Joshua; Darrah, Rebecca; Drumm, Mitchell L; Brady-Kalnay, Susann M; Steinmetz, Nicole F; Yu, Xin; Griswold, Mark A; Flask, Chris A

2017-08-16

Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC - MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.

Collective circular motion in synchronized and balanced formations with second-order rotational dynamics

NASA Astrophysics Data System (ADS)

Jain, Anoop; Ghose, Debasish

2018-01-01

This paper considers collective circular motion of multi-agent systems in which all the agents are required to traverse different circles or a common circle at a prescribed angular velocity. It is required to achieve these collective motions with the heading angles of the agents synchronized or balanced. In synchronization, the agents and their centroid have a common velocity direction, while in balancing, the movement of agents causes the location of the centroid to become stationary. The agents are initially considered to move at unit speed around individual circles at different angular velocities. It is assumed that the agents are subjected to limited communication constraints, and exchange relative information according to a time-invariant undirected graph. We present suitable feedback control laws for each of these motion coordination tasks by considering a second-order rotational dynamics of the agent. Simulations are given to illustrate the theoretical findings.

Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR

DTIC Science & Technology

2005-12-31

recognize and predict prospective toxicity among covalent -binding AChE inhibitors of potential application to nerve agent prophylaxis and...is below since many authors do not follow the 200 word limit 14. SUBJECT TERMS nerve agents , acetylcholinesterase, prophylaxis, QSAR, virtual...Report: Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR Report Title ABSTRACT Organophosphorus (OP) nerve agents are among the

Exploration of Force Transition in Stability Operations Using Multi-Agent Simulation

DTIC Science & Technology

2006-09-01

risk, mission failure risk, and time in the context of the operational threat environment. The Pythagoras Multi-Agent Simulation and Data Farming...NUMBER OF PAGES 173 14. SUBJECT TERMS Stability Operations, Peace Operations, Data Farming, Pythagoras , Agent- Based Model, Multi-Agent Simulation...the operational threat environment. The Pythagoras Multi-Agent Simulation and Data Farming techniques are used to investigate force-level

Rich or poor: Who should pay higher tax rates?

NASA Astrophysics Data System (ADS)

Murilo Castro de Oliveira, Paulo

2017-08-01

A dynamic agent model is introduced with an annual random wealth multiplicative process followed by taxes paid according to a linear wealth-dependent tax rate. If poor agents pay higher tax rates than rich agents, eventually all wealth becomes concentrated in the hands of a single agent. By contrast, if poor agents are subject to lower tax rates, the economic collective process continues forever.

Population dynamics and impacts of the red-headed leafy spurge stem borer on leafy spurge (Euphorbia esula)

Treesearch

Robert A. Progar; George Markin; Joseph Milan; Tom Barbouletos; Matthew J. Rinella

2011-01-01

We evaluated the efficacy of the biological control agent, red-headed leafy spurge stem borer, against the nonnative invasive plant leafy spurge. Our three treatments were release of the biological control agent into uncaged plots, release of the biological control agent into plots caged to prevent agent escape, and control plots caged to prevent agent entry. These...

17 CFR 279.4 - Form ADV-NR, appointment of agent for service of process by non-resident general partner and non...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form ADV-NR, appointment of agent for service of process by non-resident general partner and non-resident managing agent of an... agent for service of process by non-resident general partner and non-resident managing agent of an...

Maintaining Limited-Range Connectivity Among Second-Order Agents

DTIC Science & Technology

2016-07-07

we consider ad-hoc networks of robotic agents with double integrator dynamics. For such networks, the connectivity maintenance problems are: (i) do...hoc networks of mobile autonomous agents. This loose ter- minology refers to groups of robotic agents with limited mobility and communica- tion...connectivity can be preserved. 3.1. Networks of robotic agents with second-order dynamics and the connectivity maintenance problem. We begin by

Influence of Selected Personal Characteristics and County Situational Factors on Time Allocated to Dairy Subjects by Extension Agents in Selected Tennessee Counties.

ERIC Educational Resources Information Center

Northcutt, Sherwin Dean; And Others

The study deals with various predictors of time spent on dairy subjects by Extension agents and predictors of contacts made by agents with dairy clientele. Purposes were to determine the relationships, if any, between various independent variables and groups of independent variables (agents' background and training, county dairy situation, agents'…

How do ensembles occupy space?

NASA Astrophysics Data System (ADS)

Daffertshofer, A.

2008-04-01

To find an answer to the title question, an attractiveness function between agents and locations is introduced yielding a phenomenological but generic model for the search for optimal distributions of agents over space. Agents can be seen as, e.g., members of biological populations like colonies of bacteria, swarms, and so on. The global attractiveness between agents and locations is maximized causing (self-propelled) `motion' of agents and, eventually, distinct distributions of agents over space. At the same token spontaneous changes or `decisions' are realized via competitions between agents as well as between locations. Hence, the model's solutions can be considered a sequence of decisions of agents during their search for a proper location. Depending on initial conditions both optimal as well as suboptimal configurations can be reached. For the latter early decision-making are important for avoiding possible conflicts: if the proper moment is missed, then only a few agents can find an optimal solution. Indeed, there is a delicate interplay between the values of the attractiveness function and the constraints as can be expressed by distinct terms of a potential function containing different Lagrange parameters. The model should be viewed as a top-down approach as it describes the dynamics of order parameters, i.e. macroscopic variables that reflect affiliations between agents and locations. The dynamics, however, is modified via so-called cost functions that are interpreted in terms of affinity levels. This interpretation can be seen as an original step towards an understanding of the dynamics at the underlying microscopic level. When focusing on the agent, one may say that the dynamics of an order parameter shows the evolution of an agent's intrinsic `map' for solving the problem of space occupation. Importantly, the dynamics does not necessarily distinguish between evolving (or moving) agents and evolving (or moving) locations though agents are more likely to be actors than the locations. Put differently, an order parameter describes an internal map which is linked to the expectation of an agent to find a certain location. Owing to the dynamical representation, we can therefore follow up the change of these maps over time leading from uncertainty to certainty.

Skin-derived dendritic cells acquire and degrade the scrapie agent following in vitro exposure

PubMed Central

Mohan, Joanne; Hopkins, John; Mabbott, Neil A

2005-01-01

The accumulation of the scrapie agent in lymphoid tissues following inoculation via the skin is critical for efficient neuroinvasion, but how the agent is initially transported from the skin to the draining lymph node is not known. Langerhans cells (LCs) are specialized antigen-presenting cells that continually sample their microenvironment within the epidermis and transport captured antigens to draining lymph nodes. We considered LCs probable candidates to acquire and transport the scrapie agent after inoculation via the skin. XS106 cells are dendritic cells (DCs) isolated from mouse epidermis with characteristics of mature LC cells. To investigate the potential interaction of LCs with the scrapie agent XS106 cells were exposed to the scrapie agent in vitro. We show that XS106 cells rapidly acquire the scrapie agent following in vitro exposure. In addition, XS106 cells partially degrade the scrapie agent following extended cultivation. These data suggest that LCs might acquire and degrade the scrapie agent after inoculation via the skin, but data from additional experiments demonstrate that this ability could be lost in the presence of lipopolysaccharide or other immunostimulatory molecules. Our studies also imply that LCs would not undergo maturation following uptake of the scrapie agent in the skin, as the expression of surface antigens associated with LC maturation were unaltered following exposure. In conclusion, although LCs or DCs have the potential to acquire the scrapie agent within the epidermis our data suggest it is unlikely that they become activated and stimulated to transport the agent to the draining lymph node. PMID:16108824

Male bladder cancer risk and occupational exposure according to a job-exposure matrix-a case-control study in British Columbia, Canada.

PubMed

Richardson, Kathryn; Band, Pierre R; Astrakianakis, George; Le, Nhu D

2007-12-01

The authors investigated the risk of bladder cancer in association with exposure to over 12 000 occupational chemical agents, complex mixtures, and other substances (hereafter referred to as chemical agents). Adult males diagnosed with cancer between 1983 and 1990 in British Columbia, Canada, were surveyed. Detailed occupational histories and confounding information was provided by a self-administered questionnaire. Cancer controls were matched to bladder cancer cases, resulting in 1062 cases and 8057 controls for the analysis. An extensive United-States-based job-exposure matrix was applied to estimate cumulative exposure to occupational chemical agents. Odds ratios for bladder cancer due to exposure to chemical agents were estimated via conditional logistic regression analyses, adjusted for important confounders. A significantly (P<0.05) increased risk was detected for ever exposure to 635 chemical agents, and 341 chemical agents exhibited a significantly increasing dose-response relationship. Adjustment for multiple comparisons resulted in a subset of 29 chemical agents that continued to show significant results. A principal components analysis classified these 29 chemical agents into five independent groups, distinguished mainly by job. Exposures to these chemical agents were largely due to employment in the logging and construction industries and occupations involving motor vehicles. Consistent results were observed for bladder carcinogens reported in the literature. This study suggests that several specific chemical agents were significantly associated with the risk of bladder cancer. The chemical agents were mainly derivatives or combustion products of fossil fuels. The results corroborate important findings from the literature and document a risk for specific chemical agents not previously reported.

Joint Chemical Agent Detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.; Owen, Jeffery L.

2002-06-01

The Joint Chemical Agent Detector (JCAD) will provide state of the art chemical warfare agent detection capability to ground vehicle operators. Intelligence sources estimate that over twenty counties have active chemical weapons programs. The spread of chemical weapons to third world nations, coupled with the potential for US involvement in these areas in an operational or support capacity, increases the probability that the Joint Services may encounter chemical agents and toxic industrial materials anywhere in the world. Currently, fielded chemical agent detectors are bulky, labor intensive, and subject to false readings. No legacy detector is sensitive enough to provide detection and warning of the low dose hazards associated with miosis contamination. The JCAD will provide a small, lightweight chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection components across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD will detect, identify, quantify, and warn of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector will provide local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD will also be capable of being upgraded to protect against future chemical agent threats. The JCAD will provide the vehicle operators with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Dynamics and Steady States in Excitable Mobile Agent Systems

NASA Astrophysics Data System (ADS)

Peruani, Fernando; Sibona, Gustavo J.

2008-04-01

We study the spreading of excitations in 2D systems of mobile agents where the excitation is transmitted when a quiescent agent keeps contact with an excited one during a nonvanishing time. We show that the steady states strongly depend on the spatial agent dynamics. Moreover, the coupling between exposition time (ω) and agent-agent contact rate (CR) becomes crucial to understand the excitation dynamics, which exhibits three regimes with CR: no excitation for low CR, an excited regime in which the number of quiescent agents (S) is inversely proportional to CR, and, for high CR, a novel third regime, model dependent, where S scales with an exponent ξ-1, with ξ being the scaling exponent of ω with CR.

Virtual agents in a simulated virtual training environment

NASA Technical Reports Server (NTRS)

Achorn, Brett; Badler, Norman L.

1993-01-01

A drawback to live-action training simulations is the need to gather a large group of participants in order to train a few individuals. One solution to this difficulty is the use of computer-controlled agents in a virtual training environment. This allows a human participant to be replaced by a virtual, or simulated, agent when only limited responses are needed. Each agent possesses a specified set of behaviors and is capable of limited autonomous action in response to its environment or the direction of a human trainee. The paper describes these agents in the context of a simulated hostage rescue training session, involving two human rescuers assisted by three virtual (computer-controlled) agents and opposed by three other virtual agents.

Biomaterials for mediation of chemical and biological warfare agents.

PubMed

Russell, Alan J; Berberich, Jason A; Drevon, Geraldine F; Koepsel, Richard R

2003-01-01

Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.

Social effects of an anthropomorphic help agent: humans versus computers.

PubMed

David, Prabu; Lu, Tingting; Kline, Susan; Cai, Li

2007-06-01

The purpose of this study was to examine perceptions of fairness of a computer-administered quiz as a function of the anthropomorphic features of the help agent offered within the quiz environment. The addition of simple anthropomorphic cues to a computer help agent reduced the perceived friendliness of the agent, perceived intelligence of the agent, and the perceived fairness of the quiz. These differences were observed only for male anthropomorphic cues, but not for female anthropomorphic cues. The results were not explained by the social attraction of the anthropomorphic agents used in the quiz or by gender identification with the agents. Priming of visual cues provides the best account of the data. Practical implications of the study are discussed.

TACtic- A Multi Behavioral Agent for Trading Agent Competition

NASA Astrophysics Data System (ADS)

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

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

13 CFR 120.952 - Fiscal agent.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

13 CFR 120.952 - Fiscal agent.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

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

Code of Federal Regulations, 2012 CFR

2012-07-01

... require you to designate an agent empowered to fulfill your obligations under the Act, the lease, or the... approval a local agent empowered to receive notices and submit requests, applications, notices, or...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... require you to designate an agent empowered to fulfill your obligations under the Act, the lease, or the... approval a local agent empowered to receive notices and submit requests, applications, notices, or...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... require you to designate an agent empowered to fulfill your obligations under the Act, the lease, or the... approval a local agent empowered to receive notices and submit requests, applications, notices, or...

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Conformity-driven agents support ordered phases in the spatial public goods game

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto; Antonioni, Alberto; Caravelli, Francesco

2016-05-01

We investigate the spatial Public Goods Game in the presence of fitness-driven and conformity-driven agents. This framework usually considers only the former type of agents, i.e., agents that tend to imitate the strategy of their fittest neighbors. However, whenever we study social systems, the evolution of a population might be affected also by social behaviors as conformism, stubbornness, altruism, and selfishness. Although the term evolution can assume different meanings depending on the considered domain, here it corresponds to the set of processes that lead a system towards an equilibrium or a steady state. We map fitness to the agents' payoff so that richer agents are those most imitated by fitness-driven agents, while conformity-driven agents tend to imitate the strategy assumed by the majority of their neighbors. Numerical simulations aim to identify the nature of the transition, on varying the amount of the relative density of conformity-driven agents in the population, and to study the nature of related equilibria. Remarkably, we find that conformism generally fosters ordered cooperative phases and may also lead to bistable behaviors.

Biologic agents for IBD: practical insights.

PubMed

Danese, Silvio; Vuitton, Lucine; Peyrin-Biroulet, Laurent

2015-09-01

Six biologic agents are currently approved for the treatment of IBD: four anti-TNF agents (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin agents (natalizumab and vedolizumab). In Crohn's disease and ulcerative colitis refractory to standard medications, treatment choice among available biologic agents can be challenging. Several parameters should be taken into account to help physicians through the decision-making process, including the comparative effectiveness and long-term safety profile, availability and labelling in the prescriber's country, international guidelines, and cost, as well as patient preferences (such as the route of administration). Herein, we provide practical insights on the use of biologic agents in IBD. The results of head-to-head trials between biologic agents are eagerly awaited to guide decision-making regarding the choice of first-line biologic agents and to determine whether switching within the same drug class or swapping (switching out of the drug class) is preferable after primary or secondary loss of response to the first biologic agent. In the near future, treatment algorithms might evolve with the launch of new drugs (such as ustekinumab, tofacitinib and etrolizumab) and the increased use of biosimilars.

Nash Equilibrium of Social-Learning Agents in a Restless Multiarmed Bandit Game.

PubMed

Nakayama, Kazuaki; Hisakado, Masato; Mori, Shintaro

2017-05-16

We study a simple model for social-learning agents in a restless multiarmed bandit (rMAB). The bandit has one good arm that changes to a bad one with a certain probability. Each agent stochastically selects one of the two methods, random search (individual learning) or copying information from other agents (social learning), using which he/she seeks the good arm. Fitness of an agent is the probability to know the good arm in the steady state of the agent system. In this model, we explicitly construct the unique Nash equilibrium state and show that the corresponding strategy for each agent is an evolutionarily stable strategy (ESS) in the sense of Thomas. It is shown that the fitness of an agent with ESS is superior to that of an asocial learner when the success probability of social learning is greater than a threshold determined from the probability of success of individual learning, the probability of change of state of the rMAB, and the number of agents. The ESS Nash equilibrium is a solution to Rogers' paradox.

Flotability and flotation separation of polymer materials modulated by wetting agents.

PubMed

Wang, Hui; Wang, Chong-qing; Fu, Jian-gang; Gu, Guo-hua

2014-02-01

The surface free energy, surface tension and contact angles were performed to investigate the properties of wetting agents. Adsorption of wetting agents changes wetting behavior of polymer resins. Flotability of polymer materials modulated by wetting agents was studied, and wetting agents change significantly flotability of polymer materials. The flotability decreases with increasing the concentration of wetting agents, and the wetting ability is lignin sulfonate (LS)>tannic acid (TA)>methylcellulose (MC)>triton X-100 (TX-100) (from strong to weak). There is significant difference in the flotability between polymer resins and plastics due to the presence of additives in the plastics. Flotation separation of two-component and multicomponent plastics was conducted based on the flotability modulated by wetting agents. The two-component mixtures can be efficiently separated using proper wetting agent through simple flotation flowsheet. The multicomponent plastic mixtures can be separated efficiently through multi-stage flotation using TA and LS as wetting agents, and the purity of separated component was above 94%, and the recovery was more than 93%. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Synthesis and characterization of a smart contrast agent sensitive to calcium.

PubMed

Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

2008-08-07

A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

Agent Based Fault Tolerance for the Mobile Environment

NASA Astrophysics Data System (ADS)

Park, Taesoon

This paper presents a fault-tolerance scheme based on mobile agents for the reliable mobile computing systems. Mobility of the agent is suitable to trace the mobile hosts and the intelligence of the agent makes it efficient to support the fault tolerance services. This paper presents two approaches to implement the mobile agent based fault tolerant service and their performances are evaluated and compared with other fault-tolerant schemes.

Believable Social and Emotional Agents.

DTIC Science & Technology

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

Situation awareness-based agent transparency for human-autonomy teaming effectiveness

NASA Astrophysics Data System (ADS)

Chen, Jessie Y. C.; Barnes, Michael J.; Wright, Julia L.; Stowers, Kimberly; Lakhmani, Shan G.

2017-05-01

We developed the Situation awareness-based Agent Transparency (SAT) model to support human operators' situation awareness of the mission environment through teaming with intelligent agents. The model includes the agent's current actions and plans (Level 1), its reasoning process (Level 2), and its projection of future outcomes (Level 3). Human-inthe-loop simulation experiments have been conducted (Autonomous Squad Member and IMPACT) to illustrate the utility of the model for human-autonomy team interface designs. Across studies, the results consistently showed that human operators' task performance improved as the agents became more transparent. They also perceived transparent agents as more trustworthy.

Adapting Price Predictions in TAC SCM

NASA Astrophysics Data System (ADS)

Pardoe, David; Stone, Peter

In agent-based markets, adapting to the behavior of other agents is often necessary for success. When it is not possible to directly model individual competitors, an agent may instead model and adapt to the market conditions that result from competitor behavior. Such an agent could still benefit from reasoning about specific competitor strategies by considering how various combinations of these strategies would impact the conditions being modeled. We present an application of such an approach to a specific prediction problem faced by the agent TacTex-06 in the Trading Agent Competition's Supply Chain Management scenario (TAC SCM).

Multifunctional agents for concurrent imaging and therapy in cardiovascular disease

PubMed Central

McCarthy, Jason R.

2010-01-01

The development of agents for the simultaneous detection and treatment of disease has recently gained significant attention. These multifunctional theranostic agents posses a number of advantages over their monofunctional counterparts, as they potentially allow for the concomitant determination of agent localization, release, and efficacy. Whereas the development of these agents for use in cancers has received the majority of the attention, their use in cardiovascular disease is steadily increasing. As such, this review summarized some of the most poignant recent advances in the development of theranostic agents for the treatment of this class of diseases. PMID:20654664

Nondestructive Intervention to Multi-Agent Systems through an Intelligent Agent

PubMed Central

Han, Jing; Wang, Lin

2013-01-01

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

Characterization of chemical agent transport in paints.

PubMed

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

2013-09-15

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

Not so secret agents: Event-related potentials to semantic roles in visual event comprehension.

PubMed

Cohn, Neil; Paczynski, Martin; Kutas, Marta

2017-12-01

Research across domains has suggested that agents, the doers of actions, have a processing advantage over patients, the receivers of actions. We hypothesized that agents as "event builders" for discrete actions (e.g., throwing a ball, punching) build on cues embedded in their preparatory postures (e.g., reaching back an arm to throw or punch) that lead to (predictable) culminating actions, and that these cues afford frontloading of event structure processing. To test this hypothesis, we compared event-related brain potentials (ERPs) to averbal comic panels depicting preparatory agents (ex. reaching back an arm to punch) that cued specific actions with those to non-preparatory agents (ex. arm to the side) and patients that did not cue any specific actions. We also compared subsequent completed action panels (ex. agent punching patient) across conditions, where we expected an inverse pattern of ERPs indexing the differential costs of processing completed actions asa function of preparatory cues. Preparatory agents evoked a greater frontal positivity (600-900ms) relative to non-preparatory agents and patients, while subsequent completed actions panels following non-preparatory agents elicited a smaller frontal positivity (600-900ms). These results suggest that preparatory (vs. non-) postures may differentially impact the processing of agents and subsequent actions in real time. Copyright © 2017 Elsevier Inc. All rights reserved.

Time-Extended Payoffs for Collectives of Autonomous Agents

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian K.

2002-01-01

A collective is a set of self-interested agents which try to maximize their own utilities, along with a a well-defined, time-extended world utility function which rates the performance of the entire system. In this paper, we use theory of collectives to design time-extended payoff utilities for agents that are both aligned with the world utility, and are "learnable", i.e., the agents can readily see how their behavior affects their utility. We show that in systems where each agent aims to optimize such payoff functions, coordination arises as a byproduct of the agents selfishly pursuing their own goals. A game theoretic analysis shows that such payoff functions have the net effect of aligning the Nash equilibrium, Pareto optimal solution and world utility optimum, thus eliminating undesirable behavior such as agents working at cross-purposes. We then apply collective-based payoff functions to the token collection in a gridworld problem where agents need to optimize the aggregate value of tokens collected across an episode of finite duration (i.e., an abstracted version of rovers on Mars collecting scientifically interesting rock samples, subject to power limitations). We show that, regardless of the initial token distribution, reinforcement learning agents using collective-based payoff functions significantly outperform both natural extensions of single agent algorithms and global reinforcement learning solutions based on "team games".

Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study.

PubMed

Lavorini, Federico; Spina, Domenico; Walker, Michael J; Franciosi, Lui; Page, Clive P; Fontana, Giovanni A

2016-10-01

Cough is a common presenting symptom in patients with idiopathic interstitial pneumonia (IIP); it is often disabling, and lacks effective treatment. Studies in animals suggest that carcainium chloride, a quaternary derivative of the local anesthetic lidocaine, is able to inhibit experimentally induced cough by a mechanism of action distinct from that of lidocaine. To determine the effectiveness of aerosolised carcainium chloride (VRP700) in controlling cough in patients with IIP. Eight female patients (mean age 71 years) with IIP were investigated in a double blind, randomised, placebo controlled crossover, adaptive contingency study design (EudraCT Number 2010-021350-19). The study consisted of a screening visit to assess the eligibility of patients, and two separated (48-72 h) study days. On the two study days, patients were randomised to receive either nebulized VRP700 (1.0 mg/kg) on the first study visit followed by nebulised placebo (sodium chloride 0.9%) on the second visit, or placebo on the first visit followed by VRP700 on the second visit. The primary endpoint was cough frequency over a 4-h assessment period; secondary endpoints were subjective cough-related level of discomfort as assessed by a visual analogue scale (VAS) and the subjective response to treatment as assessed by a quality of life question. Safety (ECG, spirometry, urine and blood tests) and adverse events occurring during the trial were also investigated. In all patients both VRP700 and placebo decreased cough frequency; however, mean decreases in cough frequency after treatment with VRP700 were significantly (P < 0.001) higher than with placebo. Similarly, mean reductions in VAS score were significantly (P < 0.001) higher after treatment with VRP 700 compared with placebo. All but one patient indicated that they felt better after receiving VRP700. No adverse events were reported during the study, nor were any changes in ECG variables, spirometry, urine and blood tests noted. The results of this exploratory study indicate that nebulised VRP700 improved cough and quality of life in hospitalised IIP patients with no significant side effects. A larger trial is warranted to assess these promising results. Copyright © 2016 Elsevier Ltd. All rights reserved.

On the definition of chronic cough and current treatment pathways: an international qualitative study

PubMed Central

2014-01-01

Background The pathogenesis of chronic cough is not well understood and treatment options are limited. In this study we sought to explore the current understanding and management of chronic cough across an international group of specialists. Methods This was an international study of cross sectional qualitative design. In depth interviews were carried out with “Respiratory Specialists” experienced in treating treating Chronic Obstructive Pulmonary Disease (COPD), idiopathic pulmonary fibrosis (IPF), idiopathic chronic cough (ICC) and/or lung cancer patients and with “Disease Experts” in the field of Chronic Cough. Participants in the study were recruited from the USA, UK, Germany, Ireland, Australia and Japan. Interviews with specialists were held at research facilities and with DEs over the telephone. These were preceded by the specialists completing case records of patients recently seen. All interviews were conducted by native speaking trained moderators using a semi-structured interview guide script. This was designed to elicit the definition of chronic cough, explore the unmet needs for each disease state, define therapy goals, identify patient phenotypes and give an overview of the treatment pathway. Results 76 specialists and 10 experts took part in the study. Over two thirds (70%) of respondents defined chronic cough as “cough lasting more than 8/12 weeks” (range 2 weeks to 2 years). Physicians emphasised three interdependent aspects of clinical assessment: impact on quality of life, type of cough (productive versus non-productive) and the underlying pathology. Specialists emphasised treating the underlying cause rather than the cough, this being most prominent in Japan. Experts as a group focussed on chronic cough independently. Evaluation of the respiratory system, GI tract and upper airway (ENT) for establishing an underlying cause was recommended. Type of cough (productive vs non-productive) and impact on quality of life influenced treatment initiation. 33% of patients with ICC were prescribed anti-tussives. With associated diagnoses of COPD, IPF or lung cancer the emphasis was on treating the underlying condition. Alternatives to pharmacological treatments were frequently considered. Conclusion There is significant international variation in our understanding and management of chronic cough. Further work is required to bring forth clear guidance and effective medicines for these patients. PMID:25009577

Discovery of Clinically Approved Agents That Promote Suppression of Cystic Fibrosis Transmembrane Conductance Regulator Nonsense Mutations.

PubMed

Mutyam, Venkateshwar; Du, Ming; Xue, Xiaojiao; Keeling, Kim M; White, E Lucile; Bostwick, J Robert; Rasmussen, Lynn; Liu, Bo; Mazur, Marina; Hong, Jeong S; Falk Libby, Emily; Liang, Feng; Shang, Haibo; Mense, Martin; Suto, Mark J; Bedwell, David M; Rowe, Steven M

2016-11-01

Premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Several agents are known to suppress PTCs but are poorly efficacious or toxic. To determine whether there are clinically available agents that elicit translational readthrough and improve CFTR function sufficient to confer therapeutic benefit to patients with CF with PTCs. Two independent screens, firefly luciferase and CFTR-mediated transepithelial chloride conductance assay, were performed on a library of 1,600 clinically approved compounds using fisher rat thyroid cells stably transfected with stop codons. Select agents were further evaluated using secondary screening assays including short circuit current analysis on primary cells from patients with CF. In addition, the effect of CFTR modulators (ivacaftor) was tested in combination with the most efficacious agents. From the primary screen, 48 agents were selected as potentially active. Following confirmatory tests in the transepithelial chloride conductance assay and prioritizing agents based on favorable pharmacologic properties, eight agents were advanced for secondary screening. Ivacaftor significantly increased short circuit current following forskolin stimulation in cells treated with pyranoradine tetraphosphate, potassium p-aminobenzoate, and escin as compared with vehicle control. Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR expression and function in vitro. Clinically approved drugs identified as potential readthrough agents, in combination with ivacaftor, may induce nonsense suppression to restore therapeutic levels of CFTR function. One or more agents may be suitable to advance to human testing.

Software agents and the route to the information economy.

PubMed

Kephart, Jeffrey O

2002-05-14

Humans are on the verge of losing their status as the sole economic species on the planet. In private laboratories and in the Internet laboratory, researchers and developers are creating a variety of autonomous economically motivated software agents endowed with algorithms for maximizing profit or utility. Many economic software agents will function as miniature businesses, purchasing information inputs from other agents, combining and refining them into information goods and services, and selling them to humans or other agents. Their mutual interactions will form the information economy: a complex economic web of information goods and services that will adapt to the ever-changing needs of people and agents. The information economy will be the largest multiagent system ever conceived and an integral part of the world's economy. I discuss a possible route toward this vision, beginning with present-day Internet trends suggesting that agents will charge one another for information goods and services. Then, to establish that agents can be competent price setters, I describe some laboratory experiments pitting software bidding agents against human bidders. The agents' superior performance suggests they will be used on a broad scale, which in turn suggests that interactions among agents will become frequent and significant. How will this affect macroscopic economic behavior? I describe some interesting phenomena that my colleagues and I have observed in simulations of large populations of automated buyers and sellers, such as price war cycles. I conclude by discussing fundamental scientific challenges that remain to be addressed as we journey toward the information economy.

Moral actor, selfish agent.

PubMed

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.

Preparation and mechanism analysis of an environment-friendly maize seed coating agent.

PubMed

Zeng, Defang; Fan, Zhao; Tian, Xu; Wang, Wenjin; Zhou, Mingchun; Li, Haochuan

2018-06-01

Traditional seed coating agents often contain toxic ingredients, which contaminate the environment and threaten human health. This paper expounds a method of preparing a novel environment-friendly seed coating agent for maize and researches its mechanism of action. The natural polysaccharide polymer, which is the main active ingredient of this environment-friendly seed coating agent, has the characteristics of innocuity and harmlessness, and it can replace the toxic ingredients used in traditional seed coating agents. This environment-friendly seed coating agent for maize was mainly made up of the natural polysaccharide polymer and other additives. The field trials results showed that the control efficacy of Helminthosporium maydis came to 93.72%, the anti-feeding rate of cutworms came to 81.29%, and the maize yield was increased by 17.75%. Besides, the LD 50 value (half the lethal dose in rats) of this seed coating agent was 10 times higher than that of the traditional seed coating agents. This seed coating agent could improve the activity of plant protective enzymes (peroxidase, catalase and superoxidase dismutase) and increase the chlorophyll content. This seed coating agent has four characteristics of disease prevention, desinsectization, increasing yield and safety. Results of mechanism analyses showed that this seed coating agent could enhance disease control effectiveness by improving plant protective enzymes activity and increase maize yield by improving chlorophyll content. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

A real-time architecture for time-aware agents.

PubMed

Prouskas, Konstantinos-Vassileios; Pitt, Jeremy V

2004-06-01

This paper describes the specification and implementation of a new three-layer time-aware agent architecture. This architecture is designed for applications and environments where societies of humans and agents play equally active roles, but interact and operate in completely different time frames. The architecture consists of three layers: the April real-time run-time (ART) layer, the time aware layer (TAL), and the application agents layer (AAL). The ART layer forms the underlying real-time agent platform. An original online, real-time, dynamic priority-based scheduling algorithm is described for scheduling the computation time of agent processes, and it is shown that the algorithm's O(n) complexity and scalable performance are sufficient for application in real-time domains. The TAL layer forms an abstraction layer through which human and agent interactions are temporally unified, that is, handled in a common way irrespective of their temporal representation and scale. A novel O(n2) interaction scheduling algorithm is described for predicting and guaranteeing interactions' initiation and completion times. The time-aware predicting component of a workflow management system is also presented as an instance of the AAL layer. The described time-aware architecture addresses two key challenges in enabling agents to be effectively configured and applied in environments where humans and agents play equally active roles. It provides flexibility and adaptability in its real-time mechanisms while placing them under direct agent control, and it temporally unifies human and agent interactions.

A Methodology For Developing an Agent Systems Reference Architecture

DTIC Science & Technology

2010-05-01

agent framworks , we create an abstraction noting similarities and differences. The differences are documented as points of variation. The result...situated in the physical en- vironment. Addressing how conceptual components of an agent system is beneficial to agent system architects, developers, and

A Multi-Agent System for Intelligent Online Education.

ERIC Educational Resources Information Center

O'Riordan, Colm; Griffith, Josephine

1999-01-01

Describes the system architecture of an intelligent Web-based education system that includes user modeling agents, information filtering agents for automatic information gathering, and the multi-agent interaction. Discusses information management; user interaction; support for collaborative peer-peer learning; implementation; testing; and future…

Heat-resistant agent used for control sand of steam huff and puff heavy oil well

NASA Astrophysics Data System (ADS)

Zhang, F. S.; Liu, G. L.; Lu, Y. J.; Xiong, X. C.; Ma, J. H.; Su, H. M.

2018-01-01

Heat-resistant agent containing hydroxymethyl group was synthesized from coal tar, which has similar structure with phenolic resin and could improve the heat resistance of phenolic resin sand control agent. The results showed that the heat resistance of the sand control agent was improved by adding 10% to 30% heat-resistant agent, after 280°C high temperature treatment for 7d, the compressive strength of consolidated core was increased to more than 5MPa. The compressive strength of consolidation core was not decreased after immersion in formation water, crude oil, acid or alkaline medium, which showed good resistance to medium immersion. The sand control agent had small core damage and the core permeability damage ratio of sand control agent consolidation was only 18.7%.

Formal Modeling of Multi-Agent Systems using the Pi-Calculus and Epistemic Logic

NASA Technical Reports Server (NTRS)

Rorie, Toinette; Esterline, Albert

1998-01-01

Multi-agent systems have become important recently in computer science, especially in artificial intelligence (AI). We allow a broad sense of agent, but require at least that an agent has some measure of autonomy and interacts with other agents via some kind of agent communication language. We are concerned in this paper with formal modeling of multi-agent systems, with emphasis on communication. We propose for this purpose to use the pi-calculus, an extension of the process algebra CCS. Although the literature on the pi-calculus refers to agents, the term is used there in the sense of a process in general. It is our contention, however, that viewing agents in the AI sense as agents in the pi-calculus sense affords significant formal insight. One formalism that has been applied to agents in the AI sense is epistemic logic, the logic of knowledge. The success of epistemic logic in computer science in general has come in large part from its ability to handle concepts of knowledge that apply to groups. We maintain that the pi-calculus affords a natural yet rigorous means by which groups that are significant to epistemic logic may be identified, encapsulated, structured into hierarchies, and restructured in a principled way. This paper is organized as follows: Section 2 introduces the pi-calculus; Section 3 takes a scenario from the classical paper on agent-oriented programming [Sh93] and translates it into a very simple subset of the n-calculus; Section 4 then shows how more sophisticated features of the pi-calculus may bc brought into play; Section 5 discusses how the pi-calculus may be used to define groups for epistemic logic; and Section 6 is the conclusion.

Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika

Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex withmore » the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.« less

Can an agent’s false belief be corrected by an appropriate communication? Psychological reasoning in 18-month-old infants

PubMed Central

Song, Hyun-joo; Onishi, Kristine H.; Baillargeon, Renée; Fisher, Cynthia

2008-01-01

Do 18-month-olds understand that an agent’s false belief can be corrected by an appropriate, though not an inappropriate, communication? In Experiment 1, infants watched a series of events involving two agents, a ball, and two containers: a box and a cup. To start, agent1 played with the ball and then hid it in the box, while agent2 looked on. Next, in agent1’s absence, agent2 moved the ball from the box to the cup. When agent1 returned, agent2 told her “The ball is in the cup!” (informative-intervention condition) or “I like the cup!” (uninformative-intervention condition). During test, agent1 reached for either the box (box event) or the cup (cup event). In the informative-intervention condition, infants who saw the box event looked reliably longer than those who saw the cup event; in the uninformative-intervention condition, the reverse pattern was found. These results suggest that infants expected agent1’s false belief about the ball’s location to be corrected when she was told “The ball is in the cup!”, but not “I like the cup!”. In Experiment 2, agent2 simply pointed to the ball’s new location, and infants again expected agent1’s false belief to be corrected. These and control results provide additional evidence that infants in the second year of life can attribute false beliefs to agents. In addition, the results suggest that by 18 months of age infants expect agents’ false beliefs to be corrected by relevant communications involving words or gestures. PMID:18976745

Analysis of Nerve Agent Metabolites from Hair for Long-Term Verification of Nerve Agent Exposure

DTIC Science & Technology

2016-05-09

Analysis of Nerve Agent Metabolites from Hair for Long-Term Verification of Nerve Agent Exposure Amanda S. Appel,† John H. McDonough,‡ Joseph D...feasible. In this study, hair was evaluated as a long-term repository of nerve agent hydrolysis products. Pinacolyl methylphosphonic acid (PMPA...hydrolysis product of soman) and isopropyl methylphosphonic acid (IMPA; hydrolysis product of sarin) were extracted from hair samples with N,N

Can an Agent's False Belief Be Corrected by an Appropriate Communication? Psychological Reasoning in 18-Month-Old Infants

ERIC Educational Resources Information Center

Song, Hyun-joo; Onishi, Kristine H.; Baillargeon, Renee; Fisher, Cynthia

2008-01-01

Do 18-month-olds understand that an agent's false belief can be corrected by an appropriate, though not an inappropriate, communication? In Experiment 1, infants watched a series of events involving two agents, a ball, and two containers: a box and a cup. To start, agent 1 played with the ball and then hid it in the box, while agent 2 looked on.…

A Model of Human Teamwork for Agent-Assisted Search Operations

DTIC Science & Technology

2008-04-01

agent technology in providing effective team assistance , better understanding of robust human-agent teamwork is crucial. The goal of our research project...to various unexpected events. In order to fulfil the promise of agent technology in providing effective team assistance , better understanding of...distributed decision making. In Command and Control Research and Technology Symposium, 2004. A MODEL OF AGENT- ASSISTED SEARCH OPERATIONS 20 - 20 PUB REF NBR (e.g. RTO-MP-IST-999)

Collaborative Information Agents on the World Wide Web

NASA Technical Reports Server (NTRS)

Chen, James R.; Mathe, Nathalie; Wolfe, Shawn; Koga, Dennis J. (Technical Monitor)

1998-01-01

In this paper, we present DIAMS, a system of distributed, collaborative information agents which help users access, collect, organize, and exchange information on the World Wide Web. Personal agents provide their owners dynamic displays of well organized information collections, as well as friendly information management utilities. Personal agents exchange information with one another. They also work with other types of information agents such as matchmakers and knowledge experts to facilitate collaboration and communication.

Harnessing the Power of Collaborative Relationships to Improve National Preparedness and Responsiveness

DTIC Science & Technology

2011-09-01

to their history of interaction and sharing worldviews. Agents respond to both external pressures (from environment or other agents , e.g,. leaders...hierarchically, but rather by interaction among heterogeneous agents and across agent networks. They go on to note that a CAS is comprised of... agents or organizations, who resonate through sharing common interests, knowledge, and goals due to their history of interaction such as in the NRF

Minimal Representation and Decision Making for Networked Autonomous Agents

DTIC Science & Technology

2015-08-27

to a multi-vehicle version of the Travelling Salesman Problem (TSP). We further provided a direct formula for computing the number of robots...the sensor. As a first stab at this, the two-agent rendezvous problem is considered where one agent (the target) is equipped with no sensors and is...by the total distance traveled by all agents. For agents with limited sensing and communication capabilities, we give a formula that computes the

New agents for prostate cancer.

PubMed

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

2014-09-01

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid and denosumab. Finally, all of these modalities do not appear curative, suggesting that clinical trial enrollment and a better understanding of biology remain of paramount importance. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Biological agents with potential for misuse: a historical perspective and defensive measures.

PubMed

Bhalla, Deepak K; Warheit, David B

2004-08-15

Biological and chemical agents capable of producing serious illness or mortality have been used in biowarfare from ancient times. Use of these agents has progressed from crude forms in early and middle ages, when snakes and infected cadavers were used as weapons in battles, to sophisticated preparations for use during and after the second World War. Cults and terrorist organizations have attempted the use of biological agents with an aim to immobilize populations or cause serious harm. The reasons for interest in these agents by individuals and organizations include relative ease of acquisition, potential for causing mass casualty or panic, modest financing requirement, availability of technology, and relative ease of delivery. The Centers for Disease Control and Prevention has classified Critical Biological Agents into three major categories. This classification was based on several criteria, which include severity of impact on human health, potential for delivery in a weapon, capacity to cause panic and special needs for development, and stockpiling of medication. Agents that could cause the greatest harm following deliberate use were placed in category A. Category B included agents capable of producing serious harm and significant mortality but of lower magnitude than category A agents. Category C included emerging pathogens that could be developed for mass dispersion in future and their potential as a major health threat. A brief description of the category A bioagents is included and the pathophysiology of two particularly prominent agents, namely anthrax and smallpox, is discussed in detail. The potential danger from biological agents and their ever increasing threat to human populations have created a need for developing technologies for their early detection, for developing treatment strategies, and for refinement of procedures to ensure survival of affected individuals so as to attain the ultimate goal of eliminating the threat from intentional use of these agents. International treaties limiting development and proliferation of weapons and continuing development of defense strategies and safe guards against agents of concern are important elements of plans for eliminating this threat.

Multi-Agent Framework for Virtual Learning Spaces.

ERIC Educational Resources Information Center

Sheremetov, Leonid; Nunez, Gustavo

1999-01-01

Discussion of computer-supported collaborative learning, distributed artificial intelligence, and intelligent tutoring systems focuses on the concept of agents, and describes a virtual learning environment that has a multi-agent system. Describes a model of interactions in collaborative learning and discusses agents for Web-based virtual…

42 CFR 73.4 - Overlap select agents and toxins.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION... its naturally occurring environment provided that the select agent or toxin has not been intentionally... such agent or toxin or destroys the agent or toxin by a recognized sterilization or inactivation...

20 CFR 655.133 - Requirements for agents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Requirements for agents. 655.133 Section 655.133 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR TEMPORARY... Procedures § 655.133 Requirements for agents. (a) An agent filing an Application for Temporary Employment...

14 CFR 29.1197 - Fire extinguishing agents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fire extinguishing agents. 29.1197 Section... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Powerplant Fire Protection § 29.1197 Fire extinguishing agents. (a) Fire extinguishing agents must— (1) Be capable of extinguishing flames emanating from...

A New Approach To Secure Federated Information Bases Using Agent Technology.

ERIC Educational Resources Information Center

Weippi, Edgar; Klug, Ludwig; Essmayr, Wolfgang

2003-01-01

Discusses database agents which can be used to establish federated information bases by integrating heterogeneous databases. Highlights include characteristics of federated information bases, including incompatible database management systems, schemata, and frequently changing context; software agent technology; Java agents; system architecture;…

Application and Implications of Agent Technology for Librarians.

ERIC Educational Resources Information Center

Nardi, Bonnie A.; O'Day, Vicki L.

1998-01-01

Examines intelligent software agents, presents nine design principles aimed specifically at the technology perspective (to personalize task performance and general principles), and discusses what librarians can do that software agents (agents defined as activity-aware software programs) cannot do. Describes an information ecology that integrates…

Mobile Agents Applications.

ERIC Educational Resources Information Center

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

2001-01-01

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

Quantifying cancer cell receptors with paired-agent fluorescent imaging: a novel method to account for tissue optical property effects

NASA Astrophysics Data System (ADS)

Sadeghipour, Negar; Davis, Scott C.; Tichauer, Kenneth M.

2018-02-01

Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptors in vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing factor to correct for tissue optical property differences. In this study, the kinetic model used for paired-agent imaging analysis (i.e., simplified reference tissue model) is modified and tested in simulation and experimental data in a way that accounts for the scaling correction within the kinetic model fit to the data to ultimately extract an estimate of the targeted biomarker concentration.

Natural chelating agents for radionuclide decorporation

DOEpatents

Premuzic, E.T.

1985-06-11

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

Military chemical warfare agent human subjects testing: part 2--long-term health effects among participants of U.S. military chemical warfare agent testing.

PubMed

Brown, Mark

2009-10-01

Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns about how their participation affected their health. A companion article describes the history of these experiments, and how the lack of clinical data hampers evaluation of long-term health consequences. Conversely, much information is available about specific agents tested and their long-term health effects in other populations, which may be invaluable for helping clinicians respond effectively to the health care and other needs of affected veterans. The following review describes tested agents and their known long-term health consequences. Although hundreds of chemicals were tested, they fall into only about a half-dozen pharmaceutical classes, including common pharmaceuticals; anticholinesterase agents including military nerve agents and pesticides; anticholinergic glycolic acid esters such as atropine; acetylcholine reactivators such as 2-PAM; psychoactive compounds including cannabinoids, phencyclidine, and LSD; and irritants including tear gas and riot control agents.

Agent-Supported Mission Operations Teamwork

NASA Technical Reports Server (NTRS)

Malin, Jane T.

2003-01-01

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

Wealth distribution, Pareto law, and stretched exponential decay of money: Computer simulations analysis of agent-based models

NASA Astrophysics Data System (ADS)

Aydiner, Ekrem; Cherstvy, Andrey G.; Metzler, Ralf

2018-01-01

We study by Monte Carlo simulations a kinetic exchange trading model for both fixed and distributed saving propensities of the agents and rationalize the person and wealth distributions. We show that the newly introduced wealth distribution - that may be more amenable in certain situations - features a different power-law exponent, particularly for distributed saving propensities of the agents. For open agent-based systems, we analyze the person and wealth distributions and find that the presence of trap agents alters their amplitude, leaving however the scaling exponents nearly unaffected. For an open system, we show that the total wealth - for different trap agent densities and saving propensities of the agents - decreases in time according to the classical Kohlrausch-Williams-Watts stretched exponential law. Interestingly, this decay does not depend on the trap agent density, but rather on saving propensities. The system relaxation for fixed and distributed saving schemes are found to be different.

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

PubMed

Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

2017-04-01

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Two decades of dendrimers as versatile MRI agents: a tale with and without metals.

PubMed

McMahon, Michael T; Bulte, Jeff W M

2018-05-01

Dendrimers or dendritic polymers are a class of compounds with great potential for nanomedical use. Some of their properties, including their rigidity, low polydispersity and the ease with which their surfaces can be modified make them particularly well suited for use as MRI diagnostic or theranostic agents. For the past 20 years, researchers have recognized this potential and refined dendrimer formulations to optimize these nanocarriers for a host of MRI applications, including blood pool imaging agents, lymph node imaging agents, tumor-targeted theranostic agents and cell tracking agents. This review summarizes the various types of dendrimers according to the type of MR contrast they can provide. This includes the metallic T 1 , T 2 and paraCEST imaging agents, and the non-metallic diaCEST and fluorinated ( 19 F) heteronuclear imaging agents. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals, Inc.

Current and Developing Technologies for Monitoring Agents of Bioterrorism and Biowarfare

PubMed Central

Lim, Daniel V.; Simpson, Joyce M.; Kearns, Elizabeth A.; Kramer, Marianne F.

2005-01-01

Recent events have made public health officials acutely aware of the importance of rapidly and accurately detecting acts of bioterrorism. Because bioterrorism is difficult to predict or prevent, reliable platforms to rapidly detect and identify biothreat agents are important to minimize the spread of these agents and to protect the public health. These platforms must not only be sensitive and specific, but must also be able to accurately detect a variety of pathogens, including modified or previously uncharacterized agents, directly from complex sample matrices. Various commercial tests utilizing biochemical, immunological, nucleic acid, and bioluminescence procedures are currently available to identify biological threat agents. Newer tests have also been developed to identify such agents using aptamers, biochips, evanescent wave biosensors, cantilevers, living cells, and other innovative technologies. This review describes these current and developing technologies and considers challenges to rapid, accurate detection of biothreat agents. Although there is no ideal platform, many of these technologies have proved invaluable for the detection and identification of biothreat agents. PMID:16223949

Protection of Mobile Agents Execution Using a Modified Self-Validating Branch-Based Software Watermarking with External Sentinel

NASA Astrophysics Data System (ADS)

Tomàs-Buliart, Joan; Fernández, Marcel; Soriano, Miguel

Critical infrastructures are usually controlled by software entities. To monitor the well-function of these entities, a solution based in the use of mobile agents is proposed. Some proposals to detect modifications of mobile agents, as digital signature of code, exist but they are oriented to protect software against modification or to verify that an agent have been executed correctly. The aim of our proposal is to guarantee that the software is being executed correctly by a non trusted host. The way proposed to achieve this objective is by the improvement of the Self-Validating Branch-Based Software Watermarking by Myles et al.. The proposed modification is the incorporation of an external element called sentinel which controls branch targets. This technique applied in mobile agents can guarantee the correct operation of an agent or, at least, can detect suspicious behaviours of a malicious host during the execution of the agent instead of detecting when the execution of the agent have finished.

Scoping Planning Agents With Shared Models

NASA Technical Reports Server (NTRS)

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

2003-01-01

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

A CSP-Based Agent Modeling Framework for the Cougaar Agent-Based Architecture

NASA Technical Reports Server (NTRS)

Gracanin, Denis; Singh, H. Lally; Eltoweissy, Mohamed; Hinchey, Michael G.; Bohner, Shawn A.

2005-01-01

Cognitive Agent Architecture (Cougaar) is a Java-based architecture for large-scale distributed agent-based applications. A Cougaar agent is an autonomous software entity with behaviors that represent a real-world entity (e.g., a business process). A Cougaar-based Model Driven Architecture approach, currently under development, uses a description of system's functionality (requirements) to automatically implement the system in Cougaar. The Communicating Sequential Processes (CSP) formalism is used for the formal validation of the generated system. Two main agent components, a blackboard and a plugin, are modeled as CSP processes. A set of channels represents communications between the blackboard and individual plugins. The blackboard is represented as a CSP process that communicates with every agent in the collection. The developed CSP-based Cougaar modeling framework provides a starting point for a more complete formal verification of the automatically generated Cougaar code. Currently it is used to verify the behavior of an individual agent in terms of CSP properties and to analyze the corresponding Cougaar society.

Fibrous Filter to Protect Building Environments from Polluting Agents: A Review

NASA Astrophysics Data System (ADS)

Chavhan, Md. Vaseem; Mukhopadhyay, Arunangshu

2016-04-01

This paper discusses the use of fibrous filter to protect the building environments from air born polluting agents and especially of concern chemical, biological and radiological agents. Air-filtration includes removal of particulate from air and toxic gases from air. In air filtration, particulate which are mostly biological and radioactive types of agents can be removed by using mechanical and electrostatic filters. Some biological agents, which cannot be removed by air filtration alone, special techniques like antimicrobial finish, UV germicides, coated filters etc. are required. Biocide agent can be added into the fibre itself by grafting reaction to impart antimicrobial activity. Chemical agents like toxic gases can be removed by integrating adsorbents and sorbents in filters or by fibre modifications. It is also possible to impart catalytic conversion properties into the fibre to remove volatile gasous. Radioactive agents can be removed by particulate filter if present in the form of aerosol or by gas cleaning by the use of specific fibre impregnate.

Agent-based models of cellular systems.

PubMed

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

2013-01-01

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

Method, apparatus and system for managing queue operations of a test bench environment

DOEpatents

Ostler, Farrell Lynn

2016-07-19

Techniques and mechanisms for performing dequeue operations for agents of a test bench environment. In an embodiment, a first group of agents are each allocated a respective ripe reservation and a second set of agents are each allocated a respective unripe reservation. Over time, queue management logic allocates respective reservations to agents and variously changes one or more such reservations from unripe to ripe. In another embodiment, an order of servicing agents allocated unripe reservations is based on relative priorities of the unripe reservations with respect to one another. An order of servicing agents allocated ripe reservations is on a first come, first served basis.

Method for photo-altering a biological system to improve biological effect

DOEpatents

Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

2000-08-01

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

Exact solution of a modified El Farol's bar problem: Efficiency and the role of market impact

NASA Astrophysics Data System (ADS)

Marsili, Matteo; Challet, Damien; Zecchina, Riccardo

2000-06-01

We discuss a model of heterogeneous, inductive rational agents inspired by the El Farol Bar problem and the Minority Game. As in markets, agents interact through a collective aggregate variable - which plays a role similar to price - whose value is fixed by all of them. Agents follow a simple reinforcement-learning dynamics where the reinforcement, for each of their available strategies, is related to the payoff delivered by that strategy. We derive the exact solution of the model in the “thermodynamic” limit of infinitely many agents using tools of statistical physics of disordered systems. Our results show that the impact of agents on the market price plays a key role: even though price has a weak dependence on the behavior of each individual agent, the collective behavior crucially depends on whether agents account for such dependence or not. Remarkably, if the adaptive behavior of agents accounts even “infinitesimally” for this dependence they can, in a whole range of parameters, reduce global fluctuations by a finite amount. Both global efficiency and individual utility improve with respect to a “price taker” behavior if agents account for their market impact.

Intelligent Design of Nano-Scale Molecular Imaging Agents

PubMed Central

Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

2012-01-01

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents. PMID:23235326

Rigorous Proof of the Boltzmann-Gibbs Distribution of Money on Connected Graphs

NASA Astrophysics Data System (ADS)

Lanchier, Nicolas

2017-04-01

Models in econophysics, i.e., the emerging field of statistical physics that applies the main concepts of traditional physics to economics, typically consist of large systems of economic agents who are characterized by the amount of money they have. In the simplest model, at each time step, one agent gives one dollar to another agent, with both agents being chosen independently and uniformly at random from the system. Numerical simulations of this model suggest that, at least when the number of agents and the average amount of money per agent are large, the distribution of money converges to an exponential distribution reminiscent of the Boltzmann-Gibbs distribution of energy in physics. The main objective of this paper is to give a rigorous proof of this result and show that the convergence to the exponential distribution holds more generally when the economic agents are located on the vertices of a connected graph and interact locally with their neighbors rather than globally with all the other agents. We also study a closely related model where, at each time step, agents buy with a probability proportional to the amount of money they have, and prove that in this case the limiting distribution of money is Poissonian.

Intelligent design of nano-scale molecular imaging agents.

PubMed

Kim, Sung Bae; Hattori, Mitsuru; Ozawa, Takeaki

2012-12-12

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on-off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

Uncertainty in a spatial evacuation model

NASA Astrophysics Data System (ADS)

Mohd Ibrahim, Azhar; Venkat, Ibrahim; Wilde, Philippe De

2017-08-01

Pedestrian movements in crowd motion can be perceived in terms of agents who basically exhibit patient or impatient behavior. We model crowd motion subject to exit congestion under uncertainty conditions in a continuous space and compare the proposed model via simulations with the classical social force model. During a typical emergency evacuation scenario, agents might not be able to perceive with certainty the strategies of opponents (other agents) owing to the dynamic changes entailed by the neighborhood of opponents. In such uncertain scenarios, agents will try to update their strategy based on their own rules or their intrinsic behavior. We study risk seeking, risk averse and risk neutral behaviors of such agents via certain game theory notions. We found that risk averse agents tend to achieve faster evacuation time whenever the time delay in conflicts appears to be longer. The results of our simulations also comply with previous work and conform to the fact that evacuation time of agents becomes shorter once mutual cooperation among agents is achieved. Although the impatient strategy appears to be the rational strategy that might lead to faster evacuation times, our study scientifically shows that the more the agents are impatient, the slower is the egress time.