Rosiglitazone: a disappointing DREAM.

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Nissen, Steven

2007-09-01

Dr Steven Nissen is a heart specialist and currently holds the position of chairman of cardiovascular medicine at the Cleveland Clinic, OH, USA. His work has involved the development of miniaturised ultrasound imaging devices that can be threaded into a patient's heart that allow measurement of the size and composition of plaques, which indicate early artery damage. The ability to characterize and measure the size of plaques provided a novel, effective method to evaluate the efficacy of anticholesterol medications, and for the past two decades Dr Nissen has been using these and other techniques to examine the efficacy of drugs. He has also developed a strong interest in drug safety. His work linked COX-2 inhibitors such as Celebrex and Vioxx (Merck, NJ, USA) with heart attacks, and prevented Merck's similar product, Arcoxia, from being approved. He also highlighted the serious heart attack risk associated with the experimental drug Pargluva and the drug was subsequently not approved by the US FDA. More recently, Dr Nissen's work has focused on the drug rosiglitazone, which was shown to have high cardiovascular risks and has since been given a FDA warning. Here, Dr Nissen discusses the publication of the rosiglitazone meta-analysis and why he considers work in this area to be crucially important for patients.

Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

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Shi-Bing Wong

Full Text Available Peroxisomal proliferator-activated receptor gamma (PPARγ is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA receptor-mediated temporal lobe epilepsy (TLE. We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects

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Hruska, M W; Amico, J A; Langaee, T Y; Ferrell, R E; Fitzgerald, S M; Frye, R F

2005-01-01

Aims Rosiglitazone, a thiazolidinedione antidiabetic medication used in the treatment of Type 2 diabetes mellitus, is predominantly metabolized by the cytochrome P450 (CYP) enzyme CYP2C8. The anti-infective drug trimethoprim has been shown in vitro to be a selective inhibitor of CYP2C8. The purpose of this study was to evaluate the effect of trimethoprim on the CYP2C8 mediated metabolism of rosiglitazone in vivo and in vitro. Methods The effect of trimethoprim on the metabolism of rosiglitazone in vitro was assessed in pooled human liver microsomes. The effect in vivo was determined by evaluating rosiglitazone pharmacokinetics in the presence and absence of trimethoprim. Eight healthy subjects (four men and four women) completed a randomized, cross-over study. Subjects received single dose rosiglitazone (8 mg) in the presence and absence of trimethoprim 200 mg given twice daily for 5 days. Results Trimethoprim inhibited rosiglitazone metabolism both in vitro and in vivo. Inhibition of rosiglitazone para-hydroxylation by trimethoprim in vitro was found to be competitive with apparent Ki and IC50 values of 29 µm and 54.5 µm, respectively. In the presence of trimethoprim, rosiglitazone plasma AUC was increased by 31% (P = 0.01) from 2774 ± 645 µg l−1 h to 3643 ± 1051 µg l−1 h (95% confidence interval (Cl) for difference 189, 1549), and half-life was increased by 27% (P = 0.006) from 3.3 ± 0.5 to 4.2 ± 0.8 h (95% Cl for difference 0.36, 1.5). Trimethoprim reduced the para-O-sulphate rosiglitazone/rosiglitazone and the N-desmethylrosiglitazone/rosiglitazone AUC(0–24) ratios by 22% and 38%, respectively. Conclusions These results indicate that trimethoprim is a competitive inhibitor of CYP2C8-mediated rosiglitazone metabolism in vitro and that trimethoprim administration increases plasma rosiglitazone concentrations in healthy subjects. PMID:15606443

Simple method for the determination of rosiglitazone in human plasma using a commercially available internal standard.

Science.gov (United States)

Mamidi, Rao N V S; Benjamin, Biju; Ramesh, Mullangi; Srinivas, Nuggehally R

2003-09-01

To the best of our knowledge, bioanalytical methods to determine rosiglitazone in human plasma reported in literature use internal standards that are not commercially available. Our purpose was to develop a simple method for the determination of rosiglitazone in plasma employing a commercially available internal standard (IS). After the addition of celecoxib (IS), plasma (0.25 mL) samples were extracted into ethyl acetate. The residue after evaporation of the organic layer was dissolved in 750 microL of mobile phase and 50 microL was injected on to HPLC. The separation was achieved using a Hichrom KR 100, 250 x 4.6 mm C(18) with a mobile phase composition potassium dihydrogen phosphate buffer (0.01 m, pH 6.5):acetonitrile:methanol (40:50:10, v/v/v). The flow-rate of the mobile phase was set at 1 mL/min. The column eluate was monitored by fluorescence detector set at an excitation wavelength of 247 nm and emission wavelength of 367 nm. Linear relationships (r(2) > 0.99) were observed between the peak area ratio rosiglitazone to IS vs rosiglitazone concentrations across the concentration range 5-1000 ng/mL. The intra-run precision (%RSD) and accuracy (%Dev) in the measurement of rosiglitazone were 80% for both rosiglitazone and IS from human plasma. The lower limit of quantitation of the assay was 5 ng/mL. In summary, the methodology for rosiglitazone measurement in plasma was simple, sensitive and employed a commercially available IS. Copyright 2003 John Wiley & Sons, Ltd.

Microdialysis combined blood sampling technique for the determination of rosiglitazone and glucose in brain and blood of gerbils subjected to cerebral ischemia.

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Sheu, Wayne H-H; Chuang, Hsiu-Chun; Cheng, Shiu-Min; Lee, Maw-Rong; Chou, Chi-Chi; Cheng, Fu-Chou

2011-03-25

Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 μg L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06±0.28 μg L(-1) and 296.82±44.67 μg min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105±17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81±85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (pblood glucose levels to 80% at 1h after pretreatment of rosiglitazone (pglucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect. Copyright © 2010 Elsevier B.V. All rights reserved.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

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Atamer, Y. [Department of Medical Biochemistry, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Atamer, A. [Ministry of Health Haydarpaşa Numune Training and Research Hospital, Division of Gastroenterology, Department of Internal Medicine, Istanbul, Turkey, Division of Gastroenterology, Department of Internal Medicine, Ministry of Health Haydarpaşa Numune Training and Research Hospital, Istanbul (Turkey); Can, A.S. [Termal Professional School, Yalova University, Yalova (Turkey); Hekimoğlu, A. [Dicle University, Department of Pharmacology, Faculty of Medicine, Diyarbakir, Turkey, Department of Pharmacology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Ilhan, N. [Firat University, Department of Medical Biochemistry, Faculty of Medicine, Elaziğ, Turkey, Department of Medical Biochemistry, Faculty of Medicine, Fırat University, Elazığ (Turkey); Yenice, N. [Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Harran University, Urfa (Turkey); Koçyiğit, Y. [Dicle University, Department of Physiology, Faculty of Medicine, Diyarbakir, Turkey, Department of Physiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey)

2013-06-25

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m{sup 2}], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Atamer, Y.; Atamer, A.; Can, A.S.; Hekimoğlu, A.; Ilhan, N.; Yenice, N.; Koçyiğit, Y.

2013-01-01

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m 2 ], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality

Combination of vildagliptin and rosiglitazone ameliorates nonalcoholic fatty liver disease in C57BL/6 mice.

Science.gov (United States)

Mookkan, Jeyamurugan; De, Soumita; Shetty, Pranesha; Kulkarni, Nagaraj M; Devisingh, Vijayaraj; Jaji, Mallikarjun S; Lakshmi, Vinitha P; Chaudhary, Shilpee; Kulathingal, Jayanarayan; Rajesh, Navin B; Narayanan, Shridhar

2014-01-01

To evaluate the effect of vildagliptin alone and in combination with metformin or rosiglitazone on murine hepatic steatosis in diet-induced nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were fed with high fat diet (60 Kcal %) and fructose (40%) in drinking water for 60 days to induce NAFLD. After the induction period, animals were divided into different groups and treated with vildagliptin (10 mg/kg), metformin (350 mg/kg), rosiglitazone (10 mg/kg), vildagliptin (10 mg/kg) + metformin (350 mg/kg), or vildagliptin (10 mg/kg) + rosiglitazone (10 mg/kg) orally for 28 days. Following parameters were measured: body weight, food intake, plasma glucose, triglyceride (TG), total cholesterol, liver function tests, and liver TG. Liver histopathology was also examined. Oral administration of vildagliptin and rosiglitazone in combination showed a significant reduction in fasting plasma glucose, hepatic steatosis, and liver TGs. While other treatments showed less or no improvement in the measured parameters. These preliminary results demonstrate that administration of vildagliptin in combination with rosiglitazone could be a promising therapeutic strategy for the treatment of NAFLD.

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone

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Wakui, Yuta; Inoue, Jun; Ueno, Yoshiyuki; Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru

2010-01-01

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-α, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPARα ligand, bezafibrate, and a PPARγ ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPARγ, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-α-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-{gamma} ligand, rosiglitazone

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Wakui, Yuta; Inoue, Jun [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Ueno, Yoshiyuki, E-mail: yueno@mail.tains.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan)

2010-05-28

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-{alpha}, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPAR{alpha} ligand, bezafibrate, and a PPAR{gamma} ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPAR{gamma}, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-{alpha}-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

Prolonged effect of Rosiglitazone one year after discontinuation

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Gram-Kampmann, Eva-Marie; Olesen, Thomas Bastholm; Olsen, Michael Hecht

2015-01-01

: This study is a continuation of the two-year study SDDS, where 371 patients were randomized to eight groups and treated with Insulin aspart three times daily or NPH insulin once daily, metformin or placebo and Rosiglitazone or placebo, respectively. During a 12-month run-out, use of insulin was continued...... and oral antidiabetics/placebo was changed to 2000 mg of metformin a day. During the following four visits, insulin was adjusted according to a treat-to-target algoritm with avoidance of hypoglycemia. Resultater: After 12 months, there was no difference in HbA1c. As expected, in the group formerly...... receiving insulin and two times placebo, insulindose could be lowered after institution of metformin. Compared to the insulin, metformin and placebo-group, insulin dose was significantly lower in the insulin, rosiglitazone and placebo-group (56,9 IUvs 73,6IU, p =0,05) after 12 months. The Insulin...

Can modeling of health outcomes facilitate regulatory decision making? The benefit-risk tradeoff for rosiglitazone in 1999 vs. 2007.

Science.gov (United States)

Cross, J T; Veenstra, D L; Gardner, J S; Garrison, L P

2011-03-01

Rosiglitazone was initially approved for type 2 diabetes monotherapy. We tested health-outcomes modeling as an aid to regulatory decision making by quantifying the incremental net benefit (INB) value of rosiglitazone (relative to a comparator), both at the time of first approval (1999) and at the FDA advisory committee review (2007). Using 1999 data, rosiglitazone was projected to provide an additional 0.639 years of life (0.373 quality-adjusted life years (QALYs)) relative to placebo but a loss of 0.312 years (0.173 QALYs) relative to glyburide, with uncertainty in reduction of hemoglobin A(1c) (HbA(1c)) level having the greatest impact on the benefit-risk profile. By 2007, rosiglitazone was projected to provide an additional 0.222 years (0.091 QALYs) vs. glyburide and 0.026 years vs. metformin (0.009 QALYs). Modeling suggested that the use of rosiglitazone as monotherapy was not initially warranted, given the uncertainty with regard to benefit. Despite similar net benefit (NB) as metformin shown in postmarketing data, residual cardiovascular (CV) concerns did not support the use of rosiglitazone as first-line therapy. We adapted a mathematical diabetes model to estimate NB and uncertainty of diabetes monotherapy.

Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

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Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

2008-12-01

To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

International Nuclear Information System (INIS)

Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

2008-01-01

To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD 50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

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Cerquetti, Lidia; Sampaoli, Camilla; Amendola, Donatella; Bucci, Barbara; Masuelli, Laura; Marchese, Rodolfo; Misiti, Silvia; De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo; Stigliano, Antonio

2011-01-01

Thiazolidinediones, specific peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-γ-inhibitor, showed that rosiglitazone acts through both PPAR-γ-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-γ. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPKα and beclin-1. The autophagy seems to be independent of PPAR-γ activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

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Cerquetti, Lidia; Sampaoli, Camilla [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Amendola, Donatella; Bucci, Barbara [Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Masuelli, Laura [Department of Experimental Medicine, ' Sapienza' University of Rome, Rome (Italy); Marchese, Rodolfo [Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Misiti, Silvia [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Stigliano, Antonio, E-mail: antonio.stigliano@uniroma1.it [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy)

2011-06-10

Thiazolidinediones, specific peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-{gamma}-inhibitor, showed that rosiglitazone acts through both PPAR-{gamma}-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-{gamma}. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPK{alpha} and beclin-1. The autophagy seems to be independent of PPAR-{gamma} activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

Gradient HPLC method development and validation for Simultaneous estimation of Rosiglitazone and Gliclazide.

Directory of Open Access Journals (Sweden)

Uttam Singh Baghel

2012-10-01

Full Text Available Objective: The aim of present work was to develop a gradient RP-HPLC method for simultaneous analysis of rosiglitazone and gliclazide, in a tablet dosage form. Method: Chromatographic system was optimized using a hypersil C18 (250mm x 4.6mm, 5毺 m column with potassium dihydrogen phosphate (pH-7.0 and acetonitrile in the ratio of 60:40, as mobile phase, at a flow rate of 1.0 ml/min. Detection was carried out at 225 nm by a SPD-20A prominence UV/Vis detector. Result: Rosiglitazone and gliclazide were eluted with retention times of 17.36 and 7.06 min, respectively. Beer’s Lambert ’s Law was obeyed over the concentration ranges of 5 to 70 毺 g/ml and 2 to 12 毺 g/ml for rosiglitazone and gliclazide, respectively. Conclusion: The high recovery and low coefficients of variation confirm the suitability of the method for simultaneous analysis of both drugs in a tablets dosage form. Statistical analysis proves that the method is sensitive and significant for the analysis of rosiglitazone and gliclazide in pure and in pharmaceutical dosage form without any interference from the excipients. The method was validated in accordance with ICH guidelines. Validation revealed the method is specific, rapid, accurate, precise, reliable, and reproducible.

Characterization of actions of octanoate on porcine preadipocytes and adipocytes differentiated in vitro

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Suzuki, Shunichi, E-mail: shunsuzu@affrc.go.jp [Transgenic Pig Research Unit, National Institute of Agrobiological Sciences, 2 Ikenodai, Tsukuba, Ibaraki 305-0901 (Japan); Suzuki, Misae; Sembon, Shoichiro; Fuchimoto, Daiichiro; Onishi, Akira [Transgenic Pig Research Unit, National Institute of Agrobiological Sciences, 2 Ikenodai, Tsukuba, Ibaraki 305-0901 (Japan)

2013-03-01

Highlights: ► Octanoate regulated gene expressions in a way distinct from rosiglitasone. ► Octanoate upregulatedPPRE and LXRE reporter activities. ► Octanoate may act on some PPARγ-target genes competitively with other ligands. - Abstract: Octanoate is used to induce adipogenic differentiation and/or lipid accumulation in preadipocytes of domestic animals. However, information on detailed actions of octanoate and the characteristics of octanoate-induced adipocytes is limited. The aim of this study was to examine these issues by comparing the outcomes of the effects of octanoate with those of rosiglitazone, which is a well-defined activator of peroxisome proliferator-activated receptor (PPAR)-γ. The adipocytes that were differentiated with 5 mM of octanoate had dispersed and diversely sized lipid droplets compared to those that were differentiated with 1 μM of rosiglitazone. The gene expression levels of adiponectin, glycerol-3-phosphate dehydrogenase, perilipin 1, and perilipin 4 were much higher in the adipocytes that were differentiated with rosiglitazone than in those differentiated with octanoate, while the gene expression levels of lipoprotein lipase and perilipin 2 were decreased in rosiglitazone-differentiated adipocytes compared to octanoate-differentiated adipocytes. However, the expressions of aP2 and CD36 genes were comparably induced. Luciferase reporter assays revealed that PPAR and liver-X-receptor activities were upregulated by octanoate more effectively than by rosiglitazone. Overall, these results suggested that the action of octanoate was complicated and may be dependent on the targeted genes and cellular status.

Effects of Rosiglitazone, Glyburide, and Metformin on β-Cell Function and Insulin Sensitivity in ADOPT

Science.gov (United States)

Kahn, Steven E.; Lachin, John M.; Zinman, Bernard; Haffner, Steven M.; Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.; Herman, William H.; Viberti, Giancarlo; Holman, Rury R.

2011-01-01

OBJECTIVE ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of β-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS Recently diagnosed, drug-naïve patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS Measures of β-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of β-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes. PMID:21415383

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.

Science.gov (United States)

Minge, Cadence E; Bennett, Brenton D; Norman, Robert J; Robker, Rebecca L

2008-05-01

Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg.d; sodium salicylate, IkappaK inhibitor that reverses insulin resistance, 50 mg/kg.d; or peroxisome proliferator activated receptor-gamma agonist rosiglitazone, 10 mg/kg.d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating

Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism

DEFF Research Database (Denmark)

Vestergaard, H; Lund, S; Pedersen, O

2001-01-01

Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment...

Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation

Science.gov (United States)

Leung, Vivien; Chiu, Ya-Lin; Kotler, Donald P.; Albu, Jeanine; Zhu, Yuan-Shan; Ham, Kirsis; Engelson, Ellen S.; Hammad, Hoda; Christos, Paul; Donovan, Daniel S.; Ginsberg, Henry N.; Glesby, Marshall J.

2016-01-01

Background/Objective In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of recombinant human growth hormone (rhGH) and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. Methods 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n = 63) and 12 (n = 46-48) were assessed for adiponectin, C-reactive protein (CRP), homocysteine, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator (tPA) antigen. Results Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH alone arm. There were no significant changes in the other biomarkers amongst the different treatment groups. Discussion In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with combination rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT. PMID:27077672

Improvement in psoriasis with rosiglitazone in a diabetic and a nondiabetic patient.

Science.gov (United States)

Pershadsingh, Harrihar A; Benson, Steven C; Ellis, Charles N

2005-01-01

The authors conducted a prospective, open-label, pilot trial of the effects of the antidiabetic thiazolidinedione (TZD) rosiglitazone in two patients with moderate to severe plaque psoriasis. Case 1: A lean, euglycemic 43-year-old nondiabetic man with a 2-year history of plaque psoriasis presented with lesions involving 10% of his body surface (Figures 1A, 1B, 1C). He had no other chronic or acute medical problems. He had previously been managed sporadically with topical triamcinolone acetonide, an intermediate-strength glucocorticoid, and was off antipsoriatic medication for 5 months. He was started on rosiglitazone p.o., 8 mg q.d. After 10 weeks on rosiglitazone, the lesions developed increased erythema, spreading, and shedding of scale (Figures 2A, 2B, 2C). After an additional 26 weeks, the lesions had largely disappeared (Figures 3A, 3B, 3C). The patient remained euglycemic throughout the study. His liver function enzymes (alanine transferase [ALT] and aspartate transferase [AST]) remained normal throughout the study: ALT, 23 IU/L; AST, 47 IU/L before treatment; ALT, 25 IU/L; AST, 33 IU/L after treatment. There were no adverse events. Case 2: An overweight 68-year-old woman (body mass index, 29 kg/m2; with a 12-year history of type 2 diabetes and 5-year history of psoriasis presented with generalized plaque psoriasis over 20% of her body, including two large, thick, silvery plaques with the texture of leather over the lower part of the back (Figure 4A). She was given rosiglitazone p.o., 4 mg b.i.d. for 24 weeks, which resulted in significant improvement in psoriasis (Figure 4B). After an additional 26 weeks on rosiglitazone, the plaques had cleared on her back (Figure 4C) and over her entire body, including scalp, ears, and posterior forearms (not shown). Her glycemic control improved (hemoglobin A1c decreased from 7.7% to 7.2%) and liver function remained normal throughout the study (ALT, 24 IU/L; AST, 14 IU/L before treatment; and ALT, 26 IU/L; AST, 15 IU

Interactions of Rosiglitazone and Anti.Arrhythmic Drugs in Animal ...

African Journals Online (AJOL)

Interactions of Rosiglitazone and Anti.Arrhythmic Drugs in Animal Model. YM Mohammed, EI Mohammed, N Mohiuddin, SS Syeda. Abstract. Background: Diabetes increases the risk of vascular problems by two times compared with a healthy individual, with deposition of fats in blood vessel and this includes cardiovascular ...

Short-Term Therapy with Rosiglitazone, a PPAR-γ Agonist, Improves Metabolic Profile and Vascular Function in Nonobese Lean Wistar Rats

OpenAIRE

Naderali, Mohammad M.; Itua, Imose; Abubakari, Abdul-Razak; Naderali, Ebrahim K.

2012-01-01

A number of preclinical and clinical studies have reported blood-pressure-lowering benefits of thiazolidinediones in diabetic subjects and animal models of diabetes. This study was designed to further elucidate vascular effects of rosiglitazone, on healthy nonobese, lean animals. Adult male Wistar rats were randomized and assigned to control and rosiglitazone-treated groups and were dosed daily with either vehicle or rosiglitazone (10 mg kg−1 day−1) by oral gavage for 5 days. Compared with co...

Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation

International Nuclear Information System (INIS)

Hirakata, Masao; Tozawa, Ryuichi; Imura, Yoshimi; Sugiyama, Yasuo

2004-01-01

In order to elucidate the antiatherogenic effects of pioglitazone (a peroxisome proliferator-activated receptor [PPAR]γ agonist with PPARα agonistic activity) and rosiglitazone (a more selective PPARγ agonist), we examined gene expression and cholesteryl ester accumulation in THP-1-derived macrophages. Pioglitazone enhanced the mRNA expression of the proatherogenic factors CD36 and adipophilin, but was approximately 10 times less potent than rosiglitazone. The potencies of the two agents appeared to correspond to their PPARγ agonistic activities in this respect. However, both agents were similarly potent in enhancing the mRNA expression of the antiatherogenic factors liver X receptor α and ATP-binding cassette-transporter A1. Furthermore, both agents enhanced cholesteryl ester hydrolase mRNA expression and inhibited acyl-CoA cholesterol acyltransferase-1 mRNA expression and cholesteryl ester accumulation in macrophages. In this respect, their potencies appeared to correspond to their PPARα agonistic activities. These results suggest that pioglitazone has an equally beneficial effect on antiatherogenic events to rosiglitazone, despite being almost 10 times less potent than a PPARγ agonist

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

International Nuclear Information System (INIS)

Jin, Gong Yong; Bok, Se Mi; Han, Young Min; Chung, Myung Ja; Yoon, Kwon-Ha; Kim, So Ri; Lee, Yong Chul

2012-01-01

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPARγ agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

Energy Technology Data Exchange (ETDEWEB)

Jin, Gong Yong; Bok, Se Mi; Han, Young Min [Department of Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Chung, Myung Ja [Department of Pathology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Yoon, Kwon-Ha [Department of Radiology, Iksan Hospital, Iksan (Korea, Republic of); Kim, So Ri [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Yong Chul, E-mail: leeyc@jbnu.ac.kr [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

2012-08-15

Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR{gamma} agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

Rosiglitazone and Cardiovascular Risk – A Review | Isa | Bayero ...

African Journals Online (AJOL)

The thiazolidinediones (TZDs) are a class of oral drugs used for the management of type 2 diabetes mellitus and act as ligands for the transcription factor Peroxisome Proliferator-Activated Receptor gamma (PPARγ). Rosiglitazone, an example of TZD, is an anti-diabetic agent acting as a potent insulin sensitizer and is used ...

In vivo metabolic phenotyping of myocardial substrate metabolism in rodents: differential efficacy of metformin and rosiglitazone monotherapy.

Science.gov (United States)

Shoghi, Kooresh I; Finck, Brian N; Schechtman, Kenneth B; Sharp, Terry; Herrero, Pilar; Gropler, Robert J; Welch, Michael J

2009-09-01

Cardiovascular disease is the leading cause of death among diabetic patients, with alteration in myocardial substrate metabolism being a likely contributor. We aimed to assess noninvasively the efficacy of metformin and rosiglitazone monotherapy in normalizing myocardial substrate metabolism in an animal model of type 2 diabetes mellitus. The study used 18 male ZDF rats (fa/fa) with 6 rats in each group: an untreated group; a group treated with metformin (16.6 mg/kg/d), and a group treated with rosiglitazone (4 mg/kg). Each rat was scanned at age 14 weeks (baseline) and subsequently at 19 weeks with small-animal positron emission tomography to estimate myocardial glucose utilization (MGU) and myocardial utilization (MFAU), oxidation (MFAO), and esterification (MFAE). Treatment lasted for 5 weeks after baseline imaging. At week 19, rats were euthanized and hearts were extracted for expression analysis of select genes encoding for GLUT transporters and fatty acid transport and oxidation genes. In addition, echocardiography measurements were obtained at weeks 13 and 18 to characterize cardiac function. Metformin had no significant effect on either MGU or MFAU and MFAO. In contrast, rosiglitazone tended to enhance MGU and significantly reduced MFAU and MFAO. Rosiglitazone-induced increase in glucose uptake correlated significantly with increased expression of GLUT4, whereas diminished MFAO correlated significantly with decreased expression of FATP-1 and MCAD. Finally, changes in fractional shortening as a measure of cardiac function were unchanged throughout the study. Treatment with rosiglitazone enhanced glucose utilization and diminished MFAO, thus reversing the metabolic phenotype of the diabetic heart.

Effect of pomegranate peel alone and in combination with rosiglitazone on hyperglycemia and dyslipidemia in type 2 diabetes mellitus

International Nuclear Information System (INIS)

Shujaat, A.; Hussain, M.M.

2016-01-01

To evaluate the effect of pomegranate peel extract with or without rosiglitazone on plasma glucose and lipid profile in insulin resistant diabetic rats. Study Design: Randomized controlled trial. Place and Duration of Study: Department of Physiology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health (N.I.H), Islamabad from 1st January 2011 to 28th May 2011. Material and Methods: Type 2 diabetes mellitus was induced in sixty healthy rats. The diabetic rats were divided into four groups, namely diabetic control group which received intraperitoneal injection of normal saline daily, pomegranate group which was treated similar to control group and also received pomegranate peel extract (200mg/kg body weight) orally once daily, rosiglitazone group which received intraperitoneal injection of rosiglitazone (5mg/kg body weight) daily and the combined group received both pomegranate extract (100 mg/kg body weight, orally) and intraperitoneal injection of rosiglitazone (2.5 mg/kg body weight) daily for 28 days. After four weeks of treatment, terminal intracardiac sampling was done to measure plasma glucose and lipid profile. Results: The plasma glucose and mean serum levels of cholesterol, triglyceride, low density lipoproteins and very low density lipoproteins was significantly reduced (p<0.001) in pomegranate, rosiglitazone and combined groups respectively as compared to the diabetic control. The mean serum levels of high density lipoproteins were significantly (p<0.001) elevated in above mentioned groups as compared to the diabetic control. Conclusion: Pomegranate peel extract is hypoglycemic and hypolipidemic agent in low doses when used alone or in combination with rosiglitazone in type 2 diabetic rats. (author)

Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression.

Science.gov (United States)

Toyota, Yosuke; Nomura, Sayaka; Makishima, Makoto; Hashimoto, Yuichi; Ishikawa, Minoru

2017-06-15

Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC 50 : 14μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of human CYP2C8 genotype and fluvoxamine on the pharmacokinetics of rosiglitazone in healthy subjects

DEFF Research Database (Denmark)

Pedersen, Rasmus S; Damkier, Per; Brosen, Kim

2006-01-01

= 0.0066) increase in the AUC(0-infinity) of rosiglitazone, with a geometric mean ratio of 1.21 [95% confidence interval (CI) 1.06-1.39]. The elimination half-life (t(1/2)) was also significantly higher (P = 0.0203) with a geometric mean ratio of 1.38 [95% CI 1.06-1.79]. The coadministration...... of fluvoxamine had no influence on the pharmacokinetics of N-desmethylrosiglitazone. CONCLUSION: The importance of the CYP2C8*3 mutation in the in vivo metabolism of rosiglitazone could not be confirmed. Fluvoxamine increased the AUC(0-infinity) and t(1/2) of rosiglitazone moderately and hence may be a weak...

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.

Science.gov (United States)

Zhang, Yun-Fang; Zou, Xun-Liang; Wu, Jun; Yu, Xue-Qing; Yang, Xiao

2015-12-01

We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.

A Study of Effects of Pioglitazone and Rosiglitazone on Various Parameters in Patients of Type-2 Diabetes Mellitus with Special Reference to Lipid Profile.

Science.gov (United States)

Sharma, S K; Verma, S H

2016-09-01

To study the complete fasting lipid profile and other parameters (weight, body mass index, HbA1c, fasting blood sugar and postprandial blood sugar)in Type 2 diabetes mellitus patients on OHA/insulin, to study the effect of addition of pioglitazone on lipid profile and other parameters in Type 2 diabetes mellitus patients on OHA/insulin, to study the effect of addition of rosiglitazone on lipid profile and other parameters in Type 2 diabetes mellitus patients on OHA/insulin and to compare the effect of pioglitazone and rosiglitazone on lipid profile and other parameters in Type 2 diabetes mellitus patients on OHA/insulin. In the study, 100 Type 2 diabetes cases on oral hypoglycemic agent/insulin with deranged lipid profile were chosen and divided into 2 groups 50 and 50 in group A and group B respectively.Pioglitazone was given initially 15mg/day then if required increasing upto 45mg/day in group A for period of 18 weeks and rosiglitazone was given initially 2 mg/day then if required increasing upto 8 mg/day in group B for period of 18 weeks. Detailed clinical history was obtained and thorough physical examination was done and following parameters were established-Age, Height, Weight, Body mass index, Fasting and Postprandial blood sugar, HbA1c levels and fasting complete lipid profile done at 0 and 18 weeks. Each patient itself served as a control for this study. Maximum no. of patients were in sixth decade (53.30%) and minimum patients were in seventh decade (6.6%). Males were 63.3% and females were 36.8%. Fasting blood sugar levels decreased by 23% with pioglitazone in group A and 14.07% with rosiglitazone in group B. The postprandial blood sugar levels decreased by 29.9% with pioglitazone in group A and 20.17% with rosiglitazone in group B.The mean HbA1c decreased by 2.13 % pioglitazone in group A and 3.8% with rosiglitazone in group B after 18 weeks of therapy. The effects of both drugs on BMI and weight were not significant. In group A the total cholesterol

Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial

DEFF Research Database (Denmark)

Home, Philip D; Pocock, Stuart J; Beck-Nielsen, Henning

2009-01-01

.80-1.63) for myocardial infarction, and 0.72 (0.49-1.06) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 2.10, 1.35-3.27, risk difference per 1000 person-years 2.6, 1.1-4.1). Upper and distal lower limb fracture rates...... failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs. FUNDING: GlaxoSmithKline plc, UK.......BACKGROUND: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared...

Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH.

Science.gov (United States)

Rashid, Jahidur; Alobaida, Ahmad; Al-Hilal, Taslim A; Hammouda, Samia; McMurtry, Ivan F; Nozik-Grayck, Eva; Stenmark, Kurt R; Ahsan, Fakhrul

2018-06-28

Peroxisome-proliferator-activated-receptor-gamma (PPAR-γ) is implicated, in some capacity, in the pathogenesis of pulmonary arterial hypertension (PAH). Rosiglitazone, an oral antidiabetic and PPAR-γ agonist, has the potential to dilate pulmonary arteries and to attenuate arterial remodeling in PAH. Here, we sought to test the hypothesis that rosiglitazone can be repurposed as inhaled formulation for the treatment of PAH. We have tested this conjecture by preparing and optimizing poly(lactic-co-glycolic) acid (PLGA) based particles of rosiglitazone, assessing the drug particles for pulmonary absorption, investigating the efficacy of the plain versus particulate drug formulation in improving the respiratory hemodynamics in PAH animals, and finally studying the effect of the drug in regulating the molecular markers associated with PAH pathogenesis. The optimized particles were slightly porous and spherical, and released 87.9% ± 6.7% of the drug in 24 h. The elimination half-life of the drug formulated in PLGA particles was 2.5-fold greater than that of the plain drug administered via the same route at the same dose. The optimized formulation, given via the pulmonary route, produced pulmonary selective vasodilation in PAH animals, but oral rosiglitazone had no effect in pulmonary hemodynamics. Rosiglitazone ameliorates the pathogenesis of PAH by balancing the molecular regulators involved in the vasoconstriction and vasodilation of human pulmonary arterial smooth muscle cells. All in all, data generated using intact animal and cellular models point to the conclusion that PLGA particles of an antidiabetic drug can be used for the treatment of a different disease, PAH. Copyright © 2018 Elsevier B.V. All rights reserved.

Determination of glibenclamide, metformin hydrochloride and rosiglitazone maleate by reversed phase liquid chromatographic technique in tablet dosage form

Directory of Open Access Journals (Sweden)

Havele Shweta S.

2014-01-01

Full Text Available A simple, precise and accurate high performance liquid chromatography (HPLC method was developed for the simultaneous estimation of metformin hydrochloride, rosiglitazone maleate, glibenclamide present in multicomponent dosage forms. Chromatography was performed on a 25 cm × 4.6 mm i.d., 5-μm particle, C18 column with 78:22 (v/v methanol: 20 mM potassium dihydrogen phosphate buffer as mobile phase at a flow rate of 1.0 ml/min and UV detection at 238 nm for metformin hydrochloride, rosiglitazone maleate, and glibenclamide. The total elution time was shorter than 9 min. This method was found to be precise and reproducible. This proposed method was successfully applied for the analysis of metformin hydrochloride, rosiglitazone maleate, glibenclamide as a bulk drug and in pharmaceutical formulation without any interference from the excipients.

Rosiglitazone Decreases Plasma Levels of Osteoprotegerin in a Randomized Clinical Trial with Type 2 Diabetes Patients

DEFF Research Database (Denmark)

Nybo, Mads; Preil, Simone Rørdam; Juhl, Henning Friis

2011-01-01

regarding cardiovascular disease. The South Danish Diabetes Study, an investigator-driven, randomized, controlled clinical trial lasting 2 years, was used to test this hypothesis in patient groups with different medication strategies (insulin aspart or NPH insulin, added either metformin...... (R = 0.29, p = 0.0002), while this correlation was poor in those not receiving rosiglitazone (R = 0.06, p = 0.48). Treatment with rosiglitazone among patients with T2DM reduces the concentration of plasma OPG. This is not seen with metformin despite similar reductions in HbA(1c) . Alteration...

Effects of rosiglitazone on metabolic parameters and large artery sclerosis in nondiabetic patients with metabolic sydrome

International Nuclear Information System (INIS)

Shen Zhenhai; Lu Yun; Feng Yinbo; Jin Xian

2010-01-01

Objective: To observe the effects of rosiglitazone on metabolic parameters, carotid intimamedia thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) in nondiabetic patients with metabolic syndrome. Methods: Seventy-nine nondiabetic patients with metabolic syndrome were randomly divided into treatment group (n = 41) and control group (n = 38). The patients in treatment group were treated with rosiglitazone on the basis of life-style intervention, those in control group were treated with life-style intervention for 9 months. All patients were followed up every 3 months. Body mass index (BMI) ,waist circumference(WC), systolic blood pressure (SBP), diastolic blood pressure(DBP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), highdendity lipoprotein (HDL-C), Low-density lipoprotein (LDL), high sensitivity C-reactive protein (hsCRP), HbA 1 C, fasting insulin (FIns), HOMA-IR, IMT, baPWV and ABI were measured in both groups before treatment and at the 6th, 9th month after treatment. Results: (1) After treatment with rosiglitazone for 6 months, FPG, TG, HDL-C, hsC RP, HbA 1 C, Fins and HOMA-IR in treatment group were improved (P 1 C, Fins and HOMA-IR got further improvement at the 9th month after treatment (P 1 C, Fins and HOMA-IR were changed significantly in treatment group compared to those in control group (P 1 C and HOMA-IR was independently related to the improvement of ABI by multivarient analysis. Conclusion: In nondiabetic patients with metabolic syndrome, rosiglitazone can significantly improve insulin resistance, correct metabolic disorders, has anti-inflammatory effect and retard atherosclerosis at some extent. (authors)

A novel translabial platform utilizing bioexcipients from Litchi chinesis for the delivery of rosiglitazone maleate

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N.V. Satheesh Madhav

2013-12-01

Full Text Available The aim of this study was to formulate drug-loaded bio-lipstrips using novel bioexcipients isolated from the fruit pulp of Litchi chinesis (biomaterial L and to explore the potentiality of lip skin as a novel translabial drug delivery system. The biomaterial, prepared by a simplified economical process and purified by hot dialysis, was subjected to various physicochemical evaluations along with spectral analysis including UV, FT-IR, Mass and 1H NMR. The lipstrip formulated with the novel bioexcipients was screened for its functional properties, including filmability using a film-casting method, and bio/muco-adhesitivity using a shear-stress method, the Park and Robinson method and a rotating cylinder method. Rosiglitazone-loaded bio-lipstrips were formulated by using biomaterial L as a strip former and dextrose as a flexicizer. The formulated strips were subjected to various evaluations, including thickness, folding endurance, in-vitro release and in-vivo release. The release of rosiglitazone maleate was maintained over 24 h, which was confirmed in in-vitro and in-vivo release experiments. Our results reveal that this biopolymer possesses promising stripability as well as bio-adhesitivity. The formulated bio-lipstrips are feasible for delivering rosiglitazone maleate by translabial administration.

Effects of Rosiglitazone on the Expression of PPAR-γ and on the ...

African Journals Online (AJOL)

Purpose: Peroxisome proliferator-activated receptor (PPAR)-γ ligand is known to repress the expression of pro-inflammatory mediators. However, it is unclear how it affects PPAR-γ expression and the inflammatory response in the human lung. We investigated the effects of rosiglitazone (synthetic PPAR-γ ligand) on the ...

Mirroring "meaningful" actions: sensorimotor learning modulates imitation of goal-directed actions.

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Catmur, Caroline; Heyes, Cecilia

2017-06-19

Imitation is important in the development of social and technological skills throughout the lifespan. Experiments investigating the acquisition and modulation of imitation (and of its proposed neural substrate, the mirror neuron system) have produced evidence that the capacity for imitation depends on associative learning in which connections are formed between sensory and motor representations of actions. However, evidence that the development of imitation depends on associative learning has been found only for non-goal-directed actions. One reason for the lack of research on goal-directed actions is that imitation of such actions is commonly confounded with the tendency to respond in a spatially compatible manner. However, since the most prominent account of mirror neuron function, and hence of imitation, suggests that these cells encode goal-directed actions, it is important to establish whether sensorimotor learning can also modulate imitation of goal-directed actions. Experiment 1 demonstrated that imitation of goal-directed grasping can be measured while controlling for spatial compatibility, and Experiment 2 showed that this imitation effect can be modulated by sensorimotor training. Together these data support the hypothesis that the capacity for behavioural imitation, and the properties of the mirror neuron system, are constructed in the course of development through associative learning.

Effect of the addition of rosiglitazone to metformin or sulfonylureas versus metformin/sulfonylurea combination therapy on ambulatory blood pressure in people with type 2 diabetes

DEFF Research Database (Denmark)

Komajda, Michel; Curtis, Paula; Hanefeld, Markolf

2008-01-01

BACKGROUND: Hypertension and type 2 diabetes are common co-morbidities. Preliminary studies suggest that thiazolidinediones reduce blood pressure (BP). We therefore used ambulatory BP to quantify BP lowering at 6-12 months with rosiglitazone used in combination with metformin or sulfonylureas...... compared to metformin and sulfonylureas in people with type 2 diabetes. METHODS: Participants (n = 759) in the multicentre RECORD study were studied. Those taking metformin were randomized (open label) to add-on rosiglitazone or sulfonylureas, and those on sulfonylurea to add-on rosiglitazone or metformin....... RESULTS: 24-Hour ambulatory BP was measured at baseline, 6 months and 12 months. At 6 and 12 months, reductions in 24-hour ambulatory systolic BP (sBP) were greater with rosiglitazone versus metformin (difference at 6 months 2.7 [95% CI 0.5-4.9] mmHg, p = 0.015; 12 months 2.5 [95% CI 0.2-4.8] mmHg, p = 0...

Theory of direct interparticle action

International Nuclear Information System (INIS)

Vladimirov, Yu.S.; Turygin, A.Yu.

1986-01-01

Unusual point of view on the physical picture of the Universe and ratio between main physical categories is considered. Principal moments and theory peculiarities based on the conception of direct interparticle action are underlined. The direct interparticle action theory (DIAT) is considered from the position of choosing one or another axiomatics. At first the Fokker action principle is postulated there and then identical satisfiability of field equations is proved. All that relates to vacuum DIAT ignores and actions of matter formations are used as the basis. DIAT bears up against a global factor-account of absrbers of all surroundings (the Mach principle). The DIAT pretended to relativistic description of only additional concepts with the previously asigned space-time ratios. Concept for construction of the physical picture of the Universe, where classical space-time ratios being of secondary character, is suggested

Resistin production from adipose tissue is decreased in db/db obese mice, and is reversed by rosiglitazone.

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Hongying Ye

Full Text Available OBJECTIVE: This study was designed to (1 investigate the expression profiles of resistin in db/db mice and its dynamic association with metabolic parameters; and (2 evaluate the effects of Rosiglitazone on production of resistin. METHODS: Db/db mice and their lean litter mates were used for this study. Epididymal fat tissue was excised from mice of different age (from 5 to 12 weeks for ex vivo incubation. Resistin,along with adiponectin,in serum and conditioned culture medium of epididymal fat pads were measured with immunoassays. The gene expression of resistin was determined by real-time PCR. Rosiglitazone or the vehicle (PBS was administered into db/db mice by daily intra-gastric gavage. Differentiated 3T3-L1 adipocytes were used for in vitro evaluation. RESULTS: The secretion of resistin from the fat pads in db/db mice was significantly lower than that in lean mice (P<0.01. The mRNA expression of the resistin gene in fat tissue of db/db mice at the age of 5 weeks was decreased by 60.5% compared to lean controls (p<0.05. Serum levels of resistin were comparable between the obese and lean groups, perhaps due to the increased total fat mass in db/db mice. Correlation analysis showed that serum resistin levels were positively correlated to resistin secretion from fat pads(r = 0.844,P = 0.000, while negatively associated with the body weight (r = -0.515, P = 0.000 and fasting glucose level (r = -0.357, P = 0.002. Notably, treatment with rosiglitazone increased the serum resistin levels by 66.4%(P<0.05in db/db mice. In 3T3-L1 adipocytes, Rosiglitazone (10 uM markedly enhanced the secretion of resistin by 120% (P<0.01 and its gene expression by 78.1% (P<0.05. CONCLUSION: Both resistin gene expression and its secretion from the epididymal adipose tissue were decreased in db/db obese mice, while the insulin-sensitizing drug rosiglitazone increased resistin production. Our results do not support the role of resistin as an

Insulin Sensitizing and Antioxidant Effects of Hesperidin and Low Dose Gamma Irradiation in Combination with Rosiglitazone in Type 2 Diabetic Rats

International Nuclear Information System (INIS)

Morcos, N.Y.; Abdel-Ghaffar, A.B.; Osman, S.A.; Mohamed, M.Kh.; Arbid, M.S.; El-Eraky, W.I.

2012-01-01

The present study was designed to investigate the possible ameliorative effect of hesperidin and low dose fÁ-irradiation (LDR) in combination with rosiglitazone in an experimental model of insulin resistance. Type 2 diabetes mellitus (T2DM) was induced in rats by single intraperitoneal injection of streptozotocin (STZ) followed by nicotinamide (NIC) (65 and 110 mg/kg b.wt; i.p respectively). After verifying T2DM in rats, they were subjected to LDR (50 cGy) and then treated with rosiglitazone (4 mg/kg b.wt; p.o) and hesperidin (100 mg/kg b.wt; p.o) for 30 days. Results showed that STZ injection significantly elevated blood glucose, glycosylated hemoglobin (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid peroxides (TBARS; MDA) accompanied with a reduction in adiponectin plasma level, reduced glutathione (GSH) and superoxide dismutase (SOD) serum level. Treatment of diabetic rats with rosiglitazone, hesperidin and LDR significantly reduced blood glucose, HbA1c, insulin, HOMA-IR and MDA levels. Whereas, plasma adiponectin, SOD in serum and GSH plasma level were significantly elevated. Therefore, our data suggest that hesperidin and LDR might be useful adjuvants with rosiglitazone and attenuate insulin resistance and oxidative stress in T2DM.

Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics.

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Ratner, Robert E; Cannon, Christopher P; Gerstein, Hertzel C; Nesto, Richard W; Serruys, Patrick W; Van Es, Gerrit-Anne; Kolatkar, Nikheel S; Kravitz, Barbara G; Zalewski, Andrew; Fitzgerald, Peter J

2008-12-01

Rosiglitazone, a thiazolidinedione, has effects on insulin sensitivity and cardiovascular risk factors that may favorably impact the progression of coronary atherosclerosis. APPROACH is a double-blind randomized clinical trial comparing the effects of the insulin sensitizer rosiglitazone with the insulin secretagogue glipizide on the progression of coronary atherosclerosis. Patients with type 2 diabetes and coronary artery disease undergoing clinically indicated coronary angiography or percutaneous coronary intervention are randomized to receive rosiglitazone or glipizide for 18 months using a titration algorithm designed to provide comparable glycemic control between treatment groups. The primary end point is change in percent atheroma volume from baseline to study completion in a nonintervened coronary artery, as measured by intravascular ultrasound. Cardiovascular events are adjudicated by an end point committee. A total of 672 patients were randomized. The mean age was 61 years, hemoglobin A(1c) (HbA(1c)) 7.2%, body mass index 29.5 kg/m(2), and median duration of diabetes 4.8 years. At baseline, approximately half of the participants were receiving oral antidiabetic monotherapy (53.9%) with 27.5% receiving dual combination therapy and 17.9% treated with diet and exercise alone. Approximately two thirds of the participants (68%) had dyslipidemia, 79.9% hypertension, and 24% prior myocardial infarction. APPROACH has fully enrolled a high-risk patient population and will compare the glucose-independent effects of rosiglitazone and glipizide on the progression of coronary atherosclerosis, as well as provide additional data on the cardiovascular safety of rosiglitazone in patients with type 2 diabetes and coronary artery disease.

Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

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Marshall J Glesby

Full Text Available Recombinant human growth hormone (rhGH reduces visceral adipose tissue (VAT volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI and subcutaneous adipose tissue (SAT volume.Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI and dual Xray absorptiometry (DEXA. Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02; by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03 differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004, increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH but not in the rosiglitazone alone (-2.5% or control arms (-1.9%. SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter.The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT.Clinicaltrials.gov NCT00130286.

Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

Science.gov (United States)

Glesby, Marshall J; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P

2013-01-01

Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Clinicaltrials.gov NCT00130286.

Mechanism of action study to evaluate the effect of rosiglitazone on bone in postmenopausal women with type 2 diabetes mellitus: rationale, study design and baseline characteristics

Science.gov (United States)

Fitzpatrick, Lorraine A.; Bilezikian, John P.; Wooddell, Margaret; Paul, Gitanjali; Kolatkar, Nikheel S.; Nino, Antonio J.; Miller, Colin G.; Bogado, Cesar E.; Arnaud, Claude D.; Cobitz, Alexander R.

2012-01-01

Objectives Post-hoc analyses have shown an increase incidence of fractures among type 2 diabetes (T2DM) patients treated with thiazolidinediones (TZDs). The mechanisms by which TZDs may be associated with increased fracture risk is not well understood. This article describes the study design and baseline characteristics for a prospective, randomized, double-blind, active-controlled trial to evaluate the effects of rosiglitazone on changes in measures of skeletal structure, surrogates of bone strength and metabolism. Methods Postmenopausal women without osteoporosis and diagnosed with T2DM were randomized in a double-blind design to either rosiglitazone or metformin for 52 weeks, then all subjects received open-label metformin for 24 weeks. Study endpoints included changes in bone mineral density (BMD), quantitative computed tomography (QCT), digitized hip radiography (HXR) and high resolution magnetic resonance imaging (hrMRI). Serum markers of bone metabolism and indices of glycemic control were assessed within and between treatment groups. Results A total of 226 subjects were randomized. Baseline characteristics included: age 63.8 ± 6.5 years; years postmenopausal 16.9 ± 8.4; duration of diabetes 3.5 (1.8–7.8) years; body mass index (BMI) 31.4 ± 5.9 kg/m2; and glycated hemoglobin (HbA1c) 6.4 ± 0.65%. At baseline, mean T-scores were −0.95 ± 0.91 at the femoral neck, −0.02 ± 0.97 at the total hip and −0.55 ± 1.25 at the total spine. Since there are no well recognized techniques to determine bone mass and structure at the distal limbs (cortical bone sites where fractures were reported in RSG subjects), using the femoral neck as a surrogate for these areas may be a potential limitation of the study. Conclusion This is the first randomized trial utilizing multiple techniques to evaluate bone mass, structure, serum markers of bone remodeling, and potential reversibility of changes after discontinuation of rosiglitazone. This

Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.

Science.gov (United States)

Tfayli, Hala; Ulnach, Julia Warren; Lee, SoJung; Sutton-Tyrrell, Kim; Arslanian, Silva

2011-05-01

Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome. Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS. We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients. The primary outcome measure was insulin sensitivity, hepatic with [6,6-(2)H(2)]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan. Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity. In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to

Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

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Bundhun, Pravesh Kumar; Janoo, Girish; Teeluck, Abhishek Rishikesh; Huang, Feng

2017-10-23

Vildagliptin and pioglitazone/rosiglitazone are emerging Oral Hypoglycemic Agents (OHAs) which are used to treat patients suffering from Type 2 Diabetes Mellitus (T2DM). In this analysis, we aimed to systematically compare the adverse drug events which were observed with the use of vildagliptin versus pioglitazone or rosiglitazone respectively. Online databases were searched for studies comparing vildagliptin with pioglitazone/rosiglitazone. Adverse drug events were considered as the clinical endpoints in this analysis. We calculated Odds Ratios (OR) with 95% Confidence Intervals (CIs) using the RevMan 5.3 software. All the authors had full access to the data which were used and approved the final version of the manuscript. A total number of 2396 patients were analyzed (1486 and 910 patients were treated with vildagliptin and pioglitazone/rosiglitazone respectively). Vildagliptin and pioglitazone/rosiglitazone were both associated with similar overall adverse drug events (OR: 1.00, 95% CI: 0.81-1.24; P = 1.00). Headache (OR: 0.88, 95% CI: 0.60-1.27; P = 0.49) and upper respiratory tract infection (OR: 0.95, 95% CI: 0.71-1.27; P = 0.75) were similarly observed. However, dizziness was significantly lower with pioglitazone/rosiglitazone (OR: 0.63, 95% CI: 0.43-0.92; P = 0.02). Back pain, diarrhea and nausea were insignificantly lower with pioglitazone/rosiglitazone (OR: 0.81, 95% CI: 0.49-1.33; P = 0.40), (OR: 0.83, 95% CI: 0.48-1.44; P = 0.52) and (OR: 0.52, 95% CI: 0.25-1.05; P = 0.07) respectively, whereas peripheral edema and weight gain were insignificantly higher (OR: 1.21, 95% CI: 0.56-2.62; P = 0.63) and (OR: 2.29, 95% CI: 0.51-10.34; P = 0.28) respectively. Nevertheless, when pioglitazone and rosiglitazone were separately compared with vildagliptin, peripheral edema and weight gain were significantly higher with rosiglitazone (OR: 2.36, 95% CI: 1.40-3.99; P = 0.001) and (OR: 5.20, 95% CI: 2.47-10.92; P = 0.0001) respectively. Both

Simpson's paradox visualized: The example of the Rosiglitazone meta-analysis

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Schumacher Martin

2008-05-01

Full Text Available Abstract Background Simpson's paradox is sometimes referred to in the areas of epidemiology and clinical research. It can also be found in meta-analysis of randomized clinical trials. However, though readers are able to recalculate examples from hypothetical as well as real data, they may have problems to easily figure where it emerges from. Method First, two kinds of plots are proposed to illustrate the phenomenon graphically, a scatter plot and a line graph. Subsequently, these can be overlaid, resulting in a overlay plot. The plots are applied to the recent large meta-analysis of adverse effects of rosiglitazone on myocardial infarction and to an example from the literature. A large set of meta-analyses is screened for further examples. Results As noted earlier by others, occurrence of Simpson's paradox in the meta-analytic setting, if present, is associated with imbalance of treatment arm size. This is well illustrated by the proposed plots. The rosiglitazone meta-analysis shows an effect reversion if all trials are pooled. In a sample of 157 meta-analyses, nine showed an effect reversion after pooling, though non-significant in all cases. Conclusion The plots give insight on how the imbalance of trial arm size works as a confounder, thus producing Simpson's paradox. Readers can see why meta-analytic methods must be used and what is wrong with simple pooling.

Hyper-inflammation and skin destruction mediated by rosiglitazone activation of macrophages in IL-6 deficiency

DEFF Research Database (Denmark)

Das, Lopa M; Rosenjack, Julie; Au, Liemin

2015-01-01

Injury initiates recruitment of macrophages to support tissue repair; however, excessive macrophage activity may exacerbate tissue damage causing further destruction and subsequent delay in wound repair. Here we show that the peroxisome proliferation-activated receptor-γ agonist, rosiglitazone (R...

Fenofibrate and rosiglitazone improve quality of lipoproteins in patients with type 2 diabetes mellitus

Czech Academy of Sciences Publication Activity Database

Vrablík, M.; Dobiášová, Milada; Štulc, T.; Kasalová, Z.; Doležalová, R.; Prázný, M.; Fait, T.; Češka, R.

2008-01-01

Roč. 29, č. 1 (2008), s. 146-150 ISSN 0172-780X R&D Projects: GA MZd(CZ) NR8328 Institutional research plan: CEZ:AV0Z50110509 Keywords : fenofibrate * rosiglitazone * type 2 diabetes mellitus Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.359, year: 2008

Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome.

Science.gov (United States)

Belli, Susana H; Graffigna, Mabel N; Oneto, Adriana; Otero, Patricia; Schurman, Leon; Levalle, Oscar A

2004-03-01

To evaluate the effects of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome (PCOS). Prospective study. Women with PCOS attending as outpatients of the Endocrine Division, Hospital Durand, Buenos Aires. Twenty-four insulin-resistant women with PCOS. Hormonal evaluations and a standardized oral glucose tolerance test before and after a 3-month trial of 4 mg of rosiglitazone daily. Serum LH, FSH, T, IGF-1, IGFBP-1, IGFBP-3, leptin, 17alpha-hydroxyprogesterone, insulin, and glucose concentrations. The area under insulin curve (AUC-insulin), the HOMA index (insulin resistance), the QUICKI index (insulin sensitivity), and the beta-cell function were calculated. Body mass index (BMI) and the waist/hip ratio were evaluated. A significant decrease was observed in serum fasting insulin, AUC insulin, HOMA index, beta-cell function, IGF-1, LH, and waist/hip ratio. The QUICKI index and IGFBP-1 increased significantly. Serum sex hormone-binding globulin, androgens, leptin, IGFBP-3, and BMI remained unchanged. Twenty-two of 23 females had their menses restored, and three patients became pregnant. One patient was excluded because she became pregnant at the second month. Associated with the decrease in LH, rosiglitazone improved insulin-resistance parameters and normalized the menstrual cycle, which suggests that this drug could improve the endocrine-reproductive condition in insulin-resistant women with PCOS.

Exposure to rosiglitazone, a PPAR-γ agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus.

Science.gov (United States)

Lie, Shervi; Hui, Melisa; McMillen, I Caroline; Muhlhausler, Beverly S; Posterino, Giuseppe S; Dunn, Stacey L; Wang, Kimberley C; Botting, Kimberley J; Morrison, Janna L

2014-03-15

It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca(2+) sensitivity and maximum Ca(2+)-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and

Metformin, but not rosiglitazone, attenuates the increasing plasma levels of a new cardiovascular marker, fibulin-1, in patients with type 2 diabetes

DEFF Research Database (Denmark)

Skov, Vibe; Cangemi, Claudia; Gram, Jeppe

2013-01-01

ObjectiveThe extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes and circulates in increased concentrations in diabetes. Metformin is an anti-diabetic drug with beneficial CVD effects in diabetes. We hypothesized that metformin would influence the increased...... level of plasma fibulin-1 in diabetes.Research Design and MethodsAfter a four-week run-in period, 371 eligible patients with type 2 diabetes were randomized to treatment groups in a factorial design including insulin alone (control), +metformin, +rosiglitazone, or +both metformin and rosiglitazone...

Selective block of KATP channels: why the anti-diabetic sulphonylureas and rosiglitazone have more in common than we thought

Science.gov (United States)

Dart, Caroline

2012-01-01

Rosiglitazone, the thiazolidinedione class anti-diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP-sensitive potassium (KATP) channels. This seems little cause for excitement given that the closure of pancreatic KATP channels is integral to insulin secretion; and sulphonylureas, which inhibit KATP channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks KATP channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow–regulating vascular KATP channels. Identification of a new molecule that modulates KATP channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress – a claim that has dogged the sulphonylureas for many years. LINKED ARTICLE This article is a commentary on Yu et al., pp. 26–36 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.01934.x PMID:22506686

Resistin production from adipose tissue is decreased in db/db obese mice, and is reversed by rosiglitazone.

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Ye, Hongying; Zhang, Herbert J; Xu, Aimin; Hoo, Ruby L C

2013-01-01

This study was designed to (1) investigate the expression profiles of resistin in db/db mice and its dynamic association with metabolic parameters; and (2) evaluate the effects of Rosiglitazone on production of resistin. Db/db mice and their lean litter mates were used for this study. Epididymal fat tissue was excised from mice of different age (from 5 to 12 weeks) for ex vivo incubation. Resistin,along with adiponectin,in serum and conditioned culture medium of epididymal fat pads were measured with immunoassays. The gene expression of resistin was determined by real-time PCR. Rosiglitazone or the vehicle (PBS) was administered into db/db mice by daily intra-gastric gavage. Differentiated 3T3-L1 adipocytes were used for in vitro evaluation. The secretion of resistin from the fat pads in db/db mice was significantly lower than that in lean mice (Plean controls (plean groups, perhaps due to the increased total fat mass in db/db mice. Correlation analysis showed that serum resistin levels were positively correlated to resistin secretion from fat pads(r = 0.844,P = 0.000), while negatively associated with the body weight (r = -0.515, P = 0.000) and fasting glucose level (r = -0.357, P = 0.002). Notably, treatment with rosiglitazone increased the serum resistin levels by 66.4%(Pproduction. Our results do not support the role of resistin as an etiological link between obesity and diabetes.

Rangers and the Strategic Requirements for Direct Action Forces

National Research Council Canada - National Science Library

Zunde, Aidis

1998-01-01

.... This analysis indicates that the achievement of strategic ends also requires a large-scale special operations ground direct action force to accomplish direct action missions beyond the capabilities of other assets...

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

Science.gov (United States)

Home, P D; Kahn, S E; Jones, N P; Noronha, D; Beck-Nielsen, H; Viberti, G

2010-09-01

Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone. Neoplasm occurrences were collected as adverse events in these studies. We reviewed and re-analysed the individual participant data in both studies for serious adverse events, malignancies reported as adverse events and related neoplasms of special interest. In ADOPT, 50 participants (3.4%) on metformin and 55 (3.8%) on each of rosiglitazone and glibenclamide (known as glyburide in the USA and Canada) developed serious adverse event malignancies (excluding non-melanoma skin cancers). This corresponds to 1.03, 1.12 and 1.31 per 100 person-years, giving hazard ratios for metformin of 0.92 (95% CI 0.63-1.35) vs rosiglitazone and 0.78 (0.53-1.14) vs glibenclamide. In RECORD, on a background of sulfonylurea, 69 (6.1%) participants developed malignant neoplasms in the metformin group, compared with 56 (5.1%) in the rosiglitazone group (HR 1.22 [0.86-1.74]). On a background of metformin, 74 (6.7%) participants in the sulfonylurea group developed malignant neoplasms, compared with 57 (5.1%) in the rosiglitazone group (HR 1.33 [0.94-1.88]). The malignancy rates in these two randomised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone. However, they do not refute the possibility of a difference compared with sulfonylureas.

Action recognition and movement direction discrimination tasks are associated with different adaptation patterns

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Stephan eDe La Rosa

2016-02-01

Full Text Available The ability to discriminate between different actions is essential for action recognition and social interaction. Surprisingly previous research has often probed action recognition mechanisms with tasks that did not require participants to discriminate between actions, e.g. left-right direction discrimination tasks. It is not known to what degree visual processes in direction discrimination tasks are also involved in the discrimination of actions, e.g. when telling apart a handshake from a high-five. Here, we examined whether action discrimination is influenced by movement direction and whether direction discrimination depends on the type of action. We used an action adaptation paradigm to target action and direction discrimination specific visual processes. In separate conditions participants visually adapted to forward and backward moving handshake and high-five actions. Participants subsequently either categorized the action or the movement direction of an ambiguous action. The results showed that direction discrimination adaptation effects were modulated by the type of action but action discrimination adaptation effects were unaffected by movement direction. These results suggest that action discrimination and direction categorization rely on partly different visual information. We propose that action discrimination tasks should be considered for the exploration of visual action recognition mechanisms.

Action and reaction in the theories of direct interparticle action

International Nuclear Information System (INIS)

Narlikar, J.V.

1975-01-01

Newton's third law of motion is examined in the context of the theories of direct interpaticle action. In such theories, interactions between particles travel backward and forward in time at speeds not exceeding the speed of light. It is shown that while in the flat spacetime the equality of action and reaction can be clearly demonstrated, the situation is considerably more complicated in the curved spacetime. The phenomenon of gravitational scattering intervenes to destroy the equality of action and reaction. Nevertheless, when gravitation is taken into account, there is no violation of the conservation law of energy and momentum. These results are discussed in the framework of general relativity for the case of the electromagnetic interaction

Rosiglitazone stimulates the release and synthesis of insulin by enhancing GLUT-2, glucokinase and BETA2/NeuroD expression

International Nuclear Information System (INIS)

Kim, Hyo-Sup; Noh, Jung-Hyun; Hong, Seung-Hyun; Hwang, You-Cheol; Yang, Tae-Young; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

2008-01-01

Peroxisome proliferator-activated receptor (PPAR)-γ is a member of the nuclear receptor superfamily, and its ligands, the thiazolidinediones, might directly stimulate insulin release and insulin synthesis in pancreatic β-cells. In the present study, we examined the effects of rosiglitazone (RGZ) on insulin release and synthesis in pancreatic β-cell (INS-1). Insulin release and synthesis were stimulated by treatment with RGZ for 24 h. RGZ upregulated the expressions of GLUT-2 and glucokinase (GCK). Moreover, it was found that RGZ increased the expression of BETA2/NeuroD gene which could regulate insulin gene expression. These results suggest that RGZ could stimulate the release and synthesis of insulin through the upregulation of GLUT-2, GCK, and BETA2/NeuroD gene expression

Rosiglitazone attenuates the metalloprotease/anti-metalloprotease imbalance in emphysema induced by cigarette smoke: involvement of extracellular signal-regulated kinase and NFκB signaling

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Hou G

2015-04-01

Full Text Available Gang Hou, Yan Yin, Dan Han, Qiu-yue Wang, Jian Kang Department of Respiratory Medicine, the First Hospital of China Medical University, Shenyang, People’s Republic of China Objective: We investigated how rosiglitazone attenuated cigarette smoke (CS-induced emphysema in a rat model. In particular, we focused on its possible effects on the imbalance between metalloprotease (MMP and anti-MMP activity, mitogen-activated protein kinase (MAPK phosphorylation, and nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB signaling pathway over-activation.Methods: A total of 36 Wistar rats were divided into three groups (n=12 each: animals were exposed to CS for 12 weeks in the absence (the CS group or presence of 30 mg/kg rosiglitazone (the rosiglitazone-CS [RCS] group; a control group was treated with the rosiglitazone vehicle only, without any CS exposure. Histopathology of lung tissue in all groups was evaluated to grade severity of the disease. Expression levels of peroxisome proliferator-activated receptor γ (PPARγ, MMP2, and MMP9 in lung tissue were determined and compared using Western blotting and immunohistochemistry. Activation of MAPKs, NFκB, and the nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor, alpha (IκBα phosphorylation in lung tissue was examined by Western blotting.Results: Emphysema-related pathology, based on inter-alveolar wall distance and alveolar density, was less severe in the RCS group than in the CS group. Compared with the CS group, levels of PPARγ were higher in the RCS group, and levels of MMP2 and MMP9 proteins were lower in the RCS rats. Levels of activated MAPKs and NFκB were also lower, while the IκBαphosphorylation was increased in the lung tissue of RCS rats.Conclusion: Our findings suggest that oral administration of rosiglitazone attenuates the metalloprotease activity induced by CS, and the underlying mechanism might involve the activation of signaling pathways

Rosiglitazone attenuates NF-κB-dependent ICAM-1 and TNF-α production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation

International Nuclear Information System (INIS)

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia; Song, Tao; You, Yu; Tang, Zhen-Yan; Li, Yuan-Jian; Zhang, Guo-Gang

2007-01-01

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-κB) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-κB-mediated sICAM-1, TNF-α production and the possible involvement of ERK 1/2 /p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-α in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-κB inhibitor; PD98059, MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK 1/2 /p38MAPK pathway and NF-κB activity in HUVECs. The results show that Hcy activated both ERK 1/2 /p38MAPK pathway and NF-κB-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK 1/2 /p38MAPK phosphorylation, suggesting that Hcy-induced ERK 1/2 /p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-κB activation was mediated by activation of ERK 1/2 /p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-κB-mediated sICAM-1 and TNF-α production induced by Hcy via inhibition of ERK 1/2 /p38MAPK pathway

Rosiglitazone Reduces Plasma Levels of Inflammatory and Hemostatic Biomarkers and Improves Global Endothelial Function in Habitual Heavy Smokers Without Diabetes Mellitus or Metabolic Syndrome

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I-Chih Chen

2010-02-01

Conclusion: Rosiglitazone significantly reduces plasma levels of inflammatory and hemostatic biomarkers, and restores global endothelial dysfunction, independently from insulin sensitization, in healthy smokers.

Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia

OpenAIRE

Asp, Michelle L.; Tian, Min; Kliewer, Kara L.; Belury, Martha A.

2011-01-01

Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoc...

Activation of PPAR by Rosiglitazone Does Not Negatively Impact Male Sex Steroid Hormones in Diabetic Rats

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Mahmoud Mansour

2009-01-01

Full Text Available Peroxisome proliferator-activated receptor gamma (PPAR activation decreased serum testosterone (T in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2 in female rats. This implies modulation of female sex steroid hormones by PPAR. It is not clear if PPAR modulates sex steroid hormones in diabetic males. Because PPAR activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPAR activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPAR activation on serum and intratesticular T, luteinizing hormone (LH, follicle stimulating hormone (FSH and E2 concentrations in male Zucker diabetic fatty (ZDF rats treated with the PPAR agonist rosiglitazone (a thiazolidinedione. Treatment for eight weeks increased PPAR mRNA and protein in the testis and elevated serum adiponectin, an adipokine marker for PPAR activation. PPAR activation did not alter serum or intratesticular T concentrations. In contrast, serum T level but not intratesticular T was reduced by diabetes. Neither diabetes nor PPAR activation altered serum E2 or gonadotropins FSH and LH concentrations. The results suggest that activation of PPAR by rosiglitazone has no negative impact on sex hormones in male ZDF rats.

A pilot study investigating the effects of rosiglitazone on performance in neuropsychological tests in patients with mild-to-moderate Alzheimer's disease

NARCIS (Netherlands)

Peers, P.V.; Semple, J.; Lai, R.Y.K.; Smith, G.R.; Altman, J.; Risner, M.; Riedel, W.J.

2006-01-01

Background: Rosiglitazone (a PPARg agonist) has shown beneficial effects on memory and executive function tasks in Alzheimer’s disease (AD)[1] Objective(s): To examine the use of standard clinical measures (e.g ADAS-cog) and experimental measures of simple and choice reaction time (examining

Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

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Kun Ho Yoon

2011-02-01

Full Text Available BackgroundAlthough many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.MethodsWe evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.ResultsHbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001, from 7.9% to 7.0% in the metformin group (P<0.001, and from 7.8% to 7.0% (P<0.001 in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.ConclusionThe efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

Synergic effect of n-3 polyunsaturated fatty acids and rosiglitazone in the amelioration of insulin resistance and adipose tissue inflammatinon

Czech Academy of Sciences Publication Activity Database

Kuda, Ondřej; Jílková, Zuzana; Rossmeisl, Martin; Flachs, Pavel; Ogston, N. C.; Mohamed-Ali, V.; Cinti, S.; Kopecký, Jan

2007-01-01

Roč. 50, Suppl.1 (2007), S260-S260 ISSN 0012-186X. [Annual Meeting of the European Association for the Study of Diabetes /43./. 18.09.2007-21.09.2007, Amsterdam] R&D Projects: GA ČR(CZ) GD303/03/H065 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * insulin * rosiglitazone * PUFA Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.

Science.gov (United States)

Hashiguchi, Hiroshi; Sheng, Zhenyu; Routh, Vanessa; Gerzanich, Volodymyr; Simard, J Marc; Bryan, Joseph

2017-01-01

Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices. Depolarization resulted from a decreased input resistance (IR) in ~70% of neurons (15/22) or an increased IR in the remainder (7/22), consistent with the opening or closing of ion channels, respectively. Although tetrodotoxin (TTX) blockade of presynaptic action potentials reduced ghrelin-induced changes in MP and IR, ghrelin still significantly depolarized the MP and decreased IR in TTX-treated neurons, suggesting that ghrelin directly opens cation channel(s) in NPY neurons. In isolated NPY-GFP neurons, ghrelin produced a sustained rise of [Ca2+]c, with an EC50 ~110 pM. Pharmacologic studies confirmed that the direct action of ghrelin was through occupation of the growth hormone secretagogue receptor, GHS-R, and demonstrated the importance of the adenylate cyclase/cAMP/protein kinase A (PKA) and phospholipase C/inositol triphosphate (PLC/IP3) pathways as activators of 5' AMP-activated protein kinase (AMPK). Activation of isolated neurons was not affected by CNQX or TTX, but reducing [Na+]o suppressed activation, suggesting a role for Na+-permeable cation channels. SUR1 and two channel partners, Kir6.2 and Trpm4, were identified immunologically in NPY-GFP neurons in situ. The actions of SUR1 and Trpm4 modulators were informative: like ghrelin, diazoxide, a SUR1 agonist, elevated [Ca2+]c and glibenclamide, a SUR1 antagonist, partially suppressed ghrelin action, while 9-phenanthrol and flufenamic acid, selective Trpm4 antagonists, blocked ghrelin actions on isolated neurons. Ghrelin activation was unaffected by nifedipine and

Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

Science.gov (United States)

Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

2014-11-01

Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Direct and indirect pathways for choosing objects and actions.

Science.gov (United States)

Hikosaka, Okihide; Kim, Hyoung F; Amita, Hidetoshi; Yasuda, Masaharu; Isoda, Masaki; Tachibana, Yoshihisa; Yoshida, Atsushi

2018-02-23

A prominent target of the basal ganglia is the superior colliculus (SC) which controls gaze orientation (saccadic eye movement in primates) to an important object. This 'object choice' is crucial for choosing an action on the object. SC is innervated by the substantia nigra pars reticulata (SNr) which is controlled mainly by the caudate nucleus (CD). This CD-SNr-SC circuit is sensitive to the values of individual objects and facilitates saccades to good objects. The object values are processed differently in two parallel circuits: flexibly by the caudate head (CDh) and stably by the caudate tail (CDt). To choose good objects, we need to reject bad objects. In fact, these contrasting functions are accomplished by the circuit originating from CDt: The direct pathway focuses on good objects and facilitates saccades to them; the indirect pathway focuses on bad objects and suppresses saccades to them. Inactivation of CDt deteriorated the object choice, because saccades to bad objects were no longer suppressed. This suggests that the indirect pathway is important for object choice. However, the direct and indirect pathways for 'object choice', which aim at the same action (i.e., saccade), may not work for 'action choice'. One possibility is that circuits controlling different actions are connected through the indirect pathway. Additional connections of the indirect pathway with brain areas outside the basal ganglia may also provide a wider range of behavioral choice. In conclusion, basal ganglia circuits are composed of the basic direct/indirect pathways and additional connections and thus have acquired multiple functions. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Inhibitory effect of leptin on rosiglitazone-induced differentiation of primary adipocytes prepared from TallyHO/Jng mice

Energy Technology Data Exchange (ETDEWEB)

Kim, Ki Young; Kim, Joo Young; Sung, Yoon-Young; Jung, Won Hoon; Kim, Hee-Youn; Park, Ji Seon; Cheon, Hyae Gyeong [Medicinal Science Division, Korea Research Institute of Chemical Technology, 100 Jang-dong, Yuseong, 305-600 Daejon (Korea, Republic of); Rhee, Sang Dal, E-mail: sdrhee@krict.re.kr [Medicinal Science Division, Korea Research Institute of Chemical Technology, 100 Jang-dong, Yuseong, 305-600 Daejon (Korea, Republic of)

2011-03-25

Research highlights: {yields} In this study, we investigated the effects of leptin on adipocyte differentiation prepared from subcutaneous fat of TallyHo mice. {yields} Leptin inhibited the adipocytes differentiation at physiological concentration via inhibition of PPAR{gamma} expression. {yields} Inhibitors of ERK and STAT1 restored the leptin's inhibitory activity both in vitro and in vivo. -- Abstract: The effects of leptin on rosiglitazone-induced adipocyte differentiation were investigated in the primary adipocytes prepared from subcutaneous fat of TallyHO/Jng (TallyHO) mouse, a recently developed model animal for type 2 diabetes mellitus (T2DM). The treatment of leptin inhibited the rosiglitazone-induced adipocyte differentiation with a decreased expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) a key adipogenic transcription factor, both in mRNA and protein levels. Leptin (10 nM) was sufficient to inhibit the adipocyte differentiation, which seemed to come from increased expression of leptin receptor genes in the fat of TallyHO mice. The inhibition of adipogenesis by leptin was restored by the treatment of inhibitors for extracellular-signal-regulated kinase (ERK) (PD98059) and signal transducer and activator of transcription-1 (STAT1) (fludarabine). Furthermore, in vivo intraperitoneal administration of PD98059 and fludarabine increased the PPAR{gamma} expression in the subcutaneous fat of TallyHO mice. These data suggest that leptin could inhibit the PPAR{gamma} expression and adipocyte differentiation in its physiological concentration in TallyHO mice.

Preservation of metabolic flexibility in skeletal muscle by a combined use of n-3 PUFA and rosiglitazone in dietary obese mice.

Directory of Open Access Journals (Sweden)

Olga Horakova

Full Text Available Insulin resistance, the key defect in type 2 diabetes (T2D, is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA and thiazolidinediones (TZDs, anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F, cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI, cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.

Response actions influence the categorization of directions in auditory space

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Marcella de Castro Campos Velten

2015-08-01

Full Text Available Spatial region concepts such as front, back, left and right reflect our typical interaction with space, and the corresponding surrounding regions have different statuses in memory. We examined the representation of spatial directions in the auditory space, specifically in how far natural response actions, such as orientation movements towards a sound source, would affect the categorization of egocentric auditory space. While standing in the middle of a circle with 16 loudspeakers, participants were presented acoustic stimuli coming from the loudspeakers in randomized order, and verbally described their directions by using the concept labels front, back, left, right, front-right, front-left, back-right and back-left. Response actions varied in three blocked conditions: 1 facing front, 2 turning the head and upper body to face the stimulus, and 3 turning the head and upper body plus pointing with the hand and outstretched arm towards the stimulus. In addition to a protocol of the verbal utterances, motion capture and video recording generated a detailed corpus for subsequent analysis of the participants’ behavior. Chi-square tests revealed an effect of response condition for directions within the left and right sides. We conclude that movement-based response actions influence the representation of auditory space, especially within the sides’ regions.

Experimental study on coil of direct action solenoid valve with temperature increasing

International Nuclear Information System (INIS)

Wang Lu; Liu Qianfeng; Bo Hanliang

2012-01-01

Hydraulic control rod drive technology (HCRDT) is a newly invented patent and Institute of Nuclear and New Energy Technology of Tsinghua University owns HCRDT's independent intellectual property rights. The integrated valve which is made up of three direct action solenoid valves is the key part of this technology, so the performance of the solenoid valve directly affects the function of the integrated valve and the HCRDT. Based on the conditions occurring in the operation of the control rod hydraulic drive system, the coil of the direct action solenoid valve with temperature increasing was studied by the experiment and analyzed by ANSYS code. The result shows that the temperature of the coil for the solenoid valve increases with the current increasing firstly. The temperature of the inner wall of the coil is higher than that of the exterior wall. The temperature of the middle coil is higher than that of the edge of the coil. The design of the direct action solenoid valve can be optimized. (authors)

Analysis of electromagnetic field of direct action solenoid valve with current changing

International Nuclear Information System (INIS)

Liu Qianfeng; Bo Hanliang; Qin Benke

2009-01-01

Control rod hydraulic drive mechanism(CRHDM) is a newly invented patent of Institute of Nuclear and New Energy Technology of Tsinghua University. The direct action solenoid valve is the key part of this technology, so the performance of the solenoid valve directly affects the function of the CRHDM. With the current and the air gap changing,the electromagnetic field of the direct action solenoid valve was analyzed using the ANSYS software,which was validated by the experiment. The result shows that the electromagnetic force of the solenoid valve increases with the current increasing or the gap between the two armatures decreasing. Further more, the working current was confirmed. (authors)

Facilitation of voluntary goal-directed action by reward cues.

Science.gov (United States)

Lovibond, Peter F; Colagiuri, Ben

2013-10-01

Reward-associated cues are known to influence motivation to approach both natural and man-made rewards, such as food and drugs. However, the mechanisms underlying these effects are not well understood. To model these processes in the laboratory with humans, we developed an appetitive Pavlovian-instrumental transfer procedure with a chocolate reward. We used a single unconstrained response that led to an actual rather than symbolic reward to assess the strength of reward motivation. Presentation of a chocolate-paired cue, but not an unpaired cue, markedly enhanced instrumental responding over a 30-s period. The same pattern was observed with 10-s and 30-s cues, showing that close cue-reward contiguity is not necessary for facilitation of reward-directed action. The results confirm that reward-related cues can instigate voluntary action to obtain that reward. The effectiveness of long-duration cues suggests that in clinical settings, attention should be directed to both proximal and distal cues for reward.

John porter lecture: waves of protest--direct action, deliberation, and diffusion.

Science.gov (United States)

Wood, Lesley

2015-02-01

The book Direct Action, Deliberation and Diffusion: Collective Action After the WTO Protests in Seattle argues that the process of diffusion is dependent on social processes in the receiving context. The most important in social movements is an egalitarian and reflexive deliberation among diverse actors. The book traces the direct action tactics associated with the Seattle protests against the World Trade Organization in 1999 and how these spread to activists in Toronto and New York City. It shows how the structure of the political field, racial and class inequalities, identity boundaries, and organizational and conversational dynamics limited deliberation among activists, and thus limited the diffusion of the Seattle tactics. By constraining the spread of the Seattle tactics, this slowed the global justice movement's wave of protest. In this paper, I explore the application of and implications of this model of protest tactic diffusion to the recent Idle No More mobilizations. © 2015 Canadian Sociological Association/La Société canadienne de sociologie.

Dielectric fluid directional spreading under the action of corona discharge

Science.gov (United States)

Zhou, Shangru; Liu, Jie; Hu, Qun; Jiang, Teng; Yang, Jinchu; Liu, Sheng; Zheng, Huai

2018-01-01

Liquid spreading is a very common nature phenomenon and of significant importance for a broad range of applications. In this study, a dielectric fluid directional spreading phenomenon is presented. Under the action of corona discharge, a dielectric fluid, here a typical silicone directionally spreads along conductive patterns on conductive/nonconductive substrates. Directional spreading behaviors of silicone were experimentally observed on different conductive patterns in detail. Spreading speeds were analyzed at different driving voltages, which induced the corona discharge. The presented phenomenon may be useful to inspire several techniques of manipulating liquid transportation and fabricating micropatterns.

Goal-directed action control in children with autism spectrum disorders

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Geurts, H.M.; de Wit, S.

2014-01-01

Repetitive behavior is a key characteristic of autism spectrum disorders. Our aim was to investigate the hypothesis that this abnormal behavioral repetition results from a tendency to over-rely on habits at the expense of flexible, goal-directed action. Twenty-four children with autism spectrum

Rosiglitazone decreases postprandial production of acylation stimulating protein in type 2 diabetics

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Tan Garry D

2007-05-01

Full Text Available Abstract Background We evaluated plasma ASP and its precursor C3 in type 2 diabetic men with/without rosiglitazone (ROSI treatment compared to healthy non-obese men. We tested (1 whether plasma ASP or C3 are altered postprandially in subcutaneous adipose tissue or forearm muscle effluent assessed by arteriovenous (A-V differences in healthy lean men and older obese diabetic men and (2 whether treatment with ROSI changes the arteriovenous gradient of ASP and/or C3. Methods In this ongoing placebo-controlled, crossover, double-blinded study, AV differences following a mixed meal were measured in diabetic men (n = 6 as compared to healthy men (n = 9. Results Postprandial arterial and adipose venous TG and venous NEFA were increased in diabetics vs. controls (p Conclusion Increased postprandial venous production of ASP is specific for adipose tissue (absent in forearm muscle. Increased postprandial C3 and ASP in diabetic subjects is consistent with an ASP resistant state, this state is partially normalized by treatment with ROSI.

Antimatter in the Direct-Action Theory of Fields

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Ruth E. Kastner

2016-01-01

Full Text Available One of Feynman's greatest contributions to physics was the interpretation of negative energies as antimatter in quantum field theory. A key component of this interpretation is the Feynman propagator, which seeks to describe the behavior of antimatter at the virtual particle level. Ironically, it turns out that one can dispense with the Feynman propagator in a direct-action theory of fields, while still retaining the interpretation of negative energy solutions as antiparticles. Quanta 2016; 5: 12–18.

n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet

Czech Academy of Sciences Publication Activity Database

Kuda, Ondřej; Jeleník, Tomáš; Jílková, Zuzana; Flachs, Pavel; Rossmeisl, Martin; Hensler, Michal; Kazdová, L.; Ogston, N.; Baranowski, M.; Gorski, J.; Janovská, Petra; Kůs, Vladimír; Polák, J.; Mohamed-Ali, V.; Burcelin, R.; Cinti, S.; Bryhn, M.; Kopecký, Jan

2009-01-01

Roč. 52, č. 5 (2009), s. 941-951 ISSN 0012-186X R&D Projects: GA ČR(CZ) GA303/08/0664; GA MŠk(CZ) 1M0520; GA MŠk(CZ) OC08007 Grant - others:EC(XE) LSMH-CT-2004005272 Institutional research plan: CEZ:AV0Z50110509 Keywords : fish oil * rosiglitazone * obesity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 6.551, year: 2009

SHOULD I STAY OR SHOULD I GO? CONCEPTUAL UNDERPINNINGS OF GOAL-DIRECTED ACTIONS

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GIOVANNI eMIRABELLA

2014-11-01

Full Text Available All actions, even the simplest like moving an arm to grasp a pen, are associated with energy costs. Thus all mobile organisms possess the ability to evaluate resources and select those behaviours that are most likely to lead to the greatest accrual of valuable items (rewards in the near or, especially in the case of humans, distant future. The evaluation process is performed at all possible stages of the series of decisions that lead to the building of a goal-directed action or to its suppression. This is because all animals have a limited amount of energy and resources; to survive and be able to reproduce they have to minimize the costs and maximize the outcomes of their actions. These computations are at the root of behavioral flexibility. Two executive functions play a major role in generating flexible behaviors: i the ability to predict future outcomes of goal-directed actions; and ii the ability to cancel them when they are unlikely to accomplish valuable results. These two processes operate continuously during the entire course of a movement: during its genesis, its planning and even its execution, so that the motor output can be modulated or suppressed at any time before its execution.In this review, functional interactions of the extended neural network subserving generation and inhibition of goal-directed movements will be outlined, leading to the intriguing hypothesis that the performance of actions and their suppression are not specified by independent sets of brain regions. Rather, it will be proposed that acting and stopping are functions emerging from specific interactions between largely overlapping brain regions, whose activity is intimately linked (directly or indirectly to the evaluations of pros and cons of an action. Such mechanism would allow the brain to perform as a highly efficient and flexible system, as different functions could be computed exploiting the same components operating in different configurations.

Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes

DEFF Research Database (Denmark)

Stage, Tore Bjerregaard; Christensen, Mette-Marie Hougaard; Jørgensen, Niklas Rye

2018-01-01

BACKGROUND: Fracture risk is increased in individuals with type 2 diabetes (T2D). The pathophysiological mechanisms accentuating fracture risk in T2D are convoluted, incorporating factors such as hyperglycaemia, insulinopenia, and antidiabetic drugs. The objectives of this study were to assess...... treatment in 371 T2D patients. Participants were randomized to short or long-acting human insulin (non-blinded) and then further randomized to metformin + placebo, rosiglitazone + placebo, metformin + rosiglitazone or placebo + placebo (blinded). Fasting bone turnover markers (BTM) representing bone......-up of the trial were analysed in mixed-effects models that included adjustments for age, gender, BMI, renal function and repeated measures of HbA1c. RESULTS: BTMs increased from baseline to month 12 and remained higher at month 24, with CTX and PINP increasing 28.5% and 23.0% (all: p 

Goal-Directed Action Control in Children with Autism Spectrum Disorders

Science.gov (United States)

Geurts, Hilde M; de Wit, Sanne

2014-01-01

Repetitive behavior is a key characteristic of autism spectrum disorders. Our aim was to investigate the hypothesis that this abnormal behavioral repetition results from a tendency to over-rely on habits at the expense of flexible, goal-directed action. Twenty-four children with autism spectrum disorders and 24 age- and gender-matched controls…

Directive and incentive functions of affective action consequences: an ideomotor approach.

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Eder, Andreas B; Rothermund, Klaus; De Houwer, Jan; Hommel, Bernhard

2015-07-01

Five experiments examined whether affective consequences become associated with the responses producing them and whether anticipations of positive and negative action outcomes influence action control differently. In a learning phase, one response produced pleasant and another response unpleasant visual effects. In a subsequent test phase, the same actions were carried out in response to a neutral feature of affective stimuli. Results showed that responses were faster when the irrelevant valence of the response cue matched the valence of the response outcome, but only when the responses still produced outcomes. These results suggest that affective action consequences have a directive function in that they facilitate the selection of the associated response over other responses, even when the response outcome is unpleasant (Experiment 4A). Results of another experiment showed that affective action consequences can also have an incentive function in that responses with pleasant outcomes are generally facilitated relative to responses with unpleasant outcomes. However, this motivational effect was seen only in a free-choice test (Experiment 5). The results suggest that behavioral impulses induced by ideomotor processes are constrained by the motivational evaluation of the anticipated action outcome. A model that integrates motivational factors into ideomotor theory is presented.

Evidence Synthesis in Harm Assessment of Medicines Using the Example of Rosiglitazone and Myocardial Infarction

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Charlotte Rietbergen

2018-02-01

Full Text Available The current system of harm assessment of medicines has been criticized for relying on intuitive expert judgment. There is a call for more quantitative approaches and transparency in decision-making. Illustrated with the case of cardiovascular safety concerns for rosiglitazone, we aimed to explore a structured procedure for the collection, quality assessment, and statistical modeling of safety data from observational and randomized studies. We distinguished five stages in the synthesis process. In Stage I, the general research question, population and outcome, and general inclusion and exclusion criteria are defined and a systematic search is performed. Stage II focusses on the identification of sub-questions examined in the included studies and the classification of the studies into the different categories of sub-questions. In Stage III, the quality of the identified studies is assessed. Coding and data extraction are performed in Stage IV. Finally, meta-analyses on the study results per sub-question are performed in Stage V. A Pubmed search identified 30 randomized and 14 observational studies meeting our search criteria. From these studies, we identified 4 higher level sub-questions and 4 lower level sub-questions. We were able to categorize 29 individual treatment comparisons into one or more of the sub-question categories, and selected study duration as an important covariate. We extracted covariate, outcome, and sample size information at the treatment arm level of the studies. We extracted absolute numbers of myocardial infarctions from the randomized study, and adjusted risk estimates with 95% confidence intervals from the observational studies. Overall, few events were observed in the randomized studies that were frequently of relatively short duration. The large observational studies provided more information since these were often of longer duration. A Bayesian random effects meta-analysis on these data showed no significant increase

Fronto-parietal coding of goal-directed actions performed by artificial agents.

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Kupferberg, Aleksandra; Iacoboni, Marco; Flanagin, Virginia; Huber, Markus; Kasparbauer, Anna; Baumgartner, Thomas; Hasler, Gregor; Schmidt, Florian; Borst, Christoph; Glasauer, Stefan

2018-03-01

With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto-parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self-related action) and pointing actions (other-related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto-parietal network not only for observing a human but also a robotic agent for both self-related and social actions. The debriefing after the experiment has shown that actions of human-like artificial agents can be perceived as being goal-directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment. © 2017 Wiley Periodicals, Inc.

Principles Of Directed Energy Action In Food Nanotechnologies

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Burdo O.G.

2015-04-01

Full Text Available The prospects of technologies of directed en ergy action (DEA are discussed. Classification of DEA-technologies is offered. The purpose of the wo rk is to give analysis of possibilities of DEA in food nanotechnologies. Combined processes of mass tr ansfer during the extraction and drying are con- sidered by methods of mathematical modeling. The physical model of combined processes in DEA- technologies is analyzed. The classification of hy drodynamic flow from the capillary structures of food raw materials is given. Conditions of upgrowth of laminar and turbulent barodiffusion are set. Problems of experimental modeling are grounded. A new number of similarities, the number of ener- getic action, is discussed. That number correctly ta kes into account the specific of combined processes of DEA-technologies. It has been shown that im pulse electromagnetic field is effective tool for realization DEA-technologies. Degree of intensification processes of mass transfer with application of barodiffusion and DEA-technologies can be by th e order greater than possibilities of traditional technologies.

76 FR 47237 - Notice of Realty Action: Direct Sale of Public Land in Monterey County, CA

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2011-08-04

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLCA9300000 L58790000 EU0000; CACA 50168-14] Notice of Realty Action: Direct Sale of Public Land in Monterey County, CA AGENCY: Bureau of Land Management, Interior. ACTION: Notice of realty action. SUMMARY: The Bureau of Land Management (BLM...

Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

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Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

2012-01-01

Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

Collective Nostalgia Is Associated With Stronger Outgroup-Directed Anger and Participation in Ingroup-Favoring Collective Action

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Wing-Yee Cheung

2017-08-01

Full Text Available Collective nostalgia refers to longing for the way society used to be. We tested whether collective nostalgia is associated with ingroup-favoring collective action and whether this association is mediated by outgroup-directed anger and outgroup-directed contempt. We conducted an online study of Hong Kong residents (N = 111 during a large-scale democratic social movement, the Umbrella Movement, that took place in Hong Kong in 2014 in response to proposed electoral reforms by the Chinese government in Mainland China. Reported collective nostalgia for Hong Kong’s past was high in our sample and collective nostalgia predicted stronger involvement in ingroup-favoring collective action, and it did so indirectly via higher intensity of outgroup-directed anger (but not through outgroup-directed contempt. We argue that collective nostalgia has implications for strengthening ingroup-serving collective action, and we highlight the importance of arousal of group-based emotions in this process.

Infants distinguish antisocial actions directed towards fair and unfair agents.

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Marek Meristo

Full Text Available Three experiments provide evidence of an incipient sense of fairness in preverbal infants. Ten-month-old infants were shown cartoon videos with two agents, the 'donors', who distributed resources to two identical recipients. One donor always distributed the goods equally, while the other performed unequal distributions by giving everything to one recipient. In the test phase, a third agent hit or took resources away from either the fair or the unfair donor. We found that infants looked longer when the antisocial actions were directed towards the unfair rather than the fair donor. These findings support the view that infants are able to evaluate agents based on their distributive actions and suggest that the foundations of human socio-moral competence are acquired independently of parental feedback and linguistic experience.

Impairments in goal-directed actions predict treatment response to cognitive-behavioral therapy in social anxiety disorder.

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Gail A Alvares

Full Text Available Social anxiety disorder is characterized by excessive fear and habitual avoidance of social situations. Decision-making models suggest that patients with anxiety disorders may fail to exhibit goal-directed control over actions. We therefore investigated whether such biases may also be associated with social anxiety and to examine the relationship between such behavior with outcomes from cognitive-behavioral therapy. Patients diagnosed with social anxiety and controls completed an instrumental learning task in which two actions were performed to earn food outcomes. After outcome devaluation, where one outcome was consumed to satiety, participants were re-tested in extinction. Results indicated that, as expected, controls were goal-directed, selectively reducing responding on the action that previously delivered the devalued outcome. Patients with social anxiety, however, exhibited no difference in responding on either action. This loss of a devaluation effect was associated with greater symptom severity and poorer response to therapy. These findings indicate that variations in goal-directed control in social anxiety may represent both a behavioral endophenotype and may be used to predict individuals who will respond to learning-based therapies.

Modeling Geometric-Temporal Context With Directional Pyramid Co-Occurrence for Action Recognition.

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Yuan, Chunfeng; Li, Xi; Hu, Weiming; Ling, Haibin; Maybank, Stephen J

2014-02-01

In this paper, we present a new geometric-temporal representation for visual action recognition based on local spatio-temporal features. First, we propose a modified covariance descriptor under the log-Euclidean Riemannian metric to represent the spatio-temporal cuboids detected in the video sequences. Compared with previously proposed covariance descriptors, our descriptor can be measured and clustered in Euclidian space. Second, to capture the geometric-temporal contextual information, we construct a directional pyramid co-occurrence matrix (DPCM) to describe the spatio-temporal distribution of the vector-quantized local feature descriptors extracted from a video. DPCM characterizes the co-occurrence statistics of local features as well as the spatio-temporal positional relationships among the concurrent features. These statistics provide strong descriptive power for action recognition. To use DPCM for action recognition, we propose a directional pyramid co-occurrence matching kernel to measure the similarity of videos. The proposed method achieves the state-of-the-art performance and improves on the recognition performance of the bag-of-visual-words (BOVWs) models by a large margin on six public data sets. For example, on the KTH data set, it achieves 98.78% accuracy while the BOVW approach only achieves 88.06%. On both Weizmann and UCF CIL data sets, the highest possible accuracy of 100% is achieved.

Rosiglitazone inhibits chlorpyrifos-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon; Jang, Sea Jeong [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

2014-07-15

Oxidative stress can lead to expression of inflammatory transcription factors, which are important regulatory elements in the induction of inflammatory responses. One of the transcription factors, nuclear transcription factor kappa-B (NF-κB) plays a significant role in the inflammation regulatory process. Inflammatory cell death has been implicated in neuronal cell death in some neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying apoptosis initiated by chlorpyrifos (CPF)-mediated oxidative stress. Based on the cytotoxic mechanism of CPF, we examined the neuroprotective effects of rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, against CPF-induced neuronal cell death. The treatment of SH-SY5Y cells with CPF induced oxidative stress. In addition, CPF activated the p38, JNK and ERK mitogen-activated protein kinases (MAPKs), and induced increases in the inflammatory genes such as COX-2 and TNF-α. CPF also induced nuclear translocation of NF-κB and inhibitors of NF-κB abolished the CPF-induced COX-2 expression. Pretreatment with RGZ significantly reduced ROS generation and enhanced HO-1 expression in CPF-exposed cells. RGZ blocked the activation of both p38 and JNK signaling, while ERK activation was strengthened. RGZ also attenuated CPF-induced cell death through the reduction of NF-κB-mediated proinflammatory factors. Results from this study suggest that RGZ may exert an anti-apoptotic effect against CPF-induced cytotoxicity by attenuation of oxidative stress as well as inhibition of the inflammatory cascade via inactivation of signaling by p38 and JNK, and NF-κB. - Highlights: • CPF induces apoptotic cell death in SH-SY5Y cells • ROS involved in CPF-mediated apoptotic cell death • Inflammation involved in CPF-mediated apoptotic cell death • Rosiglitazone modulates ROS and inflammatory response in CPF-treated cells.

Alcohol-paired contextual cues produce an immediate and selective loss of goal-directed action in rats

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Sean B Ostlund

2010-07-01

Full Text Available We assessed whether the presence of contextual cues paired with alcohol would disrupt rats’ capacity to express appropriate goal-directed action control. Rats were first given differential context conditioning such that one set of contextual cues was paired with the injection of ethanol and a second, distinctive set of cues was paired with the injection of saline. All rats were then trained in a third, neutral context to press one lever for grain pellets and another lever for sucrose pellets. They were then given two extinction tests to evaluate their ability to choose between the two actions in response to the devaluation of one of the two food outcomes with one test conducted in the alcohol-paired context and the other conducted in the control (saline-paired context. In the control context, rats exhibited goal-directed action control; i.e., they were able selectively to withhold the action that previously earned the now devalued outcome. However, these same rats were impaired when tested in the alcohol-paired context, performing both actions at the same rate regardless of the current value of their respective outcomes. Subsequent testing revealed that the rats were capable of overcoming this impairment if they were giving response-contingent feedback about the current value of the food outcomes. These results provide a clear demonstration of the disruptive influence that alcohol-paired cues can exert on decision-making in general and goal-directed action selection and choice in particular.

76 FR 50492 - Notice of Realty Action: Direct Sale of Public Land in San Benito County, CA

Science.gov (United States)

2011-08-15

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLCA930000.L58790000.EU0000; CACA 50168 13] Notice of Realty Action: Direct Sale of Public Land in San Benito County, CA AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Realty Action. SUMMARY: The Bureau of Land Management (BLM...

Abscisic acid synergizes with rosiglitazone to improve glucose tolerance, down-modulate macrophage accumulation in adipose tissue: possible action of the cAMP/PKA/PPAR γ axis

Science.gov (United States)

Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-01-01

Background & Aims Abscisic acid (ABA) is effective in preventing insulin resistance and obesity-related inflammation through a PPAR γ-dependent mechanism. The objective of this study was to assess the efficacy ABA in improving glucose homeostasis and suppress inflammation when administered in combination with rosiglitazone (Ros) and to determine whether PPAR γ activation by ABA is initiated via cAMP/protein kinase A (PKA) signaling. Methods Obese db/db mice were fed high-fat diets containing 0, 10, or 70 mg/kg Ros with and without racemic ABA (100 mg/kg) for 60 days. Glucose tolerance and fasting insulin levels were assessed at 6 and 8 weeks, respectively, and adipose tissue macrophage (ATM) infiltration was examined by flow cytometry. Gene expression was examined on white adipose tissue (WAT) and stromal vascular cells (SVCs) cultured with ABA, Ros, or an ABA/Ros combination. Results Both Ros and ABA improved glucose tolerance, and ABA decreased plasma insulin levels while having no effect on Ros-induced weight gain. ABA in combination with low-dose Ros (10 mg/kg; Roslo) synergistically inhibited ATM infiltration. Treatment of SVCs with Ros, ABA or ABA/Ros suppressed expression of the M1 marker CCL17. ABA and Ros synergistically increased PPAR γ activity and pretreatment with a cAMP-inhibitor or a PKA-inhibitor abrogated ABA-induced PPAR γ activation. Conclusions ABA and Ros act synergistically to modulate PPAR γ activity and macrophage accumulation in WAT and ABA enhances PPAR γ activity through a membrane-initiated mechanism dependent on cAMP/PKA signaling. PMID:20207056

Strategic directions and actions for advanced practice nursing in China

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Martha N. Hill

2017-01-01

Full Text Available There is a need and opportunity for China to develop education and practice innovations given that advance practice nurses (APNs improve health care and outcomes. The China Medical Board (CMB China Nursing Network (CCNN began planning for an Advanced Nursing Practice Program for education and career development that will facilitate CCNN's contributions to meeting national nursing policy priorities. This paper presents the discussion, recommendations and action plans developed at the inaugural planning meeting on June 26, 2015 at Fudan University in Shanghai. The recommendations are: Develop standards for advanced nursing practice; Develop Master's level curricula based on the standards; Commence pilot projects across a number of University affiliated hospitals; and Prepare clinical tutors and faculty. The strategic directions and actions are: Develop a clinical career ladder system; Expand the nursing role from hospital to community; and Build a specialty nurse accreditation system.

Insider Threat: Preventing Direct Action Attacks Within the United States Army

Science.gov (United States)

2017-06-09

Intelligence Agency, 2012. Joint Chiefs of Staff. Joint Publication (JP) 3-07.2, Antiterrorism. Washington, DC: Government Printing Office, 2010. 81...Federal Bureau of Investigation GEN General (Army rank, O-10) HIPAA Health Insurance Portability and Accountability Act of 1996 INSCOM Intelligence and...commanders, and the intelligence community to prevent insider threats from developing into direct action attacks, this study sought to answer the

77 FR 61023 - Notice of Realty Action: Direct Sale of Public Land in Shasta County, CA

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2012-10-05

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLCA930000.L1430000.EU0000. CACA 053115] Notice of Realty Action: Direct Sale of Public Land in Shasta County, CA AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: The Bureau of Land Management (BLM), Redding Field Office...

Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling

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Luconi Michaela

2008-07-01

Full Text Available Rosiglitazone (RGZ, a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR-γ, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R of human adrenocortical carcinoma (ACC and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR. We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K-Akt, and extracellular signal-regulated kinase (ERK1/2 cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.

Action Video Games Improve Direction Discrimination of Parafoveal Translational Global Motion but Not Reaction Times.

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Pavan, Andrea; Boyce, Matthew; Ghin, Filippo

2016-10-01

Playing action video games enhances visual motion perception. However, there is psychophysical evidence that action video games do not improve motion sensitivity for translational global moving patterns presented in fovea. This study investigates global motion perception in action video game players and compares their performance to that of non-action video game players and non-video game players. Stimuli were random dot kinematograms presented in the parafovea. Observers discriminated the motion direction of a target random dot kinematogram presented in one of the four visual quadrants. Action video game players showed lower motion coherence thresholds than the other groups. However, when the task was performed at threshold, we did not find differences between groups in terms of distributions of reaction times. These results suggest that action video games improve visual motion sensitivity in the near periphery of the visual field, rather than speed response. © The Author(s) 2016.

The Coordination Dynamics of Observational Learning: Relative Motion Direction and Relative Phase as Informational Content Linking Action-Perception to Action-Production.

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Buchanan, John J

2016-01-01

The primary goal of this chapter is to merge together the visual perception perspective of observational learning and the coordination dynamics theory of pattern formation in perception and action. Emphasis is placed on identifying movement features that constrain and inform action-perception and action-production processes. Two sources of visual information are examined, relative motion direction and relative phase. The visual perception perspective states that the topological features of relative motion between limbs and joints remains invariant across an actor's motion and therefore are available for pickup by an observer. Relative phase has been put forth as an informational variable that links perception to action within the coordination dynamics theory. A primary assumption of the coordination dynamics approach is that environmental information is meaningful only in terms of the behavior it modifies. Across a series of single limb tasks and bimanual tasks it is shown that the relative motion and relative phase between limbs and joints is picked up through visual processes and supports observational learning of motor skills. Moreover, internal estimations of motor skill proficiency and competency are linked to the informational content found in relative motion and relative phase. Thus, the chapter links action to perception and vice versa and also links cognitive evaluations to the coordination dynamics that support action-perception and action-production processes.

Planning Ahead: Object-Directed Sequential Actions Decoded from Human Frontoparietal and Occipitotemporal Networks

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Gallivan, Jason P.; Johnsrude, Ingrid S.; Randall Flanagan, J.

2016-01-01

Object-manipulation tasks (e.g., drinking from a cup) typically involve sequencing together a series of distinct motor acts (e.g., reaching toward, grasping, lifting, and transporting the cup) in order to accomplish some overarching goal (e.g., quenching thirst). Although several studies in humans have investigated the neural mechanisms supporting the planning of visually guided movements directed toward objects (such as reaching or pointing), only a handful have examined how manipulatory sequences of actions—those that occur after an object has been grasped—are planned and represented in the brain. Here, using event-related functional MRI and pattern decoding methods, we investigated the neural basis of real-object manipulation using a delayed-movement task in which participants first prepared and then executed different object-directed action sequences that varied either in their complexity or final spatial goals. Consistent with previous reports of preparatory brain activity in non-human primates, we found that activity patterns in several frontoparietal areas reliably predicted entire action sequences in advance of movement. Notably, we found that similar sequence-related information could also be decoded from pre-movement signals in object- and body-selective occipitotemporal cortex (OTC). These findings suggest that both frontoparietal and occipitotemporal circuits are engaged in transforming object-related information into complex, goal-directed movements. PMID:25576538

The Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis

Science.gov (United States)

Sardone, Laura Donata

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Direct construction of the effective action of chiral gauge fermions in the anomalous sector

International Nuclear Information System (INIS)

Salcedo, L.L.

2009-01-01

The anomaly implies an obstruction to a fully chiral covariant calculation of the effective action in the abnormal-parity sector of chiral theories. The standard approach then is to reconstruct the anomalous effective action from its covariant current. In this work, we use a recently introduced formulation which allows one to directly construct the non-trivial chiral invariant part of the effective action within a fully covariant formalism. To this end we develop an appropriate version of Chan's approach to carry out the calculation within the derivative expansion. The result to four derivatives, i.e., to leading order in two and four dimensions and next-to-leading order in two dimensions, is explicitly worked out. Fairly compact expressions are found for these terms. (orig.)

Abscisic acid synergizes with rosiglitazone to improve glucose tolerance and down-modulate macrophage accumulation in adipose tissue: possible action of the cAMP/PKA/PPAR γ axis.

Science.gov (United States)

Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

2010-10-01

Abscisic acid (ABA) is effective in preventing insulin resistance and obesity-related inflammation through a PPAR γ-dependent mechanism. The objective of this study was to assess the efficacy ABA in improving glucose homeostasis and suppress inflammation when administered in combination with rosiglitazone (Ros) and to determine whether PPAR γ activation by ABA is initiated via cAMP/protein kinase A (PKA) signaling. Obese db/db mice were fed high-fat diets containing 0, 10, or 70 mg/kg Ros with and without racemic ABA (100 mg/kg) for 60 days. Glucose tolerance and fasting insulin levels were assessed at 6 and 8 weeks, respectively, and adipose tissue macrophage (ATM) infiltration was examined by flow cytometry. Gene expression was examined on white adipose tissue (WAT) and stromal vascular cells (SVCs) cultured with ABA, Ros, or an ABA/Ros combination. Both Ros and ABA improved glucose tolerance, and ABA decreased plasma insulin levels while having no effect on Ros-induced weight gain. ABA in combination with low-dose Ros (10 mg/kg; Roslo) synergistically inhibited ATM infiltration. Treatment of SVCs with Ros, ABA or ABA/Ros suppressed expression of the M1 marker CCL17. ABA and Ros synergistically increased PPAR γ activity and pretreatment with a cAMP-inhibitor or a PKA-inhibitor abrogated ABA-induced PPAR γ activation. ABA and Ros act synergistically to modulate PPAR γ activity and macrophage accumulation in WAT and ABA enhances PPAR γ activity through a membrane-initiated mechanism dependent on cAMP/PKA signaling. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Dopaminergic modulation of positive expectations for goal-directed action: evidence from Parkinson’s disease

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Noham eWolpe

2015-10-01

Full Text Available Parkinson’s disease (PD impairs the control of movement and cognition, including the planning of action and its consequences. This provides the opportunity to study the dopaminergic influences on the perception and awareness of action. Here we examined the perception of the outcome of a goal-directed action made by medicated patients with PD. A visuomotor task probed the integration of sensorimotor signals with the positive expectations of outcomes (Self priors, which in healthy adults bias perception towards success in proportion to trait optimism. We tested the hypotheses that (i the priors on the perception of the consequences of one’s own actions differ between patients and age- and sex-matched controls, and (ii that these priors are modulated by the levodopa dose equivalent in patients. There was no overall difference between patients and controls in the perceptual priors used. However, the precision of patient priors was inversely related to their levodopa dose equivalent. Patients with high levodopa dose equivalent showed more accurate priors, representing predictions that were closer to the true distribution of performance. Such accuracy has previously been demonstrated when observing the actions of others, suggesting abnormal awareness of action in these patients. These results confirm a link between dopamine and the positive expectation of the outcome of one’s own actions, and may have implications for the management of PD.

Direct and indirect cardiovascular actions of cathinone and MDMA in the anaesthetized rat.

Science.gov (United States)

Alsufyani, Hadeel A; Docherty, James R

2015-07-05

The stimulants cathinone (from Khat leaves) and methylenedioxymeth-amphetamine (MDMA) produce adrenoceptor mediated tachycardia and vasopressor actions that may be the result of direct receptor stimulation, actions on the noradrenaline transporter, and/or displacement of noradrenaline from nerve terminals. Effects of cathinone or MDMA were compared with those of the indirect sympathomimetic tyramine. Male Wistar rats were anaesthetized with pentobarbitone for blood pressure and heart rate recording. Some rats were sympathectomised by treatment with 6-hydroxydopamine. In the anaesthetised rat, cathinone, MDMA and tyramine (all 0.001-1 mg/kg) produced marked tachycardia, tyramine produced marked pressor responses and MDMA produced small pressor responses. The tachycardia to cathinone and MDMA was almost abolished by propranolol (1mg/kg). Pretreatment with cocaine (1mg/kg) did not significantly affect the tachycardia to cathinone or MDMA, but reduced the response to tyramine. However, in sympathectomised rats, the tachycardia to cathinone or MDMA was markedly attenuated, but the tachycardia to tyramine was only partially reduced. Blood pressure effects of tyramine and MDMA were also markedly attenuated by sympathectomy. The results demonstrate firstly that cocaine may not be the most suitable agent for assessing direct versus indirect agonism in cardiovascular studies. Secondly, the use of chemical sympathectomy achieved the desired goal of demonstrating that cardiac β-adrenoceptor mediated actions of cathinone and MDMA are probably largely indirect. Copyright © 2015 Elsevier B.V. All rights reserved.

Anodal transcranial direct current stimulation of parietal cortex enhances action naming in Corticobasal Syndrome

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Rosa eManenti

2015-04-01

Full Text Available Background: Corticobasal Syndrome (CBS is a neurodegenerative disorder that overlaps both clinically and neuropathologically with Frontotemporal dementia and is characterized by apraxia, alien limb phenomena, cortical sensory loss, cognitive impairment, behavioural changes and aphasia. It has been recently demonstrated that transcranial direct current stimulation (tDCS improves naming in healthy subjects and in subjects with language deficits.Objective: The aim of the present study was to explore the extent to which anodal transcranial direct current stimulation (anodal tDCS over the parietal cortex (PARC could facilitate naming performance in CBS subjects. Methods: Anodal tDCS was applied to the left and right PARC during object and action naming in seventeen patients with a diagnosis of possible CBS. Participants underwent two sessions of anodal tDCS (left and right and one session of placebo tDCS. Vocal responses were recorded and analyzed for accuracy and vocal Reaction Times (vRTs. Results: A shortening of naming latency for actions was observed only after active anodal stimulation over the left PARC, as compared to placebo and right stimulations. No effects have been reported for accuracy.Conclusions: Our preliminary finding demonstrated that tDCS decreased vocal reaction time during action naming in a sample of patients with CBS. A possible explanation of our results is that anodal tDCS over the left PARC effects the brain network implicated in action observation and representation. Further studies, based on larger patient samples, should be conducted to investigate the usefulness of tDCS as an additional treatment of linguistic deficits in CBS patients.

Characterization of alendronic- and undecylenic acid coated magnetic nanoparticles for the targeted delivery of rosiglitazone to subcutaneous adipose tissue.

Science.gov (United States)

Saatchi, Katayoun; Tod, Sarah E; Leung, Donna; Nicholson, Kenton E; Andreu, Irene; Buchwalder, Christian; Schmitt, Veronika; Häfeli, Urs O; Gray, Sarah L

2017-02-01

Obesity is a state of positive energy balance where excess white adipose tissue accumulates to the detriment of metabolic health. Improving adipocyte function with systemic administration of thiazolidinediones (TZDs) improves metabolic outcomes in obesity, however TZD use is limited clinically due to undesirable side effects. Here we evaluate magnetic nanoparticles (MNPs) as a tool to target rosiglitazone (Rosi) specifically to adipose tissue. Results show Rosi can be adsorbed to MNPs (Rosi-MNPs) with hydrophobic coatings for which we present binding and release kinetics. Rosi adsorbed to MNPs retained the ability to induce PPARγ target gene expression in cells. Biodistribution analysis of radiolabeled Rosi-MNPs revealed a fat-implanted magnet significantly enhanced localization of Rosi to the targeted adipose tissue when administered by subcutaneous injection to obese mice. We propose MNPs for targeted delivery of anti-diabetic agents to superficially located subcutaneous adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

Anticlockwise or Clockwise? A Dynamic Perception-Action-Laterality Model for Directionality Bias in Visuospatial Functioning

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Karim, A.K.M. Rezaul; Proulx, Michael J.; Likova, Lora T.

2016-01-01

Reviewing the relevant literature in visual psychophysics and visual neuroscience we propose a three-stage model of directionality bias in visuospatial functioning. We call this model the ‘Perception-Action-Laterality’ (PAL) hypothesis. We analyzed the research findings for a wide range of visuospatial tasks, showing that there are two major directionality trends: clockwise versus anticlockwise. It appears these preferences are combinatorial, such that a majority of people fall in the first category demonstrating a preference for stimuli/objects arranged from left-to-right rather than from right-to-left, while people in the second category show an opposite trend. These perceptual biases can guide sensorimotor integration and action, creating two corresponding turner groups in the population. In support of PAL, we propose another model explaining the origins of the biases– how the neurogenetic factors and the cultural factors interact in a biased competition framework to determine the direction and extent of biases. This dynamic model can explain not only the two major categories of biases, but also the unbiased, unreliably biased or mildly biased cases in visuosptial functioning. PMID:27350096

The role of genetic variants in CYP2C8, LPIN1, PPARGC1A and PPARγ on the trough steady-state plasma concentrations of rosiglitazone and on glycosylated haemoglobin A1c in type 2 diabetes

DEFF Research Database (Denmark)

Stage, Tore B; Christensen, Mette M H; Feddersen, Søren

2013-01-01

OBJECTIVE: The aim of this study was to examine the effect of single nucleotide polymorphisms in CYP2C8, LPIN1, PPARGC1A and PPARγ on rosiglitazone's (i) trough steady-state plasma concentration (C(ss,min)), (ii) on glycosylated haemoglobin A1c (HbA1c) and (iii) the risk of developing adverse eve...

HERCA Action Plan in relation to the transposition and implementation of Directive 2013/59/Euratom (Euratom BSS)

International Nuclear Information System (INIS)

Fremout, An; Vanderlinck, Annie; Berlamont, Jolien; Van Bladel, Lodewijk; Petrova, Karla; Ulbak, Kaare; Mundigl, Stefan; ); Markkanen, Mika; Godet, Jean-Luc; Tran-Thien, Vivien; Koch, Isabell Christin; Hackstein, Matthias; Griebel, Juergen; Kamenopoulou, Vasiliki; Fennel, Stephan; Ryan, Tom; Schreiner, Alexandra; Majerus, Patrick; Vermeulen, Ton; Holo, Eldri; Wiklund, Asa; RYF, Salome; Thomas, Gareth; Wellens, Rob; Ebdon-Jackson, Steve

2014-10-01

On 5 December 2013, the Council of the European Union adopted Council Directive 2013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation.1 Member States have to transpose the new Basic Safety Standards Directive (BSS Directive) into their national legal systems by 6 February 2018 at the latest. At the 13. meeting of the Board of HERCA (BoH) in Vilnius in June 2014, a proposal to establish a special Task Force (TF) to make proposals in relation to HERCA activities in support of the transposition and implementation of the new Euratom BSS Directive was agreed. The BSS-TF was established, commenced its work on the basis of a 'non-questionnaire' and a discussion document. It met on one occasion on 7 October 2014 and agreed an action plan for consideration by the BoH. The agreed action plan proposal was approved by the BoH on the occasion of its 14. meeting in Stockholm, on 21-22 October 2014. The approved Action Plan covers the following areas: - Identification of HERCA's role in the transposition of the new Euratom BSS; - Definition of actions for HERCA in relation to the transposition of the BSS; - Coordination between HERCA and the EC in relation to BSS transposition activities. The Actions identified relate to several subject areas: Emergency preparedness and response; Medical exposures; Radon; Non-medical imaging exposures; RPE/RPO; General exchange of information. HERCA is a voluntary association, in which the Heads of European Radiological Protection Competent Authorities work together in order to identify common issues and propose practical solutions for these issues. It has no statutory role in relation to the transposition of the Euratom BSS. However, additional work by HERCA can support the transposition process as indicated in the Action Plan. Uniform transposition or implementation in the Member States is not an objective of HERCA activities. Clearly it will remain a matter for

Rosiglitazone Improves Survival and Hastens Recovery from Pancreatic Inflammation in Obese Mice

Science.gov (United States)

Pini, Maria; Rhodes, Davina H.; Castellanos, Karla J.; Cabay, Robert J.; Grady, Eileen F.; Fantuzzi, Giamila

2012-01-01

Obesity increases severity of acute pancreatitis (AP) by unclear mechanisms. We investigated the effect of the PPAR-gamma agonist rosiglitazone (RGZ, 0.01% in the diet) on severity of AP induced by administration of IL-12+ IL-18 in male C57BL6 mice fed a low fat (LFD) or high fat diet (HFD), under the hypothesis that RGZ would reduce disease severity in HFD-fed obese animals. In both LFD and HFD mice without AP, RGZ significantly increased body weight and % fat mass, with significant upregulation of adiponectin and suppression of erythropoiesis. In HFD mice with AP, RGZ significantly increased survival and hastened recovery from pancreatic inflammation, as evaluated by significantly improved pancreatic histology, reduced saponification of visceral adipose tissue and less severe suppression of erythropoiesis at Day 7 post-AP. This was associated with significantly lower circulating and pancreas-associated levels of IL-6, Galectin-3, osteopontin and TIMP-1 in HFD + RGZ mice, particularly at Day 7 post-AP. In LFD mice with AP, RGZ significantly worsened the degree of intrapancreatic acinar and fat necrosis as well as visceral fat saponification, without affecting other parameters of disease severity or inflammation. Induction of AP lead to major suppression of adiponectin levels at Day 7 in both HFD and HFD + RGZ mice. In conclusion, RGZ prevents development of severe AP in obese mice even though it significantly increases adiposity, indicating that obesity can be dissociated from AP severity by improving the metabolic and inflammatory milieu. However, RGZ worsens selective parameters of AP severity in LFD mice. PMID:22815875

Adductor magnus: An EMG investigation into proximal and distal portions and direction specific action.

Science.gov (United States)

Benn, Matthew L; Pizzari, Tania; Rath, Leanne; Tucker, Kylie; Semciw, Adam I

2018-05-01

Cadaveric studies indicate that adductor magnus is structurally partitioned into at least two regions. The aim of this study was to investigate the direction-specific actions of proximal and distal portions of adductor magnus, and in doing so determine if these segments have distinct functional roles. Fine-wire EMG electrodes were inserted into two portions of adductor magnus of 12 healthy young adults. Muscle activity was recorded during maximum voluntary isometric contractions (MVICs) across eight tests (hip flexion/extension, internal/external rotation, abduction, and adduction at 0°, 45°, and 90° hip flexion). Median activity within each action (normalized to peak) was compared between segments using repeated measures nonparametric tests (α = 0.05). An effect size (ES = z-score/√sample size) was calculated to determine the magnitude of difference between muscle segments. The relative contribution of each muscle segment differed significantly during internal rotation (P magnus has at least two functionally unique regions. Differences were most evident during rotation. The different direction-specific actions may imply that each segment performs separate roles in hip stability and movement. These findings may have implications on injury prevention and rehabilitation for adductor-related groin injuries, hamstring strain injury, and hip pathology. Clin. Anat. 31:535-543, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Electroacupuncture Reduces Weight Gain Induced by Rosiglitazone through PPARγ and Leptin Receptor in CNS

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Xinyue Jing

2016-01-01

Full Text Available We investigate the effect of electroacupuncture (EA on protecting the weight gain side effect of rosiglitazone (RSG in type 2 diabetes mellitus (T2DM rats and its possible mechanism in central nervous system (CNS. Our study showed that RSG (5 mg/kg significantly increased the body weight and food intake of the T2DM rats. After six-week treatment with RSG combined with EA, body weight, food intake, and the ratio of IWAT to body weight decreased significantly, whereas the ratio of BAT to body weight increased markedly. HE staining indicated that the T2DM-RSG rats had increased size of adipocytes in their IWAT, but EA treatment reduced the size of adipocytes. EA effectively reduced the lipid contents without affecting the antidiabetic effect of RSG. Furthermore, we noticed that the expression of PPARγ gene in hypothalamus was reduced by EA, while the expressions of leptin receptor and signal transducer and activator of transcription 3 (STAT3 were increased. Our results suggest that EA is an effective approach for inhibiting weight gain in T2DM rats treated by RSG. The possible mechanism might be through increased levels of leptin receptor and STAT3 and decreased PPARγ expression, by which food intake of the rats was reduced and RSG-induced weight gain was inhibited.

Bidirectional modulation of goal-directed actions by prefrontal cortical dopamine.

Science.gov (United States)

Hitchcott, Paul K; Quinn, Jennifer J; Taylor, Jane R

2007-12-01

Instrumental actions are a vital cognitive asset that endows an organism with sensitivity to the consequences of its behavior. Response-outcome feedback allows responding to be shaped in order to maximize beneficial, and minimize detrimental, outcomes. Lesions of the medial prefrontal cortex (mPFC) result in behavior that is insensitive to changes in outcome value in animals and compulsive behavior in several human psychopathologies. Such insensitivity to changes in outcome value is a defining characteristic of instrumental habits: responses that are controlled by antecedent stimuli rather than goal expectancy. Little is known regarding the neurochemical substrates mediating this sensitivity. The present experiments used sensitivity to posttraining outcome devaluation to index the action-habit status of instrumental responding. Infusions of dopamine into the ventral mPFC (vmPFC), but not dorsal mPFC, restored outcome sensitivity bidirectionally-decreasing responding following outcome devaluation and increasing responding when the outcome was not devalued. This bidirectionality makes the possibility that these infusions nonspecifically dysregulated vmPFC dopamine transmission unlikely. VmPFC dopamine promoted instrumental responding appropriate to outcome value. Reinforcer consumption data indicated that this was not a consequence of altered sensitivity to the reinforcer itself. We suggest that vmPFC dopamine reengages attentional processes underlying goal-directed behavior.

Direct action of low doses of radiation of neurons

International Nuclear Information System (INIS)

Peimer, S.I.; Dudkin, A.O.; Sverdlov, A.G.

1986-01-01

The authors experiment with new technology of surviving mammalian brain sections for the detection of the direct action of ionizing radiation on the functioning neurons of mammals. The authors selected the rat hippocampus as the object of investigation. Sections of the hippocampus were prepared according to standard procedure, 0.3 mm thick, and incubated for several hours under the following conditions: temperature 35.5 0 C, rate of perfusion 2-3 ml/min, rate of delivery of a mixture of oxygen (95%), and carbon monoxide (5%), in the perfusion solution 35 ml/min. Composition of solution (mM): NaCl 124, KCl 5, CACl 2 2.4, MgSO 4 1.3, NaHCO 3 26, glucose 10; pH 7.4. In an individual series of experiments, calcium was not added to the solution, but an excess of magnesium ions was introduced up to 2.6 mM. Extracellular takeoffs were performed with glass microelectrodes. For irradiation, the authors used sources of x-rays and gamma radiation. In the 5-DI x-ray apparatus, the working voltage and current on the tube were 50 quanta and 8 mA, respectively; there were no filters. Gamma irradiation was performed using ampuls with the radionuclide cesium-137 (IGI-C-3 type), which can be delivered on a holder directly to the section for 1 min

How to Build an Intentional Android: Infants' Imitation of a Robot's Goal-Directed Actions

Science.gov (United States)

Itakura, Shoji; Ishida, Hiraku; Kanda, Takayuki; Shimada, Yohko; Ishiguro, Hiroshi; Lee, Kang

2008-01-01

This study examined whether young children are able to imitate a robot's goal-directed actions. Children (24-35 months old) viewed videos showing a robot attempting to manipulate an object (e.g., putting beads inside a cup) but failing to achieve its goal (e.g., beads fell outside the cup). In 1 video, the robot made eye contact with a human…

The direct perception hypothesis: perceiving the intention of another’s action hinders its precise imitation

Science.gov (United States)

Froese, Tom; Leavens, David A.

2014-01-01

We argue that imitation is a learning response to unintelligible actions, especially to social conventions. Various strands of evidence are converging on this conclusion, but further progress has been hampered by an outdated theory of perceptual experience. Comparative psychology continues to be premised on the doctrine that humans and non-human primates only perceive others’ physical “surface behavior,” while mental states are perceptually inaccessible. However, a growing consensus in social cognition research accepts the direct perception hypothesis: primarily we see what others aim to do; we do not infer it from their motions. Indeed, physical details are overlooked – unless the action is unintelligible. On this basis we hypothesize that apes’ propensity to copy the goal of an action, rather than its precise means, is largely dependent on its perceived intelligibility. Conversely, children copy means more often than adults and apes because, uniquely, much adult human behavior is completely unintelligible to unenculturated observers due to the pervasiveness of arbitrary social conventions, as exemplified by customs, rituals, and languages. We expect the propensity to imitate to be inversely correlated with the familiarity of cultural practices, as indexed by age and/or socio-cultural competence. The direct perception hypothesis thereby helps to parsimoniously explain the most important findings of imitation research, including children’s over-imitation and other species-typical and age-related variations. PMID:24600413

Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis

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LaTonia Taliaferro-Smith

2013-01-01

Full Text Available The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B, which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast

Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.

Science.gov (United States)

Piscianz, Elisa; Candilera, Vanessa; Valencic, Erica; Loganes, Claudia; Paron, Greta; De Iudicibus, Sara; Decorti, Giuliana; Tommasini, Alberto

2016-07-01

Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation

Extension of the Method of Direct Separation of Motions for Problems of Oscillating Action on Dynamical Systems

DEFF Research Database (Denmark)

Blekhman, Iliya I.; Sorokin, Vladislav

2016-01-01

A general approach to study oscillating action on nonlinear dynamical systems is developed. It implies a transition from initial governing equations of motion to much more simple equations describing only the main slow component of motions (the vibro-transformed dynamics equations). The approach...... is named as the Oscillatory Strobodynamics, since motions are perceived as under a stroboscopic light. The vibro-transformed dynamics equations comprise terms that represent the averaged effect of the oscillating action. The method of direct separation of motions (MDSM) appears to be an efficient...

Habits as action sequences: hierarchical action control and changes in outcome value.

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Dezfouli, Amir; Lingawi, Nura W; Balleine, Bernard W

2014-11-05

Goal-directed action involves making high-level choices that are implemented using previously acquired action sequences to attain desired goals. Such a hierarchical schema is necessary for goal-directed actions to be scalable to real-life situations, but results in decision-making that is less flexible than when action sequences are unfolded and the decision-maker deliberates step-by-step over the outcome of each individual action. In particular, from this perspective, the offline revaluation of any outcomes that fall within action sequence boundaries will be invisible to the high-level planner resulting in decisions that are insensitive to such changes. Here, within the context of a two-stage decision-making task, we demonstrate that this property can explain the emergence of habits. Next, we show how this hierarchical account explains the insensitivity of over-trained actions to changes in outcome value. Finally, we provide new data that show that, under extended extinction conditions, habitual behaviour can revert to goal-directed control, presumably as a consequence of decomposing action sequences into single actions. This hierarchical view suggests that the development of action sequences and the insensitivity of actions to changes in outcome value are essentially two sides of the same coin, explaining why these two aspects of automatic behaviour involve a shared neural structure. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Quantitative determination of the contribution of indirect and direct radiation action to the production of lethal lesions in mammalian cells

International Nuclear Information System (INIS)

Pohlit, W.; Drenkard, S.

1985-01-01

For quantitative models of radiation action in living cells it is necessary to know what fraction of the absorbed dose affects the target molecule by direct radiation action and what fraction by indirect radiation action. Mammalian cells were irradiated in suspension, saturated with N 2 O or CO 2 . With these gases the production of OH-radicals is changed by a factor of two in aqueous solutions and a corresponding change in cell survival would be expected, if only indirect radiation action is involved in the production of lethal lesions in the living cell. No difference could be detected, however, and it is concluded that indirect radiation action does not contribute to radiation lethality in mammalian cells. (author)

On the relationship between feelings and action tendencies in the emotional regulation of goal-directed behaviour

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Robert eLowe

2011-12-01

Full Text Available In this article, we review the nature of the functional and causal relationship between neurophysiologically/psychologically generated states of emotional feeling and action tendencies and extrapolate a novel perspective. Emotion research, over the past century and beyond, has tended to view feeling and action tendency as independent phenomena: Attempts to outline the functional and causal relationship that exists between them have been framed therein. Classically, such relationships have been viewed as unidirectional, but an argument for bidirectionality rooted in a dynamic systems perspective has gained strength in recent years whereby the feeling-action tendency relationship is viewed as a composite whole. On the basis of our review of somatic-visceral theories of feelings, we argue that feelings are grounded upon neural-dynamic representations (elevated and stable activation patterns of action tendency. Such representations amount to predictions, updated by cognitive and bodily feedback. Specifically, we view emotional feelings as minimalist predictions of the action tendency (what the agent is likely to do in a given situation. The essence of this point is captured by our exposition of action tendency prediction-feedback loops (ATPFL which we consider, above all, in the context of emotion regulation, and in particular, of emotion regulation of goal-directed behaviour. The perspective outlined may be of use to emotion theorists, computational modellers and roboticists.

Change of Direction Speed: Toward a Strength Training Approach with Accentuated Eccentric Muscle Actions.

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Chaabene, Helmi; Prieske, Olaf; Negra, Yassine; Granacher, Urs

2018-03-28

There is growing evidence that eccentric strength training appears to have benefits over traditional strength training (i.e., strength training with combined concentric and eccentric muscle actions) from muscular, neuromuscular, tendinous, and metabolic perspectives. Eccentric muscle strength is particularly needed to decelerate and stabilize the body during the braking phase of a jump exercise or during rapid changes of direction (CoD) tasks. However, surprisingly little research has been conducted to elucidate the effects of eccentric strength training or strength training with accentuated eccentric muscle actions on CoD speed performance. In this current opinion article, we present findings from cross-sectional studies on the relationship between measures of eccentric muscle strength and CoD speed performance. In addition, we summarize the few available studies on the effects of strength training with accentuated eccentric muscle actions on CoD speed performance in athletic populations. Finally, we propose strength training with accentuated eccentric muscle actions as a promising element in strength and conditioning programs of sports with high CoD speed demands. Our findings from five cross-sectional studies revealed statistically significant moderate- to large-sized correlations (r = 0.45-0.89) between measures of eccentric muscle strength and CoD speed performance in athletic populations. The identified three intervention studies were of limited methodological quality and reported small- to large-sized effects (d = 0.46-1.31) of strength training with accentuated eccentric muscle actions on CoD speed performance in athletes. With reference to the available but preliminary literature and from a performance-related point of view, we recommend strength and conditioning coaches to include strength training with accentuated eccentric muscle actions in training routines of sports with high CoD speed demands (e.g., soccer, handball, basketball, hockey) to

Slips of action and sequential decisions: a cross-validation study of tasks assessing habitual and goal-directed action control

Directory of Open Access Journals (Sweden)

Zsuzsika Sjoerds

2016-12-01

Full Text Available Instrumental learning and decision-making rely on two parallel systems: a goal-directed and a habitual system. In the past decade, several paradigms have been developed to study these systems in animals and humans by means of e.g. overtraining, devaluation procedures and sequential decision-making. These different paradigms are thought to measure the same constructs, but cross-validation has rarely been investigated. In this study we compared two widely used paradigms that assess aspects of goal-directed and habitual behavior. We correlated parameters from a two-step sequential decision-making task that assesses model-based and model-free learning with a slips-of-action paradigm that assesses the ability to suppress cue-triggered, learnt responses when the outcome has been devalued and is therefore no longer desirable. Model-based control during the two-step task showed a very moderately positive correlation with goal-directed devaluation sensitivity, whereas model-free control did not. Interestingly, parameter estimates of model-based and goal-directed behavior in the two tasks were positively correlated with higher-order cognitive measures (e.g. visual short-term memory. These cognitive measures seemed to (at least partly mediate the association between model-based control during sequential decision-making and goal-directed behavior after instructed devaluation. This study provides moderate support for a common framework to describe the propensity towards goal-directed behavior as measured with two frequently used tasks. However, we have to caution that the amount of shared variance between the goal-directed and model-based system in both tasks was rather low, suggesting that each task does also pick up distinct aspects of goal-directed behavior. Further investigation of the commonalities and differences between the model-free and habit systems as measured with these, and other, tasks is needed. Also, a follow-up cross-validation on the neural

76 FR 62831 - Notice of Realty Action: Direct Sale of Public Land in Shasta County, CA

Science.gov (United States)

2011-10-11

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLCA930000.L58790000.EU0000; CACA 48506] Notice of Realty Action: Direct Sale of Public Land in Shasta County, CA AGENCY: Bureau of Land... serial number CACA 24929 and a ROW for a telephone line issued under serial number CACA 26611. 4. A...

Processing and Integration of Contextual Information in Monkey Ventrolateral Prefrontal Neurons during Selection and Execution of Goal-Directed Manipulative Actions.

Science.gov (United States)

Bruni, Stefania; Giorgetti, Valentina; Bonini, Luca; Fogassi, Leonardo

2015-08-26

The prefrontal cortex (PFC) is deemed to underlie the complexity, flexibility, and goal-directedness of primates' behavior. Most neurophysiological studies performed so far investigated PFC functions with arm-reaching or oculomotor tasks, thus leaving unclear whether, and to which extent, PFC neurons also play a role in goal-directed manipulative actions, such as those commonly used by primates during most of their daily activities. Here we trained two macaques to perform or withhold grasp-to-eat and grasp-to-place actions, depending on the combination of two subsequently presented cues: an auditory go/no-go cue (high/low tone) and a visually presented target (food/object). By varying the order of presentation of the two cues, we could segment and independently evaluate the processing and integration of contextual information allowing the monkey to make a decision on whether or not to act, and what action to perform. We recorded 403 task-related neurons from the ventrolateral prefrontal cortex (VLPFC): unimodal sensory-driven (37%), motor-related (21%), unimodal sensory-and-motor (23%), and multisensory (19%) neurons. Target and go/no-go selectivity characterized most of the recorded neurons, particularly those endowed with motor-related discharge. Interestingly, multisensory neurons appeared to encode a behavioral decision independently from the sensory modality of the stimulus allowing the monkey to make it: some of them reflected the decision to act or refraining from acting (56%), whereas others (44%) encoded the decision to perform (or withhold) a specific action (e.g., grasp-to-eat). Our findings indicate that VLPFC neurons play a role in the processing of contextual information underlying motor decision during goal-directed manipulative actions. We demonstrated that macaque ventrolateral prefrontal cortex (VLPFC) neurons show remarkable selectivity for different aspects of the contextual information allowing the monkey to select and execute goal-directed

77 FR 13145 - Notice of Realty Action: Direct Sale of Public Land in Esmeralda County, Nevada

Science.gov (United States)

2012-03-05

... DEPARTMENT OF THE INTERIOR Bureau of Land Management [LLNVB00000. 14300000. EU0000. LXSS129F0000 241A; N-88014; 11-08807; MO 4500022284; TAS: 14X1109] Notice of Realty Action: Direct Sale of Public... sale offer is received. Payments must be by certified check, U.S. postal money order, bank draft, or...

Facilitating Dissident Action

DEFF Research Database (Denmark)

Thydal, Signe; Svensson, Christian Franklin

2018-01-01

Firefund.net. crowdfunds and provides resources for direct action movements. The organisation positions itself within a political struggle to create a global solidarity network. Firefund.net’s challenges and possibilities are analysed in relation to juridical issues and issues of control and shar......Firefund.net. crowdfunds and provides resources for direct action movements. The organisation positions itself within a political struggle to create a global solidarity network. Firefund.net’s challenges and possibilities are analysed in relation to juridical issues and issues of control...... to support radical initiatives without breaking the law: some activists sympathise with movements in a juridical grey zone. Both issues are relevant to social movements and current direct action....

Effect of chromium enriched fermentation product of barley and brewer’s yeast and its combination with rosiglitazone on experimentally induced hyperglycaemia in mice

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Cekić Vlada

2011-01-01

Full Text Available Introduction. In the recent years, herbal preparations have been more used to treat diabetes. Dietetic supplement based on barley and beer yeast enriched with chromium (BBCr is registered in Serbia as a supplement in the treatment of type 2 diabetes. Objective. To investigate the effect of the preparation based on barley and brewer’s yeast with chromium (BBCr, rosiglitazone (R and their combination (BBCr+R on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. Methods. The animals were divided into three groups: glucose 500 mg/kg (I; adrenalin 0.2 mg/kg (II; and alloxan 100 mg/kg (III and into subgroups according to the substance they received (BBCr: 750 mg/kg, R: 0.75 mg/kg and BBCr+R. Each animal was its own control in respect of glycaemia before and after the treatment with test substances, except for group III which contained a placebo subgroup. Results. BBCr caused a significant decrease of fasting glycaemia and significant reduction of glycaemia after glucose load compared to the values before treatment (7.4±0.6 mmol/l vs 9.2±0.6 mmol/l; p=0.01. R and BBCr+R significantly decreased glycaemia after adrenalin load (R: 8.6±1.8 mmol/l vs 15.4±3.2 mmol/l; p=0.004; BBCr+R: 9.6±2.4 mmol/l vs 15.0±4.4 mmol/l; p=0.04. After alloxan application the glycaemia was significantly lower in the subgroups treated with BBCr, R and BBCr+R compared to placebo subgroup (10.1±8.0 mmol/l vs 6.8±2.7 mmol/l vs 13.5±9.7 mmol/l vs 24.5±4.7 mmol/l; p=0.001. Conclusion. Pretreatment with BBCr caused a significant reduction of fasting glycaemia and glycaemia after glucose load. Rosiglitazone and BBCr+R caused a significant reduction of glycaemia after adrenalin load. Pretreatment with BBCr, R and BBCr+R prevented the onset of experimental diabetes caused by alloxan, which was confirmed by histological analysis of pancreas tissue.

Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

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Le Sun

Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

77 FR 31034 - Notice of Realty Action: Non-Competitive Direct Sale of Reversionary Interest Recreation and...

Science.gov (United States)

2012-05-24

...-08807; MO 4500030924; TAS: 14X5232] Notice of Realty Action: Non-Competitive Direct Sale of Reversionary... check, U.S. postal money order, or bank draft, and made payable in U.S. dollars to the ``Department of... percent deposit. Payment must be submitted in the form of a certified check, U.S. postal money order, bank...

Enactment versus observation: item-specific and relational processing in goal-directed action sequences (and lists of single actions.

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Janette Schult

Full Text Available What are the memory-related consequences of learning actions (such as "apply the patch" by enactment during study, as compared to action observation? Theories converge in postulating that enactment encoding increases item-specific processing, but not the processing of relational information. Typically, in the laboratory enactment encoding is studied for lists of unrelated single actions in which one action execution has no overarching purpose or relation with other actions. In contrast, real-life actions are usually carried out with the intention to achieve such a purpose. When actions are embedded in action sequences, relational information provides efficient retrieval cues. We contrasted memory for single actions with memory for action sequences in three experiments. We found more reliance on relational processing for action-sequences than single actions. To what degree can this relational information be used after enactment versus after the observation of an actor? We found indicators of superior relational processing after observation than enactment in ordered pair recall (Experiment 1A and in emerging subjective organization of repeated recall protocols (recall runs 2-3, Experiment 2. An indicator of superior item-specific processing after enactment compared to observation was recognition (Experiment 1B, Experiment 2. Similar net recall suggests that observation can be as good a learning strategy as enactment. We discuss possible reasons why these findings only partly converge with previous research and theorizing.

76 FR 68784 - Notice of Realty Action: Direct Sale of Public Land in Santa Clara County, CA

Science.gov (United States)

2011-11-07

... California Limited Liability Company, for the appraised fair market value of $16,000. DATES: Written comments...] Notice of Realty Action: Direct Sale of Public Land in Santa Clara County, CA AGENCY: Bureau of Land...), Hollister Field Office, proposes to sell a parcel of public land consisting of approximately 15.97 acres...

Contestation internationale contre élites mondiales : l’action directe et la politique délibérative sont-elles conciliables ?

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Francis Dupuis-Déri

2012-04-01

Full Text Available Dans cet article, j’analyse à la lumière des normes libérales de la politique délibérative le bien-fondé de l’action directe contre les institutions internationales associées au néolibéralisme et à la mondialisation du capitalisme (Banque mondiale, Organisation mondiale du commerce, etc.. Le processus délibératif de ces organismes étant illégitime du point de vue de la théorie de la politique délibérative, les activistes du mouvement altermondialiste sont en droit de contester ces organismes. De plus, une attitude de contestation peut avoir en elle-même une valeur délibérative pour au moins sept raisons : (1 lancer une délibération ; (2 élargir la participation à la délibération ; (3 renforcer la représentativité ; (4 faire circuler l’information et faire connaître les arguments (publicité ; (5 stimuler l’imagination ; (6 pousser à l’action ; (7 relancer la délibération. Finalement, les mouvements sociaux tels que le mouvement altermondialiste peuvent être vus comme des forums délibératifs. Ainsi, qui veut évaluer la légitimité de l’action directe doit prendre en considération la nature délibérative du processus par lequel les activistes choisissent les moyens les plus efficaces à utiliser pour corriger les défauts du processus délibératif officiel et pour faire avancer l’égalité, la liberté et la justice.In this article I examine the legitimacy of direct action in relation to liberal deliberative norms and global institutions (World Bank, World Trade Organization, etc.. Since the deliberative processes of these institutions are illegitimate according to the theory of deliberative politics, the activists of the movement for global justice should be legitimate to confront these institutions. Moreover, confrontational action in itself may have a deliberative value for at least seven reasons: (1 initiating deliberation (agenda-setting ; (2 enlarging participation ; (3 enlarging

Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats.

Science.gov (United States)

Johnson, Julia A; Trasino, Steven E; Ferrante, Anthony W; Vasselli, Joseph R

2007-11-01

The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin-sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied. Adult female Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight (BW), a high-fat (HF) diet (45% fat) for 6 weeks. Rats were initially randomized to groups (n = 12) fed either low-fat or HF diets, with or without the TZD rosiglitazone (ROSI; 5 mg/kg per day), for 6 weeks. ROSI was then discontinued, and all animals were fed HF for another 6 weeks before sacrifice. Retroperitoneal (RP) adipose tissue morphology was determined from tissue collected by serial biopsies before and after 6 weeks of ROSI treatment and at sacrifice. Measures of BW and adiposity did not differ among groups 6 weeks after stopping ROSI treatment. However, during treatment, ROSI in both diets significantly decreased RP adipocyte size and increased RP DNA content, and these effects continued to be observed after discontinuing treatment. ROSI administration also decreased circulating insulin, leptin, and triglycerides and increased circulating adiponectin levels; however, these effects were reversed on stopping treatment. These results demonstrated that TZD-induced effects on adipocyte size and number were maintained after discontinuing treatment, even with consumption of an obesigenic diet. However, additional studies are needed to determine whether TZD-treated animals eventually achieve an adipocyte size similar to that of untreated animals at the expense of a higher BW.

The Neural Representation of Goal-Directed Actions and Outcomes in the Ventral Striatum's Olfactory Tubercle

Science.gov (United States)

Gadziola, Marie A.

2016-01-01

The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders. SIGNIFICANCE STATEMENT Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we

Action-based mechanisms of attention.

OpenAIRE

Tipper, S P; Howard, L A; Houghton, G

1998-01-01

Actions, which have effects in the external world, must be spatiotopically represented in the brain. The brain is capable of representing space in many different forms (e.g. retinotopic-, environment-, head- or shoulder-centred), but we maintain that actions are represented in action-centred space, meaning that, at the cellular level, the direction of movement is defined by the activity of cells. In reaching, for example, object location is defined as the direction and distance between the or...

Mechanism of action of direct-acting antiviral agents in treatment of chronic hepatitis C

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WEN Xiaoyu

2016-09-01

Full Text Available With the development and launch of direct-acting antiviral agents (DAAs in the world in recent years, therapeutic regimens for chronic hepatitis C are constantly evolving. DAAs will also be launched in China in the near future. DAAs mainly target at the non-structural proteins of HCV and can inhibit HCV RNA replication. This article introduces the targets, mechanism of action, and resistance characteristics of different DAAs, as well as their current research and development in China and the results of phase Ⅲ clinical studies, in order to provide a reference for combined therapeutic strategies with DAAs in the treatment for chronic hepatitis C.

IL-1β and TNFα inhibit GPR120 (FFAR4) and stimulate GPR84 (EX33) and GPR41 (FFAR3) fatty acid receptor expression in human adipocytes: implications for the anti-inflammatory action of n-3 fatty acids.

Science.gov (United States)

Muredda, Laura; Kępczyńska, Małgorzata A; Zaibi, Mohamed S; Alomar, Suliman Y; Trayhurn, Paul

2018-05-01

Regulation of the expression of GPCR fatty acid receptor genes has been examined in human adipocytes differentiated in culture. TNFα and IL-1β induced a marked reduction in GPR120 expression, mRNA level falling 17-fold at 24 h in adipocytes incubated with TNFα. In contrast, GPR84 mRNA was dramatically increased by these cytokines (>500-fold for IL-1β at 4 h); GPR41 expression was also stimulated. Rosiglitazone did not affect GPR84 expression, but GPR120 and GPR41 expression increased. Dexamethasone, insulin, linoleic and docosahexaenoic acids (DHA), and TUG891 (GPR120 agonist) had little effect on GPR120 and GPR84 expression. TUG891 did not attenuate the pro-inflammatory actions of TNFα and IL-1β. DHA slightly countered the actions of IL-1β on CCL2, IL6 and ADIPOQ expression, though not on secretion of these adipokines. GPR120 and GP84 gene expression in human adipocytes is highly sensitive to pro-inflammatory mediators; the inflammation-induced inhibition of GPR120 expression may compromise the anti-inflammatory action of GPR120 agonists.

Use of time and materials and cost reimbursement subcontracts for remedial actions under the alternative remedial contracting strategy contracts. Directive

International Nuclear Information System (INIS)

1992-01-01

The directive is intended to establish agency guidance on the use of time and materials and cost reimbursement contracts for remedial actions in general and to provide specific instruction regarding the use of these approaches in subcontracting under the Alternative Remedial Contracting Strategy (ARCS) contracts

Turning over renal osteodystrophy dogma: direct actions of FGF23 on osteoblast β-catenin pathway.

Science.gov (United States)

Schiavi, Susan C; Moysés, Rosa M A

2016-07-01

Although recognized as a major complication of chronic kidney disease (CKD), the pathophysiology of the CKD-related mineral and bone disorder (CKD-MBD) is not completely understood. Recently, the inhibition of Wnt/β-catenin pathway in osteocytes by sclerostin has been shown to play a role in CKD-MBD. The study by Carrilo-Lopez et al. confirms this inhibition in an experimental model of CKD. Moreover, they describe direct actions of FGF23-Klotho on osteoblasts, increasing the expression of DKK1, another Wnt/β-catenin pathway inhibitor. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

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Boris Betz

2012-01-01

Full Text Available Background. Nitric oxide (NO-signal transduction plays an important role in renal ischemia/reperfusion (I/R injury. NO produced by endothelial NO-synthase (eNOS has protective functions whereas NO from inducible NO-synthase (iNOS induces impairment. Rosiglitazone (RGZ, a peroxisome proliferator-activated receptor (PPAR-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg was administered i.p. to SD-rats (f subjected to bilateral renal ischemia (60 min. Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3 was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

Science.gov (United States)

Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

2014-05-01

Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

78 FR 46600 - Notice of Realty Action: Direct Sale of Public Land (N-91073) for Affordable Housing Purposes in...

Science.gov (United States)

2013-08-01

...; 13-08807; MO 4500052481; TAS: 14X5232] Notice of Realty Action: Direct Sale of Public Land (N-91073... BLM serial number N-91073, and must be made in the form of certified check, postal money order, bank... through escrow by Electronic Fund Transfer (EFT), or in the form of a certified check, postal money order...

Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect Pathway Activation in the Dorsolateral Striatum in Mice

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Muriel Laurent

2017-12-01

Full Text Available The striatum is a key brain structure involved in the processing of cognitive flexibility, which results from the balance between the flexibility demanded for novel learning of motor actions and the inflexibility required to preserve previously learned actions. In particular, the dorsolateral portion of the striatum (DLS is engaged in the learning of action sequence. This process is temporally driven by fine adjustments in the function of the two main neuronal populations of the striatum, known as the direct pathway medium spiny neurons (dMSNs and indirect pathway medium spiny neurons (iMSNs. Here, using optogenetics, behavioral, and electrophysiological tools, we addressed the relative role of both neuronal populations in the acquisition of a reversal dual action sequence in the DLS. While the channelrhodopsin-induced activation of dMSNs and iMSNs of the DLS did not induce changes in the learning rate of the sequence, the specific activation of the dMSNs of the DLS facilitated the acquisition of a reversal dual action sequence; the activation of iMSNs induced a significant deficit in the acquisition of the same task. Taken together our results indicate an antagonistic relationship between dMSNs and iMSNs on the acquisition of a reversal dual action sequence.

Counterfactual Processing of Economic Action-Outcome Alternatives in Obsessive-Compulsive Disorder: Further Evidence of Impaired Goal-Directed Behavior

Science.gov (United States)

Gillan, Claire M.; Morein-Zamir, Sharon; Kaser, Muzaffer; Fineberg, Naomi A.; Sule, Akeem; Sahakian, Barbara J.; Cardinal, Rudolf N.; Robbins, Trevor W.

2014-01-01

Background Obsessive-compulsive disorder (OCD) is a disorder of automatic, uncontrollable behaviors and obsessive rumination. There is evidence that OCD patients have difficulties performing goal-directed actions, instead exhibiting repetitive stimulus-response habit behaviors. This might result from the excessive formation of stimulus-response habit associations or from an impairment in the ability to use outcome value to guide behavior. We investigated the latter by examining counterfactual decision making, which is the ability to use comparisons of prospective action-outcome scenarios to guide economic choice. Methods We tested decision making (forward counterfactual) and affective responses (backward counterfactual) in 20 OCD patients and 20 matched healthy control subjects using an economic choice paradigm that previously revealed attenuation of both the experience and avoidance of counterfactual emotion in schizophrenia patients and patients with orbitofrontal cortex lesions. Results The use of counterfactual comparison to guide decision making was diminished in OCD patients, who relied primarily on expected value. Unlike the apathetic affective responses previously shown to accompany this decision style, OCD patients reported increased emotional responsivity to the outcomes of their choices and to the counterfactual comparisons that typify regret and relief. Conclusions Obsessive-compulsive disorder patients exhibit a pattern of decision making consistent with a disruption in goal-directed forward modeling, basing decisions instead on the temporally present (and more rational) calculation of expected value. In contrast to this style of decision making, emotional responses in OCD were more extreme and reactive than control subjects. These results are in line with an account of disrupted goal-directed cognitive control in OCD. PMID:23452663

On the role played by direct protection of the haemopoietic system cells in radioprotective action of some biogenous amines on the animal organism

International Nuclear Information System (INIS)

Smirnova, I.B.; Dontsova, G.V.; Yanushevskaya, M.I.; Graevskij, E.Ya.

1975-01-01

It has been found in mice, by a method of splenic exocolonies, that: (1) serotonin, adrenaline and noradrenaline can protect both isolated bone marrow cells and cells in situ (2) a considerable contribution to a radioprotective action of the amines under study on the animal organism is made by their direct protective effect on cells, (3) with serotonin and adrenaline, ''cell'' protection in the organism is added by a radioprotective action of tissue hypoxia caused by these amines

PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice

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Unger Thomas

2010-10-01

Full Text Available Abstract Background Inflammation of adipose tissue (AT has been recently accepted as a first step towards obesity-mediated insulin resistance. We could previously show that mice fed with high fat diet (HFD develop systemic insulin resistance (IR and glucose intolerance (GI associated with CD4-positive T-lymphocyte infiltration into visceral AT. These T-lymphocytes, when enriched in AT, participate in the development of fat tissue inflammation and subsequent recruitment of proinflammatory macrophages. The aim of this work was to elucidate the action of the insulin sensitizing PPARgamma on T-lymphocyte infiltration during development of IR, and comparison of the PPARgamma-mediated anti-inflammatory effects of rosiglitazone and telmisartan in diet-induced obesity model (DIO-model in mice. Methods In order to investigate the molecular mechanisms underlying early development of systemic insulin resistance and glucose intolerance male C57BL/6J mice were fed with high fat diet (HFD for 10-weeks in parallel to the pharmacological intervention with rosiglitazone, telmisartan, or vehicle. Results Both rosiglitazone and telmisartan were able to reduce T-lymphocyte infiltration into AT analyzed by quantitative analysis of the T-cell marker CD3gamma and the chemokine SDF1alpha. Subsequently, both PPARgamma agonists were able to attenuate macrophage infiltration into AT, measured by the reduction of MCP1 and F4/80 expression. In parallel to the reduction of AT-inflammation, ligand-activated PPARgamma improved diet-induced IR and GI. Conclusion Together the present study demonstrates a close connection between PPARgamma-mediated anti-inflammation in AT and systemic improvement of glucose metabolism identifying T-lymphocytes as one cellular mediator of PPARgamma´s action.

Beneficial effects of co-enzyme Q10 and rosiglitazone in fructose-induced metabolic syndrome in rats

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Suzan M. Mansour

2013-06-01

Full Text Available Increased fructose consumption is strongly associated with metabolic syndrome (MS. This study was performed to elucidate the role of co-enzyme Q10 (CoQ and/or rosiglitazone (Rosi in fructose induced MS. Four groups of rats (n = 8–10 were fed on fructose-enriched diet (FED for 16 weeks. One served as FED-control while the remaining groups were treated with CoQ (10 mg/kg/day, Rosi (4 mg/kg/day or their combination during the last 6 weeks. Another group was fed on normal laboratory chow (normal control. At the end of the experiment, blood samples were collected for estimation of markers related to MS. In addition, histological examination of liver, kidney and pancreas samples was done. Induction of the MS was associated with increased body weight gain (34% coupled with elevated levels of blood glucose (48%, insulin (86%, insulin resistance (270%, uric acid (69%, urea (155%, creatinine (129% and blood lipids with different degrees. Fructose-induced MS also reduced plasma catalase (62% and glutathione peroxidase (89% activities parallel to increased serum leptin and tumor necrosis factor-alpha (TNF-α levels. These changes were coupled by marked histological changes in the examined tissues. Treatment with CoQ or Rosi attenuated most of MS-induced changes. Besides, the combination of both agents further reduced blood glucose, total cholesterol, triglycerides and urea levels, as well as, normalized serum levels of leptin and TNF-α. In addition, combined therapy of both agents elevated HDL-cholesterol level and glutathione peroxidase activity. In conclusion, the present study proves the benefits of co-supplementation of CoQ and Rosi in a fructose-induced model of insulin resistance.

Side effect of acting on the world: Acquisition of action-outcome statistic relation alters visual interpretation of action outcome

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Takahiro eKawabe

2013-09-01

Full Text Available Humans can acquire the statistical features of the external world and employ them to control behaviors. Some external events occur in harmony with an agent’s action, and thus humans should also be able to acquire the statistical features between an action and its external outcome. We report that the acquired action-outcome statistical features alter the visual appearance of the action outcome. Pressing either of two assigned keys triggered visual motion whose direction was statistically biased either upward or downward, and observers judged the stimulus motion direction. Points of subjective equality (PSE for judging motion direction were shifted repulsively from the mean of the distribution associated with each key. Our Bayesian model accounted for the PSE shifts, indicating the optimal acquisition of the action-effect statistical relation. The PSE shifts were moderately attenuated when the action-outcome contingency was reduced. The Bayesian model again accounted for the attenuated PSE shifts. On the other hand, when the action-outcome contiguity was greatly reduced, the PSE shifts were greatly attenuated, and however, the Bayesian model could not accounted for the shifts. The results indicate that visual appearance can be modified by prediction based on the optimal acquisition of action-effect causal relation.

Direct action of endocrine disrupting chemicals on human sperm

DEFF Research Database (Denmark)

Schiffer, Christian; Müller, Astrid; Egeberg, Dorte L

2014-01-01

Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on huma...

Counterfactual processing of economic action-outcome alternatives in obsessive-compulsive disorder: further evidence of impaired goal-directed behavior.

Science.gov (United States)

Gillan, Claire M; Morein-Zamir, Sharon; Kaser, Muzaffer; Fineberg, Naomi A; Sule, Akeem; Sahakian, Barbara J; Cardinal, Rudolf N; Robbins, Trevor W

2014-04-15

Obsessive-compulsive disorder (OCD) is a disorder of automatic, uncontrollable behaviors and obsessive rumination. There is evidence that OCD patients have difficulties performing goal-directed actions, instead exhibiting repetitive stimulus-response habit behaviors. This might result from the excessive formation of stimulus-response habit associations or from an impairment in the ability to use outcome value to guide behavior. We investigated the latter by examining counterfactual decision making, which is the ability to use comparisons of prospective action-outcome scenarios to guide economic choice. We tested decision making (forward counterfactual) and affective responses (backward counterfactual) in 20 OCD patients and 20 matched healthy control subjects using an economic choice paradigm that previously revealed attenuation of both the experience and avoidance of counterfactual emotion in schizophrenia patients and patients with orbitofrontal cortex lesions. The use of counterfactual comparison to guide decision making was diminished in OCD patients, who relied primarily on expected value. Unlike the apathetic affective responses previously shown to accompany this decision style, OCD patients reported increased emotional responsivity to the outcomes of their choices and to the counterfactual comparisons that typify regret and relief. Obsessive-compulsive disorder patients exhibit a pattern of decision making consistent with a disruption in goal-directed forward modeling, basing decisions instead on the temporally present (and more rational) calculation of expected value. In contrast to this style of decision making, emotional responses in OCD were more extreme and reactive than control subjects. These results are in line with an account of disrupted goal-directed cognitive control in OCD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Adverse hepatic and cardiac responses to rosiglitazone in a new mouse model of type 2 diabetes: relation to dysregulated phosphatidylcholine metabolism.

Science.gov (United States)

Pan, Huei-Ju; Lin, Yiming; Chen, Yuqing E; Vance, Dennis E; Leiter, Edward H

2006-07-01

Given the heterogeneous nature of metabolic dysfunctions associated with insulin resistance and type 2 diabetes (T2D), a single pharmaceutical cannot be expected to provide complication-free therapy in all patients. Thiazolidinediones (TZD) increase insulin sensitivity, reduce blood glucose and improve cardiovascular parameters. However, in addition to increasing fat mass, TZD have the potential in certain individuals to exacerbate underlying hepatosteatosis and diabetic cardiomyopathy. Pharmacogenetics should allow patient selection to maximize therapy and minimize risk. To this end, we have combined two genetically diverse inbred strains, NON/Lt and NZO/Lt, to produce a "negative heterosis" increasing the frequency of T2D in F1 males. As in humans with T2D, treatment of diabetic and hyperlipemic F1 males with rosiglitazone (Rosi), an agonist of peroxisome proliferator-activated gamma receptor (PPARgamma), reverses these disease phenotypes. However, the hybrid genome perturbed both major pathways for phosphatidylcholine (PC) biosynthesis in the liver, and effected remarkable alterations in the composition of cardiolipin in heart mitochondria. These metabolic defects severely exacerbated an underlying hepatosteatosis and increased levels of the adipokine, plasminogen activator inhibitor-1 (PAI-1), a risk factor for cardiovascular events. This model system demonstrates how the power of mouse genetics can be used to identify the metabolic signatures of individuals who may be prone to drug side effects.

Electroacupuncture and Rosiglitazone Combined Therapy as a Means of Treating Insulin Resistance and Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Rong-Tsung Lin

2013-01-01

Full Text Available Aims. To evaluate the efficacy of rosiglitazone (TZD and electroacupuncture (EA combined therapy as a treatment for type 2 diabetes mellitus (T2DM patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N=15 and the experimental group (TZD + EA, N=16. Changes in their plasma free fatty acid (FFA, glucose, and insulin levels, together with their homeostasis model assessment (HOMA indices, were statistically compared before and after treatment. Hypoglycemic activity (% was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

7. april 2005 inter-departmental directive on the actions of public authority in case of event leading to an emergency radiological situation (1); Directive interministerielle du 7 avril 2005 sur l'action des pouvoirs publics en cas d'evenement entrainant une situation d'urgence radiologique (1)

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-07-01

This directive concerns the management of a nuclear crisis. A correct information of Public Authorities is necessary at every level in order that actions to be lead can be in agreement with the situation. The protection of person, possessions and environment is the priority objective of Publics Authorities. This imperative is taken into account by the modalities exposed in the present directive, that determines the frame of the Public Authorities organization as well as the arrangements to take by Authorities in case of nuclear event. (N.C.)

Spatial Working Memory Is Necessary for Actions to Guide Thought

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Thomas, Laura E.

2013-01-01

Directed actions can play a causal role in cognition, shaping thought processes. What drives this cross-talk between action and thought? I investigated the hypothesis that representations in spatial working memory mediate interactions between directed actions and problem solving. Participants attempted to solve an insight problem while…

Habitual versus goal-directed action control in Parkinson disease.

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de Wit, Sanne; Barker, Roger A; Dickinson, Anthony D; Cools, Roshan

2011-05-01

This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus-response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that patients are able to rely on direct stimulus-response associations when a goal-directed strategy causes response conflict, suggesting that habit formation is not impaired. If anything our results suggest a disease severity-dependent deficit in goal-directed behavior. These results are discussed in the context of Parkinson disease and the neurobiology of habitual and goal-directed behavior.

Effects of PPARs agonists on cardiac metabolism in littermate and cardiomyocyte-specific PPAR-γ-knockout (CM-PGKO mice.

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Michelangela Barbieri

Full Text Available Understanding the molecular regulatory mechanisms controlling for myocardial lipid metabolism is of critical importance for the development of new therapeutic strategies for heart diseases. The role of PPARγ and thiazolidinediones in regulation of myocardial lipid metabolism is controversial. The aim of our study was to assess the role of PPARγ on myocardial lipid metabolism and function and differentiate local/from systemic actions of PPARs agonists using cardiomyocyte-specific PPARγ -knockout (CM-PGKO mice. To this aim, the effect of PPARγ, PPARγ/PPARα and PPARα agonists on cardiac function, intra-myocyte lipid accumulation and myocardial expression profile of genes and proteins, affecting lipid oxidation, uptake, synthesis, and storage (CD36, CPT1MIIA, AOX, FAS, SREBP1-c and ADPR was evaluated in cardiomyocyte-specific PPARγ-knockout (CM-PGKO and littermate control mice undergoing standard and high fat diet (HFD. At baseline, protein levels and mRNA expression of genes involved in lipid uptake, oxidation, synthesis, and accumulation of CM-PGKO mice were not significantly different from those of their littermate controls. At baseline, no difference in myocardial lipid content was found between CM-PGKO and littermate controls. In standard condition, pioglitazone and rosiglitazone do not affect myocardial metabolism while, fenofibrate treatment significantly increased CD36 and CPT1MIIA gene expression. In both CM-PGKO and control mice submitted to HFD, six weeks of treatment with rosiglitazone, fenofibrate and pioglitazone lowered myocardial lipid accumulation shifting myocardial substrate utilization towards greater contribution of glucose. In conclusion, at baseline, PPARγ does not play a crucial role in regulating cardiac metabolism in mice, probably due to its low myocardial expression. PPARs agonists, indirectly protect myocardium from lipotoxic damage likely reducing fatty acids delivery to the heart through the actions on adipose

The allocation of attention to learning of goal-directed actions: A cognitive neuroscience framework focusing on the basal ganglia

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Liz eFranz

2012-12-01

Full Text Available The present paper builds on the idea that attention is largely in service of our actions. A framework and model which captures the allocation of attention for learning of goal-directed actions is proposed and developed. This framework highlights an evolutionary model based on the notion that rudimentary brain functions have become embedded into increasingly higher levels of networks which all contribute to adaptive learning. Background literature is presented alongside key evidence based on experimental studies in the so-called ‘split-brain’ (surgically divided cerebral hemispheres with a key focus on bimanual actions. The proposed multilevel cognitive-neural system of attention is built upon key processes of a highly-adaptive basal-ganglia-thalamic-cortical system. Although overlap with other existing findings and models is acknowledged where appropriate, the proposed framework is an original synthesis of cognitive experimental findings with supporting evidence of a neural system and a carefully formulated model of attention. It is the hope that this new synthesis will be informative in fields of cognition and other fields of brain sciences and will lead to new avenues for experimentation across domains.

Photon Energy Threshold in Direct Photocatalysis with Metal Nanoparticles: Key Evidence from the Action Spectrum of the Reaction.

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Sarina, Sarina; Jaatinen, Esa; Xiao, Qi; Huang, Yi Ming; Christopher, Philip; Zhao, Jin Cai; Zhu, Huai Yong

2017-06-01

By investigating the action spectra (the relationship between the irradiation wavelength and apparent quantum efficiency of reactions under constant irradiance) of a number of reactions catalyzed by nanoparticles including plasmonic metals, nonplasmonic metals, and their alloys at near-ambient temperatures, we found that a photon energy threshold exists in each photocatalytic reaction; only photons with sufficient energy (e.g., higher than the energy level of the lowest unoccupied molecular orbitals) can initiate the reactions. This energy alignment (and the photon energy threshold) is determined by various factors, including the wavelength and intensity of irradiation, molecule structure, reaction temperature, and so forth. Hence, distinct action spectra were observed in the same type of reaction catalyzed by the same catalyst due to a different substituent group, a slightly changed reaction temperature. These results indicate that photon-electron excitations, instead of the photothermal effect, play a dominant role in direct photocatalysis of metal nanoparticles for many reactions.

Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

International Nuclear Information System (INIS)

Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

2008-01-01

CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

Emotions as pragmatic and epistemic actions

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Wilutzky, Wendy

2015-01-01

This paper explores the idea that emotions in social contexts and their intentionality may be conceived of as pragmatic or epistemic actions. That is, emotions are often aimed at achieving certain goals within a social context, so that they resemble pragmatic actions; and in other cases emotions can be plausibly construed as acts of probing the social environment so as to extract or uncover important information, thus complying with the functions of epistemic actions (cf. Kirsh and Maglio, 1994). This view of emotions stands at odds with the wide-held conception that emotions' intentionality can be cashed out in terms of representations of value. On such a position, emotions' intentionality has only a mind-to-world direction of fit while any world-to-mind direction of fit is deemed secondary or is even outrightly denied. However, acknowledging that emotions (qua actions) also have a world-to-mind direction fit has several advantages over the typical rendition of emotions as representations of value, such as accounting for emotions' sensitivity to contextual factors, variations in emotion expression and, importantly, assessing the appropriateness of emotional reactions. To substantiate this claim, several cases of emotions in social contexts are discussed, as the social dimension of emotions highlights that emotions are inherently ways of interacting with one's social environment. In sum, the construal of emotions in social contexts as pragmatic or epistemic actions yields a more fine-grained and accurate understanding of emotions' intentionality and their roles in social contexts than the insistence on a purely mind-to-world direction of fit. PMID:26578999

Affirmative Action in Higher Education: A Sourcebook.

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VanderWaerdt, Lois

A comprehensive guide to the implementation of affirmative action in colleges and universities is presented. Information is provided on the preparation of an affirmative action plan subject to review by the federal Office of Contract Compliance. Attention is directed to qualifications for staffing affirmative action offices; procedures for hiring…

Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

International Nuclear Information System (INIS)

Salem, M.A.M.; Phares, C.K.

1986-01-01

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U- 14 C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10 5 cells/ml) were incubated with either [ 125 I]insulin or [ 125 I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and 14 C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro

Impairments in action-outcome learning in schizophrenia.

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Morris, Richard W; Cyrzon, Chad; Green, Melissa J; Le Pelley, Mike E; Balleine, Bernard W

2018-03-03

Learning the causal relation between actions and their outcomes (AO learning) is critical for goal-directed behavior when actions are guided by desire for the outcome. This can be contrasted with habits that are acquired by reinforcement and primed by prevailing stimuli, in which causal learning plays no part. Recently, we demonstrated that goal-directed actions are impaired in schizophrenia; however, whether this deficit exists alongside impairments in habit or reinforcement learning is unknown. The present study distinguished deficits in causal learning from reinforcement learning in schizophrenia. We tested people with schizophrenia (SZ, n = 25) and healthy adults (HA, n = 25) in a vending machine task. Participants learned two action-outcome contingencies (e.g., push left to get a chocolate M&M, push right to get a cracker), and they also learned one contingency was degraded by delivery of noncontingent outcomes (e.g., free M&Ms), as well as changes in value by outcome devaluation. Both groups learned the best action to obtain rewards; however, SZ did not distinguish the more causal action when one AO contingency was degraded. Moreover, action selection in SZ was insensitive to changes in outcome value unless feedback was provided, and this was related to the deficit in AO learning. The failure to encode the causal relation between action and outcome in schizophrenia occurred without any apparent deficit in reinforcement learning. This implies that poor goal-directed behavior in schizophrenia cannot be explained by a more primary deficit in reward learning such as insensitivity to reward value or reward prediction errors.

Good is up – Spatial metaphors in action observation

Directory of Open Access Journals (Sweden)

Janna Marleen Gottwald

2015-10-01

Full Text Available Positive objects or actions are associated with physical highness, whereas negative objects or actions are related to physical lowness. Previous research suggests that metaphorical connection (good is up or bad is down between spatial experience and evaluation of objects is grounded in actual experience with the body. Prior studies investigated effects of spatial metaphors with respect to verticality of either static objects or self-performed actions. By presenting videos of object placements, the current three experiments combined vertically-located stimuli with observation of vertically-directed actions. As expected, participants’ ratings of emotionally-neutral objects were systematically influenced by the observed vertical positioning, that is, ratings were more positive for objects that were observed being placed up as compared to down. Moreover, effects were slightly more pronounced for bad is down, because only the observed downward, but not the upward, action led to different ratings as compared to a medium-positioned action. Last, some ratings were even affected by observing only the upward/downward action, without seeing the final vertical placement of the object. Thus, both, a combination of observing a vertically-directed action and seeing a vertically-located object, and observing a vertically-directed action alone, affected participants’ evaluation of emotional valence of the involved object. The present findings expand the relevance of spatial metaphors to action observation, thereby giving new impetus to embodied-cognition research.

INFORMAS (International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support): summary and future directions.

Science.gov (United States)

Kumanyika, S

2013-10-01

This supplement presents the foundational elements for INFORMAS (International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support). As explained in the overview article by Swinburn and colleagues, INFORMAS has a compelling rationale and has set forth clear objectives, outcomes, principles and frameworks for monitoring and benchmarking key aspects of food environments and the policies and actions that influence the healthiness of food environments. This summary highlights the proposed monitoring approaches for the 10 interrelated INFORMAS modules: public and private sector policies and actions; key aspects of food environments (food composition, labelling, promotion, provision, retail, prices, and trade and investment) and population outcomes (diet quality). This ambitious effort should be feasible when approached in a step-wise manner, taking into account existing monitoring efforts, data sources, country contexts and capacity, and when adequately resourced. After protocol development and pilot testing of the modules, INFORMAS aims to be a sustainable, low-cost monitoring framework. Future directions relate to institutionalization, implementation and, ultimately, to leveraging INFORMAS data in ways that will bring key drivers of food environments into alignment with public health goals. © 2013 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of the International Association for the Study of Obesity.

7. april 2005 inter-departmental directive on the actions of public authority in case of event leading to an emergency radiological situation (1)

International Nuclear Information System (INIS)

2005-01-01

This directive concerns the management of a nuclear crisis. A correct information of Public Authorities is necessary at every level in order that actions to be lead can be in agreement with the situation. The protection of person, possessions and environment is the priority objective of Publics Authorities. This imperative is taken into account by the modalities exposed in the present directive, that determines the frame of the Public Authorities organization as well as the arrangements to take by Authorities in case of nuclear event. (N.C.)

Abstract Representations of Object-Directed Action in the Left Inferior Parietal Lobule.

Science.gov (United States)

Chen, Quanjing; Garcea, Frank E; Jacobs, Robert A; Mahon, Bradford Z

2018-06-01

Prior neuroimaging and neuropsychological research indicates that the left inferior parietal lobule in the human brain is a critical substrate for representing object manipulation knowledge. In the present functional MRI study we used multivoxel pattern analyses to test whether action similarity among objects can be decoded in the inferior parietal lobule independent of the task applied to objects (identification or pantomime) and stimulus format in which stimuli are presented (pictures or printed words). Participants pantomimed the use of objects, cued by printed words, or identified pictures of objects. Classifiers were trained and tested across task (e.g., training data: pantomime; testing data: identification), stimulus format (e.g., training data: word format; testing format: picture) and specific objects (e.g., training data: scissors vs. corkscrew; testing data: pliers vs. screwdriver). The only brain region in which action relations among objects could be decoded across task, stimulus format and objects was the inferior parietal lobule. By contrast, medial aspects of the ventral surface of the left temporal lobe represented object function, albeit not at the same level of abstractness as actions in the inferior parietal lobule. These results suggest compulsory access to abstract action information in the inferior parietal lobe even when simply identifying objects.

The Mirror Neuron System and Action Recognition

Science.gov (United States)

Buccino, Giovanni; Binkofski, Ferdinand; Riggio, Lucia

2004-01-01

Mirror neurons, first described in the rostral part of monkey ventral premotor cortex (area F5), discharge both when the animal performs a goal-directed hand action and when it observes another individual performing the same or a similar action. More recently, in the same area mirror neurons responding to the observation of mouth actions have been…

Activation of peroxisome proliferator-activated receptor gamma by rosiglitazone increases sirt6 expression and ameliorates hepatic steatosis in rats.

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Soo Jin Yang

Full Text Available BACKGROUND: Sirt6 has been implicated in the regulation of hepatic lipid metabolism and the development of hepatic steatosis. The aim of this study was to address the potential role of Sirt6 in the protective effects of rosiglitazone (RGZ on hepatic steatosis. METHODS: To investigate the effect of RGZ on hepatic steatosis, rats were treated with RGZ (4 mg·kg⁻¹·day⁻¹ by stomach gavage for 6 weeks. The involvement of Sirt6 in the RGZ's regulation was evaluated by Sirt6 knockdown in AML12 mouse hepatocytes. RESULTS: RGZ treatment ameliorated hepatic lipid accumulation and increased expression of Sirt6, peroxisome proliferator-activated receptor gamma coactivtor-1-α (Ppargc1a/PGC1-α and Forkhead box O1 (Foxo1 in rat livers. AMP-activated protein kinase (AMPK phosphorylation was also increased by RGZ, accompanied by alterations in phosphorylation of LKB1. Interestingly, in free fatty acid-treated cells, Sirt6 knockdown increased hepatocyte lipid accumulation measured as increased triglyceride contents (p = 0.035, suggesting that Sirt6 may be beneficial in reducing hepatic fat accumulation. In addition, Sirt6 knockdown abolished the effects of RGZ on hepatocyte fat accumulation, mRNA and protein expression of Ppargc1a/PGC1-α and Foxo1, and phosphorylation levels of LKB1 and AMPK, suggesting that Sirt6 is involved in RGZ-mediated metabolic effects. CONCLUSION: Our results demonstrate that RGZ significantly decreased hepatic lipid accumulation, and that this process appeared to be mediated by the activation of the Sirt6-AMPK pathway. We propose Sirt6 as a possible therapeutic target for hepatic steatosis.

Magnetorotational Dynamo Action in the Shearing Box

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Walker, Justin; Boldyrev, Stanislav

2017-10-01

Magnetic dynamo action caused by the magnetorotational instability is studied in the shearing-box approximation with no imposed net magnetic flux. Consistent with recent studies, the dynamo action is found to be sensitive to the aspect ratio of the box: it is much easier to obtain in tall boxes (stretched in the direction normal to the disk plane) than in long boxes (stretched in the radial direction). Our direct numerical simulations indicate that the dynamo is possible in both cases, given a large enough magnetic Reynolds number. To explain the relatively larger effort required to obtain the dynamo action in a long box, we propose that the turbulent eddies caused by the instability most efficiently fold and mix the magnetic field lines in the radial direction. As a result, in the long box the scale of the generated strong azimuthal (stream-wise directed) magnetic field is always comparable to the scale of the turbulent eddies. In contrast, in the tall box the azimuthal magnetic flux spreads in the vertical direction over a distance exceeding the scale of the turbulent eddies. As a result, different vertical sections of the tall box are permeated by large-scale nonzero azimuthal magnetic fluxes, facilitating the instability. NSF AGS-1261659, Vilas Associates Award, NSF-Teragrid Project TG-PHY110016.

Infants Show Stability of Goal-Directed Imitation

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Sakkalou, Elena; Ellis-Davies, Kate; Fowler, Nia C.; Hilbrink, Elma E.; Gattis, Merideth

2013-01-01

Previous studies have reported that infants selectively reproduce observed actions and have argued that this selectivity reflects understanding of intentions and goals, or goal-directed imitation. We reasoned that if selective imitation of goal-directed actions reflects understanding of intentions, infants should demonstrate stability across…

Action Research as a Network

DEFF Research Database (Denmark)

Boulus-Rødje, Nina

2012-01-01

This paper explores roles and interventions in IS action research. I draw upon a four-year research project about electronic medical records, conducted in close collaboration with a community partner. Following a self-reflexive stance, I trace the trajectory of the research engagement...... and the different roles I occupied. To better understand the complex nature of collaboration found within action research projects, I propose conceptualizing action research as a network. The network framework directs our attention to the collective production and the conditions through which roles...... this influences the researcher’s agency....

Rosiglitazone

Science.gov (United States)

... manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye ...

The Action Observation System when Observing Hand Actions in Autism and Typical Development.

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Pokorny, Jennifer J; Hatt, Naomi V; Colombi, Costanza; Vivanti, Giacomo; Rogers, Sally J; Rivera, Susan M

2015-06-01

Social impairments in individuals with autism spectrum disorders (ASD) may be in part due to difficulty perceiving and recognizing the actions of others. Evidence from imitation studies, which involves both observation and execution of an action, suggests differences, in individuals with ASD, between the ability to imitate goal-directed actions involving objects (transitive actions) and the ability to imitate actions that do not involve objects (intransitive actions). In the present study, we examined whether there were differences in how ASD adolescents encoded transitive and intransitive actions compared to typically developing (TD) adolescents, by having participants view videos of a hand reaching across a screen toward an object or to where an object would be while functional magnetic resonance images were collected. Analyses focused on areas within the action observation network (AON), which is activated during the observation of actions performed by others. We hypothesized that the AON would differentiate transitive from intransitive actions only in the ASD group. However, results revealed that object presence modulated activity in the right inferior frontal gyrus and supramarginal gyrus of the TD group, a differentiation that was not seen in the ASD group. Furthermore, there were no significant group differences between the TD and ASD groups in any of the conditions. This suggests that there is not a global deficit of the AON in individuals with ASD while observing transitive and intransitive actions. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

The Neurobiology of Collective Action

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Paul Joseph Zak

2013-11-01

Full Text Available This essay introduces a neurologically-informed mathematical model of collective action that reveals the role for empathy and distress in motivating costly helping behaviors. We report three direct tests of model with a key focus on the neuropeptide oxytocin as well as a variety of indirect tests. These studies, from our lab and other researchers, show support for the model. Our findings indicate that empathic concern, via the brain's release of oxytocin, is a trigger for collective action. We discuss the implications from this model for our understanding why human beings engage in costly collective action.

Differential Effects of Systemic Cholinergic Receptor Blockade on Pavlovian Incentive Motivation and Goal-Directed Action Selection

Science.gov (United States)

Ostlund, Sean B; Kosheleff, Alisa R; Maidment, Nigel T

2014-01-01

Reward-seeking actions can be guided by external cues that signal reward availability. For instance, when confronted with a stimulus that signals sugar, rats will prefer an action that produces sugar over a second action that produces grain pellets. Action selection is also sensitive to changes in the incentive value of potential rewards. Thus, rats that have been prefed a large meal of sucrose will prefer a grain-seeking action to a sucrose-seeking action. The current study investigated the dependence of these different aspects of action selection on cholinergic transmission. Hungry rats were given differential training with two unique stimulus-outcome (S1-O1 and S2-O2) and action-outcome (A1-O1 and A2-O2) contingencies during separate training phases. Rats were then given a series of Pavlovian-to-instrumental transfer tests, an assay of cue-triggered responding. Before each test, rats were injected with scopolamine (0, 0.03, or 0.1 mg/kg, intraperitoneally), a muscarinic receptor antagonist, or mecamylamine (0, 0.75, or 2.25 mg/kg, intraperitoneally), a nicotinic receptor antagonist. Although the reward-paired cues were capable of biasing action selection when rats were tested off-drug, both anticholinergic treatments were effective in disrupting this effect. During a subsequent round of outcome devaluation testing—used to assess the sensitivity of action selection to a change in reward value—we found no effect of either scopolamine or mecamylamine. These results reveal that cholinergic signaling at both muscarinic and nicotinic receptors mediates action selection based on Pavlovian reward expectations, but is not critical for flexibly selecting actions using current reward values. PMID:24370780

Dissociable brain systems mediate vicarious learning of stimulus-response and action-outcome contingencies.

Science.gov (United States)

Liljeholm, Mimi; Molloy, Ciara J; O'Doherty, John P

2012-07-18

Two distinct strategies have been suggested to support action selection in humans and other animals on the basis of experiential learning: a goal-directed strategy that generates decisions based on the value and causal antecedents of action outcomes, and a habitual strategy that relies on the automatic elicitation of actions by environmental stimuli. In the present study, we investigated whether a similar dichotomy exists for actions that are acquired vicariously, through observation of other individuals rather than through direct experience, and assessed whether these strategies are mediated by distinct brain regions. We scanned participants with functional magnetic resonance imaging while they performed an observational learning task designed to encourage either goal-directed encoding of the consequences of observed actions, or a mapping of observed actions to conditional discriminative cues. Activity in different parts of the action observation network discriminated between the two conditions during observational learning and correlated with the degree of insensitivity to outcome devaluation in subsequent performance. Our findings suggest that, in striking parallel to experiential learning, neural systems mediating the observational acquisition of actions may be dissociated into distinct components: a goal-directed, outcome-sensitive component and a less flexible stimulus-response component.

Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

Directory of Open Access Journals (Sweden)

Sabrina Le Bouter

2010-01-01

Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

Taking off the square root of Nambu-Goto action and obtaining Filippov-Lie algebra gauge theory action

International Nuclear Information System (INIS)

Park, Jeong-Hyuck; Sochichiu, Corneliu

2009-01-01

We propose a novel prescription to take off the square root of the Nambu-Goto action for a p-brane, which generalizes the Brink-Di Vecchia-Howe-Tucker, also known as the Polyakov method. With an arbitrary decomposition, d+n=p+1, our resulting action is a modified d-dimensional Polyakov action, which is gauged and possesses a Nambu n-bracket squared potential. We first spell out how the (p+1)-dimensional diffeomorphism is realized in the lower dimensional action. Then we discuss a possible gauge fixing of it to a direct product of d-dimensional diffeomorphism and n-dimensional volume preserving diffeomorphism. We show that the latter naturally leads to a novel Filippov-Lie n-algebra based gauge theory action in d dimensions. (orig.)

Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action

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Carvalho Poyraz, Fernanda; Holzner, Eva; Bailey, Matthew R.; Meszaros, Jozsef; Kenney, Lindsay; Kheirbek, Mazen A.

2016-01-01

Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal “no-go” pathway. To this end, we expressed the Gαi-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal-directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization. SIGNIFICANCE STATEMENT Motivation involves a directional component that allows subjects to efficiently select the behavior that will lead to an optimal outcome and an activational component that initiates and maintains the vigor and persistence of actions. Striatal output pathways modulate motivated behavior, but it remains unknown how these pathways regulate specific

Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action.

Science.gov (United States)

Carvalho Poyraz, Fernanda; Holzner, Eva; Bailey, Matthew R; Meszaros, Jozsef; Kenney, Lindsay; Kheirbek, Mazen A; Balsam, Peter D; Kellendonk, Christoph

2016-06-01

Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal "no-go" pathway. To this end, we expressed the Gαi-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N-oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal-directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization. Motivation involves a directional component that allows subjects to efficiently select the behavior that will lead to an optimal outcome and an activational component that initiates and maintains the vigor and persistence of actions. Striatal output pathways modulate motivated behavior, but it remains unknown how these pathways regulate specific components of motivation. Here

Retinaldehyde dehydrogenase 1 deficiency inhibits PPARγ-mediated bone loss and marrow adiposity.

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Nallamshetty, Shriram; Le, Phuong T; Wang, Hong; Issacsohn, Maya J; Reeder, David J; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Rosen, Clifford J; Plutzky, Jorge

2014-10-01

PPARγ, a ligand-activated nuclear receptor, regulates fundamental aspects of bone homeostasis and skeletal remodeling. PPARγ-activating anti-diabetic thiazolidinediones in clinical use promote marrow adiposity, bone loss, and skeletal fractures. As such, delineating novel regulatory pathways that modulate the action of PPARγ, and its obligate heterodimeric partner RXR, may have important implications for our understanding and treatment of disorders of low bone mineral density. We present data here establishing retinaldehyde dehydrogenase 1 (Aldh1a1) and its substrate retinaldehyde (Rald) as novel determinants of PPARγ-RXR actions in the skeleton. When compared to wild type (WT) controls, retinaldehyde dehydrogenase-deficient (Aldh1a1(-/-)) mice were protected against bone loss and marrow adiposity induced by either the thiazolidinedione rosiglitazone or a high fat diet, both of which potently activate the PPARγ-RXR complex. Consistent with these results, Rald, which accumulates in vivo in Aldh1a1(-/-) mice, protects against rosiglitazone-mediated inhibition of osteoblastogenesis in vitro. In addition, Rald potently inhibits in vitro adipogenesis and osteoclastogenesis in WT mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) respectively. Primary Aldh1a1(-/-) HSCs also demonstrate impaired osteoclastogenesis in vitro compared to WT controls. Collectively, these findings identify Rald and retinoid metabolism through Aldh1a1 as important novel modulators of PPARγ-RXR transactivation in the marrow niche. Copyright © 2014 Elsevier Inc. All rights reserved.

Organotins Are Potent Activators of PPARγ and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

Science.gov (United States)

Yanik, Susan C.; Baker, Amelia H.; Mann, Koren K.; Schlezinger, Jennifer J.

2011-01-01

Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazone, a PPARγ agonist, bexarotene, an RXR agonist, or a series of organotins. Rosiglitazone and bexarotene potently activated adipocyte differentiation; however, bexarotene had a maximal efficacy of only 20% of that induced by rosiglitazone. Organotins (tributyltin [TBT], triphenyltin, and dibutyltin) also stimulated adipocyte differentiation (EC50 of 10–20nM) but with submaximal, structure-dependent efficacy. In coexposures, both bexarotene and TBT enhanced rosiglitazone-induced adipogenesis. To investigate the contribution of PPARγ to TBT-induced adipogenesis, we examined expression of PPARγ2, as well as its transcriptional target FABP4. TBT-induced PPARγ2 and FABP4 protein expression with an efficacy intermediate between rosiglitazone and bexarotene, similar to lipid accumulation. A PPARγ antagonist and PPARγ-specific small hairpin RNA suppressed TBT-induced differentiation, although to a lesser extent than rosiglitazone-induced differentiation, suggesting that TBT may engage alternate pathways. TBT and bexarotene, but not rosiglitazone, also induced the expression of TGM2 (an RXR target) and ABCA1 (a liver X receptor target). The results show that an environmental contaminant, acting with the same potency as a therapeutic drug, induces PPARγ-dependent adipocyte differentiation in bone marrow MSCs. Activation of multiple nuclear receptor pathways by organotins may have significant implications for bone physiology. PMID:21622945

Multi-objective optimization strategy based on desirability functions used for electrophoratic separation and quantification of rosiglitazone and glimepiride in plasma and formulations.

Science.gov (United States)

Hefnawy, Mohamed M; Sultan, Maha A; Al-Johar, Haya I; Kassem, Mohamed G; Aboul-Enein, Hassan Y

2012-01-01

Multiple response simultaneous optimization employing Derringer's desirability function was used for the development of a capillary electrophoresis method for the simultaneous determination of rosiglitazone (RSG) and glimepiride (GLM) in plasma and formulations. Twenty experiments, taking the two resolutions, the analysis time, and the capillary current as the responses with three important factors--buffer morality, volte and column temperature--were used to design mathematical models. The experimental responses were fitted into a second order polynomial and the six responses were simultaneously optimized to predict the optimum conditions for the effective separation of the studied compounds. The separation was carried out by using capillary zone electrophoresis (CZE) with a silica capillary column and diode array detector at 210 nm. The optimum assay conditions were 52 mmol l⁻¹ phosphate buffer, pH 7, and voltage of 22 kV at 29 °C. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The assay limit of detection was 0.02 µg ml⁻¹ and the effective working range at relative standard deviation (RSD) of ≤ 5% was 0.05-16 µg ml⁻¹ (r = 0.999) for both drugs. Analytical recoveries of the studied drugs from spiked plasma were 97.2-101.9 ± 0.31-3.0%. The precision of the assay was satisfactory; RSD was 1.07 and 1.14 for intra- and inter-assay precision, respectively. The proposed method has a great value in routine analysis of RSG and GLM for its therapeutic monitoring and pharmacokinetic studies. Copyright © 2011 John Wiley & Sons, Ltd.

Direct analysis by time-of-flight secondary ion mass spectrometry reveals action of bacterial laccase-mediator systems on both hardwood and softwood samples.

Science.gov (United States)

Goacher, Robyn E; Braham, Erick J; Michienzi, Courtney L; Flick, Robert M; Yakunin, Alexander F; Master, Emma R

2017-12-29

The modification and degradation of lignin play a vital role in carbon cycling as well as production of biofuels and bioproducts. The possibility of using bacterial laccases for the oxidation of lignin offers a route to utilize existing industrial protein expression techniques. However, bacterial laccases are most frequently studied on small model compounds that do not capture the complexity of lignocellulosic materials. This work studied the action of laccases from Bacillus subtilis and Salmonella typhimurium (EC 1.10.3.2) on ground wood samples from yellow birch (Betula alleghaniensis) and red spruce (Picea rubens). The ability of bacterial laccases to modify wood can be facilitated by small molecule mediators. Herein, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), gallic acid and sinapic acid mediators were tested. Direct analysis of the wood samples was achieved by time-of-flight secondary ion mass spectrometry (ToF-SIMS), a surface sensitive mass spectrometry technique that has characteristic peaks for H, G and S lignin. The action of the bacterial laccases on both wood samples was demonstrated and revealed a strong mediator influence. The ABTS mediator led to delignification, evident in an overall increase of polysaccharide peaks in the residual solid, along with equal loss of G and S-lignin peaks. The gallic acid mediator demonstrated minimal laccase activity. Meanwhile, the sinapic acid mediator altered the S/G peak ratio consistent with mediator attaching to the wood solids. The current investigation demonstrates the action of bacterial laccase-mediator systems directly on woody materials, and the potential of using ToF-SIMS to uncover the fundamental and applied role of bacterial enzymes in lignocellulose conversion. © 2017 Scandinavian Plant Physiology Society.

Interdisciplinarity in Vocational Guidance: An Action Theory Perspective

Science.gov (United States)

Valach, Ladislav; Young, Richard A.

2009-01-01

In addressing the issue of interdisciplinary research in vocational guidance, twelve propositions important for understanding the vocational guidance process as joint, goal-directed action are presented. They address the encounter between client and counsellor leading to relational ethics, the relevance of everyday action theory and methods for…

Environmental health action plan for Europe

International Nuclear Information System (INIS)

1994-06-01

This Environmental Health Action Plan for Europe was endorsed by the second European Conference on Environment and Health, held in Helsinki, 20 to 22 June 1994. It sets out directions for the attainment of long term environment and health policy objectives define in the European Charter on Environment and Health. The Action Plan is primarily addressed at the public health and environmental protection sectors. 10 refs, 4 figs, 2 tabs

Motivating women and men to take protective action against rape: examining direct and indirect persuasive fear appeals.

Science.gov (United States)

Morrison, Kelly

2005-01-01

This article examines the effectiveness of persuasive fear appeals in motivating women to enroll in self-defense classes to take protective action against rape. Witte's extended parallel process model is used as a framework to examine the relations between perceived invulnerability, perceived fear, and fear control processes. Because women may perceive invulnerability to rape, persuasive fear appeals targeted toward them may be ineffective in achieving attitude, intention, and behavioral change toward protecting themselves. One possible solution is to persuade men to talk with women about whom they care. Results indicated that women did not perceive invulnerability to rape, and although there was no differential impact between high- and low-threat messages, women did report positive intention and behaviors in response to direct fear appeals. Moreover, men reported positive intention and behaviors in response to indirect fear appeals.

Linking perception and action by structure or process? Toward an integrative perspective.

Science.gov (United States)

Herwig, Arvid

2015-05-01

Over the past decades cognitive neuroscience's renewed interest in action has intensified the search of principles explaining how the cognitive system links perception to action and vice versa. To date, at least two seemingly alternative approaches can be distinguished. Perception and action might be linked either by common representational structures, as assumed by the ideomotor approach, or by common attentional processes, as assumed by the attention approach. This article first reviews the evidence from different paradigms supporting each approach. It becomes clear that most studies selectively focus either on actions directed at goals outside the actors' perceptual range (supporting the ideomotor approach) or on actions directed at targets within the actors' perceptual range (supporting the attention approach). In a second step, I will try to reconcile both approaches by reviewing recent eye movement studies that abolish the classical combination of approach and goals under study. Demonstrating that both approaches cover target- as well as goal-directed actions, it is proposed that operations addressed in both conceptual frameworks interact with each other. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exercise Regulation of Marrow Adipose Tissue

Directory of Open Access Journals (Sweden)

Gabriel M Pagnotti

2016-07-01

Full Text Available Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally-supportive tissues, inhibits bone resorption and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot, or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a 5-fold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

Reafferent copies of imitated actions in the right superior temporal cortex

Science.gov (United States)

Iacoboni, Marco; Koski, Lisa M.; Brass, Marcel; Bekkering, Harold; Woods, Roger P.; Dubeau, Marie-Charlotte; Mazziotta, John C.; Rizzolatti, Giacomo

2001-01-01

Imitation is a complex phenomenon, the neural mechanisms of which are still largely unknown. When individuals imitate an action that already is present in their motor repertoire, a mechanism matching the observed action onto an internal motor representation of that action should suffice for the purpose. When one has to copy a new action, however, or to adjust an action present in one's motor repertoire to a different observed action, an additional mechanism is needed that allows the observer to compare the action made by another individual with the sensory consequences of the same action made by himself. Previous experiments have shown that a mechanism that directly matches observed actions on their motor counterparts exists in the premotor cortex of monkeys and humans. Here we report the results of functional magnetic resonance experiments, suggesting that in the superior temporal sulcus, a higher order visual region, there is a sector that becomes active both during hand action observation and during imitation even in the absence of direct vision of the imitator's hand. The motor-related activity is greater during imitation than during control motor tasks. This newly identified region has all the requisites for being the region at which the observed actions, and the reafferent motor-related copies of actions made by the imitator, interact. PMID:11717457

Direct marketing

Directory of Open Access Journals (Sweden)

Čičić Muris

2002-01-01

Full Text Available Direct Marketing (DM is usually treated as unworthy activity, with actions at the edge of legality and activities minded cheating. Despite obvious problems regarding ethics and privacy threat, DM with its size, importance and role in a concept of integrated marketing communication deserves respect and sufficient analysis and review

Intact and Impaired Mechanisms of Action Understanding in Autism

Science.gov (United States)

Vivanti, Giacomo; McCormick, Carolyn; Young, Gregory S.; Abucayan, Floridette; Hatt, Naomi; Nadig, Aparna; Ozonoff, Sally; Rogers, Sally J.

2016-01-01

Typically developing children understand and predict others’ behavior by extracting and processing relevant information such as the logic of their actions within the situational constraints and the intentions conveyed by their gaze direction and emotional expressions. Children with autism have difficulties understanding and predicting others’ actions. With the use of eye tracking and behavioral measures, we investigated action understanding mechanisms used by 18 children with autism and a well-matched group of 18 typically developing children. Results showed that children with autism (a) consider situational constraints in order to understand the logic of an agent’s action and (b) show typical usage of the agent’s emotional expressions to infer his or her intentions. We found (c) subtle atypicalities in the way children with autism respond to an agent’s direct gaze and (d) marked impairments in their ability to attend to and interpret referential cues such as a head turn for understanding an agent’s intentions. PMID:21401220

Efficacy of peroxisome proliferator activated receptor agonist in the treatment of virus-associated haemophagocytic syndrome in a rabbit model.

Science.gov (United States)

Hsieh, Wen-Chuan; Lan, Bau-Shin; Chen, Yi-Ling; Chang, Yao; Chuang, Huai-Chia; Su, Ih-Jen

2010-01-01

Virus-associated haemophagocytic syndrome (VAHS) is a fatal complication of viral infections, such as Epstein-Barr virus and H5N1 influenza, that results from macrophage activation and pro inflammatory cytokine injuries. The high comorbidity and mortality of current therapy urgently demands an ideal agent based on VAHS pathogenesis. Peroxisome proliferator activated receptor (PPAR) agonists, regulators of metabolic syndrome, can exhibit immunomodulatory effects on macrophage activation and cytokine secretion. In this study, we adopted rosiglitazone, a PPAR-gamma agonist, for VAHS control in a Herpesvirus papio (HVP)-infected rabbit model. Various doses of rosiglitazone were orally administered to rabbits on day 7 or day 20 after intravenous challenge with 5 x 10(7) copies of HVP. The rabbits that received 4 mg/day rosiglitazone had significantly increased survival when treated at an early stage of infection (P<0.01), whereas a higher dose (8 mg/day) was required at the advanced stage of the disease (P<0.05). All rosiglitazone-treated rabbits had significantly improved laboratory parameters and plasma tumour necrosis factor-alpha levels. Importantly, rosiglitazone could also inhibit viral replication in vitro and in vivo. PPAR agonists could represent a potentially new agent for the therapy of VAHS.

Action video game training reduces the Simon Effect.

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Hutchinson, Claire V; Barrett, Doug J K; Nitka, Aleksander; Raynes, Kerry

2016-04-01

A number of studies have shown that training on action video games improves various aspects of visual cognition including selective attention and inhibitory control. Here, we demonstrate that action video game play can also reduce the Simon Effect, and, hence, may have the potential to improve response selection during the planning and execution of goal-directed action. Non-game-players were randomly assigned to one of four groups; two trained on a first-person-shooter game (Call of Duty) on either Microsoft Xbox or Nintendo DS, one trained on a visual training game for Nintendo DS, and a control group who received no training. Response times were used to contrast performance before and after training on a behavioral assay designed to manipulate stimulus-response compatibility (the Simon Task). The results revealed significantly faster response times and a reduced cost of stimulus-response incompatibility in the groups trained on the first-person-shooter game. No benefit of training was observed in the control group or the group trained on the visual training game. These findings are consistent with previous evidence that action game play elicits plastic changes in the neural circuits that serve attentional control, and suggest training may facilitate goal-directed action by improving players' ability to resolve conflict during response selection and execution.

Finite action for Chern-Simons Ads gravity

Energy Technology Data Exchange (ETDEWEB)

Mora, P.; Olea, R.; Troncoso, R.; Zanelli, J. E-mail: jz@cecs.cl

2004-06-01

A finite principle for Chern-Simons AdS gravity is presented. The construction is carried out in detail first in five dimensions, where the bulk action is given by a particular combination of the Einstein-Hilbert action with negative cosmological constant and a Gauss-Bonnet term; and is then generalized for arbitrary odd dimensions. The boundary term needed to render the action finite is singled out demanding the action to attain an extremum for an appropriate set of boundary conditions. The boundary term is a local function of the fields at the boundary and is sufficient to render the action finite for asymptotically AdS solutions, without requiring background fields. It is shown that the Euclidean continuation of the action correctly describes black hole thermodynamics in the canonical ensemble. Additionally, background independent conserved charges associated with the asymptotic symmetries can be written as surface integrals by direct application of Noether's theorem. (author)

Corrective Action Decision Document for Corrective Action Unit 417: Central Nevada Test Area Surface, Nevada

International Nuclear Information System (INIS)

1999-01-01

This Corrective Action Decision Document (CADD) identifies and rationalizes the U.S. Department of Energy, Nevada Operations Office's selection of a recommended corrective action alternative (CAA) appropriate to facilitate the closure of Corrective Action Unit (CAU) 417: Central Nevada Test Area Surface, Nevada, under the Federal Facility Agreement and Consent Order. Located in Hot Creek Valley in Nye County, Nevada, and consisting of three separate land withdrawal areas (UC-1, UC-3, and UC-4), CAU 417 is comprised of 34 corrective action sites (CASs) including 2 underground storage tanks, 5 septic systems, 8 shaker pad/cuttings disposal areas, 1 decontamination facility pit, 1 burn area, 1 scrap/trash dump, 1 outlier area, 8 housekeeping sites, and 16 mud pits. Four field events were conducted between September 1996 and June 1998 to complete a corrective action investigation indicating that the only contaminant of concern was total petroleum hydrocarbon (TPH) which was found in 18 of the CASs. A total of 1,028 samples were analyzed. During this investigation, a statistical approach was used to determine which depth intervals or layers inside individual mud pits and shaker pad areas were above the State action levels for the TPH. Other related field sampling activities (i.e., expedited site characterization methods, surface geophysical surveys, direct-push geophysical surveys, direct-push soil sampling, and rotosonic drilling located septic leachfields) were conducted in this four-phase investigation; however, no further contaminants of concern (COCs) were identified. During and after the investigation activities, several of the sites which had surface debris but no COCs were cleaned up as housekeeping sites, two septic tanks were closed in place, and two underground storage tanks were removed. The focus of this CADD was to identify CAAs which would promote the prevention or mitigation of human exposure to surface and subsurface soils with contaminant

Action adaptation during natural unfolding social scenes influences action recognition and inferences made about actor beliefs.

Science.gov (United States)

Keefe, Bruce D; Wincenciak, Joanna; Jellema, Tjeerd; Ward, James W; Barraclough, Nick E

2016-07-01

When observing another individual's actions, we can both recognize their actions and infer their beliefs concerning the physical and social environment. The extent to which visual adaptation influences action recognition and conceptually later stages of processing involved in deriving the belief state of the actor remains unknown. To explore this we used virtual reality (life-size photorealistic actors presented in stereoscopic three dimensions) to see how visual adaptation influences the perception of individuals in naturally unfolding social scenes at increasingly higher levels of action understanding. We presented scenes in which one actor picked up boxes (of varying number and weight), after which a second actor picked up a single box. Adaptation to the first actor's behavior systematically changed perception of the second actor. Aftereffects increased with the duration of the first actor's behavior, declined exponentially over time, and were independent of view direction. Inferences about the second actor's expectation of box weight were also distorted by adaptation to the first actor. Distortions in action recognition and actor expectations did not, however, extend across different actions, indicating that adaptation is not acting at an action-independent abstract level but rather at an action-dependent level. We conclude that although adaptation influences more complex inferences about belief states of individuals, this is likely to be a result of adaptation at an earlier action recognition stage rather than adaptation operating at a higher, more abstract level in mentalizing or simulation systems.

Deference to the attorney general? The probability of success of the AG on the direct actions of unconstitutionality

Directory of Open Access Journals (Sweden)

Ivar Alberto Martins Hartmann

2016-01-01

Full Text Available The Brazilian equivalent of the Attorney General, as a brief historical analysis shows, plays an essential role in concentrated constitutional review. However, empirical studies of its performance remain scarce. Our goal is to test the AGs track record in Direct Actions of Unconstitutionality (ADIs at the Brazilian Supreme Court. We use a data set obtained from the Supreme Court in Numbers project’s database in order to run regressions with different models. The hypothesis we tested is that there is no statistically significant relationship between the performance of the AG as plaintiff in concentrated constitutional review and the outcome of the cases. This hypothesis was found to be disproved:  ADIs started by the AG, as well as those proposed by representatives of the Executive branch, have, in fact, greater statistical probability of success.

78 FR 53635 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-08-30

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Airbus Model A330-200 and... Sec. 39.13 by adding the following new airworthiness directive (AD): 2013-17-03 Airbus: Amendment 39...

Action-Specific Influences on Perception and Post-Perceptual Processes: Present Controversies and Future Directions

Science.gov (United States)

Philbeck, John W.; Witt, Jessica K.

2015-01-01

The action-specific perception account holds that people perceive the environment in terms of their ability to act in it. In this view, for example, decreased ability to climb a hill due to fatigue makes the hill visually appear to be steeper. Though influential, this account has not been universally accepted, and in fact a heated controversy has emerged. The opposing view holds that action capability has little or no influence on perception. Heretofore, the debate has been quite polarized, with efforts largely being focused on supporting one view and dismantling the other. We argue here that polarized debate can impede scientific progress and that the search for similarities between two sides of a debate can sharpen the theoretical focus of both sides and illuminate important avenues for future research. In this paper, we present a synthetic review of this debate, drawing from the literatures of both approaches, to clarify both the surprising similarities and the core differences between them. We critically evaluate existing evidence, discuss possible mechanisms of action-specific effects, and make recommendations for future research. A primary focus of future work will involve not only the development of methods that guard against action-specific post-perceptual effects, but also development of concrete, well-constrained underlying mechanisms. The criteria for what constitutes acceptable control of post-perceptual effects and what constitutes an appropriately specific mechanism vary between approaches, and bridging this gap is a central challenge for future research. PMID:26501227

Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

International Nuclear Information System (INIS)

Hu, Dan; Wu, Chun-qi; Li, Ze-jun; Liu, Yue; Fan, Xing; Wang, Quan-jun; Ding, Ri-gao

2015-01-01

Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity

Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

Energy Technology Data Exchange (ETDEWEB)

Hu, Dan; Wu, Chun-qi [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Li, Ze-jun [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Guang Dong Pharmaceutical University, Guangzhou 510006 (China); Liu, Yue; Fan, Xing [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Wang, Quan-jun, E-mail: wangquanjunbeijing@163.com [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China); Ding, Ri-gao, E-mail: dingrigao@nic.bmi.ac.cn [State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850 (China)

2015-04-15

Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity.

Culture-specific familiarity equally mediates action representations across cultures.

Science.gov (United States)

Umla-Runge, Katja; Fu, Xiaolan; Wang, Lamei; Zimmer, Hubert D

2014-01-01

Previous studies have shown that we need to distinguish between means and end information about actions. It is unclear how these two subtypes of action information relate to each other with theoretical accounts postulating the superiority of end over means information and others linking separate means and end routes of processing to actions of differential meaningfulness. Action meaningfulness or familiarity differs between cultures. In a cross-cultural setting, we investigated how action familiarity influences recognition memory for means and end information. Object directed actions of differential familiarity were presented to Chinese and German participants. Action familiarity modulated the representation of means and end information in both cultures in the same way, although the effects were based on different stimulus sets. Our results suggest that, in the representation of actions in memory, end information is superordinate to means information. This effect is independent of culture whereas action familiarity is not.

Influence of verbal instructions on effect-based action control.

Science.gov (United States)

Eder, Andreas B; Dignath, David

2017-03-01

According to ideomotor theory, people use bidirectional associations between movements and their effects for action selection and initiation. Our experiments examined how verbal instructions of action effects influence response selection without prior experience of action effects in a separate acquisition phase. Instructions for different groups of participants specified whether they should ignore, attend, learn, or intentionally produce acoustic effects produced by button presses. Results showed that explicit instructions of action-effect relations trigger effect-congruent action tendencies in the first trials following the instruction; in contrast, no evidence for effect-based action control was observed in these trials when instructions were to ignore or to attend to the action effects. These findings show that action-effect knowledge acquired through verbal instruction and direct experience is similarly effective for effect-based action control as long as the relation between the movement and the effect is clearly spelled out in the instruction.

Training Of Manual Actions Improves Language Understanding of Semantically-Related Action Sentences

Directory of Open Access Journals (Sweden)

Matteo eLocatelli

2012-12-01

Full Text Available Conceptual knowledge accessed by language may involve the re-activation of the associated primary sensory-motor processes. Whether these embodied representations are indeed constitutive to conceptual knowledge is hotly debated, particularly since direct evidence that sensory-motor expertise can improve conceptual processing is scarce.In this study, we sought for this crucial piece of evidence, by training naive healthy subjects to perform complex manual actions and by measuring, before and after training, their performance in a semantic language task. 19 participants engaged in 3 weeks of motor training. Each participant was trained in 3 complex manual actions (e.g. origami. Before and after the training period, each subject underwent a series of manual dexterity tests and a semantic language task. The latter consisted of a sentence-picture semantic congruency judgment task, with 6 target congruent sentence-picture pairs (semantically related to the trained manual actions, 6 non-target congruent pairs (semantically unrelated, and 12 filler incongruent pairs.Manual action training induced a significant improvement in all manual dexterity tests, demonstrating the successful acquisition of sensory-motor expertise. In the semantic language task, the reaction times to both target and non-target congruent sentence-image pairs decreased after action training, indicating a more efficient conceptual-semantic processing. Noteworthy, the reaction times for target pairs decreased more than those for non-target pairs, as indicated by the 2x2 interaction. These results were confirmed when controlling for the potential bias of increased frequency of use of target lexical items during manual training.The results of the present study suggest that sensory-motor expertise gained by training of specific manual actions can lead to an improvement of cognitive-linguistic skills related to the specific conceptual-semantic domain associated to the trained actions.

Rosiglitazone inhibits metastasis development of a murine mammary tumor cell line LMM3

International Nuclear Information System (INIS)

Magenta, Gabriela; Borenstein, Ximena; Rolando, Romina; Jasnis, María Adela

2008-01-01

Activation of peroxisome proliferator-activated receptors γ (PPARγ) induces diverse effects on cancer cells. The thiazolidinediones (TZDs), such as troglitazone and ciglitazone, are PPARγ agonists exhibiting antitumor activities; however, the underlying mechanism remains inconclusive. Rosiglitazone (RGZ), a synthetic ligand of PPARγ used in the treatment of Type 2 diabetes, inhibits growth of some tumor cells and is involved in other processes related to cancer progression. Opposing results have also been reported with different ligands on tumor cells. The purpose of this study was to determine if RGZ and 15d-PGJ 2 induce antitumor effects in vivo and in vitro on the murine mammary tumor cell line LMM3. The effect on LMM3 cell viability and nitric oxide (NO) production of different doses of RGZ, 15-dPGJ 2 , BADGE and GW9662 were determined using the MTS colorimetric assay and the Griess reaction respectively. In vivo effect of orally administration of RGZ on tumor progression was evaluated either on s.c. primary tumors as well as on experimental metastasis. Cell adhesion, migration (wound assay) and invasion in Transwells were performed. Metalloproteinase activity (MMP) was determined by zymography in conditioned media from RGZ treated tumor cells. PPARγ expression was detected by inmunohistochemistry in formalin fixed tumors and by western blot in tumor cell lysates. RGZ orally administered to tumor-bearing mice decreased the number of experimental lung metastases without affecting primary s.c. tumor growth. Tumor cell adhesion and migration, as well as metalloproteinase MMP-9 activity, decreased in the presence of 1 μM RGZ (non-cytotoxic dose). RGZ induced PPARγ protein expression in LMM3 tumors. Although metabolic activity -measured by MTS assay- diminished with 1–100 μM RGZ, 1 μM-treated cells recovered their proliferating capacity while 100 μM treated cells died. The PPARγ antagonist Biphenol A diglicydyl ether (BADGE) did not affect RGZ activity

'Action 2016': AREVA's strategic action plan

International Nuclear Information System (INIS)

Marie, Patricia; Briand, Pauline; Floquet-Daubigeon, Fleur; Michaut, Maxime; De Scorbiac, Marie; Du Repaire, Philippine

2011-01-01

On December 13, 2011, Luc Oursel, CEO, and Pierre Aubouin, Chief Financial Officer presented the group's strategic plan for the period 2012-2016. The plan has been drawn up collectively and is based on a thorough-going analysis and a realistic assessment of perspectives for all group activities and associated resources. Development of nuclear and renewable energies: the fundamentals are unchanged. In this context, the German decision remains an isolated case and the great majority of nuclear programs around the world have been confirmed. More conservative in its projections than the International Energy Agency, the group expects growth of 2.2% annually, reaching 583 GW of installed nuclear capacity by 2030, against 378 GW today. However, the Fukushima accident will lead to delays in launching new programs. 'Action 2016' plan aims to consolidate AREVA's leadership in nuclear energy and become a leading player in renewable energy. The group's strategic action plan 'Action 2016' is based on the following strategic choices: - commercial priority given to value creation, - selectivity in investments, - strengthening of the financial structure. These demand an improvement in the group's performance by 2015. This plan makes nuclear safety a strategic priority for the industrial and commercial performance of the group. This ambitious performance plan for the period 2012-2016 will give the group the wherewithal to withstand a temporary slowdown in the market resulting from the Fukushima accident and to deliver safe and sustainable growth of the business. The plan sets out the strategic direction for the group's employees for the years ahead: taking advantage of the expected growth in nuclear and renewable energies, targeted investment programs, and return to self-financing as of 2014

Neural theory for the perception of causal actions.

Science.gov (United States)

Fleischer, Falk; Christensen, Andrea; Caggiano, Vittorio; Thier, Peter; Giese, Martin A

2012-07-01

The efficient prediction of the behavior of others requires the recognition of their actions and an understanding of their action goals. In humans, this process is fast and extremely robust, as demonstrated by classical experiments showing that human observers reliably judge causal relationships and attribute interactive social behavior to strongly simplified stimuli consisting of simple moving geometrical shapes. While psychophysical experiments have identified critical visual features that determine the perception of causality and agency from such stimuli, the underlying detailed neural mechanisms remain largely unclear, and it is an open question why humans developed this advanced visual capability at all. We created pairs of naturalistic and abstract stimuli of hand actions that were exactly matched in terms of their motion parameters. We show that varying critical stimulus parameters for both stimulus types leads to very similar modulations of the perception of causality. However, the additional form information about the hand shape and its relationship with the object supports more fine-grained distinctions for the naturalistic stimuli. Moreover, we show that a physiologically plausible model for the recognition of goal-directed hand actions reproduces the observed dependencies of causality perception on critical stimulus parameters. These results support the hypothesis that selectivity for abstract action stimuli might emerge from the same neural mechanisms that underlie the visual processing of natural goal-directed action stimuli. Furthermore, the model proposes specific detailed neural circuits underlying this visual function, which can be evaluated in future experiments.

Contribution of direct actions of the oxime HI-6 in reversing soman-induced muscle weakness in the rat diaphragm

Energy Technology Data Exchange (ETDEWEB)

Alder, M.; Maxwell, D.M.; Filbert, M.G.; Deshpande, S.S.

1994-12-31

The actions of the bispyridinium oxime HI-6 ((4-AMINOCARBONYL) PYRIDINO-methoxymethyl- 2-(HYDROXYIMINO)METHYL- pyridinium dichloride) were investigated in vitro on rat phrenic nerve-hemidiaphragm preparations. Isometric twitch and tetanic tensions were elicited at 37 deg C with supramaximal nerve stimulation at frequencies of 20 and 50 Hz. To approximate normal respiration patterns, trials consisting of 30 successive 0.55 5 trains were alternated with 1.25 5 rest periods. Under control conditions, the above stimulation pattern generated tensions that were well maintained at both frequencies. In contrast, a marked depression of muscle tension was observed in diaphragms removed from rats administered 339 ug/kg soman (3 LD50) and tested in vitro. Addition of HI-6, 4 h after soman exposure, led to a nearly complete recovery of muscle tension at 20 Hz. At 50 Hz, muscle tensions still declined especially when trains were elicited at 1.25 and 3 5 intervals. The recovery by HI-6 observed in this study appears to be mediated by mechanisms unrelated to acetylcholinesterase reactivation since no increase of enzymatic activity was detected and the effect was reversed by a brief washout in oxime-free physiological solution. The results suggest that the direct action of HI-6 may play a role in restoring soman-induced diaphragmatic failure but this effect would be significant primarily under low use conditions.

Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits.

Science.gov (United States)

Renteria, Rafael; Baltz, Emily T; Gremel, Christina M

2018-01-15

Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

12 CFR 567.4 - Capital directives.

Science.gov (United States)

2010-01-01

... requirement, the leverage ratio requirement, the tangible capital requirement, or individual minimum capital... capital directive, it may become effective immediately. A capital directive shall remain in effect and... plan shall continue in full force and effect. (b) Relation to other administrative actions. The Office...

Just do it: action-dependent learning allows sensory prediction.

Directory of Open Access Journals (Sweden)

Itai Novick

Full Text Available Sensory-motor learning is commonly considered as a mapping process, whereby sensory information is transformed into the motor commands that drive actions. However, this directional mapping, from inputs to outputs, is part of a loop; sensory stimuli cause actions and vice versa. Here, we explore whether actions affect the understanding of the sensory input that they cause. Using a visuo-motor task in humans, we demonstrate two types of learning-related behavioral effects. Stimulus-dependent effects reflect stimulus-response learning, while action-dependent effects reflect a distinct learning component, allowing the brain to predict the forthcoming sensory outcome of actions. Together, the stimulus-dependent and the action-dependent learning components allow the brain to construct a complete internal representation of the sensory-motor loop.

Impaired acquisition of goal-directed action in healthy aging

NARCIS (Netherlands)

de Wit, S.; van de Vijver, I.; Ridderinkhof, K.R.

2014-01-01

According to dual-system theories, instrumental learning is supported by dissociable goal-directed and habitual systems. Previous investigations of the dual-system balance in healthy aging have yielded mixed results. To further investigate this issue, we compared performance of young (17-24 years)

Habitual versus goal-directed action control in Parkinson disease

NARCIS (Netherlands)

de Wit, S.; Barker, R.A.; Dickinson, A.D.; Cools, R.

2011-01-01

This study presents the first direct investigation of the hypothesis that dopamine depletion of the dorsal striatum in mild Parkinson disease leads to impaired stimulus-response habit formation, thereby rendering behavior slow and effortful. However, using an instrumental conflict task, we show that

Neurons in primary motor cortex engaged during action observation.

Science.gov (United States)

Dushanova, Juliana; Donoghue, John

2010-01-01

Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These 'view' neurons were spatially intermingled with 'do' neurons, which are active only during movement performance. Simultaneously recorded 'view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. 'View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 'view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action.

Yukon Government climate change action plan

International Nuclear Information System (INIS)

2009-02-01

This Climate Change Action Plan described the measures that are being taken by the Yukon Government to adapt to, understand, and reduce contributions to climate change. The action plan is the result of input received from more than 100 individuals and organizations and provides clear direction for a strategy that will minimize the negative impacts of climate change and provide economic, social and other environmental benefits through climate change mitigation. The Yukon government has already taken many actions that respond to climate change, such as: developing the Yukon Cold Climate Innovation Centre; supporting the Northern Climate Exchange for public education and outreach; funding community recycling depots and other groups that reduce waste generation, promote public awareness and divert solid waste; and working with provincial and territorial counterparts to enhance national building standards. The main objectives of the climate change actions are to enhance knowledge and understanding of climate change; adapt to climate change; reduce greenhouse gas emissions; and lead Yukon action in response to climate change. tabs., figs.

Compensatory plasticity in the action observation network: virtual lesions of STS enhance anticipatory simulation of seen actions.

Science.gov (United States)

Avenanti, Alessio; Annella, Laura; Candidi, Matteo; Urgesi, Cosimo; Aglioti, Salvatore M

2013-03-01

Observation of snapshots depicting ongoing motor acts increases corticospinal motor excitability. Such motor facilitation indexes the anticipatory simulation of observed (implied) actions and likely reflects computations occurring in the parietofrontal nodes of a cortical network subserving action perception (action observation network, AON). However, direct evidence for the active role of AON in simulating the future of seen actions is lacking. Using a perturb-and-measure transcranial magnetic stimulation (TMS) approach, we show that off-line TMS disruption of regions within (inferior frontal cortex, IFC) and upstream (superior temporal sulcus, STS) the parietofrontal AON transiently abolishes and enhances the motor facilitation to observed implied actions, respectively. Our findings highlight the critical role of IFC in anticipatory motor simulation. More importantly, they show that disruption of STS calls into play compensatory motor simulation activity, fundamental for counteracting the noisy visual processing induced by TMS. Thus, short-term plastic changes in the AON allow motor simulation to deal with any gap or ambiguity of ever-changing perceptual worlds. These findings support the active, compensatory, and predictive role of frontoparietal nodes of the AON in the perception and anticipatory simulation of implied actions.

Statistical learning in social action contexts.

Science.gov (United States)

Monroy, Claire; Meyer, Marlene; Gerson, Sarah; Hunnius, Sabine

2017-01-01

Sensitivity to the regularities and structure contained within sequential, goal-directed actions is an important building block for generating expectations about the actions we observe. Until now, research on statistical learning for actions has solely focused on individual action sequences, but many actions in daily life involve multiple actors in various interaction contexts. The current study is the first to investigate the role of statistical learning in tracking regularities between actions performed by different actors, and whether the social context characterizing their interaction influences learning. That is, are observers more likely to track regularities across actors if they are perceived as acting jointly as opposed to in parallel? We tested adults and toddlers to explore whether social context guides statistical learning and-if so-whether it does so from early in development. In a between-subjects eye-tracking experiment, participants were primed with a social context cue between two actors who either shared a goal of playing together ('Joint' condition) or stated the intention to act alone ('Parallel' condition). In subsequent videos, the actors performed sequential actions in which, for certain action pairs, the first actor's action reliably predicted the second actor's action. We analyzed predictive eye movements to upcoming actions as a measure of learning, and found that both adults and toddlers learned the statistical regularities across actors when their actions caused an effect. Further, adults with high statistical learning performance were sensitive to social context: those who observed actors with a shared goal were more likely to correctly predict upcoming actions. In contrast, there was no effect of social context in the toddler group, regardless of learning performance. These findings shed light on how adults and toddlers perceive statistical regularities across actors depending on the nature of the observed social situation and the

Action video games make dyslexic children read better.

Science.gov (United States)

Franceschini, Sandro; Gori, Simone; Ruffino, Milena; Viola, Simona; Molteni, Massimo; Facoetti, Andrea

2013-03-18

Learning to read is extremely difficult for about 10% of children; they are affected by a neurodevelopmental disorder called dyslexia [1, 2]. The neurocognitive causes of dyslexia are still hotly debated [3-12]. Dyslexia remediation is far from being fully achieved [13], and the current treatments demand high levels of resources [1]. Here, we demonstrate that only 12 hr of playing action video games-not involving any direct phonological or orthographic training-drastically improve the reading abilities of children with dyslexia. We tested reading, phonological, and attentional skills in two matched groups of children with dyslexia before and after they played action or nonaction video games for nine sessions of 80 min per day. We found that only playing action video games improved children's reading speed, without any cost in accuracy, more so than 1 year of spontaneous reading development and more than or equal to highly demanding traditional reading treatments. Attentional skills also improved during action video game training. It has been demonstrated that action video games efficiently improve attention abilities [14, 15]; our results showed that this attention improvement can directly translate into better reading abilities, providing a new, fast, fun remediation of dyslexia that has theoretical relevance in unveiling the causal role of attention in reading acquisition. Copyright © 2013 Elsevier Ltd. All rights reserved.

Participatory Action Research in Health Systems: Empowering ...

International Development Research Centre (IDRC) Digital Library (Canada)

2014-12-02

Dec 2, 2014 ... Home · Resources · Publications ... A new publication, Participatory Action Research in Health Systems: a methods ... organizations, most African countries adopted direct payment for health services as the primary means.

Comparable mechanisms for action and language: Neural systems behind intentions, goals and means

NARCIS (Netherlands)

Schie, H.T. van; Toni, I.; Bekkering, H.

2006-01-01

In this position paper we explore correspondence between neural systems for language and action starting from recent electrophysiological findings on the roles of posterior and frontal areas in goal-directed grasping actions. The paper compares the perceptual and motor organization for action and

Hazardous Waste Remedial Actions Program: integrating waste management

International Nuclear Information System (INIS)

Petty, J.L.; Sharples, F.E.

1986-01-01

The Hazardous Waste Remedial Actions Program was established to integrate Defense Programs' activities in hazardous and mixed waste management. The Program currently provides centralized planning and technical support to the Office of the Assistant Secretary for Defense Programs. More direct project management responsibilities may be assumed in the future. The Program, under the direction of the ASDP's Office of Defense Waste and Transportation Management, interacts with numerous organizational entities of the Department. The Oak Ridge Operations Office has been designated as the Lead Field Office. The Program's four current components cover remedial action project identification and prioritization; technology adaptation; an informative system; and a strategy study for long-term, ''corporate'' project and facility planning

A Retrospective Review of Thiazolidinediones with Development of a Troglitazone Conversion Protocol

Directory of Open Access Journals (Sweden)

Cameron Lindsey

2003-01-01

Full Text Available The objective of this paper was (1 to assess compliance with the National Veterans Affairs Guidelines for the use of troglitazone and rosiglitazone and (2 to develop and implement a conversion protocol that allows effective management of patients receiving troglitazone. A retrospective chart review was conducted to assess adherence to guidelines for all patients receiving troglitazone and rosiglitazone at the medical center. Appropriateness of therapy through indication evaluation, safety through alanine aminotransferase (ALT monitoring compliance, and efficacy through hemoglobin A1c (HbA1c changes were used to assess adherence. According to National Veterans Affairs (VA Guidelines, 68% of troglitazone and 63% of rosiglitazone patients had an appropriate indication for the use of these agents. Baseline ALT levels were obtained in 40% of troglitazone and 71% of rosiglitazone patients. Full compliance with continual ALT monitoring was seen in 6 and 54% of patients, respectively. Goal HbA1c was achieved in 57 and 29% of patients, respectively. Of the 33 patients receiving troglitazone, 19 were converted to rosiglitazone therapy; 11 were maintained on current regimens without troglitazone, and 3 were lost to follow up. Adherence to guidelines needs to be reinforced, in particular, compliance with ALT monitoring. However, there were no reported cases of hepatotoxicity in the patients reviewed. Many patients did not achieve a HbA1c

Learning Visual Representations for Perception-Action Systems

DEFF Research Database (Denmark)

Piater, Justus; Jodogne, Sebastien; Detry, Renaud

2011-01-01

and RLJC, our second method learns structural object models for robust object detection and pose estimation by probabilistic inference. To these models, the method associates grasp experiences autonomously learned by trial and error. These experiences form a nonparametric representation of grasp success......We discuss vision as a sensory modality for systems that effect actions in response to perceptions. While the internal representations informed by vision may be arbitrarily complex, we argue that in many cases it is advantageous to link them rather directly to action via learned mappings....... These arguments are illustrated by two examples of our own work. First, our RLVC algorithm performs reinforcement learning directly on the visual input space. To make this very large space manageable, RLVC interleaves the reinforcement learner with a supervised classification algorithm that seeks to split...

Corrective Action Decision Document for Corrective Action Unit 417: Central Nevada Test Area Surface, Nevada Appendix D - Corrective Action Investigation Report, Central Nevada Test Area, CAU 417

International Nuclear Information System (INIS)

1999-01-01

This Corrective Action Decision Document (CADD) identifies and rationalizes the U.S. Department of Energy, Nevada Operations Office's selection of a recommended corrective action alternative (CAA) appropriate to facilitate the closure of Corrective Action Unit (CAU) 417: Central Nevada Test Area Surface, Nevada, under the Federal Facility Agreement and Consent Order. Located in Hot Creek Valley in Nye County, Nevada, and consisting of three separate land withdrawal areas (UC-1, UC-3, and UC-4), CAU 417 is comprised of 34 corrective action sites (CASs) including 2 underground storage tanks, 5 septic systems, 8 shaker pad/cuttings disposal areas, 1 decontamination facility pit, 1 burn area, 1 scrap/trash dump, 1 outlier area, 8 housekeeping sites, and 16 mud pits. Four field events were conducted between September 1996 and June 1998 to complete a corrective action investigation indicating that the only contaminant of concern was total petroleum hydrocarbon (TPH) which was found in 18 of the CASs. A total of 1,028 samples were analyzed. During this investigation, a statistical approach was used to determine which depth intervals or layers inside individual mud pits and shaker pad areas were above the State action levels for the TPH. Other related field sampling activities (i.e., expedited site characterization methods, surface geophysical surveys, direct-push geophysical surveys, direct-push soil sampling, and rotosonic drilling located septic leachfields) were conducted in this four-phase investigation; however, no further contaminants of concern (COCs) were identified. During and after the investigation activities, several of the sites which had surface debris but no COCs were cleaned up as housekeeping sites, two septic tanks were closed in place, and two underground storage tanks were removed. The focus of this CADD was to identify CAAs which would promote the prevention or mitigation of human exposure to surface and subsurface soils with contaminant

Indirect effects in dual radiation action

International Nuclear Information System (INIS)

Zaider, M.; Rossi, H.H.

1988-01-01

The basic aim in this paper is to establish the link between indirect effects of radiation action and the spatial distribution of radicals at the time of energy deposition as well as throughout subsequent diffusion and interaction. The fact that radicals diffuse for a finite distance before damaging a biomolecule has dramatic effects on their subsequent probability to result in lesions. Thus at very low DMSO concentrations, where p = 0.5, one expects - all other things being equal - some 75% of the lesions to result from indirect or semidirect lesions. The number calculated here is lower (15%), a direct result of the fact that such lesions involve proximity functions modulated by diffusion. At higher DMSO concentrations this percentage becomes progressively smaller, as expected. It appears thus that for low-LET radiation, the relative amount of indirect damage in single tracks (also termed intratrack or single events) action is very small. By contrast, intertrack (or two-event) contributions will have the ratio between direct and (indirect + semidirect) contributions given by p 2 /(1-p 2 ). The reason for this is that sublesions from different tracks are uniformly distributed throughout the cell nucleus; their probability of interaction should not depend on any previous diffusional processes. For the example given above (p = 0.5) they do expect 65% of intertrack (two-hit) lesions to have resulted from indirect or semidirect mechanisms. This contrast between the almost exclusively direct character of intratrack lesions and the dominant role of indirect action in intertrack lesions produced by low-LET radiation is an important conclusion of this study

Novel mechanisms for DHEA action.

Science.gov (United States)

Prough, Russell A; Clark, Barbara J; Klinge, Carolyn M

2016-04-01

Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA), secreted by the adrenal cortex, gastrointestinal tract, gonads, and brain, and its sulfated metabolite DHEA-S are the most abundant endogeneous circulating steroid hormones. DHEA actions are classically associated with age-related changes in cardiovascular tissues, female fertility, metabolism, and neuronal/CNS functions. Early work on DHEA action focused on the metabolism to more potent sex hormones, testosterone and estradiol, and the subsequent effect on the activation of the androgen and estrogen steroid receptors. However, it is now clear that DHEA and DHEA-S act directly as ligands for many hepatic nuclear receptors and G-protein-coupled receptors. In addition, it can function to mediate acute cell signaling pathways. This review summarizes the molecular mechanisms by which DHEA acts in cells and animal models with a focus on the 'novel' and physiological modes of DHEA action. © 2016 Society for Endocrinology.

78 FR 1723 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-01-09

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule; request for comments. SUMMARY: We are adopting a new airworthiness directive (AD) for all Airbus... Friday, except Federal holidays. For service information identified in this AD, contact Airbus...

LXA4 actions direct fibroblast function and wound closure

International Nuclear Information System (INIS)

Herrera, Bruno S.; Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice; Leung, Kai P.; Van Dyke, Thomas E.

2015-01-01

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A 4 (LXA 4 ), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA 4 on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA 4 receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA 4 receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA 4 slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA 4 tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA 4 in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF-β1 up-regulates LXA 4 receptor (ALX

Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

Directory of Open Access Journals (Sweden)

Wassila Ouelaa

Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

Effect of metal complexation to anti-inflammatory over the action against oxidative and free radicals: ketoprofen action

International Nuclear Information System (INIS)

Manente, Francine Alessandra; Mello, Lucas Rosolen de Almeida; Vellosa, Jose Carlos Rebuglio; Khalil, Omar Arafat Kdudsi; Carvalho, Claudio Teodoro de; Bannach, Gilbert

2011-01-01

Free radicals are highly reactive species generated in living organisms for the purpose of protection. However, in some circumstances, they are responsible for the occurrence or aggravation of tissue damage. Many anti-inflammatory drugs have a direct effect on free radicals and not radical reactive species, which contributes to its actions against inflammation. Ketoprofen is a nonsteroidal anti-inflammatory agent that generates free radicals by photo irradiation and has an important hemolytic effect with that. The complexation of metals to different drugs has been used as a strategy to improve the pharmacological action of different molecules and reduce their side effects. This paper presents the results of ketoprofen and their metallic complexes action on erythrocytes and free radicals. It was observed that the cerium enhances the scavenger properties of ketoprofen on free radicals, while copper enhances its action over non-radical oxidants. Copper also reduced the hemolytic effect presented by ketoprofen meanwhile its cerium derivative maintained it. (author)

Comparing topological charge definitions using topology fixing actions

International Nuclear Information System (INIS)

Bruckmann, Falk; Gruber, Florian; Jansen, Karl; Marinkovic, Marina; Urbach, Carsten; Wagner, Marc

2009-05-01

We investigate both the hyperbolic action and the determinant ratio action designed to fix the topological charge on the lattice. We show to what extent topology is fixed depending on the parameters of these actions, keeping the physical situation fixed. At the same time the agreement between different definitions of topological charge - the field theoretic and the index definition - is directly correlated to the degree topology is fixed. Moreover, it turns out that the two definitions agree very well. We also study finite volume effects arising in the static potential and related quantities due to topology fixing. (orig.)

Liver metastasis from neuroendocrine carcinoma after the use of the new direct-action antivirals against hepatitis C virus in a patient with past history of hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

María Caldas

Full Text Available The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process. However, due to the controversy concerning this subject and the absence of long-term follow-up studies in clinical practice, caution is needed before definitive conclusions are settled. We present the case report of a patient diagnosed of chronic liver disease secondary to hepatitis C virus infection and a past history of hepatocellular carcinoma in complete remission after radiofrequency ablation. He was treated with the new direct-action antivirals reaching sustained viral response. Six months later, the patient was diagnosed with liver metastasis from a small-cell neuroendocrine tumor of unknown primary site.

77 FR 49386 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2012-08-16

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all Airbus..., except Federal holidays. For Airbus service information identified in this proposed AD, contact Airbus...

77 FR 12989 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2012-03-05

... Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Airbus Model.... Airbus carried out an investigation, demonstrating that the life limit of retraction brackets must be...

78 FR 76572 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-12-18

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all Airbus..., except Federal holidays. For Airbus service information identified in this proposed AD, contact Airbus...

Intrinsically motivated action-outcome learning and goal-based action recall: a system-level bio-constrained computational model.

Science.gov (United States)

Baldassarre, Gianluca; Mannella, Francesco; Fiore, Vincenzo G; Redgrave, Peter; Gurney, Kevin; Mirolli, Marco

2013-05-01

Reinforcement (trial-and-error) learning in animals is driven by a multitude of processes. Most animals have evolved several sophisticated systems of 'extrinsic motivations' (EMs) that guide them to acquire behaviours allowing them to maintain their bodies, defend against threat, and reproduce. Animals have also evolved various systems of 'intrinsic motivations' (IMs) that allow them to acquire actions in the absence of extrinsic rewards. These actions are used later to pursue such rewards when they become available. Intrinsic motivations have been studied in Psychology for many decades and their biological substrates are now being elucidated by neuroscientists. In the last two decades, investigators in computational modelling, robotics and machine learning have proposed various mechanisms that capture certain aspects of IMs. However, we still lack models of IMs that attempt to integrate all key aspects of intrinsically motivated learning and behaviour while taking into account the relevant neurobiological constraints. This paper proposes a bio-constrained system-level model that contributes a major step towards this integration. The model focusses on three processes related to IMs and on the neural mechanisms underlying them: (a) the acquisition of action-outcome associations (internal models of the agent-environment interaction) driven by phasic dopamine signals caused by sudden, unexpected changes in the environment; (b) the transient focussing of visual gaze and actions on salient portions of the environment; (c) the subsequent recall of actions to pursue extrinsic rewards based on goal-directed reactivation of the representations of their outcomes. The tests of the model, including a series of selective lesions, show how the focussing processes lead to a faster learning of action-outcome associations, and how these associations can be recruited for accomplishing goal-directed behaviours. The model, together with the background knowledge reviewed in the paper

Thought Action Fusion in Obsessive Compulsive Disorder

Directory of Open Access Journals (Sweden)

Sahin CIFTCI

2013-11-01

Full Text Available Thought Action Fusion (TAF is defined as tought and action percieved as equivalent to each other or as an exaggerated power given to idea. With the usage of “Thought Action Fusion Scale” which is created by Shafran (1996, is began to investigate its role in psychopathologies. Researches about the three-component structure which has TAF-Likelihood-Self, TAF-Likelihood-Others, TAF-Moral, are concentrated especially around the obsessive compulsive disorder (OCD. TAF alleged including a certain level also in the normal population, was seen in the relationship with the inflated responsability in OCD, thought suppression and neutralising, was tried to explain the direction of this relationship in the mediationel model framework.

The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1-infected individuals: a randomized clinical trial.

Science.gov (United States)

Kotler, Donald P; He, Qing; Engelson, Ellen S; Albu, Jeanine B; Glesby, Marshall J

2016-01-01

Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. HIV+ subjects with abdominal obesity and IR (QUICKI≤0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy, visceral fat by MRI and IR by frequently sampled intravenous glucose tolerance tests at baseline and week 12. 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r=0.41; P=0.02) and QUICKI (r=0.39; P<0.05) were seen at baseline. IR rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percentage change decreased significantly (P<0.05) but did not change in Rosi (P=0.71). There were no correlations between changes in hepatic fat and VAT (P=0.4) or QUICKI (P=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum insulin-like growth factor-1 (IGF-1; P=0.09). Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of GH or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286).

OH radicals from the indirect actions of X-rays induce cell lethality and mediate the majority of the oxygen enhancement effect.

Science.gov (United States)

Hirayama, Ryoichi; Ito, Atsushi; Noguchi, Miho; Matsumoto, Yoshitaka; Uzawa, Akiko; Kobashi, Gen; Okayasu, Ryuichi; Furusawa, Yoshiya

2013-11-01

We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.

Prairie Conservation in Canada: The Prairie Conservation Action Plan Experience

Science.gov (United States)

Dean Nernberg; David Ingstrup

2005-01-01

In Canada, grassland conservation has been mobilized and directed through the development of Prairie Conservation Action Plans and Action Plan Committees in the three prairie provinces of Alberta (45 partner agencies and organizations), Saskatchewan (26 partners), and Manitoba (26 partners). In Alberta, 43 percent of the native prairie remains; in Saskatchewan and...

77 FR 73340 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2012-12-10

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... earlier proposed airworthiness directive (AD) for all Airbus Model A318, A319, A320, and A321 series..., contact Airbus, Airworthiness Office--EAS, 1 Rond Point Maurice Bellonte, 31707 Blagnac Cedex, France...

78 FR 23105 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-04-18

... Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Airbus Model... Agency] has received a report via Airbus and Messier-Bugatti-Dowty Ltd, from a Maintenance repair...

77 FR 15636 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2012-03-16

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all Airbus... identified in this proposed AD, contact Airbus, Airworthiness Office--EAS, 1 Rond Point Maurice Bellonte...

76 FR 78524 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2011-12-19

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for Airbus... an aeroplane from the Airbus production line, a fault message was triggered on FDU1 [fire detection...

Sex differences in impulsive action and impulsive choice

OpenAIRE

Weafer, Jessica; de Wit, Harriet

2013-01-01

Here, we review the evidence for sex differences in behavioral measures of impulsivity for both humans and laboratory animals. We focus on two specific components of impulsivity: impulsive action (i.e., difficulty inhibiting a prepotent response) and impulsive choice (i.e., difficulty delaying gratification). Sex differences appear to exist on these measures, but the direction and magnitude of the differences vary. In laboratory animals, impulsive action is typically greater in males than fem...

Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation.

Science.gov (United States)

Kim, Ki Young; Ahn, Jin Hee; Cheon, Hyae Gyeong

2007-09-01

Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we elucidated the apoptotic mechanism of PPARgamma activation in human lung cancers by using a novel PPARgamma agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPARgamma activation selectively inhibited cell viability of non-small-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPARgamma activation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompanied by increased expression of proline oxidase (POX), a redox enzyme expressed in mitochondria, upon incubation with the agonists. POX RNA interference treatment blocked PPARgamma-induced ROS formation and cytotoxicity, suggesting that POX plays a functional role in apoptosis through ROS formation. The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl ether, a PPARgamma antagonist, and by knockdown of PPARgamma expression, indicating the involvement of PPARgamma in these actions. The results of the present study suggest that PPARgamma activation induces apoptotic cell death in non-small-cell lung carcinoma mainly through ROS formation via POX induction.

The left IPL represents stored hand-postures for object use and action prediction

Directory of Open Access Journals (Sweden)

Michiel evan Elk

2014-04-01

Full Text Available Action semantics enables us to plan actions with objects and to predict others’ object-directed actions as well. Previous studies have suggested that action semantics are represented in a fronto-parietal action network that has also been implicated to play a role in action observation. In the present fMRI study it was investigated how activity within this network changes as a function of the predictability of an action involving multiple objects and requiring the use of action semantics. Participants performed an action prediction task in which they were required to anticipate the use of a centrally presented object that could be moved to an associated target object (e.g. hammer - nail. The availability of actor information (i.e. presenting a hand grasping the central object and the number of possible target objects (i.e. 0, 1 or 2 target objects were independently manipulated, resulting in different levels of predictability. It was found that making an action prediction based on actor information resulted in an increased activation in the extrastriate body area (EBA and the fronto-parietal action observation network (AON. Predicting actions involving a target object resulted in increased activation in the bilateral IPL and frontal motor areas. Within the AON, activity in the left inferior parietal lobe (IPL and the left premotor cortex (PMC increased as a function of the level of action predictability. Together these findings suggest that the left IPL represents stored hand-postures that can be used for planning object-directed actions and for predicting other’s actions as well.

Deciding as Intentional Action: Control over Decisions

Science.gov (United States)

Shepherd, Joshua

2015-01-01

Common-sense folk psychology and mainstream philosophy of action agree about decisions: these are under an agent's direct control, and are thus intentional actions for which agents can be held responsible. I begin this paper by presenting a problem for this view. In short, since the content of the motivational attitudes that drive deliberation and decision remains open-ended until the moment of decision, it is unclear how agents can be thought to exercise control over what they decide at the moment of deciding. I note that this problem might motivate a non-actional view of deciding—a view that decisions are not actions, but are instead passive events of intention acquisition. For without an understanding of how an agent might exercise control over what is decided at the moment of deciding, we lack a good reason for maintaining commitment to an actional view of deciding. However, I then offer the required account of how agents exercise control over decisions at the moment of deciding. Crucial to this account is an understanding of the relation of practical deliberation to deciding, an understanding of skilled deliberative activity, and the role of attention in the mental action of deciding. PMID:26321765

Lethal action of soluble metallic salts on fishes

Energy Technology Data Exchange (ETDEWEB)

Carpenter, K E

1927-01-01

A study of pollution of Welsh rivers by lead-mine effluents revealed the fact that fishes were killed by the action of soluble salts of lead, which proved lethal at concentrations so low as pb i : 3,000,000. A physiological investigation of the action of lead-salts revealed the following facts: the action does not correspond to the normal toxic type. The graph of survival-times in different concentrations closely follows the equation: K = i/t log i/conc. The speed of the reaction is dependent upon the total quantity of metallic ion present, as well as upon the actual concentrations. The speed of the reaction varies in inverse relation to the size and weight of fishes employed. The most marked symptom is the formation of a film over gills and skin, by interaction of the metallic ion with a mucus-constituent. Death by suffocation is the final result. Where insufficient lead ion is present, the film is shed off, and complete recovery takes place. The speed of the reaction varies in direct relation to the temperature. Chemical analysis of residues shows that no trace of metallic ion penetrates into the body itself. The action is thus held to be purely external in process, chemical in type, and mechanical in effect; i.e., it is not a toxic action in the ordinary sense of the term. The action of soluble salts of zinc, iron, copper, cadmium, and mercury is shown to follow the same law as that of lead. Attention is directed to the economic importance of the facts, in connection with the pollution of rivers.

The investigation of Mitogen-Activated Protein kinase Phosphatase-1 as a potential pharmacological target in non-small cell lung carcinomas, assisted by non-invasive molecular imaging

International Nuclear Information System (INIS)

Tai, Cheng-Jeng; Lee, Horng-Mo; Deng, Win-Ping; Wu, Alexander TH; Chiou, Jeng-Feng; Jan, Hsun-Jin; Wei, Hon-Jian; Hsu, Chung-Huei; Lin, Che-Tong; Chiu, Wen-Ta; Wu, Cheng-Wen

2010-01-01

Invasiveness and metastasis are the most common characteristics of non small cell lung cancer (NSCLC) and causes of tumour-related morbidity and mortality. Mitogen-activated protein kinases (MAPKs) signalling pathways have been shown to play critical roles in tumorigenesis. However, the precise pathological role(s) of mitogen-activated protein kinase phosphatase-1 (MKP-1) in different cancers has been controversial such that the up-regulation of MKP-1 in different cancers does not always correlate to a better prognosis. In this study, we showed that the induction of MKP-1 lead to a significant retardation of proliferation and metastasis in NSCLC cells. We also established that rosiglitazone (a PPARγ agonist) elevated MKP-1 expression level in NSCLC cells and inhibited tumour metastasis. Both wildtype and dominant negative forms of MKP-1 were constitutively expressed in NSCLC cell line H441GL. The migration and invasion abilities of these cells were examined in vitro. MKP-1 modulating agents such as rosiglitazone and triptolide were used to demonstrate MKP-1's role in tumorigenesis. Bioluminescent imaging was utilized to study tumorigenesis of MKP-1 over-expressing H441GL cells and anti-metastatic effect of rosiglitazone. Over-expression of MKP-1 reduced NSCLC cell proliferation rate as well as cell invasive and migratory abilities, evident by the reduced expression levels of MMP-2 and CXCR4. Mice inoculated with MKP-1 over-expressing H441 cells did not develop NSCLC while their control wildtype H441 inoculated littermates developed NSCLC and bone metastasis. Pharmacologically, rosiglitazone, a peroxisome proliferator activated receptor-γ (PPARγ) agonist appeared to induce MKP-1 expression while reduce MMP-2 and CXCR4 expression. H441GL-inoculated mice receiving daily oral rosiglitazone treatment demonstrated a significant inhibition of bone metastasis when compared to mice receiving sham treatment. We found that rosiglitazone treatment impeded the ability

Cognitive framing in action.

Science.gov (United States)

Huhn, John M; Potts, Cory Adam; Rosenbaum, David A

2016-06-01

Cognitive framing effects have been widely reported in higher-level decision-making and have been ascribed to rules of thumb for quick thinking. No such demonstrations have been reported for physical action, as far as we know, but they would be expected if cognition for physical action is fundamentally similar to cognition for higher-level decision-making. To test for such effects, we asked participants to reach for a horizontally-oriented pipe to move it from one height to another while turning the pipe 180° to bring one end (the "business end") to a target on the left or right. From a physical perspective, participants could have always rotated the pipe in the same angular direction no matter which end was the business end; a given participant could have always turned the pipe clockwise or counter-clockwise. Instead, our participants turned the business end counter-clockwise for left targets and clockwise for right targets. Thus, the way the identical physical task was framed altered the way it was performed. This finding is consistent with the hypothesis that cognition for physical action is fundamentally similar to cognition for higher-level decision-making. A tantalizing possibility is that higher-level decision heuristics have roots in the control of physical action, a hypothesis that accords with embodied views of cognition. Copyright © 2016 Elsevier B.V. All rights reserved.

78 FR 17071 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-03-20

... Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Airbus Model A330-200, -300, and -200 Freighter series airplanes; and all Airbus Model A340-200 and -300 series...

Over-imitation is not automatic: context sensitivity in children's overimitation and action interpretation of causally irrelevant actions.

Science.gov (United States)

Keupp, Stefanie; Behne, Tanya; Zachow, Joanna; Kasbohm, Alina; Rakoczy, Hannes

2015-02-01

Recent research has documented the robust tendency of children to "over-imitate," that is, to copy causally irrelevant action elements in goal-directed action sequences. Different explanations for over-imitation have been proposed. Causal accounts claim that children mistakenly perceive such action elements as causally relevant and, therefore, imitate them. Affiliation accounts claim that children over-imitate to affiliate with the model. Normative accounts claim that children conceive of causally irrelevant actions as essential parts of an overarching conventional activity. These different accounts generally hold the same predictions regarding children's imitative response. However, it is possible to distinguish between them when one considers additional parameters. The normative account predicts wide-ranging flexibility with regard to action interpretation and the occurrence of over-imitation. First, it predicts spontaneous protest against norm violators who omit the causally irrelevant actions. Second, children should perform the causally irrelevant actions less frequently, and criticize others less frequently for omitting them, when the actions take place in a different context from the one of the initial demonstration. Such flexibility is not predicted by causal accounts and is predicted for only a limited range of contexts by affiliation accounts. Study 1 investigated children's own imitative response and found less over-imitation when children acted in a different context from when they acted in the same context as the initial demonstration. In Study 2, children criticized a puppet less frequently for omitting irrelevant actions when the puppet acted in a different context. The results support the notion that over-imitation is not an automatic and inflexible phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Thought Action Fusion in Obsessive Compulsive Disorder

Directory of Open Access Journals (Sweden)

Þahin ÇÝFTÇÝ

2013-12-01

Full Text Available Thought Action Fusion (TAF is defined as tought and action percieved as equivalent to each other or as an exaggerated power given to idea. With the usage of “Thought Action Fusion Scale” which is created by Shafran (1996, is began to investigate its role in psychopathologies. Researches about the three-component structure which has TAF-Likelihood-Self, TAF-Likelihood-Others, TAF-Moral, are concentrated especially around the obsessive compulsive disorder (OCD. TAF alleged including a certain level also in the normal population, was seen in the relationship with the inflated responsability in OCD, thought suppression and neutralising, was tried to explain the direction of this relationship in the mediationel model framework. [JCBPR 2013; 2(3.000: 138-146

Functional Dissociation between Perception and Action Is Evident Early in Life

Science.gov (United States)

Hadad, Bat-Sheva; Avidan, Galia; Ganel, Tzvi

2012-01-01

The functional distinction between vision for perception and vision for action is well documented in the mature visual system. Ganel and colleagues recently provided direct evidence for this dissociation, showing that while visual processing for perception follows Weber's fundamental law of psychophysics, action violates this law. We tracked the…

Comprehending Sentences with the Body: Action Compatibility in British Sign Language?

Science.gov (United States)

Vinson, David; Perniss, Pamela; Fox, Neil; Vigliocco, Gabriella

2017-01-01

Previous studies show that reading sentences about actions leads to specific motor activity associated with actually performing those actions. We investigate how sign language input may modulate motor activation, using British Sign Language (BSL) sentences, some of which explicitly encode direction of motion, versus written English, where motion…

78 FR 32345 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-05-30

... Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for all Airbus Model A300... FedEx requested that copies of Airbus Service Bulletin A300-53- 6170, dated May 16, 2011, be provided...

APT: Action localization Proposals from dense Trajectories

NARCIS (Netherlands)

van Gemert, J.C.; Jain, M.; Gati, E.; Snoek, C.G.M.; Xie, X.; Jones, M.W.; Tam, G.K.L.

2015-01-01

This paper is on action localization in video with the aid of spatio-temporal proposals. To alleviate the computational expensive video segmentation step of existing proposals, we propose bypassing the segmentations completely by generating proposals directly from the dense trajectories used to

Transit green building action plan : report to congress

Science.gov (United States)

2009-06-04

The explanatory statement accompanying the fiscal year 2009 Omnibus appropriations : act1 directed the Federal Transit Administration (FTA) to submit a transit facility green : building action plan to the House and Senate Committees on Appropriati...

Radioactive contamination, what actions for the polluted sites; Contamination radioactive, quelles actions pour les sites pollues

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-07-01

The nuclear safety authority and the direction of prevention of pollutions and risks have organised the first edition of the national colloquium: radioactive contamination: what actions for polluted sites. Four axes can be taken to follow this colloquium: prevention, outstanding tools to evaluate risks and rehabilitation, a better responsibility of operators and memory keeping. (N.C.)

PROTECTIVE EFFECT OF THE PROBIOTIC Saccharomyces boulardii IN Toxocara canis INFECTION IS NOT DUE TO DIRECT ACTION ON THE LARVAE

Directory of Open Access Journals (Sweden)

Luciana Farias da Costa de Avila

2013-09-01

Full Text Available SUMMARY In a previous study our group found that the probiotic Saccharomyces boulardii was capable of reducing the intensity of infection in mice with toxocariasis. In order to assess whether the mechanism involved would be a direct action of the probiotic on Toxocara canis larvae, this study was designed. Both probiotics were singly cultivated in plates containing RPMI 1640 medium and T. canis larvae. S. boulardii and B. cereus var. toyoi cultures presented 97.6% and 95.7% of larvae with positive motility, respectively, and absence of color by the dye trypan blue, not representing significant difference to the control group (p > 0.05. We conclude that none of the probiotics showed in vitro effects on T. canis larvae and that the interaction with the intestinal mucosa is necessary for the development of the protective effect of S. boulardii.

Protective effect of the probiotic Saccharomyces boulardii in Toxocara canis infection is not due to direct action on the larvae.

Science.gov (United States)

Avila, Luciana Farias da Costa de; Telmo, Paula de Lima; Martins, Lourdes Helena Rodrigues; Glaeser, Thaís Aimeé; Conceição, Fabricio Rochedo; Leite, Fábio Pereira Leivas; Scaini, Carlos James

2013-01-01

In a previous study our group found that the probiotic Saccharomyces boulardii was capable of reducing the intensity of infection in mice with toxocariasis. In order to assess whether the mechanism involved would be a direct action of the probiotic on Toxocara canis larvae, this study was designed. Both probiotics were singly cultivated in plates containing RPMI 1640 medium and T. canis larvae. S. boulardii and B. cereus var. toyoi cultures presented 97.6% and 95.7% of larvae with positive motility, respectively, and absence of color by the dye trypan blue, not representing significant difference to the control group (p > 0.05). We conclude that none of the probiotics showed in vitro effects on T. canis larvae and that the interaction with the intestinal mucosa is necessary for the development of the protective effect of S. boulardii.

Moral theological analysis of direct versus indirect abortion.

Science.gov (United States)

Haas, John M

2017-08-01

Cases of a vital conflict, where the lives of both the mother and child are at risk during pregnancy, have been the subject of recent vigorous debate. The basic principles put forth in the Ethical and Religious Directives are reviewed, as is the principle of double effect. An illustrative case of severe cardiomyopathy in a pregnant woman is described and it is noted that the principle of double effect would not apply. Counter arguments are noted, focusing on Martin Rhonheimer who posits that in the case of vital conflicts, such as performing a craniotomy on a baby stuck in the birth canal, taking the baby's life does not constitute a direct abortion because moral norms do not apply in the extreme conflict situation where both mother and child will die. He states that the death of the fetus is not intentional in these cases. He overlooks "how the life is being saved" and that a choice has been made, which implies a moral act, not just a physical one. Rhonheimer wants to make his moral judgment solely on the basis of intention, prescinding from what actually occurs in the physical world of cause and effect. This is clearly against the teaching in Evangelium vitae. Ethics deal with the deliberate chosen actions in space and time of embodied human beings; it deals inescapably with material actions, with specifications of intentions. Rhonheimer states, "a killing or an abortion is 'direct,' not because the death of the fetus is caused in some physically direct way, but because it is willed as the means to an end." However the death of the child cannot be excluded from the act and is therefore of necessity included in it. What the acting person chooses includes what happens physically in this act. If the action theory proposed by Rhonheimer is accepted, it could be very difficult to avoid death-dealing actions from taking place in Catholic hospitals. This is a moral analysis of cases of "vital conflicts," where the lives of both the mother and child are at risk during a

The action principle for a system of differential equations

International Nuclear Information System (INIS)

Gitman, D M; Kupriyanov, V G

2007-01-01

We consider the problem of constructing an action functional for physical systems whose classical equations of motion cannot be directly identified with Euler-Lagrange equations for an action principle. Two ways of constructing the action principle are presented. From simple consideration, we derive the necessary and sufficient conditions for the existence of a multiplier matrix which can endow a prescribed set of second-order differential equations with the structure of the Euler-Lagrange equations. An explicit form of the action is constructed if such a multiplier exists. If a given set of differential equations cannot be derived from an action principle, one can reformulate such a set in an equivalent first-order form which can always be treated as the Euler-Lagrange equations of a certain action. We construct such an action explicitly. There exists an ambiguity (not reduced to a total time derivative) in associating a Lagrange function with a given set of equations. We present a complete description of this ambiguity. The general procedure is illustrated by several examples

The action principle for a system of differential equations

Energy Technology Data Exchange (ETDEWEB)

Gitman, D M [Instituto de FIsica, Universidade de Sao Paulo (Brazil); Kupriyanov, V G [Instituto de FIsica, Universidade de Sao Paulo (Brazil)

2007-08-17

We consider the problem of constructing an action functional for physical systems whose classical equations of motion cannot be directly identified with Euler-Lagrange equations for an action principle. Two ways of constructing the action principle are presented. From simple consideration, we derive the necessary and sufficient conditions for the existence of a multiplier matrix which can endow a prescribed set of second-order differential equations with the structure of the Euler-Lagrange equations. An explicit form of the action is constructed if such a multiplier exists. If a given set of differential equations cannot be derived from an action principle, one can reformulate such a set in an equivalent first-order form which can always be treated as the Euler-Lagrange equations of a certain action. We construct such an action explicitly. There exists an ambiguity (not reduced to a total time derivative) in associating a Lagrange function with a given set of equations. We present a complete description of this ambiguity. The general procedure is illustrated by several examples.

Human Action Recognition Using Ordinal Measure of Accumulated Motion

Directory of Open Access Journals (Sweden)

Kim Wonjun

2010-01-01

Full Text Available This paper presents a method for recognizing human actions from a single query action video. We propose an action recognition scheme based on the ordinal measure of accumulated motion, which is robust to variations of appearances. To this end, we first define the accumulated motion image (AMI using image differences. Then the AMI of the query action video is resized to a subimage by intensity averaging and a rank matrix is generated by ordering the sample values in the sub-image. By computing the distances from the rank matrix of the query action video to the rank matrices of all local windows in the target video, local windows close to the query action are detected as candidates. To find the best match among the candidates, their energy histograms, which are obtained by projecting AMI values in horizontal and vertical directions, respectively, are compared with those of the query action video. The proposed method does not require any preprocessing task such as learning and segmentation. To justify the efficiency and robustness of our approach, the experiments are conducted on various datasets.

Action Learning: Avoiding Conflict or Enabling Action

Science.gov (United States)

Corley, Aileen; Thorne, Ann

2006-01-01

Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

Molecular and elemental effects underlying the biochemical action of transcranial direct current stimulation (tDCS) in appetite control

Science.gov (United States)

Surowka, Artur D.; Ziomber, Agata; Czyzycki, Mateusz; Migliori, Alessandro; Kasper, Kaja; Szczerbowska-Boruchowska, Magdalena

2018-04-01

Recent studies highlight that obesity may alter the electric activity in brain areas triggering appetite and craving. Transcranial direct current brain stimulation (tDCS) has recently emerged as a safe alternative for treating food addiction via modulating cortical excitability without any high-risk surgical procedure to be utilized. As for anodal-type tDCS (atDCS), we observe increased excitability and spontaneous firing of the cortical neurons, whilst for the cathodal-type tDCS (ctDCS) a significant decrease is induced. Unfortunately, for the method to be fully used in a clinical setting, its biochemical action mechanism must be precisely defined, although it is proposed that molecular remodelling processes play in concert with brain activity changes involving the ions of: Na, Cl, K and Ca. Herein, we proposed for the first time Fourier transform infrared (FTIR) and synchrotron X-ray fluorescence (SRXRF) microprobes for a combined molecular and elemental analysis in the brain areas implicated appetite control, upon experimental treatment by either atDCS or ctDCS. The study, although preliminary, shows that by stimulating the prefrontal cortex in the rats fed high-caloric nutrients, the feeding behavior can be significantly changed, resulting in significantly inhibited appetite. Both, atDCS and ctDCS produced significant molecular changes involving qualitative and structural properties of lipids, whereas atDCS was found with a somewhat more significant effect on protein secondary structure in all the brain areas investigated. Also, tDCS was reported to reduce surface masses of Na, Cl, K, and Ca in almost all brain areas investigated, although the atDCS deemed to have a stronger neuro-modulating effect. Taken together, one can report that tDCS is an effective treatment technique, and its action mechanism in the appetite control seems to involve a variety of lipid-, protein- and metal/non-metal-ion-driven biochemical changes, regardless the current polarization.

The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1 infected individuals; a randomized clinical trial

Science.gov (United States)

Kotler, Donald P; He, Qing; Engelson, Ellen S; Albu, Jeanine B; Glesby, Marshall J

2016-01-01

Background Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. Methods HIV+ subjects with abdominal obesity and IR (QUICKI ≤ 0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination, or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy (MRS), visceral fat by MRI, and IR by frequently sampled IV glucose tolerance tests at baseline and week 12. Results 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r = 0.41, p=0.02) and QUICKI (r = 0.39, p<0.05) were seen at baseline. Insulin resistance rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percent change decreased significantly (p<0.05) but did not change in Rosi (p=0.71). There were no correlations between changes in hepatic fat and VAT (p=0.4) or QUICKI (p=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum IGF-1 (p=0.09). Conclusions Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of growth hormone or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286). PMID:25536669

Challenges in drug discovery for thiazolidinedione substitute

Directory of Open Access Journals (Sweden)

Jian-ping Ye

2011-10-01

Full Text Available Thiazolidinedione (TZD is a powerful insulin sensitizer in the treatment of type 2 diabetes. It acts as a ligand to the nuclear receptor PPARγ (peroxisome proliferator-activated receptor-gamma and induces transcription of PPARγ-responsive genes. TZD controls lipid synthesis and storage in adipose tissue, liver and many other tissues through PPARγ. Derivatives of TZD, such as rosiglitazone (Avandia and pioglitazone (Actos, are more powerful than metformin or berberine in insulin sensitization. Although they have common side effects such as weight gain and edema, these did not influence their clinical application in general. However, recent findings of risk for congestive heart failure and bladder cancer have significantly impaired their future in many countries. European countries have prohibited those drugs, and US will terminate application of rosiglitazone in clinics and hospitals. The multiple country actions may mark the end of TZD era. As a result, there is a strong demand for identification of TZD substitute in the treatment of type 2 diabetes. In this regard, literature about PPARγ ligands and potential TZD substitute are reviewed in this article. Histone deacetylase (HDAC inhibitor is emphasized as a new class of insulin sensitizer here. Regulators of SIRT1, CREB, NO, p38, ERK and Cdk5 are discussed in the activation of PPARγ.

Response selection difficulty modulates the behavioral impact of rapidly learnt action effects.

Directory of Open Access Journals (Sweden)

Uta eWolfensteller

2014-12-01

Full Text Available It is well established that we can pick up action effect associations when acting in a free-choice intentional mode. However, it is less clear whether and when action effect associations are learnt and actually affect behavior if we are acting in a forced-choice mode, applying a specific stimulus-response (S-R rule. In the present study, we investigated whether response selection difficulty imposed by S-R rules influences the initial rapid learning and the behavioral expression of previously learnt but weakly practiced action effect associations when those are re-activated by effect exposure. Experiment 1 showed that the rapid acquisition of action effect associations is not directly influenced by response selection difficulty. By contrast, the behavioral expression of re-activated action effect associations is prevented when actions are directly activated by highly over-learnt response cues and thus response selection difficulty is low. However, all three experiments showed that if response selection difficulty is sufficiently high during re-activation, the same action effect associations do influence behavior. Experiment 2 and 3 revealed that the effect of response selection difficulty cannot be fully reduced to giving action effects more time to prime an action, but seems to reflect competition during response selection. Finally, the present data suggest that when multiple novel rules are rapidly learnt in succession, which requires a lot of flexibility, action effect associations continue to influence behavior only if response selection difficulty is sufficiently high. Thus, response selection difficulty might modulate the impact of experiencing multiple learning episodes on action effect expression and learning, possibly via inducing different strategies.

Radioactivity in the phosphate field: actions undertaken by IMPHOS

International Nuclear Information System (INIS)

Mrabet, T.; Kotti, M.M.

2008-01-01

In order to prevent a potentially negative impact on the phosphate industry of the European Council Directive 96/29/Euratom, IMPHOS participated in several events where discussions were held on the issue of NORM and the consequences of the application of the Directive for the non-nuclear industries, including all the NORM symposia from September 1997 to May 2004. In addition, IMPHOS has undertaken actions to establish an ad hoc committee with members designated by member companies and to initiate a desktop study conducted by CEPN to review the implications of applying the Directive for the phosphate industry. This study is an important collection of data on radiological protection, including doses expected to be received by exposed individuals and monitoring considerations. The main conclusions of these actions are that the radioactivity in the phosphate industry is relatively insignificant, with the total annual exposure of a phosphate worker being less than three thousandths of the limit recommended by the ICRP. (author)

Sleep Deprivation Promotes Habitual Control over Goal-Directed Control: Behavioral and Neuroimaging Evidence.

Science.gov (United States)

Chen, Jie; Liang, Jie; Lin, Xiao; Zhang, Yang; Zhang, Yan; Lu, Lin; Shi, Jie

2017-12-06

Sleep is one of the most fundamental processes of life, playing an important role in the regulation of brain function. The long-term lack of sleep can cause memory impairments, declines in learning ability, and executive dysfunction. In the present study, we evaluated the effects of sleep deprivation on instrumental learning behavior, particularly goal-directed and habitual actions in humans, and investigated the underlying neural mechanisms. Healthy college students of either gender were enrolled and randomly divided into sleep deprivation group and sleep control group. fMRI data were collected. We found that one night of sleep deprivation led to greater responsiveness to stimuli that were associated with devalued outcomes in the slips-of-action test, indicating a deficit in the formation of goal-directed control and an overreliance on habits. Furthermore, sleep deprivation had no effect on the expression of acquired goal-directed action. The level of goal-directed action after sleep deprivation was positively correlated with baseline working memory capacity. The neuroimaging data indicated that goal-directed learning mainly recruited the ventromedial PFC (vmPFC), the activation of which was less pronounced during goal-directed learning after sleep deprivation. Activation of the vmPFC during goal-directed learning during training was positively correlated with the level of goal-directed action performance. The present study suggests that people rely predominantly on habits at the expense of goal-directed control after sleep deprivation, and this process involves the vmPFC. These results contribute to a better understanding of the effects of sleep loss on decision-making. SIGNIFICANCE STATEMENT Understanding the cognitive consequences of sleep deprivation has become extremely important over the past half century, given the continued decline in sleep duration in industrialized societies. Our results provide novel evidence that goal-directed action may be

77 FR 76414 - William D. Ford Federal Direct Loan Program

Science.gov (United States)

2012-12-28

... Federal Direct Loan Program AGENCY: Department of Education. ACTION: Final regulations; correction... Loan (Perkins Loan) Program; the Federal Family Education Loan (FFEL) Program; and the William D. Ford Federal Direct Loan (Direct Loan) Program, including the Public Service Loan Forgiveness (PSLF) Program...

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-05-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1989-06-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

78 FR 70003 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-11-22

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: We propose to adopt a new airworthiness directive (AD) for all Airbus Model A300 series airplanes; Airbus Model A300 B4-600, B4-600R, and F4-600R series airplanes, and Model...

Effects of low intensity laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes

Science.gov (United States)

Xiong, Guoxin; Xiong, Leilei; Li, Xinzhong

2016-09-01

To investigate the effects of low intensity semiconductor laser acupoint irradiation on inhibiting islet beta-cell apoptosis in rats with type 2 diabetes, a method using a high-fat diet and low-dose intraperitoneal injections of streptozotocin established a type 2 diabetes mellitus rat model. Model rats were randomly divided into a laser acupoint irradiation group, rosiglitazone control group, and placebo group; each group had 10 rats. In addition, 10 normal male rats were selected for the normal control group. The Housanli, Neiting and Yishu acupoints of the rats in the laser acupoint irradiation group were irradiated with a 10 mW semiconductor laser; each point was irradiated for 15 min, once every 2 d over 28 d, for a total of 14 episodes of irradiation. The rosiglitazone group rats were given rosiglitazone (0.2 mg kg-1) intragastrically; the placebo group rats were given 0.9% brine (0.2 mg kg-1) intragastrically, once daily, for four consecutive weeks. The change of fasting blood glucose was determined before and after each treatment. The islet beta-cell apoptosis was determined. The islet beta-cell apoptosis rates of the laser acupoint irradiation group and the rosiglitazone group were significantly lower than the rate of the placebo group. Even though the rate was lower in the laser acupoint irradiation group than in the rosiglitazone group, there was no significant difference between them. It is shown that acupoint irradiation with a semiconductor laser can effectively inhibit islet beta-cell apoptosis in rats with type 2 diabetes.

78 FR 7642 - Airworthiness Directives; Piper Aircraft, Inc.

Science.gov (United States)

2013-02-04

... Airworthiness Directives; Piper Aircraft, Inc. AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Piper Aircraft, Inc. (type certificate previously held by The New Piper Aircraft Inc.) PA-28, PA-32, PA-34, and PA-44...

75 FR 22165 - Publication of Open Government Directive

Science.gov (United States)

2010-04-27

... MERIT SYSTEMS PROTECTION BOARD Publication of Open Government Directive AGENCY: U.S. Merit Systems... specific actions are: (1) Publication of three high- value data sets; (2) designation of a senior agency... Open Government Web page; and (4) development and publication of an Open Government Plan. The Directive...

The Water Framework Directive and the Strategic Environmental Assessment Directive: Exploring the linkages

International Nuclear Information System (INIS)

Carter, Jeremy; Howe, Joe

2006-01-01

This paper highlights, explores and reflects on the linkages between the Water Framework Directive (WFD) and the Strategic Environmental Assessment (SEA) Directive. The assessment of river basin management plans (RBMPs), the key procedural linkage between the two Directives, is addressed. The assessment of other actions affecting the water environment, particularly land use plans, could also aid the achievement of the aims of the Water Framework Directive. As water quality is related intimately to the development and use of land, this significant issue is considered. There are numerous potential benefits that could arise from exploring the linkages between these two pieces of EU environmental legislation. These are highlighted, and include encouraging resource savings, generating a holistic approach to water resource management and ultimately the promotion of more sustainable forms of development

77 FR 72960 - William D. Ford Federal Direct Loan Program

Science.gov (United States)

2012-12-07

... Federal Direct Loan Program AGENCY: Office of Postsecondary Education, Department of Education. ACTION... document to establish the date for the early implementation of William D. Ford Federal Direct Loan (Direct Loan) program regulations that establish a new income-contingent repayment plan based on the President...

RCRA corrective action program guide (Interim)

Energy Technology Data Exchange (ETDEWEB)

1993-05-01

The US Department of Energy (DOE) is responsible for compliance with an increasingly complex spectrum of environmental regulations. One of the most complex programs is the corrective action program proposed by the US Environmental Protection Agency (EPA) under the authority of the Resource Conservation and Recovery Act (RCRA) as amended by the Hazardous and Solid Waste Amendments (HSWA). The proposed regulations were published on July 27, 1990. The proposed Subpart S rule creates a comprehensive program for investigating and remediating releases of hazardous wastes and hazardous waste constituents from solid waste management units (SWMUs) at facilities permitted to treat, store, or dispose of hazardous wastes. This proposed rule directly impacts many DOE facilities which conduct such activities. This guidance document explains the entire RCRA Corrective Action process as outlined by the proposed Subpart S rule, and provides guidance intended to assist those persons responsible for implementing RCRA Corrective Action at DOE facilities.

Enough Skill to Kill: Intentionality Judgments and the Moral Valence of Action

Science.gov (United States)

Guglielmo, Steve; Malle, Bertram F.

2010-01-01

Extant models of moral judgment assume that an action's intentionality precedes assignments of blame. Knobe (2003b) challenged this fundamental order and proposed instead that the badness or blameworthiness of an action directs (and thus unduly biases) people's intentionality judgments. His and other researchers' studies suggested that blameworthy…

Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

Science.gov (United States)

Homma, S; Nakajima, Y; Hayashi, K; Toma, S

1986-01-01

Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

LXA{sub 4} actions direct fibroblast function and wound closure

Energy Technology Data Exchange (ETDEWEB)

Herrera, Bruno S. [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Leung, Kai P., E-mail: kai.p.leung.civ@mail.mil [Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Van Dyke, Thomas E., E-mail: tvandyke@forsyth.org [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States)

2015-09-04

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF

Probabilistic safety assessment; actions and priorities in the EC-frame

International Nuclear Information System (INIS)

Amendola, A.; Mancini, G.; Volta, G.

1987-01-01

An overview is given of PSA research activities at the JRC and through shared cost actions with national laboratories under the nuclear reactor safety and major hazards of industrial installations programmes. These activities are directed towards the development of methods for PSA, the validation methods and the setting up of appropriate data bases. PSA is also directly or indirectly an emerging theme for the coordination activities in the area of nuclear safety criteria and safety objectives. Finally probabilistic techniques being increasing by being used for safety and reliability in various industrial sectors the CEC supported the preparation and setting up of a European Safety and Reliability Association that carries different types of actions. (orig.)

The renormalized action principle in quantum field theory

International Nuclear Information System (INIS)

Balasin, H.

1990-03-01

The renormalized action principle holds a central position in field theory, since it offers a variety of applications. The main concern of this work is the proof of the action principle within the so-called BPHZ-scheme of renormalization. Following the classical proof given by Lam and Lowenstein, some loopholes are detected and closed. The second part of the work deals with the application of the action principle to pure Yang-Mills-theories within the axial gauge (n 2 ≠ 0). With the help of the action principle we investigate the decoupling of the Faddeev-Popov-ghost-fields from the gauge field. The consistency of this procedure, suggested by three-graph approximation, is proven to survive quantization. Finally we deal with the breaking of Lorentz-symmetry caused by the presence of the gauge-direction n. Using BRST-like techniques and the semi-simplicity of the Lorentz-group, it is shown that no new breakings arise from quantization. Again the main step of the proof is provided by the action principle. (Author, shortened by G.Q.)

Application of adiponectin, TNF-α and ferrtin in type 2 diabetes with intrahepatic lipid infiltration

International Nuclear Information System (INIS)

Zhu Cuiying; Zhou Huan; Han Yuan; Ling Liqun; Huang Gang

2008-01-01

The aim of this study was to find and establish the serum marker which can reflect the degree of intrahepatic lipid infiltration in Type 2 diabetes patients and assess the therapeutic effect. It helps us to observe the improvement of intrahepatic lipid deposit under controlled serum glucose metabolism. Twenty-three Type 2 diabetes patients with obvious intrahepatic lipid infiltration diagnosed by CT scan were divided into two groups, one group took rosiglitazone orally (male: female 5:6), and the combined treatment group took rosiglitazone and metformin simultaneously (male: female 6:6), in daily therapeutic dose of 4 mg rosiglitazone and 2 g metformin for 24 weeks. Before and after treatment, we measured fasting serum glucose, glycated hemoglobin (GHb), insulin, insulin resistant index, plasma adiponectin, leptin, tumor necrotic factor α (TNF-α), ferrtin respectively. After the treatment, fasting serum glucose and GHb decreased obvious, especially the combined treatment group. Intrahepatic lipid content percent decreased, too, in both groups (the rosiglitazone group: 43.3±25.8 vs 29.1±18.7, P<0.01, the combined group: 43.4±21.8 vs 22.0±16.7, P<0.01). Plasma adiponectin and TNF-α had correlation to intrahepatic lipid contend percent change. Plasma adiponectin and TNF-α was obviously improved in the rosiglitazone group and the combined treatment group (Adiponectin: 11.96±7.3 vs 20.61±12.0 ng/mL, 12.76±6.7 vs 25.81±12.8 ng/mL; TNFα: 6.92±2.5 vs 5.89±1.9 pg/mL, 6.81±2.14 vs 5.45±2.0 pg/mL; P<0.01). In addition, serum ferrtin concentration decreased obviously, especially the combined treatment group (rosiglitazone group: 345±116 vs 288±71ng/mL, P<0.05, combined treatment group: 362±194 vs 258±109 ng/mL, P<0.01). It can be concluded that 1) rosiglitazone and metformin controls serum glucose metabolism and improves intrahepatic lipid infiltration by especially the combined treatment, 2) plasma adiponectic and TNF-α are effective markers to reflect

[Genetic aspects of the action of immunosuppressive agents].

Science.gov (United States)

Pevnitskiĭ, L A; Pisarev, V M; Telegin, L Iu; Tutel'ian, A V

1992-01-01

The data were obtained formerly that mice of certain strains essentially differ in the sensitivity to the immunodepressive and antiproliferative action of the alkylating agents (so-called opposite strains: DBA/2--highly sensitive, BALB/c--resistant). It is shown in the present work that with the use of the other non-alkylating immunodepressive agents (cytarabine, cyclosporin A, dexamethasone) that differ in the action mode, DBA/2 mice retain a high sensitivity whereas BALB/c mice a low sensitivity to all the immunodepressants. The sensitivity to the immunodepressive action in vivo directly correlates with that of the immunocompetent cells in vitro. Potential mechanisms determining the same type sensitivity to diverse immunodepressant in mice belonging to the above-indicated genotypes are under discussion.

Impaired inhibition of prepotent motor actions in patients with Tourette syndrome.

Science.gov (United States)

Wylie, Scott A; Claassen, Daniel O; Kanoff, Kristen E; Ridderinkhof, K Richard; van den Wildenberg, Wery P M

2013-09-01

Evidence that tic behaviour in individuals with Tourette syndrome reflects difficulties inhibiting prepotent motor actions is mixed. Response conflict tasks produce sensitive measures of response interference from prepotent motor impulses and the proficiency of inhibiting these impulses as an act of cognitive control. We tested the hypothesis that individuals with Tourette syndrome show a deficit in inhibiting prepotent motor actions. Healthy controls and older adolescents/adults with persistent Tourette syndrome without a history of obsessive-compulsive disorder or attention-deficit/hyperactivity disorder and presenting with stable mood functioning (i.e., no history of well-treated anxiety or depression) participated in this study. They performed a Simon task that induced conflict between prepotent actions and goal-directed actions. A novel theoretical framework distinguished group differences in acting impulsively (i.e., fast motor errors) from the proficiency of inhibiting interference by prepotent actions (i.e., slope of interference reduction). We included 27 controls and 28 individuals with Tourette syndrome in our study. Both groups showed similar susceptibility to making fast, impulsive motor errors (Tourette syndrome 26% v. control 23%; p = 0.10). The slope (m) reduction of the interference effect was significantly less pronounced among participants with Tourette syndrome than controls (Tourette syndrome: m = -0.07 v. control: m = -0.23; p = 0.022), consistent with deficient inhibitory control over prepotent actions in Tourette syndrome. This study does not address directly the role of psychiatric comorbidities and medication effects on inhibitory control over impulsive actions in individuals with Tourette syndrome. The results offer empirical evidence for deficient inhibitory control over prepotent motor actions in individuals with persistent Tourette syndrome with minimal to absent psychiatric comorbidities. These findings also suggest that the frontal

Controlling Attention through Action: Observing Actions Primes Action-Related Stimulus Dimensions

Science.gov (United States)

Fagioli, Sabrina; Ferlazzo, Fabio; Hommel, Bernhard

2007-01-01

Previous findings suggest that planning an action "backward-primes" perceptual dimension related to this action: planning a grasp facilitates the processing of visual size information, while planning a reach facilitates the processing of location information. Here we show that dimensional priming of perception through action occurs even in the…

QCD bosonization and the meson effective action

International Nuclear Information System (INIS)

Praschifka, J.; Roberts, C.D.; Cahill, R.T.

1987-01-01

A bosonization of quantum chromodynamics (QCD) is employed to derive a meson effective action, thus providing a direct link between QCD and meson phenomenology. As an example of this approach expressions are obtained for the meson parameters associated with the analysis of ω→3π decay. The bosonization also directly motivates a divergence-free, global color-symmetry model for mesons, which is seen to be a generalization of various phenomenological models. Good estimates are obtained for the values of several of the meson parameters

Toxicogenomics-based identification of mechanisms for direct immunotoxicity.

Science.gov (United States)

Shao, Jia; Katika, Madhumohan R; Schmeits, Peter C J; Hendriksen, Peter J M; van Loveren, Henk; Peijnenburg, Ad A C M; Volger, Oscar L

2013-10-01

Compounds with direct immunotoxic properties, including metals, mycotoxins, agricultural pesticides, and industrial chemicals, form potential human health risks due to exposure through food, drinking water, and the environment. Insights into the mechanisms of action are currently lacking for the majority of these direct immunotoxicants. Therefore, the present work aimed to gain insights into the molecular mechanisms underlying direct immunotoxicity. To this end, we assessed in vitro the effects of 31 test compounds on the transcriptome of the human Jurkat T-cell line. These compounds included direct immunotoxicants, immunosuppressive drugs with different mode of actions, and nonimmunotoxic control chemicals. Pathway analysis of the microarray data allowed us to identify canonical pathways and Gene Ontology processes that were transcriptionally regulated in common by immunotoxicants (1) with structural similarities, such as tributyltin chloride and tributyltin oxide that activated the retinoic acid/X receptor signaling pathway and (2) without structural similarities, such as As2O3, dibutyltin chloride, diazinon, MeHg, ochratoxin A (OTA), S9-treated OTA, S9-treated cyclophosphamide, and S9-treated benzo[a]pyrene, which activated unfolded protein response, and FTY720, lindane, and propanil, which activated the cholesterol biosynthesis pathway. In addition, processes uniquely affected by individual immunotoxicants were identified, such as the induction of Notch receptor signaling and the downregulation of acute-phase response genes by OTA. These findings were validated by quantitative real-time PCR analysis of genes involved in these processes. Our study indicated that diverse modes of action are involved in direct immunotoxicity and that a set of pathways or genes, rather than one single gene, can be used to screen compounds for direct immunotoxicity.

Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

OpenAIRE

de Wit, Sanne; Standing, Holly R.; DeVito, Elise E.; Robinson, Oliver J.; Ridderinkhof, K. Richard; Robbins, Trevor W.; Sahakian, Barbara J.

2011-01-01

Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus?response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. Objectives We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. Metho...

Direct effects of exendin-(9,39) and GLP-1-(9,36)amide on insulin action, β-cell function, and glucose metabolism in nondiabetic subjects.

Science.gov (United States)

Sathananthan, Matheni; Farrugia, Luca P; Miles, John M; Piccinini, Francesca; Dalla Man, Chiara; Zinsmeister, Alan R; Cobelli, Claudio; Rizza, Robert A; Vella, Adrian

2013-08-01

Exendin-(9,39) is a competitive antagonist of glucagon-like peptide-1 (GLP-1) at its receptor. However, it is unclear if it has direct and unique effects of its own. We tested the hypothesis that exendin-(9,39) and GLP-1-(9,36)amide have direct effects on hormone secretion and β-cell function as well as glucose metabolism in healthy subjects. Glucose containing [3-(3)H]glucose was infused to mimic the systemic appearance of glucose after a meal. Saline, GLP-1-(9,36)amide, or exendin-(9,39) at 30 pmol/kg/min (Ex 30) or 300 pmol/kg/min (Ex 300) were infused in random order on separate days. Integrated glucose concentrations were slightly but significantly increased by exendin-(9,39) (365 ± 43 vs. 383 ± 35 vs. 492 ± 49 vs. 337 ± 50 mmol per 6 h, saline, Ex 30, Ex 300, and GLP-1-[9,36]amide, respectively; P = 0.05). Insulin secretion did not differ among groups. However, insulin action was lowered by exendin-(9,39) (25 ± 4 vs. 20 ± 4 vs. 18 ± 3 vs. 21 ± 4 10(-4) dL/kg[min per μU/mL]; P = 0.02), resulting in a lower disposition index (DI) during exendin-(9,39) infusion (1,118 ± 118 vs. 816 ± 83 vs. 725 ± 127 vs. 955 ± 166 10(-14) dL/kg/min(2) per pmol/L; P = 0.003). Endogenous glucose production and glucose disappearance did not differ significantly among groups. We conclude that exendin-(9,39), but not GLP-1-(9,36)amide, decreases insulin action and DI in healthy humans.

Statistical learning of action: the role of conditional probability.

Science.gov (United States)

Meyer, Meredith; Baldwin, Dare

2011-12-01

Identification of distinct units within a continuous flow of human action is fundamental to action processing. Such segmentation may rest in part on statistical learning. In a series of four experiments, we examined what types of statistics people can use to segment a continuous stream involving many brief, goal-directed action elements. The results of Experiment 1 showed no evidence for sensitivity to conditional probability, whereas Experiment 2 displayed learning based on joint probability. In Experiment 3, we demonstrated that additional exposure to the input failed to engender sensitivity to conditional probability. However, the results of Experiment 4 showed that a subset of adults-namely, those more successful at identifying actions that had been seen more frequently than comparison sequences-were also successful at learning conditional-probability statistics. These experiments help to clarify the mechanisms subserving processing of intentional action, and they highlight important differences from, as well as similarities to, prior studies of statistical learning in other domains, including language.

Comparing Pictures and Videos for Teaching Action Labels to Children with Communication Delays

Science.gov (United States)

Schebell, Shannon; Shepley, Collin; Mataras, Theologia; Wunderlich, Kara

2018-01-01

Children with communication delays often display difficulties labeling stimuli in their environment, particularly related to actions. Research supports direct instruction with video and picture stimuli for increasing children's action labeling repertoires; however, no studies have compared which type of stimuli results in more efficient,…

77 FR 30232 - Airworthiness Directives; Bell Helicopter Textron Helicopters

Science.gov (United States)

2012-05-22

...-0530; Directorate Identifier 2011-SW-075-AD] RIN 2120-AA64 Airworthiness Directives; Bell Helicopter Textron Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: We propose to adopt a new airworthiness directive (AD) for Bell Helicopter...

76 FR 60367 - Airworthiness Directives; Piper Aircraft, Inc. Airplanes

Science.gov (United States)

2011-09-29

... Airworthiness Directives; Piper Aircraft, Inc. Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are revising an existing airworthiness directive (AD) for certain Piper...). ADDRESSES: For service information identified in this AD, contact Piper Aircraft, Inc., 2926 Piper Drive...

Mechanisms of action of hormonal emergency contraceptives.

Science.gov (United States)

Leung, Vivian W Y; Levine, Marc; Soon, Judith A

2010-02-01

Hormonal emergency contraceptives have been used to prevent unwanted pregnancy for more than 3 decades. The mechanisms of action of the regimen containing a combination of estrogen and progestin, known as the Yuzpe regimen, and those of the levonorgestrel regimen continue to be controversial, especially over the possibility that these regimens might act by interfering with implantation of the fertilized ovum. We performed a search of the PubMed (1949-July 2009) and EMBASE (1980-July 2009) databases to identify literature on the mechanisms of action of these contraceptive regimens, and data were extracted from pertinent English-language studies. We classified studies according to the approach taken by the investigators to study the actions of emergency contraceptives on pregnancy: an indirect method that uses statistical models to determine whether emergency contraceptives would be as effective as reported if they act only by disrupting ovulation; direct observation of the effects of emergency contraceptives on surrogate outcomes, including ovulation, sperm activity, hormonal levels, and endometrial receptivity to implantation; and analysis of directly observed pregnancy outcomes against statistical data. Acceptability of emergency contraceptives by women and clinicians may depend on personal opinions about when life or pregnancy begins. The evidence strongly supports disruption of ovulation as a mechanism of action. The data suggest that emergency contraceptives are unlikely to act by interfering with implantation, although the possibility has not been completely excluded. The data also suggest that emergency contraceptives are ineffective after ovulation. Women and clinicians who consider implantation or later events to be the beginning of pregnancy should be aware that emergency contraceptives are likely nonabortive by this definition of pregnancy.

The influence of action-effect anticipation on bistable perception: Differences between onset rivalry and ambiguous motion

NARCIS (Netherlands)

Dogge, M.; Gayet, S.; Custers, R.; Aarts, H.A.G.

2018-01-01

Perception is strongly shaped by the actions we perform. According to the theory of event coding, and forward models of motor control, goal-directed action preparation activates representations of desired effects. These expectations about the precise stimulus identity of one's action-outcomes (i.e.

Adaptive control of ionic polymer–metal composite in air and under water using a modified direct self-tuning regulator embedded with integral action

International Nuclear Information System (INIS)

Fang, Bo-Kai; Ju, Ming-Shuang; Lin, Chou-Ching K

2011-01-01

Due to its large deformation response to a low voltage, ionic polymer–metal composite (IPMC) is a highly attractive actuator for many applications in air or under water. However, the dynamic characteristics of IPMC are nonlinear and vary with time, especially in water actuations. In this study, a modified direct self-tuning regulator (DSTR) with integral action was designed to control the tip-displacement of the IPMC, which is a non-minimum phase system to serve in air and underwater applications. The modified DSTR consisted of a pole-placement controller embedded with integral action, a reference model, and a self-tuning mechanism. The reference model specified the dynamic characteristic of the closed-loop IPMC system, and the controller parameters were automatically adjusted by the self-tuning mechanism to minimize the tracking error from the comparison between the response and the reference model output. The integral action may circumvent low-frequency distortions such as the back-relaxation phenomenon. Also, the DSTR may easily control the non-minimum phase system of the IPMC by tuning a delay factor in the reference model. The DSTR was implemented to control an IPMC (0.2 mm × 5 mm × 35 mm) actuated in air and under water, and the tracking performances were compared with a proportional-integral-derivative controller (PID). In contrast with the PID, the parameters of which were determined by the Ziegler–Nichols rule and produced large root-mean-squared tracking errors, the DSTR yielded good tracking performances for actuations both in air and under water from 0.01 to 1 Hz. Through control of the modified DSTR, IPMC may have a wide range of applications in the future

Reliance on habits at the expense of goal-directed control following dopamine precursor depletion.

Science.gov (United States)

de Wit, Sanne; Standing, Holly R; Devito, Elise E; Robinson, Oliver J; Ridderinkhof, K Richard; Robbins, Trevor W; Sahakian, Barbara J

2012-01-01

Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. The dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes. APTD did not prevent stimulus-response learning, nor did we find evidence for impaired response-outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers. We provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies.

Corrective Action Investigation Plan for Corrective Action Unit 528: Polychlorinated Biphenyls Contamination, Nevada Test Site, Nevada, Rev. 0

Energy Technology Data Exchange (ETDEWEB)

U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

2003-05-08

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 528, Polychlorinated Biphenyls Contamination (PCBs), Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. Located in the southwestern portion of Area 25 on the NTS in Jackass Flats (adjacent to Test Cell C [TCC]), CAU 528 consists of Corrective Action Site 25-27-03, Polychlorinated Biphenyls Surface Contamination. Test Cell C was built to support the Nuclear Rocket Development Station (operational between 1959 and 1973) activities including conducting ground tests and static firings of nuclear engine reactors. Although CAU 528 was not considered as a direct potential source of PCBs and petroleum contamination, two potential sources of contamination have nevertheless been identified from an unknown source in concentrations that could potentially pose an unacceptable risk to human health and/or the environment. This CAU's close proximity to TCC prompted Shaw to collect surface soil samples, which have indicated the presence of PCBs extending throughout the area to the north, east, south, and even to the edge of the western boundary. Based on this information, more extensive field investigation activities are being planned, the results of which are to be used to support a defensible evaluation of corrective action alternatives in the corrective action decision document.

Location-coding account versus affordance-activation account in handle-to-hand correspondence effects: Evidence of Simon-like effects based on the coding of action direction.

Science.gov (United States)

Pellicano, Antonello; Koch, Iring; Binkofski, Ferdinand

2017-09-01

An increasing number of studies have shown a close link between perception and action, which is supposed to be responsible for the automatic activation of actions compatible with objects' properties, such as the orientation of their graspable parts. It has been observed that left and right hand responses to objects (e.g., cups) are faster and more accurate if the handle orientation corresponds to the response location than when it does not. Two alternative explanations have been proposed for this handle-to-hand correspondence effect : location coding and affordance activation. The aim of the present study was to provide disambiguating evidence on the origin of this effect by employing object sets for which the visually salient portion was separated from, and opposite to the graspable 1, and vice versa. Seven experiments were conducted employing both single objects and object pairs as visual stimuli to enhance the contextual information about objects' graspability and usability. Notwithstanding these manipulations intended to favor affordance activation, results fully supported the location-coding account displaying significant Simon-like effects that involved the orientation of the visually salient portion of the object stimulus and the location of the response. Crucially, we provided evidence of Simon-like effects based on higher-level cognitive, iconic representations of action directions rather than based on lower-level spatial coding of the pure position of protruding portions of the visual stimuli. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

77 FR 68055 - Airworthiness Directives; Bell Helicopter Textron Helicopters

Science.gov (United States)

2012-11-15

... Airworthiness Directives; Bell Helicopter Textron Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for Bell Helicopter Textron (BHT) Model 412, 412EP, and 412CF helicopters. This AD requires a repetitive inspection of the...

77 FR 71723 - Airworthiness Directives; The Boeing Company Airplanes

Science.gov (United States)

2012-12-04

... Airworthiness Directives; The Boeing Company Airplanes AGENCY: Federal Aviation Administration (FAA), DOT... directive (AD) that applies to certain The Boeing Company Model 737-200, -200C, - 300, and -400 series... related investigative and corrective actions, and revise certain inspection types. This proposed AD would...

Final audit report of remedial action construction at the UMTRA project site Rifle, Colorado. Rev. 1

International Nuclear Information System (INIS)

1997-01-01

This final audit report summarizes the assessments performed by the U.S. Department of Energy (DOE) Environmental Restoration Division (ERD) and its Technical Assistance Contractor (TAC) of remedial action compliance with approved plans, specifications, standards, and 40 CFR Part 192 at the Rifle, Colorado, Uranium Mill Tailings Remedial Action (UMTRA) Project site. Remedial action construction was directed by the Remedial Action Contractor (RAC)

Perception and action de-coupling in congenital amusia: sensitivity to task demands.

Science.gov (United States)

Williamson, Victoria J; Liu, Fang; Peryer, Guy; Grierson, Mick; Stewart, Lauren

2012-01-01

Theories that purport the existence of a distinct auditory action stream have received support from the finding that individuals with congenital amusia, a disorder of pitch perception, are able to reproduce the direction of a pitch change that they are unable to identify (Loui, Guenther, Mathys, & Schlaug, 2008). Although this finding has proved influential in theorizing about the existence of an auditory action-stream, aspects of the original study warrant further investigation. The present report attempts to replicate the original study's findings across a sizeable cohort of individuals with amusia (n=14), obtaining action (production) and perception thresholds for pitch direction. In contrast to the original study, we find evidence of a double dissociation: while a minority of amusics had lower (better) thresholds for production compared to perception of pitch, more than half showed the reverse pattern. To explore the impact of task demands, perception thresholds were also measured using a two alternative, criterion-free, forced choice task that avoided labeling demands. Controls' thresholds were task-invariant while amusics' thresholds were significantly task-dependent. We argue that the direction and extent of a perception/production dissociation in this population reflects individual differences in the mapping of pitch representations to labels ("up"; "down") and to the vocal apparatus, as opposed to anything intrinsically yoked to perception or action per se. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-09-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1994-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-05-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-09-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-11-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-08-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-02-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-06-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1990-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-07-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-05-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-12-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1993-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1991-11-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-03-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1992-11-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July - September 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Enforcement actions: Significant actions resolved

International Nuclear Information System (INIS)

1989-12-01

This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

Research in Water Permeability of Poly(ethylene) Terephthalate Track Membranes Modified by Polymerization of Dimethylaniline under the Action of Direct Current Discharge

CERN Document Server

Kravets, L I; Drachev, A I

2004-01-01

The properties of poly(ethylene) terephthalate track membranes modified by polymerization of dimethylaniline in a discharge of direct current are investigated. The influence of conditions of plasma treatment on the basic characteristics of the membranes (pore size, wettability, surface charge, water permeability) is studied. It is shown that under the action of discharge, a polymeric layer is formed on the membrane surface that can swell in solutions with low pH values. It has been found that the degree of the swelling stipulated by the conformation transfer of macromolecules of the deposited polymeric layer depends upon the size of relative magnification of the mass of the membrane during its plasma treatment. It is also shown that the obtained membranes can reversibly react to changing the pH of solution and applied pressure.

Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

International Nuclear Information System (INIS)

Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha; Beisiegel, Ulrike; Heeren, Joerg

2008-01-01

There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARγ agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARγ-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake

Recognition of Action as a Bayesian Parameter Estimation Problem over Time

DEFF Research Database (Denmark)

Krüger, Volker

2007-01-01

In this paper we will discuss two problems related to action recognition: The first problem is the one of identifying in a surveillance scenario whether a person is walking or running and in what rough direction. The second problem is concerned with the recovery of action primitives from observed...... complex actions. Both problems will be discussed within a statistical framework. Bayesian propagation over time offers a framework to treat likelihood observations at each time step and the dynamics between the time steps in a unified manner. The first problem will be approached as a patter recognition...... of the Bayesian framework for action recognition and round up our discussion....

Perspectives on object manipulation and action grammar for percussive actions in primates.

Science.gov (United States)

Hayashi, Misato

2015-11-19

The skill of object manipulation is a common feature of primates including humans, although there are species-typical patterns of manipulation. Object manipulation can be used as a comparative scale of cognitive development, focusing on its complexity. Nut cracking in chimpanzees has the highest hierarchical complexity of tool use reported in non-human primates. An analysis of the patterns of object manipulation in naive chimpanzees after nut-cracking demonstrations revealed the cause of difficulties in learning nut-cracking behaviour. Various types of behaviours exhibited within a nut-cracking context can be examined in terms of the application of problem-solving strategies, focusing on their basis in causal understanding or insightful intentionality. Captive chimpanzees also exhibit complex forms of combinatory manipulation, which is the precursor of tool use. A new notation system of object manipulation was invented to assess grammatical rules in manipulative actions. The notation system of action grammar enabled direct comparisons to be made between primates including humans in a variety of object-manipulation tasks, including percussive-tool use. © 2015 The Author(s).

Action preferences and the anticipation of action outcomes

NARCIS (Netherlands)

Mann, D.L.; Schaefers, T.; Canal Bruland, R.

2014-01-01

Skilled performers of time-constrained motor actions acquire information about the action preferences of their opponents in an effort to better anticipate the outcome of that opponent's actions. However, there is reason to doubt that knowledge of an opponent's action preferences would unequivocally

Actions of a separately strict cpo-monoid on pointed directed complete posets

Directory of Open Access Journals (Sweden)

Halimeh Moghbeli Damaneh

2015-07-01

Full Text Available ‎ In the present article‎, ‎we study some categorical properties of the category {$bf‎ Cpo_{Sep}$-$S$} of all {separately strict $S$-cpo's}; cpo's equipped with‎ a compatible right action of a separately strict cpo-monoid $S$ which is‎ strict continuous in each component‎. ‎In particular‎, we show that this category is reflective and coreflective in the‎ category of $S$-cpo's‎, ‎find the free and cofree functors‎, characterize products and coproducts‎. ‎Furthermore‎, ‎epimorphisms and‎  monomorphisms in {$bf Cpo_{Sep}$-$S$} are studied‎, ‎and show that‎ {$bf Cpo_{Sep}$-$S$} is not cartesian closed‎.

Political struggles in disability’s visibilization: direct actions, counter-conducts and resistance

Directory of Open Access Journals (Sweden)

Alejandro Martín Contino

2013-12-01

Full Text Available Since the examination of the current situation of persons under disability, the hypothesis of conceiving disability as a device is carried out, according to the French philosopher Michel Foucault. Thus, the negative aspects experienced by subjects in situation of disability, not implying malfunction of public policy, would be logical and expected effects, the typical function of a disability device that works according to the guidelines of the Medical-Individual model. This article intends to present the tactics of counter-conduct as ways of subjectivation that resist current governmentality, becoming the visibilization of such actions, a key aspect of any strategy of political transformation.

A model for production, perception, and acquisition of actions in face-to-face communication.

Science.gov (United States)

Kröger, Bernd J; Kopp, Stefan; Lowit, Anja

2010-08-01

The concept of action as basic motor control unit for goal-directed movement behavior has been used primarily for private or non-communicative actions like walking, reaching, or grasping. In this paper, literature is reviewed indicating that this concept can also be used in all domains of face-to-face communication like speech, co-verbal facial expression, and co-verbal gesturing. Three domain-specific types of actions, i.e. speech actions, facial actions, and hand-arm actions, are defined in this paper and a model is proposed that elucidates the underlying biological mechanisms of action production, action perception, and action acquisition in all domains of face-to-face communication. This model can be used as theoretical framework for empirical analysis or simulation with embodied conversational agents, and thus for advanced human-computer interaction technologies.

Resolution of conflict between goal-directed actions: outcome encoding and neural control processes.

Science.gov (United States)

de Wit, Sanne; Ostlund, Sean B; Balleine, Bernard W; Dickinson, Anthony

2009-07-01

According to O-R theory of instrumental learning, incongruent biconditional discriminations should be impossible to solve in a goal-directed manner because the event acting as the outcome of one response also acts as a discriminative stimulus for an opposite response. Each event should therefore be associated with two competing responses. However, Dickinson and de Wit (2003) have presented evidence that rats can learn incongruent discriminations. The present study investigated whether rats were able to engage additional processes to solve incongruent discriminations in a goal-directed manner. Experiment 1 provides evidence that rats resolve the response conflict that arises in the incongruent discrimination by differentially encoding events in their roles as discriminative stimulus and as outcome. Furthermore, Experiment 2 shows that once goal-directed control has been established the dorsomedial prefrontal cortex is not directly involved in its maintenance but rather plays a central role in conflict resolution processes.

Six-and-a-Half-Month-Old Children Positively Attribute Goals to Human Action and to Humanoid-Robot Motion

Science.gov (United States)

Kamewari, K.; Kato, M.; Kanda, T.; Ishiguro, H.; Hiraki, K.

2005-01-01

Recent infant studies indicate that goal attribution (understanding of goal-directed action) is present very early in infancy. We examined whether 6.5-month-olds attribute goals to agents and whether infants change the interpretation of goal-directed action according to the kind of agent. We conducted three experiments using the visual habituation…

New trouble brewing: environmental associations are granted the right to institute group action

International Nuclear Information System (INIS)

Heller, W.

2005-01-01

An important legislative project is the transposition of Directive 2003/35/EC of the European Parliament and the Council about public participation in the development of certain plans and programs related to the environment, and the amendment of Directives 85/337/EEC and 96/61EC of the Council about public participation and access to courts of law. These directives must be transposed into national law and administrative regulations by June 25, 2005. The Directive on Public Participation introduced the right to institute group action. If these provisions were adopted as planned, environmental associations henceforth would be in a position, among other things, to bring action against plant permits, permits under water management and atomic energy laws, allocations of certificates under the new emissions trading system, etc. On February 21, 2005, the German Federal Ministry for the Environment (BMU) presented a first draft bill about supplementary provisions on legal remedies in environmental cases under the EU Directive (Environmental Legal Remedies Act), which is to be discussed with the Associations in the near future. The preface to the ministerial draft bill does not preclude the possibility of the introduction of group action giving rise to procedural delays in specific cases and, as a consequence, to additional expenses in investment projects. Legislation has ways and means to minimize negative consequences. (orig.)

Thyroid hormone action: Astrocyte-neuron communication.

Directory of Open Access Journals (Sweden)

Beatriz eMorte

2014-05-01

Full Text Available Thyroid hormone action is exerted mainly through regulation of gene expression by binding of T3 to the nuclear receptors. T4 plays an important role as a source of intracellular T3 in the central nervous system via the action of the type 2 deiodinase, expressed in the astrocytes. A model of T3 availability to neural cells has been proposed and validated. The model contemplates that brain T3 has a double origin: a fraction is available directly from the circulation, and another is produced locally from T4 in the astrocytes by type 2 deiodinase. The fetal brain depends almost entirely on the T3 generated locally. The contribution of systemic T3 increases subsequently during development to account for approximately 50% of total brain T3 in the late postnatal and adult stages. In this article we review the experimental data in support of this model, and how the factors affecting T3 availability in the brain, such as deiodinases and transporters, play a decisive role in modulating local thyroid hormone action during development.

12 CFR 702.203 - Prompt corrective action for “significantly undercapitalized” credit unions.

Science.gov (United States)

2010-01-01

... the applicable procedures for issuing, reviewing and enforcing directives set forth in subpart L of... union pays on shares as provided in § 702.202(b)(3); (4) Prohibiting or reducing asset growth. Prohibit... share to such officer; (11) Other actions to carry out prompt corrective action. Restrict or require...

The mode of inotropic action of ciguatoxin on guinea-pig cardiac muscle.

Science.gov (United States)

Seino, A.; Kobayashi, M.; Momose, K.; Yasumoto, T.; Ohizumi, Y.

1988-01-01

1. Ciguatoxin (CTX) caused a dose-dependent increase in the contractile force of the guinea-pig isolated left atria at concentrations ranging from 0.1 to 10 ng ml-1 with the ED50 value of 0.5 ng ml-1. 2. In the atria, tetrodotoxin (5 x 10(-7) M) inhibited markedly the inotropic action of CTX. The inotropic effect of CTX at low concentrations was abolished by practolol (10(-5) M) and reserpine (2 mg kg-1 daily, for 3 days), whereas that of CTX at high concentrations was partially inhibited by both drugs. 3. In single atrial cells, CTX (3 ng ml-1) produced a marked increase in the amplitude of longitudinal contractions. 4. CTX (3 ng ml-1) caused marked prolongation in the falling phase of action potentials of atrial strips without affecting the maximum rate of rise of action potentials and membrane resting potentials. The effect of CTX on action potentials was abolished by tetrodotoxin (10(-6) M). 5. The whole-cell patch-clamp experiments on myocytes revealed that CTX (20 ng ml-1) shifted the current-voltage curve of Na inward currents by 40 mV in the negative direction. CTX caused a small sustained Na inward current even at resting membrane potentials. 6. These results suggest that the inotropic action of lower concentrations of CTX is primarily due to an indirect action via noradrenaline release, whereas that of higher concentrations is caused not only by an indirect action but also by a direct action on voltage-dependent Na channels of cardiac muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3207997

Thought-action fusion: review of the literature and future directions.

Science.gov (United States)

Berle, David; Starcevic, Vladan

2005-05-01

Thought-action fusion (TAF) is the tendency for individuals to assume that certain thoughts either imply the immorality of their character or increase the likelihood of catastrophic events. The burgeoning literature on TAF is reviewed. It is not clear whether TAF refers to a specific appraisal style, a more enduring belief, or a combination of both. Inconsistent definitions of magical thinking have hindered better understanding of the relationship between TAF and magical thinking. Much work remains to be done to improve assessment and measurement of TAF. TAF is associated with tendencies towards obsessive-compulsive disorder (OCD) and may contribute to its symptoms. However, the literature investigating TAF and other variables implicated in OCD remains inconclusive. It is suggested that TAF is not specific to OCD, but also prevalent in other anxiety disorders. TAF appears to be moderately related to depressive symptoms and a similar bias may contribute to preoccupations in eating disorders. TAF is also associated with the presence of psychological disorders in children and adolescents. Educational and cognitive therapy approaches to reduce TAF and consequent symptoms are discussed, and suggestions for further research made.

Evidence of directional and stabilizing selection in contemporary humans.

Science.gov (United States)

Sanjak, Jaleal S; Sidorenko, Julia; Robinson, Matthew R; Thornton, Kevin R; Visscher, Peter M

2018-01-02

Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.

Revisiting Jürgen Habermas's notion of communicative action and ...

African Journals Online (AJOL)

Erna Kinsey

its relevance for South African school governance: can it succeed? Nonceba ... Keywords: communicative action; Department of Education; governance framework .... view was open-ended and conducted in an informal, non-directive manner so ..... Issues in Social Science Research Methodology (Module 1). Ethiopia:.

12 CFR 585.30 - What actions are prohibited?

Science.gov (United States)

2010-01-01

... SAVINGS AND LOAN HOLDING COMPANIES Prohibition § 585.30 What actions are prohibited? (a) Person. If a...: (1) Become, or continue as, an institution-affiliated party with respect to any savings and loan holding company. (2) Own or control, directly or indirectly, any savings and loan holding company. A...

DAPs: Deep Action Proposals for Action Understanding

KAUST Repository

Escorcia, Victor

2016-09-17

Object proposals have contributed significantly to recent advances in object understanding in images. Inspired by the success of this approach, we introduce Deep Action Proposals (DAPs), an effective and efficient algorithm for generating temporal action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates that our approach outperforms previous work on a large scale action benchmark, runs at 134 FPS making it practical for large-scale scenarios, and exhibits an appealing ability to generalize, i.e. to retrieve good quality temporal proposals of actions unseen in training.

Assessment of Evacuation Protective Action Strategies For Emergency Preparedness Plan

Energy Technology Data Exchange (ETDEWEB)

Lee, Joomyung; Jae, Moosung [Hanyang Univ., Seoul (Korea, Republic of); Ahn, Kwangil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

This report which studies about evacuation formation suggests some considerable factors to reduce damage of radiological accidents. Additional details would be required to study in depth and more elements should be considered for updating emergency preparedness. However, this methodology with sensitivity analysis could adapt to specific plant which has total information such as geological data, weather data and population data. In this point of view the evacuation study could be contribute to set up emergency preparedness plan and propose the direction to enhance protective action strategies. In radiological emergency, residents nearby nuclear power plant should perform protective action that is suggested by emergency preparedness plan. The objective of emergency preparedness plan is that damages, such as casualties and environmental damages, due to radioactive accident should be minimized. The recent PAR study includes a number of subjects to improve the quality of protective action strategies. For enhancing protective action strategies, researches that evaluate many factors related with emergency response scenario are essential parts to update emergency preparedness plan. Evacuation is very important response action as protective action strategy.

Assessment of Evacuation Protective Action Strategies For Emergency Preparedness Plan

International Nuclear Information System (INIS)

Lee, Joomyung; Jae, Moosung; Ahn, Kwangil

2013-01-01

This report which studies about evacuation formation suggests some considerable factors to reduce damage of radiological accidents. Additional details would be required to study in depth and more elements should be considered for updating emergency preparedness. However, this methodology with sensitivity analysis could adapt to specific plant which has total information such as geological data, weather data and population data. In this point of view the evacuation study could be contribute to set up emergency preparedness plan and propose the direction to enhance protective action strategies. In radiological emergency, residents nearby nuclear power plant should perform protective action that is suggested by emergency preparedness plan. The objective of emergency preparedness plan is that damages, such as casualties and environmental damages, due to radioactive accident should be minimized. The recent PAR study includes a number of subjects to improve the quality of protective action strategies. For enhancing protective action strategies, researches that evaluate many factors related with emergency response scenario are essential parts to update emergency preparedness plan. Evacuation is very important response action as protective action strategy

Information actions in science and technology: institutionalities, agencies and subjects

Directory of Open Access Journals (Sweden)

Rodrigo Rabello

Full Text Available Considering the influence of new agency forms - intervention and interaction among subjects - in the context of information intermediation, we aim to approach information actions in Science and Technology (S&T taking into consideration the institutionalities involved. For such, we assume there is an influence of a theoretical model emerging in Information Science (IS regarding current inventive and interactive form propitiated by the Web. The text is structured in two central topics bringing: i theoretical and epistemic constructions of the "information action" concept; and ii a certain interpretation oriented by the "informational action in S&T" construct, taking as its object the actions performed by IBICT (Brazilian Institute for Information in Science and Technology, directed towards excellence in information. Finally, we discuss how limitations of the "systemic model" propitiate the construction of new study objects in the model emerging in IS from theoretical innovations and counterpoints thoughts facing the diverse forms of information action, considering, for instance, the action of subjects on what concerns the validation of information in the current scenery of institutional intermediation.

A reasoned action approach to health promotion.

Science.gov (United States)

Fishbein, Martin

2008-01-01

This article describes the integrative model of behavioral prediction (IM), the latest formulation of a reasoned action approach. The IM attempts to identify a limited set of variables that can account for a considerable proportion of the variance in any given behavior. More specifically, consistent with the original theory of reasoned action, the IM assumes that intentions are the immediate antecedents of behavior, but in addition, the IM recognizes that environmental factors and skills and abilities can moderate the intention-behavior relationship. Similar to the theory of planned behavior, the IM also assumes that intentions are a function of attitudes, perceived normative pressure and self-efficacy, but it views perceived normative pressure as a function of descriptive as well as of injunctive (i.e., subjective) norms. After describing the theory and addressing some of the criticisms directed at a reasoned action approach, the paper illustrates how the theory can be applied to understanding and changing health related behaviors.

Modelling Dowel Action of Discrete Reinforcing Bars in Cracked Concrete Structures

International Nuclear Information System (INIS)

Kwan, A. K. H.; Ng, P. L.; Lam, J. Y. K.

2010-01-01

Dowel action is one of the component actions for shear force transfer in cracked reinforced concrete. In finite element analysis of concrete structures, the use of discrete representation of reinforcing bars is considered advantageous over the smeared representation due to the relative ease of modelling the bond-slip behaviour. However, there is very limited research on how to simulate the dowel action of discrete reinforcing bars. Herein, a numerical model for dowel action of discrete reinforcing bars crossing cracks in concrete is developed. The model features the derivation of dowel stiffness matrix based on beam-on-elastic-foundation theory and the direct assemblage of dowel stiffness into the concrete element stiffness matrices. The dowel action model is incorporated in a nonlinear finite element programme with secant stiffness formulation. Deep beams tested in the literature are analysed and it is found that the incorporation of dowel action model improves the accuracy of analysis.

Givental action and trivialisation of circle action

NARCIS (Netherlands)

Dotsenko, V.; Shadrin, S.; Vallette, B.

2015-01-01

In this paper, we show that the Givental group action on genus zero cohomological field theories, also known as formal Frobenius manifolds or hypercommutative algebras, naturally arises in the deformation theory of Batalin-Vilkovisky algebras. We prove that the Givental action is equal to an action

77 FR 46855 - Small Business Technology Transfer Program Policy Directive

Science.gov (United States)

2012-08-06

... SMALL BUSINESS ADMINISTRATION 13 CFR Chapter I RIN 3245-AF45 Small Business Technology Transfer Program Policy Directive AGENCY: Small Business Administration. ACTION: Final policy directive with request for comments. SUMMARY: The U.S. Small Business Administration (SBA) is amending its Small Business...

75 FR 15756 - Small Business Innovation Research Program Policy Directive

Science.gov (United States)

2010-03-30

... SMALL BUSINESS ADMINISTRATION RIN 3244-AF61 Small Business Innovation Research Program Policy Directive AGENCY: U.S. Small Business Administration. ACTION: Notice of Final Amendments to Policy Directive. SUMMARY: This document announces a final amendment to the Small Business Innovation Research (SBIR...

Corrective Action Investigation Plan for Corrective Action Unit 230: Area 22 Sewage Lagoons and Corrective Action Unit 320: Area 22 Desert Rock Airport Strainer Box, Nevada Test Site, Nevada

International Nuclear Information System (INIS)

1999-01-01

This Corrective Action Investigation Plan contains the U.S. Department of Energy, Nevada Operation Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 230/320 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 230 consists of Corrective Action Site (CAS) 22-03-01, Sewage Lagoon; while CAU 320 consists of CAS 22-99-01, Strainer Box. These CAUs are referred to as CAU 230/320 or the Sewage Lagoons Site. The Sewage Lagoons Site also includes an Imhoff tank, sludge bed, and associated buried sewer piping. Located in Area 22, the site was used between 1951 to 1958 for disposal of sanitary sewage effluent from the historic Camp Desert Rock Facility at the Nevada Test Site in Nevada. Based on site history, the contaminants of potential concern include volatile organic compounds (VOCs), semivolatile organic compounds, total petroleum hydrocarbons (TPH), and radionuclides. Vertical migration is estimated to be less than 12 feet below ground surface, and lateral migration is limited to the soil immediately adjacent to or within areas of concern. The proposed investigation will involve a combination of field screening for VOCs and TPH using the direct-push method and excavation using a backhoe to gather soil samples for analysis. Gamma spectroscopy will also be conducted for waste management purposes. Sampling locations will be biased to suspected worst-case areas including the nearby sludge bed, sewage lagoon inlet(s) and outlet(s), disturbed soil surrounding the lagoons, surface drainage channel south of the lagoons, and the area near the Imhoff tank. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document

Understanding intentional actions from observers' viewpoints: A social neuroscience perspective.

Science.gov (United States)

Isoda, Masaki

2016-11-01

When we see others, we also try to 'see' their unobservable states of minds, such as beliefs, desires, and intentions. We carefully monitor others' actions, as we assume that those actions are outward manifestations of their internal states. Actors and observers can have divergent views on the cause of the same actions. Critically, it is often the observers' view that affects important decisions in social life, from deciding the optimal level of cooperation to judging moral responsibility and court's decisions. Thus, the judgment about intentionality and agency in others' actions determines the way in which the observer deals with the actor. The primate brain has two separate neural systems that function in understanding others' actions and intentions. The mirror system is activated by others' visible actions and predicts their physical consequences in goal terms, whereas the mentalizing system is primarily involved in the prediction of others' intentions and upcoming actions regardless of whether others' actions are directly observable or not. The functional roles of the two systems have sometimes been described as mutually independent or even oppositional. I propose a hypothesis that the two systems may collaborate closely for judging the sense of other-agency. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

75 FR 51841 - Notice of Realty Action: Proposed sale of Public Lands, Churchill County, NV

Science.gov (United States)

2010-08-23

... Lands, Churchill County, NV AGENCY: Bureau of Land Management, Interior. ACTION: Notice of realty action... value, approximately 800 acres of public lands in Churchill County, Nevada, through direct [email protected] . SUPPLEMENTARY INFORMATION: The following described public lands in Churchill County...

Management of cardiac fibrosis in diabetic rats; the role of peroxisome proliferator activated receptor gamma (PPAR-gamma and calcium channel blockers (CCBs

Directory of Open Access Journals (Sweden)

Mohamad Hoda E

2011-03-01

Full Text Available Abstract Background Diabetes mellitus (DM and hypertension (HTN are accused of being responsible for the development of the cardiac fibrosis due to severe cardiomyopathy. Methods Blood glucose (BG test was carried out, lipid concentrations, tumor necrosis factor alpha (TNF-α, transforming growth factor beta (TGF-β, matrix metalloproteinase (MMP-2, collagen-I and collagen-III were measured in male Albino rats weighing 179-219 g. The rats were divided into five groups, kept on either control diet or high fat diet (HFD, and simultaneously treated with rosiglitazone (PPAR-gamma only for one group with 3 mg/kg/day via oral route for 30 days, and with rosiglitazone and felodipine combination for another group with 3 mg/kg/day and 5 mg/kg/day, respectively via oral route for 30 days. Results Diabetic hypertensive (DH rats which fed on a HFD, injected with streptozotocin (STZ (i.p. and obstruction for its right kidney was occurred develop hyperglycemia, hypertension, cardiac fibrosis, hypertriglyceridemia, hypercholesterolemia, increased TNF-α, increased TGF-β, decreased MMP-2, increased collagen-I and increased collagen-III, when compared to rats fed on control diet. Treating the DH rats with rosiglitazone only causes a significant decrease for BG levels by 52.79%, triglycerides (TGs by 24.05%, total cholesterol (T-Chol by 30.23%, low density lipoprotein cholesterol (LDL-C by 40.53%, TNF-α by 20.81%, TGF-β by 46.54%, collagen-I by 48.11% and collagen-III by 53.85% but causes a significant increase for MMP-2 by 272.73%. Moreover, Treating the DH rats with rosiglitazone and felodipine combination causes a significant decrease for BG levels by 61.08%, blood pressure (BP by 16.78%, TGs by 23.80%, T-Chol by 33.27%, LDL-C by 45.18%, TNF-α by 22.82%, TGF-β by 49.31%, collagen-I by 64.15% and collagen-III by 53.85% but causes a significant increase for MMP-2 by 290.91%. Rosiglitazone alone failed to decrease the BP in DH rats in the current dosage and

Action Prediction Allows Hypothesis Testing via Internal Forward Models at 6 Months of Age

Directory of Open Access Journals (Sweden)

Gustaf Gredebäck

2018-03-01

Full Text Available We propose that action prediction provides a cornerstone in a learning process known as internal forward models. According to this suggestion infants’ predictions (looking to the mouth of someone moving a spoon upward will moments later be validated or proven false (spoon was in fact directed toward a bowl, information that is directly perceived as the distance between the predicted and actual goal. Using an individual difference approach we demonstrate that action prediction correlates with the tendency to react with surprise when social interactions are not acted out as expected (action evaluation. This association is demonstrated across tasks and in a large sample (n = 118 at 6 months of age. These results provide the first indication that infants might rely on internal forward models to structure their social world. Additional analysis, consistent with prior work and assumptions from embodied cognition, demonstrates that the latency of infants’ action predictions correlate with the infant’s own manual proficiency.

Is credit for early action credible early action?

International Nuclear Information System (INIS)

Rolfe, C.; Michaelowa, A.; Dutschke, M.

1999-12-01

Credit for early action as a tool for greenhouse gas emissions reduction is compared with various market instruments as a means of narrowing the gap between projected emissions and those of the Kyoto Protocol. Market instruments work by creating a market price for emissions and use the market to encourage reductions at the lowest price, which is done by placing limits on greenhouse gas emissions and allowing the market to decide where reductions occur, or by imposing a carbon tax or emissions charge. While they can be applied within a sector, they are usually used to encourage reductions throughout the economy or across large sectors. Credit for early action also creates an incentive for emissions reductions throughout the economy or at least across many sectors. Credit for early action tools do not work by either imposing a carbon tax or emissions charge or placing limits on emissions, rather they promise that entities that take action against greenhouse gases prior to the imposition of a carbon tax or emissions limits will receive a credit against future taxes or limits. An overview is provided of the Kyoto Protocol and the rationale for taking early action, and a review is included of the theory and specific proposals for market instruments and credit for early action. A comparative analysis is provided of these approaches by examining their relative efficiency, environmental effectiveness, and impacts on the redistribution of wealth. Credit for early action is viewed as problematic on a number of counts and is seen as an interim strategy for imposition while political support for market instruments develop. The environmental effectiveness of credit for early action is very difficult to predict, and credit for early action programs do not yield the lowest cost emissions reductions. Credit for early action programs will not achieve compliance with the Kyoto Protocol at the lowest cost, and credits for early action will increase the compliance costs for those who

A continuous-time neural model for sequential action.

Science.gov (United States)

Kachergis, George; Wyatte, Dean; O'Reilly, Randall C; de Kleijn, Roy; Hommel, Bernhard

2014-11-05

Action selection, planning and execution are continuous processes that evolve over time, responding to perceptual feedback as well as evolving top-down constraints. Existing models of routine sequential action (e.g. coffee- or pancake-making) generally fall into one of two classes: hierarchical models that include hand-built task representations, or heterarchical models that must learn to represent hierarchy via temporal context, but thus far lack goal-orientedness. We present a biologically motivated model of the latter class that, because it is situated in the Leabra neural architecture, affords an opportunity to include both unsupervised and goal-directed learning mechanisms. Moreover, we embed this neurocomputational model in the theoretical framework of the theory of event coding (TEC), which posits that actions and perceptions share a common representation with bidirectional associations between the two. Thus, in this view, not only does perception select actions (along with task context), but actions are also used to generate perceptions (i.e. intended effects). We propose a neural model that implements TEC to carry out sequential action control in hierarchically structured tasks such as coffee-making. Unlike traditional feedforward discrete-time neural network models, which use static percepts to generate static outputs, our biological model accepts continuous-time inputs and likewise generates non-stationary outputs, making short-timescale dynamic predictions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

34 CFR 200.51 - Notice of SEA action.

Science.gov (United States)

2010-07-01

... Programs Operated by Local Educational Agencies Lea and School Improvement § 200.51 Notice of SEA action... parents— (A) In an understandable and uniform format, including alternative formats upon request; and (B... information to the parents of each student enrolled in a school served by the LEA— (i) Directly, through such...

Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

Science.gov (United States)

Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe

2011-01-01

Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126

How Perception Guides Action: Figure-Ground Segmentation Modulates Integration of Context Features into S-R Episodes

Science.gov (United States)

Frings, Christian; Rothermund, Klaus

2017-01-01

Perception and action are closely related. Responses are assumed to be represented in terms of their perceptual effects, allowing direct links between action and perception. In this regard, the integration of features of stimuli (S) and responses (R) into S-R bindings is a key mechanism for action control. Previous research focused on the…

Corrective Action Decision Document/Corrective Action Plan for Corrective Action Unit 547: Miscellaneous Contaminated Waste Sites, Nevada National Security Site, Nevada, Revision 0

Energy Technology Data Exchange (ETDEWEB)

Mark Krauss

2011-09-01

The purpose of this CADD/CAP is to present the corrective action alternatives (CAAs) evaluated for CAU 547, provide justification for selection of the recommended alternative, and describe the plan for implementing the selected alternative. Corrective Action Unit 547 consists of the following three corrective action sites (CASs): (1) CAS 02-37-02, Gas Sampling Assembly; (2) CAS 03-99-19, Gas Sampling Assembly; and(3) CAS 09-99-06, Gas Sampling Assembly. The gas sampling assemblies consist of inactive process piping, equipment, and instrumentation that were left in place after completion of underground safety experiments. The purpose of these safety experiments was to confirm that a nuclear explosion would not occur in the case of an accidental detonation of the high-explosive component of the device. The gas sampling assemblies allowed for the direct sampling of the gases and particulates produced by the safety experiments. Corrective Action Site 02-37-02 is located in Area 2 of the Nevada National Security Site (NNSS) and is associated with the Mullet safety experiment conducted in emplacement borehole U2ag on October 17, 1963. Corrective Action Site 03-99-19 is located in Area 3 of the NNSS and is associated with the Tejon safety experiment conducted in emplacement borehole U3cg on May 17, 1963. Corrective Action Site 09-99-06 is located in Area 9 of the NNSS and is associated with the Player safety experiment conducted in emplacement borehole U9cc on August 27, 1964. The CAU 547 CASs were investigated in accordance with the data quality objectives (DQOs) developed by representatives of the Nevada Division of Environmental Protection (NDEP) and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office. The DQO process was used to identify and define the type, amount, and quality of data needed to determine and implement appropriate corrective actions for CAU 547. Existing radiological survey data and historical knowledge of

A Comparison of Beliefs and Disbeliefs and Reference Category Characteristics as Directive Factors of Social Action in Five Cultures.

Science.gov (United States)

Reeder, William W.; And Others

In order to illustrate the cross-culture applicability of Reeder's Theory of Beliefs, Disbeliefs, and Social Action and its usefulness in predicting and explaining social actions, studies conducted in communities in India, Sudan, Lebanon, northeastern United States, and western United States are examined. Using this theory, beliefs and disbeliefs…

Social Action among Social Work Practitioners: Examining the Micro-Macro Divide.

Science.gov (United States)

Mattocks, Nicole Olivia

2018-01-01

Social work is a profession that seeks to enhance the well-being of all people and promote social justice and social change through a range of activities, such as direct practice, community organizing, social and political action, and policy development. However, the current literature suggests that the profession's focus on social justice and social action are weakening, replaced by individualism and therapeutic interventions. This article examines data derived from a survey of 188 National Association of Social Workers members from Maryland; Virginia; and Washington, DC, to explore levels of social action participation among social workers and determine whether identifying as a macro-level practitioner would predict higher levels of social action activity compared with being a micro-level practitioner. Findings indicate that social workers in this sample engage in only a moderate level of social action behavior. In addition, identifying oneself as a mezzo- or macro-level practitioner predicts increased frequency of social action behavior. Implications include emphasizing the importance of social action in schools of social work and practice settings and adequately preparing social work professionals to engage in social action. © 2017 National Association of Social Workers.

MHD dynamo action in space plasmas

International Nuclear Information System (INIS)

Faelthammar, C.G.

1984-05-01

Electric currents are now recognized to play a major role in the physical process of the Earths magnetosphere as well as in distant astrophysical plasmas. In driving these currents MHD dynamos as well as generators of a thermoelectric nature are important. The primary source of power for the Earths magnetospheric process is the solar wind, which supplies a voltage of the order of 200 kV across the magnetosphere. The direction of the large-scale solar wind electric field varies of many different time scales. The power input to the magnetosphere is closely correlated with the direction of the large-scale solar wind electric field in such a fashion as to mimick the response of a half-wave rectifier with a down-to-dusk conduction direction. Behind this apparently simple response there are complex plasma physical processes that are still very incompletely understood. They are intimately related to auroras, magnetic storms, radiation belts and changes in magnetospheric plasma populations. Similar dynamo actions should occur at other planets having magnetospheres. Recent observations seem to indicate that part of the power input to the Earths magnetosphere comes through MHD dynamo action of a forced plasma flow inside the flanks of the magnetopause and may play a role in other parts of the magnetosphere, too. An example of a cosmical MHD connected to a solid load is the corotating plasma of Jupiters inner magnetosphere, sweeping past the plants inner satelites. In particular the electric currents thereby driven to and from the satellite Io have attracted considerable interest.(author)

Action-based flood forecasting for triggering humanitarian action

Science.gov (United States)

Coughlan de Perez, Erin; van den Hurk, Bart; van Aalst, Maarten K.; Amuron, Irene; Bamanya, Deus; Hauser, Tristan; Jongma, Brenden; Lopez, Ana; Mason, Simon; Mendler de Suarez, Janot; Pappenberger, Florian; Rueth, Alexandra; Stephens, Elisabeth; Suarez, Pablo; Wagemaker, Jurjen; Zsoter, Ervin

2016-09-01

Too often, credible scientific early warning information of increased disaster risk does not result in humanitarian action. With financial resources tilted heavily towards response after a disaster, disaster managers have limited incentive and ability to process complex scientific data, including uncertainties. These incentives are beginning to change, with the advent of several new forecast-based financing systems that provide funding based on a forecast of an extreme event. Given the changing landscape, here we demonstrate a method to select and use appropriate forecasts for specific humanitarian disaster prevention actions, even in a data-scarce location. This action-based forecasting methodology takes into account the parameters of each action, such as action lifetime, when verifying a forecast. Forecasts are linked with action based on an understanding of (1) the magnitude of previous flooding events and (2) the willingness to act "in vain" for specific actions. This is applied in the context of the Uganda Red Cross Society forecast-based financing pilot project, with forecasts from the Global Flood Awareness System (GloFAS). Using this method, we define the "danger level" of flooding, and we select the probabilistic forecast triggers that are appropriate for specific actions. Results from this methodology can be applied globally across hazards and fed into a financing system that ensures that automatic, pre-funded early action will be triggered by forecasts.

The Charlotte Action Research Project: A Model for Direct and Mutually Beneficial Community-University Engagement

Science.gov (United States)

Morrell, Elizabeth; Sorensen, Janni; Howarth, Joe

2015-01-01

This article describes the evolution of the Charlotte Action Research Project (CHARP), a community-university partnership founded in 2008 at the University of North Carolina at Charlotte, and focuses particularly on the program's unique organizational structure. Research findings of a project evaluation suggest that the CHARP model's unique…

Everyday robotic action: Lessons from human action control

Directory of Open Access Journals (Sweden)

Roy eDe Kleijn

2014-03-01

Full Text Available Robots are increasingly capable of performing everyday human activities such as cooking, cleaning, and doing the laundry. This requires the real-time planning and execution of complex, temporally-extended sequential actions under high degrees of uncertainty, which provides many challenges to traditional approaches to robot action control. We argue that important lessons in this respect can be learned from research on human action control. We provide a brief overview of available psychological insights into this issue and focus on four principles that we think could be particularly beneficial for robot control: the integration of symbolic and subsymbolic planning of action sequences, the integration of feedforward and feedback control, the clustering of complex actions into subcomponents, and the contextualization of action-control structures through goal representations.

75 FR 36588 - Veterinary Feed Directive; Extension of Comment Period

Science.gov (United States)

2010-06-28

... 558 [Docket No. FDA-2010-N-0155] Veterinary Feed Directive; Extension of Comment Period AGENCY: Food... veterinary feed directive (VFD) regulation. The agency is taking this action in response to requests for an... CONTACT: Neal Bataller, Center for Veterinary Medicine (HFV-230), Food and Drug Administration, 7500...

Five Steps for Structuring Data-Informed Conversations and Action in Education. REL 2013-001

Science.gov (United States)

Kekahio, Wendy; Baker, Myriam

2013-01-01

Using data strategically to guide decisions and actions can have a positive effect on education practices and processes. This facilitation guide shows education data teams how to move beyond simply reporting data to applying data to direct strategic action. Using guiding questions, suggested activities, and activity forms, this guide provides…

A Polyakov action on Riemann surfaces. Pt. 2

International Nuclear Information System (INIS)

Zucchini, R.

1991-11-01

The model independent study of the Polyakov action is continued on an arbitrary compact surface without boundary of genus larger than 2 as the general solution of the relevant conformal Ward identity. A general formula for the Polyakov action and an explicit calculation of the energy-momentum tensor density is provided. The general geometric setting of the construction is described in detail. It is shown that the Polyakov action defines a distribution of finite dimensional directions in the holomorphic tangent bundle of the manifold of Beltrami differentials. It is further argued that motions parallel to such distribution correspond to Polyakov's SL(2,C) symmetry transformations. Owing to the existence of renormalization ambiguities on a topologically non-trivial surface, the energy-momentum tensor needs not be invariant under the full SL(2,C) symmetry. The residual SL(2,C) symmetry is characterized geometrically. (author) 31 refs

Application of ultrasonic extraction method in the preparation of the directive action beverage from black currant

Directory of Open Access Journals (Sweden)

N. S. Rodionova

2016-01-01

Full Text Available The article presents the results of experimental determination of physical-and chemical parameters, the amount of anthocyanins, the definition of color and organoleptic characteristics of the beverage prepared with ultrasonic extraction method in comparison with the fruit-drink, obtained according to traditional recipe. Black currant was chosen the main raw material for the development of the beverage production technology. It is characterized by a high content of bioactive components that increase the adaptive abilities of human body. The purpose is to use ultrasonic extraction method in the preparation of functionally directed actions beverages. Extractor with submerged ultrasonic emitter was used as an experimental device. The essence of its operation is as follows: a mixture of the extractant and the plant substrate in different ratios was loaded into a container with the emitter, then the ultrasonic generator was turned on. The vibrations of ultrasonic frequency (22 kHz made high-frequency mechanical vibrations that caused the formation of intense cavitation areas and diffuse dissolution of cell substrates in the extractant in the treated mixture. The ultrasonic extraction technique involves brief contact of berries and extractant (up to 15 minutes upon application of ultrasonic vibrations. With an increase in exposure time, the yield of biologically active substances increases to reach an equilibrium state corresponding to the most complete exhaustion of raw materials. All this leads to a significant acceleration of the transition from the active ingredients from the raw materials into the extractant to obtain a product with improved physical - and chemical, organoleptic characteristics, as well as a higher antioxidant activity.

Hearing sounds, understanding actions: action representation in mirror neurons.

Science.gov (United States)

Kohler, Evelyne; Keysers, Christian; Umiltà, M Alessandra; Fogassi, Leonardo; Gallese, Vittorio; Rizzolatti, Giacomo

2002-08-02

Many object-related actions can be recognized by their sound. We found neurons in monkey premotor cortex that discharge when the animal performs a specific action and when it hears the related sound. Most of the neurons also discharge when the monkey observes the same action. These audiovisual mirror neurons code actions independently of whether these actions are performed, heard, or seen. This discovery in the monkey homolog of Broca's area might shed light on the origin of language: audiovisual mirror neurons code abstract contents-the meaning of actions-and have the auditory access typical of human language to these contents.

Uranium mill tailings remedial action technology

International Nuclear Information System (INIS)

Hartley, J.N.; Gee, G.W.

1984-01-01

The uranium milling process involves the hydrometallurgical extraction of uranium from ores and the resultant generation of large quantities of waste referred to as tailings. Uranium mill tailings have been identified as requiring remediation because they contain residual radioactive material that is not removed in the milling process. Potential radiation exposure can result from direct contact with the tailings, from radon gas emitted by the tailings, and from radioactive contamination of groundwater. As a result, the technology developed under the US Department of Energy (DOE) Uranium Mill Tailings Remedial Action Project (UMTRAP) and the US Nuclear Regulatory Commission (NRC) Uranium Recovery Program have focused on radon control, groundwater contamination and the long-term protection of the containment system. This paper briefly summarizes the UMTRAP and NRC remedial action technology development. 33 references, 9 figures, 5 tables

Early markers of ongoing action-effect learning

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Hannes eRuge

2012-11-01

Full Text Available Acquiring knowledge about the relationship between stimulus conditions, one’s own actions, and the resulting consequences or effects, is one prerequisite for intentional action. Previous studies have shown that such contextualized associations between actions and their effects (S-R-E associations can be picked up very quickly. The present study examined how such weakly practiced associations might affect overt behavior during the process of initial learning and during subsequent retrieval, and how these two measures are inter-related. We examined incidental (S-R-E learning in the context of trial-and-error S-R learning and in the context of instruction-based S-R learning. Furthermore, as a control condition, common outcome (CO learning blocks were included in which all responses produced one common sound effect, hence precluding differential (S-R-E learning. Post-learning retrieval of R-E associations was tested by re-using previously produced sound effects as novel imperative stimuli combined with actions that were either compatible or incompatible with the previously encountered R-E mapping. The central result was that the size of the compatibility effect could be predicted by the size of relative response slowing during ongoing learning in the preceding acquisition phase, both in trial-and-error learning and in instruction-based learning. Importantly, this correlation was absent for the common outcome control condition, precluding accounts based on unspecific factors. Instead, the results suggest that differential outcomes are ‘actively’ integrated into action planning and that this takes additional planning time. We speculate that this might be especially true for weakly practiced (S-R-E associations before an initial goal-directed action mode transitions into a more stimulus-based action mode.

How Action Understanding can be Rational, Bayesian and Tractable

NARCIS (Netherlands)

Blokpoel, M.; Kwisthout, J.H.P.; Weide, Th.P. van der; Rooij, I.J.E.I. van; Ohlsson, S.; Catrambone, R.

2010-01-01

An important aspect of human sociality is our ability to understand the actions of others as being goal-directed. Recently, the now classic rational approach to explaining this ability has been given a formal incarnation in the Bayesian Inverse Planning (BIP) model of Baker, Saxe, and Tenenbaum

Effect of PPAR-α and -γ agonist on the expression of visfatin, adiponectin, and TNF-α in visceral fat of OLETF rats

International Nuclear Information System (INIS)

Choi, K.C.; Ryu, O.H.; Lee, K.W.; Kim, H.Y.; Seo, J.A.; Kim, S.G.; Kim, N.H.; Choi, D.S.; Baik, S.H.; Choi, K.M.

2005-01-01

A variety of adipocytokines and peptides secreted from adipocytes have been considered to play a crucial role in obesity, insulin resistance, and type 2 diabetes. Recently, visfatin, a new adipocytokine, known as a pre-B cell colony-enhancing factor, has been isolated from visceral fat deposits. It has been shown to activate insulin receptors in a manner different from insulin. To understand the role of adipocytokines in improving insulin sensitivity via activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) and -γ (PPAR-γ), we examined the expression of visfatin, adiponectin, and TNF-α in visceral fat depots of Otsuka Long-Evans Tokushima fatty (OLETF) rats from early to advanced diabetic stage (from 28 to 40 weeks of age). Serum glucose and insulin concentrations significantly (P < 0.05) decreased in rosiglitazone or fenofibrate-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone significantly increased serum adiponectin concentration from 20 to 40 weeks of age (P < 0.05), whereas fenofibrate reduced TNF-α concentration. The expression of visfatin and adiponectin mRNA in visceral fat deposits was elevated by rosiglitazone or fenofibrate treatments when compared to untreated OLETF rats (P < 0.05), whereas, TNF-α mRNA was down-regulated by these drugs (P < 0.05). These results suggest that rosiglitazone and fenofibrate may prevent type 2 diabetes by regulating adipocytokines including visfatin, adiponectin, and TNF-α

Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

Directory of Open Access Journals (Sweden)

Guang-xing Shui

2017-01-01

Full Text Available Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD on chronic aristolochic acid nephropathy (AAN in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN, the saline-treated group (AAN + vehicle, the normal dose DFD-treated group (AAN + NDFD, the high dose DFD-treated group (AAN + HDFD, and the rosiglitazone treated group (AAN + Rosi. After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA, mitochondrial membrane potential (MMP, ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

Effects of Na/K-ATPase and its ligands on bone marrow stromal cell differentiation

Directory of Open Access Journals (Sweden)

Moustafa Sayed

2014-07-01

Full Text Available Endogenous ligands of Na/K-ATPase have been demonstrated to increase in kidney dysfunction and heart failure. It is also reported that Na/K-ATPase signaling function effects stem cell differentiation. This study evaluated whether Na/K-ATPase activation through its ligands and associated signaling functions affect bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells differentiation capacity. BMSCs were isolated from male Sprague–Dawley rats and cultured in minimal essential medium alpha (MEM-α supplemented with 15% Fetal Bovine serum (FBS. The results showed that marinobufagenin (MBG, a specific Na/K-ATPase ligand, potentiated rosiglitazone-induced adipogenesis in these BMSCs. Meanwhile, it attenuated BMSC osteogenesis. Mechanistically, MBG increased CCAAT/enhancer binding protein alpha (C/EBPα protein expression through activation of an extracellular regulated kinase (ERK signaling pathway, which leads to enhanced rosiglitazone-induced adipogenesis. Inhibition of ERK activation by U0126 blocks the effect of MBG on C/EBPα expression and on rosiglitazone-induced adipogenesis. Reciprocally, MBG reduced runt-related transcription factor 2 (RunX2 expression, which resulted in the inhibition of osteogenesis induced by β-glycerophosphate/ascorbic acid. MBG also potentiated rosiglitazone-induced adipogenesis in 3T3-L1 cells and in mouse BMSCs. These results suggest that Na/K-ATPase and its signaling functions are involved in the regulation of BMSCs differentiation.

Abstract spatial concept priming dynamically influences real-world actions

Directory of Open Access Journals (Sweden)

Sarah M Tower-Richardi

2012-09-01

Full Text Available Experienced regularities in our perceptions and actions play important roles in grounding abstract concepts such as social status, time, and emotion. Might we similarly ground abstract spatial concepts in more experienced-based domains? The present experiment explores this possibility by implicitly priming abstract spatial terms (north, south, east, west and then measuring participants’ hand movement trajectories while they respond to a body-referenced spatial target (up, down, left, right in a verbal (Exp. 1 or spatial (Exp. 2 format. Results from two experiments demonstrate temporally-dynamic and prime-biased movement trajectories when the primes are incongruent with the targets (e.g., north – left, west – up. That is, priming abstract coordinate directions influences subsequent actions in response to concrete target directions. These findings provide the first evidence that abstract concepts of world-centered coordinate axes are implicitly understood in the context of concrete body-referenced axes; critically, this abstract-concrete relationship manifests in motor movements, and may have implications for spatial memory organization.

Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

Directory of Open Access Journals (Sweden)

Robert C. Allen

2015-01-01

Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

77 FR 24344 - Airworthiness Directives; Learjet Inc.

Science.gov (United States)

2012-04-24

... Airworthiness Directives; Learjet Inc. AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule... manual, which adds life-limits, revises life-limits, or adds inspections not previously identified. This AD requires revising the maintenance program to include new or more restrictive life-limits and...

Finding minimal action sequences with a simple evaluation of actions

Science.gov (United States)

Shah, Ashvin; Gurney, Kevin N.

2014-01-01

Animals are able to discover the minimal number of actions that achieves an outcome (the minimal action sequence). In most accounts of this, actions are associated with a measure of behavior that is higher for actions that lead to the outcome with a shorter action sequence, and learning mechanisms find the actions associated with the highest measure. In this sense, previous accounts focus on more than the simple binary signal of “was the outcome achieved?”; they focus on “how well was the outcome achieved?” However, such mechanisms may not govern all types of behavioral development. In particular, in the process of action discovery (Redgrave and Gurney, 2006), actions are reinforced if they simply lead to a salient outcome because biological reinforcement signals occur too quickly to evaluate the consequences of an action beyond an indication of the outcome's occurrence. Thus, action discovery mechanisms focus on the simple evaluation of “was the outcome achieved?” and not “how well was the outcome achieved?” Notwithstanding this impoverishment of information, can the process of action discovery find the minimal action sequence? We address this question by implementing computational mechanisms, referred to in this paper as no-cost learning rules, in which each action that leads to the outcome is associated with the same measure of behavior. No-cost rules focus on “was the outcome achieved?” and are consistent with action discovery. No-cost rules discover the minimal action sequence in simulated tasks and execute it for a substantial amount of time. Extensive training, however, results in extraneous actions, suggesting that a separate process (which has been proposed in action discovery) must attenuate learning if no-cost rules participate in behavioral development. We describe how no-cost rules develop behavior, what happens when attenuation is disrupted, and relate the new mechanisms to wider computational and biological context. PMID:25506326

Hybrid Action Systems

DEFF Research Database (Denmark)

Rönnkö, M.; Ravn, Anders Peter; Sere, K.

2003-01-01

In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time......-derivatives in modelling continuous-time dynamics. The generalized differential action has an intuitively appealing predicate transformer semantics, which we show to be both conjunctive and monotonic. In addition, we show that differential actions blend smoothly with conventional actions in action systems, even under...... parallel composition. Moreover, as the strength of the action system formalism is the support for stepwise development by refinement, we investigate refinement involving a differential action. We show that, due to the predicate transformer semantics, standard action refinement techniques apply also...

Goal-Directed Decision Making with Spiking Neurons.

Science.gov (United States)

Friedrich, Johannes; Lengyel, Máté

2016-02-03

Behavioral and neuroscientific data on reward-based decision making point to a fundamental distinction between habitual and goal-directed action selection. The formation of habits, which requires simple updating of cached values, has been studied in great detail, and the reward prediction error theory of dopamine function has enjoyed prominent success in accounting for its neural bases. In contrast, the neural circuit mechanisms of goal-directed decision making, requiring extended iterative computations to estimate values online, are still unknown. Here we present a spiking neural network that provably solves the difficult online value estimation problem underlying goal-directed decision making in a near-optimal way and reproduces behavioral as well as neurophysiological experimental data on tasks ranging from simple binary choice to sequential decision making. Our model uses local plasticity rules to learn the synaptic weights of a simple neural network to achieve optimal performance and solves one-step decision-making tasks, commonly considered in neuroeconomics, as well as more challenging sequential decision-making tasks within 1 s. These decision times, and their parametric dependence on task parameters, as well as the final choice probabilities match behavioral data, whereas the evolution of neural activities in the network closely mimics neural responses recorded in frontal cortices during the execution of such tasks. Our theory provides a principled framework to understand the neural underpinning of goal-directed decision making and makes novel predictions for sequential decision-making tasks with multiple rewards. Goal-directed actions requiring prospective planning pervade decision making, but their circuit-level mechanisms remain elusive. We show how a model circuit of biologically realistic spiking neurons can solve this computationally challenging problem in a novel way. The synaptic weights of our network can be learned using local plasticity rules

Radioactive contamination, what actions for the polluted sites

International Nuclear Information System (INIS)

2004-01-01

The nuclear safety authority and the direction of prevention of pollutions and risks have organised the first edition of the national colloquium: radioactive contamination: what actions for polluted sites. Four axes can be taken to follow this colloquium: prevention, outstanding tools to evaluate risks and rehabilitation, a better responsibility of operators and memory keeping. (N.C.)

Action plan in response to March 1981 report to NFPQT Committee

International Nuclear Information System (INIS)

1981-03-01

This plan of action has been prepared at the direction of the Acting Under Secretary in response to the report of the Nuclear Facilities Personnel Qualifications and Training (NFPQT) Committee on A Safety Assessment of Department of Energy Nuclear Reactors. Senior Department officials with Headquarters responsibilities for the safety of nuclear facilities owned by and operated for the Department have developed this plan with input from the operations office managers having operational responsibility for such facilities. A summary of the plan's objectives and a cross-reference to the findings of the NFPQT Committee Report is attached to the plan. Appendix A contains implementing actions and Appendix B contains a summary of actions responsive to lessons learned from the TMI accident that have been completed or are well underway. Although the plan is written in definitive language, the specific actions (such as organization realignments and proposals) will be subject to appropriate review and approval. Also, other adjustments may be required as the actions are implemented

Effects of social intention on movement kinematics in cooperative actions

Directory of Open Access Journals (Sweden)

Francois eQuesque

2013-10-01

Full Text Available Optimal control models of biological movements are used to account for those internal variables that constrain voluntary goal-directed actions. They however do not take into account external environmental constraints as those associated to social intention. We investigated here the effects of the social context on kinematic characteristics of sequential actions consisting in placing an object on an initial pad (preparatory action before reaching and grasping as fast as possible the object to move it to another location (main action. Reach-to-grasp actions were performed either in an isolated condition or in the presence of a partner (audience effect, located in the near or far space (effect of shared reachable space, and who could intervene on the object in a systematic fashion (effect of social intention effect or not (effect of social uncertainty. Results showed an absence of audience effect but nevertheless an influence of the social context both on the main and the preparatory actions. In particular, a localized effect of shared reachable space was observed on the main action, which was smoother when performed within the reachable space of the partner. Furthermore, a global effect of social uncertainty was observed on both actions with faster and jerkier movements. Finally, social intention affected the preparatory action with higher wrist displacements and slower movements when the object was placed for the partner rather than placed for self-use. Overall, these results demonstrate specific effects of action space, social uncertainty and social intention on the planning of reach-to-grasp actions, in particular on the preparatory action, which was performed with no specific execution constraint. These findings underline the importance of considering the social context in optimal models of action control for human-robot interactions, in particular when focusing on the implementation of motor parameters required to afford intuitive

Making smart social judgments takes time: infants' recruitment of goal information when generating action predictions.

Science.gov (United States)

Krogh-Jespersen, Sheila; Woodward, Amanda L

2014-01-01

Previous research has shown that young infants perceive others' actions as structured by goals. One open question is whether the recruitment of this understanding when predicting others' actions imposes a cognitive challenge for young infants. The current study explored infants' ability to utilize their knowledge of others' goals to rapidly predict future behavior in complex social environments and distinguish goal-directed actions from other kinds of movements. Fifteen-month-olds (N = 40) viewed videos of an actor engaged in either a goal-directed (grasping) or an ambiguous (brushing the back of her hand) action on a Tobii eye-tracker. At test, critical elements of the scene were changed and infants' predictive fixations were examined to determine whether they relied on goal information to anticipate the actor's future behavior. Results revealed that infants reliably generated goal-based visual predictions for the grasping action, but not for the back-of-hand behavior. Moreover, response latencies were longer for goal-based predictions than for location-based predictions, suggesting that goal-based predictions are cognitively taxing. Analyses of areas of interest indicated that heightened attention to the overall scene, as opposed to specific patterns of attention, was the critical indicator of successful judgments regarding an actor's future goal-directed behavior. These findings shed light on the processes that support "smart" social behavior in infants, as it may be a challenge for young infants to use information about others' intentions to inform rapid predictions.

Proceedings of the Radon national action plan workshop

International Nuclear Information System (INIS)

Chevet, Pierre-Franck; Godet, Jean-Luc; Tirmarche, Margot; Strand, Per; Mrdakovic Popic, Jelena; Dysvik, Solveig; Skjold, Anne Marit; Vallet, Benoit; Van Deventer, Emilie; Colgan, Tony; ); Mundigl, Stefan; ); Magnusson, S.; Long, Bill; McBurney, Ruth; Thompson, P.A; Pollard, David; Fenton, David; Long, Stephanie; Dehandschutter, Boris; Murith, Christophe; Skeppstroem, Kirlna; Petrova, Karla; Davidkova, Jana; Pravdova, Eva; Kiselev, Sergey; Mc Coll, Neil; Vallet, Jeremie; Rannou, Alain; Kurttio, Paivi; Martinsen, Finn; Roulet, Claude-Alain; Goyette, Joelle; Frutos, Borja; Olaya, Manuel; Linares Alemparte, Pilar; Marinko, Janez; Garcia-Talavera, Marta; Pedrazzi, Lisa; Mc Laughlin, James; Gutierrez-Villanueva, Jose-Luis; Janssens, Augustin

2015-01-01

Following the publication of the new European Basic Safety Standards Directive (the Council Directive 2013/59/EURATOM ), published in January 2014, Member States of the European Union have 4 years to incorporate it and to prepare or update their strategy for reducing radon concentration and the associated national radon action plan. Under a joint initiative from ASN and NRPA, 20 European countries, represented by authorities in charge of Radiation Protection, Health, Labour and Housing and Landscaping were brought together during a workshop on national radon action plans. The objective of the workshop, held in ASN's premises, was to share the views and experiences concerning national strategies for reducing radon exposure of the population and associated lung cancer risk. The radon workshop was supported by the World Health Organisation (WHO), the International Atomic Energy Agency (IAEA), the Heads of European Radiation protection Control Authorities (HERCA) and the European Commission (EC). Authorities from USA (EPA, CRCPD), Canada (CNSC) and Russia (FMBA) and the European Radon Association (ERA) also participated in the workshop. This radon workshop has offered the opportunity to compare the actions in place or in preparation in different countries aiming at reducing radon exposure in home and dwellings, in buildings with public access (i.e. schools) and in workplaces. Preventive and corrective solutions, associated with incentives and communication to increase the public awareness, as well as education and training actions for different actors concerned, have been presented and discussed. The question about the relative place of regulation in the national strategy has been considered as an important key point. This document brings together the presentations (slides) given at the workshop. The main conclusions of the workshop are presented at the end of the document

The positive and negative framing of affirmative action: a group dominance perspective.

Science.gov (United States)

Haley, Hillary; Sidanius, Jim

2006-05-01

Using a sample of 328 White, Latino, and Black Los Angeles County adults, the authors examined the tendency to employ various affirmative action "frames" (e.g., affirmative action as a "tie-breaking" device or as a quota-based policy). All three groups agreed about which frames cast affirmative action in a positive light and which cast it in a negative light. Although minorities had a tendency to frame affirmative action in terms that most people find morally acceptable, Whites had a tendency to frame affirmative action in terms most people find unacceptable. In addition, compared to minorities, Whites were less supportive of affirmative action regardless of how it was framed. LISREL modeling also was employed to test two competing models regarding predictors of the tendency to use frames that one personally finds to be relatively negative versus positive. Consistent with the expectations of social dominance theory and a motivated cognition perspective, the authors found that social dominance orientation (SDO) had significant net direct and indirect effects on one's framing of affirmative action.

[A Structural Equation Model of Pressure Ulcer Prevention Action in Clinical Nurses].

Science.gov (United States)

Lee, Sook Ja; Park, Ok Kyoung; Park, Mi Yeon

2016-08-01

The purpose of this study was to construct and test a structural equation model for pressure ulcer prevention action by clinical nurses. The Health Belief Model and the Theory of Planned Behavior were used as the basis for the study. A structured questionnaire was completed by 251 clinical nurses to analyze the relationships between concepts of perceived benefits, perceived barriers, attitude, subjective norm, perceived control, intention to perform action and behavior. SPSS 22.0 and AMOS 22.0 programs were used to analyze the efficiency of the hypothesized model and calculate the direct and indirect effects of factors affecting pressure ulcer prevention action among clinical nurses. The model fitness statistics of the hypothetical model fitted to the recommended levels. Attitude, subjective norm and perceived control on pressure ulcer prevention action explained 64.2% for intention to perform prevention action. The major findings of this study indicate that it is essential to recognize improvement in positive attitude for pressure ulcer prevention action and a need for systematic education programs to increase perceived control for prevention action.

Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools.

Science.gov (United States)

Frey, Scott H; Povinelli, Daniel J

2012-01-12

The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use.

Action spectra in mammalian cells exposed to ultraviolet radiation

International Nuclear Information System (INIS)

Anon.

1981-01-01

A review is given of the literature published since 1977 on action spectra in mammalian cells exposed to ultraviolet radiation in the wavelength region above 220 nm. Action spectra for lethal events are discussed for cell inactivation in normal cells, growth arrested cells and photosensitive cells. Action spectra for non-lethal events are also discussed in relation to pyrimidine dimer formation, photoreactivation and the use of photosensitisers. It was concluded from these studies that damage to the DNA, and the extent of the repair of this damage, seems to determine a cell's response to such parameters as inactivation, mutation, transformation, latent viral activation, cellular viral capacity and ultraviolet enhanced viral reactivation. In addition to the direct effects of UV on DNA, photosensitization of cellular responses with chemicals such as 8-MOP extend the wavelength range at which damage can be demonstrated. (U.K.)

Sex differences in impulsive action and impulsive choice.

Science.gov (United States)

Weafer, Jessica; de Wit, Harriet

2014-11-01

Here, we review the evidence for sex differences in behavioral measures of impulsivity for both humans and laboratory animals. We focus on two specific components of impulsivity: impulsive action (i.e., difficulty inhibiting a prepotent response) and impulsive choice (i.e., difficulty delaying gratification). Sex differences appear to exist on these measures, but the direction and magnitude of the differences vary. In laboratory animals, impulsive action is typically greater in males than females, whereas impulsive choice is typically greater in females. In humans, women discount more steeply than men, but sex differences on measures of impulsive action depend on tasks and subject samples. We discuss implications of these findings as they relate to drug addiction. We also point out the major gaps in this research to date, including the lack of studies designed specifically to examine sex differences in behavioral impulsivity, and the lack of consideration of menstrual or estrous phase or sex hormone levels in the studies. © 2013.

Beyond rational imitation: learning arbitrary means actions from communicative demonstrations.

Science.gov (United States)

Király, Ildikó; Csibra, Gergely; Gergely, György

2013-10-01

The principle of rationality has been invoked to explain that infants expect agents to perform the most efficient means action to attain a goal. It has also been demonstrated that infants take into account the efficiency of observed actions to achieve a goal outcome when deciding whether to reenact a specific behavior or not. It is puzzling, however, that they also tend to imitate an apparently suboptimal unfamiliar action even when they can bring about the same outcome more efficiently by applying a more rational action alternative available to them. We propose that this apparently paradoxical behavior is explained by infants' interpretation of action demonstrations as communicative manifestations of novel and culturally relevant means actions to be acquired, and we present empirical evidence supporting this proposal. In Experiment 1, we found that 14-month-olds reenacted novel arbitrary means actions only following a communicative demonstration. Experiment 2 showed that infants' inclination to reproduce communicatively manifested novel actions is restricted to behaviors they can construe as goal-directed instrumental acts. The study also provides evidence that infants' reenactment of the demonstrated novel actions reflects epistemic motives rather than purely social motives. We argue that ostensive communication enables infants to represent the teleological structure of novel actions even when the causal relations between means and end are cognitively opaque and apparently violate the efficiency expectation derived from the principle of rationality. This new account of imitative learning of novel means shows how the teleological stance and natural pedagogy--two separate cognitive adaptations to interpret instrumental versus communicative actions--are integrated as a system for learning socially constituted instrumental knowledge in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

77 FR 74628 - Airworthiness Directives; Embraer S.A. Airplanes

Science.gov (United States)

2012-12-17

... aviation authority for Brazil, has issued Brazilian Airworthiness Directive 2012-01-01, effective January... actions include replacing or repairing the MLG side stay or MLG side stay assembly, and removing corrosion...

Knowledge in action in weaving

Directory of Open Access Journals (Sweden)

Viveka Berggren Torell

2014-04-01

Full Text Available The project “Design, craft and culture” had the purpose of co-production of knowledge between the University of Borås and the small-scale enterprise Vävkompaniet (The weaving company. The practitioners’ wanted to get insights into competences previously “hidden” in their knowledge in action; competences that could be the base for development of products and ways to reach customers. From academic point of view the main goal was to produce films aimed shedding light on knowledge in action. The result is four educational films aimed at students.This article is based on interpretations of films and interviews from places where the handweavers produce their products. A researcher and a weaving teacher studied their work, while the photographer filmed the artisans’ body movements. Questions and words, in a language which fits the events of the practice, can make practitioners sharpen their attention and direct it at critical points in the practice that they accomplish. By interviews done in a conversation-like way during observations, a space for such reflections was created. The weavers shared meanings on their position in the field of craft and detailed descriptions of crafting practices with the research team. Regarding the design process, because of their material rather than conceptual approach to craftwork, the weavers brought up the importance of sample weaving. While work with dressing the looms and weaving then continued many empirical examples of aspects of knowledge in action could be observed. The importance of routine, rhythm, bodily skills, senses, judgement and experience are brought up in the text.Key words: textile craft, weaving, tacit knowledge, knowledge in action, senses, visual ethnography

Sailing: Cognition, action, communication

Directory of Open Access Journals (Sweden)

Thora Tenbrink

2017-12-01

Full Text Available How do humans perceive and think about space, and how can this be represented adequately? For everyday activities such as locating objects or places, route planning, and the like, many insights have been gained over the past few decades, feeding into theories of spatial cognition and frameworks for spatial information science. In this paper, we explore sailing as a more specialized domain that has not yet been considered in this way, but has a lot to offer precisely because of its peculiarities. Sailing involves ways of thinking about space that are not normally required (or even acquired in everyday life. Movement in this domain is based on a combination of external forces and internal (human intentions that impose various kinds of directionality, affecting local action as well as global planning. Sailing terminology is spatial to a high extent, and involves a range of concepts that have received little attention in the spatial cognition community. We explore the area by focusing on the core features of cognition, action, and communication, and suggest a range of promising future areas of research in this domain as a showcase of the fascinating flexibility of human spatial cognition.

Recommendations for actions concerning supporting ITS developments for VRUs

NARCIS (Netherlands)

Mans, D.; Giannelos, I.; Breemen, R. van; Rood, M.; Silla, A.; Rämä, P.; Scholliers, J.; Perez, O.M.; Malone, K.

2017-01-01

Introduction: This paper presents some of the work conducted in FP7 VRUITS project to draw a set of general recommendations for actions at the EU level aiming to enhance the deployment of ITS systems directed to improve the safety, mobility and comfort of vulnerable road users. Method: The work

Our actions in my mind: Motor imagery of joint action

DEFF Research Database (Denmark)

Vesper, Cordula; Knoblich, Günther; Sebanz, Natalie

2014-01-01

How do people imagine performing actions together? The present study investigated motor imagery of joint actions that requires integrating one's own and another's part of an action. In two experiments, individual participants imagined jumping alone or jointly next to an imagined partner. The joint...... condition required coordinating one's own imagined actions with an imagined partner's actions to synchronize landing times. We investigated whether the timing of participants' own imagined jumps would reflect the difference in jump distance to their imagined partner's jumps. The results showed...... of joint jumping. These findings link research on motor imagery and joint action, demonstrating that individuals are able to integrate simulations of different parts of a joint action....

Action understanding and imitation learning in a robot-human task

NARCIS (Netherlands)

Erlhagen, W.; Mukovskiy, A.; Bicho, E.; Panin, G.; Kiss, C.; Knoll, A.; Schie, H.T. van; Bekkering, H.

2005-01-01

We report results of an interdisciplinary project which aims at endowing a real robot system with the capacity for learning by goal-directed imitation. The control architecture is biologically inspired as it reflects recent experimental findings in action observation/execution studies. We test its

[Pharmacogenetic aspects of the immunodepressive action of cyclophosphamide].

Science.gov (United States)

Telegin, L Iu

1979-03-01

The alkylating and immunodepressive activity of the serum of CBA, BALB/c and DBA/2 mice was studied after the cyclophosphamide administration. The interstrain differences between the indices under study were revealed; no direct correlation was shown between them. DBA/2 mice were found to be the most sensitive to the immunodepressive action of cyclophosphamide, and had the highest blood serum immunodepressive activity.

77 FR 51751 - Information Collection Request; Farm Loan Programs, Direct Loan Making

Science.gov (United States)

2012-08-27

... DEPARTMENT OF AGRICULTURE Farm Service Agency Information Collection Request; Farm Loan Programs, Direct Loan Making AGENCY: Farm Service Agency, USDA. ACTION: Notice; request for comments. SUMMARY: In... approved information collection that supports Direct Loan Making programs. The information collection is in...

hebp3, a novel member of the heme-binding protein gene family, is expressed in the medaka meninges with higher abundance in females due to a direct stimulating action of ovarian estrogens.

Science.gov (United States)

Nakasone, Kiyoshi; Nagahama, Yoshitaka; Okubo, Kataaki

2013-02-01

The brains of teleost fish exhibit remarkable sexual plasticity throughout their life span. To dissect the molecular basis for the development and reversal of sex differences in the teleost brain, we screened for genes differentially expressed between sexes in the brain of medaka (Oryzias latipes). One of the genes identified in the screen as being preferentially expressed in females was found to be a new member of the heme-binding protein gene family that includes hebp1 and hebp2 and was designated here as hebp3. The medaka hebp3 is expressed in the meninges with higher abundance in females, whereas there is no expression within the brain parenchyma. This female-biased expression of hebp3 is not attributable to the direct action of sex chromosome genes but results from the transient and reversible action of estrogens derived from the ovary. Moreover, estrogens directly activate the transcription of hebp3 via a palindromic estrogen-responsive element in the hebp3 promoter. Taken together, our findings demonstrate that hebp3 is a novel transcriptional target of estrogens, with female-biased expression in the meninges. The definite but reversible sexual dimorphism of the meningeal hebp3 expression may contribute to the development and reversal of sex differences in the teleost brain.

46 CFR 1.03-40 - Appeals from decisions or actions of the National Maritime Center.

Science.gov (United States)

2010-10-01

... Maritime Center. 1.03-40 Section 1.03-40 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES... Appeal § 1.03-40 Appeals from decisions or actions of the National Maritime Center. Any person directly affected by a decision or action of an officer or employee of the National Maritime Center (NMC) involving...

Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

Directory of Open Access Journals (Sweden)

Guihong Li

2016-01-01

Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

Complex action support from coincidences of couplings

International Nuclear Information System (INIS)

Nielsen, H.B.

2011-01-01

Our model (Refs. 1–7) with a complex action in a functional integral formulation with path integrals extending over all times, both past and future, is reviewed. Several numerical relations between coupling constants are presented as supporting evidence. The new evidence is that several more hitherto unexplained coincidences are explained by our model: (1) The "scale problem" is solved because the Higgs field expectation value is predicted to be very small compared to say some fundamental scale, that might be the Planck scale. (2) The Higgs VEV need not be just zero, but rather is predicted to be so that the running top-quark Yukawa coupling just is about to be unity at this scale; in this way the (weak) scale easily becomes "exponentially small." Instead of the top-Yukawa we should rather say the highest flavor Yukawa coupling here. These predictions are only achieved by allowing the principle of minimization of the imaginary part of the action SI(history) to a certain extent adjust some coupling constants in addition to the initial conditions. If supersymmetric partners are not found at LHC it would strengthen the need for a "solution" to the hierarchy problem in our direction of an explanation via a fine-tuning scheme inside the Standard Model, from say minimizing "the imaginary part of the action" in our complex action model. (author)

Harmonization: A Need for EU Action on Consumer Credit?

DEFF Research Database (Denmark)

Jørgensen, Tanja

2015-01-01

seem small, there is still a need for EU action, but with a different approach that considers the nature of consumer credit. This means a focus on preventing overindebtedness and ensuring financial stability as well as a high level of consumer protection in a financialized and thereby more complex......As in the consumer area in general, the objective of the internal market has been applied as a reason why there is a EU need for action regarding consumer credit. Even though it is more than 25 years ago since the first Consumer Credit Directive harmonized aspects of the legislation in the Member...... States, cross-border activities are still extremely low. The achievement of the internal market depends on the consumers’ and the creditors’ overall incentives to cross-border activities, where harmonized aspects of the legislation are only an insignificant motivation. Despite a need for EU action may...

Local and regional smokefree and tobacco-free action in New Zealand: highlights and directions.

Science.gov (United States)

Thomson, George; Wilson, Nick

2017-09-22

In this viewpoint we highlight and discuss some recent local and regional level advances in tobacco control in Aotearoa/New Zealand. In this country a wide range of local actors are helping drive smokefree and tobacco-free policies, with an increasing presence of businesses in this field. There has been progress in the areas of smokefree dining, large outdoor worksites and ski fields, and parts of downtown areas such as squares and streets. In 2015 and 2016, three councils (Palmerston North, Napier and Hastings) have used pavement lease policies and bylaws to start introducing an element of requirement into smokefree outdoor dining. Elsewhere (eg, Rotorua, Ashburton, Westland and Christchurch) significant smokefree outdoor dining moves have been made by, or in conjunction with, local councils. Tobacco-free retailing continues to expand, particularly in Northland. In the absence of meaningful central government action on smokefree places in the last decade (despite the Smokefree 2025 goal), local activity is leading the way. It is particularly important in providing models for smokefree outdoor hospitality areas, where smoking normalisation and relapse are significant health risks. Nevertheless, there is a need for the local smokefree and tobacco-free activity to be nationally evaluated, particularly for assessing the prevalence of smoking in areas covered by 'smokefree' policies. Action by central government could help local actors by providing a more definite legislative basis for bylaws, by minimum outdoor smokefree laws and by the funding of effective tobacco control mass media.

The Quench Action

Science.gov (United States)

Caux, Jean-Sébastien

2016-06-01

We give a pedagogical introduction to the methodology of the Quench Action, which is an effective representation for the calculation of time-dependent expectation values of physical operators following a generic out-of-equilibrium state preparation protocol (for example a quantum quench). The representation, originally introduced in Caux and Essler (2013 Phys. Rev. Lett. 110 257203), is founded on a mixture of exact data for overlaps together with variational reasonings. It is argued to be quite generally valid and thermodynamically exact for arbitrary times after the quench (from short times all the way up to the steady state), and applicable to a wide class of physically relevant observables. Here, we introduce the method and its language, give an overview of some recent results, suggest a roadmap and offer some perspectives on possible future research directions.

Iodine-125 induced DNA strand breakage: Contributions of different physical and chemical radiation action mechanisms

International Nuclear Information System (INIS)

Li, W.

2002-01-01

The decay of the radioisotope 125 I into 125 Te is typically followed by the emission of two groups of approximately 10 electrons each. In deoxyribonucleic acid (DNA) with 125 I incorporated, these electrons produce various types of damage to DNA, e.g. single and double strand breaks. They occur through direct actions of physical tracks, or indirect actions of radicals produced in water. Among the direct actions one should consider not only the excitation and ionization of DNA by electrons but also the neutralization of highly charged 125m Te ions with electrons from neighboring molecules. The present work begins with a detailed description of electron tracks with the use of the PARTRAC code, compares results with recent experiments, and concludes with a firm assessment of the contribution to the strand break yields from the neutralization effect. (orig.)

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

Energy Technology Data Exchange (ETDEWEB)

Taub, Mary, E-mail: biochtau@buffalo.edu

2016-03-11

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

International Nuclear Information System (INIS)

Taub, Mary

2016-01-01

Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

The time between intention and action affect the experience of action

Directory of Open Access Journals (Sweden)

Mikkel C. Vinding

2015-06-01

Full Text Available We present a study investigating how the delay between the intention to act and the following action, influenced the experience of action. In experiments investigating sense of agency and experience of action, the contrast is most often between voluntary and involuntary actions. It is rarely asked whether different types of intentions influence the experience of action differently. To investigate this we distinguished between proximal intentions (i.e. intentions for immediate actions and delayed intentions (i.e. intentions with a temporal delay between intention and action. The distinction was implemented in an intentional binding paradigm, by varying the delay between the time where participants formed the intention to act and the time at which they performed the action. The results showed that delayed intentions were followed by a stronger binding effect for the tone following the action compared to proximal intentions. The actions were reported to have occurred earlier for delayed intentions than for proximal intentions. This effect was independent of the binding effect usually found in intentional binding experiments. This suggests that two perceptual shifts occurred in the contrast between delayed intentions and proximal intentions: The first being the binding effect, the second a general shift in the perceived time of action. Neither the stronger binding effect for tone, nor the earlier reports of action, differed across delays for delayed intentions. The results imply that delayed intentions and proximal intentions have a different impact on the experience of action.

Ready! Set! Go! An Action Research Agenda for Software Architecture

DEFF Research Database (Denmark)

Christensen, Henrik Bærbak; Hansen, Klaus Marius; Schougaard, Kari Rye

2008-01-01

Software architecture practice is highly complex. Software architects interact with business as well as technical aspects of systems, often embedded in large and changing organizations. We first make an argument that an appropriate research agenda for understanding, describing, and changing...... architectural practice in this context is based on an action research agenda in which researchers use ethnographic techniques to understand practice and engages directly with and in practice when proposing and designing new practices. Secondly, we present an overview of an ongoing project which applies action...... research techniques to understand and potentially change architectural practice in four Danish software companies....

DAPs: Deep Action Proposals for Action Understanding

KAUST Repository

Escorcia, Victor; Caba Heilbron, Fabian; Niebles, Juan Carlos; Ghanem, Bernard

2016-01-01

action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates

78 FR 28540 - Airworthiness Directives; Hawker Beechcraft Corporation

Science.gov (United States)

2013-05-15

... Corporation AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Supplemental notice of proposed... directive (AD) for certain Hawker Beechcraft Corporation (HBC) Models 58, 58TC, 58P, 95C55, E55, and 56TC... identified in this proposed AD, contact Hawker [[Page 28541

The photodynamic and non-photodynamic actions of porphyrins

Directory of Open Access Journals (Sweden)

S.G. Afonso

1999-03-01

Full Text Available Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions or with molecular oxygen, generating excited singlet oxygen (type II reactions. Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

Observing complex action sequences: The role of the fronto-parietal mirror neuron system.

Science.gov (United States)

Molnar-Szakacs, Istvan; Kaplan, Jonas; Greenfield, Patricia M; Iacoboni, Marco

2006-11-15

A fronto-parietal mirror neuron network in the human brain supports the ability to represent and understand observed actions allowing us to successfully interact with others and our environment. Using functional magnetic resonance imaging (fMRI), we wanted to investigate the response of this network in adults during observation of hierarchically organized action sequences of varying complexity that emerge at different developmental stages. We hypothesized that fronto-parietal systems may play a role in coding the hierarchical structure of object-directed actions. The observation of all action sequences recruited a common bilateral network including the fronto-parietal mirror neuron system and occipito-temporal visual motion areas. Activity in mirror neuron areas varied according to the motoric complexity of the observed actions, but not according to the developmental sequence of action structures, possibly due to the fact that our subjects were all adults. These results suggest that the mirror neuron system provides a fairly accurate simulation process of observed actions, mimicking internally the level of motoric complexity. We also discuss the results in terms of the links between mirror neurons, language development and evolution.

Associative theories of goal-directed behaviour: a case for animal-human translational models

NARCIS (Netherlands)

de Wit, S.; Dickinson, A.

2009-01-01

Associative accounts of goal-directed action, developed in the fields of human ideomotor action and that of animal learning, can capture cognitive belief-desire psychology of human decision-making. Whereas outcome-response accounts can account for the fact that the thought of a goal can call to mind

Food Waste Avoidance Actions in Food Retailing

DEFF Research Database (Denmark)

Kulikovskaja, Viktorija; Aschemann-Witzel, Jessica

2017-01-01

Food waste occurs throughout the entire food supply chain, from production to consumption of food in households. Retailers are in a unique position to contribute to food waste avoidance, not only by minimizing the amount of waste in their distribution channels but also by influencing consumer...... attitudes and behaviors. This explorative study aims to identify which food waste avoidance actions are conducted by retailers in Denmark, to which extent, and how they vary across food categories and supermarket chain. Based on an analysis of secondary and empirical data collected via observations...... at retail stores, the authors identify 22 food waste avoidance actions in Danish retail. The results provide new insights into food waste avoidance in retail. Based on the findings, suggestions for further research directions are developed that should serve to identify the most efficient customer targeted...

Transfer action of cyclodextrin glycosyltransferase on starch

Energy Technology Data Exchange (ETDEWEB)

Kitahata, S; Okada, S [Osaka City Technical Research Inst. (Japan)

1975-11-01

The transglycosylation reaction of the cyclodextrin glycosyltransferase from Bacillus megaterium (No. 5 enzyme) and Bacillus macerans (BMA) were examined. No.5 enzyme was more efficient in transglycosylation reaction than BMA in the every acceptor employed in the present study. The order of the efficient acceptors for No. 5 enzyme was maltose (G2), glucose (G1), maltotriose (G3) and sucrose (GF). On the other hand, that found for BMA was G1, G2, GF and G3. The transglycosylation products to glucose formed by the action of No. 5 enzyme on starch were G2, G3, maltotetraose (G4), maltopentaose (G5), maltohexaose (G6) and maltoheptaose (G7) in the order of their quantities, while, in the case of BMA, they were G2, G3, G5, G7 = G4 and G6. The larger transglycosylation products to sucrose formed by the action of No. 5 enzyme on starch were maltosylfructose. On the other hand, that formed by the action of BMA was maltoheptaosylfructose. It was suggested that cyclodextrin glycosyltransferase could transfer the glucosyl residues to an acceptor directly from starch, as well as through cyclodextrin.

77 FR 20987 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Science.gov (United States)

2012-04-09

... Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... the Federal Register. That AD applies to RB211-Trent 800 series turbofan engines. The last comment...

Using Action Research Projects to Examine Teacher Technology Integration Practices

Science.gov (United States)