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Sample records for agonist win 55212-2

  1. Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

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    Miñarro José

    2010-03-01

    Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

  2. The Study of Destructive Effects of Exposure to WIN 55212-2, an Agonist of Cannabinoid Receptor, during Pregnancy on CNS Function of Rats’ Offspring

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    Mohammad Shabani

    2011-08-01

    Full Text Available Introduction: Cannabinoid consumption including hashish and WIN55212-2 during pregnancy has destructive affect on the development of fetus and the performance of CNS. Method: WIN treated group received daily 0.5 or 1mg/kg WIN suspended in 1% tween 80 saline (s.c. at a volume of 1 ml/kg from days 5 to 20 of pregnancy. Third, fifth and seventh weeks after birth, the effects of maternal WIN consumption on infants body weight, mortality, histological changes, motor performance and memory function were assessed. Results: Prenatal WIN consumption associated with atrophy of cerebellum cortex in granular and Purkinje cells layers. WIN treatment of pregnant rats produced a significant decrease in the rearing frequency of the offspring, but significantly increased the grooming frequency at 22, 36 and 50 days of age. During the acquisition trials, approach latencies were not significantly different between all groups of rats (50 days old.When the trial was repeated 24 hours and seven days later (retention trial, the avoidance latencies of the WIN-exposed group were significantly shorter than those of control and sham animals. The mortality percent was increased significantly and litter size was decreased significantly in WIN (1mg/kg treated rats compared to the control, sham and WIN (0/5 mg/kg treatment groups. Conclusion: These findings suggest that prenatal exposure to WIN, cannabinoid agonist, induces possibly a long-term alteration on histological, motor performance and learning and memory parameters.

  3. CB1 receptor agonist WIN55212-2 improves motor complications in Parkinson's disease%CB1受体激动剂WIN55212-2改善帕金森病运动并发症的实验研究

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    马雅萍; 宋璐; 刘振国; 巴茂文; 卞雷斯

    2011-01-01

    目的 探讨CB1受体激动剂WIN55212-2对左旋多巴诱发的运动并发症的行为学及细胞学作用.方法通过6-OHDA立体定向注射至大鼠右侧前脑内侧束建立PD动物模型,成功的PD大鼠模型分别接受左旋多巴/苄丝肼(50mg/kg加12.5mg/kg苄丝肼,每天2次)+溶剂、左旋多巴/苄丝肼+WIN55212-2(1 mg/kg)腹腔注射,共持续21d.评估用药后大鼠的旋转反应时间、剂峰旋转圈数变化和关期发生率;采用Western blot方法检测纹状体信号转导蛋白DARPP-32(Thr75)和ERK1/2 (Thr202/Tyr204)的磷酸化表达.结果长期联合应用WIN55212-2和左旋多巴,缓解了左旋多巴单独用药所致的PD大鼠旋转反应时间缩短、剂峰旋转圈数增加的趋势,并明显降低关期发生频率.WIN55212-2与左旋多巴合用显著降低了纹状体内DARPP-32(Thr75)的磷酸化;但未使ERK1/2磷酸化表达降低至对照组水平.结论激动CB1受体可能有益于预防帕金森病运动并发症.%Objective To investigate cellular and behavioural effects of CB1 receptor agonist WIN55212-2 in a rat model of levodopa-induced motor complications. Methods The hemi-Parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle( MFB). Animals were intraperitoneally treated with levodopa/ benserazide (50mg/kg levodopa plus 12.5mg/kg benserazide) or WIN55212-2( lmg/kg) + levodopa/benserazide twice a day for 21 days. Rotational duration,peak rotation and the frequency of failures to L-dopa were estimated. After sacrificed,the phosphorylation of dopamine and cAMP- regulated phosphoprotein of Mr 32,000( DARPP-32) at Thr75 site and extracellular signal-regulated kinase (ERK) at Thr202 and Tyr204 site was observed by Western blot. Results W1N55212-2 plus L-dopa treatment prolonged the duration of the motor response and reduced peak turning. WIN55212-2 plus L-dopa also decreased the frequency of failures to L-dopa. The long-term use of L-dopa reduced the

  4. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

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    M. Rodríguez-Arias

    2016-01-01

    Full Text Available Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p. in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg, or cannabinoid antagonist rimonabant (1 mg/kg and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p. or cocaine (1 or 6 mg/kg, i.p.. Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction.

  5. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait

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    Rodríguez-Arias, M.; Roger-Sánchez, C.; Vilanova, I.; Revert, N.; Manzanedo, C.; Miñarro, J.; Aguilar, M. A.

    2016-01-01

    Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction. PMID:26881125

  6. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait.

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    Rodríguez-Arias, M; Roger-Sánchez, C; Vilanova, I; Revert, N; Manzanedo, C; Miñarro, J; Aguilar, M A

    2016-01-01

    Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction.

  7. Benzophenanthridine alkaloid, piperonyl butoxide and (S)-methoprene action at the cannabinoid-1 receptor (CB1-receptor) pathway of mouse brain: Interference with [(3)H]CP55940 and [(3)H]SR141716A binding and modification of WIN55212-2-dependent inhibition of synaptosomal l-glutamate release.

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    Dhopeshwarkar, Amey Sadashiv; Nicholson, Russell Alfred

    2014-01-15

    Benzophenanthridine alkaloids (chelerythrine and sanguinarine) inhibited binding of [(3)H]SR141716A to mouse brain membranes (IC50s: CB1 receptors versus spleen CB2 receptors. All compounds reduced Bmax of [(3)H]SR141716A binding to CB1 receptors, but only methoprene and piperonyl butoxide increased Kd (3-5-fold). Benzophenanthridines increased the Kd of [(3)H]CP55940 binding (6-fold), but did not alter Bmax. (S)-methoprene increased the Kd of [(3)H]CP55940 binding (by almost 4-fold) and reduced Bmax by 60%. Piperonyl butoxide lowered the Bmax of [(3)H]CP55940 binding by 50%, but did not influence Kd. All compounds reduced [(3)H]SR141716A and [(3)H]CP55940 association with CB1 receptors. Combined with a saturating concentration of SR141716A, only piperonyl butoxide and (S)-methoprene increased dissociation of [(3)H]SR141716A above that of SR141716A alone. Only piperonyl butoxide increased dissociation of [(3)H]CP55940 to a level greater than CP55940 alone. Binding results indicate predominantly allosteric components to the study compounds action. 4-Aminopyridine-(4-AP-) evoked release of l-glutamate from synaptosomes was partially inhibited by WIN55212-2, an effect completely neutralized by AM251, (S)-methoprene and piperonyl butoxide. With WIN55212-2 present, benzophenanthridines enhanced 4-AP-evoked l-glutamate release above 4-AP alone. Modulatory patterns of l-glutamate release (with WIN-55212-2 present) align with previous antagonist/inverse agonist profiling based on [(35)S]GTPγS binding. Although these compounds exhibit lower potencies compared to many classical CB1 receptor inhibitors, they may have potential to modify CB1-receptor-dependent behavioral/physiological outcomes in the whole animal.

  8. Antagonistic and inverse agonistic effect of M J15 on cannabinoid receptors Ⅰ%MJ15对大麻素Ⅰ型受体的阻滞及反相激动作用的研究

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    曹宁; 杨洋; 周晓棉; 徐成; 王莉莉

    2011-01-01

    Objective: To observe the antagonistic and inverse agonistic effect of MJ15 on cannabinoid receptors Ⅰ (CB1). Methods: The samples of the ileum smooth muscle isolated from guinea pigs and vas deferens isolated from mice were put into the Magnus' bath, and the contractive activities were investigated. Results: The CB1 receptor agonist WIN55212-2 ( 10 - 10 ~ 10 - 6 mol · L - 1 ) inhibited electrically induced contraction of mouse vas deferens; the concentration-dependency was significant. The concentration-response curse was completely inhibited by SR141716A and MJ15(l0-7 mol· L-1). WIN55212-2 inhibited contraction of mouse vas deferens and guinea pig ileum smooth muscle; while SR141716A and MJ15 accelerated the contraction. Conclusion: MJ15 is an antagonist of CB1 receptor with inverse agonistic activity.%目的:观察MJ15对大麻素Ⅰ型(cannabinoid receptors Ⅰ,CB1)受体的阻滞及反相激动作用.方法:制备小鼠输精管和豚鼠回肠平滑肌的离体标本,观察CB1受体激动剂WIN55212-2以及阻滞剂利莫那班(SR141716A)和MJ15对其收缩特性的影响.结果:CB1受体激动剂WIN55212-2(10-10~10-6 mol·L-1)可抑制电刺激所引起小鼠输精管的收缩作用,呈现明显的剂量依赖性,而SR141716A和MJ15(10-7mol·L-1)能阻滞WIN55212-2的抑制作用;CB1受体激动剂WIN55212-2可抑制豚鼠回肠和小鼠输精管平滑肌的收缩,而SR141716A和MJ15能促进豚鼠回肠和小鼠输精管平滑肌的收缩.结论:MJ15是CB1受体的阻滞剂,同时具有反相激动作用.

  9. Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice.

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    Smith, S R; Terminelli, C; Denhardt, G

    2000-04-01

    Previous studies have shown that mice primed with Corynebacterium parvum produce higher levels of inflammatory cytokines than unprimed mice upon challenge with lipopolysaccharide (LPS). Herein, we describe experiments in which two cannabinoid (CB) agonists, WIN 55212-2 [(R)-(+)-[2, 3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]1, 4-benzoxazin-6-yl](1-naphthyl)methanone) and HU-210 [(-)-11-hydroxy-delta(8) tetrahydrocannabinol-dimethylheptyl], were examined for their effects on LPS-induced cytokines in C. parvum-primed and unprimed mice. These agonists have been reported to bind selectively to the CB2 and CB1 receptor subtypes, respectively. WIN 55212-2 (3.1-50 mg/kg i.p.) and HU-210 (0.05-0.4 mg/kg i.p.) decreased serum tumor necrosis factor-alpha and interleukin-12 (IL-12) and increased IL-10 when administered to mice before LPS. The drugs also protected C. parvum mice (but not unprimed mice) against the lethal effects of LPS. The protection afforded to C. parvum mice could not be attributed to the higher levels of IL-10 present in these mice after agonist treatment. The WIN 55212-2- and HU-210-mediated changes in the responsiveness of mice to LPS were antagonized by SR141716A [N-(piperdin-1-yl)-5-(4-chloropheny)-1-(2, 4-dichloropheny)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride], a selective CB1 receptor antagonist, but not by SR144528 [N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2. 1]heptan-2-yl]5-(4-choro-3-methylphenyl)-1-(4-methylbenzyl)p yrazole-3 -carboxamide], a selective antagonist at the CB2 receptor. Therefore, both CB agonists modulated LPS responses through the CB1 receptor. Surprisingly, SR141716A itself modulated cytokine responses in a manner identical with that of WIN 55212-2 and HU-210 when administered alone to mice. The agonist-like effects of SR141716A, which were more striking in unprimed than in primed mice, suggested that the antagonist also could function as a partial agonist at the CB1 receptor. Our findings indicate a role

  10. Functional responses to the cannabinoid agonist WIN 55,212-2 in neonatal rats of both genders: influence of weaning.

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    Borcel, Erika; Pérez-Alvarez, Laura; de Ceballos, María L; Ramirez, Belén G; Marco, Eva Maria; Fernández, Beatriz; Rubio, Marina; Guaza, Carmen; Viveros, Ma-Paz

    2004-07-01

    We have studied behavioural, biochemical and endocrine responses to the cannabinoid agonist WIN 55,212-2 (WIN) in neonatal rats, as well as the effects of weaning on such responses. We used preweanling rats (20 days of age), 25-day-old weaned rats (weaning at Day 22) and 25-day-old nonweaned rats of both sexes. The behavioural effects of WIN were assessed in the nociceptive tail immersion test and in the open field. We also analysed the effect of weaning on corticosterone responses to WIN (radioimmunoassay) as well as on WIN-stimulated [35S] GTPgammaS binding in periaqueductal grey (PAG) and striatum. The cannabinoid agonist induced a modest increase in pain thresholds, whereas the effect of the drug on open-field activity, particularly on vertical activity, was much more marked. The weaning process appeared to reduce the baseline nociceptive latencies of the female rats. No significant effect of weaning on the behavioural responses to WIN was found. However, the group of weaned females (but not males) showed a significantly reduced WIN-stimulated [35S] GTPgammaS binding in the striatum. The cannabinoid agonist significantly increased the corticosterone levels of 25-day-old rats with the effect being more marked in weaned than in nonweaned animals. The results suggest that the weaning process might produce some sexually dimorphic developmental changes in CB1 receptor function.

  11. Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia.

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    Martínez-Orgado, José; Fernández-Frutos, Beatriz; González, Rita; Romero, Eva; Urigüen, Leire; Romero, Julián; Viveros, M Paz

    2003-06-10

    This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.

  12. Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory bulbectomized rats: evaluation of possible serotonergic and dopaminergic underlying mechanisms

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    Petra eAmchova

    2014-03-01

    Full Text Available Depression has been associated with drug consumption, including heavy or problematic cannabis use. According to an animal model of depression and substance use disorder comorbidity, we combined the olfactory bulbectomy model of depression with intravenous drug self-administration procedure to verify whether depressive-like rats displayed higher voluntary intake of the CB1 receptor agonist WIN55,212-2 (WIN, 12.5 µg/kg/infusion. To this aim, olfactory-bulbectomized (OBX and sham-operated (SHAM Lister Hooded rats were allowed to self-administer WIN by lever-pressing under a continuous (FR-1 schedule of reinforcement in 2h daily sessions. Data showed that both OBX and SHAM rats developed stable WIN intake; yet, responses in OBX were constantly higher than in SHAM rats soon after the first week of training. In addition, OBX rats took significantly longer to extinguish the drug-seeking behaviour after vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist, CGS-12066B (2.5-10 mg/kg, did not significantly modify WIN intake in OBX and SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and 15 mg/kg did not alter responses in parallel groups of OBX and SHAM Sprague Dawley rats self-administering methamphetamine under higher (FR-2 reinforcement schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus accumbens of OBX rats did not increase in response to a WIN challenge, as in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats. Altogether, our findings suggest that a depressive state may alter cannabinoid CB1 receptor agonist-induced brain reward function and that a dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN self-administration in OBX rats.

  13. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme;

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment....... Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...

  14. The Neuroprotective Effect of Cannabinoid Receptor Agonist (WIN55,212-2 in Paraoxon Induced Neurotoxicity in PC12 Cells and N-methyl-D-aspartate Receptor Interaction

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    Hedayat Sahraei

    2010-01-01

    Full Text Available Objective: Considering that cannabinoids protect neurons against neurodegeneration, inthis study, the neuroprotective effect of WIN55,212-2 in paraoxon induced neurotoxicity inPC12 cells and the role of the N-methyl-D-aspartate (NMDA receptor were evaluated.Materials and Methods: In this study PC12 cells were maintained in Dulbecco's modifiedeagle’s medium (DMEM+F12 culture medium supplemented with 10% fetal bovineserum. The cells were treated with paraoxon (200 μM in the presence or absence ofWIN55,212-2 (0.1 μM, NMDA receptor agonist NMDA (100 μM, cannabinoid receptorantagonist AM251 and NMDA receptor antagonist MK801 (1 μM at 15 minutes intervals.After 48 hours of exposure, cellular viability and protein expression of the CB1 receptorwere evaluated in PC12 cells.Results: Following the exposure of PC12 cells to paraoxon (200 μM, a reduction in cellsurvival and protein level of the CB1 receptor was observed (p<0.01. Treatment of thecells with WIN55,212-2 (0.1 μM and NMDA (100 μM prior to paraoxon exposure significantlyelevated cell survival and protein level of the CB1 receptor (p<0.01. Also, AM251(1μM did not inhibit the cell survival and protein level of the CB1 receptor increase inducedby WIN55,212-2 (p<0.001. However, MK801 (1 μM did inhibit cell survival andprotein expression of the CB1 receptor increase induced by NMDA (p<0.001.Conclusion: The results indicate that WIN55,212-2 and NMDA protect PC12 cellsagainst paraoxon induced toxicity. In addition, the neuroprotective effect of WIN55,212-2and NMDA was cannabinoid receptor-independent and NMDA receptor dependent, respectively.

  15. Effects of glucagon-like peptide-1 receptor stimulation and blockade on food consumption and body weight in rats treated with a cannabinoid CB1 receptor agonist WIN 55,212-2

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    Radziszewska, Elżbieta; Bojanowska, Ewa

    2013-01-01

    Background Glucagon-like peptide-1 (GLP-1) and endocannabinoids are involved in appetite control. Recently we have demonstrated that cannabinoid (CB)1 receptor antagonist and GLP-1 receptor agonist synergistically suppress food intake in the rat. The aim of the present study was to determine the effects of GLP-1 receptor stimulation or blockade on feeding behavior in rats treated with WIN 55,212-2, a CB1 receptor agonist. Material/Methods Experiments were performed on adult male Wistar rats. In the first experiment the effects of increasing doses (0.5–4.0 mg/kg) of WIN 55,212-2 injected intraperitoneally on 24-hour food consumption were tested. In further experiments a GLP-1 receptor antagonist, exendin (9-39), and WIN 55,212-2 or a GLP-1 receptor agonist, exendin-4, and WIN 55,212-2 were injected intraperitoneally at subthreshold doses (that alone did not change food intake and body weight) to investigate whether these agents may interact to affect food intake in rats. Results WIN 55,212-2 administered at low doses (0.5–2 mg/kg) did not markedly change 24-hour food consumption; however, at the highest dose, daily food intake was inhibited. Combined administration of WIN 55,212-2 and exendin (9-39) did not change the amount of food consumed compared to either the control group or to each agent injected alone. Combined injection of WIN 55,212-2 and exendin-4 at subthreshold doses resulted in a significant decrease in food intake and body weight in rats. Conclusions Stimulation of the peripheral CB1 receptor by its agonist WIN 55,212-2 can induce anorexigenic effects or potentiate, even at a subthreshold dose, the effects of exendin-4, a known anorectic agent. Hence, this dual action of the cannabinoid system should be considered in the medical use of CB1 agonists. PMID:23291632

  16. Chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 during puberty or adulthood reverses 3,4 methylenedioxymetamphetamine (MDMA)-induced deficits in recognition memory but not in effort-based decision making.

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    Schulz, Sybille; Becker, Thorsten; Nagel, Ulrich; von Ameln-Mayerhofer, Andreas; Koch, Michael

    2013-05-01

    Cannabis and 3,4 methylenedioxymetamphetamine (MDMA, "ecstasy") are the most frequently combined illegal drugs among young adults in western societies. This study examined the effects of chronic co-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) and MDMA on working memory and effort-based decision making in rats. Treatment consisted of MDMA (7.5 mg/kg), WIN (1.2 mg/kg), a combination of these substances (MDMA+WIN) or vehicle over a period of 25 days during puberty (PD40-65) or adulthood (PD80-105). Ten days after the last treatment, WIN reversed MDMA-induced working memory deficits in the object recognition test in animals treated during adulthood or puberty, but had no influence on impairment of adult rats in the effort-based T-maze task. No differences were observed between groups of pubertally treated rats in the decision making task. During a subsequent acute drug challenge MDMA and MDMA+WIN decreased high reward choices in both age groups, indicating MDMA-induced cost-aversive choice. Differential long-term interactions on the neuronal level in the hippocampus and MDMA-induced disturbances in cortico-limbic connections are suggested. PMID:23541493

  17. Mitigation win-win

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    Moran, Dominic; Lucas, Amanda; Barnes, Andrew

    2013-07-01

    Win-win messages regarding climate change mitigation policies in agriculture tend to oversimplify farmer motivation. Contributions from psychology, cultural evolution and behavioural economics should help to design more effective policy.

  18. Effects of WIN 55,212-2 (a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of various classical antiepileptic drugs in the mouse 6 Hz psychomotor seizure model

    OpenAIRE

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Kondrat-Wrobel, Maria W.; Tutka, Piotr; Jarogniew J Luszczki

    2014-01-01

    The aim of this study was to characterize the influence of WIN 55,212-2 (WIN—a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant effects of various classical antiepileptic drugs (clobazam, clonazepam, phenobarbital and valproate) in the mouse 6 Hz-induced psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via ocular electrodes. Drug-related adverse effects were...

  19. 大麻素受体激动剂WIN55,212-2预处理对大鼠脊髓缺血再灌注损伤的保护作用研究%Protective effects of cannabinoid receptor agonist WIN55,212-2 preconditioning on spinal cord ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    荆娜; 马虹

    2015-01-01

    目的 探讨大麻素受体激动剂WIN55,212-2预处理对大鼠脊髓缺血再灌注损伤的保护作用.方法 32只SD大鼠按随机数字表法分为4组(n=8),分别为Sham组(假手术组)、Control组(单纯缺血对照组)、二甲基亚砜(DMSO)组(溶剂组)、WIN组(WIN55,212-2预处理组).Control组在诱导脊髓缺血前30 min腹腔内注射生理盐水0.3ml,DMSO组在诱导脊髓缺血前30 min腹腔内注射DMSO 0.3 ml,WIN组在诱导脊髓缺血前30 min腹腔内注射WIN55,212-2 1 mg/kg.分别于再灌注24、48 h采用Tarlov评分标准对后肢运动功能进行评价,之后取L4~L6脊髓组织行病理学检查.结果 再灌注24h和48 h,缺血组Tarlov评分均低于Sham组(P<0.05),WIN组Tarlov评分明显高于Control组和DMSO组(P<0.05).缺血组前角正常神经元数量少于Sham组(P<0.05),WIN组明显多于Control组和DMSO组(P<0.05).结论 大麻素受体激动剂WIN55,212-2预处理能够减轻大鼠脊髓缺血再灌注损伤.%Objective To explore the effects of cannabinoid receptor agonist WIN55,212-2 preconditioning on spinal cord ischemia reperfusion injury in rats.Methods A total of 32 male Sprague-Dawley rats was randomly divided into four groups (n =8):sham group,control group,dimethyl sulfoxide(DMSO) group which was given intraperitoneally DMSO 0.3 ml 30 min before ischemia reperfusion,and WIN group which was given intraperitoneally WIN55,212-2 1 mg/kg 30 min before ischemia reperfusion.Each rat was neurologically assessed at 24 h and 48 h after reperfusion by Tarlov scale,and the number of normal motor neurons at anterior horn of the spinal cord was recorded.Res uits The Tarlov scale of WIN group was significantly higher than that control and DMSO groups (P < 0.05).There were more normal motor neurons at anterior horn of the spinal cord in WIN group than those in control and DMSO groups (P < 0.05).Conclusions Cannabinoid receptor agonist WIN55,212-2 preconditioning might attenuate spinal cord ischemia

  20. Win-win initiatives

    Energy Technology Data Exchange (ETDEWEB)

    Specter, Herschel

    1999-03-01

    This paper explores the use of win-win initiatives as a means of making safety improvements while simultaneously reducing plant operating costs. A two-phased process for implementing these initiatives is provided. Near-term progress is emphasized in the first phase by using presently available information. The second phase addresses complex issues such as closure in the regulatory process, modernizing the role of determinism in decisionmaking, closer coupling of performance-based regulation and risk-informed regulation, modernizing the testing of important plant equipment, and the treatment of uncertainties.

  1. Chronic Cannabinoid Administration in Vivo Compromises Extinction of Fear Memory

    Science.gov (United States)

    Lin, Hui-Ching; Mao, Sheng-Chun; Chen, Po-See; Gean, Po-Wu

    2008-01-01

    Endocannabinoids are critically involved in the extinction of fear memory. Here we examined the effects of repeated cannabinoid administration on the extinction of fear memory in rats and on inhibitory synaptic transmission in medial prefrontal cortex (mPFC) slices. Rats were treated with the CB1 receptor agonist WIN55212-2 (WIN 10 mg/kg, i.p.)…

  2. WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid β1-42 effects on astrocytes in primary culture.

    Directory of Open Access Journals (Sweden)

    Diana Aguirre-Rueda

    Full Text Available Alzheimer's disease (AD, a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death. Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS, and changes in this system are related to many human diseases, including AD. However, studies on the effects of cannabinoids on astrocytes functions are scarce. In primary cultured astrocytes we studied cellular viability using MTT assay. Inflammatory and oxidative stress mediators were determined by ELISA and Western-blot techniques both in the presence and absence of Aβ1-42 peptide. Effects of WIN 55,212-2 (a synthetic cannabinoid on cell viability, inflammatory mediators and oxidative stress were also determined. Aβ1-42 diminished astrocytes viability, increased TNF-α and IL-1β levels and p-65, COX-2 and iNOS protein expression while decreased PPAR-γ and antioxidant enzyme Cu/Zn SOD. WIN 55,212-2 pretreatment prevents all effects elicited by Aβ1-42. Furthermore, cannabinoid WIN 55,212-2 also increased cell viability and PPAR-γ expression in control astrocytes. In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes. Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer's disease patients.

  3. Green, Reform, Win-Win

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Boao Forum for Asia this year enjoys three high lights, namely "Green, Reform and Win-Win".The old but hot topics attracted accumulated attention from the whole world, and more fresh ideas were ushered in.

  4. She wins You win

    Institute of Scientific and Technical Information of China (English)

    杨品文

    2006-01-01

    对于那些执著于人生理想的商业领袖们,他们背后的女人们也是不甘寂寞的,甚至可能成为这些企业传奇中最让人津津乐道的故事。在这个弥漫女性色彩的三月,我们想起“She wins You win”这句西方的古老谚语,发现它非常精确地描述了现代商业社会中这些大师和女人的某种相处方式。

  5. What's so Hard about Win-Win?

    Science.gov (United States)

    Bluestein, Jane

    2011-01-01

    The win-win approach to solving conflicts, which has become popular in the business world, should be a natural for the school environment. Win-win thinking can foster a cooperative school climate by meeting educators' and students' needs for dignity, belonging, and respect. Yet win-win thinking faces a number of obstacles in schools, writes…

  6. Induction of proteinuria by cannabinoid receptors 1 signaling activation in CB1 transgenic mice.

    Science.gov (United States)

    Hsu, Yung-Chien; Lei, Chen-Chou; Shih, Ya-Hsueh; Ho, Cheng; Lin, Chun-Liang

    2015-02-01

    Proteinuria is not only a sign of kidney damage but is also involved in the progression of renal disease as an independent pathologic factor. Although patients with mutated type 1 cannabinoid receptors (CB1) polymorphism are associated with renal microvascular damage, the biologic role of CB1 signaling in proteinuria remains uncharacterized till now. Herein, we investigate whether CB1 participates in glomerular proteinuria in CB1 transgenic mice and treatment with CB1 agonist WIN55212-2 rat, neither of which are diabetic models. The CB1 transgenic mice and rats treated with CB1 agonist WIN55212-2 had higher kidney weight and urinary protein concentrations but not blood glucose levels compared with the wild-type group. A combination of laser-capture microsdissection, quantitative reverse transcription-polymerase chain reaction, immunoblotting and immunohistochemical validation revealed that CB1 transgenic mice and rats treated with CB1 agonist WIN55212-2 had higher vascular endothelial growth factor (VEGF) expression in renal glomeruli than that of the wild-type group. Geneticorpharmacological activation of CB1 by transgenic CB1 mice or treatment with WIN55212-2 reduced nephrin expression in the renal glomeruli compared with that of the wild-type group in the glomerular mesanglium. Taken together, CB1 transgenic mice and rats treated with CB1 agonist WIN55212-2 induced proteinuria with upregulation of CB1 resulting in impaired nephrin expression, by inducing excess VEGF reaction in the renal glomeruli. Genetic and pharmacological manipulation of CB1 signaling revealed VEGF-dependent nephrin depression of glomerulopathy. Controlling CB1 activity can be used an alternative strategy for sustaining renal function in the presence of CB1 activation.

  7. Weapons plutonium for electricity: a win-win-win solution

    Energy Technology Data Exchange (ETDEWEB)

    Goldschmidt, P. [Synatom, Brussels (Belgium)

    1997-12-31

    Incorporating recovered weapons-grade plutonium into mixed-oxide (MOX) fuel to produce electricity in currently operating reactors is presented as the best option for its disposition from a European utilities perspective. It would be a win-win-win solution. Firstly, it would be a win for the US government as the only technology readily available on an industrial scale and therefore the fastest way to convert the surplus plutonium to a highly proliferation resistant spent fuel form, as well as being the most cost-effective option. It would also have the political advantages of proving to the world that the US is dedicated to the elimination of its surplus plutonium without delay, receiving support from the Western allies of the US, and encouraging the Russians to take the same route. Secondly, it would be a win for the US utilities both in economic terms and in improving their public image through their contribution to world disarmament. Finally, it would be a win for the world as the fastest route to making disarmament irreversible and as the only solution that conserves natural resources. (8 figures; 14 references) (UK).

  8. The Combined Inhibitory Effect of the Adenosine A1 and Cannabinoid CB1 Receptors on cAMP Accumulation in the Hippocampus Is Additive and Independent of A1 Receptor Desensitization

    Directory of Open Access Journals (Sweden)

    André Serpa

    2015-01-01

    Full Text Available Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3–30 μM decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6 ± 2.7 μM and an Emax⁡ of 31% ± 2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10–150 nM, an EC50 of 35 ± 19 nM, and an Emax⁡ of 29% ± 5 were obtained. The combined inhibitory effect of WIN55212-2 (30 μM and CPA (100 nM on cAMP accumulation was 41% ± 6% (n=4, which did not differ (P>0.7 from the sum of the individual effects of each agonist (43% ± 8% but was different (P<0.05 from the effects of CPA or WIN55212-2 alone. Preincubation with CPA (100 nM for 95 min caused desensitization of adenosine A1 activity, which did not modify the effect of WIN55212-2 (30 μM on cAMP accumulation. In conclusion, the combined effect of CB1 and A1 receptors on cAMP formation is additive and CB1 receptor activity is not affected by short-term A1 receptor desensitization.

  9. Continuous improvement: A win... win process

    International Nuclear Information System (INIS)

    Implementing a continuous improvement (CI) process within PanCanadian's oil and gas production operations might have been a simple assignment if one were not also trying to capture the hearts and imaginations of the people in a changing work environment. Meeting the challenge is resulting in big payoffs to both the organization and its people. The plan used within the Company's Production Division to successfully introduce the CI process is discussed. A brief insight is provided on the process philosophy, with emphasis placed on planning, training and coaching used to launch the process. Also reviewed at length are the impediments to change and the challenges faced when changing an organization's culture. In a CI work environment, the supervisor's traditional role changes from one of monitoring and controlling to one of inspiring, motivating and leading people by communicating a clear vision. Employees at all levels in the work environment are organized into teams and armed with a good working knowledge of the problem solving tools which allow them to pursue and implement improvement initiatives. The outcome of the process is an ongoing 'win-win' situation for both the Company and its people. Employees are gaining more trust, eliminating job irritants and enjoying their work more in a team environment. The Company is winning through increased production, improved safety and reduced operating expenses, thanks to many innovative ideas which the employees have implemented. 4 refs

  10. Modulation of cannabinoid to GABA currents in retinal ganglion cells in human and mice%大麻素对人和小鼠视网膜神经节细胞GABA电流的调控差异

    Institute of Scientific and Technical Information of China (English)

    罗雪; 刘诗亮; 江梦南; 沈雨濛; 胡单萍; 沈吟

    2015-01-01

    目的 比较人和小鼠视网膜内源性大麻素类受体1(cannabinoid receptor,CB1)的表达差异,观察大麻素受体激动剂WIN55212-2对不同种属视网膜神经节细胞GABA电流的调控作用.方法 采用冰冻切片免疫荧光染色,观察CB1受体在视网膜中的表达.制备视网膜薄片,行全细胞膜片钳记录.在神经节细胞上给予100 μmol/L GABA快速加药诱导出电流I GABA,而后观察孵育大麻素受体激动剂WIN55212-2时GABA诱导的IGABA及同时孵育WIN 55212-2和大麻素受体拮抗剂SR141716A的电流IGABA.结果 人和小鼠视网膜CB1受体的分布有所不同,人的内核层、外核层、神经节细胞层有显著的CB1表达,但小鼠CB1受体主要表达在内网状层、外网状层上;膜片钳结果显示不管是在人还是在小鼠的视网膜上,孵育WIN55212-2后的GABA诱导电流幅度均有显著减小.不同的是,在人视网膜神经节细胞上,WIN55212-2明显减慢了GABA电流的反应速度,表现在电流达峰时间明显延长,恢复时间缩短(P<0.05).WIN55212-2对小鼠视网膜神经节细胞GABA的反应速度无明显差别(P>0.05).结论 CB1受体在人和小鼠视网膜中有差异性分布,对神经节细胞的GABA电流影响也不同.孵育WIN55212-2可抑制人和小鼠神经节细胞GABA电流幅度,但仅对人的神经节细胞的GABA电流的动力学速度有影响.%Objective To compare the expression of endogenous cannabinoid receptor 1 (CB1) in human and mouse retinal ganglion cells and observe the modulation of CB1 receptor agonist WIN55212-2 to γ-aminobutyric acid (GABA) currents.Methods Immunofluorescence assay was applied to study the expression pattern of CB1 receptors in the retina.Whole-cell patch-clamp technology was used to record GABA currents in the retinal ganglion cells after applying 2 μmol/L WIN55212-2 or 2 μmol/L WIN55212-2 + 4 μmol/L SR141716A (CB1 receptor antagonist).Results CB1 receptors were expressed in the human outer nuclear

  11. Biofuels: A win-win strategy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    This article looks at the overall goal of stabilizing global climate change while achieving a sustainable energy future. On Earth Day 1993, President Clinton announced that the U.S. would comply with the Rio accord and bring U.S. greenhouse gas emissions back to 1990 levels by the year 2000. Since the transportation sector accounts for over 30 percent of domestic CO{sub 2} emissions, the large-scale use and deployment of biofuels would be a useful tool in achieving the Administration`s goals of limiting greenhouse gases. Biofuels such as ethanol, methanol, and biodiesel are expected to have lower emissions of greenhouse gases than those derived from petroleum or other fossil fuels. This marked difference is due to the {open_quotes}CO{sub 2} recycling effect{close_quotes} associated with the growth process of biomass renewable resources such as trees and grasses. This article covers the following topics: global climate change an future energy consumption, reducing greenhouse transportation sector emissions: improving fuel economy and switching to low-carbon emission fuel sources; integration of fuel economy and alternative fuels; biofuels as a transportation strategy for mitigating global climate change; a win-win strategy: biofuels reduce carbon dioxide while promoting sustainable economic growth; increasing biofuels utilization through government and industry cooperation. 5 figs.

  12. Continuous improvement: A win-win process

    International Nuclear Information System (INIS)

    The strategies used within PanCanadian Petroleum Limited's production division to successfully introduce the continuous improvement (CI) process are discussed. Continuous improvement is an operating philosophy and management style which allows all employees to participate in and improve the way an organization performs its day-to-day business. In the CI work environment the supervisor's traditional role changes from one of monitoring and controlling, to one of inspiring, motivating and leading people by communicating a clear vision. Employees at all levels in the work environment are organized into teams and armed with a good working knowledge of the problem-solving tools which allow them to pursue and implement improvement initiatives. The outcome of the process is an ongoing win-win situation for both PanCanadian and its people. Employees are gaining more trust, eliminating job irritants, and enjoying their work in a team environment. The company is benefiting through increased production, improved safety and reduced operating expenses, thanks to the many innovative ideas introduced by employees. 4 refs

  13. Indemnification: Win/lose or win/win

    Energy Technology Data Exchange (ETDEWEB)

    Booth, G.M.

    1996-08-01

    Some of you may be wondering how an oil company employee came to be speaking on indemnity. I`ve been wondering that myself and have even considered the possibility that the conference thought it might be interesting to have a presentation in which the sacrificial lamb is led to the slaughter. I hope that`s not the case. I am not speaking today as a representative of Conoco or as a spokesperson for the operator perspective. I do not intend to tell you what position to take with respect to contractual indemnification. My purpose is to share with you some of my thoughts on indemnification and provide you with some perspective in which to consider your own objectives in structuring indemnities and evaluate whether your current positions meet those objectives. What is contractual indemnification? To some, it is a vehicle by which to transfer all the risk inherent in their operations to another party. Others view it as a means of protecting a deductible or self-insured retention. Some think of it as a bloodbath. There are a few who believe that it is a game in which the only way to win is to ensure the other party loses. The states of Texas and Louisiana believe contractual indemnities are {open_quotes}inequities foisted on certain contractors.{close_quotes} I would like to propose that indemnity can be nothing more than an economic transaction which attempts to allocate risk in a cost effective manner.

  14. 2014 WIN3 Workshop

    CERN Document Server

    Long, Ling; Pries, Rachel; Stange, Katherine

    2016-01-01

    Exploring the interplay between deep theory and intricate computation, this volume is a compilation of research and survey papers in number theory, written by members of the Women In Numbers (WIN) network, principally by the collaborative research groups formed at Women In Numbers 3, a conference at the Banff International Research Station in Banff, Alberta, on April 21-25, 2014. The papers span a wide range of research areas: arithmetic geometry; analytic number theory; algebraic number theory; and applications to coding and cryptography. The WIN conference series began in 2008, with the aim of strengthening the research careers of female number theorists. The series introduced a novel research-mentorship model: women at all career stages, from graduate students to senior members of the community, joined forces to work in focused research groups on cutting-edge projects designed and led by experienced researchers. The goals for Women In Numbers 3 were to establish ambitious new collaborations between women i...

  15. Winning hearts and minds

    International Nuclear Information System (INIS)

    'The greatest problem in communication is the illusion that it has been accomplished' (George Bernard Shaw). Over the past few decades we have seen major shifts in opinion as to what makes a business successful. The 1950's and 1960's saw a production focus whilst the 1970's and 1980's saw progressive change towards quality and 'customer is king' as key business drivers. A popular view now suggests that the next step change will be towards internal marketing, based on the concept that, in the future, winning employee support will be seen as the single biggest contributor to driving business performances. In summary, to win hearts and minds you must understand the needs of your audience, the intent of your communication activity, adopt a suitable style and match your deeds to your words

  16. The Win-Win of Adult Degree Programs

    Science.gov (United States)

    Ellis, J. Richard

    2012-01-01

    Adult degree programs have been seen as a win-win solution for private colleges and adult learners, but their innovative and often-entrepreneurial postures are not a natural fit with governance structures in more traditional institutions. Through narrative and illustrative vignettes, this chapter presents an overview of efforts employed by some…

  17. Win-win Imageries in a Soap Bubble World

    DEFF Research Database (Denmark)

    Ekman, Susanne

    2015-01-01

    This article explores the imagery and notions of personhood underlying the willingness to undertake extreme work among creative knowledge workers. The core argument is that extreme work is informed by pervasive win-win fantasies which can be recognized in a number of current organizational trends...

  18. Win Market by Brand

    Institute of Scientific and Technical Information of China (English)

    FENG Zhende

    2002-01-01

    Brand is symbol of product quality and strength of enterprise. As a typical culture in market economy, it has great influences in everyday life. Famous brands attract purchasing, which prospers enterprise. After China' s entry to WTO, Chinese economy has turned into a new page.As the world manufacturing base, China is to win international market with its own brands. Chunsheng Refractory Ltd., which specialized in quality silica bricks, has grown in size and strength. And our experiences proved how important the brand is for an enterprise.

  19. Cannabinoids inhibit ATP-activated currents in rat trigeminal ganglionic neuroas%大麻素抑制大鼠三叉神经节神经元ATP激活电流

    Institute of Scientific and Technical Information of China (English)

    申晶晶; 刘长金; 李爱; 胡新武; 陆永利; 陈蕾; 周莹; 刘烈炬

    2007-01-01

    本文在培养的大鼠三叉神经节(trigeminal ganglion,TG)神经元上采用全细胞膜片钳技术,探讨大麻素对大鼠TG神经元ATP激活电流(ATP-activated currents,IATP)的影响.结果显示:(1)胞外给予ATP,大部分受检细胞(67/75,89.33%)可记录到一个内向电流,且具有剂量依赖性.该电流可被P2X嘌呤受体特异性拮抗剂PPADS所阻断.(2)预加WIN55212-2[大麻素受体1(cannabinoid receptor 1,CB1受体)激动剂]可对IATP产生抑制作用,此作用呈剂量依赖性,并可被CB1受体特异性拮抗剂AM281阻断.预加不同浓度的WIN55212-2(1x10-13、1x10-12、1x10-11、1x10-10、1x10-9和1x10-8mol/L)对IATP(1x10-4mol/L ATP)的抑制作用分别为(8.14±3.14)%、(20.11±2.72)%、(46.62±3.51)%、(72.16±5.64)%、(80.21±2.80)%和(80.59±3.55)%.(3)预加WIN55212-2后IATP的浓度-反应曲线明显下移;最大反应浓度时的IATP幅值减小了(58.02±4.21)%,而阈值基本不变;预加WIN55212.2前后曲线的EC50值非常接近(1.15x10-4mol/L vs 1.27x10-4 mol/L).(4)预加forskolin[腺苷酸环化酶(adenylyl cyclase,AC)激动剂]或8-Br-cAMP可以逆转WIN55212-2对IATP的抑制作用.以上结果表明,大麻素可能作用于CB1受体,通过抑制AC-cAMP-PKA途径发挥对IATP的抑制作用.%The present study aimed to investigate whether cannabinoids could modulate the response mediated by ATP receptor (P2X purinoceptor).Whole-cell patch-clamp recording was performed on cultured rat trigeminal ganglionic (TG)neurons.The majority of TG neurons were sensitive to ATP(67/75,89.33%).Extracellular pretreatment with WIN55212-2,a cannabinoid receptor 1(CB1 receptor)agonist,reduced ATP-activated current(IATP)significantly.This inhibitory effect was concentration-dependent and was blocked by AM281,a specific CB1 receptor antagonist.Pretreatment with WIN55212-2 at 1x10-13,1x10-12,1x10-11,1x10-10,1×10-9 and 1x10-8mol/L reduced IATP(induced by 1x10-4mol/L ATP)by(8.14±3.14)%,(20.11±2.72)%,(46.62±3.51)%,(72.16±5

  20. Who Will Win the Game?

    Institute of Scientific and Technical Information of China (English)

    一维

    2007-01-01

    <正>Peter:Do you think Brazil will win? Paul:Could be.Peter:I bet you that Brazil will win the game. Paul:Don’t be so sure.Italy is also one of the best teams in Europe.Peter:But Brazil had won five World Cup Champions.Paul:Things are changing! Peter:It’s

  1. WIN Belarus report 2007

    Energy Technology Data Exchange (ETDEWEB)

    Vastchenko, Svetlana [Institute of Power and Nuclear Research, Sosny (Belarus)

    2008-07-01

    national WIN: WIN Belarus was established in December 1998 and at present has 17 members. Highlights of the last year and trends in Belarus: There are some problems with the natural gas supply in Belarus from Russia. Energy policy directed to use the local fuel resources and energy saving, but these resources can not provide for Belarus energy demand. Therefore made a decision of NPP construction. At present the NPP site is selected. WIN activities: Collection and analysis of articles in newspapers and journals on energy problems in Belarus and construction of nuclear power plant in our republic. Publication and distribution of newsletters on nuclear problems for public information and authorities, which are available for the press too. We took part in debates with environmental and other opponents on the ecological, economical and safety problems of nuclear technology. We published articles about nuclear energy (safety problems, environment and climate). Female communication: Collaboration with women organizations in Belarus (Women Alliance, Women group in physics and others). Future plans and goals for WIN: Participation in several international conferences and seminars. Publication and distribution of newsletters on nuclear problems for public information and authorities, which are available for the press too. Collection and analysis of articles in newspapers and journals on energy problems in Belarus and construction of nuclear power plant in our republic. Publication articles in newspapers and 'Industrial Safety' journal about using nuclear technology and radiation and power problems. Investigation problems of radioactive waste handling. Preparation trainings for journalists and public organizations on radiation problems, nuclear power and on un-traditional renewed sources of energy. We shall continue debates with opponents on the ecological, economical and safety problems of NPP. Collaboration with women and ecological organizations in Belarus (Women

  2. Country Report WIN Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shin [Atomic Energy Council, 6F, No 80, Sec 1, Cheng-Gong Road, Yonghe City, 23452 Taipei, Taiwan (China)

    2008-07-01

    assessment for Chinshan NPP, nuclear power up-rate for existing NPPs, NPP license renewal related studies, development of D and D technology, development of fuel cells and solar and wind power generation systems, and development and commercialization of radiopharmaceuticals. Among major nuclear regulatory activities during the past year include: establishment of a nuclear knowledge management web site, completion of review for power up-rate for Kuosheng NPP, oversight of the installation of automatic scram systems at NPPs during strong earthquakes, advancement of the electronically oriented radiation protection control operations, strengthening of safety controls of high-risk radiation sources, development of a mammography quality control program, and review and conditional approval of the preliminary safety analysis report (PSAR) of the construction license application for the spent nuclear fuel dry storage facility at the Chinshan NPP. C - WIN Taiwan: Founded in 1994, WIN Taiwan now has 110 national members and 33 global members. 2007-2008 Activities and Achievements: 15. WIN Global Annual Meeting held (21-27 April 2007, Bali, Indonesia); Science Excursions at TPC's Northern Visitors Center and at radwaste volume reduction center (12 July 2007); WIN-Taiwan and ANS Taiwan Joint Annual Meeting at the National Tsing Hua University's newly re-established Institute of Nuclear Engineering and Science (9 August 2007); workshop on 'understanding radiation and radioactive waste' (28 September 2007), Fall Seminar (7 December 2007), Steering and Advisory Committee Meetings (1 June and 1 November 2006, 11 January and 18 March, 2008)

  3. FairWinWin: Approach for fair win-win requirements negotiation%FairWinWin:以公平共赢为目标的需求协商方法

    Institute of Scientific and Technical Information of China (English)

    赵玉柱; 李娟

    2009-01-01

    公平分配是协商理论中选择共赢协议的基本原则.基于最小潜在价值比例最大化公平分配方法和经典的WinWin需求协商过程,提出一种以公平共赢为目标的需求协商方法FairWinWin.该方法包括一个实现公平共赢的需求协商过程和一个选择帕累托最优共赢需求协议的算法.通过一个案例对FairWinWin方法进行验证,实验结果表明,FairWinWin方法可以有效促进涉众对共赢决策的理解,帮助涉众得到帕累托最优的共赢需求协议.%In the negotiation theory, fair division is a basic principle for selecting the win-win contract. Based on the Maximin POP fair division approach and the classical WinWin requirements negotiation process, an approach named FairWinWin is presented. The goal of the approach is to help stakeholders get the Pareto optimal fair win-win outcome in the requirements negotiation process. The ap-proach is applied in a case study. The ease shows that FairWinWin can effectively facilitate stakeholders' understanding of the win-win decisions, and help stakeholders get the Pareto optimal win-win requirements contract.

  4. Win-Win transportation solutions price reforms with multiple benefits

    International Nuclear Information System (INIS)

    Reform strategies in the transportation market, such as the Win-Win Transportation Solutions, can provide several economic, social and environmental benefits. The strategies are cost effective, technically feasible reforms based on market principles which help create a more equitable and efficient transportation system that supports sustainable economic development. The benefits they provide include reduced traffic congestion, road and parking facility savings, consumer savings, equity, safety and environmental protection. They also increase economic productivity. If fully implemented, they could reduce motor vehicle impacts by 15 to 30 per cent and could help achieve the Kyoto emission reduction targets. Examples of Win-Win strategies at the federal level include: (1) removal of subsidies to oil production and internalized costs, and (2) tax exempt employer provided transfer benefits. Examples of Win-Win strategies at the state/provincial level include: (1) distance-based vehicle insurance and registration fees, (2) least-coast transportation planning and funding, (3) revenue-neutral tax shifting, (4) road pricing, (5) reform motor carrier regulations for competition and efficiency, (6) local and regional transportation demand management programs, (7) more efficient land use, (8) more flexible zoning requirements, (9) parking cash out, (10) transportation management associations, (11) location-efficient housing and mortgages, (12) school and campus trip management, (13) car sharing, (14) non-motorized transport improvements, and (15) traffic calming. It was noted that any market reform that leads to more efficient use of existing transportation systems can provide better economic development benefits. 9 refs., 1 tab., 1 fig

  5. Win-Win transportation solutions price reforms with multiple benefits

    Energy Technology Data Exchange (ETDEWEB)

    Litman, T. [Victoria Transport Policy Institute, BC (Canada)

    2001-07-01

    Reform strategies in the transportation market, such as the Win-Win Transportation Solutions, can provide several economic, social and environmental benefits. The strategies are cost effective, technically feasible reforms based on market principles which help create a more equitable and efficient transportation system that supports sustainable economic development. The benefits they provide include reduced traffic congestion, road and parking facility savings, consumer savings, equity, safety and environmental protection. They also increase economic productivity. If fully implemented, they could reduce motor vehicle impacts by 15 to 30 per cent and could help achieve the Kyoto emission reduction targets. Examples of Win-Win strategies at the federal level include: (1) removal of subsidies to oil production and internalized costs, and (2) tax exempt employer provided transfer benefits. Examples of Win-Win strategies at the state/provincial level include: (1) distance-based vehicle insurance and registration fees, (2) least-coast transportation planning and funding, (3) revenue-neutral tax shifting, (4) road pricing, (5) reform motor carrier regulations for competition and efficiency, (6) local and regional transportation demand management programs, (7) more efficient land use, (8) more flexible zoning requirements, (9) parking cash out, (10) transportation management associations, (11) location-efficient housing and mortgages, (12) school and campus trip management, (13) car sharing, (14) non-motorized transport improvements, and (15) traffic calming. It was noted that any market reform that leads to more efficient use of existing transportation systems can provide better economic development benefits. 9 refs., 1 tab., 1 fig.

  6. QIN Dahe wins IMO prize

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Prof.QIN Dahe,a glaciologist and climatologist from the CAS Cold and Arid Regions Environmental and Engineering Research,has been elected to win the prestigious Prize of the International Meteorology Organization (IMO) in 2008.

  7. In the winning mood

    Directory of Open Access Journals (Sweden)

    Marieke de Vries

    2008-01-01

    Full Text Available The present research aimed to test the role of mood in the Iowa Gambling Task (IGT; Bechara et al., 1994. In the IGT, participants can win or lose money by picking cards from four different decks. They have to learn by experience that two decks are overall advantageous and two decks are overall disadvantageous. Previous studies have shown that at an early stage in this card-game, players begin to display a tendency towards the advantageous decks. Subsequent research suggested that at this stage, people base their decisions on conscious gut feelings (Wagar and Dixon, 2006. Based on empirical evidence for the relation between mood and cognitive processing-styles, we expected and consistently found that, compared to a negative mood state, reported and induced positive mood states increased this early tendency towards advantageous decks. Our results provide support for the idea that a positive mood causes stronger reliance on affective signals in decision-making than a negative mood.

  8. The combined inhibitory effect of the adenosine A1 and cannabinoid CB1 receptors on cAMP accumulation in the hippocampus is additive and independent of A1 receptor desensitization.

    Science.gov (United States)

    Serpa, André; Correia, Sara; Ribeiro, Joaquim A; Sebastião, Ana M; Cascalheira, José F

    2015-01-01

    Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3-30 μM) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6±2.7 μM and an Emax of 31%±2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10-150 nM), an EC50 of 35±19 nM, and an Emax of 29%±5 were obtained. The combined inhibitory effect of WIN55212-2 (30 μM) and CPA (100 nM) on cAMP accumulation was 41%±6% (n=4), which did not differ (P>0.7) from the sum of the individual effects of each agonist (43%±8%) but was different (PCB1 and A1 receptors on cAMP formation is additive and CB1 receptor activity is not affected by short-term A1 receptor desensitization.

  9. Creating a winning organizational culture.

    Science.gov (United States)

    Campbell, Robert James

    2009-01-01

    This article explores the idea of how to create a winning organizational culture. By definition, a winning organizational culture is one that is able to make current innovations stick, while continuously changing based on the demands of the marketplace. More importantly, the article explores the notion that a winning organizational culture can have a profound impact on the conscious of the workforce, helping each individual to become a better, more productive person, who provides important services and products to the community. To form a basis toward defining the structure of what a winning organization culture looks like, 4 experts were asked 12 questions related to the development of an organizational culture. Three of the experts have worked intimately within the health care industry, while a fourth has been charged with turning around an organization that has had a losing culture for 17 years. The article provides insight into the role that values, norms, goals, leadership style, familiarity, and hiring practices play in developing a winning organizational culture. The article also emphasizes the important role that leaders perform in developing an organizational culture.

  10. Eastern countries - WIN activity review

    International Nuclear Information System (INIS)

    Women can play this important role in informing people about nuclear energy. WIN is a world-wide association of women working professionally in the fields of nuclear energy and radiation application who want to devote their time to public information. The main goal of the WIN is to establish an objective and effective communication with the public through educational programmes, information exchange and arranging study visits. The membership includes women working in medicine and health care, in regulatory authorities, in industry and as independent researches at Universities. They want to contribute to objectively informing the public by making presentation, discussing and giving information materials on subjects such as; radiation, radioactivity and health effects medical applications nuclear energy nuclear power plants and their safety nuclear and environment uranium mining radiation protection energy sustainable development WIN is also open to men, supporting the goals of WIN. The intention of this paper was to underline the main aspects which reflect WIN activity in some Eastern and Central countries. There are common features and also specific elements for each country. But the goal is the same: to assure an effective and a real information of the public related to the nuclear field

  11. Win at Work! The Everybody Wins Approach to Conflict Resolution

    CERN Document Server

    Katz, Diane

    2010-01-01

    Proven techniques for resolving workplace conflicts. After years of seeing clients struggling and their businesses suffering with destructive conflicts, Diane Katz developed The Working Circle, a step-by-step process that helps everyone in business resolve conflict in a non-confrontational, creative, collaborative way. Win at Work! provides you with a no-nonsense guide based on real-life examples of people at pivotal points in their careers. Filled with practical wisdom, it reveals how you can move around the roadblocks that, if left unattanded, can stop you in your tracks. Win at Work! also h

  12. Winning Faces Vary By Ideology

    DEFF Research Database (Denmark)

    Laustsen, Lasse; Petersen, Michael Bang

    2016-01-01

    for others. Utilizing research on ideological stereotypes and the determinants of facial preferences, we focus on the relationship between the facial dominance of the source and the ideology of the receiver. Across five studies, we demonstrate that a dominant face is a winning face when the audience...... is conservative but backfires and decreases success when the audience is liberal. On the other hand, a non-dominant face constitutes a winning face among liberal audiences but backfires among conservatives. These effects seemingly stem from deep-seated psychological responses and shape both the election...

  13. Customers and markets. International components for win-win relations; Kunden und Maerkte. Internationale Bausteine fuer Win-Win-Relationen

    Energy Technology Data Exchange (ETDEWEB)

    Lamprecht, F.

    1998-09-01

    In deregulated energy markets, power supply companies change from commodity suppliers to service providers. The core of the process of change is a change in attitude, from producer to customer-oriented marketer; the means applied in the process are a diversified and integrated marketing strategy, targeting both external and internal conditions, which fits into a comprehensive concept of an integrated communications strategy. An international conference held in mid-June in Lisbon, organised by the associations Unipede and EURELECTRIC as well as the International Energy Agency (IEA), supplied a wealth of information on this topical issue spanning a broad range of interesting aspects, as eg. approaches to identify customer needs and correspondingly develop new services, or the quest for new business segments and possibilities of finding win-win relations for both customers and power producers. (orig./CB) [Deutsch] Auf liberalisierten Strommaerkten entwickeln sich die Energieversorger zu Dienstleistern. Kern des Wandels ist der Weg von der Produktions- zur Kundenorientierung, Mittel eine differenzierte und integrierte Marketingstrategie, die nach aussen wie nach innen gerichtet ist und in ein umfassendes Konzept einer integrierten Kommunikationsstrategie eingepasst ist. Eine von den Verbaenden Unipede und EURELECTRIC sowie der Internationalen Energie-Agentur (IEA) Mitte Juni in Lissabon ausgerichtete internationale Konferenz lieferte hierzu eine Fuelle an Material. Es wurde thematisch ein weiter Bogen gespannt. Von der Ermittlung unterschiedlicher Kundenbeduerfnisse ueber Methoden, sich danach auszurichten sowie speziell entwickelte Marketingstrategien, bis hin zu neuen Betaetigungsfeldern wurde nach Moeglichkeiten gesucht, Win-Win-Relationen fuer Kunden und EVU darzustellen. (orig.)

  14. Do quantum strategies always win?

    Science.gov (United States)

    Anand, Namit; Benjamin, Colin

    2015-11-01

    In a seminal paper, Meyer (Phys Rev Lett 82:1052, 1999) described the advantages of quantum game theory by looking at the classical penny flip game. A player using a quantum strategy can win against a classical player almost 100 % of the time. Here we make a slight modification to the quantum game, with the two players sharing an entangled state to begin with. We then analyze two different scenarios: First in which quantum player makes unitary transformations to his qubit, while the classical player uses a pure strategy of either flipping or not flipping the state of his qubit. In this case, the quantum player always wins against the classical player. In the second scenario, we have the quantum player making similar unitary transformations, while the classical player makes use of a mixed strategy wherein he either flips or not with some probability " p." We show that in the second scenario, 100 % win record of a quantum player is drastically reduced and for a particular probability " p" the classical player can even win against the quantum player. This is of possible relevance to the field of quantum computation as we show that in this quantum game of preserving versus destroying entanglement a particular classical algorithm can beat the quantum algorithm.

  15. Winning fights induces hyperaggression via the action of the biogenic amine octopamine in crickets.

    Directory of Open Access Journals (Sweden)

    Jan Rillich

    Full Text Available Winning an agonistic interaction against a conspecific is known to heighten aggressiveness, but the underlying events and mechanism are poorly understood. We quantified the effect of experiencing successive wins on aggression in adult male crickets (Gryllus bimaculatus by staging knockout tournaments and investigated its dependence on biogenic amines by treatment with amine receptor antagonists. For an inter-fight interval of 5 min, fights between winners escalated to higher levels of aggression and lasted significantly longer than the preceding round. This winner effect is transient, and no longer evident for an inter-fight interval of 20 min, indicating that it does not result from selecting individuals that were hyper-aggressive from the outset. A winner effect was also evident in crickets that experienced wins without physical exertion, or that engaged in fights that were interrupted before a win was experienced. Finally, the winner effect was abolished by prior treatment with epinastine, a highly selective octopamine receptor blocker, but not by propranolol, a ß-adrenergic receptor antagonist, nor by yohimbine, an insect tyramine receptor blocker nor by fluphenazine an insect dopamine-receptor blocker. Taken together our study in the cricket indicates that the physical exertion of fighting, together with some rewarding aspect of the actual winning experience, leads to a transient increase in aggressive motivation via activation of the octopaminergic system, the invertebrate equivalent to the adrenergic system of vertebrates.

  16. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart;

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...

  17. Does a win bonus help to increase profit or wins in professional team sports?

    OpenAIRE

    Késenne, Stefan

    2007-01-01

    In a sports league, team owners can expect to increase player performance, and the team’s winning percentage or profits, by providing a win bonus on top of the players’ fixed salary level. In some clubs, the guaranteed player salary is relatively low and the premium, in case of a winning game, relatively high, whereas in other clubs, hardly any win bonus is paid. In this theoretical paper, we investigate what the impact of a win bonus is on the winning percentage, the competitive balance, the...

  18. The Methods Behind PH WINS.

    Science.gov (United States)

    Leider, Jonathon P; Bharthapudi, Kiran; Pineau, Vicki; Liu, Lin; Harper, Elizabeth

    2015-01-01

    The Public Health Workforce Interests and Needs Survey (PH WINS) has yielded the first-ever nationally representative sample of state health agency central office employees. The survey represents a step forward in rigorous, systematic data collection to inform the public health workforce development agenda in the United States. PH WINS is a Web-based survey and was developed with guidance from a panel of public health workforce experts including practitioners and researchers. It draws heavily from existing and validated items and focuses on 4 main areas: workforce perceptions about training needs, workplace environment and job satisfaction, perceptions about national trends, and demographics. This article outlines the conceptualization, development, and implementation of PH WINS, as well as considerations and limitations. It also describes the creation of 2 new data sets that will be available in public use for public health officials and researchers--a nationally representative data set for permanently employed state health agency central office employees comprising over 10,000 responses, and a pilot data set with approximately 12,000 local and regional health department staff responses. PMID:26422490

  19. Discussion of "Win-Win concession period determination methodology" by Xueqing Zhang

    OpenAIRE

    Wu, M; Chau, KW; Shen, QP

    2011-01-01

    'Win-win concession period determination methodology' By: Zhang, Xueqing. Journal of Construction Engineering & Management, Jun2009, Vol. 135 Issue 6, p550-558, 9 p; DOI: 10.1061/(ASCE)CO.1943-7862.0000012; (AN 39786304)

  20. 26 CFR 1.50B-1 - Definitions of WIN expenses and WIN employees.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Definitions of WIN expenses and WIN employees. 1.50B-1 Section 1.50B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Rules for Computing Credit for Expenses of Work Incentive Programs § 1.50B-1 Definitions of WIN expenses and WIN employees. (a)...

  1. Winning margins in British Thoroughbred Racehorses

    OpenAIRE

    Allen, Kate; Procter, Tessa

    2016-01-01

    In human sporting events the difference between finishing first and second is often less than 1%. For each sporting discipline it is important to know how large an enhancement of performance needs to be before it makes a difference to the medal winning prospects of that athlete. In contrast to the known winning margins in many human sporting disciplines, the winning margins in horse racing are unknown. The winning margins for Group 1, 2 and 3 flat and national hunt races over a 5 year period ...

  2. Opportunistic Cognitive Relaying: A Win-Win Spectrum Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Luo Haiyan

    2010-01-01

    Full Text Available A cost-effective spectrum sharing architecture is proposed to enable the legacy noncognitive secondary system to coexist with the primary system. Specifically, we suggest to install a few intermediate nodes, namely, the cognitive relays, to conduct the spectrum sensing and coordinate the spectrum access. To achieve the goal of win-win between primary and secondary systems, the cognitive relay may act as a cooperator for both of them, and an Opportunistic Cognitive Relaying (OCR scheme is specially devised. In this scheme, the cognitive relay opportunistically switches among three different working modes, that is, Relay for Primary Link (RPL, Relay for Secondary Link (RSL, or Relay for Neither of the Links (RNL, respectively, based on the channel-dependent observation of both systems. In addition, the transmit power for cognitive relay and secondary transmitter in each mode are optimally determined by maximizing the transmission rate of secondary system while keeping or even reducing the outage probability of primary system. Simulation results validate the efficiency of the proposed spectrum sharing scheme.

  3. Ways to Win at Vocabulary Learning

    Science.gov (United States)

    Goodwin, Amanda P.; Cho, Sun-Joo; Nichols, Sally

    2016-01-01

    This teaching tip identifies ways to "WIN" at vocabulary learning. Specifically, the approach conveys three morphological strategies in the mnemonic "WIN." These three strategies remind students to find smaller units of meaning within bigger words, look for those units in other words that they know, and notice the context. Each…

  4. Bayesian modeling using WinBUGS

    CERN Document Server

    Ntzoufras, Ioannis

    2009-01-01

    A hands-on introduction to the principles of Bayesian modeling using WinBUGS Bayesian Modeling Using WinBUGS provides an easily accessible introduction to the use of WinBUGS programming techniques in a variety of Bayesian modeling settings. The author provides an accessible treatment of the topic, offering readers a smooth introduction to the principles of Bayesian modeling with detailed guidance on the practical implementation of key principles. The book begins with a basic introduction to Bayesian inference and the WinBUGS software and goes on to cover key topics, including: Markov Chain Monte Carlo algorithms in Bayesian inference Generalized linear models Bayesian hierarchical models Predictive distribution and model checking Bayesian model and variable evaluation Computational notes and screen captures illustrate the use of both WinBUGS as well as R software to apply the discussed techniques. Exercises at the end of each chapter allow readers to test their understanding of the presented concepts and all ...

  5. A natural history of "agonist".

    Science.gov (United States)

    Russo, Ruth

    2002-01-01

    This paper constructs a brief history of the biochemical term agonist by exploring the multiple meanings of the root agôn in ancient Greek literature and describing how agonist first appeared in the scientific literature of the 20th century in the context of neurophysiologists' debates about the existence and properties of cellular receptors. While the narrow scientific definition of agonist may appear colorless and dead when compared with the web of allusions spun by the ancient Greek agôn, the scientific power and creativity of agonist actually resides precisely in its exact, restricted meaning for biomedical researchers.

  6. Winning strategies in congested traffic

    CERN Document Server

    Jarai-Szabo, Ferenc

    2012-01-01

    One-directional traffic on two-lanes is modeled in the framework of a spring-block type model. A fraction $q$ of the cars are allowed to change lanes, following simple dynamical rules, while the other cars keep their initial lane. The advance of cars, starting from equivalent positions and following the two driving strategies is studied and compared. As a function of the parameter $q$ the winning probability and the average gain in the advancement for the lane-changing strategy is computed. An interesting phase-transition like behavior is revealed and conclusions are drawn regarding the conditions when the lane changing strategy is the better option for the drivers.

  7. Dopaminergic agonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

  8. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists...... presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development. Areas covered: The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide and...... liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...

  9. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    Introduction: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists...... presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development. Areas covered: The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide...... and liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...

  10. Who will win the Nobel Prize?

    OpenAIRE

    Terence tai-leung Chong; Cally Choi; Benjamin Everard

    2009-01-01

    This paper identifies the determinants of the Nobel Prize Award. The analysis is analogous in spirit to Hamermesh and Schmidt (Econometrica, 2003) on the election of Econometric Society fellows. It is found that the number of citations, age and nationality have significant impacts on the odds of winning the Nobel. We provide the first statistical evidence that John Bates Clark medalists and individuals affiliated with the University of Chicago have a higher chance of winning the Prize.

  11. Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy.

    Science.gov (United States)

    Carletti, Fabio; Gambino, Giuditta; Rizzo, Valerio; Ferraro, Giuseppe; Sardo, Pierangelo

    2016-05-01

    The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our results showed that the TRPV1 agonist, capsaicin, increased epileptic outcomes; whilst antagonizing TRPV1 with capsazepine exerts a protective role on paroxysmal discharge. When capsaicin is co-administered with WIN effective dose of 10mg/kg is able to reduce its antiepileptic strength, especially on the triggering of MDA response. Accordingly, capsazepine at the protective dose of 2mg/kg managed to potentiate WIN antiepileptic effects, when co-treated. Moreover, WIN subeffective dose of 5mg/kg was turned into effective when capsazepine comes into play. This evidence suggests that systemic administration of TRPV1-active drugs influences electrically induced epilepsy, with a noticeable protective activity for capsazepine. Furthermore, results from the pharmacological interaction with WIN support an interplay between cannabinoid and TRPV1 signaling that could represent a promising approach for a future pharmacological strategy to challenge hyperexcitability-based diseases.

  12. A Win-Win-Win Proposition -- Academia and Industry Working Together for Students

    Science.gov (United States)

    Cogswell, J.

    2011-12-01

    geoscience, to include having applied real problem solving via a robust field camp experience. In addition, we look for the maturity and ability to conduct independent research, to integrate broad suites of data, and to work as a team. We look for the ability to communicate results. We do not look for a focus on petroleum. We have many decades of experience in how to best develop that particular discipline quickly, to meet current and future business conditions. There are recurring themes that facilitate successful transition from Academia to a practicing industry geoscientist. These themes include giving students a good grounding in STEM, not just geology; one-on-one mentoring; sharing our passion for the science by sharing our research; and sharing the entire breadth of career opportunities. Similar best practices have been identified to encourage under-represented minority students and women to study STEM. Perhaps this is a suite of habits we should be practicing more broadly. This suite of habits takes extra time, extra effort, and extra money. But if geoscience mentors in Academia, Industry, and professional societies work together, we will be able to create a win for Academia, a win for Industry, and a win for students. (1) Gonzales and Keane, 2011, "Status of the Geoscience Workforce -- 2011," AGI, p. 123.

  13. The effects of win-win conditions on revenue-sharing contracts

    NARCIS (Netherlands)

    Timmer, J.B.

    2004-01-01

    This paper studies revenue-sharing contracts in distribution chains in the presence of win-win conditions. Revenue-sharing contracts are a mechanism to coordinate the firms in a distribution chain. Under these contracts the retailer shares its revenue with the supplier in exchange for a lower wholes

  14. Challenging the win-win discourse on conservation and development: analyzing support for marine protected areas

    Directory of Open Access Journals (Sweden)

    Tomas Chaigneau

    2016-03-01

    Full Text Available Conservation designations such as protected areas are increasing in numbers around the world, yet it is widely reported that many are failing to reach their objectives. They are frequently promoted as opportunities for win-win outcomes that can both protect biodiversity and lead to economic benefits for affected communities. This win-win view characterizes the dominant discourse surrounding many protected areas. Although this discourse and the arguments derived from it may lead to initial acceptance of conservation interventions, this study shows how it does not necessarily result in compliance and positive attitudes toward specific protected areas. Consequently, the discourse has important implications not just for making the case for protected area implementation, but also for the likelihood of protected areas reaching their objectives. We explain how the win-win discourse influences support for marine protected areas (MPAs and, ultimately, their success. Using data from focus groups, questionnaires, and in-depth interviews at three MPA sites in the Philippines, we identified three reasons why the win-win discourse can negatively influence prolonged support for MPAs: dashed expectations, inequity, and temptation. Through an understanding of these issues, it becomes possible to suggest improvements that can be made pre-MPA implementation that can lead to prolonged support of MPAs. A focus on less tangible and economic MPA benefits, aligning MPA goals with cultural and social values, and higher levels of transparency when describing MPA outcomes are all ways in which prolonged support of MPAs can be bolstered.

  15. Teaching Win-Win Better Prepares Students for Subsequent Experiences in Life.

    Science.gov (United States)

    Brainard, Alan J.

    The psychology of competition and winning, especially in relation to learning and motivation, is discussed. The Personalized System of Instruction (PSI) approach to coursework is proposed as a means of using the winning philosophy in education. Also suggested is the inclusion into coursework design of a form of rhetoric developed by Carl Rogers…

  16. The secreted protein acidic and rich in cysteine is a critical mediator of cell death program induced by WIN/TRAIL combined treatment in osteosarcoma cells.

    Science.gov (United States)

    Notaro, Antonietta; Sabella, Selenia; Pellerito, Ornella; Vento, Renza; Calvaruso, Giuseppe; Giuliano, Michela

    2016-03-01

    Secreted protein acidic and rich in cysteine (SPARC) is a multi-functional protein which modulates cell-cell and cell-matrix interactions. In cancer cells, SPARC behaves as a tumor promoter in a number of tumors, but it can also act as a tumor suppressor factor. Our previous results showed that the synthetic cannabinoid WIN55,212-2 (WIN), a potent cannabinoid receptor agonist, is able to sensitize osteosarcoma MG63 cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis which is accompanied with endoplasmic reticulum (ER)-stress induction and the increase in autophagic markers. In the present investigation, we studied the role of SPARC in WIN/TRAIL-induced apoptosis demonstrating that WIN increased the level of SPARC protein and mRNA in a time-dependent manner. This event was functional to WIN/TRAIL-dependent apoptosis as demonstrated by RNA interfering analysis which indicated that SPARC-silenced cells were less sensitive to cytotoxic effects induced by the combined treatment. Our experiments also demonstrate that SPARC interacts with caspase-8 thus probably favoring its translocation to plasma membrane and the activation of extrinsic apoptotic pathway. In conclusion, to the best of our knowledge, our results are the first to show that WIN-dependent increase in the level of SPARC plays a critical role in sensitizing osteosarcoma cells to TRAIL action.

  17. Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors.

    Directory of Open Access Journals (Sweden)

    Svantje Tauber

    Full Text Available The cannabinoid system is known to be involved in the regulation of inflammatory processes. Therefore, drugs targeting cannabinoid receptors are considered as candidates for anti-inflammatory and tissue protective therapy. We demonstrated that the prototypical cannabinoid agonist R(+WIN55,212-2 (WIN reduced the secretion of matrix metalloproteinase-9 (MMP-9 in a murine model of cigarette-smoke induced lung inflammation. In experiments using primary cells and cell lines of the monocyte-macrophage-system we found that binding of the cannabinoid-receptor agonist WIN to a stereo-selective, specific binding site in cells of the monocyte-macrophage-system induced a significant down-regulation of MMP-9 secretion and disturbance of intracellular processing, which subsequently down-regulated MMP-9 mRNA expression via a ERK1/2-phosphorylation-dependent pathway. Surprisingly, the anti-inflammatory effect was independent from classical cannabinoid receptors. Our experiments supposed an involvement of TRPV1, but other yet unidentified sites are also possible. We conclude that cannabinoid-induced control of MMP-9 in the monocyte-macrophage system via a cannabinoid-receptor independent pathway represents a general option for tissue protection during inflammation, such as during lung inflammation and other diseases associated with inflammatory tissue damage.

  18. Selective lack of tolerance to delayed gastric emptying after daily administration of WIN 55,212-2 in the rat.

    Science.gov (United States)

    Abalo, R; Cabezos, P A; López-Miranda, V; Vera, G; González, C; Castillo, M; Fernández-Pujol, R; Martín, M I

    2009-09-01

    The use of cannabinoids to treat gastrointestinal (GI) motor disorders has considerable potential. However, it is not clear if tolerance to their actions develops peripherally, as it does centrally. The aim of this study was to examine the chronic effects of the cannabinoid agonist WIN 55,212-2 (WIN) on GI motility, as well as those in the central nervous and cardiovascular systems. WIN was administered for 14 days, at either non-psychoactive or psychoactive doses. Cardiovascular parameters were measured in anaesthetized rats, whereas central effects and alterations in GI motor function were assessed in conscious animals using the cannabinoid tetrad and non-invasive radiographic methods, respectively. Tests were performed after first (acute effects) and last (chronic effects) administration of WIN, and 1 week after discontinuing treatment (residual effects). Food intake and body weight were also recorded throughout treatment. Blood pressure and heart rate remained unchanged after acute or chronic administration of WIN. Central activity and GI motility were acutely depressed at psychoactive doses, whereas non-psychoactive doses only slightly reduced intestinal transit. Most effects were reduced after the last administration. However, delayed gastric emptying was not and could, at least partially, account for a concomitant reduction in food intake and body weight gain. The remaining effects of WIN administration in GI motility were blocked by the CB1 antagonist AM 251, which slightly accelerated motility when administered alone. No residual effects were found 1 week after discontinuing cannabinoid treatment. The different systems show differential sensitivity to cannabinoids and tolerance developed at different rates, with delayed gastric emptying being particularly resistant to attenuation upon chronic treatment. PMID:19413685

  19. WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Jing SUN; Yin-quan FANG; Hong REN; Tao CHEN; Jing-jing GUO; Jun YAN; Shu SONG; Lu-yong ZHANG; Hong LIAO

    2013-01-01

    Aim:To explore whether the synthetic cannabinoid receptor agonist WIN55,212-2 could protect oligodendrocyte precursor cells (OPCs)in stroke penumbra,thereby providing neuroprotection following permanent focal cerebral ischemia in rats.Methods:Adult male SD rats were subjected to permanent middle cerebral artery occlusion (p-MCAO).The animals were administered WIN55,212-2 at 2 h,and sacrificed at 24 h after the ischemic insult.The infarct volumes and brain swelling were assessed.The expression of cannabinoid receptor type 1 (CB1) in the stroke penumbra was examined using Western blot assay.The pathological changes and proliferation of neural glial antigen 2-positive OPCs (NG2+ cells) in the stroke penumbra were studied using immunohistochemistry staining.Results:p-MCAO significantly increased the expression of CB1 within the stroke penumbra with the highest level appearing at 2 h following the ischemic insult.Administration of WIN55,212-2 (9 mg/kg,iv) significantly attenuated the brain swelling,and reduced the infarct volume as well as the number of tau-immunoreactive NG2+ cells (tau-1+/NG2+ cells) in the stroke penumbra.Moreover,WIN55,212-2 significantly promoted the proliferation of NG2+ cells in the stroke penumbra and in the ipsilateral subventricular zone at 24 h following the ischemic insult.Administration of the selective CB1 antagonist rimonabant (1 mg/kg,iv) partially blocked the effects caused by WIN55,212-2.Conclusion:Tau-1 is expressed in NG2+ cells following permanent focal cerebral ischemic injury.Treatment with WIN55,212-2 reduces the number of tau-1+/NG2+ cells and promotes NG2+ cell proliferation in the stroke penumbra,which are mediated partially via CB1 and may contribute to its neuroprotective effects.

  20. The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats

    NARCIS (Netherlands)

    Suleymanova, E.M.; Shangaraeva, V.A.; Rijn, C.M. van; Vinogradova, L.V.

    2016-01-01

    An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acu

  1. FTW (For the Win / Fuck the World)

    OpenAIRE

    Summers, Francis; Minkin, Louisa

    2012-01-01

    Participation in the group exhibition curated by Bernice Donszelmann, Tim Renshaw and Mary McLean. Exhibited the work FTW (For the Win / Fuck the World) made in collaboration with Louisa Minkin. Here we use the format of the triumphal procession to pose questions around the twinned states of glory and nihilism. FTW! (For The Win / Fuck The World) is a banner that combines a letter to a generic addressee alongside a selection of internet memes, rage comic figures and images of disaster and cel...

  2. Examining How Manufacturing Corporations Win Orders

    Directory of Open Access Journals (Sweden)

    Sang-Bing Tsai

    2013-11-01

    Full Text Available This study adopted 14 criteria for order-winners and qualifiers as the attributes for evaluation. The first stage used a simultaneous importance-performance analysis to analyse the competitive market situations of a corporation and its competitors. The second stage used the decision-making trial and evaluation laboratory method to analyse the attributes causal relationships and levels of influence; then two methods of analysis were integrated to analyse and re-formulate the competitive strategies for the winning orders. As well as serving as a novel theory-based method to examine how manufacturers win orders, the proposals in this study can be applied to practical industry experiences.

  3. How to win friends and influence people

    CERN Document Server

    Carnegie, Dale

    2010-01-01

    For more than sixty years the rock-solid, time-tested advice in this book has carried thousands of now famous people up the ladder of success in their business and personal lives. With more than fifteen million copies sold, How to Win Friends and Influence People is one of the best known motivational books in history, with proven advice for achieving success in life. You’ll learn: three fundamental techniques in handling people; six ways to make people like you; twelve ways to win people to you way of thinking; nine ways to change people without arousing resentment; and much, much more!

  4. Labor Supply Effects of Winning a Lottery

    NARCIS (Netherlands)

    Picchio, Matteo; Suetens, Sigrid; van Ours, Jan

    2015-01-01

    This paper investigates how winning a substantial lottery prize affects labor supply. Analyzing data from Dutch State Lottery winners, we find that earnings are affected but not employment. Lottery prize winners reduce their hours of work but they are not very likely to withdraw from the labor force

  5. Deisgn of Win32-based EPICS IOC

    International Nuclear Information System (INIS)

    Design and implementation of Win32-based EPICS IOC are discussed in this paper. Some approaches for integrating EPICS IOC and Microsoft technologies are proposed. Some high performance oscilloscopes are developed as EPICS IOCs and work well with the whole EPICS control system. (authors)

  6. The "One Belt and One Road" is an Important Mutually Beneficial and Win-win Strategy

    Institute of Scientific and Technical Information of China (English)

    Long; Kaifeng

    2015-01-01

    The"One Belt and One Road"strategic conception carries the dream of development and prosperity of countries concerned,and gives the ancient Silk Road a brand new content of the time.In September and October 2013,President Xi Jinping proposed building the"New Silk Road Economic Belt"(One Belt)and the"Twenty-first Century Maritime Silk Road"(One Road)strategic conception respectively,emphasizing a mutual-beneficial and win-win

  7. Win-win strategies in directing low-carbon resilient development path

    International Nuclear Information System (INIS)

    This section explores big win-win strategies in directing low carbon resilient development path. There are lots of “leapfrog” development possibilities in developing countries, which go directly from a status of under-development through to efficient and environmentally benign lifestyle. To achieve low carbon resilient paths, not only technology development but also institutional and behavioral changes are required. Science-policy nexus is also discussed.

  8. Vascular Dysfunction in a Transgenic Model of Alzheimer's Disease: Effects of CB1R and CB2R Cannabinoid Agonists

    Science.gov (United States)

    Navarro-Dorado, Jorge; Villalba, Nuria; Prieto, Dolores; Brera, Begoña; Martín-Moreno, Ana M.; Tejerina, Teresa; de Ceballos, María L.

    2016-01-01

    There is evidence of altered vascular function, including cerebrovascular, in Alzheimer's disease (AD) and transgenic models of the disease. Indeed vasoconstrictor responses are increased, while vasodilation is reduced in both conditions. β-Amyloid (Aβ) appears to be responsible, at least in part, of alterations in vascular function. Cannabinoids, neuroprotective and anti-inflammatory agents, induce vasodilation both in vivo and in vitro. We have demonstrated a beneficial effect of cannabinoids in models of AD by preventing glial activation. In this work we have studied the effects of these compounds on vessel density in amyloid precursor protein (APP) transgenic mice, line 2576, and on altered vascular responses in aortae isolated ring. First we showed increased collagen IV positive vessels in AD brain compared to control subjects, with a similar increase in TgAPP mice, which was normalized by prolonged oral treatment with the CB1/CB2 mixed agonist WIN 55,212-2 (WIN) and the CB2 selective agonist JWH-133 (JWH). In Tg APP mice the vasoconstriction induced by phenylephrine and the thromboxane agonist U46619 was significantly increased, and no change in the vasodilation to acetylcholine (ACh) was observed. Tg APP displayed decreased vasodilation to both cannabinoid agonists, which were able to prevent decreased ACh relaxation in the presence of Aβ. In summary, we have confirmed and extended the existence of altered vascular responses in Tg APP mice. Moreover, our results suggest that treatment with cannabinoids may ameliorate the vascular responses in AD-type pathology. PMID:27695396

  9. Short- and long-term effects of cannabinoids on the extinction of contextual fear memory in rats.

    Science.gov (United States)

    Pamplona, Fabrício A; Bitencourt, Rafael M; Takahashi, Reinaldo N

    2008-07-01

    Facilitation of memory extinction by manipulation of the endocannabinoid (eCB) system has been recently studied in several paradigms. Our previous results pointed to facilitation of contextual fear memory extinction by a low dose of a cannabinoid agonist, with a suggestion of short-term effects. The aim of the present study was to further investigate the effects of cannabinoid drugs in the short- and long-term extinction of conditioned fear using an extended extinction protocol. Male Wistar rats were placed in a conditioning chamber and after 3min received a footshock (1.5mA, 1s). On the next day, they received i.p. drug treatment (WIN55212-2 0.25mg/kg, AM404 10mg/kg, SR141716A 1mg/kg) and were re-exposed to the conditioning chamber for 30min (extinction training). No-Extinction groups received the same drug treatment, but were exposed for 3min to the conditioning chamber. A drug-free test of contextual memory (3min) was performed 7 days later. The cannabinoid agonist WI55212-2 and the inhibitor of eCB metabolism/uptake AM404 facilitated short-term extinction. In addition, long-term effects induced by treatments with WIN55212 and AM404 were completely divergent to those of SR141716A treatment. The present results confirm and extend previous findings showing that the eCB system modulates short-term fear memory extinction with long-lasting consequences.

  10. WIN Global. 1977/98 Activities at a First Glance

    International Nuclear Information System (INIS)

    WIN is a worldwide association of women working professionally in the fields of nuclear energy and applications of radiation. The goal of WIN is to contribute to objectively inform the public on nuclear and radiation. WIN's principal objective is to emphasis and support the role that women can and do have in addressing the general public's concerns about nuclear energy and the application of radiation and nuclear technology. WIN is doing this through educational programmes, information exchange and arranging study visits. Members of WIN all have one thing in common: they want the general public to have a better understanding of nuclear and radiation matters. Membership status as ao April 21, 1998 was 605 members from 39 countries. During the year 7 new countries have joined to WIN ant two national WIN groups have been formed. Purpose of this paper is to present, to the Spanish Nuclear Society members, the WIN Global activities all over the world for the period 1997/98. The information included herein comes from different sources and WIN members and is, of course, a quick look over those activities. Win Spain activities for the period will be presented in a different paper of this Annual Meeting. (Author) 2 refs

  11. On Auctions with Withdrawable Winning Bids

    OpenAIRE

    Michael H. Rothkopf

    1991-01-01

    This paper considers sealed bidding in which bidders may submit two or more bids and after the bids are opened may, perhaps at a cost, withdraw bids that are more aggressive than would be necessary to win. Such withdrawal strategies are sometimes followed, but currently are surreptitious. However, legitimization of them would create potentially useful market mechanisms of potential interest to government agencies. These market mechanisms are also of theoretical interest since they are interme...

  12. WinXP和FreeBSD的IPSec通信

    Institute of Scientific and Technical Information of China (English)

    董晖

    2007-01-01

    如今,网络通信的数据安全成为一个重要的课题.各种针对TCP/IP通信的安全协议不断涌现.其中,IPSec协议是保证基于IP通信的重要数据安全的有力手段.具体地描述了实现WinXP和FreeBSD间IPSec通信的具体方法.

  13. What makes for prize-winning television?

    OpenAIRE

    Connolly, Sara; HANRETTY, Chris; Hargreaves-Heap, Shaun; Street, John

    2015-01-01

    We investigate the determinants of success in four international television awards festivals between 1994 and 2012. We find that countries with larger markets and greater expenditure on public broadcasting tend to win more awards, but that the degree of concentration in the market for television and rates of penetration of pay-per-view television are unrelated to success. These findings are consistent with general industrial organisation literature on quality and market size, and with media p...

  14. GnRH agonist triggering

    DEFF Research Database (Denmark)

    Kol, Shahar; Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2013-01-01

    The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. Recent developments in the area strengthen this premise. GnRHa trigger offers important advantages...... triggering concept should be challenged and that the GnRHa trigger is the way to move forward with thoughtful consideration of the needs, safety and comfort of our patients. Routinely, human chorionic gonadotrophin (HCG) is used to induce ovulation in fertility treatments. This approach deviates...... significantly from physiology and often results in insufficient hormonal support in early pregnancy and in ovarian hyperstimulation syndrome (OHSS). An alternative approach is to use a gonadotrophin-releasing hormone (GnRH) agonist which allows a more physiological trigger of ovulation and, most importantly...

  15. Using Win-Win Strategies to Implement Health in All Policies: A Cross-Case Analysis.

    Directory of Open Access Journals (Sweden)

    Agnes Molnar

    Full Text Available In spite of increasing research into intersections of public policy and health, little evidence shows how policy processes impact the implementation of Health in All Policies (HiAP initiatives. Our research sought to understand how and why strategies for engaging partners from diverse policy sectors in the implementation of HiAP succeed or fail in order to uncover the underlying social mechanisms contributing to sustainable implementation of HiAP.In this explanatory multiple case study, we analyzed grey and peer-review literature and key informant interviews to identify mechanisms leading to implementation successes and failures in relation to different strategies for engagement across three case studies (Sweden, Quebec and South Australia, after accounting for the role of different contextual conditions.Our results yielded no support for the use of awareness-raising or directive strategies as standalone approaches for engaging partners to implement HiAP. However, we found strong evidence that mechanisms related to "win-win" strategies facilitated implementation by increasing perceived acceptability (or buy-in and feasibility of HiAP implementation across sectors. Win-win strategies were facilitated by mechanisms related to several activities, including: the development of a shared language to facilitate communication between actors from different sectors; integrating health into other policy agendas (eg., sustainability and use of dual outcomes to appeal to the interests of diverse policy sectors; use of scientific evidence to demonstrate the effectiveness of HiAP; and using health impact assessment to make policy coordination for public health outcomes more feasible and to give credibility to policies being developed by diverse policy sectors.Our findings enrich theoretical understanding in an under-unexplored area of intersectoral action. They also provide policy makers with examples of HiAP across wealthy welfare regimes, and improve

  16. Win-win opportunities & environmental regulation: Testing of porter hypothesis for Indian manufacturing industries

    OpenAIRE

    M.N. Murthy; Surender Kumar

    2001-01-01

    This paper studies the effect of environmental regulation relating to water pollution by the Indian industry on the productive efficiency of firms. The panel data of 92 water- polluting firms for the three years 1996-97, 1997-98, and 1998-99 are used to test the Porter hypothesis of having win-win opportunities for the firms subjected to the regulation. The main empirical result is that the technical efficiency of firms increases with the intensity of environmental regulation and the water co...

  17. A winning strategy for 3 x n Cylindrical Hex

    DEFF Research Database (Denmark)

    Huneke, S. C.; Hayward, R.; Toft, Bjarne

    2014-01-01

    For Cylindrical Hex on a board with circumference 3, we give a winning strategy for the end-to-end player. This is the first known winning strategy for odd circumference at least 3, answering a question of David Gale. (C) 2014 Elsevier B.V. All rights reserved.......For Cylindrical Hex on a board with circumference 3, we give a winning strategy for the end-to-end player. This is the first known winning strategy for odd circumference at least 3, answering a question of David Gale. (C) 2014 Elsevier B.V. All rights reserved....

  18. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels;

    2015-01-01

    antagonists and describes the development of potent antagonists from partial agonists originally derived from the potent GABAAR agonist muscimol. In this process, several heterocyclic aromatic systems have been used in combination with structural models in order to map the orthosteric binding site...... and to reveal structural details to be used for obtaining potency and subtype selectivity. The challenges connected to functional characterization of orthosteric GABAAR partial agonists and antagonists, especially with regard to GABAAR stoichiometry and alternative binding sites are discussed. GABAAR...

  19. Cannabinoid agonists rearrange synaptic vesicles at excitatory synapses and depress motoneuron activity in vivo.

    Science.gov (United States)

    García-Morales, Victoria; Montero, Fernando; Moreno-López, Bernardo

    2015-05-01

    Impairment of motor skills is one of the most common acute adverse effects of cannabis. Related studies have focused mainly on psychomotor alterations, and little is known about the direct impact of cannabinoids (CBs) on motoneuron physiology. As key modulators of synaptic function, CBs regulate multiple neuronal functions and behaviors. Presynaptic CB1 mediates synaptic strength depression by inhibiting neurotransmitter release, via a poorly understood mechanism. The present study examined the effect of CB agonists on excitatory synaptic inputs incoming to hypoglossal motoneurons (HMNs) in vitro and in vivo. The endocannabinoid anandamide (AEA) and the synthetic CB agonist WIN 55,212-2 rapidly and reversibly induced short-term depression (STD) of glutamatergic synapses on motoneurons by a presynaptic mechanism. Presynaptic effects were fully reversed by the CB1-selective antagonist AM281. Electrophysiological and electron microscopy analysis showed that WIN 55,212-2 reduced the number of synaptic vesicles (SVs) docked to active zones in excitatory boutons. Given that AM281 fully abolished depolarization-induced depression of excitation, motoneurons can be feasible sources of CBs, which in turn act as retrograde messengers regulating synaptic function. Finally, microiontophoretic application of the CB agonist O-2545 reversibly depressed, presumably via CB1, glutamatergic inspiratory-related activity of HMNs in vivo. Therefore, evidence support that CBs, via presynaptic CB1, induce excitatory STD by reducing the readily releasable pool of SVs at excitatory synapses, then attenuating motoneuron activity. These outcomes contribute a possible mechanistic basis for cannabis-associated motor performance disturbances such as ataxia, dysarthria and dyscoordination. PMID:25595101

  20. Setting Win Limits: An Alternative Approach to "Responsible Gambling"?

    Science.gov (United States)

    Walker, Douglas M; Litvin, Stephen W; Sobel, Russell S; St-Pierre, Renée A

    2015-09-01

    Social scientists, governments, and the casino industry have all emphasized the need for casino patrons to "gamble responsibly." Strategies for responsible gambling include self-imposed time limits and loss limits on gambling. Such strategies help prevent people from losing more than they can afford and may help prevent excessive gambling behavior. Yet, loss limits also make it more likely that casino patrons leave when they are losing. Oddly, the literature makes no mention of "win limits" as a potential approach to responsible gambling. A win limit would be similar to a loss limit, except the gambler would leave the casino upon reaching a pre-set level of winnings. We anticipate that a self-imposed win limit will reduce the gambler's average loss and, by default, also reduce the casino's profit. We test the effect of a self-imposed win limit by running slot machine simulations in which the treatment group of players has self-imposed and self-enforced win and loss limits, while the control group has a self-imposed loss limit or no limit. We find that the results conform to our expectations: the win limit results in improved player performance and reduced casino profits. Additional research is needed, however, to determine whether win limits could be a useful component of a responsible gambling strategy. PMID:24567070

  1. An Application to WIN/ISIS Database on Local Network

    Directory of Open Access Journals (Sweden)

    Robert Lechien

    2005-07-01

    Full Text Available A Translated Article containing an application to how WIN/ISIS database work on local network. It starts with main definitions, and how to install WIN/ISIS on PC, and how to install it on the local network server.

  2. No effect of blue on winning contests in judo

    NARCIS (Netherlands)

    Dijkstra, Peter D.; Preenen, Paul T. Y.

    2008-01-01

    A study by Rowe et al. reported a winning bias for judo athletes wearing a blue outfit relative to those wearing a white one during the 2004 Olympics. It was suggested that blue is associated with a higher likelihood of winning through differential effects of colour on opponent visibility and/or an

  3. CERN exhibition wins yet another design prize

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    The “Universe of Particles” exhibition in CERN’s Globe wins the silver design prize from the German direct business communications association FAMAB.   Not only do tens of thousands of people visit the “Universe of Particles” exhibition each year, but juries for design prizes are crossing its threshold more and more frequently too. In 2011 alone it claimed 8 awards, including winning outright the 2011 Annual Multimedia award, the iF Communication Design for Corporate Architecture award and the Modern Decoration Media award (the Bulletin already reported on some of these in July 2011). The FAMAB award is the latest to join the prestigious list. The jury of FAMAB’s “ADAM 2011” award was particularly impressed by the hands-on nature of the exhibition, which encourages visitors to get interested in science. They also appreciated the way that the space in the Globe is not just a container for the exhibits, but itself ...

  4. Functional Selectivity of CB2 Cannabinoid Receptor Ligands at a Canonical and Noncanonical Pathway.

    Science.gov (United States)

    Dhopeshwarkar, Amey; Mackie, Ken

    2016-08-01

    The CB2 cannabinoid receptor (CB2) remains a tantalizing, but unrealized therapeutic target. CB2 receptor ligands belong to varied structural classes and display extreme functional selectivity. Here, we have screened diverse CB2 receptor ligands at canonical (inhibition of adenylyl cyclase) and noncanonical (arrestin recruitment) pathways. The nonclassic cannabinoid (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55940) was the most potent agonist for both pathways, while the classic cannabinoid ligand (6aR,10aR)-3-(1,1-Dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran JWH133) was the most efficacious agonist among all the ligands profiled in cyclase assays. In the cyclase assay, other classic cannabinoids showed little [(-)-trans-Δ(9)-tetrahydrocannabinol and (-)-(6aR,7,10,10aR)-tetrahydro-6,6,9-trimethyl-3-(1-methyl-1-phenylethyl)-6H-dibenzo[b,d]pyran-1-ol] (KM233) to no efficacy [(6aR,10aR)-1-methoxy-6,6,9-trimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene(L759633) and (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,8,9,10,10a-hexahydro-1-methoxy-6,6-dimethyl-9-methylene-6H-dibenzo[b,d]pyran]L759656. Most aminoalkylindoles, including [(3R)-​2,​3-​dihydro-​5-​methyl-​3-​(4-​morpholinylmethyl)pyrrolo[1,​2,​3-​de]-​1,​4-​benzoxazin-​6-​yl]-​1-​naphthalenyl-​methanone,​ monomethanesulfonate (WIN55212-2), were moderate efficacy agonists. The cannabilactone 3-(1,1-dimethyl-heptyl)-1-hydroxy-9-methoxy-benzo(c)chromen-6-one (AM1710) was equiefficacious to CP55940 to inhibit adenylyl cyclase, albeit with lower potency. In the arrestin recruitment assays, all classic cannabinoid ligands failed to recruit arrestins, indicating a bias toward G-protein coupling for this class of compound. All aminoalkylindoles tested, except for WIN55212-2 and (1-​pentyl-​1H-​indol-​3-​yl)(2,​2,​3,​3-​tetramethylcyclopropyl)-​methanone (UR144), failed

  5. Win-Win-Win

    Science.gov (United States)

    Jackson, Nancy Mann

    2012-01-01

    Two years ago, members of a strategic planning committee at Woodberry Forest School set a goal to re-engage African-American and Hispanic alumni, many of whom had lost touch with the Virginia boarding school for boys. One of the committee's ideas was to launch a mentoring program to connect current minority students with minority alumni. Two years…

  6. Barselsrettigheder til danske fædre – en win win situation

    DEFF Research Database (Denmark)

    Bloksgaard, Lotte; Borchorst, Anette

    2011-01-01

    Det er vigtigt at sikre selvstændige orlovsrettigheder til mænd i Danmark. Danske fædres orlovsrettigheder er i dag de svageste i Norden, og det er forklaringen på, at de også tager den næstkorteste orlov i nordisk sammenhæng. Den danske orlovslovgivning har været præget af blokpolitik, og forskn...... forskning og viden har ikke spillet nogen større rolle for beslutningerne. Det er beklageligt, fordi det peger i retning af, at øremærket orlov til far skaber en win-win situation for fædre, børn og mødre, mener forskerne Lotte Bloksgaard og Anette Borchorst....

  7. β2-agonist therapy in lung disease.

    Science.gov (United States)

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  8. Win-CC Control Extension Development: Pressure-Enthalpy Win-CC Panel

    CERN Document Server

    Gaona, Daniel

    2013-01-01

    This report reviews in detail the development and implementation of a Win-CC Control Extension for both Windows and Linux Platforms. The Control Extension consists in a Win-CC panel linked by dynamic libraries (*.dll or *.so) to the NIST Thermodynamics properties library. This linking permits to handle in real time different thermodynamic properties of a wide range of refrigerants. The Win-CC panel uses this information to produce a Pressure-Enthalpy Diagram of any required refrigeration cycle. In general, the p-H diagram enhance the understanding of the refrigeration cycle and facilitate the control and supervision of the system. Ideally, this control extension will be part of several Cooling Projects at CERN such as ATLAS IBL and CMS TIF. The development of this tool required several weeks of programming in C++ in both Linux and Windows platforms. At the end, the tool was constructed successfully and tested in both operating systems. The following sections go deeper into the develop, operation, and impleme...

  9. Antinociceptive effects of the selective CB2 agonist MT178 in inflammatory and chronic rodent pain models.

    Science.gov (United States)

    Vincenzi, Fabrizio; Targa, Martina; Corciulo, Carmen; Tabrizi, Mojgan Aghazadeh; Merighi, Stefania; Gessi, Stefania; Saponaro, Giulia; Baraldi, Pier Giovanni; Borea, Pier Andrea; Varani, Katia

    2013-06-01

    Cannabinoid CB(2) receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory, neuropathic, and bone cancer pain. In this study the effect of a novel CB(2)agonist (MT178) was evaluated in different animal models of pain. First of all, in vitro competition binding experiments performed on rat, mouse, or human CB receptors revealed a high affinity, selectivity, and potency of MT178. The analgesic properties of the novel CB(2) agonist were evaluated in various in vivo experiments, such as writhing and formalin assays, showing a good efficacy comparable with that produced by the nonselective CB agonist WIN 55,212-2. A dose-dependent antiallodynic effect of the novel CB(2) compound in the streptozotocin-induced diabetic neuropathy was found. In a bone cancer pain model and in the acid-induced muscle pain model, MT178 was able to significantly reduce mechanical hyperalgesia in a dose-related manner. Notably, MT178 failed to provoke locomotor disturbance and catalepsy, which were observed following the administration of WIN 55,212-2. CB(2) receptor mechanism of action was investigated in dorsal root ganglia where MT178 mediated a reduction of [(3)H]-d-aspartate release. MT178 was also able to inhibit capsaicin-induced substance P release and NF-κB activation. These results demonstrate that systemic administration of MT178 produced a robust analgesia in different pain models via CB(2) receptors, providing an interesting approach to analgesic therapy in inflammatory and chronic pain without CB(1)-mediated central side effects.

  10. Customer Satisfaction Perceptions of Dislocated Workers Served by WIN Job Centers in the Mississippi Corridor Consortium

    Science.gov (United States)

    Washburn, Dava Michelle

    2009-01-01

    The purpose of this study was to determine the perceptions of satisfaction of dislocated workers served by WIN Job Centers in the Mississippi Corridor Consortium. Four WIN Job Centers participated in this study: Northeast Mississippi Community College WIN Job Center in Corinth, Northwest Mississippi Community College WIN Job Center in Oxford,…

  11. Winning Strategies in Multimove Chess (i,j)

    OpenAIRE

    Berger, Emily Rita; Dubbs, Alexander

    2014-01-01

    We propose a class of chess variants, Multimove Chess (i,j), in which White gets i moves per turn and Black gets j moves per turn. One side is said to win when it takes the opponent's king. All other rules of chess apply. We prove that if (i,j) is not (1,1) or (2,2), and if $i \\geq \\min(j,4)$, then White always has a winning strategy, and otherwise Black always has a winning strategy.

  12. Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.

    Science.gov (United States)

    Gutierrez, Tannia; Crystal, Jonathon D; Zvonok, Alexander M; Makriyannis, Alexandros; Hohmann, Andrea G

    2011-09-01

    Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB(2) agonist to attenuate a neuropathic pain state. Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal thresholds in sham-operated or naive animals. The percentage of active lever responding was similar in naive groups self-administering vehicle or (R,S)-AM1241. The CB(2) antagonist SR144528 blocked both antiallodynic effects of (R,S)-AM1241 self-medication and the percentage of active lever responding in neuropathic (but not naive) rats. Neuropathic and sham groups exhibited similar percentages of active lever responding for (R,S)-AM1241 on a fixed ratio 1 (FR1) schedule. However, neuropathic animals worked harder than shams to obtain (R,S)-AM1241 when the schedule of reinforcement was increased (to FR6). (R,S)-AM1241 self-medication on FR1, FR3, or FR6 schedules attenuated nerve injury-induced mechanical allodynia. (R,S)-AM1241 (900μg intravenously) failed to produce motor ataxia observed after administration of the mixed CB(1)/CB(2) agonist WIN55,212-2 (0.5mg/kg intravenously). Our results suggest that cannabinoid CB(2) agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system side effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential. These methods offer potential to elucidate novel analgesics that suppress spontaneous neuropathic pain that is not measured by traditional assessments of evoked pain. PMID:21550725

  13. College of Engineering robotics students win awards around the world

    OpenAIRE

    Crumbley, Liz

    2007-01-01

    Students from the Virginia Tech College of Engineering's Robotics and Mechanics Laboratory have traveled the United States and abroad this summer, winning a number of honors for robotics research and development.

  14. Safety profile of WinRho anti-D.

    Science.gov (United States)

    Hong, F; Ruiz, R; Price, H; Griffiths, A; Malinoski, F; Woloski, M

    1998-01-01

    WinRho anti-D is manufactured with multiple processes to minimize the risk of transmitting blood-borne diseases such as viruses. These safety features include donor selection, plasma testing, solvent-detergent viral inactivation, and nanofiltration. To date, there has not been any case of viral transmission in association with use of WinRho anti-D. Adverse drug reactions are infrequent and generally mild; the most common are headache, fever, and chills. Some degree of hemolysis is inevitable due to the mechanism of action of WinRho anti-D, but this is predictable and transient. A few cases of intravascular hemolysis have been reported; hypersensitivity reactions are very rare. WinRho anti-D has been shown in both clinical trials and postmarketing surveillance to be safe and effective in the treatment of idiopathic thrombocytopenic purpura (ITP) and in the prevention of Rh isoimmunization. PMID:9523744

  15. Virginia Tech students win national championship in financial planning

    OpenAIRE

    Elliott, Jean

    2004-01-01

    Three Virginia Tech students, all seniors studying financial planning in the College of Liberal Arts and Human Sciences, teamed up to win the 2004 American Express Financial Planning Invitational, bringing home $10,000 in scholarship money for the institution.

  16. Leaders in high temperature superconductivity commercialization win superconductor industry award

    CERN Multimedia

    2007-01-01

    CERN's Large Hadron Collider curretn leads project head Amalia Ballarino named superconductor industry person of the year 2006. Former high temperature superconductivity program manager at the US Department of energy James Daley wins lifetime achievement award. (1,5 page)

  17. BMC Ecology Image Competition 2016: the winning images.

    Science.gov (United States)

    Simundza, Julia; Palmer, Matthew; Settele, Josef; Jacobus, Luke M; Hughes, David P; Mazzi, Dominique; Blanchet, Simon

    2016-01-01

    The 2016 BMC Ecology Image Competition marked another celebration of the astounding biodiversity, natural beauty, and biological interactions documented by talented ecologists worldwide. For our fourth annual competition, we welcomed guest judge Dr. Matthew Palmer of Columbia University, who chose the winning image from over 140 entries. In this editorial, we highlight the award winning images along with a selection of highly commended honorable mentions. PMID:27503341

  18. Who Wins The Olympic Games: Economic Development and Medal Totals

    OpenAIRE

    Andrew B. Bernard; Busse, Meghan R.

    2000-01-01

    This paper examines determinants of Olympic success at the country level. Does the U.S. win its fair share of Olympic medals? Why does China win 6% of the medals even though it has 1/5 of the world's population? We consider the role of population and economic development in determining medal totals from 1960-1996. We also provide out of sample predictions for the 2000 Olympics in Sydney.

  19. Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy

    OpenAIRE

    Jakubík, J; Janíčková, H; El-Fakahany, EE; Doležal, V

    2011-01-01

    BACKGROUND AND PURPOSE Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5′-γ−thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M2 muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. EXPERIMENTAL APPROACH Filtration and scintillation proximity ass...

  20. On Winning Conditions of High Borel Complexity in Pushdown Games

    CERN Document Server

    Finkel, Olivier

    2008-01-01

    Some decidable winning conditions of arbitrarily high finite Borel complexity for games on finite graphs or on pushdown graphs have been recently presented by O. Serre in [ Games with Winning Conditions of High Borel Complexity, in the Proceedings of the International Conference ICALP 2004, LNCS, Volume 3142, p. 1150-1162 ]. We answer in this paper several questions which were raised by Serre in the above cited paper. We first show that, for every positive integer n, the class C_n(A), which arises in the definition of decidable winning conditions, is included in the class of non-ambiguous context free omega languages, and that it is neither closed under union nor under intersection. We prove also that there exists pushdown games, equipped with such decidable winning conditions, where the winning sets are not deterministic context free languages, giving examples of winning sets which are non-deterministic non-ambiguous context free languages, inherently ambiguous context free languages, or even non context fre...

  1. A model for establishing a win-win relationship between a wood pellets manufacturer and its customers

    Energy Technology Data Exchange (ETDEWEB)

    Uran, Vedran [ENERGETSKE USLUGE Ltd., Ilica 52, 10000, Zagreb (Croatia)

    2010-05-15

    This paper investigates the possibility of establishing a win-win relationship between a wood pellets manufacturer and its customers when the manufacturer possesses a power plant fueled by biomass and buys wood material from forest companies. Two prerequisites must be fulfilled for this relationship. First, the price of wood pellets should be lower than the fuel currently used by potential wood pellets customers and, second, the price of wood material as a raw material for producing the wood pellets should not jeopardize the profitability of the operations of the wood pellets manufacturer, who also produces electricity from biomass and sells it to the state at the feed-in tariff price. A mathematical model has been developed for each prerequisite and applied to several examples. The results demonstrate that a win-win relation can be established in Croatia and most of the Member States of the EU. (author)

  2. Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina.

    Science.gov (United States)

    Wang, Xiao-Han; Wu, Yi; Yang, Xiao-Fang; Miao, Yanying; Zhang, Chuan-Qiang; Dong, Ling-Dan; Yang, Xiong-Li; Wang, Zhongfeng

    2016-01-01

    In the inner retina, ganglion cells (RGCs) integrate and process excitatory signal from bipolar cells (BCs) and inhibitory signal from amacrine cells (ACs). Using multiple labeling immunohistochemistry, we first revealed the expression of the cannabinoid CB1 receptor (CB1R) at the terminals of ACs and BCs in rat retina. By patch-clamp techniques, we then showed how the activation of this receptor dichotomously regulated miniature inhibitory postsynaptic currents (mIPSCs), mediated by GABAA receptors and glycine receptors, and miniature excitatory postsynaptic currents (mEPSCs), mediated by AMPA receptors, of RGCs in rat retinal slices. WIN55212-2 (WIN), a CB1R agonist, reduced the mIPSC frequency due to an inhibition of L-type Ca(2+) channels no matter whether AMPA receptors were blocked. In contrast, WIN reduced the mEPSC frequency by suppressing T-type Ca(2+) channels only when inhibitory inputs to RGCs were present, which could be in part due to less T-type Ca(2+) channels of cone BCs, presynaptic to RGCs, being in an inactivation state under such condition. This unique feature of CB1R-mediated retrograde regulation provides a novel mechanism for modulating excitatory synaptic transmission in the inner retina. Moreover, depolarization of RGCs suppressed mIPSCs of these cells, an effect that was eliminated by the CB1R antagonist SR141716, suggesting that endocannabinoid is indeed released from RGCs.

  3. PPAR Agonists and Cardiovascular Disease in Diabetes.

    Science.gov (United States)

    Calkin, Anna C; Thomas, Merlin C

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARalpha agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARgamma agonists, and more recently dual PPARalpha/gamma coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARgamma receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  4. PPAR Agonists and Cardiovascular Disease in Diabetes

    Directory of Open Access Journals (Sweden)

    Anna C. Calkin

    2008-01-01

    Full Text Available Peroxisome proliferators activated receptors (PPARs are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPAR agonists, and more recently dual PPAR/ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPAR receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.

  5. Dihydrocodeine / Agonists for Alcohol Dependents

    Directory of Open Access Journals (Sweden)

    Albrecht eUlmer

    2012-03-01

    Full Text Available Objective: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients.Methods: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC to 102 heavily alcohol addict-ed patients, later, also Buprenorphine, Clomethiazole (>6 weeks, Baclofen and in one case Amphetamine, each on individual indication. This paper focuses on the data with DH, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. Results: The 102 patients with the DHC-treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-step scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details.Conclusions: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around ¼ of the patients already. Many further

  6. The "Win-Win" Strategy for Sustainable Development : A Case Study of Recycling System in European Countries <論説>

    OpenAIRE

    Ueda, Yoshifumi

    1999-01-01

    According to static mindset, any regulation for ecological preservation means an unavoidable cost imposed on private economic activities, and promotes only a "end-of-pipe" type of technology. However, regulations devised from the view point of evolutionary mindset can reconcile economic development with ecological sustainability by encouraging an ecologically benign technology on micro level. However, the "win-win" strategy may result in "wrong-wrong" strategies, unless the private initiative...

  7. CERN repeats last year's running win

    CERN Multimedia

    2000-01-01

    The CERN first team successfully defended the title won last year in the 20th annual Cross Inter-Entreprises held at Collex-Bossy on Saturday 7 October. 101 teams of four runners representing firms from all over the Geneva area finished the 6.2 km race, through forest and over fields. In spite of two members of last year’s winning team being absent through injury this time, the first team was still 38 seconds faster than in 1999. The second and third CERN teams also excelled with places in the first 15 teams. In this race the teams start at one-minute intervals and the time of each team is that of its third runner to finish, so they try to run in a group of three or four all the way. The full results of all teams can be found at: http://www.Club-association.ch/CHP Placings of the CERN teams 1st 21:53 Cornelis, Ecarnot, Ehmele, Nisbet 6th 22:50 Cornet, Eklund, Rick, Ruiz Llamas 13th 24:24 Dunkel, Guillot, Montejo Raez, Zamiatin 35th 28:22 Cameron, Galbraith, Revol, Scalisi

  8. Win a lift to the future!

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The Communication Group is organising a competition offering people at CERN the chance to submit their ideas and win a ticket to the Lift10 Conference, which will be held in Geneva from 5 to7 May.   Lift is a community of technology "pioneers", created in 2006. It now involves more than 4,000 people from over 60 countries, who meet regularly in Europe and in Asia to explore the social implications of new technologies and the major shifts ahead. CERN is one of the academic partners of the next Lift conference, whose theme is "Connected people”. For this occasion, 10 free tickets to the conference will be awarded to the "CERNois" who come up with the best answers to the question: “How would you contribute to Lift10?” Those taking part in the competition can choose from among the following categories: - run workshop(s); - cover the conference on a blog; - coordinate a discussion during the breaks; - organize a lift@home ...

  9. A Win-Win Strategy for economic wealth and climate protection -equally important for the first and the third world

    Energy Technology Data Exchange (ETDEWEB)

    Bach, W. [Muenster Univ. (Germany). Abt. fuer Klima- und Energieforschung

    1997-09-01

    Reduction targets for a desired degree of climate protection are negotiated at the international circuit. Concrete measures for reaching such targets are implemented at the national and city levels. Demonstrated here for electricity use in the commercial sector of the City of Muenster is a ``Win-Win Strategy`` which, if correctly done will result on in winners. Specifically, it is shown that electricity use between 1990 and 2005 in a Trend Scenario would increase by ca. 25%, while in the Climate Protection Scenario it could decrease by ca.23% due to savings and substitution measures. The benefits, costs, and net gains are computed for different price developments. Rough estimates show that over the next 10 years the ``Win Win Strategy`` could provide 256 additional jobs in the commercial sector of Muenster, and about 700000 new jobs when projected for Germany as a whole. Additionally, studies show that implementing the electricity efficiency potential in five Western European countries by 2020 could save between 20 and 50 Bil. (billion) ECU, whilst the need for some 90 additional 1000 MW power plants could be avoided. Finally, the policy options discussed here can help tap this huge available energy efficiency gold mine by the North and the South alike. The function of the ``Win Win Strategy`` is to help supply the funds for paving the way toward a sustainable future. (author)

  10. Ombud's Corner: fellows and students – a win-win equation

    CERN Multimedia

    Sudeshna Datta-Cockerill

    2014-01-01

    The hundreds of Fellows and students working at CERN bring precious new blood into the Laboratory. At the same time, CERN offers them invaluable work experience that will have a significant impact on their future careers. It is important that we all work together to make this a win-win situation with lasting positive effects for all concerned over the years to come.   Fellows and students are just setting out on a great professional adventure.  Some of them are very young, others are a bit more experienced … and what happens during this early period can have vast consequences on their approach to work and indeed on their overall careers. They all come here with their hard earned skills and a high degree of motivation, ready to make the most out of an internship at CERN. Sometimes, they are called to integrate into well-established units; at other times, they are asked to join complex collaborations. Almost always they have to deal with new information, new cultures, new t...

  11. Achieving ecological restoration by working with local people: a Chinese scholar seeks win-win paths

    Directory of Open Access Journals (Sweden)

    Heran Zheng

    2014-09-01

    Full Text Available Environmental degradation and poverty are linked, and this means that conservation and poverty reduction must be tackled together. However, finding a successful integrated strategy has been an elusive goal. We describe the career of a Chinese scholar, Shixiong Cao, whose persistent efforts to find and follow win-win paths have led to ecological restoration accompanied by long-term benefits for local residents. Cao’s story illustrates how development that combines environmental and economic perspectives can both help people to escape the poverty trap and restore degraded environments. His experience demonstrates that when environmental managers find solutions that can mitigate or eliminate poverty through the development of green enterprises, they can combine them with environmental restoration efforts to produce long-term sustainable solutions. In this paper, we share Cao’s 28 years of experience because we believe that his scientific and practical spirit, and his belief that it is necessary to work directly with the people affected by environmental projects, will inspire other scholars and practitioners to achieve similar successes.

  12. CDM. Is it a 'win-win' strategy for rural poverty alleviation in India?

    Energy Technology Data Exchange (ETDEWEB)

    Sirohi, Smita [Department of Dairy Economics, Statistics and Management, National Dairy Research Institute, Karnal, Haryana, 132001 (India)

    2007-09-15

    India is perceived to be one of the most attractive Non-Annex I countries for CDM project development. There are more than 350 projects in the CDM pipeline, largely in the areas of renewable energy, energy efficiency in industries and fossil fuel switching. This paper examines the socio-economic component of sustainable development commitments of the CDM projects to see if they can make any impact on rural poverty in India, since the goal of poverty alleviation lies at the core of the country's development priorities. The study concludes that CDM is not contributing to rural poverty alleviation to any notable extent. Nearly all the projects have a business orientation and are not directed to the development of rural poor. Even the renewable energy projects will have limited role in up-liftment of the masses below poverty line due to their weak resource base. For CDM to emerge as a 'win-win' strategy for poverty alleviation projects should be aimed at the rural communities and designed to accelerate agricultural growth in the rain-fed regions of the country.

  13. WINS. Market Simulation Tool for Facilitating Wind Energy Integration

    Energy Technology Data Exchange (ETDEWEB)

    Shahidehpour, Mohammad [Illinois Inst. of Technology, Chicago, IL (United States)

    2012-10-30

    Integrating 20% or more wind energy into the system and transmitting large sums of wind energy over long distances will require a decision making capability that can handle very large scale power systems with tens of thousands of buses and lines. There is a need to explore innovative analytical and implementation solutions for continuing reliable operations with the most economical integration of additional wind energy in power systems. A number of wind integration solution paths involve the adoption of new operating policies, dynamic scheduling of wind power across interties, pooling integration services, and adopting new transmission scheduling practices. Such practices can be examined by the decision tool developed by this project. This project developed a very efficient decision tool called Wind INtegration Simulator (WINS) and applied WINS to facilitate wind energy integration studies. WINS focused on augmenting the existing power utility capabilities to support collaborative planning, analysis, and wind integration project implementations. WINS also had the capability of simulating energy storage facilities so that feasibility studies of integrated wind energy system applications can be performed for systems with high wind energy penetrations. The development of WINS represents a major expansion of a very efficient decision tool called POwer Market Simulator (POMS), which was developed by IIT and has been used extensively for power system studies for decades. Specifically, WINS provides the following superiorities; (1) An integrated framework is included in WINS for the comprehensive modeling of DC transmission configurations, including mono-pole, bi-pole, tri-pole, back-to-back, and multi-terminal connection, as well as AC/DC converter models including current source converters (CSC) and voltage source converters (VSC); (2) An existing shortcoming of traditional decision tools for wind integration is the limited availability of user interface, i.e., decision

  14. The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats

    Directory of Open Access Journals (Sweden)

    Samane Jahanabadi

    2016-04-01

    Conclusion: These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain.

  15. Therapeutic Potentials and uses of Cannabinoid Agonists in Health and Disease Conditions

    Directory of Open Access Journals (Sweden)

    A.O. Ibegbu

    2012-04-01

    Full Text Available Cannabis and its derivatives have great therapeutic potential and have been used for centuries for medicinal purposes. The side effects of cannabinoids include euphoric mood changes, acute psychotic episodes, initiation and exacerbation of schizophrenic psychosis in predisposed persons, impaired cognitive and psychomotor performance, tachycardia and hypotension. The production of complex behavioural effects by cannabinoids are mediated by cannabinoid receptors (CB1 and CB2 and by interactions with other neurochemical systems. It has been shown that the therapeutic and physiological effects of cannabinoids are dependent upon whether the administration is acute or chronic and on the route of administration. The physiological effects of cannabis and its derivatives include: reduction in psychomotor coordination and performance, alterations in thermoregulation, endocrine and reproductive functions and gut motility. There is also evidence of agonist selectivity for CB1 receptors coupled to different subtypes of Gi proteins or to Gi versus Go proteins. Cannabinoid-activated receptors distinct from CB1 or CB2 exist in the central nervous system. Cannabinoids are known to inhibit GABA-mediated inhibitory postsynaptic currents in the hippocampus via a presynaptic action at CB1 receptors located on GABAergic terminals. CB1 receptors have also been implicated in the inhibition of glutamatergic excitatory postsynaptic currents. The synthetic cannabinoid, Win 55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was found to attenuate hyperalgesia in a rat model of neuropathic pain and suppress opioid-induced emesis in ferrets.

  16. The effect of WIN 55,212-2 suggests a cannabinoid-sensitive component in the early toxicity induced by organic acids accumulating in glutaric acidemia type I and in related disorders of propionate metabolism in rat brain synaptosomes.

    Science.gov (United States)

    Colín-González, A L; Paz-Loyola, A L; Serratos, I N; Seminotti, B; Ribeiro, C A J; Leipnitz, G; Souza, D O; Wajner, M; Santamaría, A

    2015-12-01

    Several physiological processes in the CNS are regulated by the endocannabinoid system (ECS). Cannabinoid receptors (CBr) and CBr agonists have been involved in the modulation of the N-methyl-D-aspartate receptor (NMDAr) activation. Glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids are endogenous metabolites produced and accumulated in the brain of children affected by severe organic acidemias (OAs) with neurodegeneration. Oxidative stress and excitotoxicity have been involved in the toxic pattern exerted by these organic acids. Studying the early pattern of toxicity exerted by these metabolites is crucial to explain the extent of damage that they can produce in the brain. Herein, we investigated the effects of the synthetic CBr agonist WIN 55,212-2 (WIN) on early markers of GA-, 3-OHGA-, MMA- and PA-induced toxicity in brain synaptosomes from adult (90-day-old) and adolescent (30-day-old) rats. As pre-treatment, WIN exerted protective effects on the GA- and MMA-induced mitochondrial dysfunction, and prevented the reactive oxygen species (ROS) formation and lipid peroxidation induced by all metabolites. Our findings support a protective and modulatory role of cannabinoids in the early toxic events elicited by toxic metabolites involved in OAs.

  17. beta2-Agonists at the Olympic Games.

    Science.gov (United States)

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  18. Winning at litigation through decision analysis creating and executing winning strategies in any litigation or dispute

    CERN Document Server

    Celona, John

    2016-01-01

    This book is the first in-depth guide to applying the philosophy, theory, and methods of decision analysis to creating and executing winning legal strategies. With explanations that progress from introductory to advanced and practice problems at the end of each chapter, this is a book the reader will want to use and refer to for years to come. Practicing decision analysts, operations research and management science students, attorneys and law students will find this book an invaluable addition to their knowledge and skills. John Celona has over three decades of experience in teaching and applying decision analysis. John lectures in the School of Engineering at Stanford University and is on faculty at The Stanford Center for Professional Development, the American Course on Drug Development and Regulatory Sciences, and the Academy of the American Society for Healthcare Risk Management.

  19. Winning at Pocker and Games of Chance Winning at Pocker and Games of Chance

    Directory of Open Access Journals (Sweden)

    Anita Flanders Rebelo

    2008-04-01

    Full Text Available It's the modern consumer mind - compete to eat, save to the grave, throw to the wind to win! Never the game that's im portant - it's the beer , the fag. . . and if you're broke it's just the "odds" to turn you on. "Socrates didn't play dice games. He drank a lot. And when he was drunk he would go watch the game and give advice. It was because of bad advice that he was eventually sentenced to death. . . Back then it was more fun. Nobody knew anything about odds. It was just put down your money, you toss the dice, you laugh, you take another drink." - to Cassidy,it's knowing the odds that's put everybody on pot. Rack Cassidy's Winning at Poker and Games of Chance lampoons the illogic logic of modern "instructed" man. It is a disturbingly funny caricature of a nonsensical consumer's mind trying to ratio nalize the game of life, and what comes out is "hash" - not meat and potatoes. The book is high philosophical slapstick comedy ila Charlie Chaplin on paper in today's scene. To Cassidy, consumer thinking has made intellectual nitwits of us. We're always ex plaining in detail about what we don't have the slightest real understanding of, but we go on and on like automats spitting out words and words which in the long run make no sense to our__ selves and much less to the other poor broken down human calculat ing machines - especially when we try to give logic to our il/logical vices and fears.

  20. Winning the jackpot and depression: Money cannot buy happiness.

    Science.gov (United States)

    Nisslé, Sonja; Bschor, Tom

    2002-01-01

    Life event research examines the effect of life events on the course of psychiatric diseases, but the published literature considers almost only negative events. We describe the cases of two female patients who had to be hospitalized for depression after lottery winnings of over 1M DM. The 4-year follow-up shows a good outcome in both patients. Case analyses suggest that in both patients, winning was a life event relevant to the development of the depressive episode. Desirable life events might influence the course of a psychiatric illness just as negative events do. (Int J Psych Clin Pract 2002; 6: 183-186). PMID:24945208

  1. BMC Ecology image competition 2014: the winning images.

    Science.gov (United States)

    Harold, Simon; Henderson, Caspar; Baguette, Michel; Bonsall, Michael B; Hughes, David; Settele, Josef

    2014-08-29

    BMC Ecology showcases the winning entries from its second Ecology Image Competition. More than 300 individual images were submitted from an international array of research scientists, depicting life on every continent on earth. The journal's Editorial Board and guest judge Caspar Henderson outline why their winning selections demonstrated high levels of technical skill and aesthetic sense in depicting the science of ecology, and we also highlight a small selection of highly commended images that we simply couldn't let you miss out on.

  2. The Exploitation of USB Drivers Based on WinDriver%基于WinDriver的USB驱动程序开发

    Institute of Scientific and Technical Information of China (English)

    杨新友; 邹岚; 钟建军

    2015-01-01

    USB Interface has become the most important peripheral equipment extended interface of personal computer with the de⁃velopment of computer technology. But in Windows operating system, cannot operate on hardware interface directly, so must use drivers as bridge. The comparison analysis of USB driver development methods is given in the paper, obtaining advantages, disad⁃vantages and adaptation situation of different method. USB drivers based on WinDriver further research. The architecture of equip⁃ment drivers using WinDriver is analysised, and the development step and working flow of USB drivers based on WinDriver is giv⁃en in the paper.%随着计算机技术的更新换代,USB接口已经成为个人计算机上最重要的外部设备扩展接口,但Windows操作系统中,通常采用驱动程序作桥梁。文章对USB驱动程序开发的方法进行了对比分析,得出各种方法的优缺点和适应情况。重点对基于WinDriver的USB驱动程序开发进行了深入研究,分析了WinDriver开发设备驱动程序时的体系结构,给出了基于WinDriver的USB驱动程序的开发步骤和具体工作流程。

  3. Abstinence and Relapse Rates Following a College Campus-Based Quit & Win Contest

    Science.gov (United States)

    Thomas, Janet L.; An, Larry; Luo, Xianghua; Scherber, Robyn M.; Berg, Carla J.; Golden, Dave; Ehlinger, Edward P.; Murphy, Sharon E.; Hecht, Stephen S.; Ahluwalia, Jasjit S.

    2010-01-01

    Objective: To conduct and evaluate Quit & Win contests at 2 2-year college and 2 4-year university campuses. Participants: During Spring semester, 2006, undergraduates (N = 588) interested in quitting smoking signed up for a Quit & Win 30-day cessation contest for a chance to win a lottery prize. Methods: Participants (N = 588) completed a…

  4. Windows Calorimeter Control (WinCal) program computer software design description

    International Nuclear Information System (INIS)

    The Windows Calorimeter Control (WinCal) Program System Design Description contains a discussion of the design details for the WinCal product. Information in this document will assist a developer in maintaining the WinCal system. The content of this document follows the guidance in WHC-CM-3-10, Software Engineering Standards, Standard for Software User Documentation

  5. 新版GMP与Simatic WinCC%The New Version of GMP and Simatic WinCC

    Institute of Scientific and Technical Information of China (English)

    孙鸿祥

    2011-01-01

    介绍新版GMP发布的背景及对制药行业自动化系统提出的新要求。GMP认证规范以及Simatic WinCC对于FDA 21 CFR Part 11法规的遵从情况。%This essay maily describe the background of new released GMP and fresh demand on automation system of pharmaceutical industry.The certification specifications of GMP and compliance response FDA 21 CFR Part 11 for Simatic WinCC are introduced in detail.

  6. Assessing carbon stocks and modelling win-win scenarios of carbon sequestration through land-use changes

    Energy Technology Data Exchange (ETDEWEB)

    Ponce-Hernandez, R.; Koohafkan, P.; Antoine, J. (eds.)

    2004-07-01

    This publication presents a methodology and software tools for assessing carbon stocks and modelling scenarios of carbon sequestration that were developed and tested in pilot field studies in Mexico and Cuba. The models and tools enable the analysis of land use change scenarios in order to identify in a given area (watershed or district) land use alternatives and land management practices that simultaneously maximize food production, maximize soil carbon sequestration, maximize biodiversity conservation and minimize land degradation. The objective is to develop and implement 'win-win' options that satisfy the multiple goals of farmers, land users and other stakeholders in relation to food security, carbon sequestration, biodiversity and land conservation.

  7. FXR agonist activity of conformationally constrained analogs of GW 4064

    Energy Technology Data Exchange (ETDEWEB)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce; (GSKNC)

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  8. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  9. Exploring prospects of β3-adrenoceptor agonists and inverse agonists for colon mobility control

    Directory of Open Access Journals (Sweden)

    Maria Grazia Perrone

    2013-07-01

    Full Text Available Inverse agonists are useful active ingredient of drugs clinically used to treat diseases mainly involving receptors endowed with non-endogenous agonist induced activity (constitutive or basal activity. SP-1e and SP-1g are the first two potent and highly selective β3-adrenoceptor inverse agonists [EC50=181 nM (IA=- 64% and 136 nM (IA=-73%, respectively], which their peculiar activity seems due to the absolute configurations of the two stereogenic centres present in each molecule. Rat proximal colon motility measurements allowed their further pharmacological characterization and pA2 values determination by Schild analysis (7.89 and 8.16, respectively. The purpose of our work is a further characterization of our novel β3-adrenoceptor agonists (SP-1a-d, SP-1f,1h and inverse agonists (SP-1e and SP-1g on rat proximal colon motility and a confirmation of their inverse agonist nature in a more complex system like the functional test on rat proximal colon. Male Wistar rats segment of the proximal colon were placed in organ baths containing Krebs solution. Muscle tension was recorded isotonically. Cumulative β3-AR agonists doses experiments were performed for each test compound: isoprenaline, BRL37344, SP-1a-d, SP-1f and SP-1h were dissolved in Krebs. The EC50 values of each agonists and pA2 of inverse agonists were determined. SP- 1a-d, SP-1f and SP-1h in rat colon have a muscle relaxing effect thus confirming their partial agonist activity found in CHO-K1 cell line. SP-1e and SP-1g behaved as antagonists with pA2 values of 7.89 and 8.16, respectively. In conclusion, experiments carried out by using isolated rat proximal colon allowed us to determine the pA2 values of the two β3-AR inverse agonists and add knowledge on the behavior of a novel set of compounds and their possible value as agents useful whenever is necessary to also control the colon motility.

  10. Blackboard Wins Payment from Competitor in Patent Case

    Science.gov (United States)

    Mangan, Katherine

    2008-01-01

    A federal jury in Texas awarded Blackboard Inc. $3.1-million last month, saying that a smaller Canadian competitor, Desire2Learn Inc., had infringed Blackboard's patent for a system of delivering course materials online. The case has been closely watched by campus-technology officials, many of whom feared that a Blackboard win could stifle…

  11. Interior design students win two IDEC Student Design Competition awards

    OpenAIRE

    Watson-Bloch, Cathy

    2005-01-01

    Interior Design students in the School of Architecture + Design at Virginia Tech won two of the four awards presented in the 2004-2005 Interior Design Educators Council (IDEC) Student Design Competition. Winners were selected at the International IDEC Conference in Savannah, Ga. with Virginia Tech Interior Design students winning second place and honorable mention.

  12. Tight Focus on Instruction Wins Texas District Prize

    Science.gov (United States)

    Maxwell, Lesli A.

    2009-01-01

    It took a while for four-time finalist Aldine, Texas, to win the Broad Prize for Urban Education. But it took even longer to craft the system that ultimately put the district over the top. Educators in Aldine district have been working for more than a decade to refine their "managed instruction" system. Reviewers examined how the school district,…

  13. Method for the unmanned winning of thin, flat coal strata

    Energy Technology Data Exchange (ETDEWEB)

    Levkovich, P.Ye.; Bratishcheva, L.L.; Kiselev, Ye.I.; Savich, N.S.; Tverezyy, Yu.F.

    1981-09-05

    The purpose of the invention is to reduce the coal losses in interchamber pillars through their partial liquidation. The formulated purpose is achieved through the fact that the back fill of the rock into the chamber is accomplished by using one branch of drives and the winning of the coal from the interchamber pillars is done simultaneously using the second branch of the drives.

  14. Winning in straight sets helps in Grand Slam tennis

    NARCIS (Netherlands)

    Goossens, Dries R.; Kempeneers, Jurgen; Koning, Ruud H.; Spieksma, Frits C. R.

    2015-01-01

    In this contribution, we study whether fatigue resulting from the previous match affects a player's chances of winning his (or her) next match in Grand Slum tennis. We measure relative fatigue levels of two opponents by looking at the difference in number of sets played in their previous match. We d

  15. Win, Women, and Money: Collegiate Athletics Today and Tomorrow.

    Science.gov (United States)

    Nyquist, Ewald B.

    1979-01-01

    Problems associated with collegiate athletics involve winning at any cost, accommodating women, and financing sports in an era of declining resources and rising costs. Abuses in athletics programs, presidential responsibility, research of the problems and its results, and predictions for the future are examined with regard to these issues. (JMD)

  16. Engineering students win autonomous vehicle competition for third year

    OpenAIRE

    Crumbley, Liz

    2006-01-01

    For the third year in a row, the Virginia Tech College of Engineering's Autonomous Vehicle Team swept the international Intelligent Ground Vehicle Competition (IGVC), winning best and second-best overall and placing first in the three top event categories. The team of mechanical engineering (ME) students also was awarded $15,000 in prize money.

  17. Researcher for Virginia Tech program wins Nobel Prize

    OpenAIRE

    Virginia Tech News

    2009-01-01

    The first woman to win a Nobel Prize in economics is a researcher for a Virginia Tech-managed international program. Elinor Ostrom has won a share of the 2009 prize based on her work on how community institutions can prevent conflict.

  18. Nobel Prize-winning economist to speak on Oct. 3

    OpenAIRE

    Doss, Catherine

    2009-01-01

    Nobel Prize winning economist Eric Maskin, professor of social science at the Institute for Advanced Study, Princeton, will present "Mechanism Design: How to Implement Social Goals," on Saturday, Oct. 3 at 2 p.m. in Pamplin Hall Room 1045 on the Virginia Tech campus.

  19. Liquid Biofuels: We Lose More than We Win

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Hedegaard, Karsten; Thyø, Kathrine;

    2013-01-01

    purpose will imply a loss of alternative uses of the same biomass. If the lost alternatives are, then, significantly more efficient as well as economically more attractive in fossil fuels substitution and CO2 reduction, we lose more than we win. It is our claim that this is the case for most liquid...

  20. Winning Facebook - and the Rest of the World?

    DEFF Research Database (Denmark)

    Hoff, Jens Villiam; Hansen, Kasper Møller; Schwartz, Sander Andreas;

    2014-01-01

    This article presents a study of nine leading candidates’ communication on Facebook during the parliament election campaign in Denmark in fall 2011. It relates their communication to the historical use of social media in Denmark by politicians, to Danish candidate campaign communication in general...... conclude that certain types of content may win Facebook, but the election itself is still largely won through TV....

  1. WinDAM C earthen embankment internal erosion analysis software

    Science.gov (United States)

    Two primary causes of dam failure are overtopping and internal erosion. For the purpose of evaluating dam safety for existing earthen embankment dams and proposed earthen embankment dams, Windows Dam Analysis Modules C (WinDAM C) software will simulate either internal erosion or erosion resulting f...

  2. The Probability of Winning a Lotto Jackpot Twice.

    Science.gov (United States)

    Noone, Emeric T., Jr.

    2000-01-01

    Proposes lotto games as a source of problems and exercises for classroom activities as well as applications of basic probability concepts in a practical setting which leads to a greater understanding of the remote chance anyone has of winning a lottery game. (KHR)

  3. The Sport League's Dilemma : Competitive Balance versus Incentives to Win

    NARCIS (Netherlands)

    Palomino, F.A.; Rigotti, L.

    2000-01-01

    We analyze a dynamic model of strategic interaction between a professional sport league that organizes a tournament, the teams competing to win it, and the broadcasters paying for the rights to televise it.Teams and broadcasters maximize expected profits, while the league's objective may be either t

  4. WinKKS - the management system for cathodic protection; WinKKS - Das Fuehrungssystem fuer den kathodischen Korrosionsschutz

    Energy Technology Data Exchange (ETDEWEB)

    Froehling, D. [PRO DV Software AG, Dortmund (Germany)

    2002-07-01

    The described software solution WinKKS serves the purpose to integrate the systems required in the field of cathodic protection. Particularly, and in addition to common measurement applications, these are geographic information systems (GIS) and enterprise resource planning (ERP) systems that have been introduced by many utility companies during essential modernisations and reorganisations. As standard products, these applications can only insufficiently meet the demands of cathodic protection. Besides of this integrational aspect, WinKKS features a lot of analysis options specific to cathodic protection. (orig.) [German] Die beschriebene Software-Loesung WinKKS dient der Integration der im Bereich des kathodischen Korrosionsschutzes benoetigten Systeme. Neben den ueblichen Messanwendungen sind dies vor allem die im Zuge von notwendigen Modernisierungen und Restrukturierungen bei vielen Energieversorgungsunternehmen eingefuehrten Geografischen Informationssysteme (GIS) und Betriebsfuehrungssysteme (ERP, Enterprise Resource Planning), die als Standardprodukte den Belangen des KKS nur unzureichend gerecht werden koennen. Zusaetzlich zu dieser Integrationsleistung bietet WinKKS eine Fuelle von KKS-spezifischen Auswertungsmoeglichkeiten. (orig.)

  5. Recent advances in the discovery of alpha1-adrenoceptor agonists.

    Science.gov (United States)

    Bishop, Michael J

    2007-01-01

    The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve. This review will focus on recent advances in the discovery, development and clinical utility of subtype-specific alpha(1) agonists as well as contributions to our understanding of agonist-receptor interactions.

  6. Effects of cannabinoid-1 receptor on pancreatic beta-cell function in obese rats%大麻素受体1激动剂和抑制剂对肥胖大鼠胰岛β细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    樊大贝; 秦贵军; 余勤; 贾贺堂; 马晓君; 闫晓洁

    2009-01-01

    目的 研究大麻素受体1对肥胖大鼠胰岛β细胞功能的影响.方法 30只8周龄清洁级健康雄性SD大鼠,体质最150~200 g,采用数字表法随机分至正常对照组(n=6)和肥胖组(n=24).正常对照组给予普通鼠饲料喂养,肥胖组给予高脂鼠饲料喂养.8周后,与正常对照组比较,肥胖纽大鼠体质量增加36%,总胆固醇增加52%,提示24只肥胖大鼠制作成功.肥胖大鼠以数字表法随机分至生理盐水组(n=8)、WIN55212-2组(n=8)、AM251组(n=8).测定大鼠体质量、血脂、胰岛素、胰岛素原等指标,采用高葡萄糖钳央试验评价胰岛β细胞功能和胰岛素敏感性.采用LSD检验进行统计学分析.结果 腹腔注射药物2周后,生理盐水组、WIN55212-2组体质量、血脂、卒腹血糖、C肽、胰岛素、胰岛素原、胰岛素原/C肽、胰岛素原/胰岛素、胰岛素10~90 min分泌量及胰岛素最大分泌量均高于正常对照组(P<0.05),WIN55212-2组上述指标均高于生理盐水组(P<0.05),AM251组上述指标均低于生理盐水组和WIN55212-2组(P<0.05).生理盐水组、WIN55212-2组胰岛素0~10 min分泌量、匍萄糖输注率低于正常对照组(P<0.05),WIN55212-2组胰岛素0~10 min分泌量、葡萄糖输注率低于生理盐水组(P<0.05).AM251组胰岛素0~10 min分泌量、葡萄糖输注率高于生理盐水组和WIN55212-2组(P<0.05).结论 大麻素受体1受体激动可增加肥胖大鼠体质量,升高血脂水平,加重胰岛素抵抗和胰岛β细胞功能减退,抑制大麻素受体1可逆转此效应.%Objective To investigate the effects of cannabinoind-1 receptor (CB1R) on pancreatic beta-cell function in obese rats. Methods A total of 30 male 8-week healthy SD rats were randomly assigned to the control group (n=6) or obesity group (n=24). After 8 weeks' intervention, 24 obese rats were randomly divided into the saline group (n=8), WIN55212-2 injection group (n=8) and AM251 injection group (n=8). The body weight

  7. Signal Use by Octopuses in Agonistic Interactions.

    Science.gov (United States)

    Scheel, David; Godfrey-Smith, Peter; Lawrence, Matthew

    2016-02-01

    Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits. PMID:26832440

  8. A study on the promotion of cooperation with 'women in nuclear (WIN)- global'

    Energy Technology Data Exchange (ETDEWEB)

    Min, Byung Joo; Kim, K. R.; Kim, D. Y. [and others

    2001-04-01

    International collaboration with WIN-Global. 1) Evaluation on current status for the foundation of WIN-Korea and investigation on the 1st to 8th WIN-Global conferences for the arrangement of 9th WIN-Global conferences 2) Manifestation on the roles of WIN-Korea and WIN-Global 3) Encouragement of active participation for WIN-Global activies -Establishment of internet net working for effective communication through the internet net working between women in science in Korea and other foreign countries. 1) Preparation and Organization of Women in Korea 2) Foundation of WIN-Korea Home Page in Net 3) Assembly of data for the net work construction in Korea - Enhancement of international cooperation between WIN-Korea and WIN-Global 1) Invitation of 9th WIN-Global Conference in Seoul, Korea 2) Enrollment of one of the Executives and Strengthening the activity of WIN-Korea as member of Board members 3) Characterization on main movements of WIN-Global through the active participation in international activities. - Arrangement for the 9th WIN-Global conference 1) Opperation of Organizing Committee and Supporting Committee and Secretariat 2) Supporting the 9th WIN-Global Confernce.

  9. WinFood data from Kenya and Cambodia

    DEFF Research Database (Denmark)

    Owino, Victor O; Skau, Jutta Kloppenborg Heick; Omollo, Selina;

    2015-01-01

    during randomized, controlled trials (WinFood Study) designed to assess the efficacy of locally produced complementary foods based on traditional animal-source foods (edible termites and spiders) to support growth and nutritional status in Kenyan and Cambodian infants. METHODS: In a randomized......, controlled design, infants received WinFood or corn-soy blend (CSB) for 9 months from 6 to 15 months of age. Lean mass accrual and blood nutrition indicators (lipid profile, iron and zinc status) were measured cross-sectionally at 9 and 15 months of age, respectively. Lean mass was determined by measuring...... deuterium oxide enrichment in saliva samples following a standard dose of deuterium solution (0.5 g/kg body weight) to infants. Blood nutrition indicators were determined following the drawing of 3 mL of blood by venipuncture. RESULTS: Challenges included rapid depletion of food rations, high rate of loss...

  10. WINNING HEARTS AND MINDS IN THE NAMIBIAN BORDER WAR

    Directory of Open Access Journals (Sweden)

    Lieneke Eloff de Visser

    2011-08-01

    Full Text Available During the Namibian border war, South African counterinsurgency doctrine acknowledged the importance of securing the allegiance and cooperation of the population. This article demonstrates that, in the operational zone, the responsibility of winning the hearts and minds of the Namibian people largely fell to the SADF (South African Defence Force. Although the SADF dedicated considerable resources to this task, these efforts were often at cross-purposes with those of institutions in the political, police and administrative domains. In addition, there was a lack of unity and purpose within the SADF. This article argues that lack of unity between and within the different domains undermined the effort at winning the hearts and minds of the Namibian population, and must at least partly have contributed to SWAPO´s victory in the 1989 elections.

  11. Optimizing Distribution Problems using WinQSB Software

    Directory of Open Access Journals (Sweden)

    Daniel Mihai Amariei

    2015-07-01

    Full Text Available In the present paper we are presenting a problem of distribution using the Network Modeling Module of the WinQSB software, were we have 5 athletes which we must assign the optimal sample, function of the obtained time, so as to obtain the maximum output of the athletes. Also we analyzed the case of an accident of 2 athletes, the coupling of 3 athletes with 5 various athletic events causing the maximum coupling, done using the Hungarian algorithm.

  12. Winning end users active support to demand side response

    Energy Technology Data Exchange (ETDEWEB)

    Osorio, Jose [Rede Electrica Nacional, S.A., Lisbon (Portugal); Estanqueiro, Ana [Laboratorio Nacional de Energia e Geologia (LNEG), Lisbon (Portugal)

    2012-07-01

    While objectives proposed for Smart Grids and Smart metering may seem to be able to win easily end user's supports, a considerable amount of studies on social behavior concerning energy efficiency and sustainability show the gap between the values people would like to fulfill and their real life performance. As TSOs envision here a source of System Ancillary Services, measures to make the source really dependable, so that an adequate market design may really work are pointed out. (orig.)

  13. Does it pay to win the Stanley Cup?

    OpenAIRE

    Derek Lanoue

    2015-01-01

    Yes, it does indeed pay to win the Stanley Cup (SC). Professional sports offer a unique opportunity to examine the relationship between a player’s salary and their performance. Salary statistics have become widely available and enable individual performance scrutiny in relation to remuneration level. There is an extensive literature explaining which factors in‡uence the players’ salary in the National Hockey League (NHL), using data sets from different seasons and including various performanc...

  14. BMC Ecology Image Competition 2015: the winning images.

    Science.gov (United States)

    Potenski, Catherine J; Porzecanski, Ana Luz; Baguette, Michel; Clobert, Jean; Hughes, David; Settele, Josef

    2015-07-29

    For the third time, BMC Ecology is delighted to announce the winners of our Image Competition. This year featured entries from all over the world and showcased not only the creativity and talent of the participants, but also the exquisite beauty and diversity of our planet. We are pleased to present the winning selections of the editorial board of the journal and guest judge Dr. Ana Luz Porzecanski, as well as some highly commended images that are sure to impress.

  15. Winning end users active support to demand side response

    OpenAIRE

    Osório, José; Estanqueiro, Ana

    2012-01-01

    While objectives proposed for Smart Grids and Smart metering may seem to be able to win easily end user’s supports, a considerable amount of studies on social behavior concerning energy efficiency and sustainability show the gap between the values people would like to fulfill and their real life performance. As TSOs envision here a source of System Ancillary Services, measures to make the source really dependable, so that an adequate market design may really work are pointed out.

  16. The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Song, Lu; Yang, Xinxin; Ma, Yaping; Wu, Na; Liu, Zhenguo

    2014-01-01

    The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an effective drug for treating dopamine depletion-induced Parkinson's disease (PD). However, long-term administration of L-DOPA produces motor complications. L-DOPA has also been found to modify the two key signaling cascades, protein kinase A/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), in striatal neurons, which are thought to play a pivotal role in forming motor complications. In the present study, we tested the possible effect of a CB1 cannabinoid receptor agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo. Intermittent L-DOPA administration for 3 weeks induced motor fluctuation in a rat model of PD induced by intrastriatal infusion of dopamine-depleting neurotoxin 6-hydroxydopamine (6-OHDA). A single injection of a CB1 cannabinoid receptor agonist WIN-55,212-2 had no effect on L-DOPA-induced motor fluctuation. However, chronic injections of WIN-55,212-2 significantly attenuated abnormal behavioral responses to L-DOPA in 6-OHDA-lesioned rats. Similarly, chronic injections of WIN-55,212-2 influence the L-DOPA-induced alteration of DARPP-32 and ERK1/2 phosphorylation status in striatal neurons. These data provide evidence for the active involvement of CB1 cannabinoid receptors in the regulation of L-DOPA action during PD therapy.

  17. Effects of Repeated Electroacupuncture on Gene Expression of Cannabinoid Receptor-1 and Dopamine 1 Receptor in Nucleus Accumbens-Caudate Nucleus Region in Inflammatory-pain Rats%反复电针对佐剂性关节炎大鼠伏隔核-尾状核区大麻素CB1受体与多巴胺Dl受体基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    寿鉴; 赵颖倩; 徐鸣曙; 葛林宝

    2011-01-01

    Objective To observe the effect of repeated electroacupuncture (EA) on the expression of cannabinoid receptor-1 (CB 1 ) mRNA and dopamine 1 receptor (D 1 ) mRNA in Nucleus Accumbens (NAC)-Caudate Nucleus (CN) region in inflammatory-pain rats, so as to study its underlying mechanism in analgesia. Methods A total of 30 SD rats were randomized into normal control, model, EA, EA + AM 251 and WIN 552 12-2 groups, with 6 cases in each group. EA (2 Hz/100 Hz, 1 - 3 mA)was applied to "Zusanli"(ST 36) and "Kunlun"(BL 60) for 30 min, once every other day, and 4 sessions all together. Arthritis model was established by injection of Freund's complete adjuvant 0.05 mL in the rat's left ankle. Thermal pain threshold (paw withdrawal latency, PWL) was detected before and after modeling and after repeated EA and/or intraperitoneal injection of AM 251 (an inverse antagonist at the CB 1 cannabinoid receptor, 0. 1 mg/1 00 g) and WIN 55212-2 (a potent cannabinoid receptor agonist, 0.2 mg/100 g). The expression of CB 1 receptor mRNA and D 1 receptor mRNA in the NAC-CN region was measured by real time fluorescence quantitative-polymerase chain reaction. Results Compared with the control group, the pain threshold values of the model group was decreased significantly (P<0.01). In comparison with the model group, the pain threshold values of the EA group and WIN 55212-2 group were increased considerably on day 10 (P<0.01). No significant differences were found between the EA+AM 251 and model groups and between the EA and WIN 55212-2 groups in PWL after the treatment (P>0.05).Compared with the control group, both CB 1 R mRNA and D 1 R mRNA expression levels in the model group were increased slightly, while in comparison with the model group and EA+ AM 251 group, CB 1 R mRNA and D 1 R mRNA expression levels in the EAgroup and WIN 55212-2 group were upregulated obviously. No significant differences were found between the EA+ AM 251 and model groups and between the EA and WIN 55212-2

  18. Win-Wind. Simulation of regional decision making on wind energy; Win-Wind. Regionale besluitvorming over wind gesimuleerd

    Energy Technology Data Exchange (ETDEWEB)

    De Jong, M.I.C.A. [HASKONING Ingenieurs- en Architectenbureau, Nijmegen (Netherlands)

    1999-03-01

    From 11-13 November 1998 3 regional debates on the use of wind energy were organized by HASKONING and Resource Analysis by order of the Netherlands Agency for Energy and the Environment (Novem). Use has been made of the simulation tool Win-Wind: a role play, supported by a computer program, including maps and information on fictive, though realistic, projects in the field of wind power and policies with respect to the infrastructure and the environment (nature) in the Netherlands. The dynamic performance and the flexibility of the computer program (adjustments can be made immediately and the results can be discussed at the end of the debate) make Win-Wind an excellent tool, not only to discuss the political development and site selection for wind energy and of wind turbines on a provincial and regional level, but also to discuss other subjects with respect to spatial planning.

  19. A win-win marginal rent analysis for operator and consumer under battery leasing mode in China electric vehicle market

    Energy Technology Data Exchange (ETDEWEB)

    Li Zhe, E-mail: lizhe1212@gmail.com [State Key Laboratory of Automotive Safety and Energy, Tsinghua University, Beijing 100084 (China); Ouyang Minggao, E-mail: ouymg@tsinghua.edu.cn [State Key Laboratory of Automotive Safety and Energy, Tsinghua University, Beijing 100084 (China)

    2011-06-15

    Recently battery leasing has been introduced into the market by automobile manufacturers and power suppliers due to its potential to reduce the purchase cost of electric vehicles (EVs). However, the profit prospect of battery leasing is still uncertain. This paper takes the views of both the operators and consumers and calculates the 'win-win' marginal rent, which not only ensures the profitability of operators, but also allows consumers a lower expenditure than using Internal combustion engine vehicles (ICVs) and EVs with embedded batteries. Battery cost, vehicle weight, gasoline and electricity price, and the discount rate have impacts on the rent. Battery cost plays a dominant role and a battery cost >5 Yen /W h fails to enable the survival of battery leasing to all types of EVs. Battery leasing would be more competitive when focusing on heavier EVs. At least one of the three thresholds is required for the existence of rent pricing range for a 1000 kg EV: gasoline retail price >6 Yen /L, electricity price <0.6 Yen /kW h, or the discount rate <7%. Typically, the feasible battery rent range is 0.34-0.38 Yen /W h/year for a 1000 kg EV under the present battery cost 2 Yen /W h and China current gasoline and electricity prices. - Highlights: > Rent pricing for EV battery leasing must obey win-win rule for BLO and consumers. > Rent is affected by battery cost, vehicle weight, energy price and discount rate. > Battery cost plays dominant role for the BLO survival as described in '5-3-2' Law. > Heavier EVs are more suitable for battery leasing when battery cost is high. > The profitability of BLO is sensitive to the price of gasoline and electricity.

  20. A win-win marginal rent analysis for operator and consumer under battery leasing mode in China electric vehicle market

    International Nuclear Information System (INIS)

    Recently battery leasing has been introduced into the market by automobile manufacturers and power suppliers due to its potential to reduce the purchase cost of electric vehicles (EVs). However, the profit prospect of battery leasing is still uncertain. This paper takes the views of both the operators and consumers and calculates the 'win-win' marginal rent, which not only ensures the profitability of operators, but also allows consumers a lower expenditure than using Internal combustion engine vehicles (ICVs) and EVs with embedded batteries. Battery cost, vehicle weight, gasoline and electricity price, and the discount rate have impacts on the rent. Battery cost plays a dominant role and a battery cost >5 Yen /W h fails to enable the survival of battery leasing to all types of EVs. Battery leasing would be more competitive when focusing on heavier EVs. At least one of the three thresholds is required for the existence of rent pricing range for a 1000 kg EV: gasoline retail price >6 Yen /L, electricity price <0.6 Yen /kW h, or the discount rate <7%. Typically, the feasible battery rent range is 0.34-0.38 Yen /W h/year for a 1000 kg EV under the present battery cost 2 Yen /W h and China current gasoline and electricity prices. - Highlights: → Rent pricing for EV battery leasing must obey win-win rule for BLO and consumers. → Rent is affected by battery cost, vehicle weight, energy price and discount rate. → Battery cost plays dominant role for the BLO survival as described in '5-3-2' Law. → Heavier EVs are more suitable for battery leasing when battery cost is high. → The profitability of BLO is sensitive to the price of gasoline and electricity.

  1. GLP-1 agonists for type 2 diabetes

    DEFF Research Database (Denmark)

    Jespersen, Maria J; Knop, Filip K; Christensen, Mikkel

    2013-01-01

    Within recent years, glucagon-like peptide 1 receptor agonists (GLP-1-RA) have emerged as a new treatment option for type 2 diabetes. The GLP-1-RA are administered subcutaneously and differ substantially in pharmacokinetic profiles. AREAS COVERED: This review describes the pharmacokinetics...... and legal documents in the form of assessment reports from the European Medicines Agency and the United States Food and Drug Administration. EXPERT OPINION: GLP-1-based therapy combines several unique mechanisms of action and have the potential to gain widespread use in the fight against diabetes...

  2. Expressing determination: From ENS programme 'Women and nuclear energy' to WIN

    International Nuclear Information System (INIS)

    WIN is an international association of women working professionally in the fields of nuclear energy and radiation application and willing to devote time to public information. It is established as non-profit making. WIN'S working language is English. WIN aims to contribute to objectively informing the public, especially women, on nuclear energy and radiation, in particular by: meeting regularly to exchange ideas and experiences between countries' WIN information groups, establishing country WIN groups in nuclear countries as widely as practical, supporting each other across borders, working out shared information techniques and information materials for international use. WIN is open to female nuclear and radiation professionals and academics as well as communications specialists, from all over the world, pledged to adhere to the goals of this Charter. The first WINFO Quarterly Newsletter of Women in Nuclear has been published

  3. Study on the Winning Probability for a Bid in Procurement Combinational Auction with Tree Structure

    Institute of Scientific and Technical Information of China (English)

    CHEN Jian; HUANG He

    2004-01-01

    In this paper, the processes to determine winning probability for the correspondingbidder's deterministic bid are presented. The analysis of the winning probability is Crucial for studying the bidding equilibria and designing the mechanism of procurement combinational auctions (CAs), and it also provides the decision making support for bidders who are in commercial synergies surrounding.Finally, an example is used to illustrate the feasibility and detailed processes of calculating winning probability.

  4. Money and Mental Wellbeing: A Longitudinal Study of Medium-Sized Lottery Wins

    OpenAIRE

    Gardner, Jonathan; Oswald, Andrew J.

    2006-01-01

    One of the famous questions in social science is whether money makes people happy. We offer new evidence by using longitudinal data on a random sample of Britons who receive medium-sized lottery wins of between £1000 and £120,000 (that is, up to approximately U.S. $200,000). When compared to two control groups — one with no wins and the other with small wins — these individuals go on eventually to exhibit significantly better psychological health. Two years after a lottery win, th...

  5. An explicit classical strategy for winning a {{CHSH}}_{q} game

    Science.gov (United States)

    Pivoluska, Matej; Plesch, Martin

    2016-02-01

    A CHSH q game is a generalization of the standard two player CHSH game, with q different input and output options. In contrast to the binary game, the best classical and quantum winning strategies are not known exactly. In this paper we provide a constructive classical strategy for winning a CHSH q game, with q being a prime. Our construction achieves a winning probability better than \\frac{1}{22}{q}-\\frac{2{3}}, which is in contrast with the previously known constructive strategies achieving only the winning probability of O({q}-1).

  6. Strategies for designing synthetic immune agonists.

    Science.gov (United States)

    Wu, Tom Y-H

    2016-08-01

    Enhancing the immune system is a validated strategy to combat infectious disease, cancer and allergy. Nevertheless, the development of immune adjuvants has been hampered by safety concerns. Agents that can stimulate the immune system often bear structural similarities with pathogen-associated molecular patterns found in bacteria or viruses and are recognized by pattern recognition receptors (PRRs). Activation of these PRRs results in the immediate release of inflammatory cytokines, up-regulation of co-stimulatory molecules, and recruitment of innate immune cells. The distribution and duration of these early inflammatory events are crucial in the development of antigen-specific adaptive immunity in the forms of antibody and/or T cells capable of searching for and destroying the infectious pathogens or cancer cells. However, systemic activation of these PRRs is often poorly tolerated. Hence, different strategies have been employed to modify or deliver immune agonists in an attempt to control the early innate receptor activation through temporal or spatial restriction. These approaches include physicochemical manipulation, covalent conjugation, formulation and conditional activation/deactivation. This review will describe recent examples of discovery and optimization of synthetic immune agonists towards clinical application. PMID:27213842

  7. 大麻素CB1受体对大鼠视网膜神经节细胞诱发动作电位的作用%Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    蒋淑霞; 李倩; 王霄汉; 李芳; 王中峰

    2013-01-01

    Activation of cannabinoid CB1 receptors (CB 1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels.The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques.The results showed that under current-clamped condition perfusing WIN55212-2 (WIN,5 μmol/L),a CB1R agonist,did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs.In the presence of cocktail synaptic blockers,including excitatory postsynaptic receptor blockers CNQX and D-APV,and inhibitory receptor blockers bicuculline and strychnine,perfusion of WIN (5 μmol/L)hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA).Phaseplane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN.However,WIN significantly decreased +dV/dtmax and-dV/dtmax of action potentials,suggestive of reduced rising and descending velocities of action potentials.The effects of WIN were reversed by co-application of SR141716,a CB1R selective antagonist.Moreover,WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked.These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.%激活大麻素CB1受体(CB1Rs)通过调控多种离子通道,从而调节脊椎动物视网膜的功能.本文旨在利用膜片钳全细胞记录技术,在大鼠视网膜薄片上研究CB1Rs对神经节细胞兴奋性的作用.结果显示,在电流钳制状态下,灌流CB1R激动剂WIN55212-2 (WIN,5μmol/L)对神经节细胞的自发动作电位发放频率和静息膜电位均没有显著影响.在灌流液中加入CNQX,D-APV,bicuculline

  8. Early maternal deprivation and neonatal single administration with a cannabinoid agonist induce long-term sex-dependent psychoimmunoendocrine effects in adolescent rats.

    Science.gov (United States)

    Llorente, Ricardo; Arranz, Lorena; Marco, Eva-María; Moreno, Enrique; Puerto, Marta; Guaza, Carmen; De la Fuente, Mónica; Viveros, Maria-Paz

    2007-07-01

    Maternal deprivation [24h on postnatal day 9] might represent an animal model of schizophrenia and behavioural and neurochemical alterations observed in adulthood may be mediated by hippocampal impairments induced by abnormally increased glucocorticoids due to neonatal stress. We aimed to provide new data for psychoimmunoendocrine characterization of this animal model by evaluating its effects in adolescent rats of both genders. In previous studies we found that cannabinoid compounds counteracted the enhanced impulsivity of maternally deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed neuroprotective properties in neonatal rats. So, we hypothesised that this compound could counteract at least some of the detrimental effects that we expected to find in maternally deprived animals. Accordingly, the drug was administered immediately after the maternal deprivation period. Maternally deprived males showed significantly decreased motor activity in the holeboard and the plus-maze. The cannabinoid agonist induced, exclusively in males, a significant anxiogenic-like effect, which was reversed by maternal deprivation. In the forced swimming test, both treatments independently induced depressive-like responses. Maternal deprivation reduced immunological function whereas the drug exerted tissue-dependent effects on the immune parameters analysed. Maternally deprived females showed reduced corticosterone levels whereas the cannabinoid agonist increased hormone concentration in all groups. In general, the results show detrimental effects of both treatments as well as intriguing interactions, notably in relation to emotional behaviour and certain immunological responses.

  9. WinCC与Visual C的OPC通讯实现

    Institute of Scientific and Technical Information of China (English)

    王明月; 王松

    2012-01-01

      本文利用OPC接口实现了服务器WinCC组态软件和模型机Visual C++客户端的通讯,完成了两者之间的数据交换。详细介绍了Visual C++应用程序的代码实现过程,最终完成了OPC服务器与客户端的实时通讯。

  10. In Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable Development In Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable Development

    OpenAIRE

    Ignacy Sachs

    2010-01-01

    In Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable DevelopmentIn Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable Development

  11. Unique interaction pattern for a functionally biased ghrelin receptor agonist

    DEFF Research Database (Denmark)

    Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.;

    2011-01-01

    Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers co...

  12. Highly Potent, Chemically Stable Quorum Sensing Agonists for Vibrio Cholerae

    OpenAIRE

    Perez, Lark J; Karagounis, Theodora K.; Hurley, Amanda; Bassler, Bonnie L.; Semmelhack, Martin F.

    2013-01-01

    In the Vibrio cholerae pathogen, initiation of bacterial quorum sensing pathways serves to suppress virulence. We describe herein a potent and chemically stable small molecule agonist of V. cholerae quorum sensing, which was identified through rational drug design based on the native quorum sensing signal. This novel agonist may serve as a useful lead compound for the control of virulence in V. cholerae.

  13. The importance of β2-agonists in myocardial infarction

    DEFF Research Database (Denmark)

    Rørth, Rasmus; Fosbøl, Emil L; Mogensen, Ulrik M;

    2015-01-01

    PURPOSE: β2-Agonists are widely used for relief of respiratory symptoms. Studies so far have reported conflicting results regarding use of β2-agonists and risk of myocardial infarction (MI). Yet, coronary angiographical data and longitudinal outcomes data are sparse and could help explain...

  14. Combining GLP-1 receptor agonists with insulin

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Vilsbøll, T

    2013-01-01

    physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose......Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among......, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic...

  15. 建设“双赢”商标打造卓越品牌%Build an excellent brand by constructing win-win marks

    Institute of Scientific and Technical Information of China (English)

    张厚生

    2012-01-01

    安徽双赢再生资源集团把商标品牌建设作为提高集团核心竞争力、扩大无形资产的有效抓手。建设“双赢”商标,为集团发展注入知识产权动力,形成品牌价值,激发持续发展活力,赢得广阔的市场和无限的商机。%Anhui Win-win Recycling Resources Group made brand construction as an efficient approach to improve key competitive capability and expand invisible assets. By constructing the Win-win marks, it puts intellectual power into group development, benefits the brand construction, stimulates the sustainable vitality, and brings broad market and unlimited business op.portunities.

  16. WinCE系统UDP协议发送接收WAV文件%WinCE transmission system using UDP protocol to transmit and receive the WAV ifle

    Institute of Scientific and Technical Information of China (English)

    李华; 李付臣; 杨士富

    2014-01-01

    WinCE系统上使用UDP协议发送WAV格式的音频文件时,WinCE设备接收到的WAV声音文件是不完整的,导致声音文件无法播放。要处理这种现象需要对WAV文件的头文件进行处理,保证头文件的各标示位对应数据的正确性。%The use of the UDP protocol to send the WAV format audio ifles in the WinCE system, sound ifles WAV received the WinCE equipment is not complete, which led to the sound ifle could not be played. To deal with this phenomenon need to WAV ifle header ifle header ifle for processing, to ensure the correctness of the corresponding data label.

  17. Analysis of Elements of Award-Winning Dissertations in Education, 2005-2010

    Science.gov (United States)

    Foster, Charlotte E.

    2012-01-01

    The purpose of this study was to identify and compare common criteria and characteristics for award-winning dissertations utilized by prominent national educational organizations. Formal and informal criteria for award-winning dissertations were examined and compared to distinguish commonalities in the dissertations and award processes.…

  18. Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity

    NARCIS (Netherlands)

    Holst, R.J. van; Chase, H.W.; Clark, L.

    2014-01-01

    Frontostriatal circuitry is implicated in the cognitive distortions associated with gambling behaviour. 'Near-miss' events, where unsuccessful outcomes are proximal to a jackpot win, recruit overlapping neural circuitry with actual monetary wins. Personal control over a gamble (e.g., via choice) is

  19. EVALUATION OF THE LOADING CHARACTERISTICS OF THE EPA WINS PM 2.5 SEPARATOR

    Science.gov (United States)

    The loading characteristics of the USEPA WINS (Well Impactor Ninety Six) PM2.5 separator was an important design consideration during the separator's development. In recognition that all inertial separators eventually overload, the loading surface of the WINS was designed to be...

  20. The Orphan among Us: An Examination of Orphans in Newbery Award Winning Literature

    Science.gov (United States)

    Mattix, April A.

    2012-01-01

    Orphan stories in children's literature are rich and complex, and they have historically permeated the pages of children's books. The purpose of this study was to explore the use of orphans as protagonists in children's award-winning literature through content analysis. This study utilizes all the Newbery Award winning books…

  1. Teach for America and Teacher Ed: Heads They Win, Tails We Lose

    Science.gov (United States)

    Labaree, David

    2010-01-01

    Teach for America (TFA) is a marvel at marketing, offering elite college students a win-win option: by becoming corps members, they can do good and do well at the same time. Teacher education (TE) programs are in a hopeless position in trying to compete with TFA for prospective students. They cannot provide students with the opportunity to do…

  2. Design of a Pressure Control System with WinCC and PLC%基于WinCC和PLC的压力调节系统设计

    Institute of Scientific and Technical Information of China (English)

    万鑫森

    2013-01-01

    A method of pressure auto control is introduced,which uses WinCC configuration software and S7-200 series PLC. The process of parameter collection program with PLC,OPC date link and trendline configuration with WinCC is described in detail,with which the function of system parameter setup, trendline display, date record and memory are achieved on WinCC client. At last, the system is tested in simulated setting and the result shows that the pressure auto control of aerostst operates well.%介绍了一种采用WinCC组态软件和S7-200系列PLC实现压力自动调节的方法。详细描述了PLC参数采集编程、OPC数据链接、WinCC在线趋势组态的过程,并在WinCC客户端实现系统参数设置、在线趋势显示、数据记录和存储、报警提示等功能。最后,模拟运行测试的结果表明该系统很好的完成了浮空器的压力自动调节。

  3. Portion size me: plate-size induced consumption norms and win-win solutions for reducing food intake and waste.

    Science.gov (United States)

    Wansink, Brian; van Ittersum, Koert

    2013-12-01

    Research on the self-serving of food has empirically ignored the role that visual consumption norms play in determining how much food we serve on different sized dinnerware. We contend that dinnerware provides a visual anchor of an appropriate fill-level, which in turn, serves as a consumption norm (Study 1). The trouble with these dinnerware-suggested consumption norms is that they vary directly with dinnerware size--Study 2 shows Chinese buffet diners with large plates served 52% more, ate 45% more, and wasted 135% more food than those with smaller plates. Moreover, education does not appear effective in reducing such biases. Even a 60-min, interactive, multimedia warning on the dangers of using large plates had seemingly no impact on 209 health conference attendees, who subsequently served nearly twice as much food when given a large buffet plate 2 hr later (Study 3). These findings suggest that people may have a visual plate-fill level--perhaps 70% full--that they anchor on when determining the appropriate consumption norm and serving themselves. Study 4 suggests that the Delboeuf illusion offers an explanation why people do not fully adjust away from this fill-level anchor and continue to be biased across a large range of dishware sizes. These findings have surprisingly wide-ranging win-win implications for the welfare of consumers as well as for food service managers, restaurateurs, packaged goods managers, and public policy officials. PMID:24341317

  4. Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice

    Science.gov (United States)

    Wu, Mao-Cheng; Bing, Yan-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2016-01-01

    Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and cerebellar ataxia. In this study, we investigated the effect of ethanol on facial stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells (PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under voltage-clamp conditions, ethanol (300 mM) decreased the amplitude, half-width, rise time and decay time of facial stimulation-evoked outward currents in PCs. The ethanol-induced inhibition of facial stimulation-evoked outward currents was dose-dependent, with an IC50 of 148.5 mM. Notably, the ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1 agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway. These findings suggest that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs. PMID:27489024

  5. Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS.

    Science.gov (United States)

    Chen, Chao-Yin; Bonham, Ann C; Dean, Caron; Hopp, Francis A; Hillard, Cecilia J; Seagard, Jeanne L

    2010-12-01

    In prior studies, we found that activation of cannabinoid-1 receptors in the nucleus tractus solitarii (NTS) prolonged baroreflex-induced sympathoinhibition in rats. In many regions of the central nervous system, activation of cannabinoid-1 receptors presynaptically inhibits γ-aminobutyric acid (GABA) release, disinhibiting postsynaptic neurons. To determine if cannabinoid-1 receptor-mediated presynaptic inhibition of GABA release occurs in the NTS, we recorded miniature inhibitory postsynaptic currents in anatomically identified second-order baroreceptive NTS neurons in the presence of ionotropic glutamate receptor antagonists and tetrodotoxin. The cannabinoid-1 receptor agonists, WIN 55212-2 (0.3-30 μM) and methanandamide (3 μM) decreased the frequency of miniature inhibitory postsynaptic currents in a concentration-dependent manner, an effect that was blocked by the cannabinoid-1 receptor antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM 251, 5 μM). Importantly, depolarization of second-order baroreceptive neurons decreased the frequency of miniature inhibitory postsynaptic currents; an effect which was blocked by the cannabinoid-1 receptor antagonist. The data indicate that depolarization of second-order baroreceptive NTS neurons induces endocannabinoid release from the neurons, leading to activation of presynaptic cannabinoid-1 receptors, inhibition of GABA release and subsequent enhanced baroreflex signaling in the NTS. The data suggest that endocannabinoid signaling in the NTS regulates short-term synaptic plasticity and provide a mechanism for endocannabinoid modulation of central baroreflex control.

  6. Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice.

    Science.gov (United States)

    Wu, Mao-Cheng; Bing, Yan-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2016-01-01

    Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and cerebellar ataxia. In this study, we investigated the effect of ethanol on facial stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells (PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under voltage-clamp conditions, ethanol (300 mM) decreased the amplitude, half-width, rise time and decay time of facial stimulation-evoked outward currents in PCs. The ethanol-induced inhibition of facial stimulation-evoked outward currents was dose-dependent, with an IC50 of 148.5 mM. Notably, the ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1 agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway. These findings suggest that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs. PMID:27489024

  7. Toll-like receptor 2 agonists inhibit human fibrocyte differentiation

    Directory of Open Access Journals (Sweden)

    Maharjan Anu S

    2010-11-01

    Full Text Available Abstract Background In healing wounds, some monocytes enter the wound and differentiate into fibroblast-like cells called fibrocytes. Since Toll-like receptors (TLRs are present on monocytes, and pathogens that can infect a wound have and/or release TLR agonists, we examined whether TLR agonists affect fibrocyte differentiation. Results When human peripheral blood mononuclear cells (PBMCs were cultured with TLR3, TLR4, TLR5, TLR7, TLR8 or TLR9 agonists, there was no significant effect on fibrocyte differentiation, even though enhanced extracellular tumor necrosis factor (TNF-α accumulation and/or increased cell surface CD86 or major histocompatibility complex (MHC class II levels were observed. However, all TLR2 agonists tested inhibited fibrocyte differentiation without any significant effect on cell survival. Adding TLR2 agonists to purified monocytes had no effect on fibrocyte differentiation. However, some TLR2 agonists caused PBMCs to secrete a factor that inhibits the differentiation of purified monocytes into fibrocytes. This factor is not interferon (IFN-α, IFN-γ, interleukin (IL-12, aggregated immunoglobulin G (IgG or serum amyloid P (SAP, factors known to inhibit fibrocyte differentiation. TLR2 agonist-treated PBMCs secrete low levels of IL-6, TNF-α, IFN-γ, granulocyte colony-stimulating factor and tumor growth factor β1, but combinations of these factors had no effect on fibrocyte differentiation from purified monocytes. Conclusions Our results indicate that TLR2 agonists indirectly inhibit fibrocyte differentiation and that, for some TLR2 agonists, this inhibition involves other cell types in the PBMC population secreting an unknown factor that inhibits fibrocyte differentiation. Together, these data suggest that the presence of some bacterial signals can inhibit fibrocyte differentiation and may thus slow wound closure.

  8. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper. PMID:23686524

  9. Time Critical Social Mobilization: The DARPA Network Challenge Winning Strategy

    CERN Document Server

    Pickard, Galen; Pan, Wei; Cebrian, Manuel; Crane, Riley; Madan, Anmol; Pentland, Alex

    2010-01-01

    It is now commonplace to see the Web as a platform that can harness the collective abilities of large numbers of people to accomplish tasks with unprecedented speed, accuracy and scale. To push this idea to its limit, DARPA launched its Network Challenge, which aimed to "explore the roles the Internet and social networking play in the timely communication, wide-area team-building, and urgent mobilization required to solve broad-scope, time-critical problems." The challenge required teams to provide coordinates of ten red weather balloons placed at different locations in the continental United States. This large-scale mobilization required the ability to spread information about the tasks widely and quickly, and to incentivize individuals to act. We report on the winning team's strategy, which utilized a novel recursive incentive mechanism to find all balloons in under nine hours. We analyze the theoretical properties of the mechanism, and present data about its performance in the challenge.

  10. Proceedings of the WIN-Global 2008 conference

    International Nuclear Information System (INIS)

    WiN-France hosted the 16. WIN-Global conference May 26-30, 2008, in Marseille, France. The conference was attended by over 150 delegates, representing 30 countries. Canadian participants, from many diverse backgrounds, attended the annual conference from AECL, Bruce Power, CNSC, NB Power and OPG. The theme: Maintaining Key Competencies, Arising Key Competencies for Nuclear Energy: A Challenge and Opportunity for Diversity Development, emphasized the challenges ahead in providing a skilled workforce for the nuclear renaissance, as new build projects and a vast number of retirements are expected around the world within the next 5 years. The conference addressed such questions as 'How will nuclear, attract, develop and retain staff?' A technical tour of Marcoule invited conference attendees to visit one of: Atalante, a high level nuclear chemistry laboratory; Phenix, a fast breeding research reactor; or AVM, a vitrification plant. A subsequent technical tour visited Cadarache providing the opportunity to view ITER, the international fusion research project

  11. Effects of Cannabinoid Drugs on the Deficit of Prepulse Inhibition of Startle in an Animal Model of Schizophrenia: the SHR Strain

    Directory of Open Access Journals (Sweden)

    Raquel eLevin

    2014-02-01

    Full Text Available Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the Spontaneously Hypertensive Rats (SHR strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition of startle (PPI, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: 1 WIN55212,2 (cannabinoid agonist, 2 rimonabant (CB1 antagonist, 3 AM404 (anandamide uptake inhibitor, and 4 cannabidiol (indirect CB1/CB2 receptor antagonist, among other effects. Wistar rats (WR and SHRs were treated with vehicle or different doses of WIN55212 (0.3, 1 or 3 mg/kg, rimonabant (0.75, 1.5 or 3 mg/kg, AM404 (1, 5 or 10 mg/kg or cannabidiol (15, 30 or 60 mg/kg. Vehicle-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg cannabidiol. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.

  12. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    Science.gov (United States)

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. PMID:20579229

  13. Agonist Replacement for Stimulant Dependence: A Review of Clinical Research

    OpenAIRE

    Stoops, William W.; Rush, Craig R.

    2013-01-01

    Stimulant use disorders are an unrelenting public health concern worldwide. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. The present paper reviewed clinical data from human laboratory self-administration studies and clinical trials to determine whether agonist replacement therapy is a viable strategy for managing cocaine and/or amphetamine use disorders. The extant literature suggests that ago...

  14. Identification of M-CSF agonists and antagonists

    Science.gov (United States)

    Pandit, Jayvardhan; Jancarik, Jarmila; Kim, Sung-Hou; Koths, Kirston; Halenbeck, Robert; Fear, Anna Lisa; Taylor, Eric; Yamamoto, Ralph; Bohm, Andrew

    2000-02-15

    The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

  15. Windows Calorimeter Control (WinCal) system configuration control board (SCCB) operating procedure

    International Nuclear Information System (INIS)

    This document describes the operating procedure for the System Configuration Control Board (SCCB) performed in support of the Windows Calorimeter Control (WinCal) system. This board will consist of representatives from Babcock and Wilcox Hanford Company Babcock and Wilcox Protec, Inc.; and Lockheed Martin Services, Inc. In accordance with agreements for the joint use of the Babcock and Wilcox Hanford Company calorimeters located in the Hanford Site Plutonium Finishing Plant (PFP) Nondestructive Assay Laboratory, concurrence regarding changes to the WinCal system will be obtained from the International Atomic Energy Agency (IAEA). Further, changes to the WinCal software will be communicated to Los Alamos National Laboratory

  16. Win32 PE病毒研究%The Research of PE Virus

    Institute of Scientific and Technical Information of China (English)

    李响; 陈建熊

    2006-01-01

    计算机病毒在近年来发展很快,从早期的DOS病毒到现在的Win32病毒,它成为直接威胁计算机信息安全主要因素.Win32 PE文件格式是Windows操作系统主要的可执行文件格式.主要介绍Win32 PE文件病毒的机理、关键技术及其传染的过程,以期对其的破解和控制有助.

  17. NETPATH-WIN: an interactive user version of the mass-balance model, NETPATH

    Science.gov (United States)

    El-Kadi, A. I.; Plummer, L.N.; Aggarwal, P.

    2011-01-01

    NETPATH-WIN is an interactive user version of NETPATH, an inverse geochemical modeling code used to find mass-balance reaction models that are consistent with the observed chemical and isotopic composition of waters from aquatic systems. NETPATH-WIN was constructed to migrate NETPATH applications into the Microsoft WINDOWS® environment. The new version facilitates model utilization by eliminating difficulties in data preparation and results analysis of the DOS version of NETPATH, while preserving all of the capabilities of the original version. Through example applications, the note describes some of the features of NETPATH-WIN as applied to adjustment of radiocarbon data for geochemical reactions in groundwater systems.

  18. Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

    Directory of Open Access Journals (Sweden)

    Jennifer G. Robinson

    2008-01-01

    Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

  19. Novel selective cannabinoid CB1 receptor antagonist MJ08 with potent in vivo bioactivity and inverse agonistic effects

    Institute of Scientific and Technical Information of China (English)

    Wei CHEN; Cheng XU; Hong-ying LIU; Long LONG; Wei ZHANG; Zhi-bing ZHENG; Yun-de XIE; Li-li WANG; Song LI

    2011-01-01

    To characterize the biological profiles of M J08,a novel selective CB1 receptor antagonist.Methods:Radioligand binding assays were performed using rat brain and spleen membrane preparations.CB1 and CB2 receptor redistribution and intracellular Ca2+ ([Ca2+]1) assays were performed with IN CELL Analyzer.Inverse agonism was studied using intracellular cAMP assays,and in guinea-pig ileum and mouse vas deferens smooth muscle preparations.In vivo pharmacologic profile was assessed in diet-induced obesity (DIO) mice.Results:In radioligand binding assay,M J08 selectively antagonized CB1 receptor (IC50=99.9 nmol/L).In EGFP-CB1_U20S cells,its IC50 value against CB1 receptor activation was 30.23 nmol/L (SR141716A:32.16 nmol/L).WIN 55,212-2 (1 μmol/L) increased [Ca2+]1 in the primary cultured hippocampal neuronal cells and decreased cAMP accumulation in CHO-hCB1 cells.M J08 (10 nmol/L-1O μmol/L)blocked both the WIN 55,212-2-induced effects.Furthermore,M J08 reversed the inhibition of electrically evoked twitches of mouse vas deferens by WIN 55,212-2 (pA2=10.29±1.05).M J08 and SR141716A both showed an inverse agonism activity by markedly promoting the contraction force and frequency of guinea pig ileum muscle.M J08 significantly increased the cAMP level in CHO-hCB1 cells with an EC50 value of 78.6 nmol/L,which was lower than the EC50 value for SR141716A (159.2 nmol/L).Besides the more potent pharmacological effects of cannabinoid CB1 receptor antagonism in DIO mice,such as reducing food intake,decreasing body weight,and ameliorating dyslipidemia,M J08 (10 mg/kg) unexpectedly raised the fasted blood glucose in vivo.Conclusion:M J08 is a novel,potent and selective CB1 receptor antagonist/inverse agonist with potent bioactive responses in vitro and in vivo that may be useful for disclosure the versatile nature of CB1 receptors.

  20. The need of a win-win regulation regarding the harmonization of advantages for the renewable energy sector and the concerns about the environment

    Directory of Open Access Journals (Sweden)

    Moraru Dan

    2015-06-01

    Full Text Available The main theme of this paper is the evolution of theories and suppositions regarding environment and growth. The sustainable green growth and the sustainable green capitalism concepts have attracted the interest and imagination of policy makers and industry, and also stimulated many exciting new ideas and practical actions such as the “triple bottom line” which refers to harmonizing and balancing out the three interests that are linked with sustainable business: economic, environmental and social ones. The policy has to create a workable association between what the government can ensure and not tax and what it cannot ensure and must tax. In this manner we get a win-win regulation meaning that both sides win. National and supranational policies are part of the macro-level governance and very relevant for the sustainable development of the EU Member States and for the stability of the EU itself.

  1. Does a Least-Preferred Candidate Win a Seat? A Comparison of Three Electoral Systems

    Directory of Open Access Journals (Sweden)

    Yoichi Hizen

    2015-01-01

    Full Text Available In this paper, the differences between two variations of proportional representation (PR, open-list PR and closed-list PR, are analyzed in terms of their ability to accurately reflect voter preference. The single nontransferable vote (SNTV is also included in the comparison as a benchmark. We construct a model of voting equilibria with a candidate who is least preferred by voters in the sense that replacing the least-preferred candidate in the set of winners with any loser is Pareto improving, and our focus is on whether the least-preferred candidate wins under each electoral system. We demonstrate that the least-preferred candidate never wins under the SNTV, but can win under open-list PR, although this is less likely than winning under closed-list PR.

  2. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    Science.gov (United States)

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP. PMID:26094894

  3. Winning the Race: Lance Armstrong Shares His Struggle to Survive Cancer... and Thrive!

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Winning the Race Past Issues / Summer 2006 Table of Contents For ... consecutive victories in the Tour de France bicycle race. But, as Armstrong reveals in this exclusive interview, ...

  4. SENSITIVITY ANALYSIS OF THE USEPA WINS PM 2.5 SEPARATOR

    Science.gov (United States)

    Factors affecting the performance of the US EPA WINS PM2.5 separator have been systematically evaluated. In conjunction with the separator's laboratory calibrated penetration curve, analysis of the governing equation that describes conventional impactor performance was used to ...

  5. Predicting the Medal Wins by Country at the 2006 Winter Olympic Games: An Econometrics Approach

    OpenAIRE

    Pfau, Wade Donald

    2006-01-01

    Demographic and economic characteristics have been shown to provide important predictive power for determining a country’s success in the Olympic Games. This paper extends such research, providing a set of predictions for the gold medals and total medals each country will win at the 2006 Winter Olympics. We expected Germany to win the most medals, followed by the United States, Norway, Italy, Austria, and Canada. For total medals, the overall correlation between the predictions and the act...

  6. Faking or Convincing: Why Do Some Advertising Campaigns Win Creativity Awards?

    OpenAIRE

    Raoul V. Kübler; Proppe, Dennis

    2012-01-01

    Since the Sarbanes-Oxley Act was passed in 2002, it has become commonplace in the advertising industry to use creativity-award-show prizes instead of gross income figures to attract new customers. Therefore, achieving a top creativity ranking and winning creativity awards have become high priorities in the advertising industry. Agencies and marketers have always wondered what elements in the advertising creation process would lead to the winning of creativity awards. Although this debate has ...

  7. Forecasting Winning Bid Prices in an Online Auction Market:Data Mining Approaches

    Institute of Scientific and Technical Information of China (English)

    KIM Hongil; BAEK Seung

    2004-01-01

    To solve information asymmetry problem on online auction, this study suggests and validates a forecasting model of winning bid prices. Especially, it explores the usability of data mining approaches, such as neural network and Bayesian network in building a forecasting model. This research empirically shows that, in forecasting winning bid prices on online auction, data mining techniques have shown better performance than traditional statistical analysis, such as logistic regression and multivariate regression.

  8. ClimaWin : an intelligent window for optimal ventilation and minimum thermal loss

    OpenAIRE

    Pinto, Sandro; Castro, Tiago; Brito, Nuno; Gomes, Tiago M.; Tavares, Adriano; Mendes, José A.; Cabral, Jorge

    2013-01-01

    In this paper the ClimaWin concept is introduced. The ClimaWin project's main goals are to improve both indoor air quality and the energy efficiency of new and refurbished buildings, through the use of novel green smart windows. Generally, in order to improve windows' energy efficiency better insulation materials are used in windows frames and glasses. However, this approach leads to a severe deterioration of indoor air quality (IAQ) especially in buildings that are not equipped with heating,...

  9. THE RELATIONSHIP OF PATRIARCHY AND CAPITALISM: THE ‘WIN-WIN’ SCENARIO RECONSIDERED

    OpenAIRE

    Kocabıçak, Ece

    2015-01-01

    What are the impacts of capitalism on women’s oppression? Does capitalist development diminish gender inequality in developing countries? Do women’s autonomy, health and well-being rise together with an increase in women’s employment? Leading names of feminist economics argue that successful capitalist development and diminishing gender inequality within society can go hand in hand. They assume that the main reason why the win-win scenario has failed thus far is the laissez faire economy, so ...

  10. Windows Calorimeter Control (WinCal) program computer software test plan

    International Nuclear Information System (INIS)

    This document provides the information and guidelines necessary to conduct all the required testing of the Windows Calorimeter Control (WinCal) system. The strategy and essential components for testing the WinCal System Project are described in this test plan. The purpose of this test plan is to provide the customer and performing organizations with specific procedures for testing the specified system's functions

  11. Are Dopamine Agonists Neuroprotective in Parkinson′s Disease?

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Dopamine (DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson′s disease (PD) and in PD patient with levodopa (L-DOPA)-induced motor fluctuations,but also in early treatment of the disease.This shift has been largely due to the demonstrated L-DOPA-sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies.In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury.Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical-scavenging enzymes,and enhancing neurotrophic activity.The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase-3 in cytoplasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer′s disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists.Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on-going clinical trials are promising.Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as 18 F-L-DOPA PET and 123 I β-CIT SPECT.The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.``

  12. Are Dopamine Agonists Neuroprotective in Parkinson‘s disease?

    Institute of Scientific and Technical Information of China (English)

    乐卫东; Jank.J

    2002-01-01

    Dopamine(DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson's disease(PD) and in PD patient with levodopa(L-DO-PA)-induced motor fluctuations,but also in early treatment of the disease.This shift has been largely due to the demonstrated L-DOPA-sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies.In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury.Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical-scavenging enzymes,and enhancing neurotrophic activity.The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase-3 in cytoylasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer's disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists.Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on-going clinal trials are promising.Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as18F-L-DOPA PET and123I β-CIT SPECT.The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.

  13. The physician/hospital joint venture. Developing a win/win strategy for success. Part I: The first step: developing the environment.

    Science.gov (United States)

    Shorr, A B

    1987-02-01

    This four part series, "The Physician/Hospital Joint Venture: Developing a Win/Win Strategy," will examine the philosophical basis of marketing to physicians, the options for the organization in formulating a strategy for joint venture development, structuring and negotiating the deal, and finally how to build the physician loyalty and commitment essential for the joint venture's continued success. In this first article, the author emphasizes the organization's need to develop a strategic plan that includes a program for attracting physicians. It also points out the need for sensitivity to physicians' concerns and provides examples of successes and failures.

  14. The physician/hospital joint venture. Developing a win/win strategy for success. Part II: Joint venture strategies and considerations.

    Science.gov (United States)

    Shorr, A S

    1987-05-01

    This four part series, "The Physician/Hospital Joint Venture: Developing a Win/Win Strategy," examines the philosophical basis of marketing to physicians, the options for the organization in formulating a strategy for joint venture development, structuring and negotiating the deal, and finally how to build the physician loyalty and commitment essential for the joint venture's continued success. In this second part of the series, the author examines the internal and external issues that must be addressed to ensure success and the types of information that must be gathered.

  15. The physician/hospital joint venture: developing a win/win strategy for success. Part III: Structuring and negotiating the deal.

    Science.gov (United States)

    Shorr, A S

    1987-08-01

    This four part series, "The Physician/Hospital Joint Venture: Developing a Win/Win Strategy," examines the philosophical basis of marketing to physicians, the options for the organization in formulating a strategy for joint venture development, structuring and negotiating the deal, and finally how to build the physician loyalty and commitment essential for the joint venture's continued success. In this third part of the series, the author examines the elements essential to structure a successful joint venture and key issues that need to be addressed during the negotiation process.

  16. Design of Win32-based EPICS IOC%基于Win32 EPICS输入输出控制器的设计

    Institute of Scientific and Technical Information of China (English)

    王坚; 谢树欣; 董健; 王庆琪; 虞孝麒; 金革

    2008-01-01

    本文介绍了基于Win32实验物理和工业控制系统(Experimental Physics and Industrial Control System,EPICS)输入输出控制器(Input/Output Controller,IOC)的设计和实现,提出了EPICS IOC和微软技术的衔接方案,结合高性能数字示波器,将基于Win32的IOC很好地融入整个EPICS控制系统.

  17. 在中文Win9X微机中运行大型DOS程序%Operation of Big DOS Program in Chinese Win9X Computer

    Institute of Scientific and Technical Information of China (English)

    余宇

    2001-01-01

    介绍了分析仪器控制、分析测试数据处理系统等DOS应用程序在中文Win9X操作系统微机中运行的4种基本用法及特点。%In this paper, four principal usages and characteristics of some big DOS application programs, such as the analytical instrument control program, the analytical data processing system running under Chinese Win9X computer operating system were described.

  18. Pharmacological characterization of emerging synthetic cannabinoids in HEK293T cells and hippocampal neurons.

    Science.gov (United States)

    Costain, Willard J; Tauskela, Joseph S; Rasquinha, Ingrid; Comas, Tanya; Hewitt, Melissa; Marleau, Vincent; Soo, Evelyn C

    2016-09-01

    There has been a worldwide proliferation of synthetic cannabinoids that have become marketed as legal alternatives to cannabis (marijuana). Unfortunately, there is a dearth of information about the pharmacological effects of many of these emerging synthetic cannabinoids (ESCs), which presents a challenge for regulatory authorities that need to take such scientific evidence into consideration in order to regulate ECSs as controlled substances. We aimed to characterize the pharmacological properties of ten ESCs using two cell based assays that enabled the determination of potency and efficacy relative to a panel of well-characterized cannabinoids. Agonist-mediated inhibition of forskolin-stimulated cyclic adenosine monophosphate (cAMP) levels was monitored in live HEK293T cells transfected with human cannabinoid receptor 1 gene (CNR1) and pGloSensor-22F. Pharmacological analysis of this data indicated that all of the ESCs tested were full agonists, with the following rank order of potency: Win 55212-2≈5F-PB-22≈AB-PINACA≈EAM-2201≈MAM-2201>JWH-250≈ PB-22>AKB48 N-(5FP)>AKB-48≈STS-135>XLR-11. Assessment of agonist-stimulated depression of Ca(2+) transients was also used to confirm the efficacy of five ESCs (XLR-11, JWH-250, AB-PINACA, 5F-PB-22, and MAM-2201) in cultured primary hippocampal neurons. This work aims to help inform decisions made by regulatory agencies concerned with the profusion of these poorly characterized recreational drugs. PMID:27260125

  19. Winning in Sequential Parrondo Games by Players with Short-Term Memory

    CERN Document Server

    Cheung, Ka Wai; Wu, Degang; Lui, Ga Ching; Szeto, Kwok Yip

    2015-01-01

    Players with one-step memory can win by switching his choice of A or B game in a Parrondo game sequence. Here the winning or losing of A and B game is defined by one unit of capital. Game A is a losing game if played continuously, with winning probability $p=0.5-\\epsilon$, where $\\epsilon=0.003$. Game B is also losing and it has two coins: a good coin with winning probability $p_g=0.75-\\epsilon$ is used if the player`s capital is not divisible by $3$, otherwise a bad coin with winning probability $p_b=0.1-\\epsilon$ is used. The player can win maximally in a game sequence of (A,B) if he knows the identity of the game he plays and the state of his capital. If the player does not know the nature of the game, then he is playing a (C,D) game, where either (C=A, D=B), or (C=B,D=A). For player with one-step memory, he can achieve the highest gain with switching probability equal to $3/4$ in the (C,D) game sequence. Generalization to AB mod($M$) Parrondo game for other integer $M$ and player with longer than one-step...

  20. Faking or Convincing: Why Do Some Advertising Campaigns Win Creativity Awards?

    Directory of Open Access Journals (Sweden)

    Raoul V. Kübler

    2012-05-01

    Full Text Available Since the Sarbanes-Oxley Act was passed in 2002, it has become commonplace in the advertising industry to use creativity-award-show prizes instead of gross income figures to attract new customers. Therefore, achieving a top creativity ranking and winning creativity awards have become high priorities in the advertising industry. Agencies and marketers have always wondered what elements in the advertising creation process would lead to the winning of creativity awards. Although this debate has been dominated by pure speculation about the success of different routines, approaches and strategies in winning creativity awards, for the first time our study delivers an empirical insight into the key drivers of creativity award success. We investigate what strategies and which elements of an advertising campaign are truly likely to lead to winning the maximum number of creativity awards. Using a sample of 108 campaigns, we identify factors that influence campaign success at international advertising award shows. We identify innovativeness and the integration of multiple channels as the key drivers of creativity award success. In contrast to industry beliefs, meaningful or personally connecting approaches do not seem to generate a significant benefit in terms of winning creativity awards. Finally, our data suggest that the use of so-called “fake campaigns” to win more creativity awards does not prove to be effective.

  1. Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    glycine-free or a glycine-bound subunit. Agonist-free subunits were created by incorporating T204A and R65K mutations, which disrupted glycine binding to both (+) and (-) subunit interfaces. In heteromeric receptors comprising wild-type and R65K,T204A,R271C triple-mutant subunits, the fluorescence...... response exhibited a drastically reduced glycine sensitivity relative to the current response. Two conclusions can be drawn from this. First, because the labeled glycine-free subunits were activated by glycine binding to neighboring wild-type subunits, our results provide evidence for a cooperative...... activation mechanism. However, because the fluorescent label on glycine-free subunits does not reflect movements at the channel gate, we conclude that glycine binding also produces a local non-concerted conformational change that is not essential for receptor activation....

  2. Proceedings of the WIN-Global 2008 conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    WiN-France hosted the 16. WIN-Global conference May 26-30, 2008, in Marseille, France. The conference was attended by over 150 delegates, representing 30 countries. Canadian participants, from many diverse backgrounds, attended the annual conference from AECL, Bruce Power, CNSC, NB Power and OPG. The theme: Maintaining Key Competencies, Arising Key Competencies for Nuclear Energy: A Challenge and Opportunity for Diversity Development, emphasized the challenges ahead in providing a skilled workforce for the nuclear renaissance, as new build projects and a vast number of retirements are expected around the world within the next 5 years. The conference addressed such questions as 'How will nuclear, attract, develop and retain staff?' A technical tour of Marcoule invited conference attendees to visit one of: Atalante, a high level nuclear chemistry laboratory; Phenix, a fast breeding research reactor; or AVM, a vitrification plant. A subsequent technical tour visited Cadarache providing the opportunity to view ITER, the international fusion research project.

  3. Small wins matter in advocacy movements: giving voice to patients.

    Science.gov (United States)

    Jason, Leonard A

    2012-06-01

    In this article, the various players are delineated in a story of a contested illness and patient advocacy, played out within the corridors of federal power. It is suggested that the mistreatment and negative attitudes that health care providers and others have towards those with chronic fatigue syndrome (CFS) is possibly due to the social construction of this illness as being a "Yuppie flu" disease. Institutional factors are identified that created these norms and attributions, as well as the multiple stakeholders and constituent groups invested in exerting pressure on policy makers to effect systemic change. This article also provides examples of how the field of Community Psychology, which is fundamentally committed to/based on listening to and giving voice to patients, is broadly relevant to patient activism communities. This approach focused, over time, on epidemiological studies, the name, the case definition, and ultimately the change in CFS leadership at the Centers for Disease Control and Prevention. Keys to this "small wins" approach were coalition building, use of "oppositional experts" (professionals in the scientific community who support patient advocacy goals) to challenge federal research, and taking advantage of developing events/shifts in power. Ultimately, this approach can result in significant scientific and policy gains, and changes in medical and public perception of an illness. PMID:21858612

  4. The "Win-Win" initiative: a global, scientifically based approach to resource sparing treatment for systemic breast cancer therapy

    Directory of Open Access Journals (Sweden)

    Elzawawy Ahmed

    2009-05-01

    Full Text Available Abstract Background Worldwide, breast cancer is the most frequent malignancy among females. Its incidence shows a trend towards an increase in the next decade, particularly in developing countries where less than of 5% of resources for cancer management are available. In most breast cancer cases systemic cancer treatment remains a primary management strategy. With the increasing costs of novel drugs, amidst the growing breast cancer rate, it can be safely assumed that in the next decade, newly developed cancer drugs will become less affordable and therefore will be available to fewer patients in low and middle income countries. In light of this potentially tragic situation, a pressing need emerges for science-based innovative solutions. Methods In this article, we cite examples of recently published researches and case management approaches that have been shown to lower overall treatment costs without compromising patient outcomes. The cited approaches are not presented as wholly inclusive or definitive solutions but are offered as effective examples that we hope will inspire the development of additional evidence-based management approaches that provide both efficient and effective breast cancer treatment Results We propose a "win-win" initiative, borne in the year of 2008 of strategic information sharing through preparatory communications, publications and our conference presentations. In the year 2009, ideas developed through these mechanisms can be refined through focused small pilot meetings with interested stakeholders, including the clinical, patient advocate, and pharmaceutical communities, and as appropriate (as proposed plans emerge, governmental representatives. The objective is to draw a realistic road map for feasible and innovative scientific strategies and collaborative actions that could lead to resource sparing; i.e. cost effective and tailored breast cancer systemic treatment for low and middle income countries. Conclusion The

  5. International land deals, local people's livelihood, and environment nexus (How to create win-win land deals in Ethiopia?)

    Science.gov (United States)

    Teklemariam Gebremeskel, Dereje; Witlox, Frank; Azadi, Hossein; Haile, Mitiku; Nyssen, Jan

    2013-04-01

    Following the global raise in demand for food and biofuel production, transnational companies are acquiring large scale agricultural land in developing countries such as Ethiopia. Considering land as one of the factors to be outsourced for development, the government of Ethiopia is supplying millions of hectares of land to transnational companies in the form of longterm lease. Many of the companies which engage in large scale land acquisition are of Indian, Chinese, Ethiopian diaspora, German, Malaysian, Italian, British, Dutch, Turkish, and Saudi-Arabian origin. The boom in the acquisition of farm land in the country has sparked an all-rounded debate among civil society groups, international institutions, nongovernmental organizations and independent development experts. The common reflections concerning the land deals in Ethiopia and elsewhere contain much rhetoric and hype which lack analysis of the real situation "on the ground" giving different connotations such as 'land grabbing', 'agricultural outsourcing', 'neo-colonialism', 'agrarian colonialism', and 'land underdevelopment'. However, deforestation, soil degradation, marginalization of local indigenous communities, and minimally unfair gains from investment by the host country are among the real points of concern arising out of the long term land lease contracts. Scientific evidence is lacking concerning the pragmatic impacts of large scale agricultural land acquisitions by transnational companies upon the natural environment (forest and land), local peoples' livelihood, and the contacting parties (the host country and the companies). The major objective of this study is to investigate the impacts in the context of Ethiopia, orienting to reinvent win-win land use models which constitute sustainable land use, local peoples' livelihood and the company-host country interests. To achieve this overall objective, the study employs a number of methods and methodologies constituting both qualitative and

  6. Cannabis agonist injection effect on the coupling architecture in cortex of WAG/Rij rats during absence seizures

    Science.gov (United States)

    Sysoeva, Marina V.; Kuznetsova, Galina D.; van Rijn, Clementina M.; Sysoev, Ilya V.

    2016-04-01

    WAG/Rij rats are well known genetic model of absence epilepsy, which is traditionally considered as a nonconvulsive generalised epilepsy of unknown aetiology. In current study the effect of (R)-(+)-WIN 55,212-2 (cannabis agonist) injection on the coupling between different parts of cortex was studied on 27 male 8 month old rats using local field potentials. Recently developed non-linear adapted Granger causality approach was used as a primary method. It was shown that first 2 hours after the injection the coupling between most channel pairs rises in comparison with the spontaneous activity, whilst long after the injection (2-6 hours) it drops down. The coupling increase corresponds to the mentioned before treatment effect, when the number and the longitude of seizures significantly decreases. However the subsequent decrease of the coupling in the cortex is accompanied by the dramatic increase of the longitude and the number of seizures. This assumes the hypothesis that a relatively higher coupling in the cortical network can prevent the seizure propagation and generalisation.

  7. Principles of agonist recognition in Cys-loop receptors

    Directory of Open Access Journals (Sweden)

    Timothy eLynagh

    2014-04-01

    Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

  8. 使用Visual C++实现 Win95环境下的串行通信%Serial Communication Programming Under Win95

    Institute of Scientific and Technical Information of China (English)

    谭开忠

    2001-01-01

    概述了串行通信的原理,并就Visual C++ 4.2在Win95环境下实现串行通信编程作了说明.%This paper sums up the communication principle and explains how to attain serial Communication applications under Windows95 by using Visual C++ 4.2 .

  9. How could we realize a win-win strategy on irrigation price policy? Evaluation of a pilot reform project in Hebei Province, China

    Science.gov (United States)

    Wang, Jinxia; Zhang, Lijuan; Huang, Jikun

    2016-08-01

    The challenge of increasing irrigation prices while increasing farmers' income exists not only in China but in other countries as well. The overall goal of this paper is to evaluate whether a win-win strategy can be realized in a pilot reform in Hebei, China. The data came from a two-round field survey in 2009 and 2012, which indicated that the key mechanism of the pilot reform was that farmers received similar returns (including reallocated, increased irrigation fees and a government subsidy), but paid different irrigation fees; the difference between the returned money and payment was treated as an incentive for farmers to reduce their use of irrigation. The econometric results showed that in pilot reformed villages, local farmers' groundwater application for irrigating wheat and cotton could decrease by 21% each. If no subsidies are granted, roughly half of the region's farmers would lose money due to the reform. However, most farmers who receive subsidies were able to earn money in the pilot reformed villages. If several issues are properly resolved (such as selecting more representative villages, increasing the subsidy value, and negatively linking the subsidy with water use), it would be possible for more regions to realize a win-win price reform strategy.

  10. Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy

    NARCIS (Netherlands)

    Vinogradova, L.V.; Rijn, C.M. van

    2015-01-01

    BACKGROUND: Modulation of the endocannabinoid (eCB) transmission is a promising approach to treating epilepsy. Animal models can be used to investigate this approach. Krushinsky-Molodkina (KM) rats have, genetically, audiogenic epilepsy. Moreover, in these animals, repeated induction of audiogenic s

  11. Synthesis of Selective A3 and M1 Receptor Agonists

    OpenAIRE

    Snee, Stephen

    2011-01-01

    Detailed within this thesis is the synthesis of three A1 agonists which were designed by Muscagen using computational studies. The agonists are derived from condensation of the modified adenosine: (4S,6R)-6-(6-chloro-9H-purin-9-yl)-N,2,2-trimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide with novel heterocyclic primary amines.The amines 5-(aminomethyl)-N,N-diethyl-7-methyloxazolo[4,5-b]pyridin-2-amine, 5-(1-aminoethyl)-N,N,7-trimethyloxazolo[4,5-b]pyridin-2-amine and 5-(1-aminoethyl)-N,...

  12. DIFFERENCES IN GAME STATISTICS BETWEEN WINNING AND LOSING RUGBY TEAMS IN THE SIX NATIONS TOURNAMENT

    Directory of Open Access Journals (Sweden)

    José M. Palao

    2009-12-01

    Full Text Available The objective of the present study was to analyze the differences in rugby game statistics between winning and losing teams. The data from 58 games of round robin play from the Six Nations tournament from the 2003-2006 seasons were analyzed. The groups of variables studied were: number of points scored, way in which the points were scored; way teams obtained the ball and how the team used it; and technical and tactical aspects of the game. A univariate (t-test and multivariate (discriminant analysis of data was done. Winning teams had average values that were significantly higher in points scored, conversions, successful drops, mauls won, line breaks, possessions kicked, tackles completed, and turnovers won. Losing teams had significantly higher averages for the variables scrums lost and line-outs lost. The results showed that: a in the phases of obtaining the ball and more specifically in scrummage and line-out, winning teams lose fewer balls than losing teams (winning teams have an efficacy of 90% in both actions; b the winning team tends to play more with their feet when they obtain the ball, to utilize the maul as a way of attacking, and to break the defensive line more often than the losing team does; and c On defence, winning teams recovered more balls and completed more tackles than losing teams, and the percentage of tackles completed by winning teams was 94%. The value presented could be used as a reference for practice and competition in peak performance teams

  13. WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

    Science.gov (United States)

    Bowman, J M; Friesen, A D; Pollock, J M; Taylor, W E

    1980-12-01

    An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks' gestation and 120 microgram given after delivery to Rh-negative women at risk of Rh immunization WinRho was effective in preventing Rh immunization. Of the 870 women carrying Rh-positive fetuses who were treated with WinRho during pregnancy and were not tested several months after delivery 14 would have shown evidence of Rh immunization by the time of delivery if WinRho had been ineffective; none showed such evidence. Of the 1122 women carrying Rh-positive fetuses who were retested 4 to 6 months after delivery 83 would have shown evidence of Rh immunization at that time if WinRho had been ineffective; only 1 showed such evidence. The efficiency of yield of anti-D with the modified method of production, the fct that it can be given intravenously (a route that causes the patient less discomfort and immediately results in high anti-D levels) and the lower levels of contaminating IgA and IgM make WinRho the preparation of choice for preventing Rh immunization. PMID:6161687

  14. Suppression of Stra8 Expression in the Mouse Gonad by WIN 18,4461

    Science.gov (United States)

    Hogarth, Cathryn A.; Evanoff, Ryan; Snyder, Elizabeth; Kent, Travis; Mitchell, Debra; Small, Christopher; Amory, John K.; Griswold, Michael D.

    2011-01-01

    Bis-(dichloroacetyl)-diamines (BDADs) are compounds that inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully investigated. It has been proposed that BDADs may function via inhibition of testicular retinoic acid (RA) biosynthesis. We employed an organ culture technique and the expression of a marker for RA activity, Stra8 (stimulated by retinoic acid gene 8), to investigate if the BDAD WIN 18,446 inhibited the biosynthesis of RA from retinol (ROL) in neonatal and adult murine testis and in the embryonic murine gonad. After culturing either whole testes or germ cells isolated from mice at 2 days postpartum (dpp) with WIN 18,446 or with WIN 18,446 plus ROL, Stra8 expression was suppressed, demonstrating that WIN 18,446 inhibited the conversion of ROL to RA in both systems. We also utilized a transgenic mouse containing an RA-responsive LacZ reporter gene to demonstrate limited RA induction of LacZ expression in 2-dpp testes cultured with WIN 18,446 plus ROL. The expression of Stra8 was downregulated in adult mouse testis tubules cultured with WIN 18,446 when compared to tubules cultured with the vehicle control. WIN 18,446 also inhibited the conversion of ROL to RA in embryonic ovaries and testes cultured for 48 h. These murine results provide critical insights regarding how the BDADs can inhibit spermatogenesis by blocking the ability of vitamin A to drive germ cell development. In addition, these techniques will be useful for screening novel inhibitors of RA biosynthesis as potential male contraceptives. PMID:21209416

  15. Improvement of information on the nuclear energy health effects, the aim of win Slovakia

    International Nuclear Information System (INIS)

    International organisation WIN Global and national organisation WIN Slovakia which as a section of Slovak Nuclear Society, offer unique opportunities for the improvement of radiation risk communication. WIN Global was established in 1993 and currently has about 600 members in 39 countries. WIN Slovakia was established in the end of 1997 and has 20 members. WIN Slovakia is the association of women working professionally in the fields of nuclear energy and application of radiation and willing to devote time to public information. Members of WIN Slovakia all have one thing in common: They want the general public to have a better understanding of nuclear and radiation matter. The members of WIN Slovakia would like and plane to make presentations, discuss and give information material on subjects as: energy and sustainable development; radiation, radioactivity, and health effects; medical applications, radiation protection; nuclear energy, uranium mining; nuclear power plants and their safety; radioactive waste; nuclear and environment; natural radiation, radon. In 1996-1997 a comparative risk perception study was carried out in Slovak Republic. Real data were collected through the administration of a questionnaires distributed among a group of 14-17 years old children (N1 = 308) and teenagers (N2 = 150). The list of 44 items covered a wide range of risks and hazards, including risks from technology (nuclear power plants, water-dams etc.) pollution (air-, water-, soil, waste management) nature (floods, fire, etc.), life style (smoking, drugs, alcohol abuse) and society (crime, conflicts, war, terror etc.). The questionnaire contains the questions about the sources of risk information. The topic of the study was the self assessment of the knowledge on particular risks too. The results were summarised

  16. Win-Win Trade

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    China and Afrca find new ways to drive mutual development On May 27,a total of 210 orphans in the three states around Abuja,capital of Nigeria,went to a summer camp to celebrate the country’s Children’s Day. Huawei Technologies Co.,a leading global information and communications technology solutions provider from China,sponsored the event.

  17. Win-Win Trade

    Institute of Scientific and Technical Information of China (English)

    NI YANSHUO

    2011-01-01

    On May 27,a total of 210 orphans in the three states around Abuja,capital of Nigeria,went to a summer camp to celebrate the country's Children's Day.Huawei Technologies Co.,a leading global information and communications technology solutions provider from China,sponsored the event.

  18. Win-win finance

    Energy Technology Data Exchange (ETDEWEB)

    Panayotou, T.

    1997-07-01

    Sustainable development is grossly underfinanced. It will continue to be so, because the world is relying on conventional means to finance an unconventional idea. Official development assistance fell from 60 billion dollars in 1992 to 55 billion dollars in 1995 (in constant 1994 prices). The public sector in developing countries is underinvesting in environmental sustainability because of severe budget constraints, public sector deficits and more pressing expenditure needs. So is the private sector because, under prevailing institutional arrangements, it cannot recover costs and earn a decent rate of return from providing public goods. Other means of mobilising resources must be found. Such measures may include: phasing out subsidies, demand-scale management, better capture of resource vents, improved definition and security of property rights, and environmentally based taxation. Coal and petroleum based projects are frequently effectively subsidised. For sustainability energy efficiency measures should be subsidised, and energy consumption taxed. Increased use of economic instruments should be encouraged. 2 photos.

  19. [Opinions of the participants of 'Quit and Win' competition concerning prizes motivating to refrain from smoking].

    Science.gov (United States)

    Kowalska, Alina; Stelmach, Włodzimierz; Rzeźnicki, Adam

    2009-01-01

    Big antinicotine campaigns both in Poland and worldwide, are finished with a competition with prizes of different value. Psychologists say that a prize significantly motivates a person to certain kinds of behaviour. During educational activities carried out in the time of campaign, it is recommended to use techniques of psychological interaction that would release motives most beneficial to health. The aim of the work was to recognize frequency of being influenced mostly by the possibility of winning a prize before making a decision about quitting smoking and joining the competition, and learning the opinions of prize laureates concerning efficiency of 'Quit and Win' competitions. Empirical material comes from two sources. The first one is the selected fragments of a survey study carried out at Social and Preventive Medicine Department among 1700 participants of 'Quit and Win' competition that finished the 2nd International Antinicotine Campaign in Poland. The correctly filled survey was sent by 1285 people, that is 75.6%. The second source is a fragment of a survey study carried out in 2003 among 54 laureates of 'Quit and Win' competition in Poland. The completed survey was sent by majority of the laureates, that is 34 people (f = 0.63). Possibility of winning a prize as the most important reason for taking up the attempt to stop smoking and joining the competition was pointed to by 56 respondents (4.4%), whereas the remaining people chose other reasons as the most important ones. In the group of 34 respondents who were the laureates of competitions, majority, that is 22 people (f = 0.65) claimed the competition with prizes as a very effective method of reducing smoking. Half of the surveyed (17 people) claimed the possibility of winning a few prizes of high value would be more motivating than winning one of many prizes of smaller value. As the least attractive, prize gifts were pointed to. A prize in the form of a trip or holiday was considered very popular, as

  20. Partial Agonists Activate PPARgamma Using a Helix 12 Independent Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Bruning, J.B.; Chalmers, M.J.; Prasad, S.; Bushby, S.A.; Kamenecka, T.A.; He, Y.; Nettles, K.W.; Griffin, P.R.

    2009-05-28

    Binding to helix 12 of the ligand-binding domain of PPAR{gamma} is required for full agonist activity. Previously, the degree of stabilization of the activation function 2 (AF-2) surface was thought to correlate with the degree of agonism and transactivation. To examine this mechanism, we probed structural dynamics of PPAR{gamma} with agonists that induced graded transcriptional responses. Here we present crystal structures and amide H/D exchange (HDX) kinetics for six of these complexes. Amide HDX revealed each ligand induced unique changes to the dynamics of the ligand-binding domain (LBD). Full agonists stabilized helix 12, whereas intermediate and partial agonists did not at all, and rather differentially stabilized other regions of the binding pocket. The gradient of PPAR{gamma} transactivation cannot be accounted for solely through changes to the dynamics of AF-2. Thus, our understanding of allosteric signaling must be extended beyond the idea of a dynamic helix 12 acting as a molecular switch.

  1. Innovations in agonist maintenance treatment of opioid-dependent patients

    NARCIS (Netherlands)

    C. Haasen; W. van den Brink

    2006-01-01

    Purpose of review To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. Recent findings The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid depe

  2. Synthetic RORγt Agonists Enhance Protective Immunity.

    Science.gov (United States)

    Chang, Mi Ra; Dharmarajan, Venkatasubramanian; Doebelin, Christelle; Garcia-Ordonez, Ruben D; Novick, Scott J; Kuruvilla, Dana S; Kamenecka, Theodore M; Griffin, Patrick R

    2016-04-15

    The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer). Enhanced immunity and blockage of immune checkpoints has transformed cancer treatment; thus such a molecule would provide a unique approach for the treatment of cancer. PMID:26785144

  3. Systemic cancer immunotherapy with Toll-like receptor 7 agonists

    Science.gov (United States)

    Hotz, Christian; Bourquin, Carole

    2012-01-01

    Toll-like receptor (TLR) 7 agonists represent a promising strategy for the immunotherapy of cancer. We have recently investigated the influence of TLR tolerance on the efficacy of systemic tumor treatment with TLR7 ligands. We propose that considering the kinetics of receptor sensitivity highly improves the outcome of cancer immunotherapy. PMID:22720251

  4. The emerging therapeutic roles of κ-opioid agonists.

    Science.gov (United States)

    Jones, Mark R; Kaye, Alan D; Kaye, Aaron J; Urman, Richard D

    2016-01-01

    The current practice of μ-opioid receptor agonists such as morphine as the primary means of acute and chronic pain relief has several dangerous consequences that limit their effectiveness, including respiratory depression, gastrointestinal motility inhibition, addiction, tolerance, and abuse. Several other opioid receptors, notably the μ-opioid (KOP) receptor, have long been known to play a role in pain relief. Recent discoveries and advancements in laboratory techniques have allowed significant developments of KOP agonists as potential novel therapies for pain relief and other pathological processes. These drugs exhibit none of the classic opioid adverse effects and have displayed pronounced analgesia in several different scenarios. New formulations since 2014 have unveiled increased oral bioavailability, exceptional peripheral versus central selectivity, and a positive safety profile. Continued refinements of established μ-opioid agonist formulations have virtually eliminated the centrally mediated side effects of dysphoria and sedation that limited the applicability of previous KOP agonists. Further research is required to better elucidate the potential of these compounds in pain management, as well as in the mediation or modulation of other complex pathophysiological processes as therapeutic agents.

  5. Glucagon-like peptide 1 receptor agonist (GLP-1 RA)

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Tine Willum; Goetze, Jens Peter;

    2015-01-01

    AIMS: In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim...

  6. Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian;

    2012-01-01

    FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metaboli...

  7. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

    DEFF Research Database (Denmark)

    Goadsby, P J; Hoskin, K L; Storer, R J;

    2002-01-01

    There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperit......There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg...... from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3-100 microg/kg) had a dose-dependent inhibitory effect on SSS...... 33 +/- 2 pmol/l (n = 6) to 64 +/- 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 microg/kg; P agonist, GR190178 (30-1000 microg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion...

  8. Inhibitory effects of synthetic cannabinoid WIN55, 212-2 on nicotine-activated currents in rat trigeminal ganglion neurons

    Institute of Scientific and Technical Information of China (English)

    Yongli Lu; Changjin Liu; Hongwei Yang

    2011-01-01

    Cannabinoid and nicotinic acetylcholine receptors are strongly associated with algesia. Previous studies in our laboratory have reported inhibitory effects of synthetic cannabinoid WIN55, 212-2 on nicotine-activated currents (/nic), but the underlying mechanisms remain poorly understood. The present study used whole-cell patch clamp techniques to investigate the modulatory effects of synthetic cannabinoid WIN55, 212-2 on /nic in cultured rat trigeminal ganglion neurons. The results revealed several major findings: WIN55, 212-2 inhibited /nic in rat trigeminal ganglion neurons. In addition, when WIN55, 212-2 (3 μmol/L) was applied simultaneously with nicotine (100 μmol/L), the inhibition of WIN55, 212-2 on /nic was reversible, concentration-dependent and voltage-independent. This effect was not mediated by CB1, CB2 or VR1 receptors; neither the selective CB1 receptor antagonist AM281, CB2 receptor antagonist AM630 nor VR1 receptor antagonist capsazepine reduced the inhibitory effect of WIN55, 212-2. Further, the inhibition of nicotinic responses by WIN55, 212-2 was not sensitive to the membrane permeable cyclic adenosine monophosphate (cAMP) analog 8-Br-cAMP. The G-protein inhibitor GDP-β-S (1 mmol/L) did not block the inhibitory effects of WIN55, 212-2 on /nic, excluding the involvement of G-protein mediation. The results suggested that WIN55, 212-2 inhibits/nic directly via the neuronal nicotinic acetylcholine receptor, and that this inhibition is non-competitive. WIN55, 212-2 did not act as an open channel blocker of the neuronal nicotinic acetylcholine receptor, and did not affect the desensitization of /nic. The results suggest that nicotine receptors may be physically plugged from outside the membrane by drugs containing WIN55, 212-2.

  9. In Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable Development In Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable Development

    Directory of Open Access Journals (Sweden)

    Ignacy Sachs

    2010-12-01

    Full Text Available In Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable DevelopmentIn Search of Three-win Solutions: The Challenges of the 2012 UN Conference on Environment and Sustainable Development

  10. Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists.

    Science.gov (United States)

    Gilmore, John L; Sheppeck, James E; Wang, Jim; Dhar, T G Murali; Cavallaro, Cullen; Doweyko, Arthur M; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Nadler, Steven G; Dodd, John H; Somerville, John E; Barrish, Joel C

    2013-10-01

    SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors. PMID:23916594

  11. β-Adrenoreceptor agonists in the management of pain associated with renal colic: a systematic review

    OpenAIRE

    Tabner, Andrew John; Johnson, Graham David; Fakis, Apostolos; Surtees, Jane; Lennon, Robert Iain

    2016-01-01

    Objectives To determine whether β-adrenoreceptor agonists are effective analgesics for patients with renal colic through a systematic review of the literature. Setting Adult emergency departments or acute assessment units. Participants Human participants with proven or suspected renal colic. Interventions β-adrenoreceptor agonists. Outcome measures Primary: level of pain at 30 min following administration of the β-agonist. Secondary: level of pain at various time points following β-agonist ad...

  12. Greenhouse Gas Emission Mitigation And Agriculture, Trade-off Or Win-win Situation: Bioeconomic Farm Modelling In The Sudanian Area of Burkina Faso

    Science.gov (United States)

    Some, T. E.; Barbier, B.

    2015-12-01

    Climate changes talks regularly underline that developing countries' agriculture could play a stronger role in GHGs mitigation strategies and benefit from the Kyoto Protocol program of subsidies. Scientists explain that agriculture can contribute to carbon mitigation by storing more carbon in the soil through greener cropping systems. In this context, a growing number of research projects have started to investigate how developing countries agriculture can contribute to these objectives. The clean development mechanism (CDM) proposed in the Kyoto protocol is one particular policy instrument that can incite farmers to mitigate the GHG balance towards more sequestration and less emission. Some economists such as Michael Porter think that environmental regulation lead to a win-win outcome, in which case subsidies are not necessary. If it is a trade-off between incomes and the environment, subsidies are required. CDM can be mobilized to support the mitigation strategy. Agriculture implies the use of inputs. Reducing the emission implies the reduction of those inputs which will in turn imply a yield decrease. The study aims to assess whether this measure will imply a trade-off between environmental and economic objectives or a win-win situation. I apply this study to the case of small farmers in Burkina Faso through environmental instruments such as the emissions limits and agroforestry using a bioeconomic model, in which the farmers maximize their utility subject to constraints. The study finds that the limitation of emissions in annual crops production involves a trade-off. by impacting negatively their net cash come. By integrating perennial crops in the farming system, the farmers' utility increases. Around 6,118 kg are sequestrated individually. By computing the value on this carbon balance, farmers' net cash incomes go better. Then practicing agroforestry is a win-win situation, as they reach a higher level of income, and reduce emissions. Policymakers must

  13. Turning a Spermatogenic Wave into a Tsunami: Synchronizing Murine Spermatogenesis Using WIN 18,4461

    Science.gov (United States)

    Hogarth, Cathryn A.; Evanoff, Ryan; Mitchell, Debra; Kent, Travis; Small, Christopher; Amory, John K.; Griswold, Michael D.

    2013-01-01

    ABSTRACT The BDADs (bis-[dichloroacetyl]-diamines) are compounds that can inhibit spermatogenesis via blocking the metabolism of vitamin A. We utilized one specific BDAD, WIN 18,446, to manipulate the endogenous production of retinoic acid (RA) in the testis to further investigate the action of this compound on mammalian sperm production. Transient treatment of adult male mice with WIN 18,446 blocked spermatogonial differentiation and induced significant changes in the cycle of the seminiferous epithelium. WIN 18,446 treatment of neonatal mice also blocked spermatogonial differentiation and, followed by injection of RA, induced synchronous spermatogenesis in adulthood. The net result was pulsatile, rather than normal continuous, release of sperm from the seminiferous epithelium. This study describes a novel technique that can enrich for specific germ cell populations within the testis, representing a valuable new tool for studying spermatogenesis. PMID:23284139

  14. The WIN-Speller: A new Intuitive Auditory Brain-Computer Interface Spelling Application

    Directory of Open Access Journals (Sweden)

    Sonja C Kleih

    2015-10-01

    Full Text Available The objective of this study was to test the usability of a new auditory Brain-Computer Interface (BCI application for communication. We introduce a word based, intuitive auditory spelling paradigm the WIN-speller. In the WIN-speller letters are grouped by words, such as the word KLANG representing the letters A, G, K, L and N. Thereby, the decoding step between perceiving a code and translating it to the stimuli it represents becomes superfluous. We tested 11 healthy volunteers and 4 end-users with motor impairment in the copy spelling mode. Spelling was successful with an average accuracy of 84% in the healthy sample. Three of the end-users communicated with average accuracies of 80% or higher while one user was not able to communicate reliably. Even though further evaluation is required, the WIN-speller represents a potential alternative for BCI based communication in end-users.

  15. Do quantum strategies always win? A case study in the entangled quantum penny flip game

    CERN Document Server

    Anand, Namit

    2014-01-01

    In a seminal paper, Meyer\\cite{Meyer} described the advantages of quantum game theory by looking at the classical penny flip game. A player using quantum strategy can win against a classical player almost 100% of the time. Here we make a slight modification of the quantum game in which the two players share an entangled state to begin with. We then analyse two different scenarios one in which the quantum player makes unitary transformations to her qubit while classical player uses a pure strategy of either flipping or not flipping the state of his qubit. In the second scenario we have the quantum player making similar unitary transformations while the classical player makes use of a mixed strategy wherein he either flips or not with some probability "p". We show that in the second scenario 100% win record of a quantum player is drastically reduced and for a particular probability "p" the classical player may even win against the quantum player.

  16. EPJ Web of Conferences, Proceedings of the joint meeting QENS/WINS 2014

    International Nuclear Information System (INIS)

    The 11. QENS (Quasi-Elastic Neutron Scattering) conference and the 6. WINS (Workshop on Inelastic Neutron Spectrometers) were held for the second time together as the joint meeting QENS/WINS 2014. QENS 2014 aims to highlight topical scientific activities in the investigation of the dynamics of matter using quasi-elastic neutron scattering and to envision new applications. In dynamics of matter, matter must be considered in a very broad sense since issues like dynamics of confined matter in nano-porous materials, dynamics of biological systems in relation to function, dynamics of ionic and electrolytes, dynamics of soft matter, liquids, and liquid crystals, are of concern. The aim of the WINS 2014 workshop is to overview recent developments, forthcoming projects and practice of inelastic and quasi-elastic neutron spectrometers. Related issues such as the development of data analysis software, auxiliary devices and outlook for future scientific efforts are also dealt with

  17. Win-stay lose-shift strategy in formation changes in football

    CERN Document Server

    Tamura, Kohei

    2015-01-01

    Managerial decision making is likely to be a dominant determinant of performance of teams in team sports. Here we use Japanese and German football data to investigate correlates between temporal patterns of formation changes across matches and match results. We found that individual teams and managers both showed win-stay lose-shift behavior, a type of reinforcement learning. In other words, they tended to stick to the current formation after a win and switch to a different formation after a loss. In addition, formation changes did not affect the results of succeeding matches in most cases. The results indicate that a swift implementation of a new formation in the win-stay lose-shift manner may not be a successful managerial rule of thumb.

  18. Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Kledal, T N; Bräuner-Osborne, Hans;

    1999-01-01

    , whereas IP-10 and stromal cell-derived factor-1alpha surprisingly acted as inverse agonists. These peptides had similar pharmacological properties with regard to enhancing or inhibiting, respectively, the stimulatory effect of ORF-74 on NIH-3T3 cell proliferation. Construction of a high affinity zinc...... as demonstrated by the effect of Zn2+ on the metal ion site-engineered receptor....

  19. Win percentage: a novel measure for assessing the suitability of machine classifiers for biological problems

    Science.gov (United States)

    2012-01-01

    Background Selecting an appropriate classifier for a particular biological application poses a difficult problem for researchers and practitioners alike. In particular, choosing a classifier depends heavily on the features selected. For high-throughput biomedical datasets, feature selection is often a preprocessing step that gives an unfair advantage to the classifiers built with the same modeling assumptions. In this paper, we seek classifiers that are suitable to a particular problem independent of feature selection. We propose a novel measure, called "win percentage", for assessing the suitability of machine classifiers to a particular problem. We define win percentage as the probability a classifier will perform better than its peers on a finite random sample of feature sets, giving each classifier equal opportunity to find suitable features. Results First, we illustrate the difficulty in evaluating classifiers after feature selection. We show that several classifiers can each perform statistically significantly better than their peers given the right feature set among the top 0.001% of all feature sets. We illustrate the utility of win percentage using synthetic data, and evaluate six classifiers in analyzing eight microarray datasets representing three diseases: breast cancer, multiple myeloma, and neuroblastoma. After initially using all Gaussian gene-pairs, we show that precise estimates of win percentage (within 1%) can be achieved using a smaller random sample of all feature pairs. We show that for these data no single classifier can be considered the best without knowing the feature set. Instead, win percentage captures the non-zero probability that each classifier will outperform its peers based on an empirical estimate of performance. Conclusions Fundamentally, we illustrate that the selection of the most suitable classifier (i.e., one that is more likely to perform better than its peers) not only depends on the dataset and application but also on the

  20. Win percentage: a novel measure for assessing the suitability of machine classifiers for biological problems

    Directory of Open Access Journals (Sweden)

    Parry R Mitchell

    2012-03-01

    Full Text Available Abstract Background Selecting an appropriate classifier for a particular biological application poses a difficult problem for researchers and practitioners alike. In particular, choosing a classifier depends heavily on the features selected. For high-throughput biomedical datasets, feature selection is often a preprocessing step that gives an unfair advantage to the classifiers built with the same modeling assumptions. In this paper, we seek classifiers that are suitable to a particular problem independent of feature selection. We propose a novel measure, called "win percentage", for assessing the suitability of machine classifiers to a particular problem. We define win percentage as the probability a classifier will perform better than its peers on a finite random sample of feature sets, giving each classifier equal opportunity to find suitable features. Results First, we illustrate the difficulty in evaluating classifiers after feature selection. We show that several classifiers can each perform statistically significantly better than their peers given the right feature set among the top 0.001% of all feature sets. We illustrate the utility of win percentage using synthetic data, and evaluate six classifiers in analyzing eight microarray datasets representing three diseases: breast cancer, multiple myeloma, and neuroblastoma. After initially using all Gaussian gene-pairs, we show that precise estimates of win percentage (within 1% can be achieved using a smaller random sample of all feature pairs. We show that for these data no single classifier can be considered the best without knowing the feature set. Instead, win percentage captures the non-zero probability that each classifier will outperform its peers based on an empirical estimate of performance. Conclusions Fundamentally, we illustrate that the selection of the most suitable classifier (i.e., one that is more likely to perform better than its peers not only depends on the dataset and

  1. A win ratio approach to comparing continuous non-normal outcomes in clinical trials.

    Science.gov (United States)

    Wang, Duolao; Pocock, Stuart

    2016-05-01

    Clinical trials are often designed to compare continuous non-normal outcomes. The conventional statistical method for such a comparison is a non-parametric Mann-Whitney test, which provides a P-value for testing the hypothesis that the distributions of both treatment groups are identical, but does not provide a simple and straightforward estimate of treatment effect. For that, Hodges and Lehmann proposed estimating the shift parameter between two populations and its confidence interval (CI). However, such a shift parameter does not have a straightforward interpretation, and its CI contains zero in some cases when Mann-Whitney test produces a significant result. To overcome the aforementioned problems, we introduce the use of the win ratio for analysing such data. Patients in the new and control treatment are formed into all possible pairs. For each pair, the new treatment patient is labelled a 'winner' or a 'loser' if it is known who had the more favourable outcome. The win ratio is the total number of winners divided by the total numbers of losers. A 95% CI for the win ratio can be obtained using the bootstrap method. Statistical properties of the win ratio statistic are investigated using two real trial data sets and six simulation studies. Results show that the win ratio method has about the same power as the Mann-Whitney method. We recommend the use of the win ratio method for estimating the treatment effect (and CI) and the Mann-Whitney method for calculating the P-value for comparing continuous non-Normal outcomes when the amount of tied pairs is small. Copyright © 2016 John Wiley & Sons, Ltd.

  2. A win ratio approach to comparing continuous non-normal outcomes in clinical trials.

    Science.gov (United States)

    Wang, Duolao; Pocock, Stuart

    2016-05-01

    Clinical trials are often designed to compare continuous non-normal outcomes. The conventional statistical method for such a comparison is a non-parametric Mann-Whitney test, which provides a P-value for testing the hypothesis that the distributions of both treatment groups are identical, but does not provide a simple and straightforward estimate of treatment effect. For that, Hodges and Lehmann proposed estimating the shift parameter between two populations and its confidence interval (CI). However, such a shift parameter does not have a straightforward interpretation, and its CI contains zero in some cases when Mann-Whitney test produces a significant result. To overcome the aforementioned problems, we introduce the use of the win ratio for analysing such data. Patients in the new and control treatment are formed into all possible pairs. For each pair, the new treatment patient is labelled a 'winner' or a 'loser' if it is known who had the more favourable outcome. The win ratio is the total number of winners divided by the total numbers of losers. A 95% CI for the win ratio can be obtained using the bootstrap method. Statistical properties of the win ratio statistic are investigated using two real trial data sets and six simulation studies. Results show that the win ratio method has about the same power as the Mann-Whitney method. We recommend the use of the win ratio method for estimating the treatment effect (and CI) and the Mann-Whitney method for calculating the P-value for comparing continuous non-Normal outcomes when the amount of tied pairs is small. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26970432

  3. Winning Faces Vary by Ideology: How Nonverbal Source Cues Influence Election and Communication Success in Politics

    DEFF Research Database (Denmark)

    Laustsen, Lasse; Petersen, Michael Bang

    2016-01-01

    for others. Utilizing research on ideological stereotypes and the determinants of facial preferences, we focus on the relationship between the facial dominance of the source and the ideology of the receiver. Across five studies, we demonstrate that a dominant face is a winning face when the audience...... is conservative but backfires and decreases success when the audience is liberal. On the other hand, a non-dominant face constitutes a winning face among liberal audiences but backfires among conservatives. These effects seemingly stem from deep-seated psychological responses and shape both the election...

  4. WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

    OpenAIRE

    Bowman, J. M.; Friesen, A D; Pollock, J. M.; Taylor, W E

    1980-01-01

    An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks' gestation and 120 microgram given after delivery to Rh-negative women at risk of ...

  5. 'No Win, No Fee', Cost-Shifting and the Costs of Civil Litigation

    DEFF Research Database (Denmark)

    Fenn, Paul; Grembi, Veronica; Rickman, Neil

    Expenditure on legal services has been rising for much of the last two decades and has attracted considerable policy attention in the UK. We argue that an important reason for this increase lies within the introduction of 'no win no fee' schemes in 1995 and a subsequent amendment which allowed...... claimants to shift additional costs (introduced by the 'no win no fee' schemes) onto losing defendants in 2000. In this paper, we evaluate the effect of the second of these reforms - that relating to the shifting of costs. We describe how this may have exacerbated the negative externality often associated...

  6. 说说用WinAVIMP4压视频的小经验

    Institute of Scientific and Technical Information of China (English)

    秋去春来

    2009-01-01

    上期给大家推荐了一款史上最快的压片工具——CG WinAVI MP4,它几乎满足了日常压片的所有需求,所以我一直在用。它。前一段我重装了系统。在一个什么软件都没有安装的纯净环境下,发现了TCG WinAVI MP4的不足之处——几乎无法工作了。

  7. In vivo labeling of cocaine receptors with sup 3 H-(-) cocaine, sup 3 H-WIN 35,065-2 and sup 3 H-WIN 35,428

    Energy Technology Data Exchange (ETDEWEB)

    Scheffel, U.; Boja, J.W.; Stathis, M.; Kuhar, M.J. (Johns Hopkins Medical Institutions, Baltimore, MD (United States))

    1990-02-26

    {sup 11}C-(-)cocaine (-COC) has recently been employed to image -COC binding sites in vivo using PET. Two analogs of -COC, WIN 35,065-2 (WIN-2) and WIN 35,428 (CFT), have been shown in vitro to exhibit higher affinity for the -COC receptor than -COC. The present study evaluates {sup 3}H-WIN-2 and {sup 3}H-CFT as in vivo receptor labels in mice with a view towards the use of these compounds as PET ligands for -COC receptors in the living human brain. {sup 3}H-labeled -COC, WIN-2 and CFT were injected i.v. into mice and their specific binding in the CNS determined. Peak striatal/cerebellar (S/C) ratios were reached at 5 minutes post injection with -COC (1.56), at 45 minutes with {sup 3}H-WIN-2 (3.30) and 60 minutes with {sup 3}H-CFT (4.0). The specificity of in vivo binding of {sup 3}H-WIN-2 and {sup 3}H-CFT was tested by pre-injection of various drugs. Binding of {sup 3}H-WIN-2 and {sup 3}H-CFT was dose-dependently blocked by cold WIN-2 and CFT, and by dopamine uptake site inhibitors (mazindol, GBR 12,909, nomifensine), but not by (+)COC, paroxetine and desipramine. The data indicate that {sup 3}H-WIN-2 and {sup 3}H-CFT exhibit improved in vivo binding (higher S/C ratios, longer retention time at the -COC receptor/dopamine transporter) compared to -COC and support their testing in PET studies.

  8. A Win-Win Effect for Both the Ferromagnetism and the Dopability of p-Type Doping in ZnO:(Cu+N)

    Science.gov (United States)

    Wei, Ling; Zhang, Wei-Feng

    2013-08-01

    We investigate the electronic structures and magnetic properties of ZnO doped with N, Cu, and (Cu+N) by using a first principles method and considering the strong correlation effect. It is interesting to compare these three systems. ZnO:N has weak p-type doping and unstable ferromagnetism, while ZnO:Cu becomes insulating due to the Jahn—Teller effect. Cu and N codoping can not only greatly improve the dopability of p-type doping accompanying the Jahn—Teller fading, but also enhance the ferromagnetism at the same time. The calculation results indicate that there is a win-win effect between N and Cu dopants in the ZnO:(Cu+N) system, which could possibly find applications in spintronics besides optoelectronics.

  9. WinSim: A simple simulation program for evaluating the influence of windows on heating demand and risk of overheating

    DEFF Research Database (Denmark)

    Schultz, Jørgen Munthe; Svendsen, Sv Aa Højgaard

    1998-01-01

    A two-node model of a room has been implemented in a computer program, WinSim, devel-oped for evaluation of thermal performance of windows in new buildings and in case of retro-fitting. The program calculates the annual heating demand and the number of hours with in-door temperatures higher than...... a user defined limit. WinSim is characterised by the limited amount of required input data. Guide-lines for calculation of the effective thermal capacity of the room is given, and results obtained with WinSim have been compared to results from an advanced building simulation program. Good agreement has...... been found between the two programs with respect to calculated annual heating demand and energy savings due to win-dow exchange, and also the calculated number of hours with overtemperature is similar. Based on the limited examples used for the comparison it can be concluded that WinSim is well suited...

  10. Automotion Workshop Based on WinCC Web Navigator%基于WinCC Web Navigator技术的自动化车间模式

    Institute of Scientific and Technical Information of China (English)

    王赛

    2012-01-01

    着重研究了基于WinCC Web Navigator技术的一种自动化车间模式,利用Web Navigator这种“瘦客户”系统,有效地解决了车间远程控制方面的难题,对工厂自动化的普及具有重要的现实意义.

  11. GIS system implemented by ArcGIS Mobile on WinCE%WinCE下基于ArcGIS Mobile实现的嵌入式地图

    Institute of Scientific and Technical Information of China (English)

    陈喜春

    2012-01-01

    In this paper, the detail were given out on how to develop a mobile GIS application, achieve functions such as map handling, symbol drawing etc.%以基于WinCE平台的指控终端为例,介绍了通过ArcGISMobile实现地图操作以及态势图标绘等功能的应用。

  12. PPAR GAMMA AGONISTS: AN EFFECTIVE STRATEGY FOR CANCER TREATMENT

    Directory of Open Access Journals (Sweden)

    Divya G.S

    2013-10-01

    Full Text Available PPAR-γ regulates cellular differentiation, development and metabolism. They play these essential roles by functioning as transcription factors regulating the expression of genes. The PPARs mainly are of three types α, β and γ. The PPAR-γ expressed in three forms γ1, γ2 and γ3 present in different tissues. When PPAR binds its ligand, transcription of target gene is increased or decreased. Tzds were able to induce cell differentiation and apoptosis or inhibit cell proliferation both in vitro and in vivo. However, widespread use of thiazolidinediones (TZDs, the clinically used synthetic PPAR gamma agonists, has been limited by adverse effects. So in this review we are suggesting some new molecules other than thiazolidine diones which can act as potential anticancer agents, after explaining the mechanism of action of PPAR-γ agonists as anticancer agents especially thiazolidinediones.

  13. Grooming, rank, and agonistic support in tufted capuchin monkeys.

    Science.gov (United States)

    Schino, Gabriele; Di Giuseppe, Francesca; Visalberghi, Elisabetta

    2009-02-01

    Studies investigating the relation between allogrooming and social rank in capuchin monkeys (genus Cebus) have yielded inconsistent results. In this study, we investigated the relation between grooming, agonistic support, aggression and social rank in a captive group of tufted capuchin monkeys (C. apella). Differently from most previous studies, we based our analyses on a relatively large database and studied a group with known genealogical relationships. Tufted capuchin females did not exchange grooming for rank-related benefits such as agonistic support or reduced aggression. Coherently with this picture, they did not groom up the hierarchy and did not compete for accessing high-ranking grooming partners. It is suggested that a small group size, coupled with a strong kin bias, may make the exchange of grooming for rank-related benefits impossible or unprofitable, thus eliminating the advantages of grooming up the hierarchy. We provide several possible explanations for the heterogeneity of results across capuchin studies that have addressed similar questions.

  14. Biological Rationale for the Use of PPARγ Agonists in Glioblastoma

    OpenAIRE

    Hayley Patricia Ellis; Kathreena Mary Kurian

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common primary intrinsic central nervous system tumor and has an extremely poor overall survival with only 10% patients being alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPARγ) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for glioblastoma. Although thiazolidinediones are effective oral...

  15. Alternation of Agonists and Antagonists During Turtle Hindlimb Motor Rhythms

    OpenAIRE

    Stein, Paul S.G.

    2010-01-01

    In a variety of vertebrates, including turtle, many classical and contemporary studies of spinal cord neuronal networks generating rhythmic motor behaviors emphasize a Reciprocal Model with alternation of agonists and antagonists, alternation of excitatory and inhibitory postsynaptic potentials, and reciprocal inhibition. Some studies of spinal cord neuronal networks, including those in turtle during scratch motor rhythms, describe a Balanced Model with concurrent excitatory and inhibitory po...

  16. Melatonin agonists for treatment of sleep and depressive disorders

    OpenAIRE

    Pandi-Perumal, Seithikurippu R.; Brown, Gregory M.; Daniel P. Cardinali; Venkataramanujan Srinivasan

    2011-01-01

    Melatonin the hormone secreted by the pineal gland has been effective in improving sleep both in normal sleepers and insomniacs and has been used successfully in treating sleep and circadian rhythm sleep disorders. The lack of consistency in the reports published by the authors is attributed to the differential bioavailabilty and short half-life of melatonin. Sleep disturbances are also prominent features of depressive disorders. To overcome this problem, melatonergic agonists with sleep prom...

  17. Pharmacophore-driven identification of PPARγ agonists from natural sources

    DEFF Research Database (Denmark)

    Petersen, R. K.; Christensen, Kathrine Bisgaard; Assimopoulou, A. N.;

    2011-01-01

    In a search for more effective and safe anti-diabetic compounds, we developed a pharmacophore model based on partial agonists of PPARγ. The model was used for the virtual screening of the Chinese Natural Product Database (CNPD), a library of plant-derived natural products primarily used in folk...... at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery....

  18. Discriminative learning occasioned by the administration of a dopamine agonist

    OpenAIRE

    Keller, Sabine; Delius, Juan

    2001-01-01

    Rationale: The repeated administration of psychostimulants usually brings about a progressive increment of the behavioral responses that they induce. We examined to what extent this sensitization is due to an associative learning process. Objectives: The dopamine agonist apomorphine elicits stereotyped pecking in pigeons, a response that increases with successive intramuscular injections. We tested whether this sensitized pecking would be discriminatively directed at environmental stimuli tha...

  19. Beta-adrenergic agonists as additive in beef cattle

    Directory of Open Access Journals (Sweden)

    Marcelo Vedovatto

    2014-10-01

    Full Text Available The agonists receptor beta-adrenergic (β-AA are present in virtually all types of mammalian cells and are stimulated by catecholamines (epinephrine and norepinephrine produced by the organism itself. The β-AA agonists are synthetic substances with similar structure to these amines. When provided in the diet they alter the body composition of animals, affecting the distribution of nutrients toward to protein deposition, and decreasing lipogenesis. Although the mechanisms of action are not fully understood, these may cause morphological and physiological changes such as increased blood flow decrease in plasma insulin, decreased lipogenesis, and muscle hypertrophy mainly in type II fibers. We also observed changes in motility and secretions grastointestinal tract, beyond the direct influence on the rumen bacteria, altering the digestibility of the diet. The β-AA agonists released in some countries for use in beef cattle are ractopamine hydrochloride and zilpaterol hydrochloride. According to literature data, the inclusion of these additives in the diet of feedlot cattle has been associated with an increase infeed efficiency with the increase in daily weight gain and with equal or lower feed intake. Carcass characteristics improvement was verified in carcass weight, and increased loin eye area, but with the possibility to decrease the subcutaneous fat thickness and marbling. Reviews in sensory panel of meat from animals consuming β-AA agonists showed decreased tenderness and juiciness. Thus β-AA improve performance and carcass characteristics, but more studies are needed to confirm whether they have negative influence on the organoleptic characteristics of the meat.

  20. Biological Rationale for the Use of PPARγ Agonists in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Hayley Patricia Ellis

    2014-03-01

    Full Text Available Glioblastoma Multiforme (GBM is the most common primary intrinsic CNS tumour and has an extremely poor overall survival, despite advances in neurosurgery, chemotherapy and radiation therapy. There has been interesting preliminary evidence suggesting that patients receiving the group of anti-diabetic drugs known as PPARγ (Peroxisome proliferator-activated receptor gamma agonists have a lower incidence of glioma. The nuclear hormone receptor PPARγ has been found to be expressed in high grade gliomas, and its activation has been shown to have several antineoplastic effects on human and rat glioma cell lines, and in some instances an additional protective increase in antioxidant enzymes has been observed in normal astrocytes. At present, no clinical trials are underway with regards to treating glioma patients using PPARγ agonists, as Pioglitazone and Rosiglitazone are only FDA-approved for use in treatment of type-2 diabetes. This review presents the case for evaluating the potential of PPARγ agonists as novel adjuvants in the treatment of high grade glioma. We introduce the PPARγ pathway, PPARγ gene and its products and examine recent research in glioblastoma.

  1. Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists.

    Science.gov (United States)

    Lin, Hsiang-Ru; Chou, Tsung-Hsien; Huang, Din-Wen; Chen, Ih-Sheng

    2014-09-01

    Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a variety of health benefits. The origin of their possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and for hyperglycemia. We studied whether cryptochinones A-D, which are structurally similar to known FXR ligands, may act at this target. Indeed, in mammalian one-hybrid and transient transfection reporter assays, cryptochinones A-D transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through molecular modeling docking studies we evaluated their ability to bind to the FXR ligand binding pocket. Our results indicate that cryptochinones A-D can behave as FXR agonists. PMID:25127166

  2. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  3. Dopamine agonist activity of EMD 23,448

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G.E.; Pettibone, D.J. (Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology)

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.

  4. Suppression of atherosclerosis by synthetic REV-ERB agonist

    International Nuclear Information System (INIS)

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization

  5. Emerging strategies for exploiting cannabinoid receptor agonists as medicines.

    Science.gov (United States)

    Pertwee, Roger G

    2009-02-01

    Medicines that activate cannabinoid CB(1) and CB(2) receptor are already in the clinic. These are Cesamet (nabilone), Marinol (dronabinol; Delta(9)-tetrahydrocannabinol) and Sativex (Delta(9)-tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol can also be prescribed to stimulate appetite, while Sativex is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB(2) receptors; or (v) 'multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. PMID:19226257

  6. Winning Faces Vary by Ideology: How Nonverbal Source Cues Influence Election and Communication Success in Politics

    DEFF Research Database (Denmark)

    Laustsen, Lasse; Petersen, Michael Bang

    2016-01-01

    for others. Utilizing research on ideological stereotypes and the determinants of facial preferences, we focus on the relationship between the facial dominance of the source and the ideology of the receiver. Across five studies, we demonstrate that a dominant face is a winning face when the audience...

  7. Xbox进Win8,玩家大体验

    Institute of Scientific and Technical Information of China (English)

    RPG

    2013-01-01

    xbox,这个名字真是家喻户晓。自从2001年发布以来,微软的xbox系列游戏主机在全球已经累计卖出了7 000余万台。对于这款热卖的主机,一直以来,关于它下一代产品的猜测总是不绝于耳。终于,随着windows 8(以下简称win8)的正式发售,微软也透露了有关下一代xbox的消息。微软证实,新的xbox主机能和win8以及windows phone实现多平台间的内容共享。既然win8已经上市了,那我们就来看看win8中的xbox会是什么样吧!xbox应用,游戏迷们的大社区

  8. Handling discrete citation data and Kao’s Nobel Prize winning article in fiber optics communication

    OpenAIRE

    Liu, Yuxian; Rousseau, Ronald

    2010-01-01

    We discuss technical problems in handling discrete data such as citation data. Using Kao’s citation data it is shown that splines can provide an everywhere differentiable description over the whole data interval. We find that citations to Kao’s Nobel Prize winning article follow the main developments of the field of fiber optics communication.

  9. Winning or Losing against an Opposite-Sex Peer on a Gender-Based Competitive Task.

    Science.gov (United States)

    Gilbert, Stefanie; Thompson, J. Kevin

    1999-01-01

    Explored the effects on college students' mood and body image of a negative versus positive outcome in an opposite-sex, competitive peer interaction. Used one gender-neutral and one gender stereotypical task. There were no gender differences in reactions to winning or losing gender-neutral competitions, except marginally for depression. The…

  10. GWDC Wins the Lekhwair Drilling Contract on a Lump Lump Sum Basis in Oman

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ GWDC (Great Wall Drilling Company Ltd.) has become the first Chinese drilling contractor to win a contract on a lump sum basis in PDO (Petroleum Development Oman) to carry out a major strategic drilling campaign in Lekhwair, Oman. The Lekhwair Drilling Campaign Contract was signed in August, 2005 following acceptance of the award by PDO.

  11. Many Libraries Have Gone to Federated Searching to Win Users Back from Google. Is It Working?

    Science.gov (United States)

    King, Douglas

    2008-01-01

    In the last issue, this journal asked a question on many librarians' minds, and it was pleased with the depth and variety of responses. As suggested by this journal editorial board member Oliver Pesch, readers were asked, "Many libraries have gone to federated searching to win users back from Google. Is it working?" Respondents approached the…

  12. Firms vie to offer DOE a prize-winning recipe for cleanup

    Energy Technology Data Exchange (ETDEWEB)

    Powers, M.B.

    1994-04-25

    Eager to get the most bang for its waste cleanup bucks, the US Department of Energy is conducting its own version of the Pillsbury bake-off. DOE is pitting two environmental contractors, Rust International Corp. and Lockheed Environmental Systems and Technologies Co., against each other to come up with the prize-winning recipe for cleaning up some nasty waste problems.

  13. Prepare for X-Win32 - the new X11 server software for Windows computers

    CERN Multimedia

    IT Department

    2011-01-01

    Starnet X-Win32 will replace Exceed as the X11 Server software on Windows computers by February 2012. X11 Server software allows a Windows user to have a graphical user interface on a remote Linux server. This change, initially motivated by a significant change of license conditions for Exceed, brings an easier integration of Windows and Linux logon mechanisms. At the same time, X-Win32 addresses the common use cases while providing a more intuitive configuration interface. CERN Predefined Connections will be available as before. They offer an easy way of starting applications on LXPLUS using PuTTY or starting the KDE, GNOME or ICE window managers. Since X-Win32 is better integrated with SSH and CERN Kerberos compared to Exceed, it is much simpler to set up secure access to Linux services. The decision to choose X-Win32 as the new X11 software resulted from an evaluation that involved various user communities and support teams. More information, including the documented use cases, is available at https://...

  14. Windows Calorimeter Control (WinCal) program computer software configuration management plan

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-26

    This document describes the system configuration management activities performed in support of the Windows Calorimeter Control (WinCal) system, in accordance with Site procedures based on Institute of Electrical and Electronic Engineers (IEEE) Standard 828-1990, Standard for Software Configuration Management Plans (IEEE 1990) and IEEE Standard 1042-1987, Guide to Software Configuration Management (IEEE 1987).

  15. The Better Ways to Win a Grant: Tips from "T&L" Grant Guru

    Science.gov (United States)

    Carnow, Gary A.

    2008-01-01

    Funding from grants is often at the core of a successful technology plan, but writing proposals requires a bit of magic and a lot of time. Grants can be a good way for educators to collaborate on building strong programs, but some creative thinking is also required. In this article, the author provides tips on how to win a grant: (1) Find a…

  16. Play to Win When It Comes to Kids and Sports Pain

    Science.gov (United States)

    ... Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Latest Health News → Article URL of this page: https://medlineplus.gov/news/fullstory_160901.html Play to Win When It Comes to Kids and Sports Pain Take injuries seriously, and if no improvement ...

  17. Analysing the Subject of Peace in Award-Winning Children's and Adolescent Novels in Turkey

    Science.gov (United States)

    Aslan, Canan; Kepenekci, Yasemin Karaman; Güldenoglu, Bilge Nur Dogan; Karagül, Sedat

    2016-01-01

    The purpose of this study is to reveal how the concept of peace is addressed in the national award-winning novels written for secondary school students within the Republic of Turkey. Data for this study was obtained from child and youth literature award organizations, associations and publishers within Turkey. Each group which was researched has…

  18. Firms vie to offer DOE a prize-winning recipe for cleanup

    International Nuclear Information System (INIS)

    Eager to get the most bang for its waste cleanup bucks, the US Department of Energy is conducting its own version of the Pillsbury bake-off. DOE is pitting two environmental contractors, Rust International Corp. and Lockheed Environmental Systems and Technologies Co., against each other to come up with the prize-winning recipe for cleaning up some nasty waste problems

  19. John Bardeen: The Only Person to Win Two Nobel Prizes in Physics

    Science.gov (United States)

    Hoddeson, L.

    2011-01-01

    John Bardeen worked on the theory of solids throughout his physics career, winning two Nobel Prizes: the first in 1956 for the invention of the transistor with Walter Brattain and William Shockley; and the second in 1972 for the development with Leon Cooper and J Robert Schrieffer of the Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity.…

  20. Winning in sequential Parrondo games by players with short-term memory

    Science.gov (United States)

    Cheung, K. W.; Ma, H. F.; Wu, D.; Lui, G. C.; Szeto, K. Y.

    2016-05-01

    The original Parrondo game, denoted as AB3, contains two independent games: A and B. The winning or losing of games A and B is defined by the change of one unit of capital. Game A is a losing game if played continuously, with winning probability p=0.5-ε , where ε =0.003 . Game B is also losing and has two coins: a good coin with winning probability {{p}\\text{g}}=0.75-ε is used if the player’s capital is not divisible by 3, otherwise a bad coin with winning probability {{p}\\text{b}}=0.1-ε is used. The Parrondo paradox refers to the situation where the mixture of games A and B in a sequence leads to winning in the long run. The paradox can be resolved using Markov chain analysis. We extend this setting of the Parrondo game to involve players with one-step memory. The player can win by switching his choice of A or B game in a Parrondo game sequence. If the player knows the identity of the game he plays and the state of his capital, then the player can win maximally. On the other hand, if the player does not know the nature of the game, then he is playing a (C, D) game, where either (C  =  A, D  =  B), or (C  =  B, D  =  A). For a player with one-step memory playing the AB3 game, he can achieve the highest expected gain with switching probability equal to 3/4 in the (C, D) game sequence. This result has been found first numerically and then proven analytically. Generalization to an AB mod(M) Parrondo game for other integers M has been made for the general domain of parameters {{p}\\text{b}}\\text{A}}<{{p}\\text{g}} . We find that for odd M the Parrondo effect does exist. However, for even M, there is no Parrondo effect for two cases: the initial game is A and the initial capital is even, or the initial game is B and the initial capital is odd. There is still a possibility of the Parrondo effect for the other two cases when M is even: the initial game is A and the initial capital is odd, or the initial game is B and the initial

  1. Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor

    DEFF Research Database (Denmark)

    Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek;

    2009-01-01

    secretagogue GHRP-6) plus four nonpeptide agonists-the original benzolactam L-692,429 [3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5-yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamide], the spiroindoline sulfonamide MK-677 [N-[1(R)-1, 2-dihydro-1-ethanesulfonylspiro-3H...

  2. Better you lose than I do: neural networks involved in winning and losing in a real time strictly competitive game.

    Science.gov (United States)

    Votinov, Mikhail; Pripfl, Juergen; Windischberger, Christian; Sailer, Uta; Lamm, Claus

    2015-01-01

    Many situations in daily life require competing with others for the same goal. In this case, the joy of winning is tied to the fact that the rival suffers. In this fMRI study participants played a competitive game against another player, in which every trial had opposite consequences for the two players (i.e., if one player won, the other lost, or vice versa). Our main aim was to disentangle brain activation for two different types of winning. Participants could either win a trial in a way that it increased their payoff; or they could win a trial in a way that it incurred a monetary loss to their opponent. Two distinct brain networks were engaged in these two types of winning. Wins with a monetary gain activated the ventromedial prefrontal cortex, an area associated with the processing of rewards. In contrast, avoidance of loss/other-related monetary loss evoked activation in areas related to mentalizing, such as the temporo-parietal junction and precuneus. However, both types of winnings shared activation in the striatum. Our findings extend recent evidence from neuroeconomics by suggesting that we consider our conspecifics' payoff even when we directly compete with them. PMID:26047332

  3. Problems of normative strenght and critique within the concept of agonistic participation: Towards the complementarity of agonistic and participatory democracy

    Directory of Open Access Journals (Sweden)

    Đorđević Biljana

    2014-01-01

    Full Text Available In this article I argue that there are grounds for considering agonistic democracy and participatory democracy complementarity in order to institutionalize agonism which has thus far lacked an elaborate articulation of its institutional dimension. The two democratic theories share a commitment toward widening the scope of the political as a way of inclusion of citizens and their subsequent political subjectivation and empowerment. Furthermore, there are authors on both sides who think democracy does not need foundations. Agonistic participation and contestation, on the one hand, and the broadening and strengthening of various sectors of political participation, on the other, both open up new possibilities for critique and change, but also create new risks. Building on a redefinition of agonisitic participation, I aim to attenuate an objection that agonism is normatively weak in terms of lacking resources to motivate citizens and justify their critique of practices of domination and oppression. The article concludes that we need to embrace agonistic participation as a means towards the development of democratic political judgement, as there are no other guarantees, i.e. secure foundations, for our ability to distinguish between democratic and non-democratic agon. [Projekat Ministarstva nauke Republike Srbije, br. 47026: Konstitucionalizam i vladavina prava u izgradnji nacionalne države - slučaj Srbije

  4. The treatment of Parkinson's disease with dopamine agonists

    Directory of Open Access Journals (Sweden)

    Frank, Wilhelm

    2008-06-01

    Full Text Available Parkinson’s disease is a chronic degenerative organic disease with unknown causes. A disappearance of cells with melanin in the substantia nigra is considered as biological artefact of the disease, which causes a degenerative loss of neurons in the corpus striatum of mesencephalon. This structure produces also the transmitter substance dopamine. Due to this disappearance of cells dopamine is not produced in a sufficient quantity which is needed for movement of the body. The questions of this report are concerned the efficiency and safety of a treatment with dopamine agonists. Furthermore the cost-effectiveness is investigated as well as ethic questions. The goal is to give recommendation for the use of dopamine agonists to the German health system. A systematic literature search was done. The identified studies have different methodological quality and investigate different hypothesis and different outcome criteria. Therefore a qualitative method of information synthesis was chosen. Since the introduction of L-Dopa in the 1960´s it is considered as the most effective substance to reduce all the cardinal symptoms of Parkinson disease. This substance was improved in the course of time. Firstly some additional substances were given (decarbonxylase inhibitors, catechol-o-transferase inhibitors (COMT-inhibitors, monoaminoxydase-inhibitors (MAO-inhibitors and NMDA-antagonists (N-Methyl-d-aspartat-antagonists. In the practical therapy of Parkinson dopamine agonists play an important role, because they directly use the dopamine receptors. The monotherapy of Parkinson disease is basically possible and is used in early stages of the disease. Clinical practise has shown, that an add on therapy with dopamine agonists can led to a reduction of the dose of L-dopa and a reduction of following dyskinesia. The studies for effectiveness include studies for the initial therapy, monotherapy and add-on-therapy. Basically there is a good effectiveness of dopamine

  5. Performance Indicators Related to Points Scoring and Winning in International Rugby Sevens

    Science.gov (United States)

    Higham, Dean G.; Hopkins, Will G.; Pyne, David B.; Anson, Judith M.

    2014-01-01

    Identification of performance indicators related to scoring points and winning is needed to inform tactical approaches to international rugby sevens competition. The aim of this study was to characterize team performance indicators in international rugby sevens and quantify their relationship with a team’s points scored and probability of winning. Performance indicators of each team during 196 matches of the 2011/2012 International Rugby Board Sevens World Series were modeled for their linear relationships with points scored and likelihood of winning within (changes in team values from match to match) and between (differences between team values averaged over all matches) teams. Relationships were evaluated as the change and difference in points and probability of winning associated with a two within- and between-team standard deviations increase in performance indicator values. Inferences about relationships were assessed using a smallest meaningful difference of one point and a 10% probability of a team changing the outcome of a close match. All indicators exhibited high within-team match-to-match variability (intraclass correlation coefficients ranged from 0.00 to 0.23). Excluding indicators representing points-scoring actions or events occurring on average less than once per match, 13 of 17 indicators had substantial clear within-team relationships with points scored and/or likelihood of victory. Relationships between teams were generally similar in magnitude but unclear. Tactics that increase points scoring and likelihood of winning should be based on greater ball possession, fewer rucks, mauls, turnovers, penalties and free kicks, and limited passing. Key points Successful international rugby sevens teams tend to maintain ball possession; more frequently avoid taking the ball into contact; concede fewer turnovers, penalties and free kicks; retain possession in scrums, rucks and mauls; and limit passing the ball. Selected performance indicators may be used

  6. Identification of human dopamine receptors agonists from Chinese herbs

    Institute of Scientific and Technical Information of China (English)

    Yi-lin ZHANG; Hai-qing ZHANG; Xiao-yu LIU; Shi-neng HUA; Lu-bing ZHOU; Jun YU; Xue-hai TAN

    2007-01-01

    Aim: To find human dopamine receptors, especially D1-like receptor specific ago-nists from Chinese herbs as potential antihypertension drug leads. Methods: Two D1-like receptor cell lines carrying a β-lactamase reporter gene, and a D2 receptor cell line coexpressing a promiscuous G protein G15 were constructed using HEK293 cells. A natural compound library made from fractionated samples of herbal ex-tracts was used for high-throughput screening (HTS) against one of the cell lines,HEK/D5R/CRE-blax. The interested hits were evaluated for their activities against various dopamine receptors. Results: Fourteen hits were identified from primary screening, of which 2 of the better hit samples, HD0522 and HD0059, were selected for further material and activity analysis, and to obtain 2 compounds that ap-peared as 2 single peaks in HPLC, HD0522H01 and HD0059H01. HD0059H01 could activate D1, D2, and D5 receptors, with EC50 values of 2.28 μg/mL, 0.85 μg/mL, and 1.41 μg/mL, respectively. HD0522H01 could only activate D1R and D5R with EC50 values of 2.95 μg/mL and 8.38 μg/mL. Conclusion: We established cell-based assays for 3 different human dopamine receptors and identified specific agonists HD0522H01 and HD0059H01 through HTS. The specific agonist to D1-like receptors, HD0522H01, may become a new natural product-based drug lead for antihypertension treatment.

  7. Agonist binding to high-affinity dopamine sites

    Energy Technology Data Exchange (ETDEWEB)

    Tedesco, J.L.

    1985-01-01

    The authors have characterized the dopamine D/sub 3/ site and its binding requirements. The dopamine D/sub 3/ site in calf caudate crude homogenate has a site density of 214-230 fmoles/mg. protein by both /sup 3/H-apomorphine (/sup 3/H-AOP) and /sup 3/H-dopamine (/sup 3/H-DA) Scatchard analysis of specific binding (SB). Stereospecific subsets of /sup 3/H-APO and /sup 3/H-DA sites were defined by the use of agonist and antagonist enantiomer-pairs as a rigorous test for D/sub 3/ site heterogeneity. IC/sub 50/ values for both /sup 3/H-APO and /sup 3/H-DA SB sites were assessed for 55 agonist ligands and an excellent correlation was obtained. The authors conclude that both /sup 3/H-ligands label the same D/sub 3/ site. The D/sub 3/ site affinities of 105 dopamine-agonist ligands, in particular 2-aminotetralins,, aporphines and flexible dopamine analogues were measured. Low D/sub 3/-site affinities of N-quaternary analogues confirm the need for a lone pair. Subadditivity of substituents' effects in semi-flexible DA analogues confirms their postulate that sidechain conformation is the critical determinant of affinity. They conclude that there are at least two high-affinity ligand conformations of the DA sidechain pharmacophore. These binding requirements are presented as two interface-Geometry tetrahedral models of the double H-bond interface between the D/sub 3/ site and the ideal ligand.

  8. AG-4:A NICOTINIC AGONIST ENDOWED WITH ANTIAMNESIC PROPERTIES

    OpenAIRE

    Ghelardini, C; Galeotti, N; Di Cesare Mannelli, L.; S. Dei; F. GUALTIERI; Bartolini, A.

    2000-01-01

    The effect of the nicotinic agonist AG-4 on memory processes was evaluated in the mouse passive avoidance test. AG-4 (100 mg per mouse icv) prevented amnesia induced by scopolamine (1.5 mg kg–1 ip), mecamylamine (20 mg kg–1 ip), and dihydro-b-erythroidine (10 mg per mouse icv). In the same experimental conditions, AG-4 (100 mg per mouse icv) also prevented baclofen (2 mg kg–1 ip), clonidine (0.125 mg kg–1 ip), and diphenhydramine (20 mg kg–1 ip) amnesia in mice. AG-4 exerted an an...

  9. Discovery of a potent and selective GPR120 agonist.

    Science.gov (United States)

    Shimpukade, Bharat; Hudson, Brian D; Hovgaard, Christine Kiel; Milligan, Graeme; Ulven, Trond

    2012-05-10

    GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist.

  10. Induction of depersonalization by the serotonin agonist meta-chlorophenylpiperazine.

    Science.gov (United States)

    Simeon, D; Hollander, E; Stein, D J; DeCaria, C; Cohen, L J; Saoud, J B; Islam, N; Hwang, M

    1995-09-29

    Sixty-seven subjects, including normal volunteers and patients with obsessive-compulsive disorder, social phobia, and borderline personality disorder, received ratings of depersonalization after double-blind, placebo-controlled challenges with the partial serotonin agonist meta-chlorophenylpiperazine (m-CPP). Challenge with m-CPP induced depersonalization significantly more than did placebo. Subjects who became depersonalized did not differ in age, sex, or diagnosis from those who did not experience depersonalization. There was a significant correlation between the induction of depersonalization and increase in panic, but not nervousness, anxiety, sadness, depression, or drowsiness. This report suggests that serotonergic dysregulation may in part underlie depersonalization.

  11. Narrow SAR in odorant sensing Orco receptor agonists.

    Science.gov (United States)

    Romaine, Ian M; Taylor, Robert W; Saidu, Samsudeen P; Kim, Kwangho; Sulikowski, Gary A; Zwiebel, Laurence J; Waterson, Alex G

    2014-06-15

    The systematic exploration of a series of triazole-based agonists of the cation channel insect odorant receptor is reported. The structure-activity relationships of independent sections of the molecules are examined. Very small changes to the compound structure were found to exert a large impact on compound activity. Optimal substitutions were combined using a 'mix-and-match' strategy to produce best-in-class compounds that are capable of potently agonizing odorant receptor activity and may form the basis for the identification of a new mode of insect behavior modification. PMID:24813736

  12. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

    Energy Technology Data Exchange (ETDEWEB)

    Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Parks, Derek J.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce; (GSKNC)

    2010-09-27

    Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

  13. Discovery of potent and selective nonsteroidal indazolyl amide glucocorticoid receptor agonists.

    Science.gov (United States)

    Sheppeck, James E; Gilmore, John L; Xiao, Hai-Yun; Dhar, T G Murali; Nirschl, David; Doweyko, Arthur M; Sack, Jack S; Corbett, Martin J; Malley, Mary F; Gougoutas, Jack Z; Mckay, Lorraine; Cunningham, Mark D; Habte, Sium F; Dodd, John H; Nadler, Steven G; Somerville, John E; Barrish, Joel C

    2013-10-01

    Modification of a phenolic lead structure based on lessons learned from increasing the potency of steroidal glucocorticoid agonists lead to the discovery of exceptionally potent, nonsteroidal, indazole GR agonists. SAR was developed to achieve good selectivity against other nuclear hormone receptors with the ultimate goal of achieving a dissociated GR agonist as measured by human in vitro assays. The specific interactions by which this class of compounds inhibits GR was elucidated by solving an X-ray co-crystal structure. PMID:23953070

  14. beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

    OpenAIRE

    Cowen, P. J.; Grahame-Smith, D.G.; Green, A R; Heal, D. J.

    1982-01-01

    The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-meth...

  15. 26 CFR 7.6041-1 - Return of information as to payments of winnings from bingo, keno, and slot machines.

    Science.gov (United States)

    2010-04-01

    ... SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE TAX REFORM ACT OF 1976 § 7.6041-1 Return of information as to payments of winnings from...

  16. Long-acting beta(2)-agonists in management of childhood asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

  17. Structure and function of an irreversible agonist-β(2) adrenoceptor complex

    DEFF Research Database (Denmark)

    Rosenbaum, Daniel M; Zhang, Cheng; Lyons, Joseph A;

    2011-01-01

    G-protein-coupled receptors (GPCRs) are eukaryotic integral membrane proteins that modulate biological function by initiating cellular signalling in response to chemically diverse agonists. Despite recent progress in the structural biology of GPCRs, the molecular basis for agonist binding...... and allosteric modulation of these proteins is poorly understood. Structural knowledge of agonist-bound states is essential for deciphering the mechanism of receptor activation, and for structure-guided design and optimization of ligands. However, the crystallization of agonist-bound GPCRs has been hampered...

  18. Dopamine agonist-induced substance addiction: the next piece of the puzzle.

    Science.gov (United States)

    Evans, Andrew

    2011-02-01

    Traditional antiparkinson treatment strategies strive to balance the antiparkinson effects of dopaminergic drugs with the avoidance of motor response complications. Dopamine agonists have an established role in delaying the emergence of motor response complications or reducing motor "off" periods. The recent recognition of a range of "behavioural addictions" that are linked to dopamine agonist use has highlighted the role of dopamine in brain reward function and addiction disorders in general. Dopamine agonists have now even been linked occasionally to new substance addictions. The challenge now for the Parkinsonologist is to also balance the net benefits of using dopamine agonists for their motor effects with avoiding the harm from behavioural compulsions. PMID:20980151

  19. EP4 agonist alleviates indomethacin-induced gastric lesions and promotes chronic gastric ulcer healing

    Institute of Scientific and Technical Information of China (English)

    Guang-Liang Jiang; Wha Bin Im; Yariv Donde; Larry A Wheeler

    2009-01-01

    AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethacin (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacininduced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro , the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis. CONCLUSION: EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and indomethacin-aggravated gastric ulcers, via promoting proliferation and survival of mucous epithelial cells.

  20. On the translation of culture-loaded words in The Oil-Peddler Wins the Queen of the Flowers

    Institute of Scientific and Technical Information of China (English)

    廖心坤

    2015-01-01

    The Oil-Peddler Wins the Queen of the Flowers,as a classic Chinese literary work,has many culture-loaded words which may be considered as the most difficult part in translation process.So this assay aims at analyzing the translation of cultureloaded words in The Oil-Peddler Wins the Queen of the Flowers and tries to figure out the trianslation strategies adopted to handle culture-loaded words.

  1. Win7系统下Android开发平台的搭建

    Institute of Scientific and Technical Information of China (English)

    孟晓龙

    2011-01-01

    随着各大移动终端生产商大力开发和生产基于Android的移动设备,Android迅速得到业界和社会的认可,基于Android平台的各类人才逐渐成为各大企业竞相争夺的焦点。然而繁琐的Android平台搭建过程,再加上-9Win7操作系统的兼容性问题,使得多数Android初级开发者望而却步。基于Win7系统Android开发平台搭建的经验,给出详细的搭建步骤,引导广大Android初级开发者踏入Android开发之门。

  2. Playing the gender card: winning the hearts and minds of the female demographic

    Energy Technology Data Exchange (ETDEWEB)

    Brissette, S. [Bruce Power, Tiverton, Ontario (Canada)

    2006-07-01

    To meet future growth potential, the nuclear industry will have to compete to attract the best and brightest by positioning itself as a viable career choice for women and men of diverse backgrounds considering careers in business, engineering, sciences and the trades. This presentation will showcase the innovative work being undertaken by the Canadian chapter of Women in Nuclear (WiN). Learn more about WiN-Canada's partnership with the CNS aimed at engaging in a dialogue with women opinion leaders in Ontario, the successful international conference hosted by WiN-Canada, the efforts at recognizing and promoting the role of women in our industry with the media, and the results of recent groundbreaking WiN Canada survey on what makes nuclear an appealing career to women in our industry, and what barriers must be overcome to continue to attract women to a career in nuclear in the future. (author)

  3. Salivary testosterone change following monetary wins and losses predicts future financial risk-taking.

    Science.gov (United States)

    Apicella, Coren L; Dreber, Anna; Mollerstrom, Johanna

    2014-01-01

    While baseline testosterone has recently been implicated in risk-taking in men, less is known about the effects of changing levels of testosterone on financial risk. Here we attempt to influence testosterone in men by having them win or lose money in a chance-based competition against another male opponent. We employ two treatments where we vary the amount of money at stake so that we can directly compare winners to losers who earn the same amount, thereby abstracting from income effects. We find that men who experience a greater increase in bioactive testosterone take on more risk, an association that remains when controlling for whether the participant won the competition. In fact, whether subjects won the competition did not predict future risk. These results suggest that testosterone change, and thus individual differences in testosterone reactivity, rather than the act of winning or losing, influence financial risk-taking. PMID:24275004

  4. Effects of peat-winning on the water environment at a sedge fen ecosystem

    International Nuclear Information System (INIS)

    Peatlands are used in agriculture and forestry for vegetational growth and in peat-winning for soil improvement, horticulture production and as fuel. A prerequisite in peatland use is drainage, with influences on water conditions in the peatland and its surroundings. Environmental effects from such peatland use have been investigated at a sedge fen in central Sweden. Groundwater, runoff, water chemistry and stream water biology were studied during almost 14 years. This period started with a virgin undrained peatland, later being drained for forest production and after a period of seven years intensively drained for peat-winning and with peat harvesting going on for another seven years period with hydrological investigations. Results show a lowered groundwater level, increased runoff and both higher concentrations of most elements and higher leaching from the drained peatland. Biomass and number of individuals of the benthic fauna in stream water also increased. 7 refs, 7 figs, 2 tabs

  5. Effects of peat-winning on the water environment at a sedge fen ecosystem

    International Nuclear Information System (INIS)

    Peatlands are used in agriculture and forestry for vegetational growth and in peat-winning for soil improvement, horticulture production and as fuel. A prerequisite in peatland use is drainage, with influences on water conditions in the peatland and in its surroundings. Environmental effects from such peatland use have been investigated at a sedge fen in central Sweden. Groundwater, runoff, water chemistry and streamwater biology were studied during almost 14 years. This period started with a virgin undrained peatland, later being drained for forest production and after a period of seven years intensively drained for peat-winning and with peat harvesting going on for another seven year period with hydrological investigations. Results show a lowered groundwater level, increased runoff and both higher concentrations of most elements and higher leaching from the drained peatland. Biomass and number of individuals of the benthic fauna in streamwater also increased. 7 refs

  6. Large sample inference for a win ratio analysis of a composite outcome based on prioritized components.

    Science.gov (United States)

    Bebu, Ionut; Lachin, John M

    2016-01-01

    Composite outcomes are common in clinical trials, especially for multiple time-to-event outcomes (endpoints). The standard approach that uses the time to the first outcome event has important limitations. Several alternative approaches have been proposed to compare treatment versus control, including the proportion in favor of treatment and the win ratio. Herein, we construct tests of significance and confidence intervals in the context of composite outcomes based on prioritized components using the large sample distribution of certain multivariate multi-sample U-statistics. This non-parametric approach provides a general inference for both the proportion in favor of treatment and the win ratio, and can be extended to stratified analyses and the comparison of more than two groups. The proposed methods are illustrated with time-to-event outcomes data from a clinical trial.

  7. The one-dimensional minesweeper game: What are your chances of winning?

    Science.gov (United States)

    Rodríguez-Achach, M.; Coronel-Brizio, H. F.; Hernández-Montoya, A. R.; Huerta-Quintanilla, R.; Canto-Lugo, E.

    2016-04-01

    Minesweeper is a famous computer game consisting usually in a two-dimensional lattice, where cells can be empty or mined and gamers are required to locate the mines without dying. Even if minesweeper seems to be a very simple system, it has some complex and interesting properties as NP-completeness. In this paper and for the one-dimensional case, given a lattice of n cells and m mines, we calculate the winning probability. By numerical simulations this probability is also estimated. We also find out by mean of these simulations that there exists a critical density of mines that minimize the probability of winning the game. Analytical results and simulations are compared showing a very good agreement.

  8. Structural complexes of the agonist, inverse agonist and antagonist bound C5a receptor: insights into pharmacology and signaling.

    Science.gov (United States)

    Rana, Soumendra; Sahoo, Amita Rani; Majhi, Bharat Kumar

    2016-04-26

    The C5a receptor (C5aR) is a pharmacologically important G-protein coupled receptor (GPCR) that interacts with (h)C5a, by recruiting both the "orthosteric" sites (site1 at the N-terminus and site2 at the ECS, extra cellular surface) on C5aR in a two site-binding model. However, the complex pharmacological landscape and the distinguishing chemistry operating either at the "orthosteric" site1 or at the functionally important "orthosteric" site2 of C5aR are still not clear, which greatly limits the understanding of C5aR pharmacology. One of the major bottlenecks is the lack of an experimental structure or a refined model structure of C5aR with appropriately defined active sites. The study attempts to understand the pharmacology at the "orthosteric" site2 of C5aR rationally by generating a highly refined full-blown model structure of C5aR through advanced molecular modeling techniques, and further subjecting it to automated docking and molecular dynamics (MD) studies in the POPC bilayer. The first series of structural complexes of C5aR respectively bound to a linear native peptide agonist ((h)C5a-CT), a small molecule inverse agonist (NDT) and a cyclic peptide antagonist (PMX53) are reported, apparently establishing the unique pharmacological landscape of the "orthosteric" site2, which also illustrates an energetically distinct but coherent competitive chemistry ("cation-π" vs. "π-π" interactions) involved in distinguishing the established ligands known for targeting the "orthosteric" site2 of C5aR. Over a total of 1 μs molecular dynamics (MD) simulation in the POPC bilayer, it is evidenced that while the agonist prefers a "cation-π" interaction, the inverse agonist prefers a "cogwheel/L-shaped" interaction in contrast to the "edge-to-face/T-shaped" type π-π interactions demonstrated by the antagonist by engaging the F275(7.28) of the C5aR. In the absence of a NMR or crystallographically guided model structure of C5aR, the computational model complexes not only

  9. Strengthening Medicare Managed to Reach Tripartite Win-Win%加强医保管理达到三方共赢

    Institute of Scientific and Technical Information of China (English)

    肖进莲; 米春香; 龚放

    2014-01-01

    With the development of medical innovation,the requirement of reimbursement ratio of inpatients should be higher and higher. In order to strengthen the management of health care is the focus of the hospital medical insurance management work. To achieve health care hospital patients with tripartite win-win is the goal of the hospital medical insurance management work. This article introduced the practice of health management of exploration experience. Results show that ef ectively implement benefits of medical insurance,patients and hospital. Can be reference for other medical institutions.%随着医疗改革的不断深入,住院患者对报销比例的要求越来越高,加强医保管理,达到医保、患者、医院三方共赢是医院医保管理工作的重点和目标。本文详细介绍了医保管理工作的实际探索经验,结果分析表明,有效地实现了医保管理机构、医保定点医疗机构、住院患者三方共赢的效果,可为其它医疗机构参考。

  10. Potentials for win-win alliances among animal agriculture and forest products industries: Application of the principles of industrial ecology and sustainable development

    Institute of Scientific and Technical Information of China (English)

    Ellis; B.; Cowling; Cari; S.; Furiness

    2005-01-01

    Commercial forests in many parts of the world are deficient in nitrogen and phosphorus. These nutrient-deficient forests often exist in close proximity to large animal feeding operations, meat processing and other food, textile, or other biomass-processing plants, and municipal waste treatment facilities. Many of these facilities produce large surpluses of nitrogen,phosphorus, and organic matter as gaseous ammonia, urea, uric acid, phosphorus compounds,bacterial sludges, and partially treated municipal wastewaters. These co-existing and substantial nutrient deficiencies and surpluses offer ready-made opportunities for discovery, demonstration,and commercial development of science-based, technology-facilitated, environmentally sound,economically viable, and socially acceptable "win-win alliances" among these major industries based on the principles of industrial ecology and sustainable development. The major challenge is to discover practical means to capture the surplus nutrients and put them to work in forest stands from which value-added products can be produced and sold at a profit.

  11. Win-win emissions reductions : smart transportation emission reduction strategies can achieve Kyoto targets and provide other economic, social and environmental benefits

    Energy Technology Data Exchange (ETDEWEB)

    Litman, T.

    2005-12-02

    This paper identified 12 transportation solutions that provide a combination of economic, social and environmental benefits. The win-win strategies are cost-effective, technically feasible policy reforms that correct market distortions which promote inefficient travel patterns. In addition to energy conservation and reducing pollution and traffic congestion, the strategies save on road and parking facilities, promote traffic safety and consumer savings, and improve mobility for non-drivers. The basic economic principles that make these benefits possible were examined. The proposed solutions create a more equitable and efficient transportation system that supports economic development and helps achieve other strategic planning objectives. The strategies include planning reforms; pay-as-you-drive pricing; parking cash-out; parking pricing; road pricing; transportation demand management programs; transit and ride-share improvements; walking and cycling improvements; smart growth; freight transport management; car sharing and revenue-neutral tax shifting. The author claims that if fully implemented, these strategies could reduce motor vehicle emissions and other costs by 30 to 50 per cent, depending on geographic, demographic and economic conditions. It was suggested that the approach could help meet Kyoto emission reduction targets while promoting economic development and increasing consumer benefits. 14 refs., 4 tabs., 2 figs.

  12. Toll-Like Receptor 9 Agonists for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Davide Melisi

    2014-08-01

    Full Text Available The immune system has acquired increasing importance as a key player in cancer maintenance and growth. Thus, modulating anti-tumor immune mediators has become an attractive strategy for cancer treatment. Toll-like receptors (TLRs have gradually emerged as potential targets of newer immunotherapies. TLR-9 is preferentially expressed on endosome membranes of B-cells and plasmacytoid dendritic cells (pDC and is known for its ability to stimulate specific immune reactions through the activation of inflammation-like innate responses. Several synthetic CpG oligonucleotides (ODNs have been developed as TLR-9 agonists with the aim of enhancing cancer immune surveillance. In many preclinical models, CpG ODNs were found to suppress tumor growth and proliferation both in monotherapy and in addition to chemotherapies or target therapies. TLR-9 agonists have been also tested in several clinical trials in patients with solid tumors. These agents showed good tolerability and usually met activity endpoints in early phase trials. However, they have not yet been demonstrated to significantly impact survival, neither as single agent treatments, nor in combination with chemotherapies or cancer vaccines. Further investigations in larger prospective studies are required.

  13. Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity

    Science.gov (United States)

    Galle-Treger, Lauriane; Suzuki, Yuzo; Patel, Nisheel; Sankaranarayanan, Ishwarya; Aron, Jennifer L.; Maazi, Hadi; Chen, Lin; Akbari, Omid

    2016-01-01

    Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β. Additionally, the specific α7nAChR agonist reduces cytokine production and AHR in a humanized ILC2 mouse model. Collectively, our data suggest that α7nAChR expressed by ILC2s is a potential therapeutic target for the treatment of ILC2-mediated asthma. PMID:27752043

  14. Cariprazine:New dopamine biased agonist for neuropsychiatric disorders.

    Science.gov (United States)

    De Deurwaerdère, P

    2016-02-01

    Cariprazine (RGH-188, MP-214, Vraylar[TM]) is a new dopamine receptor ligand developed for the treatment of several neuropsychiatric diseases including schizophrenia and bipolar disorders. Cariprazine displays higher affinity at dopamine D3 receptors and a similar affinity at D2 and 5-HT2B receptors. At variance with some atypical antipsychotics, its affinity at 5-HT1A, 5-HT2A and histamine H1 receptors is modest compared with its three main targets. Cariprazine could correspond to a biased agonist at dopamine receptors, displaying either antagonist or partial agonist properties depending on the signaling pathways linked to D2/D3 receptors. The compound crosses the blood-brain barrier, as revealed by positron emission tomography and pharmacokinetic studies in various species. Two main metabolites result mainly from the activity of CYP34A and display properties similar to those of the parent drug. Behavioral data report that cariprazine is efficacious in animal models addressing positive, negative and cognitive symptoms of schizophrenia with no extrapyramidal side effects. In September 2015, the FDA approved the use of cariprazine for the treatment of schizophrenia and type I bipolar disorder. The efficacy of cariprazine in other neuropsychiatric diseases is currently being evaluated in preclinical and clinical studies. Side effects have been observed in humans, including extrapyramidal side effects and akathisia of mild to moderate intensity. PMID:27092339

  15. How does agonistic behaviour differ in albino and pigmented fish?

    Science.gov (United States)

    Horký, Pavel; Wackermannová, Marie

    2016-01-01

    In addition to hypopigmentation of the skin and red iris colouration, albino animals also display distinct physiological and behavioural alterations. However, information on the social interactions of albino animals is rare and has mostly been limited to specially bred strains of albino rodents and animals from unique environments in caves. Differentiating between the effects of albinism and domestication on behaviour in rodents can be difficult, and social behaviour in cave fish changes according to species-specific adaptations to conditions of permanent darkness. The agonistic behaviours of albino offspring of pigmented parents have yet to be described. In this study, we observed agonistic behaviour in albino and pigmented juvenile Silurus glanis catfish. We found that the total number of aggressive interactions was lower in albinos than in pigmented catfish. The distance between conspecifics was also analysed, and albinos showed a tendency towards greater separation from their same-coloured conspecifics compared with pigmented catfish. These results demonstrate that albinism can be associated with lower aggressiveness and with reduced shoaling behaviour preference, as demonstrated by a tendency towards greater separation of albinos from conspecifics. PMID:27114883

  16. Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

    Science.gov (United States)

    Gerra, Gilberto; Zaimovic, Amir; Gerra, Maria L; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo

    2010-01-01

    For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists. PMID:19832688

  17. Lost and win-back customers: towards a theoretical framework of customer relationship reactivation

    OpenAIRE

    Lopes, Luísa; Brito, Carlos Henrique; Alves, Helena

    2012-01-01

    Research has shown that there is a negative correlation between the number of "lost customers" and business income. Stauss and Friege (1999) have found that the net return on investment from a new customer is 23% compared to a 214% return on investment from the reinstatement of a customer who has defected. Customer win-back is an important part of a customer relationship management strategy and focuses on the re-initiation and management of relationships with customers that have laps...

  18. Goal or Gold: Overlapping Reward Processes in Soccer Players upon Scoring and Winning Money

    OpenAIRE

    Häusler, Alexander Niklas; Becker, Benjamin; Bartling, Marcel; Weber, Bernd

    2015-01-01

    Social rewards are important incentives for human behavior. This is especially true in team sports such as the most popular one worldwide: soccer. We investigated reward processing upon scoring a soccer goal in a standard two-versus-one situation and in comparison to winning in a monetary incentive task. The results show a strong overlap in brain activity between the two conditions in established reward regions of the mesolimbic dopaminergic system, including the ventral striatum and ventrome...

  19. Who is Going to Win the EURO 2008? A Statistical Investigation of Bookmakers Odds.

    OpenAIRE

    Leitner, Christoph; Zeileis, Achim; Hornik, Kurt

    2008-01-01

    This June one of the biggest and most popular sports tournaments will take place in Austria and Switzerland, the European soccer championship 2008 (UEFA EURO 2008). Therefore millions of soccer fans in Europe and throughout the world are asking themselves: "Who is going to win the EURO 2008?" Many people, including sports experts and former players, give their guesses and expectations in the media, but there is also a group with financial incentives, like some economists who expect economical...

  20. Winning strategies of political campaigns in hybrid electoral spaces. Case study – Iasi County

    Directory of Open Access Journals (Sweden)

    Adrian Marius Tompea

    2012-10-01

    Full Text Available Our material introduces the concept of hybrid electoral area, as a distinct electoral entity set up by special territorial and administrative processes. We analyze specific cases of such spaces in Iasi and we see how the winning electoral strategies have been configured here. We provide examples of campaign activities and actions which ensured the candidates’ success by simultaneously targeting both the electoral sub-spaces and the community seen as whole.

  1. Suppression of Stra8 Expression in the Mouse Gonad by WIN 18,4461

    OpenAIRE

    Hogarth, Cathryn A.; Evanoff, Ryan; Snyder, Elizabeth; Kent, Travis; Mitchell, Debra; Small, Christopher; Amory, John K.; Griswold, Michael D.

    2011-01-01

    Bis-(dichloroacetyl)-diamines (BDADs) are compounds that inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully investigated. It has been proposed that BDADs may function via inhibition of testicular retinoic acid (RA) biosynthesis. We employed an organ culture technique and the expression of a marker for RA activity, Stra8 (stimulated by retinoic acid gene 8), to investigate if the BDAD WIN 18,446 inhibited the bios...

  2. Winning Big but Feeling No Better? The Effect of Lottery Prizes on Physical and Mental Health

    OpenAIRE

    Apouey, Bénédicte; Clark, Andrew E.

    2010-01-01

    We use British panel data to determine the exogenous impact of income on a number of individual health outcomes: general health status, mental health, physical health problems, and health behaviors (drinking and smoking). Lottery winnings allow us to make causal statements regarding the effect of income on health, as the amount won by winners is largely exogenous. Positive income shocks have no significant effect on general health, but a large positive effect on mental health. This result see...

  3. Winning big but feeling no better? The effect of lottery prizes on physical and mental health

    OpenAIRE

    Apouey, Bénédicte H; Clark, Andrew E.

    2014-01-01

    We use British panel data to determine the exogenous impact of income on a number of individual health outcomes: general health status, mental health, physical health problems, and health behaviours (drinking and smoking). Lottery winnings allow us to make causal statements regarding the effect of income on health, as the amount won by winners is largely exogenous. Positive income shocks have no significant effect on self-assessed overall health, but a significant positive effect on mental he...

  4. Winning big but feeling no better? The effect of lottery prizes on physical and mental health

    OpenAIRE

    Apouey, Benedicte; Clark, Andrew E.

    2009-01-01

    We use British panel data to explore the exogenous impact of income on a number of individual health outcomes: general health status, mental health, physical health problems, and health behaviours (drinking and smoking). Lottery winnings allow us to make causal statements regarding the effect of income on health, as the amount won is largely exogenous. These positive income shocks have no significant effect on general health, but a large positive effect on mental health. This result seems par...

  5. Winning big but feeling no better? The effect of lottery prizes on physical and mental health

    OpenAIRE

    Apouey, Bénédicte; Clark, Andrew E.

    2013-01-01

    We use British panel data to determine the exogenous impact of income on a number of individual health outcomes: general health status, mental health, physical health problems, and health behaviors (drinking and smoking). Lottery winnings allow us to make causal statements regarding the effect of income on health, as the amount won by winners is largely exogenous. Positive income shocks have no significant effect on self-assessed overall health, but a large positive effect on mental health. T...

  6. Analysis of Noise at Coal Face by Fully-Mechanized Coal Winning Technology

    Institute of Scientific and Technical Information of China (English)

    刘照鹏

    2003-01-01

    The noise level of coal face by full-mechanized coal winning technology was measured in a coal mine. And then it was analyzed and evaluated using environment science, ergonomics and fussy mathematics analysis. Basis of the statistics and analysis of the measured noise level some measures, such as applying the new materials and improving the construction of the equipment, were carried out. The resuts show that they can reduce the noise level, improve the working environment and enhance the work efficiency.

  7. Anthropogenic contamination of a phreatic drinking water winning: 3-dimensional reactive transport modelling

    Science.gov (United States)

    Griffioen, J.; van der Grift, B.; Maas, D.; van den Brink, C.; Zaadnoordijk, J. W.

    2003-04-01

    Groundwater is contaminated at the regional scale by agricultural activities and atmospheric deposition. A 3-D transport model was set-up for a phreatic drinking water winning, where the groundwater composition was monitored accurately. The winning is situated at an area with unconsolidated Pleistocene deposits. The land use is nature and agriculture. Annual mass-balances were determined using a wide range of historic data. The modelling approach for the unsaturated zone was either simple box models (Cl, NO_3 and SO_4) or 1-D transport modelling using HYDRUS (Cd). The modelling approach for the saturated zone used a multiple solute version of MT3D, where denitrification associated with pyrite oxidation and sorption of Cd were included. The solute transport calculations were performed for the period 1950--2030. The results obtained for the year 2000 were used as input concentration for the period 2000--2030. A comparison between the calculated and the measured concentrations of groundwater abstracted for Cl, NO_3 and SO_4 yields the following. First, the input at the surface is rather well estimated. Second, the redox reactivity of the first two aquifers is negligible around the winning, which is confirmed by respiration experiments using anaerobically sampled aquifer sediments. The reactivity of the third aquifer, which is a marine deposit and lies at least 30 meters below surface, is considerable. The discrepancies between modelled and measured output are explained by lack of knowledge about the subsurface reactivity and/or wrong estimates of surface loading and leaching from the unsaturated zone. The patterns for other hydrogeochemical variables such as Ca, HCO_3 may further constrain this lack of knowledge. The results for Cd indicate that Cd becomes strongly retarded, despite the low reactivity of the sandy sediments. The winning is rather insensitive to Cd contamination (but the surface water drainage network is not). Two major uncertainties for input of Cd

  8. RandomOut: Using a convolutional gradient norm to win The Filter Lottery

    OpenAIRE

    Cohen, Joseph Paul; Lo, Henry Z.; Ding, Wei

    2016-01-01

    Convolutional neural networks are sensitive to the random initialization of filters. We call this The Filter Lottery (TFL) because the random numbers used to initialize the network determine if you will "win" and converge to a satisfactory local minimum. This issue forces networks to contain more filters (be wider) to achieve higher accuracy because they have better odds of being transformed into highly discriminative features at the risk of introducing redundant features. To deal with this, ...

  9. Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations.

    OpenAIRE

    Khan, S.; O'Brien, P. J.

    1995-01-01

    Previously we showed that tirapazamine (SR 4233, Win 59075) is cytotoxic towards hepatocytes under conditions of hypoxia but not in 10% or 95% oxygen and that bioreduction by DT-diaphorase or cytochrome P450 is not a major pathway. In the present study, we report that tirapazamine is highly cytotoxic to isolated rat hepatocytes maintained under 1% oxygen and the molecular cytotoxic mechanism has been elucidated. Cytotoxicity was prevented by the cytochrome P450 2E1 inhibitors phenyl imidazole...

  10. Prizes and Productivity- How Winning the Fields Medal Affects Scientific Output

    OpenAIRE

    Borjas, George J.; Kirk B. Doran

    2013-01-01

    Knowledge generation is key to economic growth, and scientific prizes are designed to encourage it. But how does winning a prestigious prize affect future output? We compare the productivity of Fields medalists (winners of the top mathematics prize) to that of similarly brilliant contenders. The two groups have similar publication rates until the award year, after which the winners' productivity declines. The medalists begin to "play the field," studying unfamiliar topics at the expense of wr...

  11. Television spots win national award. Part of OSF Saint Francis Medical Center's branding effort.

    Science.gov (United States)

    Rees, Tom

    2004-01-01

    "Miracles in Medicine," a series of award-winning television spots, was produced for OSF Saint Francis Medical Center, Peoria, Ill., by The Roberts Group, Inc., Waukesha, Wis. They are an integral part of a broader branding campaign, launched in May 2003, that includes newspaper, radio, and outdoor elements. The spots were deemed so successful, the branding effort was expanded to include Children's Hospital of Illinois. PMID:15162576

  12. GAME-RELATED STATISTICS THAT DISCRIMINATED WINNING, DRAWING AND LOSING TEAMS FROM THE SPANISH SOCCER LEAGUE

    Directory of Open Access Journals (Sweden)

    Carlos Lago-Peñas

    2010-06-01

    Full Text Available The aim of the present study was to analyze men's football competitions, trying to identify which game-related statistics allow to discriminate winning, drawing and losing teams. The sample used corresponded to 380 games from the 2008-2009 season of the Spanish Men's Professional League. The game-related statistics gathered were: total shots, shots on goal, effectiveness, assists, crosses, offsides commited and received, corners, ball possession, crosses against, fouls committed and received, corners against, yellow and red cards, and venue. An univariate (t-test and multivariate (discriminant analysis of data was done. The results showed that winning teams had averages that were significantly higher for the following game statistics: total shots (p < 0.001, shots on goal (p < 0.01, effectiveness (p < 0.01, assists (p < 0.01, offsides committed (p < 0.01 and crosses against (p < 0.01. Losing teams had significantly higher averages in the variable crosses (p < 0.01, offsides received (p < 0. 01 and red cards (p < 0.01. Discriminant analysis allowed to conclude the following: the variables that discriminate between winning, drawing and losing teams were the total shots, shots on goal, crosses, crosses against, ball possession and venue. Coaches and players should be aware for these different profiles in order to increase knowledge about game cognitive and motor solicitation and, therefore, to evaluate specificity at the time of practice and game planning

  13. Expressing gambling-related cognitive biases in motor behaviour: rolling dice to win prizes.

    Science.gov (United States)

    Lim, Matthew S M; Bowden-Jones, Henrietta; Rogers, Robert D

    2014-09-01

    Cognitive perspectives on gambling propose that biased thinking plays a significant role in sustaining gambling participation and, in vulnerable individuals, gambling problems. One prominent set of cognitive biases include illusions of control involving beliefs that it is possible to influence random gaming events. Sociologists have reported that (some) gamblers believe that it is possible to throw dice in different ways to achieve gaming outcomes (e.g., 'dice-setting' in craps). However, experimental demonstrations of these phenomena are lacking. Here, we asked regular gamblers to roll a computer-simulated, but fair, 6 sided die for monetary prizes. Gamblers allowed the die to roll for longer when attempting to win higher value bets, and when attempting to hit high winning numbers. This behaviour was exaggerated in gamblers motivated to keep gambling following the experience of almost-winning in gambling games. These results suggest that gambling cognitive biases find expression in the motor behaviour of rolling dice for monetary prizes, possibly reflecting embodied substrates.

  14. Win-Stay-Lose-Learn Promotes Cooperation in the Spatial Prisoner's Dilemma Game

    Science.gov (United States)

    Liu, Yongkui; Chen, Xiaojie; Zhang, Lin; Wang, Long; Perc, Matjaž

    2012-01-01

    Holding on to one's strategy is natural and common if the later warrants success and satisfaction. This goes against widespread simulation practices of evolutionary games, where players frequently consider changing their strategy even though their payoffs may be marginally different than those of the other players. Inspired by this observation, we introduce an aspiration-based win-stay-lose-learn strategy updating rule into the spatial prisoner's dilemma game. The rule is simple and intuitive, foreseeing strategy changes only by dissatisfied players, who then attempt to adopt the strategy of one of their nearest neighbors, while the strategies of satisfied players are not subject to change. We find that the proposed win-stay-lose-learn rule promotes the evolution of cooperation, and it does so very robustly and independently of the initial conditions. In fact, we show that even a minute initial fraction of cooperators may be sufficient to eventually secure a highly cooperative final state. In addition to extensive simulation results that support our conclusions, we also present results obtained by means of the pair approximation of the studied game. Our findings continue the success story of related win-stay strategy updating rules, and by doing so reveal new ways of resolving the prisoner's dilemma. PMID:22363470

  15. Tactical Trajectory Planning for Stealth Unmanned Aerial Vehicle to Win the Radar Game

    Directory of Open Access Journals (Sweden)

    Hongfu Liu

    2012-11-01

    Full Text Available In this paper, problem of planning tactical trajectory for stealth unmanned aerial vehicle (UAV to win the radar game is studied. Three principles of how to win the radar game are presented, and their utilizations for stealth UAV to evade radar tracking are analysed. The problem is formulated by integrating the model of stealth UAV, the constraints of radar detecting and the multi-objectives of the game. The pseudospectral multi-phase optimal control based trajectory planning algorithm is developed to solve the formulated problem. Pseudospectral method is employed to seek the optimal solution with satisfying convergence speed. The results of experiments show that the proposed method is feasible and effective. By following the planned trajectory with several times of switches between exposure and stealth, stealth UAV could win the radar game triumphantly.Defence Science Journal, 2012, 62(6, pp.375-381, DOI:http://dx.doi.org/10.14429/dsj.62.2686

  16. Win-stay-lose-learn promotes cooperation in the spatial prisoner's dilemma game.

    Directory of Open Access Journals (Sweden)

    Yongkui Liu

    Full Text Available Holding on to one's strategy is natural and common if the later warrants success and satisfaction. This goes against widespread simulation practices of evolutionary games, where players frequently consider changing their strategy even though their payoffs may be marginally different than those of the other players. Inspired by this observation, we introduce an aspiration-based win-stay-lose-learn strategy updating rule into the spatial prisoner's dilemma game. The rule is simple and intuitive, foreseeing strategy changes only by dissatisfied players, who then attempt to adopt the strategy of one of their nearest neighbors, while the strategies of satisfied players are not subject to change. We find that the proposed win-stay-lose-learn rule promotes the evolution of cooperation, and it does so very robustly and independently of the initial conditions. In fact, we show that even a minute initial fraction of cooperators may be sufficient to eventually secure a highly cooperative final state. In addition to extensive simulation results that support our conclusions, we also present results obtained by means of the pair approximation of the studied game. Our findings continue the success story of related win-stay strategy updating rules, and by doing so reveal new ways of resolving the prisoner's dilemma.

  17. RSAC 6.2 with WinRP 2.0 User Manual

    Energy Technology Data Exchange (ETDEWEB)

    Bradley Schrader

    2005-09-01

    The Radiological Safety Analysis Computer Program (RSAC-6.2) calculates the consequences of a release of radionuclides to the atmosphere. Using a personal computer, a user can generate a fission product inventory from either reactor operating history or a nuclear criticality accident. RSAC-6.2 models the effects of high-efficiency particulate air filters or other cleanup systems and calculates decay and ingrowth during transport through processes, facilities, and the environment. Doses are calculated for resuspension, inhalation, immersion, ground surface, and ingestion pathways. WinRP 2.0, a windows based overlay to RSAC-6.2, assists users in creating and running RSAC-6.2 input files. This users manual contains the mathematical models and operating instructions for RSAC-6.2 and WinRP 2.0. Instructions, screens, and examples are provided to guide the user through the functions provided by RSAC-6.2 and WinRP 2.0. These programs are designed for users who are familiar with radiological dose assessment methods.

  18. Expressing gambling-related cognitive biases in motor behaviour: rolling dice to win prizes.

    Science.gov (United States)

    Lim, Matthew S M; Bowden-Jones, Henrietta; Rogers, Robert D

    2014-09-01

    Cognitive perspectives on gambling propose that biased thinking plays a significant role in sustaining gambling participation and, in vulnerable individuals, gambling problems. One prominent set of cognitive biases include illusions of control involving beliefs that it is possible to influence random gaming events. Sociologists have reported that (some) gamblers believe that it is possible to throw dice in different ways to achieve gaming outcomes (e.g., 'dice-setting' in craps). However, experimental demonstrations of these phenomena are lacking. Here, we asked regular gamblers to roll a computer-simulated, but fair, 6 sided die for monetary prizes. Gamblers allowed the die to roll for longer when attempting to win higher value bets, and when attempting to hit high winning numbers. This behaviour was exaggerated in gamblers motivated to keep gambling following the experience of almost-winning in gambling games. These results suggest that gambling cognitive biases find expression in the motor behaviour of rolling dice for monetary prizes, possibly reflecting embodied substrates. PMID:23620161

  19. Residues accessible in the binding-site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor.

    Science.gov (United States)

    Nebane, Ntsang M; Hurst, Dow P; Carrasquer, Carl A; Qiao, Zhuanhong; Reggio, Patricia H; Song, Zhao-Hui

    2008-12-30

    We have used the substituted-cysteine accessibility method (SCAM) to map the residues in the sixth membrane-spanning segment of the CB2 cannabinoid receptor that contribute to the surface of the water-accessible binding-site crevice. Using a background of the mutant C2.59S which is relatively insensitive to the methanethiosulfonate (MTS) reagents, we mutated to cysteine, one at a time, 34 consecutive residues in TMH6 of the CB2 receptor. These mutant receptors were then expressed in HEK293 cells. By incubating HEK293 cells stably transfected with CB2 receptors with the small, charged, hydrophilic, thiol-specific reagent methanethiosulfonate ethylammonium (MTSEA), [(3)H]CP55940 binding was significantly inhibited for six mutant receptors. All six of the mutants that reacted with MTSEA were protected from the reaction when pretreated with the cannabinoid agonist WIN55212-2, suggesting that MTSEA modification occurred within the binding crevice. Therefore, the side chains of the residues at these reactive loci (V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62) are on the water-accessible surface of the binding-site crevice. These residues are extracellular to the TMH6 CWXP hinge motif. The pattern of accessibility is consistent with a alpha-helical conformation for this segment of TMH6. Molecular modeling studies performed in the context of the CB2 model show that V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62 face into the CB2 binding pocket, further confirming our SCAM results. These results are similar to the accessibility patterns determined by SCAM studies of TMH6 in the opioid and dopamine D2 receptors. PMID:19053233

  20. Win by Creating Win-Win Outcomes

    Institute of Scientific and Technical Information of China (English)

    Yan Manman

    2010-01-01

    @@ Mr. James Ji, President of Sovereign Properly Group (SPG) and Vice President of Australia Mega Expo & Auction Centre Pty Ltd (AMEAC) have long dream about establishing the Hume Mega Centre, a unique concept known as the China Factory Outlets (CFO). The centre will be located in the outskirts of Melbourne, Victoria at 1457-1487Sydney Road, Campbellfield.

  1. Concerns with beta2-agonists in pediatric asthma - a clinical perspective

    NARCIS (Netherlands)

    Kersten, Elin T G; Koppelman, Gerard H; Thio, Bernard J

    2016-01-01

    Beta2-adrenoreceptor agonists (β2-agonists) are extensively used in the treatment of childhood asthma. However, there have been concerns regarding their adverse effects and safety. In 2005, the FDA commissioned a "Black Box Warning" communicating the potential for an increased risk for serious asthm

  2. Major drawbacks and additional benefits of agonist trigger--not ovarian hyperstimulation syndrome related

    DEFF Research Database (Denmark)

    Shapiro, Bruce S; Andersen, Claus Yding

    2015-01-01

    . The agonist trigger might alter other paradigms as well, such as making oocyte donation more efficient per stimulation by virtually eliminating follicular-phase cycle cancellation, coasting, and premature triggering. There are both corresponding potential benefits and drawbacks of using the agonist trigger...

  3. Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

    Directory of Open Access Journals (Sweden)

    Min Gao

    Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

  4. Synthesis of urea acetates as potential PPARα/γ,dual agonists

    Institute of Scientific and Technical Information of China (English)

    Chang Yan Zhao; Chang Qing Shi; Yuan Wei Chen

    2008-01-01

    In the quest for novel PPARα/γ dual agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia,we designed and synthesized a series of urea acetates as potential PPARα/γ dual agonists.The structure of the target compounds,intermediates were characterized by 1H NMR,HRMS.

  5. The dopamine D1 receptor agonist SKF-82958 effectively increases eye blinking count in common marmosets.

    Science.gov (United States)

    Kotani, Manato; Kiyoshi, Akihiko; Murai, Takeshi; Nakako, Tomokazu; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Ogi, Yuji; Ikeda, Kazuhito

    2016-03-01

    Eye blinking is a spontaneous behavior observed in all mammals, and has been used as a well-established clinical indicator for dopamine production in neuropsychiatric disorders, including Parkinson's disease and Tourette syndrome [1,2]. Pharmacological studies in humans and non-human primates have shown that dopamine agonists/antagonists increase/decrease eye blinking rate. Common marmosets (Callithrix jacchus) have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field due to their more developed prefrontal cortex than rodents, easy handling compare to other non-human primates, and requirement for small amounts of test drugs. In this study, we evaluated the effects of dopamine D1-4 receptors agonists on eye blinking in common marmosets. Our results show that the dopamine D1 receptor agonist SKF-82958 and the non-selective dopamine receptor agonist apomorphine significantly increased common marmosets eye blinking count, whereas the dopamine D2 agonist (+)-PHNO and the dopamine D3 receptor agonist (+)-PD-128907 produced somnolence in common marmosets resulting in a decrease in eye blinking count. The dopamine D4 receptor agonists PD-168077 and A-41297 had no effect on common marmosets' eye blinking count. Finally, the dopamine D1 receptor antagonist SCH 39166 completely blocked apomorphine-induced increase in eye blinking count. These results indicate that eye blinking in common marmosets may be a useful tool for in vivo screening of novel dopamine D1 receptor agonists as antipsychotics. PMID:26675887

  6. The interplay between agonistic character displacement and reproductive interference in rubyspot damselflies (Hetaerina spp.)

    OpenAIRE

    Drury, Jonathan

    2014-01-01

    Aggressive interactions between species are common despite being relatively understudied. Agonistic character displacement (ACD) theory makes predictions about how selection should act on traits that mediate the occurrence of interspecific aggressive interactions. Previous research on rubyspot damseflies (Hetaerina spp.) documented several cases of divergent agonistic character displacement acting on wing coloration and competitor recognition to diminish wasteful interspecific aggression. How...

  7. The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

    2003-01-01

    The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu...

  8. Use of thrombopoietin receptor agonists in childhood immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Angelica Maria Garzon

    2015-08-01

    Full Text Available Most children with immune thrombocytopenia (ITP will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data is emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long term safety issues that need to be considered when using these agents

  9. N-methyl-D-aspartic acid receptor agonists

    DEFF Research Database (Denmark)

    Madsen, U; Frydenvang, Karla Andrea; Ebert, B;

    1996-01-01

    (R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of excitatory amino acid receptors. Using the Ugi "four-component condensation" method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy......) showed peak affinity for [3H]AMPA receptor sites (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM). Neither enantiomer of AMAA affected [3H]kainic acid receptor binding significantly...

  10. Locomotion induced by ventral tegmental microinjections of a nicotinic agonist.

    Science.gov (United States)

    Museo, E; Wise, R A

    1990-03-01

    Bilateral microinjections of the nicotinic agonist cytisine (0.1, 1 or 10 nanomoles per side) into the ventral tegmental area increased locomotor activity. This increase in locomotion was antagonized by mecamylamine (2 mg/kg, IP), a nicotinic antagonist that readily crosses the blood-brain barrier, and by pimozide (0.3 mg/kg, IP), a central dopaminergic antagonist. Hexamethonium (2 mg/kg, IP), a nicotinic antagonist that, unlike mecamylamine, does not cross the blood-brain barrier, had no effect; this suggests that mecamylamine's attenuation of cytisine-induced locomotor activity resulted from a blockade of central and not peripheral nicotinic receptors. The data support the notion that nicotinic and dopaminergic substrates interact at the level of the VTA to produce increases in locomotor activity.

  11. Recent advances in the development of farnesoid X receptor agonists.

    Science.gov (United States)

    Ali, Ahmad H; Carey, Elizabeth J; Lindor, Keith D

    2015-01-01

    Farnesoid X receptors (FXRs) are nuclear hormone receptors expressed in high amounts in body tissues that participate in bilirubin metabolism including the liver, intestines, and kidneys. Bile acids (BAs) are the natural ligands of the FXRs. FXRs regulate the expression of the gene encoding for cholesterol 7 alpha-hydroxylase, which is the rate-limiting enzyme in BA synthesis. In addition, FXRs play a critical role in carbohydrate and lipid metabolism and regulation of insulin sensitivity. FXRs also modulate live growth and regeneration during liver injury. Preclinical studies have shown that FXR activation protects against cholestasis-induced liver injury. Moreover, FXR activation protects against fatty liver injury in animal models of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and improved hyperlipidemia, glucose intolerance, and insulin sensitivity. Obeticholic acid (OCA), a 6α-ethyl derivative of the natural human BA chenodeoxycholic acid (CDCA) is the first-in-class selective FXR agonist that is ~100-fold more potent than CDCA. Preliminary human clinical trials have shown that OCA is safe and effective. In a phase II clinical trial, administration of OCA was well-tolerated, increased insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with type II diabetes mellitus and NAFLD. In two clinical trials of OCA in patients with primary biliary cirrhosis (PBC), a progressive cholestatic liver disease, OCA significantly reduced serum alkaline phosphatase (ALP) levels, an important disease marker that correlates well with clinical outcomes of patients with PBC. Together, these studies suggest that FXR agonists could potentially be used as therapeutic tools in patients suffering from nonalcoholic fatty and cholestatic liver diseases. Larger and Longer-term studies are currently ongoing. PMID:25705637

  12. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Directory of Open Access Journals (Sweden)

    Guido eFrank

    2014-11-01

    Full Text Available Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  13. Could dopamine agonists aid in drug development for anorexia nervosa?

    Science.gov (United States)

    Frank, Guido K W

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. PMID:25988121

  14. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases.

    Science.gov (United States)

    Yu, Shan; Li, Sijia; Henke, Adam; Muse, Evan D; Cheng, Bo; Welzel, Gustav; Chatterjee, Arnab K; Wang, Danling; Roland, Jason; Glass, Christopher K; Tremblay, Matthew

    2016-07-01

    Liver X receptor (LXR), a nuclear hormone receptor, is an essential regulator of immune responses. Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models. However, the adverse effects of these conventional LXR agonists in elevating liver lipids have impeded exploitation of this intriguing mechanism for chronic therapy. Here, we explore the ability of a series of sterol-based LXR agonists to alleviate inflammatory conditions in mice without hepatotoxicity. We show that oral treatment with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine. The anti-inflammatory property of these agonists is recapitulated in vitro in mouse lamina propria mononuclear cells, human colonic epithelial cells, and human peripheral blood mononuclear cells. In addition, treatment with LXR agonists dramatically suppresses inflammatory cytokine expression in a model of traumatic brain injury. Importantly, in both disease models, the sterol-based agonists do not affect the liver, and the conventional agonist T0901317 results in significant liver lipid accumulation and injury. Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases.-Yu, S., Li, S., Henke, A., Muse, E. D., Cheng, B., Welzel, G., Chatterjee, A. K., Wang, D., Roland, J., Glass, C. K., Tremblay, M. Dissociated sterol-based liver X receptor agonists as therapeutics for chronic inflammatory diseases. PMID:27025962

  15. Allosteric coupling from G protein to the agonist-binding pocket in GPCRs.

    Science.gov (United States)

    DeVree, Brian T; Mahoney, Jacob P; Vélez-Ruiz, Gisselle A; Rasmussen, Soren G F; Kuszak, Adam J; Edwald, Elin; Fung, Juan-Jose; Manglik, Aashish; Masureel, Matthieu; Du, Yang; Matt, Rachel A; Pardon, Els; Steyaert, Jan; Kobilka, Brian K; Sunahara, Roger K

    2016-07-01

    G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, the β2-adrenergic receptor (β2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein α-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the β2AR stabilizes a ‘closed’ receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR–G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity. PMID:27362234

  16. 基于WinCE的便携式心音监护系统设计%The Design of Heart Sounds Monitoring System Based on WinCE

    Institute of Scientific and Technical Information of China (English)

    李静; 李琪; 张修太; 张可

    2013-01-01

    由心音传感器HKY-06B在WinCE平台下设计的便携式心音监控系统可以克服传统心音监控系统依赖PC平台、不利于携带的缺点.设计给出了ARM9平台上心音监护系统的硬件组成,重点研究了针对HKY-06B的高效驱动模型.该模型可提高HKY-06B的运行效率和稳定性,实现对体温、脉搏、心率的记录、保存和上传.通过测试,该系统运行准确、稳定,可以满足便携式心音监控的要求,为心音监控在嵌入式系统下的应用提供了有效参考.%A design of the portable heart sound sensor system on the base of heart sounds sensor HKY-06B and the WinCE platform can overcome the shortcomings of traditional heart sound monitoring system that relies on the PC platform and is not conducive to carrying. The design provides the ARM9 platform of the hardware composition of heart sound monitoring system,the high efficiency drive model in HKY-06B is researched with priority. The model can improve the operating efficiency and stability of HKY-06B,which can record,save and upload the data of temperature, pulse, heart rate. The final test shows that the HKY - 06B is accurate and stable and meets the requirements of portable heart sound monitoring system.

  17. A "win-win" scenario: the use of sustainable land management technologies to improve rural livelihoods and combat desertification in semi-arid lands in Kenya

    Science.gov (United States)

    Mganga, Kevin; Musimba, Nashon; Nyariki, Dickson; Nyangito, Moses; Mwang'ombe, Agnes

    2014-05-01

    Dryland ecosystems support over 2 billion people and are major providers of critical ecosystems goods and services globally. However, desertification continues to pose a serious threat to the sustainability of the drylands and livelihoods of communities inhabiting them. The desertification problem is well exemplified in the arid and semi-arid lands (ASALs) in Kenya which cover approximately 80% of the total land area. This study aimed to 1) determine what agropastoralists attribute to be the causes of desertification in a semi-arid land in Kenya, 2) document sustainable land management (SLM) technologies being undertaken to improve livelihoods and combat desertification, and 3) identify the factors that influence the choice of the sustainable land management (SLM) technologies. Results show that agropastoralists inhabiting the semi-arid lands in southeastern Kenya mainly attribute desertification to the recurrent droughts and low amounts of rainfall. Despite the challenges posed by desertification and climate variability, agropastoralists in the study area are using a combination of SLM technologies notably dryland agroforestry using drought tolerant species (indigenous and exotic), grass reseeding using perennial native and drought tolerant grass species (vegetation reestablishment) and in-situ rainwater harvesting to improve livelihoods and by extension combat desertification. Interestingly, the choice and adoption of these SLM technologies is influenced more by the additional benefits the agropastoralists can derive from them. Therefore, it is rationale to conclude that success in dryland restoration and combating desertification lies in programs and technologies that offer a "win-win" scenario to the communities inhabiting the drylands. Key words: Agroforestry; Agropastoralists; Drylands; Grass Reseeding; Rainwater Harvesting

  18. EFFECTS OF SYNTETIC CANNABINOID RECEPTOR LIGANDS WIN 55.212-2 AND ANANDAMID UPON IN VITRO ACTIVITY OF IMMUNOCOMPETENT CELLS

    Directory of Open Access Journals (Sweden)

    E. G. Lobanova

    2009-01-01

    Full Text Available Abstract. Ability of cannabinoid receptor ligands WIN 55.212-2 and anandamid to inhibit synthesis of TNFα and IL-8 was studied in healthy donors and men with allergic disorders. To establish mechanism of action for investigated substances, the selective antagonists of the СВ1-receptor (SR141716A and for СВ2 - receptor (SR144528 were applied. Studies with whole blood dilutions allowed of approximating in vivo conditions when investigating biological properties of WIN-55.212-2 and anandamid. The synthetic cannabinoids WIN - 55.212-2 and anandamid at a concentration of 3-10 μМ were capable of reducing synthesis of TNFα and IL-8 in lipopolysaccharide-stimulated blood leukocytes, both from healthy donors and subjects with allergic disorders. It was revealed that the antagonist of СВ1-receptor (SR141716A did not exert a receptor-mediated effect for WIN-55.212-2 and anandamid. Meanwhile, a СВ2-receptor antagonist (SR144528 entirely eliminated completely the blocking effect of anandamid and WIN-55.212-2.

  19. Differences in Basic Non-Standard Situational Efficiency Indicators between Winning and Defeated European Senior Basketball Teams.

    Science.gov (United States)

    Trninić, Marko; Perica, Ante; Jeličić, Mario

    2015-07-01

    The aim of the conducted research was to identify and explain the differences in basic non-standard situational efficiency indicators between winning and defeated European senior basketball teams. Discriminant analysis and Mann-Whitney U-test were used with the purpose of investigating the differences between winning and defeated teams in the domain of basic non-standard situational variables. The grouping variable distinguished 24 defeated teams from 24 winning teams participating in 2009/2010 season of Euroleague Top 16. The research clearly reveals the differences between the winning and defeated European senior basketball teams in the domain of non-standard situational variables of position and transition offense and defense. Eight situational efficiency indicators were used which include the overall number of successful and unsuccessful position and transition defenses and offenses. Based on the results obtained by parametric and non-parametric methods, it has been noticed that successful position defense is crucial for winning, and unsuccessful position offense is an indicator of defeat prediction. Therefore, practical aims in situational training must involve balanced development of relevant abilities and skills which determine successful simultaneous performance of multiple tasks in all the phases of game flow. Such process of sport preparation improves the overall actual quality of players and whole team performance. In conclusion, it is important to emphasize that the process of improving position and transition defense stimulates the development of position and transition offense, and vice versa.

  20. 西门子人机界面组态软件WinCC flexible使用经验%Application Experiences of Siemens Man-Machine WinCC flexible Interface Configuration Software

    Institute of Scientific and Technical Information of China (English)

    廖亮

    2008-01-01

    WinCC flexible是西门子人机界面的组态软件,其功能强大、使用方便。过去用Protool组态的人机界面已被WinCC flexible组态的新产品替代。1对计算机的要求操作系统为Windows2000SP4、Windows XPSP2或更高的版本,只能用专业版,不能用Home版。特别需要指出的是WinCC flexible对计算机内存的要求较高,内存至少1GB。

  1. Neural correlates of dueling affective reactions to win–win choices

    Science.gov (United States)

    Shenhav, Amitai; Buckner, Randy L.

    2014-01-01

    Win–win choices cause anxiety, often more so than decisions lacking the opportunity for a highly desired outcome. These anxious feelings can paradoxically co-occur with positive feelings, raising important implications for individual decision styles and general well-being. Across three studies, people chose between products that varied in personal value. Participants reported feeling most positive and most anxious when choosing between similarly high-valued products. Behavioral and neural results suggested that this paradoxical experience resulted from parallel evaluations of the expected outcome (inducing positive affect) versus the cost of choosing a response (inducing anxiety). Positive feelings were reduced when there was no high-value option, and anxiety was reduced when only one option was highly valued. Dissociable regions within the striatum and the medial prefrontal cortex (mPFC) tracked these dueling affective reactions during choice. Ventral regions, associated with stimulus valuation, tracked positive feelings and the value of the best item. Dorsal regions, associated with response valuation, tracked anxiety. In addition to tracking anxiety, the dorsal mPFC was associated with conflict during the current choice, and activity levels across individual items predicted whether that choice would later be reversed during an unexpected reevaluation phase. By revealing how win–win decisions elicit responses in dissociable brain systems, these results help resolve the paradox of win–win choices. They also provide insight into behaviors that are associated with these two forms of affect, such as why we are pulled toward good options but may still decide to delay or avoid choosing among them. PMID:25024178

  2. Two designs for image digital processing applications in the nuclear area using ImaWin

    International Nuclear Information System (INIS)

    In this work two designs of image processing systems of low cost for the nuclear area are presented. They have the advantage of the adaptability given by the ImaWin software and the connection with Internet, applied to digitalisation in research and development fields. The first design is the development of a digitalisation system for inspection and study of fuel plate radiographs for test reactors, while the second one describes the specification and design of an intelligent system of intrusion signals continuous inspection and administrative control of fissile material deposits. (author)

  3. Win the game of Googleopoly unlocking the secret strategy of search engines

    CERN Document Server

    Bradley, Sean V

    2015-01-01

    Rank higher in search results with this guide to SEO and content building supremacy Google is not only the number one search engine in the world, it is also the number one website in the world. Only 5 percent of site visitors search past the first page of Google, so if you're not in those top ten results, you are essentially invisible. Winning the Game of Googleopoly is the ultimate roadmap to Page One Domination. The POD strategy is what gets you on that super-critical first page of Google results by increasing your page views. You'll learn how to shape your online presence for Search Engine

  4. WinCC与S7-200系列PLC通信的实现

    Institute of Scientific and Technical Information of China (English)

    孙连生; 刘志韬

    2006-01-01

    针对控制系统中上位机与S7—200系列PLC(Program Logic Control)通信的实际问题.总结了使用WinCC组态软件上位机与S7—200系列PLC的通信方法,这几种方法在不同的控制系统中能较好解决上位机与S7~200系列PLC通信问题。

  5. How Not to Win a Million Dollars: A Counterexample to a Conjecture of L. Breiman

    CERN Document Server

    Hayes, Thomas P

    2011-01-01

    Consider a gambling game in which we are allowed to repeatedly bet a portion of our bankroll at favorable odds. We investigate the question of how to minimize the expected number of rounds needed to increase our bankroll to a given target amount. Specifically, we disprove a 50-year old conjecture of L. Breiman, that there exists a threshold strategy that optimizes the expected number of rounds; that is, a strategy that always bets to try to win in one round whenever the bankroll is at least a certain threshold, and that makes Kelly bets (a simple proportional betting scheme) whenever the bankroll is below the threshold.

  6. How Trump’s populist ideology is stopping him from winning delegates

    OpenAIRE

    Margulies, Ben

    2016-01-01

    In the space of a few short months Donald Trump has gone from the undisputed frontrunner of the Republican Party’s 2016 presidential primary race to a candidate who is facing being on the losing side of a contested convention in July. Despite leading in the national polls, Trump has consistently shown that he is unable to win enough delegates for him to be able to secure the GOP nomination. Ben Margulies argues that part of Trump’s current difficulties lie in his ‘populist’ strategy and ideol...

  7. Strategic Planning and Performance Management Develop and Measure a Winning Strategy

    CERN Document Server

    Kenny, Graham

    2005-01-01

    Strategic Planning and Performance Measurement: Develop & Measure a Winning Strategy, provides a clear and concise roadmap for designing, implementing and measuring strategy. The focus is on strategic factors, which are defined in a unique way as the criteria on which an organization or business unit has to do well in order to succeed. For organizations to be successful, they must take a stakeholder perspective of their performance - stakeholders such as customers, suppliers, employees and owners. The book cites many case studies including: 7-Eleven, Roche, K-mart, McDonald's, Levi Strauss,

  8. 史上首部微软手机——Win-98

    Institute of Scientific and Technical Information of China (English)

    张扬

    2003-01-01

    DEM手机再次出击!而且,连名也沾了别人的光,韩国最新品牌Widnows(视窗)和Bill Gates微软一点关系都没有,但就好在用了同一个名(连中文名都是!)推出了这部Win-98出来!还在机面弄了一个窟窿来透视靓彩屏,玩透色。

  9. Bayesian Analysis Made Simple An Excel GUI for WinBUGS

    CERN Document Server

    Woodward, Philip

    2011-01-01

    From simple NLMs to complex GLMMs, this book describes how to use the GUI for WinBUGS - BugsXLA - an Excel add-in written by the author that allows a range of Bayesian models to be easily specified. With case studies throughout, the text shows how to routinely apply even the more complex aspects of model specification, such as GLMMs, outlier robust models, random effects Emax models, auto-regressive errors, and Bayesian variable selection. It provides brief, up-to-date discussions of current issues in the practical application of Bayesian methods. The author also explains how to obtain free so

  10. Modern multithreading implementing, testing, and debugging multithreaded Java and C++/Pthreads/Win32 programs

    CERN Document Server

    Carver, Richard H

    2005-01-01

    Master the essentials of concurrent programming,including testing and debuggingThis textbook examines languages and libraries for multithreaded programming. Readers learn how to create threads in Java and C++, and develop essential concurrent programming and problem-solving skills. Moreover, the textbook sets itself apart from other comparable works by helping readers to become proficient in key testing and debugging techniques. Among the topics covered, readers are introduced to the relevant aspects of Java, the POSIX Pthreads library, and the Windows Win32 Applications Programming Interface.

  11. How a swing state running mate could help Trump or Clinton win the White House

    OpenAIRE

    Heersink, Boris; Peterson, Brenton

    2016-01-01

    With the general election season now upon us, both Hillary Clinton and Donald Trump are considering who to pick to be their Vice President. In new research, Boris Heersink and Brenton D. Peterson argue that to help them win the presidency, the candidates should consider someone from a swing state. Why? They find that, in contrast to previous studies, a running mate can increase a presidential ticket’s support by nearly 3 percent in a Vice President’s home state, something which could have swu...

  12. The Effects of Social Media in the Hotel Sector: A report for WinHotels

    OpenAIRE

    Sullivan, John

    2013-01-01

    Social media usage is expanding in all age groups and across all socio-economic groups. This means it has become the focus of much attention from businesses looking to use it as a way to increase awareness of their products or services. The purpose of this report is to look at how social media is affecting the hotel business and whether Win Hotels should be using social media as a marketing tool. It offers the opportunity to engage with hotel guests before during and after a stay. This en...

  13. International Quit and Win 1996: comparative evaluation study in China and Finland

    OpenAIRE

    Sun, S.; Korhonen, T.; Uutela, A.; Korhonen, H.; Puska, P.; Jun, Y.; Chonghua, Y.; Zeyu, G.; Yonghao, W.; Wenqing, X.

    2000-01-01

    OBJECTIVES—To compare background and process variables, as well as follow up status, of the participants in the International Quit and Win '96 contests of China and Finland, and analyse factors contributing to sustained maintenance.
DESIGN—A standardised 12 month follow up was conducted in both countries with random samples of participants. The sample sizes were 3119 in China and 1448 in Finland, with response rates of 91.2% and 65.2%, respectively.
INTERVENTIONS—The International Quit and Wi...

  14. Excellence in the stacks strategies, practices and reflections of award-winning libraries

    CERN Document Server

    Hill, Jacob

    2013-01-01

    Excellence in the Stacks details the philosophies, practices and innovations of award-winning libraries over the last ten years. It will inform the profession and highlight the themes and strategies these liberal-arts colleges share, and where they differ. Using the Association of Research and College Libraries Excellence in Academic Libraries Award standards as guidelines for exploring librarianship, this book gathers the perspectives of all types of librarians at all levels of employment. By highlighting winners' holistic approaches it helps define and focus the energies of college libraries

  15. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    International Nuclear Information System (INIS)

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC50 values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC50 = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other

  16. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  17. Research and Design on the Campus Network ARP Attack Detection Based on WinPcap Defense System%基于WinPcap的校园网ARP攻击检测防御系统研究与设计

    Institute of Scientific and Technical Information of China (English)

    王晓妮

    2014-01-01

    深入研究ARP协议及其工作原理和现有ARP欺骗攻击的防御方法,并针对校园网的特点提出了一种基于WinPcap的ARP欺骗攻击的检测和防御方法。%The method of defense in-depth study of ARP protocol and its working principle and the existing ARP spoof-ing attacks,and according to the characteristics of campus network and put forward a method todetect and defense ARP spoofing attack based on WinPcap.

  18. Development of Driver for SSI Protocol Under WinCE 6.0%WinCE 6.0下的SSI协议流接口驱动程序实现

    Institute of Scientific and Technical Information of China (English)

    卓璐; 陈富林; 沈金龙

    2013-01-01

    研究了如何实现S3C6410嵌入式处理器芯片下SSI通讯协议的驱动,以此来为SSI通讯设备提供底层软件支持.本文的驱动程序运行在嵌入式操作系统WinCE6.0下,采用流驱动模型编写同时涉及WinCE6.0下的中断处理,最终经过开发板与编码器连接测试通过.

  19. Binding Mode of Insulin Receptor and Agonist Peptide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two α subunits with a molecular weight of 135 kD and twoβ subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular α subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the α subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide.We employed the extracellular domain (PDBID: 1IGR) of the insulin-like growth factor-1 receptor (IGF-1 R ) as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides.Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small

  20. PC与MAC互联大全--Win9x/Me/NT/2000与MAC机互联

    Institute of Scientific and Technical Information of China (English)

    迟小玲; 周少燕

    2004-01-01

    @@ 在实际工作中,PC与MAC的应用都很广泛,如何使这两个系统下的资源共享很重要,现介绍PC与MAC机互联的几种方法. Win9X与MAC机的互联(PC MACLan for Win9X) PC MACLan这个软件是安装在PC机上的,MAC机上无须安装任何软件.在Win98下点"Setup"后,一路"Next",这个软件就会全自动安装好,无须用户操心.重新启动机器后就可以看见这个软件的欢迎画面.

  1. Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte Grube; Frølund, Bente Flensborg; Kehler, Jan;

    2011-01-01

    A 5-HT(3) receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT(3) A receptor...... yielded substantial information concerning the analogues as 5-HT(3) receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT(3) receptor agonist, as it does not possess...

  2. Evaluation of WIN 55,212-2 self-administration in rats as a potential cannabinoid abuse liability model

    Science.gov (United States)

    Lefever, Timothy W.; Marusich, Julie A.; Antonazzo, Kateland R.; Wiley, Jenny L.

    2014-01-01

    Because Δ9-tetrahydrocannabinol (THC) has been a false negative in rat intravenous self-administration procedures, evaluation of the abuse potential of candidate cannabinoid medications has proved difficult. One lab group has successfully trained self-administration of the aminoalkylindole WIN55,212-2 in rats; however, their results have not been independently replicated. The purpose of this study was to extend their model by using a within-subjects design, with the goal of establishing a robust method suitable for substitution testing of other cannabinoids. Male Long-Evans rats were trained to self-administer WIN55,212-2 (0.01 mg/kg/infusion) on a fixed ratio 3 schedule. Dose-effect curves for WIN55,212-2 were determined, followed by vehicle substitution and a dose-effect curve with THC. WIN55,212-2 self-administration was acquired; however, substitution with THC did not maintain responding above vehicle levels. Dose-dependent attenuation by rimonabant confirmed CB1 receptor mediation of WIN55,212-2’s reinforcing effects. Vehicle substitution resulted in a session-dependent decrease in responding (i.e., extinction). While this study provides systematic replication of previous studies, lack of substitution with THC is problematic and suggests that WIN55,212-2 self-administration may be of limited usefulness as a screening tool for detection of the reinforcing effects of potential cannabinoid medications. Clarification of underlying factors responsible for failure of THC to maintain self-administration in cannabinoid-trained rats is needed. PMID:24412835

  3. NASS/CDS delta-V estimates: the influence of enhancements to the WinSmash crash reconstruction code.

    Science.gov (United States)

    Hampton, Carolyn E; Gabler, Hampton C

    2009-10-01

    The change in velocity (delta-V) crash severity metric in the NASS/CDS (National Automotive Sampling System / Crashworthiness Data System) is computed using the WinSmash crash reconstruction code. Beginning in 2008, NASS/CDS investigators have started to use an enhanced version of WinSmash, WinSmash 2008, which features a comprehensive vehicle specific library for over 5000 vehicle make-model-year combinations and updated categorical stiffness values. The use of WinSmash 2008 is expected to greatly improve delta-V estimates. However, there is concern that this may result in a step change in the NASS/CDS delta-V estimates, making it difficult to compare NASS/CDS 2008 with earlier years. A total of 1,808 collisions were recomputed using data from NASS/CDS 2007. The new version of WinSmash shows improved accuracy, but still underpredicts delta-V. The use of WinSmash 2008 increased the delta-V by 7.9% or 1.9 kph on average. The changes in delta-V were not evenly distributed. Delta-V increases were larger for side impacts (8.3%) than for back impacts (5.3%). The calculation type had little effect on the delta-V changes. For vehicles, pickup trucks showed a small increase (3.3%) and utility vehicles increased the most (9.6%). This jump in delta-V may prevent the data from NASS/CDS 2008 and later from being readily aggregated with previous years. PMID:20184836

  4. Evaluation of the Accuracy of NASS/CDS Delta-V Estimates from the Enhanced WinSmash Algorithm.

    Science.gov (United States)

    Hampton, Carolyn E; Gabler, Hampton C

    2010-01-01

    The National Automotive Sampling System / Crashworthiness Data System (NASS/CDS) uses the WinSmash program to reconstruct changes in vehicle velocity for real world crashes. Vehicle change in velocity, or delta-V, is a measure of crash severity and a predictor of injury risk. Earlier studies have demonstrated that WinSmash 2.42 underestimated the delta-V by 23% on average with the use of categorical stiffness values for vehicles identified as a source of error. An enhanced version of WinSmash, WinSmash 2008, was developed to employ vehicle specific stiffness values whenever possible. A total of 478 General Motors vehicles equipped with event data recorders (EDRs) and involved in real-world crashes were collected from years 2000 - 2008 of the NASS/CDS database and the delta-V was computed using the enhanced WinSmash. All vehicles were involved in frontal impacts. The enhanced reconstruction algorithm reduced the underestimation of delta-V from 23% to 13% on average for all vehicles. Delta-V estimates for cars only were greatly improved but still understated by 16% on average. Less than 5% error in delta-V was observed for pickup trucks and utility vehicles. The amount of structural overlap for the vehicle and investigator confidence in the reconstruction continued to have an effect on accuracy. No difference in average delta-V was observed when using either updated categorical stiffness values or vehicle specific stiffness values. The changes in WinSmash delta-Vs have important policy implications for NHTSA as the NASS/CDS delta-Vs are the basis for traffic and safety regulations as well as the speeds for vehicular crash testing and costs/benefits analyses. PMID:21050607

  5. Therapeutic applications of TRAIL receptor agonists in cancer and beyond.

    Science.gov (United States)

    Amarante-Mendes, Gustavo P; Griffith, Thomas S

    2015-11-01

    TRAIL/Apo-2L is a member of the TNF superfamily first described as an apoptosis-inducing cytokine in 1995. Similar to TNF and Fas ligand, TRAIL induces apoptosis in caspase-dependent manner following TRAIL death receptor trimerization. Because tumor cells were shown to be particularly sensitive to this cytokine while normal cells/tissues proved to be resistant along with being able to synthesize and release TRAIL, it was rapidly appreciated that TRAIL likely served as one of our major physiologic weapons against cancer. In line with this, a number of research laboratories and pharmaceutical companies have attempted to exploit the ability of TRAIL to kill cancer cells by developing recombinant forms of TRAIL or TRAIL receptor agonists (e.g., receptor-specific mAb) for therapeutic purposes. In this review article we will describe the biochemical pathways used by TRAIL to induce different cell death programs. We will also summarize the clinical trials related to this pathway and discuss possible novel uses of TRAIL-related therapies. In recent years, the physiological importance of TRAIL has expanded beyond being a tumoricidal molecule to one critical for a number of clinical settings - ranging from infectious disease and autoimmunity to cardiovascular anomalies. We will also highlight some of these conditions where modulation of the TRAIL/TRAIL receptor system may be targeted in the future. PMID:26343199

  6. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

    Directory of Open Access Journals (Sweden)

    Paul Fredrickson

    2014-01-01

    Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

  7. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  8. Agonists and Antagonists of TGF-β Family Ligands.

    Science.gov (United States)

    Chang, Chenbei

    2016-08-01

    The discovery of the transforming growth factor β (TGF-β) family ligands and the realization that their bioactivities need to be tightly controlled temporally and spatially led to intensive research that has identified a multitude of extracellular modulators of TGF-β family ligands, uncovered their functions in developmental and pathophysiological processes, defined the mechanisms of their activities, and explored potential modulator-based therapeutic applications in treating human diseases. These studies revealed a diverse repertoire of extracellular and membrane-associated molecules that are capable of modulating TGF-β family signals via control of ligand availability, processing, ligand-receptor interaction, and receptor activation. These molecules include not only soluble ligand-binding proteins that were conventionally considered as agonists and antagonists of TGF-β family of growth factors, but also extracellular matrix (ECM) proteins and proteoglycans that can serve as "sink" and control storage and release of both the TGF-β family ligands and their regulators. This extensive network of soluble and ECM modulators helps to ensure dynamic and cell-specific control of TGF-β family signals. This article reviews our knowledge of extracellular modulation of TGF-β growth factors by diverse proteins and their molecular mechanisms to regulate TGF-β family signaling.

  9. Winning big but feeling no better? The effect of lottery prizes on physical and mental health.

    Science.gov (United States)

    Apouey, Benedicte; Clark, Andrew E

    2015-05-01

    We use British panel data to determine the exogenous impact of income on a number of individual health outcomes: general health status, mental health, physical health problems, and health behaviours (drinking and smoking). Lottery winnings allow us to make causal statements regarding the effect of income on health, as the amount won by winners is largely exogenous. Positive income shocks have no significant effect on self-assessed overall health, but a significant positive effect on mental health. This result seems paradoxical on two levels. First, there is a well-known gradient in health status in cross-sectional data, and second, general health should partly reflect mental health, so that we may expect both variables to move in the same direction. We propose a solution to the first apparent paradox by underlining the endogeneity of income. For the second, we show that lottery winnings are also associated with more smoking and social drinking. General health will reflect both mental health and the effect of these behaviours and so may not improve following a positive income shock.

  10. Hitting the Goalpost: Calculating the Fine Line Between Winning and Losing a Penalty Shootout

    Science.gov (United States)

    Widenhorn, Ralf

    2016-10-01

    The Portland Timbers won their first Major League Soccer (MLS) Cup Championship in December 2015. However, if it had not been for a kind double goalpost miss during a penalty shootout a few weeks earlier, the Timbers would never have been in the finals. On Oct. 30th, after what has been called "the greatest penalty kick shootout in MLS history," featuring a combined 22 penalties that included penalties by both goalkeepers, the Timbers won their first-round playoff against Sporting Kansas City. During the thrilling shootout, which can be watched, for example, for example on the MLS website, Sporting had two potentially game-winning penalties miss by the smallest of margins. One penalty bounced off the goalpost back into the field and another was an improbable double post miss. For a physicist, this prompts an interesting research question. Could we find an estimate by what distance the double post penalty shown in Fig. 1 failed to be the game winning shot?

  11. Emotional Intelligence and Will to Win: The Invincible and Invisible Phenomenon in Basketball Sports

    Directory of Open Access Journals (Sweden)

    Davinder SINGH

    2015-12-01

    Full Text Available This study examined the emotional intelligence and will to win level among female basketball players. A group of fifty (N=50 female inter-college level basketball players of Guru Nanak Dev University, Amritsar, Punjab were selected for this study. The purposive sampling technique was used to attain the objectives of the study. All the subjects, after having been informed about the objective and protocol of the study, gave their consent and volunteered to participate in this study. Summarizing the findings we can say that significant differences were found among female basketball players on the sub-variables of Emotional Intelligence i.e., Self-awareness, Empathy, Self-development, Value orientation and Altruistic behaviour. However no-significant no significant differences were found among female basketball players on the sub-variables of Emotional Intelligence i.e., Self-motivation, Emotional stability, Managing relations, Integrity and Commitment. Conculdingly from the above findings that insignificant differences were present among female basketball players on the sub-variables of will to win.

  12. Evaluation and improvement of wastewater treatment plant performance using BioWin

    Science.gov (United States)

    Oleyiblo, Oloche James; Cao, Jiashun; Feng, Qian; Wang, Gan; Xue, Zhaoxia; Fang, Fang

    2015-03-01

    In this study, the activated sludge model implemented in the BioWin® software was validated against full-scale wastewater treatment plant data. Only two stoichiometric parameters ( Y p/acetic and the heterotrophic yield ( Y H)) required calibration. The value 0.42 was used for Y p/acetic in this study, while the default value of the BioWin® software is 0.49, making it comparable with the default values of the corresponding parameter (yield of phosphorus release to substrate uptake ) used in ASM2, ASM2d, and ASM3P, respectively. Three scenarios were evaluated to improve the performance of the wastewater treatment plant, the possibility of wasting sludge from either the aeration tank or the secondary clarifier, the construction of a new oxidation ditch, and the construction of an equalization tank. The results suggest that construction of a new oxidation ditch or an equalization tank for the wastewater treatment plant is not necessary. However, sludge should be wasted from the aeration tank during wet weather to reduce the solids loading of the clarifiers and avoid effluent violations. Therefore, it is recommended that the design of wastewater treatment plants (WWTPs) should include flexibility to operate the plants in various modes. This is helpful in selection of the appropriate operating mode when necessary, resulting in substantial reductions in operating costs.

  13. Analysis of one-dimensional Yut-Nori game: winning strategy and avalanche-size distribution

    CERN Document Server

    Park, Hye Jin; Jo, Hang-Hyun; Kim, Beom Jun

    2013-01-01

    In the Korean traditional board game Yut-Nori, teams compete by moving their pieces on the two-dimensional game board, and the team whose all pieces complete a round trip on the board wins. In every round, teams throw four wooden sticks of the shape of half-cut cylinder and the number of sticks that show belly sides, i.e., the flat sides, determines the number of steps the team's piece can advance on the board. It is possible to pile up one team's pieces if their sites are identical so that pieces as a group can move together afterwards (piling). If a piece of the opponent team is at the new site of one team's piece, the piece is caught and removed from the board, and the team is given one more chance to throw sticks and proceed (catching). For a simplicity, we simulate this game on one-dimensional board with the same number of sites as the original game, and show that catching is more advantageous strategy than piling to win. We also study the avalanche-size distribution in thermodynamic limit to find that i...

  14. WINNING BIG BUT FEELING NO BETTER? THE EFFECT OF LOTTERY PRIZES ON PHYSICAL AND MENTAL HEALTH

    Science.gov (United States)

    Apouey, Benedicte; Clark, Andrew E.

    2014-01-01

    SUMMARY We use British panel data to determine the exogenous impact of income on a number of individual health outcomes: general health status, mental health, physical health problems, and health behaviours (drinking and smoking). Lottery winnings allow us to make causal statements regarding the effect of income on health, as the amount won by winners is largely exogenous. Positive income shocks have no significant effect on self-assessed overall health, but a significant positive effect on mental health. This result seems paradoxical on two levels. First, there is a well-known gradient in health status in cross-sectional data, and second, general health should partly reflect mental health, so that we may expect both variables to move in the same direction. We propose a solution to the first apparent paradox by underlining the endogeneity of income. For the second, we show that lottery winnings are also associated with more smoking and social drinking. General health will reflect both mental health and the effect of these behaviours and so may not improve following a positive income shock. PMID:24677260

  15. Meet the best Award-winning technologies from Pacific Northwest Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    1990-09-01

    The Battelle Memorial Institute has managed the Pacific Northwest Laboratory (PNL) for the US Department of Energy for 25 years. During this time, numerous new technologies have been discovered and developed at PNL as a result of our research programs. This document will introduce you to some of the more significant discoveries and newly commercialized technologies. Each of the technologies described has received an award from Research Development magazine or the Federal Laboratory Consortium--sometimes both Each technology is available to you through PNL's technology transfer program or one of our licensees. Similarly, our award-winning scientists and engineers are available to assist you as you search for innovative technologies to solve your technical problems. These researchers are familiar with current problems confronting industry, government agencies, and the academic community. They are happy to apply their skills and PNL's resources to your problems. PNL encourages its researchers to work with government agencies, universities, and US industries. PNL technology transfer programs address the nation's drive toward increased competitiveness by being flexible and aggressive, and are designed to tailor results to fit your needs and those of your clients. If you are in search of a new technology or increased competitiveness, consider collaborative efforts with our award-winning staff, whose accomplishments are synopsized in this booklet.

  16. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

  17. Differential Regulation of Behavioral Tolerance to WIN55,212-2 by GASP1

    OpenAIRE

    Martini, Lene; Thompson, Dawn; Kharazia, Viktor; Whistler, Jennifer L.

    2010-01-01

    Cannabinoid agonists have shown some promise clinically as analgesics, in particular for cancer pain, in which they have the additional benefit of decreasing nausea. However, as for most other drugs, the long-term use of cannabinoids is limited by the development of tolerance. Several molecular mechanisms have been proposed to explain drug tolerance, including receptor downregulation. The cannabinoid 1 (CB1) receptors can be downregulated in vitro through an interaction with the G-protein-cou...

  18. Dopamine Agonist in Treatment of ADHD with Restless Legs Syndrome and ODD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-05-01

    Full Text Available A 6-year-old male with attention deficit hyperactivity disorder who responded poorly to methylphenidate (MPH was benefited following treatment with the dopamine agonist ropinirole, in a report from the Hopital Robert Debre, Paris, France.

  19. Lepidozenolide from the liverwort Lepidozia fauriana acts as a farnesoid X receptor agonist.

    Science.gov (United States)

    Lin, Hsiang-Ru

    2015-01-01

    Lepidozenolide is a sesquiterpenoid isolated from the liverwort Lepidozia fauriana and its possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and hyperglycemia. In this study, whether lepidozenolide may act as a FXR agonist was determined. Indeed, in mammalian one-hybrid and transient transfection reporter assays, lepidozenolide transactivated FXR to modulate promoter action including GAL4, CYP7A1, and PLTP promoters in a dose-dependent manner, while it exhibited slightly less agonistic activity than chenodeoxycholic acid, an endogenous FXR agonist. Through the molecular modeling docking studies lepidozenolide was shown to bind to FXR ligand binding pocket fairly well. All these results indicate that lepidozenolide acts as a FXR agonist. PMID:25315435

  20. Synthesis of 2-(Benzodioxol-2-yl)acetic Acids as PPARδ Agonists

    Institute of Scientific and Technical Information of China (English)

    Jian Lei KANG; Zhi Bing ZHENG; Dan QIN; Li Li WANG; Song LI

    2006-01-01

    A new series of compounds, 2-(benzodioxol-2-yl)acetic acids, have been synthesized. Their structures were confirmed by MS and 1H-NMR. The preliminary pharmacological screening showed that these compounds exhibited potent human PPARδ agonist activities.

  1. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

    Science.gov (United States)

    Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

    2013-01-01

    This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

  2. Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

    Institute of Scientific and Technical Information of China (English)

    YonglianSun; JonathanH.Chen; YangxinFu

    2004-01-01

    CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically. Cellular & Molecular Immunology. 2004;1(1):31-36.

  3. Immunotherapy with Agonistic Anti-CD137: Two Sides of a Coin

    Institute of Scientific and Technical Information of China (English)

    Yonglian Sun; Jonathan H.Chen; Yangxin Fu

    2004-01-01

    CD137 (4-1BB), a member of the TNF receptor superfamily, is an inducible T cell costimulatory receptor primarily expressed on activated CD4+ and CD8+ T cells. Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses. Surprisingly, these agonists also showed therapeutic effects in several autoimmune diseases. These findings suggest that in different disease environments, CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes. Therefore, CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders. However, CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically. Cellular & Molecular Immunology. 2004;1(1):31-36.

  4. Differential effects of beta-adrenoceptor partial agonists in patients with postural hypotension

    DEFF Research Database (Denmark)

    Mehlsen, J; Stadeager, C; Trap-Jensen, J

    1993-01-01

    The central haemodynamic effects of pindolol and xamoterol have been investigated in patients with postural hypotension. Pindolol is a non-selective beta-adrenoceptor partial agonist, whereas xamoterol is beta 1-selective and possesses a higher degree of agonist activity. The study comprised 16.......min-1 and LVEF from 0.57 to 0.52, and reduced mean arterial blood pressure from 103 mm Hg to 93 mm Hg. Xamoterol showed beta-adrenoceptor agonistic effects in the supine position through increments in heart rate from 72 to 90 beats.min-1 and LVEF from 0.58 to 0.66, and raised mean arterial blood...... pressure from 108 to 123 mm Hg. It is concluded that the degree of agonist activity of a beta-adrenergic agent is of importance if it is given to a patient with postural hypotension....

  5. The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis

    OpenAIRE

    Nicole A. Hofmann; Yang, Jiang; Trauger, Sunia A.; Nakayama, Hironao; Huang, Lan; Strunk, Dirk; Moses, Marsha A.; Klagsbrun, Michael; Bischoff, Joyce; Graier, Wolfgang F

    2015-01-01

    Background and Purpose Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis. Experimental Approach Secretion of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometry. Involvement of cancer cell-derived LPI on angiogenesis was tested in the in vivo ch...

  6. Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells

    OpenAIRE

    Yamasaki, M.; Masgrau, R.; Morgan, A. J.; Churchill, G. C.; Patel, S.; Ashcroft, S. J. H.; Galione, A

    2004-01-01

    How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle seleetion") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively...

  7. Discovery of Azetidinone Acids as Conformationally-Constrained Dual PPARalpha/gamma Agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.; Devasthale, P; Farrelly, D; Gu, L; Harrity, T; Cap, M; Chu, C; Kunselman, L; Morgan, N; et. al.

    2008-01-01

    A novel class of azetidinone acid-derived dual PPAR{alpha}/{gamma} agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARa and PPAR? receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

  8. A comparison of agonist-specific coupling of cloned human α2-adrenoceptor subtypes

    OpenAIRE

    Rudling, Jane E; Richardson, Jo; Evans, Peter D.

    2000-01-01

    The agonist-specific coupling properties of the three cloned human α2-adrenoceptor subtypes have been compared, when expressed at similar levels in Chinese hamster ovary (CHO) cell lines, using noradrenaline and (±)-meta-octopamine as agonists.Noradrenaline can couple the receptor to both the inhibition and stimulation of forskolin-stimulated cyclic AMP production in all three receptor subtypes, with the relative strength of the coupling to the pathways varying for each of the receptor subtyp...

  9. Perioperative use of selective alpha-2 agonists and antagonists in small animals

    OpenAIRE

    Lemke, Kip A.

    2004-01-01

    Alpha-2 agonists are the only single class of anesthetic drugs that induce reliable, dose-dependent sedation, analgesia, and muscle relaxation in dogs and cats. Used at low doses, as adjuncts to injectable and inhalational anesthetics, selective alpha-2 agonists dramatically reduce the amount of anesthetic drug required to induce and maintain anesthesia. This reduction in anesthetic requirements is achieved without significant depression of pulmonary function and with limited effects on cardi...

  10. PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

    OpenAIRE

    Silswal, Neerupma; Parelkar, Nikhil K; Michael J. Wacker; Badr, Mostafa; Andresen, Jon

    2012-01-01

    We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPAR α ) agonists using isolated mouse aortas and middle cerebral arteries (MCAs). The PPAR α agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPAR α deficient mice demonstrated that responses were also ...

  11. Biphasic Effect of Melanocortin Agonists on Metabolic Rate and Body Temperature

    OpenAIRE

    Lute, Beth; Jou, William; Lateef, Dalya M.; Goldgof, Margalit; Xiao, Cuiying; Piñol, Ramón A.; Kravitz, Alexxai V.; Miller, Nicole R.; Huang, Yuning George; Girardet, Clemence; Butler, Andrew A.; Gavrilova, Oksana; Reitman, Marc L.

    2014-01-01

    The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses. Intraperitoneal administration of the nonselective melanocortin agonist MTII causes a melanocortin-4 receptor (Mc4r) mediated hypermetabolism/hyperthermia. This is preceded by a profound, transient hypometabolism/hypothermia tha...

  12. Dopamine Agonist Increases Risk Taking but Blunts Reward-Related Brain Activity

    OpenAIRE

    Jordi Riba; Krämer, Ulrike M.; Marcus Heldmann; Sylvia Richter; Münte, Thomas F.

    2008-01-01

    The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefo...

  13. Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Scott K.; Washburn, David G.; Frazee, James S.; Madauss, Kevin P.; Hoang, Tram H.; Lapinski, Leahann; Grygielko, Eugene T.; Glace, Lindsay E.; Trizna, Walter; Williams, Shawn P.; Duraiswami, Chaya; Bray, Jeffrey D.; Laping, Nicholas J.; (GSKNC); (GSKPA)

    2010-09-03

    Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

  14. Lack of Cocaine-Like Discriminative-Stimulus Effects of σ Receptor Agonists in Rats

    OpenAIRE

    Hiranita, Takato; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L.

    2011-01-01

    Previous studies demonstrated effectiveness of selective sigma-receptor (σR) agonists (DTG, PRE-084) as reinforcers in rats trained to self-administer cocaine. Like cocaine, these drugs increased nucleus accumbens shell dopamine levels, and effects of DTG, but not PRE-084, on dopamine appeared to be mediated by σRs. Additionally, σR antagonists blocked self-administration of σR agonists, but were inactive against reinforcing and neurochemical effects of cocaine. Thus pharmacologically distinc...

  15. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors

    OpenAIRE

    Ginj, Mihaela; Zhang, Hanwen; Waser, Beatrice; Cescato, Renzo; Wild, Damian; Wang, Xuejuan; Erchegyi, Judit; Rivier, Jean; Mäcke, Helmut R.; Reubi, Jean Claude

    2006-01-01

    Targeting neuroendocrine tumors expressing somatostatin receptor subtypes (sst) with radiolabeled somatostatin agonists is an established diagnostic and therapeutic approach in oncology. While agonists readily internalize into tumor cells, permitting accumulation of radioactivity, radiolabeled antagonists do not, and they have not been considered for tumor targeting. The macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was coupled to two potent somatostatin...

  16. Identification of benzoxazole analogs as novel, S1P(3) sparing S1P(1) agonists.

    Science.gov (United States)

    Deng, Guanghui; Meng, Qinghua; Liu, Qian; Xu, Xuesong; Xu, Qiongfeng; Ren, Feng; Guo, Taylor B; Lu, Hongtao; Xiang, Jia-Ning; Elliott, John D; Lin, Xichen

    2012-06-15

    A novel series of benzoxazole-derived S1P(1) agonists were designed based on scaffold hopping molecular design strategy combined with computational approaches. Extensive SAR studies led to the discovery of compound 17d as a selective S1P(1) agonist (over S1P(3)) with high CNS penetration and favorable DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce blood lymphocyte in mice after oral administration.

  17. PPAR agonists regulate brain gene expression: Relationship to their effects on ethanol consumption

    OpenAIRE

    Ferguson, Laura B.; Most, Dana; Yuri A Blednov; Harris, R. Adron

    2014-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We teste...

  18. SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist.

    Science.gov (United States)

    Sard, Howard; Kumaran, Govindaraj; Morency, Cynthia; Roth, Bryan L; Toth, Beth Ann; He, Ping; Shuster, Louis

    2005-10-15

    An SAR study of psilocybin and psilocin derivatives reveals that 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor. The corresponding phosphate derivative, 1-methylpsilocybin, shows efficacy in an animal model for obsessive-compulsive disorder, as does 4-fluoro-N,N-dimethyltryptamine. These results suggest a new area for development of novel 5-HT(2C) agonists with applications for drug discovery.

  19. Evaluation of the beta 2 adrenoceptor agonist/antagonist activity of formoterol and salmeterol.

    OpenAIRE

    Grove, A.; Lipworth, B J

    1996-01-01

    BACKGROUND: Salmeterol and formoterol have a lower intrinsic activity at beta 2 receptors than isoprenaline in human bronchus in vitro. The aim of the present study was to evaluate in vivo the beta 2 agonist/antagonist activity of salmeterol and formoterol at rest with low endogenous adrenergic tone, on exercise with raised endogenous adrenergic tone, and in the presence of fenoterol, an exogenous full beta 2 receptor agonist. METHODS: Eight normal subjects were randomised to receive single d...

  20. Tolerance to bronchodilation during treatment with long-acting beta-agonists, a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Hancox Robert J

    2005-09-01

    Full Text Available Abstract Background Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist. Methods Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 μg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV1. Salbutamol 100, 200 and 400 μg (cumulative dose was then given at 5-minute intervals and FEV1 was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve. Results The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68% lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV1 and dose of methacholine given (p = 0.001. Conclusion The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.

  1. Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis.

    OpenAIRE

    Dekkers, O. M.; Lagro, J.; Burman, P; J. O. Jorgensen; Romijn, J.A.; A M Pereira

    2010-01-01

    CONTEXT: Dopamine agonists are the treatment of choice for prolactinomas and symptomatic idiopathic hyperprolactinemia. However, the optimal treatment strategy and treatment duration is not clear in all details. OBJECTIVE: The aim of the study was to assess the effect of dopamine agonist withdrawal in patients with idiopathic hyperprolactinemia and prolactinomas. DATA SOURCES: PubMed, the Cochrane Library, the Web of Science, and EMBASE were searched electronically. No restriction was made wi...

  2. Inhibition of glucagon secretion by GLP-1 agonists and DPP4 inhibitors

    DEFF Research Database (Denmark)

    Hansen, Morten; Juul Hare, Kristine; Holst, Jens Juul;

    2011-01-01

    with emphasis on their glucagon-lowering effects. Finally, we review available glucagon data from current clinical studies on incretin-based treatment modalities (dipeptidyl peptidase 4 [DPP4] inhibitors and GLP-1 receptor agonists). Most of these studies suggest that both DPP4 inhibitors and GLP-1 receptor...... agonists lower fasting and postprandial plasma glucagon, and recent data suggest that these effects contribute importantly to the glucose-lowering effect of these treatments....

  3. Congratulations to Academician Changxu Shi on the Occasion of His Winning the 2010 Chinese Science & Technology Grand Prize%Congratulations to Academician Changxu Shi on the Occasion of His Winning the 2010 Chinese Science & Technology Grand Prize

    Institute of Scientific and Technical Information of China (English)

    Ju Li; Kai Chen; Zhiwei Shan; Guanjun Qiao; Jun Sun; Evan Ma

    2011-01-01

    On behalf of friends and colleagues at MIT and Johns Hopkins University, as well as students and faculty at the Center for Advancing Materials Performance from the Nanoscale (CAMP-Nano) at Xi'an Jiaotong University, we would like to express our hearty congratulations to Academician Shi on the occasion of his winning the highest science and technology award of China.

  4. Alpha1 receptor coupling events initiated by methoxy-substituted tolazoline partial agonists

    International Nuclear Information System (INIS)

    A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha1 receptor, were compared with the α1 selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, 45Ca influx, 45Ca efflux, and 32P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10-5M) were 53.8, 67.6 and 99.7% of the PE (10-5M) response respectively. These same partial agonists caused a stimulation of 45Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In 45Ca efflux studies, (a measure of the intracellular Ca+2 release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. 32P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after α1 receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate α receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle

  5. Alpha/sub 1/ receptor coupling events initiated by methoxy-substituted tolazoline partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wick, P.; Keung, A.; Deth, R.

    1986-03-01

    A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha/sub 1/ receptor, were compared with the ..cap alpha../sub 1/ selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, /sup 45/Ca influx, /sup 45/Ca efflux, and /sup 32/P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10/sup -5/M) were 53.8, 67.6 and 99.7% of the PE (10/sup -5/M) response respectively. These same partial agonists caused a stimulation of /sup 45/Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In /sup 45/Ca efflux studies, (a measure of the intracellular Ca/sup +2/ release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. /sup 32/P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after ..cap alpha../sub 1/ receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate ..cap alpha.. receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle.

  6. Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections

    Science.gov (United States)

    Mhashilkar, Amruta S.; Vankayala, Sai L.; Liu, Canhui; Kearns, Fiona; Mehrotra, Priyanka; Tzertzinis, George; Palli, Subba R.; Woodcock, H. Lee; Unnasch, Thomas R.

    2016-01-01

    Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets. Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. A B. malayi ecdysone receptor ligand-binding domain was developed and used to study the ligand-receptor interactions of these agonists. An excellent correlation between the virtual screening results and the screening assay was observed. Based on both of these approaches, steroidal ecdysone agonists and the diacylhydrazine family of compounds were identified as a fruitful source of potential receptor agonists. In further confirmation of the modeling and screening results, Ponasterone A and Muristerone A, two compounds predicted to be strong ecdysone agonists stimulated expulsion of microfilaria and immature stages from adult parasites. Conclusions The studies validate the potential of the B. malayi ecdysone receptor as a drug target and provide a means to rapidly evaluate compounds for development of a new class of drugs against the human filarial parasites. PMID:27300294

  7. GLP-1 receptor agonists or DPP-4 inhibitors: how to guide the clinician?

    Science.gov (United States)

    Scheen, André J

    2013-12-01

    Pharmacological treatment of type 2 diabetes has been enriched during recent years, with the launch of incretin therapies targeting glucagon-like peptide-1 (GLP-1). Such medications comprise either GLP-1 receptor agonists, with short (one or two daily injections: exenatide, liraglutide, lixisenatide) or long duration (one injection once weekly: extended-released exenatide, albiglutide, dulaglutide, taspoglutide); or oral compounds inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme that inactives GLP-1, also called gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin). Although both pharmacological approaches target GLP-1, important differences exist concerning the mode of administration (subcutaneous injection versus oral ingestion), the efficacy (better with GLP-1 agonists), the effects on body weight and systolic blood pressure (diminution with agonists versus neutrality with gliptins), the tolerance profile (nausea and possibly vomiting with agonists) and the cost (higher with GLP-1 receptor agonists). Both agents may exert favourable cardiovascular effects. Gliptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after failure of a dual oral therapy. However, this scheme is probably too restrictive and modalities of using incretins are numerous, in almost all stages of type 2 diabetes. Physicians may guide the pharmacological choice based on clinical characteristics, therapeutic goals and patient's preference.

  8. Effect of β3-adrenergic agonists on alveolar fluid clearance in hypoxic rat lungs

    Institute of Scientific and Technical Information of China (English)

    LI Nai-jing; LI Wei; HE Ping; GU Xiu; LI Sheng-qi

    2010-01-01

    Background Recent research suggests that β_2-adrenergic agonists increase alveolar fluid clearance (AFC) under physiologic and pathologic conditions. It is unknown whether β_3-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of β_3 -adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved.Methods Hypoxic rats were exposed to 10% oxygen. BRL-37344 (β_3-adrenergic agonist) or CGP-12177 (selective β_3-adrenergic agonist) alone or combined with β receptor antagonists, sodium channel blockers, or Na~+/K~+-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content (TLW) and AFC were measured.Results AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride (a Na~+ channel blocker) and ouabain (a Na~+/K~+-ATPase inhibitor) by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177.Conclusions These findings suggest that (β3-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.

  9. PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

    Directory of Open Access Journals (Sweden)

    Neerupma Silswal

    2012-01-01

    Full Text Available We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα agonists using isolated mouse aortas and middle cerebral arteries (MCAs. The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC, and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response.

  10. A Win-Win Collaboration

    OpenAIRE

    Mary Beth Parkinson

    2013-01-01

    This brief article reports on a collaborative book-borrowing policy between The Brendlinger Library of Montgomery County Community College and the Wissahickon Valley Public Library (WVPL), both located in Blue Bell, PA.  Beginning in January 2013, WVPL will donate books periodically to the Brendlinger Library in support of the students enrolled in Reading classes.  Circulation statistics will be reported to WVPL, and the books will be returned to WVPL for sale in the WVPL Friends of the Libra...

  11. A Win-Win Game

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Nanjing looks forward to upgrading its infrastructure and stature by hosting a successful Youth Olympic Games As the inaugural Youth Olympic Games(YOG) of 2010 wrapped up in Singapore on August 26,people turned their attention to China’s Nanjing,where the next YOG will be held in 2014. The organizers said they expect the second YOG to be an accelerator for the city’s bid to become an international metropolis and for the young event to "grow up."

  12. A Win-Win Collaboration

    Directory of Open Access Journals (Sweden)

    Mary Beth Parkinson

    2013-04-01

    Full Text Available This brief article reports on a collaborative book-borrowing policy between The Brendlinger Library of Montgomery County Community College and the Wissahickon Valley Public Library (WVPL, both located in Blue Bell, PA.  Beginning in January 2013, WVPL will donate books periodically to the Brendlinger Library in support of the students enrolled in Reading classes.  Circulation statistics will be reported to WVPL, and the books will be returned to WVPL for sale in the WVPL Friends of the Library book sale. Keywords: academic library; public library,  community college library; collaboration; developmental readers; reading programs; reading instruction; literacy; Montgomery County Community College; Wissahickon Valley Public Library

  13. A Win-Win Game

    Institute of Scientific and Technical Information of China (English)

    LI LI

    2010-01-01

    @@ As the inaugural Youth Olympic Games (YOG) of 2010 wrapped up in Singapore on August 26, people turned their attention to China's Nanjing, where the next YOG will be held in 2014. The organizers said they expect the second YOG to be an accelerator for the city's bid to become an international metropolis and for the young event to "grow up."

  14. A Win-Win Forum

    Institute of Scientific and Technical Information of China (English)

    ZHANG ZHONGXIANG

    2010-01-01

    @@ The 10 years since the inauguration of the Forum on China-Africa Cooperation(FOCAC)have witnessed the most rapid growth in the history of China-Africa relations,China unveiled measures to strengthen cooperation at every FOCAC ministerial conference and these measures were effectively implemented.

  15. A Win-Win Forum

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A decade later,the FOCAC has generated tangible benefits for both China and Africa The 10 years since the inauguration of the Forum on China-Africa Cooperation(FOCAC) have witnessed the most rapid growth in the history of China-Africa relations.China unveiled measures to strengthen cooperation at every FOCAC ministerial conference and these measures were effectively implemented.

  16. Radiolabelled D2 agonists as prolactinoma imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Otto, C.A.

    1989-08-01

    During the past year, further studies on mAChR were conducted. These studies included verification of the difference in pituitary distribution based on ligand charge. The pituitary localization of TRB. A neutral mAChR ligand, was verified. The lack of QNB blockade of TRB uptake was tested by blockage with scopolamine, another mAChR antagonist and by testing the effect in a different strain of rat. Neither scopolamine or change of rat strain had any effect. We concluded that TRB uptake in pituitary is not a receptor-mediated process. Further studies were conducted with an additional quaternized mAChR ligand: MQNB. Pituitary localization of MQNB, like MTRB, could be blocked by pretreatment with QNB. We have tentatively concluded that permanent charge on a mAChR antagonist changes the mechanism of uptake in the pituitary. Time course studies and the effects of DES on myocardial uptake are reported. A brief report on preliminary results of evaluation of quaternized mAChR ligands in the heart is included. In a limited series of such ligands, we have observed a single binding site and a difference in B{sub max} values: QNB competition studies yield larger B{sub max} values than studies with {sup 3}H-NMS. Progress in the synthesis of D{sub 2} agonists includes solving a synthetic problem and preparation of the cold'' analogue of N-0437 using procedures applicable to eventual synthesis with {sup 11}C-CH{sub 3}I. 2 refs., 5 figs., 1 tab.

  17. Organization of an interphase system for the coupling of WINS-D4 and SNAP-3D programs

    International Nuclear Information System (INIS)

    In this report a modular system developed for the CC-1 critical assembly's physical calculation is described. It was based upon the WINS-D4 and SNAP-3D codes, which are coupled by means of an interphase module and a groups diffusion cross sections library

  18. A deal that's hard to refuse. Physicians use clout to win joint ventures with hospitals despite fiscal perils.

    Science.gov (United States)

    Jaklevic, M C

    2001-12-01

    Just as many hospitals rid themselves of unprofitable medical practices, a risky new strategy to win physician loyalty is gaining popularity: hospital-physician joint ventures. Some analysts say the deals could backfire, as the dangers for hospital balance sheets outweigh the benefits.

  19. Work with young people - a priority in the activities if WIN Bulgaria for popularization of nuclear energy

    International Nuclear Information System (INIS)

    One of the main goals of WIN Bulgaria is is the promotion of the developments in the nuclear technologies in the education system and to direct and coordinate the participation of young people in the learning and applying of these technologies

  20. A critical appraisal of WinEcon and its use in a first-year undergraduate Economics programme

    Directory of Open Access Journals (Sweden)

    D. J. Brooksbank

    1998-12-01

    Full Text Available WinEcon is a Windows-based introductory Economics CAL package designed for use in higher education. It is the product of the Economics Consortium of the TLTP (Teaching and Learning Technology Programme consisting of eight university Economics departments. Each of these has been responsible for producing some of the 25 chapters (tutorials of the finished product. Content is based on covering the common core of introductory Economics as revealed by a survey of higher-education Economics departments. WinEcon is provided, with an accompanying workbook, for a nominal registration fee in the UK. The package is important insofar as it is aimed at all first-year undergraduates studying Economics, which encompasses not only those taking straight Economics degrees but large numbers of students following introductory Economics as part of a Business Studies or Combined Studies course. With no competition to speak of, WinEcon is likely to become a significant feature of the learning experience of a large tranche of the undergraduate population, across a number of degree schemes. Indeed, for many of these students WinEcon will constitute their first major experience of CAL.

  1. The New Updates in CDS/ISIS for Windows : Version WIN/ISIS 1.5 .Part 1

    Directory of Open Access Journals (Sweden)

    Mohamed Salem Ghonem

    2006-03-01

    Full Text Available A Study about the last version of library system Win/ISIS 1.5, the study define the Parameters of the new version, and the components of each one and its function, and how to modify them.

  2. Mamow Ki-ken-da-ma-win: A Partnership Approach to Child, Youth, Family and Community Wellbeing

    Science.gov (United States)

    Finlay, Judy; Hardy, Micheal; Morris, Donny; Nagy, Anna

    2010-01-01

    "Mamow-Sha-way-gi-kay-win": North-South Partnership for Children represents a coalition of individuals and organizations from southern Ontario who have partnered with First Nations Chiefs, community leaders, Elders, youth and community members from 30 remote northern communities. The collective goal of the Partnership is to learn from one another…

  3. The New Updates in CDS/ISIS for Windows : Version WIN/ISIS 1.5 .Part 2

    Directory of Open Access Journals (Sweden)

    Mohamed Salem Ghonem

    2006-06-01

    Full Text Available A Study about the last version of library system Win/ISIS 1.5, the study define the Parameters of the new version, and the components of each one and its function, and how to modify them.

  4. Dopamine D3 Receptors Modulate the Ability of Win-Paired Cues to Increase Risky Choice in a Rat Gambling Task.

    Science.gov (United States)

    Barrus, Michael M; Winstanley, Catharine A

    2016-01-20

    Similar to other addiction disorders, the cues inherent in many gambling procedures are thought to play an important role in mediating their addictive nature. Animal models of gambling-related behavior, while capturing dimensions of economic decision making, have yet to address the impact that these salient cues may have in promoting maladaptive choice. Here, we determined whether adding win-associated audiovisual cues to a rat gambling task (rGT) would influence decision making. Thirty-two male Long-Evans rats were tested on either the cued or uncued rGT. In these tasks, animals chose between four options associated with different magnitudes and frequencies of reward and punishing time-out periods. As in the Iowa Gambling Task, favoring options associated with smaller per-trial rewards but smaller losses and avoiding the tempting "high-risk, high-reward" decks maximized profits. Although the reinforcement contingencies were identical in both task versions, rats' choice of the disadvantageous risky options was significantly greater on the cued task. Furthermore, a D3 receptor agonist increased choice of the disadvantageous options, whereas a D3 antagonist had the opposite effects, only on the cued task. These findings are consistent with the reported role of D3 receptors in mediating the facilitatory effects of cues in addiction. Collectively, these results indicate that the cued rGT is a valuable model with which to study the mechanism by which salient cues can invigorate maladaptive decision making, an important and understudied component of both gambling and substance use disorders. Significance statement: We used a rodent analog of the Iowa Gambling Task to determine whether the addition of audiovisual cues would affect choice preferences. Adding reward-concurrent cues significantly increased risky choice. This is the first clear demonstration that reward-paired cues can bias cost/benefit decision making against a subject's best interests in a manner concordant

  5. Risk dishabituation: in repeated gambling, risk is reduced following low-probability "surprising" events (wins or losses).

    Science.gov (United States)

    Demaree, Heath A; Burns, Kevin J; Dedonno, Michael A; Agarwala, Edward K; Everhart, D Erik

    2012-06-01

    In path-dependent risk taking, like playing a slot machine, the wager on one trial may be affected by the outcome of the preceding trial. Previous studies have shown that a person's risk-taking preferences may change as a result of the preceding trial (win or loss). For example, the "house money effect" suggests that risk taking may increase after a win, whereas the "break even effect" posits that risk taking increases after a loss. Independent of those findings, a person's emotional state has been found to influence risk taking. For example, the "mood maintenance hypothesis" supports the notion that positive affect decreases risk taking, and related research finds that increased negative affect increases risk taking. Because winning and losing may influence one's emotional state, we sought to investigate how both previous outcomes, as well as a person's emotional responses to those outcomes, independently influence subsequent risk taking. To do this, data were collected using three simplified slot machines where the chance of winning each trial was set to 13%, 50%, and 87%, respectively. Evidence for the break even and house money effects were found on the 13% and 87% games, respectively. Likewise, emotional valence was found to predict risk taking on these two tasks, with emotional valence fully explaining the break even effect observed on the 13% game. In addition to these results, the present research revealed that risk taking is reduced following low-probability ("surprising") events (i.e., a win in the 13% condition or loss in the 87% condition). Dubbed "risk dishabituation," this phenomenon is discussed, along with its likely corresponding emotional experience--surprise. PMID:22023358

  6. CERN Relay Race: the Shabbys win again, this time with music

    CERN Multimedia

    2005-01-01

    The Shabbys definitely seem unbeatable. They won the CERN Relay Race for the fifth consecutive year by a comfortable margin (picture below). It was a more neck-and-neck finish for second and third place but in the end Los Latinos Volantes came in second by a hair's breadth in front of Charmilles Technologies in third place, a reversal of last year's positions. For the less competitive participants, the Relay Race retains its traditional charm as a moment of relaxation and as an event in which taking part is more important than winning. In addition, even if the sun was noticeable by its absence, CERN's excellent Jazz Club band added a novel touch of colour and levity. Participants and spectators alike greatly appreciated their musical accompaniment on the finishing line! All the results are published in this issue on page 5 of the Staff Association section.

  7. Health evaluation of the 2nd International "Quit and Win" Antinicotine Campaign participants ten years later.

    Science.gov (United States)

    Kowalska, Alina; Stelmach, Włodzimierz; Krakowiak, Jan; Rzeźnicki, Adam; Pikala, Małgorzata; Dziankowska-Zaborszczyk, Elzbieta; Drygas, Wojciech

    2008-01-01

    Smoking is one of the most often noticed types of negative behaviour among the Poles. In the work, the results of the health evaluation are presented of the participants of the 'Quit and Win' competition ten years after making a decision to refrain from smoking, also the dependency between this evaluation and behaviour connected with smoking among the people living in big cities and small towns and villages was analysed. Among the 648 respondents, majority, which is 302 people (46.6%) evaluated their health as good, 236 (36.4%) as average, and 76 of the questioned (11.7%) as very good, 29 people (4.5%) as bad, and 5 of the questioned (0.8%) as very bad. The respondents most often evaluated negatively their health in the group of the still smoking living in the big cities, and the least often in the group of the non-smokers living in small towns and villages.

  8. Supernovae, Dark Energy and the Accelerating Universe: How DOE Helped to Win (yet another) Nobel Prize

    Energy Technology Data Exchange (ETDEWEB)

    Perlmutter, Saul

    2012-01-13

    The Department of Energy (DOE) hosted an event Friday, January 13, with 2011 Physics Nobel Laureate Saul Perlmutter. Dr. Perlmutter, a physicist at the Department’s Lawrence Berkeley National Laboratory and a professor of physics at the University of California at Berkeley, won the 2011 Nobel Prize in Physics “for the discovery of the accelerating expansion of the Universe through observations of distant supernovae.” DOE’s Office of Science has supported Dr. Perlmutter’s research at Berkeley Lab since 1983. After the introduction from Secretary of Energy Steven Chu, Dr. Perlmutter delivered a presentation entitled "Supernovae, Dark Energy and the Accelerating Universe: How DOE Helped to Win (yet another) Nobel Prize." [Copied with editing from DOE Media Advisory issued January 10th, found at http://energy.gov/articles/energy-department-host-event-2011-physics-nobel-laureate-saul-perlmutter

  9. Automated Coverage Tester for the Oracle Archiver of WinCC OA

    CERN Document Server

    Voitier, A; Gonzalez-Berges, M

    2011-01-01

    A large number of control systems at CERN are built with the commercial SCADA tool WinCC OA (formerly PVSS) [1]. They cover projects in the experiments, accelerators and infrastructure. An important component is the Oracle archiver used for long term storage of process data (events) and alarms. The archived data provide feedback to the operators and experts about how the system was behaving at particular moment in the past. In addition a subset of these data is used for offline physics analysis (conditions data). Large volumes of data are produced by the different facilities at CERN (several Terabytes per year). The consistency of the archived data has to be ensured from writing to reading as well as throughout updates of the control systems. The complexity of the archiving subsystem comes from the multiplicity of data types, required performance and other factors such as operating system, environment variables or versions of the different software components. Therefore an automatic tester has been implemente...

  10. Stochastic Win-Stay-Lose-Shift with dynamic aspirations in evolutionary social dilemmas

    CERN Document Server

    Amaral, Marco A; Perc, Matjaz; da Silva, Jafferson K L

    2016-01-01

    In times of plenty expectations rise, just as in times of crisis they fall. This can be mathematically described as a Win-Stay-Lose-Shift strategy with dynamic aspiration levels, where individuals aspire to be as wealthy as their average neighbor. Here we investigate this model in the realm of evolutionary social dilemmas on the square lattice and scale-free networks. By using the master equation and Monte Carlo simulations, we find that cooperators coexist with defectors in the whole phase diagram, even at high temptations to defect. We study the microscopic mechanism that is responsible for the striking persistence of cooperative behavior and find that cooperation spreads through second-order neighbors, rather than by means of network reciprocity that dominates in imitation-based models. For the square lattice the master equation can be solved analytically in the large temperature limit of the Fermi function, while for other cases the resulting differential equations must be solved numerically. Either way, ...

  11. A big win for the CERN Golf Club at the ASCERI tournament

    CERN Multimedia

    Katarina Anthony

    2010-01-01

    The CERN Golf Club returned victorious from the autumn ASCERI (Association of the Sports Communities of the European Research Institutes) tournament which was held from 17 to 20 September.   The CERN Golf Team (left to right: Peter Jones, Alasdair Ross, Claes Frisk and Per Werner) celebrates its victories at ASCERI. Competitions took place on the Dreihof Golf Club at Essingen in southern Germany, starting with the singles Stableford competition on the first day and a 4 ball, better ball Stableford group competition the next day. CERN’s four-man team – Peter Jones, Per Werner, Claes Frisk and Alasdair Ross – came first in the group competition, with Peter Jones, CERN’s star golfer from the IT Department, winning the individual competition. The autumn ASCERI tournament included competitions in football, tennis and cart racing as well as golf. Over 230 representatives of research institutes across Europe took part. “The CERN Golf Club only began p...

  12. Dopamine agonists, anti-progestins, anti-androgens, long-term-release GnRH agonists and anti-estrogens in canine reproduction: a review.

    Science.gov (United States)

    Gobello, C

    2006-10-01

    Over the last 10 years, new drugs have been applied to canine reproduction, widening the spectrum of therapeutic possibilities for diseases that were previously surgically treated, and facilitating better control of the estrous cycle and fertility. Some are not approved for use in dogs; their use is experimental and further clinical trials are necessary. Dopamine agonists such as cabergoline, bromocriptine or metergoline are ergoderivative alkaloids that exert an anti-prolactinergic effect via stimulation of D2 pituitary receptors or inhibition of central serotoninergic ones. Their main indication is suppression of lactation. Anti-prolactinergic compounds have also been successfully used for pregnancy termination and shortening of interestrous intervals. Anti-progestins, (e.g. mifepristone and aglepristone) are synthetic steroids that bind with high affinity to progesterone (P4) receptors, preventing P4 from exerting its biological effects. Anti-progestins have been indicated in P4-dependent conditions, such as pregnancy termination, induction of parturition and the medical treatment of pyometra. Several groups of drugs have been described to have anti-androgenic properties through different mechanisms of action: progestins, receptor binding anti-androgens (e.g. flutamide), competitive enzyme inhibitors (e.g. finasteride), aromatase inhibitors, and GnRH agonists. Their main application is medical treatment of benign prostatic hyperplasia. Long-term release formulations of GnRH agonists (e.g. leuprolide or deslorelin acetate) postponed puberty and reversibly suppressed reproductive function in male and female dogs for periods exceeding 1 year. Anti-estrogens (e.g. clomiphene and tamoxifen citrate) are synthetic non-steroidal type I anti-estrogenic compounds that competitively block estrogen receptors with a combined antagonist-agonistic effect. In dogs, their action is more agonistic than antagonistic. PMID:16542717

  13. Distance exercised during submaximal training on race winnings for Thoroughbred racehorses

    Directory of Open Access Journals (Sweden)

    Carolina Berkman

    2015-07-01

    Full Text Available Evaluations of the physical fitness of Thoroughbred racehorses have been correlated with race earnings, but few reports exist about the influence of the distance exercised during training on both physical conditioning indices and financial productivity. During one training season sixteen claiming Thoroughbred horses were subjected to submaximal training and monitored by a global positioning system (GPS coupled to a heart rate monitor. After initial and single monitoring, the horses were distributed into two groups of eight individuals each; one group exercised short distances (SD between 1600 and 1900m, while the other exercised long distances (LD between 2000 and 2350m. The duration (min and mean and maximal velocities (ms-1attained during each session were determined, as well as the difference in distances exercised (m between official races and each training session. Blood lactate concentration ([LA] during recovery was also determined. Student's t-test was used for a non-paired analysis, with P≤0.05 considered significant. The winnings (USD of each horse were correlated with the peak heart rate (HRpeak attained during the training session. The distances exercised in the training sessions were greater in relation to the official races distances by 24.7% and 40% for SD and LD, respectively. Lactatemia did not differ between the groups. The HRpeak obtained during the training session was lower in LD group. The velocity at which the heart rate reached 200 bpm (V200 was higher in LD group. There was a moderate correlation (r= 0.42 between the highest winnings and lowest HRpeak. The horses that ran longer distances during their submaximal training session had better cardiac conditioning and tendency to increase financial productivity

  14. Preference pulses and the win-stay, fix-and-sample model of choice.

    Science.gov (United States)

    Hachiga, Yosuke; Sakagami, Takayuki; Silberberg, Alan

    2015-11-01

    Two groups of six rats each were trained to respond to two levers for a food reinforcer. One group was trained on concurrent variable-ratio 20 extinction schedules of reinforcement. The second group was trained on a concurrent variable-interval 27-s extinction schedule. In both groups, lever-schedule assignments changed randomly following reinforcement; a light cued the lever providing the next reinforcer. In the next condition, the light cue was removed and reinforcer assignment strictly alternated between levers. The next two conditions redetermined, in order, the first two conditions. Preference pulses, defined as a tendency for relative response rate to decline to the just-reinforced alternative with time since reinforcement, only appeared during the extinction schedule. Although the pulse's functional form was well described by a reinforcer-induction equation, there was a large residual between actual data and a pulse-as-artifact simulation (McLean, Grace, Pitts, & Hughes, 2014) used to discern reinforcer-dependent contributions to pulsing. However, if that simulation was modified to include a win-stay tendency (a propensity to stay on the just-reinforced alternative), the residual was greatly reduced. Additional modifications of the parameter values of the pulse-as-artifact simulation enabled it to accommodate the present results as well as those it originally accommodated. In its revised form, this simulation was used to create a model that describes response runs to the preferred alternative as terminating probabilistically, and runs to the unpreferred alternative as punctate with occasional perseverative response runs. After reinforcement, choices are modeled as returning briefly to the lever location that had been just reinforced. This win-stay propensity is hypothesized as due to reinforcer induction.

  15. Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells.

    Science.gov (United States)

    Sharma, Pawan; Panebra, Alfredo; Pera, Tonio; Tiegs, Brian C; Hershfeld, Alena; Kenyon, Lawrence C; Deshpande, Deepak A

    2016-02-15

    Airway remodeling is a hallmark feature of asthma and chronic obstructive pulmonary disease. Clinical studies and animal models have demonstrated increased airway smooth muscle (ASM) mass, and ASM thickness is correlated with severity of the disease. Current medications control inflammation and reverse airway obstruction effectively but have limited effect on remodeling. Recently we identified the expression of bitter taste receptors (TAS2R) on ASM cells, and activation with known TAS2R agonists resulted in ASM relaxation and bronchodilation. These studies suggest that TAS2R can be used as new therapeutic targets in the treatment of obstructive lung diseases. To further establish their effectiveness, in this study we aimed to determine the effects of TAS2R agonists on ASM growth and promitogenic signaling. Pretreatment of healthy and asthmatic human ASM cells with TAS2R agonists resulted in a dose-dependent inhibition of ASM proliferation. The antimitogenic effect of TAS2R ligands was not dependent on activation of protein kinase A, protein kinase C, or high/intermediate-conductance calcium-activated K(+) channels. Immunoblot analyses revealed that TAS2R agonists inhibit growth factor-activated protein kinase B phosphorylation without affecting the availability of phosphatidylinositol 3,4,5-trisphosphate, suggesting TAS2R agonists block signaling downstream of phosphatidylinositol 3-kinase. Furthermore, the antimitogenic effect of TAS2R agonists involved inhibition of induced transcription factors (activator protein-1, signal transducer and activator of transcription-3, E2 factor, nuclear factor of activated T cells) and inhibition of expression of multiple cell cycle regulatory genes, suggesting a direct inhibition of cell cycle progression. Collectively, these findings establish the antimitogenic effect of TAS2R agonists and identify a novel class of receptors and signaling pathways that can be targeted to reduce or prevent airway remodeling as well as

  16. PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption.

    Science.gov (United States)

    Ferguson, Laura B; Most, Dana; Blednov, Yuri A; Harris, R Adron

    2014-11-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior. PMID:25036611

  17. Metabotropic glutamate receptor agonists modify the pyloric output of the crustacean stomatogastric ganglion.

    Science.gov (United States)

    Pérez-Acevedo, Nivia L; Krenz, Wulf D

    2005-11-16

    We have studied the effects of groups I, II, and III metabotropic glutamate receptor (mGluR) agonists and antagonists on pyloric activity in the stomatogastric ganglion (STG) of the Caribbean spiny lobster Panulirus argus. We have found that agonists for all three groups of mGluRs modify the pyloric output. The group I agonist, l-quisqualic acid (l-QA), activated the pyloric central pattern generator (CPG). When the pyloric rhythm was partially suppressed by sucrose-block of input fibers in the stomatogastric nerve (stn), l-QA accelerated the rhythmic activity. In addition, the number of spike discharges was increased in pyloric motoneurons: pyloric (PY), and lateral pyloric (LP). In completely blocked preparations, a slow pyloric rhythm was initiated by l-QA. Groups II and III agonists exerted an inhibitory effect on pyloric activity. The group II agonist, (2S,1'S,2'S)-2-(Carboxycyclopropyl)glycine (L-CCG-I), decreased both the frequency of the pyloric rhythm and the number of spike discharges in the motoneurons: ventricular dilator (VD), PY, and LP. The effects of L-CCG-I were dose-dependent. The group III agonist, l-(+)-2-Amino-4-phosphonobutyric acid (l-AP4), slightly decreased the frequency of the pyloric rhythm and suppressed spike discharges in the VD neuron. All effects of mGluR agonists were reversible. The effect of l-QA was blocked by the broad spectrum mGluR antagonist (S)-Methyl-4-carboxyphenylglycine (MCPG). The inhibitory effect of L-CCG-I was prevented by MCPG and by the group II/III mGluR antagonist (RS)-alpha-Methyl-4-phosphonophenylglycine (MPPG), and was partially blocked by the group II mGluR antagonist (RS)-1-amino-5-phosphonoindan-1-carboxylic acid (APICA). The inhibitory effect of l-AP4 was blocked by MPPG and partially blocked by APICA. PMID:16256086

  18. Gonadotropin-releasing hormone agonist use in men without a cancer registry diagnosis of prostate cancer

    Directory of Open Access Journals (Sweden)

    Kuo Yong-fang

    2008-07-01

    Full Text Available Abstract Background Use of gonadotropin-releasing hormone (GnRH agonists has become popular for virtually all stages of prostate cancer. We hypothesized that some men receive these agents after only a limited work-up for their cancer. Such cases may be missed by tumor registries, leading to underestimates of the total extent of GnRH agonist use. Methods We used linked Surveillance, Epidemiology and End-Results (SEER-Medicare data from 1993 through 2001 to identify GnRH agonist use in men with either a diagnosis of prostate cancer registered in SEER, or with a diagnosis of prostate cancer based only on Medicare claims (from the 5% control sample of Medicare beneficiaries residing in SEER areas without a registered diagnosis of cancer. The proportion of incident GnRH agonist users without a registry diagnosis of prostate cancer was calculated. Factors associated with lack of a registry diagnosis were examined in multivariable analyses. Results Of incident GnRH agonist users, 8.9% had no diagnosis of prostate cancer registered in SEER. In a multivariable logistic regression model, lack of a registry diagnosis of prostate cancer in GnRH agonist users was significantly more likely with increasing comorbidity, whereas it was less likely in men who had undergone either inpatient admission or procedures such as radical prostatectomy, prostate biopsy, or transurethral resection of the prostate. Conclusion Reliance solely on tumor registry data may underestimate the rate of GnRH agonist use in men with prostate cancer.

  19. Ascorbic acid enables reversible dopamine receptor /sup 3/H-agonist binding

    Energy Technology Data Exchange (ETDEWEB)

    Leff, S.; Sibley, D.R.; Hamblin, M.; Creese, I.

    1981-11-16

    The effects of ascorbic acid on dopaminergic /sup 3/H-agonist receptor binding were studied in membrane homogenates of bovine anterior pituitary and caudate, and rat striatum. In all tissues virtually no stereospecific binding (defined using 1uM (+)butaclamol) of the /sup 3/H-agonists N-propylnorapomorphine (NPA), apomorphine, or dopamine could be demonstrated in the absence of ascorbic acid. Although levels of total /sup 3/H-agonist binding were three to five times greater in the absence than in the presence of 0.1% ascorbic acid, the increased binding was entirely non-stereospecific. Greater amounts of dopamine-inhibitable /sup 3/H-NPA binding could be demonstrated in the absence of 0.1% ascorbic acid, but this measure of ''specific binding'' was demonstrated not to represent dopamine receptor binding since several other catecholamines and catechol were equipotent with dopamine and more potent than the dopamine agonist (+/-)amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) in inhibiting this binding. High levels of dopamine-displaceable /sup 3/H-agonist binding were detected in fresh and boiled homogenates of cerebellum, an area of brain which receives no dopaminergic innervation, further demonstrating the non-specific nature of /sup 3/H-agonist binding in the absence of ascorbic acid. These studies emphasize that under typical assay conditions ascorbic acid is required in order to demonstrate reversible and specific /sup 3/H-agonist binding to dopamine receptors.

  20. Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2013-01-01

    Full Text Available We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105 cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.