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Sample records for agonist win 55212-2

  1. Agmatine and a cannabinoid agonist, WIN 55212-2, interact to produce a hypothermic synergy.

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    Rawls, Scott M; Tallarida, Ronald J; Zisk, Jacob

    2006-12-28

    Agmatine blocks morphine withdrawal symptoms and enhances morphine analgesia in rats. Yet, the role of agmatine in the pharmacological effects of other abused drugs has not been investigated. The present study investigates the effect of agmatine administration on the hypothermic response to cannabinoids. Hypothermia is an effective endpoint because cannabinoid agonists produce a rapid, reproducible, and significant decrease in body temperature that is abolished by cannabinoid CB(1) receptor antagonists. WIN 55212-2, a cannabinoid agonist, was administered to rats by itself and with agmatine. WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.) caused a significant hypothermia. Agmatine (10, 25 and 50 mg/kg, i.p.) was ineffective. For combined administration, agmatine (50 mg/kg, i.p.) enhanced the hypothermic effect of WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.). The enhancement was strongly synergistic, indicated by a 2.7-fold increase in the relative potency of WIN 55212-2. The central administration of agmatine (25 and 50 mug/rat, i.c.v.) significantly increased the hypothermic effect of WIN 55212-2 (2.5 mg/kg, i.m.). This indicates that agmatine acts through a central mechanism to augment cannabinoid-evoked hypothermia. Idazoxan (2 mg/kg, i.p.), an imidazoline antagonist, blocked the enhancement by agmatine, thus suggesting that imidazoline receptor activation is required for agmatine to enhance cannabinoid-evoked hypothermia. The present data reveal that agmatine and a cannabinoid agonist interact to produce a hypothermic synergy in rats. These results show that agmatine acts in the brain and via imidazoline receptors to enhance cannabinoid-evoked hypothermia.

  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. 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.

  4. 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

  5. Inhibition of spontaneous neurotransmission in the nucleus of solitary tract of the rat by the cannabinoid agonist WIN 55212-2 is not via CB1 or CB2 receptors.

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    Accorsi-Mendonça, Daniela; Almado, Carlos E L; Dagostin, André L A; Machado, Benedito H; Leão, Ricardo M

    2008-03-20

    Cannabinoids have been shown to modulate central autonomic regulation and baroreflex control of blood pressure. Both CB1 and CB2 cannabinoid receptors have been described in the nucleus tractus solitarius (NTS), which receives direct afferent projections of cardiovascular reflexes. In the present study we evaluated the effects of WIN 55212-2 (WIN), a cannabinoid agonist, on fast neurotransmission in the NTS. We recorded spontaneous post-synaptic currents using the whole-cell configuration in NTS cells in brainstem slices from young rats (25-30 days old). Application of 5 microM WIN inhibited the frequency of both glutamatergic and GABAergic sPSCs, without affecting their amplitudes. Effects of WIN were not blocked by application of the CB1 antagonist AM251, the CB2 antagonist AM630 or the vanniloid receptor TRPV1 antagonist AMG9810, suggesting that the effect of WIN is via a non-CB1 non-CB2 receptor. Neither the CB1/CB2 agonist HU210 nor the CB1 agonist ACPA affected the frequency of sPSCs. We conclude WIN inhibits the neurotransmission in the NTS of young rats via a receptor distinct from CB1 or CB2.

  6. L-NAME (N omega-nitro-L-arginine methyl ester), a nitric-oxide synthase inhibitor, and WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], a cannabinoid agonist, interact to evoke synergistic hypothermia.

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    Rawls, S M; Tallarida, R J; Gray, A M; Geller, Ellen B; Adler, Martin W

    2004-02-01

    Cannabinoids evoke profound hypothermia in rats by activating central CB(1) receptors. Nitric oxide (NO), a prominent second messenger in central and peripheral neurons, also plays a crucial role in thermoregulation, with previous studies suggesting pyretic and antipyretic functions. Dense nitric-oxide synthase (NOS) staining and CB(1) receptor immunoreactivity have been detected in regions of the hypothalamus that regulate body temperature, suggesting that intimate NO-cannabinoid associations may exist in the central nervous system. The present study investigated the effect of N(omega)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, on the hypothermic response to WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenylcarbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], a selective cannabinoid agonist, in rats. WIN 55212-2 (1-5 mg/kg, i.m.) produced dose-dependent hypothermia that peaked 45 to 90 min post-injection. L-NAME (10-100 mg/kg, i.m.) by itself did not significantly alter body temperature. However, a nonhypothermic dose of L-NAME (50 mg/kg) potentiated the hypothermia caused by WIN 55212-2 (0.5-5 mg/kg). The augmentation was strongly synergistic, indicated by a 2.5-fold increase in the relative potency of WIN 55212-2. The inactive enantiomer of WIN 55212-2, WIN 55212-3 [S-(-)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl) methanone mesylate] (5 mg/kg, i.m.), did not produce hypothermia in the absence or presence of L-NAME (50 mg/kg), confirming that cannabinoid receptors mediated the synergy. The present data are the first evidence that drug combinations of NOS blockers and cannabinoid agonists produce synergistic hypothermia. Thus, NO and cannabinoid systems may interact to induce superadditive hypothermia.

  7. WIN 55212-2 impairs contextual fear conditioning through the activation of CB1 cannabinoid receptors.

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    Pamplona, Fabrício Alano; Takahashi, Reinaldo Naoto

    The memory deficits induced by cannabinoid agonists have been found in several behavioral paradigms. Nevertheless, there is evidence that not all types of memory are impaired after cannabinoid administration. The aim of this study was to investigate whether the cannabinoid agonist WIN 55212-2 (WIN) is able to influence the acquisition of fear conditioning using tone and contextual versions. For tone-fear conditioning, male Wistar rats were placed in the conditioning chamber and after 3 min, a sound (CS) was presented for 10s that terminated with a 1-s electric footshock (1.5 mA). For contextual-fear conditioning, a similar procedure was used but no sound was presented. Twenty-four hours after, the animals were re-exposed to the respective CS (tone or conditioning chamber) and the freezing behavior was registered. A subsequent experiment investigated a possible state-dependent effect of WIN by administering WIN or control solution 30 min before conditioning and before testing. WIN (2.5 and 5.0 mg/kg) administered i.p. 30 min before impaired contextual fear conditioning but did not modify the freezing behavior elicited by tone presentation. These animals did not show any state-dependent effects of WIN. Further, the impaired contextual conditioning was prevented by preadministration of SR141716A (1.0 mg/kg, i.p.) or SR147778 (1.0 mg/kg, i.p.), selective cannabinoid CB1 receptor antagonists. The present findings highlight that cannabinoid agonists effects are selective for the hippocampus-dependent aversive memories in rats. This effect appears to be related to the activation of CB1 cannabinoid receptors and confirms that cannabinoids might provide a novel approach for the treatment of unpleasant memories.

  8. 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.

  9. 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

  10. 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.

  11. Suppression of outward K⁺ currents by WIN55212-2 in rat retinal ganglion cells is independent of CB1/CB2 receptors.

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    Zhang, C-Q; Wu, H-J; Wang, S-Y; Yin, S; Lu, X-J; Miao, Y; Wang, X-H; Yang, X-L; Wang, Z

    2013-12-03

    Cannabinoid CB1 receptor (CB1R) signaling system is extensively distributed in the vertebrate retina. Activation of CB1Rs regulates a variety of functions of retinal neurons through modulating different ion channels. In the present work we studied effects of this receptor signaling on K(+) channels in retinal ganglion cells by patch-clamp techniques. The CB1R agonist WIN55212-2 (WIN) suppressed outward K(+) currents in acutely isolated rat retinal ganglion cells in a dose-dependent manner, with an IC50 of 4.7 μM. We further showed that WIN mainly suppressed the tetraethylammonium (TEA)-sensitive K(+) current component. While CB1Rs were expressed in rat retinal ganglion cells, the WIN effect on K(+) currents was not blocked by either AM251/SR141716, specific CB1R antagonists, or AM630, a selective CB2R antagonist. Consistently, cAMP-protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways were unlikely involved in the WIN-induced suppression of the K(+) currents because both PKA inhibitors H-89/Rp-cAMP and MAPK/ERK1/2 inhibitor U0126 failed to block the WIN effects. WIN-induced suppression of the K(+) currents was not observed when WIN was intracellularly applied. Furthermore, an endogenous ligand of the cannabinoid receptor anandamide, the specific CB1R agonist ACEA and the selective CB2R agonist CB65 also suppressed the K(+) currents, and the effects were not blocked by AM251/SR141716 or AM630 respectively. All these results suggest that the WIN-induced suppression of the outward K(+) currents in rat retinal ganglion cells, thereby regulating the cell excitability, were not through CB1R/CB2R signaling pathways.

  12. Protective Effect of WIN55212-2 on Ischemia-Reperfusion Injury in Isolated Rat Hearts%大麻素受体激动剂WIN55212-2对体外大鼠心肌缺血再灌注损伤的保护作用

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    阮灿军; 胡本容; 汤强; 付琴; 胡芬; 李亦武; 向继洲

    2006-01-01

    目的 探讨大麻素受体激动剂WIN55212-2对体外大鼠心肌缺血再灌注损伤的保护作用.方法 在Langendorff灌流的体外大鼠心脏上,低流速 (0.5~0.6 ml/min)灌注以制备全心缺血模型.低流速灌注(缺血)210 min后,开始以正常流速复灌60 min.WIN55212-2组于低流速灌注前15 min持续给予WIN55212-2直至缺血末.WIN55212-2+AM251和WIN55212-2+AM630组分别在低流速灌注前30 min给予AM251、AM630,作用15 min后,再分别给予WIN55212-2直至缺血末.观察复灌后左心室发展压(LVDP)、左心室最大上升、下降速率(±dp/dtmax).同时,测定复灌末冠脉流出液中乳酸脱氢酶(LDH)和肌酸激酶(CK)释放量.结果 WIN55212-2能显著地恢复缺血再灌注后的心功能,使缺血再灌注末期冠脉流出液中LDH和CK的释放量显著降低.这些作用能被CB1受体阻断剂AM251或CB2受体阻断剂AM630阻断.结论 WIN55212-2对体外大鼠心肌缺血再灌注损伤有保护作用,该作用是通过CB1受体和CB2受体介导的.

  13. 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.

  14. 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.

  15. 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.

  16. (+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters.

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    Richter, A; Löscher, W

    1994-11-03

    The effects of the novel high affinity cannabinoid receptor agonist (+)-WIN 55,212-2 ((R)-4,5-dihydro-2-methyl-4(4-morphoinylmethyl)-1-(1-naphthalen ylcarbonyl)-6H-pyrrolo[3,2,1-ij]quinolin-6-one) on severity of dystonia were investigated in mutant Syrian hamsters with primary generalized dystonia. Following injections of (+)-WIN 55,212-2 (1.0-5.0 mg/kg i.p.) a dose-dependent reduction of the severity of dystonia was observed. At antidystonic doses (2.5 and 5.0 mg/kg i.p.) (+)-WIN 55,212-2 caused a reduction of spontaneous motor activity and catalepsy. 1 mg/kg of (+)-WIN 55,212-2 exhibited neither antidystonic effects nor any side effects. However, the coadministration of 1.0 mg/kg (+)-WIN 55,212-2 with an ineffective dose of diazepam (0.1 mg/kg i.p.) exerted antidystonic effects in the absence of severe side effects. Although psychotropic effects of cannabinoids, such as (+)-WIN 55,212-2, limit the therapeutical utility of cannabinoids, the present data indicate that cannabinoids exert antidystonic effects and that low doses of cannabinoids may increase antidystonic efficacy of benzodiazepines.

  17. BIASED AGONISM OF THREE DIFFERENT CANNABINOID RECEPTOR AGONISTS IN MOUSE BRAIN CORTEX

    Directory of Open Access Journals (Sweden)

    Rebeca Diez-Alarcia

    2016-11-01

    Full Text Available Cannabinoid receptors are able to couple to different families of G-proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, THC, WIN55212-2 and ACEA in mouse brain cortex.Stimulation of the [35S]GTPS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13, in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 µM was determined by Scintillation Proximity Assay (SPA technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs.

  18. Biased Agonism of Three Different Cannabinoid Receptor Agonists in Mouse Brain Cortex

    Science.gov (United States)

    Diez-Alarcia, Rebeca; Ibarra-Lecue, Inés; Lopez-Cardona, Ángela P.; Meana, Javier; Gutierrez-Adán, Alfonso; Callado, Luis F.; Agirregoitia, Ekaitz; Urigüen, Leyre

    2016-01-01

    Cannabinoid receptors are able to couple to different families of G proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, Δ9-THC, WIN55212-2, and ACEA in mouse brain cortex. Stimulation of the [35S]GTPγS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13), in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 μM) was determined by scintillation proximity assay (SPA) technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs. PMID:27867358

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

    Science.gov (United States)

    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.

  20. Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner.

    Science.gov (United States)

    Blume, Lawrence C; Leone-Kabler, Sandra; Luessen, Deborah J; Marrs, Glen S; Lyons, Erica; Bass, Caroline E; Chen, Rong; Selley, Dana E; Howlett, Allyn C

    2016-11-01

    Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1 R) distal C-terminus-associated protein that modulates CB1 R signaling via G proteins, and CB1 R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1 R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB1 Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1 R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1 R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1 R by a dynamin- and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1 R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30-120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB1 Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)-mediated increase in cell surface CB1 Rs, which is postulated to be as a result of rimonabant effects on 'non-agonist-driven' internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1 R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface.

  1. Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors

    Science.gov (United States)

    Maya-López, Marisol; Colín-González, Ana Laura; Aguilera, Gabriela; de Lima, María Eduarda; Colpo-Ceolin, Ana; Rangel-López, Edgar; Villeda-Hernández, Juana; Rembao-Bojórquez, Daniel; Túnez, Isaac; Luna-López, Armando; Lazzarini-Lechuga, Roberto; González-Puertos, Viridiana Yazmín; Posadas-Rodríguez, Pedro; Silva-Palacios, Alejandro; Königsberg, Mina; Santamaría, Abel

    2017-01-01

    The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington’s disease patients. Herein, the effects of WIN55,212-2 were tested on different endpoints of the 3-NP-induced toxicity in rat brain synaptosomes and striatal tissue. Motor activity was also evaluated. The 3-NP (1 mM)-induced mitochondrial dysfunction and lipid peroxidation was attenuated by WIN55,212-2 (1 µM) in synaptosomal fractions. The intrastriatal bilateral injection of 3-NP (500 nmol/µL) to rats increased lipid peroxidation and locomotor activity, augmented the rate of cell damage, and decreased the striatal density of neuronal cells. These alterations were accompanied by transcriptional changes in the NMDA (NR1 subunit) content. The administration of WIN55212-2 (1 mg/kg, i.p.) to rats for six consecutive days, before the 3-NP injection, exerted preventive effects on all alterations elicited by the toxin. The prevention of the 3-NP-induced NR1 transcriptional alterations by the CBr agonist together with the increase of CB1 content suggest an early reduction of the excitotoxic process via CBr activation. Our results demonstrate a protective role of WIN55,212-2 on the 3-NP-induced striatal neurotoxicity that could be partially related to the ECS stimulation and induction of NMDAr hypofunction, representing an effective therapeutic strategy at the experimental level for further studies.

  2. WIN55,212-2, a Cannabinoid Receptor Agonist, Protects Against Nigrostriatal Cell Loss in the MPTP Mouse Model of Parkinson’s Disease

    OpenAIRE

    Price, David A.; Martinez, Alex A; Seillier, Alexandre; Koek, Wouter; Acosta, Yolanda; Fernandez, Elizabeth; Strong, John R.; Lutz, Beat; Marsicano, Giovanni; Roberts, James L.; Giuffrida, Andrea

    2009-01-01

    Parkinson’s disease (PD) is characterized by the progressive loss of nigrostriatal dopamine (DA) neurons leading to motor disturbances and cognitive impairment. Current pharmacotherapies relieve PD symptoms temporarily but fail to prevent or slow down the disease progression. In this study, we investigated the molecular mechanisms by which the non-selective cannabinoid receptor agonist WIN55,212-2 (WIN) protects mouse nigrostriatal neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MP...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro.

    Science.gov (United States)

    Luca, Tonia; Di Benedetto, Giulia; Scuderi, Mariagrazia Rita; Palumbo, Marco; Clementi, Silvia; Bernardini, Renato; Cantarella, Giuseppina

    2009-08-15

    Kaposi's sarcoma is a highly vascularized mesenchymal neoplasm arising with multiple lesions of the skin. Endogenous cannabinoids have been shown to inhibit proliferation of a wide spectrum of tumor cells. We studied the effects of cannabinoids on human Kaposi's sarcoma cell proliferation in vitro. To do so, we first investigated the presence of the cannabinoid receptors CB(1) and CB(2) mRNAs in the human Kaposi's sarcoma cell line KS-IMM by RT-PCR and, subsequently, the effects of the mixed CB(1)/CB(2) agonist WIN-55,212-2 (WIN) on cell proliferation in vitro. WIN showed antimitogenic effects on Kaposi's sarcoma cells. Western blot analysis of Kaposi's sarcoma lysates suggested that WIN treatment induced activation of both caspase-3 and -6, as well as increased phosphorylation of the stress kinase p38 and JNK, along with transient phosphorylation of ERK(1/2). To better characterize the involvement of each single CB receptor in cannabinoid-induced cell death, we incubated Kaposi's sarcoma cells with different selective cannabinoid receptor agonists, respectively ACEA (CB(1)) and JWH-133 (CB(2)). None of the agonists was able to induce KS-IMM cell apoptosis. Moreover, we co-incubated Kaposi's sarcoma cells with WIN-55,212-2 and either the CB(1) receptor antagonist AM251, the CB(2) receptor antagonist AM630, or a combination of both substances. The CB(2) receptor antagonist AM630 was able to significantly increase survival of Kaposi's sarcoma cells treated with WIN. In view of the antiproliferative effects of cannabinoids on KS-IMM cells, one could envision the cannabinoid system as a potential target for pharmacological treatment of Kaposi's sarcoma.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Influence of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist (WIN 55,212-2) and inverse agonist (AM 251) on the regulation of food intake and hypothalamic serotonin levels.

    Science.gov (United States)

    Merroun, Ikram; Errami, Mohammed; Hoddah, Hanaa; Urbano, Gloria; Porres, Jesús M; Aranda, Pilar; Llopis, Juan; López-Jurado, María

    2009-05-01

    The effect of intracerebroventricular or intraperitoneal administration of cannabinoid receptor agonist WIN 55,212-2 or inverse agonist AM 251 on food intake and extracellular levels of serotonin and acetic acid 5-hydroxy-indol from presatiated rats was studied. Compared to the vehicle-injected control, the intracerebroventricular administration of WIN 55,212-2 was associated with a significant increase in food intake, whereas the administration of AM 251 caused a significant reduction in this respect. These results were accompanied by considerable reductions or increases in serotonin and acetic acid 5-hydroxy-indol levels compared to the vehicle-injected control and the baseline values for the different experimental groups studied. Intraperitoneal administration of WIN 55,212-2 at doses of 1 and 2 mg/kg promoted hyperphagia up to 6 h after injection, whereas administration of a higher dose (5 mg/kg) significantly inhibited food intake and motor behaviour in partially satiated rats. Administration of any of the AM 251 doses studied (0.5, 1, 2, 5 mg/kg) led to a significant decrease in the amount of food ingested from 2 h after the injection, compared to the vehicle-injected control group, with the most striking effect being observed when the 5 mg/kg dose was injected.

  7. 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

    Science.gov (United States)

    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

  8. Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK

    Science.gov (United States)

    Feng, Ya-Jing; Li, Yong-Yu; Lin, Xu-Hong; Li, Kun; Cao, Ming-Hua

    2016-01-01

    AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals’ water supply with 4% dextran sulfate sodium (DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and the myeloperoxidase (MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase (p38MAPK) and its phosphorylated form (p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580 (SB), an inhibitor of p38, was investigated in parallel experiments, and the data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38

  9. Effects of the CB1R agonist WIN-55,212-2 and the CB1R antagonists SR-141716 and AM-1387: open-field examination in rats.

    Science.gov (United States)

    Järbe, T U C; Ross, T; DiPatrizio, N V; Pandarinathan, L; Makriyannis, A

    2006-09-01

    This study examined the open-field (O-F) effects in rats of the cannabinoid 1 receptor (CB1R) agonist WIN-55,212-2 (WIN; 1 to 5.6 mg/kg) and its interaction with the CB1R antagonist/inverse agonist SR-141716 (1 to 5.6 mg/kg). Additionally, separate studies examined the O-F effects of SR-141716 (1 to 10 mg/kg) and a newly synthesized CB1R selective antagonist/inverse agonist AM-1387 (3 and 10 mg/kg) when these ligands were administered alone. Both antagonists are characterized in vitro by decreased of GTPgammaS binding and increased cAMP accumulation (inverse agonism). WIN dose dependently reduced ambulation (horizontal activity) and rearing (vertical activity); SR-141716 completely (WIN 3 mg/kg) or partially (WIN 5.6 mg/kg) normalized these behaviors. WIN alone resulted in circling and in an increased latency to leave the start area of the O-F, effects blocked by all doses of SR-141716. Both the increased scratching and grooming, associated with SR-141716 administration, were attenuated but not abolished by WIN. SR-141716 alone tended to reduce ambulation (significant at 10 mg/kg) and rearing (non-significant), had no effect on latency, and increased scratching and grooming (both frequency and duration), at doses of 3 mg/kg and up. At the doses examined, AM-1387 had no effect on ambulation, rearing, latency but significantly increased scratching (10 mg/kg); there was also a trend for increased grooming (both frequency and duration). The O-F profile of WIN suggests more similarity with the effects of THC rather than methanandamide (and presumably also anandamide). Intrinsic activity (scratching and grooming) by SR-141716 was re-affirmed and seemed to be associated with administration of AM-1387 as well. AM-1387 was less potent than SR-141716.

  10. Mitigation win-win

    Science.gov (United States)

    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.

  11. Effects of WIN 55,212-2 (a synthetic cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.

    Science.gov (United States)

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Zagaja, Mirosław; Andres-Mach, Marta; Kondrat-Wrobel, Maria W; Luszczki, Jarogniew J

    2015-03-01

    The purpose of this study was to determine the influence of WIN 55,212-2 mesylate (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various second- and third-generation antiepileptic drugs (i.e., gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin and tiagabine) in the mouse 6 Hz-induced psychomotor seizure model. Psychomotor seizures were evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes. Additionally, total brain antiepileptic drug concentrations were measured. Results indicate that WIN (5 mg/kg, administered i.p.) significantly potentiated the anticonvulsant action of gabapentin (P < 0.05) and levetiracetam (P < 0.01), but not that of lacosamide, oxcarbazepine, pregabalin or tiagabine in the mouse psychomotor seizure model. Moreover, WIN (2.5 mg/kg) had no significant effect on the anticonvulsant activity of all tested antiepileptic drugs in the 6 Hz test in mice. Measurement of total brain antiepileptic drug concentrations revealed that WIN (5 mg/kg) had no impact on gabapentin or levetiracetam total brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse 6Hz model. In conclusion, WIN in combination with gabapentin and levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in the mouse psychomotor seizure model.

  12. CB1 Cannabinoid Agonist (WIN55,212-2) Within the Basolateral Amygdala Induced Sensitization to Morphine and Increased the Level of μ-Opioid Receptor and c-fos in the Nucleus Accumbens.

    Science.gov (United States)

    Molaei, Marzieh; Fatahi, Zahra; Zaringhalam, Jalal; Haghparast, Abbas

    2016-04-01

    The basolateral amygdala (BLA) is rich of CB1 cannabinoid receptors (CB1R) and has reciprocal connections with the nucleus accumbens (NAc) which is involved in opioid sensitization. In this study, effects of intra-BLA administration of CB1R agonist on sensitization to antinociceptive effect of morphine and changes in the levels of μ-opioid receptor (MOR), p-CREB, and c-fos in the NAc were investigated. Animals received intra-BLA microinjection of CB1R agonist (WIN55,212-2) once daily for 3 days consecutively (sensitization period). After 5 days free of drug, tail-flick test was performed before and after the administration of an ineffective dose of morphine. Afterward, the levels of MOR, p-CREB, and c-fos proteins were measured in the NAc by Western blot analysis. The results indicated that intra-BLA injection of WIN55,212-2 during sensitization period resulted in the induction of antinociceptive responses by ineffective dose of morphine and caused a significant increase in the MOR and c-fos levels but not p-CREB/CREB ratio in the NAc. These finding revealed that CB1 receptor agonist in the BLA induces development of morphine sensitization and increases expression of MOR in the NAc. It seems that c-fos is one of the important factors involved in the induction of sensitization to antinociceptive effect of morphine.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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。

  18. 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.)…

  19. 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…

  20. 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.

  1. 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).

  2. Differential Effects of Cannabinoid Receptor Agonist on Social Discrimination and Contextual Fear in Amygdala and Hippocampus

    Science.gov (United States)

    Segev, Amir; Akirav, Irit

    2011-01-01

    We examined whether the cannabinoid receptor agonist WIN55,212-2 (WIN; 5 [mu]g/side) microinjected into the hippocampus or the amygdala would differentially affect memory processes in a neutral vs. an aversive task. In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval.…

  3. Nonlinear isobologram and superadditive withdrawal from cocaine: cannabinoid combinations in planarians.

    Science.gov (United States)

    Raffa, Robert B; Stagliano, Gregory W; Tallarida, Ronald J

    2007-02-05

    Elucidation of interactions between drugs used in polydrug abuse is especially important. However, the necessary experimental conditions for precise quantitative analysis are difficult to establish. Because withdrawal effects of cocaine and the cannabinoid receptor agonist WIN 55212-2 are easily quantified in planarians, demonstration of synergistic effects (P<0.01) of certain ratios of this combination was possible. This synergy, here analyzed with the latest (nonlinear) isobolographic methodology, is now quantitatively established for the first time.

  4. Nonlinear isobologram and superadditive withdrawal from cocaine:cannabinoid combinations in planarians

    OpenAIRE

    Raffa, Robert B.; Stagliano, Gregory W.; Tallarida, Ronald J.

    2006-01-01

    Elucidation of interactions between drugs used in polydrug abuse is especially important. However, the necessary experimental conditions for precise quantitative analysis are difficult to establish. Because withdrawal effects of cocaine and the cannabinoid receptor agonist WIN 55212-2 are easily quantified in planarians, demonstration of synergistic effects (P < 0.01) of certain ratios of this combination was possible. This synergy, here analyzed with the latest (nonlinear) isobolographic met...

  5. Prenatal exposure to the CB1 and CB2 cannabinoid receptor agonist WIN 55,212-2 alters migration of early-born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex.

    Science.gov (United States)

    Saez, Trinidad M M; Aronne, María P; Caltana, Laura; Brusco, Alicia H

    2014-05-01

    The endocannabinoid system, composed of cannabinoid receptors, endocannabinoids, and synthesis and degradation enzymes, is present since early stages of brain development. During this period, the endocannabinoid system is involved in the regulation of neural progenitor proliferation and specification as well as the migration and differentiation of pyramidal neurons and interneurons. Marijuana consumption during pregnancy represents a serious risk in relation to the fetal brain development since Δ(9) -tetrahidrocannabinol, the main active compound of cannabis, can reach the fetus through placenta and hemato-encephalic barrier. Cohort studies performed on children and adolescents of mothers who consumed marijuana during pregnancy reported cognitive and comportamental abnormalities. In the present study, we examined the expression of the cannabinoid receptor CB1 R during corticogenesis in radially and tangentially migrating post-mitotic neurons. We found that prenatal exposure to WIN impaired tangential and radial migration of post-mitotic neurons in the dorsal pallium. In addition, we described alterations of two transcription factors associated with proliferating and newly post-mitotic glutamatergic cells in the dorsal pallium, Tbr1 and Tbr2, and disruption in the number of Cajal-Retzius cells. The present results contribute to the knowledge of neurobiological substrates that determine neuro-comportamental changes that will persist through post-natal life.

  6. 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.

  7. 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 (Peffects 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.

  8. The Importance of Teaching a Win-Win Philosophy.

    Science.gov (United States)

    Brainard, Alan J.

    Most people are raised in a traditional environment which teaches that someone-winning implies that someone-loses. However, psychology and the examples provided in the Watergate scandal demonstrate that such a philosophy is neither productive nor beneficial. A "win-win" philosophy of cooperation, not competition, is needed for…

  9. 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.

  10. 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.

  11. 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...

  12. Vestas- Will To Win

    OpenAIRE

    2015-01-01

    Abstract In 2005 the new CEO of Vestas, Ditlev Engel introduces the corporate strategy Will to Win and with that Vestas experiences a streamlining of the organization. The internal environment is optimized and a focus towards reduction of variable costs through implementation of performance systems and reassignments of the company’s production plant is made. The overall financial position of the company is improved by the new incentives and by end 2008 Vestas has mamaged to reach a EBIT-ma...

  13. 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.

  14. 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…

  15. 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...

  16. 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

  17. 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

  18. 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

  19. 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)

  20. Winning the interviewing game.

    Science.gov (United States)

    Lyons, M F

    2000-01-01

    Those who don't "interview well" are not likely to receive the job offer, despite their qualifications. A job interview is actually a fierce competitive activity that offers only two grades: an A or F. By nature, physicians are competitive; they like to win. Infrequent interviewees are prone to making easily corrected mistakes, such as showing no enthusiasm or having poor eye contact. The key for interviewing success is preparation--doing research, developing a personal statement, and role-playing practice interviews. View the interview as a sales call whose bottom-line goal is to achieve an offer, or at least to let you leave with the option to return for future discussions.

  1. Wins, winning and winners: the commercial advertising of lottery gambling.

    Science.gov (United States)

    McMullan, John L; Miller, Delthia

    2009-09-01

    This study analyzed a sample of 920 lottery ads that were placed or played in Atlantic Canada from January 2005 to December 2006. A content analysis, involving quantitative and qualitative techniques, was conducted to examine the design features, exposure profiles and focal messages of these ads and to explore the connections between lottery advertising and consumer culture. We found that there was an "ethos of winning" in these commercials that provided the embedded words, signs, myths, and symbols surrounding lottery gambling and conveyed a powerful imagery of plentitude and certitude in a world of potential loss where there was little reference to the actual odds of winning. The tangible and emotional qualities in the ads were especially inviting to young people creating a positive orientation to wins, winning and winners, and lottery products that, in turn, reinforced this form of gambling as part of youthful consumption practices. We concluded that enticing people with the prospects of huge jackpots, attractive consumer goods and easy wins, showcasing top prize winners, and providing dubious depictions that winning is life-changing was narrow and misleading and exploited some of the factors associated with at-risk gambling.

  2. 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.

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

    OpenAIRE

    SUN, JING; Fang, Yin-quan; Ren, Hong; Tao CHEN; Guo, Jing-Jing; Yan, Jun; SONG, SHU; Zhang, Lu-yong; Liao, Hong

    2012-01-01

    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 e...

  4. 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.

  5. 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.

  6. 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

  7. GLP-1 Receptor Agonists

    Science.gov (United States)

    ... in Balance › GLP-1 Receptor Agonists Fact Sheet GLP-1 Receptor Agonists May, 2012 Download PDFs English Espanol Editors Silvio ... are too high or too low. What are GLP-1 receptor agonist medicines? GLP-1 receptor agonist medicines, also called ...

  8. 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

  9. 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...

  10. A Photo Contest: Everybody Wins!

    Science.gov (United States)

    Carroll, Cathryn

    1996-01-01

    Profiles the winners of a national photography contest for students who are deaf and includes the prize-winning photographs. Information is provided on how to sponsor a photography contest, including choosing the theme, size range, contestants, and timelines for exhibition. Ways to have the photos judged and exhibited are also addressed. (CR)

  11. 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.)

  12. 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.

  13. 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.

  14. 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)...

  15. 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.

  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...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  17. 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…

  18. 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 ...

  19. 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.

  20. Pretreatment with clonidine caused desensitization to WIN 55,212-2 in guinea pig ileum.

    Science.gov (United States)

    Rezania, F; Mohaghegh Shalmani, L; Rahimian, R; Dehpour, A R; Ejtemaei Mehr, S

    2014-01-01

    Considering the existence of cross-tolerance between clonidine and morphine besides the same interaction between morphine and WIN 55,212-2 persuaded us to verify this fact between WIN 55,212-2 and clonidine in guinea pig ileum, which is a well-known model to examine the mode of action of cannabinoids and α2 -adenoceptor agonists The rectangular pulses were passed to the 0.5 g stretched ileum segments that were fixed in 20-ml organ bath. PowerLab system and Graphpad Prism were applied to record twitches and analyse the data. Electrically evoked contractions were dose-dependently inhibited by WIN 55,212-2 and clonidine (pD2 = 8.56 ± 0.41 and 7.65 ± 0.15, respectively). Tolerance to this effect could be induced by 4-h incubation with WIN 55,212-2 (3 × IC50 ) (pD2  = 6.36 ± 0.26, degree of tolerance: 159.32) (P systems interaction in the enteric nervous system as a simplified representative for central nervous system.

  1. 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.

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

    NARCIS (Netherlands)

    Sysoeva, M.V.; Kuznetsova, G.D.; Rijn, C.M. van; Sysoev, I.V.

    2016-01-01

    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 studie

  3. 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…

  4. 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

  5. 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.

  6. Payments for ecosystem services and the fatal attraction of win-win solutions

    NARCIS (Netherlands)

    Muradian Sarache, R.P.; Arsel, M.; Pellegrini, L.; Adaman, F.; Aguilar, B.; Agarwal, B.; Corbera, E.; Ezzine de Blas, D.; Farley, J.; Froger, G.; Garcia-Frapolli, E.; Gómez-Baggethun, E.; Gowdy, J.; Kosoy, N.; Le Coq, J.F.; Leroy, P.; May, P.H.; Méral, P.; Mibielli, P.; Norgaard, R.; Ozkaynak, B.; Pascual, U.; Pengue, W.; Perez, M.; Pesche, D.; Pirard, R.; Ramos-Martin, J.; Rival, L.; Saenz-Segura, F.; Hecken, G. van; Vatn, A.; Vira, B.; Urama, K.

    2013-01-01

    In this commentary we critically discuss the suitability of payments for ecosystem services and the most important challenges they face. While such instruments can play a role in improving environmental governance, we argue that over-reliance on payments as win-win solutions might lead to ineffectiv

  7. Toward Win-win Cooperation Through Amity, Sincerity, Mutual Benefit and Inclusiveness

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    We will work with other members of the international community to boost green development, advocate low-carbon way of life, emphasize sharing of energy-saving and environmental protection technologies, and foster a global climate governance system that is fair, reasonable, and focused on win-win cooperation.

  8. [Melatonin receptor agonist].

    Science.gov (United States)

    Uchiyama, Makoto

    2015-06-01

    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  9. Winning Vaidman's game without unspeakable information

    CERN Document Server

    Cabello, A

    2003-01-01

    Vaidman described how a team of three players, each of them isolated in a remote booth, could use a three-qubit Greenberger-Horne-Zeilinger state to always win a game which would be impossible to always win without quantum resources. However, Vaidman's method requires all three players to share a common reference frame; it does not work if the adversary is allowed to disorientate one player. Here we show how to always win the game, even if the players do not share any reference frame. The introduced method uses a 12-qubit state which is invariant under any transformation $R_a \\otimes R_b \\otimes R_c$ (where $R_a = U_a \\otimes U_a \\otimes U_a \\otimes U_a$, where $U_j$ is a unitary operation on a single qubit) and requires only single-qubit measurements. A number of further applications of this 12-qubit state are described.

  10. 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.

  11. PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

    NARCIS (Netherlands)

    HOYER, D; BODDEKE, HWGM

    1993-01-01

    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or antagonist

  12. Stellar students win fantastic prizes

    Science.gov (United States)

    2008-05-01

    School students and teachers across Europe and around the world are discovering today who has won fantastic prizes in "Catch a Star", the international astronomical competition run by ESO and the European Association for Astronomy Education (EAAE). CAS2008 artwork ESO PR Photo 14/08 One of the winning artworks "We were extremely impressed by the high quality of the entries, and the number of participants was even higher than last year. We wish to congratulate everybody who took part," said Douglas Pierce-Price, Education Officer at ESO. "'Catch a Star' clearly shows astronomy's power to inspire and excite students of all ages," added Fernand Wagner, President of the EAAE. The top prize, of a week-long trip to Chile to visit the ESO Very Large Telescope (VLT) on Paranal, was won by students Roeland Heerema, Liesbeth Schenkels, and Gerben Van Ranst from the Instituut Spijker in Hoogstraten, Belgium, together with their teacher Ann Verstralen. With their "story of aged binary stars... Live and Let Die", they take us on a vivid tour of the amazing zoo of binary stars, and the life and death of stars like our Sun. The students show how state-of-the-art telescopes, particularly those at ESO's sites of La Silla and Paranal, help us understand these stars. They take as an illustrative example the binary star system V390 Velorum. In the last phases of its life, V390 Velorum will shed its outer shell of gas and dust, turning from a celestial chrysalis into a beautiful cosmic butterfly. The students also involved other pupils from their school, showing them how to test their eyesight by observing the binary star system of Alcor and Mizar. But perhaps the most important discovery they made is that, as they write in their report, "Astronomy lives! Discoveries are being made each day and there is still very much to be found and learned by astronomers!" The team will travel to Chile and visit the ESO VLT - the world's most advanced optical/infrared telescope. At Paranal, they

  13. 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.

  14. 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!

  15. Strategy changes in subsequent fights as consequences of winning and losing in fruit fly fights.

    Science.gov (United States)

    Trannoy, Séverine; Kravitz, Edward A

    2016-11-11

    In competition for food, territory and mates, male fruit flies (Drosophila melanogaster) engage in agonistic encounters with conspecifics. The fighting strategies used to obtain these resources are influenced by previous and present experience, environmental cues, and the internal state of the animal including hormonal and genetic influences. Animals that experience prior defeats show submissive behavior and are more likely to lose 2(nd) contests, while animals that win 1(st) fights are more aggressive and have a higher probability of winning 2(nd) contests. In a recent report, we examined these loser and winner effects in greater detail and demonstrated that both winners and losers show short-term memory of the results of previous bouts while only losers demonstrate a longer-term memory that requires protein synthesis. The recent findings also suggested that an individual recognition mechanism likely exists that can serve important roles in evaluating the fighting ability of opponents and influencing future fighting strategy. In this article, we follow up on these results by asking how previous defeated and victorious flies change their fighting strategies in the presence of 2(nd) losing and winning flies, by searching for evidence of territory marking, and discussing the existing literature in light of our findings.

  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. Involvement of dorsal hippocampal and medial septal nicotinic receptors in cross state-dependent memory between WIN55, 212-2 and nicotine or ethanol in mice.

    Science.gov (United States)

    Alijanpour, S; Rezayof, A

    2013-08-15

    The present study examined whether nicotinic acetylcholine receptors (nAChRs) of the CA1 regions of the dorsal hippocampus and medial septum (MS) are involved in cross state-dependent memory retrieval between WIN55, 212-2 (WIN, a non-selective CB1/CB2 receptor agonist) and nicotine or ethanol. Memory retrieval was measured in one-trial step-down type passive avoidance apparatus in male adult mice. Pre-training intraperitoneal administration of WIN (0.1-1mg/kg) dose-dependently impaired memory retrieval when it was tested 24h later. Pre-test systemic administration of nicotine (0.6 and 0.7mg/kg, s.c.) or ethanol (0.5g/kg, i.p.) improved WIN-induced memory impairment, suggesting a cross state-dependent memory retrieval between the drugs. Pre-test intra-CA1 microinjection of nicotine (1 and 2μg/mouse) before systemic administration of an ineffective dose of nicotine (0.5mg/kg, s.c.) or ethanol (0.25g/kg) significantly reversed WIN-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (1 and 3μg/mouse) inhibited cross state-dependent memory between WIN and nicotine or ethanol. Moreover, pre-test intra-MS microinjection of nicotine (1 and 2μg/mouse) in combination with systemic administration of a lower dose of nicotine (0.5mg/kg), but not ethanol (0.25g/kg), improved memory impairment induced by pre-training administration of WIN. On the other hand, in the animals that received pre-training WIN and pre-test systemic administration of nicotine (0.7mg/kg), but not ethanol (0.5g/kg), pre-test intra-MS microinjection of mecamylamine (1-5μg/mouse) inhibited WIN-nicotine state-dependent memory retrieval. It should be noted that pre-test intra-CA1 or intra-MS microinjection of nicotine or mecamylamine by itself had no effect on memory retrieval and also could not reverse memory impairment induced by pre-training administration of WIN. It can be concluded that WIN and nicotine or WIN and ethanol can induce state-dependent memory retrieval. In

  18. 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.

  19. Addressing disruptive behaviors in the organizational setting: the win-win approach.

    Science.gov (United States)

    Rosenstein, Alan H

    2013-01-01

    Disruptive behaviors can have a significant impact on organizational dynamics and work relationships and a profound negative effect on staff and patient satisfaction, performance efficiency, and patient outcomes. Despite the growing call for action, many organizations still have difficulty in addressing these issues in a consistent, effective manner. Presented below is a model that focuses on causes and barriers and offers solutions designed to promote a "What's in it for me?" win-win approach for improving morale, job satisfaction, and patient care.

  20. Enhancing the Level of Opening up to Achieve Mutual Benefit and Win-win Results

    Institute of Scientific and Technical Information of China (English)

    Chen Feixiang

    2015-01-01

    From upholding opening up strategy of mutual benefit and win-win results to developing top-level design of higher level open economy,then further to putting forward targets of actively participating in global economic governance and supplying public products and enhancing voice in institutional building,and still further to opening the developing concepts and planning,the CPC Central Committee has commanded the deep insights for

  1. 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

  2. Melatonin agonists and insomnia.

    Science.gov (United States)

    Ferguson, Sally A; Rajaratnam, Shantha M W; Dawson, Drew

    2010-02-01

    The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here - ramelteon, tasimelteon and agomelatine - all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the agonists requires a good understanding of their phase-dependent properties. Long-term effects of melatonin should be evaluated in large-scale, independent randomized controlled trials.

  3. 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.

  4. Win-Win-Win: Reflections from a Work-Integrated Learning Project in a Non-Profit Organization

    Directory of Open Access Journals (Sweden)

    Dale C MacKrell

    2016-05-01

    Full Text Available This paper reports on the educational aspects of an information systems work-integrated learning (WIL capstone project for an organization which operates to alleviate homelessness in the Australian non-profit sector. The methodology adopted for the study is Action Design Research (ADR which draws on action research and design research as a means for framing a project's progress. Reflective insights by the project stakeholders, namely, students, academics, and the non-profit client, reveal a curriculum at work through internal features of the organization; personal features of the participants and features of the external environment. Preliminary findings suggest that students in a WIL project for a non-profit are highly engaged, especially when they become aware of the project’s social value. As well, the improvement of professional skills and emotional intelligence by students is more likely in real-life practice settings than in other less authentic WIL activities, equipping graduates for the workforce with both strong disciplinary and generic skills. Win-win-win synergies through project collaboration represent worthwhile outcomes to education, industry and research.

  5. Pharmacogenetics of β2-Agonists

    OpenAIRE

    Nobuyuki Hizawa

    2011-01-01

    Short-acting β2-agonists (SABAs) and long-acting β2-agonists (LABAs) are both important for treatment of asthma and chronic obstructive pulmonary disease (COPD) because of their bronchodilator and bronchoprotective effects. However, the use of these agonists, at least for asthma, has generated some controversy because of their association with increased mortality. Pharmacogenetics is the study of genetically determined variation in response to medications, which might prove useful for target ...

  6. 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.

  7. 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...

  8. 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

  9. Near wins prolong gambling on a video lottery terminal.

    Science.gov (United States)

    Côté, Denis; Caron, Anne; Aubert, Jonathan; Desrochers, Véronique; Ladouceur, Robert

    2003-01-01

    The purpose of the present study was to evaluate whether near wins can prolong gambling activity on a video lottery terminal. In a three-reel game, near wins were operationally defined as two identical symbols followed by a third different symbol. Players in an experimental condition were exposed to 27% near wins in a series of continuous losses, whereas players in a control group were exposed to none. Participants played as long as they wished, and received real money for their wins. The results showed that players in the near win condition played 33% more games than did the control group. The results of this study suggest that near wins can be added to the list of factors that may motivate people to gamble despite the probability of monetary loss.

  10. 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...

  11. GABAA receptors modulate cannabinoid-evoked hypothermia.

    Science.gov (United States)

    Rawls, S M; Tallarida, R J; Kon, D A; Geller, E B; Adler, Martin W

    2004-05-01

    Cannabinoids evoke hypothermia by stimulating central CB(1) receptors. GABA induces hypothermia via GABA(A) or GABA(B) receptor activation. CB(1) receptor activation increases GABA release in the hypothalamus, a central locus for thermoregulation, suggesting that cannabinoid and GABA systems may be functionally linked in body temperature regulation. We investigated whether GABA receptors modulate the hypothermic actions of [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one] (WIN 55212-2), a selective cannabinoid agonist, in male Sprague-Dawley rats. WIN 55212-2 (2.5 mg/kg im) produced a rapid hypothermia that peaked 45-90 min postinjection. The hypothermia was attenuated by bicuculline (2 mg/kg ip), a GABA(A) antagonist. However, SCH 50911 (1-10 mg/kg ip), a GABA(B) blocker, did not antagonize the hypothermia. Neither bicuculline (2 mg/kg) nor SCH 50911 (10 mg/kg) by itself altered body temperature. We also investigated a possible role for CB(1) receptors in GABA-generated hypothermia. Muscimol (2.5 mg/kg ip), a GABA(A) agonist, or baclofen (5 mg/kg ip), a GABA(B) agonist, evoked a significant hypothermia. Blockade of CB(1) receptors with SR141716A (2.5 mg/kg im) did not antagonize muscimol- or baclofen-induced hypothermia, indicating that GABA-evoked hypothermia does not contain a CB(1)-sensitive component. Our results implicate GABA(A) receptors in the hypothermic actions of cannabinoids and provide further evidence of a functional link between cannabinoid and GABA systems.

  12. Modulation of NMDA and AMPA-mediated synaptic transmission by CB1 receptors in frontal cortical pyramidal cells.

    Science.gov (United States)

    Li, Qiang; Yan, Haidun; Wilson, Wilkie A; Swartzwelder, H Scott

    2010-06-25

    Although the endogenous cannabinoid system modulates a variety of physiological and pharmacological processes, the specific role of cannabinoid CB1 receptors in the modulation of glutamatergic neurotransmission and neural plasticity is not well understood. Using whole-cell patch clamp recording techniques, evoked or spontaneous excitatory postsynaptic currents (eEPSCs or sEPSCs) were recorded from visualized, layer II/III pyramidal cells in frontal cortical slices from rat brain. Bath application of the CB1 receptor agonist, WIN 55212-2 (WIN), reduced the amplitude of NMDA receptor-mediated EPSCs in a concentration-dependent manner. When co-applied with the specific CB1 antagonists, AM251 or AM281, WIN did not suppress NMDA receptor-mediated EPSCs. WIN also reduced the amplitude of evoked AMPA receptor-mediated EPSCs, an effect that was also reversed by AM251. Both the frequency and amplitude of spontaneous AMPA receptor-mediated EPSCs were significantly reduced by WIN. In contrast, WIN reduced the frequency, but not the amplitude of miniature EPSCs, suggesting that the suppression of glutamatergic activity by CB1 receptors in the frontal neocortex is mediated by a presynaptic mechanism. Taken together, these data indicate a critical role for endocannabinoid signaling in the regulation of excitatory synaptic transmission in frontal neocortex, and suggest a possible neuronal mechanism whereby THC regulates cortical function.

  13. Oscars 2010:Kathryn Bigelow Wins Best Director

    Institute of Scientific and Technical Information of China (English)

    侍小军; 李新

    2010-01-01

    @@ "The Hurt Locker"defeated"Avatar"-the biggest movie of all time-to win Best Picture at the 82nd Academy Awards Sunday. "Hurt Locker" won five other Oscars,including,in a surprising main sweep,Best Director for Kathryn Bigelow. She made history as the first woman to receive the honor. Only three other women have been nominated(提名): Lina Wertmüller for "Seven Beauties",Jane Campion for "The Piano" and Sofia Coppola for "Lost in Translation".

  14. Why do winners keep winning? Androgen mediation of winner but not loser effects in cichlid fish

    Science.gov (United States)

    Oliveira, Rui F.; Silva, Ana; Canário, Adelino V.M.

    2009-01-01

    Animal conflicts are influenced by social experience such that a previous winning experience increases the probability of winning the next agonistic interaction, whereas a previous losing experience has the opposite effect. Since androgens respond to social interactions, increasing in winners and decreasing in losers, we hypothesized that socially induced transient changes in androgen levels could be a causal mediator of winner/loser effects. To test this hypothesis, we staged fights between dyads of size-matched males of the Mozambique tilapia (Oreochromis mossambicus). After the first contest, winners were treated with the anti-androgen cyproterone acetate and losers were supplemented with 11-ketotestosterone. Two hours after the end of the first fight, two contests were staged simultaneously between the winner of the first fight and a naive male and between the loser of first fight and another naive male. The majority (88%) of control winners also won the second interaction, whereas the majority of control losers (87%) lost their second fight, thus confirming the presence of winner/loser effects in this species. As predicted, the success of anti-androgen-treated winners in the second fight decreased significantly to chance levels (44%), but the success of androgenized losers (19%) did not show a significant increase. In summary, the treatment with anti-androgen blocks the winner effect, whereas androgen administration fails to reverse the loser effect, suggesting an involvement of androgens on the winner but not on the loser effect. PMID:19324741

  15. Intergroup conflict: Ecological predictors of winning and consequences of defeat in a wild primate population.

    Science.gov (United States)

    Markham, A Catherine; Alberts, Susan C; Altmann, Jeanne

    2012-08-01

    In many social species, competition between groups is a major factor proximately affecting group-level movement patterns and space use and ultimately shaping the evolution of group living and complex sociality. Here we evaluated the factors influencing group-level dominance among 5 social groups of wild baboons (Papio cynocephalus), in particular focusing on the spatial determinants of dominance and the consequences of defeat. When direct conflict occurred between conspecific baboon groups, the winning group was predicted by differences in the number of adult males in each group and/or groups that had used the areas surrounding the encounter location more intensively than their opponent in the preceding 9 or 12 months. Relative intensity of space use over shorter timescales examined (3 and 6 months) was a poor predictor of the interaction's outcome. Losing groups but not winning groups experienced clear short-term costs. Losing groups used the area surrounding the interaction less following an agonistic encounter (relative to their intensity of use of the area prior to the interaction). These findings offer insight into the influences and consequences of intergroup competition on group-level patterns of space use.

  16. 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 ...

  17. 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.

  18. On winning sets and non-normal numbers

    OpenAIRE

    Mance, Bill

    2010-01-01

    In \\cite{SchmidtGames}, W. Schmidt proved that the set of non-normal numbers in base $b$ is a {\\it winning set}. We generalize this result by proving that many sets of non-normal numbers with respect to the Cantor series expansion are winning sets. As an immediate consequence, these sets will be shown to have full Hausdorff dimension.

  19. 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....

  20. 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

  1. Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles—A New Family of High Affinity CB1 Cannabinoid Ligands

    Directory of Open Access Journals (Sweden)

    Patricio Iturriaga-Vásquez

    2013-04-01

    Full Text Available A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used as a template for optimization. In the present series, 21 compounds displayed high affinities with Ki values in the nanomolar range. JM-39 (compound 39 was the most active of the series (KiCB1 = 0.53 nM, while compounds 31 and 44 exhibited similar affinities to WIN 55212-2. CoMFA analysis was performed based on the biological data obtained and resulted in a statistically significant CoMFA model with high predictive value (q2 = 0.710, r2 = 0.998, r2pred = 0.823.

  2. 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…

  3. 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.

  4. 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....

  5. 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

  6. 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...

  7. Effects of ethanol in an open field apparatus: modification by U50488H and WIN 44441-3.

    Science.gov (United States)

    Pohorecky, L A; Patel, V; Roberts, P

    1989-02-01

    The effects of U50488H, a kappa agonist, and WIN 44441-3, a kappa antagonist, and their modification of the effects of ethanol, on the behavior of rats in a modified open field apparatus, was examined. Crossover activity was increased by U50488H. Headpoke activity was decreased by WIN 44441-3 and increased by U50488H. Rearing activity was increased by WIN 44441-3 but was not affected by U50488H. The effect of both drugs was dose related, with the largest doses having no effect. Ethanol (0.5 g/kg) stimulated crossover activity while it depressed rearing, headpoke and corner activities; except for crossover activity the 2.0 g/kg dose of ethanol depressed these activities. Pretreatment with WIN 44441-3 (0.5 mg/kg) potentiated the stimulant effect of ethanol on crossover activity and partially reversed the depressant effect of ethanol on rearing and headpoke activities. U50488H potentiated the ethanol-induced depression of headpoke and reversed the depression of corner activity. Pretreatment with U50488H had no effect on ethanol's action on crossover and rearing behaviors. Our results indicate that kappa opiate receptors may mediate some behaviors exhibited by rats in a modified open field apparatus. Activation of these receptors increases locomotor and headpoke activity but had no effect on rearing activity. Furthermore, the 0.5 g/kg dose of ethanol has differential effects on different measures of open field behavior, while the 2.0 g/kg dose was largely depressant. Our data suggest that some of these effects of ethanol may be mediated via kappa opioid receptors.

  8. Interaction between cannabinoid compounds and diazepam on anxiety-like behaviour of mice.

    Science.gov (United States)

    Naderi, Nima; Haghparast, Abbas; Saber-Tehrani, Ali; Rezaii, Neguine; Alizadeh, Amir-Mohammad; Khani, Abbas; Motamedi, Fereshteh

    2008-03-01

    Previous studies have suggested that cannabinoidergic system is involved in anxiety. However, a complete picture of cannabinoid association in the anxiety is still lacking. In the present study, we investigated the possible interaction between cannabinoidergic and GABAergic systems in the anxiety-like behaviour of mice. Intraperitoneal (i.p.) administration of the cannabinoid receptor agonist WIN55212-2 (0.25-5 mg/kg), the endocannabinoid transport inhibitor AM404 (0.25-2 mg/kg) and diazepam (0.25-8 mg/kg) dose dependently exhibited an anxiolytic effect evaluated in terms of increase in the percentage of time spent in the open arms in the elevated plus maze (EPM) test. Administration of certain fixed-ratio combinations (3:1 and 1:1) of WIN55212-2 and diazepam produced a synergistic anxiolytic effect, while the 1:3 combination produced an additive effect. In hole-board test, administration of certain ratios of WIN55212-2-diazepam combination significantly altered the animal behaviour compared to groups that received each drug alone. Co-administration of AM404 (1 and 2 mg/kg) and diazepam (0.5 mg/kg) abolished the anxiolytic effect of the former drug in EPM and the latter in hole-board test, respectively. The combination of an ineffective dose of the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3 mg/kg, i.p.) on anxiety-related responses with an ineffective dose of diazepam (0.25 mg/kg, i.p.) led to a synergistic effect. Co-administration of the CB1 receptor antagonist, AM251 (5 mg/kg) and an effective dose of diazepam (2 mg/kg, i.p.) attenuated diazepam-induced elevation of percentage of time spent in open arm, while lower dose of AM251 (0.5 mg/kg) failed to inhibit diazepam-induced anxiolytic effect. Taken together, the present study showed that co-administration of exogenous cannabinoids and diazepam produce additive or synergistic effect at different combinations. Moreover, it has been shown that enhancement of the function of endocannabinoids could

  9. Pharmacogenetics of β2-Agonists

    Directory of Open Access Journals (Sweden)

    Nobuyuki Hizawa

    2011-01-01

    Full Text Available Short-acting β2-agonists (SABAs and long-acting β2-agonists (LABAs are both important for treatment of asthma and chronic obstructive pulmonary disease (COPD because of their bronchodilator and bronchoprotective effects. However, the use of these agonists, at least for asthma, has generated some controversy because of their association with increased mortality. Pharmacogenetics is the study of genetically determined variation in response to medications, which might prove useful for target therapies in highly responsive patients, especially for more expensive therapies or those with increased risk of side effects. Variation in response to both SABAs and LABAs has been observed in patients with polymorphisms in the β2 adrenoceptor gene (ADRB2. This review summarizes results from various studies on the possible relationship between ADRB2 polymorphisms and the bronchodilator or bronchoprotective effects of inhaled β2-agonists. By assessing the ADRB2 genotype, the hope is that it will be possible to predict the responsiveness to chronic administration of β2-agonists. Genetic testing, however, is of limited usefulness at this stage for ADRB2 because the common variants identified thus far account for only a small proportion of the variation observed for given responses. Carefully performed and adequately powered clinical trials continue to be important for achieving the goal of pharmacogenetic approaches to therapy.

  10. On winning sets and non-normal numbers

    CERN Document Server

    Mance, Bill

    2010-01-01

    In \\cite{SchmidtGames}, W. Schmidt proved that the set of non-normal numbers in base $b$ is a {\\it winning set}. We generalize this result by proving that the set of non-normal numbers with respect to the $\\beta$-expansion, where $\\beta$ is a Pisot-Vijayaraghavan number, is a winning set. Additionally, we show that several sets of non-normal numbers with respect to the Cantor series expansion are winning sets. As an immediate consequence, all of these sets will be shown to have full Hausdorff dimension.

  11. 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,…

  12. 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)

  13. 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.

  14. A Survey of ’Quick Wins’ in Modern War

    Science.gov (United States)

    1975-10-01

    out over the vast area of northern Manchuria , in a rectangle formed by Kailar, Tsitsihar, Harbin and Sakhalian. It con- sisted of three infantry...of Manchuria , August 1945 5 Third Arab-Israeli War, 1967 6 Almost Quick Wins German Invasion of Russia (Operation "Barbarossa"), 1941 7...1941-1942 Soviet Invasion of Manchuria . August 1945 Third Arab-Israeli War, 1967 Almost Quick Wins Operation Barbarossa, The German Campaign in

  15. Who Wins the Olympic Games: Economic Development and Medal Totals

    OpenAIRE

    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.

  16. 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...

  17. 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

  18. 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 ...

  19. 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)

  20. 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)

  1. 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.

  2. 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...

  3. 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.

  4. Cannabinoid type 1 receptor ligands WIN 55,212-2 and AM 251 alter anxiety-like behaviors of marmoset monkeys in an open-field test.

    Science.gov (United States)

    Cagni, Priscila; Barros, Marilia

    2013-03-01

    Cannabinoid type 1 receptors (CB1r) are an important modulatory site for emotional behavior. However, little is known on the effects of CB1r ligands on emotionality aspects of primates, even with their highly similar behavioral response and receptor density/distribution as humans. Thus, we analyzed the effects of the CB1r agonist WIN 55,212-2 (WIN; 1mg/kg) and the antagonist AM 251 (AM; 2mg/kg), systemically administered prior to a single brief (15 min) exposure to a novel open-field (OF) environment, on the behavior of individually tested adult black tufted-ear marmosets. Both WIN- and AM-treated subjects, compared to vehicle controls, had significantly lower rates of long (contact) calls and exploration, while higher levels of vigilance-related behaviors (scan/glance); these are indicators of anxiolysis in this setup. Changes in locomotion were not detected. However, in the vehicle and AM-groups, sojourn in the peripheral zone of the OF was significantly higher than in its central region. WIN-treated marmosets spent an equivalent amount of time in both zones. Therefore, activation or blockade CB1r function prior to a short and individual exposure to an unfamiliar environment exerted a significant and complex influence on different behavioral indicators of anxiety in these monkeys (i.e., a partially overlapping anxiolytic-like profile). AM 251, however, has no anxiolytic effect when the time spent in the center of the OF is considered. This is a major difference when compared to the WIN-treated group. Data were compared to the response profile reported in other pre-clinical (rodent) and clinical studies.

  5. Role for neuronal nitric-oxide synthase in cannabinoid-induced neurogenesis.

    Science.gov (United States)

    Kim, Sun Hee; Won, Seok Joon; Mao, Xiao Ou; Ledent, Catherine; Jin, Kunlin; Greenberg, David A

    2006-10-01

    Cannabinoids, acting through the CB1 cannabinoid receptor (CB1R), protect the brain against ischemia and related forms of injury. This may involve inhibiting the neurotoxicity of endogenous excitatory amino acids and downstream effectors, such as nitric oxide (NO). Cannabinoids also stimulate neurogenesis in the adult brain through activation of CB1R. Because NO has been implicated in neurogenesis, we investigated whether cannabinoid-induced neurogenesis, like cannabinoid neuroprotection, might be mediated through alterations in NO production. Accordingly, we measured neurogenesis in dentate gyrus (DG) and subventricular zone (SVZ) of CB1R-knockout (KO) and wild-type mice, some of whom were treated with the cannabinoid agonist R(+)-Win 55212-2 [(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone] or the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI). NOS activity was increased by approximately 25%, whereas bromodeoxyuridine (BrdU) labeling of newborn cells in DG and SVZ was reduced by approximately 50% in CB1R-KO compared with wild-type mice. 7-NI increased BrdU labeling in both DG and SVZ and to a greater extent in CB1R-KO than in wild-type mice. In addition, R(+)-Win 55212-2 and 7-NI enhanced BrdU incorporation into neuron-enriched cerebral cortical cultures to a similar maximal extent and in nonadditive fashion, consistent with a shared mechanism of action. Double-label confocal microscopy showed coexpression of BrdU and the neuronal lineage marker doublecortin (Dcx) in DG and SVZ of untreated and 7-NI-treated CB1R-KO mice, and 7-NI increased the number of Dcx- and BrdU/Dcx-immunoreactive cells in SVZ and DG. Thus, cannabinoids appear to stimulate adult neurogenesis by opposing the antineurogenic effect of NO.

  6. Cosmic Bubble Image Wins NRAO Contest

    Science.gov (United States)

    2006-10-01

    A striking image of an enormous bubble blown into the dusty gas disk of our own Milky Way galaxy has won first place in the National Radio Astronomy Observatory's second annual Radio Astronomy Image Contest. Dr. Jayanne English of the University of Manitoba led the team that made the winning image using data from the National Science Foundation's Very Large Array (VLA) in New Mexico and Robert C. Byrd Green Bank Telescope (GBT) in West Virginia. Cosmic Bubble Image Giant "Bubble" in Milky Way's Gas CREDIT: English et al., NRAO/AUI/NSF Click on image for large files and full information English and her collaborators Jeroen Stil and Russ Taylor, from the University of Calgary, will share the grand prize of $1,000 from Associated Universities, Inc., the research corporation that operates the observatory for the NSF. "We congratulate Dr. English for producing an outstanding image that beautifully illustrates the power of our radio telescopes," said NRAO Director Fred K.Y. Lo. The image contest is part of a broader NRAO effort to make radio astronomical data and images easily accessible and widely available to scientists, students, teachers, the general public, news media and science-education professionals. That effort includes an expanding image gallery on the observatory's Web site. English's winning image shows a giant bubble in the Milky Way's dusty gas disk. The bubble has been sculpted by the wind and radiation force from a few dozen hot, massive stars along with the explosive force of supernova explosions from dying stars. The bubble, seen in the faint radio glow of hydrogen gas, is some 30,000 light-years from Earth and measures 1,100 by 520 light-years. If the bubble, in the constellation Vulpecula, were visible to human eyes, it would appear to be eight times the diameter of the full Moon in the sky. The image was made using data collected as part of the VLA Galactic Plane Survey (VGPS), a set of systematic observations of the Milky Way. This survey, led by

  7. 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

  8. 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...

  9. 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.

  10. 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.

  11. Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy.

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; Sombati, Sompong; Elphick, Maurice R; Martin, Billy R; DeLorenzo, Robert J

    2009-09-01

    Cannabinoids have been shown to cause CB1-receptor-dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor-dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg(2+) induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg(2+) induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 h. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent downregulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg(2+) treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1-receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype.

  12. Prolonged exposure to WIN55,212-2 causes down-regulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy

    Science.gov (United States)

    Blair, Robert E.; Deshpande, Laxmikant S.; Sombati, Sompong; Elphick, Maurice R.; Martin, Billy R.; DeLorenzo, Robert J.

    2009-01-01

    Summary Cannabinoids have been shown to cause CB1-receptor dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg2+ induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg2+ induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 hours. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent down-regulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg2+ treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1 receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype. PMID:19540252

  13. Regulation of membrane cholecystokinin-2 receptor by agonists enables classification of partial agonists as biased agonists.

    Science.gov (United States)

    Magnan, Rémi; Masri, Bernard; Escrieut, Chantal; Foucaud, Magali; Cordelier, Pierre; Fourmy, Daniel

    2011-02-25

    Given the importance of G-protein-coupled receptors as pharmacological targets in medicine, efforts directed at understanding the molecular mechanism by which pharmacological compounds regulate their presence at the cell surface is of paramount importance. In this context, using confocal microscopy and bioluminescence resonance energy transfer, we have investigated internalization and intracellular trafficking of the cholecystokinin-2 receptor (CCK2R) in response to both natural and synthetic ligands with different pharmacological features. We found that CCK and gastrin, which are full agonists on CCK2R-induced inositol phosphate production, rapidly and abundantly stimulate internalization. Internalized CCK2R did not rapidly recycle to plasma membrane but instead was directed to late endosomes/lysosomes. CCK2R endocytosis involves clathrin-coated pits and dynamin and high affinity and prolonged binding of β-arrestin1 or -2. Partial agonists and antagonists on CCK2R-induced inositol phosphate formation and ERK1/2 phosphorylation did not stimulate CCK2R internalization or β-arrestin recruitment to the CCK2R but blocked full agonist-induced internalization and β-arrestin recruitment. The extreme C-terminal region of the CCK2R (and more precisely phosphorylatable residues Ser(437)-Xaa(438)-Thr(439)-Thr(440)-Xaa(441)-Ser(442)-Thr(443)) were critical for β-arrestin recruitment. However, this region and β-arrestins were dispensable for CCK2R internalization. In conclusion, this study allowed us to classify the human CCK2R as a member of class B G-protein-coupled receptors with regard to its endocytosis features and identified biased agonists of the CCK2R. These new important insights will allow us to investigate the role of internalized CCK2R·β-arrestin complexes in cancers expressing this receptor and to develop new diagnosis and therapeutic strategies targeting this receptor.

  14. 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.

  15. Vascular dysfunction in a transgenic model of Alzheimer’s disease: Effects of CB1R and CB2R cannabinoid agonists.

    Directory of Open Access Journals (Sweden)

    Jorge Navarro-Dorado

    2016-09-01

    Full Text Available 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.

  16. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  17. 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.

  18. 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.

  19. 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…

  20. D2 dining center wins whole grains challenge

    OpenAIRE

    Dawson, Brandi

    2007-01-01

    The Whole Grains Council and Oldways food issues advocacy group challenged restaurants and foodservice operations across the country to step up to the plate and offer more whole grain options this summer. Virginia Tech's Dining Services did just that and swept the competition, winning the college/university category, as well as the grand prize, beating out entries from nine other categories.

  1. 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

  2. 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,…

  3. 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...

  4. Steal These Ideas! Winning Activities from Real Teachers

    Science.gov (United States)

    Instructor, 2007

    2007-01-01

    This article presents several winning activities for students in the classroom. These activities include: (1) making Abraham Lincoln costumes; (2) creating frosty scenes from torn-paper collage for a grammar activity; (3) listening to Dr. Martin Luther King's "I have a Dream" speech; (4) hosting an architectural challenge for a kindergarten class;…

  5. 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

  6. Cogeneration: a winning game for the players who risk it

    Energy Technology Data Exchange (ETDEWEB)

    1985-11-01

    Cogeneration holds out the tantalizing prospect of lower utility rates and affordable energy. But the stakes are high. Now an expert player - the cogen developer - offers to negotiate the gameboard and guarantee a win to those willing to take a chance on his services.

  7. Economic Education Experiences of Award Winning Alaska Teachers.

    Science.gov (United States)

    Thomas, Monica, Ed.

    Award-winning economic education projects devised by Alaska teachers included three elementary (K-6) projects and three second level (7-12) ones. Faith Greenough's students (Chinook Elementary School, Anchorage) compared Tlingit traditional and market economies in Alaska, so economics became an integrated part of elementary instruction. Marie…

  8. LGBT Caucus sponsors award-winning film and PBS director

    OpenAIRE

    Elliott, Jean

    2007-01-01

    The LGBT faculty-staff caucus at Virginia Tech will host the award-winning PBS film director Daniel Karslake, and an educational screening of "For the Bible Tells Me So" at The Lyric Theatre Thursday, Nov. 29 at 7 p.m.

  9. 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....

  10. A SAS Interface for Bayesian Analysis with WinBUGS

    Science.gov (United States)

    Zhang, Zhiyong; McArdle, John J.; Wang, Lijuan; Hamagami, Fumiaki

    2008-01-01

    Bayesian methods are becoming very popular despite some practical difficulties in implementation. To assist in the practical application of Bayesian methods, we show how to implement Bayesian analysis with WinBUGS as part of a standard set of SAS routines. This implementation procedure is first illustrated by fitting a multiple regression model…

  11. AGONISTIC BEHAVIOR OF LABORATORY MICE

    Directory of Open Access Journals (Sweden)

    D. Cinghiţă

    2005-01-01

    Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

  12. 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.

  13. 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.

  14. 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.

  15. WinRAR 添加新的右键菜单

    Institute of Scientific and Technical Information of China (English)

    刘杰

    2007-01-01

    @@ WinRAR是我们经常使用的压缩软件,而其中最常用的功能直接用右键菜单进行压缩或是解压缩操作.不过,WinRAR自带的几项菜单项总有这样或那样的不便之处,下面我们就来为WinRAR的右键菜单增加新选项(注意:根据情况修改WinRAR的安装路径,本文以WinRAR安装在C:\\Program files\\Winrar\\为例).

  16. 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.

  17. Beta-agonists and animal welfare

    Science.gov (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  18. 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.

  19. How Insurgents Win: Examining the Dynamics of Modern Insurgencies

    Science.gov (United States)

    2014-06-01

    insurgents that do not. These are by no means the only literary works covering the use of safe havens by insurgent groups. Almost every book, article, or...19. 23 Ivan Arreguín-Toft, “How the Weak Win Wars: A Theory of Asymmetric Conflict,” International Security 26, no. 1 (2001): 93–128. 9...conflict. 2. Hypotheses This thesis separates the theories discussed in the previous literature review into five independent hypotheses. Each hypothesis

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Dopamine Agonists and Pathologic Behaviors

    Directory of Open Access Journals (Sweden)

    Brendan J. Kelley

    2012-01-01

    Full Text Available The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson’s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.

  5. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  6. 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.

  7. 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.

  8. 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, PPARα 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 PPARγ agonists, and more recently dual PPARα/γ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARγ 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. PMID:18288280

  9. 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.

  10. 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.

  11. The Social Security Administration's Youth Transition Demonstration Projects: Interim Report on Colorado Youth WINS

    OpenAIRE

    2011-01-01

    This report presents first-year evaluation findings for the Colorado Youth WINS (Work Incentive Network of Supports) project, which served youth in four counties from August 2006 to December 2009. Using process analysis, the report found Youth WINS, as implemented, deviated from the program model in ways that may have reduced its potential to achieve certain critical objectives. However, Youth WINS participants were more likely to have used services to promote employment than the control group.

  12. 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

  13. The WinBraille approach to producing Braille wuickly and effectively

    OpenAIRE

    Blomquist, Mats; Burman, Per

    2002-01-01

    With WinBraille it is possible to emboss directly from a word processor like Microsoft Word on any of Index Braille's embossers, and on-the-fly contract the document into grade 2 Braille. The benefit of WinBraille is that it has a simple interface for the novice, but is still powerful for the advanced user. WinBraille contains Windows drivers for Index Braille's embossers, the WinBraille application, contraction rules for more than 20 languages, a contraction rule editor, predefined profiles ...

  14. QR Code Recognition System Based on WinCE Embedded Platform%基于WinCE平台的QR条码识别系统

    Institute of Scientific and Technical Information of China (English)

    刘伟

    2010-01-01

    简单介绍了QR码的基本结构,分析了在基于WinCE的嵌入式平台上QR码图像数据的灰度化、滤波、二值化、定位及矫正等预处理的实现过程.重点讨论了系统在WinCE平台上如何实现实时图像采集的问题,并设计了一个基于WinCE手机移动平台的QR码识别系统.

  15. 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。

  16. Aminergic control of social status in crayfish agonistic encounters.

    Directory of Open Access Journals (Sweden)

    Yuto Momohara

    Full Text Available Using pairings of male crayfish Procambarus clarkii with a 3-7% difference in size, we confirmed that physically larger crayfish were more likely to win encounters (winning probability of over 80%. Despite a physical disadvantage, small winners of the first pairings were more likely to win their subsequent conflicts with larger naive animals (winning probability was about 70%. By contrast, the losers of the first pairings rarely won their subsequent conflicts with smaller naive animals (winning probability of 6%. These winner and loser effects were mimicked by injection of serotonin and octopamine. Serotonin-injected naive small crayfish were more likely to win in pairings with untreated larger naive crayfish (winning probability of over 60%, while octopamine-injected naive large animals were beaten by untreated smaller naive animals (winning probability of 20%. Furthermore, the winner effects of dominant crayfish were cancelled by the injection of mianserin, an antagonist of serotonin receptors and were reinforced by the injection of fluoxetin, serotonin reuptake inhibitor, just after the establishment of social order of the first pairings. Injection of octopamine channel blockers, phentolamine and epinastine, by contrast, cancelled the loser effects. These results strongly suggested that serotonin and octopamine were responsible for winner and loser effects, respectively.

  17. Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ-aminobutyric acid type B receptor activity.

    Science.gov (United States)

    Messer, Ricka D; Levine, Eric S

    2012-07-01

    The anticonvulsant properties of marijuana have been known for centuries. The recently characterized endogenous cannabinoid system thus represents a promising target for novel anticonvulsant agents; however, administration of exogenous cannabinoids has shown mixed results in both human epilepsy and animal models. The ability of cannabinoids to attenuate release of both excitatory and inhibitory neurotransmitters may explain the variable effects of cannabinoids in different models of epilepsy, but this has not been well explored. Using acute mouse brain slices, we monitored field potentials in the CA1 region of the hippocampus to characterize systematically the effects of the cannabinoid agonist WIN55212-2 (WIN) on evoked basal and epileptiform activity. WIN, acting presynaptically, significantly reduced the amplitude and slope of basal field excitatory postsynaptic potentials as well as stimulus-evoked epileptiform responses induced by omission of magnesium from the extracellular solution. In contrast, the combination of omission of magnesium plus elevation of potassium induced an epileptiform response that was refractory to attenuation by WIN. The effect of WIN in this model was partially restored by blocking γ-aminobutyric acid type B (GABA(B) ), but not GABA(A) , receptors. Subtle differences in models of epileptiform activity can profoundly alter the efficacy of cannabinoids. Endogenous GABA(B) receptor activation played a role in the decreased cannabinoid sensitivity observed for epileptiform activity induced by omission of magnesium plus elevation of potassium. These results suggest that interplay between presynaptic G protein-coupled receptors with overlapping downstream targets may underlie the variable efficacy of cannabinoids in different models of epilepsy.

  18. OpenGL Programming under Win32 Environment%Win32环境下的OpenGL程序设计

    Institute of Scientific and Technical Information of China (English)

    郑竞华

    2006-01-01

    OpenGL是目前公认的三维图形开发标准,在Win32环境下开发高质量高性能的三维图形应用程序,OpenGL是比较理想的选择.简要介绍Win32环境下,使用OpenGL进行图形操作的具体步骤,详细介绍Win32环境下进行OpenGL编程涉及的相关技术细节,如关联设备描述表和绘制描述表、图形显示与重绘、实时动画与交互操作等,并编写一个简单的动画例程,较全面地演示了Win32环境下的OpenGL编程方法.

  19. 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.

  20. 26 CFR 31.3402(q)-1 - Extension of withholding to certain gambling winnings.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Extension of withholding to certain gambling... to certain gambling winnings. (a)(1) General rule. Every person, including the Government of the.... With respect to reporting requirements for certain payments of gambling winnings not subject...

  1. 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

  2. 26 CFR 1.6011-3 - Requirement of statement from payees of certain gambling winnings.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Requirement of statement from payees of certain gambling winnings. 1.6011-3 Section 1.6011-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... of statement from payees of certain gambling winnings. (a) General rule. Except as provided...

  3. 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。

  4. Muscimol as an ionotropic GABA receptor agonist.

    Science.gov (United States)

    Johnston, Graham A R

    2014-10-01

    Muscimol, a psychoactive isoxazole from Amanita muscaria and related mushrooms, has proved to be a remarkably selective agonist at ionotropic receptors for the inhibitory neurotransmitter GABA. This historic overview highlights the discovery and development of muscimol and related compounds as a GABA agonist by Danish and Australian neurochemists. Muscimol is widely used as a ligand to probe GABA receptors and was the lead compound in the development of a range of GABAergic agents including nipecotic acid, tiagabine, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, (Gaboxadol(®)) and 4-PIOL.

  5. Identification of Selective ERRγ Inverse Agonists

    Directory of Open Access Journals (Sweden)

    Jina Kim

    2016-01-01

    Full Text Available GSK5182 (4 is currently one of the lead compounds for the development of estrogen-related receptor gamma (ERRγ inverse agonists. Here, we report the design, synthesis, pharmacological and in vitro absorption, distribution, metabolism, excretion, toxicity (ADMET properties of a series of compounds related to 4. Starting from 4, a series of analogs were structurally modified and their ERRγ inverse agonist activity was measured. A key pharmacophore feature of this novel class of ligands is the introduction of a heterocyclic group for A-ring substitution in the core scaffold. Among the tested compounds, several of them are potent ERRγ inverse agonists as determined by binding and functional assays. The most promising compound, 15g, had excellent binding selectivity over related subtypes (IC50 = 0.44, >10, >10, and 10 μM at the ERRγ, ERRα, ERRβ, and ERα subtypes, respectively. Compound 15g also resulted in 95% transcriptional repression at a concentration of 10 μM, while still maintaining an acceptable in vitro ADMET profile. This novel class of ERRγ inverse agonists shows promise in the development of drugs targeting ERRγ-related diseases.

  6. 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.

  7. Survey of electrochemical metal winning processes. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Vaaler, L.E.

    1979-03-01

    The subject program was undertaken to find electrometallurgical technology that could be developed into energy saving commercial metal winning processes. Metals whose current production processes consume significant energy (excepting copper and aluminum) are magnesium, zinc, lead, chromium, manganese, sodium, and titanium. The technology of these metals, with the exception of titanium, was reviewed. Growth of titanium demand has been too small to justify the installation of an electrolyte process that has been developed. This fact and the uncertainty of estimates of future demand dissuaded us from reviewing titanium technology. Opportunities for developing energy saving processes were found for magnesium, zinc, lead, and sodium. Costs for R and D and demonstration plants have been estimated. It appeared that electrolytic methods for chromium and manganese cannot compete energywise or economically with the pyrometallurgical methods of producing the ferroalloys, which are satisfactory for most uses of chromium and manganese.

  8. 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

  9. 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.

  10. 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.

  11. Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by cannabinoid agonists.

    Science.gov (United States)

    Pascual, A C; Martín-Moreno, A M; Giusto, N M; de Ceballos, M L; Pasquaré, S J

    2014-12-01

    Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aβ(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging.

  12. 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.

  13. 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.

  14. Application of configuration software WinCC in logistics automatic control system

    Science.gov (United States)

    Weng, Yifang; Duan, Zhengang; Lian, Xiaoqin; Zhang, Xiaoli; Yang, Wenying

    2006-11-01

    This paper presents the application of WinCC in Logistics Automatic Control System on the experiment facility of miniature warehouse. The information management system, the supervisory control system and the PLC execution part are developed. The communication between WinCC and PLC based on the PROFIBUS protocol is implemented. DDE Communication, VB as server and WinCC as client, is realized. The system combines information management and supervisory control together and works well. It would be applicable to industry after deeper study.

  15. 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.

  16. In vitro and non-invasive in vivo effects of the cannabinoid-1 receptor (CB1R) agonist AM841 on gastrointestinal motor function in the rat

    Science.gov (United States)

    Abalo, R; Chen, C; Vera, G; Fichna, J; Thakur, GA; López-Pérez, AE; Makriyannis, A; Martín-Fontelles, MI; Storr, M

    2015-01-01

    Background Cannabinoids have been traditionally used for the treatment of gastrointestinal (GI) symptoms, but the associated central effects, through cannabinoid-1 receptors (CB1R), constitute an important drawback. Our aims were to characterize the effects of the recently developed highly potent long-acting megagonist AM841 on GI motor function and to determine its central effects in rats. Methods Male Wistar rats were used for in vitro and in vivo studies. The effect of AM841 was tested on electrically-induced twitch contractions of GI preparations (in vitro) and on GI motility measured radiographically after contrast administration (in vivo). Central effects of AM841 were evaluated using the cannabinoid tetrad. The non-selective cannabinoid agonist WIN 55,212-2 (WIN) was used for comparison. The CB1R (AM251) and CB2R (AM630) antagonists were used to characterize cannabinoid receptor-mediated effects of AM841. Key results AM841 dose-dependently reduced in vitro contractile activity of rat GI preparations via CB1R, but not CB2R or opioid receptors. In vivo, AM841 acutely and potently reduced gastric emptying and intestinal transit in a dose-dependent and AM251-sensitive manner. The in vivo GI effects of AM841 at 0.1 mg kg−1 were comparable to those induced by WIN at 5 mg kg−1. However, at this dose, AM841 did not induce any sign of the cannabinoid tetrad, whereas WIN induced significant central effects. Conclusions & Inferences The CB1R megagonist AM841 may potently depress GI motor function in the absence of central effects. This effect may be mediated peripherally and may be useful in the treatment of GI motility disorders. PMID:26387676

  17. 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

  18. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  19. Agonistic and reproductive interactions in Betta splendens.

    Science.gov (United States)

    Bronstein, P M

    1984-12-01

    Reproductive and agonistic behaviors in Siamese fighting fish were investigated in eight experiments, and some consequences and determinants of these sequences were isolated. First, fights and the formation of dominance-subordinancy relations were studied. Second, it was determined that large body size as well as males' prior residency in a tank produced an agonistic advantage; the magnitude of this advantage was positively related to the duration of residency. Third, the prior-residency effect in Bettas was determined by males' familiarity with visual and/or tactile cues in their home tanks. Fourth, dominant males had greater access to living space and were more likely to display at a mirror, build nests, and approach females than were subordinates. Finally, it was discovered that chemical cues associated with presumedly inert plastic tank dividers influence Bettas' social behavior.

  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. Signal Use by Octopuses in Agonistic Interactions.

    Science.gov (United States)

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

    2016-02-08

    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.

  2. 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.

  3. 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.

  4. 基于WinGate代理服务器访问Internet%Using WinGate Proxy Server to Access Internet

    Institute of Scientific and Technical Information of China (English)

    贾超; 闫桂芹

    2002-01-01

    论述了代理服务器(Proxy Server)在实现Internet访问中的特殊作用;探讨了利用代理服务器软件(WinGate等)组建局域网上的代理服务器,使得工作站通过代理服务器上网的方法;介绍了代理服务器软件(WinGate)的安装及配置等.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. The transcription factor WIN1/SHN1 regulates Cutin biosynthesis in Arabidopsis thaliana.

    Science.gov (United States)

    Kannangara, Rubini; Branigan, Caroline; Liu, Yan; Penfield, Teresa; Rao, Vijaya; Mouille, Grégory; Höfte, Herman; Pauly, Markus; Riechmann, José Luis; Broun, Pierre

    2007-04-01

    The composition and permeability of the cuticle has a large influence on its ability to protect the plant against various forms of biotic and abiotic stress. WAX INDUCER1 (WIN1) and related transcription factors have recently been shown to trigger wax production, enhance drought tolerance, and modulate cuticular permeability when overexpressed in Arabidopsis thaliana. We found that WIN1 influences the composition of cutin, a polyester that forms the backbone of the cuticle. WIN1 overexpression induces compositional changes and an overall increase in cutin production in vegetative and reproductive organs, while its downregulation has the opposite effect. Changes in cutin composition are preceded by the rapid and coordinated induction of several genes known or likely to be involved in cutin biosynthesis. This transcriptional response is followed after a delay by the induction of genes associated with wax biosynthesis, suggesting that the regulation of cutin and wax production by WIN1 is a two-step process. We demonstrate that at least one of the cutin pathway genes, which encodes long-chain acyl-CoA synthetase LACS2, is likely to be directly targeted by WIN1. Overall, our results suggest that WIN1 modulates cuticle permeability in Arabidopsis by regulating genes encoding cutin pathway enzymes.

  12. CERN Club Football wins 40 year old tradition cup

    CERN Multimedia

    Dave Underhill

    2016-01-01

    Already two weeks since the CERN football team, representing the Dave Underhill XI in the annual match with the Geneva Scottish Football Club, made a late, late rally to win the Jean Pierre Fillettaz Trophy. They started well with some good passing movements, but the Scots were also playing well and began to take control towards the end of the first half. Then, following a series of poor finishing and good goalkeeping by the CERN keeper, they finally found the back of the net, and the lads in white trooped off for well-earned oranges and water, just 1-0 down at half time. The second half was again evenly matched, but while we were not making the goal chances the Scots were squandering theirs. THEN with just 10 minutes to go a sudden resurgence of energy and aggression, the CERNites made the chances which counted, and in the space 5 minutes turned the score around and were happy to hear the final whistle and celebrate a famous 2-1 victory. Victory and commiserations were celebrated in the "Club Ho...

  13. 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.

  14. 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

  15. 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

  16. Agonist trigger: what is the best approach? Agonist trigger and low dose hCG

    DEFF Research Database (Denmark)

    Humaidan, Peter; Al Humaidan, Peter Samir Heskjær

    2012-01-01

    Low-dose hCG supplementation after GnRH agonist trigger may normalize reproductive outcome while minimizing the occurrence of OHSS in high risk IVF patients. (Fertil Steril (R) 2012;97:529-30. (C) 2012 by American Society for Reproductive Medicine.)......Low-dose hCG supplementation after GnRH agonist trigger may normalize reproductive outcome while minimizing the occurrence of OHSS in high risk IVF patients. (Fertil Steril (R) 2012;97:529-30. (C) 2012 by American Society for Reproductive Medicine.)...

  17. Short and long-lasting behavioral consequences of agonistic encounters between male Drosophila melanogaster.

    Science.gov (United States)

    Trannoy, Séverine; Penn, Jill; Lucey, Kenia; Popovic, David; Kravitz, Edward A

    2016-04-26

    In many animal species, learning and memory have been found to play important roles in regulating intra- and interspecific behavioral interactions in varying environments. In such contexts, aggression is commonly used to obtain desired resources. Previous defeats or victories during aggressive interactions have been shown to influence the outcome of later contests, revealing loser and winner effects. In this study, we asked whether short- and/or long-term behavioral consequences accompany victories and defeats in dyadic pairings between male Drosophila melanogaster and how long those effects remain. The results demonstrated that single fights induced important behavioral changes in both combatants and resulted in the formation of short-term loser and winner effects. These decayed over several hours, with the duration depending on the level of familiarity of the opponents. Repeated defeats induced a long-lasting loser effect that was dependent on de novo protein synthesis, whereas repeated victories had no long-term behavioral consequences. This suggests that separate mechanisms govern the formation of loser and winner effects. These studies aim to lay a foundation for future investigations exploring the molecular mechanisms and circuitry underlying the nervous system changes induced by winning and losing bouts during agonistic encounters.

  18. 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.

  19. 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.

  20. 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.

  1. 基于WinCE的远程数据采集系统设计%Design of Remote Data Acquisition System Based on WinCE

    Institute of Scientific and Technical Information of China (English)

    苏扬; 耿三钧

    2009-01-01

    To solve several problems of data acquisition system based on PC, a restate data acquisition system adopting WinCE. NET is presented. The total structure of the system is designed. The stream interface driver code of ADC converter is designed and in use of Winsockets, data transport and remote instructions receiving through network are developed. The system realizes data acquisition, network transporting, remote controlling functions with the characteristics of flexibility and streamlin-ing.%针对基于PC的数据采集系统组建复杂、灵活性差等缺点,提出采用WinCE平台的嵌入式数据采集系统设计方案.进行系统整体设计,并设计WinCE平台下AD转化器流接口驱动程序,利用WinSockets实现网络数据传输和远程控制功能.系统实现了数据采集、网络传榆、远程控制等功能,具有结构精简,组网灵活等优点.

  2. 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.

  3. 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 .

  4. Dopamine agonist: pathological gambling and hypersexuality.

    Science.gov (United States)

    2008-10-01

    (1) Pathological gambling and increased sexual activity can occur in patients taking dopaminergic drugs. Detailed case reports and small case series mention serious familial and social consequences. The frequency is poorly documented; (2) Most affected patients are being treated for Parkinson's disease, but cases have been reported among patients prescribed a dopamine agonist for restless legs syndrome or pituitary adenoma; (3) Patients treated with this type of drug, and their relatives, should be informed of these risks so that they can watch for changes in behaviour. If such disorders occur, it may be necessary to reduce the dose or to withdraw the drug or replace it with another medication.

  5. 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...... potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose. In this review, the physiological and pharmacological rationale...

  6. SNC 80 and related delta opioid agonists.

    Science.gov (United States)

    Calderon, S N; Coop, A

    2004-01-01

    The discovery of the selective delta (delta) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, was a major advance in the field of delta-opioid ligands. Much research has been performed to uncover the structure-activity relationships (SAR) of this class of ligands and also to compare the diarylmethylpiperazines with the traditional morphinan-based delta opioids. This review focuses on the development of the SAR of this unique series of ligands, and discusses questions which remain unanswered.

  7. Sports doping: emerging designer and therapeutic β2-agonists.

    Science.gov (United States)

    Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

    2013-10-21

    Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future.

  8. 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

  9. 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

  10. 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.

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

    OpenAIRE

    Maharjan Anu S; Pilling Darrell; Gomer Richard H

    2010-01-01

    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 fi...

  12. Propagation of cortical spreading depression into the hippocampus: The role of the entorhinal cortex.

    Science.gov (United States)

    Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali

    2014-07-22

    Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABAA receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  13. 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.

  14. A quantum protocol to win the graph colouring game on all Hadamard graphs

    CERN Document Server

    Avis, D; Kikuchi, Y; Sasaki, Y; Avis, David; Hasegawa, Jun; Kikuchi, Yosuke; Sasaki, Yuuya

    2005-01-01

    This paper deals with graph colouring games, an example of pseudo-telepathy, in which two provers can convince a verifier that a graph $G$ is $c$-colourable where $c$ is less than the chromatic number of the graph. They win the game if they convince the verifier. It is known that the players cannot win if they share only classical information, but they can win in some cases by sharing entanglement. The smallest known graph where the players win in the quantum setting, but not in the classical setting, was found by Galliard, Tapp and Wolf and has 32,768 vertices. It is a connected component of the Hadamard graph $G_N$ with $N=c=16$. Their protocol applies only to Hadamard graphs where $N$ is a power of 2. We propose a protocol that applies to all Hadamard graphs. Combined with a result of Frankl, this shows that the players can win on any induced subgraph of $G_{12}$ having 1609 vertices, with $c=12$. Combined with a result of Frankl and Rodl, our result shows that all sufficiently large Hadamard graphs yield ...

  15. Match statistics related to winning in the group stage of 2014 Brazil FIFA World Cup.

    Science.gov (United States)

    Liu, Hongyou; Gomez, Miguel-Ángel; Lago-Peñas, Carlos; Sampaio, Jaime

    2015-01-01

    Identifying match statistics that strongly contribute to winning in football matches is a very important step towards a more predictive and prescriptive performance analysis. The current study aimed to determine relationships between 24 match statistics and the match outcome (win, loss and draw) in all games and close games of the group stage of FIFA World Cup (2014, Brazil) by employing the generalised linear model. The cumulative logistic regression was run in the model taking the value of each match statistic as independent variable to predict the logarithm of the odds of winning. Relationships were assessed as effects of a two-standard-deviation increase in the value of each variable on the change in the probability of a team winning a match. Non-clinical magnitude-based inferences were employed and were evaluated by using the smallest worthwhile change. Results showed that for all the games, nine match statistics had clearly positive effects on the probability of winning (Shot, Shot on Target, Shot from Counter Attack, Shot from Inside Area, Ball Possession, Short Pass, Average Pass Streak, Aerial Advantage and Tackle), four had clearly negative effects (Shot Blocked, Cross, Dribble and Red Card), other 12 statistics had either trivial or unclear effects. While for the close games, the effects of Aerial Advantage and Yellow Card turned to trivial and clearly negative, respectively. Information from the tactical modelling can provide a more thorough and objective match understanding to coaches and performance analysts for evaluating post-match performances and for scouting upcoming oppositions.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. Estrogen receptor beta agonists in neurobehavioral investigations.

    Science.gov (United States)

    Choleris, Elena; Clipperton, Amy E; Phan, Anna; Kavaliers, Martin

    2008-07-01

    Neurobehavioral investigations into the functions of estrogen receptor (ER)alpha and ERbeta have utilized 'knockout' mice, phytoestrogens and, more recently, ER-specific agonists. Feeding, sexual, aggressive and social behavior, anxiety, depression, drug abuse, pain perception, and learning (and associated synaptic plasticity) are affected by ERalpha and ERbeta in a manner that is dependent upon the specific behavior studied, gender and developmental stage. Overall, ERalpha and ERbeta appear to function together to foster sociosexual behavior while inhibiting behaviors that, if occurring at the time of behavioral estrous, may compete with reproduction (eg, feeding). Recently developed pharmacological tools have limited selectivity and availability to the research community at large, as they are not commercially available. The development of highly selective, commercially available ERbeta-specific antagonists would greatly benefit preclinical and applied research.

  6. [3H]WIN 35,065-2: a ligand for cocaine receptors in striatum.

    Science.gov (United States)

    Ritz, M C; Boja, J W; Grigoriadis, D; Zaczek, R; Carroll, F I; Lewis, A H; Kuhar, M J

    1990-11-01

    [3H]WIN 35,065-2 binding to striatal membranes was characterized, primarily by centrifugation assay. Like [3H]cocaine, [3H]WIN 35,065-2 binds to both high- and low-affinity sites. [3H]WIN 35,065-2, however, exhibits consistently higher affinities than [3H]cocaine. Saturation experiments indicate a low-affinity binding site with an apparent KD of approximately 160 nM and a Bmax of 135 fmol/mg of tissue. A high-affinity site has also been identified with an apparent KD of 5.6 nM and a Bmax of 5.2 fmol/mg of tissue. The specific-to-nonspecific binding ratios with [3H]WIN 35,065-2 were higher than with [3H]cocaine in both centrifugation and filtration assays. Pharmacological characterization suggests that [3H]WIN 35,065-2 binds to the dopamine transporter. Mazindol, GBR 12909, nomifensine, and (-)-cocaine are potent inhibitors of [3H]WIN 35,065-2 binding. In contrast, the norepinephrine transporter ligand desipramine is a weak inhibitor, and the serotonin transporter ligand citalopram does not inhibit binding. The effect of sodium on binding was examined under conditions in which (a) the low-affinity site was primarily (87%) occupied and (b) approximately 50% of both sites were occupied. The results indicate that both sites are sodium dependent. Injection of 6-hydroxydopamine into the striatum results in a significant loss of both high- and low-affinity sites, a finding suggesting that both sites are on dopaminergic nerve terminals. Taken together, these data are consistent with the presence of multiple cocaine binding sites associated with the dopamine transporter.

  7. 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

  8. 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.

  9. 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...

  10. Representations in Award-Winning LGBTQ Young Adult Literature from 2000-2013.

    Science.gov (United States)

    Jiménez, Laura M

    2015-01-01

    Lesbian, gay, bisexual, transgendered, and queer (LGBTQ) young adult (YA) literature is increasing in popularity, with novels like Bil Wright's Putting Makeup on the Fat Boy winning the two LGBTQ YA honors--the Lambda Literary and Stonewall Book Awards--as well awards commending their cultural diversity. Despite the upsurge of celebrated LGBTQ YA literature, a study of the protagonists in Lambda- and Stonewall-winning YA novels from 2000-2013 reveals three findings: the dominance of White, gay, male characters contradicts the trend toward strong female protagonists in mainstream YA; stories about lesbians are primarily tragic; and there are no bisexual protagonists.

  11. Winning strategies for pseudo-telepathy games using single non-local box

    OpenAIRE

    Kunkri, Samir; Kar, Guruprasad; Ghosh, Sibasish; Roy, Anirban

    2006-01-01

    Using a single NL-box, a winning strategy is given for the impossible colouring pseudo-telepathy game for the set of vectors having Kochen-Specker property in four dimension. A sufficient condition to have a winning strategy for the impossible colouring pseudo-telepathy game for general $d$-dimension, with single use of NL-box, is then described. It is also shown that the magic square pseudo-telepathy game of any size can be won by using just two ebits of entanglement -- for quantum strategy,...

  12. Win-stay-lose-learn promotes cooperation in the prisoner's dilemma game with voluntary participation.

    Science.gov (United States)

    Chu, Chen; Liu, Jinzhuo; Shen, Chen; Jin, Jiahua; Shi, Lei

    2017-01-01

    Voluntary participation, demonstrated to be a simple yet effective mechanism to promote persistent cooperative behavior, has been extensively studied. It has also been verified that the aspiration-based win-stay-lose-learn strategy updating rule promotes the evolution of cooperation. Inspired by this well-known fact, we combine the Win-Stay-Lose-Learn updating rule with voluntary participation: Players maintain their strategies when they are satisfied, or players attempt to imitate the strategy of one randomly chosen neighbor. We find that this mechanism maintains persistent cooperative behavior, even further promotes the evolution of cooperation under certain conditions.

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

    Science.gov (United States)

    Cowling, Ellis B; Furiness, Cari S

    2005-09-01

    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.

  14. 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.

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

    Science.gov (United States)

    Cowling, Ellis B; Furiness, Carl S

    2005-12-01

    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.

  16. 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

    ..., keno, and slot machines. (a) In general. On or after May 1, 1977, every person engaged in a trade or business and making a payment in the course of such trade or business of winnings (including winnings which are exempt from withholding under section 3402(q)(5)) of $1,200 or more from a bingo game or...

  17. 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。

  18. 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...

  19. 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

  20. 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

    . 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...

  1. 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.

  2. The cardiovascular effects of peroxisome proliferator-activated receptor agonists.

    Science.gov (United States)

    Friedland, Sayuri N; Leong, Aaron; Filion, Kristian B; Genest, Jacques; Lega, Iliana C; Mottillo, Salvatore; Poirier, Paul; Reoch, Jennifer; Eisenberg, Mark J

    2012-02-01

    Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiovascular outcomes only in select subgroups: fenofibrate in diabetic patients with metabolic syndrome, gemfibrozil in patients with dyslipidemia, and bezafibrate in patients with diabetes or metabolic syndrome. The cardiovascular safety of the new pan agonist aleglitazar, currently in phase II trials, remains to be determined. The heterogenous effects of peroxisome proliferator-activated receptor agonists to date highlight the importance of postmarketing surveillance. The critical question of why peroxisome proliferator-activated receptor agonists seem to improve cardiovascular risk factors without significantly improving cardiovascular outcomes requires further investigation.

  3. 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.

  4. 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 ...

  5. 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://...

  6. 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.

  7. Winning in NCAA Women?s Soccer: Does the Gender of the Coach Matter?

    Science.gov (United States)

    Brush, Brian C.; Naples, Gregory J.

    2011-01-01

    While women's intercollegiate soccer has grown rapidly over the past three decades, men still hold nearly two-thirds of all head coaching positions in NCAA Division I women's soccer programs. This paper explores whether the gender of the head coach affects success in winning games. After considering various reasons why gender might matter, we…

  8. Which skills and factors better predict winning and losing in high-level men's volleyball?

    Science.gov (United States)

    Peña, Javier; Rodríguez-Guerra, Jorge; Buscà, Bernat; Serra, Núria

    2013-09-01

    The aim of this study was to determine which skills and factors better predicted the outcomes of regular season volleyball matches in the Spanish "Superliga" and were significant for obtaining positive results in the game. The study sample consisted of 125 matches played during the 2010-11 Spanish men's first division volleyball championship. Matches were played by 12 teams composed of 148 players from 17 different nations from October 2010 to March 2011. The variables analyzed were the result of the game, team category, home/away court factors, points obtained in the break point phase, number of service errors, number of service aces, number of reception errors, percentage of positive receptions, percentage of perfect receptions, reception efficiency, number of attack errors, number of blocked attacks, attack points, percentage of attack points, attack efficiency, and number of blocks performed by both teams participating in the match. The results showed that the variables of team category, points obtained in the break point phase, number of reception errors, and number of blocked attacks by the opponent were significant predictors of winning or losing the matches. Odds ratios indicated that the odds of winning a volleyball match were 6.7 times greater for the teams belonging to higher rankings and that every additional point in Complex II increased the odds of winning a match by 1.5 times. Every reception and blocked ball error decreased the possibility of winning by 0.6 and 0.7 times, respectively.

  9. 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).

  10. 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.…

  11. 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

  12. 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…

  13. '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...

  14. New Liquid Crystal Smart Window and its Production Process (SmartWin II)

    DEFF Research Database (Denmark)

    Jensen, Karsten Ingerslev; Kristiansen, Finn Harken; Schultz, Jørgen Munthe

    2005-01-01

    This project is an example of applied nanotechnology, namely development of a smart window with three operating mode by means of Polymer Network Liquid Crystal (PNLC). The main objective is the implementation, owing to the conception and the realisation of a pre-industrial machine, of a smart win...

  15. The Portrayal of Older People in Award-Winning Literature for Children.

    Science.gov (United States)

    Dellmann-Jenkins, Mary; Yang, Lisa

    1997-01-01

    Examined illustrations for portrayal of older adult characters in Caldecott Medal-winning picture books, comparing 1972-83 and 1984-95 winners. Found that recent books portray elderly in a more positive manner than earlier winners. In addition, only two significant gender differences in a field of 36 possibilities were found over the entire…

  16. Telling Tales about Gender: A Critical Analysis of Caldecott Medal-Winning Picturebooks, 1938-2011

    Science.gov (United States)

    Crisp, Thomas; Hiller, Brittany

    2011-01-01

    In the world of children's literature, analyses of the distribution and representation of gender, biological sex, and gendered behavior in picturebooks often focused on Caldecott Award-winning literature. As the most prestigious award for American children's picturebooks, titles that receive this honor have a profound influence on the field of…

  17. Winning in the Rural Zone: How Cam Henderson Invented the Zone Defense.

    Science.gov (United States)

    Barnett, Bob

    1992-01-01

    Assesses the distinguished coaching career of Cam Henderson, who won over 611 games in 36 seasons of college basketball and coached over 151 college football wins at West Virginia colleges, mainly at Marshall University (Huntington). His influence has been so pervasive that Marshall University's basketball arena is named in his honor. (LP)

  18. Clients' Experience with Vouchered On-The-Job Training in the Portland Win Program.

    Science.gov (United States)

    Wulf, Douglas; And Others

    From 1974 through 1976, a program to test the feasibility of vouchering manpower training was incorporated into the existing Work Incentive (WIN) program in Portland, Oregon. The purpose of the second phase of the program was to evaluate the feasibility of incorporating vouchers into an on-the-job (OJT) program as an optional component that…

  19. Deploying the Win TR-20 computational engine as a web service

    Science.gov (United States)

    Despite its simplicity and limitations, the runoff curve number method remains a widely-used hydrologic modeling tool, and its use through the USDA Natural Resources Conservation Service (NRCS) computer application WinTR-20 is expected to continue for the foreseeable future. To facilitate timely up...

  20. WinAmphcal: A Windows program for the IMA-04 amphibole classification

    Science.gov (United States)

    Yavuz, Fuat

    2007-01-01

    A Microsoft© Visual Basic (6.0) program, called WinAmphcal, has been developed to calculate structural formulae of both wet-chemical and microprobe-derived amphibole analyses. On the basis of the standard International Mineralogical Association (IMA-04) classification procedure, WinAmphcal classifies amphibole analyses into five groups and then determines a specific amphibole name with prefixes and modifiers. This software is developed to predict cation site allocations at the different structural positions as well as to estimate stoichiometric Fe3+ and H2O contents from microprobe analyses. If Fe2O3 content is unknown, the program calculates ferric iron content on the basis of the minimum Fe3+ (15eNK) and maximum (13eCNK) criteria considering the site assignments and stoichiometric constraints. Other user-defined calculation and normalization factors can also be carried out by current software for the process of amphibole chemical analyses. Using the charge-balance method, WinAmphcal permits the user to determine the Mn2+ and Mn3+ states from Mn3+-rich microprobe-derived sodic amphiboles. WinAmphcal stores all the calculated results in an Excel file. Hence output of the program can also be displayed and processed by any other software for general data manipulation and graphing purposes.

  1. Results of a Test and Win Contest to Raise Radon Awareness in Urban and Rural Settings

    Science.gov (United States)

    Hahn, Ellen J.; Rayens, Mary Kay; Kercsmar, Sarah E.; Robertson, Heather; Adkins, Sarah M.

    2014-01-01

    Background: Radon is a leading cause of lung cancer, but few test their homes to determine radon levels. Purpose: The study assessed feasibility and success of a Test and Win Contest to promote radon testing in rural and urban communities. Methods: The prospective, quasi-experimental study tested a novel contest to raise radon awareness. Paid and…

  2. Issues of Exceptionality, Gender, and Power: Exploring Canadian Children's Award-Winning Literature

    Science.gov (United States)

    Taber, Nancy; Woloshyn, Vera

    2011-01-01

    This article explores the gendered ways in which issues of ability and exceptionality are presented in Governor-General award-winning Canadian children's literature. In much of contemporary feminist thought, there is a strong focus on intersecting oppressions with gender as a central analytic lens. However, ability is still largely absent. Our aim…

  3. 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

  4. 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

    /13) pathway. The recognition pattern of wFw-Isn-NH(2) with the ghrelin receptor also differed significantly from that of all previously characterized unbiased agonists. Most importantly, wFw-Isn-NH(2) was not dependent on GluIII:09 (Glu3.33), which otherwise is an obligatory TM III anchor point residue...... orientation as compared with, for example, the wFw peptide agonists. It is concluded that the novel peptide-mimetic ligand wFw-Isn-NH(2) is a biased ghrelin receptor agonist and that the selective signaling pattern presumably is due to its unique receptor recognition pattern lacking interaction with key...

  5. Nicotine receptor partial agonists for smoking cessation

    Directory of Open Access Journals (Sweden)

    Kate Cahill

    Full Text Available BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist and reducing smoking satisfaction (acting as an antagonist. OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist' in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialized register was in December 2011. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up. The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs, using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two recent cytisine trials (937 people

  6. MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

    Directory of Open Access Journals (Sweden)

    Ni Luh Putu Ayu Maha Iswari

    2013-04-01

    Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

  7. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    Science.gov (United States)

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs.

  8. Toll-like receptor agonists in cancer therapy

    OpenAIRE

    Adams, Sylvia

    2009-01-01

    Toll-like receptors (TLRs) are pattern-recognition receptors related to the Drosophila Toll protein. TLR activation alerts the immune system to microbial products and initiates innate and adaptive immune responses. The naturally powerful immunostimulatory property of TLR agonists can be exploited for active immunotherapy against cancer. Antitumor activity has been demonstrated in several cancers, and TLR agonists are now undergoing extensive clinical investigation. This review discusses recen...

  9. Short-Acting Beta-Agonist Research: A Perspective

    Directory of Open Access Journals (Sweden)

    Malcolm R Sears

    2001-01-01

    Full Text Available Asthma mortality increased sharply in New Zealand in 1977, prompting a national investigation into circumstances of asthma deaths. Subsequent observations of improved asthma control in subjects withdrawn from regular beta2-agonist treatment raised the question of whether asthma severity and, therefore, mortality could relate to frequent beta-agonist use. A randomized controlled trial of regular inhaled fenoterol versus as-needed bronchodilator use showed worsened asthma control during regular treatment despite concomitant use of inhaled corticosteroids. Assessment of these findings led to delay in the publishing of the American Asthma Guidelines, which were modified to suggest caution in using beta2-agonist treatments. Simultaneously, case control studies in New Zealand suggested that prescription of fenoterol was a substantial risk factor for asthma mortality. The causal association was hotly debated, but increasing evidence pointed to an adverse effect of fenoterol on asthma severity and, hence, mortality. This was supported by dramatic decreases in both morbidity and mortality when fenoterol was effectively withdrawn from use in New Zealand. The link between worsening asthma morbidity and mortality, and the use of potent short-acting beta2-agonists fulfills the Bradford Hill criteria for attributing causality. Application of evidence from randomized, controlled trials of short-acting beta-agonist use has led to a major shift in therapy in asthma to the recommendation of as-needed use only of short-acting beta-agonists and decreased patient reliance on regular bronchodilator therapy.

  10. Histamine H3-receptor inverse agonists as novel antipsychotics.

    Science.gov (United States)

    Ito, Chihiro

    2009-06-01

    Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.

  11. WinCE上SIP移动终端的设计与实现%Design and Implementation of SIP Mobile Terminal on WinCE

    Institute of Scientific and Technical Information of China (English)

    雷为民; 李文锋; 李世杰

    2008-01-01

    VoIP(Voice Over IP)和WLAN(Wireless LAN)两种主导技术的结合,产生了一种新的应用,VoIP on WLAN(无线局域网上的VoIP).本文在系统分析WLAN和VoIP相关技术的基础上,设计实现了一个基于嵌入式平台WinCE的VoIP无线终端软件,并给出了测试结果和评价.

  12. 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

    2014-05-01

    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 pointsSuccessful 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 to

  13. 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

  14. 用模拟仿真技术补充WinCC的显示功能%Studies on the Application of Simulation Technology to Supplement WinCC's Display Function

    Institute of Scientific and Technical Information of China (English)

    王辉

    2010-01-01

    通过介绍WinCC,Creator,LynX,Vega等软件的功能以及使用这些软件传送数据的方法,创建了三维场景Vega应用程序定义文件,最终调用Vega API函数实时操纵三维场景中模型的运动,补充了WinCC的显示功能.

  15. 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.

  16. A point-by-point analysis of performance in a fencing match: psychological processes associated with winning and losing streaks.

    Science.gov (United States)

    Doron, Julie; Gaudreau, Patrick

    2014-02-01

    This study aimed to revisit the complex nature of serial dependency of performance during a match, examining the prospective associations between psychological processes and subsequent performance at the within-person level of analysis, and explore whether psychological processes are associated with the likelihood of winning series of points. A process-oriented sequential approach was used with 16 elite fencers during a simulated competition. Multilevel regression analyses revealed that serial dependency of performance fluctuates within a match. Results of a Bayesian multilevel structural equation model showed that prior performance subsequently influenced psychological processes. Although psychological processes did not predict performance in the subsequent point, successive winnings were associated with higher perceived control and task-oriented coping and lower negative affectivity compared with both losing streaks and nonstreaks. Overall, serial dependencies of performance are nonstationary during a match whereas psychological processes significantly differ in episodes of winning after winning versus losing after losing.

  17. Cytisine-based nicotinic partial agonists as novel antidepressant compounds.

    Science.gov (United States)

    Mineur, Yann S; Eibl, Christoph; Young, Grace; Kochevar, Christopher; Papke, Roger L; Gündisch, Daniela; Picciotto, Marina R

    2009-04-01

    Nicotine and other nicotinic agents are thought to regulate mood in human subjects and have antidepressant-like properties in animal models. Recent studies have demonstrated that blockade of nicotinic acetylcholine receptors (nAChRs) including those containing the beta2 subunit (beta2(*)), results in antidepressant-like effects. Previous studies have shown that cytisine, a partial agonist at alpha4/beta2(*) nAChRs, and a full agonist at alpha3/beta4(*) and alpha7 nAChRs, has antidepressant-like properties in several rodent models of antidepressant efficacy; however, it is not clear whether more selective partial agonists will also be effective in these models. We tested cytisine and two derivatives, 5-bromo-cytisine (5-Br-Cyt) and 3-(pyridin-3'-yl)-cytisine (3-pyr-Cyt) for their ability to act as a partial agonist of different nAChR subtypes and to show antidepressant-like activity in C57/BL6 mice in the tail suspension, the forced-swim, and the novelty-suppressed feeding tests. 3-pyr-Cyt was a partial agonist with very low efficacy at alpha4/beta2(*) nAChRS but had no agonist effects at other nAChRs normally targeted by cytisine, and it was effective in mouse models of antidepressant efficacy. Animals showed dose-dependent antidepressant-like effects in all three behavioral paradigms. 5-Br-Cyt was not effective in behavioral tests when administered peripherally, probably because of its inability to penetrate the blood-brain barrier, because it efficiently reduced immobility in the tail suspension test when administered intraventricularly. These results suggest that novel nicotinic partial agonists may provide new possibilities for development of drugs to treat mood disorders.

  18. 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.

  19. 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.``

  20. Romiplostim: a second-generation thrombopoietin agonist.

    Science.gov (United States)

    Cohn, Claudia S; Bussel, James B

    2009-03-01

    in bone marrow reticulin have been reported. Other TPO nonpeptide mimetics have been created by using a similar strategy with libraries of nonpeptide molecules that can stimulate TPO-dependent cell lines. Eltrombopag and AKR-501 are two drugs of this type that have shown positive results in clinical trials. In addition, antibodies that can stimulate the c-Mpl receptor are being engineered to act as potent TPO agonists. These and other drugs in preclinical development represent a new line of therapy for thrombocytopenic patients.

  1. 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.

  2. 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.

  3. 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。

  4. 揭秘Win7新的命令行Power Shell

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Win7中集成了PowerShell2.0,如今任何GUI执行的管理任务(例如控制系统,访问注册表、系统日志和数字签名证书等数据)都能通过PowerShell脚本来完成了,如果你的系统是WinXP/Vista/2003/2008,只需到http://support.microsoft.corn/kb/968929下载安装PowerShell2.0,即可使用这个新一代的命令行工具!

  5. 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.

  6. 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.

  7. Win32环境下微机与GPS模块的串行通信编程%Computer-GPS Serial Communication Technique under Win32 Environment

    Institute of Scientific and Technical Information of China (English)

    李蓉艳; 何正耀; 张翼鹏

    2003-01-01

    文中结合实际应用对GPS全球定位系统的定位导航信息的接收和参数数据的提取进行了讨论,在Win32环境下(Windows9x/NT/2000)基于Borland C++ Builder开发平台实现微计算机与GPS接收模块的串行通信编程.详细介绍了GPS数据通信的基本概念和数据格式,以及在Windows消息机制下的多线程异步串行通信机制,采用VCL组件技术实现Win32环境下与GPS数据通信程序的快速开发.应用该方法编写的程序简单方便,可以将卫星定位导航信息从GPS接收机完整传送到微计算机中,数据通信功能稳定可靠.

  8. What Trump and Clinton must do to win Monday’s first\\ud presidential debate

    OpenAIRE

    Klaas, Brian

    2016-01-01

    Hillary Clinton and Donald Trump will go head to head in the first presidential election debate on\\ud Monday. Brian Klaas writes that debates matter; just one gaffe can derail a candidacy. He writes\\ud that to win, Clinton should knock Trump off script, address her email scandal head on, and\\ud showcase her steady temperament. For Trump to come out on top he must stay relaxed, soften his\\ud image, and lower expectations.

  9. 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.

  10. 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

  11. 勇于挑战丽台WinFast PX7600GT TDH超频版

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    丽台科技(Leadtek)推出了一款采用GeForce7600GT图形芯片的WinFast PX7600GT TDH超频版显卡.这敕显卡是丽台为中端用户精心设计的产品.采用1.2ns的DDR3内存颗粒.总容量256MB.位宽128bit。工作频率方面.WinFast PX7600GT TDH超频版的核心,显存工作频率分别为590/1600MHz.超过了nVIDIA官方的默认工作频率.而且GDDR3显存还具有很出色的超频能力。针对超频玩家.丽台对WinFast PX7600GT TDH超频版显卡的散热部分进行全新设计.较大的散热片能够迅速吸收核心瞬间产生的巨大热量.使冷却性能较公板提升30%-35%。

  12. Winning and losing tree species of reassembly in Minnesota's mixed and broadleaf forests.

    Science.gov (United States)

    Hanberry, Brice B; Palik, Brian J; He, Hong S

    2013-01-01

    We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota's mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity.

  13. Winning and Losing Tree Species of Reassembly in Minnesota’s Mixed and Broadleaf Forests

    Science.gov (United States)

    Hanberry, Brice B.; Palik, Brian J.; He, Hong S.

    2013-01-01

    We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota’s mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity. PMID:23613911

  14. Winning and losing tree species of reassembly in Minnesota's mixed and broadleaf forests.

    Directory of Open Access Journals (Sweden)

    Brice B Hanberry

    Full Text Available We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota's mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity.

  15. 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

  16. 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

  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.

  19. 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.

  20. 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.

  1. 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.

  2. Role of dopamine agonists in Parkinson's disease: an update.

    Science.gov (United States)

    Bonuccelli, Ubaldo; Pavese, Nicola

    2007-10-01

    At present, dopamine agonists play an important role in antiparkinsonian therapy since they were proved effective in the management of both advanced- and early-stage Parkinson's disease. In the latter, they are often regarded as first-choice medication to delay the introduction of levodopa therapy. Despite sharing the capacity to directly stimulate dopamine receptors, dopamine agonists show different pharmacological properties as they act on different subsets of dopamine receptors. This, in theory, provides the advantage of obtaining a different antiparkinsonian activity or safety profile with each agent. However, there is very little evidence that any of the marketed dopamine agonists should be consistently preferred in the management of patients with Parkinson's disease. Pergolide and cabergoline are now considered a second-line choice after the proven association with valvular fibrosis. Transdermal administration (rotigotine) and subcutaneous infusion (apomorphine) of dopamine receptor agonists are now available alternatives to oral administration and provide continuous dopaminergic stimulation. Continuous subcutaneous apomorphine infusion during waking hours leads to a large reduction in daily 'off' time, dyskinesias and levodopa daily dose. Almost all currently used dopamine agonists are able to provide neuroprotective effects towards dopaminergic neurons during in vitro and in vivo experiments. This neuroprotection may be the result of different mechanisms including antioxidation, scavenging of free radicals, suppression of lipid peroxidation and inhibition of apoptosis. However, the disease-modifying effect of these agents in Parkinson's disease remains to be ascertained.

  3. Intracerebroventricular administration of kappa-agonists induces convulsions in mice.

    Science.gov (United States)

    Bansinath, M; Ramabadran, K; Turndorf, H; Shukla, V K

    1991-07-01

    Intracerebroventricular (ICV) administration of kappa-agonists (PD 117302, U-50488H and U-69593) induced convulsions in a dose-related manner in mice. The dose at which 50% of animals convulsed (CD50) was in nmol ranges for all opioids. Among the opioids used, PD 117302 was the most potent convulsant. ICV administration of either vehicle alone or U-53445E, a non-kappa-opioid (+) enantiomer of U-50488H did not induce convulsions. The convulsive response of kappa-agonists was differentially susceptible for antagonism by naloxone and/or MR 2266. Collectively, these findings support the view that convulsions induced by kappa-agonists in mice involve stereospecific opioid receptor mechanisms. Furthermore, the convulsant effect of kappa-agonists could not be modified by pretreatment with MK-801, ketamine, muscimol or baclofen. It is concluded that kappa-opioid but not NMDA or GABA receptor mechanisms are involved in convulsions induced by kappa-agonists. These results are the first experimental evidence implicating stereospecific kappa-receptor mechanisms in opioid-induced convulsions in mice.

  4. In silico discovery of novel Retinoic Acid Receptor agonist structures

    Directory of Open Access Journals (Sweden)

    Samuels Herbert H

    2001-06-01

    Full Text Available Abstract Background Several Retinoic Acid Receptors (RAR agonists have therapeutic activity against a variety of cancer types; however, unacceptable toxicity profiles have hindered the development of drugs. RAR agonists presenting novel structural and chemical features could therefore open new avenues for the discovery of leads against breast, lung and prostate cancer or leukemia. Results We have analysed the induced fit of the active site residues upon binding of a known ligand. The derived binding site models were used to dock over 150,000 molecules in silico (or virtually to the structure of the receptor with the Internal Coordinates Mechanics (ICM program. Thirty ligand candidates were tested in vitro. Conclusions Two novel agonists resulting from the predicted receptor model were active at 50 nM. One of them displays novel structural features which may translate into the development of new ligands for cancer therapy.

  5. Compulsive eating and weight gain related to dopamine agonist use.

    Science.gov (United States)

    Nirenberg, Melissa J; Waters, Cheryl

    2006-04-01

    Dopamine agonists have been implicated in causing compulsive behaviors in patients with Parkinson's disease (PD). These have included gambling, hypersexuality, hobbyism, and other repetitive, purposeless behaviors ("punding"). In this report, we describe 7 patients in whom compulsive eating developed in the context of pramipexole use. All of the affected patients had significant, undesired weight gain; 4 had other comorbid compulsive behaviors. In the 5 patients who lowered the dose of pramipexole or discontinued dopamine agonist treatment, the behavior remitted and no further weight gain occurred. Physicians should be aware that compulsive eating resulting in significant weight gain may occur in PD as a side-effect of dopamine agonist medications such as pramipexole. Given the known risks of the associated weight gain and obesity, further investigation is warranted.

  6. 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.

  7. 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 was to inve......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...

  8. Partial agonistic action of endomorphins in the mouse spinal cord.

    Science.gov (United States)

    Mizoguchi, H; Wu, H E; Narita, M

    2001-09-07

    The partial agonistic properties of endogenous mu-opioid peptides endomorphin-1 and endomorphin-2 for G-protein activation were determined in the mouse spinal cord, monitoring the increases in guanosine-5'-o-(3-[35S]thio)triphosphate binding. The G-protein activation induced by endogenous opioid peptide beta-endorphin in the spinal cord was significantly, but partially, attenuated by co-incubation with endomorphin-1 or endomorphin-2. The data indicates that endomorphin-1 and endomorphin-2 are endogenous partial agonists for mu-opioid receptor in the mouse spinal cord.

  9. Pyrrolo- and pyridomorphinans: non-selective opioid antagonists and delta opioid agonists/mu opioid partial agonists.

    Science.gov (United States)

    Kumar, V; Clark, M J; Traynor, J R; Lewis, J W; Husbands, S M

    2014-08-01

    Opioid ligands have found use in a number of therapeutic areas, including for the treatment of pain and opiate addiction (using agonists) and alcohol addiction (using antagonists such as naltrexone and nalmefene). The reaction of imines, derived from the opioid ligands oxymorphone and naltrexone, with Michael acceptors leads to pyridomorphinans with structures similar to known pyrrolo- and indolomorphinans. One of the synthesized compounds, 5e, derived from oxymorphone had substantial agonist activity at delta opioid receptors but not at mu and/or kappa opioid receptors and in that sense profiled as a selective delta opioid receptor agonist. The pyridomorphinans derived from naltrexone and naloxone were all found to be non-selective potent antagonists and as such could have utility as treatments for alcohol abuse.

  10. 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

  11. Design for Paperless Recorder Based on ARM and WinCE%基于ARM&WinCE的无纸记录仪

    Institute of Scientific and Technical Information of China (English)

    刘立阳; 张金成

    2011-01-01

    采用ARM微处理器作为主控芯片,基于嵌入式Windows CE操作系统设计了一种新型的无纸记录仪系统.数据采集底层硬件采用万能输入采集控制电路,可以实现64路标准电压、电流、电阻等万能信号隔离输入.软件设计实现了在Platform Builder 5.0环境中支持开发板的WinCE系统层定制,应用程序部分采用多线程编程技术,提高了程序的运行性能.该系统配置高亮度彩色液晶屏、CCFL背光使画面显示更加清晰,支持触控式人机交互功能.%Using ARM microprocessor as the MPU,this paper designed a new paperless recorder system based on embedded Windows CE operating system. It used universal input record and control circuit,and could realize signal universal isolated input from 64 paths,such as standard pressure,current,resistance,etc. In respect of software,it realizes WinCE system layer' s custom made which supported development board in environment of Platform Builder 5. 0. In part of application, the system employed multithreaded programming technique which increases program' s operating capability. At the same time, high light color LCD and CCFL backlight makes the picture clearer which also supports touch control interactive function.

  12. Driver Design of nRF24L01 under ARM and WinCE6.0%ARM和WinCE6.0下nRF24L01的驱动设计

    Institute of Scientific and Technical Information of China (English)

    朱志斌; 刘振来

    2012-01-01

    随着嵌入式WinCE系统的发展和近距离无线通信的广泛使用,有必要为近距离无线通信芯片编写驱动。由于nRF24L01在WinCE系统下驱动的缺乏,使得WinCE与nRF24L01芯片之间的直接通信成为困难。本文的驱动设计正好解决了这一难题。%With the development of embedded WinCE system and extensive use of short range wireless communication, it is necessary to write drivers for short range wireless communication chip. Because of lack of drivers, it is difficult to complete direct communication be- tween WinCE and nRF24L01. Designed driver in this paper just solves the difficult problem.

  13. Melatonin agonists for treatment of sleep and depressive disorders

    Directory of Open Access Journals (Sweden)

    Seithikurippu R. Pandi-Perumal

    2011-06-01

    Full Text Available 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 promoting properties have been introduced in clinical practice. Ramelteon, the MT1/ MT2 melatonergic agonist, has been used in a large number of clinical trials involving chronic insomniacs and has been found effective in improving the total sleep time and sleep efficiency of insomniacs and has not manifested serious adverse effects. The development of another MT1/MT2 melatonergic agonist agomelatine with antagonsim to 5-HT2c serotonin receptors has been found useful not only in treating sleep problems of patients but also as a first line antidepressant with earlier onset of actions in patients with major depressive disorder. An agonist for MT3 melatonin receptor has also been found effective in animal models of depression. [J Exp Integr Med 2011; 1(3.000: 149-158

  14. [Alpha 2-adrenoceptor agonists for the treatment of chronic pain].

    Science.gov (United States)

    Kulka, P J

    1996-04-25

    The antinociceptive effect of alpha(2)-adrenoceptor agonists is mediated by activation of descending inhibiting noradrenergic systems, which modulates 'wide-dynamic-range' neurones. Furthermore, they inhibit the liberation of substance P and endorphines and activate serotoninergic neurones. Despite this variety of antinociceptive actions, there is still little experience with alpha(2)-adrenoceptor agonists as therapeutic agents for use in chronic pain syndromes. Studies in animals and patients have shown that the transdermal, epidural and intravenous administration of the alpha(2)-adrenoceptor agonist clonidine reduces pain intensity in neuropathic pain syndromes for periods varying from some hours up to 1 month. Patients suffering from lancinating or sharp pain respond best to this therapy. Topically applied clonidine (200-300 microg) relieves hyperalgesia in sympathetically maintained pain. Epidural administration of 300 microg clonidine dissolved in 5 ml NaCl 0.9 % has also been shown to be effective. In patients suffering from cancer pain tolerant to opioids, pain control has proved possible again with combinations of opioids and clonidine. In isolated cases clonidine has been administered epidurally at a dose of 1500 microg/day for almost 5 months without evidence for any histotoxic property of clonidine. Side effects often observed during administration of alpha(2)-adrenoceptor agonists are dry mouth, sedation, hypotension and bradycardia. Therapeutic interventions are usually not required.

  15. 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...

  16. Use of ß-adrenergic agonists in hybrid catfish

    Science.gov (United States)

    Ractopamine hydrochloride (RH) is a potent ß-adrenergic agonist that has been used in some species of fish to improve growth performance and dress out characteristics. While this metabolic modifier has been shown to have positive effects on growth of fish, little research has focused on the mechani...

  17. 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...

  18. 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.

  19. Principles of agonist recognition in Cys-loop receptors

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Pless, Stephan Alexander

    2014-01-01

    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...

  20. 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.

  1. 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.

  2. 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

  3. Melatonin receptor agonists: new options for insomnia and depression treatment.

    Science.gov (United States)

    Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Mor, Marco

    2011-12-01

    The circadian nature of melatonin (MLT) secretion, coupled with the localization of MLT receptors to the suprachiasmatic nucleus, has led to numerous studies of the role of MLT in modulation of the sleep-wake cycle and circadian rhythms in humans. Although much more needs to be understood about the various functions exerted by MLT and its mechanisms of action, three therapeutic agents (ramelteon, prolonged-release MLT, and agomelatine) are already in use, and MLT receptor agonists are now appearing as new promising treatment options for sleep and circadian-rhythm related disorders. In this review, emphasis has been placed on medicinal chemistry strategies leading to MLT receptor agonists, and on the evidence supporting therapeutic efficacy of compounds undergoing clinical evaluation. A wide range of clinical trials demonstrated that ramelteon, prolonged-release MLT and tasimelteon have sleep-promoting effects, providing an important treatment option for insomnia and transient insomnia, even if the improvements of sleep maintenance appear moderate. Well-documented effects of agomelatine suggest that this MLT agonist offers an attractive alternative for the treatment of depression, combining efficacy with a favorable side effect profile. Despite a large number of high affinity nonselective MLT receptor agonists, only limited data on MT₁ or MT₂ subtype-selective compounds are available up to now. Administration of the MT₂-selective agonist IIK7 to rats has proved to decrease NREM sleep onset latency, suggesting that MT₂ receptor subtype is involved in the acute sleep-promoting action of MLT; rigorous clinical studies are needed to demonstrate this hypothesis. Further clinical candidates based on selective activation of MT₁ or MT₂ receptors are expected in coming years.

  4. 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

  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. WIN EPISCOPE 2.0: improved epidemiological software for veterinary medicine.

    Science.gov (United States)

    Thrusfield, M; Ortega, C; de Blas, I; Noordhuizen, J P; Frankena, K

    2001-05-05

    Recent changes in veterinary medicine have required quantitative epidemiological techniques for designing field surveys, identifying risk factors for multifactorial diseases, and assessing diagnostic tests. Several relevant techniques are brought together in the package of veterinary epidemiological computer software, WIN EPISCOPE 2.0, described in this paper. It is based on Microsoft Windows and includes modules for the design and analysis of field surveys, control campaigns and observational studies, and a simple mathematical model. It provides comprehensive 'Help' screens and should therefore be useful not only in field investigations but also for teaching veterinary epidemiology.

  7. 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。

  8. 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...

  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. Winning with Green Remediation Practices at the Former McClellan AFB, Sacramento CA

    Science.gov (United States)

    2011-05-12

    Winning with Green Remediation Practices at the Former McClellan AFB , Sacramento CA Mr. Steve Mayer, PMP, P.E. McClellan Remediation Program Manger...with Green Remediation Practices at the Former McClellan AFB , Sacramento CA 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...Hughes Ave., Suite 121,Lackland AFB ,TX,78236-9821 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES

  11. 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。

  12. 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

  13. 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.

  14. Structural determinants of agonist-specific kinetics at the ionotropic glutamate receptor 2

    DEFF Research Database (Denmark)

    Holm, Mai Marie; Lunn, Marie-Louise; Traynelis, Stephen F;

    2005-01-01

    Glutamate receptors (GluRs) are the most abundant mediators of the fast excitatory neurotransmission in the human brain. Agonists will, after activation of the receptors, induce different degrees of desensitization. The efficacy of agonists strongly correlates with the agonist-induced closure of ...

  15. Agonist signalling properties of radiotracers used for imaging of dopamine D-2/3 receptors

    NARCIS (Netherlands)

    van Wieringen, Jan-Peter; Michel, Martin C.; Janssen, Henk M.; Janssen, Anton G.; Elsinga, Philip H.; Booij, Jan

    2014-01-01

    Background: Dopamine D-2/3 receptor (D2/3R) agonist radiopharmaceuticals are considered superior to antagonists to detect dopamine release, e.g. induced by amphetamines. Agonists bind preferentially to the high-affinity state of the dopamine D2R, which has been proposed as the reason why agonists ar

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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?

  1. Close games versus blowouts: Optimal challenge reinforces one's intrinsic motivation to win.

    Science.gov (United States)

    Meng, Liang; Pei, Guanxiong; Zheng, Jiehui; Ma, Qingguo

    2016-12-01

    When immersed in intrinsically motivating activities, individuals actively seek optimal challenge, which generally brings the most satisfaction as they play hard and finally win. To better simulate real-life scenarios in the controlled laboratory setting, a two-player online StopWatch (SW) game was developed, whose format is similar to that of a badminton tournament. During the game, a male opponent played by a confederate ensured that the same-sex participant paired with him won both matches, one with a wide margin (the lack of challenge condition) and another with a narrow one (the optimal challenge condition). Electrophysiological data were recorded during the entire experiment. An enlarged Stimulus-preceding negativity (SPN) was observed in the optimal challenge condition, indicating a more concentrated anticipatory attention toward the feedback and a stronger intrinsic motivation during close games. Thus, this study provided original neural evidence for predictions of Self-determination theory (SDT) and Flow theory, and confirmed and emphasized the significant role of optimal challenge in promoting one's intrinsic motivation to win.

  2. 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.

  3. 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.

  4. A win for HROs. Employing high-reliability organization characteristics in EMS.

    Science.gov (United States)

    Heightman, A J

    2013-06-01

    Was I insubordinate, arrogant or disrespectful? You may feel that I was. But in reality, I was educated to a level that could have been validated and should have been respected by command. I was, in fact, practicing a key aspect of HRO. I was stopping an obvious dangerous condition before it could harm or kill emergency responders. My IC colleague knew it from the facts presented and, in fact, joked with me about my "subtle sarcasm" and moved the perimeter to the recommended half-mile distance. Did I win, or did a proactive HRO win? Actually, HRO won and potentially saved 30 lives. I simply presented the hazards of CFC inhalation. A high-reliability organization must not rely on only one source of data when detailed information on a hazard isn't immediately available, or if it isn't very informative during an emergency decision-making process. Read "EMS & High Reliability Organizing: Achieving safety & reliability in the dynamic, high-risk environment and practice its important principles," pp. 60-63. It's really common sense, not rocket science, and may save you, your crews or others in your community.

  5. 基于BioWin的MBR工艺模拟%Bio Win-based MBR process modeling

    Institute of Scientific and Technical Information of China (English)

    艾冰; 郝二成; 顾剑; 许世伟; 李胜田; 周军

    2011-01-01

    以实际运行污水处理厂MBR工艺为研究对象,利用BioWinTM软件平台及其内嵌的通用活性污泥模型和厌氧消化模型(ASDM),建立了工艺模拟模型并进行初步模拟及校正,利用校正的模型对MBR工艺的运行参数进行了模拟分析,得到出水水质对工艺参数的敏感度,从而总结出了部分运行指南.%Taking the actual operating MBR process in wastewater treatment plant as the object, and using the BioWinTM software platform and the embedded general activated sludge/anaerobic digestion model (ASDM), this paper set up a process simulation model and carried the primary simulation and calibration. The simulation analysis of the MBR operation parameters was carried out with the calibrated model, and the sensitivity of the water quality to the process parameters was figured out and partial operation manual was also summarized.

  6. Modeling Sensitivities to the 20% Wind Scenario Report with the WinDS Model

    Energy Technology Data Exchange (ETDEWEB)

    Blair, N.; Hand, M.; Short, W.; Sullivan, P.

    2008-06-01

    In May 2008, DOE published '20% Wind Energy by 2030', a report which describes the costs and benefits of producing 20% of the nation's projected electricity demand in 2030 from wind technology. The total electricity system cost resulting from this scenario was modestly higher than a scenario in which no additional wind was installed after 2006. NREL's Wind Deployment System (WinDS) model was used to support this analysis. With its 358 regions, explicit treatment of transmission expansion, onshore siting considerations, shallow- and deep-water wind resources, 2030 outlook, explicit financing assumptions, endogenous learning, and stochastic treatment of wind resource variability, WinDS is unique in the level of detail it can bring to this analysis. For the 20% Wind Energy by 2030 analysis, the group chose various model structures (such as the ability to wheel power within an interconnect), and the wind industry agreed on a variety of model inputs (such as the cost of transmission or new wind turbines). For this paper, the analysis examined the sensitivity of the results to variations in those input values and model structure choices. These included wind cost and performance improvements over time, seasonal/diurnal wind resource variations, transmission access and costs, siting costs, conventional fuel cost trajectories, and conventional capital costs.

  7. WinClastour—a Visual Basic program for tourmaline formula calculation and classification

    Science.gov (United States)

    Yavuz, Fuat; Yavuz, Vural; Sasmaz, Ahmet

    2006-10-01

    WinClastour is a Microsoft ® Visual Basic 6.0 program that enables the user to enter and calculate structural formulae of tourmaline analyses obtained both by the electron-microprobe or wet-chemical analyses. It is developed to predict cation site-allocations at the different structural positions, as well as to estimate mole percent of the end-members of the calcic-, alkali-, and X-site vacant group tourmalines. Using the different normalization schemes, such as 24.5 oxygens, 31 anions, 15 cations ( T+ Z+ Y), and 6 silicons, the present program classifies tourmaline data based on the classification scheme proposed by Hawthorne and Henry [1999. Classification of the minerals of the tourmaline group. European Journal of Mineralogy 11, 201-215]. The present program also enables the user Al-Mg disorder between Y and Z sites. WinClastour stores all the calculated results in a comma-delimited ASCII file format. Hence, output of the program can be displayed and processed by any other software for general data manipulation and graphing purposes. The compiled program code together with a test data file and related graphic files, which are designed to produce a high-quality printout from the Grapher program of Golden Software, is approximately 3 Mb as a self-extracting setup file.

  8. 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.

  9. Controller of heat pump water heater based on WinCE%基于WinCE的热泵热水机控制器

    Institute of Scientific and Technical Information of China (English)

    吴宇明; 姜周曙; 黄国辉; 徐平

    2011-01-01

    针对目前市场上大型热泵热水机控制器价格高、硬件模块多及远程监控性能不足等问题,研制了一种基于ARM9和WinCE操作系统的热泵热水机控制器.以S3C2410A和STM32F103VC为硬件平台核心,设计了人机交互单元和数据采集控制单元;以嵌入式Windows CE 5.0为操作系统,利用EVC开发应用软件,并重点阐述了系统结构、各主要模块的硬件电路及工作原理和应用程序的设计方法及编程要点.实际应用结果表明,该控制系统操作简便、功能完善、性能稳定,控制精度达到了使用要求.%Aiming at high cost,more hardware modules and the poor performance of remote monitoring of large heat pump water heater controller in the current market,a new heat pump water heater controller based on ARM9 and WinCE operating system was developed. Human-computer interaction,data acquisition and control unit were designed,taking S3C2410A and STM32F103VC as the cores of hardware platform. Application software was developed using EVC under Windows CE 5.0 embedded operating system. And the overall structure of the controller, the working principle of main modules and the method of applications design and programming essentials were elaborated. Practical application result indicates that the control system is easy for operation,has perfect function and stable in performance,and the control precision meets the requirements of needs.

  10. A "win-win" nanoplatform: TiO2:Yb,Ho,F for NIR light-induced synergistic therapy and imaging.

    Science.gov (United States)

    Zhou, Jie; Luo, Pei; Sun, Chong; Meng, Lingchang; Ye, Weiran; Chen, Shanshan; Du, Bin

    2017-03-14

    To avoid the defect of low energy transfer efficiency in core-shell UCNP-TiO2 NPs, doping rare earth into TiO2 and improving the photocatalytic activity of TiO2 itself under Vis-NIR light might be a more direct and efficient strategy for high (1)O2 production. Here, we designed a TiO2:Yb,Ho,F-β-CD@DTX/HA nanoplatform using TiO2:Yb,Ho,F as the core, β-CD as the drug carrier, hyaluronic acid (HA) as the capping agent and target, and then applied it for 808 nm induced photodynamic-chemotherapy and 980 nm upconversion fluorescence/MR imaging. The results were as follows: (i) for TiO2 as a photosensitizer, after doping Yb, Ho, F into TiO2, it could directly generate reactive oxygen species under an 808 nm laser; the dopants enhanced the absorption under the UV-Vis-NIR region and increased the electron-hole pair separation. (ii) For TiO2 as the upconversion host, F and Ho also endowed TiO2:Yb,Ho,F with enhanced upconversion fluorescence under a 980 nm laser and T2-MRI contrast performance (r2 = 30.71 mM(-1) s(-1)), respectively, thus, facilitating imaging for deep tissues. (iii) The HA shell outside of β-CD prevented the unexpected leaking of DTX, which improved the target abilities and achieved the enzyme-responsive drug release. The in vitro and in vivo studies also demonstrated the nanosystem could efficiently suppress tumor growth by combination therapy and had excellent imaging (UCL/MR) ability. Particularly, our work was the first example that utilized TiO2 simultaneously as a photosensitizer and upconversion host, which simplified the core-shell UCNP-TiO2 nanocomposites and reached a "win-win" cooperation in NIR-induced photodynamic therapy and UCL imaging.

  11. Win-stay-lose-learn promotes cooperation in the prisoner’s dilemma game with voluntary participation

    Science.gov (United States)

    Chu, Chen; Liu, Jinzhuo; Shen, Chen; Jin, Jiahua; Shi, Lei

    2017-01-01

    Voluntary participation, demonstrated to be a simple yet effective mechanism to promote persistent cooperative behavior, has been extensively studied. It has also been verified that the aspiration-based win-stay-lose-learn strategy updating rule promotes the evolution of cooperation. Inspired by this well-known fact, we combine the Win-Stay-Lose-Learn updating rule with voluntary participation: Players maintain their strategies when they are satisfied, or players attempt to imitate the strategy of one randomly chosen neighbor. We find that this mechanism maintains persistent cooperative behavior, even further promotes the evolution of cooperation under certain conditions. PMID:28182707

  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. 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.

  15. 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...

  16. 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."

  17. 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

  18. 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."

  19. 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.

  20. Improving the developability profile of pyrrolidine progesterone receptor partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.; Frazee, James S.; Stoy, Patrick; Johnson, Latisha; Lu, Qing; Hammond, Marlys; Barton, Linda S.; Patterson, Jaclyn R.; Azzarano, Leonard M.; Nagilla, Rakesh; Madauss, Kevin P.; Williams, Shawn P.; Stewart, Eugene L.; Duraiswami, Chaya; Grygielko, Eugene T.; Xu, Xiaoping; Laping, Nicholas J.; Bray, Jeffrey D.; Thompson, Scott K. (GSKPA)

    2010-09-17

    The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

  1. Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond.

    Science.gov (United States)

    Xia, Yang; Kellems, Rodney E

    2013-06-21

    Hypertensive disorders are life-threatening diseases with high morbidity and mortality, affecting billions of individuals worldwide. A multitude of underlying conditions may contribute to hypertension, thus the need for a plethora of treatment options to identify the approach that best meets the needs of individual patients. A growing body of evidence indicates that (1) autoantibodies that bind to and activate the major angiotensin II type I (AT₁) receptor exist in the circulation of patients with hypertensive disorders, (2) these autoantibodies contribute to disease pathophysiology, (3) antibody titers correlate to the severity of the disease, and (4) efforts to block or remove these pathogenic autoantibodies have therapeutic potential. These autoantibodies, termed AT₁ agonistic autoantibodies have been extensively characterized in preeclampsia, a life-threatening hypertensive condition of pregnancy. As reviewed here, these autoantibodies cause symptoms of preeclampsia when injected into pregnant mice. Somewhat surprisingly, these auto antibodies also appear in 3 animal models of preeclampsia. However, the occurrence of AT₁ agonistic autoantibodies is not restricted to pregnancy. These autoantibodies are prevalent among kidney transplant recipients who develop severe transplant rejection and malignant hypertension during the first week after transplantation. AT₁ agonistic autoantibodies are also highly abundant among a group of patients with essential hypertension that are refractory to standard therapy. More recently these autoantibodies have been seen in patients with the autoimmune disease, systemic sclerosis. These 3 examples extend the clinical impact of AT₁ agonistic autoantibodies beyond pregnancy. Research reviewed here raises the intriguing possibility that preeclampsia and other hypertensive conditions are autoimmune diseases characterized by the presence of pathogenic autoantibodies that activate the major angiotensin receptor, AT₁. These

  2. Agonistic Vocalisations in Domestic Cats : A Case Study

    OpenAIRE

    Schötz, Susanne

    2015-01-01

    Introducing a new cat to a home with resident cats may lead to stress, aggression and even fights. In this case study 468 agonistic cat vocalisations were recorded as one cat was introduced to three resident cats in her new home. Six vocalisation types were identified: growl, howl, howl-growl, hiss, spit and snarl. Numerous other intermediate and complex vocalisations were also observed. An acoustic analysis showed differences within and between all types. Future studies include further acous...

  3. 基于WinPcap和ARP欺骗实现交换环境嗅探%Packet sniffing in switched ethernet by WinPcap and ARP spoofing

    Institute of Scientific and Technical Information of China (English)

    孙海峰; 宋丽丽

    2007-01-01

    传统的数据嗅探方法不能在交换式局域网环境下实现.在分析了局域网的共享环境和交换环境各自特点后,基于地址解析协议ARP的工作原理,提出一种利用ARP欺骗实现中间人攻击,从而实现交换环境数据嗅探的方法.利用WinPcap驱动实现的嗅探软件降低了对操作系统版本的依赖程度,整个过程包括了ARP欺骗和欺骗后的恢复,以及数据嗅探和数据转发功能.实验表明利用ARP欺骗所实现的数据嗅探完全能够在交换式的局域网中工作,并且不会中断被攻击主机之间的正常通信.

  4. 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.

  5. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    Directory of Open Access Journals (Sweden)

    Fergus Keane

    2016-06-01

    Full Text Available Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour.

  6. 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.

  7. LHRH Agonists for the Treatment of Prostate Cancer: 2012.

    Science.gov (United States)

    Lepor, Herbert; Shore, Neal D

    2012-01-01

    The most recent guidelines on prostate cancer screening from the American Urological Association (2009), the National Comprehensive Cancer Network (2011), and the European Association of Urology (2011), as well as treatment and advances in disease monitoring, have increased the androgen deprivation therapy (ADT) population and the duration of ADT usage as the first-line treatment for metastatic prostate cancer. According to the European Association of Urology, gonadotropin-releasing hormone (GnRH) agonists have become the leading therapeutic option for ADT because they avoid the physical and psychological discomforts associated with orchiectomy. However, GnRH agonists display several shortcomings, including testosterone (T) surge ("clinical flare") and microsurges. T surge delays the intended serologic endpoint of T suppression and may exacerbate clinical symptoms. Furthermore, ADT manifests an adverse-event spectrum that can impact quality of life with its attendant well-documented morbidities. Strategies to improve ADT tolerability include a holistic management approach, improved diet and exercise, and more specific monitoring to detect and prevent T depletion toxicities. Intermittent ADT, which allows hormonal recovery between treatment periods, has become increasingly utilized as a methodology for improving quality of life while not diminishing chronic ADT efficacy, and may also provide healthcare cost savings. This review assesses the present and potential future role of GnRH agonists in prostate cancer and explores strategies to minimize the adverse-event profile for patients receiving ADT.

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

    Science.gov (United States)

    Petersen, Rasmus K.; Christensen, Kathrine B.; Assimopoulou, Andreana N.; Fretté, Xavier; Papageorgiou, Vassilios P.; Kristiansen, Karsten; Kouskoumvekaki, Irene

    2011-02-01

    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 medicine. From the resulting hits, we selected methyl oleanonate, a compound found, among others, in Pistacia lentiscus var. Chia oleoresin (Chios mastic gum). The acid of methyl oleanonate, oleanonic acid, was identified as a PPARγ agonist through bioassay-guided chromatographic fractionations of Chios mastic gum fractions, whereas some other sub-fractions exhibited also biological activity towards PPARγ. The results from the present work are two-fold: on the one hand we demonstrate that the pharmacophore model we developed is able to select novel ligand scaffolds that act as PPARγ agonists; while at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery.

  9. 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.

  10. VB程序在Win32 API及Windows消息开发中的应用%The Development Application of VB Program in the Win32 API and Windows Message

    Institute of Scientific and Technical Information of China (English)

    陈勇孝; 陆宜清

    2005-01-01

    讨论了如何在VB程序中利用Win32 API(Application Programming Interface)动态连接库DLL(Dynamic Linked Library)和Windows消息开发(Message)的程序及控制对象的方法,并扩充了VB的常规方法开发应用程序.

  11. Inhibition of retinoic acid biosynthesis by the bisdichloroacetyldiamine WIN 18,446 markedly suppresses spermatogenesis and alters retinoid metabolism in mice.

    Science.gov (United States)

    Paik, Jisun; Haenisch, Michael; Muller, Charles H; Goldstein, Alex S; Arnold, Samuel; Isoherranen, Nina; Brabb, Thea; Treuting, Piper M; Amory, John K

    2014-05-23

    Knowledge of the regulation of testicular retinoic acid synthesis is crucial for understanding its role in spermatogenesis. Bisdichloroacetyldiamines strongly inhibit spermatogenesis. We reported previously that one of these compounds, WIN 18,446, potently inhibited spermatogenesis in rabbits by inhibiting retinoic acid synthesis. To understand how WIN 18,446 inhibits retinoic acid synthesis, we characterized its effects on human retinal dehydrogenase ALDH1A2 in vitro as well as its effects on retinoid metabolism in vivo using mice. WIN 18,446 strongly and irreversibly inhibited ALDH1A2 in vitro. In vivo, WIN 18,446 treatment completely abolished spermatogenesis after 4 weeks of treatment and modestly reduced adiposity in mice fed a chow diet. Effects of WIN 18,446 on retinoid concentrations were tissue-dependent. Although lung and liver retinyl ester concentrations were lower in WIN 18,446-treated animals, adipose retinyl ester levels were increased following the treatment. Interestingly, animals treated with WIN 18,446 had significantly higher circulating retinol concentrations compared with control mice. The effect on spermatogenesis by WIN 18,446 was not prevented by simultaneous treatment with retinoic acid, whereas effects on other tissues were partially or completely reversed. Cessation of WIN 18,446 treatment for 4 weeks reversed most retinoid-related phenotypes except for inhibition of spermatogenesis. Our data suggest that WIN 18,446 may be a useful model of systemic acquired retinoic acid deficiency. Given the effects observed in our study, inhibition of retinoic acid biosynthesis may have relevance for the treatment of obesity and in the development of novel male contraceptives.

  12. 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

    A number of CXC chemokines competed with similar, nanomolar affinity against 125I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125I-labeled growth-related oncogene (GRO)-alpha, the ORF-74...... receptor was highly selective for GRO peptides, with IL-8 being 10,000-fold less potent. The constitutive stimulating activity of ORF-74 on phosphatidylinositol turnover was not influenced by, for example, IL-8 binding. In contrast, GRO peptides acted as potent agonists in stimulating ORF-74 signaling......, 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...

  13. eWin - european Waste information network - strategic planning and development of a European waste information network; eWin- european Waste information network - Strategische Planung und Entwicklung eines europaeischen Abfall-Informations-Netzwerkes

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, M. [eWin - europaen Waste information network, Witzenhausen (Germany); Aravossis, K. [Arvis and Co., Athens (Greece)

    2001-07-01

    Eight commercial and scientific institutions of six EC member states started in January 1999 with the development of a novel, internet-based European waste information system. The two-year project was co-ordinated by Gesamthochschule Kassel University, Hessischer Forschungsverbund Abfall (HFvA) and was funded by the European Union in the context of the INFO 2000 programme. The project eWin was to provide an internet portal to a wide range of information from different fields of waste management and research. In particular, all waste-relevant national databases were to be contained in eWin. They were to be constantly updated and accessed. [German] Acht kommerzielle und wissenschaftliche Institutionen aus sechs EU-Mitgliedslaendern haben im Januar 1999 damit begonnen, ein neuartiges europaeisches Abfall-Informationssystem aufzubauen, das im Internet angeboten werden sollte. Die Entwicklung des Gemeinschaftsprojektes war auf zwei Jahre konzipiert, die Projektkoordination lag beim Hessischen Forschungsverbund Abfall (HFvA) an der Gesamthochschule Kassel. Das Vorhaben wurde von der Europaeischen Union im Rahmen des EU-Programms INFO 2000 gefoerdert. Mit dem Projekt eWin (european Waste information network) sollte im Internet eine Plattform geschaffen werden, mit der laenderuebergreifend gezielt und effektiv ein breites Spektrum von Informationen aus verschiedenen Bereichen der Abfallwirtschaft und -forschung erreichbar gemacht wird. Durch eWin sollten die verstreut vorliegenden Informationen aufbereitet und ueber die Web-Technologie nach internationalen Standards allgemein zugaenglich gemacht werden. Vor allem sollten alle abfallrelevanten Datenbanken in den verschiedenen Laendern zum Bestandteil von eWin werden. Die dort gespeicherten Informationen sollten zugleich auf den aktuellen Stand fortgeschrieben und regelmaessig abgerufen werden. (orig.)

  14. 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

  15. NOD2 Agonist Promotes the Production of Inflammatory Cytokines in VSMC in Synergy with TLR2 and TLR4 Agonists

    Directory of Open Access Journals (Sweden)

    Jinghua Sun

    2012-01-01

    Full Text Available Objective. To investigate the expression of NOD2 in human VSMCs, its role in the production of inflammatory cytokines in VSMC and the possible interaction of NOD2-mediated signaling pathway with those mediated by TLR2 and TLR4. Methods. Human coronary artery smooth muscle cells were stimulated with NOD2 agonist MDP alone or in combination with either TLR2 agonist PAM3 or TLR4 agonist LPSs. The mRNA expression of NOD2 and FGF-2 were measured by RT-PCR. The concentration of IL-8 and TNF-α in the culture supernatants was determined by ELISA. VSMC proliferation ability was analyzed by MTT assay. Results. MDP up regulated the expression of NOD2 mRNA in VSMC in a time-dependent manner, up regulated the expression of FGF-2 mRNA in VSMC, induced the production of IL-8 and TNF-α, and promoted the proliferation of VSMC. Additionally, MDP synergied with LPS and PAM3 to promote the proliferation of VSMC and induce the production of IL-8 and TNF-α. Conclusion. The activation of NOD2-mediated innate immune signaling pathway can increase the proliferation ability of VSMC and induce the production of inflammatory cytokines in VSMC. It is also shown a synergistic effect with TLR2- and TLR4-mediated signaling pathways in this process.

  16. The birth of a community, the death of the win: Player production of the Middle-earth Collectible Card Game

    Directory of Open Access Journals (Sweden)

    Joe Bisz

    2009-03-01

    Full Text Available Collectible card games (CCGs are at the midpoint of the spectrum of gameplaying: half game, half story. An examination of a CCG based on Tolkien's Middle-earth illustrates the ways in which fans of the story have changed the game, especially in removing the focus on winning.

  17. Go Slow Whoa Meal Patterns: Cafeteria Staff and Teacher Perceptions of Effectiveness in "Winning with Wellness" Schools

    Science.gov (United States)

    Slawson, Deborah L.; Southerland, Jodi; Lowe, Elizabeth F.; Dalton, William T.; Pfortmiller, Deborah T.; Schetzina, Karen

    2013-01-01

    Background: School-based interventions hold promise for child obesity prevention. Implemented as a part of the "Winning with Wellness" obesity prevention project, the "Go Slow Whoa" meal pattern (GSW) was designed to promote healthier foods in school cafeterias. This investigation determined perceived program effectiveness and…

  18. 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.

  19. 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.

  20. On beyond "The Cat in the Hat": Theodor Seuss Geisel Award-Winning Books for Beginning Readers

    Science.gov (United States)

    Chatton, Barbara

    2007-01-01

    This article features the Theodor Seuss Geisel Award and its award-winning books for beginning readers. The award-giving body was established in 2004 by the Association of Library Service to Children, a division of the American Library Association, to honor the most distinguished contribution to the body of American children's literature known as…

  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. Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.

    Science.gov (United States)

    Middleton, T P; Protti, D A

    2011-09-01

    The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

  5. Pros and cons of healthcare information technology implementation: the pros win.

    Science.gov (United States)

    Maffei, Roxana

    2006-01-01

    Countless studies and investigations have been performed siding either for or against the implementation of technology in the healthcare setting. This article presents both sides of this debate, with an obvious conclusion that the pros of this debate win. The practice of information technology in the medical domain lags behind its knowledge and discovery by at least 7 years. The key to closing this gap is to show, through various studies, how information technology systems provide decision support to users at the point in time when decisions are needed. What the reader will obtain from this article is that the pros for information technology implementation in healthcare settings weigh much more and have a greater effect than the cons.

  6. 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.

  7. 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.

  8. 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, ...

  9. 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

  10. Bidding process in online auctions and winning strategy: Rate equation approach

    Science.gov (United States)

    Yang, I.; Kahng, B.

    2006-06-01

    Online auctions have expanded rapidly over the last decade and have become a fascinating new type of business or commercial transaction in this digital era. Here we introduce a master equation for the bidding process that takes place in online auctions. We find that the number of distinct bidders who bid k times up to the t th bidding progresses, called the k -frequent bidder, seems to scale as nk(t)˜tk-2.4 . The successfully transmitted bidding rate by the k -frequent bidder is likely to scale as qk(t)˜k-1.4 , independent of t for large t . This theoretical prediction is close to empirical data. These results imply that bidding at the last moment is a rational and effective strategy to win in an eBay auction.

  11. Bidding process in online auctions and winning strategy:rate equation approach

    CERN Document Server

    Yang, I

    2006-01-01

    Online auctions have expanded rapidly over the last decade and have become a fascinating new type of business or commercial transaction in this digital era. Here we introduce a master equation for the bidding process that takes place in online auctions. We find that the number of distinct bidders who bid $k$ times, called the $k$-frequent bidder, up to the $t$-th bidding progresses as $n_k(t)\\sim tk^{-2.4}$. The successfully transmitted bidding rate by the $k$-frequent bidder is obtained as $q_k(t) \\sim k^{-1.4}$, independent of $t$ for large $t$. This theoretical prediction is in agreement with empirical data. These results imply that bidding at the last moment is a rational and effective strategy to win in an eBay auction.

  12. 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...

  13. 基于WinCE的嵌入式网络通信系统设计

    Institute of Scientific and Technical Information of China (English)

    魏文; 李常磊

    2012-01-01

    介绍了基于Windows CE系统的嵌入式网络通讯客户端的设计方法.在Visual Studio 2010平台下,利用MFC的CSocket 类完成PC机的网络通讯客户端的设计,同时在Visual Studio 2005平台下,完成嵌入式WinCE操作系统的网络通讯客户端设计.PC与ARM通讯采用客户/服务器通信模型,PC与ARM均可选择为服务嚣,系统可完成网络文本通讯功能.

  14. 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

  15. [WinDiet. Support decision system for the assessment of nutritional status and diet prescription].

    Science.gov (United States)

    Esteves, E A; Siqueira, A D; Monteiro, J B; Ludwig, A

    1998-09-01

    A "Sistema de Apoio à Decisão para Avaliação do Estado Nutricional e Prescrição de Dietas" called "WinDiet" was developed. The system was developed on a computer compatible to IBM-PC standard. For system processing procedures through the computer, that is, interpretation, compilation, table generation en others, it was selected the Delphi version 1.0 software, from Borland International, for its using facilities, data basis accomplishment, communication environment and mainly an ample availability of mathematic, impression and programming resources besides allowing for all the programming operations to be accomplished on Windows environment. Knowing the procedures for nutritional evaluation and diet prescription was possible by consulting to text books, periodicals and the area experts. This system allows for individual nutritional assessment applying the anthropometric methods such as weight, height, skinfold thickness measurings, the lab methods such as albumin, transferrin, height/creatinin index and others, the dietary methods by food consumption recall, and the clinical methods that give emphasis to pathological antecedents and indicative sings of nutritional status. The software also turns possible to prescribe and calculate diets from recommendation besides having an actual data basis which may be changed or modified. Yet it maintains the individual description from all evaluation and menus, emitting its complete reports. It was verified that it reduce significantly the working time and increase the precision of estimate and nutritional diagnosis. Thus, the WinDiet may be used in nutritionist's offices, ambulatories, hospitals as well as on nutritional researches and education.

  16. 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.

  17. Combining Multifunctionality and Ecosystem Services into a Win-Win Solution. The Case Study of the Serchio River Basin (Tuscany—Italy

    Directory of Open Access Journals (Sweden)

    Massimo Rovai

    2016-09-01

    Full Text Available Post-war development—characterized by intensive processes of urbanization, concentration of agriculture on the most fertile lands, and abandonment of mountainous and marginal areas—brought about negative environmental and socio-economic consequences. They have been particularly severe in terms of increase of hydrogeological risk, which is high in most Italian regions. Over time, there has been an increasing awareness of the multiple functions played by agriculture in terms of provision of Ecosystem Services (ES, which contribute fundamentally to human well-being. In particular, some ES provided by farmers may help to reduce the hydrogeological risk of territories prone to landslides and floods. In this framework, the paper presents as a case study the project “Farmers as Custodians of a Territory.” This project was implemented in the Serchio River basin, Tuscany (Italy, and combines a multifunctional farm strategy of diversification with the provision of Ecosystem Services related to the hydraulic and hydrogeological protection of the river-basin territory. Although this case study should be read within the framework of the theories of agricultural multifunctionality and ES provision, it nevertheless took a very pragmatic and innovative approach, which differentiates it from most of the case studies given in the literature. Results of our analysis show that, by involving farmers as custodians of the territory, it is possible to reach a “win-win” solution characterized, on the one hand, by better services for the community at a lower cost for the Land Reclamation Consortia involved with hydrogeological risk prevention, thus improving the effectiveness and efficiency of ES provision; and on the other hand, by improving the economic situation and survival chances of local farms.

  18. 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.

  19. 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.

  20. Melatonin and Melatonin Agonists as Adjunctive Treatments in Bipolar Disorders.

    Science.gov (United States)

    Geoffroy, Pierre Alexis; Etain, Bruno; Franchi, Jean-Arthur Micoulaud; Bellivier, Frank; Ritter, Philipp

    2015-01-01

    Bipolar disorders (BD) present with abnormalities of circadian rhythmicity and sleep homeostasis, even during phases of remission. These abnormalities are linked to the underlying neurobiology of genetic susceptibility to BD. Melatonin is a pineal gland secreted neurohormone that induces circadian-related and sleep-related responses. Exogenous melatonin has demonstrated efficacy in treating primary insomnia, delayed sleep phase disorder, improving sleep parameters and overall sleep quality, and some psychiatric disorders like autistic spectrum disorders. In order to evaluate the efficacy of melatonin among patients with BD, this comprehensive review emphasizes the abnormal melatonin function in BD, the rationale of melatonin action in BD, the available data about the exogenous administration of melatonin, and melatonin agonists (ramelteon and tasimelteon), and recommendations of use in patients with BD. There is a scientific rationale to propose melatonin-agonists as an adjunctive treatment of mood stabilizers in treating sleep disorders in BD and thus to possibly prevent relapses when administered during remission phases. We emphasized the need to treat insomnia, sleep delayed latencies and sleep abnormalities in BD that are prodromal markers of an emerging mood episode and possible targets to prevent future relapses. An additional interesting adjunctive therapeutic effect might be on preventing metabolic syndrome, particularly in patients treated with antipsychotics. Finally, melatonin is well tolerated and has little dependence potential in contrast to most available sleep medications. Further studies are expected to be able to produce stronger evidence-based therapeutic guidelines to confirm and delineate the routine use of melatonin-agonists in the treatment of BD.

  1. Comparative endpoint sensitivity of in vitro estrogen agonist assays.

    Science.gov (United States)

    Dreier, David A; Connors, Kristin A; Brooks, Bryan W

    2015-07-01

    Environmental and human health implications of endocrine disrupting chemicals (EDCs), particularly xenoestrogens, have received extensive study. In vitro assays are increasingly employed as diagnostic tools to comparatively evaluate chemicals, whole effluent toxicity and surface water quality, and to identify causative EDCs during toxicity identification evaluations. Recently, the U.S. Environmental Protection Agency (USEPA) initiated ToxCast under the Tox21 program to generate novel bioactivity data through high throughput screening. This information is useful for prioritizing chemicals requiring additional hazard information, including endocrine active chemicals. Though multiple in vitro and in vivo techniques have been developed to assess estrogen agonist activity, the relative endpoint sensitivity of these approaches and agreement of their conclusions remain unclear during environmental diagnostic applications. Probabilistic hazard assessment (PHA) approaches, including chemical toxicity distributions (CTD), are useful for understanding the relative sensitivity of endpoints associated with in vitro and in vivo toxicity assays by predicting the likelihood of chemicals eliciting undesirable outcomes at or above environmentally relevant concentrations. In the present study, PHAs were employed to examine the comparative endpoint sensitivity of 16 in vitro assays for estrogen agonist activity using a diverse group of compounds from the USEPA ToxCast dataset. Reporter gene assays were generally observed to possess greater endpoint sensitivity than other assay types, and the Tox21 ERa LUC BG1 Agonist assay was identified as the most sensitive in vitro endpoint for detecting an estrogenic response. When the sensitivity of this most sensitive ToxCast in vitro endpoint was compared to the human MCF-7 cell proliferation assay, a common in vitro model for biomedical and environmental monitoring applications, the ERa LUC BG1 assay was several orders of magnitude less

  2. Biased signaling by peptide agonists of protease activated receptor 2.

    Science.gov (United States)

    Jiang, Yuhong; Yau, Mei-Kwan; Kok, W Mei; Lim, Junxian; Wu, Kai-Chen; Liu, Ligong; Hill, Timothy A; Suen, Jacky Y; Fairlie, David P

    2017-02-07

    Protease activated receptor 2 (PAR2) is associated with metabolism, obesity, inflammatory, respiratory and gastrointestinal disorders, pain, cancer and other diseases. The extracellular N-terminus of PAR2 is a common target for multiple proteases, which cleave it at different sites to generate different N-termini that activate different PAR2-mediated intracellular signaling pathways. There are no synthetic PAR2 ligands that reproduce the same signaling profiles and potencies as proteases. Structure-activity relationships here for 26 compounds spanned a signaling bias over 3 log units, culminating in three small ligands as biased agonist tools for interrogating PAR2 functions. DF253 (2f-LAAAAI-NH2) triggered PAR2-mediated calcium release (EC50 2 μM) but not ERK1/2 phosphorylation (EC50 > 100 μM) in CHO cells transfected with hPAR2. AY77 (Isox-Cha-Chg-NH2) was a more potent calcium-biased agonist (EC50 40 nM, Ca2+; EC50 2 μM, ERK1/2), while its analogue AY254 (Isox-Cha-Chg-A-R-NH2) was an ERK-biased agonist (EC50 2 nM, ERK1/2; EC50 80 nM, Ca2+). Signaling bias led to different functional responses in human colorectal carcinoma cells (HT29). AY254, but not AY77 or DF253, attenuated cytokine-induced caspase 3/8 activation, promoted scratch-wound healing and induced IL-8 secretion, all via PAR2-ERK1/2 signaling. Different ligand components were responsible for different PAR2 signaling and functions, clues that can potentially lead to drugs that modulate different pathway-selective cellular and physiological responses.

  3. 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

  4. Ramelteon: A melatonin receptor agonist for the treatment of insomnia

    Directory of Open Access Journals (Sweden)

    Devi V

    2008-01-01

    Full Text Available Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist recently approved for the treatment of insomnia characterized by difficulty in sleep onset. It is a nonscheduled drug since it lacks the potential for abuse and does not interact with neurotransmitter receptors most associated with these phenomena. Although the effects of ramelteon use> 5 weeks are unknown, the available data confirms its safety and efficacy for short-term use. Clinical use and future research should uncover more information about ramelteon′s properties.

  5. 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.

  6. 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.

  7. Estrogen Receptor Agonists and Antagonists in the Yeast Estrogen Bioassay.

    Science.gov (United States)

    Wang, Si; Bovee, Toine F H

    2016-01-01

    Cell-based bioassays can be used to predict the eventual biological activity of a substance on a living organism. In vitro reporter gene bioassays are based on recombinant vertebrate cell lines or yeast strains and especially the latter are easy-to-handle, cheap, and fast. Moreover, yeast cells do not express estrogen, androgen, progesterone or glucocorticoid receptors, and are thus powerful tools in the development of specific reporter gene systems that are devoid of crosstalk from other hormone pathways. This chapter describes our experience with an in-house developed RIKILT yeast estrogen bioassay for testing estrogen receptor agonists and antagonists, focusing on the applicability of the latter.

  8. Standardized butanol fraction of WIN-34B suppresses cartilage destruction via inhibited production of matrix metalloproteinase and inflammatory mediator in osteoarthritis human cartilage explants culture and chondrocytes

    Directory of Open Access Journals (Sweden)

    Huh Jeong-Eun

    2012-12-01

    Full Text Available Abstract Background WIN-34B is a novel Oriental medicine, which represents the n-butanol fraction prepared from dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE. The component herb of WIN-34B is used for arthritis treatment in East Asian countries. The aim of this study was to determine the cartilage-protective effects and mechanisms of WIN-34B and its major phenolic compounds, chlorogenic acid and mangiferin, in osteoarthritis (OA human cartilage explants culture and chondrocytes. Methods The investigation focused on whether WIN-34B and its standard compounds protected cartilage in interleukin (IL-1β-stimulated cartilage explants culture and chondrocytes derived from OA patients. Also, the mechanisms of WIN-34B on matrix metalloproteinases (MMPs, tissue inhibitor of matrix metalloproteinases (TIMPs, inflammatory mediators, and mitogen-activated protein kinases (MAPKs pathways were assessed. Results WIN-34B was not cytotoxic to cultured cartilage explants or chondrocytes. WIN-34B dose-dependently inhibited the release of glycosaminoglycan and type II collagen, increased the mRNA expression of aggrecan and type II collagen, and recovered the intensity of proteoglycan and collagen by histological analysis in IL-1β-stimulated human cartilage explants culture. The cartilage protective effect of WIN-34B was similar to or better than that of chlorogenic acid and mangiferin. Compared to chlorogenic acid and mangiferin, WIN-34B displayed equal or greater decreases in the levels of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, and markedly up-regulated TIMP-1 and TIMP-3. WIN-34B inhibited inflammatory mediators involved in cartilage destruction, such as prostaglandin E2, nitric oxide, tumor necrosis factor-alpha, and IL-1β. The phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK, and p38 was significantly reduced by WIN-34B treatment, while phosphorylation of JNK was only

  9. Standardized butanol fraction of WIN-34B suppresses cartilage destruction via inhibited production of matrix metalloproteinase and inflammatory mediator in osteoarthritis human cartilage explants culture and chondrocytes

    Science.gov (United States)

    2012-01-01

    Background WIN-34B is a novel Oriental medicine, which represents the n-butanol fraction prepared from dried flowers of Lonicera japonica Thunb and dried roots of Anemarrhena asphodeloides BUNGE. The component herb of WIN-34B is used for arthritis treatment in East Asian countries. The aim of this study was to determine the cartilage-protective effects and mechanisms of WIN-34B and its major phenolic compounds, chlorogenic acid and mangiferin, in osteoarthritis (OA) human cartilage explants culture and chondrocytes. Methods The investigation focused on whether WIN-34B and its standard compounds protected cartilage in interleukin (IL)-1β-stimulated cartilage explants culture and chondrocytes derived from OA patients. Also, the mechanisms of WIN-34B on matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinases (TIMPs), inflammatory mediators, and mitogen-activated protein kinases (MAPKs) pathways were assessed. Results WIN-34B was not cytotoxic to cultured cartilage explants or chondrocytes. WIN-34B dose-dependently inhibited the release of glycosaminoglycan and type II collagen, increased the mRNA expression of aggrecan and type II collagen, and recovered the intensity of proteoglycan and collagen by histological analysis in IL-1β-stimulated human cartilage explants culture. The cartilage protective effect of WIN-34B was similar to or better than that of chlorogenic acid and mangiferin. Compared to chlorogenic acid and mangiferin, WIN-34B displayed equal or greater decreases in the levels of MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, and markedly up-regulated TIMP-1 and TIMP-3. WIN-34B inhibited inflammatory mediators involved in cartilage destruction, such as prostaglandin E2, nitric oxide, tumor necrosis factor-alpha, and IL-1β. The phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38 was significantly reduced by WIN-34B treatment, while phosphorylation of JNK was only inhibited by chlorogenic

  10. In vitro and in vivo efficacy of a potent opioid receptor agonist, biphalin, compared to subtype-selective opioid receptor agonists for stroke treatment.

    Science.gov (United States)

    Yang, Li; Islam, Mohammad R; Karamyan, Vardan T; Abbruscato, Thomas J

    2015-06-03

    To meet the challenge of identification of new treatments for stroke, this study was designed to evaluate a potent, nonselective opioid receptor (OR) agonist, biphalin, in comparison to subtype selective OR agonists, as a potential neuroprotective drug candidate using in vitro and in vivo models of ischemic stroke. Our in vitro approach included mouse primary neuronal cells that were challenged with glutamate and hypoxic/aglycemic (H/A) conditions. We observed that 10nM biphalin, exerted a statistically significant neuroprotective effect after glutamate challenge, compared to all selective opioid agonists, according to lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, 10nM biphalin provided superior neuroprotection after H/A-reoxygenation compared to selective opioid agonists in all cases. Our in vitro investigations were supported by in vivo studies which indicate that the nonselective opioid agonist, biphalin, achieves enhanced neuroprotective potency compared to any of the selective opioid agonists, evidenced by reduced edema and infarct ratios. Reduction of edema and infarction was accompanied by neurological improvement of the animals in two independent behavioral tests. Collectively these data strongly suggest that concurrent agonist stimulation of mu, kappa and delta ORs with biphalin is neuroprotective and superior to neuroprotection by activation of any single OR subtype.

  11. 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.

  12. Pathological hypersexuality predominantly linked to adjuvant dopamine agonist therapy in Parkinson's disease and multiple system atrophy.

    Science.gov (United States)

    Klos, Kevin J; Bower, James H; Josephs, Keith A; Matsumoto, Joseph Y; Ahlskog, J Eric

    2005-09-01

    Pathological hypersexuality developed in 13 patients with PD and two patients ultimately diagnosed clinically with MSA. Hypersexuality began within 8 months after starting dopamine agonist therapy in 14 of 15 cases, including four on agonist monotherapy. It resolved in the four cases where the agonist was stopped, despite continued levodopa therapy. This was not an isolated behavioral problem in most, with additional compulsive or addictive behaviors coinciding in nine patients (60%). A systematic literature review of pathological hypersexuality in PD revealed similar medication histories; combining these cases with our series, 26 of 29 patients (90%) were on adjuvant dopamine agonists.

  13. 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....

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Ondřej Slavík

    2016-04-01

    Full Text Available 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.

  16. The evolution of histamine H₃ antagonists/inverse agonists.

    Science.gov (United States)

    Lebois, Evan P; Jones, Carrie K; Lindsley, Craig W

    2011-01-01

    This article describes our efforts along with recent advances in the development, biological evaluation and clinical proof of concept of small molecule histamine H₃ antagonists/inverse agonists. The H3 receptor is a presynaptic autoreceptor within the Class A GPCR family, but also functions as a heteroreceptor modulating levels of neurotransmitters such as dopamine, acetylcholine, norepinephrine, serotonin, GABA and glutamate. Thus, H₃R has garnered a great deal of interest from the pharmaceutical industry for the possible treatment of obesity, epilepsy, sleep/wake, schizophrenia, Alzheimer's disease, neuropathic pain and ADHD. Within the two main classes of H₃ ligands, both imidazole and non-imidazole derived, have shown sufficient potency and specificity which culminated with efficacy in preclinical models for various CNS disorders. Importantly, conserved elements have been identified within the small molecule H₃ ligand scaffolds that resulted in a highly predictive pharmacophore model. Understanding of the pharmacophore model has allowed several groups to dial H₃R activity into scaffolds designed for other CNS targets, and engender directed polypharmacology. Moreover, Abbott, GSK, Pfizer and several others have reported positive Phase I and/or Phase II data with structurally diverse H₃R antagonists/inverse agonists.

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

    Science.gov (United States)

    Slavík, Ondřej; 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.

  18. 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

  19. Receptor discrimination and control of agonist-antagonist binding.

    Science.gov (United States)

    Tallarida, R J

    1995-08-01

    The law of mass action is the common model for the interaction of agonist and antagonist compounds with cellular receptors. Parameters of the interaction, obtained from functional and radioligand-binding studies, allow discrimination and subtyping of receptors and aid in understanding specific mechanisms. This article reviews the theory and associated mathematical models and graphical transformations of data that underlie the determination of receptor parameters. The main theory assumes that agonist and antagonist compounds bind to cells that have a fixed number of receptors and provides the framework for obtaining drug-receptor parameters from data and their graphical transformations. Conditions that produce a change in receptor number, a newer concept in pharmacology, can have an important effect on the parameter values derived in the usual way. This review concludes with a discussion of the quantitative study of receptor-mediated feedback control of endogenous ligands, a very new topic with potentially important implications for understanding antagonist effectiveness, loss of control, and chaos in regulated mass action binding.

  20. Identification of agonists for a group of human odorant receptors

    Directory of Open Access Journals (Sweden)

    Daniela eGonzalez-Kristeller

    2015-03-01

    Full Text Available Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose. The information provided by the activation of different combinations of ORs in the nose is transmitted to the brain, leading to odorant perception and emotional and behavioral responses. There are ~400 intact human ORs, and to date only a small percentage of these receptors (~10% have known agonists. The determination of the specificity of the human ORs will contribute to a better understanding of how odorants are discriminated by the olfactory system. In this work, we aimed to identify human specific ORs, that is, ORs that are present in humans but absent from other species, and their corresponding agonists. To do this, we first selected 22 OR gene sequences from the human genome with no counterparts in the mouse, rat or dog genomes. Then we used a heterologous expression system to screen a subset of these human ORs against a panel of odorants of biological relevance, including foodborne aroma volatiles. We found that different types of odorants are able to activate some of these previously uncharacterized human ORs.

  1. 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.

  2. AMP is an adenosine A1 receptor agonist.

    Science.gov (United States)

    Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

    2012-02-17

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

  3. GLP-1 receptor agonist-induced polyarthritis: a case report.

    Science.gov (United States)

    Ambrosio, Maria Luisa; Monami, Matteo; Sati, Lavinia; Marchionni, Niccolò; Di Bari, Mauro; Mannucci, Edoardo

    2014-08-01

    Occasional cases of bilateral, symmetrical, seronegative polyarthritis have been reported in patients treated with dipeptidyl peptidase-4 inhibitors (Crickx et al. in Rheumatol Int, 2013). We report here a similar case observed during treatment with a GLP-1 receptor agonist. A 42-year-old man with type 2 diabetes treated with metformin 1,500 mg/day and liraglutide 1.8 mg/day. After 6 months from the beginning of treatment, the patient complained of bilateral arthralgia (hands, feet, ankles, knees, and hips). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and leukocytes were increased. Rheumatoid factor, anticyclic citrullinated protein antibody, antinuclear antibodies, anti-Borrelia, and burgdorferi antibodies were all negative, and myoglobin and calcitonin were normal. Liraglutide was withdrawn, and the symptoms completely disappeared within 1 week, with normalization of ESR, CRP, fibrinogen, and leukocytes. Previously described cases of polyarthritis associated with DPP4 inhibitors had been attributed to a direct effect of the drugs on inflammatory cells expressing the enzyme. The present case, occurred during treatment with a GLP-1 receptor agonists, suggests a possibly different mechanism, mediated by GLP-1 receptor stimulation, which deserved further investigation.

  4. Melatonin and melatonin agonist for delirium in the elderly patients.

    Science.gov (United States)

    Chakraborti, Dwaipayan; Tampi, Deena J; Tampi, Rajesh R

    2015-03-01

    The objective of this review is to summarize the available data on the use of melatonin and melatonin agonist for the prevention and management of delirium in the elderly patients from randomized controlled trials (RCTs). A systematic search of 5 major databases PubMed, MEDLINE, PsychINFO, Embase, and Cochrane Library was conducted. This search yielded a total of 2 RCTs for melatonin. One study compared melatonin to midazolam, clonidine, and control groups for the prevention and management of delirium in individuals who were pre- and posthip post-hip arthroplasty. The other study compared melatonin to placebo for the prevention of delirium in older adults admitted to an inpatient internal medicine service. Data from these 2 studies indicate that melatonin may have some benefit in the prevention and management of delirium in older adults. However, there is no evidence that melatonin reduces the severity of delirium or has any effect on behaviors or functions in these individuals. Melatonin was well tolerated in these 2 studies. The search for a melatonin agonist for delirium in the elderly patients yielded 1 study of ramelteon. In this study, ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo. Ramelteon was well tolerated in this study.

  5. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  6. 北石顶驱WinCC趋势画面在故障分析中的应用%Application of WinCC Trend Pictures of BPM Top Drive in Fault Anlysis

    Institute of Scientific and Technical Information of China (English)

    张尧; 王博; 孙明寰; 马瑞; 谢海欢

    2015-01-01

    北石顶驱采用WinCC系统作为上位机监控系统,西门子S7-300型PLC作为控制器,通过WinCC与PLC之间的MPI通讯,实现了对顶驱参数的图形显示,实时监测,数据记录.在出现问题时,可以通过趋势画面查看数据记录,帮助分析问题.通过实例,介绍了如何分析趋势画面的数据,了解、判断顶驱出现的问题.

  7. 一种用WinDrive实现生物图像采集、显示的可视化系统%A Viewdata and Display System of Biologic Image by WinDriver

    Institute of Scientific and Technical Information of China (English)

    吴鸿修; 叶进洲; 张川

    2001-01-01

    This paper introduces a viewdata and display system of biologic image by WinDriver, which mainly includes a data acquistion card of image, the ASIC design of its control and an introduction of a method to drive I/O of PC.%介绍一种用于生物图像的数据采集、显示的可视化系统,主要包括图像的数据采集卡及其控制部分的ASIC(专用集成电路)设计,并介绍使用WinDriver驱动PC机硬件I/O的方法。

  8. WinCC用户归档在压合机组配方中的研究%Study of WinCC User Archive in Recipes of Pressure Machine Array

    Institute of Scientific and Technical Information of China (English)

    张锋; 张腾; 李英春

    2008-01-01

    通过利用WinCC UserArChive选件和其中的内部控制函数,解决了实际工程中配方系统的数据交换问题.通过编写C_Script脚本语言并使用WinCC的标准函数,使配方的"上传"与"下载"功能得以更加灵活的使用,并使其具有系统所期望的功能.由该方法制作的配方系统已在实际工程中取得了良好效果,可以推广和移植到其他行业的配方系统中.

  9. Software Communication between WinCC Software and Bently Unit Status Monitoring System%本特利机组状态监控系统与WinCC的通信方法

    Institute of Scientific and Technical Information of China (English)

    安富平

    2012-01-01

    The communication between Bently unit status monitoring system and HMI software of the host computer was discussed; and through the function of network communication of Windows DDE and DDE Server from Bently Data Acquisition software, the data were successfully transmitted to WinCC.%围绕本特利公司机组状态监控系统实现与上位计算机HMI软件通信的方法进行论述.利用Windows DDE的网络通信功能和本特利公司Data Acquisition软件提供的DDE server功能,成功地将数据传精到WinCC监控软件包中.

  10. A full support for healthcare in Western China is a win-win way in the hospital's construction%支援西部地区医疗卫生工作取得双赢效果

    Institute of Scientific and Technical Information of China (English)

    王冬; 张思兵

    2011-01-01

    Through analyzing the experiences of the PLA Ceneral Hospital in offering assistance to the Western China, this paper probes into the issue of how a general hospital can achieve a win-win solution in the medical assisting programs and comes up with some measures: to estahlish a communication channel with mutual heliefs, to extend cooperation fields, and to constantly summarize the work for revision.%通过回顾总结解放军总医院在支援西部地区医疗卫生工作的主要经验,探讨综合性医院在医疗帮带工作中取得双赢效果的具体做法,提出要建立全面互信的沟通渠道,努力扩大双方合作领域,定期总结不断提高帮带水平.

  11. The performance evaluation of WinOSPM model for urban street canyons of Nantes in France.

    Science.gov (United States)

    Gokhale, Sharad B; Rebours, Arnaud; Pavageau, Michel

    2005-01-01

    Air quality modelling is primarily the quantative approach. It is more difficult as it demands input data accuracy, uncertainties and the efficient methodologies to judge the extent of models accuracy. As a result, model validation has to be regarded as an integral part of the modelling process. Furthermore, models are often validated on a limited number of testcases therefore, appropriate evaluation procedure must be implemented to ensure these models will be applicable for various conditions. The study presented here was carried out to evaluate the WinOSPM (Preliminary version of windows based Operational Street Pollution Model) for air pollutants viz. CO, NO, NO2, NOx and C6H6 for three street canyons of Nantes (France) and for the three base years 1999, 2000, and 2001. Each street canyon selected for this study has typical and unidentical features. The rue de Strasbourg and Boulevard Victor Hugo have many building exceptions whereas rue Crébillon has not any. Application of the model above to the three street canyons revealed that WinOSPM could be used in the case when measurements are not available. This was justified from the results at rue Crébillon. The special interest was in the benzene modelled values as its content in fuel has been targeted to reduce to 1% for the years 2000 and onwards (from its 5% until the year 1999). The 50 to 70% reduction in the benzene concentrations is found for both the years i.e. in 2000 and 2001. This has further justified that air quality models are useful and interesting tools in optimising emission reduction strategies. Moreover, it is also the new pollutant added to the measurement campaign of Air Pays de la Loire (APL) for the city of Nantes. For benzene weekly averages are estimated from the hourly-modelled values for all the streets and compared with that of measurements. They are found in excellent agreement with each other's. For other pollutants annual means and percentiles were compared. The statistical analysis

  12. A study on the role of women experts to enhance public confidence on nuclear and to establish cooperation and collaboration strategies with the Women In Nuclear (WIN)

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-12-15

    This study conducted 'R and D Planning' for the projects which will be partially terminated at 2004. In each field, there are three projects in reactor and nuclear fuel field, seven in nuclear safety field and two projects in RI production and radiation application field. The followings are the detailed contents for each project. Research of present states of WIN web site world-widely, Introduction of activity of women in nuclear working in our country through web site of WIN-Global, Acquisition of information materials through active participation in WIN-Global association(10th WIN-Global Annual Meeting), Construction of database of women in nuclear and technical exchange infra in nation.

  13. The impact of gender and nationality on winning a professional society award

    Science.gov (United States)

    Holmes, Mary Anne; McKenzie, Judith

    2016-04-01

    Women are under-represented for science awards and fellow status in professional science societies (accounting for career stage) and are over-represented for teaching and service awards (Ball et al., 2015; Lincoln et al., 2012; Holmes et al., 2011). In addition, for the American Geophysical Union, non-U.S. members are under-represented among all awardees. Gender bias in evaluation processes are well-documented (e.g., Valian, 1999), and cultural differences are at play in the under-representation of non U.S. members. U.S. members are more likely to nominate their peers for awards, and to write effusive letters to support the nomination (Ball et al., 2015). There are effective mechanisms to reduce bias in both nomination and evaluation processes, a few of which are: 1) separate the nomination and evaluation processes by creating nomination committees of a diverse group of people who actively seek potential nominees and promote their nominations; this expands the pool of nominees; 2) educate nomination and evaluation committees on the research that demonstrates the impact of implicit bias on nomination and selection processes (e.g., http://www.enei.org.uk/pages/unconscious-bias.html; http://wiseli.engr.wisc.edu/bias.php); 3) minimize use of simple bibliometric indices, which are known to exhibit gender bias (men self-cite more than women; Maliniak et al., 2013) and nationality bias (papers in English language journals are more likely to be cited than non-English journals (Bornmann et al., 2012; González-Alcaide et al., 2012); 4) members of the selection committee should understand the effects of gender on the quality of letters written for women (Trix and Psenka, 2003); 5) establish and follow clear criteria for the award. Professional societies can promote fairness and inclusion by self-study: find and compile the data on the gender, race, ethnicity and nationality of members who are nominated for and win awards, as well as on who is doing the nominating. Compare

  14. Good times, bad times: how personal disadvantage moderates the relationship between social dominance and efforts to win.

    Science.gov (United States)

    Cozzolino, Philip J; Snyder, Mark

    2008-10-01

    Recent work has linked social dominance orientation (SDO) to ruthless, uncaring individuals who see the world as a competitive jungle. This need to "rule the jungle," then, should become activated when high SDOs are in positions that threaten their chances of victory. In Study 1, the authors manipulated advantage and disadvantage in the form of resources; in an ensuing task, they observed higher levels of greed only among disadvantaged high SDOs. In Study 2, high SDOs with less opportunity to compete relative to others evidenced significantly more extra-effort to win, even though their effort broke the rules. In Study 3, the authors replicated this effect and demonstrated that extra-effort predicted increased beliefs in actual performance, which in turn predicted decisions to argue for a higher score. In sum, the results provide support for the notion of SDO reflecting underlying needs to compete and win at all costs.

  15. Army Communicator. Volume 33, Number 3, Summer 2008. WIN-T: Increasing the Power of Battlefield Communications

    Science.gov (United States)

    2008-01-01

    States CPN – Command Post Nodes DCATS – Defense Communica- tions and Army Transmission Systems DISN – Defense Information Systems Network ESB ...information Geoffrey Wells 66 Requirements for ESB recognized following OIF Billy Johnson 67 WIN-T Personnel Requirements MAJ Alprentice “Al” Smith and John...approved Type 1 Communica- tions Security equipment. Wireless transmission links are also encrypted using NSA-approved Transmission Security. The

  16. A Trio of Inference Problems That Could Win You a Nobel Prize in Statistics (If You Help Fund It)

    OpenAIRE

    Meng, Xiao-Li

    2014-01-01

    Statistical inference is a field full of problems whose solutions require the same intellectual force needed to win a Nobel Prize in other scientific fields. Multi-resolution inference is the oldest of the trio. But emerging applications such as individualized medicine have challenged us to the limit: Infer estimands with resolution levels that far exceed those of any feasible estimator. Multi-phase inference is another reality because (big) data are almost never collected, processed, and ana...

  17. PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings.

    Directory of Open Access Journals (Sweden)

    Monica Puligheddu

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are involved in seizure mechanisms. Hence, nocturnal frontal lobe epilepsy was the first idiopathic epilepsy linked with specific mutations in α4 or β2 nAChR subunit genes. These mutations confer gain of function to nAChRs by increasing sensitivity toward acetylcholine. Consistently, nicotine elicits seizures through nAChRs and mimics the excessive nAChR activation observed in animal models of the disease. Treatments aimed at reducing nicotinic inputs are sought as therapies for epilepsies where these receptors contribute to neuronal excitation and synchronization. Previous studies demonstrated that peroxisome proliferator-activated receptors-α (PPARα, nuclear receptor transcription factors, suppress nicotine-induced behavioral and electrophysiological effects by modulating nAChRs containing β2 subunits. On these bases, we tested whether PPARα agonists were protective against nicotine-induced seizures. To this aim we utilized behavioral and electroencephalographic (EEG experiments in C57BL/J6 mice and in vitro patch clamp recordings from mice and rats. Convulsive doses of nicotine evoked severe seizures and bursts of spike-waves discharges in ∼100% of mice. A single dose of the synthetic PPARα agonist WY14643 (WY, 80 mg/kg, i.p. or chronic administration of fenofibrate, clinically available for lipid metabolism disorders, in the diet (0.2% for 14 days significantly reduced or abolished behavioral and EEG expressions of nicotine-induced seizures. Acute WY effects were reverted by the PPARα antagonist MK886 (3 mg/kg, i.p.. Since neocortical networks are crucial in the generation of ictal activity and synchrony, we performed patch clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs from frontal cortex layer II/III pyramidal neurons. We found that both acute and chronic treatment with PPARα agonists abolished nicotine-induced sIPSC increases. PPARα within the CNS are key

  18. Reports of wins and risk taking: an investigation of the mediating effect of the illusion of control.

    Science.gov (United States)

    Martinez, Frédéric; Le Floch, Valérie; Gaffié, Bernard; Villejoubert, Gaëlle

    2011-06-01

    Two experiments examined the relationships between the knowledge that another person has won in a gamble, the illusion of control and risk taking. Participants played a computer-simulated French roulette game individually. Before playing, some participants learnt that another person won a large amount of money. Results from a first experiment (n = 24) validated a causal model where the knowledge of another person's win increased the illusion of control, measured with betting times, expectancy and self-reports on scales, which in turn encourages risk taking. In the second experiment (n = 36), some participants were told the previous player acknowledged the win to be fortuitous. The suppression of the belief that the previous winner had himself exerted control over the outcome resulted in lower rates of risk-taking behaviors. This suggests that it was not the knowledge of another person's win in itself that increased risk taking, but rather, the belief that the other person had some control over the gamble's outcome. Theoretical implications for the study of social mechanisms involved in gambling behavior are discussed.

  19. "I was that close": Investigating Players' Reactions to Losses, Wins, and Near-Misses on Scratch Cards.

    Science.gov (United States)

    Stange, Madison; Graydon, Candice; Dixon, Mike J

    2016-03-01

    While scratch cards are a popular, accessible, and inexpensive form of gambling, very little is known about how they affect and influence the player. This study sought to understand the physiological and subjective experience of scratch card play, with special emphasis on the effect of near-miss outcomes (i.e. uncovering two out of three "grand prize" symbols needed to win said prize), which are remarkably prevalent in scratch card games. Thirty-eight undergraduate students from the University of Waterloo each played two custom scratch card games and experienced three types of outcomes (losses, wins and near-misses) while their skin conductance levels (SCLs) and post-reinforcement pauses were recorded. Each participant also rated each outcome in terms of its subjective level of arousal, valence, and frustration. Our results indicate that players interpreted near-misses as negatively valenced, highly arousing, frustrating losses, and were faster to move onto the next game following this type of outcome than following winning outcomes. Additionally, near-miss outcomes were associated with the largest amount of change in SCLs as the outcome was revealed. This work has implications for the problem gambling literature as it provides evidence of the frustration hypothesis of near-misses in scratch cards, and is the first study to examine the physiological and psychological experiences of scratch card players.

  20. Litigating reproductive health rights in the Inter-American System: what does a winning case look like?

    Science.gov (United States)

    O'Connell, Ciara

    2014-12-11

    Remedies and reparation measures emerging from the Inter-American System of Human Rights in reproductive health cases have consistently highlighted the need to develop, and subsequently implement, non-repetition remedies that protect, promote, and fulfill women's reproductive health rights. Litigation outcomes that determine there have been violations of reproductive rights are regarded as a "win" for health rights litigation, but when implementation fails, is a "win" still a win? There has been considerable success in litigating reproductive health rights cases, yet the Inter-American Commission on Human Rights and the Inter-American Court of Human Rights are not adequately equipped to follow up on cases after they have been won. Successful and sustainable implementation of reproductive health rights law requires incorporation of non-repetition remedies in the form of legislation, education, and training that seeks to remodel existing social and cultural practices that hinder women's enjoyment of their reproductive rights. In order for a reproductive health rights case to ultimately be a "winner," case recommendations and decisions emerging from the Commission and Court must incorporate perspectives from members of civil society, with the ultimate goal being to develop measurable remedies that address underlying obstacles to domestic implementation.

  1. Impact of efficacy at the μ-opioid receptor on antinociceptive effects of combinations of μ-opioid receptor agonists and cannabinoid receptor agonists.

    Science.gov (United States)

    Maguire, David R; France, Charles P

    2014-11-01

    Cannabinoid receptor agonists, such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC), enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combining cannabinoids with opioids would improve pain treatment. Combinations with lower efficacy agonists might be preferred and could avoid adverse effects associated with large doses; however, it is unclear whether interactions between opioids and cannabinoids vary across drugs with different efficacy. The antinociceptive effects of μ-opioid receptor agonists alone and in combination with cannabinoid receptor agonists were studied in rhesus monkeys (n = 4) using a warm water tail withdrawal procedure. Etorphine, fentanyl, morphine, buprenorphine, nalbuphine, Δ(9)-THC, and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol) each increased tail withdrawal latency. Pretreatment with doses of Δ(9)-THC (1.0 mg/kg) or CP 55,940 (0.032 mg/kg) that were ineffective alone shifted the fentanyl dose-effect curve leftward 20.6- and 52.9-fold, respectively, and the etorphine dose-effect curve leftward 12.4- and 19.6-fold, respectively. Δ(9)-THC and CP 55,940 shifted the morphine dose-effect curve leftward only 3.4- and 7.9-fold, respectively, and the buprenorphine curve only 5.4- and 4.1-fold, respectively. Neither Δ(9)-THC nor CP 55,940 significantly altered the effects of nalbuphine. Cannabinoid receptor agonists increase the antinociceptive potency of higher efficacy opioid receptor agonists more than lower efficacy agonists; however, because much smaller doses of each drug can be administered in combinations while achieving adequate pain relief and that other (e.g., abuse-related) effects of opioids do not appear to be enhanced by cannabinoids, these results provide additional support for combining opioids with cannabinoids to treat pain.

  2. Behavioural and neural modulation of win-stay but not lose-shift strategies as a function of outcome value in Rock, Paper, Scissors.

    Science.gov (United States)

    Forder, Lewis; Dyson, Benjamin James

    2016-09-23

    Competitive environments in which individuals compete for mutually-exclusive outcomes require rational decision making in order to maximize gains but often result in poor quality heuristics. Reasons for the greater reliance on lose-shift relative to win-stay behaviour shown in previous studies were explored using the game of Rock, Paper, Scissors and by manipulating the value of winning and losing. Decision-making following a loss was characterized as relatively fast and relatively inflexible both in terms of the failure to modulate the magnitude of lose-shift strategy and the lack of significant neural modulation. In contrast, decision-making following a win was characterized as relatively slow and relatively flexible both in terms of a behavioural increase in the magnitude of win-stay strategy and a neural modulation of feedback-related negativity (FRN) and stimulus-preceding negativity (SPN) following outcome value modulation. The win-stay/lose-shift heuristic appears not to be a unified mechanism, with the former relying on System 2 processes and the latter relying on System 1 processes. Our ability to play rationally appears more likely when the outcome is positive and when the value of wins are low, highlighting how vulnerable we can be when trying to succeed during competition.

  3. Behavioural and neural modulation of win-stay but not lose-shift strategies as a function of outcome value in Rock, Paper, Scissors

    Science.gov (United States)

    Forder, Lewis; Dyson, Benjamin James

    2016-01-01

    Competitive environments in which individuals compete for mutually-exclusive outcomes require rational decision making in order to maximize gains but often result in poor quality heuristics. Reasons for the greater reliance on lose-shift relative to win-stay behaviour shown in previous studies were explored using the game of Rock, Paper, Scissors and by manipulating the value of winning and losing. Decision-making following a loss was characterized as relatively fast and relatively inflexible both in terms of the failure to modulate the magnitude of lose-shift strategy and the lack of significant neural modulation. In contrast, decision-making following a win was characterized as relatively slow and relatively flexible both in terms of a behavioural increase in the magnitude of win-stay strategy and a neural modulation of feedback-related negativity (FRN) and stimulus-preceding negativity (SPN) following outcome value modulation. The win-stay/lose-shift heuristic appears not to be a unified mechanism, with the former relying on System 2 processes and the latter relying on System 1 processes. Our ability to play rationally appears more likely when the outcome is positive and when the value of wins are low, highlighting how vulnerable we can be when trying to succeed during competition. PMID:27658703

  4. Large-scale expansion of agriculture in Amazonia may be a no-win scenario

    Science.gov (United States)

    Oliveira, Leydimere J. C.; Costa, Marcos H.; Soares-Filho, Britaldo S.; Coe, Michael T.

    2013-06-01

    Using simplified climate and land-use models, we evaluated primary forests’ carbon storage and soybean and pasture productivity in the Brazilian Legal Amazon under several scenarios of deforestation and increased CO2. The four scenarios for the year 2050 that we analyzed consider (1) radiative effects of increased CO2, (2) radiative and physiological effects of increased CO2, (3) effects of land-use changes on the regional climate and (4) radiative and physiological effects of increased CO2 plus land-use climate feedbacks. Under current conditions, means for aboveground forest live biomass (AGB), soybean yield and pasture yield are 179 Mg-C ha-1, 2.7 Mg-grains ha-1 and 16.2 Mg-dry mass ha-1 yr-1, respectively. Our results indicate that expansion of agriculture in Amazonia may be a no-win scenario: in addition to reductions in carbon storage due to deforestation, total agriculture output may either increase much less than proportionally to the potential expansion in agricultural area, or even decrease, as a consequence of climate feedbacks from changes in land use. These climate feedbacks, usually ignored in previous studies, impose a reduction in precipitation that would lead agriculture expansion in Amazonia to become self-defeating: the more agriculture expands, the less productive it becomes.

  5. Seeking a Game in which the standard model Group shall Win

    CERN Document Server

    Bennett, Don

    2013-01-01

    It is attempted to construct a group-dependent quantity that could be used to single out the Standard Model group S(U(2) x U(3)) as being the "winner" by this quantity being the biggest possible for just the Standard Model group. The suggested quantity is first of all based on the inverse quadratic Cassimir for the fundamental or better smallest faithful representation in a notation in which the adjoint representation quadratic Cassimir is normalized to unity. Then a further correction is added to help the wanted Standard Model group to win and the rule comes even to involve the Abelian group U(1) to be multiplied into the group to get this correction be allowed. The scheme is suggestively explained to have some physical interpretation(s). By some appropriate proceedure for extending the group dependent quantity to groups that are not simple we find a way to make the Standard Model Group the absolute "winner". Thus we provide an indication for what could be the reason for the Standard Model Group having been ...

  6. Performing to win unlocking the secrets of the arts for personal and business success

    CERN Document Server

    Powell, Mark

    2016-01-01

    This book explores and demonstrates the transformative learning experiences that organizations and their leaders can derive from the arts. It is through the arts that we have always explored our humanity: through dance and music; art and sculpture; theatre and poetry. The arts allow us to explore our own selves and our relationship to others and to the world around us. This central role of the arts is commonly accepted in everyday life, but the implications of this are not typically extended to the world of business. The authors argues strongly that, to the contrary, the methodologies and approaches that are fundamental to performing artists of all kinds can provide exactly the kind of inspirational, people-centred and performance-related techniques that are missing from much of the typically mechanistic, systems-based and process-driven training and development of managers and executives. Technical proficiency and expertise are not enough to deliver an award-winning result; what enables a truly outstanding p...

  7. Technical and Tactical Aspects that Differentiate Winning and Losing Performances in Elite Male Karate Fighters.

    Science.gov (United States)

    Vidranski, Tihomir; Sertić, Hrvoje; Jukić, Josefina

    2015-07-01

    The purpose of this research was to identify the fighters' technical and tactical activity indicators in order to determine indicator significance regarding situational efficiency and designation between winning and losing performances in a karate match. We scientifically observed a sample of 274 male contesters of 137 karate matches during the 2008 World Karate Championship in Tokyo. Each individual competitor was observed in maximum of three matches. The matches were recorded using a DVD camera in order to collect data for further analysis, and the sample was further described using 48 technical and tactical indicators of situational efficiency and match outcome variables. The obtained results indicate that a karate match is composed of 91% of non-scoring techniques and 9% of scoring techniques in the total technique frequency. On this basis a significant difference in the situational efficiency between the match winners and the losing contesters has been discovered. Those two groups of fighters exhibit a statistically significant difference (pkarate match are in the largest extent defined by non-scoring techniques. Therefore, it would be a grave mistake to disregard non-scoring karate techniques in any future situational efficiency studies. It has been discovered that the winners differ from the defeated contesters by a higher level of situational efficiency in their executed techniques, which incorporate versatility, biomechanical and structural complexity, topological diversity and a specific tactical concept of technique use in the attack phase.

  8. Goal or gold: overlapping reward processes in soccer players upon scoring and winning money.

    Directory of Open Access Journals (Sweden)

    Alexander Niklas Häusler

    Full Text Available 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 ventromedial pre-frontal cortex. The three main components of reward-associated learning, i.e., reward probability (RP, reward reception (RR and reward prediction errors (RPE showed highly similar activation in both con-texts, with only the RR and RPE components displaying overlapping reward activity. Passing and shooting behavior did not correlate with individual egoism scores, but we observe a positive correlation be-tween egoism and activity in the left middle frontal gyrus upon scoring after a pass versus a direct shot. Our findings suggest that rewards in the context of soccer and monetary incentives are based on similar neural processes.

  9. Chronic Heart Failure: We Are Fighting the Battle, but Are We Winning the War?

    Directory of Open Access Journals (Sweden)

    John J. Atherton

    2012-01-01

    Full Text Available Heart failure represents an end-stage phenotype of a number of cardiovascular diseases and is generally associated with a poor prognosis. A number of organized battles fought over the last two to three decades have resulted in considerable advances in treatment including the use of drugs that interfere with neurohormonal activation and device-based therapies such as implantable cardioverter defibrillators and cardiac resynchronization therapy. Despite this, the prevalence of heart failure continues to rise related to both the aging population and better survival in patients with cardiovascular disease. Registries have identified treatment gaps and variation in the application of evidenced-based practice, including the use of echocardiography and prescribing of disease-modifying drugs. Quality initiatives often coupled with multidisciplinary, heart failure disease management promote self-care and minimize variation in the application of evidenced-based practice leading to better long-term clinical outcomes. However, to address the rising prevalence of heart failure and win the war, we must also turn our attention to disease prevention. A combined approach is required that includes public health measures applied at a population level and screening strategies to identify individuals at high risk of developing heart failure in the future.

  10. Cinema, imaginário e identidade em falsche bewegung (1975, de win wenders

    Directory of Open Access Journals (Sweden)

    Menine Júnior, Mauro de Araújo

    2009-01-01

    Full Text Available O cineasta Win Wenders, na direção de Movimento em Falso (1975, assim como em Alice nas cidades (1974 e No decorrer do tempo (1976, encerra uma trilogia cujas representações do imaginário e da identidade alemã se mostram impregnadas de um violento niilismo quanto à noção da possibilidade de um projeto coletivo, de um precário comum-pertencer dentro de determinado estado político e herança histórica, da decadência do cinema enquanto linguagem atrelada a uma ética-estética do passado. O presente artigo propõe uma leitura crítica acerca das representações identitárias em Movimento em Falso (Falsche Bewegung, 1975 e de como os mesmos são operacionalizados como reprodutores de sentido(s à memória, aos mitos, às histórias de uma determinada geografia imaginária

  11. The Viral Concept: the Winning Ticket of the Romanian Online Advertising Industry

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available The connection between the steady development of the Internet in Romania in the last five years, as channel of transmitting the marketing message, and the viral concept, as method of transmitting the message, may become the winning ticket for the Romanian online advertising market. Thus, in the current socio-economic context, any company who wishes to be successful in the virtual space cannot ignore the viral marketing techniques for several reasons. Firstly, we are talking about the profile of Internet users who tend to constitute a new social group. Secondly, we are talking about the thirst for information. And, last but not least, we are talking about the appetite for online chatting, statistics showing that 62% of the Roma-nian Internet users consider it a very "savory" information channel. This article tries to explain, in brief, what viral marketing is, which are its peculiarities, advantages, risks, as well as the limitations of its use, and which the strategies of a viral marketing campaign are. We will illustrate by giving successful examples from the Romanian online market.

  12. Stochastic win-stay-lose-shift strategy with dynamic aspirations in evolutionary social dilemmas

    Science.gov (United States)

    Amaral, Marco A.; Wardil, Lucas; Perc, Matjaž; da Silva, Jafferson K. L.

    2016-09-01

    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, we find good qualitative agreement with the Monte Carlo simulation results. Our analysis also reveals that the evolutionary outcomes are to a large degree independent of the network topology, including the number of neighbors that are considered for payoff determination on lattices, which further corroborates the local character of the microscopic dynamics. Unlike large-scale spatial patterns that typically emerge due to network reciprocity, here local checkerboard-like patterns remain virtually unaffected by differences in the macroscopic properties of the interaction network.

  13. Fear of failure: why american science is not winning the war on cancer.

    Science.gov (United States)

    Ness, Roberta B

    2010-02-01

    How to maximize creativity in biological science is a topic rarely discussed and yet critical to success in improving health. I believe that the needed approaches are not simply to flog individuals to try harder but to build systems and infrastructures that enhance creative effort. Lateral thinking can and should be taught. My hope for the future is that every graduate science curriculum will have a course in innovation. Institutions must provide time, space, and individual credit to the long and slow process of creative output. Highly multidisciplinary science should be supported, some of which may require seed or infrastructure support. Funders can separate idea generation from implementation. Scientists can minimize costs of failure by piloting and modeling ideas through incremental research, if supported by funders. But perhaps the very first step is to initiate a vibrant discussion of what we can do to enhance creativity in American biological science-it is time to stop complaining and to start winning the war on cancer.

  14. Antinociceptive interactions between Mu-opioid receptor agonists and the serotonin uptake inhibitor clomipramine in rhesus monkeys: role of Mu agonist efficacy.

    Science.gov (United States)

    Banks, Matthew L; Rice, Kenner C; Negus, S Stevens

    2010-11-01

    Mu-opioid agonists are effective analgesics but have undesirable effects such as sedation and abuse liability that limit their clinical effectiveness. Serotonergic systems also modulate nociception, and serotonin uptake inhibitors may be useful as adjuncts to enhance analgesic effects and/or attenuate undesirable effects of mu agonists. This study examined the effects of the serotonin uptake inhibitor clomipramine on behavioral effects produced in rhesus monkeys by mu agonists with varying efficacy at mu receptors (nalbuphine morphine > methadone. In the assay of capsaicin-induced allodynia, nalbuphine produced dose-dependent antiallodynia. Clomipramine alone was inactive, but as in the assay of thermal nociception, it produced a proportion-dependent enhancement in the effects of nalbuphine. These findings suggest that serotonin uptake inhibitors can selectively enhance the antinociceptive effects of mu agonists in nonhuman primates. These effects of serotonin uptake inhibitors may depend on the proportion of the serotonin uptake inhibitor and the efficacy of the mu agonist. The greatest enhancement was observed with intermediate proportions of clomipramine in combination with the low-efficacy mu agonist nalbuphine.

  15. Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice

    Science.gov (United States)

    Sharma, Pawan; Yi, Roslyn; Nayak, Ajay P.; Wang, Nadan; Tang, Francesca; Knight, Morgan J.; Pan, Shi; Oliver, Brian; Deshpande, Deepak A.

    2017-01-01

    Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma. Asthma was induced in mice using intranasal house dust mite or aerosol ova-albumin challenge, and chloroquine or quinine were tested in both prophylactic and treatment models. Allergen challenge resulted in airway inflammation as evidenced by increased immune cells infiltration and release of cytokines and chemokines in the lungs, which were significantly attenuated in TAS2R agonists treated mice. TAS2R agonists attenuated features of airway remodeling including smooth muscle mass, extracellular matrix deposition and pro-fibrotic signaling, and also prevented mucus accumulation and development of AHR in mice. Mechanistic studies using human neutrophils demonstrated that inhibition of immune cell chemotaxis is a key mechanism by which TAS2R agonists blocked allergic airway inflammation and exerted anti-asthma effects. Our comprehensive studies establish the effectiveness of TAS2R agonists in mitigating multiple features of allergic asthma.

  16. Trialkyltin rexinoid-X receptor agonists selectively potentiate thyroid hormone induced programs of xenopus laevis metamorphosis

    NARCIS (Netherlands)

    Mengeling, Brenda J.; Murk, Albertinka J.; Furlow, J.D.

    2016-01-01

    The trialkyltins tributyltin (TBT) and triphenyltin (TPT) can function as rexinoid-X receptor (RXR) agonists. We recently showed that RXR agonists can alter thyroid hormone (TH) signaling in a mammalian pituitary TH-responsive reporter cell line, GH3.TRE-Luc. The prevalence of TBT and TPT in the

  17. Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists Administration: A Rapid Overview.

    Science.gov (United States)

    Soltani, Hoda; Pardakhty, Abbas

    2016-04-01

    Novel drug delivery systems for controlled-release of opioid agonists as a long time painkillers or opioid antagonists for opium, heroin, and alcohol addiction are under development or in clinical use today. In this article, the field of "new drug delivery systems" is momentarily reviewed from the viewpoint of the marketed opioid agonists/antagonists dosage forms today.

  18. 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.

  19. Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists Administration: A Rapid Overview

    OpenAIRE

    Soltani, Hoda; Pardakhty, Abbas

    2016-01-01

    Novel drug delivery systems for controlled-release of opioid agonists as a long time painkillers or opioid antagonists for opium, heroin, and alcohol addiction are under development or in clinical use today. In this article, the field of “new drug delivery systems” is momentarily reviewed from the viewpoint of the marketed opioid agonists/antagonists dosage forms today.

  20. Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder

    NARCIS (Netherlands)

    Pian, KLH; Westerberg, HGM; van Megen, HJGM; den Boer, JA

    1998-01-01

    The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another nonselective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients.