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Sample records for 5-ht2c antagonist sb

  1. SB 242084, a selective and brain penetrant 5-HT2C receptor antagonist.

    PubMed

    Kennett, G A; Wood, M D; Bright, F; Trail, B; Riley, G; Holland, V; Avenell, K Y; Stean, T; Upton, N; Bromidge, S; Forbes, I T; Brown, A M; Middlemiss, D N; Blackburn, T P

    1997-01-01

    SB 242084 has a high affinity (pKi 9.0) for the cloned human 5-HT2C receptor and 100- and 158-fold selectivity over the closely related cloned human 5-HT2B and 5-HT2A subtypes respectively. SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity. SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding. A large acute dose of SB 242084 (30 mg/kg p.o.) had no effect on seizure susceptibility in the rat maximal electroshock seizure threshold test. Also, while SB 242084 (2 and 6 mg/kg p.o. 1 hr pre-test) antagonized the hypophagic response to mCPP, neither acute nor subchronic administration of the drug, for 5 days at 2 or 6 mg/kg p.o. twice daily, affected food intake or weight gain. The results suggest that SB 242084 is the first reported selective potent and brain penetrant 5-HT2C receptor antagonist and has anxiolytic-like activity, but does not possess either proconvulsant or hyperphagic properties which are characteristic of mutant mice lacking the 5-HT2C receptor. PMID:9225286

  2. (1R, 3S)-(−)-Trans-PAT: A novel full-efficacy serotonin 5-HT2C receptor agonist with 5-HT2A and 5-HT2B receptor inverse agonist/antagonist activity

    PubMed Central

    Booth, Raymond G.; Fang, Lijuan; Huang, Yingsu; Wilczynski, Andrzej; Sivendran, Sashikala

    2009-01-01

    The serotonin 5-HT2A, 5-HT2B, and 5-HT2C G protein-coupled receptors signal primarily through Gαq to activate phospholipase C (PLC) and formation of inositol phosphates (IP) and diacylglycerol. The human 5-HT2C receptor, expressed exclusively in the central nervous system, is involved in several physiological and psychological processes. Development of 5-HT2C agonists that do not also activate 5-HT2A or 5-HT2B receptors is challenging because transmembrane domain identity is about 75% among 5-HT2 subtypes. This paper reports 5-HT2 receptor affinity and function of (1R,3S)-(−)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (PAT), a small molecule that produces anorexia and weight-loss after peripheral administration to mice. (−)-Trans-PAT is a stereoselective full-efficacy agonist at human 5-HT2C receptors, plus, it is a 5-HT2A/5-HT2B inverse agonist and competitive antagonist. The Ki of (−)-trans-PAT at 5-HT2A, 5-HT2B, and 5-HT2C receptors is 410, 1200, and 37 nM, respectively. Functional studies measured activation of PLC/[3H]-IP formation in clonal cells expressing human 5-HT2 receptors. At 5-HT2C receptors, (−)-trans-PAT is an agonist (EC50 = 20 nM) comparable to serotonin in potency and efficacy. At 5-HT2A and 5-HT2B receptors, (−)-trans-PAT is an inverse agonist (IC50 = 490 and 1,000 nM, respectively) and competitive antagonist (KB = 460 and 1400 nM, respectively) of serotonin. Experimental results are interpreted in light of molecular modeling studies indicating the (−)-trans-PAT protonated amine can form an ionic bond with D3.32 of 5-HT2A and 5-HT2C receptors, but, not with 5-HT2B receptors. In addition to probing 5-HT2 receptor structure and function, (−)-trans-PAT is a novel lead regarding 5-HT2C agonist/5-HT2A inverse agonist drug development for obesity and neuropsychiatric disorders. PMID:19397907

  3. Nucleus accumbens shell excitability is decreased by methamphetamine self-administration and increased by 5-HT2C receptor inverse agonism and agonism

    PubMed Central

    Graves, Steven M.; Clark, Mary J.; Traynor, John R.; Hu, Xiu-Ti; Napier, T. Celeste

    2014-01-01

    Methamphetamine profoundly increases brain monoamines and is a widely abused psychostimulant. The effects of methamphetamine self-administration on neuron function are not known for the nucleus accumbens, a brain region involved in addictive behaviors, including drug-seeking. One therapeutic target showing preclinical promise at attenuating psychostimulant-seeking is 5-HT2C receptors; however, the effects of 5-HT2C receptor ligands on neuronal physiology are unclear. 5-HT2C receptor agonism decreases psychostimulant-mediated behaviors, and the putative 5-HT2C receptor inverse agonist, SB 206553, attenuates methamphetamine-seeking in rats. To ascertain the effects of methamphetamine, and 5-HT2C receptor inverse agonism and agonism, on neuronal function in the nucleus accumbens, we evaluated methamphetamine, SB 206553, and the 5-HT2C receptor agonist and Ro 60-0175, on neuronal excitability within the accumbens shell subregion using whole-cell current-clamp recordings in forebrain slices ex vivo. We reveal that methamphetamine self-administration decreased generation of evoked action potentials. In contrast, SB 206553 and Ro 60-0175 increased evoked spiking, effects that were prevented by the 5-HT2C receptor antagonist, SB 242084. We also assessed signaling mechanisms engaged by 5-HT2C receptors, and determined that accumbal 5-HT2C receptors stimulated Gq, but not Gi/o. These findings demonstrate that methamphetamine-induced decreases in excitability of neurons within the nucleus accumbens shell were abrogated by both 5-HT2C inverse agonism and agonism, and this effect likely involved activation of Gq–mediated signaling pathways. PMID:25229719

  4. A novel aminotetralin-type serotonin (5-HT) 2C receptor-specific agonist and 5-HT2A competitive antagonist/5-HT2B inverse agonist with preclinical efficacy for psychoses.

    PubMed

    Canal, Clinton E; Morgan, Drake; Felsing, Daniel; Kondabolu, Krishnakanth; Rowland, Neil E; Robertson, Kimberly L; Sakhuja, Rajeev; Booth, Raymond G

    2014-05-01

    Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (-)-trans-(2S,4R)-4-(3'[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (-)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. (-)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug-induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4-iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine maleate)]; and hyperlocomotion induced by amphetamine. (-)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (-)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared with (-)-MBP, the enantiomer (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (-)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation, or motoric disorders. PMID:24563531

  5. A Novel Aminotetralin-Type Serotonin (5-HT) 2C Receptor-Specific Agonist and 5-HT2A Competitive Antagonist/5-HT2B Inverse Agonist with Preclinical Efficacy for Psychoses

    PubMed Central

    Morgan, Drake; Felsing, Daniel; Kondabolu, Krishnakanth; Rowland, Neil E.; Robertson, Kimberly L.; Sakhuja, Rajeev; Booth, Raymond G.

    2014-01-01

    Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (−)-trans-(2S,4R)-4-(3′[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (−)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. (−)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug-induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4-iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine maleate)]; and hyperlocomotion induced by amphetamine. (−)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (−)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared with (−)-MBP, the enantiomer (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (−)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation, or motoric disorders. PMID:24563531

  6. Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice.

    PubMed

    Zhang, Gongliang; Wu, Xian; Zhang, Yong-Mei; Liu, Huan; Jiang, Qin; Pang, Gang; Tao, Xinrong; Dong, Liuyi; Stackman, Robert W

    2016-02-01

    Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine. Serotonin 5-HT(2C) receptor (5-HT(2C)R) agonists suppress psychostimulant nicotine or cocaine-induced behavioral sensitization and drug-seeking behavior; however, the impact of 5-HT(2C)R agonists on behaviors relevant to opioid abuse and dependence has not been reported. In the present study, the effects of 5-HT(2C)R activation on the behavioral sensitization and naloxone-precipitated withdrawal symptoms were examined in mice underwent repeated exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop behavioral sensitization. Lorcaserin, a 5-HT(2C)R agonist, prevented the induction and expression, but not the development, of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT(2C)R antagonist, prevented the lorcaserin-mediated suppression of behavioral sensitization and withdrawal. Chronic morphine treatment was associated with an increase in the expression of 5-HT(2C)R protein in the ventral tegmental area, locus coeruleus and nucleus accumbens. These findings suggest that 5-HT(2C)R can modulate behavioral sensitization and withdrawal in morphine-dependent mice, and the activation of 5-HT(2C)R may represent a new avenue for the treatment of opioid addiction. PMID:26432939

  7. Decreased Incentive Motivation Following Knockout or Acute Blockade of the Serotonin Transporter: Role of the 5-HT2C Receptor.

    PubMed

    Browne, Caleb J; Fletcher, Paul J

    2016-09-01

    Acute pharmacological elevation of serotonin (5-hydroxytryptamine; 5-HT) activity decreases operant responding for primary reinforcers, suggesting that 5-HT reduces incentive motivation. The mechanism by which 5-HT alters incentive motivation is unknown, but parallel evidence that 5-HT2C receptor agonists also reduce responding for primary reinforcers implicates this receptor as a potential candidate. These experiments examined whether chronic and acute disruptions of serotonin transporter (SERT) activity altered incentive motivation, and whether the 5-HT2C receptor mediated the effects of elevated 5-HT on behavior. To assess incentive motivation, we measured responding for three different reinforcers: a primary reinforcer (saccharin), a conditioned reinforcer (CRf), and an unconditioned sensory reinforcer (USRf). In the chronic condition, responding was compared between SERT knockout (SERT-KO) mice and their wild-type littermates. In the acute condition, responding was examined in wild-type mice following treatment with 10 or 20 mg/kg citalopram, or its vehicle. The ability of the selective 5-HT2C antagonist SB 242084 to prevent the effects of SERT-KO and citalopram on responding was subsequently examined. Both SERT-KO and citalopram reduced responding for saccharin, a CRf, and a USRf. Treatment with SB 242084 enhanced responding for a CRf and a USRf in SERT-KO mice and blocked the effects of citalopram on CRf and USRf responding. However, SB 242084 was unable to prevent the effects of SERT-KO or citalopram on responding for saccharin. These results support a powerful inhibitory function for 5-HT in the control of incentive motivation, and indicate that the 5-HT2C receptor mediates these effects of 5-HT in a reinforcer-dependent manner. PMID:27125304

  8. Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of the stria terminalis: implications for anxiety during ethanol withdrawal.

    PubMed

    Marcinkiewcz, Catherine A; Dorrier, Cayce E; Lopez, Alberto J; Kash, Thomas L

    2015-02-01

    One of the hallmarks of alcohol dependence is the presence of a withdrawal syndrome during abstinence, which manifests as physical craving for alcohol accompanied by subjective feelings of anxiety. Using a model of chronic intermittent ethanol (CIE) vapor in mice, we investigated the role of serotonin2c receptor (5HT2c-R) signaling in the BNST as a neural substrate underlying ethanol-induced anxiety during withdrawal. Mice were subjected to a 5-day CIE regimen of 16 h of ethanol vapor exposure followed by an 8 h "withdrawal" period between exposures. After the 5th and final exposure, mice were withdrawn for 24 h or 1 week before experiments began. Anxiety-like behavior was assessed in the social approach, light dark, and open field tests with mice showing deficits in social, but not general anxiety-like behavior that was alleviated by pretreatment with the 5HT2c-R antagonist SB 242,084 (3 mg/kg, i.p.) 24 h and 1 week post-CIE. Using immunohistochemistry and whole cell patch clamp electrophysiology, we also found that CIE increased FOS-IR and enhanced neuronal excitability in the ventral BNST (vBNST) 24 h into withdrawal in a 5HT2c-R dependent manner. This enhanced excitability persisted for 1 week post-CIE. We also found that mCPP, a 5HT2c/b agonist, induced a more robust depolarization in cells of the vBNST in CIE mice, confirming that 5HT2c-R signaling is upregulated in the vBNST following CIE. Taken together, these results suggest that CIE upregulates 5HT2c-R signaling in the vBNST, leading to increased excitability. This enhanced excitability of the vBNST may drive increased anxiety-like behavior during ethanol withdrawal. PMID:25229718

  9. Effects of RO 60 0175, a 5-HT(2C) receptor agonist, in three animal models of anxiety.

    PubMed

    Kennett, G; Lightowler, S; Trail, B; Bright, F; Bromidge, S

    2000-01-10

    There is some controversy as to whether 5-HT(2C) receptor agonists are anxiogenic or anxiolytic. The effects of the novel 5-HT(2C) receptor agonist, (S)-2-chloro-5-fluoro-indol-1-yl)-1-methyl ethylamine fumarate (RO 60 0175), in three models of anxiety were therefore tested. RO 60 0175 was found to induce hypolocomotion in rats at doses greater than 0.5 mg/kg s.c., an effect reversed by the selective 5-HT(2C) receptor antagonist, SB-242084. RO 60 0175 did not elicit anxiolytic-like responses in the social interaction test under high light unfamiliar conditions, but suppressed both time spent in social interaction and locomotion at doses of 1 and 3 mg/kg s.c., suggesting a sedative response. In the Vogel conflict test, RO 60 0175 had no significant action on the number of shocks taken. In the Geller-Seifter test, RO 60 0175 (0.3 and 1 mg/kg s.c.) simultaneously reduced both unpunished and punished lever pressing, a profile consistent with sedation. Finally, RO 60 0175 was tested in a rat social interaction test under low light familiar conditions optimal for the detection of anxiogenic-like responses. At 1 and 3 mg/kg s.c., RO 60 0175 reduced both time spent in social interaction and concurrent locomotion, a profile more consistent with sedation than anxiogenesis. In conclusion, RO 60 0175 induced sedative-like responses via 5-HT(2C) receptor activation, but was neither anxiolytic, nor clearly anxiogenic at the doses tested. PMID:10650160

  10. Convergence of melatonin and serotonin (5-HT) signaling at MT2/5-HT2C receptor heteromers.

    PubMed

    Kamal, Maud; Gbahou, Florence; Guillaume, Jean-Luc; Daulat, Avais M; Benleulmi-Chaachoua, Abla; Luka, Marine; Chen, Patty; Kalbasi Anaraki, Dina; Baroncini, Marc; Mannoury la Cour, Clotilde; Millan, Mark J; Prevot, Vincent; Delagrange, Philippe; Jockers, Ralf

    2015-05-01

    Inasmuch as the neurohormone melatonin is synthetically derived from serotonin (5-HT), a close interrelationship between both has long been suspected. The present study reveals a hitherto unrecognized cross-talk mediated via physical association of melatonin MT2 and 5-HT2C receptors into functional heteromers. This is of particular interest in light of the "synergistic" melatonin agonist/5-HT2C antagonist profile of the novel antidepressant agomelatine. A suite of co-immunoprecipitation, bioluminescence resonance energy transfer, and pharmacological techniques was exploited to demonstrate formation of functional MT2 and 5-HT2C receptor heteromers both in transfected cells and in human cortex and hippocampus. MT2/5-HT2C heteromers amplified the 5-HT-mediated Gq/phospholipase C response and triggered melatonin-induced unidirectional transactivation of the 5-HT2C protomer of MT2/5-HT2C heteromers. Pharmacological studies revealed distinct functional properties for agomelatine, which shows "biased signaling." These observations demonstrate the existence of functionally unique MT2/5-HT2C heteromers and suggest that the antidepressant agomelatine has a distinctive profile at these sites potentially involved in its therapeutic effects on major depression and generalized anxiety disorder. Finally, MT2/5-HT2C heteromers provide a new strategy for the discovery of novel agents for the treatment of psychiatric disorders. PMID:25770211

  11. Selective 5-HT2C agonists as potential antidepressants.

    PubMed

    Leysen, D C

    1999-02-01

    The antidepressants currently used need improvement, especially in terms of efficacy, relapse rate and onset of action. In this review the clinical and experimental data which support the rationale for 5-HT2C agonists in the treatment of depression are listed. Next, the results obtained with the non-selective 5-HT2C agonists on the market and in clinical development are described. Finally, the preclinical data on the more selective 5-HT2C agonists are summarized. These recent preclinical results reveal a greater potency and effect size compared to fluoxetine, good tolerability and no evidence of tolerance development. Selective 5-HT2C agonists might become innovative drugs for the treatment of depression, panic, obsessive-compulsive disorder (OCD), some forms of aggression and eating disorders. PMID:16160946

  12. Role of 5-HT2C Receptors in Effects of Monoamine Releasers on Intracranial Self-Stimulation in Rats

    PubMed Central

    Bauer, Clayton T.; Banks, Matthew L.; Blough, Bruce E.; Negus, S. Stevens

    2015-01-01

    Rationale Many monoamine releasers are abused by humans and produce abuse-related facilitation of intracranial self-stimulation (ICSS) in rats. Facilitation of ICSS in rats can be limited by monoamine releaser-induced serotonin (5-HT) release, but receptors that mediate 5-HT effects of monoamine releasers are unknown. Objectives Investigate whether 5-HT2C receptor activation is necessary for rate-decreasing effects produced in an ICSS procedure in rats by the 5-HT-selective monoamine releaser fenfluramine and the non-selective releasers napthylisopropylamine (PAL-287) and (+)-3,4-methylenedioxymethamphetamine ((+)-MDMA). Methods Adult male Sprague-Dawley rats with electrodes implanted in the medial forebrain bundle were trained to lever press for brain stimulation under a “frequency-rate” ICSS procedure. Effectiveness of the 5-HT2C antagonist SB 242,084 was evaluated to block rate-decreasing effects produced by (1) the 5-HT2C agonist Ro 60-0175, (2) the 5-HT-selective releaser fenfluramine, and (3) the mixed-action dopamine (DA)/norepinephrine (NE)/5-HT releasers PAL-287 (1.0-5.6 mg/kg), and (+)-MDMA (1.0-3.2 mg/kg). For comparison, effectiveness of SB 242,084 to alter rate-decreasing effects of the kappa opioid receptor agonist U69,593 and rate-increasing effects of the DA>5-HT releaser amphetamine were also examined. Results SB 242,084 pretreatment blocked rate-decreasing effects of Ro 60-0175 and fenfluramine, but not the rate-decreasing effects of U69,593 or the rate-increasing effects of amphetamine. SB 242,084 blunted the rate-decreasing effects and enhanced expression of rate-increasing effects of PAL-287 and (+)-MDMA. Conclusions These data suggest that 5-HT2C receptor activation contributes to rate-decreasing effects that are produced by selective and mixed-action 5-HT releasers in rats and that may oppose and limit the expression of abuse-related ICSS facilitation by these compounds. PMID:26041338

  13. Stimulation of medial prefrontal cortex serotonin 2C (5-HT(2C)) receptors attenuates cocaine-seeking behavior.

    PubMed

    Pentkowski, Nathan S; Duke, Felicia D; Weber, Suzanne M; Pockros, Lara A; Teer, Andrew P; Hamilton, Elizabeth C; Thiel, Kenneth J; Neisewander, Janet L

    2010-09-01

    Serotonin 2C receptor (5-HT(2C)R) agonists administered systemically attenuate both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior. To further elucidate the function of these receptors in addiction-like processes, this study examined the effects of microinfusing the 5-HT(2C)R agonist MK212 (0, 10, 30, 100 ng/side/0.2 microl) into the medial prefrontal cortex (mPFC) on cocaine self-administration and reinstatement of extinguished cocaine-seeking behavior. Male Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. Once responding stabilized, rats received MK212 microinfusions before tests for maintenance of cocaine self-administration. Next, extinction training to reduce cocaine-seeking behavior, defined as responses performed without cocaine reinforcement available, occurred until low extinction baselines were achieved. Rats then received MK212 microinfusions before tests for reinstatement of extinguished cocaine-seeking behavior elicited by cocaine-priming injections (10 mg/kg, i.p.) or response-contingent presentations of the cocaine-associated cues; operant responses during cocaine-primed reinstatement tests produced no consequences. MK212 microinfusions into the prelimbic and infralimbic, but not anterior cingulate, regions of the mPFC dose-dependently attenuated both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior, but did not reliably affect cocaine self-administration. A subsequent experiment showed that the effects of MK212 (100 ng/side/0.2 microl) on reinstatement of extinguished cocaine-seeking behavior were blocked by co-administration of the 5-HT(2C)R antagonist SB242084 (200 ng/side/0.2 microl). MK212 administered alone into the mPFC as a drug prime produced no discernable effects on cocaine-seeking behavior. These findings suggest that stimulation of 5-HT(2C)Rs in the mPFC attenuates the incentive motivational effects

  14. New therapeutic opportunities for 5-HT2C receptor ligands in neuropsychiatric disorders.

    PubMed

    Di Giovanni, Giuseppe; De Deurwaerdère, Philippe

    2016-01-01

    The 5-HT2C receptor (R) displays a widespread distribution in the CNS and is involved in the action of 5-HT in all brain areas. Knowledge of its functional role in the CNS pathophysiology has been impaired for many years due to the lack of drugs capable of discriminating among 5-HT2R subtypes, and to a lesser extent to the 5-HT1B, 5-HT5, 5-HT6 and 5-HT7Rs. The situation has changed since the mid-90s due to the increased availability of new and selective synthesized compounds, the creation of 5-HT2C knock out mice, and the progress made in molecular biology. Many pharmacological classes of drugs including antipsychotics, antidepressants and anxiolytics display affinities toward 5-HT2CRs and new 5-HT2C ligands have been developed for various neuropsychiatric disorders. The 5-HT2CR is presumed to mediate tonic/constitutive and phasic controls on the activity of different central neurobiological networks. Preclinical data illustrate this complexity to a point that pharmaceutical companies developed either agonists or antagonists for the same disease. In order to better comprehend this complexity, this review will briefly describe the molecular pharmacology of 5-HT2CRs, as well as their cellular impacts in general, before addressing its central distribution in the mammalian brain. Thereafter, we review the preclinical efficacy of 5-HT2C ligands in numerous behavioral tests modeling human diseases, highlighting the multiple and competing actions of the 5-HT2CRs in neurobiological networks and monoaminergic systems. Notably, we will focus this evidence in the context of the physiopathology of psychiatric and neurological disorders including Parkinson's disease, levodopa-induced dyskinesia, and epilepsy. PMID:26617215

  15. Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity

    PubMed Central

    Bazovkina, Darya V.; Kondaurova, Elena M.; Naumenko, Vladimir S.; Ponimaskin, Evgeni

    2015-01-01

    In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors. PMID:26380122

  16. Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity.

    PubMed

    Bazovkina, Darya V; Kondaurova, Elena M; Naumenko, Vladimir S; Ponimaskin, Evgeni

    2015-01-01

    In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors. PMID:26380122

  17. Effect of 5-HT2A and 5-HT2C receptors on temporal discrimination by mice.

    PubMed

    Halberstadt, Adam L; Sindhunata, Ivan S; Scheffers, Kees; Flynn, Aaron D; Sharp, Richard F; Geyer, Mark A; Young, Jared W

    2016-08-01

    Timing deficits are observed in patients with schizophrenia. Serotonergic hallucinogens can also alter the subjective experience of time. Characterizing the mechanism through which the serotonergic system regulates timing will increase our understanding of the linkage between serotonin (5-HT) and schizophrenia, and will provide insight into the mechanism of action of hallucinogens. We investigated whether interval timing in mice is altered by hallucinogens and other 5-HT2 receptor ligands. C57BL/6J mice were trained to perform a discrete-trials temporal discrimination task. In the discrete-trials task, mice were presented with two levers after a variable interval. Responding on lever A was reinforced if the interval was <6.5 s, and responding on lever B was reinforced if the interval was >6.5 s. A 2-parameter logistic function was fitted to the proportional choice for lever B (%B responding), yielding estimates of the indifference point (T50) and the Weber fraction (a measure of timing precision). The 5-HT2A antagonist M100907 increased T50, whereas the 5-HT2C antagonist SB-242,084 reduced T50. The results indicate that 5-HT2A and 5-HT2C receptors have countervailing effects on the speed of the internal pacemaker. The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI; 3 mg/kg IP), a 5-HT2 agonist, flattened the response curve at long stimulus intervals and shifted it to the right, causing both T50 and the Weber fraction to increase. The effect of DOI was antagonized by M100907 (0.03 mg/kg SC) but was unaffected by SB-242,084 (0.1 mg/kg SC). Similar to DOI, the selective 5-HT2A agonist 25CN-NBOH (6 mg/kg SC) reduced %B responding at long stimulus intervals, and increased T50 and the Weber fraction. These results demonstrate that hallucinogens alter temporal perception in mice, effects that are mediated by the 5-HT2A receptor. It appears that 5-HT regulates temporal perception, suggesting that altered serotonergic signaling may contribute to the timing deficits

  18. Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.

    PubMed

    Smith, R L; Canton, H; Barrett, R J; Sanders-Bush, E

    1998-11-01

    Extensive behavioral and biochemical evidence suggests an agonist role at the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of hallucinogenic drugs. However the published in vitro pharmacological properties of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not consistent with this hypothesis. We, therefore, undertook an extensive investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT activated the major intracellular signaling pathway (phosphoinositide hydrolysis) to an extent comparable to that produced by serotonin. Because drug efficacy changes with receptor density and cellular microenvironment, we also examined the properties of DMT in native preparations using a behavioral and biochemical approach. Rats were trained to discriminate an antagonist ketanserin from an agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice paradigm. Pharmacological studies showed that responding on the DOI and ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors, and hence, was a suitable model for evaluating the in vivo functional properties of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and 5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time. This difference is interesting in light of the recent report that the hallucinogenic activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor plays a less prominent role in the action of DMT. PMID:9768567

  19. Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures.

    PubMed

    Venzi, Marcello; David, François; Bellet, Joachim; Cavaccini, Anna; Bombardi, Cristiano; Crunelli, Vincenzo; Di Giovanni, Giuseppe

    2016-09-01

    Absence seizures (ASs) are the hallmark of childhood/juvenile absence epilepsy. Monotherapy with first-line anti-absence drugs only controls ASs in 50% of patients, indicating the need for novel therapeutic targets. Since serotonin family-2 receptors (5-HT2Rs) are known to modulate neuronal activity in the cortico-thalamo-cortical loop, the main network involved in AS generation, we investigated the effect of selective 5-HT2AR and 5-HT2CR ligands on ASs in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well established polygenic rat model of these non-convulsive seizures. GAERS rats were implanted with fronto-parietal EEG electrodes under general anesthesia, and their ASs were later recorded under freely moving conditions before and after intraperitoneal administration of various 5-HT2AR and 5-HT2CR ligands. The 5-HT2A agonist TCB-2 dose-dependently decreased the total time spent in ASs, an effect that was blocked by the selective 5-HT2A antagonist MDL11,939. Both MDL11,939 and another selective 5-HT2A antagonist (M100,907) increased the length of individual seizures when injected alone. The 5-HT2C agonists lorcaserin and CP-809,101 dose-dependently suppressed ASs, an effect blocked by the selective 5-HT2C antagonist SB 242984. In summary, 5-HT2ARs and 5-HT2CRs negatively control the expression of experimental ASs, indicating that selective agonists at these 5-HT2R subtypes might be potential novel anti-absence drugs. PMID:27085605

  20. Compulsive behavior in the 5-HT2C receptor knockout mouse.

    PubMed

    Chou-Green, Jennifer M; Holscher, Todd D; Dallman, Mary F; Akana, Susan F

    2003-04-01

    The efficacy of serotonergic pharmacotherapy indicates that serotonin (5-HT) plays a role in the treatment, if not the etiology, of obsessive-compulsive disorder (OCD). While some clinical evidence implicates 5-HT(2C) receptors in this disorder, a definitive function has yet to be validated. We hypothesized that 5-HT(2C) receptor knockout (KO) mice may display compulsive-like behavior. This paper describes characterization of several distinct, highly organized behaviors in mice lacking functional 5-HT(2C) receptors, which supports a compulsive-like syndrome.Compulsive-like behavior was assessed in male 5-HT(2C) receptor KO and wildtype (WT) mice. Chewing of non-nutritive clay, chewing patterns on plastic-mesh screens, and the frequency of head dipping were measured. 5-HT(2C) receptor KO mice chewed more clay, produced a distinct pattern of "neat" chewing of plastic screens and exhibited reduced habituation of head dipping activity compared to WT mice. We conclude that the 5-HT(2C) receptor null mutant mouse provides a promising model of compulsive behavior and a means to further explore the role of 5-HT in OCD. PMID:12782219

  1. Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists

    PubMed Central

    2015-01-01

    A series of pyrido[3,4-d]azepines that are potent and selective 5-HT2C receptor agonists is disclosed. Compound 7 (PF-04781340) is identified as a suitable lead owing to good 5-HT2C potency, selectivity over 5-HT2B agonism, and in vitro ADME properties commensurate with an orally available and CNS penetrant profile. The synthesis of a novel bicyclic tetrasubstituted pyridine core template is outlined, including rationale to account for the unexpected formation of aminopyridine 13 resulting from an ammonia cascade cyclization. PMID:25815155

  2. Therapeutic Potential of 5-HT2C Receptor Agonists for Addictive Disorders.

    PubMed

    Higgins, Guy A; Fletcher, Paul J

    2015-07-15

    The neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) has long been associated with the control of a variety of motivated behaviors, including feeding. Much of the evidence linking 5-HT and feeding behavior was obtained from studies of the effects of the 5-HT releaser (dex)fenfluramine in laboratory animals and humans. Recently, the selective 5-HT2C receptor agonist lorcaserin received FDA approval for the treatment of obesity. This review examines evidence to support the use of selective 5-HT2C receptor agonists as treatments for conditions beyond obesity, including substance abuse (particularly nicotine, psychostimulant, and alcohol dependence), obsessive compulsive, and excessive gambling disorder. Following a brief survey of the early literature supporting a role for 5-HT in modulating food and drug reinforcement, we propose that intrinsic differences between SSRI and serotonin releasers may have underestimated the value of serotonin-based pharmacotherapeutics to treat clinical forms of addictive behavior beyond obesity. We then highlight the critical involvement of the 5-HT2C receptor in mediating the effect of (dex)fenfluramine on feeding and body weight gain and the evidence that 5-HT2C receptor agonists reduce measures of drug reward and impulsivity. A recent report of lorcaserin efficacy in a smoking cessation trial further strengthens the idea that 5-HT2C receptor agonists may have potential as a treatment for addiction. This review was prepared as a contribution to the proceedings of the 11th International Society for Serotonin Research Meeting held in Hermanus, South Africa, July 9-12, 2014. PMID:25870913

  3. Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity.

    PubMed

    Miller, Keith J

    2005-10-01

    Obesity continues to be a burgeoning health problem worldwide. Before their removal from the market, fenfluramine and the more active enantiomer dexfenfluramine were considered to be among the most effective of weight loss agents. Much of the weight loss produced by fenfluramine was attributed to the direct activation of serotonin 5-HT(2C) receptors in the central nervous system via the desmethyl-metabolite of fenfluramine, norfenfluramine. Norfenfluramine, however, is non-selective, activating additional serotonin receptors, such as 5-HT(2A) and 5-HT(2B), which likely mediated the heart valve hypertrophy seen in many patients. Development of highly selective 5-HT(2C) agonists may recapitulate the clinical anti-obesity properties observed with fenfluramine while avoiding the significant cardiovascular and pulmonary side effects. PMID:16249524

  4. Selective 5-HT2C receptor agonists: Design and synthesis of pyridazine-fused azepines.

    PubMed

    Green, Martin P; McMurray, Gordon; Storer, R Ian

    2016-08-15

    Heterocycle-fused azepines are discussed as potent 5-HT2C receptor agonists with excellent selectivity over 5-HT2B agonism. Synthesis and structure activity relationships are outlined for a series of bicyclic pyridazino[3,4-d]azepines. By comparison with earlier published work, in vitro assays predict a high probability for achieving CNS penetration for a potent and selective compound 15a, a pre-requisite to achieve in vivo efficacy. PMID:27381086

  5. The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

    PubMed Central

    Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

    2014-01-01

    Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

  6. 5-HT(2C) serotonin receptor blockade prevents tau protein hyperphosphorylation and corrects the defect in hippocampal synaptic plasticity caused by a combination of environmental stressors in mice.

    PubMed

    Busceti, Carla Letizia; Di Pietro, Paola; Riozzi, Barbara; Traficante, Anna; Biagioni, Francesca; Nisticò, Robert; Fornai, Francesco; Battaglia, Giuseppe; Nicoletti, Ferdinando; Bruno, Valeria

    2015-09-01

    Exposure to multimodal sensory stressors is an everyday occurrence and sometimes becomes very intense, such as during rave parties or other recreational events. A growing body of evidence suggests that strong environmental stressors might cause neuronal dysfunction on their own in addition to their synergistic action with illicit drugs. Mice were exposed to a combination of physical and sensory stressors that are reminiscent of those encountered in a rave party. However, this is not a model of rave because it lacks the rewarding properties of rave. A 14-h exposure to environmental stressors caused an impairment of hippocampal long-term potentiation (LTP) and spatial memory, and an enhanced phosphorylation of tau protein in the CA1 and CA3 regions. These effects were transient and critically depended on the activation of 5-HT2C serotonin receptors, which are highly expressed in the CA1 region. Acute systemic injection of the selective 5-HT2C antagonist, RS-102,221 (2 mg/kg, i.p., 2 min prior the onset of stress), prevented tau hyperphosphorylation and also corrected the defects in hippocampal LTP and spatial memory. These findings suggest that passive exposure to a combination of physical and sensory stressors causes a reversible hippocampal dysfunction, which might compromise mechanisms of synaptic plasticity and spatial memory for a few days. Drugs that block 5-HT2C receptors might protect the hippocampus against the detrimental effect of environmental stressors. PMID:26145279

  7. 5-HT(2A) receptor blockade and 5-HT(2C) receptor activation interact to reduce cocaine hyperlocomotion and Fos protein expression in the caudate-putamen.

    PubMed

    Pockros, Lara A; Pentkowski, Nathan S; Conway, Sineadh M; Ullman, Teresa E; Zwick, Kimberly R; Neisewander, Janet L

    2012-12-01

    Both the 5-HT(2A) receptor (R) antagonist M100907 and the 5-HT(2C) R agonist MK212 attenuate cocaine-induced dopamine release and hyperlocomotion. This study examined whether these drugs interact to reduce cocaine hyperlocomotion and Fos expression in the striatum and prefrontal cortex. We first determined from dose-effect functions a low dose of both M100907 and MK212 that failed to alter cocaine (15 mg/kg, i.p.) hyperlocomotion. Subsequently, we examined whether these subthreshold doses given together would attenuate cocaine hyperlocomotion, consistent with a 5-HT(2A)/5-HT(2C) R interaction. Separate groups of rats received two sequential drug injections 5 min apart immediately before a 1-h locomotion test as follows: (1) saline + saline, (2) saline + cocaine, (3) 0.025 mg/kg M100907 + cocaine, (4) 0.125 mg/kg MK212 + cocaine, or (5) cocktail combination of 0.025 mg/kg M100907 and 0.125 mg/kg MK212 + cocaine. Brains were extracted for Fos immunohistochemistry 90 min after the second injection. We next examined the effects of 0.025 mg/kg M100907 and 0.125 mg/kg MK212, alone and in combination, on spontaneous locomotor activity. While neither drug given alone produced any effects, the M100907/MK212 cocktail attenuated cocaine hyperlocomotion as well as cocaine-induced Fos expression in the dorsolateral caudate-putamen (CPu), but had no effect on spontaneous locomotion. The findings suggest that 5-HT(2A) Rs and 5-HT(2C) Rs interact to attenuate cocaine hyperlocomotion and Fos expression in the CPu, and that the CPu is a potential locus of the interactive effects between these 5-HT(2) R subtypes on behavior. Further research investigating combined 5-HT(2A) R antagonism and 5-HT(2C) R agonism as a treatment for cocaine dependence is warranted. PMID:22886755

  8. Native serotonin 5-HT2C receptors are expressed as homodimers on the apical surface of choroid plexus epithelial cells.

    PubMed

    Herrick-Davis, Katharine; Grinde, Ellinor; Lindsley, Tara; Teitler, Milt; Mancia, Filippo; Cowan, Ann; Mazurkiewicz, Joseph E

    2015-04-01

    G protein-coupled receptors (GPCRs) are a prominent class of plasma membrane proteins that regulate physiologic responses to a wide variety of stimuli and therapeutic agents. Although GPCR oligomerization has been studied extensively in recombinant cells, it remains uncertain whether native receptors expressed in their natural cellular environment are monomers, dimers, or oligomers. The goal of this study was to determine the monomer/oligomer status of a native GPCR endogenously expressed in its natural cellular environment. Native 5-HT2C receptors in choroid plexus epithelial cells were evaluated using fluorescence correlation spectroscopy (FCS) with photon counting histogram (PCH). An anti-5-HT2C fragment antigen binding protein was used to label native 5-HT2C receptors. A known monomeric receptor (CD-86) served as a control for decoding the oligomer status of native 5-HT2C receptors by molecular brightness analysis. FCS with PCH revealed molecular brightness values for native 5-HT2C receptors equivalent to the molecular brightness of a homodimer. 5-HT2C receptors displayed a diffusion coefficient of 5 × 10(-9) cm(2)/s and were expressed at 32 receptors/μm(2) on the apical surface of choroid plexus epithelial cells. The functional significance and signaling capabilities of the homodimer were investigated in human embryonic kidney 293 cells using agonists that bind in a wash-resistant manner to one or both protomers of the homodimer. Whereas agonist binding to one protomer resulted in G protein activation, maximal stimulation required occupancy of both protomers. This study is the first to demonstrate the homodimeric structure of 5-HT2C receptors endogenously expressed in their native cellular environment, and identifies the homodimer as a functional signaling unit. PMID:25609374

  9. Native Serotonin 5-HT2C Receptors Are Expressed as Homodimers on the Apical Surface of Choroid Plexus Epithelial Cells

    PubMed Central

    Grinde, Ellinor; Lindsley, Tara; Teitler, Milt; Mancia, Filippo; Cowan, Ann; Mazurkiewicz, Joseph E.

    2015-01-01

    G protein–coupled receptors (GPCRs) are a prominent class of plasma membrane proteins that regulate physiologic responses to a wide variety of stimuli and therapeutic agents. Although GPCR oligomerization has been studied extensively in recombinant cells, it remains uncertain whether native receptors expressed in their natural cellular environment are monomers, dimers, or oligomers. The goal of this study was to determine the monomer/oligomer status of a native GPCR endogenously expressed in its natural cellular environment. Native 5-HT2C receptors in choroid plexus epithelial cells were evaluated using fluorescence correlation spectroscopy (FCS) with photon counting histogram (PCH). An anti–5-HT2C fragment antigen binding protein was used to label native 5-HT2C receptors. A known monomeric receptor (CD-86) served as a control for decoding the oligomer status of native 5-HT2C receptors by molecular brightness analysis. FCS with PCH revealed molecular brightness values for native 5-HT2C receptors equivalent to the molecular brightness of a homodimer. 5-HT2C receptors displayed a diffusion coefficient of 5 × 10−9 cm2/s and were expressed at 32 receptors/μm2 on the apical surface of choroid plexus epithelial cells. The functional significance and signaling capabilities of the homodimer were investigated in human embryonic kidney 293 cells using agonists that bind in a wash-resistant manner to one or both protomers of the homodimer. Whereas agonist binding to one protomer resulted in G protein activation, maximal stimulation required occupancy of both protomers. This study is the first to demonstrate the homodimeric structure of 5-HT2C receptors endogenously expressed in their native cellular environment, and identifies the homodimer as a functional signaling unit. PMID:25609374

  10. Regulation of Oligomeric Organization of the Serotonin 5-Hydroxytryptamine 2C (5-HT2C) Receptor Observed by Spatial Intensity Distribution Analysis*

    PubMed Central

    Ward, Richard J.; Pediani, John D.; Godin, Antoine G.; Milligan, Graeme

    2015-01-01

    The questions of whether G protein-coupled receptors exist as monomers, dimers, and/or oligomers and if these species interconvert in a ligand-dependent manner are among the most contentious current issues in biology. When employing spatial intensity distribution analysis to laser scanning confocal microscope images of cells stably expressing either a plasma membrane-associated form of monomeric enhanced green fluorescent protein (eGFP) or a tandem version of this fluorophore, the eGFP tandem was identified as a dimer. Similar studies on cells stably expressing an eGFP-tagged form of the epidermal growth factor receptor demonstrated that, although largely a monomer in the basal state, this receptor rapidly became predominantly dimeric upon the addition of its ligand epidermal growth factor. In cells induced to express an eGFP-tagged form of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor, global analysis of construct quantal brightness was consistent with the predominant form of the receptor being dimeric. However, detailed spatial intensity distribution analysis demonstrated the presence of multiple forms ranging from monomers to higher-order oligomers. Furthermore, treatment with chemically distinct 5-HT2C receptor antagonists resulted in a time-dependent change in the quaternary organization to one in which there was a preponderance of receptor monomers. This antagonist-mediated effect was reversible, because washout of the ligand resulted in the regeneration of many of the oligomeric forms of the receptor. PMID:25825490

  11. Sound-induced seizures in serotonin 5-HT2c receptor mutant mice.

    PubMed

    Brennan, T J; Seeley, W W; Kilgard, M; Schreiner, C E; Tecott, L H

    1997-08-01

    The epilepsies are a heterogeneous collection of seizure disorders with a lifetime expectancy risk rate of 2-4%. A convergence of evidence indicates that heritable factors contribute significantly to seizure susceptibility. Genetically epilepsy-prone rodent strains have been frequently used to examine the effect of genetic factors on seizure susceptibility. The most extensively studied of these have been strains that are susceptible to sound-induced convulsions (audiogenic seizures, or AGSs). Early observations of the AGS phenomenon were made in the laboratory of Dr. Ivan Pavlov; in the course of appetite-conditioning experiments in mice, the loud bell used to signal food presentation unexpectedly produced seizures in some animals. In 1947, DBA/2 (D2) mice were found to exhibit a genetic susceptibility to AGSs stimulated by a doorbell mounted in an iron tub. Since this discovery, AGSs have been among the most intensively studied phenotypes in behavioural genetics. Although several genetic loci confer susceptibility to AGSs, the corresponding genes have not been cloned. We report that null mutant mice lacking serotonin 5-HT2C receptors are extremely susceptible to AGSs. The onset of susceptibility is between two and three months of age, with complete penetrance in adult animals. AGS-induced immediate early gene expression indicates that AGSs are subcortical phenomena in auditory circuits. This AGS syndrome is the first produced by a known genetic defect; it provides a robust model for the examination of serotoninergic mechanisms in epilepsy. PMID:9241279

  12. Aromatic interactions impact ligand binding and function at serotonin 5-HT2C G protein-coupled receptors: receptor homology modelling, ligand docking, and molecular dynamics results validated by experimental studies

    NASA Astrophysics Data System (ADS)

    Córdova-Sintjago, Tania; Villa, Nancy; Fang, Lijuan; Booth, Raymond G.

    2014-02-01

    The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 G protein-coupled receptor (GPCR) family consists of types 2A, 2B, and 2C that share ∼75% transmembrane (TM) sequence identity. Agonists for 5-HT2C receptors are under development for psychoses; whereas, at 5-HT2A receptors, antipsychotic effects are associated with antagonists - in fact, 5-HT2A agonists can cause hallucinations and 5-HT2B agonists cause cardiotoxicity. It is known that 5-HT2A TM6 residues W6.48, F6.51, and F6.52 impact ligand binding and function; however, ligand interactions with these residues at the 5-HT2C receptor have not been reported. To predict and validate molecular determinants for 5-HT2C-specific activation, results from receptor homology modelling, ligand docking, and molecular dynamics simulation studies were compared with experimental results for ligand binding and function at wild type and W6.48A, F6.51A, and F6.52A point-mutated 5-HT2C receptors.

  13. Modulation of dopamine transmission by 5HT2C and 5HT3 receptors: a role in the antidepressant response.

    PubMed

    Dremencov, Eliyahu; Weizmann, Yifat; Kinor, Noa; Gispan-Herman, Iris; Yadid, Gal

    2006-02-01

    Dopaminergic mesolimbic and mesocortical systems are fundamental in hedonia and motivation. Therefore their regulation should be central in understanding depression treatment. This review highlights the dopaminergic activity in relation to depressive behavior and suggests two putative receptors as potential targets for research and development of future antidepressants. In this article we review data that describe the role of serotonin in regulating dopamine release, via 5HT2C and 5HT3 receptors. This action of serotonin appears to be linked to depressive-like behavior and to onset of behavioral effects of antidepressants in an animal model of depression. We suggest that drugs or strategies that decrease 5HT2C and increase 5HT3 receptor-mediated dopamine release in the limbic areas of the brain may provide a fast onset of therapeutic effect. Clinical and basic research data supporting this hypothesis are discussed. PMID:16475958

  14. RNA editing of the human serotonin 5-HT(2C) receptor delays agonist-stimulated calcium release.

    PubMed

    Price, R D; Sanders-Bush, E

    2000-10-01

    RNA encoding the human 5-HT(2C) receptor undergoes adenosine-to-inosine RNA editing events at five positions in the putative second intracellular loop, with a corresponding reduction in receptor/G-protein coupling. Agonist-stimulated calcium release was examined in NIH-3T3 fibroblasts stably expressing the nonedited human INI (hINI) or the edited hVSV or hVGV variants. We hypothesized that different receptor isoforms would show altered dynamics of agonist-induced calcium release. The three isoforms showed a rightward shift in agonist concentration-response curves for eliciting calcium release (EC(50) values: hINI, 2.2 nM; hVSV, 15 nM; hVGV, 49 nM). Additionally, the hVGV receptor showed a blunted and delayed [Ca(2+)](i) peak compared with the hINI or hVSV receptor isoforms. These distinctions in agonist-induced [Ca(2+)](i) release imply that edited 5-HT(2C) receptors may produce distinct physiological responses within the central nervous system. PMID:10999958

  15. We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders

    PubMed Central

    Cheng, Jianjun; Kozikowski, Alan P.

    2016-01-01

    The serotonin 2C (5-HT2C) receptor has been identified as a potential drug target for the treatment of a variety of central nervous system (CNS) disorders, such as obesity, substance abuse, and schizophrenia. In this Viewpoint article, recent progress in developing selective 5-HT2C agonists for use in treating these disorders is summarized, including the work of our group. Challenges in this field and the possible future directions are described. Homology modeling as a method to predict the binding modes of 5-HT2C ligands to the receptor is also discussed. Compared to known ligands, the improved pharmacological profiles of the 2-phenylcyclopropylmethylamine-based 5-HT2C agonists make them preferred candidates for further studies. PMID:26507582

  16. Human Serotonin 5-HT2C G Protein-Coupled Receptor Homology Model from the β2 Adrenoceptor Structure: Ligand Docking and Mutagenesis Studies

    PubMed Central

    RDOVA-SINTJAGO, TANIA CÓ; VILLA, NANCY; CANAL, CLINTON; BOOTH, RAYMOND

    2013-01-01

    Activation of the serotonin (5-hydroxytryptamine, 5-HT) 5HT2C G protein-coupled receptor (GPCR) is proposed as novel pharmacotherapy for obesity and neuropsychiatric disorders. In contrast, activation of the 5-HT2A and 5-HT2B GPCRs is associated with untoward hallucinogenic and cardiopulmonary effects, respectively. There is no crystal structure available to guide design of 5-HT2C receptor-specific ligands. For this reason, a homology model of the 5-HT2C receptor was built based on the crystal structure of the human β2 adrenoceptor GPCR to delineate molecular determinants of ligand–receptor interactions for drug design purposes. Computational and experimental studies were carried out to validate the model. Binding of N(CH3)2-PAT [(1R, 3S)-(−)-trans-1-phenyl-3-N,N-dimethylamino-1,2,3,4-tetrahydronaphthalene], a novel 5-HT2C agonist/5-HT2A/2B inverse agonist, and its secondary [NH(CH3)-PAT] and primary (NH2-PAT) amine analogs were studied at the 5-HT2C wild type (WT) and D3.32A, S3.36A, and Y7.43A 5-HT2C point-mutated receptors. Reference ligands included the tertiary amines lisuride and mesulergine and the primary amine 5-HT. Modeling results indicated that 5-HT2C residues D3.32, S3.36, and Y7.43 play a role in ligand binding. Experimental ligand binding results with WT and point-mutated receptors confirmed the impact of D3.32, S3.36, and Y7.43 on ligand affinity. PMID:24244046

  17. Endogenous 5-HT2C Receptors Phosphorylate the cAMP Response Element Binding Protein via Protein Kinase C-Promoted Activation of Extracellular-Regulated Kinases-1/2 in Hypothalamic mHypoA-2/10 Cells.

    PubMed

    Lauffer, Lisa; Glas, Evi; Gudermann, Thomas; Breit, Andreas

    2016-07-01

    Serotonin 5-HT2C receptors (5-HT2CR) activate Gq proteins and are expressed in the central nervous system (CNS). 5-HT2CR regulate emotion, feeding, reward, or cognition and may serve as promising drug targets to treat psychiatric disorders or obesity. Owing to technical difficulties in isolating cells from the CNS and the lack of suitable cell lines endogenously expressing 5-HT2CR, our knowledge about this receptor subtype in native environments is rather limited. The hypothalamic mHypoA-2/10 cell line was recently established and resembles appetite-regulating hypothalamic neurons of the paraventricular nucleus (PVN), where 5-HT2CR have been detected in vivo. Therefore, we tested mHypoA-2/10 cells for endogenous 5-HT2CR expression. Serotonin or the 5-HT2CR preferential agonist WAY-161,503 initiated cAMP response element (CRE)-dependent gene transcription with EC50 values of 15.5 ± 9.8 and 1.1 ± 0.9 nM, respectively. Both responses were blocked by two unrelated 5-HT2CR-selective antagonists (SB-242,084, RS-102,221) but not by a 5-HT2AR (EMD-281,014) or 5-HT2BR (RS-127,455) antagonists. By single-cell calcium imaging, we found that serotonin and WAY-161,503 induced robust calcium transients, which were also blunted by both 5-HT2CR antagonists. Additionally we revealed, first, that 5-HT2CR induced CRE activation via protein kinase C (PKC)-mediated engagement of extracellular-regulated kinases-1/2 and, second, that intrinsic activity of WAY-161,503 was in the range of 0.3-0.5 compared with serotonin, defining the frequently used 5-HT2CR agonist as a partial agonist of endogenous 5-HT2CR. In conclusion, we have shown that hypothalamic mHypoA-2/10 cells endogenously express 5-HT2CR and thus are the first cell line in which to analyze 5-HT2CR pharmacology, signaling, and regulation in its natural environment. PMID:27189964

  18. Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases alcohol intake in female alcohol preferring rats.

    PubMed

    Rezvani, Amir H; Cauley, Marty C; Levin, Edward D

    2014-10-01

    Serotonergic systems in the brain have been found to be important in the addiction to alcohol. The purpose of this study was to evaluate the efficacy of a novel 5-HT2c receptor agonist, lorcaserin for reducing alcohol consumption in alcohol-preferring (P) rats. Adult female rats were allowed to drink water or alcohol (12%, v/v) using a standard two-bottle choice procedure. Once stable baselines were established, the acute (0, 0.3125, 0.625 and 1.25 mg/kg, s.c.), and chronic (0, 0.625 mg/kg, sc for 10 days) effects of lorcaserin on alcohol intake and preference were assessed at different time points. In a separate experiment, the effects of lorcaserin on locomotor activity were determined. Our results show that both 0.625 and 1.25 mg/kg lorcaserin significantly reduced alcohol intake at 2, 4 and 6 h. after the drug administration. The chronic administration of 0.625 mg/kg lorcaserin significantly reduced alcohol intake up to 6h every day after the injection and there was no sign of diminished efficacy of the drug during 10-day treatment. To determine the effects of lorcaserin on sucrose intake, rats were put on a two-bottle choice of water vs a solution of 7% sucrose. The high dose of lorcaserin (1.25 mg/kg, s.c.) reduced sucrose intake only for up to 2 h. When tested for locomotor activity, lorcaserin injected 20 min before testing significantly reduced locomotor activity at all doses. However, when it was injected 5.5h before the start of the 1-h session, neither dose had a significant effect on locomotor activity. These results show the efficacy of lorcaserin in reducing alcohol intake without a significant effect on water intake and locomotion suggesting the involvement of 5-HT2c receptors in alcohol seeking behavior. Further research is warranted to determine the possible efficacy of lorcaserin or similar drugs as treatments for the treatment of alcoholism. PMID:25109272

  19. Lorcaserin (APD356), a selective 5-HT(2C) agonist, reduces body weight in obese men and women.

    PubMed

    Smith, Steven R; Prosser, Warren A; Donahue, David J; Morgan, Michael E; Anderson, Christen M; Shanahan, William R

    2009-03-01

    Lorcaserin (APD356) is a potent, selective 5-HT(2C) agonist with ~15-fold and 100-fold selectivity vs. 5-HT(2A) and 5-HT(2B) receptors, respectively. This study evaluated the safety and efficacy of lorcaserin for weight reduction in obese patients during a 12-week period. The randomized, double-blind, placebo-controlled, parallel-arm study enrolled 469 men and women between ages 18 and 65 and with BMI 30-45 kg/m(2). Patients received placebo, lorcaserin 10 mg q.d., lorcaserin 15 mg q.d., or lorcaserin 10 mg b.i.d. for 12 weeks, and were counseled to maintain their usual diet and activity. The primary end point was change in weight from baseline to day 85 by completer analysis. Safety analyses included echocardiograms at Screening and day 85/study exit. Lorcaserin was associated with progressive weight loss of 1.8 kg, 2.6 kg, and 3.6 kg at 10 mg q.d., 15 mg q.d., and 10 mg b.i.d., respectively, compared to placebo weight loss of 0.3 kg (P < 0.001 for each group). Similar results were seen by intent-to-treat last observation-carried forward (ITT-LOCF) analysis. The proportions of completers achieving > or =5% of initial body weight were 12.8, 19.5, 31.2, and 2.3% in the 10 mg q.d., 15 mg q.d., 10 mg b.i.d., and placebo groups, respectively. The most frequent adverse events (AEs) were transient headache, nausea, and dizziness. Echocardiograms showed no apparent drug-related effects on heart valves or pulmonary artery pressure (PAP). Lorcaserin was well tolerated and efficacious for weight reduction in this 12-week study. Longer-term trials employing behavior modification will be needed to more fully assess its safety and efficacy. PMID:19057523

  20. Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity

    PubMed Central

    Anastasio, N C; Liu, S; Maili, L; Swinford, S E; Lane, S D; Fox, R G; Hamon, S C; Nielsen, D A; Cunningham, K A; Moeller, F G

    2014-01-01

    Cocaine dependence remains a challenging public health problem with relapse cited as a major determinant in its chronicity and severity. Environmental contexts and stimuli become reliably associated with its use leading to durable conditioned responses (‘cue reactivity') that can predict relapse as well as treatment success. Individual variation in the magnitude and influence of cue reactivity over behavior in humans and animals suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse. In the present translational study, we investigated the contribution of variation in the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system in individual differences in cocaine cue reactivity in humans and rodents. We found that cocaine-dependent subjects carrying a single nucleotide polymorphism (SNP) in the HTR2C gene that encodes for the conversion of cysteine to serine at codon 23 (Ser23 variant) exhibited significantly higher attentional bias to cocaine cues in the cocaine-word Stroop task than those carrying the Cys23 variant. In a model of individual differences in cocaine cue reactivity in rats, we identified that high cocaine cue reactivity measured as appetitive approach behavior (lever presses reinforced by the discrete cue complex) correlated with lower 5-HT2CR protein expression in the medial prefrontal cortex and blunted sensitivity to the suppressive effects of the selective 5-HT2CR agonist WAY163909. Our translational findings suggest that the functional status of the 5-HT2CR system is a mechanistic factor in the generation of vulnerability to cocaine-associated cues, an observation that opens new avenues for future development of biomarker and therapeutic approaches to suppress relapse in cocaine dependence. PMID:24618688

  1. Stimulation of 5-HT2C Receptors Improves Cognitive Deficits Induced by Human Tryptophan Hydroxylase 2 Loss of Function Mutation

    PubMed Central

    Del'Guidice, Thomas; Lemay, Francis; Lemasson, Morgane; Levasseur-Moreau, Jean; Manta, Stella; Etievant, Adeline; Escoffier, Guy; Doré, François Y; Roman, François S; Beaulieu, Jean-Martin

    2014-01-01

    Polymorphisms in the gene encoding the serotonin synthesis enzyme Tph2 have been identified in mental illnesses, including bipolar disorder, major depression, autism, schizophrenia, and ADHD. Deficits in cognitive flexibility and perseverative behaviors are shared common symptoms in these disorders. However, little is known about the impact of Tph2 gene variants on cognition. Mice expressing a human TPH2 variant (Tph2-KI) were used to investigate cognitive consequences of TPH2 loss of function and pharmacological treatments. We applied a recently developed behavioral assay, the automated H-maze, to study cognitive functions in Tph2-KI mice. This assay involves the consecutive discovery of three different rules: a delayed alternation task, a non-alternation task, and a delayed reversal task. Possible contribution of locomotion, reward, and sensory perception were also investigated. The expression of loss-of-function mutant Tph2 in mice was associated with impairments in reversal learning and cognitive flexibility, accompanied by perseverative behaviors similar to those observed in human clinical studies. Pharmacological restoration of 5-HT synthesis with 5-hydroxytryptophan or treatment with the 5-HT2C receptor agonist CP809.101 reduced cognitive deficits in Tph2-KI mice and abolished perseveration. In contrast, treatment with the psychostimulant methylphenidate exacerbated cognitive deficits in mutant mice. Results from this study suggest a contribution of TPH2 in the regulation of cognition. Furthermore, identification of a role for a 5-HT2 receptor agonist as a cognition-enhancing agent in mutant mice suggests a potential avenue to explore for the personalized treatment of cognitive symptoms in humans with reduced 5-HT synthesis and TPH2 polymorphisms. PMID:24196946

  2. Lorcaserin, A 5-HT2C Receptor Agonist, Reduces Body Weight by Decreasing Energy Intake without Influencing Energy Expenditure

    PubMed Central

    Martin, Corby K.; Redman, Leanne M.; Zhang, Jinkun; Sanchez, Matilde; Anderson, Christen M.; Smith, Steven R.

    2011-01-01

    Context: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)2C receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). Objective: This study tested the effect of lorcaserin on EI and EE. Design, Participants, and Intervention: In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27–45 kg/m2) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1–7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. Outcomes: At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. Results: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced with lorcaserin but not placebo (mean ± sem for lorcaserin, −286 ± 86 kcal; placebo, −147 ± 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, −3.8 ± 0.4 kg; placebo, −2.2 ± 0.5 kg; P < 0.01), EI (lorcaserin, −470 ± 87 kcal; placebo, −205 ± 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. Conclusions: Lorcaserin reduces body weight through reduced EI, not altered EE or RQ. PMID:21190985

  3. Role of serotonin 5-HT2C and histamine H1 receptors in antipsychotic-induced diabetes: A pharmacoepidemiological-pharmacodynamic study in VigiBase.

    PubMed

    Montastruc, François; Palmaro, Aurore; Bagheri, Haleh; Schmitt, Laurent; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse

    2015-10-01

    Pharmacodynamic mechanisms of diabetes induced by antipsychotic drugs remain unclear, while numerous receptors have been suspected to be involved in the genesis of this Adverse Drug Reaction (ADR). We investigated potential relationships between antipsychotics׳ receptor occupancy (serotonin 5-HT1A, 5-HT2A, 5-HT2C, histamine H1, muscarinic M3, adrenergic α1, α2 or dopaminergic D2 D3 occupancies) and reports of diabetes using VigiBase(®), the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. All ADR reports from 15 first and second generation antipsychotic drugs recorded in VigiBase(®) were extracted. Logistic regression models, completed by disproportionality analysis, were used to determine the associations between antipsychotics׳ receptor occupancy and ICSRs of diabetes on VigiBase(®). During the study period, 94,460 ICSRs involved at least one of the 15 antipsychotics of interest. Diabetes was reported in 1799 (1.9%) patients. Clozapine was the most frequently suspected drug (n=953; 53.0%). A significant and positive association was found between histamine H1, muscarinic M3 and serotonin 5-HT2C, 5-HT2A receptor occupancies and reports of diabetes. A multivariable stepwise regression model showed that only serotonin 5-HT2c (AOR=2.13, CI 95% 1.72-2.64) and histamine H1 (AOR=1.91, CI 95% 1.38-2.64) predicted the risk for diabetes mellitus (p<0.001). Using an original pharmacoepidemiology-pharmacodynamic (PE-PD) approach, our study supports that antipsychotic drugs blocking simultaneously histamine H1 and serotonin 5-HT2C receptors are more frequently associated with diabetes reports in VigiBase(®) than other antipsychotics. These findings should encourage investigation of histamine H1 and serotonin 5-HT2C properties for predicting the risk of glycemic effects in candidate antipsychotics. PMID:26256010

  4. 5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence

    PubMed Central

    Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence

    2015-01-01

    Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398

  5. Synthesis and pharmacological evaluation of dual ligands for melatonin (MT1/MT2) and serotonin 5-HT2C receptor subtypes (II).

    PubMed

    Ettaoussi, Mohamed; Pérès, Basile; Errazani, Aïcha; Boutin, Jean A; Caignard, Daniel-Henri; Delagrange, Philippe; Melnyk, Patricia; Berthelot, Pascal; Yous, Saïd

    2015-01-27

    In this paper we report the investigation of C-3 and β-acetamide positions of agomelatine analogues. Concomitant insertion of a hydroxymethyl in the β-acetamide position and aliphatic groups in C-3 position produced a positive effect on both melatonin (MT1, MT2) and serotonin (5-HT2C) binding affinities. In particular, the allyl 6b and ethyl 15a represented the more interesting compounds of this series. Furthermore, the introduction of methyl cycloalkyl groups (compounds 11a, 12a) exhibited no change in both MT2 and 5-HT2C binding affinities while a decrease of MT1 binding affinity occurred leading to an MT2 selectivity. Finally, the acetamide modulation has led to methyl thiourea 11h, with a weak MT2 selectivity. PMID:25528336

  6. Application of an Integrated GPCR SAR-Modeling Platform To Explain the Activation Selectivity of Human 5-HT2C over 5-HT2B.

    PubMed

    Heifetz, Alexander; Storer, R Ian; McMurray, Gordon; James, Tim; Morao, Inaki; Aldeghi, Matteo; Bodkin, Mike J; Biggin, Philip C

    2016-05-20

    Agonism of the 5-HT2C serotonin receptor has been associated with the treatment of a number of diseases including obesity, psychiatric disorders, sexual health, and urology. However, the development of effective 5-HT2C agonists has been hampered by the difficulty in obtaining selectivity over the closely related 5-HT2B receptor, agonism of which is associated with irreversible cardiac valvulopathy. Understanding how to design selective agonists requires exploration of the structural features governing the functional uniqueness of the target receptor relative to related off targets. X-ray crystallography, the major experimental source of structural information, is a slow and challenging process for integral membrane proteins, and so is currently not feasible for every GPCR or GPCR-ligand complex. Therefore, the integration of existing ligand SAR data with GPCR modeling can be a practical alternative to provide this essential structural insight. To demonstrate this, we integrated SAR data from 39 azepine series 5-HT2C agonists, comprising both selective and unselective examples, with our hierarchical GPCR modeling protocol (HGMP). Through this work we have been able to demonstrate how relatively small differences in the amino acid sequences of GPCRs can lead to significant differences in secondary structure and function, as supported by experimental data. In particular, this study suggests that conformational differences in the tilt of TM7 between 5-HT2B and 5-HT2C, which result from differences in interhelical interactions, may be the major source of selectivity in G-protein activation between these two receptors. Our approach also demonstrates how the use of GPCR models in conjunction with SAR data can be used to explain activity cliffs. PMID:26900768

  7. Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.

    PubMed

    Moya, Pablo R; Berg, Kelly A; Gutiérrez-Hernandez, Manuel A; Sáez-Briones, Patricio; Reyes-Parada, Miguel; Cassels, Bruce K; Clarke, William P

    2007-06-01

    2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile. PMID:17337633

  8. Serotonin 5-HT2C receptor-independent expression of hypothalamic NOR1, a novel modulator of food intake and energy balance, in mice

    SciTech Connect

    Nonogaki, Katsunori; Kaji, Takao; Ohba, Yukie; Sumii, Makiko; Wakameda, Mamoru; Tamari, Tomohiro

    2009-08-21

    NOR1, Nur77 and Nurr1 are orphan nuclear receptors and members of the NR4A subfamily. Here, we report that the expression of hypothalamic NOR1 was remarkably decreased in mildly obese {beta}-endorphin-deficient mice and obese db/db mice with the leptin receptor mutation, compared with age-matched wild-type mice, whereas there were no genotypic differences in the expression of hypothalamic Nur77 or Nurr1 in these animals. The injection of NOR1 siRNA oligonucleotide into the third cerebral ventricle significantly suppressed food intake and body weight in mice. On the other hand, the decreases in hypothalamic NOR1 expression were not found in non-obese 5-HT2C receptor-deficient mice. Moreover, systemic administration of m-chlorophenylpiperazine (mCPP), a 5-HT2C/1B receptor agonist, had no effect on hypothalamic NOR1 expression, while suppressing food intake in {beta}-endorphin-deficient mice. These findings suggest that 5-HT2C receptor-independent proopiomelanocortin-derived peptides regulate the expression of hypothalamic NOR1, which is a novel modulator of feeding behavior and energy balance.

  9. Imaging Evaluation of 5HT2C Agonists, [11C]WAY-163909 and [11C]Vabicaserin, Formed by Pictet–Spengler Cyclization

    PubMed Central

    2015-01-01

    The serotonin subtype 2C (5HT2C) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent and selective 5HT2C full agonists, WAY-163909 (2) and vabicaserin (3), were radiolabeled with carbon-11 via Pictet–Spengler cyclization with [11C]formaldehyde and used in positron emission tomography (PET) imaging. Reaction conditions were optimized to exclude the major source of isotope dilution caused by the previously unknown breakdown of N,N-dimethylformamide (DMF) to formaldehyde at high temperature under mildly acid conditions. In vivo PET imaging was utilized to evaluate the pharmacokinetics and distribution of the carbon-11 labeled 5HT2C agonists. Both radiolabeled molecules exhibit high blood–brain barrier (BBB) penetration and nonspecific binding, which was unaltered by preadministration of the unlabeled agonist. Our work demonstrates that Pictet–Spengler cyclization can be used to label drugs with carbon-11 to study their pharmacokinetics and for evaluation as PET radiotracers. PMID:24491146

  10. Rat exposure in mice with neuropathic pain induces fear and antinociception that is not reversed by 5-HT2C receptor activation in the dorsal periaqueductal gray.

    PubMed

    Furuya-da-Cunha, Elke Mayumi; Souza, Rimenez Rodrigues de; Canto-de-Souza, Azair

    2016-07-01

    Previous studies have demonstrated that serotonin 5-HT2C receptors in the dorsal periaqueductal gray (dPAG) mediate both anxiety and antinociception in mice submitted to the elevated plus maze. The present study examined the effects of intra-dPAG infusion of the serotonin 5-HT2C receptor agonist (MK-212) in the defensive reactions and antinociception in mice with neurophatic pain confronted by a predator. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve, and predator confrontation was performed using the rat exposure test (RET). Our results demonstrated that both sham-operated and CCI mice exhibited intense defensive reactions when confronted by rats. However, rat-exposed CCI mice showed reduced pain reactivity in comparison to CCI mice exposed to a toy rat. Intra-dPAG infusion of MK-212 prior to predator exposure did not significantly alter defensive or antinociceptive responses. To our knowledge, our results represent the first evidence of RET-induced antinociception in mice. Moreover, the results of the present study suggest that 5-HT2C receptor activation in the dPAG is not critically involved in the control of predator-evoked fearful or antinociceptive responses. PMID:27059332

  11. Stimulation of Medial Prefrontal Cortex Serotonin 2C (5-HT2C) Receptors Attenuates Cocaine-Seeking Behavior

    PubMed Central

    Pentkowski, Nathan S; Duke, Felicia D; Weber, Suzanne M; Pockros, Lara A; Teer, Andrew P; Hamilton, Elizabeth C; Thiel, Kenneth J; Neisewander, Janet L

    2010-01-01

    Serotonin 2C receptor (5-HT2CR) agonists administered systemically attenuate both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior. To further elucidate the function of these receptors in addiction-like processes, this study examined the effects of microinfusing the 5-HT2CR agonist MK212 (0, 10, 30, 100 ng/side/0.2 μl) into the medial prefrontal cortex (mPFC) on cocaine self-administration and reinstatement of extinguished cocaine-seeking behavior. Male Sprague–Dawley rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. Once responding stabilized, rats received MK212 microinfusions before tests for maintenance of cocaine self-administration. Next, extinction training to reduce cocaine-seeking behavior, defined as responses performed without cocaine reinforcement available, occurred until low extinction baselines were achieved. Rats then received MK212 microinfusions before tests for reinstatement of extinguished cocaine-seeking behavior elicited by cocaine-priming injections (10 mg/kg, i.p.) or response-contingent presentations of the cocaine-associated cues; operant responses during cocaine-primed reinstatement tests produced no consequences. MK212 microinfusions into the prelimbic and infralimbic, but not anterior cingulate, regions of the mPFC dose-dependently attenuated both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior, but did not reliably affect cocaine self-administration. A subsequent experiment showed that the effects of MK212 (100 ng/side/0.2 μl) on reinstatement of extinguished cocaine-seeking behavior were blocked by co-administration of the 5-HT2CR antagonist SB242084 (200 ng/side/0.2 μl). MK212 administered alone into the mPFC as a drug prime produced no discernable effects on cocaine-seeking behavior. These findings suggest that stimulation of 5-HT2CRs in the mPFC attenuates the incentive motivational

  12. The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.

    PubMed

    Harvey-Lewis, Colin; Li, Zhaoxia; Higgins, Guy A; Fletcher, Paul J

    2016-02-01

    Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction. PMID:26427596

  13. Expression of hippocampal serotonin receptors 5-HT2C and 5-HT5A in a rat model of diet-induced obesity supplemented with tryptophan.

    PubMed

    Lopez-Esparza, Sarahi; Berumen, Laura C; Padilla, Karla; Miledi, Ricardo; García-Alcocer, Guadalupe

    2015-05-01

    Food intake regulation is a complex mechanism that involves endogenous substances and central nervous system structures like hypothalamus or even hippocampus. The neurotransmitter serotonin is distinguished as food intake mediator; within its multiples receptors, the 5-HT2C type is characterized by its inhibitory appetite action but there is no information about 5-HT5A receptors involvement in obesity disease. It is also unknown if there are any changes in the receptors expression in rats hippocampus with induced obesity during development through a high energy diet (HED) supplemented with tryptophan (W). To appreciate the receptors expression pattern in the hippocampus, obesity was induced to young Sprague Dawley rats through a HED and supplemented with W. Immunocytochemical and western blot techniques were used to study the receptor distribution and quantify the protein expression. The rats with HED diet developed obesity until week 13 of treatment. The 5-HT2C receptor expression decreased in CA1, CA2, CA3 and DG of HED group; and also in CA2, CA3 and DG for HEDW group. The 5-HT5A receptor expression only decreased in DG for HED group. Variations of the two serotonin receptors subtypes support their potential role in obesity. PMID:25720309

  14. Molecular interactions of agonist and inverse agonist ligands at serotonin 5-HT2C G protein-coupled receptors: computational ligand docking and molecular dynamics studies validated by experimental mutagenesis results

    NASA Astrophysics Data System (ADS)

    Córdova-Sintjago, Tania C.; Liu, Yue; Booth, Raymond G.

    2015-02-01

    To understand molecular determinants for ligand activation of the serotonin 5-HT2C G protein-coupled receptor (GPCR), a drug target for obesity and neuropsychiatric disorders, a 5-HT2C homology model was built according to an adrenergic β2 GPCR (β2AR) structure and validated using a 5-HT2B GPCR crystal structure. The models were equilibrated in a simulated phosphatidyl choline membrane for ligand docking and molecular dynamics studies. Ligands included (2S, 4R)-(-)-trans-4-(3'-bromo- and trifluoro-phenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalene-2-amine (3'-Br-PAT and 3'-CF3-PAT), a 5-HT2C agonist and inverse agonist, respectively. Distinct interactions of 3'-Br-PAT and 3'-CF3-PAT at the wild-type (WT) 5-HT2C receptor model were observed and experimental 5-HT2C receptor mutagenesis studies were undertaken to validate the modelling results. For example, the inverse agonist 3'-CF3-PAT docked deeper in the WT 5-HT2C binding pocket and altered the orientation of transmembrane helices (TM) 6 in comparison to the agonist 3'-Br-PAT, suggesting that changes in TM orientation that result from ligand binding impact function. For both PATs, mutation of 5-HT2C residues S3.36, T3.37, and F5.47 to alanine resulted in significantly decreased affinity, as predicted from modelling results. It was concluded that upon PAT binding, 5-HT2C residues T3.37 and F5.47 in TMs 3 and 5, respectively, engage in inter-helical interactions with TMs 4 and 6, respectively. The movement of TMs 5 and 6 upon agonist and inverse agonist ligand binding observed in the 5-HT2C receptor modelling studies was similar to movements reported for the activation and deactivation of the β2AR, suggesting common mechanisms among aminergic neurotransmitter GPCRs.

  15. Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model

    PubMed Central

    Liu, J; Ogden, A; Comery, T A; Spiros, A; Roberts, P; Geerts, H

    2014-01-01

    A quantitative systems pharmacology model that combines in vitro/preclinical neurophysiology data, human imaging data, and patient disease information was used to blindly predict steady-state clinical efficacy of vabicaserin, a 5-HT2C full agonist, in monotherapy and, subsequently, to assess adjunctive therapy in schizophrenia. The model predicted a concentration-dependent improvement of positive and negative syndrome scales (PANSS) in schizophrenia monotherapy with vabicaserin. At the exposures of 100 and 200 mg b.i.d., the predicted improvements on PANSS in virtual patient trials were 5.12 (2.20, 8.56) and 6.37 (2.27, 10.40) (mean (95% confidence interval)), respectively, which are comparable to the observed phase IIa results. At the current clinical exposure limit of vabicaserin, the model predicted an ~9-point PANSS improvement in monotherapy, and <4-point PANSS improvement adjunctive with various antipsychotics, suggesting limited clinical benefit of vabicaserin in schizophrenia treatment. In conclusion, the updated quantitative systems pharmacology model of PANSS informed the clinical development decision of vabicaserin in schizophrenia. PMID:24759548

  16. Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.

    PubMed

    Wu, Xian; Pang, Gang; Zhang, Yong-Mei; Li, Guangwu; Xu, Shengchun; Dong, Liuyi; Stackman, Robert W; Zhang, Gongliang

    2015-10-21

    Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID:26375926

  17. 759C/T Variants of the Serotonin (5-HT2C) Receptor Gene and Weight Gain in Children and Adolescents in Long-Term Risperidone Treatment

    PubMed Central

    del Castillo, Nicole; Zimmerman M, Bridget; Tyler, Billie; Ellingrod, Vicki L; Calarge, Chadi

    2014-01-01

    Background Great inter-individual variability exists in the susceptibility to gain weight during antipsychotic treatment. Thus, we examined whether the −759C/T variants in the promoter region of the 5HT2C receptor gene were differentially associated with weight gain in children and adolescents in long-term risperidone treatment. Methods Medically healthy 7 to 17 year-olds, treated with risperidone for ≥ six months, were enrolled. Anthropometric measurements, laboratory tests, and treatment history were obtained upon enrollment and from medical records. The effect of the genotype on the trajectory of age-sex-adjusted weight and body mass index (BMI) z scores before and after the onset of risperidone treatment was investigated. Results In 124 subjects (90% males, mean age: 11.8 years) treated with risperidone for a mean of 2.8 years, weight and BMI z scores significantly increased after starting risperidone. This change was similar across the two genotype groups as were changes in several cardiometabolic variables. Conclusion In contrast to other reports, the T allele failed to confer protection against excessive weight gain or cardiometabolic abnormalities in this group of children and adolescents chronically treated with risperidone. PMID:24772381

  18. Serotonin (5-HT) 2C Receptor (5-HT2CR) Protein Expression is Enriched in Synaptosomal and Postsynaptic Compartments of Rat Cortex

    PubMed Central

    Anastasio, Noelle C.; Lanfranco, Maria Fe; Bubar, Marcy J.; Seitz, Patricia K.; Stutz, Sonja J.; McGinnis, Andrew G.; Watson, Cheryl S.; Cunningham, Kathryn A.

    2010-01-01

    The action of serotonin (5-HT) at the 5-HT2C receptor (5-HT2CR) in cerebral cortex is emerging as a candidate modulator of neural processes that mediate core phenotypic facets of several psychiatric and neurological disorders. However, our understanding of the neurobiology of the cortical 5-HT2CR protein complex is currently limited. The goal of the present study was to explore the subcellular localization of the 5-HT2CR in synaptosomes and the postsynaptic density, an electron-dense thickening specialized for postsynaptic signaling and neuronal plasticity. Utilizing multiples tissues (brain, peripheral tissues), protein fractions (synaptosomal, postsynaptic density), and controls (peptide neutralization, 5-HT2CR stable-expressing cells), we established the selectivity of two commercially available 5-HT2CR antibodies and employed the antibodies in Western blot and immunoprecipitation studies of PFC and motor cortex, two regions implicated in cognitive, emotional and motor dysfunction. For the first time, we demonstrated the expression of the 5-HT2CR in postsynaptic density-enriched fractions from both PFC and motor cortex. Co-immunoprecipitation studies revealed the presence of PSD-95 within the 5-HT2CR protein complex expressed in PFC and motor cortex. Taken together, these data support the hypothesis that the 5-HT2CR is localized within the postsynaptic thickening of synapses and is therefore positioned to directly modulate synaptic plasticity in cortical neurons. PMID:20345755

  19. Oligomer size of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor revealed by fluorescence correlation spectroscopy with photon counting histogram analysis: evidence for homodimers without monomers or tetramers.

    PubMed

    Herrick-Davis, Katharine; Grinde, Ellinor; Lindsley, Tara; Cowan, Ann; Mazurkiewicz, Joseph E

    2012-07-01

    Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) are techniques with single molecule sensitivity that are well suited for examining the biophysical properties of protein complexes in living cells. In the present study, FCS and PCH were applied to determine the diffusion coefficient and oligomeric size of G-protein-coupled receptors. FCS was used to record fluctuations in fluorescence intensity arising from fluorescence-tagged 5-hydroxytryptamine 2C (5-HT(2C)) receptors diffusing within the plasma membrane of HEK293 cells and rat hippocampal neurons. Autocorrelation analysis yielded diffusion coefficients ranging from 0.8 to 1.2 μm(2)/s for fluorescence-tagged receptors. Because the molecular brightness of a fluorescent protein is directly proportional to the number of fluorescent proteins traveling together within a protein complex, it can be used to determine the oligomeric size of the protein complex. FCS and PCH analysis of fluorescence-tagged 5-HT(2C) receptors provided molecular brightness values that were twice that of GFP and YFP monomeric controls, similar to a dimeric GFP control, and unaltered by 5-HT. Bimolecular fluorescence complementation of the N- and C-terminal halves of YFP attached to 5-HT(2C) receptors was observed in endoplasmic reticulum/Golgi and plasma membranes with a brightness equal to monomeric YFP. When GFP-tagged 5-HT(2C) receptors were co-expressed with a large excess of untagged, non-fluorescent 5-HT(2C) receptors, the molecular brightness was reduced by half. PCH analysis of the FCS data were best described by a one-component dimer model without monomers or tetramers. Therefore, it is concluded that 5-HT(2C) receptors freely diffusing within the plasma membrane are dimeric. PMID:22593582

  20. 5-HT2 Receptor Regulation of Mitochondrial Genes: Unexpected Pharmacological Effects of Agonists and Antagonists.

    PubMed

    Harmon, Jennifer L; Wills, Lauren P; McOmish, Caitlin E; Demireva, Elena Y; Gingrich, Jay A; Beeson, Craig C; Schnellmann, Rick G

    2016-04-01

    In acute organ injuries, mitochondria are often dysfunctional, and recent research has revealed that recovery of mitochondrial and renal functions is accelerated by induction of mitochondrial biogenesis (MB). We previously reported that the nonselective 5-HT2 receptor agonist DOI [1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine] induced MB in renal proximal tubular cells (RPTCs). The goal of this study was to determine the role of 5-HT2 receptors in the regulation of mitochondrial genes and oxidative metabolism in the kidney. The 5-HT2C receptor agonist CP-809,101 [2-[(3-chlorophenyl)methoxy]-6-(1-piperazinyl)pyrazine] and antagonist SB-242,084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] were used to examine the induction of renal mitochondrial genes and oxidative metabolism in RPTCs and in mouse kidneys in the presence and absence of the 5-HT2C receptor. Unexpectedly, both CP-809,101 and SB-242,084 increased RPTC respiration and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA expression in RPTCs at 1-10 nM. In addition, CP-809,101 and SB-242,084 increased mRNA expression of PGC-1α and the mitochondrial proteins NADH dehydrogenase subunit 1 and NADH dehydrogenase (ubiquinone) β subcomplex 8 in mice. These compounds increased mitochondrial genes in RPTCs in which the 5-HT2C receptor was downregulated with small interfering RNA and in the renal cortex of mice lacking the 5-HT2C receptor. By contrast, the ability of these compounds to increase PGC-1α mRNA and respiration was blocked in RPTCs treated with 5-HT2A receptor small interfering RNA or the 5-HT2A receptor antagonist eplivanserin. In addition, the 5-HT2A receptor agonist NBOH-2C-CN [4-[2-[[(2-hydroxyphenyl)methyl]amino]ethyl]-2,5-dimethoxybenzonitrile] increased RPTC respiration at 1-100 nM. These results suggest that agonism of the 5-HT2A receptor induces MB and that the classic 5-HT2C receptor agonist CP

  1. Functional Status of the Serotonin 5-HT2C Receptor (5-HT2CR) Drives Interlocked Phenotypes that Precipitate Relapse-Like Behaviors in Cocaine Dependence

    PubMed Central

    Anastasio, Noelle C; Stutz, Sonja J; Fox, Robert G; Sears, Robert M; Emeson, Ronald B; DiLeone, Ralph J; O'Neil, Richard T; Fink, Latham H; Li, Dingge; Green, Thomas A; Gerard Moeller, F; Cunningham, Kathryn A

    2014-01-01

    Relapse vulnerability in cocaine dependence is rooted in genetic and environmental determinants, and propelled by both impulsivity and the responsivity to cocaine-linked cues (‘cue reactivity'). The serotonin (5-hydroxytryptamine, 5-HT) 5-HT2C receptor (5-HT2CR) within the medial prefrontal cortex (mPFC) is uniquely poised to serve as a strategic nexus to mechanistically control these behaviors. The 5-HT2CR functional capacity is regulated by a number of factors including availability of active membrane receptor pools, the composition of the 5-HT2CR macromolecular protein complex, and editing of the 5-HT2CR pre-mRNA. The one-choice serial reaction time (1-CSRT) task was used to identify impulsive action phenotypes in an outbred rat population before cocaine self-administration and assessment of cue reactivity in the form of lever presses reinforced by the cocaine-associated discrete cue complex during forced abstinence. The 1-CSRT task reliably and reproducibly identified high impulsive (HI) and low impulsive (LI) action phenotypes; HI action predicted high cue reactivity. Lower cortical 5-HT2CR membrane protein levels concomitant with higher levels of 5-HT2CR:postsynaptic density 95 complex distinguished HI rats from LI rats. The frequency of edited 5-HT2CR mRNA variants was elevated with the prediction that the protein population in HI rats favors those isoforms linked to reduced signaling capacity. Genetic loss of the mPFC 5-HT2CR induced aggregate impulsive action/cue reactivity, suggesting that depressed cortical 5-HT2CR tone confers vulnerability to these interlocked behaviors. Thus, impulsive action and cue reactivity appear to neuromechanistically overlap in rodents, with the 5-HT2CR functional status acting as a neural rheostat to regulate, in part, the intersection between these vulnerability behaviors. PMID:23939424

  2. Peptide Inhibitors Disrupt the Serotonin 5-HT2C Receptor Interaction with Phosphatase and Tensin Homolog to Allosterically Modulate Cellular Signaling and Behavior

    PubMed Central

    Anastasio, Noelle C.; Gilbertson, Scott R.; Bubar, Marcy J.; Agarkov, Anton; Stutz, Sonja J.; Jeng, Yowjiun; Bremer, Nicole M.; Smith, Thressa D.; Fox, Robert G.; Swinford, Sarah E.; Seitz, Patricia K.; Charendoff, Marc N.; Craft, John W.; Laezza, Fernanda M.; Watson, Cheryl S.; Briggs, James M.; Cunningham, Kathryn A.

    2013-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) signaling through the 5-HT2C receptor (5-HT2CR) is essential in normal physiology, whereas aberrant 5-HT2CR function is thought to contribute to the pathogenesis of multiple neural disorders. The 5-HT2CR interacts with specific protein partners, but the impact of such interactions on 5-HT2CR function is poorly understood. Here, we report convergent cellular and behavioral data that the interaction between the 5-HT2CR and protein phosphatase and tensin homolog (PTEN) serves as a regulatory mechanism to control 5-HT2CR-mediated biology but not that of the closely homologous 5-HT2AR. A peptide derived from the third intracellular loop of the human 5-HT2CR [3L4F (third loop, fourth fragment)] disrupted the association, allosterically augmented 5-HT2CR-mediated signaling in live cells, and acted as a positive allosteric modulator in rats in vivo. We identified the critical residues within an 8 aa fragment of the 3L4F peptide that maintained efficacy (within the picomolar range) in live cells similar to that of the 3L4F peptide. Last, molecular modeling identified key structural features and potential interaction sites of the active 3L4F peptides against PTEN. These compelling data demonstrate the specificity and importance of this protein assembly in cellular events and behaviors mediated by 5-HT2CR signaling and provide a chemical guidepost to the future development of drug-like peptide or small-molecule inhibitors as neuroprobes to study 5-HT2CR allostery and therapeutics for 5-HT2CR-mediated disorders. PMID:23345234

  3. The serotonin transporter (5-HTTLPR) but not serotonin receptor (5-HT2C Cys23Ser) variant is associated with bipolar I disorder in Kurdish population from Western Iran.

    PubMed

    Mohammadi, Sahar; Khazaie, Habibolah; Rahimi, Ziba; Vaisi-Raygani, Asad; Zargooshi, Newsha; Rahimi, Zohreh

    2015-03-17

    The role of 5-HTTLPR and 5-HT2C Cys23Ser polymorphisms in the psychopathology of mood disorders and suicide behavior is controversial. The aim of present study was to investigate the association between 5-HTTLPR and 5-HT2C Cys23Ser variants and susceptibility to bipolar I disorder (BID). The 5-HT2C genotypes were studied in 152 patients with BID and 173 gender- and age-matched healthy individuals with Kurds ethnic background from Western Iran using PCR and PCR-RFLP methods. In recessive model (SS vs. LL+LS) the SS genotype was associated with 1.79-fold increased risk of BID (p=0.018). Also, the presence of S allele increased the risk of adult-onset BID by 1.76-fold (p=0.027). No association was detected between 5-HTTLPR genotypes and alleles with suicide attempt. The frequency of 5-HT2C Ser allele in patients and controls were 12.3 and 12.5%, respectively. Mutant allele of HT2C Ser had higher frequency in female (14.7%) than male (10.5%, p=0.27) patients. The frequency of HT2C Ser allele in patients with a family history of BID tended to be higher (15.7%) than those without a family history of the disease (11.8%). The frequency of HT2C Ser allele in suicide attempter women was higher (16.7%) than those without a suicide attempt (14.3%). Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and adult-onset BID in Kurds population. However, we found the lack of an association between 5-HT2C Cys/Ser variants and the risk of BID. PMID:25596490

  4. Food intake inhibition in rainbow trout induced by activation of serotonin 5-HT2C receptors is associated with increases in POMC, CART and CRF mRNA abundance in hypothalamus.

    PubMed

    Pérez-Maceira, Jorge J; Otero-Rodiño, Cristina; Mancebo, María J; Soengas, José L; Aldegunde, Manuel

    2016-04-01

    In rainbow trout, the food intake inhibition induced by serotonin occurs through 5-HT2C and 5-HT1A receptors, though the mechanisms involved are still unknown. Therefore, we assessed if a direct stimulation of 5-HT2C and 5-HT1A serotonin receptors (resulting in decreased food intake in rainbow trout), affects gene expression of neuropeptides involved in the control of food intake, such as pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing factor (CRF), and agouti-related peptide (AgRP). In a first set of experiments, the injection of the 5-HT2C receptor agonists MK212 (60 μg kg(-1) icv) and WAY 161503 (1 mg kg(-1) ip), and of the 5-HT1A receptor agonist 8-OH-DPAT (1 mg kg(-1) ip and 30 μg kg(-1) icv) induced food intake inhibition. In a second set of experiments, we observed that the injection of MK212 or WAY 161503 (1 and 3 mg kg(-1)) significantly increased hypothalamic POMC mRNA abundance. CART mRNA abundance in hypothalamus was enhanced by treatment with MK212 and unaffected by WAY 161503. The administration of the 5-HT1A receptor agonist 8-OH-DPAT did not induce any significant variation in the hypothalamic POMC or CART mRNA levels. CRF mRNA abundance was only affected by MK212 that increased hypothalamic values. Finally, hypothalamic AgRP mRNA abundance was only evaluated with the agonist 5-HT2C MK212 resulting in no significant effects. The results show that the reduction in food intake mediated by 5-HT2C receptors is associated with increases in hypothalamic POMC, CART and CRF mRNA abundance. PMID:26832922

  5. Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity

    PubMed Central

    Higgins, Guy A; Desnoyer, Jill; Van Niekerk, Annalise; Silenieks, Leo B; Lau, Winnie; Thevarkunnel, Sandy; Izhakova, Julia; DeLannoy, Ines AM; Fletcher, Paul J; DeLay, Josepha; Dobson, Howard

    2015-01-01

    The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague–Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1–2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma Cmin and Cmax were in the range 13–160 ng/mL (1 mg/kg b.i.d.) and 34–264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0–5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity. PMID:25692009

  6. Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity.

    PubMed

    Higgins, Guy A; Desnoyer, Jill; Van Niekerk, Annalise; Silenieks, Leo B; Lau, Winnie; Thevarkunnel, Sandy; Izhakova, Julia; DeLannoy, Ines Am; Fletcher, Paul J; DeLay, Josepha; Dobson, Howard

    2015-02-01

    The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague-Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1-2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma C min and C max were in the range 13-160 ng/mL (1 mg/kg b.i.d.) and 34-264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0-5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity. PMID:25692009

  7. Effects of the 5-HT2C receptor agonist CP809101 in the amygdala on reinstatement of cocaine-seeking behavior and anxiety-like behavior.

    PubMed

    Pockros-Burgess, Lara A; Pentkowski, Nathan S; Der-Ghazarian, Taleen; Neisewander, Janet L

    2014-11-01

    Serotonin 2C receptor (5-HT2CR) agonists attenuate reinstatement of cocaine-seeking behavior. These receptors are found throughout the limbic system, including the basolateral amygdala (BlA), which is involved in forming associations between emotional stimuli and environmental cues, and the central amygdala (CeA), which is implicated in the expression of conditioned responding to emotional stimuli. This study investigated whether 5-HT2CRs in the amygdala are involved in cue and cocaine-primed reinstatement of cocaine-seeking behavior. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) which that was paired with light and tone cues, and then subsequently they underwent daily extinction training. Rats then received bilateral microinfusions of the 5-HT2CR agonist CP809101 (0.01-1.0 μg/0.2 μl/side) into either the BlA or CeA prior to tests for cue or cocaine-primed (10 mg/kg, i.p.) reinstatement. Rats were also tested for CP809101 effects on anxiety-like behavior on the elevated plus-maze (EPM). Surprisingly, intra-BlA CP809101 had no effect on cue reinstatement, though it did increase anxiety-like behavior on the EPM. Intra-CeA infusions of CP809101 attenuated cocaine-primed reinstatement, an effect that was prevented with concurrent administration of the 5-HT2CR antagonist SB242084 (0.1 μg/0.2 μl/side). CP809101 had no effect on cue reinstatement or anxiety-like behavior on the EPM. These findings suggest that 5-HT2CRs in the BlA modulate anxiety, whereas those in the CeA modulate incentive motivational effects induced by cocaine priming injections. PMID:24984080

  8. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats.

    PubMed

    Knapp, Darin J; Overstreet, David H; Moy, Sheryl S; Breese, George R

    2004-02-01

    Anxiety-like behaviors are integral features of withdrawal from chronic ethanol exposure. In the experiments in the current study, we tested the hypothesis that anxiety can be regulated independently of other withdrawal signs and thus may be responsive to selective pharmacological agents. For 17 days, rats were fed ethanol (8-12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of ethanol treatment, rats were tested in either the social interaction or plus-maze test of anxiety-like behavior after treatment with drugs hypothesized to have anxiolytic action. SB242084, flumazenil, and CRA1000-antagonists for 5-hydroxytryptamine (serotonin) (5-HT) 2C (5-HT(2C)), benzodiazepine, and corticotropin-releasing factor type 1 (CRF(1)) receptors, respectively-attenuated decreased social interaction without concomitant effects on activity measures. In contrast, ifenprodil, MDL 72222, and zolpidem-antagonists for N-methyl-d-aspartate (NMDA) and 5-HT(3) receptors, and agonist for benzodiazepine type 1 receptors, respectively-did not share this effect. Results for SB242084, flumazenil, and ifenprodil in the elevated plus-maze test were comparable to those in the social interaction test. These results support the suggestion that multiple neuronal systems (CRF(1), 5-HT(2C), and benzodiazepine receptors) contribute to the ethanol withdrawal sign of decreased social interaction. Furthermore, the selective effects of pharmacological agents on social interaction seem to indicate that this behavior can be dissociated from other signs. Because anxiety may be a complicating factor in alcohol withdrawal and relapse, future studies of this type are needed to provide focus for the effort to define selective and novel antianxiety agents for these disorders. PMID:15163561

  9. 5-HT2A receptor blockade and 5-HT2C receptor activation interact to reduce cocaine hyperlocomotion and Fos protein expression in the caudate-putamen

    PubMed Central

    Pockros, Lara A.; Pentkowski, Nathan S.; Conway, Sineadh M.; Ullman, Teresa E.; Zwick, Kimberly R.; Neisewander, Janet L.

    2012-01-01

    Both the 5-HT2A receptor (R) antagonist M100907 and the 5-HT2CR agonist MK212 attenuate cocaine-induced dopamine release and hyperlocomotion. This study examined whether these drugs interact to reduce cocaine hyperlocomotion and Fos expression in the striatum and prefrontal cortex. We first determined from dose-effect functions a low dose of both M100907 and MK212 that failed to alter cocaine (15 mg/kg, i.p.) hyperlocomotion. Subsequently we examined whether these subthreshold doses given together would attenuate cocaine hyperlocomotion, consistent with a 5-HT2A/5-HT2CR interaction. Separate groups of rats received two sequential drug injections 5 min apart immediately before a 1-h locomotion test as follows: 1) saline + saline, 2) saline + cocaine, 3) 0.025 mg/kg M100907 + cocaine, 4) 0.125 mg/kg MK212 + cocaine, or 5) cocktail combination of 0.025 mg/kg M100907 and 0.125 mg/kg MK212 + cocaine. Brains were extracted for Fos immunohistochemistry 90 min after the second injection. We next examined the effects of 0.025 mg/kg M100907 and 0.125 mg/kg MK212, alone and in combination, on spontaneous locomotor activity. While neither drug given alone produced any effects, the M100907/MK212 cocktail attenuated cocaine hyperlocomotion as well as cocaine-induced Fos expression in the dorsolateral caudate-putamen (CPu), but had no effect on spontaneous locomotion. The findings suggest that 5-HT2ARs and 5-HT2CRs interact to attenuate cocaine hyperlocomotion and Fos expression in the CPu, and that the CPu is a potential locus of the interactive effects between these 5-HT2R subtypes on behavior. Further research investigating combined 5-HT2AR antagonism and 5-HT2CR agonism as a treatment for cocaine dependence is warranted. PMID:22886755

  10. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects.

    PubMed

    Opal, M D; Klenotich, S C; Morais, M; Bessa, J; Winkle, J; Doukas, D; Kay, L J; Sousa, N; Dulawa, S M

    2014-10-01

    Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling. PMID:24166413

  11. 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptor mRNA modulation by antidepressant treatment in the chronic mild stress model of depression: sex differences exposed.

    PubMed

    Pitychoutis, P M; Dalla, C; Sideris, A C; Tsonis, P A; Papadopoulou-Daifoti, Z

    2012-05-17

    It is well established that women experience major depression at roughly twice the rate of men. Interestingly, accumulating clinical and experimental evidence shows that the responsiveness of males and females to antidepressant pharmacotherapy, and particularly to tricyclic antidepressants (TCAs), is sex-differentiated. Herein, we investigated whether exposure of male and female rats to the chronic mild stress (CMS) model of depression, as well as treatment with the TCA clomipramine may affect serotonergic receptors' (5-HTRs) mRNA expression in a sex-dependent manner. Male and female rats were subjected to CMS for 4 weeks and during the next 4 weeks they concurrently received clomipramine treatment (10 mg/ml/kg). CMS and clomipramine's effects on 5-HT(1A)R, 5-HT(2A)R, and 5-HT(2C)R mRNA expression were assessed by in situ hybridization histochemistry in selected subfields of the hippocampus and in the lateral orbitofrontal cortex (OFC), two regions implicated in the pathophysiology of major depression. CMS and clomipramine treatment induced sex-differentiated effects on rats' hedonic status and enhanced 5-HT(1A)R mRNA expression in the cornu ammonis 1 (CA1) hippocampal region of male rats. Additionally, CMS attenuated 5-HT(1A)R mRNA expression in the OFC of male rats and clomipramine reversed this effect. Moreover, 5-HT(2A)R mRNA levels in the OFC were enhanced in females but decreased in males, while clomipramine reversed this effect only in females. CMS increased 5-HT2CR mRNA expression in the CA4 region of both sexes and this effect was attenuated by clomipramine. Present data exposed that both CMS and clomipramine treatment may induce sex-differentiated and region-distinctive effects on 5-HTRs mRNA expression and further implicate the serotonergic system in the manifestation of sexually dimorphic neurobehavioral responses to stress. PMID:22441040

  12. Inhibition of capsaicin-driven nasal hyper-reactivity by SB-705498, a TRPV1 antagonist

    PubMed Central

    Holland, Carlijn; Drunen, Cornelis Van; Denyer, Jane; Smart, Kevin; Segboer, Christine; Terreehorst, Ingrid; Newlands, Amy; Beerahee, Misba; Fokkens, Wytske; Tsitoura, Daphne C

    2014-01-01

    AIMS To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal SB-705498, a selective TRPV1 antagonist. METHODS Two randomized, double-blind, placebo-controlled, clinical studies were performed: (i) an intranasal SB-705498 first time in human study to examine the safety and PK of five single escalating doses from 0.5 to 12 mg and of repeat dosing with 6 mg and 12 mg twice daily for 14 days and (ii) a PD efficacy study in subjects with non-allergic rhinitis (NAR) to evaluate the effect of 12 mg intranasal SB-705498 against nasal capsaicin challenge. RESULTS Single and repeat dosing with intranasal SB-705498 was safe and well tolerated. The overall frequency of adverse events was similar for SB-705498 and placebo and no dose-dependent increase was observed. Administration of SB-705498 resulted in less than dose proportional AUC(0,12 h) and Cmax, while repeat dosing from day 1 to day 14 led to its accumulation. SB-705498 receptor occupancy in nasal tissue was estimated to be high (>80%). Administration of 12 mg SB-705498 to patients with NAR induced a marked reduction in total symptom scores triggered by nasal capsaicin challenge. Inhibition of rhinorrhoea, nasal congestion and burning sensation was associated with 2-to 4-fold shift in capsaicin potency. CONCLUSIONS Intranasal SB-705498 has an appropriate safety and PK profile for development in humans and achieves clinically relevant attenuation of capsaicin-provoked rhinitis symptoms in patients with NAR. The potential impact intranasal SB-705498 may have in rhinitis treatment deserves further evaluation. PMID:23909699

  13. Distribution of cells responsive to 5-HT6 receptor antagonist-induced hypophagia

    PubMed Central

    Garfield, Alastair S.; Burke, Luke K.; Shaw, Jill; Evans, Mark L.; Heisler, Lora K.

    2014-01-01

    The central 5-hydroxytryptamine (5-HT; serotonin) system is well established as an important regulator of appetite and continues to remain a focus of obesity research. While much emphasis has focussed on the 5-HT2C receptor (5-HT2CR) in 5-HT's anorectic effect, pharmacological manipulation of the 5-HT6 receptor (5-HT6R) also reduces appetite and body weight and may be amenable to obesity treatment. However, the neurological circuits that underlie 5-HT6R-induced hypophagia remain to be identified. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation, here we mapped the neuroanatomical targets activated by an anorectic dose of the 5-HT6R antagonist SB-399885 throughout the brain. Furthermore, we quantified SB-399855 activated cells within brain appetitive nuclei, the hypothalamus, dorsal raphe nucleus (DRN) and nucleus of the solitary tract (NTS). Our results reveal that 5-HT6R antagonist-induced hypophagia is associated with significantly increased neuronal activation in two nuclei with an established role in the central control of appetite, the paraventricular nucleus of the hypothalamus (PVH) and the NTS. In contrast, no changes in FOS-IR were observed between treatment groups within other hypothalamic nuclei or DRN. The data presented here provide a first insight into the neural circuitry underlying 5-HT6R antagonist-induced appetite suppression and highlight the PVH and NTS in the coordination of 5-HT6R hypophagia. PMID:24566060

  14. Complete Genome Sequence of Paenibacillus polymyxa Strain Sb3-1, a Soilborne Bacterium with Antagonistic Activity toward Plant Pathogens

    PubMed Central

    Wetzlinger, Ute; Müller, Henry; Berg, Gabriele

    2015-01-01

    The genome of Paenibacillus polymyxa Sb3-1, a strain that shows antagonistic activities against pathogenic fungi and bacteria, consists of one 5.6-Mb circular chromosome and two plasmids of 223 kb and 8 kb. The genome reveals several genes that potentially contribute to its antagonistic and plant growth promotion activity. PMID:25767224

  15. Anxiolytic-like actions of the selective 5-HT4 receptor antagonists SB 204070A and SB 207266A in rats.

    PubMed

    Kennett, G A; Bright, F; Trail, B; Blackburn, T P; Sanger, G J

    1997-01-01

    The highly selective 5-HT4 receptor antagonists, SB 204070A (0.001-0.1 mg/kg s.c., 30 min pretest) and SB 207266A (0.01, 1 and 10 mg/kg p.o., 1 hr pre-test), increased time spent in social interaction without affecting locomotor activity, in a rat 15 min social interaction test under high light, unfamiliar conditions. At 1 and 10 mg/kg s.c., SB 204070A was no longer active. These results are consistent with the profile expected of anxiolytic treatments in this procedure. In a rat 5 min elevated x-maze test, SB 204070A (0.01 and 1 mg/kg s.c., 30 min pre-test) significantly increased the percentage of time spent on the open arms. SB 204070A (0.01 mg/kg s.c.) and SB 207266A (1 mg/kg p.o., 1 hr pre-test) also increased percentage entries to the open arms. Neither compound affected locomotion at any dose tested in the procedure. The effects of both compounds in this procedure are also consistent with anxiolysis. Neither SB 204070A (0.1 or 1 mg/kg s.c., 30 min pre-test) nor SB 207266A (0.1 or 1 mg/kg p.o., 1 hr pre-test) affected either unpunished or punished responding, in a rat Geller-Seifter conflict model of anxiety. The maximal efficacy of both SB 204070A and SB 207266A in the rat social interaction test was similar to that of the benzodiazepine anxiolytic chlordiazepoxide (5 mg/kg s.c. or p.o.) used as a positive control, but was considerably less in the elevated x-maze procedure. The results suggest that 5-HT4 receptor antagonists may have modest anxiolytic-like actions in rats. PMID:9225297

  16. Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task.

    PubMed

    Perez-García, Georgina; Meneses, Alfredo

    2005-07-01

    In this work we aimed to re-examine the 5-HT6 receptor role, by testing the selective antagonists SB-357134 (1-30 mg/kg p.o.) and SB-399885 (1-30 mg/kg p.o.) during memory consolidation of conditioned responses (CR%), in an autoshaping Pavlovian/instrumental learning task. Bioavailability, half-life and minimum effective dose to induce inappetence for SB-357134 were 65%, 3.4 h, and 30 mg/kg p.o., and for SB-399885 were 52%, 2.2 h, and 50 mg/kg p.o., respectively. Oral acute and chronic administration of either SB-357134 or SB-399885 improved memory consolidation compared to control groups. Acute administration of SB-357134, at 1, 3, 10 and 30 mg/kg, produced a CR% inverted-U curve, eliciting the latter dose a 7-fold increase relative to saline group. Acute injection of SB-399885 produced significant CR% increments, being 1 mg/kg the most effective dose. Repeated administration (7 days) of either SB-357134 (10 mg/kg) or SB-399885 (1 mg/kg) elicited the most significant CR% increments. Moreover, modeling the potential therapeutic benefits of 5-HT6 receptor blockade, acute or repeated administration of SB-399885, at 10 mg/kg reversed memory deficits produced by scopolamine or dizocilpine, and SB-357134 (3 and 10 mg/kg) prevented amnesia and even improved performance. These data support the notion that endogenously 5-HT acting, via 5-HT6 receptor, improves memory consolidation. PMID:15964617

  17. Characterization of SB-269970-A, a selective 5-HT7 receptor antagonist

    PubMed Central

    Hagan, Jim J; Price, Gary W; Jeffrey, Phillip; Deeks, Nigel J; Stean, Tania; Piper, David; Smith, Martin I; Upton, Neil; Medhurst, Andrew D; Middlemiss, Derek N; Riley, Graham J; Lovell, Peter J; Bromidge, Steven M; Thomas, David R

    2000-01-01

    The novel 5-HT7 receptor antagonist, SB-269970-A, potently displaced [3H]-5-CT from human 5-HT7(a) (pKi 8.9±0.1) and 5-HT7 receptors in guinea-pig cortex (pKi 8.3±0.2).5-CT stimulated adenylyl cyclase activity in 5-HT7(a)/HEK293 membranes (pEC50 7.5±0.1) and SB-269970-A (0.03–1 μM) inhibited the 5-CT concentration-response with no significant alteration in the maximal response. The pA2 (8.5±0.2) for SB-269970-A agreed well with the pKi determined from [3H]-5-CT binding studies.5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes (pEC50 of 8.4±0.2) was inhibited by SB-269970-A (0.3 μM) with a pKB (8.3±0.1) in good agreement with its antagonist potency at the human cloned 5-HT7(a) receptor and its binding affinity at guinea-pig cortical membranes.5-HT7 receptor mRNA was highly expressed in human hypothalamus, amygdala, thalamus, hippocampus and testis.SB-269970-A was CNS penetrant (steady-state brain : blood ratio of ca. 0.83 : 1 in rats) but was rapidly cleared from the blood (CLb=ca. 140 ml min−1 kg−1). Following a single dose (3 mg kg−1) SB-269970 was detectable in rat brain at 30 (87 nM) and 60 min (58 nM). In guinea-pigs, brain levels averaged 31 and 51 nM respectively at 30 and 60 min after dosing, although the compound was undetectable in one of the three animals tested.5-CT (0.3 mg kg−1 i.p.) induced hypothermia in guinea-pigs was blocked by SB-269970-A (ED50 2.96 mg kg−1 i.p.) and the non-selective 5-HT7 receptor antagonist metergoline (0.3–3 mg kg−1 s.c.), suggesting a role for 5-HT7 receptor stimulation in 5-CT induced hypothermia in guinea-pigs.SB-269970-A (30 mg kg−1) administered at the start of the sleep period, significantly reduced time spent in Paradoxical Sleep (PS) during the first 3  h of EEG recording in conscious rats. PMID:10821781

  18. Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development.

    PubMed

    Rami, Harshad K; Thompson, Mervyn; Stemp, Geoffrey; Fell, Steve; Jerman, Jeffrey C; Stevens, Alexander J; Smart, Darren; Sargent, Becky; Sanderson, Dominic; Randall, Andrew D; Gunthorpe, Martin J; Davis, John B

    2006-06-15

    Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat). Furthermore, 15 possessed suitable developability properties to enable progression of this compound into in vivo studies and subsequently clinical development. PMID:16580202

  19. Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction.

    PubMed

    Cunningham, Kathryn A; Anastasio, Noelle C; Fox, Robert G; Stutz, Sonja J; Bubar, Marcy J; Swinford, Sarah E; Watson, Cheryl S; Gilbertson, Scott R; Rice, Kenner C; Rosenzweig-Lipson, Sharon; Moeller, F Gerard

    2013-01-16

    Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT(2A) receptor (5-HT(2A)R) and 5-HT(2C)R; either a selective 5-HT(2A)R antagonist or a 5-HT(2C)R agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT(2A)R antagonist plus 5-HT(2C)R agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT(2A)R antagonist M100907 plus the 5-HT(2C)R agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT(2A)R antagonist plus a 5-HT(2C)R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules. PMID:23336050

  20. Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating.

    PubMed

    Hardaway, J Andrew; Jensen, Jennifer; Kim, Michelle; Mazzone, Christopher M; Sugam, Jonathan A; Diberto, Jeffrey F; Lowery-Gionta, Emily G; Hwa, Lara S; Pleil, Kristen E; Bulik, Cynthia M; Kash, Thomas L

    2016-07-01

    Binge eating is a dysregulated form of feeding behavior that occurs in multiple eating disorders including binge-eating disorder, the most common eating disorder. Feeding is a complex behavioral program supported through the function of multiple brain regions and influenced by a diverse array of receptor signaling pathways. Previous studies have shown the overexpression of the opioid neuropeptide nociceptin (orphanin FQ, N/OFQ) can induce hyperphagia, but the role of endogenous nociceptin receptor (NOP) in naturally occurring palatability-induced hyperphagia is unknown. In this study we adapted a simple, replicable form of binge eating of high fat food (HFD). We found that male and female C57BL/6J mice provided with daily one-hour access sessions to HFD eat significantly more during this period than those provided with continuous 24h access. This form of feeding is rapid and entrained. Chronic intermittent HFD binge eating produced hyperactivity and increased light zone exploration in the open field and light-dark assays respectively. Treatment with the potent and selective NOP antagonist SB 612111 resulted in a significant dose-dependent reduction in binge intake in both male and female mice, and, unlike treatment with the serotonin selective reuptake inhibitor fluoxetine, produced no change in total 24-h food intake. SB 612111 treatment also significantly decreased non-binge-like acute HFD consumption in male mice. These data are consistent with the hypothesis that high fat binge eating is modulated by NOP signaling and that the NOP system may represent a promising novel receptor to explore for the treatment of binge eating. PMID:27036650

  1. Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating

    PubMed Central

    Hardaway, J. Andrew; Jensen, Jennifer; Kim, Michelle; Mazzone, Christopher M.; Sugam, Jonathan A.; Diberto, Jeffrey F.; Lowery-Gionta, Emily G.; Hwa, Lara S.; Pleil, Kristen E.; Bulik, Cynthia M.; Kash, Thomas L.

    2016-01-01

    Binge eating is a dysregulated form of feeding behavior that occurs in multiple eating disorders including binge-eating disorder, the most common eating disorder. Feeding is a complex behavioral program supported through the function of multiple brain regions and influenced by a diverse array of receptor signaling pathways. Previous studies have shown the overexpression of the opioid neuropeptide nociceptin (orphanin FQ, N/OFQ) can induce hyperphagia, but the role of endogenous nociceptin receptor (NOP) in naturally occurring palatability-induced hyperphagia is unknown. In this study we adapted a simple, replicable form of binge eating of high fat food (HFD). We found that male and female C57BL/6J mice provided with daily one-hour access sessions to HFD eat significantly more during this period than those provided with continuous 24 hour access. This form of feeding is rapid and entrained. Chronic intermittent HFD binge eating produced hyperactivity and increased light zone exploration in the open field and light-dark assays respectively. Treatment with the potent and selective NOP antagonist SB 612111 resulted in a significant dose-dependent reduction in binge intake in both male and female mice, and, unlike treatment with the serotonin selective reuptake inhibitor fluoxetine, produced no change in total 24-hour food intake. SB 612111 treatment also significantly decreased non-binge-like acute HFD consumption in male mice. These data are consistent with the hypothesis that high fat binge eating is modulated by NOP signaling and that the NOP system may represent a promising novel receptor to explore for the treatment of binge eating. PMID:27036650

  2. Antagonistic activity and mechanisms of Bacillus subtilis SB1 against Ralstonia solanacearum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A potential biocontrol agent of bacterial wilt, Bacillus subtilis SB1, showed a broad-spectrum of antimicrobial activity in vitro experiments. In addition to Ralstonia solanacearum, strain SB1 inhibited the growth of many other plant pathogens, including Fusarium oxysporum, Botrytis cinerea, Phytoph...

  3. Antagonistic activity of Bacillus subtilis SB1 and its biocontrol effect on tomato bacterial wilt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A potential biocontrol agent of bacterial wilt, Bacillus subtilis SB1, isolated from tomato roots, showed a broad-spectrum of antimicrobial activity in in vitro experiments. It inhibited the growth of many plant pathogens, including Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, Fusarium ox...

  4. Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men

    PubMed Central

    Liem-Moolenaar, Marieke; Rad, Mandana; Zamuner, Stefano; Cohen, Adam F; Lemme, Francesca; Franson, Kari L; van Gerven, Joop M A; Pich, Emilio Merlo

    2011-01-01

    AIM Several lines of evidence suggest a possible role of 5-HT6receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT6 antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P = 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P = 0.016). No significant effects of SB-742457 alone were found. CONCLUSION The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established. PMID:21223356

  5. The selective D₃ receptor antagonist SB-277011A attenuates morphine-triggered reactivation of expression of cocaine-induced conditioned place preference.

    PubMed

    Rice, Onarae V; Heidbreder, Christian A; Gardner, Eliot L; Schonhar, Charles D; Ashby, Charles R

    2013-08-01

    We examined the effect of acute administration of the selective D3 receptor antagonist SB-277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB-277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB-277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB-277011A decreases the incentive motivational actions of morphine. The present findings suggest that central D₃ dopamine receptors are involved in relapse to cocaine-seeking behavior, that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D₃ receptor antagonists constitute promising compounds for treating addiction. PMID:23404528

  6. A-to-I editing of the 5HT2C receptor and behaviour.

    PubMed

    Gardiner, Katheleen; Du, Yunzhi

    2006-03-01

    Site-specific deamination of five adenosine residues in the pre-mRNA of the serotonin 2C receptor, 5HT2CR, alters the amino acid sequence of the encoded protein. Such RNA editing can produce 32 mRNA variants, encoding 24 protein isoforms that vary in biochemical and pharmacological properties. Because serotonin functions in the regulation of mood and behaviour, modulation of serotonin signalling by RNA editing may be relevant to such psychiatric disorders as anxiety and depression. Several recent human studies have reported changes in 5HT2CR editing in schizophrenia, major depression or suicide, but results are variable and not conclusive. Rodent studies have begun to examine effects of drug treatments and stress. Understanding the importance of 5HT2CR editing in mood and behaviour will be assisted by experiments designed to analyse multiple strains of mice, in different behavioural tests, with optimal evaluation of the time course of molecular changes. PMID:16769676

  7. Urotensin-ⅡReceptor Antagonist SB-710411 Protects Rat Heart against Ischemia-Reperfusion Injury via RhoA/ROCK Pathway

    PubMed Central

    Luo, Sheng-Yong; Chen, Shuo; Qin, Yi-De; Chen, Zhi-Wu

    2016-01-01

    Aim SB-710411 is a rat selective urotensin-II (U-II) receptor antagonist, which can block U-II-induced contraction of the aorta and inhibit U-II-induced myocardial fibrosis in rats. However, the effect of SB-710411 on myocardial ischemia-reperfusion (I/R) injury is unclear. The present study was designed to investigate whether SB-710411 has a protective effect on myocardial I/R injury in rats and the possible mechanisms. Methods and Results Myocardial I/R injury was induced by occluding the left anterior descending coronary artery in adult male Sprague-Dawley rats. Hemodynamic parameters, electrocardiogram (ECG), infarct size, histological alteration, lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), cardiac troponin I (cTnI), RhoA, and the protein expressions of U-II receptor (UTR), ROCK1 and ROCK2 were evaluated. Cardiac I/R injury significantly up-regulated the expressions of UTR, ROCK1 and ROCK2 proteins in rat myocardium. SB-710411 1.0 and 2.0 μg/kg significantly reduced cardiac I/R-induced the infarct size and histological damage in rat myocardium, markedly inhibited the changes of hemodynamic parameters and the increases of ST-segment in ECG, the serum LDH and CK-MB activities and cTnI level in rats subjected to myocardial I/R injury. Furthermore, SB-710411 obviously prevented myocardial I/R-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions. Conclusions Our results indicate that cardiac I/R injury increases myocardial UTR expression, and SB-710411 has a potent protective effect on myocardial I/R injury in rats. The cardioprotection may be associated with the inhibition of UTR-RhoA/ROCK pathway. PMID:26771557

  8. Classification of dopamine, serotonin, and dual antagonists by decision trees.

    PubMed

    Kim, Hye-Jung; Choo, Hyunah; Cho, Yong Seo; Koh, Hun Yeong; No, Kyoung Tai; Pae, Ae Nim

    2006-04-15

    Dopamine antagonists (DA), serotonin antagonists (SA), and serotonin-dopamine dual antagonists (Dual) are being used as antipsychotics. A lot of dopamine and serotonin antagonists reveal non-selective binding affinity against these two receptors because the antagonists share structurally common features originated from conserved residues of binding site of the aminergic receptor family. Therefore, classification of dopamine and serotonin antagonists into their own receptors can be useful in the designing of selective antagonist for individual therapy of antipsychotic disorders. Data set containing 1135 dopamine antagonists (D2, D3, and D4), 1251 serotonin antagonists (5-HT1A, 5-HT2A, and 5-HT2C), and 386 serotonin-dopamine dual antagonists was collected from the MDDR database. Cerius2 descriptors were employed to develop a classification model for the 2772 compounds with antipsychotic activity. LDA (linear discriminant analysis), SIMCA (soft independent modeling of class analogy), RP (recursive partitioning), and ANN (artificial neural network) algorithms successfully classified the active class of each compound at the average 73.6% and predicted at the average 69.8%. The decision trees from RP, the best model, were generated to identify and interpret those descriptors that discriminate the active classes more easily. These classification models could be used as a virtual screening tool to predict the active class of new candidates. PMID:16387502

  9. The Orexin-1 Receptor Antagonist SB-334867 Reduces Alcohol Relapse Drinking, but not Alcohol-Seeking, in Alcohol-Preferring (P) Rats

    PubMed Central

    Dhaher, Ronnie; Hauser, Sheketha R.; Getachew, Bruk; Bell, Richard L.; McBride, William J.; McKinzie, David L.; Rodd, Zachary A.

    2010-01-01

    Principle The orexin system has been hypothesized to regulate drug-seeking and drug self-administration behaviors, including ethanol (EtOH) seeking and consumption. However, studies on the effects of orexin receptor antagonists have not been conducted on robust alcohol-relapse behavior. Objectives This study assessed the effects of the orexin-1 receptor antagonist, SB-334867, on alcohol-seeking behavior and responding for alcohol under relapse conditions. Methods Adult alcohol-preferring (P) rats self-trained in 2-lever operant chambers to administer 15% EtOH (vol/vol) on a fixed-ratio-5 and water on a fixed-ratio-1 schedule of reinforcement. After 10 weeks, rats underwent extinction training for 7 sessions. Animals were then maintained in their home cages for 2 weeks before being tested for Pavlovian Spontaneous Recovery (PSR; a measure of alcohol seeking) for 4 sessions. Rats were then allowed a week in their home cages before being returned to the operant chamber with access to EtOH and water (relapse). Thirty minutes before the PSR and relapse test sessions, rats received 0, 10, or 20 mg/kg SB-334867. Results Responses on the EtOH lever during the 1st PSR test session were ~70 presses/session (3-fold higher than baseline); SB-334867 did not alter responses on the EtOH lever. Under relapse conditions, P rats increased responding on the EtOH lever from 250 (at baseline) to 350 responses/session; both doses of SD-334867 prevented this increase. Conclusions The results of this study suggest that activation of orexin-1 receptors is not involved in intrinsically initiated EtOH seeking, but may regulate the consummatory behavior of EtOH consumption. PMID:20871792

  10. Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat.

    PubMed Central

    Ruetten, H.; Thiemermann, C.; Vane, J. R.

    1996-01-01

    1. This study investigates the effects of the non-selective ETA/ETB receptor antagonist, SB 209670, on systemic haemodynamics, renal function, liver function, acid-base balance and survival in a rat model of endotoxic shock. 2. Injection of E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.) resulted in increases in the serum levels of tumour necrosis factor-alpha (TNF-alpha, maximum 60 min after LPS), endothelin-1, (ET-1; maximum 120 min after LPS), and interferon-gamma (IFN-gamma, maximum 180 min after LPS). 3. Injection of LPS also resulted in a fall in blood pressure from 113 +/- 3 mmHg (time = 0) to 84 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the vasoconstrictor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with a continuous infusion of SB 209670 (3 mg kg-1, i.v. bolus + 100 micrograms kg-1, i.v. infusion commencing 15 min prior to LPS) significantly augmented the hypotension as well as the vascular hyporeactivity to NA caused by endotoxaemia. 4. Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus given 15 min prior to LPS) or infusion of SB 209670 (bolus dose and infusion as above) resulted in a reduction in 6 h-survival from 71% (control) to 30% and 13%, respectively. 5. Endotoxaemia for 4 h resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), but not in the serum levels of bilirubin, GPT and GOT (indicators of liver dysfunction and/or hepatocellular injury). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus 15 min prior to LPS) significantly augmented the serum levels of creatinine, bilirubin, GPT and GOT caused by endotoxin. In addition, endotoxaemia caused, within 15 min, an acute metabolic acidosis (falls in pH, HCO3- and base excess) which was compensated by hyperventilation (fall in PaCO2). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus) significantly augmented the metabolic acidosis caused by LPS. 6. Thus, the non

  11. The effects of SB 216469, an antagonist which discriminates between the alpha 1A-adrenoceptor and the human prostatic alpha 1-adrenoceptor.

    PubMed Central

    Chess-Williams, R.; Chapple, C. R.; Verfurth, F.; Noble, A. J.; Couldwell, C. J.; Michel, M. C.

    1996-01-01

    1. The affinity of the alpha 1-adrenoceptor antagonist SB 216469 (also known as REC 15/2739) has been determined at native and cloned alpha 1-adrenoceptor subtypes by radioligand binding and at functional alpha 1-adrenoceptor subtypes in isolated tissues. 2. In radioligand binding studies with [3H]-prazosin, SB 216469 had a high affinity at the alpha 1A-adrenoceptors of the rat cerebral cortex and kidney (9.5-9.8) but a lower affinity at the alpha 1B-adrenoceptors of the rat spleen and liver (7.7-8.2). 3. At cloned rat alpha 1-adrenoceptor subtypes transiently expressed in COS-1 cells and also at cloned human alpha 1-adrenoceptor subtypes stably transfected in Rat-1 cells, SB 216469 exhibited a high affinity at the alpha 1a-adrenoceptors (9.6-10.4) with a significantly lower affinity at the alpha 1b-adrenoceptor (8.0-8.4) and an intermediate affinity at the alpha 1d-adrenoceptor (8.7-9.2). 4. At functional alpha 1-adrenoceptors, SB 216469 had a similar pharmacological profile, with a high affinity at the alpha 1A-adrenoceptors of the rat vas deferens and anococcygeus muscle (pA2 = 9.5-10.0), a low affinity at the alpha 1B-adrenoceptors of the rat spleen (6.7) and guinea-pig aorta (8.0), and an intermediate affinity at the alpha 1D-adrenoceptors of the rat aorta (8.8). 5. Several recent studies have concluded that the alpha 1-adrenoceptor present in the human prostate has the pharmacological characteristics of the alpha 1A-adrenoceptor subtype. However, the affinity of SB 216469 at human prostatic alpha 1-adrenoceptors (pA2 = 8.1) determined in isolated tissue strips, was significantly lower than the values obtained at either the cloned alpha 1a-adrenoceptors (human, rat, bovine) or the native alpha 1A-adrenoceptors in radioligand binding and functional studies in the rat. 6. Our results with SB 216469, therefore, suggest that the alpha 1-adrenoceptor mediating contractile responses of the human prostate has properties which distinguish it from the cloned alpha 1a

  12. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions.

    PubMed

    Pak, Arlene C; Ashby, Charles R; Heidbreder, Christian A; Pilla, Maria; Gilbert, Jeremy; Xi, Zheng-Xiong; Gardner, Eliot L

    2006-10-01

    Increasing evidence suggests that enhanced dopamine (DA) neurotransmission in the nucleus accumbens (NAc) may play a role in mediating the reward and reinforcement produced by addictive drugs and in the attentional processing of drug-associated environmental cues. The meso-accumbens DA system is selectively enriched with DA D3 receptors, a DA receptor subtype increasingly implicated in reward-related brain and behavioural processes. From a variety of evidence, it has been suggested that selective DA D3 receptor antagonism may be a useful pharmacotherapeutic approach for treating addiction. The present experiments tested the efficacy of SB-277011A, a selective DA D3 receptor antagonist, in rat models of nicotine-enhanced electrical brain-stimulation reward (BSR), nicotine-induced conditioned locomotor activity (LMA), and nicotine-induced conditioned place preference (CPP). Nicotine was given subcutaneously within the dose range of 0.25-0.6 mg/kg (nicotine-free base). SB-277011A, given intraperitoneally within the dose range of 1-12 mg/kg, dose-dependently reduced nicotine-enhanced BSR, nicotine-induced conditioned LMA, and nicotine-induced CPP. The results suggest that selective D3 receptor antagonism constitutes a new and promising pharmacotherapeutic approach to the treatment of nicotine dependence. PMID:16942635

  13. Social Behavioral Deficits Coincide with the Onset of Seizure Susceptibility in Mice Lacking Serotonin Receptor 2c.

    PubMed

    Séjourné, Julien; Llaneza, Danielle; Kuti, Orsolya J; Page, Damon T

    2015-01-01

    The development of social behavior is strongly influenced by the serotonin system. Serotonin 2c receptor (5-HT2cR) is particularly interesting in this context considering that pharmacological modulation of 5-HT2cR activity alters social interaction in adult rodents. However, the role of 5-HT2cR in the development of social behavior is unexplored. Here we address this using Htr2c knockout mice, which lack 5-HT2cR. We found that these animals exhibit social behavior deficits as adults but not as juveniles. Moreover, we found that the age of onset of these deficits displays similar timing as the onset of susceptibility to spontaneous death and audiogenic-seizures, consistent with the hypothesis that imbalanced excitation and inhibition (E/I) may contribute to social behavioral deficits. Given that autism spectrum disorder (ASD) features social behavioral deficits and is often co-morbid with epilepsy, and given that 5-HT2cR physically interacts with Pten, we tested whether a second site mutation in the ASD risk gene Pten can modify these phenotypes. The age of spontaneous death is accelerated in mice double mutant for Pten and Htr2c relative to single mutants. We hypothesized that pharmacological antagonism of 5-HT2cR activity in adult animals, which does not cause seizures, might modify social behavioral deficits in Pten haploinsufficient mice. SB 242084, a 5-HT2cR selective antagonist, can reverse the social behavior deficits observed in Pten haploinsufficient mice. Together, these results elucidate a role of 5-HT2cR in the modulation of social behavior and seizure susceptibility in the context of normal development and Pten haploinsufficiency. PMID:26308619

  14. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

    PubMed

    Martin-Gronert, Malgorzata S; Stocker, Claire J; Wargent, Edward T; Cripps, Roselle L; Garfield, Alastair S; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S H; Cawthorne, Michael A; Arch, Jonathan R S; Heisler, Lora K; Ozanne, Susan E

    2016-04-01

    Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. PMID:26769798

  15. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

    PubMed Central

    Martin-Gronert, Malgorzata S.; Stocker, Claire J.; Wargent, Edward T.; Cripps, Roselle L.; Garfield, Alastair S.; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S. H.; Cawthorne, Michael A.; Arch, Jonathan R. S.; Heisler, Lora K.; Ozanne, Susan E.

    2016-01-01

    ABSTRACT Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. PMID:26769798

  16. Serotonin2C receptors modulate dopamine transmission in the nucleus accumbens independently of dopamine release: behavioral, neurochemical and molecular studies with cocaine.

    PubMed

    Cathala, Adeline; Devroye, Céline; Maitre, Marlène; Piazza, Pier Vincenzo; Abrous, Djoher Nora; Revest, Jean-Michel; Spampinato, Umberto

    2015-05-01

    In keeping with its ability to control the mesoaccumbens dopamine (DA) pathway, the serotonin2C receptor (5-HT2C R) plays a key role in mediating the behavioral and neurochemical effects of drugs of abuse. Studies assessing the influence of 5-HT2C R agonists on cocaine-induced responses have suggested that 5-HT2C Rs can modulate mesoaccumbens DA pathway activity independently of accumbal DA release, thereby controlling DA transmission in the nucleus accumbens (NAc). In the present study, we assessed this hypothesis by studying the influence of the 5-HT2C R agonist Ro 60-0175 on cocaine-induced behavioral, neurochemical and molecular responses. The i.p. administration of 1 mg/kg Ro 60-0175 inhibited hyperlocomotion induced by cocaine (15 mg/kg, i.p.), had no effect on cocaine-induced DA outflow in the shell, and increased it in the core subregion of the NAc. Furthermore, Ro 60-0175 inhibited the late-onset locomotion induced by the subcutaneous administration of the DA-D2 R agonist quinpirole (0.5 mg/kg), as well as cocaine-induced increase in c-Fos immunoreactivity in NAc subregions. Finally, Ro 60-0175 inhibited cocaine-induced phosphorylation of the DA and c-AMP regulated phosphoprotein of Mr 32 kDa (DARPP-32) at threonine residues in the NAc core, this effect being reversed by the selective 5-HT2C R antagonist SB 242084 (0.5 mg/kg, i.p.). Altogether, these findings demonstrate that 5-HT2C Rs are capable of modulating mesoaccumbens DA pathway activity at post-synaptic level by specifically controlling DA signaling in the NAc core subregion. In keeping with the tight relationship between locomotor activity and NAc DA function, this interaction could participate in the inhibitory control of cocaine-induced locomotor activity. PMID:24661380

  17. Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system.

    PubMed

    Swinford-Jackson, S E; Anastasio, N C; Fox, R G; Stutz, S J; Cunningham, K A

    2016-06-01

    Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity ("incubation") is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective serotonin (5-HT) 5-HT2C​ receptor (5-HT2CR) agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity. PMID:26926963

  18. Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their possible relevance to antimigraine efficacy

    PubMed Central

    Schaerlinger, B; Hickel, P; Etienne, N; Guesnier, L; Maroteaux, L

    2003-01-01

    The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT2 subtype. To elucidate if 5-HT2 receptors (5-HT2Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8′-hydroxy-DHE (8′-OH-DHE) at the 5-HT2B and 5-HT2CRs by binding, inositol triphosphate (IP3) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. DHE and 8′-OH-DHE are competitive compounds at 5-HT2B and 5-HT2CRs. 8′-OH-DHE interaction at (5-HT2BRs) was best fitted by a biphasic competition curve and displayed the highest affinity with a Ki of 5 nM. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC50 of 8.32±0.09 for 8′-OH-DHE at 5-HT2B and 7.83±0.06 at 5-HT2CRs. Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8′-OH-DHE. The number of 5-HT2BR-binding sites was always more affected than 5-HT2CRs. At 5-HT2BRs, 8′-OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP3 or cGMP. By contrast, the 5-HT2CR coupling was reversible after either treatment. Chronic exposure to 8′-OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT2B, but not 5-HT2CRs. This may be of relevance to therapeutic actions of the compound. PMID:12970106

  19. Calcium antagonists.

    PubMed

    Grossman, Ehud; Messerli, Franz H

    2004-01-01

    Calcium antagonists were introduced for the treatment of hypertension in the 1980s. Their use was subsequently expanded to additional disorders, such as angina pectoris, paroxysmal supraventricular tachycardias, hypertrophic cardiomyopathy, Raynaud phenomenon, pulmonary hypertension, diffuse esophageal spasms, and migraine. Calcium antagonists as a group are heterogeneous and include 3 main classes--phenylalkylamines, benzothiazepines, and dihydropyridines--that differ in their molecular structure, sites and modes of action, and effects on various other cardiovascular functions. Calcium antagonists lower blood pressure mainly through vasodilation and reduction of peripheral resistance. They maintain blood flow to vital organs, and are safe in patients with renal impairment. Unlike diuretics and beta-blockers, calcium antagonists do not impair glucose metabolism or lipid profile and may even attenuate the development of arteriosclerotic lesions. In long-term follow-up, patients treated with calcium antagonists had development of less overt diabetes mellitus than those who were treated with diuretics and beta-blockers. Moreover, calcium antagonists are able to reduce left ventricular mass and are effective in improving anginal pain. Recent prospective randomized studies attested to the beneficial effects of calcium antagonists in hypertensive patients. In comparison with placebo, calcium antagonist-based therapy reduced major cardiovascular events and cardiovascular death significantly in elderly hypertensive patients and in diabetic patients. In several comparative studies in hypertensive patients, treatment with calcium antagonists was equally effective as treatment with diuretics, beta-blockers, or angiotensin-converting enzyme inhibitors. From these studies, it seems that a calcium antagonist-based regimen is superior to other regimens in preventing stroke, equivalent in preventing ischemic heart disease, and inferior in preventing congestive heart failure

  20. Synthesis and biological evaluation of 4-nitroindole derivatives as 5-HT2A receptor antagonists.

    PubMed

    Hayat, Faisal; Viswanath, Ambily Nath Indu; Pae, Ae Nim; Rhim, Hyewhon; Park, Woo-Kyu; Choo, Hea-Young Park

    2015-03-15

    A novel series of 4-nitroindole sulfonamides containing a methyleneamino-N,N-dimethylformamidine were prepared. The binding of these compounds to 5-HT2A and 5-HT2C was evaluated, and most of the compounds showed IC50 values of less than 1μM, and exhibited high selectivity for the 5-HT2C receptor. However, little selectivity was observed in the functional assay for 5-HT6 receptors. The computational modeling studies further validated the biological results and also demonstrated a reasonable correlation between the activity of compounds and the mode of superimposition with specified pharmacophoric features. PMID:25684421

  1. Oxazolidinones as novel human CCR8 antagonists.

    PubMed

    Jin, Jian; Wang, Yonghui; Wang, Feng; Kerns, Jeffery K; Vinader, Victoria M; Hancock, Ashley P; Lindon, Matthew J; Stevenson, Graeme I; Morrow, Dwight M; Rao, Parvathi; Nguyen, Cuc; Barrett, Victoria J; Browning, Chris; Hartmann, Guido; Andrew, David P; Sarau, Henry M; Foley, James J; Jurewicz, Anthony J; Fornwald, James A; Harker, Andy J; Moore, Michael L; Rivero, Ralph A; Belmonte, Kristen E; Connor, Helen E

    2007-03-15

    High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described. PMID:17267215

  2. A Novel Translational Assay of Response Inhibition and Impulsivity: Effects of Prefrontal Cortex Lesions, Drugs Used in ADHD, and Serotonin 2C Receptor Antagonism

    PubMed Central

    Humby, Trevor; Eddy, Jessica B; Good, Mark A; Reichelt, Amy C; Wilkinson, Lawrence S

    2013-01-01

    Animal models are making an increasing contribution to our understanding of the psychology and brain mechanisms underlying behavioral inhibition and impulsivity. The aim here was to develop, for the first time, a mouse analog of the stop-signal reaction time task with high translational validity in order to be able to exploit this species in genetic and molecular investigations of impulsive behaviors. Cohorts of mice were trained to nose-poke to presentations of visual stimuli. Control of responding was manipulated by altering the onset of an auditory ‘stop-signal' during the go response. The anticipated systematic changes in action cancellation were observed as stopping was made more difficult by placing the stop-signal closer to the execution of the action. Excitotoxic lesions of medial prefrontal cortex resulted in impaired stopping, while the clinically effective drugs methylphenidate and atomoxetine enhanced stopping abilities. The specific 5-HT2C receptor antagonist SB242084 also led to enhanced response control in this task. We conclude that stop-signal reaction time task performance can be successfully modeled in mice and is sensitive to prefrontal cortex dysfunction and drug treatments in a qualitatively similar manner to humans and previous rat models. Additionally, using this model we show novel and highly discrete effects of 5-HT2C receptor antagonism that suggest manipulation of 5-HT2C receptor function may be of use in correcting maladaptive impulsive behaviors and provide further evidence for dissociable contributions of serotonergic transmission to response control. PMID:23657439

  3. The Serotonin 2C Receptor Agonist Lorcaserin Attenuates Intracranial Self-Stimulation and Blocks the Reward-Enhancing Effects of Nicotine.

    PubMed

    Zeeb, Fiona D; Higgins, Guy A; Fletcher, Paul J

    2015-07-15

    Lorcaserin, a serotonin (5-hydroxytryptamine, 5-HT) 2C receptor agonist, was recently approved for the treatment of obesity. We previously suggested that 5-HT2C receptor agonists affect reward processes and reduce the rewarding effects of drugs of abuse. Here, we determined whether lorcaserin (1) decreases responding for brain stimulation reward (BSR) and (2) prevents nicotine from enhancing the efficacy of BSR. Rats were trained on the intracranial self-stimulation (ICSS) paradigm to nosepoke for BSR of either the dorsal raphé nucleus or left medial forebrain bundle. In Experiment 1, lorcaserin (0.3-1.0 mg/kg) dose-dependently reduced the efficacy of BSR. This effect was blocked by prior administration of the 5-HT2C receptor antagonist SB242084. In Experiment 2, separate groups of rats received saline or nicotine (0.4 mg/kg) for eight sessions prior to testing. Although thresholds were unaltered in saline-treated rats, nicotine reduced reward thresholds. An injection of lorcaserin (0.3 mg/kg) prior to nicotine prevented the reward-enhancing effect of nicotine across multiple test sessions. These results demonstrated that lorcaserin reduces the rewarding value of BSR and also prevents nicotine from facilitating ICSS. Hence, lorcaserin may be effective in treating psychiatric disorders, including obesity and nicotine addiction, by reducing the value of food or drug rewards. PMID:25781911

  4. Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation.

    PubMed

    Heisler, Lora K; Pronchuk, Nina; Nonogaki, Katsunori; Zhou, Ligang; Raber, Jacob; Tung, Loraine; Yeo, Giles S H; O'Rahilly, Stephen; Colmers, William F; Elmquist, Joel K; Tecott, Laurence H

    2007-06-27

    The dynamic interplay between serotonin [5-hydroxytryptamine (5-HT)] neurotransmission and the hypothalamic-pituitary-adrenal (HPA) axis has been extensively studied over the past 30 years, but the underlying mechanism of this interaction has not been defined. A possibility receiving little attention is that 5-HT regulates upstream corticotropin-releasing hormone (CRH) signaling systems via activation of serotonin 2C receptors (5-HT(2C)Rs) in the paraventricular nucleus of the hypothalamus (PVH). Through complementary approaches in wild-type rodents and 5-HT(2C)R-deficient mice, we determined that 5-HT(2C)Rs are necessary for 5-HT-induced HPA axis activation. We used laser-capture PVH microdissection followed by microarray analysis to compare the expression of 13 5-HTRs. Only 5-HT(2C)R and 5-HT(1D)R transcripts were consistently identified as present in the PVH, and of these, the 5-HT(2C)R was expressed at a substantially higher level. The abundant expression of 5-HT(2C)Rs in the PVH was confirmed with in situ hybridization histochemistry. Dual-neurohistochemical labeling revealed that approximately one-half of PVH CRH-containing neurons coexpressed 5-HT(2C)R mRNA. We observed that PVH CRH neurons consistently depolarized in the presence of a high-affinity 5-HT(2C)R agonist, an effect blocked by a 5-HT(2C)R antagonist. Supporting the importance of 5-HT(2C)Rs in CRH neuronal activity, genetic inactivation of 5-HT(2C)Rs produced a downregulation of CRH mRNA and blunted CRH and corticosterone release after 5-HT compound administration. These findings thus provide a mechanistic explanation for the longstanding observation of HPA axis stimulation in response to 5-HT and thereby give insight into the neural circuitry mediating the complex neuroendocrine responses to stress. PMID:17596444

  5. Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice.

    PubMed

    Halberstadt, Adam L; Koedood, Liselore; Powell, Susan B; Geyer, Mark A

    2011-11-01

    Psilocin (4-hydroxy-N,N-dimethyltryptamine) is a hallucinogen that acts as an agonist at 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors. Psilocin is the active metabolite of psilocybin, a hallucinogen that is currently being investigated clinically as a potential therapeutic agent. In the present investigation, we used a combination of genetic and pharmacological approaches to identify the serotonin (5-HT) receptor subtypes responsible for mediating the effects of psilocin on head twitch response (HTR) and the behavioral pattern monitor (BPM) in C57BL/6J mice. We also compared the effects of psilocin with those of the putative 5-HT(2C) receptor-selective agonist 1-methylpsilocin and the hallucinogen and non-selective serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Psilocin, 1-methylpsilocin, and 5-MeO-DMT induced the HTR, effects that were absent in mice lacking the 5-HT(2A) receptor gene. When tested in the BPM, psilocin decreased locomotor activity, holepoking, and time spent in the center of the chamber, effects that were blocked by the selective 5-HT(1A) antagonist WAY-100635 but were not altered by the selective 5-HT(2C) antagonist SB 242,084 or by 5-HT(2A) receptor gene deletion. 5-MeO-DMT produced similar effects when tested in the BPM, and the action of 5-MeO-DMT was significantly attenuated by WAY-100635. Psilocin and 5-MeO-DMT also decreased the linearity of locomotor paths, effects that were mediated by 5-HT(2C) and 5-HT(1A) receptors, respectively. In contrast to psilocin and 5-MeO-DMT, 1-methylpsilocin (0.6-9.6 mg/kg) was completely inactive in the BPM. These findings confirm that psilocin acts as an agonist at 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors in mice, whereas the behavioral effects of 1-methylpsilocin indicate that this compound is acting at 5-HT(2A) sites but is inactive at the 5-HT(1A) receptor. The fact that 1-methylpsilocin displays greater pharmacological selectivity than psilocin indicates that 1-methylpsilocin

  6. ACTH Antagonists.

    PubMed

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing's disease and ectopic ACTH syndrome - especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia - as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  7. ACTH Antagonists

    PubMed Central

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing’s disease and ectopic ACTH syndrome – especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  8. Stimulation of serotonin2C receptors elicits abnormal oral movements by acting on pathways other than the sensorimotor one in the rat basal ganglia.

    PubMed

    Beyeler, A; Kadiri, N; Navailles, S; Boujema, M Ben; Gonon, F; Moine, C Le; Gross, C; De Deurwaerdère, P

    2010-08-11

    Serotonin2C (5-HT(2C)) receptors act in the basal ganglia, a group of sub-cortical structures involved in motor behavior, where they are thought to modulate oral activity and participate in iatrogenic motor side-effects in Parkinson's disease and Schizophrenia. Whether abnormal movements initiated by 5-HT(2C) receptors are directly consequent to dysfunctions of the motor circuit is uncertain. In the present study, we combined behavioral, immunohistochemical and extracellular single-cell recordings approaches in rats to investigate the effect of the 5-HT(2C) agonist Ro-60-0175 respectively on orofacial dyskinesia, the expression of the marker of neuronal activity c-Fos in basal ganglia and the electrophysiological activity of substantia nigra pars reticulata (SNr) neuron connected to the orofacial motor cortex (OfMC) or the medial prefrontal cortex (mPFC). The results show that Ro-60-0175 (1 mg/kg) caused bouts of orofacial movements that were suppressed by the 5-HT(2C) antagonist SB-243213 (1 mg/kg). Ro-60-0175 (0.3, 1, 3 mg/kg) dose-dependently enhanced Fos expression in the striatum and the nucleus accumbens. At the highest dose, it enhanced Fos expression in the subthalamic nucleus, the SNr and the entopeduncular nucleus but not in the external globus pallidus. However, the effect of Ro-60-0175 was mainly associated with associative/limbic regions of basal ganglia whereas subregions of basal ganglia corresponding to sensorimotor territories were devoid of Fos labeling. Ro-60-0175 (1-3 mg/kg) did not affect the electrophysiological activity of SNr neurons connected to the OfMC nor their excitatory-inhibitory-excitatory responses to the OfMC electrical stimulation. Conversely, Ro-60-0175 (1 mg/kg) enhanced the late excitatory response of SNr neurons evoked by the mPFC electrical stimulation. These results suggest that oral dyskinesia induced by 5-HT(2C) agonists are not restricted to aberrant signalling in the orofacial motor circuit and demonstrate discrete

  9. Serotonin-2C Receptor Agonists Decrease Potassium-Stimulated GABA Release In the Nucleus Accumbens

    PubMed Central

    Kasper, James M; Booth, Raymond G; Peris, Joanna

    2014-01-01

    The serotonin 5-HT2C receptor has shown promise in vivo as a pharmacotherapeutic target for alcoholism. For example, recently, a novel 4-phenyl-2-N,N-dimethylaminotetralin (PAT) drug candidate, that demonstrates 5-HT2C receptor agonist activity together with 5-HT2A/2B receptor inverse agonist activity, was shown to reduce operant responding for ethanol after peripheral administration to rats. Previous studies have shown that the 5-HT2C receptor is found throughout the mesoaccumbens pathway and that 5-HT2C receptor agonism causes activation of ventral tegmental area (VTA) GABA neurons. It is unknown what effect 5-HT2C receptor modulation has on GABA release in the nucleus accumbens core (NAcc). To this end, microdialysis coupled to capillary electrophoresis with laser-induced fluorescence was used to quantify extracellular neurotransmitter concentrations in the NAcc under basal and after potassium stimulation conditions, in response to PAT analogs and other 5-HT2C receptor modulators administered by reverse dialysis to rats. 5-HT2C receptor agonists specifically attenuated stimulated GABA release in the NAcc while 5-HT2C antagonists or inverse agonists had no effect. Agents with activity at 5-HT2A receptors had no effect on GABA release. Thus, in contrast to results reported for the VTA, current results suggest 5-HT2C receptor agonists decrease stimulated GABA release in the NAcc, and provide a possible mechanism of action for 5HT2C-mediated negative modulation of ethanol self-administration. PMID:25382408

  10. Sex differences and serotonergic mechanisms in the behavioural effects of psilocin.

    PubMed

    Tylš, Filip; Páleníček, Tomáš; Kadeřábek, Lukáš; Lipski, Michaela; Kubešová, Anna; Horáček, Jiří

    2016-06-01

    Psilocybin has recently attracted a great deal of attention as a clinical research and therapeutic tool. The aim of this paper is to bridge two major knowledge gaps regarding its behavioural pharmacology - sex differences and the underlying receptor mechanisms. We used psilocin (0.25, 1 and 4 mg/kg), an active metabolite of psilocybin, in two behavioural paradigms - the open-field test and prepulse inhibition (PPI) of the acoustic startle reaction. Sex differences were evaluated with respect to the phase of the female cycle. The contribution of serotonin receptors in the behavioural action was tested in male rats with selective serotonin receptor antagonists: 5-HT1A receptor antagonist (WAY100635 1 mg/kg), 5-HT2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT2B receptor antagonist (SB215505 1 mg/kg) and 5-HT2C receptor antagonist (SB242084 1 mg/kg). Psilocin induced dose-dependent inhibition of locomotion and suppression of normal behaviour in rats (behavioural serotonin syndrome, impaired PPI). The effects were more pronounced in male rats than in females. The inhibition of locomotion was normalized by 5-HT1A and 5-HT2B/C antagonists; however, PPI was not affected significantly by these antagonists. Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT2A-mediated effects 5-HT1A and 5-HT2C/B receptors also play an important role. These findings have implications for recent clinical trials. PMID:26461483

  11. Discovery of small molecule antagonists of TRPV1.

    PubMed

    Rami, Harshad K; Thompson, Mervyn; Wyman, Paul; Jerman, Jeffrey C; Egerton, Julie; Brough, Stephen; Stevens, Alexander J; Randall, Andrew D; Smart, Darren; Gunthorpe, Martin J; Davis, John B

    2004-07-16

    Small molecule antagonists of the vanilloid receptor 1 (TRPV1, also known as VR1) are disclosed. Ureas such as 5 (SB-452533) were used to explore the structure activity relationship with several potent analogues identified. Pharmacological studies using electrophysiological and FLIPR Ca(2+) based assays showed compound 5 was an antagonist versus capsaicin, noxious heat and acid mediated activation of TRPV1. Study of a quaternary salt of 5 supports a mode of action in which compounds from this series cause inhibition via an extracellularly accessible binding site on the TRPV1 receptor. PMID:15203132

  12. Synergistic actions of apomorphine and m-chlorophenylpiperazine on ejaculation, but not penile erection in rats.

    PubMed

    Yonezawa, Akihiko; Yoshizumi, Masaru; Ise, Shin-Nosuke; Watanabe, Chizuko; Mizoguchi, Hirokazu; Furukawa, Katsuo; Tsuru, Hiromichi; Kimura, Yukio; Kawatani, Masahito; Sakurada, Shinobu

    2009-04-01

    It has been suggested that dopamine (DA) and serotonin (5-HT) and their receptors, particularly D(2)-like and 5-HT(2C) receptors, may play a significant role in the control of male sexual function. The purpose of this study was to investigate whether the combination of a dopamine receptor agonist apomorphine and a 5-HT(2) receptor agonist m-CPP would potentiate penile erection and ejaculation in male rats. Systemic administration of either apomorphine (0.01-0.1 mg/kg, s.c.) or m-CPP (0.01-0.3 mg/kg, i.p.) dose-dependently elicited penile erections, but did not induce ejaculation. When combined, there was a drastic increase in both the incidence of ejaculation and the amount of ejaculated seminal materials, while the proerectile effect induced by each drug was not potentiated. The proejaculatory effect induced by the combination of apomorphine (0.1 mg/kg, s.c.) and m-CPP (0.3 mg/kg, i.p.) was completely blocked by pretreatment with the D(2)-like receptor antagonists haloperidol and sulpiride, but not by the D(1)-like receptor antagonist SCH-23390. The synergistic action for ejaculation was also blocked by domperidone, the D(2)-like receptor antagonist that dose not cross the blood-brain barrier. The rats pretreated with the 5-HT(2C) receptor antagonist SB242084 did not show the synergistic action by the combination of apomorphine and m-CPP, whereas the rats pretreated with the 5-HT(2A) receptor antagonist ketanserin and the 5-HT(2B) receptor antagonist SB204741 showed the combination-induced synergistic action. These results suggest that the combination of a small dose of apomorphine and m-CPP potently and selectively facilitates the ejaculatory response through the activation of D(2)-like and 5-HT(2C) receptors, respectively. The D(2)-like receptors involved in the synergistic action may be, at least in part, located in the peripheral sites. PMID:19420729

  13. Solidification of InSb-GaSb alloy and InSb with vibration

    NASA Technical Reports Server (NTRS)

    Yuan, Weijun

    1992-01-01

    The objective of this project is to determine the influence of vibration on the composition homogeneity and microstructure of alloy semiconductors solidified with the Vertical Bridgman-Stockbarger (VBS) technique. InSb-GaSb and InSb were directionally solidified in a VBS apparatus with axial vibration of the ampoule.

  14. Vasopressin receptor antagonists.

    PubMed

    Palmer, Biff F

    2015-01-01

    Arginine vasopressin (AVP) is the principal hormone involved in regulating the tonicity of body fluids. Less appreciated is the role that AVP plays in a variety of other physiologic functions including glucose metabolism, cardiovascular homeostasis, bone metabolism, and cognitive behavior. AVP receptor antagonists are now available and currently approved to treat hyponatremia. There is a great deal of interest in exploring the potential benefits that these drugs may play in blocking AVP-mediated effects in other organ systems. The purpose of this report is to provide an update on the expanding role of AVP receptor antagonists and what disease states these drugs may eventually be used for. PMID:25604388

  15. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    PubMed Central

    Janssen, Wiebke; Schymura, Yves; Novoyatleva, Tatyana; Luitel, Himal; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Weissmann, Norbert; Seeger, Werner; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo

    2015-01-01

    Objective. The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions in right ventricular failure (RVF) remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B receptor antagonist) on right heart function and structure upon pulmonary artery banding (PAB) in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid) or SB204741 (5 mg/kg day). Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF. PMID:25667920

  16. Opioid Antagonist Impedes Exposure.

    ERIC Educational Resources Information Center

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  17. Spiropiperidine CCR5 antagonists.

    PubMed

    Rotstein, David M; Gabriel, Stephen D; Makra, Ferenc; Filonova, Lubov; Gleason, Shelley; Brotherton-Pleiss, Christine; Setti, Lina Q; Trejo-Martin, Alejandra; Lee, Eun Kyung; Sankuratri, Surya; Ji, Changhua; Derosier, Andre; Dioszegi, Marianna; Heilek, Gabrielle; Jekle, Andreas; Berry, Pamela; Weller, Paul; Mau, Cheng-I

    2009-09-15

    A novel series of CCR5 antagonists has been identified, utilizing leads from high-throughput screening which were further modified based on insights from competitor molecules. Lead optimization was pursued by balancing opposing trends of metabolic stability and potency. Selective and potent analogs with good pharmacokinetic properties were successfully developed. PMID:19674898

  18. Xanthines as Adenosine Receptor Antagonists

    PubMed Central

    Jacobson, Kenneth A.

    2013-01-01

    The natural plant alkaloids caffeine and theophylline were the first adenosine receptor (AR) antagonists described in the literature. They exhibit micromolar affinities and are non-selective. A large number of derivatives and analogs have subsequently been synthesized and evaluated as AR antagonists. Very potent antagonists have thus been developed with selectivity for each of the four AR subtypes. PMID:20859796

  19. SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1

    PubMed Central

    Leal, Paulo C.; Bhasin, Manoj K.; Zenatti, Priscila Pini; Nunes, Ricardo J.; Yunes, Rosendo A.; Nowill, Alexandre E.; Libermann, Towia A.; Zerbini, Luiz Fernando; Yunes, José Andrés

    2015-01-01

    Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N’-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1, a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1, seems to underlie the anti-leukemic effect of SB225002. PMID:26302043

  20. SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1.

    PubMed

    de Vasconcellos, Jaíra Ferreira; Laranjeira, Angelo Brunelli Albertoni; Leal, Paulo C; Bhasin, Manoj K; Zenatti, Priscila Pini; Nunes, Ricardo J; Yunes, Rosendo A; Nowill, Alexandre E; Libermann, Towia A; Zerbini, Luiz Fernando; Yunes, José Andrés

    2015-01-01

    Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1, a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1, seems to underlie the anti-leukemic effect of SB225002. PMID:26302043

  1. Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists.

    PubMed

    Kim, Jeeyeon; Kim, Youngjae; Tae, Jinsung; Yeom, Miyoung; Moon, Bongjin; Huang, Xi-Ping; Roth, Bryan L; Lee, Kangho; Rhim, Hyewhon; Choo, Il Han; Chong, Youhoon; Keum, Gyochang; Nam, Ghilsoo; Choo, Hyunah

    2013-11-01

    The 5-HT7 receptor (5-HT7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT7 R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7 R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7 R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT7 R. Among the synthesized compounds, 1-([2'-methoxy-(1,1'-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7 R (pKi =7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7 R over other serotonin receptor subtypes, such as 5-HT1 R, 5-HT2 R, 5-HT3 R, and 5-HT6 R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function. PMID:24039134

  2. Molar and excess volumes of liquid In-Sb, Mg-Sb, and Pb-Sb alloys

    SciTech Connect

    Hansen, A.R.; Kaminski, M.A. ); Eckert, C.A. )

    1990-04-01

    By a direct Archimedes' technique, volumetric data were obtained for liquid In, Mg, Pb, and Sb and mixtures of In-Sb, Mg-Sb, and Pb-Sb. In this paper the excess volumes for the alloys studied are presented and discussed.

  3. Vought SB2U-2 Vindicator

    NASA Technical Reports Server (NTRS)

    1939-01-01

    Vought SB2U-2 Vindicator: The Navy was in the transition from biplanes to monoplanes when it ordered the SB2U. Used for diving tests, this Vought SB2U-2 Vindicator was one of approximately 169 SB2Us built.

  4. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models.

    PubMed

    Anderson, Rachel I; Becker, Howard C; Adams, Benjamin L; Jesudason, Cynthia D; Rorick-Kehn, Linda M

    2014-01-01

    To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX) receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573) on home cage ethanol consumption were tested in ethanol-preferring (P) rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark) model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting non-specific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting non-specific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol consumption

  5. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models

    PubMed Central

    Anderson, Rachel I.; Becker, Howard C.; Adams, Benjamin L.; Jesudason, Cynthia D.; Rorick-Kehn, Linda M.

    2014-01-01

    To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX) receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573) on home cage ethanol consumption were tested in ethanol-preferring (P) rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark) model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting non-specific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting non-specific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol consumption

  6. Selective orexin receptor antagonists.

    PubMed

    Lebold, Terry P; Bonaventure, Pascal; Shireman, Brock T

    2013-09-01

    The orexin, or hypocretin, neuropeptides (orexin-A and orexin-B) are produced on neurons in the hypothalamus which project to key areas of the brain that control sleep-wake states, modulation of food intake, panic, anxiety, emotion, reward and addictive behaviors. These neuropeptides exert their effects on a pair of G-protein coupled receptors termed the orexin-1 (OX1) and orexin-2 (OX2) receptors. Emerging biology suggests the involvement of these receptors in psychiatric disorders as they are thought to play a key role in the regulation of multiple systems. This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists. PMID:23891187

  7. Calmodulin antagonists induce platelet apoptosis.

    PubMed

    Wang, Zhicheng; Li, Suping; Shi, Quanwei; Yan, Rong; Liu, Guanglei; Dai, Kesheng

    2010-04-01

    Calmodulin (CaM) antagonists induce apoptosis in various tumor models and inhibit tumor cell invasion and metastasis, thus some of which have been extensively used as anti-cancer agents. In platelets, CaM has been found to bind directly to the cytoplasmic domains of several platelet receptors. Incubation of platelets with CaM antagonists impairs the receptors-related platelet functions. However, it is still unknown whether CaM antagonists induce platelet apoptosis. Here we show that CaM antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), tamoxifen (TMX), and trifluoperazine (TFP) induce apoptotic events in human platelets, including depolarization of mitochondrial inner transmembrane potential, caspase-3 activation, and phosphatidylserine exposure. CaM antagonists did not incur platelet activation as detected by P-selectin surface expression and PAC-1 binding. However, ADP-, botrocetin-, and alpha-thrombin-induced platelet aggregation, platelet adhesion and spreading on von Willebrand factor surface were significantly reduced in platelets pre-treated with CaM antagonists. Furthermore, cytosolic Ca(2+) levels were obviously elevated by both W7 and TMX, and membrane-permeable Ca(2+) chelator BAPTA-AM significantly reduced apoptotic events in platelets induced by W7. Therefore, these findings indicate that CaM antagonists induce platelet apoptosis. The elevation of the cytosolic Ca(2+) levels may be involved in the regulation of CaM antagonists-induced platelet apoptosis. PMID:20172594

  8. Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption.

    PubMed

    Vengeliene, Valentina; Noori, Hamid R; Spanagel, Rainer

    2015-12-01

    Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effects on alcohol consumption. We conclude that targeting the melatonergic system in alcohol-dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behavior. PMID:25994077

  9. DWPF SB6 INITIAL CPC FLOWSHEET TESTING SB6-1 TO SB6-4L TESTS OF SB6-A AND SB6-B SIMULANTS

    SciTech Connect

    Lambert, D.; Pickenheim, B.; Best, D.

    2009-09-09

    The Defense Waste Processing Facility (DWPF) will transition from Sludge Batch 5 (SB5) processing to Sludge Batch 6 (SB6) processing in late fiscal year 2010. Tests were conducted using non-radioactive simulants of the expected SB6 composition to determine the impact of varying the acid stoichiometry during the Sludge Receipt and Adjustment Tank (SRAT) and Slurry Mix Evaporator (SME) processes. The work was conducted to meet the Technical Task Request (TTR) HLW/DWPF/TTR-2008-0043, Rev.0 and followed the guidelines of a Task Technical and Quality Assurance Plan (TT&QAP). The flowsheet studies are performed to evaluate the potential chemical processing issues, hydrogen generation rates, and process slurry rheological properties as a function of acid stoichiometry. These studies were conducted with the estimated SB6 composition at the time of the study. This composition assumed a blend of 101,085 kg of Tank 4 insoluble solids and 179,000 kg of Tank 12 insoluble solids. The current plans are to subject Tank 12 sludge to aluminum dissolution. Liquid Waste Operations assumed that 75% of the aluminum would be dissolved during this process. After dissolution and blending of Tank 4 sludge slurry, plans included washing the contents of Tank 51 to {approx}1M Na. After the completion of washing, the plan assumes that 40 inches on Tank 40 slurry would remain for blending with the qualified SB6 material. There are several parameters that are noteworthy concerning SB6 sludge: (1) This is the second batch DWPF will be processing that contains sludge that has had a significant fraction of aluminum removed through aluminum dissolution; (2) The sludge is high in mercury, but the projected concentration is lower than SB5; (3) The sludge is high in noble metals, but the projected concentrations are lower than SB5; and(4) The sludge is high in U and Pu - components that are not added in sludge simulants. Six DWPF process simulations were completed in 4-L laboratory-scale equipment using

  10. [Sb4Au4Sb4]2-: A designer all-metal aromatic sandwich

    NASA Astrophysics Data System (ADS)

    Tian, Wen-Juan; Guo, Jin-Chang; Li, Da-Zhi; You, Xue-Rui; Wang, Ying-Jin; Sun, Zhong-Ming; Zhai, Hua-Jin

    2016-07-01

    We report on the computational design of an all-metal aromatic sandwich, [Sb4Au4Sb4]2-. The triple-layered, square-prismatic sandwich complex is the global minimum of the system from Coalescence Kick and Minima Hopping structural searches. Following a standard, qualitative chemical bonding analysis via canonical molecular orbitals, the sandwich complex can be formally described as [Sb4]+[Au4]4-[Sb4]+, showing ionic bonding characters with electron transfers in between the Sb4/Au4/Sb4 layers. For an in-depth understanding of the system, one needs to go beyond the above picture. Significant Sb → Au donation and Sb ← Au back-donation occur, redistributing electrons from the Sb4/Au4/Sb4 layers to the interlayer Sb-Au-Sb edges, which effectively lead to four Sb-Au-Sb three-center two-electron bonds. The complex is a system with 30 valence electrons, excluding the Sb 5s and Au 5d lone-pairs. The two [Sb4]+ ligands constitute an unusual three-fold (π and σ) aromatic system with all 22 electrons being delocalized. An energy gap of ˜1.6 eV is predicted for this all-metal sandwich. The complex is a rare example for rational design of cluster compounds and invites forth-coming synthetic efforts.

  11. Drug Challenges Reveal Differences in Mediation of Stress Facilitation of Voluntary Alcohol Drinking and Withdrawal-Induced Anxiety in Alcohol-Preferring P Rats

    PubMed Central

    Overstreet, David H.; Knapp, Darin J.; Breese, George R.

    2010-01-01

    Background There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal-induced anxiety-like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol-preferring P rats on both voluntary alcohol drinking and withdrawal-induced anxiety. Methods P rats were subjected to 3 cycles of 5 days of voluntary alcohol drinking and 2 days of deprivation. Restraint stress (60 min) was applied to some animals during the first and second deprivations/withdrawals (at 4 h). Drugs (flumazenil, buspirone, SB242,084, CP154,526, CRA1000, naloxone, haloperidol, olanzapine, naloxone, and haloperidol) were given to some rats 30 min prior to restraint stress. Results Stressed, deprived P rats exhibited both a longer duration of elevated alcohol drinking and anxiety-like behavior in the social interaction test upon withdrawal after the third cycle of voluntary alcohol drinking. When given prior to each of the restraint stresses, the benzodiazepine receptor antagonist flumazenil (5 mg/kg), the corticotrophin releasing factor receptor antagonists CRA1000 (3 mg/kg) and CP154,526 (10 mg/kg), the serotonin 5-HT1A receptor partial agonist buspirone (0.6 mg/kg), and the mixed 5-HT2C/D2 receptor antagonist olanzapine were effective in reducing the increased duration of elevated alcohol drinking and the withdrawal-induced anxiety-like behavior. In contrast, while the opiate receptor antagonist naloxone (20 mg/kg), the 5-HT2C receptor antagonist SB242084 (3 mg/kg), and the dopamine receptor antagonist haloperidol (0.1 mg/kg) also reduced drinking, they did not significantly alter anxiety like behavior. Conclusion These results suggest that stress-induced facilitation of alcohol drinking and withdrawal-induced anxiety

  12. [Vitamin K antagonists overdose].

    PubMed

    Groszek, Barbara; Piszczek, Paweł

    2015-01-01

    Nowadays, anticoagulant therapy belongs to the most commonly used forms of pharmacotherapy in modern medicine. The most important representatives of anticoagulants are heparins (unfractionated heparin and low-molecular-weight heparin) and coumarin derivatives (vitamin K antagonists--VKA). Next to the many advantages of traditional oral anticoagulants may also have disadvantages. In Poland most often used two VKA: acenocoumarol and warfarin. The aim of the work is the analysis of the causes of the occurrence of bleeding disorders and symptoms of overdose VKA in patients to be hospitalized. In the years 2012 to 2014 were hospitalized 62 patients with overdose VKA (40 women and 22 men). The average age of patients was 75.3 years) and clotting disturbances and/or bleeding. At the time of the admission in all patients a significant increase in the value of the INR was stated, in 22 patients INR result was " no clot detected", on the remaining value of the INR were in the range of 7 to 13.1. On 51 patients observed different severe symptoms of bleeding (hematuria, bleeding from mucous membranes of the nose or gums ecchymoses on the extremities, bleeding from the gastrointestinal tract--as in 5 patients has led to significant anemia and transfusion of concentrated red blood cells. Up on 33 patients kidney function disorder were found--exacerbated chronic renal failure and urinary tract infection. 8 diagnosed inflammatory changes in the airways. On 13 patients, it was found a significant degree of neuropsychiatric disorders (dementia, cognitive impairment), which made impossible the understanding the sense of treatment and cooperation with the patient. In 6 patients the symptoms of overdose were probably dependent on the interaction with the congestants at the same time (change the preparation of anticoagulant, NSAIDs, antibiotics). In 2 cases, the overdose was a suicide attempt in nature. In addition to the above mentioned disorders, on two of those patients diagnosed

  13. Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated.

    PubMed

    Kennett, G A; Trail, B; Bright, F

    1998-12-01

    The 5-HT2B receptor agonist, BW 723C86 (10, 30(mg/kg i.p. 30 min pre-test), increased the number of punishments accepted in a rat Vogel drinking conflict paradigm over 3 min, as did the benzodiazepine anxiolytics, chlordiazepoxide (2.5-10 mg/kg p.o. 1 h pre-test) and alprazolam (0.2-5 mg/kg p.o. 1 h pre-test), but not the 5-HT2C/2B receptor agonist, m-chlorophenylpiperazine (mCPP, 0.3-3 mg/kg i.p) or the 5-HT1A receptor agonist, buspirone (5-20 mg/kg p.o. 1 h pre-test). The effect of BW 723C86 was unlikely to be secondary to enhanced thirst, as BW 723C86 did not increase the time that rats with free access to water spent drinking, nor did it reduce sensitivity to shock in the apparatus. The anti-punishment effect of BW 723C86 was opposed by prior treatment with the 5-HT2/2B receptor antagonist, SB-206553 (10 and 20 mg/kg p.o. 1 h pre-test), and the selective 5-HT2B receptor antagonist, SB-215505 (1 and 3 mg/kg p.o. 1 h pre-test), but not by the selective 5-HT2C receptor antagonist, SB-242084 (5 mg/kg p.o.), or the 5-HT1A receptor antagonist, WAY 100635 (0.1 or 0.3 mg/kg s.c. 30 min pre-test). Thus, the anti-punishment action of BW 723C86 is likely to be 5-HT2B receptor mediated. This is consistent with previous reports that BW 723C86 exhibited anxiolytic-like properties in both the social interaction and Geller-Seifter conflict tests. PMID:9886683

  14. MOVPE of GaSb/InGaAsSb Multilayers and Fabrication of Dual Band Photodetectors

    NASA Technical Reports Server (NTRS)

    Xiao, Ye-Gao; Bhat, Ishwara; Refaat, Tamer F.; Abedin, M. Nurul; Shao, Qing-Hui

    2005-01-01

    Metalorganic vapor phase epitaxy (MOVPE) of GaSb/InGaAsSb multilayer thin films and fabrication of bias-selectable dual band photodetectors are reported. For the dual band photodetectors the short wavelength detector, or the upper p- GaSb/n-GaSb junction photodiode, is placed optically ahead of the long wavelength one, or the lower photodiode. The latter is based on latticed-matched In0.13Ga0.87As0.11Sb0.89 with bandgap near 0.6 eV. Specifically, high quality multilayer thin films are grown sequentially from top to bottom as p+-GaSb/p-GaSb/n-GaSb/n-InGaAsSb/p-InGaAsSb/p-GaSb on undoped p-type GaSb substrate, and as n-GaSb/p-GaSb/p-InGaAsSb/n-InGaAsSb/n-GaSb on Te-doped n-type GaSb substrate respectively. The multilayer thin films are characterized by optical microscope, atomic force microscope (AFM), electron microprobe analyses etc. The photodiode mesa steps are patterned by photolithography with wet chemical etching and the front metallization is carried out by e-beam evaporation with Pd/Ge/Au/Ti/Au to give ohmic contact on both n- and p-type Sb based layer surfaces. Dark I-V measurements show typical diode behavior for both the upper and lower photodiodes. The photoresponsivity measurements indicate that both the upper and lower photodiodes can sense the infrared illumination corresponding to their cutoff wavelengths respectively, comparable with the simulation results. More work is underway to bring the long wavelength band to the medium infrared wavelength region near 4 micrometers.

  15. Sexually antagonistic genes: experimental evidence.

    PubMed

    Rice, W R

    1992-06-01

    When selection differs between the sexes, a mutation beneficial to one sex may be harmful to the other (sexually antagonistic). Because the sexes share a common gene pool, selection in one sex can interfere with the other's adaptive evolution. Theory predicts that sexually antagonistic mutations should accumulate in tight linkage with a new sex-determining gene, even when the harm to benefit ratio is high. Genetic markers and artificial selection were used to make a pair of autosomal genes segregate like a new pair of sex-determining genes in a Drosophila melanogaster model system. A 29-generation study provides experimental evidence that sexually antagonistic genes may be common in nature and will accumulate in response to a new sex-determining gene. PMID:1604317

  16. AlSb/InAs/AlSb quantum wells

    NASA Technical Reports Server (NTRS)

    Kroemer, Herbert

    1990-01-01

    Researchers studied the InAs/AlSb system recently, obtaining 12nm wide quantum wells with room temperature mobilities up to 28,000 cm(exp 2)/V center dot S and low-temperature mobilities up to 325,000 cm(exp 2)/V center dot S, both at high electron sheet concentrations in the 10(exp 12)/cm(exp 2) range (corresponding to volume concentrations in the 10(exp 18)/cm(exp 2) range). These wells were not intentionally doped; the combination of high carrier concentrations and high mobilities suggest that the electrons are due to not-intentional modulation doping by an unknown donor in the AlSb barriers, presumably a stoichiometric defect, like an antisite donor. Inasmuch as not intentionally doped bulk AlSb is semi-insulating, the donor must be a deep one, being ionized only by draining into the even deeper InAs quantum well. The excellent transport properties are confirmed by other observations, like excellent quantum Hall effect data, and the successful use of the quantum wells as superconductive weak links between Nb electrodes, with unprecendentedly high critical current densities. The system is promising for future field effect transistors (FETs), but many processing problems must first be solved. Although the researchers have achieved FETs, the results so far have not been competitive with GaAs FETs.

  17. Orexin 1 receptor antagonists in compulsive behavior and anxiety: possible therapeutic use

    PubMed Central

    Merlo Pich, Emilio; Melotto, Sergio

    2014-01-01

    Fifteen years after the discovery of hypocretin/orexin a large body of evidence has been collected supporting its critical role in the modulation of several regulatory physiological functions. While reduced levels of hypocretin/orexin were initially associated with narcolepsy, increased levels have been linked in recent years to pathological states of hypervigilance and, in particular, to insomnia. The filing to FDA of the dual-activity orexin receptor antagonist (DORA) suvorexant for the indication of insomnia further corroborates the robustness of such evidences. However, as excessive vigilance is also typical of anxiety and panic episodes, as well as of abstinence and craving in substance misuse disorders. In this review we briefly discuss the evidence supporting the development of hypocretin/orexin receptor 1 (OX1) antagonists for these indications. Experiments using the OX1 antagonist SB-334867 and mutant mice have involved the OX1 receptor in mediating the compulsive reinstatement of drug seeking for ethanol, nicotine, cocaine, cannabinoids and morphine. More recently, data have been generated with the novel selective OX1 antagonists GSK1059865 and ACT-335827 on behavioral and cardiovascular response to stressors and panic-inducing agents in animals. Concluding, while waiting for pharmacologic data to become available in humans, risks and benefits for the development of an OX1 receptor antagonist for Binge Eating and Anxiety Disorders are discussed. PMID:24592206

  18. Sequential and simultaneous adsorption of Sb(III) and Sb(V) on ferrihydrite: Implications for oxidation and competition.

    PubMed

    Qi, Pengfei; Pichler, Thomas

    2016-02-01

    Antimony (Sb) is a naturally occurring element of growing environmental concern whose toxicity, adsorption behavior and other chemical properties are similar to that of arsenic (As). However, less is known about Sb compared to As. Individual and simultaneous adsorption experiments with Sb(III) and Sb(V) were conducted in batch mode with focus on the Sb speciation of the remaining liquid phase during individual Sb(III) adsorption experiments. The simultaneous adsorption and oxidation of Sb(III) was confirmed by the appearance of Sb(V) in the solution at varying Fe/Sb ratios (500, 100 and 8) and varying pH values (3.8, 7 and 9). This newly formed Sb(V) was subsequently removed from solution at a Fe/Sb ratio of 500 or at a pH of 3.8. However, more or less only Sb(V) was observed in the liquid phase at the end of the experiments at lower Fe/Sb ratios and higher pH, indicating that competition took place between the newly formed Sb(V) and Sb(III), and that Sb(III) outcompeted Sb(V). This was independently confirmed by simultaneous adsorption experiments of Sb(III) and Sb(V) in binary systems. Under such conditions, the presence of Sb(V) had no influence on the adsorption of Sb(III) while Sb(V) adsorption was significantly inhibited by Sb(III) over a wide pH range (4-10). Thus, in the presence of ferrihydrite and under redox conditions, which allow the presence of both Sb species, Sb(V) should be the dominant species in aquatic environments, since Sb(III) is adsorbed preferentially and at the same time oxidized to Sb(V). PMID:26688239

  19. Lattice-Matched GaInAsSb/A1GaAsSb/GaSb Materials for Thermophotovoltaic Devices

    SciTech Connect

    C.A. Wang; C.J. Vineis; H.K. Choi; M.K. Connors; R.H. Huang; L.R. Daielson; G. Nichols; G.W. Charache; D. Donetsky; S. Anikeef; G. Belenky

    2002-09-19

    High-performance GaInAsSb/AlGaAsSb/GaSb thermophotovoltaic (TPV) devices with quantum efficiency and fill factor near theoretical limits and open-circuit voltage within about 15% of the limit can be routinely fabricated. To achieve further improvements in TPV device performance, detailed materials studies of GaInAsSb epitaxial growth, the microstructure, and minority carrier lifetime, along with device structure considerations are reported. This paper discusses the materials and device issues, and their implications on TPV device performance. In addition, improvements in TPV performance with integrated distributed Bragg reflectors and back-surface reflectors are discussed.

  20. Anisotropic interface induced formation of Sb nanowires on GaSb(111)A substrates.

    PubMed

    Proessdorf, A; Grosse, F; Perumal, K; Braun, W; Riechert, H

    2012-06-15

    The growth of Sb nanowires on GaSb(111)A substrates is studied by in situ azimuthal scan reflection high-energy electron diffraction (ARHEED). Bulk and layer contributions can be distinguished in the ARHEED transmission pattern through the Sb nanowires. The three-dimensional structure of the growing Sb nanowires is identified by post-growth atomic force microscopy (AFM) and x-ray diffraction (XRD). The lattice match of the Sb crystal along the [Formula: see text] and the GaSb crystal along [Formula: see text] directions lead to a preferential orientation of the Sb nanowires. The Sb adsorption and desorption kinetics is studied by thermal desorption spectroscopy. PMID:22595679

  1. Anisotropic interface induced formation of Sb nanowires on GaSb(111)A substrates

    NASA Astrophysics Data System (ADS)

    Proessdorf, A.; Grosse, F.; Perumal, K.; Braun, W.; Riechert, H.

    2012-06-01

    The growth of Sb nanowires on GaSb(111)A substrates is studied by in situ azimuthal scan reflection high-energy electron diffraction (ARHEED). Bulk and layer contributions can be distinguished in the ARHEED transmission pattern through the Sb nanowires. The three-dimensional structure of the growing Sb nanowires is identified by post-growth atomic force microscopy (AFM) and x-ray diffraction (XRD). The lattice match of the Sb crystal along the \\langle \\bar {2}10\\rangle and the GaSb crystal along \\langle \\bar {1}10\\rangle directions lead to a preferential orientation of the Sb nanowires. The Sb adsorption and desorption kinetics is studied by thermal desorption spectroscopy.

  2. SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

    PubMed Central

    Cassilly, Chelsi D.; Maddox, Marcus M.; Cherian, Philip T.; Bowling, John J.; Hamann, Mark T.; Lee, Richard E.; Reynolds, Todd B.

    2016-01-01

    In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism of the toxin papuamide A (Pap-A). Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ) do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A) as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A), but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins. PMID:27183222

  3. The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia.

    PubMed

    Malik, Peter; Andersen, Maibritt B; Peacock, Linda

    2004-08-01

    Tardive dyskinesia (TD), a serious complication of antipsychotic dopamine (DA) antagonist treatment, has been hypothesised to develop due to a dominant DA D1 relative to DA D2 receptor function. Recent genetic and pharmacological studies implicate the DA D3 receptor in TD. The present study examined the role of the DA D3 receptor in relation to the DA D1/D2 imbalance hypothesis of TD in nonhuman primates. Eight Cebus monkeys displaying mild to severe TD due to previous chronic exposure to DA D2 antagonists were acutely injected with SKF 81297 (DA D1 agonist) 0.3 and 0.6 mg/kg, pramipexole (DA D3>D2 agonist) 0.025-0.1 mg/kg, CIS-8-OH-PBZI (DA D3 agonist) 5-10 mg/kg and SB-27701-A (DA D3 antagonist) 1-5 mg/kg and rated for oral dyskinesia. SKF 81297, 0.3 and 0.6 mg/kg, exacerbated TD. Pramipexole and CIS-8-OH-PBZI reduced SKF 81297-induced TD, while SB-27701-A had no effect. When administered alone, SB-27701-A increased TD relative to placebo, while pramipexole and CIS-8-OH-PBZI had no significant effect. Pramipexole did, however, ameliorate TD in those monkeys with severe TD. These results point towards a role of the DA D3 receptor in TD, but indicate that the DA D2 receptor may also play an essential role. PMID:15301939

  4. Method of making an InAsSb/InAsSbP diode lasers

    DOEpatents

    Razeghi, Manijeh

    1997-01-01

    InAsSb/InAsSbP/InAs Double Heterostructures (DH) and Separate Confinement Heterostructure Multiple Quantum Well (SCH-MQW) structures are taught wherein the ability to tune to a specific wavelength within 3 .mu.m to 5 .mu.m is possible by varying the ratio of As:Sb in the active layer.

  5. Transport properties in AlInSb/InAsSb heterostructures

    SciTech Connect

    Zhang, Yuwei; Zhang, Yang Wang, Chengyan; Zeng, Yiping

    2013-12-28

    Based on theoretical studies of transport properties in InAsSb-based quantum well heterostructures, we propose a material design for InAsSb quantum well with AlInSb barrier. Variation of electron mobility and two-dimensional electron gas concentration in Al{sub y}In{sub 1−y}Sb/InAs{sub 1−x}Sb{sub x} heterostructures over the compositional range of which InAsSb is fully strained to AlInSb are investigated, where impact from dislocation scattering could be minimized. In comparison with InAs and InSb based quantum well heterostructures, InAsSb is advantageous in achieving the highest electron mobility despite of alloy disorder scattering. The maximum mobility of 37 000 cm{sup 2}/V s is attainable in 15 nm InAs{sub 0.2}Sb{sub 0.8} quantum well with Al{sub 0.24}In{sub 0.76}Sb barrier and there is great potential for further improvement. Our InAsSb based quantum well heterostructure is proved to be a robust structure for high-speed applications.

  6. Method of making an InAsSb/InAsSbP diode lasers

    DOEpatents

    Razeghi, M.

    1997-08-19

    InAsSb/InAsSbP/InAs Double Heterostructures (DH) and Separate Confinement Heterostructure Multiple Quantum Well (SCH-MQW) structures are taught wherein the ability to tune to a specific wavelength within 3 {micro}m to 5 {micro}m is possible by varying the ratio of As:Sb in the active layer. 9 figs.

  7. Investigation of photoelectrochemical-oxidized p-GaSb films

    NASA Astrophysics Data System (ADS)

    Lee, Hsin-Ying; Huang, Hung-Lin; Lee, Ching-Ting; Petrovich Pchelyakov, Oleg; Andreevich Pakhanov, Nikolay

    2012-12-01

    GaSb oxide films were directly formed on the p-GaSb films using the bias-assisted photoelectrochemical (PEC) oxidation method. X-ray photoelectron spectroscopy analysis indicated that the resulting GaSb oxide films consisted of Ga2O3, Sb2O3, and Sb2O5. Different from the non-PEC oxides, the PEC derived oxide contained much more Sb2O5 than Sb2O3. Besides, the interface state density between the PEC oxide and p-GaSb was lower than that of the ordinary oxide/p-GaSb interface. The high quality of the PEC-oxidized GaSb films was attributed to the increase of the stable Sb2O5 content and decrease of the elemental Sb content in the films.

  8. Astronomical imaging with InSb arrays

    NASA Astrophysics Data System (ADS)

    Pipher, Judith L.

    Ten years ago, Forrest presented the first astronomical images with a Santa Barbara Research Center (SBRC) 32 x 32 InSb array camera at the first NASA-Ames Infrared Detector Technology Work-shop. Soon after, SBRC began development of 58 x 62 InSb arrays, both for ground-based astronomy and for the Space Infrared Telescope Facility (SIRTF). By the time of the 1987 Hilo workshop 'Ground-based Astronomical Observations with Infrared Array Dectectors' astronomical results from cameras based on SBRC 32 x 32 and 58 x 62 InSb arrays, a CE linear InSb array, and a French 32 x 32 InSb charge injection device (CID) array were presented. And at the Tucson 1990 meeting 'Astrophysics with Infrared Arrays', it was clear that this new technology was no longer the province of 'IR pundits', but provided a tool for all astronomers. At this meeting, the first astronomical observations with SBRC's new, gateless passivation 256 x 256 InSb arrays will be presented: they perform spectacularly] In this review, I can only broadly brush on the interesting science completed with InSb array cameras. Because of the broad wavelength coverage (1-5.5 micrometer) of InSb, and the extremely high performance levels throughout the band, InSb cameras are used not only in the near IR, but also from 3-5.5 micrometer, where unique science is achieved. For example, the point-like central engines of active galactic nuclei (AGN) are delineated at L' and M', and Bra and 3.29 micrometer dust emission images of galactic and extragalactic objects yield excitation conditions. Examples of imaging spectroscopy, high spatial resolution imaging, as well as deep, broad-band imaging with InSb cameras at this meeting illustrate the power of InSb array cameras.

  9. Dissimilatory Sb(V) reduction by microorganisms isolated from Sb-contaminated sediment

    NASA Astrophysics Data System (ADS)

    Dovick, M. A.; Kulp, T. R.

    2013-12-01

    Mining and smelting are major sources of trace metal contamination in freshwater systems. Arsenic (As) is a common contaminant derived from certain mining operations and is a known toxic metalloid and carcinogen. Antimony (Sb) is listed as a pollutant of priority interest by the EPA and is presumed to share similar geochemical and toxicological properties with arsenic. Both elements can occur in four different oxidation states (V, III, 0, and -III) under naturally occurring conditions. In aqueous solutions As(V) and Sb(V) predominate in oxygenated surface waters whereas As(III) and Sb(III) are stable in anoxic settings. Numerous studies have examined microbiological redox pathways that utilize As(V) as a terminal electron acceptor for anaerobic respiration, however there have been few studies on microbial mechanisms that may affect the biogeochemical cycling of Sb in the environment. Here we report bacterial reduction of Sb(V) to Sb(III) in anoxic enrichment cultures and bacterial isolates grown from sediment collected from an Sb contaminated pond at a mine tailings site in Idaho (total pond water Sb concentration = 235.2 +/- 136.3 ug/L). Anaerobic sediment microcosms (40 mL) were established in artificial freshwater mineral salt medium, amended with millimolar concentrations of Sb(V), acetate or lactate, and incubated at 27°C for several days. Antimony(V), lactate, and acetate concentrations were monitored during incubation by High Performance Liquid Chromatography (HPLC) and Ion Chromatography (IC). Live sediment microcosms reduced millimolar amendments of Sb(V) to Sb(III) coupled to the oxidation of acetate and lactate, while no activity occurred in killed controls. Enrichment cultures were established by serially diluting Sb(V)-reducing microcosms in mineral salt medium with Sb(V) and acetate, and a Sb(V)-reducing bacterial strain was isolated by plating on anaerobic agar plates amended with millimolar Sb(V) and acetate. Direct cell counting demonstrated that

  10. AlInAsSb/GaSb staircase avalanche photodiode

    NASA Astrophysics Data System (ADS)

    Ren, Min; Maddox, Scott; Chen, Yaojia; Woodson, Madison; Campbell, Joe C.; Bank, Seth

    2016-02-01

    Over 30 years ago, Capasso and co-workers [IEEE Trans. Electron Devices 30, 381 (1982)] proposed the staircase avalanche photodetector (APD) as a solid-state analog of the photomultiplier tube. In this structure, electron multiplication occurs deterministically at steps in the conduction band profile, which function as the dynodes of a photomultiplier tube, leading to low excess multiplication noise. Unlike traditional APDs, the origin of staircase gain is band engineering rather than large applied electric fields. Unfortunately, the materials available at the time, principally AlxGa1-xAs/GaAs, did not offer sufficiently large conduction band offsets and energy separations between the direct and indirect valleys to realize the full potential of the staircase gain mechanism. Here, we report a true staircase APD operation using alloys of a rather underexplored material, AlxIn1-xAsySb1-y, lattice-matched to GaSb. Single step "staircase" devices exhibited a constant gain of ˜2×, over a broad range of applied bias, operating temperature, and excitation wavelengths/intensities, consistent with Monte Carlo calculations.

  11. Effect of MnSb clusters recharge on ferromagnetism in GaSb-MnSb thin films

    NASA Astrophysics Data System (ADS)

    Talantsev, A.; Koplak, O.; Morgunov, R.

    2016-07-01

    The concentration effect of charge carriers on the magnetic moment of ferromagnetic MnSb nanoclusters embedded in GaSbMn thin films is reported. High concentration of holes enhances the probability of their tunneling through the barrier between the semiconductor matrix and the MnSb nanocluster. Enrichment of the MnSb clusters by Mn2+ ions instead of Mn3+ enhances their ferromagnetism. Dynamics of magnetization relaxation of the MnSb clusters under applied magnetic field has been studied in the 8-300 K temperature range. Magnetic anisotropy constant ∼3.2·104 erg/cm3 has been determined. The fluctuation field HF = 7 Oe and the activation volume VA = 1.7·10-16 cm3 have been extracted from magnetic viscosity data.

  12. Vought SB2U-1 Vindicator

    NASA Technical Reports Server (NTRS)

    1937-01-01

    Vought SB2U-1 Vindicator: The graceful lines of an airplane were aided by a concerted effort in drag reduction. Here a Vought SB2U-1 Vindicator is studied in Langley's 30 x 60 Full Scale Tunnel. This evaluation took place in September 1937.

  13. 2.4 Micrometer Cutoff Wavelength AlGaAsSb/InGaAsSb Phototransistors

    NASA Technical Reports Server (NTRS)

    Sulima, O. V.; Swaminathan, K.; Refaat, T. F.; Faleev, N. N.; Semenov, A. N.; Solov'ev, V. A.; Ivanov, S. V.; Abedin, M. N.; Singh, U. N.; Prather, D.

    2006-01-01

    We report the first AlGaAsSb/InGaAsSb phototransistors with a cutoff wavelength (50% of peak responsivity) of 2.4 micrometers operating in a broad range of temperatures. These devices are also the first AlGaAsSb/InGaAsSb heterojunction phototransistors (HPT) grown by molecular beam epitaxy (MBE). This work is a continuation of a preceding study, which was carried out using LPE (liquid phase epitaxy)-grown AlGaAsSb/InGaAsSb/GaSb heterostructures. Although the LPE-related work resulted in the fabrication of an HPT with excellent parameters [1-4], the room temperature cutoff wavelength of these devices (approximately 2.15 micrometers) was determined by fundamental limitations implied by the close-to-equilibrium growth from Al-In-Ga-As-Sb melts. As the MBE technique is free from the above limitations, AlGaAsSb/InGaAsSb/GaSb heterostructures for HPT with a narrower bandgap of the InGaAsSb base and collector - and hence sensitivity at longer wavelengths (lambda) - were grown in this work. Moreover, MBE - compared to LPE - provides better control over doping levels, composition and width of the AlGaAsSb and InGaAsSb layers, compositional and doping profiles, especially with regard to abrupt heterojunctions. The new MBE-grown HPT exhibited both high responsivity R (up to 2334 A/W for lambda=2.05 micrometers at -20 deg C.) and specific detectivity D* (up to 2.1 x 10(exp 11) cmHz(exp 1/2)/W for lambda=2.05 micrometers at -20 deg C).

  14. AsSb energetics in argentian sulfosalts

    NASA Astrophysics Data System (ADS)

    Ghosal, Subhabrata; Sack, Richard O.

    1995-09-01

    Experimental brackets on As-Sb partitioning between polybasite-pearceite {Pbp; (Cu, Ag) 16(Sb, As) 2S 11} and pyrargyrite-proustite {Ppr; (Cu, Ag) 3(Sb, As)S 3}, and between pyrargyrite-proustite, and miargyrite and smithite {αMi, βMi, Smt; Ag(Sb, As)S 2} (350-400°C; evacuated silica tubes) define standard state Gibbs energies of theAsSb exchange reactions {Ag 16As 2S 11+Ag 3SbS 3=Ag 16Sb 2S 11 + Ag 3AsS 3, Δ Gro Pbp-Ppr = 0.65 ± 0.60 kJ/gfw; Ag 3AsS 3, + AgSbS 2 = Ag 3SbS 3 + AgASS 2, Δ overlineGro Ppr-α Mi = 3.10 ± 0.50 kJ/gfw, Δ Gro PPr-Smt = 1.70 ± 0.50 kJ/gfw and the nonidealities associated with the AsSb substitutions in these minerals (measured by symmetric regular-solution parameters for formula units on a one AsSb site basis; WAsSbPbp = 4.00 ± 0.25 kJ/gfw; WAsSbPpr =6.00 ± 0 .60 kJ/gfw; WAsSbαMi = WAsSbSmt = 7.00 ± 0.50 kJ/gfw). The above constraints applied to the miscibility gap between Ag (Sb, As) S 2 solutions with α-miargyrite and smithite structures at 350°C determine the relative stabilities of these structures in the As and Sb endmembers to be: ( GSbo, α Mi - GSbo, Smt) ˜ -0.63 kJ/gfw; ( GAso, α Mi - GAsSmt) ˜ 0.77 kJ/gfw. Combining these constraints with the calorimetric data of Bryndzia and Kleppa (1988, 1989) and our melting point determinations we have constructed a phase diagram for the AgSbS 2AgAsS 2 subsystem. The salient features of this diagram are (1) eutectic behaviour ( T ˜ 396°C, XAs ˜ 0.50), (2) modest increase in the temperature of the α → β miargyrite transition with As substitution (˜380°C in Sb-subsystem; 386.6°C at XAsMi ˜ 0.36), (3) a 42.5°C depression of the trechmannite-smithite transition with preferential incorporation of Sb in smithite { smithite ( XAs ˜ 0.62) → α-miargyrite ( XAs ˜ 0.34) + trechmannite (X As ˜ 1.00) at ˜277.5°C}, and (4) widening of the miargyrite-trechmannite gap at lower temperatures. The latter feature is consistent with the inference that the most As

  15. Endothelin receptors and their antagonists.

    PubMed

    Maguire, Janet J; Davenport, Anthony P

    2015-03-01

    All three members of the endothelin (ET) family of peptides, ET-1, ET-2, and ET-3, are expressed in the human kidney, with ET-1 being the predominant isoform. ET-1 and ET-2 bind to two G-protein-coupled receptors, ETA and ETB, whereas at physiological concentrations ET-3 has little affinity for the ET(A) receptor. The human kidney is unusual among the peripheral organs in expressing a high density of ET(B). The renal vascular endothelium only expresses the ET(B) subtype and ET-1 acts in an autocrine or paracrine manner to release vasodilators. Endothelial ETB in kidney, as well as liver and lungs, also has a critical role in scavenging ET-1 from the plasma. The third major function is ET-1 activation of ET(B) in in the nephron to reduce salt and water re-absorption. In contrast, ET(A) predominate on smooth muscle, causing vasoconstriction and mediating many of the pathophysiological actions of ET-1. The role of the two receptors has been delineated using highly selective ET(A) (BQ123, TAK-044) and ET(B) (BQ788) peptide antagonists. Nonpeptide antagonists, bosentan, macitentan, and ambrisentan, that are either mixed ET(A)/ET(B) antagonists or display ET(A) selectivity, have been approved for clinical use but to date are limited to pulmonary hypertension. Ambrisentan is in clinical trials in patients with type 2 diabetic nephropathy. This review summarizes ET-receptor antagonism in the human kidney, and considers the relative merits of selective versus nonselective antagonism in renal disease. PMID:25966344

  16. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks.

    PubMed

    Wong, Gilbert Y; Gavva, Narender R

    2009-04-01

    The vanilloid receptor TRPV1 is a homotetrameric, non-selective cation channel abundantly expressed in the nociceptors (c-fibers). TRPV1 is considered as a highly validated pain target because, i) its agonists such as capsaicin cause desensitization of TRPV1 channels that relieves pain behaviors in preclinical species, and ii) its antagonists relieve pain behaviors in rodent models of inflammation, osteoarthritis, and cancer. Hence, both agonists and antagonists of TRPV1 are being evaluated as potential analgesics in clinical trials. Clinical trial results of TRPV1 agonists such as resiniferatoxin in interstitial cystitis, NGX 4010 in post-herpetic neuralgia, and 4975 (Adlea) in osteoarthritis, bunionectomy, and Morton's neuroma have been reported. Similarly, clinical trial results of TRPV1 antagonists such as SB-705498 and AMG 517 have also been published recently. Overall, some molecules (e.g., capsaicin) demonstrated potential analgesia in certain conditions (postsurgical pain, postherpetic neuralgia, pain in diabetic neuropathy, osteoarthritis, bunionectomy, and Morton's neuroma), whereas others fell out of the clinic due to on-target liabilities or failed to demonstrate efficacy. This review summarizes recent advances and setbacks of TRPV1 agonists and antagonists in the clinic and predicts future directions. PMID:19150372

  17. Peculiarities of thermoelectric half-Heusler phase formation in Gd-Ni-Sb and Lu-Ni-Sb ternary systems

    NASA Astrophysics Data System (ADS)

    Romaka, V. V.; Romaka, L.; Horyn, A.; Rogl, P.; Stadnyk, Yu; Melnychenko, N.; Orlovskyy, M.; Krayovskyy, V.

    2016-07-01

    The phase equilibria in the Gd-Ni-Sb and Lu-Ni-Sb ternary systems were studied at 873 K by X-ray and metallographic analyses in the whole concentration range. The interaction of the elements in the Gd-Ni-Sb system results the formation of five ternary compounds at investigated temperature: Gd5Ni2Sb (Mo5SiB2-type), Gd5NiSb2 (Yb5Sb3-type), GdNiSb (MgAgAs-type), Gd3Ni6Sb5 (Y3Ni6Sb5-type), and GdNi0.72Sb2 (HfCuSi2-type). At investigated temperature the Lu-Ni-Sb system is characterized by formation of the LuNiSb (MgAgAs-type), Lu5Ni2Sb (Mo5SiB2-type), and Lu5Ni0.56Sb2.44 (Yb5Sb3-type) compounds. The disordering in the crystal structure of half-Heusler GdNiSb and LuNiSb was revealed by EPMA and studied by means of Rietveld refinement and DFT modeling. The performed electronic structure calculations are in good agreement with electrical transport property studies.

  18. Tachykinin antagonists and the airways.

    PubMed

    Joos, G F; Kips, J C; Peleman, R A; Pauwels, R A

    1995-01-01

    There is now convincing evidence for the presence of substance P (SP) and neurokinin A (NKA) in human airway nerves. Studies on autopsy tissue, on bronchoalveolar lavage fluid and on sputum suggest that SP may be present in increased amounts in the asthmatic airway. Substance P and NKA are potent bronchoconstrictors of human airways, asthmatics being more sensitive than normal persons. The major enzyme responsible for the degradation of the tachykinins, the neutral endopeptidase, is present in the airways and is involved in the breakdown of exogenously administered SP and NKA, both in normal and asthmatic persons. Other, less well documented airway effects of SP and NKA include mucus secretion, vasodilation and plasma extravasation, as well as the chemoattraction and stimulation of various cells presumed to be involved in asthmatic airway inflammation. NK2 receptors and, to a lesser extent, NK1 receptors have been shown to be involved in bronchoconstriction, whereas NK1 receptors were found to be involved in mucus secretion, microvascular leakage and vasodilatation, and in most of the effects on inflammatory cells. The first clinical trial with FK224, a peptide NK1 and NK2 receptor antagonist, and CP99994, a nonpeptide NK1 receptor antagonist, are negative. However, FK224 failed to block the bronchoconstrictor effect of NKA in asthmatics and the dose of CP99994, needed to antagonize tachykinin effects in man, remains to be determined. PMID:7543746

  19. Breeding Value of the qSB9b and qSB12a QTLs in RiceBreeding Value of the qSB9b and qSB12a QTLs in Rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sheath blight (SB) caused by Rhizoctonia solani Kuhn is a serious rice disease worldwide. The results of 123 TeQing-into-Lemont (TILs) showed those with introgressions containing qSB9b and/or qSB12a were among the most SB resistant TILs. TIL:615, TIL:642 and TIL:567 have consistently appeared modera...

  20. Relation between the magnetization and the electrical properties of alloy GaSb-MnSb films

    SciTech Connect

    Koplak, O. V.; Polyakov, A. A.; Davydov, A. B.; Morgunov, R. B.; Talantsev, A. D.; Kochura, A. V.; Fedorchenko, I. V.; Novodvorskii, O. A.; Parshina, L. S.; Khramova, O. D.; Shorokhova, A. V.; Aronzon, B. A.

    2015-06-15

    The influence of the charge carrier concentration on the magnetic properties of GaSb-MnSb alloys is studied. The ferromagnetism of GaSb-MnSb films is caused by the presence of MnSb granules and manifests itself in both magnetometric measurements and the presence of an anisotropic magnetoresistance and the anomalous Hall effect. Electric conduction is executed by charge carriers (holes) in a GaSb matrix. The magnetization of clusters depends on stoichiometry and the concentration of Mn{sup 2+} and Mn{sup 3+} ions, which is specified by the film growth conditions. At high film growth temperatures, ferromagnetic clusters containing Mn{sup 2+} ions mainly form. At low growth temperatures, an antiferromagnetic phase containing Mn{sup 3+} ions forms.

  1. Growth mechanisms of GaSb heteroepitaxial films on Si with an AlSb buffer layer

    SciTech Connect

    Vajargah, S. Hosseini; Botton, G. A.; Brockhouse Institute for Materials Research, McMaster University, Hamilton, Ontario L8S 4M1; Canadian Centre for Electron Microscopy, McMaster University, Hamilton, Ontario L8S 4M1 ; Ghanad-Tavakoli, S.; Preston, J. S.; Kleiman, R. N.; Centre for Emerging Device Technologies, McMaster University, Hamilton, Ontario L8S 4L7; Department of Engineering Physics, McMaster University, Hamilton, Ontario L8S 4L7

    2013-09-21

    The initial growth stages of GaSb epilayers on Si substrates and the role of the AlSb buffer layer were studied by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). Heteroepitaxy of GaSb and AlSb on Si both occur by Volmer-Weber (i.e., island mode) growth. However, the AlSb and GaSb islands have distinctly different characteristics as revealed through an atomic-resolution structural study using Z-contrast of HAADF-STEM imaging. While GaSb islands are sparse and three dimensional, AlSb islands are numerous and flattened. The introduction of 3D island-forming AlSb buffer layer facilitates the nucleation of GaSb islands. The AlSb islands-assisted nucleation of GaSb islands results in the formation of drastically higher quality planar film at a significantly smaller thickness of films. The interface of the AlSb and GaSb epilayers with the Si substrate was further investigated with energy dispersive X-ray spectrometry to elucidate the key role of the AlSb buffer layer in the growth of GaSb epilayers on Si substrates.

  2. SEMICONDUCTOR MATERIALS: AlGaSb/GaSb quantum wells grown on an optimized AlSb nucleation layer

    NASA Astrophysics Data System (ADS)

    Hanchao, Gao; Cai, Wen; Wenxin, Wang; Zhongwei, Jiang; Haitao, Tian; Tao, He; Hui, Li; Hong, Chen

    2010-05-01

    Five-period AlGaSb/GaSb multiple quantum wells (MQW) are grown on a GaSb buffer. Through optimizing the AlSb nucleation layer, the low threading dislocation density of the MQW is found to be (2.50 ± 0.91) × 108 cm-2 in 1-μm GaSb buffer, as determined by plan-view transmission election microscopy (TEM) images. High resolution TEM clearly shows the presence of 90° misfit dislocations with an average spacing of 5.4 nm at the AlSb/GaAs interface, which effectively relieve most of the strain energy. In the temperature range from T = 26 K to 300 K, photoluminescence of the MQW is dominated by the ground state electron to ground state heavy hole (e1-hh1) transition, while a high energy shoulder clearly seen at T > 76 K can be attributed to the ground state electron to ground state light hole (e1-lh1) transition.

  3. Sb-induced phase control of InAsSb nanowires grown by molecular beam epitaxy.

    PubMed

    Zhuang, Q D; Anyebe, Ezekiel A; Chen, R; Liu, H; Sanchez, Ana M; Rajpalke, Mohana K; Veal, Tim D; Wang, Z M; Huang, Y Z; Sun, H D

    2015-02-11

    For the first time, we report a complete control of crystal structure in InAs(1-x)Sb(x) NWs by tuning the antimony (Sb) composition. This claim is substantiated by high-resolution transmission electron microscopy combined with photoluminescence spectroscopy. The pure InAs nanowires generally show a mixture of wurtzite (WZ) and zinc-blende (ZB) phases, where addition of a small amount of Sb (∼2-4%) led to quasi-pure WZ InAsSb NWs, while further increase of Sb (∼10%) resulted in quasi-pure ZB InAsSb NWs. This phase transition is further evidenced by photoluminescence (PL) studies, where a dominant emission associated with the coexistence of WZ and ZB phases is present in the pure InAs NWs but absent in the PL spectrum of InAs0.96Sb0.04 NWs that instead shows a band-to-band emission. We also demonstrate that the Sb addition significantly reduces the stacking fault density in the NWs. This study provides new insights on the role of Sb addition for effective control of nanowire crystal structure. PMID:25559370

  4. ACCELERATED PROCESSING OF SB4 AND PREPARATION FOR SB5 PROCESSING AT DWPF

    SciTech Connect

    Herman, C

    2008-12-01

    The Defense Waste Processing Facility (DWPF) initiated processing of Sludge Batch 4 (SB4) in May 2007. SB4 was the first DWPF sludge batch to contain significant quantities of HM or high Al sludge. Initial testing with SB4 simulants showed potential negative impacts to DWPF processing; therefore, Savannah River National Laboratory (SRNL) performed extensive testing in an attempt to optimize processing. SRNL's testing has resulted in the highest DWPF production rates since start-up. During SB4 processing, DWPF also began incorporating waste streams from the interim salt processing facilities to initiate coupled operations. While DWPF has been processing SB4, the Liquid Waste Organization (LWO) and the SRNL have been preparing Sludge Batch 5 (SB5). SB5 has undergone low-temperature aluminum dissolution to reduce the mass of sludge for vitrification and will contain a small fraction of Purex sludge. A high-level review of SB4 processing and the SB5 preparation studies will be provided.

  5. Long-acting muscarinic antagonists.

    PubMed

    Melani, Andrea S

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide. Inhaled bronchodilators are the mainstay of COPD pharmacological treatment. Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators. Some LAMA/device systems with different characteristics and dosing schedules are currently approved for maintenance therapy of COPD and a range of other products are being developed. They improve lung function and patient-reported outcomes and reduce acute bronchial exacerbations with good safety. LAMAs are used either alone or associated with long-acting β₂-agonists, eventually in fixed dose combinations. Long-acting β₂-agonist/LAMA combinations assure additional benefits over the individual components alone. The reader will obtain a view of the safety and efficacy of the different LAMA/device systems in COPD patients. PMID:26109098

  6. A new alcohol antagonist: Phaclofen

    SciTech Connect

    Allan, A.M. ); Harris, R.A. )

    1989-01-01

    The ability of the GABA{sub B} receptor antagonist, phaclofen to alter behavioral effects of ethanol was evaluated by loss of righting reflex (sleep time), motor incoordination (bar holding), spontaneous locomotion (open field activity) and hypothermia. Pretreatment with phaclofen significantly decreased the effects of ethanol on motor incoordination, locomotor activity and hypothermia. However, phaclofen had no effect on either pentobarbital- or diazepam-induced motor incoordination. Phaclofen slightly increased the ED{sub 50} for loss of the righting reflex but did not alter either the duration of reflex loss produced by ethanol or blood ethanol levels at awakening. Our results suggest phaclofen is rapidly inactivated resulting in difficulty in observing antagonism of long duration ethanol effects. These findings suggest that the GABA{sub B} system may play a role in mediating several important actions of ethanol.

  7. Native point defects in GaSb

    SciTech Connect

    Kujala, J.; Segercrantz, N.; Tuomisto, F.; Slotte, J.

    2014-10-14

    We have applied positron annihilation spectroscopy to study native point defects in Te-doped n-type and nominally undoped p-type GaSb single crystals. The results show that the dominant vacancy defect trapping positrons in bulk GaSb is the gallium monovacancy. The temperature dependence of the average positron lifetime in both p- and n-type GaSb indicates that negative ion type defects with no associated open volume compete with the Ga vacancies. Based on comparison with theoretical predictions, these negative ions are identified as Ga antisites. The concentrations of these negatively charged defects exceed the Ga vacancy concentrations nearly by an order of magnitude. We conclude that the Ga antisite is the native defect responsible for p-type conductivity in GaSb single crystals.

  8. Client Perceptions of Two Antagonist Programs.

    ERIC Educational Resources Information Center

    Capone, Thomas A.; And Others

    1980-01-01

    Reports results of a questionnaire administered to participants in an antagonist drug outpatient clinic and an antagonist drug work-release program to obtain awareness of acceptance of the program participants. Naltrexone patients recommended an alternative method of administering the drug and changing the money system to award deserving inmates…

  9. Vought SB2U-1 Vindicator

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Vought SB2U-1 Vindicator: This Vought SB2U-1 Vindicator was acquired for one month in late 1938 from NAS Anacostia, Washington, D. C. Anacostia was the source of many of the naval aircraft flown by the NACA, in part due to its proximity and in part became it was the Navy's flight test base. The nose slot cowling was aimed at improving engine cooling.

  10. Sb2Se3 under pressure

    PubMed Central

    Efthimiopoulos, Ilias; Zhang, Jiaming; Kucway, Melvin; Park, Changyong; Ewing, Rodney C.; Wang, Yuejian

    2013-01-01

    Selected members of the A2B3 (A = Sb, Bi; B = Se, Te) family are topological insulators. The Sb2Se3 compound does not exhibit any topological properties at ambient conditions; a recent high-pressure study, however, indicated that pressure transforms Sb2Se3 from a band insulator into a topological insulator above ~2 GPa; in addition, three structural transitions were proposed to occur up to 25 GPa. Partly motivated by these results, we have performed x-ray diffraction and Raman spectroscopy investigations on Sb2Se3 under pressure up to 65 GPa. We have identified only one reversible structural transition: the initial Pnma structure transforms into a disordered cubic bcc alloy above 51 GPa. On the other hand, our high-pressure Raman study did not reproduce the previous results; we attribute the discrepancies to the effects of the different pressure transmitting media used in the high-pressure experiments. We discuss the structural behavior of Sb2Se3 within the A2B3 (A = Sb, Bi; B = Se, Te) series. PMID:24045363

  11. PSD-95 is Essential for Hallucinogen and Atypical Antipsychotic Drug Actions at Serotonin Receptors

    PubMed Central

    Abbas, Atheir I.; Yadav, Prem N.; Yao, Wei-Dong; Arbuckle, Margaret I.; Grant, Seth G.; Caron, Marc G.; Roth, Bryan L.

    2009-01-01

    Here we report that PSD-95, a postsynaptic density scaffolding protein classically conceptualized as being essential for the regulation of ionotropic glutamatergic signaling at the post-synaptic membrane, plays an unanticipated and essential role in mediating the actions of hallucinogens and atypical antipsychotic drugs at 5-HT2A and 5-HT2C serotonergic G protein-coupled receptors (GPCRs). We show that PSD-95 is crucial for normal 5-HT2A and 5- HT2C expression in vivo, and that PSD-95 maintains normal receptor expression by promoting apical dendritic targeting and stabilizing receptor turnover in vivo. Significantly, 5-HT2A and 5-HT2C-mediated downstream signaling is impaired in PSD-95null mice, and the 5-HT2A-mediated head twitch response is abnormal. Furthermore, the ability of 5-HT2A inverse agonists to normalize behavioral changes induced by glutamate receptor antagonists is abolished in the absence of PSD-95 in vivo. These results demonstrate that PSD-95, in addition to the well known role it plays in scaffolding macromolecular glutamatergic signaling complexes, profoundly modulates metabotropic 5-HT2A and 5-HT2C receptor function. PMID:19494135

  12. Controlled CVD growth of Cu-Sb alloy nanostructures

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Yin, Zongyou; Sim, Daohao; Tay, Yee Yan; Zhang, Hua; Ma, Jan; Hng, Huey Hoon; Yan, Qingyu

    2011-08-01

    Sb based alloy nanostructures have attracted much attention due to their many promising applications, e.g. as battery electrodes, thermoelectric materials and magnetic semiconductors. In many cases, these applications require controlled growth of Sb based alloys with desired sizes and shapes to achieve enhanced performance. Here, we report a flexible catalyst-free chemical vapor deposition (CVD) process to prepare Cu-Sb nanostructures with tunable shapes (e.g. nanowires and nanoparticles) by transporting Sb vapor to react with copper foils, which also serve as the substrate. By simply controlling the substrate temperature and distance, various Sb-Cu alloy nanostructures, e.g. Cu11Sb3 nanowires (NWs), Cu2Sb nanoparticles (NPs), or pure Sb nanoplates, were obtained. We also found that the growth of Cu11Sb3 NWs in such a catalyst-free CVD process was dependent on the substrate surface roughness. For example, smooth Cu foils could not lead to the growth of Cu11Sb3 nanowires while roughening these smooth Cu foils with rough sand papers could result in the growth of Cu11Sb3 nanowires. The effects of gas flow rate on the size and morphology of the Cu-Sb alloy nanostructures were also investigated. Such a flexible growth strategy could be of practical interest as the growth of some Sb based alloy nanostructures by CVD may not be easy due to the large difference between the condensation temperature of Sb and the other element, e.g. Cu or Co.

  13. The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist.

    PubMed

    Palabiyik, Saziye S; Karakus, Emre; Akpinar, Erol; Halici, Zekai; Bayir, Yasin; Yayla, Muhammed; Kose, Duygu

    2016-02-01

    We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor-alpha (TNF-α) and IL-1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre-treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre-treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti-inflammatory effects on high-dose PARA-induced hepatotoxicity in mice. PMID:26176337

  14. Growth of InSb on GaAs Using InAlSb Buffer Layers

    SciTech Connect

    BIEFELD, ROBERT M.; PHILLIPS, JAMIE D.

    1999-09-20

    We report the growth of InSb on GaAs using InAlSb buffers of high interest for magnetic field sensors. We have grown samples by metal-organic chemical vapor deposition consisting of {approximately} 0.55 {micro}m thick InSb layers with resistive InAlSb buffers on GaAs substrates with measured electron nobilities of {approximately}40,000 cm{sup 2}/V.s. We have investigated the In{sub 1{minus}x}Al{sub x}Sb buffers for compositions x{le}0.22 and have found that the best results are obtained near x=0.12 due to the tradeoff of buffer layer bandgap and lattice mismatch.

  15. Lattice-matched epitaxial GaInAsSb/GaSb thermophotovoltaic devices

    SciTech Connect

    Wang, C.A.; Choi, H.K.; Turner, G.W.; Spears, D.L.; Manfra, M.J.; Charache, G.W.

    1997-05-01

    The materials development of Ga{sub 1{minus}x}In{sub x}As{sub y}Sb{sub 1{minus}y} alloys for lattice-matched thermophotovoltaic (TPV) devices is reported. Epilayers with cutoff wavelength 2--2.4 {micro}m at room temperature and lattice-matched to GaSb substrates were grown by both low-pressure organometallic vapor phase epitaxy and molecular beam epitaxy. These layers exhibit high optical and structural quality. For demonstrating lattice-matched thermophotovoltaic devices, p- and n-type doping studies were performed. Several TPV device structures were investigated, with variations in the base/emitter thicknesses and the incorporation of a high bandgap GaSb or AlGaAsSb window layer. Significant improvement in the external quantum efficiency is observed for devices with an AlGaAsSb window layer compared to those without one.

  16. ``Quasi-direct'' narrow GaSb-AlSb (100) quantum wells

    NASA Astrophysics Data System (ADS)

    Brar, Berinder; Kroemer, Herbert; English, John

    1993-02-01

    In GaSb-AlSb quantum wells, GaSb is expected to make a transition to an X-valley semiconductor for well widths less than 2 nm. For narrow X-valley quantum wells the unassisted radiative transitions are no longer forbidden, allowing for the possibility of a "quasi-direct" transition from the X conduction band to the Γ valence band. Photoluminescence characterization of such narrow well GaSb-AlSb multi-quantum well structures has been performed. Spectra from wells as thin as a few monolayers were observed. A comparison of the measured transition energy with a simple calculation supports the idea that the observed transitions are indeed quasi-direct transitions.

  17. Performance improvement of Ge-Sb-Te material by GaSb doping for phase change memory

    NASA Astrophysics Data System (ADS)

    Lu, Yegang; Zhang, Zhonghua; Song, Sannian; Shen, Xiang; Wang, Guoxiang; Cheng, Limin; Dai, Shixun; Song, Zhitang

    2013-06-01

    Effects of GaSb doping on phase change characteristics of Ge-Sb-Te material are investigated by in situ resistance and x-ray diffraction measurement, optical spectroscopy, and x-ray photoelectron spectroscopy. The crystallization temperature and data retention of Ge-Sb-Te material increase significantly by the addition of GaSb, which results from the high thermal stability of amorphous GaSb. In addition, GaSb-doped Ge-Sb-Te material exhibits faster crystallization speed due to the change in electronic states as a result of the formation of chemical bonds with Ga element. Incorporation of GaSb is highly effective way to enhance the comprehensive performance of Ge-Sb-Te material for phase change memory.

  18. Performance improvement of Ge-Sb-Te material by GaSb doping for phase change memory

    SciTech Connect

    Lu, Yegang; Zhang, Zhonghua; Song, Sannian; Cheng, Limin; Song, Zhitang; Shen, Xiang; Wang, Guoxiang; Dai, Shixun

    2013-06-17

    Effects of GaSb doping on phase change characteristics of Ge-Sb-Te material are investigated by in situ resistance and x-ray diffraction measurement, optical spectroscopy, and x-ray photoelectron spectroscopy. The crystallization temperature and data retention of Ge-Sb-Te material increase significantly by the addition of GaSb, which results from the high thermal stability of amorphous GaSb. In addition, GaSb-doped Ge-Sb-Te material exhibits faster crystallization speed due to the change in electronic states as a result of the formation of chemical bonds with Ga element. Incorporation of GaSb is highly effective way to enhance the comprehensive performance of Ge-Sb-Te material for phase change memory.

  19. DWPF simulant CPC studies for SB8

    SciTech Connect

    Koopman, D. C.; Zamecnik, J. R.

    2013-06-25

    The Savannah River National Laboratory (SRNL) accepted a technical task request (TTR) from Waste Solidification Engineering to perform simulant tests to support the qualification of Sludge Batch 8 (SB8) and to develop the flowsheet for SB8 in the Defense Waste Processing Facility (DWPF). These efforts pertained to the DWPF Chemical Process Cell (CPC). Separate studies were conducted for frit development and glass properties (including REDOX). The SRNL CPC effort had two primary phases divided by the decision to drop Tank 12 from the SB8 constituents. This report focuses on the second phase with SB8 compositions that do not contain the Tank 12 piece. A separate report will document the initial phase of SB8 testing that included Tank 12. The second phase of SB8 studies consisted of two sets of CPC studies. The first study involved CPC testing of an SB8 simulant for Tank 51 to support the CPC demonstration of the washed Tank 51 qualification sample in the SRNL Shielded Cells facility. SB8-Tank 51 was a high iron-low aluminum waste with fairly high mercury and moderate noble metal concentrations. Tank 51 was ultimately washed to about 1.5 M sodium which is the highest wash endpoint since SB3-Tank 51. This study included three simulations of the DWPF Sludge Receipt and Adjustment Tank (SRAT) cycle and Slurry Mix Evaporator (SME) cycle with the sludge-only flowsheet at nominal DWPF processing conditions and three different acid stoichiometries. These runs produced a set of recommendations that were used to guide the successful SRNL qualification SRAT/SME demonstration with actual Tank 51 washed waste. The second study involved five SRAT/SME runs with SB8-Tank 40 simulant. Four of the runs were designed to define the acid requirements for sludge-only processing in DWPF with respect to nitrite destruction and hydrogen generation. The fifth run was an intermediate acid stoichiometry demonstration of the coupled flowsheet for SB8. These runs produced a set of processing

  20. Adsorption of Sb(III) and Sb(V) on Freshly Prepared Ferric Hydroxide (FeOxHy)

    PubMed Central

    He, Zan; Liu, Ruiping; Liu, Huijuan; Qu, Jiuhui

    2015-01-01

    Abstract This study prepared fresh ferric hydroxide (in-situ FeOxHy) by the enhanced hydrolysis of Fe3+ ions, and investigates its adsorptive behaviors toward Sb(III) and Sb(V) through laboratory and pilot-scale studies. A contact time of 120-min was enough to achieve adsorption equilibrium for Sb(III) and Sb(V) on the in-situ FeOxHy, and the Elovich model was best to describe the adsorption kinetics of Sb(III) and Sb(V). The Freundlich model was better than Langmuir model to describe the adsorption of Sb(III) and Sb(V) on the in-situ FeOxHy, and the maximum adsorption capacity of Sb(III) and Sb(V) was determined to be 12.77 and 10.21 mmol/g the in-situ FeOxHy as Fe, respectively. Adsorption of Sb(V) decreased whereas that of Sb(III) increased with elevated pH over pH 3–10, owing to the different electrical properties of Sb(III) and Sb(V). Adsorption of Sb(III) and Sb(V) was slightly affected by ionic strength, and thus indicated the formation of inner sphere complexes between Sb and the adsorbent. Sulfate and carbonate showed little effect on the adsorption of Sb(III) and Sb(V). Phosphate significantly inhibited the adsorption of Sb(V), whereas slightly effected that of Sb(III) due to its similar chemical structure to Sb(V). Pilot-scale continuous experiment indicated the feasibility of using in-situ FeOxHy to remove Sb(V), and equilibrium adsorption capacity at the equilibrium Sb(V) concentration of 10 μg/L was determined to be 0.11, 0.07, 0.07, 0.11, and 0.12 mg/g the in-situ FeOxHy as Fe at equilibrium pH of 7.5–7.7, 6.9–7.0, 6.3–6.6, 5.9–6.4, and 5.2–5.9, respectively. PMID:25741175

  1. Sb (111) Abnormal Behavior under Ion Etching

    NASA Astrophysics Data System (ADS)

    Smirnov, A. A.; Bozhko, S. I.; Ionov, A. M.; Protasova, S. G.; Chekmazov, S. V.; Kapustin, A. A.

    Due to a strong spin-orbit interaction (SOI), the surface states of Sb (111) are similar to those for topological insulators (TI) Sugawara et al. (2006). The surface states are protected by time-reversal symmetry and energy dispersion is a linear function of momentum. Defects in crystal structure lead to a local break of the surface translational symmetry and can modify surface states. It is the primary reason to study defects of Sb crystal structure and their effect on the surface states dispersion. Etching of the Sb (111) surface using Ar+ ions is a common way to create defects both in a bulk and on the surface of the crystal. Sb (111) ion etching at room temperature reveals anomalous behavior of surface crystal structure. It results in formation of flat terraces of 2 nm in size. Investigation of electronic structure of the etched Sb (111) surface has demonstrated increase of density of states (DOS) at the Fermi level. The results are discussed in terms of local break of conditions of Peierls transition.

  2. Plant Evolution: Evolving Antagonistic Gene Regulatory Networks.

    PubMed

    Cooper, Endymion D

    2016-06-20

    Developing a structurally complex phenotype requires a complex regulatory network. A new study shows how gene duplication provides a potential source of antagonistic interactions, an important component of gene regulatory networks. PMID:27326708

  3. Benzodiazepinone Derivatives as CRTH2 Antagonists.

    PubMed

    Liu, Jiwen Jim; Cheng, Alan C; Tang, H Lucy; Medina, Julio C

    2011-07-14

    Multiple CRTH2 antagonists are currently evaluated in human clinical trials for asthma and chronic obstructive pulmonary disease (COPD). During our lead optimization for CRTH2 antagonists, an observation of an intramolecular hydrogen bond in ortho-phenylsulfonamido benzophenone derivatives led to the design and synthesis of conformationally constrained benzodiazepinones as potent CRTH2 antagonists. The benzodiazepinones are 2 orders of magnitude more potent than the original flexible bisaryl ethers in our binding assay. Selected benzodiazepinones, such as compound 6, were also potent in the human eosinophil shape change assay. Analysis of the rigid conformations of these benzodiazepinones and ortho-phenylsulfonamido benzophenones provided an explanation for the structure-activity relationship and revealed the possible bound conformations to CRTH2, which may be useful for building a pharmacophore model of CRTH2 antagonists. PMID:24900341

  4. Tannins as Gibberellin Antagonists 1

    PubMed Central

    Corcoran, Mary Ritzel; Geissman, T. A.; Phinney, Bernard O.

    1972-01-01

    Fourteen chemically defined hydrolyzable tannins and six impure mixtures of either condensed or hydrolyzable tannins were found to inhibit the gibberellin-induced growth of light-grown dwarf pea seedlings. The highest ratio of tannins to gibberellic acid tested (1000: 1 by weight) inhibited from 80 to 95% of the induced growth for all tannins tested except for two monogalloyl glucose tannins which inhibited only 50% of the induced growth. The lowest ratio tested (10: 1) inhibited the induced growth by less than 25% except for the case of terchebin where 50% inhibition was found. The inhibition of gibberellin-induced growth was found to be completely reversed by increasing the amount of gibberellin in three cases tested. Tannins alone did not inhibit endogenous growth of either dwarf or nondwarf pea seedlings. Eight compounds related to tannins, including coumarin, trans-cinnamic acid, and a number of phenolic compounds were also tested as gibberellin antagonists. Most of these compounds showed some inhibition of gibberellin-induced growth, but less than that of the tannins. At the highest ratio (1000: 1) the greatest inhibition was 55%; at the lowest ratio (10: 1) no more than 17% was observed. These compounds did not inhibit endogenous growth, and the inhibition of gibberellin-induced growth could be reversed by increasing the amount of gibberellin in two cases tested. Six chemically defined tannins were found to inhibit hypocotyl growth induced by gibberellic acid in cucumber seedlings. Growth induced by indoleacetic acid in the same test was not inhibited. The highest ratio of tannin to promotor tested gave strong inhibition of gibberellic acid-induced growth, but actually enhanced the growth induced by indoleacetic acid. This difference in action suggests a specificity between the tannins and gibberellic acid. PMID:16657953

  5. Tetrahydroquinoline derivatives as opioid receptor antagonists.

    PubMed

    Zhang, Cunyu; Westaway, Susan M; Speake, Jason D; Bishop, Michael J; Goetz, Aaron S; Carballo, Luz Helena; Hu, Mike; Epperly, Andrea H

    2011-01-15

    Opioid receptors play an important role in both behavioral and homeostatic functions. We herein report tetrahydroquinoline derivatives as opioid receptor antagonists. SAR studies led to the identification of the potent antagonist 2v, endowed with 1.58nM (K(i)) functional activity against the μ opioid receptor. DMPK data suggest that novel tetrahydroquinoline analogs may be advantageous in peripheral applications. PMID:21193310

  6. Electronic and thermoelectric properties of CoSbS and FeSbS

    SciTech Connect

    Parker, David S; Singh, David J; Sales, Brian C; McGuire, Michael A; May, Andrew F; Wang, Hsin

    2013-01-01

    We present a combined theoretical and experimental study of the potential thermoelectric performance of three transition metal antimonide sulfides, CoSbS, FeSbS and NiSbS. From theory we find that NiSbS is metallic and hence of little interest regarding thermoelectric performance. CoSbS and FeSbS are both semiconductors with rather heavy valence and conduction bands, whose thermopower can exceed 200 $\\mu$V/K at temperatures of 900 K and carrier concentrations of 10$^{21}$cm$^{-3}$, which is similar to the $n$-type high performance thermoelectric filled skutterudites. The experimental results on several non-optimized $n$-type CoSbS samples confirm its semiconducting nature and indicate a potential for good high temperature thermoelectric performance, finding a ZT for two of the samples of 0.35 at 773 K. Substantially higher ZT values may be possible if the lattice thermal conductivity can be reduced by alloying and the effects of extrinsic scattering, which appear to be substantial in the experimental results, are reduced.

  7. An All-Metal Aromatic Sandwich Complex [Sb3Au3Sb3](3-).

    PubMed

    Pan, Fu-Xing; Li, Lei-Jiao; Wang, Ying-Jin; Guo, Jin-Chang; Zhai, Hua-Jin; Xu, Li; Sun, Zhong-Ming

    2015-09-01

    A sandwich complex, as exemplified by ferrocene in the 1950s, usually refers to one metal center bound by two arene ligands. The subject has subsequently been extended to carbon-free aromatic ligands and multiple-metal-atom "monolayered" center, but not to an all-metal species. Here, we describe the synthesis of an unprecedented all-metal aromatic sandwich complex, [Sb3Au3Sb3](3-), which was isolated as K([2.2.2]crypt)(+) salt and identified by single-crystal X-ray diffraction. Quantum chemical calculations indicate that intramolecular electron transfers for the three metallic layers (Sb → Au donation and Sb ← Au back-donation) markedly redistribute the valence electrons from the cyclo-Sb3 ligands and Au3 interlayer to the Au-Sb bonds, which hold the complex together via σ bonding. Each cyclo-Sb3 possesses aromaticity with delocalized three-center three-electron (3c-3e) π bonds, which are essentially equivalent to a 3c-4e ππ* triplet system, following the reversed 4n Hückel rule for aromaticity in a triplet state. PMID:26275027

  8. Determination of traces of Sb(III) using ASV in Sb-rich water samples affected by mining.

    PubMed

    Cidu, Rosa; Biddau, Riccardo; Dore, Elisabetta

    2015-01-01

    Chemical speciation [Sb(V) and Sb(III)] affects the mobility, bioavailability and toxicity of antimony. In oxygenated environments Sb(V) dominates whereas thermodynamically unstable Sb(III) may occur. In this study, a simple method for the determination of Sb(III) in non acidic, oxygenated water contaminated with antimony is proposed. The determination of Sb(III) was performed by anodic stripping voltammetry (ASV, 1-20 μg L(-1) working range), the total antimony, Sb(tot), was determined either by inductively coupled plasma mass spectrometry (ICP-MS, 1-100μgL(-1) working range) or inductively coupled plasma optical emission spectrometry (ICP-OES, 100-10,000 μg L(-1) working range) depending on concentration. Water samples were filtered on site through 0.45 μm pore size filters. The aliquot for determination of Sb(tot) was acidified with 1% (v/v) HNO3. Different preservatives, namely HCl, L(+) ascorbic acid or L(+) tartaric acid plus HNO3, were used to assess the stability of Sb(III) in synthetic solutions. The method was tested on groundwater and surface water draining the abandoned mine of Su Suergiu (Sardinia, Italy), an area heavily contaminated with Sb. The waters interacting with Sb-rich mining residues were non acidic, oxygenated, and showed extreme concentrations of Sb(tot) (up to 13,000 μg L(-1)), with Sb(III) <10% of total antimony. The stabilization with L(+) tartaric acid plus HNO3 appears useful for the determination of Sb(III) in oxygenated, Sb-rich waters. Due to the instability of Sb(III), analyses should be carried out within 7 days upon the water collection. The main advantage of the proposed method is that it does not require time-consuming preparation steps prior to analysis of Sb(III). PMID:25479865

  9. Life Beyond Kinases: Structure-based Discovery of Sorafenib as Nanomolar Antagonist of 5-HT Receptors

    PubMed Central

    Lin, Xingyu; Huang, Xi-Ping; Chen, Gang; Whaley, Ryan; Peng, Shiming; Wang, Yanli; Zhang, Guoliang; Wang, Simon X.; Wang, Shaohui; Roth, Bryan L.; Huang, Niu

    2012-01-01

    Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an “induced-fit” protocol to improve the homology models of 5-HT2A receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT2A models, and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib has shown unexpected promiscuous 5-HTRs binding affinities, Ki = 1959, 56 and 417 nM against 5-HT2A, 5-HT2B and 5-HT2C, respectively. Our preliminary SAR exploration supports the predicted binding mode, and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its “off-target” 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects. PMID:22694093

  10. Lattice dynamics in the FeSb[subscript 3] skutterudite

    SciTech Connect

    Moechel, A.; Sergueev, I.; Nguyen, N.; Long, Gary J.; Grandjean, Fernande; Johnson, D.C.; Hermann, R.P.

    2011-11-17

    Thin films of FeSb{sub 3} were characterized by electronic transport, magnetometry, x-ray diffraction, {sup 57}Fe and {sup 121}Sb nuclear inelastic scattering, and {sup 57}Fe Moessbauer spectroscopy. Resistivity and magnetometry measurements reveal semiconducting behavior with a 16.3(4) meV band gap and an effective paramagnetic moment of 0.57(6) {mu}B, respectively. A systematic comparison of the lattice dynamics with CoSb{sub 3} and EuFe{sub 4}Sb{sub 12} reveals that the Fe{sub 4}Sb{sub 12} framework is softer than the Co{sub 4}Sb{sub 12} framework, and that the observed softening and the associated lowering of the lattice thermal conductivity in the RFe{sub 4}Sb{sub 12} filled skutterudites are not only related to the filler but also to the Fe{sub 4}Sb{sub 12} framework.

  11. SbF(5)-mediated reactions of oxafluorodiazirines.

    PubMed

    Moss, R A; Fedé, J M; Yan, S

    2001-07-26

    [reaction: see text] The reaction of benzyloxyfluorodiazirine (3) with SbF(5) in benzene gives PhCH(2)OCF, which undergoes SbF(5)-mediated fragmentation to PhCH(2)(+), CO, and SbF(6)(-); the benzyl cation alkylates benzene to yield diphenylmethane. Phenoxyfluorodiazirine (4) reacts with SbF(5) in benzene to give PhOCF and (ultimately) triphenylmethane by a pathway that avoids fragmentation. PMID:11463302

  12. Electrical performance of InAs/AlSb/GaSb superlattice photodetectors

    NASA Astrophysics Data System (ADS)

    Tansel, T.; Hostut, M.; Elagoz, S.; Kilic, A.; Ergun, Y.; Aydinli, A.

    2016-03-01

    Temperature dependence of dark current measurements is an efficient way to verify the quality of an infrared detector. Low dark current density values are needed for high performance detector applications. Identification of dominant current mechanisms in each operating temperature can be used to extract minority carrier lifetimes which are highly important for understanding carrier transport and improving the detector performance. InAs/AlSb/GaSb based T2SL N-structures with AlSb unipolar barriers are designed for low dark current with high resistance and detectivity. Here we present electrical and optical performance of such N-structure photodetectors.

  13. Collective and noncollective states in 116Sb

    NASA Astrophysics Data System (ADS)

    Wang, S. Y.; Sun, D. P.; Qi, B.; Chen, Z. Q.; Hu, X. B.; Wang, G.; Liu, C.; Xu, C. J.; Liu, L.; Zhang, P.; Li, Z. Q.; Guo, M. Z.; Cai, Y. Y.; Li, Y. Q.; Liu, S. Y.; Wyngaardt, S. M.; Zhu, L. H.; Wu, X. G.; He, C. Y.; Zheng, Y.; Li, G. S.

    2012-12-01

    Excited states of 116Sb were investigated using in-beam γ-ray spectroscopy techniques with the 114Cd(7Li, 5n) reaction. About 25 new states and 35 new transitions were added into the level scheme of 116Sb. The previously known two rotational bands based on the πg9/2-1⊗νh11/2 and πg9/2-1⊗νd5/2 configurations have been extended up to (16)- and (13)+ states, respectively. A new ΔI=1 band was identified, and interpreted in terms of the triaxial particle rotor model calculations.

  14. The crystal structures of Hg 4Sb 2I 3 and Cd 4Sb 2I 3

    NASA Astrophysics Data System (ADS)

    Shevelkov, A. V.; Dikarev, E. V.; Popovkin, B. A.

    1991-08-01

    The crystal structures of Hg 4Sb 2I 3 and Cd 4Sb 2I 3 have been solved by X-ray single crystal techniques. Hg 4Sb 2I 3 and Cd 4Sb 2I 3 are isostructural and crystallize in the cubic system, space group Pa3, Z = 8, with cell dimensions a = 13.4392(6) Å for Hg 4Sb 2I 3 and a = 13.4876(5) Å for Cd 4Sb 2I 3. The compounds have a three-dimensional array built from six-membered rings containing mercury (cadmium), antimony, and iodine atoms. One-half of the antimony atoms are bound into Sb 4-2 pairs with an SbSb distance of 2.75 Å. The absence of HgHg (or CdCd) and SbI bonding was determined.

  15. In-situ monitoring of GaSb, GaInAsSb, and AlGaAsSb

    SciTech Connect

    Vineis, C.J. |; Wang, C.A.; Jensen, K.F.; Breiland, W.G.

    1998-06-01

    Suitability of silicon photodiode detector arrays for monitoring the spectral reflectance during epitaxial growths of GaSb, AlGaAsSb, and GaInAsSb, which have cutoff wavelengths of 1.7, 1.2, and 2.3 {micro}m, respectively, is demonstrated. These alloys were grown lattice matched to GaSb in a vertical rotating-disk reactor, which was modified to accommodate near normal reflectance without affecting epilayer uniformity. By using a virtual interface model, the growth rate and complex refractive index at the growth temperature are extracted for these alloys over the 600 to 950 nm spectral range. Excellent agreement is obtained between the extracted growth rate and that determined by ex-situ measurement. Optical constants are compared to theoretical predictions based on an existing dielectric function model for these materials. Furthermore, quantitative analysis of the entire reflectance spectrum yields valuable information on the approximate thickness of overlayers on the pregrowth substrate.

  16. Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

    PubMed Central

    Pandey, S C; Davis, J M; Pandey, G N

    1995-01-01

    Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors. PMID:7786883

  17. Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors.

    PubMed

    Callander, Gabrielle E; Olorunda, Morenike; Monna, Dominique; Schuepbach, Edi; Langenegger, Daniel; Betschart, Claudia; Hintermann, Samuel; Behnke, Dirk; Cotesta, Simona; Fendt, Markus; Laue, Grit; Ofner, Silvio; Briard, Emmanuelle; Gee, Christine E; Jacobson, Laura H; Hoyer, Daniel

    2013-01-01

    Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various "dual" orexin receptor antagonists and the orexin receptors, OX1R and OX2R, over time using saturation and competition radioligand binding with [(3)H]-BBAC ((S)-N-([1,1'-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide). In addition, the kinetics of these compounds were investigated in cells expressing human, mouse and rat OX1R and OX2R using FLIPR® assays for calcium accumulation. We demonstrate that almorexant reaches equilibrium very slowly at OX2R, whereas SB-649868, suvorexant, and filorexant may take hours to reach steady state at both orexin receptors. By contrast, compounds such as BBAC or the selective OX2R antagonist IPSU ((2-((1H-Indol-3-yl)methyl)-9-(4-methoxypyrimidin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one) bind rapidly and reach equilibrium very quickly in binding and/or functional assays. Overall, the "dual" antagonists tested here tend to be rather unselective under non-equilibrium conditions and reach equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the "dual" antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo. PMID:24376396

  18. Kinetic properties of “dual” orexin receptor antagonists at OX1R and OX2R orexin receptors

    PubMed Central

    Callander, Gabrielle E.; Olorunda, Morenike; Monna, Dominique; Schuepbach, Edi; Langenegger, Daniel; Betschart, Claudia; Hintermann, Samuel; Behnke, Dirk; Cotesta, Simona; Fendt, Markus; Laue, Grit; Ofner, Silvio; Briard, Emmanuelle; Gee, Christine E.; Jacobson, Laura H.; Hoyer, Daniel

    2013-01-01

    Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various “dual” orexin receptor antagonists and the orexin receptors, OX1R and OX2R, over time using saturation and competition radioligand binding with [3H]-BBAC ((S)-N-([1,1′-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide). In addition, the kinetics of these compounds were investigated in cells expressing human, mouse and rat OX1R and OX2R using FLIPR® assays for calcium accumulation. We demonstrate that almorexant reaches equilibrium very slowly at OX2R, whereas SB-649868, suvorexant, and filorexant may take hours to reach steady state at both orexin receptors. By contrast, compounds such as BBAC or the selective OX2R antagonist IPSU ((2-((1H-Indol-3-yl)methyl)-9-(4-methoxypyrimidin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one) bind rapidly and reach equilibrium very quickly in binding and/or functional assays. Overall, the “dual” antagonists tested here tend to be rather unselective under non-equilibrium conditions and reach equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the “dual” antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo. PMID:24376396

  19. Antimony bonding in Ge-Sb-Te phase change materials

    NASA Astrophysics Data System (ADS)

    Bobela, David C.; Taylor, P. Craig; Kuhns, Phillip; Reyes, Arneil; Edwards, Arthur

    2011-01-01

    The amorphous phase in some technologically important Ge-Sb-Te systems is still not well understood despite many models that exist to explain it. Using nuclear magnetic resonance, we demonstrate that Sb bonding in these systems follows the 8-Nrule for chemical bonding in amorphous solids. We find that the Sb atoms preferentially bond to three atoms in a pyramidal configuration analogous to the sites occurring in Sb-S or Sb-Se systems. The data we present should be used as a guide for structural modeling of the amorphous phase.

  20. Electron g-factor in bulk Ga1-xInxAsySb1-y/GaSb quaternary alloy and in GaSb/Ga1-xInxAsySb1-y/GaSb Spherical quantum dots

    NASA Astrophysics Data System (ADS)

    Sánchez-Cano, R.; Porras-Montenegro, N.

    2011-12-01

    Secure quantum communications require an entanglement-preserving photo-detector in which quantum information is transmitted by photon polarization through an mid infrared optical fiber system and then transferred to electron spin in a optoelectronic semiconductor device. Using interpolation scheme we have investigated the electron g-factor in bulk Ga1-xInxAsySb1-y quaternary alloy matched to GaSb as a function of Indium and Arsenic concentration on the complete range 0≤x,y≤1. A specific g-factor as a function of the radius in a spherical GaSb/Ga1-xInxAsySb1-y/GaSb quantum dot heterostructure is calculated. Furthermore, we present calculations of the energy states including the Zeeman effect on the electrons confined in quaternary heterostructure quantum dots, with a parabolic confining potential under applied magnetic fields. Our calculations have been worked out by using interpolating methods to find the band gap as a function of the Indium concentration in order to determine the conduction band-offset at room temperature in GaSb/Ga1-xInxAsySb1-y/GaSb heterostructure, within the effective-mass approximation. Experimental or theoretical electron g-factor, spin-orbit splitting Δso, and coupling matrix elements Ep = (2/m0)||2 value between the states of the lowest conduction band Γ6 and the upper valence bands Γ8 for Ga1-xInxAsySb1-y/GaSb quaternary alloy are not readily available. Our predictions show that electron g-factor values are in the range between the electron g-factor measured in bulk GaSb when x→0 (g = -9.25) and that measured in InAs when x→1 (g = -18.08), but there is a remarkable minimum in the g-factor value (g≃-23.14) at x≃0.67.

  1. Antagonistic formation motion of cooperative agents

    NASA Astrophysics Data System (ADS)

    Lu, Wan-Ting; Dai, Ming-Xiang; Xue, Fang-Zheng

    2015-02-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonistic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all of the agents make an antagonistic formation motion in a distributed manner. It is shown that all of the agents can be spontaneously divided into several groups and that agents in the same group collaborate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61203080 and 61473051) and the Natural Science Foundation of Chongqing City (Grant No. CSTC 2011BB0081).

  2. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Channick, Richard N; Sitbon, Olivier; Barst, Robyn J; Manes, Alessandra; Rubin, Lewis J

    2004-06-16

    Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation. PMID:15194180

  3. Histamine-2 Receptor Antagonists and Semen Quality.

    PubMed

    Banihani, Saleem A

    2016-01-01

    Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists. PMID:26176290

  4. Controlled CVD growth of Cu-Sb alloy nanostructures.

    PubMed

    Chen, Jing; Yin, Zongyou; Sim, Daohao; Tay, Yee Yan; Zhang, Hua; Ma, Jan; Hng, Huey Hoon; Yan, Qingyu

    2011-08-12

    Sb based alloy nanostructures have attracted much attention due to their many promising applications, e.g. as battery electrodes, thermoelectric materials and magnetic semiconductors. In many cases, these applications require controlled growth of Sb based alloys with desired sizes and shapes to achieve enhanced performance. Here, we report a flexible catalyst-free chemical vapor deposition (CVD) process to prepare Cu-Sb nanostructures with tunable shapes (e.g. nanowires and nanoparticles) by transporting Sb vapor to react with copper foils, which also serve as the substrate. By simply controlling the substrate temperature and distance, various Sb-Cu alloy nanostructures, e.g. Cu(11)Sb(3) nanowires (NWs), Cu(2)Sb nanoparticles (NPs), or pure Sb nanoplates, were obtained. We also found that the growth of Cu(11)Sb(3) NWs in such a catalyst-free CVD process was dependent on the substrate surface roughness. For example, smooth Cu foils could not lead to the growth of Cu(11)Sb(3) nanowires while roughening these smooth Cu foils with rough sand papers could result in the growth of Cu(11)Sb(3) nanowires. The effects of gas flow rate on the size and morphology of the Cu-Sb alloy nanostructures were also investigated. Such a flexible growth strategy could be of practical interest as the growth of some Sb based alloy nanostructures by CVD may not be easy due to the large difference between the condensation temperature of Sb and the other element, e.g. Cu or Co. PMID:21757793

  5. The new Zintl phases Eu21Cd4Sb18 and Eu21Mn4Sb18

    NASA Astrophysics Data System (ADS)

    Wang, Yi; Darone, Gregory M.; Bobev, Svilen

    2016-06-01

    Crystals of two new Zintl compounds, Eu21Mn4Sb18 and Eu21Cd4Sb18 have been synthesized using the molten metal flux method, and their structures have been established by single-crystal X-ray diffraction. Both compounds are isotypic and crystallize in the monoclinic space group C2/m (No. 12, Z=4). The structures are based on edge- and corner-shared MnSb4 or CdSb4 tetrahedra, which make octameric [Mn8Sb22] or [Cd8Sb22] polyanions. Homoatomic Sb-Sb bonds are present in both structures. The Eu atoms take the role of Eu2+cations with seven unpaired 4f electrons, as suggested by the temperature-dependent magnetization measurements. The magnetic susceptibilities of Eu21Mn4Sb18 and Eu21Cd4Sb18 indicate that both phases order anti-ferromagnetically with Néel temperatures of ca. 7 K and ca. 10 K, respectively. The unpaired 3d electrons of the Mn atoms in Eu21Mn4Sb18 do contribute to the magnetic response, however, the bulk magnetization measurements do not provide evidence for long-range ordering of the Mn spins down to 5 K. Electrical resistivity measurements suggest that both compounds are narrow band gap semiconductors.

  6. Growth of InSb and InAs(1-x)Sb(x) by OM-CVD

    NASA Technical Reports Server (NTRS)

    Chiang, P. K.; Bedair, S. M.

    1984-01-01

    Organometallic chemical vapor deposition (OM-CVD) growth of InSb and InAs(1-x)Sb(x) has been obtained using triethylindium (TEI), trimethylantimony (TMS), and arsine (AsH3) on (100) GaAs, (100) InSb, and (111)-B InSb substrates. InSb with excellent morphology was achieved on both (100) InSb and (111)-B InSb substrates. The measured electron mobility at 300 K of undoped InSb grown on (100) GaAs semi-insulating substrates was 40,000 sq cm/V-s at a carrier concentration of ND-NA = 2.0 x 10 to the 16th per cu cm. Carrier concentration of ND-NA = 1.2 x 10 to the 15th per cu cm has been measured at 77 K. InAs(1-x)Sb(x) (x = 0.07-0.75) with mirror-like surfaces have been grown on (100) InSb and InAs substrates. This composition range of x between 0.55 and 0.75 (Eg = 0.1 eV) has been successfully achieved for the first time. Solid composition variations as a function of growth temperature and InSb substrate orientations are also discussed.

  7. Determination of Sb(III) and Sb(V) by HPLC-Online isotopic dilution-ICP MS.

    PubMed

    Fontanella, Maria Chiara; Beone, Gian Maria

    2016-01-01

    This work provides a method with application of valid techniques to extract and determinate inorganic species of antimony (Sb) for water. The procedure involves•the simultaneous accumulation of Sb(III) and Sb(V) on passive samplers like Diffusive Gradient in Thin Films (DGT) with iron (Fe) oxide gel, eliminating the risk of speciation changes due to transport and storage;•application of less concentrated acid (50 mM Na2EDTA) for elution and preservation of Sb species from DGT resin;•subsequent analytical determination of inorganic species with High Performance Liquid Chromatography-Isotopic Dilution-Inductively Coupled Plasma Mass Spectrometer (HPLC-ID-ICP MS) based on determination of the isotope ratio ((123)Sb/(121)Sb) of isotopes in the samples after spiking with 123Sb enriched standard solution, reducing the effect of signal drift and matrix effect on the final value. PMID:27408828

  8. Administration of orexin receptor 1 antagonist into the rostral ventromedial medulla increased swim stress-induced antinociception in rat

    PubMed Central

    Soliemani, Neda; Moslem, Alireza; Shamsizadeh, Ali; Azhdari-Zarmehri, Hassan

    2016-01-01

    Objective(s): Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA). Materials and Methods: Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive responses were measured by formalin test (50 µl injection of formalin 2% subcutaneously into hind paw) and, pain related behaviors were monitored for 90 min following intra-microinjection of SB-334867 (orexin receptor 1 antagonist) into RVM. Results: Exposure to swimming stress test after administration of SB-334867 into RVM significantly reduces the formalin-induced nociceptive behaviors in phase1, interphase, and phase 2 in rats. Conclusion: The result demonstrated the involvement of OXR1 in antinociceptive behaviors induced by swim stress in RVM. PMID:27403261

  9. Recent progress in InGaAsSb/GaSb TPV devices

    SciTech Connect

    Shellenbarger, Z.A.; Mauk, M.G.; DiNetta, L.C.; Charache, G.W.

    1996-05-01

    AstroPower is developing InGaAsSb thermophotovoltaic (TPV) devices. This photovoltaic cell is a two-layer epitaxial InGaAsSb structure formed by liquid-phase epitaxy on a GaSb substrate. The (direct) bandgap of the In{sub 1{minus}x}Ga{sub x}As{sub 1{minus}y}Sb{sub y} alloy is 0.50 to 0.55 eV, depending on its exact alloy composition (x,y); and is closely lattice-matched to the GaSb substrate. The use of the quaternary alloy, as opposed to a ternary alloy--such as, for example InGaAs/InP--permits low bandgap devices optimized for 1,000 to 1,500 C thermal sources with, at the same time, near-exact lattice matching to the GaSb substrate. Lattice matching is important since even a small degree of lattice mismatch degrades device performance and reliability and increases processing complexity. Internal quantum efficiencies as high as 95% have been measured at a wavelength of 2 microns. At 1 micron wavelengths, internal quantum efficiencies of 55% have been observed. The open-circuit voltage at currents of 0.3 A/cm{sup 2} is 0.220 volts and 0.280 V for current densities of 2 A/cm{sup 2}. Fill factors of 56% have been measured at 60 mA/cm{sup 2}. However, as current density increases there is some decrease in fill factor. The results to date show that the GaSb-based quaternary compounds provide a viable and high performance energy conversion solution for thermophotovoltaic systems operating with 1,000 to 1,500 C source temperatures.

  10. Effect of a D3 receptor antagonist on context-induced reinstatement of nicotine seeking.

    PubMed

    Sabioni, Pamela; Di Ciano, Patricia; Le Foll, Bernard

    2016-01-01

    Despite the existence of several treatment options for smoking cessation, the rate of relapse after treatment is very high. We and others have proposed that targeting the dopamine D3 receptor (DRD3) may be a good strategy for treatment of nicotine dependence. In human participants, reintroduction to an environment previously associated with drug-taking may induce relapse. In animals, such phenomenon can be studied using the context-induced reinstatement paradigm. As the role of DRD3 in context-induced reinstatement of nicotine-seeking has not yet been explored, we investigated the effects of different doses of the selective DRD3 antagonist SB-277011-A on this reinstatement. Sprague-Dawley adult rats were first trained to self-administer nicotine and subsequently underwent extinction in a second context for 5-7 days. We evaluated the effect of 1, 3 or 10mg/kg of SB-277011-A administered prior to the reintroduction to the training context. We used two different designs: 1) a between-subjects design with a unique reinstatement test; and 2) a counterbalanced within-subjects design, with 4 reinstatement tests. Our findings indicate that, in the within-subjects design, the magnitude of responding induced by the context-induced reinstatement of nicotine seeking was robust during the first reinstatement test, but significantly decreased with repeated testing. SB-277011-A (10mg/kg) blocked context-induced reinstatement of nicotine-seeking at first exposure to the context (between-subjects design), but not after repeated context exposure which produced weaker reinstatement over days. Our results support a role for DRD3 mediating context-induced reinstatement of nicotine seeking, but these effects may not be sustained over time. Further studies should explore this in human participants for validation. PMID:26279138

  11. Microbiological reduction of Sb(V) in anoxic freshwater sediments.

    PubMed

    Kulp, Thomas R; Miller, Laurence G; Braiotta, Franco; Webb, Samuel M; Kocar, Benjamin D; Blum, Jodi S; Oremland, Ronald S

    2014-01-01

    Microbiological reduction of millimolar concentrations of Sb(V) to Sb(III) was observed in anoxic sediments from two freshwater settings: (1) a Sb- and As-contaminated mine site (Stibnite Mine) in central Idaho and 2) an uncontaminated suburban lake (Searsville Lake) in the San Francisco Bay Area. Rates of Sb(V) reduction in anoxic sediment microcosms and enrichment cultures were enhanced by amendment with lactate or acetate as electron donors but not by H2, and no reduction occurred in sterilized controls. Addition of 2-(14)C-acetate to Stibnite Mine microcosms resulted in the production of (14)CO2 coupled to Sb(V) reduction, suggesting that this process proceeds by a dissimilatory respiratory pathway in those sediments. Antimony(V) reduction in Searsville Lake sediments was not coupled to acetate mineralization and may be associated with Sb-resistance. The microcosms and enrichment cultures also reduced sulfate, and the precipitation of insoluble Sb(III)-sulfide complexes was a major sink for reduced Sb. The reduction of Sb(V) by Stibnite Mine sediments was inhibited by As(V), suggesting that As(V) is a preferred electron acceptor for the indigenous community. These findings indicate a novel pathway for anaerobic microbiological respiration and suggest that communities capable of reducing high concentrations of Sb(V) commonly occur naturally in the environment. PMID:24274659

  12. Ba2Sb4GeS10

    PubMed Central

    Geng, Lei

    2013-01-01

    The title quaternary compound, dibarium tetra­anti­mony germanium deca­sulfide, Ba2Sb4GeS10, crystallizes in a novel three-dimensional ∞ 3[Sb4GeS10]4− network structure, which is composed of triangular pyramidal SbS3 (site symmetry m..), distorted SbS5 (m..) polyhedra and regular GeS4 (-4..) tetra­hedra. The SbS3 and SbS5 units are connected with each other through corner- and edge-sharing, forming a Sb4S10 layer in the ab plane. The GeS4 tetra­hedra further bridge two neighbouring Sb4S10 layers, forming a three-dimensional ∞ 3[Sb4GeS10]4− network. The Ba2+ cation (..2) is located between two Sb4S10 layers and is coordinated by ten S atoms with Ba—S bond lengths in the range 3.2505 (9)–3.4121 (2) Å. PMID:23723748

  13. Microbiological reduction of Sb(V) in anoxic freshwater sediments

    USGS Publications Warehouse

    Oremland, Ronald S.; Kulp, Thomas R.; Miller, Laurence G.; Braiotta, Franco; Webb, Samuel M.; Kocar, Benjamin D; Blum, Jodi S.

    2013-01-01

    Microbiological reduction of millimolar concentrations of Sb(V) to Sb(III) was observed in anoxic sediments from two freshwater settings: (1) a Sb- and As-contaminated mine site (Stibnite Mine) in central Idaho and 2) an uncontaminated suburban lake (Searsville Lake) in the San Francisco Bay Area. Rates of Sb(V) reduction in anoxic sediment microcosms and enrichment cultures were enhanced by amendment with lactate or acetate as electron donors but not by H2, and no reduction occurred in sterilized controls. Addition of 2-14C-acetate to Stibnite Mine microcosms resulted in the production of 14CO2 coupled to Sb(V) reduction, suggesting that this process proceeds by a dissimilatory respiratory pathway in those sediments. Antimony(V) reduction in Searsville Lake sediments was not coupled to acetate mineralization and may be associated with Sb-resistance. The microcosms and enrichment cultures also reduced sulfate, and the precipitation of insoluble Sb(III)-sulfide complexes was a major sink for reduced Sb. The reduction of Sb(V) by Stibnite Mine sediments was inhibited by As(V), suggesting that As(V) is a preferred electron acceptor for the indigenous community. These findings indicate a novel pathway for anaerobic microbiological respiration and suggest that communities capable of reducing high concentrations of Sb(V) commonly occur naturally in the environment.

  14. Azines as histamine H4 receptor antagonists.

    PubMed

    Lazewska, Dorota; Kiec-Kononowicz, Katarzyna

    2012-01-01

    Since 2000, when the histamine H4 receptor (H4R) was cloned, it has constituted an interesting target for drug development. Pharmacological studies suggest the potential utility of histamine H4R antagonists/inverse agonists in the treatment of inflammatory diseases, e.g. allergic rhinitis, asthma, atopic dermatitis, colitis, or pruritus. The first H4R ligands were non-selective compounds, but intensive chemical and pharmacological work has led to the discovery of highly potent and selective H4R antagonists (e.g. JNJ7777120, CZC-13788, PF-2988403, A-940894, A-987306). The first compound (UR-63325) has finally entered into clinical studies for the treatment of allergic respiratory diseases (completing the phase I ascending dose trial) and has been found to be safe and well tolerated. The number of scientific publications and patent applications in the H4 field is increasing annually. Among the diverse chemical structures of the H4R antagonists described a 2-aminopyrimidine scaffold is repeatedly found. This review looked at recent advances in the search for H4R antagonists as reflected in patent applications/patents and peer-reviewed publications over the last two years. The work concerns azines (mono-, di-, triazines) and their fused analogues. The chemistry and pharmacology has been described. PMID:22202103

  15. Transport Measurements on Sb doped Silicon Nanowires

    NASA Astrophysics Data System (ADS)

    Nukala, Prathyusha; Zare, Marzieh; Sapkota, Gopal; Gali, Pradeep; Philipose, Usha

    2011-03-01

    Semiconductor nanowires (NWs) present an alternative approach for device scaling. N-type Si NWs are generally grown with silane as source with phosphine and arsenic as dopants, all of which are toxic in nature. We present a safe, cost-effective approach for synthesis of n- doped Si NWs using Sb. Structural and compositional characterization using electron microscopy and X-ray spectroscopy will be presented for crystallographic information on the quality and morphology. Ohmic contacts established to a single and on an array of doped and undoped NWs in an FET type of device configuration will provide information on several parameters such as type of majority carriers, mobility and concentration. We will highlight the promise of Sb doped Si NWs for electronic applications such as nano-scale field effect transistors and sensors.

  16. Carrier spin relaxation in GaInNAsSb/GaNAsSb/GaAs quantum well

    SciTech Connect

    Asami, T.; Nosho, H.; Tackeuchi, A.; Li, L. H.; Harmand, J. C.; Lu, S. L.

    2011-12-23

    We have investigated the carrier spin relaxation in GaInNAsSb/GaNAsSb/GaAs quantum well (QW) by time-resolved photoluminescence (PL) measurement. The sample consists of an 8-nm-thick GaIn{sub 0.36}N{sub 0.006}AsSb{sub 0.015} well, 5-nm-thick GaN{sub 0.01}AsSb{sub 0.11} intermediate barriers and 100-nm-thick GaAs barriers grown by molecular beam epitaxy on a GaAs(100) substrate. The spin relaxation time and recombination lifetime at 10 K are measured to be 228 ps and 151 ps, respectively. As a reference, we have also obtained a spin relaxation time of 125 ps and a recombination lifetime of 63 ps for GaInNAs/GaNAs/GaAs QW. This result shows that crystal quality is slightly improved by adding Sb, although these short carrier lifetimes mainly originate from a nonradiative recombination. These spin relaxation times are longer than the 36 ps spin relaxation time of InGaAs/InP QWs and shorter than the 2 ns spin relaxation time of GaInNAs/GaAs QW.

  17. Growth and characterization of epitaxial NiMnSb/ZnTe/NiMnSb magnetic multilayers

    NASA Astrophysics Data System (ADS)

    Gerhard, F.; Naydenova, T.; Baussenwein, M.; Schumacher, C.; Gould, C.; Molenkamp, L. W.

    2016-02-01

    The half-metal ferromagnet NiMnSb, with its high spin polarization, low magnetic damping and tunable magnetic anisotropy, is a promising material for applications in spin torque devices. We develop the epitaxial growth of NiMnSb/ZnTe/NiMnSb heterostructures, aiming towards the realization of an all-NiMnSb based magnetic tunneling junction (MTJ). Layers are grown in situ by Molecular Beam Epitaxy (MBE) and Atomic Layer Epitaxy (ALE) methods. By tuning Mn content, the magnetic anisotropy of each of the two NiMnSb layers is adjusted in order to achieve mutually orthogonal uniaxial anisotropies. SQUID measurements of the magnetization along orthogonal crystal directions [110] and [ 1 1 bar 0] confirm that the two layers have mutually orthogonal anisotropy. High Resolution X-Ray Diffraction measurements and simulations confirm the nominal layer stack and demonstrate the high crystalline quality of the individual layers. Such layer stacks provide a potential basis for TMR-based spin-torque devices such as spin-torque oscillators.

  18. Lattice-matched epitaxial GaInAsSb/GaSb thermophotovoltaic devices

    SciTech Connect

    Wang, C.A.; Choi, H.K.; Turner, G.W.; Spears, D.L.; Manfra, M.J.; Charache, G.W.

    1997-03-01

    The materials development of Ga{sub 1{minus}x}In{sub x}As{sub y}Sb{sub 1{minus}y} alloys for lattice-matched thermophotovoltaic (TPV) devices is reported. Epilayers with cutoff wavelength 2{endash}2.4 {mu}m at room temperature and lattice-matched to GaSb substrates were grown by both low-pressure organometallic vapor phase epitaxy and molecular beam epitaxy. These layers exhibit high optical and structural quality. For demonstrating lattice-matched TPV devices, p- and n-type doping studies were performed. Several TPV device structures were investigated, with variations in the base/emitter thicknesses, and some with the incorporation of a high-bandgap GaSb or AlGaAsSb window layer. Significant improvement in the external quantum efficiency and open circuit voltage is observed for devices with an AlGaAsSb window layer compared to those without one. {copyright} {ital 1997 American Institute of Physics.}

  19. Nearly massless Dirac fermions hosted by Sb square net in BaMnSb2

    PubMed Central

    Liu, Jinyu; Hu, Jin; Cao, Huibo; Zhu, Yanglin; Chuang, Alyssa; Graf, D.; Adams, D. J.; Radmanesh, S. M. A.; Spinu, L.; Chiorescu, I.; Mao, Zhiqiang

    2016-01-01

    Layered compounds AMnBi2 (A = Ca, Sr, Ba, or rare earth element) have been established as Dirac materials. Dirac electrons generated by the two-dimensional (2D) Bi square net in these materials are normally massive due to the presence of a spin-orbital coupling (SOC) induced gap at Dirac nodes. Here we report that the Sb square net in an isostructural compound BaMnSb2 can host nearly massless Dirac fermions. We observed strong Shubnikov-de Haas (SdH) oscillations in this material. From the analyses of the SdH oscillations, we find key signatures of Dirac fermions, including light effective mass (~0.052m0; m0, mass of free electron), high quantum mobility (1280 cm2V−1S−1) and a π Berry phase accumulated along cyclotron orbit. Compared with AMnBi2, BaMnSb2 also exhibits much more significant quasi two-dimensional (2D) electronic structure, with the out-of-plane transport showing nonmetallic conduction below 120 K and the ratio of the out-of-plane and in-plane resistivity reaching ~670. Additionally, BaMnSb2 also exhibits a G-type antiferromagnetic order below 283 K. The combination of nearly massless Dirac fermions on quasi-2D planes with a magnetic order makes BaMnSb2 an intriguing platform for seeking novel exotic phenomena of massless Dirac electrons. PMID:27466151

  20. Nearly massless Dirac fermions hosted by Sb square net in BaMnSb2

    NASA Astrophysics Data System (ADS)

    Liu, Jinyu; Hu, Jin; Cao, Huibo; Zhu, Yanglin; Chuang, Alyssa; Graf, D.; Adams, D. J.; Radmanesh, S. M. A.; Spinu, L.; Chiorescu, I.; Mao, Zhiqiang

    2016-07-01

    Layered compounds AMnBi2 (A = Ca, Sr, Ba, or rare earth element) have been established as Dirac materials. Dirac electrons generated by the two-dimensional (2D) Bi square net in these materials are normally massive due to the presence of a spin-orbital coupling (SOC) induced gap at Dirac nodes. Here we report that the Sb square net in an isostructural compound BaMnSb2 can host nearly massless Dirac fermions. We observed strong Shubnikov-de Haas (SdH) oscillations in this material. From the analyses of the SdH oscillations, we find key signatures of Dirac fermions, including light effective mass (~0.052m0 m0, mass of free electron), high quantum mobility (1280 cm2V‑1S‑1) and a π Berry phase accumulated along cyclotron orbit. Compared with AMnBi2, BaMnSb2 also exhibits much more significant quasi two-dimensional (2D) electronic structure, with the out-of-plane transport showing nonmetallic conduction below 120 K and the ratio of the out-of-plane and in-plane resistivity reaching ~670. Additionally, BaMnSb2 also exhibits a G-type antiferromagnetic order below 283 K. The combination of nearly massless Dirac fermions on quasi-2D planes with a magnetic order makes BaMnSb2 an intriguing platform for seeking novel exotic phenomena of massless Dirac electrons.

  1. Nearly massless Dirac fermions hosted by Sb square net in BaMnSb2.

    PubMed

    Liu, Jinyu; Hu, Jin; Cao, Huibo; Zhu, Yanglin; Chuang, Alyssa; Graf, D; Adams, D J; Radmanesh, S M A; Spinu, L; Chiorescu, I; Mao, Zhiqiang

    2016-01-01

    Layered compounds AMnBi2 (A = Ca, Sr, Ba, or rare earth element) have been established as Dirac materials. Dirac electrons generated by the two-dimensional (2D) Bi square net in these materials are normally massive due to the presence of a spin-orbital coupling (SOC) induced gap at Dirac nodes. Here we report that the Sb square net in an isostructural compound BaMnSb2 can host nearly massless Dirac fermions. We observed strong Shubnikov-de Haas (SdH) oscillations in this material. From the analyses of the SdH oscillations, we find key signatures of Dirac fermions, including light effective mass (~0.052m0; m0, mass of free electron), high quantum mobility (1280 cm(2)V(-1)S(-1)) and a π Berry phase accumulated along cyclotron orbit. Compared with AMnBi2, BaMnSb2 also exhibits much more significant quasi two-dimensional (2D) electronic structure, with the out-of-plane transport showing nonmetallic conduction below 120 K and the ratio of the out-of-plane and in-plane resistivity reaching ~670. Additionally, BaMnSb2 also exhibits a G-type antiferromagnetic order below 283 K. The combination of nearly massless Dirac fermions on quasi-2D planes with a magnetic order makes BaMnSb2 an intriguing platform for seeking novel exotic phenomena of massless Dirac electrons. PMID:27466151

  2. FAST TRACK COMMUNICATION: Emission wavelength extension of mid-infrared InAsSb/InP nanostructures using InGaAsSb sandwich layers

    NASA Astrophysics Data System (ADS)

    Lei, W.; Tan, H. H.; Jagadish, C.

    2010-08-01

    This paper presents a study on the emission wavelength extension of InAsSb nanostructures using InGaAsSb sandwich layers. Due to the reduced lattice mismatch between InAsSb nanostructure layer and buffer/capping layer, the introduction of InGaAsSb sandwich layers leads to larger island size, reduced compressive strain and lower confinement barrier for InAsSb nanostructures, thus resulting in a longer emission wavelength. For InGaAsSb sandwich layers with nominal Sb concentration higher than 10%, type II band alignment is observed for the InAsSb/InGaAsSb heterostructure, which also contributes to the extension of emission wavelength. The InGaAsSb sandwich layers provide an effective approach to extend the emission wavelength of InAsSb nanostructures well beyond 2 µm, which is very useful for device applications in the mid-infrared region.

  3. Electrochemically Synthesized Sb/Sb2O3 Composites as High-Capacity Anode Materials Utilizing a Reversible Conversion Reaction for Na-Ion Batteries.

    PubMed

    Hong, Kyung-Sik; Nam, Do-Hwan; Lim, Sung-Jin; Sohn, DongRak; Kim, Tae-Hee; Kwon, HyukSang

    2015-08-12

    Sb/Sb2O3 composites are synthesized by a one-step electrodeposition process from an aqueous electrolytic bath containing a potassium antimony tartrate complex. The synthesis process involves the electrodeposition of Sb simultaneously with the chemical deposition of Sb2O3, which allows for the direct deposition of morula-like Sb/Sb2O3 particles on the current collector without using a binder. Structural characterization confirms that the Sb/Sb2O3 composites are composed of approximately 90 mol % metallic Sb and 10 mol % crystalline Sb2O3. The composite exhibits a high reversible capacity (670 mAh g(-1)) that is higher than the theoretical capacity of Sb (660 mAh g(-1)). The high reversible capacity results from the conversion reaction between Na2O and Sb2O3 that occurs additionally to the alloying/dealloying reaction of Sb with Na. Moreover, the Sb/Sb2O3 composite shows excellent cycle performance with 91.8% capacity retention over 100 cycles, and a superior rate capability of 212 mAh g(-1) at a high current density of 3300 mA g(-1). The outstanding cycle performance is attributed to an amorphous Na2O phase generated by the conversion reaction, which inhibits agglomeration of Sb particles and acts as an effective buffer against volume change of Sb during cycling. PMID:26185914

  4. Discovery of novel and potent CRTH2 antagonists.

    PubMed

    Ito, Shinji; Terasaka, Tadashi; Zenkoh, Tatsuya; Matsuda, Hiroshi; Hayashida, Hisashi; Nagata, Hiroshi; Imamura, Yoshimasa; Kobayashi, Miki; Takeuchi, Makoto; Ohta, Mitsuaki

    2012-01-15

    High throughput screening of our chemical library for CRTH2 antagonists provided a lead compound 1a. Initial optimization of the lead led to the discovery of a novel, potent and orally bioavailable CRTH2 antagonist 17. PMID:22178554

  5. GaInSb and GaInAsSb thermophotovoltaic device fabrication and characterization

    SciTech Connect

    Hitchcock, C.; Gutmann, R.; Borrego, J.; Ehsani, H.; Bhat, I.; Freeman, M.; Charache, G.

    1997-05-01

    Thermophotovoltaic (TPV) devices have been fabricated using epitaxial ternary and quaternary layers grown on GaSb substrates. The GaInSb layers were grown by organometallic vapor phase epitaxy (OMVPE) and the InGaAsSb lattice-matched layers were grown by liquid phase epitaxy (LPE). Device fabrication steps include unannealed p-type ohmic contacts, annealed Sn/Au n-type ohmic contacts, and a thick Ag top-surface contact using a lift-off process. Devices are characterized primarily by dark I-V, photo I-V, and quantum efficiency measurements, which are correlated to microscopic and macroscopic material properties. Particular emphasis has been on material enhancements to increase quantum efficiency and decrease dark saturation current density. TPV device performance is presently limited by the base diffusion length, typically 1 to 2 microns.

  6. The influence of 5-HT2 and 5-HT4 receptor antagonists to modify drug induced disinhibitory effects in the mouse light/dark test

    PubMed Central

    Costall, Brenda; Naylor, Robert J

    1997-01-01

    The ability of 5-HT2 and 5-HT4 receptor antagonists to modify the disinhibitory profile of diazepam and other agents was investigated in male BKW mice in the light/dark test box. The 5-HT2A/2B/2C receptor antagonists ritanserin, MDL11939 and RP62203 and also methysergide, which failed to modify mouse behaviour when administered alone, caused dose-related enhancements (4 to 8 fold) in the potency of diazepam to disinhibit behavioural responding to the aversive situation of the test box. Ritanserin was shown to enhance the disinhibitory potency of other benzodiazepines, chlordiazepoxide (4 fold), temazepam (10 fold) and lorazepam (10 fold), the 5-HT1A receptor ligands, 8-OH-DPAT (25 fold), buspirone (100 fold) and lesopitron (500 fold), the 5-HT3 receptor antagonists, ondansetron (100 fold) R(+)-zacopride (100 fold) and S(−)-zacopride (greater than a 1000 fold), the substituted benzamides, sulpiride (10 fold) and tiapride (5 to 10 fold) and the cholecystokinin (CCK)A receptor antagonist, devazepide (100 fold). It also reduced the onset of action of disinhibition following treatment with the 5-HT synthesis inhibitor parachlorophenylalanine. Ritanserin failed to enhance the disinhibitory effects of the CCKB receptor antagonist CI-988, the angiotensin AT1 receptor antagonist losarten or the angiotensin converting enzyme inhibitor ceranapril. The 5-HT4 receptor antagonists SDZ205-557, GR113808 and SB204070 caused dose-related reductions in the disinhibitory effect of diazepam, returning values to those shown in vehicle treated controls. The antagonists failed to modify mouse behaviour when administered alone. GR113808 was also shown to cause a dose-related antagonism of the disinhibitory effects of chlordiazepoxide, lorazepam, 8-OH-DPAT, buspirone, lesopitron, ondansetron, R(+)-zacopride, sulpiride, tiapride, devazepide, CI-988, losarten, ceranapril and parachlorophenylalanine. It was concluded that in BKW mice (a) the failure of 5-HT2 and 5-HT4 receptor antagonists

  7. DWPF Simulant CPC Studies For SB8

    SciTech Connect

    Newell, J. D.

    2013-09-25

    Prior to processing a Sludge Batch (SB) in the Defense Waste Processing Facility (DWPF), flowsheet studies using simulants are performed. Typically, the flowsheet studies are conducted based on projected composition(s). The results from the flowsheet testing are used to 1) guide decisions during sludge batch preparation, 2) serve as a preliminary evaluation of potential processing issues, and 3) provide a basis to support the Shielded Cells qualification runs performed at the Savannah River National Laboratory (SRNL). SB8 was initially projected to be a combination of the Tank 40 heel (Sludge Batch 7b), Tank 13, Tank 12, and the Tank 51 heel. In order to accelerate preparation of SB8, the decision was made to delay the oxalate-rich material from Tank 12 to a future sludge batch. SB8 simulant studies without Tank 12 were reported in a separate report.1 The data presented in this report will be useful when processing future sludge batches containing Tank 12. The wash endpoint target for SB8 was set at a significantly higher sodium concentration to allow acceptable glass compositions at the targeted waste loading. Four non-coupled tests were conducted using simulant representing Tank 40 at 110-146% of the Koopman Minimum Acid requirement. Hydrogen was generated during high acid stoichiometry (146% acid) SRAT testing up to 31% of the DWPF hydrogen limit. SME hydrogen generation reached 48% of of the DWPF limit for the high acid run. Two non-coupled tests were conducted using simulant representing Tank 51 at 110-146% of the Koopman Minimum Acid requirement. Hydrogen was generated during high acid stoichiometry SRAT testing up to 16% of the DWPF limit. SME hydrogen generation reached 49% of the DWPF limit for hydrogen in the SME for the high acid run. Simulant processing was successful using previously established antifoam addition strategy. Foaming during formic acid addition was not observed in any of the runs. Nitrite was destroyed in all runs and no N2O was detected

  8. Thermal instability of GaSb surface oxide

    NASA Astrophysics Data System (ADS)

    Tsunoda, K.; Matsukura, Y.; Suzuki, R.; Aoki, M.

    2016-05-01

    In the development of InAs/GaSb Type-II superlattice (T2SL) infrared photodetectors, the surface leakage current at the mesa sidewall must be suppressed. To achieve this requirement, both the surface treatment and the passivation layer are key technologies. As a starting point to design these processes, we investigated the GaSb oxide in terms of its growth and thermal stability. We found that the formation of GaSb oxide was very different from those of GaAs. Both Ga and Sb are oxidized at the surface of GaSb. In contrast, only Ga is oxidized and As is barely oxidized in the case of GaAs. Interestingly, the GaSb oxide can be formed even in DI water, which results in a very thick oxide film over 40 nm after 120 minutes. To examine the thermal stability, the GaSb native oxide was annealed in a vacuum and analyzed by XPS and Raman spectroscopy. These analyses suggest that SbOx in the GaSb native oxide will be reduced to metallic Sb above 300°C. To directly evaluate the effect of oxide instability on the device performance, a T2SL p-i-n photodetector was fabricated that has a cutoff wavelength of about 4 μm at 80 K. As a result, the surface leakage component was increased by the post annealing at 325°C. On the basis of these results, it is possible to speculate that a part of GaSb oxide on the sidewall surface will be reduced to metallic Sb, which acts as an origin of additional leakage current path.

  9. Discovery and development of orexin receptor antagonists as therapeutics for insomnia

    PubMed Central

    Winrow, CJ; Renger, JJ

    2014-01-01

    Insomnia persistently affects the quality and quantity of sleep. Currently approved treatments for insomnia primarily target γ-aminobutyric acid-A (GABA-A) receptor signalling and include benzodiazepines and GABA-A receptor modulators. These drugs are used to address this sleep disorder, but have the potential for side effects such as tolerance and dependence, making them less attractive as maintenance therapy. Forward and reverse genetic approaches in animals have implicated orexin signalling (also referred to as hypocretin signalling) in the control of vigilance and sleep/wake states. Screening for orexin receptor antagonists using in vitro and in vivo methods in animals has identified compounds that block one or other of the orexin receptors (single or dual orexin receptor antagonists [SORAs and DORAs], respectively) in animals and humans. SORAs have primarily been used as probes to further elucidate the roles of the individual orexin receptors, while a number of DORAs have progressed to clinical development as pharmaceutical candidates for insomnia. The DORA almorexant demonstrated significant improvements in a number of clinically relevant sleep parameters in animal models and in patients with insomnia but its development was halted. SB-649868 and suvorexant have demonstrated efficacy and tolerability in Phase II and III trials respectively. Furthermore, suvorexant is currently under review by the Food and Drug Administration for the treatment of insomnia. Based on the publication of recent non-clinical and clinical data, orexin receptor antagonists potentially represent a targeted, effective and well-tolerated new class of medications for insomnia. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2 PMID:23731216

  10. A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

    PubMed Central

    Yun, Sujin; Johnson, Philip L.; Shekhar, Anantha; Fitz, Stephanie D.; Shireman, Brock T.; Lebold, Terry P.; Nepomuceno, Diane; Lord, Brian; Wennerholm, Michelle; Shelton, Jonathan; Carruthers, Nicholas; Lovenberg, Timothy; Dugovic, Christine

    2015-01-01

    Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate–induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states. PMID:25583879

  11. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects.

    PubMed

    Bonaventure, Pascal; Yun, Sujin; Johnson, Philip L; Shekhar, Anantha; Fitz, Stephanie D; Shireman, Brock T; Lebold, Terry P; Nepomuceno, Diane; Lord, Brian; Wennerholm, Michelle; Shelton, Jonathan; Carruthers, Nicholas; Lovenberg, Timothy; Dugovic, Christine

    2015-03-01

    Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate-induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states. PMID:25583879

  12. Thermal Treatment Improvement of CuSbS2 Absorbers

    SciTech Connect

    de Souza Lucas, Francisco Willian; Welch, Adam W.; Baranowski, Lauryn L.; Dippo, Patricia C.; Mascaro, Lucia H.; Zakutayev, Andriy

    2015-06-14

    Thermal treatment in Sb2S3 vapor was used to improve the quality of CuSbS2 thin films, a promising non-toxic and earth-abundant absorber. A change in the CuSbS2 crystallographic texture and a decrease in the lattice stress were observed, as well as increases in the grain size, photoluminescence intensity and photoconductivity. To eliminate the influence of the possible Sb2S3 rich surface layer on photovoltaic performance, a selective chemical etching with KOH was developed.

  13. Intrinsic interface states in InAs-AlSb heterostructures.

    PubMed

    Raouafi, F; Benchamekh, R; Nestoklon, M O; Jancu, J-M; Voisin, P

    2016-02-01

    We examine the formation of intrinsic interface states bound to the plane of In-Sb chemical bonds at InAs-AlSb interfaces. Careful parameterization of the bulk materials in the frame of the extended-basis spds (*)tight-binding model and recent progress in predictions of band offsets severely limit the span of tight-binding parameters describing this system. We find that a heavy-hole-like interface state bound to the plane of In-Sb bonds exists for a large range of values of the InSb-InAs band offset. PMID:26732184

  14. Numerical analysis of InSb parameters and InSb 2D infrared focal plane arrays

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaolei; Zhang, Hongfei; Sun, Weiguo; Zhang, Lei; Meng, Chao; Lu, Zhengxiong

    2012-10-01

    Accurate and reliable numerical simulation tools are necessary for the development of advanced semiconductor devices. InSb is using the MATLAB and TCAD simulation tool to calculatet the InSb body bandstructure, blackbody's radiant emittance and simultaneously solve the Poisson, Continuity and transport equations for 2D detector structures. In this work the material complexities of InSb, such as non-parabolicity, degenergcy, mobility and Auger recombination/generation are explained, and physics based models are developed. The Empirical Tight Binding Method (ETBM) was been using to calculate the bandstructure for InSb at 77 K by Matlab. We describe a set of systematic experiments performed in order to calibrate the simulation to semiconductor devices backside illuminated InSb focal plane arrays realized with planar technology. The spectral photoresponse and crosstalk characteristic for mid-wavelength InSb infrared focal plane arrays have been numerically studied.

  15. Fluorescent Human EP3 Receptor Antagonists.

    PubMed

    Tomasch, Miriam; Schwed, J Stephan; Kuczka, Karina; Meyer Dos Santos, Sascha; Harder, Sebastian; Nüsing, Rolf M; Paulke, Alexander; Stark, Holger

    2012-09-13

    Exchange of the lipophilc part of ortho-substituted cinnamic acid lead structures with different small molecule fluorophoric moieties via a dimethylene spacer resulted in hEP3R ligands with affinities in the nanomolar concentration range. Synthesized compounds emit fluorescence in the blue, green, and red range of light and have been tested concerning their potential as a pharmacological tool. hEP3Rs were visualized by confocal laser scanning microscopy on HT-29 cells, on murine kidney tissues, and on human brain tissues and functionally were characterized as antagonists on human platelets. Inhibition of PGE2 and collagen-induced platelet aggregation was measured after preincubation with novel hEP3R ligands. The pyryllium-labeled ligand 8 has been shown as one of the most promising structures, displaying a useful fluorescence and highly affine hEP3R antagonists. PMID:24900547

  16. Vasopressin receptor antagonists: Characteristics and clinical role.

    PubMed

    Rondon-Berrios, Helbert; Berl, Tomas

    2016-03-01

    Hyponatremia, the most common electrolyte disorder in hospitalized patients is associated with increased risk of mortality even when mild and apparently asymptomatic. Likewise morbidity manifested as attention deficits, gait disturbances, falls, fractures, and osteoporosis is more prevalent in hyponatremic subjects. Hyponatremia also generates a significant financial burden. Therefore, it is important to explore approaches that effectively and safely treat hyponatremia. Currently available strategies are physiologically sound and affordable but lack evidence from clinical trials and are limited by variable efficacy, slow response, and/or poor compliance. The recent emergence of vasopressin receptor antagonists provides a class of drugs that target the primary pathophysiological mechanism, namely vasopressin mediated impairment of free water excretion. This review summarizes the historical development, pharmacology, clinical trials supporting efficacy and safety, shortcomings, as well as practical suggestions for the use of vasopressin receptor antagonists. PMID:27156765

  17. Numerical Simulation of the Dissolution Process of GaSb into InSb Melt under Normal and Microgravity Conditions

    NASA Astrophysics Data System (ADS)

    Takagi, Youhei; Suzuki, Natsuki; Okano, Yasunori; Tanaka, Akira; Hayakawa, Yasuhiro; Dost, Sadik

    Temperature Gradient Growth experiments of InxGa1-xSb will be performed on the International Space Station (ISS) in 2012. In the GaSb/InSb/GaSb-sandwich system used, before growth, the dissolution process of GaSb into InSb takes place during the formation of the growth solution (melt). Solutal mass transport occurring during dissolution plays a significant role. In crystal growth on Earth, the large difference between the densities of InSb and GaSb leads to gravitational segregation in the melt and axial non-uniformity in crystal composition. In addition, the large separation between the liquidus and solidus curves in the phase diagram of this system further contributes to compositional non-uniformity. In order to have a better understanding for the effect of gravity on solutal transport during in this system, the dissolution process was numerically simulated under both Earth’s gravity and a microgravity level on the ISS. Numerical simulations showed that under Earth’s gravity, dissolution of the GaSb seed was enhanced due to the contribution of solutal natural convection. However, under microgravity diffusion mass transport was dominant in the melt, and the contribution of natural convection was not significant.

  18. Sb/Cu2Sb-TiC-C Composite Anode for High-Performance Sodium-Ion Batteries.

    PubMed

    Chae, Seung Chul; Hur, Jaehyun; Kim, Il Tae

    2016-02-01

    A novel nanostructure consisting of copper-antimony alloy (Cu2Sb) particles dispersed in a conductive hybrid matrix of titanium carbide (TiC) and carbon (C) has been developed by high energy mechanical milling (HEMM) and explored for use as an anode in sodium-ion batteries. By controlling the molar ratio of Cu and Sb, Cu2Sb and Sb are able to co-exist in a matrix. The (Sb)/Cu2Sb-TiC-C samples have been characterized by X-ray diffraction and by high-resolution transmission electron microscopy. Specifically, the Cu2Sb-TiC-C composite anode demonstrates better cyclic performance as well as better rate-capability compared to Sb/Cu2Sb-TiC-C. Addition- ally, the introduction of the fluoroethylene carbonate (FEC) additive into the electrolyte leads to improved electrochemical performance even at high-rate current densities, when compared to the electrodes without the FEC additive, owing to the formation of a stable and thin SEI layer. PMID:27433694

  19. Investigation of interfaces in AlSb/InAs/Ga₀.₇₁In₀.₂₉Sb quantum wells by photoluminescence

    SciTech Connect

    Junliang, Xing; Yu, Zhang; Yongping, Liao; Juan, Wang; Wei, Xiang; Hongyue, Hao; Yingqiang, Xu; Zhichuan, Niu

    2014-09-28

    We have investigated excitation power and temperature dependent PL spectra to systematically study the influences of the interfaces in the both InAs/Ga₀.₇₁In₀.₂₉Sb and InAs/AlSb on the optical properties of AlSb/Ga₀.₇₁In₀.₂₉Sb/InAs quantum wells (QWs). The localized states as well as the activation energy were analyzed to discuss the possible thermal quenching and non-radiative recombination mechanisms. We found two non-radiative recombination processes were involved in the thermal quenching of radiative emission for the QW structures. The GaAs-like interface in InAs/Ga₀.₇₁In₀.₂₉Sb with higher activation energy (62.7 meV) in high temperature region (70 K–300 K) supplies a deeper hole confinement and less roughness than the InSb-like one, which suppress non-radiative recombination process and promote the optical qualities of the quantum wells. The peak energy of the InSb-like sample exhibited “step-curve” behavior with increase temperature. Neither InSb-like nor AlAs-like interface in InAs/AlSb favored the radiative emission efficiency.

  20. Preclinical pharmacology of alpha1-adrenoceptor antagonists.

    PubMed

    Martin, D J

    1999-01-01

    The implication of a single adrenoceptor subtype in the contractility of prostatic and urethral smooth muscle cells led to the concept that drugs with selectivity for this subtype may exhibit functional uroselectivity. Comparison of the affinities of the alpha1-adrenoceptor antagonists revealed that few compounds show selectivity for one of the three cloned alpha1-adrenoceptor subtypes (alpha1a/A, alpha1b/B, alpha1d/D) whereas most of them had a similar affinity for the three subtypes. Moreover, data supporting a relationship between selectivity for the alpha1a/A-adrenoceptor subtype and functional uroselectivity are still lacking and recent data challenged the relevance of the selectivity for a given cloned alpha1-adrenoceptor subtype in predicting functional uroselectivity. In vivo data showed that alpha1-adrenoceptor antagonists without adrenoceptor subtype selectivity, like alfuzosin or to a minor extent doxazosin, showed functional uroselectivity whereas prazosin and terazosin were not shown to be uroselective. Compounds considered to be selective for the alpha1a/A-adrenoceptor, like tamsulosin or 5-Me-urapidil, did not show functional uroselectivity since they modified urethral and blood pressures in a manner which was not correlated to their selectivity for the cloned alpha1-adrenoceptor subtypes. Meanwhile, the identification in prostatic tissue, of a new sub-family of alpha1-adrenoceptors with low affinity for prazosin and denominated alpha1L gave rise to numerous studies. However, its functional role as well as the affinity of the known antagonists for this receptor subtype remains to be clarified. In conclusion, the existing alpha1-adrenoceptor antagonists have different pharmacological profiles in vivo which are yet not predictable from their receptor pharmacology based on the actual state of knowledge of the alpha1-adrenoceptor classification. PMID:10393471

  1. The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia.

    PubMed

    Nikiforuk, Agnieszka; Hołuj, Małgorzata; Kos, Tomasz; Popik, Piotr

    2016-06-01

    Serotonin (5-HT) receptors still represent promising targets for the development of novel multireceptor or stand-alone antipsychotic drugs with a potential to ameliorate cognitive impairments and negative symptoms in schizophrenia. The 5-HT5A receptor, one of the least known members of the serotonin receptor family, has also drawn attention in this regard. Although the antipsychotic efficacy of 5-HT5A antagonists is still equivocal, recent experimental data suggest the cognitive-enhancing activity of this strategy. The aim of the present study was to evaluate pro-cognitive and pro-social efficacies of the 5-HT5A receptor antagonist in a rat pharmacological model of schizophrenia employing the administration of the NMDA receptor antagonist, ketamine. The ability of SB-699551 to reverse ketamine-induced cognitive deficits in the attentional set-shifting task (ASST) and novel object recognition task (NORT) was examined. The compound's efficacy against ketamine-induced social withdrawal was assessed in the social interaction test (SIT) and in the social choice test (SCT). The results demonstrated the efficacy of SB-699551 in ameliorating ketamine-induced impairments on the ASST and NORT. Moreover, the tested compound also enhanced set-shifting performance in cognitively unimpaired control rats and improved object recognition memory in conditions of delay-induced natural forgetting. The pro-social activity of SB-699551 was demonstrated on both employed paradigms, the SIT and SCT. The present study suggests the preclinical efficacy of a strategy based on the blockade of 5-HT5A receptors against schizophrenia-like cognitive deficits and negative symptoms. The utility of this receptor as a target for improvement of cognitive and social dysfunctions warrants further studies. PMID:26826431

  2. Medicinal chemistry of competitive kainate receptor antagonists.

    PubMed

    Larsen, Ann M; Bunch, Lennart

    2011-02-16

    Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1-5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure-activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

  3. Calcium antagonists and their mode of action

    PubMed Central

    Nayler, Winifred G.; Dillon, J. S.

    1986-01-01

    1 The Ca2+ antagonists are a novel group of drugs useful in management of a variety of cardiac disorders. They differ from one another in terms of their chemistry, tissue specificity and selectivity. As a group, however, they share the common property of slowing Ca2+ entry through voltage-activated, ion-selective channels. Some of them exhibit other properties, including that of interfering with Na+ transport. At least one of them, diltiazem, has an intracellular action. 2 Specific high and low affinity binding sites have been identified for two of the major groups of Ca2+-antagonists, with the binding sites for verapamil and its derivatives being distinct from those which can be occupied by the dihydropyridines. The number (Bmax) and affinity (KD) of these binding sites changes under certain pathological conditions—including a reduction in ischaemia and in spontaneous hypertension, an increase in the latter, at present, only demonstrated for the dihydropyridine binding sites. 3 The sensitivity of a particular tissue to these drugs will depend upon a number of factors including the number of binding sites that are present, the contribution made by the Ca2+ entering through the voltage-activated channels to the functioning of the tissue, and properties which are peculiar to a particular type of Ca2+ antagonist, for example, whether, as in the case of verapamil, they exhibit use-dependence. PMID:3019374

  4. The Sexually Antagonistic Genes of Drosophila melanogaster

    PubMed Central

    Innocenti, Paolo; Morrow, Edward H.

    2010-01-01

    When selective pressures differ between males and females, the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic. Although the phenotypic effect of these genes has been documented in both wild and laboratory populations, their identity, number, and location remains unknown. Here, by combining data on sex-specific fitness and genome-wide transcript abundance in a quantitative genetic framework, we identified a group of candidate genes experiencing sexually antagonistic selection in the adult, which correspond to 8% of Drosophila melanogaster genes. As predicted, the X chromosome is enriched for these genes, but surprisingly they represent only a small proportion of the total number of sex-biased transcripts, indicating that the latter is a poor predictor of sexual antagonism. Furthermore, the majority of genes whose expression profiles showed a significant relationship with either male or female adult fitness are also sexually antagonistic. These results provide a first insight into the genetic basis of intralocus sexual conflict and indicate that genetic variation for fitness is dominated and maintained by sexual antagonism, potentially neutralizing any indirect genetic benefits of sexual selection. PMID:20305719

  5. Strained InGaSb/AlGa(As)Sb Quantum Wells for p-Channel Transistors

    NASA Astrophysics Data System (ADS)

    Bennett, Brian R.; Podpirka, Adrian A.; Boos, J. B.; Kumar, Satvika L.

    2016-06-01

    Quantum wells of InGaSb clad by AlGa(As)Sb were grown by molecular beam epitaxy. Well and barrier compositions were chosen to yield biaxial compressive strain and enhanced hole mobility in the InGaSb. Wells with thickness of 7.5 nm exhibited room-temperature mobilities of 1000 cm2/V s to 1100 cm2/V s, with the surface-layer material influencing two-dimensional hole densities. The introduction of As into the barrier material allows a wider range of p-channel well/barrier combinations and lattice constants. These could be compatible with n-channel InGaAs wells for complementary field-effect transistor circuits which utilize a common buffer layer. InGaSb wells with thicknesses of 20 nm to 30 nm and compressive strains of 1.0% to 1.5% exhibited hole mobilities of 700 cm2/V s to 900 cm2/V s.

  6. Layer-resolved spin polarization in Sb overlayers on NiMnSb

    SciTech Connect

    Skomski, R.; Komesu, T.; Borca, C. N.; Jeong, H.-K.; Dowben, P. A.; Ristoiu, D.; Nozi {grave e}res, J. P.

    2001-06-01

    The magnetism of antimony overlayers on a ferromagnetic substrate is investigated by spin-polarized inverse photoemission and explained in terms of a spin-dependent envelope-function approximation (SDEFA). The atomic structure of the films, which were deposited by sputtering Sb onto a NiMnSb(001) substrate, is characterized by a unique combination of three features: (i) NiMnSb is a highly spin-polarized semi-Heusler alloy predicted to be halfmetallic, (ii) antimony is a semimetal, exhibiting a band structure reminiscent of indirect-gap semiconductors, and (iii) the small lattice mismatch ensures a well-controlled interface. Combined x-ray absorption spectroscopy and spin-polarized inverse photoemission yield a layer-resolved spin polarization decaying on a length scale of the order of 1 nm. The unusual range of the spin polarization in the paramagnetic overlayer is explained by considering the alloy{endash}antimony interface as a spin-dependent perturbation potential and taking into account the low effective masses of the Sb conduction electrons (only about 0.1 for both electrons and holes). {copyright} 2001 American Institute of Physics.

  7. From the Cover: Glutamate antagonists limit tumor growth

    NASA Astrophysics Data System (ADS)

    Rzeski, Wojciech; Turski, Lechoslaw; Ikonomidou, Chrysanthy

    2001-05-01

    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-D-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the -amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca2+ dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.

  8. K2CsSb Cathode Development

    SciTech Connect

    Smedley,J.; Rao, T.; Wang, E.

    2008-10-01

    K{sub 2}CsSb is an attractive photocathode for high current applications. With a quantum efficiency of >4% at 532nm and >10% at 355nm, it is the only cathode to have demonstrated an average current of 35mA in an accelerator environment We describe ongoing cathode development work. for the energy recovery linac being constructed at BNL Several cathodes have been created on both copper and stainless steel substrates, and their spatial uniformity and spectral response have been characterized. Preliminary lifetime measurements have been performed at high average current densities (>1 mA/mm{sup 2}).

  9. InAs/GaSb superlattice technology

    NASA Astrophysics Data System (ADS)

    Rutz, Frank; Rehm, Robert; Walther, Martin; Schmitz, Johannes; Kirste, Lutz; Wörl, Andreas; Masur, Jan-Michael; Scheibner, Ralf; Ziegler, Johann

    2011-05-01

    We present the InAs/GaSb type-II superlattice dual-color technology developed at Fraunhofer IAF. This includes insights into some of the test methodologies employed at various stages during the fabrication process, which ensure that the basic requirements for achieving high detector performance are met. Much effort is put in improving and monitoring the quality of the substrate and the epilayers. We also present performance data from a dual-color mid-wavelength infrared (MWIR) camera which incorporates the latest backside process technology.

  10. Management of calcium channel antagonist overdose.

    PubMed

    Salhanick, Steven D; Shannon, Michael W

    2003-01-01

    Calcium channel antagonists are used primarily for the treatment of hypertension and tachyarrhythmias. Overdose of calcium channel antagonists can be lethal. Calcium channel antagonists act at the L-type calcium channels primarily in cardiac and vascular smooth muscle preventing calcium influx into cells with resultant decreases in vascular tone and cardiac inotropy and chronotropy. The L-type calcium channel is a complex structure and is thus affected by a large number of structurally diverse antagonists. In the setting of overdose, patients may experience vasodilatation and bradycardia leading to a shock state. Patients may also be hyperglycaemic and acidotic due to the blockade of L-type calcium channels in the pancreatic islet cells that affect insulin secretion. Aggressive therapy is warranted in the setting of toxicity. Gut decontamination with charcoal, or whole bowel irrigation or multiple-dose charcoal in the setting of extended-release products is indicated. Specific antidotes include calcium salts, glucagon and insulin. Calcium salts may be given in bolus doses or may be employed as a continuous infusion. Care should be exercised to avoid the administration of calcium in the setting of concomitant digoxin toxicity. Insulin administration has been used effectively to increase cardiac inotropy and survival. The likely mechanism involves a shift to carbohydrate metabolism in the setting of decreased availability of carbohydrates due to decreased insulin secretion secondary to blockade of calcium channels in pancreatic islet cells. Glucose should be administered as well to maintain euglycaemia. Supportive care including the use of phosphodiesterase inhibitors, adrenergic agents, cardiac pacing, balloon pump or extracorporeal bypass is frequently indicated if antidotal therapy is not effective. Careful evaluation of asymptomatic patients, including and electrocardiogram and a period of observation, is indicated. Patients ingesting a nonsustained

  11. Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats.

    PubMed

    Pelloux, Yann; Dilleen, Ruth; Economidou, Daina; Theobald, David; Everitt, Barry J

    2012-10-01

    Whereas the majority of cocaine users quit as they experience the negative consequences of drug use, some lose control over their drug taking and compulsively seek drugs. We report that 20% of rats compulsively seek cocaine despite intermittent negative outcomes after escalating their cocaine self-administration. This compulsive subgroup showed marked reductions in forebrain serotonin utilization; increasing serotonin transmission reduced their compulsive cocaine seeking. Depleting forebrain serotonin induced compulsive cocaine seeking in rats with a limited cocaine taking history; this was reversed by systemic treatment with a 5-hydroxytryptamine (5-HT2C) receptor agonist and mimicked by systemic treatment with a 5-HT2C receptor antagonist in intact animals. These results indicate the causal involvement of reduced serotoninergic transmission in the emergence of compulsive drug seeking after a long cocaine-taking history. PMID:22763621

  12. Antimony (Sb) and arsenic (As) in Sb mining impacted paddy soil from Xikuangshan, China: differences in mechanisms controlling soil sequestration and uptake in rice.

    PubMed

    Okkenhaug, Gudny; Zhu, Yong-Guan; He, Junwen; Li, Xi; Luo, Lei; Mulder, Jan

    2012-03-20

    Foods produced on soils impacted by antimony (Sb) mining activities are a potential health risk due to plant uptake of the contaminant metalloids (Sb) and arsenic (As). Here we report for the first time the chemical speciation of Sb in soil and porewater of flooded paddy soil, impacted by active Sb mining, and its effect on uptake and speciation in rice plants (Oryza sativa L. cv Jiahua). Results are compared with behavior and uptake of As. Pot experiments were conducted under controlled conditions in a climate chamber over a period of 50 days. In pots without rice plants, flooding increased both the concentration of dissolved Sb (up to ca. 2000 μg L(-1)) and As (up to ca. 1500 μg L(-1)). When rice was present, Fe plaque developing on rice roots acted as a scavenger for both As and Sb, whereby the concentration of As, but not Sb, in porewater decreased substantially. Dissolved Sb in porewater, which occurred mainly as Sb(V), correlated with Ca, indicating a solubility governed by Ca antimonate. No significant differences in bioaccumulation factor and translocation factor between Sb and As were observed. Greater relative concentration of Sb(V) was found in rice shoots compared to rice root and porewater, indicating either a preferred uptake of Sb(V) or possibly an oxidation of Sb(III) to Sb(V) in shoots. Adding soil amendments (olivine, hematite) to the paddy soil had no effect on Sb and As concentrations in porewater. PMID:22309044

  13. Prediction of the 3D structure for the rat urotensin II receptor and comparison of the antagonist binding sites and binding selectivity between human and rat from atomistic simulations

    PubMed Central

    Kim, Soo-Kyung; Li, Youyong; Park, Changmoon; Abrol, Ravinder

    2012-01-01

    Urotensin-II (U-II) has been shown to be the most potent mammalian vasoconstrictor known.[1, 2] Thus a U-II antagonist might be of therapeutic value in a number of cardiovascular disorders.[3] However, interspecies variability of several nonpeptidic ligands complicates the interpretation of in vivo studies of such antagonists in pre-clinical animal models of disease. Thus compound ACT058362 is a selective antagonist for human U-II receptor (hUT2R) with a reported Kd ~ 4 nM in a molecular binding assay, but it is reported to bind weakly to rat UT2R (rUT2R), with Kd ~ 1,500 nM.[4] In contrast, the arylsulphonamide SB706375 is a selective antagonist against both hUT2R (Kd: ~ 9 nM) and rUT2R (Kd: ~ 21 nM).[3] To understand the species selectivity of the UT2R, we investigated the binding site of ACT058362 and SB706375 complex with both hUT2R and rUT2R to explain the dramatic (~ 400-fold) lower affinity of ACT058362 for rUT2R and the similar (~10 nM) affinity of SB706375 for both UT2R. These studies.used MembStruk and MSCDock to predict the UT2R structure and the binding site for ACT058362 and SB706375. Based on binding energy, we found two binding modes each with D1303.32 as the crucial anchoring point. We predict that ACT058362 (an aryl-amine-aryl or ANA ligand) binds in the TM 3456 region while we predict that SB706375 (an aryl-aryl-amine or AAN ligand) binds in the TM 1237 region. These predicted sites explain the known differences in binding the ANA ligand to rat and human while explaining the similar binding of the AAN compound to rat and human. Moreover the predictions explain currently available SAR data. To further validate the predicted binding site of these ligands to hUT2R and rUT2R, we propose several mutations that would help define the structural origins of differential responses of UT2R among species potentially indicating novel UT2R antagonists with cross-species high affinity. PMID:20683923

  14. PathCase-SB architecture and database design

    PubMed Central

    2011-01-01

    Background Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks. Description PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database and KEGG), and to provide more powerful and/or new capabilities via the new web-based integrative framework. This paper describes architecture and database design issues encountered in PathCase-SB's design and implementation, and presents the current design of PathCase-SB's architecture and database. Conclusions PathCase-SB architecture and database provide a highly extensible and scalable environment with easy and fast (real-time) access to the data in the database. PathCase-SB itself is already being used by researchers across the world. PMID:22070889

  15. Memristive Switching in Bi(1-x)Sb(x) Nanowires.

    PubMed

    Han, Nalae; Park, Myung Uk; Yoo, Kyung-Hwa

    2016-04-13

    We investigated the memristive switching behavior in bismuth-antimony alloy (Bi(1-x)Sb(x)) single nanowire devices at 0.1 ≤ x ≤ 0.42. At 0.15 ≤ x ≤ 0.42, most Bi(1-x)Sb(x) single nanowire devices exhibited bipolar resistive switching (RS) behavior with on/off ratios of approximately 10(4) and narrow variations in switching parameters. Moreover, the resistance values in the low-resistance state (LRS) were insensitive to x. On the other hand, at 0.1 ≤ x ≤ 0.15, some Bi(1-x)Sb(x) single nanowire devices showed complementary RS-like behavior, which was ascribed to asymmetric contact properties. Transmission electron microscopy and elemental mapping images of Bi, Sb, and O obtained from the cross sections of the Bi(1-x)Sb(x) single nanowire devices, which were cut before and after RS, revealed that the mobile species was Sb ions, and the migration of the Sb ions to the nanowire surface brought the switch to LRS. In addition, we demonstrated that two types of synaptic plasticity, namely, short-term plasticity and long-term potentiation, could be implemented in Bi(1-x)Sb(x) nanowires by applying a sequence of voltage pulses with different repetition intervals. PMID:27042861

  16. Fragile structural transition in Mo3Sb7

    DOE PAGESBeta

    Yan, Jiaqiang -Q.; McGuire, Michael A; May, Andrew F; Parker, David S.; Mandrus, D. G.; Sales, Brian C.

    2015-08-10

    Mo3Sb7 single crystals lightly doped with Cr, Ru, or Te are studied in order to explore the interplay between superconductivity, magnetism, and the cubic-tetragonal structural transition. The structural transition at 53 K is extremely sensitive to Ru or Te substitution which introduces additional electrons, but robust against Cr substitution. We observed no sign of a structural transition in superconducting Mo2.91Ru0.09Sb7 and Mo3Sb6.975Te0.025. In contrast, 3 at.% Cr doping only slightly suppresses the structural transition to 48 K while leaving no trace of superconductivity above 1.8 K. Analysis of magnetic properties suggests that the interdimer interaction in Mo3Sb7 is near amore » critical value and essential for the structural transition. Futhermore, all dopants suppress the superconductivity of Mo3Sb7. The tetragonal structure is not necessary for superconductivity.« less

  17. Anomalous transport of Sb in laser irradiated Ge

    SciTech Connect

    Bruno, E.; Scapellato, G. G.; Boninelli, S.; Priolo, F.; Privitera, V.; La Magna, A.; Cuscuna, M.; Fortunato, G.; Napolitani, E.

    2012-10-22

    Excimer laser annealing is shown to be very promising to promote Sb incorporation in Ge up to concentrations as high as 1 Multiplication-Sign 10{sup 21} at./cm{sup 3}. However, we demonstrate that when Ge is melted by laser irradiation, a high excess of vacancies is generated in the molten region. These vacancies induce Sb electrical deactivation at the melt depth through the formation of Sb{sub m}-V{sub n} complexes that act as a sink for further Sb atoms, even leading Sb to back-diffuse towards the surface, against the concentration gradient. These results are fundamental for the realization of new generation Ge-based micro and optoelectronic devices.

  18. Thermally induced native defect transform in annealed GaSb

    NASA Astrophysics Data System (ADS)

    Jie, Su; Tong, Liu; Jing-Ming, Liu; Jun, Yang; Yong-Biao, Bai; Gui-Ying, Shen; Zhi-Yuan, Dong; Fang-Fang, Wang; You-Wen, Zhao

    2016-07-01

    Undoped p-type GaSb single crystals were annealed at 550–600 °C for 100 h in ambient antimony. The annealed GaSb samples were investigated by Hall effect measurement, glow discharge mass spectroscopy (GDMS), infrared (IR) optical transmission and photoluminescence (PL) spectroscopy. Compared with the as-grown GaSb single crystal, the annealed GaSb samples have lower hole concentrations and weak native acceptor related PL peaks, indicating the reduction of the concentration of gallium antisite related native acceptor defects. Consequently, the below gap infrared transmission of the GaSb samples is enhanced after the thermal treatment. The mechanism about the reduction of the native defect concentration and its influence on the material property were discussed. Project supported by the National Natural Science Foundation of China (Grant Nos. 61474104 and 61504131).

  19. Fragile structural transition in Mo3Sb7

    NASA Astrophysics Data System (ADS)

    Yan, J.-Q.; McGuire, M. A.; May, A. F.; Parker, D.; Mandrus, D. G.; Sales, B. C.

    2015-08-01

    Mo3Sb7 single crystals lightly doped with Cr, Ru, or Te are studied in order to explore the interplay between superconductivity, magnetism, and the cubic-tetragonal structural transition. The structural transition at 53 K is extremely sensitive to Ru or Te substitution which introduces additional electrons, but robust against Cr substitution. No sign of a structural transition was observed in superconducting Mo2.91Ru0.09Sb7 and Mo3Sb6.975Te0.025 . In contrast, 3 at.% Cr doping only slightly suppresses the structural transition to 48 K while leaving no trace of superconductivity above 1.8 K. Analysis of magnetic properties suggests that the interdimer interaction in Mo3Sb7 is near a critical value and essential for the structural transition. All dopants suppress the superconductivity of Mo3Sb7 . The tetragonal structure is not necessary for superconductivity.

  20. Near-surface depletion of antimony during the growth of GaAsSb and GaAs/GaAsSb nanowires

    SciTech Connect

    Kauko, H.; Helvoort, A. T. J. van; Fimland, B. O.; Munshi, A. M.; Grieb, T.; Müller, K.; Rosenauer, A.

    2014-10-14

    The near-surface reduction of the Sb mole fraction during the growth of GaAsSb nanowires (NWs) and GaAs NWs with GaAsSb inserts has been studied using quantitative high-angle annular dark field scanning transmission electron microscopy (STEM). A model for diffusion of Sb in the hexagonal NWs was developed and employed in combination with the quantitative STEM analysis. GaAsSb NWs grown by Ga-assisted molecular beam epitaxy (MBE) and GaAs/GaAsSb NWs grown by Ga- and Au-assisted MBE were investigated. At the high temperatures employed in the NW growth, As-Sb exchange at and outward diffusion of Sb towards the surface take place, resulting in reduction of the Sb concentration at and near the surface in the GaAsSb NWs and the GaAsSb inserts. In GaAsSb NWs, an increasing near-surface depletion of Sb was observed towards the bottom of the NW due to longer exposure to the As beam flux. In GaAsSb inserts, an increasing change in the Sb concentration profile was observed with increasing post-insert axial GaAs growth time, resulting from a combined effect of radial GaAs overgrowth and diffusion of Sb. The effect of growth temperature on the diffusion of Sb in the GaAsSb inserts was identified. The consequences of these findings for growth optimization and the optoelectronic properties of GaAsSb are discussed.

  1. Thermoelectric Performance of Bi0.5Sb1.5Te3/Sb Composites Fabricated by Electroless Plating and Spark Plasma Sintering

    NASA Astrophysics Data System (ADS)

    Sie, F. R.; Hwang, C. S.; Kuo, C. H.; Chou, Y. W.; Yeh, C. H.; Ho, H. Y.; Lin, Y. L.; Lan, C. H.

    2015-06-01

    This study reports semi-metal/semi-conductor composites with enhanced thermoelectric performance that results from interface effects between Sb clusters and the Bi0.5Sb1.5Te3 matrix. The Sb clusters were dispersed on the surface of Bi0.5Sb1.5Te3 powders by electroless plating and then the powders were rapidly compacted by spark plasma sintering at 673 K and 50 MPa. The thermoelectric properties for Bi0.5Sb1.5Te3 and Bi0.5Sb1.5Te3/Sb bulk samples were measured in the temperature range of 300 K to 500 K. The electrical conductivity of Bi0.5Sb1.5Te3/Sb composites was enhanced at room temperature due to the increase in carrier concentration with increasing Sb content. The enhancement in the power factor of Bi0.5Sb1.5Te3/Sb composites was due to a high Seebeck coefficient at high measured temperature. Moreover, the Sb clusters acted as effective phonon scattering centers, which decreased the lattice thermal conductivity at high temperature. In comparison with Bi0.5Sb1.5Te3, the maximum value of ZT for Bi0.5Sb1.5Te3/Sb (2.8 wt.%) samples was enhanced from 0.21 to 0.54 at 500 K. Consequently, the optimal operation temperature of Bi0.5Sb1.5Te3/Sb composites shifted to higher temperature compared to that for Bi0.5Sb1.5Te3 bulk.

  2. Autocrine control of MIP-2 secretion from metastatic breast cancer cells is mediated by CXCR2: a mechanism for possible resistance to CXCR2 antagonists.

    PubMed

    Erin, Nuray; Nizam, Esra; Tanrıöver, Gamze; Köksoy, Sadi

    2015-02-01

    CXCR2 interacts with a wide range of chemokines and CXCR2 antagonists may have therapeutic value for treatment-resistant metastatic carcinomas. We aimed to explore regulation of activity of CXCR2 and its ligand, MIP-2, in metastatic breast carcinoma. We used mouse breast carcinoma cells metastasize to brain (4TBM), liver (4TLM), and heart (4THM) and explored the extra- and intracellular mechanisms effecting MIP-2 secretion using CXCR2 antagonist and inhibitors of downstream signaling molecules. 4TBM, 4TLM, and 4THM cells include cancer stem cell features and metastasize extensively. We also determined kinetics of MIP-2 secretion in 4T1 and non-metastatic 67NR mouse breast carcinoma cells. We found that there is an autocrine-inhibition of MIP-2 secretion. Specifically, metastatic cells selectively express CXCR2 only, and not CXCR1 and attenuating CXCR2 activity with SB225002 increased MIP-2 secretion. This may be due to the inhibition of protein kinase C (PKC) activity since RO318220; a specific inhibitor of PKC also increased MIP-2 secretion. Attenuating CXCR2 activity with SB225002, otherwise suppressed proliferation of 4THM and 4TBM cells. Tumor explants and cancer-associated fibroblasts obtained from 4TLM, 4THM, and 4TBM primary tumors secreted high levels of MIP-2. Surprisingly, CXCR2 expression was low in 4TLM cells demonstrating that liver metastatic cells might be resistant to the anti-tumoral effects of CXCR2 antagonists. Our results demonstrated that resistance to anti-proliferative effects of CXCR2 may also arise from feedback increases in MIP-2 secretion. Activation of PI3 K pathway augments MIP-2 secretion, hence possible resistance to the antitumor effects of CXCR2 antagonists might be prevented with inhibitors of PI3 K. PMID:25682075

  3. Demonstration of Sn-seeded GaSb homo- and GaAs-GaSb heterostructural nanowires

    NASA Astrophysics Data System (ADS)

    Tornberg, Marcus; Mårtensson, Erik K.; Zamani, Reza R.; Lehmann, Sebastian; Dick, Kimberly A.; Gorji Ghalamestani, Sepideh

    2016-04-01

    The particle-assisted epitaxial growth of antimonide-based nanowires has mainly been realized using gold as the seed material. However, the Au-seeded epitaxial growth of antimonide-based nanowires such as GaSb nanowires presents several challenges such as for example direct nucleation issues and crystal structure tuning. Therefore, it is of great importance to understand the role of seed material choice and properties in the growth behavior of antimonide-based nanowires to obtain a deeper understanding and a better control on their formation processes. In this report, we have investigated the epitaxial growth of GaSb and GaAs-GaSb nanowires using in situ-formed tin seeds by means of metalorganic vapor phase epitaxy technique. This comprehensive report covers the growth of in situ-formed tin seeds and Sn-seeded GaSb nanowires on both GaAs and GaSb (111)B substrates, as well as GaAs-GaSb nanowires on GaAs (111)B substrates. The growth behavior and structural properties of the obtained GaSb nanowires are further investigated and compared with the Au-seeded counterparts. The results provided by this study demonstrate that Sn is a promising seed material for the growth of GaSb nanowires.

  4. Ge2Sb2Te5/Sb superlattice-like thin film for high speed phase change memory application

    NASA Astrophysics Data System (ADS)

    Hu, Yifeng; Zou, Hua; Zhang, Jianhao; Xue, Jianzhong; Sui, Yongxing; Wu, Weihua; Yuan, Li; Zhu, Xiaoqin; Song, Sannian; Song, Zhitang

    2015-12-01

    In order to improve the operation speed of phase change memory (PCM), superlattice-like Ge2Sb2Te5/Sb (SLL GST/Sb) thin films were prepared in a sputtering method to explore the suitability as an active material for PCM application. Compared with GST, SLL GST/Sb thin film has a lower crystallization temperature, crystallization activation energy, thermal conductivity, and smaller crystalline grain size. A faster SET/RESET switching speed (10 ns) and a lower operation power consumption (the energy for RESET operation 9.1 × 10-13 J) are obtained. In addition, GST/Sb shows a good endurance of 8.3 × 104 cycles.

  5. Effect of antimony nano-scale surface-structures on a GaSb/AlAsSb distributed Bragg reflector

    SciTech Connect

    Husaini, S.; Shima, D.; Ahirwar, P.; Rotter, T. J.; Hains, C. P.; Dang, T.; Bedford, R. G.; Balakrishnan, G.

    2013-02-11

    Effects of antimony crystallization on the surface of GaSb during low temperature molecular beam epitaxy growth are investigated. The geometry of these structures is studied via transmission electron and atomic force microscopies, which show the surface metal forms triangular-shaped, elongated nano-wires with a structured orientation composed entirely of crystalline antimony. By depositing antimony on a GaSb/AlAsSb distributed Bragg reflector, the field is localized within the antimony layer. Polarization dependent transmission measurements are carried out on these nano-structures deposited on a GaSb/AlAsSb distributed Bragg reflector. It is shown that the antimony-based structures at the surface favor transmission of light polarized perpendicular to the wires.

  6. Ohmic Contacts to n-type GaSb and n-type GaInAsSb

    SciTech Connect

    R.K. Huang; C.A. Wang; C.T. Harris; M.K. Connors; D.A. Shiau

    2003-06-16

    An investigation with the objective of improving n-type ohmic contacts to GaSb-based devices is described. This study involves a series of n-GaInAsSb and n-GaSb samples with varying doping, grown on both n-GaSb and semi-insulating GaAs substrates. These samples were fabricated into mesa-etched TLM structures, and the specific contact resistivity and sheet resistance of these layers as a function of majority electron concentration were measured. Extremely low specific contact resistivities of about 2 x 10{sup -6} {Omega}-cm{sup 2} and sheet resistances of about 4 {Omega}/{open_square} are found for n-type GaInAsSb doped at about 3 x 10{sup 18} cm{sup -3}.

  7. Inductively Coupled Plasma Reactive Ion Etching of AlGaAsSb and InGaAsSb for Quaternary Antimonide MIM Thermophotovoltaics

    SciTech Connect

    Palmisiano, M. N.; Peake, G. M.; Shul, R. J.; Ashby, C. I.; Cederberg, J. G.; Hafich, M. J.; Biefeld, R. M.

    2002-10-01

    In this letter we report on the inductively coupled plasma reactive ion etching (ICP-RIE) of InGaAsSb and AlGaAsSb for the fabrication of quaternary monolithic interconnected module (MIM) thermophotovoltaic (TPV) devices. A rapid dry etch process is described that produces smooth surfaces using BCl[sub]3 for AlGaAsSb and InGaAsSb capped with GaSb. Uncapped InGaAsSb was etched by adding an H[sub]2 plasma preclean to reduce surface oxides. InGaAsSb etch rate was studied as a function of accelerating voltage, RF power, temperature and pressure. The etch conditions found for InGaAsSb were used for AlGaAsSb etching to determine the effectiveness for isolation of the MIM cells.

  8. Pharmacodynamic properties of leukotriene receptor antagonists.

    PubMed

    Nicosia, S

    1999-06-01

    Leukotrienes (LTs) are among the most important mediators of asthma; cysteine-containing LTs (cysteinyl-LTs, i.e. LTC4, LTD4 and LTE4) are very potent bronchoconstrictors and participate in the inflammatory component of asthma by inducing mucus hypersecretion, plasma extravasation, mucosal oedema and eosinophil recruitment. Therefore, compounds able to inhibit either the formation or the action of LTs are potential antiasthma drugs and, at present, the cysteinyl-LT receptor antagonists (LTRAs) appear to be the most promising. The receptors for cysteinyl-LTs, termed CysLT receptors, are heterogeneous; at least two different classes have so far been recognized, named CysLT1 (blocked by the so-called classical antagonists, such as FPL 55712, ICI 198,615, ICI 204,219, SK&F 104353, MK-476 and others) and CysLT2 (insensitive to the classical antagonists, but sensitive to BAY u9773). The authors' results indicate that even more receptor subclasses might exist in human airways, which discriminate between LTC4 and LTD4, both asthma mediators. Among the many LTRAs, zafirlukast (Accolate, ICI 204,219), montelukast (Singulair, MK-476) and pranlukast (Onon, ONO-1078) are available for clinical use. All the LTRAs are able to inhibit LTD4-induced bronchoconstriction in humans, albeit with different potencies. With respect to antigen challenge, all of them inhibit the early phase of response, whereas only the most recently developed and potent ones are effective in the late phase. LTRAs are effective in asthma triggered by exercise, cold or aspirin. Furthermore, although they are not bronchodilators per se, they increase basal forced expiratory volume in one second in patients with mild-to-moderate asthma, indicating that, in these individuals, constant cysteinyl-LT release contributes to maintaining increased bronchial tone. Finally, the effect of LTRAs is additive to that of beta-agonists and is potentiated by antihistamine compounds. In conclusion, the available results clearly

  9. Novel paramagnetic AT1 receptor antagonists.

    PubMed

    Tan, Nichole P H; Taylor, Michelle K; Bottle, Steven E; Wright, Christine E; Ziogas, James; White, Jonathan M; Schiesser, Carl H; Jani, Nitya V

    2011-11-28

    Novel paramagnetic selective angiotensin AT(1) receptor antagonists (sartans) bearing nitroxides (3, 4) have been prepared and their pharmacology evaluated in vitro as well as in vivo. Compounds 3, 4 proved to be effective sartans with pK(B) estimates in the range 6.2-9.1. In addition, the sodium salt (11) of 4 (R = Bu) is able to protect against vascular injury in hypertensive rats as determined by its ability to attenuate the development of intimal thickening caused by balloon injury of the carotid artery. PMID:21963998

  10. Mineralocorticoid receptor antagonists and endothelial function

    PubMed Central

    Maron, Bradley A.; Leopold, Jane A.

    2010-01-01

    Hyperaldosteronism has been associated with endothelial dysfunction and impaired vascular reactivity in patients with hypertension or congestive heart failure. The mineralocorticoid receptor (MR) antagonists spironolactone and eplerenone have been shown to reduce morbidity and mortality, in part, by ameliorating the adverse effects of aldosterone on vascular function. Although spironolactone and eplerenone are increasingly utilized in patients with cardiovascular disease, widespread clinical use is limited by the development of gynecomastia with spironolactone and hyperkalemia with both agents. This suggests that the development of newer agents with favorable side effect profiles is warranted. PMID:18729003

  11. Agonists and antagonists for P2 receptors

    PubMed Central

    Jacobson, Kenneth A.; Costanzi, Stefano; Joshi, Bhalchandra V.; Besada, Pedro; Shin, Dae Hong; Ko, Hyojin; Ivanov, Andrei A.; Mamedova, Liaman

    2015-01-01

    Recent work has identified nucleotide agonists selective for P2Y1, P2Y2 and P2Y6 receptors and nucleotide antagonists selective for P2Y1, P2Y12 and P2X1 receptors. Selective non-nucleotide antagonists have been reported for P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, P2X2/3/P2X3 and P2X7 receptors. For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non-nucleotide antagonist A-317491 is selective for P2X2/3/P2X3 receptors. Nucleotide analogues in which the ribose moiety is substituted by a variety of novel ring systems, including conformation-ally locked moieties, have been synthesized as ligands for P2Y receptors. The focus on conformational factors of the ribose-like moiety allows the inclusion of general modifications that lead to enhanced potency and selectivity. At P2Y1,2,4,11 receptors, there is a preference for the North conformation as indicated with (N)-methanocarba analogues. The P2Y1 antagonist MRS2500 inhibited ADP-induced human platelet aggregation with an IC50 of 0.95 nM. MRS2365, an (N)-methanocarba analogue of 2-MeSADP, displayed potency (EC50) of 0.4 nM at the P2Y1 receptor, with >10 000-fold selectivity in comparison to P2Y12 and P2Y13 receptors. At P2Y6 receptors there is a dramatic preference for the South conformation. Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies. Detailed three-dimensional structures of P2X receptors have not yet been proposed. PMID:16805423

  12. Enhanced separation efficiency of photoinduced charges for antimony-doped tin oxide (Sb-SnO2)/TiO2 heterojunction semiconductors with varied Sb doping concentration

    NASA Astrophysics Data System (ADS)

    Zhang, Zhen-Long; Ma, Wen-Hai; Mao, Yan-Li

    2014-09-01

    In this paper, antimony-doped tin oxide (Sb-SnO2) nanoparticles were synthesized with varied Sb doping concentration, and the Sb-SnO2/TiO2 heterojunction semiconductors were prepared with Sb-SnO2 and TiO2. The separation efficiency of photoinduced charges was characterized with surface photovoltage (SPV) technique. Compared with Sb-SnO2 and TiO2, Sb-SnO2/TiO2 presents an enhanced separation efficiency of photoinduced charges, and the SPV enhancements were estimated to be 1.40, 1.43, and 1.99 for Sb-SnO2/TiO2 composed of Sb-SnO2 with the Sb doping concentration of 5%, 10%, and 15%, respectively. To understand the enhancement, the band structure of Sb-SnO2 and TiO2 in the heterojunction semiconductor was determined, and the conduction band offsets (CBO) between Sb-SnO2 and TiO2 were estimated to be 0.56, 0.64, and 0.98 eV for Sb-SnO2/TiO2 composed of Sb-SnO2 with the Sb doping concentration of 5%, 10%, and 15%, respectively. These results indicate that the separation efficiency enhancement is resulting from the energy level matching, and the increase of enhancement is due to the rising of CBO.

  13. Maximizing SB3 Waste Throughput Melt Rate Tests

    SciTech Connect

    Smith, M. E.; Miller, D. H.

    2005-09-01

    The Defense Waste Processing Facility (DWPF) is presently vitrifying Sludge Batch 3 (SB3) and preparing to process Sludge Batch 4 (SB4) in late 2006 or early 2007. Previous laboratory testing and DWPF operational experience has indicated that the maximum waste throughput peak for the Sludge Batch 2 (SB2) system occurs at a waste loading in the mid-30's. This trend has been shown as well for SB3 on a lab-scale basis. These SB3 tests used SRAT product that targeted a REDuction/OXidation (REDOX) of 0.2 and an acid stoichiometry of 135%. Acid stoichiometry, however, has been shown to impact melt rate of MRF tests at one waste loading (35%). Due to the impact of acid stoichiometry on melt rate, it is possible that the current target acid stoichiometry (155%) with SB3 may not exhibit the same maximum waste throughput peak, or there may not even be a discernable peak. In fact, current DWPF operational experience with SB3 and Frit 418 has not shown the same drop off in melt rate and hence waste throughput as was observed with SB2 and Frit 320. The objective of this testing is to determine if increasing the overall alkali content in the feed (via using the higher alkali Frit 320 versus Frit 418) will either result in a shift in the waste throughput to higher waste loadings or an increase in the overall waste throughput at waste loadings of interest (31 to 41%). For these tests, the target Sludge Receipt and Adjustment Tank (SRAT) product REDOX was 0.2 and the target acid stoichiometry was 155%. The incentive for this series of tests stems from a previous Slurry-Fed Melt Rate Furnace (SMRF) test with SB3/Frit 320 feed which showed an increase in melt rate versus SB3/Frit 418 at 35% waste loading. This single data point suggests that overall waste throughput for the SB3/Frit 320 system is higher at 35% waste loading (i.e., the melt rate versus waste loading curve has potentially shifted upward). To address the potential shift in waste throughput, the strategy was to fully

  14. Photoelectrochemical Properties of Nanocrystalline Sb6O13, MgSb2O6, and ZnSb2O6-Based Electrodes for Dye-Sensitized Solar Cells

    NASA Astrophysics Data System (ADS)

    Jang, Jiyeon; Kim, Seung-Joo

    2012-10-01

    Three kinds of antimony compounds - Sb6O13, MgSb2O6 and ZnSb2O6 - were prepared in the form of nanocrystalline film and their photo-electrochemical properties were investigated. The preparation of Sb6O13 was based on thermolysis of a colloidal Sb2O5·4H2O suspension. MgSb2O6 and ZnSb2O6 were prepared via low-temperature hydrothermal methods. All the compounds exhibited semiconducting properties applicable to dye-sensitized solar cell (DSSC). The energy band gaps were estimated to be 3.39 eV for Sb6O13, 3.60 eV for MgSb2O6, and 3.31 eV for ZnSb2O6, respectively. After sensitization with a conventional ruthenium-dye (N719), Sb6O13-based solar cell exhibited the highest open circuit voltage (Voc = 0.76 V) whereas the Voc values (0.44-0.46 V) of MgSb2O6 and ZnSb2O6 are relatively low. The Voc values were proven to be related to the flat band potentials of the antimony compounds. The overall solar-to-electric energy conversion efficiencies were in the range of 0.7-1.0% under AM 1.5, 100 mW/cm2 illumination.

  15. The reaction mechanism of SnSb and Sb thin film anodes for Na-ion batteries studied by X-ray diffraction, 119Sn and 121Sb Mössbauer spectroscopies

    DOE PAGESBeta

    Baggetto, Loïc; Hah, Hien-Yoong; Jumas, Jean-Claude; Johnson, Charles E.; Johnson, Jacqueline A.; Keum, Jong K.; Bridges, Craig A.; Veith, Gabriel M.

    2014-06-01

    The electrochemical reaction of Sb and SnSb anode materials with Na results in the formation of amorphous materials. To understand the resulting phases and electrochemical capacities we studied the reaction products local order using 119Sn and 121Sb Mössbauer spectroscopies in conjunction with measurements performed on model powder compounds of Na-Sn and Na-Sb to further clarify the reactions steps. For pure Sb the discharge (sodiation) starts with the formation of an amorphous phase composed of atomic environments similar to those found in NaSb, and proceeds further by the formation of environments similar to that present in Na3Sb. The reversible reaction takesmore » place during a large portion of the charge process. At full charge the anode material still contains a substantial fraction of Na, which explains the lack of recrystallization into crystalline Sb. The reaction of SnSb yields Na3Sb crystalline phase at full discharge at higher temperatures (65 and 95°C) while the room temperature reaction yields amorphous compounds. The electrochemically-driven, solid-state amorphization reaction occurring at room temperature is governed by the simultaneous formation of Na-coordinated Sn and Sb environments, as monitored by the decrease (increase) of the 119Sn (121Sb) Mössbauer isomer shifts. Overall, the monitoring of the hyperfine parameters enables to correlate the changes in Na content to the individual Sn and Sb local chemical environments.« less

  16. Rational discovery of novel nuclear hormone receptor antagonists

    NASA Astrophysics Data System (ADS)

    Schapira, Matthieu; Raaka, Bruce M.; Samuels, Herbert H.; Abagyan, Ruben

    2000-02-01

    Nuclear hormone receptors (NRs) are potential targets for therapeutic approaches to many clinical conditions, including cancer, diabetes, and neurological diseases. The crystal structure of the ligand binding domain of agonist-bound NRs enables the design of compounds with agonist activity. However, with the exception of the human estrogen receptor-, the lack of antagonist-bound "inactive" receptor structures hinders the rational design of receptor antagonists. In this study, we present a strategy for designing such antagonists. We constructed a model of the inactive conformation of human retinoic acid receptor- by using information derived from antagonist-bound estrogen receptor-α and applied a computer-based virtual screening algorithm to identify retinoic acid receptor antagonists. Thus, the currently available crystal structures of NRs may be used for the rational design of antagonists, which could lead to the development of novel drugs for a variety of diseases.

  17. Subthreshold behavior of AlInSb/InSb high electron mobility transistors

    NASA Astrophysics Data System (ADS)

    Theodore Chandra, S.; B. Balamurugan, N.; G. Lakshmi, Priya; Manikandan, S.

    2015-07-01

    We propose a scaling theory for single gate AlInSb/InSb high electron mobility transistors (HEMTs) by solving the two-dimensional (2D) Poisson equation. In our model, the effective conductive path effect (ECPE) is taken into account to overcome the problems arising from the device scaling. The potential in the effective conducting path is developed and a simple scaling equation is derived. This equation is solved to obtain the minimum channel potential Φdeff,min and the new scaling factor α to model the subthreshold behavior of the HEMTs. The developed model minimizes the leakage current and improves the subthreshold swing degradation of the HEMTs. The results of the analytical model are verified by numerical simulation with a Sentaurus TCAD device simulator. Project supported by the Council of Scientific & Industrial Research (CSIR), Government of India under the SRF Scheme (Sanction Letter No: 08/237(0005)/2012-EMR-I).

  18. Lattice thermal conductivity of Bi, Sb, and Bi-Sb alloy from first principles

    NASA Astrophysics Data System (ADS)

    Lee, Sangyeop; Esfarjani, Keivan; Mendoza, Jonathan; Dresselhaus, Mildred S.; Chen, Gang

    2014-02-01

    Using first principles, we calculate the lattice thermal conductivity of Bi, Sb, and Bi-Sb alloys, which are of great importance for thermoelectric and thermomagnetic cooling applications. Our calculation reveals that the ninth-neighbor harmonic and anharmonic force constants are significant; accordingly, they largely affect the lattice thermal conductivity. Several features of the thermal transport in these materials are studied: (1) the relative contributions from phonons and electrons to the total thermal conductivity as a function of temperature are estimated by comparing the calculated lattice thermal conductivity to the measured total thermal conductivity, (2) the anisotropy of the lattice thermal conductivity is calculated and compared to that of the electronic contribution in Bi, and (3) the phonon mean free path distributions, which are useful for developing nanostructures to reduce the lattice thermal conductivity, are calculated. The phonon mean free paths are found to range from 10 to 100 nm for Bi at 100 K.

  19. InGaAsSb/AlGaAsSb Heterojunction Phototransistors for Infrared Applications

    NASA Technical Reports Server (NTRS)

    Refaat, Tamer F.; Abedin, M. N.; Sulima, Oleg V.; Ismail, Syed; Singh, Upendra N.

    2006-01-01

    High quality infrared (IR) quantum detectors are important for several applications, such as atmospheric remote sensing, chemical detection and absorption spectroscopy. Although several IR detectors are commercially available, with different materials and structures, they provide limited performance regarding the signal-to-noise ratio and the corresponding minimum detectable signal. InGaAsSb/AlGaAsSb heterojunction based phototransistors show strong potential for developing IR sensors with improved performance. In this paper, the performance of a novel npn InGaAsSb/AlGaAsSb heterojunction phototransistor is presented. This performance study is based on experimental characterization of the device dark current, noise and spectral response. Detectivity of 1.7x10(exp 9) cmHz(exp 1/2)/W at 2 microns was obtained at 100 C temperature and 2 V bias voltage. This corresponds to a responsivity of 94.7 A/W and an internal gain of 156 with about 37.7% quantum efficiency. Reducing the temperature to -30 C allows to increase the bias to 3V and enhance the detectivity to 8.7x10(exp 10) cmHz(exp 1/2)/W at the same wavelength, which corresponds to a responsivity of 386.5 A/W and an internal gain of 288.2 with about 83.3% quantum efficiency. The device impulse response and linearity, including the corresponding dynamic range, also are presented. Impulse response analysis indicated a settling time of about 1.1 s at 2V and 100 C, while linearity measurements indicated a constant responsivity in the radiation intensity range of 1.6x10(exp -7) W/sq cm and 31.6 mW/sq cm.

  20. Unusual crystallization behavior in Ga-Sb phase change alloys

    SciTech Connect

    Putero, Magali Coulet, Marie-Vanessa; Ouled-Khachroum, Toufik; Muller, Christophe; Baehtz, Carsten; Raoux, Simone

    2013-12-01

    Combined in situ X-ray scattering techniques using synchrotron radiation were applied to investigate the crystallization behavior of Sb-rich Ga-Sb alloys. Measurements of the sheet resistance during heating indicated a reduced crystallization temperature with increased Sb content, which was confirmed by in situ X-ray diffraction. The electrical contrast increased with increasing Sb content and the resistivities in both the amorphous and crystalline phases decreased. It was found that by tuning the composition between Ga:Sb = 9:91 (in at.%) and Ga:Sb = 45:55, the change in mass density upon crystallization changes from an increase in mass density which is typical for most phase change materials to a decrease in mass density. At the composition of Ga:Sb = 30:70, no mass density change is observed which should be very beneficial for phase change random access memory (PCRAM) applications where a change in mass density during cycling is assumed to cause void formation and PCRAM device failure.

  1. InSb thin films grown by electrodeposition

    SciTech Connect

    Singh, Joginder Rajaram, P.

    2014-04-24

    We have grown InSb thin films on Cu substrates using the electrodeposition technique. The electrochemical bath from which the InSb thin films were grown was made up of a mixture of aqueous solutions of 0.05 M InCl{sub 3} and 0.03M SbCl{sub 3}, 0 .20M citric acid and 0.30M sodium citrate. Citric acid and sodium citrate were used as complexing agents to bring the reduction potential of In and Sb closer to maintain binary growth. The electrodeposited films were characterized by structural, morphological and optical studies. X-ray diffraction studies show that the films are polycrystalline InSb having the zinc blende structure. Scanning electron microscopy (SEM) studies reveal that the surface of the films is uniformly covered with submicron sized spherical particles. FTIR spectra of InSb thin films show a sharp absorption peak at wave number 1022 cm{sup −1} corresponding to the band gap. Hot probe analysis shows that the InSb thin films have p type conductivity.

  2. InSb thin films grown by electrodeposition

    NASA Astrophysics Data System (ADS)

    Singh, Joginder; Rajaram, P.

    2014-04-01

    We have grown InSb thin films on Cu substrates using the electrodeposition technique. The electrochemical bath from which the InSb thin films were grown was made up of a mixture of aqueous solutions of 0.05 M InCl3 and 0.03M SbCl3, 0 .20M citric acid and 0.30M sodium citrate. Citric acid and sodium citrate were used as complexing agents to bring the reduction potential of In and Sb closer to maintain binary growth. The electrodeposited films were characterized by structural, morphological and optical studies. X-ray diffraction studies show that the films are polycrystalline InSb having the zinc blende structure. Scanning electron microscopy (SEM) studies reveal that the surface of the films is uniformly covered with submicron sized spherical particles. FTIR spectra of InSb thin films show a sharp absorption peak at wave number 1022 cm-1 corresponding to the band gap. Hot probe analysis shows that the InSb thin films have p type conductivity.

  3. Synthesis of actively adjustable springs by antagonistic redundant actuation

    NASA Technical Reports Server (NTRS)

    Yi, Byung-Ju; Freeman, Robert A.

    1992-01-01

    A methodology for active spring generation is presented based on antagonistic redundant actuation. Antagonistic properties are characterized using an effective system stiffness. 'Antagonistic stiffness' is generated by preloading a closed-chain (parallel) linkage system. Internal load distribution is investigated along with the necessary conditions for spring synthesis. The performance and stability of a proposed active spring are shown by simulation, and applications are discussed.

  4. Sexually antagonistic selection in human male homosexuality.

    PubMed

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni

    2008-01-01

    Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness), accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait. PMID:18560521

  5. Sexually Antagonistic Selection in Human Male Homosexuality

    PubMed Central

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni

    2008-01-01

    Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling ‘Darwinian paradox’. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness), accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait. PMID:18560521

  6. Small molecule TSHR agonists and antagonists.

    PubMed

    Neumann, S; Gershengorn, M C

    2011-04-01

    TSH activates the TSH receptor (TSHR) thereby stimulating the function of thyroid follicular cells (thyrocytes) leading to biosynthesis and secretion of thyroid hormones. Because TSHR is involved in several thyroid pathologies, there is a strong rationale for the design of small molecule "drug-like" ligands. Recombinant human TSH (rhTSH, Thyrogen(®)) has been used in the follow-up of patients with thyroid cancer to increase the sensitivity for detection of recurrence or metastasis. rhTSH is difficult to produce and must be administered by injection. A small molecule TSHR agonist could produce the same beneficial effects as rhTSH but with greater ease of oral administration. We developed a small molecule ligand that is a full agonist at TSHR. Importantly for its clinical potential, this agonist elevated serum thyroxine and stimulated thyroidal radioiodide uptake in mice after its absorption from the gastrointestinal tract following oral administration. Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate TSHR. We identified the first small molecule TSHR antagonists that inhibited TSH- and TSAb-stimulated signalling in primary cultures of human thyrocytes. Our results provide proof-of-principle for effectiveness of small molecule agonists and antagonists for TSHR. We suggest that these small molecule ligands are lead compounds for the development of higher potency ligands that can be used as probes of TSHR biology with therapeutic potential. PMID:21511239

  7. Antagonistic coevolution between quantitative and Mendelian traits.

    PubMed

    Yamamichi, Masato; Ellner, Stephen P

    2016-03-30

    Coevolution is relentlessly creating and maintaining biodiversity and therefore has been a central topic in evolutionary biology. Previous theoretical studies have mostly considered coevolution between genetically symmetric traits (i.e. coevolution between two continuous quantitative traits or two discrete Mendelian traits). However, recent empirical evidence indicates that coevolution can occur between genetically asymmetric traits (e.g. between quantitative and Mendelian traits). We examine consequences of antagonistic coevolution mediated by a quantitative predator trait and a Mendelian prey trait, such that predation is more intense with decreased phenotypic distance between their traits (phenotype matching). This antagonistic coevolution produces a complex pattern of bifurcations with bistability (initial state dependence) in a two-dimensional model for trait coevolution. Furthermore, with eco-evolutionary dynamics (so that the trait evolution affects predator-prey population dynamics), we find that coevolution can cause rich dynamics including anti-phase cycles, in-phase cycles, chaotic dynamics and deterministic predator extinction. Predator extinction is more likely to occur when the prey trait exhibits complete dominance rather than semidominance and when the predator trait evolves very rapidly. Our study illustrates how recognizing the genetic architectures of interacting ecological traits can be essential for understanding the population and evolutionary dynamics of coevolving species. PMID:27009218

  8. Lattice-Matched GaInAsSb on GaSb for TPV Cells

    NASA Astrophysics Data System (ADS)

    Welser, E.; Dimroth, F.; Ohm, A.; Guter, W.; Siefer, G.; Philipps, S.; Schöne, J.; Polychroniadis, E. K.; Konidaris, S.; Bett, A. W.

    2007-02-01

    GaInAsSb layers and TPV cells were grown by metalorganic vapor phase epitaxy (MOVPE) on GaSb substrates. GaInAsSb layers show two forms of phase separation, one inclined and the other one perpendicular to the surface. The latter was found to be sensitive to the reactor pressure and correlated to the rotation frequency of the wafers in the AIXTRON-2600G MOVPE reactor. TPV cell structures grown at different growth temperatures, V/III ratios and susceptor rotation frequencies have been investigated. The cells show efficiencies between 0.5 and 1.7 % under AM1.5g one-sun illumination conditions. Unfortunately, all cells have a low parallel resistance. The relative External Quantum Efficiency shows no significant difference between cells with different parallel resistance and short-circuit current density. This can be explained either through the inclined phase separation or by crystal defects resulting in a low shunt resistance at the pn-junction.

  9. Effect of aqueous Fe(II) on Sb(V) sorption on soil and goethite.

    PubMed

    Fan, Jian-Xin; Wang, Yu-Jun; Fan, Ting-Ting; Dang, Fei; Zhou, Dong-Mei

    2016-03-01

    The effects of Fe(II) on the sorption and precipitation of Sb(V) on soils and goethite were investigated using batch experiments and X-ray photoelectron spectroscopy (XPS) in this study. The sorption capacity of Sb(V) were much higher in anoxic soil than oxic soil. Typically, dissolved Fe(II) concentration in anoxic soils decreased significantly with increasing Sb(V), which may be suggestive of Fe-Sb precipitation. The elevated concentrations of Fe(II) (1 mM) enhanced the sorption capacity of Sb(V) on goethite significantly. However, synchrotron radiation X-ray diffraction showed no new characteristic peak, indicating that this Fe-Sb precipitate might be poor crystallinity or amorphous. Moreover, Sb(III) was detected in anoxic soil, and the reduction of Sb(V) to Sb (III) improved the sorption capacity of Sb in anoxic soil because of the low solubility and migration of Sb(III). Nevertheless, Fe-Sb co-precipitation and Sb(V) reduction to Sb(III) might contribute simultaneously to the increased sorption capacity of Sb(V) on anoxic soils. This research could improve our current understanding of soil Sb chemistry in paddy and wetland soils. PMID:26761596

  10. High Performance InGaAsSb TPV Cells

    SciTech Connect

    ZA Shellengarger; GC Taylor; RU Martinelli; JM Carpinelli

    2004-06-09

    Lattice-matched 0.52 eV InGaAsSb/GaSb thermophotovoltaic (TPV) cells are grown using a multi-wafer metal-organic-chemical-vapor-deposition (MOCVD) system. MOCVD growth series of P/N junction epitaxial structures consisting of as many as 30 wafers demonstrate good run-to-run reproducibility, good uniformity across the wafer and exhibit high performance with open circuit voltages of {approx}300mV and fill factors of 70% at 25 C. Growth parameters, including temperature, surface preparation and substrate orientation, that directly affect growth have been optimized for the active 0.52 eV InGaAsSb region and GaSb confinement layers. Focus is on increasing TPV diode performance through architectural improvements, specifically by reducing the minority carrier recombination velocity at the emitter and base front and back interfaces. Work in support of incorporating a back surface reflector (BSR) including the growth of N/P diode architectures and the addition of a lattice-matched InAsSb etch stop layer for substrate removal and wafer bonding, is reported. The lattice matched InAsSb stop etch exhibits resiliency to the substrate removal and wafer bonding processes. Substantial improvement in carrier lifetime on test structures with P-type AlGaAsSb layers indicated incorporation of these layers into the TPV cell structure should provide significant improvement in open-circuit voltage. Addition of AlGaAsSb confinement layers to the standard P/N cell structure gave some of the best InGaAsSb TPV cell results to date.

  11. InSb DRO array characteristics

    NASA Technical Reports Server (NTRS)

    Forrest, W. J.; Pipher, J. L.; Ninkov, Z.; Garnett, J. D.

    1989-01-01

    Researchers tested 58 x 62 low-doped InSb diode arrays bonded to MOSFET readouts for their performance potential in a low background space environment. Of primary concern were the quantum efficiency, dark current and read noise. The quantum efficiency (45 percent at 3.3 microns) and dark current (less than 2.4e(-)/s) were found to be adequate for the Space Infrared Telescope Facility (SIRTF) experiments, while the read noise (200 e(-) RMS) was found to be wanting. More subtle concerns, such as image quality, linearity/calibratibility and flat fielding were also investigated. In these respects the arrays appear to be well suited for the high sensitivity, photometric accuracy, and image clarity demanded by the SIRTF experiments.

  12. Modelling And Manufacturing GaSb TPV Converters

    NASA Astrophysics Data System (ADS)

    Algora, Carlos; Martín, Diego

    2003-01-01

    A complete model for GaSb TPV converters considering multiple real conditions (spectra, temperature, ARC, size, number and characteristics of grid fingers, size of busbar, etc.) is presented. The model has been applied to GaSb TPV converters fabricated in our laboratory by single zinc diffusion. The agreement between theory and experiments is very good. Future guides of performance improvement like the passivation of the surface together with the correspondent structure optimisation and the achievement of a better GaSb quality available more widespread are suggested.

  13. Point defect balance in epitaxial GaSb

    SciTech Connect

    Segercrantz, N. Slotte, J.; Makkonen, I.; Kujala, J.; Tuomisto, F.; Song, Y.; Wang, S.

    2014-08-25

    Positron annihilation spectroscopy in both conventional and coincidence Doppler broadening mode is used for studying the effect of growth conditions on the point defect balance in GaSb:Bi epitaxial layers grown by molecular beam epitaxy. Positron annihilation characteristics in GaSb are also calculated using density functional theory and compared to experimental results. We conclude that while the main positron trapping defect in bulk samples is the Ga antisite, the Ga vacancy is the most prominent trap in the samples grown by molecular beam epitaxy. The results suggest that the p–type conductivity is caused by different defects in GaSb grown with different methods.

  14. SB9: The ninth catalogue of spectroscopic binary orbits

    NASA Astrophysics Data System (ADS)

    Pourbaix, D.; Tokovinin, A. A.; Batten, A. H.; Fekel, F. C.; Hartkopf, W. I.; Levato, H.; Morrell, N. I.; Torres, G.; Udry, S.

    2004-09-01

    The Ninth Catalogue of Spectroscopic Binary Orbits (http://sb9.astro.ulb.ac.be) continues the series of compilations of spectroscopic orbits carried out over the past 35 years by Batten and collaborators. As of 2004 May 1st, the new Catalogue holds orbits for 2386 systems. Some essential differences between this catalogue and its predecessors are outlined and three straightforward applications are presented: (1) completeness assessment: period distribution of SB1s and SB2s; (2) shortest periods across the H-R diagram; (3) period-eccentricity relation.

  15. Thermophotovoltaic Converters Based on Poly-crystalline GaSb

    NASA Astrophysics Data System (ADS)

    Corregidor, V.; Vincent, J.; Algora, C.; Diéguez, E.

    2007-02-01

    In this work we present the development obtained on GaSb converters manufactured from GaSb polycrystals substrates since the last TPV Conference. As one of the main problem of these GaSb converters was the surface preparation, we present new surface treatments, besides higher structural quality of the ingots. The substrates were selected from polycrystalline ingots grown by vertical Bridgman technique. The electrical measurements show the n-type mobility values up to 1000 cm2ṡV-1ṡs-1. On these substrates, 4 mm2 thermophotovoltaic cells were manufactured and characterized by illuminated J-V curves and quantum efficiency techniques.

  16. Undercooling and solidification behavior in the InSb-Sb system. M.S. Thesis. Final Report

    NASA Technical Reports Server (NTRS)

    Graves, J. A.

    1985-01-01

    Use of the droplet emulsion technique has been successful in studying the undercooling and crystallization behavior of Sb, InSb, and an InSb-Sb eutectic alloy. Both droplet size and imposed cooling rate were influential in controlling the extent of liquid undercooling. The droplet surface coating was of significant importance in determining the resultant solidification product structure through its effect on nucleation kinetics. The maximum undercooling for pure Sb was extended from 0.08 to 0.23 T sub m. While simple crushing techniques provided a dramatic increase in droplet undercooling over the bulk material, emulsification treatments both enhanced this undercooling and allowed successful formation of a metastable simple cubic Sb phase. This phase was stable to temperatures approaching the melting point. The simple cubic phase was detected in droplet samples processed using DTA, air and water quenching, and drop tube processing under a helium gas atmosphere. A deviation in the InSb parent ingot composition limited interpretation of the line compound results, however, emulsification techniques extended the undercooling of this material to 0.17 T sub L and provided a stable, protective surface coating for the droplets. Emulsification of the eutectic alloy was effective at producing various levels of undercooling from 0.1 to 0.2 T sub E. Microstructural examination revealed a normal-type eutectic structure in the undercooled droplets indicating that solidification occurred within the coupled zone and that this zone is somewhat symmetric about the eutectic composition.

  17. High-performance GaInAsSb thermophotovoltaic devices with an AlGaAsSb window

    SciTech Connect

    Choi, H.K.; Wang, C.A.; Turner, G.W.; Manfra, M.J.; Spears, D.L.; Charache, G.W.; Danielson, L.R.; Depoy, D.M.

    1997-12-01

    A large increase in the quantum efficiency (QE) and open-circuit voltage V{sub oc} of GaInAsSb thermophotovoltaic (TPV) devices is obtained by the use of an AlGaAsSb window layer compared with devices without a window layer. The TPV structure, grown on GaSb substrates by organometallic vapor phase epitaxy or molecular beam epitaxy, consists of a 1-{mu}m-thick n-GaInAsSb base layer, a 3-{mu}m-thick p-GaInAsSb emitter layer, a 100-nm-thick AlGaAsSb window layer, and a 25-nm-thick GaSb contacting layer. The band-gap energy of the lattice-matched GaInAsSb is 0.53{endash}0.55 eV. The peak internal QE of the TPV cells with the window is {gt}90{percent}, compared with less than 60{percent} for those without the window. At a short-circuit current density of {approximately}1000mA/cm{sup 2}, V{sub oc} of {approximately}300meV is obtained for cells with the window layer, compared with less than 220 meV without the window layer. These increases are attributed to a substantial decrease in the surface recombination velocity with the window layer. Based on a standard calculation, the electron diffusion length in the p-GaInAsSb layer is at least 5 {mu}m. {copyright} {ital 1997 American Institute of Physics.}

  18. Hydrazine solution processed Sb2S3, Sb2Se3 and Sb2(S1−xSex)3 film: molecular precursor identification, film fabrication and band gap tuning

    PubMed Central

    Yang, Bo; Xue, Ding-Jiang; Leng, Meiying; Zhong, Jie; Wang, Liang; Song, Huaibing; Zhou, Ying; Tang, Jiang

    2015-01-01

    Sb2(S1−xSex)3 (0 ≤ x ≤ 1) compounds have been proposed as promising light-absorbing materials for photovoltaic device applications. However, no systematic study on the synthesis and characterization of polycrystalline Sb2(S1−xSex)3 thin films has been reported. Here, using a hydrazine based solution process, single-phase Sb2(S1−xSex)3 films were successfully obtained. Through Raman spectroscopy, we have investigated the dissolution mechanism of Sb in hydrazine: 1) the reaction between Sb and S/Se yields [Sb4S7]2-/[Sb4Se7]2- ions within their respective solutions; 2) in the Sb-S-Se precursor solutions, Sb, S, and Se were mixed on a molecular level, facilitating the formation of highly uniform polycrystalline Sb2(S1−xSex)3 thin films at a relatively low temperature. UV-vis-NIR transmission spectroscopy revealed that the band gap of Sb2(S1−xSex)3 alloy films had a quadratical relationship with the Se concentration x and it followed the equation , where the bowing parameter was 0.118 eV. Our study provides a valuable guidance for the adjustment and optimization of the band gap in hydrazine solution processed Sb2(S1−xSex)3 alloy films for the future fabrication of improved photovoltaic devices. PMID:26042519

  19. Hydrazine solution processed Sb2S3, Sb2Se3 and Sb2(S1-xSex)3 film: molecular precursor identification, film fabrication and band gap tuning

    NASA Astrophysics Data System (ADS)

    Yang, Bo; Xue, Ding-Jiang; Leng, Meiying; Zhong, Jie; Wang, Liang; Song, Huaibing; Zhou, Ying; Tang, Jiang

    2015-06-01

    Sb2(S1-xSex)3 (0 ≤ x ≤ 1) compounds have been proposed as promising light-absorbing materials for photovoltaic device applications. However, no systematic study on the synthesis and characterization of polycrystalline Sb2(S1-xSex)3 thin films has been reported. Here, using a hydrazine based solution process, single-phase Sb2(S1-xSex)3 films were successfully obtained. Through Raman spectroscopy, we have investigated the dissolution mechanism of Sb in hydrazine: 1) the reaction between Sb and S/Se yields [Sb4S7]2-/[Sb4Se7]2- ions within their respective solutions; 2) in the Sb-S-Se precursor solutions, Sb, S, and Se were mixed on a molecular level, facilitating the formation of highly uniform polycrystalline Sb2(S1-xSex)3 thin films at a relatively low temperature. UV-vis-NIR transmission spectroscopy revealed that the band gap of Sb2(S1-xSex)3 alloy films had a quadratical relationship with the Se concentration x and it followed the equation , where the bowing parameter was 0.118 eV. Our study provides a valuable guidance for the adjustment and optimization of the band gap in hydrazine solution processed Sb2(S1-xSex)3 alloy films for the future fabrication of improved photovoltaic devices.

  20. Corticospinal control of antagonistic muscles in the cat.

    PubMed

    Ethier, Christian; Brizzi, Laurent; Giguère, Dominic; Capaday, Charles

    2007-09-01

    We recently suggested that movement-related inter-joint muscle synergies are recruited by selected excitation and selected release from inhibition of cortical points. Here we asked whether a similar cortical mechanism operates in the functional linking of antagonistic muscles. To this end experiments were done on ketamine-anesthetized cats. Intracortical microstimulation (ICMS) and intramuscular electromyographic recordings were used to find and characterize wrist, elbow and shoulder antagonistic motor cortical points. Simultaneous ICMS applied at two cortical points, each evoking activity in one of a pair of antagonistic muscles, produced co-contraction of antagonistic muscle pairs. However, we found an obvious asymmetry in the strength of reciprocal inhibition; it was always significantly stronger on physiological extensors than flexors. Following intravenous injection of a single bolus of strychnine, a cortical point at which only a physiological flexor was previously activated also elicited simultaneous activation of its antagonist. This demonstrates that antagonistic corticospinal neurons are closely grouped, or intermingled. To test whether releasing a cortical point from inhibition allows it to be functionally linked with an antagonistic cortical point, one of three GABA(A) receptor antagonists, bicuculline, gabazine or picrotoxin, was injected iontophoretically at one cortical point while stimulation was applied to an antagonistic cortical point. This coupling always resulted in co-contraction of the represented antagonistic muscles. Thus, antagonistic motor cortical points are linked by excitatory intracortical connections held in check by local GABAergic inhibition, with reciprocal inhibition occurring at the spinal level. Importantly, the asymmetry of cortically mediated reciprocal inhibition would appear significantly to bias muscle maps obtained by ICMS in favor of physiological flexors. PMID:17880397

  1. The effect of reduced dopamine D4 receptor expression in the 5-choice continuous performance task: Separating response inhibition from premature responding

    PubMed Central

    Young, Jared W.; Powell, Susan B.; Scott, Christine N.; Zhou, Xianjin; Geyer, Mark A.

    2012-01-01

    Impairments in attention/vigilance and response disinhibition are commonly observed in several neuropsychiatric disorders. Validating animal models could help in developing therapeutics for cognitive deficits and improving functional outcomes in such disorders. The 5-choice continuous performance test (5C-CPT) in mice offers the opportunity to assess vigilance and two forms of impulsivity. Since reduced dopamine D4 receptor (DRD4) function is implicated in several disorders, DRD4 is a potential therapeutic target for cognition enhancement. We trained wildtype (WT), heterozygous (HT), and knockout (KO) mice of the murine Drd4 to perform the 5C-CPT under baseline and variable stimulus duration conditions. To dissect motor impulsivity (premature responding) from behavioral disinhibition (false alarms), we administered the 5-HT2C antagonist SB242084 during an extended inter-trial-interval session. We also examined the preattentive and exploratory profile of these mice in prepulse inhibition (PPI) and the Behavioral Pattern Monitor (BPM). Reduced Drd4 expression in HT mice, as confirmed by quantitative RT-PCR, resulted in response dis-inhibition and impaired 5C-CPT performance, while premature responding was unaffected. Conversely, SB242084 increased premature responding without affecting response inhibition or attentional measures. No genotypic differences were observed in PPI or BPM behavior. Thus, reduced Drd4 expression impairs attentional performance, but not other behaviors associated with neuropsychiatric disorders. Moreover, the use of signal and non-signal stimuli in the 5C-CPT enabled the differentiation of response disinhibition from motor impulsivity in a vigilance task. PMID:21458500

  2. N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties.

    PubMed

    Zajdel, Paweł; Marciniec, Krzysztof; Satała, Grzegorz; Canale, Vittorio; Kos, Tomasz; Partyka, Anna; Jastrzębska-Więsek, Magdalena; Wesołowska, Anna; Basińska-Ziobroń, Agnieszka; Wójcikowski, Jacek; Daniel, Władysława A; Bojarski, Andrzej J; Popik, Piotr

    2016-06-01

    A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT6 receptor ligands. The study allowed for the identification of 25 (4-{[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT6 receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10-30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity. PMID:27326337

  3. Electronic structure, transport properties, and excited states in CoTiSb, CoZrSb, and CoHfSb half-Heusler compounds

    NASA Astrophysics Data System (ADS)

    Janotti, Anderson; Gui, Zhigang; Kawasaki, Jason; Palmstrom, Chris; Himmetoglu, Burak

    CoTiSb is a member of a large family of half-Heusler compounds with 18 valence electrons. CoTiSb is semiconductor material with a band gap a little over 1 eV, and it has been considered promising for thermoelectric applications. It can be grown on conventional III-V semiconductors, and could potentially be integrated in III-V devices. Here we present results of first-principles calculations of electronic structure, transport properties, and excited states in CoTiSb, as well as CoZrSb and CoHfSb. Electronic structures are studied using density functional theory within the local density approximation, hybrid functional and quasiparticle GW methods. Both room-temperature Seebeck coefficient and carrier mobility are calculated from first-principles. We also determine the band alignments to III-V semiconductors, and all the results are presented and discussed in the light of available experimental data. This work was supported by the DOE.

  4. Phase transformation in Mg—Sb3Te thin films

    NASA Astrophysics Data System (ADS)

    Li, Jun-Jian; Wang, Guo-Xiang; Chen, Yi-Min; Shen, Xiang; Nie, Qiu-Hua; Lü, Ye-Gang; Dai, Shi-Xun; Xu, Tie-Feng

    2014-08-01

    Mg-doped Sb3Te films are proposed to improve the performance of phase-change memory (PCM). We prepare Mg-doped Sb3Te films and investigate their crystallization behaviors, structural, optical and electrical properties. We find that Mg-doping can increase the crystallization temperature, enhance the activation energy, and improve the 10-year data retention of Sb3Te. Especially Mg25.19(Sb3Te)74.81 shows higher Tc (~ 190 °C) and larger Ea (~ 3.49 eV), which results in a better data retention maintaining for 10 yr at ~ 112 °C. Moreover Ra/Rc value is also improved. These excellent properties make Mg—Sb—Te material a promising candidate for the phase-change memory (PCM).

  5. Crystal structure of Ba5In4Sb6

    PubMed Central

    Pan, Ming-Yan; Xia, Sheng-Qing; Tao, Xu-Tang

    2015-01-01

    The title compound, penta­barium tetra­indium hexa­anti­mony, was synthesized by an indium-flux reaction and its structure features layers composed of edge-sharing In2Sb6 units. The voids between the In4Sb6 layers are filled by Ba2+ cations, which are all surrounded by six Sb atoms and form bicapped octa­hedral or triangular prismatic coordination geometries. There are five barium ions in the asymmetric unit: one has no imposed crystallographic symmetry, two lie on mirror planes and two have mm2 point symmetry. The two In atoms and four Sb atoms in the asymmetric unit all lie on general crystallographic positions. PMID:25995883

  6. Threading and Near-Surface Dislocations in InGaSb/AlSb Films with Blocking and Anti-Blocking Layers

    NASA Astrophysics Data System (ADS)

    Katz, M. B.; Twigg, M. E.; Mahadik, N. A.; Canedy, C. L.; Affouda, C. A.

    2016-04-01

    In order to mitigate the formation of threading dislocations in an In0.1Ga0.9Sb heteroepitaxial buffer layer grown on a (001) GaSb substrate, an AlSb blocking layer was grown within the buffer layer. Transmission electron microscopy measurements revealed that the film with the AlSb blocking layer had a significantly lower threading dislocation density than a buffer layer of equivalent thickness in the absence of the blocking layer. Because the AlSb blocking layer is of greater mechanical stiffness than the In0.1Ga0.9Sb buffer layer, attractive image forces that act to draw dislocations to the film surface are countered by repulsive image forces traceable to the In0.1Ga0.9Sb/AlSb interface. These experimental results are consistent with calculations based on anisotropic elasticity theory for repulsive image forces acting on a dislocation beneath the blocking layer.

  7. Origin of p-type conductivity of Sb-doped ZnO nanorods and the local structure around Sb ions

    SciTech Connect

    Liang, J. K.; Su, H. L. E-mail: ycwu@hfut.edu.cn Wu, Y. C. E-mail: ycwu@hfut.edu.cn; Chuang, P. Y.; Kuo, C. L.; Huang, S. Y.; Chan, T. S.; Huang, J. C. A. E-mail: ycwu@hfut.edu.cn

    2015-05-25

    To probe the origin of p-type conductivity in Sb-doped ZnO, a careful and detailed synchrotron radiation study was performed. The extended X-ray absorption fine structure and X-ray photoelectron spectroscopy investigations provided the evidence for the formation of the complex defects comprising substitution Sb ions at Zn sites (Sb{sub Zn}) and Zn vacancies within the Sb-doped ZnO lattice. Such complex defects result in the increases of Sb-O coordination number and the Sb valence and thereby lead to the p-type conductivity of Sb-doped ZnO. The back-gate field-effect-transistors based on single nanorod of Sb-doped ZnO were constructed, and the stable p-type conduction behavior was confirmed.

  8. Mutually-antagonistic interactions in baseball networks

    NASA Astrophysics Data System (ADS)

    Saavedra, Serguei; Powers, Scott; McCotter, Trent; Porter, Mason A.; Mucha, Peter J.

    2010-03-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.

  9. Laser ablation of AgSbS(2) and cluster analysis by time-of-flight mass spectrometry.

    PubMed

    Houska, Jan; Peña-Méndez, Eladia Maria; Kolár, Jakub; Frumar, Miloslav; Wágner, Tomás; Havel, Josef

    2009-06-01

    Thin films of AgSbS(2) are important for phase-change memory applications. This solid is deposited by various techniques, such as metal organic chemical vapour deposition or laser ablation deposition, and the structure of AgSbS(2)(s), as either amorphous or crystalline, is already well characterized. The pulsed laser ablation deposition (PLD) of solid AgSbS(2) is also used as a manufacturing process. However, the processes in plasma have not been well studied. We have studied the laser ablation of synthesized AgSbS(2)(s) using a nitrogen laser of 337 nm and the clusters formed in the laser plume were identified. The ablation leads to the formation of various single charged ternary Ag(p)Sb(q)S(r) clusters. Negatively charged AgSbS(4) (-), AgSb(2)S(3) (-), AgSb(2)S(4) (-), AgSb(2)S(5) (-) and positively charged ternary AgSbS(+), AgSb(2)S(+), AgSb(2)S(2) (+), AgSb(2)S(3) (+) clusters were identified. The formation of several singly charged Ag(+), Ag(2) (-), Ag(3) (-), Sb(3) (+), Sb(3) (-), S(8) (+) ions and binary Ag(p)S(r) clusters such as AgSb(2) (-), Ag(3)S(-), SbS(r) (-) (r = 1-5), Sb(2)S(-), Sb(2)S(2) (-), Sb(3)S(r) (-) (r = 1-4) and AgS(2) (+), SbS(+), SbS(2) (+), Sb(2)S(+), Sb(2)S(2) (+), Sb(3)S(r) (+) (r = 1-4), AgSb(2) (+) was also observed. The stoichiometry of the clusters was determined via isotopic envelope analysis and computer modeling. The relation of the composition of the clusters to the crystal structure of AgSbS(2) is discussed. PMID:19434598

  10. Modeling of InGaSb thermophotovoltaic cells and materials

    SciTech Connect

    Zierak, M.; Borrego, J.M.; Bhat, I.; Gutmann, R.J.; Charache, G.

    1997-05-01

    A closed form computer program has been developed for the simulation and optimization of In{sub x}Ga{sub 1{minus}x}Sb thermophotovoltaic cells operating at room temperature. The program includes material parameter models of the energy bandgap, optical absorption constant, electron and hole mobility, intrinsic carrier concentration and index of refraction for any composition of GaInSb alloys.

  11. Thermodynamic Description of the Ternary Sb-Sn-Zn System

    NASA Astrophysics Data System (ADS)

    Gierlotka, Wojciech

    2016-04-01

    The ternary Sb-Sn-Zn system is important for two reasons: the first one is that antimony-tin-zinc alloys are promising lead-free solders, the second one is, that zinc antimonides show thermoelectric properties. Based on available literature information, the Sb-Sn-Zn system was thermodynamically described using the Calphad approach. A good agreement between calculation and experimental information was found.

  12. Photoelectric and luminescence properties of GaSb-Based nanoheterostructures with a deep Al(As)Sb/InAsSb/Al(As)Sb quantum well grown by metalorganic vapor-phase epitaxy

    SciTech Connect

    Mikhailova, M. P.; Andreev, I. A. Ivanov, E. V.; Konovalov, G. G.; Grebentshikova, E. A.; Yakovlev, Yu. P.; Hulicius, E.; Hospodkova, A.; Pangrac, Y.

    2013-08-15

    The luminescence and photoelectric properties of heterostructures with a deep Al(As)Sb/InAsSb/Al(As)Sb quantum well grown on n-GaSb substrates by metalorganic vapor-phase epitaxy are investigated. Intense superlinear luminescence and increased optical power as a function of the pump current in the photon energy range of 0.6-0.8 eV are observed at temperatures of T = 77 and 300 K. The photoelectric, current-voltage, and capacitance characteristics of these heterostructures are studied in detail. The photosensitivity is examined with photodetectors operating in the photovoltaic mode in the spectral range of 0.9-2.0 {mu}m. The sensitivity maximum at room temperature is observed at a wavelength of 1.55 {mu}m. The quantum efficiency, detectivity, and response time of the photodetectors were estimated. The quantum efficiency and detectivity at the peak of the photosensitivity spectrum are as high as {eta} = 0.6-0.7 and D{sub {lambda}max}{sup *} = (5-7) Multiplication-Sign 10{sup 10} cm Hz{sup 1/2} W{sup -1}, respectively. The photodiode response time determined as the rise time of the photoresponse pulse from 0.1 to the level 0.9 is 100-200 ps. The photodiode transmission bandwidth is 2-3 GHz. Photodetectors with a deep Al(As)Sb/InAsSb/Al(As)Sb quantum well grown on n-GaSb substrates are promising foruse in heterodyne detection systems and in information technologies.

  13. Photoluminescence from narrow InAs-AlSb quantum wells

    NASA Technical Reports Server (NTRS)

    Brar, Berinder; Kroemer, Herbert; Ibbetson, James; English, John H.

    1993-01-01

    We report on photoluminescence spectra from narrow InAs-AlSb quantum wells. Strong, clearly resolved peaks for well widths from 2 to 8 monolayers were observed. Transmission electron micrographs show direct evidence for the structural quality of the quantum well structures. The transition energies of the narrowest wells suggest a strong influence of the AlSb X-barrier on the electronic states in the conduction band.

  14. Antagonistic and Bargaining Games in Optimal Marketing Decisions

    ERIC Educational Resources Information Center

    Lipovetsky, S.

    2007-01-01

    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  15. Microbial antagonists of Verticillium dahliae colonize cotton root system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verticillium wilt remains one of the most severe diseases affecting cotton production in Uzbekistan. We are investigating microbial antagonist to control this pathogen. To this end, we have identified several antagonists of Verticillium dahliae (Bacillus sp. 234, Bacillus sp. 3, Streptomyces roseofl...

  16. Pros and cons of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants.

    PubMed

    Riva, Nicoletta; Ageno, Walter

    2015-03-01

    Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs. PMID:25703519

  17. Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol

    PubMed Central

    Park, Chan Woo; Hwang, Yu Im; Koo, Hwa Seon; Kang, Inn Soo; Yang, Kwang Moon

    2014-01-01

    Objective To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). Methods A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. Results The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). Conclusion The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials. PMID:25599038

  18. LWIR detector research in InAsSb/InAs

    NASA Technical Reports Server (NTRS)

    Peercy, Paul S.

    1990-01-01

    The InAsSb/InSb strained-layer system forms a type-II superlattice in the Sb-rich region of the phase diagram. The band gap of InAsSb/InSb strained-layer superlattices grown on lattice-matched buffers can be varied continuously to produce semiconducting systems with band gaps ranging from that of InSb (0.23 eV with an absorption edge at 5.5 microns at 77 K) to 0. The semiconductor to semimetal transition occurs at As concentrations of approximately 33 percent, with the precise value dependent upon the strain and quantum well dimensions. At higher As content, the system is a semimetal. The authors fabricated photovoltaic detectors with high D asterisk at 77 K at wavelengths beyond 10 microns, and both photovoltaic and photoconductive detectors have been demonstrated with response to 15 microns. The photoconductive detectors exhibit gain of up to 100. Details of the materials growth, studies of the band structure and properties, device processing and the detector performance observed to date in these systems are discussed.

  19. Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases.

    PubMed

    Burness, Celeste B; Duggan, Sean T

    2016-08-01

    Etanercept (SB4) [Benepali(®)], a tumour necrosis factor inhibitor that is a biosimilar of reference etanercept (Enbrel(®)), is approved in the EU for use in all adult indications for which reference etanercept is approved, namely rheumatoid arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), psoriatic arthritis, and plaque psoriasis. The approval of etanercept (SB4) was based on the results of stringent comparability exercises designed to demonstrate similarity to reference etanercept in terms of quality, biological activity, efficacy, safety, and immunogenicity. In two well-designed clinical trials, etanercept (SB4) was equivalent to reference etanercept with regard to pharmacokinetic properties in healthy volunteers and in terms of efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Longer-term efficacy (up to 52 weeks) was also similar in both treatment groups. Etanercept (SB4) was generally well tolerated, with a similar safety profile to that of reference etanercept. Preliminary results of the open-label extension period (100 weeks) suggest that transitioning from reference etanercept to etanercept (SB4) was associated with sustained efficacy and no change in the adverse event profile or immunogenicity. In conclusion, etanercept (SB4) provides therapeutically equivalent alternative in adult patients with autoimmune inflammatory diseases requiring treatment with etanercept. PMID:27455991

  20. Pharmacokinetic interactions with calcium channel antagonists (Part I).

    PubMed

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-11-01

    Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. PMID:1773549

  1. Directly Observable Behavioral Effects of Lorcaserin in Rats

    PubMed Central

    Serafine, Katherine M.; Rice, Kenner C.

    2015-01-01

    (1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin) is approved by the United States Food and Drug Administration for treating obesity, and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032–32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n = 8). The 5-HT2C receptor selective agonist 1-(3-chlorophenyl)piperazine (mCPP, 0.032–1.0 mg/kg) and lorcaserin induced yawning which was attenuated by the 5-HT2C receptor selective antagonist 6-chloro-5-methyl-N-(6-[(2-methylpyridin-3-yl)oxy]pydidin-3-yl)indoline-1-carboxamide (1.0 mg/kg). The 5-HT2A receptor selective agonist 2,5-dimethoxy-4-methylamphetamine (0.1–3.2 mg/kg) induced head twitching, which was attenuated by the 5-HT2A receptor selective antagonist R-(+)-2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL 100907, 0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with MDL 100907 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading, which was attenuated by the 5-HT1A receptor selective antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that at larger doses it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects. PMID:26384326

  2. Directly Observable Behavioral Effects of Lorcaserin in Rats.

    PubMed

    Serafine, Katherine M; Rice, Kenner C; France, Charles P

    2015-12-01

    (1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin) is approved by the United States Food and Drug Administration for treating obesity, and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032-32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n = 8). The 5-HT2C receptor selective agonist 1-(3-chlorophenyl)piperazine (mCPP, 0.032-1.0 mg/kg) and lorcaserin induced yawning which was attenuated by the 5-HT2C receptor selective antagonist 6-chloro-5-methyl-N-(6-[(2-methylpyridin-3-yl)oxy]pydidin-3-yl)indoline-1-carboxamide (1.0 mg/kg). The 5-HT2A receptor selective agonist 2,5-dimethoxy-4-methylamphetamine (0.1-3.2 mg/kg) induced head twitching, which was attenuated by the 5-HT2A receptor selective antagonist R-(+)-2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL 100907, 0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with MDL 100907 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading, which was attenuated by the 5-HT1A receptor selective antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that at larger doses it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects. PMID:26384326

  3. Molecular and behavioral pharmacology of two novel orally-active 5HT2 modulators: potential utility as antipsychotic medications

    PubMed Central

    Morgan, Drake; Kondabolu, Krishnakanth; Kuipers, Allison; Sakhuja, Rajeev; Robertson, Kimberly L.; Rowland, Neil E.; Booth, Raymond G.

    2013-01-01

    Background Desired serotonin 5HT2 receptor pharmacology for treatment of psychoses is 5HT2A antagonism and/or 5HT2C agonism. No selective 5HT2A antagonist has been approved for psychosis and the only approved 5HT2C agonist (for obesity) also activates 5HT2A and 5HT2B receptors, which can lead to clinical complications. Studies herein tested the hypothesis that a dual-function 5HT2A antagonist/5HT2C agonist that does not activate 5HT2B receptors would be suitable for development as an antipsychotic drug, without liability for weight gain. Methods The novel compounds (+)- and (−)-trans-4-(4′-chlorophenyl)-N,N-dimethyl-2-aminotetralin (p-Cl-PAT) were synthesized, characterized in vitro for affinity and functional activity at human 5HT2 receptors, and administered by intraperitoneal (i.p.) and oral (gavage) routes to mice in behavioral paradigms that assessed antipsychotic efficacy and effects on feeding behavior. Results (+)- and (−)-p-Cl-PAT activated 5HT2C receptors, with (+)-p-Cl-PAT being 12-times more potent, consistent with its higher affinity across 5HT2 receptors. Neither p-Cl-PAT enantiomer activated 5HT2A or 5HT2B receptors at concentrations up to 300-times greater than their respective affinity (Ki), and (+)-p-Cl-PAT was shown to be a 5HT2A competitive antagonist. When administered i.p. or orally, (+)- and (−)-p-Cl-PAT attenuated the head-twitch response (HTR) in mice elicited by the 5HT2 agonist (−)-2,5-dimethoxy-4-iodoamphetamine (DOI) and reduced intake of a highly palatable food in non-food-deprived mice, with (+)-p-Cl-PAT being more potent across behavioral assays. Conclusions The novel in vitro pharmacology of (+)-p-Cl-PAT (5HT2A antagonism/5HT2C agonism without activation of 5HT2B) translated in vivo to an orally-active drug candidate with preclinical efficacy to treat psychoses without liability for weight gain. PMID:23665356

  4. Electrical and optical characteristics of AlAsSb/GaAsSb distributed Bragg reflectors for surface emitting lasers

    SciTech Connect

    Blum, O.; Hafich, M.J.; Klem, J.F.; Lear, K.L.; Chu, S.N.G.

    1995-11-27

    We demonstrate an undoped 20 1/2 pair AlAsSb/GaAsSb distributed Bragg reflector (DBR) grown lattice matched to an InP substrate by molecular beam epitaxy. Reflectivity measurements indicate a stop band centered at 1.78 {mu}m with a maximum reflectivity exceeding 99%. We also measure current--voltage characteristics in a similar 10 1/2 period {ital p}-type DBR and find that a current density of 1 {ital kA}/{ital cm}{sup 2} produces a 2.5 V drop. Hole mobilities and doping concentrations in AlAsSb and GaAsSb are also reported. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  5. Magnetic fluctuations sorted by magnetic field in MnSb clusters embedded in GaMnSb thin films

    NASA Astrophysics Data System (ADS)

    Dmitriev, A. I.; Talantsev, A. D.; Koplak, O. V.; Morgunov, R. B.

    2016-02-01

    Dynamics of magnetization relaxation of the MnSb clusters under applied magnetic field has been studied in the 8-300 K temperature range. The lognormal distribution of ferromagnetic MnSb cluster sizes f(D) has been extracted from the field and temperature dependences of magnetic viscosity S(T, H) in GaMnSb thin films. An average cluster diameter D = 55 nm is in agreement with the magnetic force microscopy data. Magnetic anisotropy constant ˜3.2 × 104 erg/cm3 has been determined. The fluctuation field HF = 7 Oe and the activation volume VA = 1.7 × 10-16 cm3 have been calculated from the magnetic viscosity data. Stepped sweeping of the magnetic field expands the windows of experimentally detectable fluctuations. The change in the reversal magnetic field provides the scanning of the MnSb clusters sorting them by fluctuation time (or frequency).

  6. Organometallic Vapor Phase Epitaxy of n-GaSb and n-GaInAsSb for Low Resistance Ohmic Contacts

    SciTech Connect

    C.A. Wang; D.A. Shiau; R.K. Huang; C.T. Harris; M.K. Connors

    2003-07-10

    A comparison of n-GaSb and n-GaInAsSb epilayers for ohmic contacts in GaSb-based devices is studied. The epilayers were grown by organometallic vapor phase epitaxy and doped with Te. At similar electron concentrations, the atomic Te concentration, as determined by secondary ion mass spectroscopy, is more than 2 times higher in n-GaSb compared to n-GaInAsSb. In addition, the electron mobility is lower in n-GaSb than n-GaInAsSb at similar electron concentrations. The electron concentration saturates at about 1.3 x 10{sup 18} cm{sup -3} for n-GaSb, but linearly increases for n-GaInAsSb. Pd/Ge/Au/Pt/Au metallization was studied for ohmic contacts. A specific contact resistivity of 1 x 10{sup -5}{Omega}-cm{sup 2} for n-GaSb was measured. The specific contact resistivity can be greatly improved by contacting n-GaInAsSb, and a significantly lower specific contact resistivity of 2 x 10{sup -6} {Omega}-cm{sup 2} for n-GaInAsSb was measured.

  7. On-line determination of Sb(III) and total Sb using baker's yeast immobilized on polyurethane foam and hydride generation inductively coupled plasma optical emission spectrometry

    NASA Astrophysics Data System (ADS)

    Menegário, Amauri A.; Silva, Ariovaldo José; Pozzi, Eloísa; Durrant, Steven F.; Abreu, Cassio H.

    2006-09-01

    The yeast Saccharomyces cerevisiae was immobilized in cubes of polyurethane foam and the ability of this immobilized material to separate Sb(III) and Sb(V) was investigated. A method based on sequential determination of total Sb (after on-line reduction of Sb(V) to Sb(III) with thiourea) and Sb(III) (after on-line solid-liquid phase extraction) by hydride generation inductively coupled plasma optical emission spectrometry is proposed. A flow system assembled with solenoid valves was used to manage all stages of the process. The effects of pH, sample loading and elution flow rates on solid-liquid phase extraction of Sb(III) were evaluated. Also, the parameters related to on-line pre-reduction (reaction coil and flow rates) were optimized. Detection limits of 0.8 and 0.15 μg L - 1 were obtained for total Sb and Sb(III), respectively. The proposed method was applied to the analysis of river water and effluent samples. The results obtained for the determination of total Sb were in agreement with expected values, including the river water Standard Reference Material 1640 certified by the National Institute of Standards and Technology (NIST). Recoveries of Sb(III) and Sb(V) in spiked samples were between 81 ± 19 and 111 ±15% when 120 s of sample loading were used.

  8. Vertical cavity surface emitting laser emitting at 1.56 microns with AlGaAsSb/AlAsSb distributed Bragg reflectors

    SciTech Connect

    Blum, O.; Klem, J.F.; Lear, K.L.; Vawter, G.A.; Kurtz, S.R.

    1998-07-01

    The authors report 77K operation of an optically pumped vertical cavity surface emitting laser with an Sb-based cavity. The structure consists of 15 and 20 pair AlGaAsSb/AlAsSb top and bottom reflectors and a bulk InGaAs active region.

  9. Prostanoid receptor antagonists: development strategies and therapeutic applications

    PubMed Central

    Jones, RL; Giembycz, MA; Woodward, DF

    2009-01-01

    Identification of the primary products of cyclo-oxygenase (COX)/prostaglandin synthase(s), which occurred between 1958 and 1976, was followed by a classification system for prostanoid receptors (DP, EP1, EP2 …) based mainly on the pharmacological actions of natural and synthetic agonists and a few antagonists. The design of potent selective antagonists was rapid for certain prostanoid receptors (EP1, TP), slow for others (FP, IP) and has yet to be achieved in certain cases (EP2). While some antagonists are structurally related to the natural agonist, most recent compounds are ‘non-prostanoid’ (often acyl-sulphonamides) and have emerged from high-throughput screening of compound libraries, made possible by the development of (functional) assays involving single recombinant prostanoid receptors. Selective antagonists have been crucial to defining the roles of PGD2 (acting on DP1 and DP2 receptors) and PGE2 (on EP1 and EP4 receptors) in various inflammatory conditions; there are clear opportunities for therapeutic intervention. The vast endeavour on TP (thromboxane) antagonists is considered in relation to their limited pharmaceutical success in the cardiovascular area. Correspondingly, the clinical utility of IP (prostacyclin) antagonists is assessed in relation to the cloud hanging over the long-term safety of selective COX-2 inhibitors. Aspirin apart, COX inhibitors broadly suppress all prostanoid pathways, while high selectivity has been a major goal in receptor antagonist development; more targeted therapy may require an intermediate position with defined antagonist selectivity profiles. This review is intended to provide overviews of each antagonist class (including prostamide antagonists), covering major development strategies and current and potential clinical usage. PMID:19624532

  10. The antimony-group 11 chemical bond: Dissociation energies of the diatomic molecules CuSb, AgSb, and AuSb

    SciTech Connect

    Carta, V.; Ciccioli, A. E-mail: andrea.ciccioli@uniroma1.it; Gigli, G. E-mail: andrea.ciccioli@uniroma1.it

    2014-02-14

    The intermetallic molecules CuSb, AgSb, and AuSb were identified in the effusive molecular beam produced at high temperature under equilibrium conditions in a double-cell-like Knudsen source. Several gaseous equilibria involving these species were studied by mass spectrometry as a function of temperature in the overall range 1349–1822 K, and the strength of the chemical bond formed between antimony and the group 11 metals was for the first time measured deriving the following thermochemical dissociation energies (D{sub 0}{sup ∘}, kJ/mol): 186.7 ± 5.1 (CuSb), 156.3 ± 4.9 (AgSb), 241.3 ± 5.8 (AuSb). The three species were also investigated computationally at the coupled cluster level with single, double, and noniterative quasiperturbative triple excitations (CCSD(T)). The spectroscopic parameters were calculated from the potential energy curves and the dissociation energies were evaluated at the Complete Basis Set limit, resulting in an overall good agreement with experimental values. An approximate evaluation of the spin-orbit effect was also performed. CCSD(T) calculations were further extended to the corresponding group 11 arsenide species which are here studied for the first time and the following dissociation energies (D{sub 0}{sup ∘}, kJ/mol): 190 ± 10 (CuAs), 151 ± 10 (AgAs), 240 ± 15 (AuAs) are proposed. Taking advantage of the new experimental and computational information here presented, the bond energy trends along group 11 and 4th and 5th periods of the periodic table were analyzed and the bond energies of the diatomic species CuBi and AuBi, yet experimentally unobserved, were predicted on an empirical basis.

  11. Magnetotransport properties of type II heterojunctions based on GaInAsSb/InAs and GaInAsSb/GaSb

    SciTech Connect

    Voronina, T. I.; Lagunova, T. S.; Mikhailova, M. P.; Moiseev, K. D. Lipaev, A. F.; Yakovlev, Yu. P.

    2006-05-15

    The results of detailed study of the magnetotransport properties of broken-gap type II heterojunctions in a GaInAsSb/InAs(GaSb) system are reported. An electron channel with a high charge-carrier mobility (as high as 50000-60000 cm{sup 2}/(V s)) is observed and studied for the first time in an isotype broken-gap p-GaInAsSb/p-InAs heterostructure. The effects of electron-channel depletion and semimetal-semiconductor transition in the case of heavy doping of the quaternary alloy with acceptors are studied. Magnetotransport properties at temperatures of 4.2-200 K are studied in detail. Data on the energy spectrum and parameters of two-dimensional charge carriers at the heteroboundary are obtained. It is ascertained experimentally that, depending on the composition, either staggered (at x = 0.85) or broken-gap (at x = 0.95) heterojunctions can be formed in the Ga{sub 1-x}In{sub x}As{sub y}Sb{sub 1-y}/GaSb, which is confirmed by theoretical calculations. The anomalous Hall effect and negative magnetoresistance were observed in GaInAsSb/InAs:Mn grown on substrates doped heavily with Mn magnetic acceptor impurity so that the hole concentration was as high as p > 5 x 10{sup 18} cm{sup -3}; these phenomena are caused by exchange interaction of Mn ions in InAs with high-mobility charge carriers in the electron channel at the heterointerface.

  12. ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB.

    PubMed

    Maier, James A; Martinez, Carmenza; Kasavajhala, Koushik; Wickstrom, Lauren; Hauser, Kevin E; Simmerling, Carlos

    2015-08-11

    Molecular mechanics is powerful for its speed in atomistic simulations, but an accurate force field is required. The Amber ff99SB force field improved protein secondary structure balance and dynamics from earlier force fields like ff99, but weaknesses in side chain rotamer and backbone secondary structure preferences have been identified. Here, we performed a complete refit of all amino acid side chain dihedral parameters, which had been carried over from ff94. The training set of conformations included multidimensional dihedral scans designed to improve transferability of the parameters. Improvement in all amino acids was obtained as compared to ff99SB. Parameters were also generated for alternate protonation states of ionizable side chains. Average errors in relative energies of pairs of conformations were under 1.0 kcal/mol as compared to QM, reduced 35% from ff99SB. We also took the opportunity to make empirical adjustments to the protein backbone dihedral parameters as compared to ff99SB. Multiple small adjustments of φ and ψ parameters were tested against NMR scalar coupling data and secondary structure content for short peptides. The best results were obtained from a physically motivated adjustment to the φ rotational profile that compensates for lack of ff99SB QM training data in the β-ppII transition region. Together, these backbone and side chain modifications (hereafter called ff14SB) not only better reproduced their benchmarks, but also improved secondary structure content in small peptides and reproduction of NMR χ1 scalar coupling measurements for proteins in solution. We also discuss the Amber ff12SB parameter set, a preliminary version of ff14SB that includes most of its improvements. PMID:26574453

  13. Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D2 and D3 Receptors

    PubMed Central

    Wood, Martyn D.; Strange, Philip G.

    2016-01-01

    Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. PMID:27379794

  14. Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D2 and D3 Receptors.

    PubMed

    Newton, Claire L; Wood, Martyn D; Strange, Philip G

    2016-01-01

    Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. PMID:27379794

  15. In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder.

    PubMed

    Barth, V; Need, A B; Tzavara, E T; Giros, B; Overshiner, C; Gleason, S D; Wade, M; Johansson, A M; Perry, K; Nomikos, G G; Witkin, J M

    2013-02-01

    Dopamine D(3) receptors have eluded definitive linkage to neurologic and psychiatric disorders since their cloning over 20 years ago. We report a new method that does not employ a radiolabel for simultaneously defining in vivo receptor occupancy of D(3) and D(2) receptors in rat brain after systemic dosing using the tracer epidepride (N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-iodo-2,3-dimethoxybenzamide). Decreases in epidepride binding in lobule 9 of cerebellum (rich in D(3) receptors) were compared with nonspecific binding in the lateral cerebellum. The in vivo occupancy of the dopamine D(3) receptors was dose dependently increased by SB-277011A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and U99194 (2,3-dihydro-5,6-dimethoxy- N,N-dipropyl-1H-inden-2-amine). Both antagonists increased extracellular levels of acetylcholine (ACh) in the medial prefrontal cortex of rats and modified brain-tissue levels of ACh and choline. Consistent with these findings, the D(3) receptor antagonists enhanced the acquisition of learning of rats either alone or in the presence of the norepinephrine uptake blocker reboxetine as with the attention-deficit-hyperactivity disorder (ADHD) drug methylphenidate. Like reboxetine, the D(3) receptor antagonists also prevented deficits induced by scopolamine in object recognition memory of rats. Mice in which the dopamine transporter (DAT) has been deleted exhibit hyperactivity that is normalized by compounds that are effective in the treatment of ADHD. Both D(3) receptor antagonists decreased the hyperactivity of DAT(-/-) mice without affecting the activity of wild type controls. The present findings indicate that dopamine D(3) receptor antagonists engender cognition-enhancing and hyperactivity-dampening effects. Thus, D(3) receptor blockade could be considered as a novel treatment approach for cognitive deficits and hyperactivity syndromes, including those observed in ADHD. PMID:23197772

  16. Neolignans from the Arils of Myristica fragrans as Potent Antagonists of CC Chemokine Receptor 3.

    PubMed

    Morikawa, Toshio; Hachiman, Ikuko; Matsuo, Kazuhiko; Nishida, Eriko; Ninomiya, Kiyofumi; Hayakawa, Takao; Yoshie, Osamu; Muraoka, Osamu; Nakayama, Takashi

    2016-08-26

    CC chemokine receptor 3 (CCR3) is expressed selectively in eosinophils, basophils, and some Th2 cells and plays a major role in allergic diseases. A methanol extract from the arils of Myristica fragrans inhibited CC chemokine ligand 11-induced chemotaxis in CCR3-expressing L1.2 cells at 100 μg/mL. From this extract, eight new neolignans, maceneolignans A-H (1-8), were isolated, and their stereostructures were elucidated from their spectroscopic values and chemical properties. Of those constituents, compounds 1, 4, 6, and 8 and (+)-erythro-(7S,8R)-Δ(8')-7-hydroxy-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (11), (-)-(8R)-Δ(8')-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (17), (+)-licarin A (20), nectandrin B (25), verrucosin (26), and myristicin (27) inhibited CCR3-mediated chemotaxis at a concentration of 1 μM. Among them, 1 (EC50 1.6 μM), 6 (1.5 μM), and 8 (1.4 μM) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 μM). PMID:27419473

  17. Structure and properties of CoMnSb in the context of half-metallic ferromagnetism

    SciTech Connect

    Ksenofontov, Vadim; Melnyk, Gennadiy; Wurmehl, Sabine; Kroth, Kristian; Reiman, Sergey; Felser, Claudia; Wojcik, Marek

    2006-10-01

    Although its X-ray powder diffraction patterns show a superstructure, the compound CoMnSb, like the well-known half-Heusler alloy NiMnSb, is often referred to the category of half-metallic ferromagnets with C1{sub b} structure. Our study assigns CoMnSb to space group Fm3m. The crystal structure of CoMnSb can be represented as an alternation of Co{sub 2}MnSb and MnSb structural units, and, in contrast to NiMnSb, displays three Mn and two Sb positions in the elementary cell. The presence of nonequivalent antimony and manganese positions was verified using NMR and Moessbauer spectroscopic measurements. Band-structure calculations based on a proposed structure confirm the experimentally found magnetic moment value of approximately 4 {mu}{sub B}/f.u. and demonstrate that CoMnSb is not a half-metallic ferromagnet.

  18. New Insights into the Origins of Sb-Induced Effects on Self-Catalyzed GaAsSb Nanowire Arrays.

    PubMed

    Ren, Dingding; Dheeraj, Dasa L; Jin, Chengjun; Nilsen, Julie S; Huh, Junghwan; Reinertsen, Johannes F; Munshi, A Mazid; Gustafsson, Anders; van Helvoort, Antonius T J; Weman, Helge; Fimland, Bjørn-Ove

    2016-02-10

    Ternary semiconductor nanowire arrays enable scalable fabrication of nano-optoelectronic devices with tunable bandgap. However, the lack of insight into the effects of the incorporation of Vy element results in lack of control on the growth of ternary III-V(1-y)Vy nanowires and hinders the development of high-performance nanowire devices based on such ternaries. Here, we report on the origins of Sb-induced effects affecting the morphology and crystal structure of self-catalyzed GaAsSb nanowire arrays. The nanowire growth by molecular beam epitaxy is changed both kinetically and thermodynamically by the introduction of Sb. An anomalous decrease of the axial growth rate with increased Sb2 flux is found to be due to both the indirect kinetic influence via the Ga adatom diffusion induced catalyst geometry evolution and the direct composition modulation. From the fundamental growth analyses and the crystal phase evolution mechanism proposed in this Letter, the phase transition/stability in catalyst-assisted ternary III-V-V nanowire growth can be well explained. Wavelength tunability with good homogeneity of the optical emission from the self-catalyzed GaAsSb nanowire arrays with high crystal phase purity is demonstrated by only adjusting the Sb2 flux. PMID:26726825

  19. In-plane electrical transport in n-type selectively doped GaSb/AlGaSb multiquantum wells

    NASA Astrophysics Data System (ADS)

    Ghezzi, C.; Cioce, B.; Magnanini, R.; Parisini, A.

    2001-11-01

    Results are reported regarding in-plane electrical transport in n-type selectively doped GaSb/AlGaSb multiquantum wells. In the samples, which were grown by molecular beam epitaxy, only the central regions of the Al0.40Ga0.60Sb barriers were Te doped. Low-field, low-temperature Hall measurements in the dark demonstrated the presence in the GaSb wells of a degenerate electron gas with nonzero occupancy only for the lowest miniband. A positive persistent photoconductivity effect, related to the DX character of the Te impurity, was also observed. This behavior enabled the μ electron mobility to be measured at T=10 K as a function of the nS sheet carrier density. Since the experimental data were consistent with a dominant role of the interface roughness scattering in the limiting of μ, the height, Δ, and the lateral size, Λ, of the interface roughness were determined from the analysis of the μ=μ(nS) dependence. Acceptable values of Δ were obtained, consistent with results of structural investigations in single quantum well samples of GaSb/Al0.40Ga0.60Sb [E. Kh. Mukhamedzhanov, C. Bocchi, S. Franchi, A. Baraldi, R. Magnanini, and L. Nasi, J. Appl. Phys. 87, 4234 (2000)].

  20. Phase equilibrium and intermediate phases in the Eu-Sb system

    SciTech Connect

    Abdusalyamova, M.N.

    2011-10-15

    Rapid heating rate thermal analysis, X-ray diffraction, fluorescence spectrometry, and differential dissolution method were used to study the high-temperature phase equilibrium in the Eu-Sb system within the composition range between 37 and 96 at% Sb. The techniques were effective in determination of the vapor-solid-liquid equilibrium since intermediate phases except Eu{sub 4}Sb{sub 3} evaporated incongruently after melting. A thermal procedure was developed to determine the liquidus and solidus lines of the T-x diagram. Six stable phases were identified: two phases, EuSb{sub 2} and Eu{sub 4}Sb{sub 3}, melt congruently at 1045{+-}10 deg. C and 1600{+-}15 deg. C, the Eu{sub 2}Sb{sub 3}, Eu{sub 11}Sb{sub 10}, Eu{sub 5}Sb{sub 4}, and Eu{sub 5}Sb{sub 3} phases melt incongruently at 850{+-}8 deg. C, 950{+-}10 deg. C, 1350{+-}15 deg. C, and 1445{+-}15 deg. C, respectively. The exact composition shifting of Sb-rich decomposable phases towards Eu{sub 4}Sb{sub 3}, the most refractory compound, was determined. The topology of the Eu-Sb phase diagram was considered together with that of the Yb-Sb system. - Graphical abstract: The high-temperature range of the T-x phase diagram for the Eu-Sb system. Highlights: > The phase relations in the Eu-Sb system were studied over a large composition and temperature scale. > The liquidus and solidus lines of the T-x diagram were well established using effective techniques. > In the system, six binary phases are stable and they melt incongruently except EuSb{sub 2} and Eu{sub 4}Sb{sub 3}. > Incongruent evaporation was found to be typical of all the phases besides Eu{sub 4}Sb{sub 3}.

  1. Effect of Growth Interruption on Surface Recombination Velocity in GaInAsSb/AlGaAsSb Heterostructures Grown by Organometallic Vapor Phase Epitaxy

    SciTech Connect

    CA Wang; DA Shiau; D Donetsky; S Anikeev; G Belenky; S Luryi

    2004-04-29

    The effects of growth interruption on the quality of GaInAsSb/AlGaAsSb heterostructures grown by organometallic vapor phase epitaxy are reported. In-situ reflectance monitoring and ex-situ characterization by high-resolution x-ray diffraction, 4K photoluminescence (PL), and time-resolved PL indicate that GaInAsSb is extremely sensitive to growth interruption time as well as the ambient atmosphere during interruption. By optimizing the interruption sequence, surface recombination velocity as low as 20 cm/s was achieved for GaInAsSb/AlGaAsSb double heterostructures.

  2. Antimalarial Activity of the Anticancer Histone Deacetylase Inhibitor SB939

    PubMed Central

    Sumanadasa, Subathdrage D. M.; Goodman, Christopher D.; Lucke, Andrew J.; Skinner-Adams, Tina; Sahama, Ishani; Haque, Ashraful; Do, Tram Anh; McFadden, Geoffrey I.; Fairlie, David P.

    2012-01-01

    Histone deacetylase (HDAC) enzymes posttranslationally modify lysines on histone and nonhistone proteins and play crucial roles in epigenetic regulation and other important cellular processes. HDAC inhibitors (e.g., suberoylanilide hydroxamic acid [SAHA; also known as vorinostat]) are used clinically to treat some cancers and are under investigation for use against many other diseases. Development of new HDAC inhibitors for noncancer indications has the potential to be accelerated by piggybacking onto cancer studies, as several HDAC inhibitors have undergone or are undergoing clinical trials. One such compound, SB939, is a new orally active hydroxamate-based HDAC inhibitor with an improved pharmacokinetic profile compared to that of SAHA. In this study, the in vitro and in vivo antiplasmodial activities of SB939 were investigated. SB939 was found to be a potent inhibitor of the growth of Plasmodium falciparum asexual-stage parasites in vitro (50% inhibitory concentration [IC50], 100 to 200 nM), causing hyperacetylation of parasite histone and nonhistone proteins. In combination with the aspartic protease inhibitor lopinavir, SB939 displayed additive activity. SB939 also potently inhibited the in vitro growth of exoerythrocytic-stage Plasmodium parasites in liver cells (IC50, ∼150 nM), suggesting that inhibitor targeting to multiple malaria parasite life cycle stages may be possible. In an experimental in vivo murine model of cerebral malaria, orally administered SB939 significantly inhibited P. berghei ANKA parasite growth, preventing development of cerebral malaria-like symptoms. These results identify SB939 as a potent new antimalarial HDAC inhibitor and underscore the potential of investigating next-generation anticancer HDAC inhibitors as prospective new drug leads for treatment of malaria. PMID:22508312

  3. Structure and dielectric behavior of TlSbS2

    NASA Astrophysics Data System (ADS)

    Parto, M.; Deger, D.; Ulutas, K.; Yakut, Ş.

    2013-09-01

    A comparison of structure and dielectric properties of TlSbS2 thin films, deposited in different thicknesses (400-4100 Å) by thermal evaporation of TlSbS2 crystals that were grown by the Stockbarger-Bridgman technique and the bulk material properties of TlSbS2 are presented. Dielectric constant ɛ 1 and dielectric loss ɛ 2 have been calculated by measuring capacitance and dielectric loss factor in the frequency range 20 Hz-10 KHz and in the temperature range 273-433 K. It is observed that at 1 kHz frequency and 293 K temperature the dielectric constant of TlSbS2 thin films is ɛ 1=1.8-6 and the dielectric loss of TlSbS2 thin films is ɛ 2=0.5-3 depending on film thickness. In the given intervals, both of dielectric constant and dielectric loss decrease with frequency, but increase with temperature. The maximum barrier height W m is calculated from the dielectric measurements. The values of W m for TlSbS2 films and bulk are obtained as 0.56 eV and 0.62 eV at room temperature, respectively. The obtained values agree with those proposed by the theory of hopping over the potential barrier. The temperature variation of ac conductivity can be reasonably interpreted in terms of the correlated barrier hopping model since it obeys the ω s law with a temperature dependent s ( s<1) and going down as the temperature is increased. The temperature coefficient of capacitance (TCC) and permittivity (TCP) are evaluated for both thin films and bulk material of TlSbS2.

  4. Enhanced optical property in quaternary GaInAsSb/AlGaAsSb quantum wells

    SciTech Connect

    Lin, Chien-Hung Lee, Chien-Ping

    2014-10-21

    High quality GaInAsSb/AlGaAsSb quantum wells (QWs) have been grown by molecular beam epitaxy using proper interface treatments. By controlling the group-V elements at interfaces, we obtained excellent optical quality QWs, which were free from undesired localized trap states, which may otherwise severely affect the exciton recombination. Strong and highly efficient exciton emissions up to room temperature with a wavelength of 2.2 μm were observed. A comprehensive investigation on the QW quality was carried out using temperature dependent and power dependent photoluminescence (PL) measurements. The PL emission intensity remains nearly constant at low temperatures and is free from the PL quenching from the defect induced localized states. The temperature dependent emission energy had a bulk-like behavior, indicating high quality well/barrier interfaces. Because of the uniformity of the QWs and smooth interfaces, the low temperature limit of inhomogeneous line width broadening is as small as 5 meV.

  5. The growth of GaSb/Al{sub 0.33}Ga{sub 0.67}Sb MQW on n-Silicon (1 0 0) with Al{sub 0.66}Ga{sub 0.34}Sb/AlSb SPS layers

    SciTech Connect

    Yoen, Kyu Hyoek; Song, Jin Dong; Lee, Eun Hye; Jang, Hye Joung; Bae, Min Han; Kim, Jun Young; Han, Il Ki; Choi, Won Jun

    2014-09-15

    Highlights: • GaSb/Al{sub 0.33}GaSb MQW layer was grown on Si (1 0 0) by MBE. • The effect of miscut angle of Si substrate was studied. • A lot of twins were removed by Al{sub 0.66}Ga{sub 0.34}Sb/AlSb SPS layers. • Good quality of GaSb/Al{sub 0.33}Ga{sub 0.67}Sb MQW layers were proved by PL spectra. • Optimum growth temperature of the AlSb buffer layer was studied. - Abstract: GaSb/Al{sub 0.33}Ga{sub 0.67}Sb multi-quantum well (MQW) film on n-Si (1 0 0) substrates is grown by molecular beam epitaxy. The effects of a miscut angle of the Si substrate (0°, 5°, and 7°) on the properties of an AlSb layer were also studied. The suppression of the anti-phase domains (APD) was observed at a miscut angle of 5° on Si (1 0 0). It was found that the growth temperature in the range of 510–670 °C affects the quality of AlSb layers on Si. Low root-mean-square surface (RMS) roughness values of 3–5 nm were measured by atomic force microscopy at growth temperatures ranging from 550 °C to 630 °C. In addition, Al{sub 0.66}Ga{sub 0.34}Sb/AlSb short period superlattice (SPS) layers were used to overcome problems associated with a large lattice mismatch. The RMS values of samples with a SPS were partially measured at approximately ∼1 nm, showing a larger APD surface area than samples without a SPS layer. Bright-field cross-sectional transmission electron microscopy images of the GaSb/Al{sub 0.33}Ga{sub 0.67}Sb MQW, the AlSb buffer layer and the Al{sub 0.66}Ga{sub 0.34}Sb/AlSb SPS layers show that numerous twins from the AlSb/Si interface were removed by the AlSb buffer layer and the Al{sub 0.66}Ga{sub 0.34}Sb/AlSb SPS. The GaSb/Al{sub 0.33}Ga{sub 0.67}Sb MQW PL spectra were obtained at 300 K and 10 K with a fixed excitation power of 103 mW. Emission peaks appeared at 1758 nm and 1620 nm, respectively.

  6. Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist

    PubMed Central

    Tai, Sherrica; Nikas, Spyros P.; Shukla, Vidyanand G.; Vemuri, Kiran; Makriyannis, Alexandros; Järbe, Torbjörn U.C.

    2015-01-01

    Rationale Previous reports shows rimonabant's inverse properties may be a limiting factor for treating cannabinoid dependence. To overcome this limitation neutral antagonists were developed, to address mechanisms by which an inverse agonist and neutral antagonist elicit withdrawal. Objective Introduces an animal model to study cannabinoid dependence by incorporating traditional methodologies and profiling novel cannabinoid ligands with distinct pharmacological properties/modes of action by evaluating their pharmacological effects on CB1-receptor (CB1R) related physiological/behavioral endpoints. Methods The cannabinergic AM2389 was acutely characterized in the tetrad (locomotor activity, analgesia, inverted screen/catalepsy bar test and temperature); with some comparisons made to Δ9-tetrahydrocannabinol (THC). Tolerance was measured in mice repeatedly administered AM2389. Antagonist-precipitated withdrawal was characterized in cannabinoid-adapted mice induced by either centrally acting antagonists, rimonabant and AM4113, or an antagonist with limited brain penetration, AM6545. Results In the tetrad, AM2389 was more potent and longer acting than THC, suggesting a novel approach for inducing dependence. Repeated administration of AM2389 led to tolerance by attenuating hypothermia that was induced by acute AM2389 administration. Antagonist-precipitated withdrawal signs were induced by rimonabant or AM4113, but not by AM6545. Antagonist-precipitated withdrawal was reversed by reinstating AM2389 or THC. Conclusions These findings suggest cannabinoid-precipitated withdrawal may not be ascribed to the inverse properties of rimonabant, but rather to rapid competition with the agonist at the CB1R. This withdrawal syndrome is likely centrally-mediated, since only the centrally acting CB1R antagonists elicited withdrawal, i.e., such responses were absent after the purported peripherally selective CB1R antagonist AM6545. PMID:25772338

  7. Facile synthesis of hybrid nanorods with the Sb2Se3/AgSbSe2 heterojunction structure for high performance photodetectors.

    PubMed

    Chen, Shuo; Qiao, Xvsheng; Wang, Fengxia; Luo, Qun; Zhang, Xianghua; Wan, Xia; Xu, Yang; Fan, Xianping

    2016-01-28

    An effective colloidal process involving the hot-injection method is developed to synthesize uniform single-crystalline Sb2Se3 nanorods in high yields. The photoconductive characteristics of the as-synthesized Sb2Se3 nanorods are investigated by developing a film-based photodetector and this device displays a remarkable response to visible light with an "ON/OFF" ratio as high as 50 (with an incident light density of 12.05 mW cm(-2)), short response/recovery times and long-term durability. To overcome the challenge of the intrinsic low electrical conductivity of Sb2Se3, hybrid nanorods with the Sb2Se3/AgSbSe2 heterojunction structure having a type-II band alignment are firstly prepared. The electric current of the photodetector based on the Sb2Se3/AgSbSe2 hybrid nanorod film has been significantly increased both in the dark and under light illumination. The responsivity of the photodetector based on the Sb2Se3/AgSbSe2 hybrid nanorod film is about 4.2 times as much as that of the photodetector based on the Sb2Se3 nanorod film. This improvement can be considered as an important step to promote Sb2Se3 based semiconductors for applications in high performance photodetectors. PMID:26743461

  8. Effect of Sb dopant amount on the structure and electrocatalytic capability of Ti/Sb-SnO2 electrodes in the oxidation of 4-chlorophenol.

    PubMed

    Kong, Jiang-tao; Shi, Shao-yuan; Zhu, Xiu-ping; Ni, Jin-ren

    2007-01-01

    Ti/Sb-SnO2 anodes were prepared by thermal decomposition to examine the influence of the amount of Sb dopant on the structure and electrocatalytic capability of the electrodes in the oxidation of 4-chlorophenol. The physicochemical properties of the Sb-SnO2 coating were markedly influenced by different amounts of Sb dopant. The electrodes, which contained 5% Sb dopant in the coating, presented a much more homogenous surface and much smaller mud-cracks, compared with Ti/Sb-SnO2 electrodes containing 10% or 15% Sb dopant, which exibited larger mud cracks and pores on the surface. However, the main microstructure remained unchanged with the addition of the Sb dopant. No new crystal phase was observed by X-ray diffraction (XRD). The electrochemical oxidation of 4-chlorophenol on the Ti/SnO2 electrode with 5% Sb dopant was inclined to electrochemical combustion; while for those containing more Sb dopant, intermediate species were accumulated. The electrodes with 5% Sb dopant showed the highest efficiency in the bulk electrolysis of 4-chlorophenol at a current density of 20 mA/cm2 for 180 min; and the removal rates of 4-chlorophenol and COD were 51.0% and 48.9%, respectively. PMID:18232235

  9. Nalmefene: radioimmunoassay for a new opioid antagonist.

    PubMed

    Dixon, R; Hsiao, J; Taaffe, W; Hahn, E; Tuttle, R

    1984-11-01

    A specific radioimmunoassay (RIA) has been developed for the quantitation of a new opioid antagonist, nalmefene, in human plasma. The method employs a rabbit antiserum to an albumin conjugate of naltrexone-6-(O-carboxymethyl)oxime and [3H]naltrexone as the radioligand. Assay specificity was achieved by extraction of nalmefene from plasma at pH 9 into ether prior to RIA. The procedure has a limit of sensitivity of 0.2 ng/mL of nalmefene using a 0.5-mL sample of plasma for analysis. The intra- and interassay coefficients of variation did not exceed 5.6 and 11%, respectively. The specificity of the RIA was established by demonstrating excellent agreement (r = 0.99) with a less sensitive and more time consuming HPLC procedure in the analysis of clinical plasma samples. The use of the RIA for the pharmacokinetic evaluation of nalmefene is illustrated with plasma concentration profiles of the drug in humans following intravenous and oral administration. PMID:6520774

  10. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. PMID:18238950

  11. Antagonistic neural networks underlying differentiated leadership roles

    PubMed Central

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  12. Indole-like Trk receptor antagonists.

    PubMed

    Tammiku-Taul, Jaana; Park, Rahel; Jaanson, Kaur; Luberg, Kristi; Dobchev, Dimitar A; Kananovich, Dzmitry; Noole, Artur; Mandel, Merle; Kaasik, Allen; Lopp, Margus; Timmusk, Tõnis; Karelson, Mati

    2016-10-01

    The virtual screening for new scaffolds for TrkA receptor antagonists resulted in potential low molecular weight drug candidates for the treatment of neuropathic pain and cancer. In particular, the compound (Z)-3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxindole and its derivatives were assessed for their inhibitory activity against Trk receptors. The IC50 values were computationally predicted in combination of molecular and fragment-based QSAR. Thereafter, based on the structure-activity relationships (SAR), a series of new compounds were designed and synthesized. Among the final selection of 13 compounds, (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-N-methyl-2-oxindole-5-sulfonamide showed the best TrkA inhibitory activity using both biochemical and cellular assays and (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-2-oxindole-5-sulfonamide was the most potent inhibitor of TrkB and TrkC. PMID:27318978

  13. Antagonists for acute oral cadmium chloride intoxication

    SciTech Connect

    Basinger, M.A.; Jones, M.M.; Holscher, M.A.; Vaughn, W.K.

    1988-01-01

    An examination has been carried out on the relative efficacy of a number of chelating agents when acting as antagonists for oral cadmium chloride intoxication in mice. The compounds were administered orally after the oral administration of cadmium chloride at 1 mmol/kg. Of the compounds examined, several were useful in terms of enhancing survival, but by far the most effective in both enhancing survival and leaving minimal residual levels of cadmium in the liver and the kidney, was meso-2,3-dimercaptosuccinic acid (DMSA). Several polyaminocarboxylic acids also enhanced survival. The most effective of these in reducing liver and kidney levels of cadmium were diethylenetriaminepentaacetic acid (DTPA), trans-1,2-diaminocyclohexane-N,N,N'N'-tetraacetic acid (CDTA), and triethylenetetraminehexaacetic acid (TTHA). D-Penicillamine (DPA) was found to promote survival but also led to kidney cadmium levels higher than those found in the controls. Sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was as effective in promoting survival as DMSA but left levels of cadmium in the kidney and liver that were approximately four times greater than those found with DMSA.

  14. Antagonistic neural networks underlying differentiated leadership roles.

    PubMed

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  15. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    PubMed Central

    Khanfar, Mohammad A.; Affini, Anna; Lutsenko, Kiril; Nikolic, Katarina; Butini, Stefania; Stark, Holger

    2016-01-01

    With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures. PMID:27303254

  16. Endothelin receptor antagonists in the treatment of pulmonary arterial hypertension.

    PubMed

    Langleben, David

    2007-03-01

    The recognition that endothelin-1 contributes to the pathogenesis of pulmonary arterial hypertension has led to the development of clinically useful endothelin receptor antagonists that improve symptoms and functional capacity and alter the natural history of the disease in a beneficial way. The antagonists have varying degrees of selectivity for the two classes of endothelin receptor, termed ETA and ETB, and the varying degrees may translate into clinical differences. Endothelin receptor antagonists have become an integral part of therapy for pulmonary arterial hypertension, and the indications for their use are expanding. PMID:17338931

  17. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists.

    PubMed

    Khanfar, Mohammad A; Affini, Anna; Lutsenko, Kiril; Nikolic, Katarina; Butini, Stefania; Stark, Holger

    2016-01-01

    With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures. PMID:27303254

  18. [Pd4(μ3-SbMe3)4(SbMe3)4]: A Pd(0) Tetrahedron with μ3-Bridging Trimethylantimony Ligands.

    PubMed

    Benjamin, Sophie L; Krämer, Tobias; Levason, William; Light, Mark E; Macgregor, Stuart A; Reid, Gillian

    2016-06-01

    The palladium(II) chlorostibine complex [PdCl2(SbMe2Cl)2]2 has a dimeric structure in the solid state, stabilized by hyper-coordination at the Lewis amphoteric Sb centers. Reaction with 8 equiv of MeLi forms [Pd4(μ3-SbMe3)4(SbMe3)4], whose structure comprises a tetrahedral Pd(0) core with four terminal SbMe3 ligands and four μ3-SbMe3 ligands, one capping each triangular Pd3 face. Density functional theory calculations, supported by energy decomposition analysis and the natural orbitals for chemical valence scheme, highlight significant donor and acceptor orbital contributions to the bonding between both the terminal and the bridging SbMe3 ligands and the Pd4 core. PMID:27200501

  19. Photovoltaic detector based on type II heterostructure with deep AlSb/InAsSb/AlSb quantum well in the active region for the midinfrared spectral range

    SciTech Connect

    Mikhailova, M. P. Andreev, I. A.; Moiseev, K. D.; Ivanov, E. V.; Konovalov, G. G.; Mikhailov, M. Yu.; Yakovlev, Yu. P.

    2011-02-15

    Photodetectors for the spectral range 2-4 {mu}m, based on an asymmetric type-II heterostructure p-InAs/AlSb/InAsSb/AlSb/(p, n)GaSb with a single deep quantum well (QW) or three deep QWs at the heterointerface, have been grown by metal-organic vapor phase epitaxy and analyzed. The transport, luminescent, photoelectric, current-voltage, and capacitance-voltage characteristics of these structures have been examined. A high-intensity positive and negative luminescence was observed in the spectral range 3-4 {mu}m at high temperatures (300-400 K). The photosensitivity spectra were in the range 1.2-3.6 {mu}m (T = 77 K). Large values of the quantum yield ({eta} = 0.6-0.7), responsivity (S{sub {lambda}} = 0.9-1.4 A W{sup -1}), and detectivity (D*{sub {lambda}} = 3.5 Multiplication-Sign 10{sup 11} to 10{sup 10} cm Hz{sup 1/2} W{sup -1}) were obtained at T = 77-200 K. The small capacitance of the structures (C = 7.5 pF at V = -1 V and T = 300 K) enabled an estimate of the response time of the photodetector at {tau} = 75 ps, which corresponds to a bandwidth of about 6 GHz. Photodetectors of this kind are promising for heterodyne detection of the emission of quantum-cascade lasers and IR spectroscopy.

  20. High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin Self-Administration in Wild-Type but not D3R Knockout Mice.

    PubMed

    Boateng, Comfort A; Bakare, Oluyomi M; Zhan, Jia; Banala, Ashwini K; Burzynski, Caitlin; Pommier, Elie; Keck, Thomas M; Donthamsetti, Prashant; Javitch, Jonathan A; Rais, Rana; Slusher, Barbara S; Xi, Zheng-Xiong; Newman, Amy Hauck

    2015-08-13

    The dopamine D3 receptor (D3R) is a promising target for the development of pharmacotherapeutics to treat substance use disorders. Several D3R-selective antagonists are effective in animal models of drug abuse, especially in models of relapse. Nevertheless, poor bioavailability, metabolic instability, and/or predicted toxicity have impeded success in translating these drug candidates to clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines with improved metabolic stability. A subset of these compounds was evaluated for D3R functional efficacy and off-target binding at selected 5-HT receptor subtypes, where significant overlap in SAR with D3R has been observed. Several high affinity D3R antagonists, including compounds 16 (Ki = 0.12 nM) and 32 (Ki = 0.35 nM), showed improved metabolic stability compared to the parent compound, PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were effective in reducing self-administration of heroin in wild-type but not D3R knockout mice. PMID:26203768

  1. The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.

    PubMed

    Lochner, Martin; Thompson, Andrew J

    2016-09-01

    Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects. PMID:27108935

  2. Single exposure of dopamine D1 antagonist prevents and D2 antagonist attenuates methylphenidate effect

    PubMed Central

    Claussen, Catherine M; Witte, Lindsey J; Dafny, Nachum

    2015-01-01

    Methylphenidate (MPD) is a readily prescribed drug for the treatment of attention deficit hyperactivity disorder (ADHD) and moreover is used illicitly by youths for its cognitive-enhancing effects and recreation. MPD exposure in rodents elicits increased locomotor activity. Repetitive MPD exposure leads to further augmentation of their locomotor activity. This behavioral response is referred to as behavioral sensitization. Behavioral sensitization is used as an experimental marker for a drug’s ability to elicit dependence. There is evidence that dopamine (DA) is a key player in the acute and chronic MPD effect; however, the role of DA in the effects elicited by MPD is still debated. The objective of this study was to investigate the role of D1 and/or D2 DA receptors in the acute and chronic effect of MPD on locomotor activity. The study lasted for 12 consecutive days. Seven groups of male Sprague Dawley® rats were used. A single D1 or D2 antagonist was given before and after acute and chronic MPD administration. Single injection of D1 DA antagonist was able to significantly attenuate the locomotor activity when given prior to the initial MPD exposure and after repetitive MPD exposure, while the D2 DA antagonist partially attenuated the locomotor activity only when given before the second MPD exposure. The results show the role, at least in part, of the D1 DA receptor in the mechanism of behavioral sensitization, whereas the D2 DA receptor only partially modulates the response to acute and chronic MPD. PMID:27186140

  3. Interface effect of InSb quantum dots embedded in SiO{sub 2} matrix

    SciTech Connect

    Chen Dongliang; Fan Jiangwei; Wei Shiqiang; Li Chaosheng; Zhu Zhengang

    2005-08-15

    The interface effect of InSb quantum dots (QDs) embedded in SiO{sub 2} matrix has been investigated by Raman scattering spectroscopy, x-ray diffraction (XRD), and x-ray absorption fine structure (both of EXAFS and XANES). The EXAFS and XRD results show clearly that the bond length of the Sb-In first shell of the InSb QDs contracts slightly about 0.02 A compared with that of the bulk InSb. The Raman scattering spectrum of the InSb QDs reveals that the lattice contraction partly weakens the phonon confinement effect. The coordination geometry at the interface of the InSb QDs is mainly Sb (In)-O covalent bridge bonds. The Sb K-XANES calculations of InSb QDs embedded in SiO{sub 2} matrix based on FEFF8 indicate that the intensity increase and the broadening of the white line peak of Sb atoms are essentially attributed to both the increase of Sb p-hole population and the change of Sb intra-atomic potential {mu}{sub 0}(E) affected by the SiO{sub 2} matrix. Our results show that the interface effect between the InSb QDs and the SiO{sub 2} matrix leads not only to the slight lattice contraction of InSb QDs and the large structural distortion in the interface area of InSb QDs, but also to the significant change of the Sb intra-atomic potential and the obvious charge redistribution around Sb atoms.

  4. The reaction mechanism of SnSb and Sb thin film anodes for Na-ion batteries studied by X-ray diffraction, 119Sn and 121Sb Mössbauer spectroscopies

    SciTech Connect

    Baggetto, Loïc; Hah, Hien-Yoong; Jumas, Jean-Claude; Johnson, Charles E.; Johnson, Jacqueline A.; Keum, Jong K.; Bridges, Craig A.; Veith, Gabriel M.

    2014-06-01

    The electrochemical reaction of Sb and SnSb anode materials with Na results in the formation of amorphous materials. To understand the resulting phases and electrochemical capacities we studied the reaction products local order using 119Sn and 121Sb Mössbauer spectroscopies in conjunction with measurements performed on model powder compounds of Na-Sn and Na-Sb to further clarify the reactions steps. For pure Sb the discharge (sodiation) starts with the formation of an amorphous phase composed of atomic environments similar to those found in NaSb, and proceeds further by the formation of environments similar to that present in Na3Sb. The reversible reaction takes place during a large portion of the charge process. At full charge the anode material still contains a substantial fraction of Na, which explains the lack of recrystallization into crystalline Sb. The reaction of SnSb yields Na3Sb crystalline phase at full discharge at higher temperatures (65 and 95°C) while the room temperature reaction yields amorphous compounds. The electrochemically-driven, solid-state amorphization reaction occurring at room temperature is governed by the simultaneous formation of Na-coordinated Sn and Sb environments, as monitored by the decrease (increase) of the 119Sn (121Sb) Mössbauer isomer shifts. Overall, the monitoring of the hyperfine parameters enables to correlate the changes in Na content to the individual Sn and Sb local chemical environments.

  5. Removal of Antimonite (Sb(III)) and Antimonate (Sb(V)) from Aqueous Solution Using Carbon Nanofibers That Are Decorated with Zirconium Oxide (ZrO2).

    PubMed

    Luo, Jinming; Luo, Xubiao; Crittenden, John; Qu, Jiuhui; Bai, Yaohui; Peng, Yue; Li, Junhua

    2015-09-15

    Zirconium oxide (ZrO2)-carbon nanofibers (ZCN) were fabricated and batch experiments were used to determine antimonite (Sb(III)) and antimonate (Sb(V)) adsorption isotherms and kinetics. ZCN have a maximum Sb(III) and Sb(V) adsorption capacity of 70.83 and 57.17 mg/g, respectively. The adsorption process between ZCN and Sb was identified to be an exothermic and follows an ion-exchange reaction. The application of ZCN was demonstrated using tap water spiked with Sb (200 μg/L). We found that the concentration of Sb was well below the maximum contaminant level for drinking water with ZCN dosages of 2 g/L. X-ray photoelectron spectroscopy (XPS) revealed that an ionic bond of Zr-O was formed with Sb(III) and Sb(V). Based on the density functional theory (DFT) calculations, Sb(III) formed Sb-O and O-Zr bonds on the surface of the tetragonal ZrO2 (t-ZrO2) (111) plane and monoclinic ZrO2 planes (m-ZrO2) (111) plane when it adsorbs. Only an O-Zr bond was formed on the surface of t-ZrO2 (111) plane and m-ZrO2 (111) plane for Sb(V) adsorption. The adsorption energy (Ead) of Sb(III) and Sb(V) onto t-ZrO2 (111) plane were 1.13 and 6.07 eV, which were higher than that of m-ZrO2 (0.76 and 3.35 eV, respectively). PMID:26301862

  6. Photophysical Property and Photocatalytic Activity of New Gd2InSbO7 and Gd2FeSbO7 Compounds under Visible Light Irradiation

    PubMed Central

    Luan, Jingfei; Xu, Yong

    2013-01-01

    Gd2InSbO7 and Gd2FeSbO7 were synthesized first, and their structural and photocatalytic properties were studied. The lattice parameters and the band gaps for Gd2InSbO7 and Gd2FeSbO7 were 10.449546 Å, 10.276026 Å, 2.897 eV and 2.151 eV. The photocatalytic degradation of rhodamine B was performed with Gd2InSbO7 and Gd2FeSbO7 under visible light irradiation. Gd2InSbO7 and Gd2FeSbO7 had higher catalytic activity compared with Bi2InTaO7. Gd2FeSbO7 exhibited higher catalytic activity than Gd2InSbO7. The photocatalytic degradation of rhodamine B followed with the first-order reaction kinetics, and the first-order rate constant k was 0.01606, 0.02220 or 0.00329 min−1 with Gd2InSbO7, Gd2FeSbO7 or Bi2InTaO7 as photocatalyst. Complete removal of rhodamine B was observed after visible light irradiation for 225 min or 260 min with Gd2FeSbO7 or Gd2InSbO7 as photocatalyst. The evolution of CO2 was realized, and it indicated continuous mineralization of rhodamine B during the photocatalytic process. The possible photocatalytic degradation pathway of rhodamine B was proposed. PMID:23296275

  7. Co-In-Sb Ternary System (I): Isothermal Sections and Liquidus Projection

    NASA Astrophysics Data System (ADS)

    Tseng, Ssu-ming; Chen, Sinn-wen; Chang, Jui-shen; Tang, Yinglu; Snyder, G. Jeffrey

    2015-12-01

    The Co-In-Sb ternary system has thermoelectric application interests. Co-In-Sb ternary alloys are prepared in this study. Their equilibrium phases at 1123.15 K and 923.15 K (850 °C and 650 °C) as well as their primary solidification phases and univariant reaction temperatures are determined. The isothermal sections at 1123.15 K and 923.15 K (850 °C and 650 °C) and the liquidus projection of the Co-In-Sb ternary system are determined based on the ternary experimental results, the phase diagrams of its three constituent binary systems, and the limited phase equilibria literature. No ternary compounds are found. The phase relationships at both 1123.15 K and 923.15 K (850 °C and 650 °C) are the same. There are five phases, seven two-phase regions, and three tie-triangles which are Co-CoSb-liquid, CoSb-CoSb2-liquid, and CoSb2-CoSb3-liquid. In the liquidus projection, there are nine primary solidification phase regions, Co, CoSb, CoSb2, CoSb3, Sb, InSb, In, CoIn2, and CoIn3. There are seven invariant reactions which are two Class I, four Class II, and one Class III.

  8. Nanostructuring of Undoped ZnSb by Cryo-Milling

    NASA Astrophysics Data System (ADS)

    Song, X.; Valset, K.; Graff, J. S.; Thøgersen, A.; Gunnæs, A. E.; Luxsacumar, S.; Løvvik, O. M.; Snyder, G. J.; Finstad, T. G.

    2015-08-01

    We report the preparation of nanosized ZnSb powder by cryo-milling. The effect of cryo-milling then hot-pressing of undoped ZnSb was investigated and compared with that of room temperature ball-milling and hot-pressing under different temperature conditions. ZnSb is a semiconductor with favorable thermoelectric properties when doped. We used undoped ZnSb to study the effect of nanostructuring on lattice thermal conductivity, and with little contribution at room temperature from electronic thermal conductivity. Grain growth was observed to occur during hot-pressing, as observed by transmission electron microscopy and x-ray diffraction. The thermal conductivity was lower for cryo-milled samples than for room-temperature ball-milled samples. The thermal conductivity also depended on hot-pressing conditions. The thermal conductivity could be varied by a factor of two by adjusting the process conditions and could be less than a third that of single-crystal ZnSb.

  9. Characterization of midwave infrared InSb avalanche photodiode

    SciTech Connect

    Abautret, J. Evirgen, A.; Perez, J. P.; Christol, P.; Rothman, J.; Cordat, A.

    2015-06-28

    This paper focuses on the InSb material potential for the elaboration of Avalanche Photodiodes (APD) for high performance infrared imaging applications, both in passive or active mode. The first InSb electron-APD structure was grown by molecular beam epitaxy, processed and electrically characterized. The device performances are at the state of the art for the InSb epi-diode technology, with a dark current density J(−50 mV) = 32 nA/cm{sup 2} at 77 K. Then, a pure electron injection was performed, and an avalanche gain, increasing exponentially, was observed with a gain value near 3 at −4 V at 77 K. The Okuto–Crowell model was used to determine the electron ionization coefficient α(E) in InSb, and the InSb gain behavior is compared with the one of InAs and MCT APDs.

  10. TANK 40 FINAL SB6 CHEMICAL CHARACTERIZATION RESULTS

    SciTech Connect

    Bannochie, C.

    2010-08-13

    A sample of Sludge Batch 6 (SB6) was taken from Tank 40 in order to obtain radionuclide inventory analyses necessary for compliance with the Waste Acceptance Product Specifications (WAPS), and a portion of the sample was designated for SB6 processing studies. The SB6 WAPS sample was also analyzed for chemical composition including noble metals and fissile composition, and these results are reported here. These analyses along with the WAPS radionuclide analyses will help define the composition of the sludge in Tank 40 that is currently being fed to DWPF as SB6. At the Savannah River National Laboratory (SRNL) the 3-L Tank 40 SB6 sample was transferred from the shipping container into a 4-L high density polyethylene vessel and solids were allowed to settle overnight. Supernate was then siphoned off and circulated through the shipping container to complete the transfer of the sample. Following thorough mixing of the 3-L sample, a 485 g sub-sample was removed. This sub-sample was then utilized for all subsequent analytical samples.

  11. (Ga,Fe)Sb: A p-type ferromagnetic semiconductor

    SciTech Connect

    Tu, Nguyen Thanh; Anh, Le Duc; Tanaka, Masaaki; Hai, Pham Nam

    2014-09-29

    A p-type ferromagnetic semiconductor (Ga{sub 1−x},Fe{sub x})Sb (x = 3.9%–13.7%) has been grown by low-temperature molecular beam epitaxy (MBE) on GaAs(001) substrates. Reflection high energy electron diffraction patterns during the MBE growth and X-ray diffraction spectra indicate that (Ga,Fe)Sb layers have the zinc-blende crystal structure without any other crystallographic phase of precipitates. Magnetic circular dichroism (MCD) spectroscopy characterizations indicate that (Ga,Fe)Sb has the zinc-blende band structure with spin-splitting induced by s,p-d exchange interactions. The magnetic field dependence of the MCD intensity and anomalous Hall resistance of (Ga,Fe)Sb show clear hysteresis, demonstrating the presence of ferromagnetic order. The Curie temperature (T{sub C}) increases with increasing x and reaches 140 K at x = 13.7%. The crystal structure analyses, magneto-transport, and magneto-optical properties indicate that (Ga,Fe)Sb is an intrinsic ferromagnetic semiconductor.

  12. Large magnetoresistance in the antiferromagnetic semimetal NdSb

    NASA Astrophysics Data System (ADS)

    Wakeham, N.; Bauer, E. D.; Neupane, M.; Ronning, F.

    2016-05-01

    There has been considerable interest in topological semimetals that exhibit extreme magnetoresistance (XMR). These have included materials lacking inversion symmetry such as TaAs, as well Dirac semimetals such as Cd3As2 . However, it was reported recently that LaSb and LaBi also exhibit XMR, even though the rocksalt structure of these materials has inversion symmetry, and the band-structure calculations do not show a Dirac dispersion in the bulk. Here, we present magnetoresistance and specific-heat measurements on NdSb, which is isostructural with LaSb. NdSb has an antiferromagnetic ground state and, in analogy with the lanthanum monopnictides, is expected to be a topologically nontrivial semimetal. We show that NdSb has an XMR of ˜104% , even within the antiferromagnetic state, illustrating that XMR can occur independently of the absence of time-reversal symmetry breaking in zero magnetic field. The persistence of XMR in a magnetic system offers the promise of new functionality when combining topological matter with electronic correlations. We also find that in an applied magnetic field below the Néel temperature there is a first-order transition, consistent with evidence from previous neutron scattering work.

  13. On the nature of chemical bonding in the all-metal aromatic [Sb3Au3Sb3](3-) sandwich complex.

    PubMed

    You, Xue-Rui; Tian, Wen-Juan; Li, Da-Zhi; Wang, Ying-Jin; Li, Rui; Feng, Lin-Yan; Zhai, Hua-Jin

    2016-05-21

    In a recent communication, an all-metal aromatic sandwich [Sb3Au3Sb3](3-) was synthesized and characterized. We report herein a density-functional theory (DFT) study on the chemical bonding of this unique cluster, which makes use of a number of computational tools, including the canonical molecular orbital (CMO), adaptive natural density partitioning (AdNDP), Wiberg bond index, and orbital composition analyses. The 24-electron, triangular prismatic sandwich is intrinsically electron-deficient, being held together via six Sb-Sb, three Au-Au, and six Sb-Au links. A standard, qualitative bonding analysis suggests that all CMOs are primarily located on the three Sb3/Au3/Sb3 layers, three Au 6s based CMOs are fully occupied, and the three extra charges are equally shared by the two cyclo-Sb3 ligands. This bonding picture is referred to as the zeroth order model, in which the cluster can be formally formulated as [Sb3(1.5+)Au3(3-)Sb3(1.5+)](3-) or [Sb3(0)Au3(3-)Sb3(0)]. However, the system is far more complex and covalent than the above picture. Seventeen CMOs out of 33 in total involve remarkable Sb → Au electron donation and Sb ← Au back-donation, which are characteristic of covalent bonding and effectively redistribute electrons from the Sb3 and Au3 layers to the interlayer edges. This effect collectively leads to three Sb-Au-Sb three-center two-electron (3c-2e) σ bonds as revealed in the AdNDP analyses, despite the fact that not a single such bond can be identified from the CMOs. Orbital composition analyses for the 17 CMOs allow a quantitative understanding of how electron donation and back-donation redistribute the charges within the system from the formal Sb3(0)/Au3(3-) charge states in the zeroth order model to the effective Sb3(1.5-)/Au3(0) charge states, the latter being revealed from the natural bond orbital analysis. PMID:27124821

  14. Biomolecular recognition of antagonists by α7 nicotinic acetylcholine receptor: Antagonistic mechanism and structure-activity relationships studies.

    PubMed

    Peng, Wei; Ding, Fei

    2015-08-30

    As the key constituent of ligand-gated ion channels in the central nervous system, nicotinic acetylcholine receptors (nAChRs) and neurodegenerative diseases are strongly coupled in the human species. In recently years the developments of selective agonists by using nAChRs as the drug target have made a large progress, but the studies of selective antagonists are severely lacked. Currently these antagonists rest mainly on the extraction of partly natural products from some animals and plants; however, the production of these crude substances is quite restricted, and artificial synthesis of nAChR antagonists is still one of the completely new research fields. In the context of this manuscript, our primary objective was to comprehensively analyze the recognition patterns and the critical interaction descriptors between target α7 nAChR and a series of the novel compounds with potentially antagonistic activity by means of virtual screening, molecular docking and molecular dynamics simulation, and meanwhile these recognition reactions were also compared with the biointeraction of α7 nAChR with a commercially natural antagonist - methyllycaconitine. The results suggested clearly that there are relatively obvious differences of molecular structures between synthetic antagonists and methyllycaconitine, while the two systems have similar recognition modes on the whole. The interaction energy and the crucially noncovalent forces of the α7 nAChR-antagonists are ascertained according to the method of Molecular Mechanics/Generalized Born Surface Area. Several amino acid residues, such as B/Tyr-93, B/Lys-143, B/Trp-147, B/Tyr-188, B/Tyr-195, A/Trp-55 and A/Leu-118 played a major role in the α7 nAChR-antagonist recognition processes, in particular, residues B/Tyr-93, B/Trp-147 and B/Tyr-188 are the most important. These outcomes tally satisfactorily with the discussions of amino acid mutations. Based on the explorations of three-dimensional quantitative structure

  15. Complications of TNF-α antagonists and iron homeostasis

    EPA Science Inventory

    TNF-α is a central regulator of inflammation and its blockade downregulates other proinflammatory cytokines, chemokines, and growth factors. Subsequently, TNF-α antagonists are currently used in treatment regimens directed toward several inflammatory diseases. Despite a beneficia...

  16. Complexes of different nitrogen donor heterocyclic ligands with SbCl3 and PhSbCl2 as potential antileishmanial agents against Sb(III)-sensitive and -resistant parasites.

    PubMed

    Lizarazo-Jaimes, Edgar H; Reis, Priscila G; Bezerra, Filipe M; Rodrigues, Bernardo L; Monte-Neto, Rubens L; Melo, Maria N; Frézard, Frédéric; Demicheli, Cynthia

    2014-03-01

    Novel trivalent antimony complexes with the nitrogen donor heterocyclic ligand 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) have been synthesized by the reaction with SbCl3 or PhSbCl2. The crystal structures of [Sb(phen)Cl3] and [PhSb(phen)Cl2]CH3COOH were determined and shown to adopt a distorted square pyramid geometry with a five-coordinated Sb center. Surprisingly, all the complexes, the ligands and PhSbCl2 showed very high antileishmanial activities, with IC50 in the nanomolar range against Sb(III)-sensitive and -resistant Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis strains. These compounds were much more active against these Leishmania strains than the old trivalent drug potassium antimonyl tartrate. [PhSb(phen)Cl2]CH3COOH complex was found to be the most active compound and the lack of cross-resistance of PhSbCl2 suggests that the transport pathways of this compound across the cell membrane differ from those responsible for the resistance of Leishmania to Sb(OH)3. In the case of the complexes with PhSbCl2, our data supports the model that both ligand and metal contributed to the overall activity of the complex. Furthermore, among the complexes with SbCl3, only bipy showed an improved activity upon complexation. Cytotoxicity evaluations of these compounds against murine peritoneal macrophages showed high selective indexes in the range of 7-70 for [Sb(phen)Cl3], [Sb(bipy)Cl3] and [Sb(dpq)Cl3] complexes, being much more selective than potassium antimonyl tartrate. In conclusion, this study presents a set of new antileishmanial agents including one of the most active Sb-based compounds ever reported, which can contribute to the development of new chemotherapeutic strategies against leishmaniasis including Sb-resistant cases. PMID:24412095

  17. Anthropomorphic finger antagonistically actuated by SMA plates.

    PubMed

    Engeberg, Erik D; Dilibal, Savas; Vatani, Morteza; Choi, Jae-Won; Lavery, John

    2015-10-01

    Most robotic applications that contain shape memory alloy (SMA) actuators use the SMA in a linear or spring shape. In contrast, a novel robotic finger was designed in this paper using SMA plates that were thermomechanically trained to take the shape of a flexed human finger when Joule heated. This flexor actuator was placed in parallel with an extensor actuator that was designed to straighten when Joule heated. Thus, alternately heating and cooling the flexor and extensor actuators caused the finger to flex and extend. Three different NiTi based SMA plates were evaluated for their ability to apply forces to a rigid and compliant object. The best of these three SMAs was able to apply a maximum fingertip force of 9.01N on average. A 3D CAD model of a human finger was used to create a solid model for the mold of the finger covering skin. Using a 3D printer, inner and outer molds were fabricated to house the actuators and a position sensor, which were assembled using a multi-stage casting process. Next, a nonlinear antagonistic controller was developed using an outer position control loop with two inner MOSFET current control loops. Sine and square wave tracking experiments demonstrated minimal errors within the operational bounds of the finger. The ability of the finger to recover from unexpected disturbances was also shown along with the frequency response up to 7 rad s(-1). The closed loop bandwidth of the system was 6.4 rad s(-1) when operated intermittently and 1.8 rad s(-1) when operated continuously. PMID:26292164

  18. Suppressing antagonistic bioengineering feedbacks doubles restoration success.

    PubMed

    Suykerbuyk, Wouter; Bouma, Tjeerd J; van der Heide, Tjisse; Faust, Cornelia; Govers, Laura L; Giesen, Wim B J T; de Jong, Dick J; van Katwijk, Marieke M

    2012-06-01

    In a seagrass restoration project, we explored the potential for enhancing the restoration process by excluding antagonistic engineering interactions (i.e., biomechanical warfare) between two ecosystem engineers: the bioturbating lugworm Arenicola marina and the sediment-stabilizing seagrass Zostera noltii Hornem. Applying a shell layer underneath half of our seagrass transplants successfully reduced adult lugworm density by over 80% and reduced lugworm-induced microtopography (a proxy for lugworm disturbance) at the wave-sheltered site. At the wave-exposed site adult lugworm densities and microtopography were already lower than at the sheltered site but were further reduced in the shell-treated units. Excluding lugworms and their bioengineering effects corresponded well with a strongly enhanced seagrass growth at the wave-sheltered site, which was absent at the exposed site. Enhanced seagrass growth in the present study was fully assigned to the removal of lugworms' negative engineering effects and not to any (indirect) evolving effects such as an altered biogeochemistry or sediment-stabilizing effects by the shell layer. The context-dependency implies that seagrass establishment at the exposed site is not constrained by negative ecosystem-engineering interactions only, but also by overriding physical stresses causing poor growth conditions. Present findings underline that, in addition to recent emphasis on considering positive (facilitating) interactions in ecological theory and practice, it is equally important to consider negative engineering interactions between ecosystem-engineering species. Removal of such negative interactions between ecosystem-engineering species can give a head start to the target species at the initial establishment phase, when positive engineering feedbacks by the target species on itself are still lacking. Though our study was carried out in a marine environment with variable levels of wave disturbance, similar principles may be

  19. Azogabazine; a photochromic antagonist of the GABAA receptor.

    PubMed

    Huckvale, Rosemary; Mortensen, Martin; Pryde, David; Smart, Trevor G; Baker, James R

    2016-07-12

    The design and synthesis of azogabazine is described, which represents a highly potent (IC50 = 23 nM) photoswitchable antagonist of the GABAA receptor. An azologization strategy is adopted, in which a benzyl phenyl ether in a high affinity gabazine analogue is replaced by an azobenzene, with resultant retention of antagonist potency. We show that cycling from blue to UV light, switching between trans and cis isomeric forms, leads to photochemically controlled antagonism of the GABA ion channel. PMID:27327397

  20. Identification of M-CSF agonists and antagonists

    DOEpatents

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

    2000-02-15

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

  1. Deficiency of interleukin-1 receptor antagonist responsive to anakinra.

    PubMed

    Schnellbacher, Charlotte; Ciocca, Giovanna; Menendez, Roxanna; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Duarte, Ana M; Rivas-Chacon, Rafael

    2013-01-01

    We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acute-phase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy. PMID:22471702

  2. Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.

    PubMed

    Alcaro, Maria C; Vinci, Valerio; D'Ursi, Anna M; Scrima, Mario; Chelli, Mario; Giuliani, Sandro; Meini, Stefania; Di Giacomo, Marcello; Colombo, Lino; Papini, Anna Maria

    2006-05-01

    Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure-activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic beta-turn inducers. PMID:16504505

  3. Rare-earth metal-rich antimonides: syntheses, structures, and properties of Tm(3)Sb and Lu(7)Sb(3).

    PubMed

    Gupta, Shalabh; Chen, Ling; Ganguli, Ashok K; Corbett, John D

    2007-03-19

    The two most metal-rich lanthanide antimony phases known were obtained from high-temperature solid state syntheses, that for Tm3Sb being of greater difficulty because of its apparent incongruent melting. The Tm3Sb phase crystallizes in the tetragonal space group P42/n (No. 86) with a Ti3P-type (Pearson: tP32) structure, a = 12.2294(5) Angstrom, c = 5.9852(5) Angstrom, and Z = 8. The phase Lu7Sb3 exhibits a Sc7As3-type tetragonal structure, I4/mcm (No. 140) (tI56), with a = 15.5974(7) Angstrom, c = 8.8130(7) Angstrom, and Z = 8. Both structures are described in terms of compact arrays of condensed chains of metal polyhedra (tetrahedral, tetrahedral star, trigonal prismatic, cubic) together with six- to nine-coordinate Sb in metal polyhedra. Magnetic susceptibility data on the paramagnetic Tm3Sb are also reported. PMID:17302406

  4. Retention of As and Sb in ombrotrophic peat bogs: records of As, Sb, and Pb deposition at four Scottish sites.

    PubMed

    Cloy, Joanna M; Farmer, John G; Graham, Margaret C; MacKenzie, Angus B

    2009-03-15

    Possible postdepositional As migration in ombrotrophic peat bogs was investigated by comparing depth profiles of As with those of Sb and Pb, two elements considered to be essentially immobile in peat, and those of redox-sensitive, potentially mobile nutrient elements such as Mn, Fe, P, and S in 210Pb-dated cores from four Scottish bogs. Concentration profiles of As were similar to those of Sb and Pb rather than these other elements, indicating that As is bound strongly to organic matter and is relatively immobile in ombrotrophic peat. Historical records of atmospheric anthropogenic As, Sb, and Pb deposition during the industrial and postindustrial periods were derived, site-specific maxima (up to 1.55, 1.33, and 45 mg m(-2) y(-1), respectively) occurring between the late 1890s and 1960s, reflecting emissions from diverse sources such as mining and smelting, coal combustion, and also, in the case of Pb, exhaust emissions from the use of leaded gasoline. Since the mid-1980s, fluxes of Pb decreased (4-7 fold) more rapidly than those of As and Sb (2-3 fold), attributable to both the gradual elimination of leaded gasoline and recent new sources of the latter elements. Relative trends in derived anthropogenic As, Sb, and Pb deposition largely agreed with other Scottish peat and moss archive records, direct measurements of deposition, and UK emissions, i.e., four different types of data source. PMID:19368168

  5. Structure of amorphous Ge8Sb2Te11 : GeTe-Sb2Te3 alloys and optical storage

    NASA Astrophysics Data System (ADS)

    Akola, J.; Jones, R. O.

    2009-04-01

    The amorphous structure of Ge8Sb2Te11 , an alloy used in the Blu-ray Disc, the de facto successor to digital versatile disk (DVD) optical storage, has been characterized by large-scale (630 atoms, 0.4 ns) density-functional/molecular-dynamics simulations using the new PBEsol approximation for the exchange-correlation energy functional. The geometry and electronic structure agree well with available x-ray diffraction data and photoelectron measurements. The total coordination numbers are Ge: 4.0, Sb: 3.7, and Te: 2.9, and the Ge-Ge partial coordination number is 0.7. Most atoms (particularly Sb) prefer octahedral coordination but 42% of Ge atoms are “tetrahedral.” Structural details, including ring statistics, local coordination, and cavities (12% of total volume), are strikingly similar to those of Ge2Sb2Te5 , which is used in DVD-random access memory. The presence of less than 10% Sb atoms leads to significant changes from GeTe.

  6. Retention of As and Sb in ombrotrophic peat bogs: records of As, Sb, and Pb deposition at four Scottish sites

    SciTech Connect

    Joanna M. Cloy; John G. Farmer; Margaret C. Graham; Angus B. MacKenzie

    2009-03-15

    Possible postdepositional As migration in ombrotrophic peat bogs was investigated by comparing depth profiles of As with those of Sb and Pb, two elements considered to be essentially immobile in peat, and those of redox-sensitive, potentially mobile nutrient elements such as Mn, Fe, P, and S in {sup 210}Pb-dated cores from four Scottish bogs. Concentration profiles of As were similar to those of Sb and Pb rather than these other elements, indicating that As is bound strongly to organic matter and is relatively immobile in ombrotrophic peat. Historical records of atmospheric anthropogenic As, Sb, and Pb deposition during the industrial and postindustrial periods were derived, site-specific maxima (up to 1.55, 1.33, and 45 mg m{sup -2} y{sup -1}, respectively) occurring between the late 1890s and 1960s, reflecting emissions from diverse sources such as mining and smelting, coal combustion, and also, in the case of Pb, exhaust emissions from the use of leaded gasoline. Since the mid-1980s, fluxes of Pb decreased (4-7 fold) more rapidly than those of As and Sb (2-3 fold), attributable to both the gradual elimination of leaded gasoline and recent new sources of the latter elements. Relative trends in derived anthropogenic As, Sb, and Pb deposition largely agreed with other Scottish peat and moss archive records, direct measurements of deposition, and UK emissions, i.e., four different types of data source. 36 refs., 3 figs., 1 tab.

  7. Effect of Sb incorporation on structure and magnetic properties of quaternary ferromagnetic semiconductor (Ga, Mn)(As, Sb) thin films

    SciTech Connect

    Deng, J. J.; Che, J. T.; Chen, J.; Wang, W. J.; Hu, B.; Wang, H. L.; Zhao, J. H.

    2013-12-28

    GaAs-based quaternary ferromagnetic semiconductor (Ga, Mn)(As, Sb) has been successfully prepared by molecular-beam epitaxy. High-resolution x-ray diffraction measurements indicate that the lattice constant has a notable alteration with changing Sb content. Magnetic measurements demonstrate the same evolution of the Curie temperature T{sub C} and the effective Mn content x{sub eff} with increasing Sb content. The incorporation of low Sb content is of benefit to increasing x{sub eff}, thus, increasing T{sub C}. However, higher Sb content degrades the crystal quality, resulting in a decrease of x{sub eff}. Experimental results show that T{sub C} is proportional to the product of x{sub eff} and p{sup 1/3}, which is consistent with the Zener Model. The exchange energy N{sub 0}β is calculated to be −1.09 eV, which is similar to that of (Ga, Mn)As.

  8. Radiation-modified structure of Ge25Sb15S60 and Ge35Sb5S60 glasses.

    PubMed

    Kavetskyy, T; Shpotyuk, O; Kaban, I; Hoyer, W

    2008-06-28

    Atomic structures of Ge(25)Sb(15)S(60) and Ge(35)Sb(5)S(60) glasses are investigated in the gamma-irradiated and annealed after gamma-irradiation states by means of high-energy synchrotron x-ray diffraction technique. The first sharp diffraction peak (FSDP) is detected at around 1.1 A(-1) in the structure factors of both alloys studied. The FSDP position is found to be stable for radiation/annealing treatment of the samples, while the FSDP intensity shows some changes between gamma-irradiated and annealed states. The peaks in the pair distribution functions observed between 2 and 4 A are related to the Ge-S, Ge-Sb, and Sb-Sb first neighbor correlations and Ge-Ge second neighbor correlations in the edge-shared GeS(42) tetrahedra, and S-S and/or Ge-Ge second neighbor correlations in the corner-shared GeS(42) tetrahedra. Three mechanisms of the radiation-/annealing-induced changes are discussed in the framework of coordination topological defect formation and bond-free solid angle concepts. PMID:18601355

  9. The two-dimensional tunnel structures of K3Sb5O14 and K2Sb4O11

    NASA Technical Reports Server (NTRS)

    Hong, H. Y.-P.

    1974-01-01

    The structures of K3Sb5O14 and K2Sb4O11 have been solved by the single-crystal X-ray direct method and the heavy-atom method, respectively. The structure of K3Sb5O14 is orthorhombic, with space group Pbam and cell parameters a = 24.247 (4), b = 7.157 (2), c = 7.334 (2) A, Z = 4. The structure of K2Sb4O11 is monoclinic, with space group C2/m and cell parameters a = 19.473 (4), b = 7.542 (1), c = 7.198 (1) A, beta = 94.82 (2) deg, Z = 4. A full-matrix least-squares refinement gave R = 0.072 and R = 0.067, respectively. In both structures, oxygen atoms form an octahedron around each Sb atom and an irregular polyhedron around each K atom. By sharing corners and edges, the octahedra form a skeleton network having intersecting b-axis and c-axis tunnels. The K(+) ions, which have more than ten oxygen near neighbors, are located in these tunnels. Evidence for K(+)-ion transport within and between tunnels comes from ion exchange of the alkali ions in molten salts and anisotropic temperature factors that are anomalously large in the direction of the tunnels.

  10. Characteristics of GaSb and GaInSb layers grown by metalorganic vapor phase epitaxy

    SciTech Connect

    Ehsani, H.; Bhat, I.; Hitchcock, C.; Borrego, J.; Gutmann, R.

    1995-07-01

    GaInSb and GaSb layers have been grown on GaSb and GaAs substrates using metalorganic vapor phase epitaxy (MOVPE) with trimethylgallium, trimethylindium and trimethylantimony as the sources. As grown layers are p type with the carrier concentration in the mid 10{sup 16} cm{sup {minus}3} range. N type layers are grown using diethyltellurium as the Te source. Incorporation of Te in high concentration showed compensation and secondary ion mass spectrometry (SIMS) result showed that only 2.5% of Te are active when 2 {times} 10{sup 19} cm{sup {minus}3} of Te was incorporated. The carrier concentration measured in n type samples increases as the temperature is lowered. This is explained by the presence of second band close to the conduction band minima. Silane which is a common n type dopant in GaAs and other III-V systems is shown to behave like p type in GaInSb. P-n junction structures have been grown on GaSb substrates to fabricate TPV cells.

  11. Antimony vibrations in skutterudites probed by 121Sb nuclear inelastic scattering

    SciTech Connect

    Wille, H. -C.; Hermann, R. P.; Sergueev, I.; Leupold, O.; van der Linden, P.; Sales, Brian C; Grandjean, F.; Long, G. J.; Ruffer, R.; Shvyd'ko, Yu. V.

    2007-01-01

    The antimony specific lattice dynamic properties in the unfilled and filled EuFe4Sb12 skutterudites have been determined by nuclear inelastic scattering at the 121Sb nuclear resonance energy of 37.1298(2) keV with a 4.5 meV high-resolution backscattering sapphire monochromator. The Sb partial vibrational density of states, DOS, shows a maximum centered at 17 and 16 meV in CoSb3 and EuFe4Sb12, respectively. The difference in the Sb DOS of CoSb3 and EuFe4Sb12 reveals that upon filling a transfer of 10% of the vibrational states towards lower energy occurs. Further, a likely indication of the coupling between the guest and the host lattice in rattler systems is observed, a coupling that is required to reduce the lattice thermal conductivity.

  12. Exposure Assessment of Sb2O3 in PET Food Contact Materials.

    PubMed

    Zhu, Lei; Wang, Zhu Tian; Xu, Hai Bin; Sun, Ru Bao; Zhang, Hong; Zhang, Jian Bo

    2016-04-01

    This study was conducted to do exposure assessment of the possible migration of antimony trioxide (Sb2O3) from Polyethylene terephthalate (PET) food contact materials (FCM). Consumption Factor (CF) and Food-type Distribution Factor (fT) were calculated from survey data with reference to the US FDA method. The most conservative migration conditions were obtained by testing Sb migration from PET FCM based on the Chinese national standard of GB/T 5009.101-2003[1]. Migration levels of Sb from PET FCM were tested and migration levels of Sb2O3 were obtained through molecular weight conversion between Sb and Sb2O3. Exposure assessment of Sb2O3 was undertaken. The Chinese Estimated Daily Intake (EDI) of Sb2O3 resulted from PET FCM was 90.7 ng p-1d-1. PMID:27241743

  13. Quaternary InGaAsSb Thermophotovoltaic Diode Technology

    SciTech Connect

    M Dashiell; J Beausang; H Ehsani; G Nichols; D DePoy; L Danielson; P Talamo; K Rahner; E Brown; S Burger; P Fourspring; W Topper; P Baldasaro; C Wang; R Huang; M Connors; G Turner; Z Shellenbarger; G Taylor; Jizhong Li; R Martinelli; D Donetski; S Anikeev; G Belenky; S Luryl

    2005-01-26

    Thermophotovoltaic (TPV) diodes fabricated from InGaAsSb alloys lattice-matched to GaSb substrates are grown by Metal Organic Vapor Phase Epitaxy (MOVPE). 0.53eV InGaAsSb TPV diodes utilizing front-surface spectral control filters have been tested in a vacuum cavity and a TPV thermal-to-electric conversion efficiency ({eta}{sub TPV}) and a power density (PD) of {eta}{sub TPV} = 19% and PD=0.58 W/cm{sup 2} were measured for T{sub radiator} = 950 C and T{sub diode} = 27 C. Recombination coefficients deduced from minority carrier measurements and the theory reviewed in this article predict a practical limit to the maximum achievable conversion efficiency and power density for 0.53eV InGaAsSb TPV. The limits for the above operating temperatures are projected to be {eta}{sub TPV} = 26% and PD = 0.75 W/cm{sup 2}. These limits are extended to {eta}{sub TPV} = 30% and PD = 0.85W/cm{sup 2} if the diode active region is bounded by a reflective back surface to enable photon recycling and a two-pass optical path length. The internal quantum efficiency of the InGaAsSb TPV diode is close to the theoretically predicted limits, with the exception of short wavelength absorption in GaSb contact layers. Experiments show that the open circuit voltage of the 0.53eV InGaAsSb TPV diodes is not strongly dependent on the device architectures studied in this work where both N/P and P/N double heterostructure diodes have been grown with various acceptor and donor doping levels, having GaSb and AlGaAsSb confinement, and also partial back surface reflectors. Lattice matched InGaAsSb TPV diodes were fabricated with bandgaps ranging from 0.6 to 0.5eV without significant degradation of the open circuit voltage factor, quantum efficiency, or fill factor as the composition approached the miscibility gap. The key diode performance parameter which is limiting efficiency and power density below the theoretical limits in InGaAsSb TPV devices is the open circuit voltage. The open circuit voltages of

  14. Limiting phase separation in epitaxial GaInAsSb

    SciTech Connect

    Wang, C.A.; Ransom, S.L.; Oakley, D.C.; Choi, H.K.; Charache, G.W.

    1998-11-01

    GaInAsSb alloys are of great interest for lattice-matched thermophotovoltaic (TPV) devices because of the high performance attainable at 2.2 {micro}m. Extension of the TPV device cutoff wavelength to beyond 2.2 {micro}m is especially desirable since the emissive power of the source is significant at these longer wavelengths. However, the GaInAsSb quaternary alloy system exhibits a miscibility gap in the wavelength range of interest, and no devices with cutoff wavelengths longer than 2.3 {micro}m have been demonstrated. This paper reports the successful growth of GaInAsSb alloys which exhibit room temperature photoluminescence (PL) at wavelengths as long as 2.5 {micro}m. TPV devices with cutoff wavelengths out to 2.5 {micro}m exhibit external quantum efficiencies of 57%. These values are comparable to those measured for 2.2 {micro}m devices.

  15. InAs/GaSb superlattice infrared detectors

    NASA Astrophysics Data System (ADS)

    Rehm, Robert; Masur, Michael; Schmitz, Johannes; Daumer, Volker; Niemasz, Jasmin; Vandervelde, Thomas; DeMeo, Dante; Luppold, Wolfgang; Wauro, Matthias; Wörl, Andreas; Rutz, Frank; Scheibner, Ralf; Ziegler, Johann; Walther, Martin

    2013-07-01

    Future heterojunction InAs/GaSb superlattice (SL) detector devices in the long-wavelength infrared regime (LWIR, 8-12 μm) require an accurate bandstructure model and a successful surface passivation. In this study, we have validated the superlattice empirical pseudopotential method developed by Dente and Tilton over a wide range of bandgap energies. Furthermore, dark current data for a novel dielectric surface passivation for LWIR devices is presented. Next, we present a technique for high-resolution, full-wafer mapping of etch pit densities on commercial (1 0 0) GaSb substrates, which allows to study the local correlation between threading dislocations in the substrate and the electro-optical pixel performance. Finally, recent performance data for 384 × 288 dual-color InAs/GaSb superlattice imagers for the mid-wavelength infrared (MWR, 3-5 μm) is given.

  16. New Interest in Intermetallic Compound ZnSb

    NASA Astrophysics Data System (ADS)

    Fedorov, M. I.; Prokof'eva, L. V.; Pshenay-Severin, D. A.; Shabaldin, A. A.; Konstantinov, P. P.

    2014-06-01

    The intermetallic compound ZnSb has been known since the 1830s. It has semiconductor properties, but its mechanical, thermal, and chemical properties are very close to those of a metallic alloy. When thermoelectrics based on (BiSb)2(TeSe)3 solid solutions were created, interest in ZnSb subsided. However, the current situation is different, as tellurium has become expensive and rare. Moreover, its compounds are too toxic, and it is too difficult to produce such materials and devices from these solid solutions. Recently, n-type material based on Mg2(SnSi) solid solution was proposed in the Laboratory of Physics for Thermoelements of the Ioffe Physical-Technical Institute. This material together with ZnSb may form a promising couple for creating various thermoelectric modules. In this paper, various properties (Hall and Seebeck coefficients, electrical and thermal conductivities) are reported in the temperature range from 80 K to 797 K. Different acceptor impurities have been tested. The Hall concentration at room temperature varied from 1.5 × 1018 cm-3 to 2.7 × 1019 cm-3. Some features have been discovered in the behavior of the thermoelectric parameters of double-doped ZnSb samples at temperatures above 500 K. Their nature points to a temperature-dependent increase of the Hall concentration. The existence of two temperature ranges with additional doping is revealed by Hall coefficient and electrical conductivity measurements in the range from 80 K to 797 K. The experimental data are discussed based on a model of the energy spectrum with impurity and native defect states localized in the energy gap. It is shown that the dimensionless thermoelectric figure of merit of ZnSb: Cd, Ag, Sn is not less than 1.0 at 600 K.

  17. Spectral ellipsometry of GaSb and GaInAsSb: Experiment and modeling

    SciTech Connect

    Charache, G.W.; Mu {tilde n}oz, M.; Wei, K.; Pollak, F.H.; Freeouf, J.L.

    1999-06-30

    The optical constants {epsilon}(E)[={epsilon}{sub 1}(E)+i{epsilon}{sub 2}(E)] of single-crystal GaSb at 300K have been measured using spectral ellipsometry in the range of 0.3-5.3 eV. The {epsilon}(E) spectra displayed distinct structures associated with critical points (CPs) at E{sub 0} (direct gap), spin-orbit split E{sub 0}+{Delta}{sub 0} component, spin-orbit split (E{sub 1}, E{sub 1}+{Delta}{sub 1}) and (E{sub 0}{prime}, E{sub 0}{prime}+{Delta}{sub 0}{prime}) doublets, as well as E{sub 2}. The experimental data over the entire measured spectral range (after oxide removal) has been fit using the Holden model dielectric function based on the electronic energy-band structure near these CPs plus excitonic and band-to-band Coulomb enhancement effects at E{sub 0}, E{sub 0}+{Delta}{sub 0} and the E{sub 1}, E{sub 1}+{Delta}{sub 1} doublet. In addition to evaluating the energies of these various band-to-band CPs, information about the binding energy (R{sub 1}) of the two-dimensional exciton related to the E{sub 1}, E{sub 1}+{Delta}{sub 1} CPs was obtained. The value of R{sub 1} was in good agreement with effective mass/k{sup {rightharpoonup}}{center_dot}p{sup {rightharpoonup}} theory. The ability to evaluate R{sub 1} has important ramifications for recent first-principles band structure calculations which include exciton effects at E{sub 0}, E{sub 1}, and E{sub 2}. The experimental results were compared to other evaluations of the optical constants of GaSb.

  18. InAs/GaSb superlattices fabricated by metalorganic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Levin, R. V.; Nevedomskii, V. N.; Pushnyi, B. V.; Bert, N. A.; Mizerov, M. N.

    2016-01-01

    The possibility of fabricating InAs/GaSb strained-layer superlattices by metalorganic chemical vapor deposition has been experimentally demonstrated. The results of transmission electron microscopy and photoluminescence spectroscopy investigations showed that the obtained structures comprise an InAs?GaSb superlattice on a GaSb substrate consisting of 2-nm-thick InAs and 3.3-nm-thick GaSb layers.

  19. Thermodynamic Modeling of the Pt-Te and Pt-Sb-Te Systems

    NASA Astrophysics Data System (ADS)

    Guo, Cuiping; Huang, Liang; Li, Changrong; Shang, Shunli; Du, Zhenmin

    2015-08-01

    The Pt-Te and the Pt-Sb-Te systems are modeled using the calculation of phase diagram (CALPHAD) technique. In the Pt-Te system, the liquid phase is modeled as (Pt, PtTe2, Te) using the associate model, and four intermediates, PtTe2, Pt2Te3, Pt3Te4 and PtTe, are treated as stoichiometric compounds and their enthalpies of formation are obtained by means of first-principles calculations. The solution phases, fcc(Pt) and hex(Te), are described as substitutional solutions. Combined with the thermodynamic models of the liquid phase in the Pt-Sb and Sb-Te systems in the literature, the liquid phase of the Pt-Sb-Te ternary system is modeled as (Pt, Sb, Te, Sb2Te3, PtTe2) also using the associate model. The compounds, PtTe2, Pt2Te3, Pt3Te4 and PtTe in the Pt-Te system and PtSb2, PtSb, Pt3Sb2 and Pt7Sb in the Pt-Sb system are treated as line compounds Pt m (Sb,Te) n in the Pt-Sb-Te system, and the compound Pt5Sb is treated as (Pt,Sb)5(Pt,Sb,Te). A set of self-consistent thermodynamic parameters is obtained. Using these thermodynamic parameters, the experimental Pt-Te phase diagram, the experimental heat capacities of PtTe and PtTe2, the enthalpies of formation from first-principles calculations for PtTe2, Pt2Te3, Pt3Te4, and PtTe, and the ternary isothermal sections at 873 K, 923 K, 1073 K and 1273 K are well reproduced.

  20. High Pressure High Temperature Study of B+Sb Mixture

    NASA Astrophysics Data System (ADS)

    Kumar, N. R. Sanjay; Shekar, N. V. Chandra; Ravindran, T. R.; Sahu, P. Ch.

    2011-07-01

    High pressure synthesis of BSb has been attempted using Laser Heated Diamond Anvil Cell facility with a CO2 laser. B:Sb in 3:1 atom ratio was laser heated at ˜7 GPa , 10 GPa and 30 GPa. In-situ characterization of the pressurized sample was done by micro-Raman technique. The micro-Raman results before and after laser heating at different pressures did not indicate compound formation. Also, Sb, which shows a series of structural transitions under pressure up to 30 GPa did not show any metastable phase in the P and T regime studied.

  1. Low cost high power GaSB photovoltaic cells

    NASA Astrophysics Data System (ADS)

    Fraas, Lewis M.; Huang, Han X.; Ye, Shi-Zhong; Hui, She; Avery, James; Ballantyne, Russell

    1997-03-01

    High power density and high capacity factor are important attributes of a thermophotovoltaics (TPV) system and GaSb cells are enabling for TPV systems. A TPV cogeneration unit at an off grid site will compliment solar arrays producing heat and electricity on cloudy days with the solar arrays generating electricity on sunny days. Herein, we project that GaSb cells generating 2 Watts each can be made in 1 MW quantities at 4 per cell. This will allow TPV circuits to be made at 2 per Watt. At this cost, the off-grid cogeneration and self-powered furnace markets will be viable.

  2. Low cost high power GaSb thermophotovoltaic cells

    NASA Astrophysics Data System (ADS)

    Fraas, Lewis M.; Huang, Han X.; Ye, Shi-Zhong; Avery, James; Ballantyne, Russell

    1997-04-01

    High power density and high capacity factor are important attributes of a TPV system and GaSb cells are enabling for TPV systems. A TPV cogeneration unit at an off grid site will compliment solar arrays producing heat and electricity on cloudy days with the solar arrays generating electricity on sunny days. Herein, we project that GaSb cells generating 2 Watts each can be made in 1 MW quantities at 4 per cell. This will allow TPV circuits to be made at 2 per Watt. At this cost, the off-grid cogeneration and self-powered furnace markets will be viable.

  3. Predicting the optimized thermoelectric performance of MgAgSb

    NASA Astrophysics Data System (ADS)

    Sheng, C. Y.; Liu, H. J.; Fan, D. D.; Cheng, L.; Zhang, J.; Wei, J.; Liang, J. H.; Jiang, P. H.; Shi, J.

    2016-05-01

    Using first-principles method and Boltzmann theory, we provide an accurate prediction of the electronic band structure and thermoelectric transport properties of α-MgAgSb. Our calculations demonstrate that only when an appropriate exchange-correlation functional is chosen can we correctly reproduce the semiconducting nature of this compound. By fine tuning the carrier concentration, the thermoelectric performance of α-MgAgSb can be significantly optimized, which exhibits a strong temperature dependence and gives a maximum ZT value of 1.7 at 550 K. We also provide a simple map by which one can efficiently find the best doping atoms and optimal doping content.

  4. Hydrazine solution processed Sb2S3, Sb2Se3 and Sb2(S(1-x)Se(x))3 film: molecular precursor identification, film fabrication and band gap tuning.

    PubMed

    Yang, Bo; Xue, Ding-Jiang; Leng, Meiying; Zhong, Jie; Wang, Liang; Song, Huaibing; Zhou, Ying; Tang, Jiang

    2015-01-01

    Sb2(S(1-x)Se(x))3 (0 ≤ x ≤ 1) compounds have been proposed as promising light-absorbing materials for photovoltaic device applications. However, no systematic study on the synthesis and characterization of polycrystalline Sb2(S(1-x)Se(x))3 thin films has been reported. Here, using a hydrazine based solution process, single-phase Sb2(S(1-x)Se(x))3 films were successfully obtained. Through Raman spectroscopy, we have investigated the dissolution mechanism of Sb in hydrazine: 1) the reaction between Sb and S/Se yields [Sb4S7](2-)/[Sb4Se7](2-) ions within their respective solutions; 2) in the Sb-S-Se precursor solutions, Sb, S, and Se were mixed on a molecular level, facilitating the formation of highly uniform polycrystalline Sb2(S(1-x)Se(x))3 thin films at a relatively low temperature. UV-vis-NIR transmission spectroscopy revealed that the band gap of Sb2(S(1-x)Se(x))3 alloy films had a quadratical relationship with the Se concentration x and it followed the equation Eg(x) = 0.118x(2) - 0.662x + 1.621eV, where the bowing parameter was 0.118 eV. Our study provides a valuable guidance for the adjustment and optimization of the band gap in hydrazine solution processed Sb2(S(1-x)Se(x))3 alloy films for the future fabrication of improved photovoltaic devices. PMID:26042519

  5. CXCR3 antagonist VUF10085 binds to an intrahelical site distinct from that of the broad spectrum antagonist TAK–779

    PubMed Central

    Nedjai, Belinda; Viney, Jonathan M; Li, Hubert; Hull, Caroline; Anderson, Caroline A; Horie, Tomoki; Horuk, Richard; Vaidehi, Nagarajan; Pease, James E

    2015-01-01

    Background and Purpose The chemokine receptor CXCR3 is implicated in a variety of clinically important diseases, notably rheumatoid arthritis and atherosclerosis. Consequently, antagonists of CXCR3 are of therapeutic interest. In this study, we set out to characterize binding sites of the specific low MW CXCR3 antagonist VUF10085 and the broad spectrum antagonist TAK-779 which blocks CXCR3 along with CCR2 and CCR5. Experimental Approach Molecular modelling of CXCR3, followed by virtual ligand docking, highlighted several CXCR3 residues likely to contact either antagonist, notably a conserved aspartate in helix 2 (Asp-1122:63), which was postulated to interact with the quaternary nitrogen of TAK-779. Validation of modelling was carried out by site-directed mutagenesis of CXCR3, followed by assays of cell surface expression, ligand binding and receptor activation. Key Results Mutation of Asn-1323.33, Phe-207 and Tyr-2716.51 within CXCR3 severely impaired both ligand binding and chemotactic responses, suggesting that these residues are critical for maintenance of a functional CXCR3 conformation. Contrary to our hypothesis, mutation of Asp-1122:63 had no observable effects on TAK-779 activity, but clearly decreased the antagonist potency of VUF 10085. Likewise, mutations of Phe-1313.32, Ile-2796.59 and Tyr-3087.43 were well tolerated and were critical for the antagonist activity of VUF 10085 but not for that of TAK-779. Conclusions and Implications This more detailed definition of a binding pocket within CXCR3 for low MW antagonists should facilitate the rational design of newer CXCR3 antagonists, with obvious clinical potential. PMID:25425280

  6. Mid-wavelength infrared heterojunction phototransistors based on type-II InAs/AlSb/GaSb superlattices

    NASA Astrophysics Data System (ADS)

    Haddadi, A.; Adhikary, S.; Dehzangi, A.; Razeghi, M.

    2016-07-01

    A mid-wavelength infrared heterojunction phototransistor based on type-II InAs/AlSb/GaSb superlattices on GaSb substrate has been demonstrated. Near a wavelength of 4 μm saturated optical gains of 668 and 639 at 77 and 150 K, respectively, are demonstrated over a wide dynamic range. At 150 K, the unity optical gain collector dark current density and DC current gain are 1 × 10-3 A/cm2 and 3710, respectively. This demonstrates the potential for use in high-speed applications. In addition, the phototransistor exhibits a specific detectivity value that is four times higher compared with a state-of-the-art type-II superlattice-based photodiode with a similar cut-off wavelength at 150 K.

  7. A comparison of the Ge-Sb-Te and Si-Sb-Te film oxidization at atmosphere

    NASA Astrophysics Data System (ADS)

    Ren, Wanchun; Liu, Bo; Song, Zhitang; Jing, Xuezhen; Xiang, Yanghui; Xiao, Haibo; Wang, Zongtao; Zhang, Beichao; Xu, Jia; Wu, Guanping; Qi, Ruijuan; Fan, Chunyan; Duan, Shuqing; Yu, Qinqin; Feng, Songlin

    New phase change materials development has become one of the most critical modules in the fabrication of low power consumption and good data retention phase change memory (PCM). Among various candidates of new phase change materials, SiSbTe (SST) is one of the most promising materials due to its benefits of low RESET current, high crystallization temperature, good adhesion and small volume shrinkage during phase change from amorphous to crystalline state. However, the oxidization of SST film was found when exposing to the atmosphere. By analyzing the depth profile of chemical states, we found oxygen more easily penetrated into the SST film and bonded with Si and Sb compared to GeSbTe (GST) film. The oxidization mechanism between SST and GST was briefly discussed. We achieved 80% improvement of oxidization issue by nitrogen and argon surface treatment. We proposed a manufacturing solution of SST for PCM.

  8. Synthesis and characterization of Ge2Sb2Te5 nanowires with memory switching effect.

    PubMed

    Jung, Yeonwoong; Lee, Se-Ho; Ko, Dong-Kyun; Agarwal, Ritesh

    2006-11-01

    Ge2Sb2Te5 nanowires (NWs) were synthesized by vaporizing GeTe, Sb, and Te precursors assisted by metal catalysts. Current-voltage measurement of the Ge2Sb2Te5 NW device displays fast and reversible switching between two distinct resistive states, which is due to the crystalline-amorphous phase transition nature of these materials PMID:17061875

  9. Synthesis Of Ir(1-x-y)Rh(x)Co(y)Sb(3) Semiconductors

    NASA Technical Reports Server (NTRS)

    Caillat, Thierry; Borshchevsky, Alexander; Fleurial, Jean-Pierre

    1994-01-01

    Ir(1-x-y)Rh(x)Co(y)Sb(3) semiconductors synthesized by gradient-freeze and sintering techniques. Sintering techniques used for variety of compositions; gradient-freeze technique used for RhSb(3) and CoSb(3).

  10. Assessing Intellectual Functioning in Young Adolescents: How Do the WISC-IV and SB5 Compare?

    ERIC Educational Resources Information Center

    Wilson, Kimberley; Gilmore, Linda

    2012-01-01

    The Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV) and the Stanford-Binet--Fifth Edition (SB5) are two of the most commonly used intelligence tests for children and adolescents. No comparative studies of the WISC-IV and SB5 have yet been published. In the current study the WISC-IV and SB5 were administered in counterbalanced…

  11. High spin polarization and the origin of unique ferromagnetic ground state in CuFeSb

    NASA Astrophysics Data System (ADS)

    Sirohi, Anshu; Singh, Chandan K.; Thakur, Gohil S.; Saha, Preetha; Gayen, Sirshendu; Gaurav, Abhishek; Jyotsna, Shubhra; Haque, Zeba; Gupta, L. C.; Kabir, Mukul; Ganguli, Ashok K.; Sheet, Goutam

    2016-06-01

    CuFeSb is isostructural to the ferro-pnictide and chalcogenide superconductors and it is one of the few materials in the family that are known to stabilize in a ferromagnetic ground state. Majority of the members of this family are either superconductors or antiferromagnets. Therefore, CuFeSb may be used as an ideal source of spin polarized current in spin-transport devices involving pnictide and the chalcogenide superconductors. However, for that the Fermi surface of CuFeSb needs to be sufficiently spin polarized. In this paper we report direct measurement of transport spin polarization in CuFeSb by spin-resolved Andreev reflection spectroscopy. From a number of measurements using multiple superconducting tips we found that the intrinsic transport spin polarization in CuFeSb is high (˜47%). In order to understand the unique ground state of CuFeSb and the origin of large spin polarization at the Fermi level, we have evaluated the spin-polarized band structure of CuFeSb through first principles calculations. Apart from supporting the observed 47% transport spin polarization, such calculations also indicate that the Sb-Fe-Sb angles and the height of Sb from the Fe plane are strikingly different for CuFeSb than the equivalent parameters in other members of the same family thereby explaining the origin of the unique ground state of CuFeSb.

  12. Structural transformations in amorphous ↔ crystalline phase change of Ga-Sb alloys

    SciTech Connect

    Edwards, T. G.; Sen, S.; Hung, I.; Gan, Z.; Kalkan, B.; Raoux, S.

    2013-12-21

    Ga-Sb alloys with compositions ranging between ∼12 and 50 at. % Ga are promising materials for phase change random access memory applications. The short-range structures of two such alloys with compositions Ga{sub 14}Sb{sub 86} and Ga{sub 46}Sb{sub 54} are investigated, in their amorphous and crystalline states, using {sup 71}Ga and {sup 121}Sb nuclear magnetic resonance spectroscopy and synchrotron x-ray diffraction. The Ga and Sb atoms are fourfold coordinated in the as-deposited amorphous Ga{sub 46}Sb{sub 54} with nearly 40% of the constituent atoms being involved in Ga-Ga and Sb-Sb homopolar bonding. This necessitates extensive bond switching and elimination of homopolar bonds during crystallization. On the other hand, Ga and Sb atoms are all threefold coordinated in the as-deposited amorphous Ga{sub 14}Sb{sub 86}. Crystallization of this material involves phase separation of GaSb domains in Sb matrix and a concomitant increase in the Ga coordination number from 3 to 4. Results from crystallization kinetics experiments suggest that the melt-quenching results in the elimination of structural “defects” such as the homopolar bonds and threefold coordinated Ga atoms in the amorphous phases of these alloys, thereby rendering them structurally more similar to the corresponding crystalline states compared to the as-deposited amorphous phases.

  13. Defect formation on the GaSb (001) surface induced by hydrogen atom adsorption

    NASA Astrophysics Data System (ADS)

    Bermudez, V. M.

    2015-06-01

    Density functional theory has been used to characterize the effects of adsorbed H on the electronic structure of the GaSb (001)-α(4×3) surface, which consists of a combination of Ga-Sb and Sb-Sb dimers. Adsorption of two H atoms at a Ga-Sb adatom dimer either has little effect on surface states above the bulk valence band maximum (VBM) or else eliminates them, depending on the mode of adsorption. However, adsorption at the Sb-Sb dimer in the terminating layer produces a state farther into the gap at ~0.10 eV above the clean-surface VBM. Relaxation accompanying the breaking of the Sb-Sb dimer bond leads to increased interactions involving three-fold-coordinated Sb sites in the terminating layer, which in turn raises the energies of the non-bonding lone-pair orbitals. This defect state, which appears to be unique to the reconstructed GaSb (001) surface, could potentially function as a hole trap on the surface of p-type GaSb.

  14. Heterostructures and infrared emitters with compressed InAsSb layers

    SciTech Connect

    Kurtz, S.R.; Biefeld, R.M.

    1995-03-01

    An overview is presented of strained InAsSb heterostructures and infrared emitters. InAsSb/InGaAs strained-layer superlattices (SLS) and InAsSb quantum wells were characterized using magneto-photoluminescence and compared with unstrained InAsSb and InAs alloys. In heterostructures with biaxially compressed InAsSb, large quantum confinement energies were observed, and the holes exhibited a decrease in effective mass, approaching that of the electrons. This study demonstrates that the electrons and holes in the InAsSb heterostructures are confined in the InAsSb layers, and the band offsets are type I. A large increase in the Auger-1 threshold energy should accompany the strain-induced change in valence-band symmetry of the InAsSb layers. Correspondingly, the InAsSb heterostructures display high radiative efficiencies and increased activation energies for nonradiative recombination compared with the unstrained alloys. LEDs and L-mrs with InAsSb heterostructure active regions are described. InAsSb/InGaAs SLS LEDs operating at 300K at wavelengths {le} 5 pm have been demonstrated. Optically pumped InAsSb/InGaAs SLS lasers, with InPSb cladding, had a maximum operating temperature of 100K.

  15. Antagonistic versus non-antagonistic models of balancing selection: Characterizing the relative timescales and hitchhiking effects of partial selective sweeps

    PubMed Central

    Connallon, Tim; Clark, Andrew G.

    2012-01-01

    Antagonistically selected alleles -- those with opposing fitness effects between sexes, environments, or fitness components -- represent an important component of additive genetic variance in fitness-related traits, with stably balanced polymorphisms often hypothesized to contribute to observed quantitative genetic variation. Balancing selection hypotheses imply that intermediate-frequency alleles disproportionately contribute to genetic variance of life history traits and fitness. Such alleles may also associate with population genetic footprints of recent selection, including reduced genetic diversity and inflated linkage disequilibrium at linked, neutral sites. Here, we compare the evolutionary dynamics of different balancing selection models, and characterize the evolutionary timescale and hitchhiking effects of partial selective sweeps generated under antagonistic versus non-antagonistic (e.g., overdominant and frequency-dependent selection) processes. We show that that the evolutionary timescales of partial sweeps tend to be much longer, and hitchhiking effects are drastically weaker, under scenarios of antagonistic selection. These results predict an interesting mismatch between molecular population genetic and quantitative genetic patterns of variation. Balanced, antagonistically selected alleles are expected to contribute more to additive genetic variance for fitness than alleles maintained by classic, non-antagonistic mechanisms. Nevertheless, classical mechanisms of balancing selection are much more likely to generate strong population genetic signatures of recent balancing selection. PMID:23461340

  16. Diversity of Arbuscular Mycorrhizal Fungi Associated with a Sb Accumulator Plant, Ramie (Boehmeria nivea), in an Active Sb Mining.

    PubMed

    Wei, Yuan; Chen, ZhiPeng; Wu, FengChang; Li, JiNing; ShangGuan, YuXian; Li, FaSheng; Zeng, Qing Ru; Hou, Hong

    2015-08-01

    Arbuscular mycorrhizal fungi (AMF) have great potential for assisting heavy metal hyperaccumulators in the remediation of contaminated soils. However, little information is available about the symbiosis of AMF associated with an antimony (Sb) accumulator plant under natural conditions. Therefore, the objective of this study was to investigate the colonization and molecular diversity of AMF associated with the Sb accumulator ramie (Boehmeria nivea) growing in Sb-contaminated soils. Four Sb mine spoils and one adjacent reference area were selected from Xikuangshan in southern China. PCR-DGGE was used to analyze the AMF community composition in ramie roots. Morphological identification was also used to analyze the species in the rhizosphere soil of ramie. Results obtained showed that mycorrhizal symbiosis was established successfully even in the most heavily polluted sites. From the unpolluted site Ref to the highest polluted site T4, the spore numbers and AMF diversity increased at first and then decreased. Colonization increased consistently with the increasing Sb concentrations in the soil. A total of 14 species were identified by morphological analysis. From the total number of species, 4 (29%) belonged to Glomus, 2 (14%) belonged to Acaulospora, 2 (14%) belonged to Funneliformis, 1 (7%) belonged to Claroideoglomus, 1 (7%) belonged to Gigaspora, 1 (7%) belonged to Paraglomus, 1 (7%) belonging to Rhizophagus, 1 (7%) belonging to Sclervocystis, and 1 (7%) belonged to Scutellospora. Some AMF sequences were present even in the most polluted site. Morphological identification and phylogenetic analysis both revealed that most species were affiliated withGlomus, suggesting that Glomus was the dominant genus in this AMF community. This study demonstrated that ramie associated with AMF may have great potential for remediation of Sb-contaminated soils. PMID:25876600

  17. Decay properties of high-spin isomers and other structures in {sup 121}Sb and {sup 123}Sb

    SciTech Connect

    Watanabe, H.; Lane, G. J.; Dracoulis, G. D.; Kibedi, T.; Nieminen, P.; Hughes, R. O.; Byrne, A. P.; Kondev, F. G.; Carpenter, M. P.; Janssens, R. V. F.; Lauritsen, T.; Seweryniak, D.; Zhu, S.; Chowdhury, P.; Moon, C.-B.

    2009-02-15

    High-spin states populated in the decay of microsecond isomers in the transitional nuclei {sup 121}Sb and {sup 123}Sb have been investigated in detail in several experiments using {gamma}-ray and electron spectroscopy. The nuclei were formed using multinucleon transfer and fusion-fission reactions with {sup 136}Xe beams and also using the {sup 120}Sn({sup 7}Li,{alpha}2n){sup 121}Sb and {sup 122}Sn({sup 7}Li,{alpha}2n){sup 123}Sb incomplete-fusion reactions. Isomeric half-lives ranging from several nanoseconds to a few hundred microseconds were determined by means of conventional decay curve analyses, whereas very short-lived isomers (T{sub 1/2}{approx}1 ns) were identified using the generalized centroid-shift method. A number of new transitions were observed, including a branch through spherical states from the 19/2{sup +} member of the 9/2{sup +} deformed band in {sup 121}Sb, in competition with the main decay path through the rotational band. This is attributed to mixing between the 19/2{sup +} band member and a 19/2{sup +} spherical state. Both levels are predicted to coincide approximately in energy in {sup 121}Sb. The fact that a 25/2{sup +} isomer occurs for A=121 and the lighter isotopes, while a 23/2{sup +} isomer is observed for A=123-131 is explained through a multistate mixing calculation, taking into account the gradual shift of the 2d{sub 5/2} and 1g{sub 7/2} proton orbitals and the change in proton-neutron effective interactions from an attractive particle-particle type in the lower part of the shell to a repulsive particle-hole type with increasing the neutron number toward the N=82 shell closure. The observed enhancement of the B(E2;19/2{sup -}{yields}15/2{sup -}) values in {sup 121}Sb and {sup 123}Sb over the B(E2;7{sup -}{yields}5{sup -}) values in the corresponding Sn cores is discussed in terms of configuration mixing between spherical and deformed states.

  18. Crystal structure and bonding characteristics of In-doped {beta}-Zn{sub 4}Sb{sub 3}

    SciTech Connect

    Tang, Dingguo; Zhao, Wenyu; Cheng, Sudan; Wei, Ping; Yu, Jian; Zhang, Qingjie

    2012-09-15

    The effects of indium impurity on the crystal structure and bonding characteristics of In-doped {beta}-Zn{sub 4}Sb{sub 3} were investigated by powder X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The XRD Rietveld refinement indicates that the indium impurity preferentially substitutes one of Sb atoms in Sb-Sb dimer at the 12c Sb(2) site and simultaneously leads to the increase of Zn occupancy. The observations of binding energy shift and a new valence state in Sb 3d core-level XPS spectra can be attributed to the charge transfer from In and Zn to Sb. As a result, more electropositive Zn atoms are needed to maintain the charge balance. The reduction of the lattice thermal conductivity is ascribed to the formation of the asymmetric Sb-In bond, resulting in much low lattice thermal conductivity of 0.49 W{sup -1} K{sup -1} of Zn{sub 4}Sb{sub 2.96}In{sub 0.04}. - Graphical abstract: The indium impurity substitutes one of Sb atoms in Sb-Sb dimer, resulting the charge transfer from In to Sb, which leads to the binding energy of Sb 3d core level XPS spectra shift to low value. Highlights: Black-Right-Pointing-Pointer The indium impurity preferentially substitutes one of Sb atoms in Sb-Sb dimer at the 12c Sb(2) site. Black-Right-Pointing-Pointer The occupancy of Zn increases by the In substitution for Sb, whereas that of Sb keeps constant. Black-Right-Pointing-Pointer The binding energy of Sb 3d shifts to low value. Black-Right-Pointing-Pointer The charge transfer occurs from In and Zn to Sb.

  19. Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia

    PubMed Central

    Broussolle, Emmanuel; Laurencin, Chloé; Bernard, Emilien; Thobois, Stéphane; Danaila, Teodor; Krack, Paul

    2015-01-01

    Background Geste antagoniste, or sensory trick, is a voluntary maneuver that temporarily reduces the severity of dystonic postures or movements. We present a historical review of early reports and illustrations of geste antagoniste. Results In 1894, Brissaud described this phenomenon in Paris in patients with torticollis. He noted that a violent muscular contraction could be reversed by a minor voluntary action. He considered the improvement obtained by what he called “simple mannerisms, childish behaviour or fake pathological movements” was proof of the psychogenic origin of what he named mental torticollis. This concept was supported by photographical illustrations of the patients. The term geste antagoniste was used by Brissaud’s pupils, Meige and Feindel, in their 1902 monograph on movement disorders. Other reports and illustrations of this sign were published in Europe between 1894 and 1906. Although not mentioned explicitly, geste antagoniste was also illustrated in a case report of generalized dystonia in Oppenheim’s 1911 seminal description of dystonia musculorum deformans in Berlin. Discussion Brissaud-Meige’s misinterpretation of the geste antagoniste unfortunately anchored the psychogenic origin of dystonia for decades. In New York, Herz brought dystonia back into the realm of organic neurology in 1944. Thereafter, it was given prominence by other authors, notably Fahn and Marsden in the 1970–1980s. Nowadays, neurologists routinely investigate for geste antagoniste when a dystonic syndrome is suspected, because it provides a further argument in favor of dystonia. The term alleviating maneuver was proposed in 2014 to replace sensory trick or geste antagoniste. This major sign is now part of the motor phenomenology of the 2013 Movement Disorder Society’s classification of dystonia. PMID:26417535

  20. Preparation and thermoelectric properties of sintered iodine-containing clathrate compounds Ge38Sb8I8 and Sn38Sb8I8

    NASA Astrophysics Data System (ADS)

    Kishimoto, Kengo; Arimura, Shuntaro; Koyanagi, Tsuyoshi

    2006-05-01

    The iodine-containing cationic type-I clathrates Ge38Sb8I8 and Sn38Sb8I8 were prepared and their thermodynamic properties as well as their thermoelectric properties were investigated. Their atomic displacement parameters were as large as those of anionic clathrates such as Ba8Ga16Ge30 and Cs8Cd4Sn42. The room temperature thermal conductivities of Ge38Sb8I8 and Sn38Sb8I8 were 7 and 12mWcm-1K-1, respectively; these values were as low as that of the above anionic clathrates. Both cationic clathrates had negative Seebeck coefficients; the band gap energies of Ge38Sb8I8 and Sn38Sb8I8 were 1.16 and 0.80eV, respectively.

  1. {sup 151}Eu and {sup 121}Sb Moessbauer spectroscopy of EuSbSe{sub 3} and EuBiSe{sub 3}

    SciTech Connect

    Schappacher, Falko M.; Poettgen, Rainer Bang Jin, Geng; Albrecht-Schmitt, Thomas E.

    2007-11-15

    {sup 151}Eu and {sup 121}Sb Moessbauer spectroscopy of EuSbSe{sub 3} and EuBiSe{sub 3} were measured at different temperatures. The presence of divalent europium and trivalent antimony were confirmed. The largely negative values of the isomer shift in {sup 151}Eu spectrum show highly ionic bonding within these two compounds. Both of them show magnetic hyperfine field splitting at 4.2 K, which indicates a change in the orientation of the EFG principal axis with respect to the magnetic hyperfine field direction. EuSbSe{sub 3} has slightly smaller electron density at the antimony nuclei, compared to Sb{sub 2}Se{sub 3.} - Graphical abstract: Experimental and simulated {sup 121}Sb Moessbauer spectrum of EuSbSe{sub 3} at 77 K.

  2. Lanthanum Gallium Tin Antimonides LaGa xSn ySb 2

    NASA Astrophysics Data System (ADS)

    Morgan, Mark G.; Wang, Meitian; Mills, Allison M.; Mar, Arthur

    2002-08-01

    A series of quaternary lanthanum gallium tin antimonides LaGa xSn ySb 2 was elaborated to trace the structural evolution between the known end members LaGaSb 2 (SmGaSb 2-type) and LaSn ySb 2 (LaSn 0.75Sb 2-type). Five members of this series were characterized by single-crystal X-ray diffraction. For low Sn content, the Sn atoms disorder with Ga atoms in zigzag chains to form solid solutions LaGa 1- ySn ySb 2 (0≤y≤0.2) adopting the SmGaSb 2-type structure, as exemplified by LaGa 0.92(3)Sn 0.08Sb 2 and LaGa 0.80(3)Sn 0.20Sb 2 (orthorhombic, space group D52- C222 1, Z=4). For higher Sn and lower Ga content, there is a segregation in which the Sn atoms appear in chains of closely spaced partially occupied sites as in the parent LaSn 0.75Sb 2-type structure whereas the Ga atoms remain in zigzag chains as in the parent SmGaSb 2-type structure. This feature is observed in the structures of LaGa 0.68(4)Sn 0.31(3)Sb 2, LaGa 0.62(3)Sn 0.32(3)Sb 2, and LaGa 0.43(3)Sn 0.39(3)Sb 2 (orthorhombic, space group D172 h- Cmcm, Z=4). The last example illustrates that the combined Ga/Sn content can be substoichiometric ( x+ y<1). These compounds have a layered nature, with the chains of Ga or Sn atoms residing between 2∞[LaSb 2] slabs.

  3. Thermoelectric nanocrystalline YbCoSb laser prepared layers

    NASA Astrophysics Data System (ADS)

    Jelínek, Miroslav; Zeipl, Radek; Kocourek, Tomáš; Remsa, Jan; Navrátil, Jiří

    2016-03-01

    Filled thermoelectric Yb x Co4Sb12 layers were prepared by pulsed laser deposition method. The Yb0.19Co4Sb12 target was fabricated by hot pressing. Various deposition conditions were tested: target—substrate distance d T-S (4 or 6 cm), ambient argon pressure (from 0.5 to 13 Pa), laser repetition rate (from 3 to 10 Hz), substrate temperature (from 250 to 400 °C) and laser fluence (in region from 0.8 to 5 J cm-2). Film roughness was determined by mechanical profilometer and by AFM. For d T-S = 4 cm we observed a deficit of Yb and surplus of Co. Sb was transferred from target to film roughly stoichiometrically (as measured by EDX). Films created at 0.8 J cm-2 exhibited generally poor stoichiometry and mechanical properties. Optimal conditions and stoichiometric transport were found for d T-S = 6 cm and 13 Pa of Ar. XRD shows that the films were nanocrystalline with CoSb3 structure. Grain size was in the range of ~50-80 nm. Temperature dependence of Seebeck coefficient and power factor was measured. Thermoelectric efficiency ZT ~ 0.04-0.05 was measured at room temperature using Harman method. In dependence on layers quality, we calculated thermal conductivity λ ~ 0.4-1.3 W K-1 m-1.

  4. Optical study of Sb-S-I glass photonic crystals

    NASA Astrophysics Data System (ADS)

    Starczewska, Anna; Kępińska, Mirosława; Nowak, Marian; Szperlich, Piotr

    2015-12-01

    This work is focused on optical investigations of Sb-S-I glass photonic crystals based on three-dimensional opal template with a closed-packed face centered cubic (fcc) lattice prepared from monodisperse silicon (SiO2) spheres by gravity sedimentation. Three types of photonic structures have been examined: SiO2-opals, opals filled with Sb-S-I glass (direct opals) and Sb-S-I inverted opals obtained after removing SiO2 templates. Optical properties have been investigated by reflectance spectroscopy for wavelengths from 250 nm to 1100 nm. These measurements exhibit Bragg's peaks connected with photonic band gap that is tunable in position and width by varying the diameter of spheres and medium filling the opal. Values of the real parts of refractive index of the Sb-S-I in the fabricated inverted opals nmed[λ ∈ (850-950) nm] = 2.42 ± 0.08 and nmed[λ ∈ (675-750) nm] = 2.39 ± 0.11 have been determined.

  5. Reforming Urban Teacher Education: SB 2042 Implementation Five Years Later

    ERIC Educational Resources Information Center

    Russell, Sharon E.

    2006-01-01

    In October 2002, the multiple and single subject credential programs at a large urban Los Angeles Basin California State University campus, were approved as Early Adopters of the SB 2042 Professional Teacher Preparation Program. These programs resulted from a complex and multi-faceted process of change supported and influenced by reform…

  6. High Bi content GaSbBi alloys

    NASA Astrophysics Data System (ADS)

    Rajpalke, M. K.; Linhart, W. M.; Birkett, M.; Yu, K. M.; Alaria, J.; Kopaczek, J.; Kudrawiec, R.; Jones, T. S.; Ashwin, M. J.; Veal, T. D.

    2014-07-01

    The epitaxial growth, structural, and optical properties of GaSb1-xBix alloys have been investigated. The Bi incorporation into GaSb is varied in the range 0 < x ≤ 9.6% by varying the growth rate (0.31-1.33 μm h-1) at two growth temperatures (250 and 275 °C). The Bi content is inversely proportional to the growth rate, but with higher Bi contents achieved at 250 than at 275 °C. A maximum Bi content of x = 9.6% is achieved with the Bi greater than 99% substitutional. Extrapolating the linear variation of lattice parameter with Bi content in the GaSbBi films enabled a zinc blende GaBi lattice parameter to be estimated of 6.272 Å. The band gap at 300 K of the GaSbBi epitaxial layers decreases linearly with increasing Bi content down to 410 ± 40 meV (3 μm) for x = 9.6%, corresponding to a reduction of ˜35 meV/%Bi. Photoluminescence indicates a band gap of 490 ± 5 meV at 15 K for x = 9.6%.

  7. Room temperature GaAsSb single nanowire infrared photodetectors

    NASA Astrophysics Data System (ADS)

    Li, Ziyuan; Yuan, Xiaoming; Fu, Lan; Peng, Kun; Wang, Fan; Fu, Xiao; Caroff, Philippe; White, Thomas P.; Tan, Hark Hoe; Jagadish, Chennupati

    2015-11-01

    Antimonide-based ternary III-V nanowires (NWs) allow for a tunable bandgap over a wide range, which is highly interesting for optoelectronics applications, and in particular for infrared photodetection. Here we demonstrate room temperature operation of GaAs0.56Sb0.44 NW infrared photodetectors grown by metal organic vapor phase epitaxy. These GaAs0.56Sb0.44 NWs have uniform axial composition and show p-type conductivity with a peak field-effect mobility of ˜12 cm2 V-1 s-1). Under light illumination, single GaAs0.56Sb0.44 NW photodetectors exhibited typical photoconductor behavior with an increased photocurrent observed with the increase of temperature owing to thermal activation of carrier trap states. A broadband infrared photoresponse with a long wavelength cutoff at ˜1.66 μm was obtained at room temperature. At a low operating bias voltage of 0.15 V a responsivity of 2.37 (1.44) A/W with corresponding detectivity of 1.08 × 109 (6.55 × 108) {{cm}}\\sqrt{{{Hz}}}/{{W}} were achieved at the wavelength of 1.3 (1.55) μm, indicating that ternary GaAs0.56Sb0.44 NWs are promising photodetector candidates for small footprint integrated optical telecommunication systems.

  8. Diverse lattice dynamics in ternary Cu-Sb-Se compounds

    PubMed Central

    Qiu, Wujie; Wu, Lihua; Ke, Xuezhi; Yang, Jihui; Zhang, Wenqing

    2015-01-01

    Searching and designing materials with extremely low lattice thermal conductivity (LTC) has attracted considerable attention in material sciences. Here we systematically demonstrate the diverse lattice dynamics of the ternary Cu-Sb-Se compounds due to the different chemical-bond environments. For Cu3SbSe4 and CuSbSe2, the chemical bond strength is nearly equally distributed in crystalline bulk, and all the atoms are constrained to be around their equilibrium positions. Their thermal transport behaviors are well interpreted by the perturbative phonon-phonon interactions. While for Cu3SbSe3 with obvious chemical-bond hierarchy, one type of atoms is weakly bonded with surrounding atoms, which leads the structure to the part-crystalline state. The part-crystalline state makes a great contribution to the reduction of thermal conductivity that can only be effectively described by including a rattling-like scattering process in addition to the perturbative method. Current results may inspire new approaches to designing materials with low lattice thermal conductivities for high-performance thermoelectric conversion and thermal barrier coatings. PMID:26328765

  9. 2 Micrometers InAsSb Quantum-dot Lasers

    NASA Technical Reports Server (NTRS)

    Qiu, Yueming; Uhl, David; Keo, Sam

    2004-01-01

    InAsSb quantum-dot lasers near 2 micrometers were demonstrated in cw operation at room temperature with a threshold current density of 733 A,/cm(sup 2), output power of 3 mW/facet and a differential quantum efficiency of 13%.

  10. Diverse lattice dynamics in ternary Cu-Sb-Se compounds

    NASA Astrophysics Data System (ADS)

    Qiu, Wujie; Wu, Lihua; Ke, Xuezhi; Yang, Jihui; Zhang, Wenqing

    2015-09-01

    Searching and designing materials with extremely low lattice thermal conductivity (LTC) has attracted considerable attention in material sciences. Here we systematically demonstrate the diverse lattice dynamics of the ternary Cu-Sb-Se compounds due to the different chemical-bond environments. For Cu3SbSe4 and CuSbSe2, the chemical bond strength is nearly equally distributed in crystalline bulk, and all the atoms are constrained to be around their equilibrium positions. Their thermal transport behaviors are well interpreted by the perturbative phonon-phonon interactions. While for Cu3SbSe3 with obvious chemical-bond hierarchy, one type of atoms is weakly bonded with surrounding atoms, which leads the structure to the part-crystalline state. The part-crystalline state makes a great contribution to the reduction of thermal conductivity that can only be effectively described by including a rattling-like scattering process in addition to the perturbative method. Current results may inspire new approaches to designing materials with low lattice thermal conductivities for high-performance thermoelectric conversion and thermal barrier coatings.

  11. Programming biological models in Python using PySB

    PubMed Central

    Lopez, Carlos F; Muhlich, Jeremy L; Bachman, John A; Sorger, Peter K

    2013-01-01

    Mathematical equations are fundamental to modeling biological networks, but as networks get large and revisions frequent, it becomes difficult to manage equations directly or to combine previously developed models. Multiple simultaneous efforts to create graphical standards, rule-based languages, and integrated software workbenches aim to simplify biological modeling but none fully meets the need for transparent, extensible, and reusable models. In this paper we describe PySB, an approach in which models are not only created using programs, they are programs. PySB draws on programmatic modeling concepts from little b and ProMot, the rule-based languages BioNetGen and Kappa and the growing library of Python numerical tools. Central to PySB is a library of macros encoding familiar biochemical actions such as binding, catalysis, and polymerization, making it possible to use a high-level, action-oriented vocabulary to construct detailed models. As Python programs, PySB models leverage tools and practices from the open-source software community, substantially advancing our ability to distribute and manage the work of testing biochemical hypotheses. We illustrate these ideas using new and previously published models of apoptosis. PMID:23423320

  12. Angle dependence of Shubnikov-de Haas effect of filled skutterudite compounds CeOs4Sb12 and NdOs4Sb12

    NASA Astrophysics Data System (ADS)

    Ho, P.-C.; Singleton, J.; Balakirev, F. F.; Maple, M. B.; Yanagisawa, T.

    Intriguingly the three filled skutterudite compounds CeOs4Sb12, PrOs4Sb12, and NdOs4Sb12 span the range from the Kondo insulator with a 1K antiferromagnetic (AFM) order, a 1.85K unconventional superconductor (SC), to a 1K mean-field type ferromagnet (FM), indicating that they reside near quantum critical points of AFM and FM with unconventional SC induced within this regime. Therefore, understanding the Fermi surfaces of NdOs4Sb12 and CeOs4Sb12 becomes crucial in elucidating the superconducting pairing mechanism in PrOs4Sb12. Penetration depths of single crystals of CeOs4Sb12 and NdOs4Sb12 were measured for temperatures down to 1.3 K and magnetic fields up to 60 tesla by using proximity detection oscillators in the Pulsed Field Facility at NHMFL/LANL. Angle dependence of Shubnikov-de Haas oscillations was detected for rotating the field with respect to the crystalline orientations [010] and [0-10]. The results indicate that LaOs4Sb12, PrOs4Sb12 and NdOs4Sb12 have similar Fermi surfaces. The Fermi surface of CeOs4Sb12 is rather isotropic and is much different from the other three compounds. Research at CSU-Fresno is supported by NSF DMR-1506677; at UCSD by NSF DMR-1206553 and US DOE DE-FG02-04ER46105; at NHMFL by DOE, NSF, and FL; at Hokkaido U by Graint-In-Aid No. 2600342,Jpn.

  13. Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety.

    PubMed

    Kennett, G A; Bright, F; Trail, B; Baxter, G S; Blackburn, T P

    1996-04-01

    1. BW 723C86 (3 and 10 mg kg-1, s.c. 30 min pretest), a 5-HT2B receptor agonist, increased total interaction, but not locomotion in a rat social interaction test, a profile consistent with anxiolysis. 2. The effect of BW 723C86 in the social interaction test is likely to be 5-HT2B receptor-mediated as it was prevented by pretreatment with the 5-HT2C/2B receptor antagonist, SB 200646A, (1 and 2 mg kg-1, p.o., 1 h pretest) which did not affect basal levels of social interaction at the doses used. 3. An anxiolytic-like action was also observed in the rat Geller-Seifter conflict test, where BW 723C86 (0.5-50 mg kg-1, s.c. 30 min pretest) modestly, but significantly increased punished, but not unpublished responding. 4. In a rat 5 min elevated x-maze test, BW 723C86 (1-10 mg kg-1, s.c.) had no significant effect. 5. The maximal anxiolytic-like effect of BW 723C86 approached that of the benzodiazepine anxiolytic, chloradiazepoxide (5 mg kg-1, s.c. 30 min pretest) in the social interaction test, but was markedly less in the Geller-Siefter test. The effect of BW 723C86 was also clearly less than chlordiazepoxide in the elevated x-maze procedure where it had no significant effect. 6. In conclusion, BW 723C86 exerted an appreciable anxiolytic-like profile in a rat social interaction test, but had a weaker effect in the Geller-Siefter and was ineffective in the elevated x-maze test used. These effects are likely to be 5-HT2B receptor-mediated. PMID:8730737

  14. Growth, photosynthesis, and defense mechanism of antimony (Sb)-contaminated Boehmeria nivea L.

    PubMed

    Chai, Li-Yuan; Mubarak, Hussani; Yang, Zhi-Hui; Yong, Wang; Tang, Chong-Jian; Mirza, Nosheen

    2016-04-01

    Ramie (Boehmeria nivea L.) is the oldest cash fiber crop in China and is widely grown in antimony (Sb) mining areas. To evaluate the extent of Sb resistance and tolerance, the growth, tolerance index (TI), Sb content in plant parts and in Hoagland solution, bioaccumulation factor (BF), photosynthesis, and physiological changes in Sb-contaminated B. nivea (20, 40, 80, and 200 mg L(-1) Sb) grown hydroponically were investigated. The Sb tolerance and resistance of ramie were clearly revealed by growth inhibition, a TI between 13 and 99 %, non-significant changes in the maximum quantum efficiency of photosystem (F v /F m ), energy-harvesting efficiency (photosystem II (PSII)) and single-photon avalanche diode (SPAD) value, a significant increase in Sb in plant parts, BF >1, and an increase in catalase (CAT) and malondialdehyde (MDA) at 200 mg L(-1) Sb. Under increasing Sb stress, nearly the same non-significant decline in the maximum quantum efficiency of photosystem (F v /F m ), energy-harvesting efficiency (PSII), relative quantum yield of photosystem II (φPSII), and photochemical quenching (qP), except for F v /F m at 20 mg L(-1) Sb, were recorded. SPAD values for chlorophyll under Sb stress showed an increasing trend, except for a slight decrease, i.e., <2 %, than the control SPAD value at 200 mg L(-1) Sb. With a continuous increase in MDA, superoxide dismutase (SOD), peroxidase (POD), and CAT activities were suppressed under Sb addition up to 40 mg L(-1) Sb and the addition of Sb enhanced enzyme production at 80 and 200 mg L(-1) Sb. A continuous decrease in SOD, POD, and CAT up to 40 mg L(-1) Sb and enhancements at ≥80 mg L(-1), along with the continuous enhancement of MDA activity and inhibited biomass production, clearly reveal the roles of these enzymes in detoxifying Sb stress and the defense mechanism of ramie at 80 mg L(-1) Sb. Thus, B. nivea constitutes a promising candidate for Sb phytoremediation at mining sites. PMID:26711292

  15. Arsenic for antimony exchange on GaSb, its impacts on surface morphology, and interface structure

    NASA Astrophysics Data System (ADS)

    Xie, Qianghua; Van Nostrand, J. E.; Brown, J. L.; Stutz, C. E.

    1999-07-01

    We quantify the rates and total amounts of the arsenic for antimony exchange on both the Sb-terminated and Ga (or In)-terminated GaSb (001) surfaces using in situ real time line-of-sight mass spectrometry (LOS-MS) during molecular beam epitaxy. On the Sb-terminated GaSb (001) surface, an As for Sb exchange is observed to occur at all values of incident As2 flux considered. At high substrate temperature, three-dimensional (3D) nanometer-sized clusters from as a consequence of As/Sb exchange and lattice mismatch strain between GaAs and GaSb. The 3D clusters are found to have lateral dimensions of ˜10-30 nm and heights of 1-3 nm by atomic force microscopy (AFM). By contrast, at lower substrate temperatures a two-dimensional surface morphology is maintained, and AFM reveals an array of atomically flat terraces. On the surface terminated by one monolayer (ML) of Ga or In, there exists a critical As2 flux below which the As/Sb exchange is greatly diminished. The net amounts of Sb leaving the surface during one period of InAs/GaSb type-II superlattice growth are measured in real time by LOS-MS and estimated to be in the range of 0-0.4 ML for the various conditions used. By supplying only an As2 beam to a GaSb surface covered by InAs, the Sb riding over the InAs layer is replaced by arsenic and the total amount of such Sb is measured. The amount of Sb riding on the InAs can be as large as 0.8 ML for the first 1 ML of InAs and it gradually decreases to zero as the number of InAs monolayer increases. X-ray diffraction data show that all the InAs/GaSb superlattices coherently match with the GaSb substrate in the growth plane. The average lattice constant along the growth direction reduces with decreasing Sb mole fraction shown by the increased Sb desorption signal. Using the information on As/Sb exchange and Sb riding on the InAs surface, we predict an average lattice constant along the growth direction to be consistent with the measured one to within 2×10-4.

  16. Quaternary InGaAsSb Thermophotovoltaic Diodes

    SciTech Connect

    MW Dashiell; JF Beausang; H Ehsani; GJ Nichols; DM Depoy; LR Danielson; P Talamo; KD Rahner; EJ Brown; SR Burger; PM Foruspring; WF Topper; PF Baldasaro; CA Wang; R Huang; M Connors; G Turner; Z Shellenbarger; G Taylor; J Li; R Martinelli; D Donetski; S Anikeev; G Belenky; S Luryi

    2006-03-09

    In{sub x}Ga{sub 1-x}As{sub y}Sb{sub 1-y} thermophotovoltaic (TPV) diodes were grown lattice-matched to GaSb substrates by Metal Organic Vapor Phase Epitaxy (MOVPE) in the bandgap range of E{sub G} = 0.5 to 0.6eV. InGaAsSb TPV diodes, utilizing front-surface spectral control filters, are measured with thermal-to-electric conversion efficiency and power density of {eta}{sub TPV} = 19.7% and PD =0.58 W/cm{sup 2} respectively for a radiator temperature of T{sub radiator} = 950 C, diode temperature of T{sub diode} = 27 C, and diode bandgap of E{sub G} = 0.53eV. Practical limits to TPV energy conversion efficiency are established using measured recombination coefficients and optical properties of front surface spectral control filters, which for 0.53eV InGaAsSb TPV energy conversion is {eta}{sub TPV} = 28% and PD = 0.85W/cm{sup 2} at the above operating temperatures. The most severe performance limits are imposed by (1) diode open-circuit voltage (VOC) limits due to intrinsic Auger recombination and (2) parasitic photon absorption in the inactive regions of the module. Experimentally, the diode V{sub OC} is 15% below the practical limit imposed by intrinsic Auger recombination processes. Analysis of InGaAsSb diode electrical performance vs. diode architecture indicate that the V{sub OC} and thus efficiency is limited by extrinsic recombination processes such as through bulk defects.

  17. Chemical ordering rather than random alloying in SbAs

    NASA Astrophysics Data System (ADS)

    Shoemaker, Daniel P.; Chasapis, Thomas C.; Do, Dat; Francisco, Melanie C.; Chung, Duck Young; Mahanti, S. D.; Llobet, Anna; Kanatzidis, Mercouri G.

    2013-03-01

    The semimetallic group-V elements display a wealth of correlated electron phenomena due to a small indirect band overlap that leads to relatively small, but equal, numbers of holes and electrons at the Fermi energy with high mobility. Their electronic bonding characteristics produce a unique crystal structure, the rhombohedral A7 structure, which accommodates lone pairs on each site. Here, we show via single-crystal and synchrotron x-ray diffraction that antimony arsenide (SbAs) is a compound and the A7 structure can display chemical ordering of Sb and As, which were previously thought to mix randomly. Formation of this compound arises due to differences in electronegativity that are common to IV-VI compounds of average group V such as GeTe, SnS, PbS, and PbTe, and also ordered intraperiod compounds such as CuAu and NiPt. High-temperature diffraction studies reveal an order-disorder transition around 550 K in SbAs, which is in stark contrast to IV-VI compounds GeTe and SnTe that become cubic at elevated temperatures but do not disorder. Transport and infrared reflectivity measurements, along with first-principles calculations, confirm that SbAs is a semimetal, albeit with a direct band separation larger than that of Sb or As. Because even subtle substitutions in the semimetals, notably Bi1-xSbx, can open semiconducting energy gaps, a further investigation of the interplay between chemical ordering and electronic structure on the A7 lattice is warranted.

  18. Role of trivalent antimony in the removal of As, Sb, and Bi impurities from copper electrolytes

    NASA Astrophysics Data System (ADS)

    Xiao, Fa-xin; Cao, Dao; Mao, Jian-wei; Shen, Xiao-ni; Ren, Feng-zhang

    2013-01-01

    The role of trivalent antimony was investigated in removing As, Sb, and Bi impurities from a copper electrolyte. Purification experiments were carried out by adding a various concentrations of Sb(III) ions in a synthetic electrolyte containing 185 g/L sulfuric acid, 45 g/L Cu2+, 10 g/L As, and 0.5 g/L Bi under stirring at 65°C for 2 h. The electrolyte was filtered, and the structure, morphology and composition of the precipitate were analyzed by means of chemical analysis, scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and IR spectroscopy. The precipitate is composed of irregular lumps which are agglomerated by fine dendritic and floccus particles, and it mainly consists of As, Sb, Bi, and O elements. Characteristic bands in the IR spectra of the precipitate are As-OX (X=As, Sb, Bi), Sb-OY (Y=Sb, Bi), O-As-O, As-OH, Sb-OH, and O-H. The precipitate is a mixture of microcrystalline SbAsO4, (Sb,As)2O3, and amorphous phases. As, Sb, and Bi impurities are effectively removed from the copper electrolyte by Sb(III) ions attributing to these precipitates.

  19. Formation mechanism of primary phases and eutectic structures within undercooled Pb-Sb-Sn ternary alloys

    NASA Astrophysics Data System (ADS)

    Wang, Weili; Dai, Fuping; Wei, Bingbo

    2007-08-01

    The solidification characteristics of three types of Pb-Sb-Sn ternary alloys with different primary phases were studied under substantial undercooling conditions. The experimental results show that primary (Pb) and SbSn phases grow in the dendritic mode, whereas primary (Sb) phase exhibits faceted growth in the form of polygonal blocks and long strips. (Pb) solid solution phase displays strong affinity with SbSn intermetallic compound so that they produce various morphologies of pseudobinary eutectics, but it can only grow in the divorced eutectic mode together with (Sb) phase. Although (Sb) solid solution phase and SbSn intermetallic compound may grow cooperatively within ternary eutectic microstructures, they seldom form pseudobinary eutectics independently. The (Pb)+(Sb)+SbSn ternary eutectic structure usually shows lamellar morphology, but appears as anomalous eutectic when its volume fraction becomes small. EDS analyses reveal that all of the three primary (Pb), (Sb) and SbSn phases exhibit conspicuous solute trapping effect during rapid solidification, which results in the remarkable extension of solute solubility.

  20. Complex doping of group 13 elements In and Ga in caged skutterudite CoSb3

    DOE PAGESBeta

    Xi, Lili; Qiu, Yting; Zheng, Shang; Shi, Xun; Yang, Jiong; Chen, Lidong; Singh, David J.; Yang, Jihui; Zhang, Wenqing

    2014-12-12

    The complex doping behavior of Ga and In in CoSb3 has been investigated using ab initio total-energy calculations and thermodynamics. The formation energies of void filling, Sb substitution and complex dual-site occupancy defects with different charge states, and their dependence on chemical potentials of species, were studied. Results show that Ga predominantly forms dual-site 2GaVF–GaSb defects and substitutes for Sb only at very high Fermi levels or electron concentrations. In, on the other hand, can play multiple roles in skutterudites, including filling in the crystalline voids, substituting for Sb atoms or forming dual-site occupancy, among which the fully charge-compensated dual-sitemore » defects (2InVF–InSb and 4InVF–2InSb) are dominant. The equilibrium concentration ratio of impurities at void-filling sites to those at Sb-substitution sites for Ga-doped CoSb3 is very close to be 2:1, while this value markedly deviates from 2:1 for In-doped CoSb3. Furthermore, the 2:1 ratio of Ga doping in CoSb3 leads to low electron concentration (~2 × 1019 cm–3) and makes the doped system a semiconductor.« less

  1. Initial Sulfate Solubility Study for Sludge Batch 4 (SB4)

    SciTech Connect

    Lorier, T

    2005-04-01

    The objective of this task is to provide the Defense Waste Processing Facility (DWPF) of the Savannah River Site (SRS) with an assessment of the viability of using the current 0.6 wt% SO{sub 4}{sup =} limit (in glass) and/or the possibility of increasing the SO{sub 4}{sup =} solubility limit to account for anticipated sulfur concentrations in Sludge Batch 4 (SB4). The 0.6 wt% SO{sub 4}{sup =} limit was implemented for processing of Frit 418-Sludge Batch 3 (SB3) to avoid the formation of sulfate inclusions in the glass and/or the formation of a molten sulfate-rich phase on the melt pool in the DWPF melter. The presence of such a phase on the surface of the melt pool increases corrosion rates of melter components, enhances the potential for steam excursions in a slurry-fed waste glass melter, and creates the potential for undesirable current paths that could deplete energy delivered to the melter due to the electrical conductivity of the molten salt layer. This suite of sulfate-solubility tests began by testing the 1200-canister, 2nd transfer case for SB4 (as defined by Lilliston and Shah, 2004)--based on this being the most conservative (having the highest predicted viscosity when coupled with specific frits, it could potentially have the greatest impact on SO{sub 4}{sup =} solubility) blending scenario of SB4 with the heel of SB3 for SO{sub 4}{sup =} solubility. Frits 320 and 418 were tested with SB4 and the tests indicated that at the current SO{sub 4}{sup =} limit (in glass) and the tested waste loadings (30% and 40%), neither Frit 320 nor Frit 418 could be utilized with SB4 (for the 1200-canister, 2nd transfer case composition originally provided). More specifically, SO{sub 4}{sup =} was observed on the surface with the SB4 composition and Frit 320 at 40% waste loading (WL) and 0.6 wt% SO{sub 4}{sup =}, and with Frit 418 at 30% and 40% WL and 0.5 wt% SO{sub 4}{sup =}. As alternative frits were being developed--Frits 447, 448, and 449, that contained CaO and/or V

  2. TANK 40 FINAL SB7B CHEMICAL CHARACTERIZATION RESULTS

    SciTech Connect

    Bannochie, C.

    2012-03-15

    A sample of Sludge Batch 7b (SB7b) was taken from Tank 40 in order to obtain radionuclide inventory analyses necessary for compliance with the Waste Acceptance Product Specifications (WAPS). The SB7b WAPS sample was also analyzed for chemical composition including noble metals and fissile constituents, and these results are reported here. These analyses along with the WAPS radionuclide analyses will help define the composition of the sludge in Tank 40 that is currently being fed to the Defense Waste Processing Facility (DWPF) as SB7b. At the Savannah River National Laboratory (SRNL) the 3-L Tank 40 SB7b sample was transferred from the shipping container into a 4-L high density polyethylene bottle and solids were allowed to settle over the weekend. Supernate was then siphoned off and circulated through the shipping container to complete the transfer of the sample. Following thorough mixing of the 3-L sample, a 558 g sub-sample was removed. This sub-sample was then utilized for all subsequent analytical samples. Eight separate aliquots of the slurry were digested, four with HNO{sub 3}/HCl (aqua regia) in sealed Teflon{reg_sign} vessels and four with NaOH/Na{sub 2}O{sub 2} (alkali or peroxide fusion) using Zr crucibles. Two Analytical Reference Glass - 1 (ARG-1) standards were digested along with a blank for each preparation. Each aqua regia digestion and blank was diluted to 1:100 mL with deionized water and submitted to Analytical Development (AD) for inductively coupled plasma - atomic emission spectroscopy (ICP-AES) analysis, inductively coupled plasma - mass spectrometry (ICP-MS) analysis, atomic absorption spectroscopy (AA) for As and Se, and cold vapor atomic absorption spectroscopy (CV-AA) for Hg. Equivalent dilutions of the alkali fusion digestions and blank were submitted to AD for ICP-AES analysis. Tank 40 SB7b supernate was collected from a mixed slurry sample in the SRNL Shielded Cells and submitted to AD for ICP-AES, ion chromatography (IC), total base

  3. Laser irradiation and thermal treatment inducing selective crystallization in Sb2O3-Sb2S3 glassy films

    NASA Astrophysics Data System (ADS)

    Avila, L. F.; Pradel, A.; Ribeiro, S. J. L.; Messaddeq, Y.; Nalin, M.

    2015-02-01

    The influence of both thermal treatment and laser irradiation on the structural and optical properties of films in the Sb2O3-Sb2S3 system was investigated. The films were prepared by RF-sputtering using glass compositions as raw materials. Irreversible photodarkening effect was observed after exposure the films to a 458 nm solid state laser. It is shown, for the first time, the use of holographic technique to measure 'in situ', simultaneously and independently, the phase and amplitude modulations in glassy films. The films were also photo-crystallized and analysed 'in situ' using a laser coupled to a micro-Raman equipment. Results showed that Sb2S3 crystalline phase was obtained after irradiation. The effect of thermal annealing on the structure of the films was carried out. Different from the result obtained by irradiation, thermal annealing induces the crystallization of the Sb2O3 phase. Photo and thermal induced effects on films were studied using UV-Vis and Raman spectroscopy, atomic force microscopy (AFM), thermal analysis (DSC), X-ray diffraction, scanning electron microscopy (MEV) and energy-dispersive X-ray spectroscopy (EDX).

  4. High temperature magnetic order in Zn1-x Mn x SnSb2+MnSb nanocomposite ferromagnetic semiconductors.

    PubMed

    Kilanski, L; Górska, M; Ślawska-Waniewska, A; Lewińska, S; Szymczak, R; Dynowska, E; Podgórni, A; Dobrowolski, W; Ralević, U; Gajić, R; Romčević, N; Fedorchenko, I V; Marenkin, S F

    2016-08-24

    We present studies of structural, magnetic, and electrical properties of Zn1-x Mn x SnSb2+MnSb nanocomposite ferromagnetic semiconductors with the average Mn-content, [Formula: see text], changing from 0.027 up to 0.138. The magnetic force microscope imaging done at room temperature shows the presence of a strong signal coming from MnSb clusters. Magnetic properties show the paramagnet-ferromagnet transition with the Curie temperature, T C, equal to about 522 K and the cluster-glass behavior with the transition temperature, T CG, equal to about 465 K, both related to MnSb clusters. The magnetotransport studies show that all investigated samples are p-type semiconductors with high hole concentration, p, changing from 10(21) to 10(22) cm(-3). A large increase in the resistivity as a function of the magnetic field is observed at T  <  10 K and small magnetic fields, [Formula: see text] mT, for all the studied samples with a maximum amplitude of the magnetoresistance about 460% at T  =  1.4 K. The large increase in the resistivity is most probably caused by the appearance of the superconducting state in the samples at T  <  4.3 K. PMID:27351672

  5. High-quantum-efficiency 0.5 eV GaInAsSb/GaSb thermophotovoltaic devices

    SciTech Connect

    Wang, C.A.; Choi, H.K.; Ransom, S.L.; Charache, G.W.; Danielson, L.R.; DePoy, D.M.

    1999-08-01

    We report high-performance lattice-matched GaInAsSb/GaSb thermophotovoltaic (TPV) devices with a 0.5 eV band gap. The TPV structures were grown on GaSb substrates by organometallic vapor phase epitaxy at a lower temperature (525 {degree}C compared to 550 {degree}C) to improve the quality of the metastable GaInAsSb alloy. The 0.5 eV TPV devices exhibit external quantum efficiency as high as 60{percent}, which corresponds to an internal quantum efficiency of 90{percent}, assuming 35{percent} reflection losses. This efficiency is comparable to the value measured for 0.53 eV devices. The ratio of the open circuit voltage to band-gap energy ratio decreases from 0.57 for 0.53 eV devices to 0.48 for 0.5 eV devices. {copyright} {ital 1999 American Institute of Physics.}

  6. Fano-like resonances sustained by Si doped InAsSb plasmonic resonators integrated in GaSb matrix.

    PubMed

    Taliercio, Thierry; Guilengui, Vilianne N Tsame; Cerutti, Laurent; Rodriguez, Jean-Baptiste; Barho, Franziska; Rodrigo, Maria-José Milla; Gonzalez-Posada, Fernando; Tournié, Eric; Niehle, Michael; Trampert, Achim

    2015-11-16

    By using metal-free plasmonics, we report on the excitation of Fano-like resonances in the mid-infrared where the Fano asymmetric parameter, q, varies when the dielectric environment of the plasmonic resonator changes. We use silicon doped InAsSb alloy deposited by molecular beam epitaxy on GaSb substrate to realize the plasmonic resonators exclusively based on semiconductors. We first demonstrate the possibility to realize high quality samples of embedded InAsSb plasmonic resonators into GaSb host using regrowth technique. The high crystalline quality of the deposited structure is confirmed by scanning transmission electron microscopy (STEM) observation. Second, we report Fano-like resonances associated to localized surface plasmons in both cases: uncovered and covered plasmonic resonators, demonstrating a strong line shape modification. The optical properties of the embedded structures correspond to those modeled by finite-difference time-domain (FDTD) method and by a model based on Fano-like line shape. Our results show that all-semiconductor plasmonics gives the opportunity to build new plasmonic structures with embedded resonators of highly doped semiconductor in a matrix of un-doped semiconductor for mid-IR applications. PMID:26698426

  7. Extending the cutoff wavelength of lattice-matched GaInAsSb/GaSb thermophotovoltaics devices

    SciTech Connect

    Wang, C.A.; Choi, H.K.; Oakley, D.C.; Charache, G.W.

    1998-10-01

    This paper reports the growth, materials characterization, and device performance of lattice-matched GaInAsSb/GaSb thermophotovoltaic (TPV) devices with cutoff wavelength as long as 2.5 {micro}m. GaInAsSb epilayers were grown lattice matched to GaSb substrates by organometallic vapor phase epitaxy (OMVPE) using all organometallic precursors including triethylgallium, trimethylindium, tertiarybutylarsine, and trimethylantimony with diethyltellurium and dimethylzinc as the n- and p-type dopants, respectively. The growth temperature was 525 C. Although these alloys are metastable, a mirror-like surface morphology and room temperature photoluminescence (PL) are obtained for alloys with PL peak emission at room temperature as long as 2.5 {micro}m. In general, however, a trend of decreasing material quality is observed as the wavelength increases. Both the surface roughness and PL full width at half-maximum increase with wavelength. In spite of the dependence of material quality on PL peak emission wavelength, the internal quantum efficiency of TPV devices with cutoff wavelengths of 2.3 to 2.5 {micro}m is as high as 86%.

  8. Effects of the estrogen receptor antagonist fulvestrant on F344 rat prolactinoma models.

    PubMed

    Cao, Lei; Gao, Hua; Gui, Songbai; Bai, Giwei; Lu, Runchun; Wang, Fei; Zhang, Yazhuo

    2014-02-01

    The relationship between estrogen and prolactinoma is well documented. But the anti-tumor effects of a pure estrogen receptor antagonist fulvestrant on prolactinomas, especially in vivo, and the possible mechanisms are still unclear. Therefore, the aim of this study was to evaluate the effects of fulvestrant and the involvement of the Wnt signaling pathway on rat prolactinoma models. Forty female F344 rat prolactinoma models were established by subcutaneous administration of 10 mg 17β-estradiol for 6 weeks. Rats were intramuscularly injected with fulvestrant (0, 0.5, 3, 20, 40 mg/kg), and tumor size, weight and serum prolactin (PRL) levels were evaluated before and after fulvestrant treatment at 3, 7 and 14 days. Expression of estrogen receptor α (ERα), β-catenin and Wnt inhibitory factor-1 (WIF-1) in prolactinomas was measured using quantitative PCR and western blotting, and methylation of the WIF-1 promoter was investigated using pyrosequencing. Tumor size, weight and serum PRL levels were inhibited in dose-dependent and time-dependent manners after fulvestrant treatments. β-catenin expression was downregulated but WIF-1 expression was upregulated following fulvestrant treatment. The methylation of the CpG site of the WIF-1 promoter was negatively correlated to the expression of WIF-1. In addition, the anti-cell proliferation of fulvestrant on GH3 cells was partly disrupted by Wnt signaling pathway agonist SB 216763. In conclusion, fulvestrant inhibited tumor proliferation and PRL secretion of prolactinomas via ERα, and the Wnt signaling pathway was involved in this anti-tumor effect. Therefore, fulvestrant may be a potential new drug for prolactinomas. PMID:24407733

  9. Electronic structures of [001]- and [111]-oriented InSb and GaSb free-standing nanowires

    SciTech Connect

    Liao, Gaohua; Luo, Ning; Yang, Zhihu; Chen, Keqiu; Xu, H. Q. E-mail: hongqi.xu@ftf.lth.se

    2015-09-07

    We report on a theoretical study of the electronic structures of InSb and GaSb nanowires oriented along the [001] and [111] crystallographic directions. The nanowires are described by atomistic, tight-binding models, including spin-orbit interaction. The band structures and the wave functions of the nanowires are calculated by means of a Lanczos iteration algorithm. For the [001]-oriented InSb and GaSb nanowires, the systems with both square and rectangular cross sections are considered. Here, it is found that all the energy bands are doubly degenerate. Although the lowest conduction bands in these nanowires show good parabolic dispersions, the top valence bands show rich and complex structures. In particular, the topmost valence bands of the nanowires with a square cross section show a double maximum structure. In the nanowires with a rectangular cross section, this double maximum structure is suppressed, and the top valence bands gradually develop into parabolic bands as the aspect ratio of the cross section is increased. For the [111]-oriented InSb and GaSb nanowires, the systems with hexagonal cross sections are considered. It is found that all the bands at the Γ-point are again doubly degenerate. However, some of them will split into non-degenerate bands when the wave vector moves away from the Γ-point. Although the lowest conduction bands again show good parabolic dispersions, the topmost valence bands do not show the double maximum structure. Instead, they show a single maximum structure with its maximum at a wave vector slightly away from the Γ-point. The wave functions of the band states near the band gaps of the [001]- and [111]-oriented InSb and GaSb nanowires are also calculated and are presented in terms of probability distributions in the cross sections. It is found that although the probability distributions of the band states in the [001]-oriented nanowires with a rectangular cross section could be qualitatively described by one-band effective

  10. Electronic structures of [001]- and [111]-oriented InSb and GaSb free-standing nanowires

    NASA Astrophysics Data System (ADS)

    Liao, Gaohua; Luo, Ning; Yang, Zhihu; Chen, Keqiu; Xu, H. Q.

    2015-09-01

    We report on a theoretical study of the electronic structures of InSb and GaSb nanowires oriented along the [001] and [111] crystallographic directions. The nanowires are described by atomistic, tight-binding models, including spin-orbit interaction. The band structures and the wave functions of the nanowires are calculated by means of a Lanczos iteration algorithm. For the [001]-oriented InSb and GaSb nanowires, the systems with both square and rectangular cross sections are considered. Here, it is found that all the energy bands are doubly degenerate. Although the lowest conduction bands in these nanowires show good parabolic dispersions, the top valence bands show rich and complex structures. In particular, the topmost valence bands of the nanowires with a square cross section show a double maximum structure. In the nanowires with a rectangular cross section, this double maximum structure is suppressed, and the top valence bands gradually develop into parabolic bands as the aspect ratio of the cross section is increased. For the [111]-oriented InSb and GaSb nanowires, the systems with hexagonal cross sections are considered. It is found that all the bands at the Γ-point are again doubly degenerate. However, some of them will split into non-degenerate bands when the wave vector moves away from the Γ-point. Although the lowest conduction bands again show good parabolic dispersions, the topmost valence bands do not show the double maximum structure. Instead, they show a single maximum structure with its maximum at a wave vector slightly away from the Γ-point. The wave functions of the band states near the band gaps of the [001]- and [111]-oriented InSb and GaSb nanowires are also calculated and are presented in terms of probability distributions in the cross sections. It is found that although the probability distributions of the band states in the [001]-oriented nanowires with a rectangular cross section could be qualitatively described by one-band effective

  11. The Genomic Location of Sexually Antagonistic Variation: Some Cautionary Comments

    PubMed Central

    Fry, James D.

    2013-01-01

    Sexually antagonistic polymorphisms are polymorphisms in which the allele that is advantageous in one sex is deleterious in the other sex. In an influential 1984 paper, W. Rice hypothesized that such polymorphisms should be relatively common on the X chromosome (or on the W in female-heterogametic species) but relatively rare on the autosomes. Here, I show that there are plausible assumptions under which the reverse is expected to be true, and point out recent studies that give evidence for sexually antagonistic variation on the autosomes. Although more work is needed to resolve the issue, it is premature to conclude that the X chromosome is a “hot spot” for the accumulation of sexually antagonistic variation. PMID:19922443

  12. Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

    PubMed Central

    Wang, Kaiyu; Gan, Longjie; Jiang, Li; Zhang, Xianhui; Yang, Xiangyue; Chen, Min

    2015-01-01

    Staphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (Kd = 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a “double-hit” mouse model of SEB-induced TSS, established via sensitization with d-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS. PMID:25624325

  13. Transient receptor potential ankyrin 1 (TRPA1) antagonists.

    PubMed

    Preti, Delia; Saponaro, Giulia; Szallasi, Arpad

    2015-01-01

    The transient receptor potential ankyrin 1 (TRPA1) channel is an irritant sensor highly expressed on nociceptive neurons. The clinical use of TRPA1 antagonists is based on the concept that TRPA1 is active during disease states like neuropathic pain. Indeed, in Phase 2a proof-of-concept studies the TRPA1 antagonist GRC17536 has shown efficacy in patients with painful diabetic neuropathy. Moreover, animal studies suggest that the therapeutic value of TRPA1 antagonists extends beyond pain to pruritus, asthma and cough with limited safety concerns. This review provides a comprehensive overview of the patent literature (since 2007) on small-molecule inhibitors of the TRPA1 channel. Despite the clear progress, many unanswered questions remain. Future advancement to Phase 3 studies will assess the real translational potential of this research field. PMID:25853468

  14. Metabotropic glutamate receptor antagonists but not NMDA antagonists affect conditioned taste aversion acquisition in the parabrachial nucleus of rats.

    PubMed

    Vales, Karel; Zach, Petr; Bielavska, Edita

    2006-02-01

    The effect of glutamate receptor antagonists on conditioned taste aversion (CTA) was studied in rats. The association of the short-term memory of a gustatory conditioned stimulus (CS) with visceral malaise (unconditioned stimulus, US) in the CTA paradigm takes place in the parabrachial nuclei (PBN) of the brainstem. The first direct evidence of participation of glutamatergic neurotransmission in the PBN during CTA demonstrated that the extracellular level of glutamate rises during saccharin drinking (Bielavska et al. in Brain Res 887:413-417, 2000). Our results show an effect of microdialysis administration of selective GluR antagonists into the PBN on the formation of CTA engram. We used four glutamate receptor (GluR) antagonists of different types (D-AP5, MK-801 as antagonists of ionotropic GluR and L-AP3, MSPG as antagonists of metabotropic GluR). The disruptive effect of MK-801 on CTA formation in the PBN is concentration-dependent, with the greatest inhibition under the higher concentrations eliciting significant disruption. The application of D-AP5 (0.1, 1, 5 mM) did not elicit a statistically significant blockade of CTA acquisition. This indicates that the association of the US-CS in the PBN is not dependent on NMDA receptors. On the contrary, application of L-AP3 (0.1, 1, 5 mM) blocked the CS-US association. PMID:16273405

  15. New CuM 2/3Sb 1/3O 2 and AgM 2/3Sb 1/3O 2 compounds with the delafossite structure

    NASA Astrophysics Data System (ADS)

    Nagarajan, R.; Uma, S.; Jayaraj, M. K.; Tate, J.; Sleight, A. W.

    2002-05-01

    Several new compounds have been prepared with the delafossite structure: CuMn 2/3Sb 1/3O 2, CuCo 2/3Sb 1/3O 2, CuNi 2/3Sb 1/3O 2, CuZn 2/3Sb 1/3O 2, CuMg 2/3Sb 1/3O 2, AgNi 2/3Sb 1/3O 2, and AgZn 2/3Sb 1/3O 2. The structures of the CuM 2/3Sb 1/3O 2 compounds are generally based on 2H stacking along the c axis, and the M 2+ and Sb 5+ cations can be ordered or disordered. The structures of the AgM 2/3Sb 1/3O 2 compounds are based on 3R stacking along c with the M 2+ and Sb 5+ cations disordered. The structures of CuMn 2/3Sb 1/3O 2 (disordered) and CuMg 2/3Sb 1/3O 2 (ordered) were refined from single crystal X-ray diffraction data. Pellets and transparent thin films of CuNi 2/3Sb 1/3O 2 with 10% Sn doping for Sb showed p-type electronic conduction.

  16. Three-Dimensional Reduced Graphene Oxide Coupled with Mn3O4 for Highly Efficient Removal of Sb(III) and Sb(V) from Water.

    PubMed

    Zou, Jian-Ping; Liu, Hui-Long; Luo, Jinming; Xing, Qiu-Ju; Du, Hong-Mei; Jiang, Xun-Heng; Luo, Xu-Biao; Luo, Sheng-Lian; Suib, Steven L

    2016-07-20

    Highly porous, three-dimensional (3D) nanostructured composite adsorbents of reduced graphene oxides/Mn3O4 (RGO/Mn3O4) were fabricated by a facile method of a combination of reflux condensation and solvothermal reactions and systemically characterized. The as-prepared RGO/Mn3O4 possesses a mesoporous 3D structure, in which Mn3O4 nanoparticles are uniformly deposited on the surface of the reduced graphene oxide. The adsorption properties of RGO/Mn3O4 to antimonite (Sb(III)) and antimonate (Sb(V)) were investigated using batch experiments of adsorption isotherms and kinetics. Experimental results show that the RGO/Mn3O4 composite has fast liquid transport and superior adsorption capacity toward antimony (Sb) species in comparison to six recent adsorbents reported in the literature and summarized in a table in this paper. Theoretical maximum adsorption capacities of RGO/Mn3O4 toward Sb(III) and Sb(V) are 151.84 and 105.50 mg/g, respectively, modeled by Langmuir isotherms. The application of RGO/Mn3O4 was demonstrated by using drinking water spiked with Sb (320 μg/L). Fixed-bed column adsorption experiments indicate that the effective breakthrough volumes were 859 and 633 mL bed volumes (BVs) for the Sb(III) and Sb(V), respectively, until the maximum contaminant level of 5 ppb was reached, which is below the maximum limits allowed in drinking water according to the most stringent regulations. The advantages of being nontoxic, highly stable, and resistant to acid and alkali and having high adsorption capacity toward Sb(III) and Sb(V) confirm the great potential application of RGO/Mn3O4 in Sb-spiked water treatment. PMID:27355752

  17. Pharmacokinetic interactions with calcium channel antagonists (Part II).

    PubMed

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-12-01

    Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity. Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents. PMID:1782739

  18. Oxytocin antagonists for the management of preterm birth: a review.

    PubMed

    Usta, Ihab M; Khalil, Ali; Nassar, Anwar H

    2011-06-01

    Preterm birth, the leading cause of neonatal morbidity and mortality, is estimated at incidence of 12.7% of all births, which has not decreased over the last four decades despite intensive antenatal care programs aimed at high-risk groups, the widespread use of tocolytics, and a series of other preventive and therapeutic interventions. Oxytocin antagonists, namely atosiban, represent an appealing choice that seems to be effective with apparently fewer side effects than the traditional tocolytics. This article reviews the available literature on the pharmacokinetics, mode of administration, and clinical utility of oxytocin antagonists for acute and maintenance tocolysis with special emphasis on its safety profile. PMID:21170825

  19. Discovery of cannabinoid-1 receptor antagonists by virtual screening.

    PubMed

    Lee, Gil Nam; Kim, Kwang Rok; Ahn, Sung-Hoon; Bae, Myung Ae; Kang, Nam Sook

    2010-09-01

    In this work, we tried to find a new scaffold for a CB1 receptor antagonist using virtual screening. We first analyzed structural features for the known cannabinoid-1 receptor antagonists and, then, we built pharmacophore models using the HipHop concept and carried out a docking study based on our homology CB1 receptor 3D structure. The most active compound, including thiazole-4-one moiety, showed an activity value of 125 nM IC(50), with a good PK profile. PMID:20667724

  20. Cholestasis of pregnancy, pruritus and 5-hydroxytryptamine 3 receptor antagonists.

    PubMed

    Schumann, Roman; Hudcova, Jana

    2004-09-01

    Pruritus, an early symptom of intrahepatic cholestasis of pregnancy, may be severe. Conventional treatment includes ursodeoxycholic acid and cholestyramine. Ondansetron, a 5-hydroxytryptamine 3 receptor antagonist antiemetic, has been shown to reduce pruritus of different etiologies including cholestasis. We now report the successful preoperative use of ondansetron in a patient with pruritus from intrahepatic cholestasis of pregnancy. While the mechanism for our patient's response is poorly understood, 5-hydroxytryptamine 3 receptor antagonists should be further evaluated and possibly considered as a treatment option for intrahepatic cholestasis of pregnancy-related pruritus. PMID:15315599

  1. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists

    SciTech Connect

    Zuercher, William J.; Buckholz†, Richard G.; Campobasso, Nino; Collins, Jon L.; Galardi, Cristin M.; Gampe, Robert T.; Hyatt, Stephen M.; Merrihew, Susan L.; Moore, John T.; Oplinger, Jeffrey A.; Reid, Paul R.; Spearing, Paul K.; Stanley, Thomas B.; Stewart, Eugene L.; Willson, Timothy M.

    2010-08-12

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  2. Histamine 2 Receptor Antagonists and Proton Pump Inhibitors.

    PubMed

    Brinkworth, Megan D; Aouthmany, Mouhammad; Sheehan, Michael

    2016-01-01

    Within the last 50 years, the pharmacologic market for gastric disease has grown exponentially. Currently, medical management with histamine 2 receptor antagonist and proton pump inhibitors are the mainstay of therapy over surgical intervention. These are generally regarded as safe medications, but there are growing numbers of cases documenting adverse effects, especially those manifesting in the skin. Here we review the pharmacology, common clinical applications, and adverse reactions of both histamine 2 receptor antagonists and proton pump inhibitors with a particular focus on the potential for allergic reactions including allergic contact dermatitis. PMID:27172303

  3. Megapixel digital InSb detector for midwave infrared imaging

    NASA Astrophysics Data System (ADS)

    Shkedy, Lior; Markovitz, Tuvy; Calahorra, Zipi; Hirsh, Itay; Shtrichman, Itay

    2011-06-01

    Since the late 1990s Semiconductor devices (SCDs) has developed and manufactured a variety of InSb two-dimensional (2D) focal plane arrays (FPAs) that were implemented in many infrared (IR) systems and applications. SCD routinely manufactures both analog and digital InSb FPAs with array formats of 320×256, 480×384, and 640×512 elements, and pitch size in the range 15 to 30 μm. These FPAs are available in many packaging configurations, including fully integrated detector-Dewar-cooler-assembly, with either closed-cycle Stirling or open-loop Joule-Thomson coolers. In response to a need for very high resolution midwave IR (MWIR) detectors and systems, SCD has developed a large format 2D InSb detector with 1280×1024 elements and pixel size of 15 μm. A digital readout integrated circuit (ROIC) is coupled by flip-chip bonding to the megapixel InSb array. The ROIC is fabricated in CMOS 0.18-μm technology, that enables the small pixel circuitry and relatively low power generation at the focal plane. The digital ROIC has an analog to digital (A/D) converter per-channel and allows for full frame readout at a rate of 100 Hz. Such on-chip A/D conversion eliminates the need for several A/D converters with fairly high power consumption at the system level. The digital readout, together with the InSb detector technology, lead to a wide linear dynamic range and low residual nonuniformity, which is stable over a long period of time following a nonuniformity correction procedure. A special Dewar was designed to withstand harsh environmental conditions while minimizing the contribution to the heat load of the detector. The Dewar together with the low power ROIC, enable a megapixel detector with overall low size, weight, and power with respect to comparable large format detectors. A variety of applications with this detector make use of different cold shields with different f-number and spectral filters. In this paper we present actual performance characteristics of the

  4. Synthesis, crystal structure, and optical property of the quaternary chalcohalide Ba4Sb3S8Cl

    NASA Astrophysics Data System (ADS)

    Zhao, Hua-Jun

    2016-03-01

    The quaternary chalcohalide Ba4Sb3S8Cl has been prepared from stoichiometric mixtures of BaCl2, Ba, Sb, and S at 1093 K in an evacuated silica tube. Ba4Sb3S8Cl crystallizes in the monoclinic P21/c space group and features a 0D structure containing totally isolated [SbS3]3- units and discrete SbS2Cl trigonal pyramids separated by Ba2+ cations. The [SbS3]3- units and SbS2Cl trigonal pyramids are further packed in a pseudolayer motif in bc plane, respectively. The [SbS3]3- units are built by dimeric Sb2S6 polyhedras and SbS3 trigonal pyramids. Within the dimeric Sb2S6 polyhedra, two SbS4 seesaws share edges, while two SbS3 trigonal pyramids share corners with dimeric Sb2S6 polyhedra. The optical gap of 2.09 eV for Ba4Sb3S8Cl was deduced from the UV/Vis reflectance spectroscopy.

  5. Thermal Processing Effects on Microstructure and Composition of Cu3SbSe3

    SciTech Connect

    Majsztrik, Paul W; Kirkham, Melanie J; Garcia Negron, Valerie; Lara-Curzio, Edgar; Skoug, Eric; Morelli, Donald

    2013-01-01

    We report on the effects of thermal processing on the microstructure and composition of a system with overall stoichiometry of 3Cu:1Sb:3Se with the aim of producing single-phase Cu3SbSe3. It was found that slowly cooling from the melt produced a multiphase material consisting of Cu2Se and CuSbSe2, but devoid of Cu3SbSe3. Cooling rapidly from the melt resulted in three-phase microstructures consisting of Cu2Se, CuSbSe2, and Cu3SbSe3. Subsequent annealing of the three-phase material between 325 C and 400 C shifted composition towards nearly pure Cu3SbSe3, the target compound of this work. The kinetics of the transformation into Cu3SbSe3 is successfully described using a modified Avrami model, which suggests that diffusion is the rate-controlling step. Values of Young s modulus and hardness, obtained by nanoindentation, are reported for Cu2Se, CuSbSe2, and Cu3SbSe3.

  6. Realization of Vertically Aligned, Ultrahigh Aspect Ratio InAsSb Nanowires on Graphite.

    PubMed

    Anyebe, E A; Sanchez, A M; Hindmarsh, S; Chen, X; Shao, J; Rajpalke, M K; Veal, T D; Robinson, B J; Kolosov, O; Anderson, F; Sundaram, R; Wang, Z M; Falko, V; Zhuang, Q

    2015-07-01

    The monolithic integration of InAs(1-x)Sb(x) semiconductor nanowires on graphitic substrates holds enormous promise for cost-effective, high-performance, and flexible devices in optoelectronics and high-speed electronics. However, the growth of InAs(1-x)Sb(x) nanowires with high aspect ratio essential for device applications is extremely challenging due to Sb-induced suppression of axial growth and enhancement in radial growth. We report the realization of high quality, vertically aligned, nontapered and ultrahigh aspect ratio InAs(1-x)Sb(x) nanowires with Sb composition (xSb(%)) up to ∼12% grown by indium-droplet assisted molecular beam epitaxy on graphite substrate. Low temperature photoluminescence measurements show that the InAs(1-x)Sb(x) nanowires exhibit bright band-to-band related emission with a distinct redshift as a function of Sb composition providing further confirmation of successful Sb incorporation in as-grown nanowires. This study reveals that the graphite substrate is a more favorable platform for InAs(1-x)Sb(x) nanowires that could lead to hybrid heterostructures possessing potential device applications in optoelectronics. PMID:26086785

  7. Structural transformations in low-temperature grown GaAs:Sb

    NASA Astrophysics Data System (ADS)

    Vasyukov, D. A.; Baidakova, M. V.; Chaldyshev, V. V.; Suvorova, A. A.; Preobrazhenskii, V. V.; Putyato, M. A.; Semyagin, B. R.

    2001-05-01

    Sb-doped and Sb-free GaAs films were grown by molecular beam epitaxy (MBE) at low temperature (LT) and were annealed in the MBE set-up at various temperatures within the range of 500-900 °C. The concentrations of arsenic antisites in as-grown samples obtained using near-infra-red optical absorption were found to be as high as 6×1019 and 7×1019 cm-3 in Sb-doped and Sb-free samples, respectively. Samples were studied by high-resolution x-ray diffractometry (HRXRD) and transmission electron microscopy (TEM). Despite the high concentration of intrinsic point defects, x-ray rocking curves demonstrated perfect crystalline quality in as-grown samples. After annealing at temperatures of 500-700 °C, the lattice mismatch decreased in both Sb-doped and Sb-free samples, but in Sb-doped samples the reduction was much higher than would be expected for the antisite defect concentration determined from optical measurements. The segregation of isovalent Sb impurity into the As clusters was suggested. Upon annealing at temperatures higher than 700 °C, Sb-doped samples manifested a strong broadening of the diffraction maximum related to the LT GaAs:Sb layer. The TEM and HRXRD studies revealed that high-temperature annealing resulted in formation of dislocation loops attached to the large As clusters.

  8. Low frequency noise in single GaAsSb nanowires with self-induced compositional gradients.

    PubMed

    Huh, Junghwan; Kim, Dong-Chul; Munshi, A Mazid; Dheeraj, Dasa L; Jang, Doyoung; Kim, Gyu-Tae; Fimland, Bjørn-Ove; Weman, Helge

    2016-09-23

    Due to bandgap tunability, GaAsSb nanowires (NWs) have received a great deal of attention for a variety of optoelectronic device applications. However, electrical and optical properties of GaAsSb are strongly affected by Sb-related defects and scattering from surface states and/or defects, which can limit the performance of GaAsSb NW devices. Thus, in order to utilize the GaAsSb NWs for high performance electronic and optoelectronic devices, it is required to study the material and interface properties (e.g. the interface trap density) in the GaAsSb NW devices. Here, we investigate the low frequency noise in single GaAsSb NWs with self-induced compositional gradients. The current noise spectral density of the GaAsSb NW device showed a typical 1/f noise behavior. The Hooge's noise parameter and the interface trap density of the GaAsSb NW device were found to be ∼2.2 × 10(-2) and ∼2 × 10(12) eV(-1) cm(-2), respectively. By applying low frequency noise measurements, the noise equivalent power, a key figure of merit of photodetectors, was calculated. The observed low frequency noise properties can be useful as guidance for quality and reliability of GaAsSb NW based electronic devices, especially for photodetectors. PMID:27528601

  9. Measurement of InAsSb bandgap energy and InAs/InAsSb band edge positions using spectroscopic ellipsometry and photoluminescence spectroscopy

    SciTech Connect

    Webster, P. T.; Riordan, N. A.; Liu, S.; Zhang, Y.-H.; Johnson, S. R.; Steenbergen, E. H.

    2015-12-28

    The structural and optical properties of lattice-matched InAs{sub 0.911}Sb{sub 0.089} bulk layers and strain-balanced InAs/InAs{sub 1−x}Sb{sub x} (x ∼ 0.1–0.4) superlattices grown on (100)-oriented GaSb substrates by molecular beam epitaxy are examined using X-ray diffraction, spectroscopic ellipsometry, and temperature dependent photoluminescence spectroscopy. The photoluminescence and ellipsometry measurements determine the ground state bandgap energy and the X-ray diffraction measurements determine the layer thickness and mole fraction of the structures studied. Detailed modeling of the X-ray diffraction data is employed to quantify unintentional incorporation of approximately 1% Sb into the InAs layers of the superlattices. A Kronig-Penney model of the superlattice miniband structure is used to analyze the valence band offset between InAs and InAsSb, and hence the InAsSb band edge positions at each mole fraction. The resulting composition dependence of the bandgap energy and band edge positions of InAsSb are described using the bandgap bowing model; the respective low and room temperature bowing parameters for bulk InAsSb are 938 and 750 meV for the bandgap, 558 and 383 meV for the conduction band, and −380 and −367 meV for the valence band.

  10. Effects of Sb Content (x) on (Bi(1-x)Sb(x))2Te3 Thermoelectric Thin Film Deposited by Effusion Cell Evaporator.

    PubMed

    Yong, Ho; Na, Sekwon; Gang, Jun-Gu; Jeon, Seong-Jae; Hyun, Seungmin; Lee, Hoo-Jeong

    2015-10-01

    This paper investigates the effects of the Sb content (x) on (Bi(1-x)Sb(x))2Te3 thermoelectric films with x changing widely from 0 (Sb2Te3) to 1 (Bi2Te3). First, the XRD analysis discloses that with the Sb content (x) increasing, the phase changed gradually from Bi2Te3 to Sb2Te3 as Sb atoms replaced substitutionally Bi atoms. Further microstructure analysis reveals that an extensive grain growth occurred during post-annealing for the samples with high Sb contents. According to the measurement of electrical and thermoelectric properties, the polarity of the charge carrier and Seebeck coefficient switched n-type to p-type in the range of x = 0.45~0.63. For the n-type samples, the power factor is highest when x = 0.18 around 46.01 μW/K(2) whereas Sb2Te3, for the p-type samples, shows the highest value, 62.48 μW/K(2)cm. PMID:26726497

  11. Effect of Sb Segregation on Conductance and Catalytic Activity at Pt/Sb-Doped SnO2 Interface: A Synergetic Computational and Experimental Study.

    PubMed

    Fu, Qiang; Colmenares Rausseo, Luis César; Martinez, Umberto; Dahl, Paul Inge; García Lastra, Juan Maria; Vullum, Per Erik; Svenum, Ingeborg-Helene; Vegge, Tejs

    2015-12-23

    Antimony-doped tin dioxide (ATO) is considered a promising support material for Pt-based fuel cell cathodes, displaying enhanced stability over carbon-based supports. In this work, the effect of Sb segregation on the conductance and catalytic activity at Pt/ATO interface was investigated through a combined computational and experimental study. It was found that Sb-dopant atoms prefer to segregate toward the ATO/Pt interface. The deposited Pt catalysts, interestingly, not only promote Sb segregation, but also suppress the occurrence of Sb(3+) species, a charge carrier neutralizer at the interface. The conductivity of ATO was found to increase, to a magnitude close to that of activated carbon, with an increment of Sb concentration before reaching a saturation point around 10%, and then decrease, indicating that Sb enrichment at the ATO surface may not always favor an increment of the electric current. In addition, the calculation results show that the presence of Sb dopants in ATO has little effect on the catalytic activity of deposited three-layer Pt toward the oxygen reduction reaction, although subsequent alloying of Pt and Sb could lower the corresponding catalytic activity. These findings help to support future applications of ATO/Pt-based materials as possible cathodes for proton exchange membrane fuel cell applications with enhanced durability under practical applications. PMID:26615834

  12. Synthesis and high temperature thermoelectric properties of Yb0.25Co4Sb12-(Ag2Te)x(Sb2Te3)1-x nanocomposites

    NASA Astrophysics Data System (ADS)

    Zheng, Jin; Peng, Jiangying; Zheng, Zhexin; Zhou, Menghan; Thompson, Emily; Yang, Junyou; Xiao, Wanli

    2015-09-01

    Nanocomposites are becoming a new paradigm in thermoelectric study: by incorporating nanophase(s) into a bulk matrix, a nanocomposite often exhibits unusual thermoelectric properties beyond its constituent phases. To date most nanophases are binary, while reports on ternary nanoinclusions are scarce. In this work, we conducted an exploratory study of introducing ternary (Ag2Te)x(Sb2Te3)1-x inclusions in the host matrix of Yb0.25Co4Sb12. Yb0.25Co4Sb12 - 4wt% (Ag2Te)x(Sb2Te3)1-x nanocomposites were prepared by a melting-milling-hot-pressing process. Microstructural analysis showed that poly-dispersed nanosized Ag-Sb-Te inclusions are distributed on the grain boundaries of Yb0.25Co4Sb12 coarse grains. Compared to the pristine nanoinclusion-free sample, the electrical conductivity, Seebeck coefficient, and thermal conductivity were optimized simultaneously upon nanocompositing, while the carrier mobility was largely remained. A maximum ZT of 1.3 was obtained in Yb0.25Co4Sb12-4wt% (Ag2Te)0.42(Sb2Te3)0.58 at 773 K, a ~ 40% increase compared to the pristine sample. The electron and phonon mean-free-path were estimated to help quantify the observed changes in the carrier mobility and lattice thermal conductivity.

  13. Rapid photooxidation of Sb(III) in the presence of different Fe(III) species

    NASA Astrophysics Data System (ADS)

    Kong, Linghao; He, Mengchang; Hu, Xingyun

    2016-05-01

    The toxicity and mobility of antimony (Sb) are strongly influenced by the redox processes associated with Sb. Dissolved iron (Fe) is widely distributed in the environment as different species and plays a significant role in Sb speciation. However, the mechanisms of Sb(III) oxidation in the presence of Fe have remained unclear because of the complexity of Fe and Sb speciation. In this study, the mechanisms of Sb(III) photooxidation in the presence of different Fe species were investigated systematically. The photooxidation of Sb(III) occurred over a wide pH range, from 1 to 10. Oxygen was not a predominant or crucial factor in the Sb(III) oxidation process. The mechanism of Sb(III) photooxidation varied depending on the Fe(III) species. In acidic solution (pH 1-3), dichloro radicals (radCl2-) and hydroxyl radicals (radOH) generated by the photocatalysis of FeCl2+ and FeOH2+ were the main oxidants for Sb(III) oxidation. Fe(III) gradually transformed into the colloid ferric hydroxide (CFH) and ferrihydrite in circumneutral and alkaline solutions (pH 4-10). Photooxidation of Sb(III) occurred through electron transfer from Sb(III) to Fe(III) along with the reduction of Fe(III) to Fe(II) through a ligand-to-metal charge-transfer (LMCT) process. The photocatalysis of different Fe(III) species may play an important role in the geochemical cycle of Sb(III) in surface soil and aquatic environments.

  14. GaSb substrates with extended IR wavelength for advanced space based applications

    SciTech Connect

    Allen, Lisa P.; Flint, Patrick; Dallas, Gordon; Bakken, Daniel; Blanchat, Kevin; Brown, Gail J.; Vangala, Shivashankar R.; Goodhue, William D.; Krishnaswami, Kannan

    2009-05-01

    GaSb substrates have advantages that make them attractive for implementation of a wide range of infrared (IR) detectors with higher operating temperatures for stealth and space based applications. A significant aspect that would enable widespread commercial application of GaSb wafers for very long wavelength IR (VLWIR) applications is the capability for transmissivity beyond 15 m. Due largely to the GaSb (antisite) defect and other point defects in undoped GaSb substrates, intrinsic GaSb is still slightly p-type and strongly absorbs in the VLWIR. This requires backside thinning of the GaSb substrate for IR transmissivity. An extremely low n-type GaSb substrate is preferred to eliminate thinning and provide a substrate solution for backside illuminated VLWIR devices. By providing a more homogeneous radial distribution of the melt solute to suppress GaSb formation and controlling the cooling rate, ultra low doped n:GaSb has been achieved. This study examines the surface properties and IR transmission spectra of ultra low doped GaSb substrates at both room and low temperatures. Atomic force microscopy (AFM), homoepitaxy by MBE, and infrared Fourier transform (FTIR) analysis was implemented to examine material quality. As compared with standard low doped GaSb, the ultra low doped substrates show over 50% transmission and consistent wavelength transparency past 23 m with improved %T at low temperature. Homoepitaxy and AFM results indicate the ultra low doped GaSb has a low thermal desorbtion character and qualified morphology. In summary, improvements in room temperature IR transmission and extended wavelength characteristics have been shown consistently for ultra low doped n:GaSb substrates.

  15. Resonant Ultrasound Studies of Mo3Sb7

    NASA Astrophysics Data System (ADS)

    Vanbebber, Lindsay; Yan, Jiaqiang; Mandrus, David; Sales, Brian; Keppens, Veerle

    2013-03-01

    The elastic behavior of a series of Mo3-xMxSb7-yXy (M= Cr, Ru, X= Te) single crystals is examined with resonant ultrasound spectroscopy (RUS) as a function of temperature (300 K - 5 K). The elastic response of the parent compound Mo3Sb7 reveals a transition at around 53K, evidenced by a dramatic softening in the shear modulus c=(c11-c12)/2. This softening is associated with a cubic-to-tetragonal structural transition as well as a spin gap formation. The transition temperature is lowered by a few degrees upon doping with Cr. Doping with Ru and Te is known to suppress the structural transition, but the softening in the shear modulus suggests that a structural instability remains present in these compounds. This research was supported by the U.S. Department of Energy, Basic Energy Sciences, Materials Sciences and Engineering Division.

  16. InAs/AlAsSb based quantum cascade detector

    SciTech Connect

    Reininger, Peter Zederbauer, Tobias; Schwarz, Benedikt; MacFarland, Donald; Andrews, Aaron Maxwell; Schrenk, Werner; Strasser, Gottfried; Detz, Hermann

    2015-08-24

    In this letter, we introduce the InAs/AlAsSb material system for quantum cascade detectors (QCDs). InAs/AlAsSb can be grown lattice matched to InAs and exhibits a conduction band offset of approximately 2.1 eV, enabling the design of very short wavelength quantum cascade detectors. Another benefit using this material system is the low effective mass of the well material that improves the total absorption of the detector and decreases the intersubband scattering rates, which increases the device resistance and thus enhances the noise behavior. We have designed, grown, and measured a QCD that detects at a wavelength of λ = 4.84 μm and shows a peak specific detectivity of approximately 2.7 × 10{sup 7 }Jones at T = 300 K.

  17. Hydrogenation of GaSb/GaAs quantum rings

    SciTech Connect

    Hodgson, P. D. Hayne, M.; Zhuang, Q. D.; Ahmad Kamarudin, M.; Birindelli, S.; Capizzi, M.

    2014-08-25

    We present the results of photoluminescence measurements on hydrogenated type-II GaSb/GaAs quantum dot/ring (QD/QR) samples at temperatures ranging from 4.2 K to 400 K. Hydrogenation is found to suppress optically induced charge depletion (associated with the presence of carbon acceptors in this system). A redshift of the QD\\QR emission energy of a few tens of meV is observed at temperatures ≥300 K, consistent with a reduction in average occupancy by ∼1 hole. These effects are accompanied by a reduction in PL intensity post-hydrogenation. We conclude that although hydrogenation may have neutralized the carbon acceptors, multiple hole occupancy of type-II GaSb/GaAs QD/QRs is very likely a precondition for intense emission, which would make extending the wavelength significantly beyond 1300 nm at room temperature difficult.

  18. Super-Hard induced gap in InSb nanowires

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Yu, Peng; Hocevar, Moïra; Plissard, Sébastien; Car, Diana; Bakkers, Erik; Frolov, Sergey

    In recent years, Majorana bound states were observed experimentally in InSb nanowire-superconductor hybrid devices, which manifested themselves as a zero-bias conductance peak (ZBP). However, there was still significant conductance inside the superconducting gap, which would smear sub-gap features. Moreover, fermionic states inside the gap would also break topological protection. Therefore, a hard gap is required in search of more deterministic signatures of Majorana bound states, and building up Majorana qubits. We report the observation of a hard induced gap in an InSb Josephson junction with an optimized superconducting contact recipe. The gap is resolved in magnetic field up to 2 Tesla, and demonstrates a peculiar kinked field dependence. In addition, we observed rich sub-gap features: Andreev levels appeared close to pinch off regime, while multiple Andreev reflection appeared in open regime.

  19. Genomic analysis of Skermanella stibiiresistens type strain SB22T

    PubMed Central

    Zhu, Wentao; Huang, Jing; Li, Mingshun; Li, Xiangyang; Wang, Gejiao

    2014-01-01

    Members of genus Skermanella were described as Gram-negative, motile, aerobic, rod-shaped, obligate-heterotrophic bacteria and unable to fix nitrogen. In this study, the genome sequence of Skermanella stibiiresistens SB22T is reported. Phylogenetic analysis using core proteins confirmed the phylogenetic assignment based on 16S rRNA gene sequences. Strain SB22T has all the proteins for complete glycolysis, tricarboxylic acid cycle and pentose phosphate pathway. The RuBisCO encoding genes cbbL1S1 and nitrogenase delta subunit gene anfG are absent, consistent with its inability to fix carbon and nitrogen, respectively. In addition, the genome possesses a series of flagellar assembly and chemotaxis genes to ensure its motility. PMID:25197493

  20. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    SciTech Connect

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  1. Antagonistic peptide technology for functional dissection of CLE peptides revisited

    PubMed Central

    Czyzewicz, Nathan; Wildhagen, Mari; Cattaneo, Pietro; Stahl, Yvonne; Pinto, Karine Gustavo; Aalen, Reidunn B.; Butenko, Melinka A.; Simon, Rüdiger; Hardtke, Christian S.; De Smet, Ive

    2015-01-01

    In the Arabidopsis thaliana genome, over 1000 putative genes encoding small, presumably secreted, signalling peptides can be recognized. However, a major obstacle in identifying the function of genes encoding small signalling peptides is the limited number of available loss-of-function mutants. To overcome this, a promising new tool, antagonistic peptide technology, was recently developed. Here, this antagonistic peptide technology was tested on selected CLE peptides and the related IDA peptide and its usefulness in the context of studies of peptide function discussed. Based on the analyses, it was concluded that the antagonistic peptide approach is not the ultimate means to overcome redundancy or lack of loss-of-function lines. However, information collected using antagonistic peptide approaches (in the broad sense) can be very useful, but these approaches do not work in all cases and require a deep insight on the interaction between the ligand and its receptor to be successful. This, as well as peptide ligand structure considerations, should be taken into account before ordering a wide range of synthetic peptide variants and/or generating transgenic plants. PMID:26136270

  2. Antagonistic peptide technology for functional dissection of CLE peptides revisited.

    PubMed

    Czyzewicz, Nathan; Wildhagen, Mari; Cattaneo, Pietro; Stahl, Yvonne; Pinto, Karine Gustavo; Aalen, Reidunn B; Butenko, Melinka A; Simon,