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Sample records for cb1 mediates baseline

  1. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis

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    Müller Anke

    2010-06-01

    Full Text Available Abstract Background Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Δ9-tetrahydrocannabinol (THC and Cannabidiol (CBD fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1 deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail. Results THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX-expressing intermediate progenitor cells. Conclusion CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.

  2. The CB1 Receptor as an Important Mediator of Hedonic Reward Processing

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    Friemel, Chris M; Zimmer, Andreas; Schneider, Miriam

    2014-01-01

    The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex—the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing. PMID:24718372

  3. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

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    Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

    2013-01-01

    Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

  4. A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens.

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    Wright, William J; Schlüter, Oliver M; Dong, Yan

    2017-04-01

    The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1 + FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1 + FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1 + FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1 + FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1 + FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc.

  5. CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

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    Shivakumar Subbanna

    2018-02-01

    Full Text Available Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD. However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7 mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2 levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB activation, and activity-regulated cytoskeleton-associated protein (Arc expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP, spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD.

  6. Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

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    Rodríguez-Muñoz María

    2009-03-01

    Full Text Available Abstract Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than

  7. CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

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    Basavarajappa, Balapal S; Subbanna, Shivakumar

    2014-02-01

    Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice. © 2013 Wiley Periodicals, Inc.

  8. AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

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    Matthias eKlugmann

    2011-07-01

    Full Text Available The endocannabinoid (ECB system is strongly involved in the regulation of cognitive processing and emotional behavior and evidence indicates that ECB signaling might affect these behavioral abilities by modulations of prefrontal cortical functions. The aim of the present study was to examine the role of the CB1 receptor in the medial prefrontal cortex (mPFC on cognitive flexibility and emotional behavior. Therefore, the CB1 receptor was overexpressed by adeno-associated virus (AAV vector-mediated gene transfer specifically in the mPFC of adult Wistar rats. Animals were then tested in different anxiety-related paradigms for emotional reactivity (e.g. elevated plus maze (EPM, light/dark emergence test (EMT, social interaction and the attentional set shift task (ASST - an adaptation of the human Wisconsin card sorting test - for cognitive abilities and behavioral flexibility. A subtle increase in exploratory behavior was found in CB1 receptor overexpressing animals (CB1-R compared to empty vector injected controls (Empty in the EMT and EPM, although general locomotor activity did not differ between the groups. During social interaction testing, social contact behavior towards the unknown conspecific was found to be decreased, whereas social withdrawal was increased in CB1-R animals and they showed an inadequate increase in exploratory behavior compared to control animals. In the ASST, impaired reversal learning abilities were detected in CB1-R animals compared to controls, indicating reduced behavioral flexibility. In conclusion, upregulation of the CB1 receptor specifically in the rat mPFC induces alterations in emotional reactivity, leads to inadequate social behavior and impairs cognitive flexibility. These findings might be relevant for neuropsychiatric disorders, since higher cortical CB1 receptor expression levels as well as similar behavioral impairments as observed in the present study have been described in schizophrenic patients.

  9. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

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    Gaffal, E; Cron, M; Glodde, N; Tüting, T

    2013-08-01

    ∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. CB1 cannabinoid receptor-mediated anandamide signaling mechanisms of the inferior colliculus modulate the haloperidol-induced catalepsy.

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    Medeiros, P; de Freitas, R L; Silva, M O; Coimbra, N C; Melo-Thomas, L

    2016-11-19

    The inferior colliculus (IC), a midbrain structure that processes acoustic information of aversive nature, is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Previous evidence relating the IC to motor behavior shows that glutamatergic and GABAergic mechanisms in the IC exert influence on systemic haloperidol-induced catalepsy. There is substantial evidence supporting a role played by the endocannabinoid system as a modulator of the glutamatergic neurotransmission, as well as the dopaminergic activity in the basal nuclei and therefore it may be considered as a potential pharmacological target for the treatment of movement disorders. The present study evaluated if the endocannabinoid system in the IC plays a role in the elaboration of systemic haloperidol-induced catalepsy. Male Wistar rats received intracollicular microinjection of either the endogenous cannabinoid anandamide (AEA) at different concentrations (5, 50 or 100pmol/0.2μl), the CB 1 cannabinoid receptor antagonist AM251 at 50, 100 or 200pmol/0.2μl or vehicle, followed by intraperitoneal (IP) administration of either haloperidol at 0.5 or 1mg/kg or physiological saline. Systemic injection of haloperidol at both doses (0.5 or 1mg/kg, IP) produced a cataleptic state, compared to vehicle/physiological saline-treated group, lasting 30 and 50min after systemic administration of the dopaminergic receptors non-selective antagonist. The midbrain microinjection of AEA at 50pmol/0.2μl increased the latency for stepping down from the horizontal bar after systemic administration of haloperidol. Moreover, the intracollicular administration of AEA at 50pmol/0.2μl was able to increase the duration of catalepsy as compared to AEA at 100pmol/0.2-μl-treated group. Intracollicular pretreatment with AM251 at the intermediate concentration (100pmol/0.2μl) was able to decrease the duration of catalepsy after systemic administration of haloperidol. However

  11. Receptor-heteromer mediated regulation of endocannabinoid signaling in activated microglia. Role of CB1 and CB2 receptors and relevance for Alzheimer's disease and levodopa-induced dyskinesia.

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    Navarro, Gemma; Borroto-Escuela, Dasiel; Angelats, Edgar; Etayo, Íñigo; Reyes-Resina, Irene; Pulido-Salgado, Marta; Rodríguez-Pérez, Ana I; Canela, Enric I; Saura, Josep; Lanciego, José Luis; Labandeira-García, José Luis; Saura, Carlos A; Fuxe, Kjell; Franco, Rafael

    2018-01-01

    Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB 1 and CB 2 receptors, which may form heteromeric complexes (CB 1 -CB 2 Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB 1 and circa 20 fold for CB 2 ), whereas receptor levels were similar for CB 1 and markedly upregulated for CB 2 ; CB 1 -CB 2 Hets were also upregulated. Unlike in resting cells, CB 2 receptors became robustly coupled to G i in activated cells, in which CB 1 -CB 2 Hets mediated a potentiation effect. Hence, resting cells were refractory while activated cells were highly responsive to cannabinoids. Interestingly, similar results were obtained in cultures treated with ß-amyloid (Aß 1-42 ). Microglial activation markers were detected in the striatum of a Parkinson's disease (PD) model and, remarkably, in primary microglia cultures from the hippocampus of mutant β-amyloid precursor protein (APP Sw,Ind ) mice, a transgenic Alzheimer's disease (AD) model. Also of note was the similar cannabinoid receptor signaling found in primary cultures of microglia from APP Sw,Ind and in cells from control animals activated using LPS plus IFN-γ. Expression of CB 1 -CB 2 Hets was increased in the striatum from rats rendered dyskinetic by chronic levodopa treatment. In summary, our results showed sensitivity of activated microglial cells to cannabinoids, increased CB 1 -CB 2 Het expression in activated microglia and in microglia from the hippocampus of an AD model, and a correlation between levodopa-induced dyskinesia and striatal microglial activation in a PD model. Cannabinoid receptors and the CB 1 -CB 2 heteroreceptor complex in activated microglia have potential as targets in the

  12. CB1 Receptor-Mediated Signaling Underlies the Hippocampal Synaptic, Learning and Memory Deficits Following Treatment with JWH-081, a New Component of Spice/K2 Preparations

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    Basavarajappa, Balapal S.; Subbanna, Shivakumar

    2014-01-01

    Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as “Spice” or “K2” to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of “Spice/K2”, including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of...

  13. GABAergic and cortical and subcortical glutamatergic axon terminals contain CB1 cannabinoid receptors in the ventromedial nucleus of the hypothalamus.

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    Leire Reguero

    Full Text Available BACKGROUND: Type-1 cannabinoid receptors (CB(1R are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH that participates in homeostatic and behavioral functions including food intake. Although CB(1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB(1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB(1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. METHODOLOGY/PRINCIPAL FINDINGS: Light and electron microscopy techniques were used to analyze CB(1R distribution in the VMH of CB(1R-WT, CB(1R-KO and conditional mutant mice bearing a selective deletion of CB(1R in cortical glutamatergic (Glu-CB(1R-KO or GABAergic neurons (GABA-CB(1R-KO. At light microscopy, CB(1R immunolabeling was observed in the VMH of CB(1R-WT and Glu-CB(1R-KO animals, being remarkably reduced in GABA-CB(1R-KO mice. In the electron microscope, CB(1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB(1R immunopositive profiles and CB(1R density in terminals making asymmetric or symmetric synapses in CB(1R-WT mice. Furthermore, the proportion of CB(1R immunopositive terminals/preterminals in CB(1R-WT and Glu-CB(1R-KO mice was reduced in GABA-CB(1R-KO mutants. CB(1R density was similar in all animal conditions. Finally, the percentage of CB(1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB(1R-KO mutants relative to CB(1R-WT mice, indicating that CB(1R was distributed in cortical and subcortical excitatory synaptic terminals. CONCLUSIONS/SIGNIFICANCE: Our anatomical results support the idea that the VMH is a relevant hub candidate in

  14. CB1 cannabinoid receptor expression in the striatum: Association with corticostriatal circuits and developmental regulation

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    Vincent eVan Waes

    2012-03-01

    Full Text Available Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains. We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25 and then progressively decreases towards adolescent (P40 and adult (P70 levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors receive inputs from cortical regions with higher expression (medial prefrontal cortex. In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.

  15. CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

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    Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

    2006-10-01

    Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

  16. The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

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    Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

    2012-01-01

    The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

  17. Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

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    Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

    2016-08-30

    Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.

  18. The central cannabinoid CB1 receptor is required for diet-induced obesity and rimonabant's antiobesity effects in mice.

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    Pang, Zhen; Wu, Nancy N; Zhao, Weiguang; Chain, David C; Schaffer, Erica; Zhang, Xin; Yamdagni, Preeti; Palejwala, Vaseem A; Fan, Chunpeng; Favara, Sarah G; Dressler, Holly M; Economides, Kyriakos D; Weinstock, Daniel; Cavallo, Jean S; Naimi, Souad; Galzin, Anne-Marie; Guillot, Etienne; Pruniaux, Marie-Pierre; Tocci, Michael J; Polites, H Greg

    2011-10-01

    Cannabinoid receptor CB1 is expressed abundantly in the brain and presumably in the peripheral tissues responsible for energy metabolism. It is unclear if the antiobesity effects of rimonabant, a CB1 antagonist, are mediated through the central or the peripheral CB1 receptors. To address this question, we generated transgenic mice with central nervous system (CNS)-specific knockdown (KD) of CB1, by expressing an artificial microRNA (AMIR) under the control of the neuronal Thy1.2 promoter. In the mutant mice, CB1 expression was reduced in the brain and spinal cord, whereas no change was observed in the superior cervical ganglia (SCG), sympathetic trunk, enteric nervous system, and pancreatic ganglia. In contrast to the neuronal tissues, CB1 was undetectable in the brown adipose tissue (BAT) or the liver. Consistent with the selective loss of central CB1, agonist-induced hypothermia was attenuated in the mutant mice, but the agonist-induced delay of gastrointestinal transit (GIT), a primarily peripheral nervous system-mediated effect, was not. Compared to wild-type (WT) littermates, the mutant mice displayed reduced body weight (BW), adiposity, and feeding efficiency, and when fed a high-fat diet (HFD), showed decreased plasma insulin, leptin, cholesterol, and triglyceride levels, and elevated adiponectin levels. Furthermore, the therapeutic effects of rimonabant on food intake (FI), BW, and serum parameters were markedly reduced and correlated with the degree of CB1 KD. Thus, KD of CB1 in the CNS recapitulates the metabolic phenotype of CB1 knockout (KO) mice and diminishes rimonabant's efficacy, indicating that blockade of central CB1 is required for rimonabant's antiobesity actions.

  19. Molecular basis of cannabinoid CB1 receptor coupling to the G protein heterotrimer Gαiβγ: identification of key CB1 contacts with the C-terminal helix α5 of Gαi.

    Science.gov (United States)

    Shim, Joong-Youn; Ahn, Kwang H; Kendall, Debra A

    2013-11-08

    The cannabinoid (CB1) receptor is a member of the rhodopsin-like G protein-coupled receptor superfamily. The human CB1 receptor, which is among the most expressed receptors in the brain, has been implicated in several disease states, including drug addiction, anxiety, depression, obesity, and chronic pain. Different classes of CB1 agonists evoke signaling pathways through the activation of specific subtypes of G proteins. The molecular basis of CB1 receptor coupling to its cognate G protein is unknown. As a first step toward understanding CB1 receptor-mediated G protein signaling, we have constructed a ternary complex structural model of the CB1 receptor and Gi heterotrimer (CB1-Gi), guided by the x-ray structure of β2-adrenergic receptor (β2AR) in complex with Gs (β2AR-Gs), through 824-ns duration molecular dynamics simulations in a fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer environment. We identified a group of residues at the juxtamembrane regions of the intracellular loops 2 and 3 (IC2 and IC3) of the CB1 receptor, including Ile-218(3.54), Tyr-224(IC2), Asp-338(6.30), Arg-340(6.32), Leu-341(6.33), and Thr-344(6.36), as potential key contacts with the extreme C-terminal helix α5 of Gαi. Ala mutations of these residues at the receptor-Gi interface resulted in little G protein coupling activity, consistent with the present model of the CB1-Gi complex, which suggests tight interactions between CB1 and the extreme C-terminal helix α5 of Gαi. The model also suggests that unique conformational changes in the extreme C-terminal helix α5 of Gα play a crucial role in the receptor-mediated G protein activation.

  20. Targeting the endocannabinoid/CB1 receptor system for treating obesity in Prader–Willi syndrome

    Directory of Open Access Journals (Sweden)

    Ibrahim Knani

    2016-12-01

    Full Text Available Objective: Extreme obesity is a core phenotypic feature of Prader–Willi syndrome (PWS. Among numerous metabolic regulators, the endocannabinoid (eCB system is critically involved in controlling feeding, body weight, and energy metabolism, and a globally acting cannabinoid-1 receptor (CB1R blockade reverses obesity both in animals and humans. The first-in-class CB1R antagonist rimonabant proved effective in inducing weight loss in adults with PWS. However, it is no longer available for clinical use because of its centrally mediated, neuropsychiatric, adverse effects. Methods: We studied eCB ‘tone’ in individuals with PWS and in the Magel2-null mouse model that recapitulates the major metabolic phenotypes of PWS and determined the efficacy of a peripherally restricted CB1R antagonist, JD5037 in treating obesity in these mice. Results: Individuals with PWS had elevated circulating levels of 2-arachidonoylglycerol and its endogenous precursor and breakdown ligand, arachidonic acid. Increased hypothalamic eCB ‘tone’, manifested by increased eCBs and upregulated CB1R, was associated with increased fat mass, reduced energy expenditure, and decreased voluntary activity in Magel2-null mice. Daily chronic treatment of obese Magel2-null mice and their littermate wild-type controls with JD5037 (3 mg/kg/d for 28 days reduced body weight, reversed hyperphagia, and improved metabolic parameters related to their obese phenotype. Conclusions: Dysregulation of the eCB/CB1R system may contribute to hyperphagia and obesity in Magel2-null mice and in individuals with PWS. Our results demonstrate that treatment with peripherally restricted CB1R antagonists may be an effective strategy for the management of severe obesity in PWS. Author Video: Author Video Watch what authors say about their articles Keywords: Endocannabinoids, PWS, Magel2, Peripheral CB1 blockade, Metabolic syndrome

  1. The role of CB1 receptors in psychostimulant addiction

    NARCIS (Netherlands)

    Wiskerke, J.; Pattij, T.; Schoffelmeer, A.N.M.; de Vries, T.J.

    2008-01-01

    Recent studies have implicated the endocannabinoid (eCB) system in the neuronal mechanisms underlying substance dependence. Here, we review results of studies using cannabinoid receptor subtype 1 (CB1) knockout mice as well as CB1 antagonists to elucidate the role of this neurotransmitter system in

  2. The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

    Science.gov (United States)

    Bow, Eric W.; Rimoldi, John M.

    2016-01-01

    The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

  3. Loss of cannabinoid receptor CB1 induces preterm birth.

    Directory of Open Access Journals (Sweden)

    Haibin Wang

    2008-10-01

    Full Text Available Preterm birth accounting approximate 10% of pregnancies in women is a tremendous social, clinical and economic burden. However, its underlying causes remain largely unknown. Emerging evidence suggests that endocannabinoid signaling via cannabinoid receptor CB1 play critical roles in multiple early pregnancy events in both animals and humans. Since our previous studies demonstrated that loss of CB1 defers the normal implantation window in mice, we surmised that CB1 deficiency would influence parturition events.Exploiting mouse models with targeted deletion of Cnr1, Cnr2 and Ptgs1 encoding CB1, CB2 and cyclooxygenase-1, respectively, we examined consequences of CB1 or CB2 silencing on the onset of parturition. We observed that genetic or pharmacological inactivation of CB1, but not CB2, induced preterm labor in mice. Radioimmunoassay analysis of circulating levels of ovarian steroid hormones revealed that premature birth resulting from CB1 inactivation is correlated with altered progesterone/estrogen ratios prior to parturition. More strikingly, the phenotypic defects of prolonged pregnancy length and parturition failure in mice missing Ptgs1 were corrected by introducing CB1 deficiency into Ptgs1 null mice. In addition, loss of CB1 resulted in aberrant secretions of corticotrophin-releasing hormone and corticosterone during late gestation. The pathophysiological significance of this altered corticotrophin-releasing hormone-driven endocrine activity in the absence of CB1 was evident from our subsequent findings that a selective corticotrophin-releasing hormone antagonist was able to restore the normal parturition timing in Cnr1 deficient mice. In contrast, wild-type females receiving excessive levels of corticosterone induced preterm birth.CB1 deficiency altering normal progesterone and estrogen levels induces preterm birth in mice. This defect is independent of prostaglandins produced by cyclooxygenase-1. Moreover, CB1 inactivation resulted in

  4. Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study

    Science.gov (United States)

    Neumeister, Alexander; Normandin, Marc D.; Pietrzak, Robert H.; Piomelli, Daniele; Zheng, Ming-Qiang; Gujarro-Anton, Ana; Potenza, Marc N.; Bailey, Christopher R.; Lin, Shu-fei; Najafzadeh, Soheila; Ropchan, Jim; Henry, Shannan; Corsi-Travali, Stefani; Carson, Richard E.; Huang, Yiyun

    2013-01-01

    Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder. PMID:23670490

  5. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte

    2010-01-01

    , the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

  6. Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory.

    Science.gov (United States)

    Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

    2011-01-01

    The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). We first tested the hypothesis that an A(1)-CB(1) interaction influences GABA and glutamate release in the hippocampus. We found that A(1) receptor activation attenuated the CB(1)-mediated inhibition of GABA and glutamate release and this interaction was manifested at the level of G-protein activation. Using in vivo and in vitro approaches, we then investigated the functional implications of the adenosine-cannabinoid interplay that may arise following chronic caffeine consumption. Chronic administration of caffeine in mice (intraperitoneally, 3 mg/kg/day, for 15 days, >12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. A(1) receptor levels were increased following chronic caffeine administration. This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory.

  7. Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

    International Nuclear Information System (INIS)

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey

    2011-01-01

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (−/−) mice. Mice of both genotypes (n = 5–6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82–95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 μM) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20–23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: ► C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. ► Wild type and cannabinoid CB1 receptor knockout littermates

  8. Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

    Energy Technology Data Exchange (ETDEWEB)

    Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

    2011-11-15

    Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

  9. Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

    Science.gov (United States)

    Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

    2013-01-01

    The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

  10. Neurophysiological evidence for the presence of cannabinoid CB1 receptors in the laterodorsal tegmental nucleus

    DEFF Research Database (Denmark)

    Soni, Neeraj; Satpathy, Shankha; Kohlmeier, Kristi Anne

    2014-01-01

    Marijuana, which acts within the endocannabinoid (eCB) system as an agonist of the cannabinoid type 1 receptor (CB1R), exhibits addictive properties and has powerful actions on the state of arousal of an organism. The laterodorsal tegmental nucleus (LDT), as a component of the reticular activating...... the firing frequency and synaptic activity of neurons in this nucleus. Therefore, endogenous eCB transmission could play a role in processes involving the LDT, such as cortical activation and motivated behaviours and, further, behavioural actions of marijuana are probably mediated, in part, via cellular...

  11. Regulation of Hippocampal Cannabinoid CB1 Receptor Actions by Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of Δ9-Tetrahydrocannabinol on Spatial Memory

    OpenAIRE

    Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

    2010-01-01

    Abstract The cannabinoid CB1 receptor-mediated modulation of ?-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A1 receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A1 receptors localized in GABAergic cells do not directly influence GABA release. CB1 and A1 receptors are the main targets for the effects of two of the most heavily consumed ps...

  12. The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis.

    Science.gov (United States)

    Sanchez, Ana-Maria; Quattrone, Federica; Pannese, Maria; Ulisse, Adele; Candiani, Massimo; Diaz-Alonso, Javier; Velasco, Guillermo; Panina-Bordignon, Paola

    2017-01-01

    Does signaling via the cannabinoid (CB 1 ) receptor play a role in the pathogenesis of endometriosis in a mouse model? Mice treated with a CB 1 agonist developed larger ectopic lesions, while less severe lesions developed in the absence of functional CB 1 expression. The expression of components of the endocannabinoid system has been demonstrated in both mouse and human uteri. CB 1 receptors are expressed in human epithelial and stromal cell lines derived from eutopic endometrium and deep infiltrating endometriosis nodules. This was a randomized study in a mouse model of endometriosis. In a first set of experiments, mice with endometriosis were treated with the CB 1 receptor agonist methanandamide (MET) (5 mg/kg, n = 20) on Days 1-5 and 8-12. In a second set of experiments, endometriosis development was evaluated in CB 1 -/- mice and in their wild-type (WT) littermates. Endometriosis-like lesions were induced in Balb/c and C57/Bl6 mice. Two weeks after disease induction, the lesions were counted, measured and either included for immunohistochemistry analysis or frozen for gene expression profiling by semi-quantitative real-time PCR. To limit the role of chance, the experiments were conducted under standardized laboratory conditions with appropriate controls. The lesion total volume was significantly higher in MET-treated compared with vehicle-treated mice (P endometriosis in a mouse model. However, the relative contribution of the CB 1 -mediated signaling pathways active in inflammatory, uterine and peritoneal cells remains to be ascertained. Since the study was performed in a mouse model, the significance of the findings in the human system warrants further investigation. Clarifying the function and regulation of CB 1 and its molecular interactions with endogenous ligands, and how endocannabinoids levels are regulated in women with endometriosis, represent critical areas of research for the potential development of a novel medical treatment of the disease. A

  13. Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

    Directory of Open Access Journals (Sweden)

    Changyu Pan

    2011-01-01

    Full Text Available Rimonabant, a selective cannabinoid-1 (CB1 receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2 or greater without diabetes from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit and randomized to rimonabant 20 mg (n=318 or placebo (n=325 for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg, P<.0001. The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp. (P<.0001. Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P<.0001. This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed.

  14. Participation of hypothalamic CB1 receptors in reproductive axis disruption during immune challenge.

    Science.gov (United States)

    Surkin, P N; Di Rosso, M E; Correa, F; Elverdin, J C; Genaro, A M; De Laurentiis, A; Fernández-Solari, J

    2017-08-01

    Immune challenge inhibits reproductive function and endocannabinoids (eCB) modulate sexual hormones. However, no studies have been performed to assess whether the eCB system mediates the inhibition of hormones that control reproduction as a result of immune system activation during systemic infections. For that reason, we evaluated the participation of the hypothalamic cannabinoid receptor CB1 on the hypothalamic-pituitary-gonadal (HPG) axis activity in rats submitted to immune challenge. Male adult rats were treated i.c.v. administration with a CB1 antagonist/inverse agonist (AM251) (500 ng/5 μL), followed by an i.p. injection of lipopolysaccharide (LPS) (5 mg/kg) 15 minutes later. Plasmatic, hypothalamic and adenohypophyseal pro-inflammatory cytokines, hormones and neuropeptides were assessed 90 or 180 minutes post-LPS. The plasma concentration of tumour necrosis factor α and adenohypophyseal mRNA expression of Tnfα and Il1β increased 90 and 180 minutes post i.p. administration of LPS. However, cytokine mRNA expression in the hypothalamus increased only 180 minutes post-LPS, suggesting an inflammatory delay in this organ. CB1 receptor blockade with AM251 increased LPS inflammatory effects, particularly in the hypothalamus. LPS also inhibited the HPG axis by decreasing gonadotrophin-releasing hormone hypothalamic content and plasma levels of luteinising hormone and testosterone. These disruptor effects were accompanied by decreased hypothalamic Kiss1 mRNA expression and prostaglandin E2 content, as well as by increased gonadotrophin-inhibitory hormone (Rfrp3) mRNA expression. All these disruptive effects were prevented by the presence of AM251. In summary, our results suggest that, in male rats, eCB mediate immune challenge-inhibitory effects on reproductive axis at least partially via hypothalamic CB1 activation. In addition, this receptor also participates in homeostasis recovery by modulating the inflammatory process taking place after LPS

  15. Modulation of Network Oscillatory Activity and GABAergic Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Medial Entorhinal Cortex

    Directory of Open Access Journals (Sweden)

    Nicola H. Morgan

    2008-01-01

    Full Text Available Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 M, an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM, increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

  16. Cannabinoid CB1 Receptors Are Localized in Striated Muscle Mitochondria and Regulate Mitochondrial Respiration

    Directory of Open Access Journals (Sweden)

    Juan Mendizabal-Zubiaga

    2016-10-01

    Full Text Available The cannabinoid type 1 (CB1 receptor is widely distributed in the brain and peripheral organs where it regulates cellular functions and metabolism. In the brain, CB1 is mainly localized on presynaptic axon terminals but is also found on mitochondria (mtCB1, where it regulates cellular respiration and energy production. Likewise, CB1 is localized on muscle mitochondria, but very little is known about it. The aim of this study was to further investigate in detail the distribution and functional role of mtCB1 in three different striated muscles. Immunoelectron microscopy for CB1 was used in skeletal muscles (gastrocnemius and rectus abdominis and myocardium from wild-type and CB1-KO mice. Functional assessments were performed in mitochondria purified from the heart of the mice and the mitochondrial oxygen consumption upon application of different acute delta-9-tetrahidrocannabinol (Δ9-THC concentrations (100 nM or 200 nM was monitored. About 26% of the mitochondrial profiles in gastrocnemius, 22% in the rectus abdominis and 17% in the myocardium expressed CB1. Furthermore, the proportion of mtCB1 versus total CB1 immunoparticles was about 60% in the gastrocnemius, 55% in the rectus abdominis and 78% in the myocardium. Importantly, the CB1 immunolabeling pattern disappeared in muscles of CB1-KO mice. Functionally, acute 100 nM or 200 nM THC treatment specifically decreased mitochondria coupled respiration between 12% and 15% in wild-type isolated mitochondria of myocardial muscles but no significant difference was noticed between THC treated and vehicle in mitochondria isolated from CB1-KO heart. Furthermore, gene expression of key enzymes involved in pyruvate synthesis, tricarboxylic acid (TCA cycle and mitochondrial respiratory chain was evaluated in the striated muscle of CB1-WT and CB1-KO. CB1-KO showed an increase in the gene expression of Eno3, Pkm2, and Pdha1, suggesting an increased production of pyruvate. In contrast, no significant

  17. The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala.

    Science.gov (United States)

    Ratano, Patrizia; Everitt, Barry J; Milton, Amy L

    2014-10-01

    We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.

  18. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

    Science.gov (United States)

    Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

    2018-01-02

    Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

  19. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    Energy Technology Data Exchange (ETDEWEB)

    Prather, Paul L. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M. [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Ford, Benjamin M.; Franks, Lirit N. [Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States); Radominska-Pandya, Anna, E-mail: RadominskaAnna@uams.edu [Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205 (United States)

    2013-11-15

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  20. CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

    International Nuclear Information System (INIS)

    Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

    2013-01-01

    Highlights: •Tamoxifen produces cytotoxicity via estrogen-receptor (ER) independent mechanisms. •Tamoxifen binds to CB1 and CB2 cannabinoid receptors and acts as an inverse agonist. •CB1 and CB2 receptors are novel molecular targets for Tamoxifen. •ER-independent effects for Tamoxifen may be mediated via CB1 and/or CB2 receptors. -- Abstract: Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for the ER-independent effects of Tam and its derivatives are poorly understood. Interestingly, similar to Tam and 4OH-Tam, cannabinoids have also been shown to exhibit anti-proliferative and apoptotic effects in ER-negative breast cancer cells, and estrogen can regulate expression levels of cannabinoid receptors (CBRs). Therefore, this study investigated whether CBRs might serve as novel molecular targets for Tam and 4OH-Tam. We report that both compounds bind to CB1 and CB2Rs with moderate affinity (0.9–3 μM). Furthermore, Tam and 4OH-Tam exhibit inverse activity at CB1 and CB2Rs in membrane preparations, reducing basal G-protein activity. Tam and 4OH-Tam also act as CB1/CB2R-inverse agonists to regulate the downstream intracellular effector adenylyl cyclase in intact cells, producing concentration-dependent increases in intracellular cAMP. These results suggest that CBRs are molecular targets for Tam and 4OH-Tam and may contribute to the ER-independent cytotoxic effects reported for these drugs. Importantly, these findings also indicate that Tam and 4OH-Tam might be used as structural scaffolds for development of novel

  1. Postnatal Development of CB1 Receptor Expression in Rodent Somatosensory Cortex

    Science.gov (United States)

    Deshmukh, Suvarna; Onozuka, Kaori; Bender, Kevin J.; Bender, Vanessa A.; Lutz, Beat; Mackie, Ken; Feldman, Daniel E.

    2007-01-01

    Endocannabinoids are powerful modulators of synaptic transmission that act on presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the dominant receptor in the CNS, and is present in many brain regions, including sensory cortex. To investigate the potential role of CB1 receptors in cortical development, we examined the developmental expression of CB1 in rodent primary somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific antibody. We found that before postnatal day (P) 6, CB1 receptor staining was present exclusively in the cortical white matter, and that CB1 staining appeared in the grey matter between P6 and P20 in a specific laminar pattern. CB1 staining was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6. CB1 null (−/−) mice showed altered anatomical barrel maps in layer 4, with enlarged inter-barrel septa, but normal barrel size. These results indicate that CB1 receptors are present in early postnatal development and influence development of sensory maps. PMID:17210229

  2. The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Francisco J. Bermudez-Silva

    2016-01-01

    Full Text Available The endocannabinoid system (ECS is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1 signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1 receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6 within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight, which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.

  3. Cannabinoid-1 receptor (CB1R) blockers as medicines: beyond obesity and cardiometabolic disorders to substance abuse/drug addiction with CB1R neutral antagonists.

    Science.gov (United States)

    Janero, David R

    2012-03-01

    Addiction to chemical substances with abuse potential presents medical needs largely unsolved by extant therapeutic strategies. Signal transmission through the cannabinoid-1 receptor (CB1R) in the central nervous system (CNS) modulates neurotransmitters/neuronal pathways contributing to the rewarding properties and hedonic effects of certain nondrug stimuli (e.g., food) and many prototypical addictive drugs, promoting excessive intake and its pathological consequences. Typical CB1R antagonists/inverse agonists reduce the rewarding effects and normalize behavioral phenotypes associated with food and abused drugs, but carry an unacceptable adverse-event profile that may reflect, at least partly, their intrinsic ability to alter basal homeostatic CB1R signaling in the CNS and elicit a negative efficacy response. Alternatively, peripherally biased CB1R inverse agonists with limited CNS permeability and putative CB1R neutral antagonists expressing modest (if any) inverse-agonist efficacy are garnering attention for treating obesity and related cardiometabolic complications with a potentially enhanced benefit-to-risk profile. This mini-review calls attention to the proposition that CB1R neutral antagonists offer attractive opportunities for pharmacotherapeutic exploitation in the substance abuse/drug addiction space, whereas the restricted CNS accessibility of peripherally biased CB1R inverse agonists circumscribes their therapeutic utility for this indication. The unique preclinical pharmacology, efficacy profiles, and reduced adverse-event risk of CB1R neutral antagonists make them worthy of translational study for their potential therapeutic application beyond obesity/cardiometabolic disease to include substance-abuse/drug-addiction disorders.

  4. Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

    DEFF Research Database (Denmark)

    Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal

    2016-01-01

    release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naive rats, CB1...

  5. Association of cannabis use during adolescence, prefrontal CB1 receptor signaling and schizophrenia

    Directory of Open Access Journals (Sweden)

    Adriana eCaballero

    2012-05-01

    Full Text Available The cannabinoid receptor 1 (CB1R is the G-protein coupled receptor responsible for the majority of the endocannabinoid signaling in the human brain. It is widely distributed in the limbic system, basal ganglia, and cerebellum, which are areas responsible for cognition, memory, and motor control. Because of this widespread distribution, it is not surprising that drugs that co-opt CB1R have expected behavioral outcomes consistent with dysregulated signaling from these areas (e.g. memory loss, cognitive deficits, etc. In the context of this review, we present evidence for the role of CB1R signaling in the prefrontal cortex (PFC, an area involved in executive functions, with emphasis on the developmental regulation of CB1R signaling in the acquisition of mature PFC function. We further hypothesize how alterations of CB1R signaling specifically during adolescent maturation might confer liability to psychiatric disorders.

  6. Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.

    Science.gov (United States)

    Mouro, Francisco M; Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Baqi, Younis; Müller, Christa E; Lopes, Luísa V; Ribeiro, Joaquim A; Sebastião, Ana M

    2017-05-01

    Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

    Science.gov (United States)

    Viñals, Xavier; Moreno, Estefanía; Lanfumey, Laurence; Cordomí, Arnau; Pastor, Antoni; de La Torre, Rafael; Gasperini, Paola; Navarro, Gemma; Howell, Lesley A; Pardo, Leonardo; Lluís, Carmen; Canela, Enric I; McCormick, Peter J; Maldonado, Rafael; Robledo, Patricia

    2015-07-01

    Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR) revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

  8. Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors.

    Directory of Open Access Journals (Sweden)

    Xavier Viñals

    2015-07-01

    Full Text Available Activation of cannabinoid CB1 receptors (CB1R by delta9-tetrahydrocannabinol (THC produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice lacking 5-HT2A receptors (5-HT2AR revealed a remarkable 5-HT2AR-dependent dissociation in the beneficial antinociceptive effects of THC and its detrimental amnesic properties. We found that specific effects of THC such as memory deficits, anxiolytic-like effects, and social interaction are under the control of 5-HT2AR, but its acute hypolocomotor, hypothermic, anxiogenic, and antinociceptive effects are not. In biochemical studies, we show that CB1R and 5-HT2AR form heteromers that are expressed and functionally active in specific brain regions involved in memory impairment. Remarkably, our functional data shows that costimulation of both receptors by agonists reduces cell signaling, antagonist binding to one receptor blocks signaling of the interacting receptor, and heteromer formation leads to a switch in G-protein coupling for 5-HT2AR from Gq to Gi proteins. Synthetic peptides with the sequence of transmembrane helices 5 and 6 of CB1R, fused to a cell-penetrating peptide, were able to disrupt receptor heteromerization in vivo, leading to a selective abrogation of memory impairments caused by exposure to THC. These data reveal a novel molecular mechanism for the functional interaction between CB1R and 5-HT2AR mediating cognitive impairment. CB1R-5-HT2AR heteromers are thus good targets to dissociate the cognitive deficits induced by THC from its beneficial antinociceptive properties.

  9. Developmental and visual input-dependent regulation of the CB1 cannabinoid receptor in the mouse visual cortex.

    Directory of Open Access Journals (Sweden)

    Taisuke Yoneda

    Full Text Available The mammalian visual system exhibits significant experience-induced plasticity in the early postnatal period. While physiological studies have revealed the contribution of the CB1 cannabinoid receptor (CB1 to developmental plasticity in the primary visual cortex (V1, it remains unknown whether the expression and localization of CB1 is regulated during development or by visual experience. To explore a possible role of the endocannabinoid system in visual cortical plasticity, we examined the expression of CB1 in the visual cortex of mice. We found intense CB1 immunoreactivity in layers II/III and VI. CB1 mainly localized at vesicular GABA transporter-positive inhibitory nerve terminals. The amount of CB1 protein increased throughout development, and the specific laminar pattern of CB1 appeared at P20 and remained until adulthood. Dark rearing from birth to P30 decreased the amount of CB1 protein in V1 and altered the synaptic localization of CB1 in the deep layer. Dark rearing until P50, however, did not influence the expression of CB1. Brief monocular deprivation for 2 days upregulated the localization of CB1 at inhibitory nerve terminals in the deep layer. Taken together, the expression and the localization of CB1 are developmentally regulated, and both parameters are influenced by visual experience.

  10. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

    Science.gov (United States)

    Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

    2012-06-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

  11. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

    OpenAIRE

    Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

    2011-01-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

  12. Effect of blockage of the endocannabinoid system by CB(1) antagonism on cardiovascular risk.

    Science.gov (United States)

    Mach, François; Montecucco, Fabrizio; Steffens, Sabine

    2009-01-01

    The endocannabinoid system is a crucial player in the inflammatory processes underlying atherosclerosis. Recently, basic research studies and animal models have strongly supported the role of the endocannabinoid system not only in the regulation of classical cardiovascular risk factors (including lipid profile and glucose homeostasis), but also in the activation of immune cells and inflammatory mediators. Clinical trials investigating treatment with rimonabant (a selective antagonist of the cannabinoid type 1 receptor) have suggested a beneficial effect of this drug in the management of obesity. Further studies are needed to explore a possible use for rimonabant in treating type 2 diabetes and acute and chronic cardiovascular disease. Despite the slight increase in adverse events (mainly psychiatric), which has led to the recent withdrawal of rimonabant from the market, CB(1) receptor antagonism might represent a very promising therapeutic strategy to reduce the cardiovascular risk. In the present review, we focused on the most important experimental investigations into the role of the endocannabinoid system in atherosclerosis and cardiovascular risk.

  13. Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling.

    Science.gov (United States)

    Rivas, Priscila M S; Vechiato, Fernanda M V; Borges, Beatriz C; Rorato, Rodrigo; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2017-07-01

    Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200ng/μl in 5μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure

    Directory of Open Access Journals (Sweden)

    Sally Miller

    2018-05-01

    Full Text Available Nearly half a century has passed since the demonstration that cannabis and its chief psychoactive component Δ9-THC lowers intraocular pressure (IOP. Elevated IOP remains the chief hallmark and therapeutic target for glaucoma, a condition that places millions at risk of blindness. It is likely that Δ9-THC exerts much of its IOP-lowering effects via the activation of CB1 cannabinoid receptors. However, the initial promise of CB1 as a target for treating glaucoma has not thus far translated into a credible therapeutic strategy. We have recently shown that blocking monoacylglycerol lipase (MAGL, an enzyme that breaks the endocannabinoid 2-arachidonoyl glycerol (2-AG, substantially lowers IOP. Another strategy is to develop cannabinoid CB1 receptor agonists that are optimized for topical application to the eye. Recently we have reported on a controlled-deactivation approach where the “soft” drug concept of enzymatic deactivation was combined with a “depot effect” that is commonly observed with Δ9-THC and other lipophilic cannabinoids. This approach allowed us to develop novel cannabinoids with a predictable duration of action and is particularly attractive for the design of CB1 activators for ophthalmic use with limited or no psychoactive effects. We have tested a novel class of compounds using a combination of electrophysiology in autaptic hippocampal neurons, a well-characterized model of endogenous cannabinoid signaling, and measurements of IOP in a mouse model. We now report that AM7410 is a reasonably potent and efficacious agonist at CB1 in neurons and that it substantially (30% lowers IOP for as long as 5 h after a single topical treatment. This effect is absent in CB1 knockout mice. Our results indicate that the direct targeting of CB1 receptors with controlled-deactivation ligands is a viable approach to lower IOP in a murine model and merits further study in other model systems.

  15. Paranoid schizophrenia is characterized by increased CB1 receptor binding in the dorsolateral prefrontal cortex.

    Science.gov (United States)

    Dalton, Victoria S; Long, Leonora E; Weickert, Cyndi Shannon; Zavitsanou, Katerina

    2011-07-01

    A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ). In the present study, we examined cannabinoid CB(1) receptor (CB(1)R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. Receptor density was investigated using autoradiography with the CB(1)R ligand [(3)H] CP 55,940 and CB(1)R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. All cases were obtained from the University of Sydney Tissue Resource Centre. Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB(1)R expression. There was a main effect of diagnosis on [(3)H] CP 55,940 binding quantified across all layers of the DLPFC (F(2,71) = 3.740, p = 0.029). Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB(1)R binding compared with the control group. When ANCOVA was employed, this effect was strengthened (F(2,67) = 6.048, p = 0.004) with paranoid SCZ patients differing significantly from the control (p = 0.004) and from the non-paranoid group (p = 0.016). In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. Our findings confirm the existence of a CB(1)R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.

  16. Mice expressing a “hyper-sensitive” form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption

    Science.gov (United States)

    Gonek, Maciej; Zee, Michael L.; Farnsworth, Jill C.; Amin, Randa A.; Andrews, Mary-Jeanette; Davis, Brian J.; Mackie, Ken; Morgan, Daniel J.

    2017-01-01

    We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a “hyper-sensitive” form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model. PMID:28426670

  17. Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

    Directory of Open Access Journals (Sweden)

    David J Marcus

    Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

  18. Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice.

    Science.gov (United States)

    Basavarajappa, Balapal S; Nagre, Nagaraja N; Xie, Shan; Subbanna, Shivakumar

    2014-07-01

    In rodents, many exogenous and endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonyl glycerol (2-AG), have been shown to play an important role in certain hippocampal memory processes. However, the mechanisms by which endogenous AEA regulate this processes are not well understood. Here the effects of AEA on long-term potentiation (LTP), hippocampal-dependent learning and memory tasks, pERK1/2, pCaMKIV, and pCREB signaling events in both cannabinoid receptor type 1 (CB1R) wild-type (WT) and knockout (KO) mice were assessed following administration of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH). Acute administration of URB597 enhanced AEA levels without affecting the levels of 2-AG or CB1R in the hippocampus and neocortex as compared to vehicle. In hippocampal slices, URB597 impaired LTP in CB1R WT but not in KO littermates. URB597 impaired object recognition, spontaneous alternation and spatial memory in the Y-maze test in CB1R WT mice but not in KO mice. Furthermore, URB597 enhanced ERK phosphorylation in WT without affecting total ERK levels in WT or KO mice. URB597 impaired CaMKIV and CREB phosphorylation in WT but not in KO mice. CB1R KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio as compared to WT littermates. Our results indicate that pharmacologically elevated AEA impair LTP, learning and memory and inhibit CaMKIV and CREB phosphorylation, via the activation of CB1Rs. Collectively, these findings also suggest that pharmacological elevation of AEA beyond normal concentrations is also detrimental for the underlying physiological responses. © 2014 Wiley Periodicals, Inc.

  19. Cannabinoid Receptors CB1 and CB2 Modulate the Electroretinographic Waves in Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Joseph Bouskila

    2016-01-01

    Full Text Available The expression patterns of the cannabinoid receptor type 1 (CB1R and the cannabinoid receptor type 2 (CB2R are well documented in rodents and primates. In vervet monkeys, CB1R is present in the retinal neurons (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells and CB2R is exclusively found in the retinal glia (Müller cells. However, the role of these cannabinoid receptors in normal primate retinal function remains elusive. Using full-field electroretinography in adult vervet monkeys, we recorded changes in neural activity following the blockade of CB1R and CB2R by the intravitreal administration of their antagonists (AM251 and AM630, resp. in photopic and scotopic conditions. Our results show that AM251 increases the photopic a-wave amplitude at high flash intensities, whereas AM630 increases the amplitude of both the photopic a- and b-waves. In scotopic conditions, both blockers increased the b-wave amplitude but did not change the a-wave amplitude. These findings suggest an important role of CB1R and CB2R in primate retinal function.

  20. Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.

    Science.gov (United States)

    Albayram, Onder; Alferink, Judith; Pitsch, Julika; Piyanova, Anastasia; Neitzert, Kim; Poppensieker, Karola; Mauer, Daniela; Michel, Kerstin; Legler, Anne; Becker, Albert; Monory, Krisztina; Lutz, Beat; Zimmer, Andreas; Bilkei-Gorzo, Andras

    2011-07-05

    Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.

  1. Het endocannabinoïdsysteem, overgewicht en de CB1-endocannabinoïdreceptorblokker rimonabant

    NARCIS (Netherlands)

    Boekholdt, S. M.; Jukema, J. W.; Peters, R. J. G.

    2007-01-01

    --Obesity is an important healthcare issue. --Recent research has led to insights into the role of the endocannabinoid system in the regulation of body weight. --Rimonabant is a CB1-endocannabinoid-receptor antagonist. --Four trials were published recently on the efficacy and safety of rimonabant in

  2. Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death

    International Nuclear Information System (INIS)

    Tomiyama, Ken-ichi; Funada, Masahiko

    2014-01-01

    The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB 1 receptor antagonist AM251, but not with the selective CB 2 receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB 1 receptor, but not by the CB 2 receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB 1 receptor, but not by the CB 2 receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB 1 receptors

  3. Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design.

    Science.gov (United States)

    Howe, George W; Beach, Steven R H; Brody, Gene H; Wyman, Peter A

    2015-01-01

    In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach.

  4. Translating genetic research into preventive intervention: The baseline target moderated mediator design

    Directory of Open Access Journals (Sweden)

    George W. Howe

    2016-01-01

    Full Text Available In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We end with a discussion of some of the advantages and limitations of this approach.

  5. Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use.

    Science.gov (United States)

    Taurisano, Paolo; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Romano, Raffaella; Porcelli, Annamaria; Masellis, Rita; Colizzi, Marco; Quarto, Tiziana; Torretta, Silvia; Di Giorgio, Annabella; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

    2016-08-01

    The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats.

    Science.gov (United States)

    Fang, Qin; Li, Fang-Qiong; Li, Yan-Qin; Xue, Yan-Xue; He, Ying-Ying; Liu, Jian-Feng; Lu, Lin; Wang, Ji-Shi

    2011-10-01

    Exposure to cues previously associated with drug intake leads to relapse by activating previously acquired memories. Based on previous findings, in which cannabinoid CB(1) receptors were found to be critically involved in specific aspects of learning and memory, we investigated the role of CB(1) receptors in nicotine reward memory using a rat conditioned place preference (CPP) model. In Experiment 1, rats were trained for CPP with alternating injections of nicotine (0.5mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To examine the effects of rimonabant on the reconsolidation of nicotine reward memory, rats were administered rimonabant (0, 0.3, and 3.0mg/kg, i.p.) immediately after reexposure to the drug-paired context. In Experiment 2, rats were trained for CPP similarly to Experiment 1. To examine the effects of rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3, and 3.0mg/kg, i.p.) was administered before the test of nicotine-induced CPP reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a reward memory, rats were trained for CPP with alternating injections of different doses of rimonabant (0, 0.3, and 3.0mg/kg) and saline. Rimonabant at a dose of 3.0mg/kg significantly disrupted the reconsolidation of nicotine memory and significantly blocked the reinstatement of nicotine-induced CPP. However, rimonabant itself did not produce CPP. These findings provide clear evidence that CB(1) receptors play a role in nicotine reward memory, suggesting that CB(1) receptor antagonists may be a potential target for managing nicotine addiction. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

    OpenAIRE

    Copley, Shelley D.; Crooks, Gwen P.

    1992-01-01

    4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed.

  8. Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

    Science.gov (United States)

    Copley, Shelley D.; Crooks, Gwen P.

    1992-01-01

    4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed. PMID:16348702

  9. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

    OpenAIRE

    Zlebnik, Natalie E.; Cheer, Joseph F.

    2016-01-01

    The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor t...

  10. Causal Mediation Analysis for the Cox Proportional Hazards Model with a Smooth Baseline Hazard Estimator.

    Science.gov (United States)

    Wang, Wei; Albert, Jeffrey M

    2017-08-01

    An important problem within the social, behavioral, and health sciences is how to partition an exposure effect (e.g. treatment or risk factor) among specific pathway effects and to quantify the importance of each pathway. Mediation analysis based on the potential outcomes framework is an important tool to address this problem and we consider the estimation of mediation effects for the proportional hazards model in this paper. We give precise definitions of the total effect, natural indirect effect, and natural direct effect in terms of the survival probability, hazard function, and restricted mean survival time within the standard two-stage mediation framework. To estimate the mediation effects on different scales, we propose a mediation formula approach in which simple parametric models (fractional polynomials or restricted cubic splines) are utilized to approximate the baseline log cumulative hazard function. Simulation study results demonstrate low bias of the mediation effect estimators and close-to-nominal coverage probability of the confidence intervals for a wide range of complex hazard shapes. We apply this method to the Jackson Heart Study data and conduct sensitivity analysis to assess the impact on the mediation effects inference when the no unmeasured mediator-outcome confounding assumption is violated.

  11. Endogenous vs Exogenous Allosteric Modulators in GPCRs: A dispute for shuttling CB1 among different membrane microenvironments

    Science.gov (United States)

    Stornaiuolo, Mariano; Bruno, Agostino; Botta, Lorenzo; Regina, Giuseppe La; Cosconati, Sandro; Silvestri, Romano; Marinelli, Luciana; Novellino, Ettore

    2015-10-01

    A Cannabinoid Receptor 1 (CB1) binding site for the selective allosteric modulator ORG27569 is here identified through an integrate approach of consensus pocket prediction, mutagenesis studies and Mass Spectrometry. This unprecedented ORG27569 pocket presents the structural features of a Cholesterol Consensus Motif, a cholesterol interacting region already found in other GPCRs. ORG27569 and cholesterol affects oppositely CB1 affinity for orthosteric ligands. Moreover, the rise in cholesterol intracellular level results in CB1 trafficking to the axonal region of neuronal cells, while, on the contrary, ORG27568 binding induces CB1 enrichment at the soma. This control of receptor migration among functionally different membrane regions of the cell further contributes to downstream signalling and adds a previously unknown mechanism underpinning CB1 modulation by ORG27569 , that goes beyond a mere control of receptor affinity for orthosteric ligands.

  12. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

    Science.gov (United States)

    Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

    2010-04-01

    Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

  13. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

    Science.gov (United States)

    Han, Jing; Kesner, Philip; Metna-Laurent, Mathilde; Duan, Tingting; Xu, Lin; Georges, Francois; Koehl, Muriel; Abrous, Djoher Nora; Mendizabal-Zubiaga, Juan; Grandes, Pedro; Liu, Qingsong; Bai, Guang; Wang, Wei; Xiong, Lize; Ren, Wei; Marsicano, Giovanni; Zhang, Xia

    2012-03-02

    Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Anandamide inhibits Theiler's virus induced VCAM-1 in brain endothelial cells and reduces leukocyte transmigration in a model of blood brain barrier by activation of CB1 receptors

    Directory of Open Access Journals (Sweden)

    Loría Frida

    2011-08-01

    Full Text Available Abstract Background VCAM-1 represents one of the most important adhesion molecule involved in the transmigration of blood leukocytes across the blood-brain barrier (BBB that is an essential step in the pathogenesis of MS. Several evidences have suggested the potential therapeutic value of cannabinoids (CBs in the treatment of MS and their experimental models. However, the effects of endocannabinoids on VCAM-1 regulation are poorly understood. In the present study we investigated the effects of anandamide (AEA in the regulation of VCAM-1 expression induced by Theiler's virus (TMEV infection of brain endothelial cells using in vitro and in vivo approaches. Methods i in vitro: VCAM-1 was measured by ELISA in supernatants of brain endothelial cells infected with TMEV and subjected to AEA and/or cannabinoid receptors antagonist treatment. To evaluate the functional effect of VCAM-1 modulation we developed a blood brain barrier model based on a system of astrocytes and brain endothelial cells co-culture. ii in vivo: CB1 receptor deficient mice (Cnr1-/- infected with TMEV were treated with the AEA uptake inhibitor UCM-707 for three days. VCAM-1 expression and microglial reactivity were evaluated by immunohistochemistry. Results Anandamide-induced inhibition of VCAM-1 expression in brain endothelial cell cultures was mediated by activation of CB1 receptors. The study of leukocyte transmigration confirmed the functional relevance of VCAM-1 inhibition by AEA. In vivo approaches also showed that the inhibition of AEA uptake reduced the expression of brain VCAM-1 in response to TMEV infection. Although a decreased expression of VCAM-1 by UCM-707 was observed in both, wild type and CB1 receptor deficient mice (Cnr1-/-, the magnitude of VCAM-1 inhibition was significantly higher in the wild type mice. Interestingly, Cnr1-/- mice showed enhanced microglial reactivity and VCAM-1 expression following TMEV infection, indicating that the lack of CB1 receptor

  15. Localization and function of the cannabinoid CB1 receptor in the anterolateral bed nucleus of the stria terminalis.

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    Nagore Puente

    Full Text Available BACKGROUND: The bed nucleus of the stria terminalis (BNST is involved in behaviors related to natural reward, drug addiction and stress. In spite of the emerging role of the endogenous cannabinoid (eCB system in these behaviors, little is known about the anatomy and function of this system in the anterolateral BNST (alBNST. The aim of this study was to provide a detailed morphological characterization of the localization of the cannabinoid 1 (CB1 receptor a necessary step toward a better understanding of the physiological roles of the eCB system in this region of the brain. METHODOLOGY/PRINCIPAL FINDINGS: We have combined anatomical approaches at the confocal and electron microscopy level to ex-vivo electrophysiological techniques. Here, we report that CB1 is localized on presynaptic membranes of about 55% of immunopositive synaptic terminals for the vesicular glutamate transporter 1 (vGluT1, which contain abundant spherical, clear synaptic vesicles and make asymmetrical synapses with alBNST neurons. About 64% of vGluT1 immunonegative synaptic terminals show CB1 immunolabeling. Furthermore, 30% and 35% of presynaptic boutons localize CB1 in alBNST of conditional mutant mice lacking CB1 mainly from GABAergic neurons (GABA-CB1-KO mice and mainly from cortical glutamatergic neurons (Glu-CB1-KO mice, respectively. Extracellular field recordings and whole cell patch clamp in the alBNST rat brain slice preparation revealed that activation of CB1 strongly inhibits excitatory and inhibitory synaptic transmission. CONCLUSIONS/SIGNIFICANCE: This study supports the anterolateral BNST as a potential neuronal substrate of the effects of cannabinoids on stress-related behaviors.

  16. Imidazopyridine CB2 agonists: optimization of CB2/CB1 selectivity and implications for in vivo analgesic efficacy.

    Science.gov (United States)

    Trotter, B Wesley; Nanda, Kausik K; Burgey, Christopher S; Potteiger, Craig M; Deng, James Z; Green, Ahren I; Hartnett, John C; Kett, Nathan R; Wu, Zhicai; Henze, Darrell A; Della Penna, Kimberly; Desai, Reshma; Leitl, Michael D; Lemaire, Wei; White, Rebecca B; Yeh, Suzie; Urban, Mark O; Kane, Stefanie A; Hartman, George D; Bilodeau, Mark T

    2011-04-15

    A new series of imidazopyridine CB2 agonists is described. Structural optimization improved CB2/CB1 selectivity in this series and conferred physical properties that facilitated high in vivo exposure, both centrally and peripherally. Administration of a highly selective CB2 agonist in a rat model of analgesia was ineffective despite substantial CNS exposure, while administration of a moderately selective CB2/CB1 agonist exhibited significant analgesic effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Ken Soderstrom

    2017-10-01

    Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

  18. Spatial distribution of cannabinoid receptor type 1 (CB1 in normal canine central and peripheral nervous system.

    Directory of Open Access Journals (Sweden)

    Jessica Freundt-Revilla

    Full Text Available The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2 and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

  19. Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

    Science.gov (United States)

    Landau, Sabine; Emsley, Richard; Dunn, Graham

    2018-06-01

    Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of

  20. Interactions of CB1 and mGlu5 receptor antagonists in food intake, anxiety and memory models in rats.

    Science.gov (United States)

    Varga, Balázs; Kassai, Ferenc; Gyertyán, István

    2012-12-01

    CB(1) receptor antagonists proved to be effective anti-obesity drugs, however, their depressive and anxiogenic effects became also evident. Finding solution to overcome these psychiatric side effects is still in focus of research. Based on the available clinical and preclinical results we hypothesized that the combination of CB(1) and mGlu(5) receptor antagonisms may result in a pharmacological intervention, where the anxiolytic mGlu(5) receptor inhibition may counteract the anxiogenic psychiatric side effects of CB(1) antagonism, while CB(1) antagonism may ameliorate the memory impairing effect of mGlu(5) receptor antagonism. Further, the two components will synergistically interact in blocking food-intake and reducing obesity. For testing the interaction of mGlu(5) and CB(1) receptor antagonism MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pridine; SIB-1757, 6-methyl-2-(phenylazo)-3-pyridinol)] (mGlu(5) antagonist) and rimonabant [(5-(4-Chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide)hydrochloride] (CB(1) antagonist) were used. All experiments were carried out in rats. Effects of the compounds on anxiety were tested in two foot shock induced ultrasonic vocalization paradigms, appetite suppression was assessed in the food intake test, while memory effects were tested in a context conditioned ultrasonic vocalization setup. MTEP abolished the anxiogenic effect of rimonabant, while there was an additive cooperation in suppressing appetite. However, rimonabant did not ameliorate the memory impairing effect of MTEP. By combination of CB(1) and mGluR5 antagonism, anxiety related side effects might be attenuated, appetite suppression maintained, nevertheless, the possible emergence of unwanted memory impairments can overshadow its therapeutic success. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

    Science.gov (United States)

    Zlebnik, Natalie E; Cheer, Joseph F

    2016-07-08

    The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ(9)-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.

  2. Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice.

    Science.gov (United States)

    Yu, Lu-lu; Wang, Xue-yi; Zhao, Mei; Liu, Yu; Li, Yan-qin; Li, Fang-qiong; Wang, Xiaoyi; Xue, Yan-xue; Lu, Lin

    2009-06-01

    Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory. The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP). Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration. Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation. Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

  3. Integrated cannabinoid CB1 receptor transmission within the amygdala-prefrontal cortical pathway modulates neuronal plasticity and emotional memory encoding.

    Science.gov (United States)

    Tan, Huibing; Lauzon, Nicole M; Bishop, Stephanie F; Bechard, Melanie A; Laviolette, Steven R

    2010-06-01

    The cannabinoid CB1 receptor system is functionally involved in the processing and encoding of emotionally salient sensory information, learning and memory. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). In addition, synaptic plasticity in the form of long-term potentiation (LTP) within the BLA > mPFC pathway is an established correlate of exposure to emotionally salient events. We performed a series of in vivo LTP studies by applying tetanic stimulation to the BLA combined with recordings of local field potentials within prelimbic cortical (PLC) region of the rat mPFC. Systemic pretreatment with AM-251 dose dependently blocked LTP along the BLA-PLC pathway and also the behavioral acquisition of conditioned fear memories. We next performed a series of microinfusion experiments wherein CB1 receptor transmission within the BLA > PLC circuit was pharmacologically blocked. Asymmetrical, interhemispheric blockade of CB1 receptor transmission along the BLA > PLC pathway prevented the acquisition of emotionally salient associative memory. Our results indicate that coordinated CB1 receptor transmission within the BLA > PLC pathway is critically involved in the encoding of emotional fear memories and modulates neural plasticity related to the encoding of emotionally salient associative learning.

  4. Mapping CB1 cannabinoid receptors with [3H]OMAR in the Flinders rodent model of depression

    DEFF Research Database (Denmark)

    Nahimi, A.; Gjedde, A.; Wong, D. F.

    2012-01-01

    not significantly different. Conclusions: Although changes in CB1 receptor expression have been demonstrated in human suicide victims with depression and in animal models of depression, the present maps of [3H]OMAR binding revealed no difference between FSL and FRL rats. We used a single concentration of [3H......Background: The endocannabinoid system regulates cognitive and emotional processes and pathology of this system is implicated in psychiatric disorders, including depression and schizophrenia. The precise role of the endocannabinoid system in psychiatric disorders remains unclear, but changes...... in expression of CB1 receptors and subsequent altered modulation of monoamines is suggested in depression (Esteban & Garcia-Sevilla, 2011). CB1 receptor agonists, such as WIN55,212-2 and CP55,940 regulate synthesis and release of monoamines and are suggested as a novel therapy in the treatment of depression...

  5. Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

    Directory of Open Access Journals (Sweden)

    Eleftheria Lakiotaki

    2015-01-01

    Full Text Available The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2, their endogenous ligands (endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43 and malignant (n=44 lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.. Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.. In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301. Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165, lymphatic (p=0.1989, and vascular invasion (p=0.0555, as well as in those with increased risk of recurrence rate (p=0.1165, at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

  6. Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum.

    Science.gov (United States)

    Moreno, Estefanía; Chiarlone, Anna; Medrano, Mireia; Puigdellívol, Mar; Bibic, Lucka; Howell, Lesley A; Resel, Eva; Puente, Nagore; Casarejos, María J; Perucho, Juan; Botta, Joaquín; Suelves, Nuria; Ciruela, Francisco; Ginés, Silvia; Galve-Roperh, Ismael; Casadó, Vicent; Grandes, Pedro; Lutz, Beat; Monory, Krisztina; Canela, Enric I; Lluís, Carmen; McCormick, Peter J; Guzmán, Manuel

    2018-04-01

    The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A 2A receptor (A 2A R) and cannabinoid CB 1 receptor (CB 1 R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A 2A R and CB 1 R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A 2A R-CB 1 R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically modified animal models, together with biochemical and pharmacological approaches, we provide a high-resolution expression map and a detailed functional characterization of A 2A R-CB 1 R heteromers in the dorsal striatum. Specifically, our data unveil that the A 2A R-CB 1 R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington's disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases.

  7. Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.

    Science.gov (United States)

    Ferreira, Jaderson V; Chaves, Gisele A; Marino, Bianca L B; Sousa, Kessia P A; Souza, Lucilene R; Brito, Maiara F B; Teixeira, Hueldem R C; da Silva, Carlos H T P; Santos, Cleydson B R; Hage-Melim, Lorane I S

    2017-08-22

    Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. By using computational tools, the aim of this study was to propose drug candidates for treating withdrawal syndrome based on the natural ligands of the cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n-pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive predictions as a human CB1 ligand and for facile synthetic accessibility. Therefore, ZINC1730183 is a favorable candidate scaffold for further research into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

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    Mohammad Reza Zarrindast

    2009-04-01

    Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

  9. CB 1/2 dual agonists with 3-carbamoyl 2-pyridone derivatives as antipruritics: reduction of CNS side effects by introducing polar functional groups.

    Science.gov (United States)

    Odan, Masahide; Ishizuka, Natsuki; Hiramatsu, Yoshiharu; Inagaki, Masanao; Hashizume, Hiroshi; Fujii, Yasuhiko; Mitsumori, Susumu; Morioka, Yasuhide; Soga, Masahiko; Deguchi, Masashi; Yasui, Kiyoshi; Arimura, Akinori

    2012-04-15

    Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

    Science.gov (United States)

    Darmani, N A

    2001-01-01

    We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1

  11. Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet-induced obese AKR/J mice.

    Directory of Open Access Journals (Sweden)

    Yuting Tang

    Full Text Available An increasing amount of evidence supports pleiotropic metabolic roles of the cannibinoid-1 receptor (CB1R in peripheral tissues such as adipose, liver, skeletal muscle and pancreas. To further understand the metabolic consequences of specific blockade of CB1R function in peripheral tissues, we performed a 10-week-study with an anti-sense oligonucleotide directed against the CB1R in diet-induced obese (DIO AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis-414930 (6.25, 12.5 and 25 mg/kg/week or control ASO Isis-141923 (25 mg/kg/week via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose-dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group (46.1±1.0 g vs veh, 51.2±0.9 g, p<0.05. Body fat mass was reduced in parallel with attenuated body weight gain. CB1R ASO treatment led to decreased fed glucose level (at week 8, 25 mg/kg/week group, 145±4 mg/dL vs veh, 195±10 mg/dL, p<0.05. Moreover, CB1R ASO treatment dose-dependently improved glucose excursion during an oral glucose tolerance test, whereas control ASO exerted no effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of the study, plasma insulin and leptin levels were significantly reduced by 25 mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led to improved insulin sensitivity and glucose homeostasis. The beneficial effects of CB1R ASO treatment strongly support the notion that selective inhibition of the peripheral CB1R, without blockade of central CB1R, may serve as an effective approach for treating type II diabetes, obesity and the metabolic syndrome.

  12. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

    Science.gov (United States)

    Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

    2015-12-01

    These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Candidate PET radioligands for cannabinoid CB1 receptors: [18F]AM5144 and related pyrazole compounds

    International Nuclear Information System (INIS)

    Li Zizhong; Gifford, Andrew; Liu Qian; Thotapally, Rajesh; Ding Yushin; Makriyannis, Alexandros; Gatley, S. John

    2005-01-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB 1 receptors that respond to Δ 9 -tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB 1 receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[ 18 F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[ 18 F]fluoroaniline. The labeled precursor was synthesized from 1-[ 18 F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/μmol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB 1 receptors, absolute uptake at 1 receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB 1 receptor that may require very lipophilic ligands

  14. NESS038C6, a novel selective CB1 antagonist agent with anti-obesity activity and improved molecular profile.

    Science.gov (United States)

    Mastinu, Andrea; Pira, Marilena; Pani, Luca; Pinna, Gérard Aimè; Lazzari, Paolo

    2012-10-01

    The present work aims to study the effects induced by a chronic treatment with a novel CB1 antagonist (NESS038C6) in C57BL/6N diet-induced obesity (DIO) mice. Mice treated with NESS038C6 and fed with a fat diet (NESS038C6 FD) were compared with the following three reference experimental groups: DIO mice fed with the same fat diet used for NESS038C6 and treated with vehicle or the reference CB1 antagonist/inverse agonist rimonabant, "VH FD" and "SR141716 FD", respectively; DIO mice treated with vehicle and switched to a normal diet (VH ND). NESS038C6 chronic treatment (30 mg/kg/day for 31 days) determined a significant reduction in DIO mice weight relative to that of VH FD. The entity of the effect was comparable to that detected in both SR141716 FD and VH ND groups. Moreover, if compared to VH FD, NESS038C6 FD evidenced: (i) improvement of cardiovascular risk factors; (ii) significant decrease in adipose tissue leptin expression; (iii) increase in mRNA expression of hypothalamic orexigenic peptides and a decrease of anorexigenic peptides; (iv) expression increase of metabolic enzymes and peroxisome proliferator-activated receptor-α in the liver; (v) normalization of monoaminergic transporters and neurotrophic expression in mesolimbic area. However, in contrast to the case of rimonabant, the novel CB1 antagonist improved the disrupted expression profile of genes linked to the hunger-satiety circuit, without altering monoaminergic transmission. In conclusion, the novel CB1 antagonist compound NESS038C6 may represent a useful candidate agent for the treatment of obesity and its metabolic complications, without or with reduced side effects relative to those instead observed with rimonabant. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography

    International Nuclear Information System (INIS)

    Terry, Garth E.; Hirvonen, Jussi; Liow, Jeih-San; Seneca, Nicholas; Morse, Cheryl L.; Pike, Victor W.; Innis, Robert B.; Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.; Halldin, Christer

    2010-01-01

    Cannabinoid subtype 1 (CB 1 ) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB 1 receptors with two PET radioligands: 11 C-MePPEP and 18 F-FMPEP-d 2 . Here we describe the biodistribution and dosimetry estimates for these two radioligands. Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with 11 C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with 18 F-FMPEP-d 2 . Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for 18 F-FMPEP-d 2 . The effective doses of 11 C-MePPEP and 18 F-FMPEP-d 2 are 4.6 and 19.7 μSv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of 11 C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from 18 F-FMPEP-d 2 showed both hepatobiliary and urinary excretion. 11 C-MePPEP and 18 F-FMPEP-d 2 yield an effective dose similar to other PET radioligands labeled with either 11 C or 18 F. The high uptake in brain confirms the utility of these two radioligands to image CB 1 receptors in brain, and both may also be useful to image CB 1 receptors in the periphery. (orig.)

  16. A cell population that strongly expresses the CB1 cannabinoid receptor in the ependyma of the rat spinal cord.

    Science.gov (United States)

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Sierra-Palomares, Yolanda; Molina-Holgado, Eduardo

    2013-01-01

    The cells surrounding the central canal of the spinal cord are a source of stem/precursor cells that may give rise to neurons, astrocytes, or oligodendrocytes. However, they are a heterogeneous population that remains poorly understood. Here we describe a subpopulation characterized by their strong expression of the CB(1) cannabinoid receptor, oval/round soma, apical nucleus, a variable number of cilia (0, 1, or 2), and the presence of a single short and occasionally ramified basal process. These cells are mainly located in the lateral and dorsal central canal throughout the spinal cord. These CB(1)(HIGH) cells are closely related to the basal lamina labyrinths or fractones derived from subependymal microglia. In addition, CB(1)(HIGH) cells express some stem/precursor cell markers, including vimentin, nestin, Sox2, Sox9, and GLAST, but not others such as CD15 or GFAP. In addition, this cell population does not proliferate in the intact adult spinal cord, although up to 50% of these cells express the proliferation marker Ki67 in newly born rats or after a spinal cord contusion. The present findings contribute to our understanding of the spinal cord central canal structure and reveal the targets for endocannabinoids inside this neurogenic niche. Copyright © 2012 Wiley Periodicals, Inc.

  17. Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2A G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

    Science.gov (United States)

    Navarro, Gemma; Carriba, Paulina; Gandí, Jorge; Ciruela, Francisco; Casadó, Vicent; Cortés, Antoni; Mallol, Josefa; Canela, Enric I.; Lluis, Carmen; Franco, Rafael

    2008-01-01

    Functional interactions in signaling occur between dopamine D2 (D2R) and cannabinoid CB1 (CB1R) receptors, between CB1R and adenosine A2A (A2AR) receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells. PMID:18956124

  18. Detection of Heteromers Formed by Cannabinoid CB1, Dopamine D2, and Adenosine A2A G-Protein-Coupled Receptors by Combining Bimolecular Fluorescence Complementation and Bioluminescence Energy Transfer

    Directory of Open Access Journals (Sweden)

    Gemma Navarro

    2008-01-01

    Full Text Available Functional interactions in signaling occur between dopamine D2 (D2R and cannabinoid CB1 (CB1R receptors, between CB1R and adenosine A2A (A2AR receptors, and between D2R and A2AR. Furthermore, direct molecular interactions have been reported for the pairs CB1R-D2R, A2AR-D2R, and CB1R-A2AR. Here a combination of bimolecular fluorescence complementation and bioluminescence energy transfer techniques was used to identify the occurrence of D2R-CB1R-A2AR hetero-oligomers in living cells.

  19. Mice Expressing a "Hyper-Sensitive" Form of the Cannabinoid Receptor 1 (CB1 Are Neither Obese Nor Diabetic.

    Directory of Open Access Journals (Sweden)

    David J Marcus

    Full Text Available Multiple lines of evidence implicate the endocannabinoid signaling system in the modulation of metabolic disease. Genetic or pharmacological inactivation of CB1 in rodents leads to reduced body weight, resistance to diet-induced obesity, decreased intake of highly palatable food, and increased energy expenditure. Cannabinoid agonists stimulate feeding in rodents and increased levels of endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that sustained endocannabinoid signaling can lead to obesity and diabetes was examined in this study using S426A/S430A mutant mice expressing a desensitization-resistant CB1 receptor. These mice display exaggerated and prolonged responses to acute administration of phytocannabinoids, synthetic cannabinoids, and endocannabinoids. As a consequence these mice represent a novel model for determining the effect of enhanced endocannabinoid signaling on metabolic disease. S426A/S430A mutants consumed equivalent amounts of both high fat (45% and low fat (10% chow control diet compared to wild-type littermate controls. S426A/S430A mutants and wild-type mice fed either high or low fat control diet displayed similar fasting blood glucose levels and normal glucose clearance following a 2 g/kg glucose challenge. Furthermore, S426A/S430A mutants and wild-type mice consumed similar amounts of chow following an overnight fast. While both THC and JZL195 significantly increased food intake two hours after injection, this increase was similar between the S426A/S430A mutant and wildtype control mice Our results indicate that S426A/S430A mutant mice expressing the desensitization-resistant form of CB1 do not exhibit differences in body weight, food intake, glucose homeostasis, or re-feeding following a fast.

  20. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

    Science.gov (United States)

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    2017-01-01

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

  1. CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A Novel Target for Marijuana.

    Science.gov (United States)

    Friend, Lindsey; Weed, Jared; Sandoval, Philip; Nufer, Teresa; Ostlund, Isaac; Edwards, Jeffrey G

    2017-11-08

    The VTA is necessary for reward behavior with dopamine cells critically involved in reward signaling. Dopamine cells in turn are innervated and regulated by neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile-adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1). LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates. Bath applied Δ 9 -tetrahydrocannabinol depressed GABA cell activity, therefore downstream dopamine cells will be disinhibited; and thus, this could potentially result in increased reward. Chronic injections of Δ 9 -tetrahydrocannabinol occluded LTD compared with vehicle injections; however, a single exposure was insufficient to do so. As synaptic modifications by drugs of abuse are often tied to addiction, these data suggest a possible mechanism for the addictive effects of Δ 9 -tetrahydrocannabinol in juvenile-adolescents, by potentially altering reward behavioral outcomes. SIGNIFICANCE STATEMENT The present study identifies a novel form of glutamatergic synaptic plasticity in VTA GABA neurons, a currently understudied cell type that is critical for the brain's reward circuit, and how Δ 9 -tetrahydrocannabinol occludes this plasticity. This study specifically addresses a potential unifying mechanism whereby marijuana could exert rewarding and addictive/withdrawal effects. Marijuana use and legalization are a pressing issue for many states in the United States. Although marijuana is the most commonly abused illicit drug, the implications of legalized, widespread, or continued usage are speculative. This study in juvenile-adolescent aged mice identifies a novel form of synaptic plasticity in VTA GABA cells, and the synaptic remodeling that can occur after Δ 9 -tetrahydrocannabinol use. Copyright © 2017 the

  2. Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

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    Dazzi, Laura; Talani, Giuseppe; Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

    2014-01-01

    Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this

  3. Involvement of the cannabinoid CB1 receptor in modulation of dopamine output in the prefrontal cortex associated with food restriction in rats.

    Directory of Open Access Journals (Sweden)

    Laura Dazzi

    Full Text Available Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1

  4. A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.

    Science.gov (United States)

    Fay, Jonathan F; Farrens, David L

    2012-09-28

    Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.

  5. Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.

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    Gabriela P Chaves-Kirsten

    Full Text Available The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson's Disease (PD. Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP, internal globus pallidus (IGP and substantia nigra pars reticulata (SNpr of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH, parvalbumin, calbindin and glutamic acid decarboxylase (GAD expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model.

  6. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

    Science.gov (United States)

    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  7. Localización de los Receptores Cannabinoides 1 (CB1) en Glándulas Salivales Submandibulares y Sublinguales de Ratones Durante el Desarrollo Postnatal

    OpenAIRE

    Hipkaeo, Wiphawi; Watanabe, Masahiko; Kondo, Hisatake

    2015-01-01

    In view of the fact that human marijuana users often show dry mouth symptom, the present study was attempted to examine the localization of CB1, which was originally identified in brain, in the submandibular and sublingual salivary glands of postnatal developing male mice by immunohistochemistry. In submandibular gland, CB1-immunoreactivity was positive in a majority of acinar cells in forms of granular appearance in their apical cytoplasm, while it was negative in the ducts at newborn stage....

  8. Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat.

    Science.gov (United States)

    Lange, M D; Daldrup, T; Remmers, F; Szkudlarek, H J; Lesting, J; Guggenhuber, S; Ruehle, S; Jüngling, K; Seidenbecher, T; Lutz, B; Pape, H C

    2017-10-01

    The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Here, we show that the endocannabinoid system acting in synaptic circuits of the extended amygdala can explain the fear response profile during exposure to unpredictable threat. Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. These results thereby identify the causal role of a defined protein in a distinct brain pathway for the temporal development of a sustained state of anxious apprehension during unpredictability of environmental influences, reminiscent of anxiety symptoms in humans.

  9. Platelet-rich plasma loaded in situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation.

    Science.gov (United States)

    Lee, Hye-Rim; Park, Kyung Min; Joung, Yoon Ki; Park, Ki Dong; Do, Sun Hee

    2012-11-01

    The efficacy of three-dimensional (3D) culture on the proliferation and maturation of chondrocytes seeded into a hydrogel scaffold was assessed. Three types of hydrogel were prepared for the 3D culture of primary isolated chondrocytes. Chondrocyte proliferation was assessed using a live/dead viability/cytotoxicity assay and semiquantitative RT-PCR after 3D culture in hydrogel. Cylindrical defects in the center of rat xyphoids were used for the implantation of platelet-rich plasma (PRP)/hydrogel composites. Rats were killed at day 7 postoperatively and evaluated histochemically and immunohistologically. Xyphoid chondrocytes proliferated well with time in hydrogels. In the PRP-containing hydrogels, xyphoid defects displayed early formation of chondroid matrix with massive peripheral infiltration of spindle cells. These results were consistent with Safranin-O staining for proteoglycans and immunohistochemistry for type II collagen. Gene expression analyses in vitro revealed aggrecan, type II collagen, and ChM-1 and CB1 upregulation by PRP/hydrogel. PRP/hydrogel provided a suitable environment for hyaline cartilaginous regeneration, leading to anti-inflammation by significant increase of CB1 and inhibiting vascular ingrowth via considerable upregulation of ChM-1. The results provide a valuable reference for the clinical application of hydrogel scaffolds for hyaline cartilage regeneration, as well as the use of autologous PRP to improve cellular proliferation and maturation of xyphoid repair. Copyright © 2012 Wiley Periodicals, Inc.

  10. Consequence of dopamine D2 receptor blockade on the hyperphagic effect induced by cannabinoid CB1 and CB2 receptors in layers.

    Science.gov (United States)

    Khodadadi, M; Zendehdel, M; Baghbanzadeh, A; Babapour, V

    2017-10-01

    1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed-intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor-induced hyperphagia in 3-h feed-deprived neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, l-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB 1 receptor agonist; 2 µg) and co-administration of l-DOPA (125 nmol) plus 2-AG (2 µg). Experiments 2-4 were similar to Experiment 1 except birds were injected with either 6-OHDA (6-hydroxydopamine as dopamine synthesis inhibitor; 150 nmol), SCH23390 (D1 receptor antagonist; 5 nmol) and AMI-193 (D2 receptor antagonist; 5 nmol) instead of l-DOPA, respectively. Additionally, Experiments 5-8 followed the previous ones using the same dose of l-DOPA, 6-OHDA and dopamine antagonists except that birds were injected with CB65 (CB2 receptor agonist; 5 µg) instead of 2-AG. Coadministrations were at the same dose for each experiment. Cumulative feed intakes were measured until 120 min after each injection. 3. ICV administration of 6-OHDA and AMI-193 significantly attenuated 2-AG-induced hyperphagia. Interestingly, the hyperphagic effect of CB65 was significantly attenuated by administration of l-DOPA, whereas the administration of 6-OHDA and AMI-193 together amplified the hyperphagic effect of CB65. 4. It was concluded that cannabinoid-induced feeding behaviour is probably modulated by dopamine receptors in neonatal layer-type chickens. It seems that their interaction may be mediated by the D2-dopamine receptor.

  11. Immunohistochemical characterisation and localisation of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and the effects of unilateral vestibular deafferentation.

    Science.gov (United States)

    Ashton, John C; Zheng, Yiwen; Liu, Ping; Darlington, Cynthia L; Smith, Paul F

    2004-09-24

    CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular pathways. We used immunohistochemistry to study the distribution of CB1 receptor protein in the VNC, and Western blotting to measure CB1 receptor expression in the VNC following unilateral vestibular deafferentation (UVD); the hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were also analysed for comparison. This study confirms a previous electrophysiological demonstration that CB1 receptors exist in significant densities in the VNC and are likely to contribute to the neurochemical control of the vestibular reflexes. Nonetheless, CB1 receptor expression did not change significantly in the VNC during vestibular compensation. In addition, despite some small but significant changes in CB1 receptor expression in the CA2/3 and the DG following UVD, in no case were these differences statistically significant in comparison to both control groups.

  12. Effect of cannabinoids CB1 receptors blockade on hemodynamic parameters and endothelial function at the immobilization stress in the experiment

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    S. V. Gavreliuk

    2017-12-01

    Full Text Available The aim of the study was to evaluate the response of hemodynamic parameters and changes in endothelial function in modeling of CB1 cannabinoid receptors blockade in chronic stress. Materials and мethods. The study was performed on four groups of hundred-day-old rats, which were examined by ultrasonic scanning during the ten-day period of the experiment. The first group consisted of intact animals; the second group – animals, which were exposed to immobilization stress; the third – animals which were given a solution of rimonabant hydrochloride at the rate of 10 mg×kg-1 of animal weight per day daily per os; the fourth group consisted of animals which daily received a solution of rimonabant hydrochloride at the rate of 10 mg×kg-1 of animal weight per day and were exposed to immobilization stress. The intraluminal vessel diameter, the intima-media complex thickness, endothelium-dependent and endothelium-independent dilation were quantified in the ultrasound examination. Quantitative characteristics of the blood flow were studied: peak systolic velocity, end diastolic velocity, resistive index and peak-systolic/end-diastolic ratio, and estimated mean blood flow velocity. Results. It has been found that the effect of chronic immobilization stress in 100-day-old male rats causes intima-media complex structure and thickness change, endothelial dysfunction and increase in the abdominal aorta intraluminal diameter. Hemodynamics changes are characterized by a decrease in the average blood flow velocity and an increase in the values of indices characterizing the vascular wall peripheral resistance. Prolonged blockade of cannabinoids CB1 receptors leads to endothelial dysfunction development, a decrease in the intraluminal diameter of the abdominal aorta and a decrease in the average blood flow velocity while vascular wall elastic properties maintaining. This affects the sensitivity of cardiovascular system to nitrogen oxide, which is manifested by

  13. Contrasting effects of lithium chloride and CB1 receptor blockade on enduring changes in the valuation of reward.

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    Giovanni eHernandez

    2011-09-01

    Full Text Available When an organism has been trained to respond for a reward, its learned behavior can be characterized as goal-directed or habitual based on whether or not it is susceptible to reward devaluation. Here, we evaluated whether instrumental responding for brain stimulation reward (BSR can devalued using a paradigm traditionally used for natural rewards. Rats were trained to lever press for BSR. Subsequently, BSR was paired with either lithium chloride (LiCl, 5 mg/kg, i.p, a pro-emetic, or AM251, a CB1 receptor antagonist (3 mg/kg, i.p.. Pairings of BSR with these two compounds or their respective vehicle were performed in a novel environment so that only unconditional effects of BSR were affected by the pharmacological manipulations. Subsequently, in a probe test, all rats were returned in the drug-free state to the boxes where they had received training instrumental responding was reassessed in the absence of BSR delivery. LiCl produced enduring decreases in the number of responses during the test session, whereas AM251 had no effect. These results show that instrumental responding for BSR is susceptible to devaluation, in accord with the proposal that this behavior is supported at least in part by associations between the response and the rewarding outcome. Furthermore, they suggest that the reward modulation observed in studies involving the use of CB1 receptor antagonists arises from changes in the organism’s motivation rather than due to drug-induced changes in the intrinsic value of reward.

  14. Contrasting Effects of Lithium Chloride and CB1 Receptor Blockade on Enduring Changes in the Valuation of Reward.

    Science.gov (United States)

    Hernandez, Giovanni; Bernstein, David; Schoenbaum, Geoffrey; Cheer, Joseph F

    2011-01-01

    When an organism responds for a reward, its learned behavior can be characterized as goal-directed or habitual based on whether or not it is susceptible to reward devaluation. Here, we evaluated whether instrumental responding for brain stimulation reward (BSR) can be devalued using a paradigm traditionally used for natural rewards. Rats were trained to lever press for BSR; afterward, BSR was paired with either lithium chloride (LiCl, 5 mg/kg, i.p.), a pro-emetic, or AM251, a CB1 receptor antagonist (3 mg/kg, i.p.) or the vehicle of these compounds. Pairings of BSR with these compounds and their vehicles were performed in a novel environment so that only unconditional effects of BSR would be affected by the pharmacological manipulations. Subsequently, in a probe test, all rats were returned in the drug-free state to the boxes where they had received training and instrumental responding was reassessed in the absence of BSR delivery. When compared to control, LiCl produced a significant decrease in the number of responses during the test session, whereas AM251 did not. These results show that instrumental responding for BSR is susceptible to devaluation, in accord with the proposal that this behavior is supported at least in part by associations between the response and the rewarding outcome. Further, they suggest that reward modulation observed in studies involving the use of CB1 receptor antagonists arises from changes in the organism's motivation rather than drug-induced changes in the intrinsic value of reward.

  15. Do baseline executive functions mediate prospective memory performance under a moderate dose of alcohol?

    Directory of Open Access Journals (Sweden)

    James Hugo Smith-Spark

    2016-08-01

    Full Text Available Prospective memory (PM is memory for delayed intentions. While deleterious effects of acute doses of alcohol on PM have been documented previously using between-subjects comparisons, the current study adopted a single blind placebo-controlled within-subjects design to explore whether the extent to which alcohol-related impairments in PM are mediated by executive functions (EFs. To this end, 52 male social drinkers with no history of substance-related treatment were tested using two parallel versions of a clinical measure of PM (the Memory for Intentions Test; Raskin, Buckheit & Sherrod, 2010, and a battery of EF measures. Testing took place on two occasions, with the order of administration of the alcohol and placebo conditions being fully counterbalanced. Overall, PM was worse under alcohol and participants showed deficits on five of the six subscales making up the clinical test. Hierarchical multiple regression analyses demonstrated that EFs did not predict PM performance decrements overall but did predict performance when time cues were presented and when verbal responses were required. Phonemic fluency was the strongest of the EF predictors; a greater capacity to gain controlled access to information in long-term memory predicted a smaller difference between placebo- and alcohol-related performance on both the time cue and verbal response scales. Prospective memory is crucial to compliance with, and response to, both therapy programmes and alcohol harm prevention campaigns. The results indicate that individual differences in cognitive function need to be taken into account when designing such interventions in order to increase their effectiveness.

  16. Do Baseline Executive Functions Mediate Prospective Memory Performance under a Moderate Dose of Alcohol?

    Science.gov (United States)

    Smith-Spark, James H; Moss, Antony C; Dyer, Kyle R

    2016-01-01

    Prospective memory (PM) is memory for delayed intentions. While deleterious effects of acute doses of alcohol on PM have been documented previously using between-subjects comparisons, the current study adopted a single blind placebo-controlled within-subjects design to explore whether the extent to which alcohol-related impairments in PM are mediated by executive functions (EFs). To this end, 52 male social drinkers with no history of substance-related treatment were tested using two parallel versions of a clinical measure of PM (the Memory for Intentions Test; Raskin et al., 2010), and a battery of EF measures. Testing took place on two occasions, with the order of administration of the alcohol and placebo conditions being fully counterbalanced. Overall, PM was worse under alcohol and participants showed deficits on five of the six subscales making up the clinical test. Hierarchical multiple regression analyses demonstrated that EFs did not predict PM performance decrements overall but did predict performance when time cues were presented and when verbal responses were required. Phonemic fluency was the strongest of the EF predictors; a greater capacity to gain controlled access to information in long-term memory predicted a smaller difference between placebo- and alcohol-related performance on both the time cue and verbal response scales. PM is crucial to compliance with, and response to, both therapy programs and alcohol harm prevention campaigns. The results indicate that individual differences in cognitive function need to be taken into account when designing such interventions in order to increase their effectiveness.

  17. Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines.

    Science.gov (United States)

    Chen, Edison; Lallai, Valeria; Sherafat, Yasmine; Grimes, Nickolas P; Pushkin, Anna N; Fowler, J P; Fowler, Christie D

    2018-02-28

    The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT (BAC) -Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT (IRES) -Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT (BAC) -Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT (BAC) -Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT (IRES) -Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT (IRES) -Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT (IRES) -Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT (IRES) -Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations. SIGNIFICANCE STATEMENT Altered

  18. Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

    International Nuclear Information System (INIS)

    Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

    2014-01-01

    Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

  19. Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks the Antinociceptive Effect of Local Injections of Anandamide in Mice

    Directory of Open Access Journals (Sweden)

    Diego C. Mascarenhas

    2017-10-01

    Full Text Available Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1 and Cannabinoid type 1 (CB1 receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG of mice exposed to the tail-flick test. Accordingly, male Swiss mice received intra-dPAG injection of AEA (CB1/TRPV1 agonist, capsaicin (TRPV1 agonist, WIN (CB1 agonist, AM251 (CB1 antagonist, and 6-iodonordihydrocapsaicin (6-IODO (TRPV1 selective antagonist and their nociceptive response was assessed with the tail-flick test. In order to assess AEA effects on nociception specifically at vanilloid or cannabinoid (CB substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251 or 6-IODO followed by local AEA injections and were subjected to the same test. While intra-dPAG AEA did not change acute pain, local injections of capsaicin or WIN induced a marked TRPV1- and CB1-dependent antinociceptive effect, respectively. Regarding the role of AEA specifically at CB/vanilloid substrates, while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear AEA-induced antinociception. It seems that the exogenous AEA-induced antinociception is unmasked when it selectively binds to vanilloid substrates, which might be useful to address acute pain in basic and perhaps clinical trials.

  20. Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2007-07-01

    Full Text Available Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation.The cannabinoid receptor type 1 (CB1 and cannabinoid receptor type 2 (CB2 are members of the G-protein coupled receptor (GPCR family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Delta(9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists.This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights into cannabinoid system involvement in ES cell

  1. Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.

    Science.gov (United States)

    Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A

    2010-11-01

    An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

  2. Why some people discount more than others: Baseline activation in the dorsal PFC mediates the link between COMT genotype and impatient choice

    Directory of Open Access Journals (Sweden)

    Lorena R. R. Gianotti

    2012-05-01

    Full Text Available Individuals differ widely in how steeply they discount future rewards. The sources of these stable individual differences in delay discounting (DD are largely unknown. One candidate is the COMT Val158Met polymorphism, known to modulate prefrontal dopamine levels and affect DD. To identify possible neural mechanisms by which this polymorphism may contribute to stable individual DD differences, we measured 73 participants’ neural baseline activation using resting electroencephalogram (EEG. Such neural baseline activation measures are highly heritable and stable over time, thus an ideal endophenotype candidate to explain how genes may influence behavior via individual differences in neural function. After EEG-recording, participants made a series of incentive-compatible intertemporal choices to determine the steepness of their DD. We found that COMT significantly affected DD and that this effect was mediated by baseline activation level in the left dorsal prefrontal cortex (DPFC: (i COMT had a significant effect on DD such that the number of Val alleles was positively correlated with steeper DD (higher numbers of Val alleles means greater COMT activity and thus lower dopamine levels. (ii A whole-brain search identified a cluster in left DPFC where baseline activation was correlated with DD; lower activation was associated with steeper DD. (iii COMT had a significant effect on the baseline activation level in this left DPFC cluster such that a higher number of Val alleles was associated with lower baseline activation. (iv The effect of COMT on DD was explained by the mediating effect of neural baseline activation in the left DPFC cluster. Our study thus establishes baseline activation level in left DPFC as salient neural signature in the form of an endophenotype that mediates the link between COMT and DD.

  3. Microbial Culturomics Application for Global Health: Noncontiguous Finished Genome Sequence and Description of Pseudomonas massiliensis Strain CB-1T sp. nov. in Brazil.

    Science.gov (United States)

    Bardet, Lucie; Cimmino, Teresa; Buffet, Clémence; Michelle, Caroline; Rathored, Jaishriram; Tandina, Fatalmoudou; Lagier, Jean-Christophe; Khelaifia, Saber; Abrahão, Jônatas; Raoult, Didier; Rolain, Jean-Marc

    2018-02-01

    Culturomics is a new postgenomics field that explores the microbial diversity of the human gut coupled with taxono-genomic strategy. Culturomics, and the microbiome science more generally, are anticipated to transform global health diagnostics and inform the ways in which gut microbial diversity contributes to human health and disease, and by extension, to personalized medicine. Using culturomics, we report in this study the description of strain CB1 T ( = CSUR P1334 = DSM 29075), a new species isolated from a stool specimen from a 37-year-old Brazilian woman. This description includes phenotypic characteristics and complete genome sequence and annotation. Strain CB1 T is a gram-negative aerobic and motile bacillus, exhibits neither catalase nor oxidase activities, and presents a 98.3% 16S rRNA sequence similarity with Pseudomonas putida. The 4,723,534 bp long genome contains 4239 protein-coding genes and 74 RNA genes, including 15 rRNA genes (5 16S rRNA, 4 23S rRNA, and 6 5S rRNA) and 59 tRNA genes. Strain CB1 T was named Pseudomonas massiliensis sp. nov. and classified into the family Pseudomonadaceae. This study demonstrates the usefulness of microbial culturomics in exploration of human microbiota in diverse geographies and offers new promise for incorporating new omics technologies for innovation in diagnostic medicine and global health.

  4. Involvement of Gaba and Cannabinoid Receptors in Central Food Intake Regulation in Neonatal Layer Chicks: Role of CB1 and Gabaa Receptors

    Directory of Open Access Journals (Sweden)

    M Zendehdel

    Full Text Available ABSTRACT Feeding behavior is regulated via a complex network which interacts via diverse signals from central and peripheral tissues. Endocannabinoids modulate release of GABA in a variety of regions of the central nervous system. Endocannabinoids and GABAergic system have an important role in the central regulation of appetite. Thus, the present study examines the possible interaction of central canabinoidergic and GABAergic systems on food intake in 3-h food-deprived (FD3 neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV injection of 2-AG (2-Arachidonoylglycerol, selective CB1 receptors agonist, 2µg significantly increased food intake and this effect of 2-AG was attenuated by Picrotoxin (GABAA antagonist, 0.5µg (P0.05. Also, hyperphagic effect of CB65 (CB2 receptors agonist, 1.25µg was not affected by Picrotoxin or CGP54626 (p>0.05. Moreover, the food intake of chicks was significantly increased by ICV injection of GABAA agonist (Gaboxadol, 0.2 µg and SR141716A (CB1 receptors antagonist, 6.25µg significantly decreased Gaboxadol-induced hyperphagia (P0.05. These data showed there might be an interaction between central cannabinoidergic and GABAergic systems via CB1 and GABAA receptors in control of food intake in neonatal layer chicks.

  5. Targeting the Endocannabinoid/CB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiaolie He

    2017-08-01

    Full Text Available Background/Aims: This study investigated the underlying mechanisms of the antidepressant effects of curcumin and dexanabinol-loaded solid lipid nanoparticles in corticosterone-induced cell and mice depression models. Methods: Curcumin and dexanabinol-loaded solid lipid nanoparticles (Cur/SLNs-HU-211 were synthesized via an emulsifcation and low-temperature solidification method. Antidepressant activities of nanoparticles in a corticosterone-induced major depression model were investigated by MTT assay, cellular uptake by flow cytometry, behaviour by Forced Swimming Test and rotarod test, neurotransmitters by High Performance Liquid Chromatography, Western blotting, qPCR and immunofluorescence. Results: Treatment with Cur/SLNs-HU-211 induced greater dopamine (DA/5-hydroxytryptamine (5-HT release with reduced corticosterone-induced apoptotic cell death in PC12 cells. Additionally, in vivo Cur/SLNs-HU-211 significantly induced recovery from depressive behaviour with increased DA/5-HT levels, CB1 mRNA levels and CB1, p-MEK1 and p-ERK1/2 protein expression levels in the hippocampus and striatum. Cur/SLNs-HU-211 improved CB1 expression and inspired the proliferation of astrocytes in the hippocampus and striatum, exerted neuroprotective effects by preventing corticosterone -induced BDNF/NeuN expression reduction. Conclusion: Our study implies that Cur/SLNs-HU-211 may be a useful approach for treatment of major depression.

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

    OpenAIRE

    Serpa, Andr?; Correia, Sara; Ribeiro, Joaquim A.; Sebasti?o, Ana M.; Cascalheira, Jos? F.

    2015-01-01

    Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3?30??M) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6 ? 2.7??M and an E max? of 31% ? 2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10?150?nM), an EC50 of 35 ? 19?nM, an...

  7. Maternal deprivation and adolescent cannabinoid exposure impact hippocampal astrocytes, CB1 receptors and brain-derived neurotrophic factor in a sexually dimorphic fashion.

    Science.gov (United States)

    López-Gallardo, M; López-Rodríguez, A B; Llorente-Berzal, Á; Rotllant, D; Mackie, K; Armario, A; Nadal, R; Viveros, M-P

    2012-03-01

    We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9-10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/kg, PND 28-42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug "per se" induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. MATERNAL DEPRIVATION AND ADOLESCENT CANNABINOID EXPOSURE IMPACT HIPPOCAMPAL ASTROCYTES, CB1 RECEPTORS AND BRAIN-DERIVED NEUROTROPHIC FACTOR IN A SEXUALLY DIMORPHIC FASHION

    Science.gov (United States)

    LÓPEZ-GALLARDO, M.; LÓPEZ-RODRÍGUEZ, A. B.; LLORENTE-BERZAL, Á.; ROTLLANT, D.; MACKIE, K.; ARMARIO, A.; NADAL, R.; VIVEROS, M.-P.

    2013-01-01

    We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9–10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/kg, PND 28–42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug “per se” induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments. PMID:22001306

  9. Modulación del tono vascular por la sobre-expresión de receptores a canabinoides CB1 y CB2 en arterioesclerosis inducida en ratas

    OpenAIRE

    Espinoza P., María Rosa

    2013-01-01

    La arteriosclerosis, es un proceso degenerativo responsable de la mayor parte de las enfermedades cardiovasculares, es una enfermedad compleja que se produce a partir de múltiples factores de riesgo. Se ha observado que los compuestos derivados de la planta cannabis sativa provocan efectos vasorelajantes por medio de receptores específicos CB1 y CB2. ACPA y JWH 133 son potentes agonistas a estos receptores, se desconoce el papel que desempeñan en la arteriosclerosis provocando una relajación ...

  10. Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda P; Werge, Thomas

    2011-01-01

    81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.......0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated...... for oral dyskinesia or dystonia. SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A....

  11. Enhanced novelty-induced corticosterone spike and upregulated serotonin 5-HT1A and cannabinoid CB1 receptors in adolescent BTBR mice.

    Science.gov (United States)

    Gould, Georgianna G; Burke, Teresa F; Osorio, Miguel D; Smolik, Corey M; Zhang, Wynne Q; Onaivi, Emmanuel S; Gu, Ting-Ting; DeSilva, Mauris N; Hensler, Julie G

    2014-01-01

    Hypothalamic pituitary adrenal (HPA) axis responses to change and social challenges during adolescence can influence mental health and behavior into adulthood. To examine how HPA tone in adolescence may contribute to psychopathology, we challenged male adolescent (5 weeks) and adult (16 weeks) BTBR T(+)tf/J (BTBR) and 129S1/SvImJ (129S) mice with novelty in sociability tests. In prior studies these strains had exaggerated or altered HPA stress responses and low sociability relative to C57BL/6J mice in adulthood. In adolescence these strains already exhibited similar or worse sociability deficits than adults or age-matched C57 mice. Yet BTBR adolescents were less hyperactive and buried fewer marbles than adults. Novelty-induced corticosterone (CORT) spikes in adolescent BTBR were double adult levels, and higher than 129S or C57 mice at either age. Due to their established role in HPA feedback, we hypothesized that hippocampal Gαi/o-coupled serotonin 5-HT1A and cannabinoid CB1 receptor function might be upregulated in BTBR mice. Adolescent BTBR mice had higher hippocampal 5-HT1A density as measured by [(3)H] 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) binding than C57 mice, and adult BTBR 8-OH-DPAT-stimulated GTPγS binding was higher than in either C57 or 129S mice in this region. Further, BTBR hippocampal CB1 density measured by [(3)H]CP55,940 binding was 15-20% higher than in C57. CP55,940-stimulated GTPγS binding in adult BTBR dentate gyrus was 30% higher then 129S (p<0.05), but was not a product of greater neuronal or cell density defined by NeuN and DAPI staining. Hence hyperactive HPA responsiveness during adolescence may underlie 5-HT1A and CB1 receptor up-regulation and behavioral phenotype of BTBR mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Cannabinoid CB1 /CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

    Science.gov (United States)

    Scherma, Maria; Satta, Valentina; Collu, Roberto; Boi, Maria Francesca; Usai, Paolo; Fratta, Walter; Fadda, Paola

    2017-08-01

    Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients. The activity-based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic-like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle. Our data show that subchronic treatment with both the natural CB 1 /CB 2 receptor agonist Δ 9 -tetrahydrocannabinol and the synthetic CB 1 /CB 2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone. Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance. © 2017 The British Pharmacological Society.

  13. Cannabinoid Regulation of Brain Reward Processing with an Emphasis on the Role of CB1 Receptors: A Step Back into the Future.

    Science.gov (United States)

    Panagis, George; Mackey, Brian; Vlachou, Styliani

    2014-01-01

    Over the last decades, the endocannabinoid system has been implicated in a large variety of functions, including a crucial modulation of brain-reward circuits and the regulation of motivational processes. Importantly, behavioral studies have shown that cannabinoid compounds activate brain reward mechanisms and circuits in a similar manner to other drugs of abuse, such as nicotine, alcohol, cocaine, and heroin, although the conditions under which cannabinoids exert their rewarding effects may be more limited. Furthermore, there is evidence on the involvement of the endocannabinoid system in the regulation of cue- and drug-induced relapsing phenomena in animal models. The aim of this review is to briefly present the available data obtained using diverse behavioral experimental approaches in experimental animals, namely, the intracranial self-stimulation paradigm, the self-administration procedure, the conditioned place preference procedure, and the reinstatement of drug-seeking behavior procedure, to provide a comprehensive picture of the current status of what is known about the endocannabinoid system mechanisms that underlie modification of brain-reward processes. Emphasis is placed on the effects of cannabinoid 1 (CB1) receptor agonists, antagonists, and endocannabinoid modulators. Further, the role of CB1 receptors in reward processes is investigated through presentation of respective genetic ablation studies in mice. The vast majority of studies in the existing literature suggest that the endocannabinoid system plays a major role in modulating motivation and reward processes. However, much remains to be done before we fully understand these interactions. Further research in the future will shed more light on these processes and, thus, could lead to the development of potential pharmacotherapies designed to treat reward-dysfunction-related disorders.

  14. Cannabinoid regulation of brain reward processing with an emphasis on the role of CB1 receptors: a step back into the future

    Directory of Open Access Journals (Sweden)

    George ePanagis

    2014-07-01

    Full Text Available Over the last decades the endocannabinoid system has been implicated in a large variety of functions, including a crucial modulation of brain reward circuits and the regulation of motivational processes. Importantly, behavioural studies have shown that cannabinoid compounds activate brain reward mechanisms and circuits in a similar manner to other drugs of abuse, such as nicotine, alcohol, cocaine and heroin, although the conditions under which cannabinoids exert their rewarding effects may be more limited. Furthermore, there is evidence on the involvement of the endocannabinoid system in the regulation of cue- and drug-induced relapsing phenomena in animal models. The aim of this review is to briefly present the available data obtained using diverse behavioural experimental approaches in experimental animals, namely, the intracranial self-stimulation paradigm, the self-administration procedure, the conditioned place preference procedure and the reinstatement of drug-seeking behaviour procedure, to provide a comprehensive picture of the current status of what is known about the endocannabinoid system mechanisms that underlie modification of brain reward processes. Emphasis is placed on the effects of cannabinoid 1 (CB1 receptor agonists, antagonists and endocannabinoid modulators. Further, the role of CB1 receptors in reward processes is investigated through presentation of respective genetic ablation studies in mice. The vast majority of studies in the existing literature suggests that the endocannabinoid system plays a major role in modulating motivation and reward processes. However, much remains to be done before we fully understand these interactions. Further research in the future will shed more light on these processes and, thus, could lead to the development of potential pharmacotherapies designed to treat reward-dysfunction related disorders.

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

    Directory of Open Access Journals (Sweden)

    Petra eAmchova

    2014-03-01

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

  16. Reinforcing and neurochemical effects of cannabinoid CB1 receptor agonists, but not cocaine, are altered by an adenosine A2A receptor antagonist.

    Science.gov (United States)

    Justinová, Zuzana; Ferré, Sergi; Redhi, Godfrey H; Mascia, Paola; Stroik, Jessica; Quarta, Davide; Yasar, Sevil; Müller, Christa E; Franco, Rafael; Goldberg, Steven R

    2011-07-01

    Several recent studies suggest functional and molecular interactions between striatal adenosine A(2A) and cannabinoid CB(1) receptors. Here, we demonstrate that A(2A) receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A(2A) receptor blockade on the reinforcing effects of delta-9-tetrahydrocannabinol (THC) and the endogenous CB(1) receptor ligand anandamide under a fixed-ratio schedule of intravenous drug injection in squirrel monkeys. A low dose of the selective adenosine A(2A) receptor antagonist MSX-3 (1 mg/kg) caused downward shifts of THC and anandamide dose-response curves. In contrast, a higher dose of MSX-3 (3 mg/kg) shifted THC and anandamide dose-response curves to the left. MSX-3 did not modify cocaine or food pellet self-administration. Also, MSX-3 neither promoted reinstatement of extinguished drug-seeking behavior nor altered reinstatement of drug-seeking behavior by non-contingent priming injections of THC. Finally, using in vivo microdialysis in freely-moving rats, a behaviorally active dose of MSX-3 significantly counteracted THC-induced, but not cocaine-induced, increases in extracellular dopamine levels in the nucleus accumbens shell. The significant and selective results obtained with the lower dose of MSX-3 suggest that adenosine A(2A) antagonists acting preferentially at presynaptic A(2A) receptors might selectively reduce reinforcing effects of cannabinoids that lead to their abuse. However, the appearance of potentiating rather than suppressing effects on cannabinoid reinforcement at the higher dose of MSX-3 would likely preclude the use of such a compound as a medication for cannabis abuse. Adenosine A(2A) antagonists with more selectivity for presynaptic versus postsynaptic receptors could be potential medications for treatment of cannabis abuse. Addiction Biology © 2010 Society for the Study of Addiction. No claim to original US government works.

  17. Prevention of drug priming- and cue-induced reinstatement of MDMA-seeking behaviors by the CB1 cannabinoid receptor antagonist AM251.

    Science.gov (United States)

    Nawata, Yoko; Kitaichi, Kiyoyuki; Yamamoto, Tsuneyuki

    2016-03-01

    3,4-Methylenedioxymethamphetamine (MDMA), a methamphetamine (METH) derivative, exhibits METH-like actions at monoamine transporters and positive reinforcing effects in rodents and primates. The purposes of the present study were to determine whether cross-reinstatement would be observed between MDMA and METH and if the cannabinoid receptor, a receptor known to play critical roles in the brain reward system, could modulate MDMA craving. Rats were trained to press a lever for intravenous MDMA (0.3mg/infusion) or METH (0.02mg/infusion) infusions under a fixed ratio 1 schedule paired with drug-associated cues (light and tone). Following drug self-administration acquisition training, rats underwent extinction training (an infusion of saline). Reinstatement tests were performed once the extinction criteria were achieved. In MDMA-trained rats, the MDMA-priming injection (3.2mg/kg, i.p.) or re-exposure to MDMA-associated cues reinstated MDMA-seeking behavior. Additionally, a priming injection of METH (1.0mg/kg, i.p.) also reinstated MDMA-seeking behavior. In contrast, none of the MDMA doses reinstated METH-seeking behavior in the METH-trained rats. The CB1 cannabinoid receptor antagonist AM251 markedly attenuated the MDMA-seeking behaviors induced by MDMA-priming injection or re-exposure to MDMA-associated cues in a dose-dependent manner. These findings show that MDMA has obvious addictive potential for reinstating drug-seeking behavior and that METH can be an effective stimulus for reinstating MDMA-seeking behaviors. Furthermore, based on the attenuating effect of AM251 in the reinstatement of MDMA-seeking behaviors, drugs that suppress CB1 receptors may be used in treatment of MDMA dependence. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABAB and cannabinoid CB1 receptors.

    Science.gov (United States)

    Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico

    2017-09-01

    COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABA B receptor. This study evaluated whether COR659 shared with previously tested GABA B PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABA B PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABA B receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB 1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABA B receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB 1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.

  19. The CB1 Neutral Antagonist Tetrahydrocannabivarin Reduces Default Mode Network and Increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.

    Science.gov (United States)

    Rzepa, Ewelina; Tudge, Luke; McCabe, Ciara

    2015-09-10

    The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  20. Endocannabinoid CB1 Receptor Mediated Rises in Ca2+ and Depolarization-Induced Suppression of Inhibition within the Laterodorsal Tegmental Nucleus

    DEFF Research Database (Denmark)

    Soni, Neeraj; Kohlmeier, Kristi Anne

    2016-01-01

    -sensitive, inhibitory postsynaptic currents (IPSCs), which was an action sensitive to presence of a Ca(2+) chelator. Finally, actions of DHPG, a mGlu1R agonist, on IPSC activity were examined and found to result in an AM251- and BAPTA-sensitive inhibition of both the frequency and amplitude of sIPSCs. Taken...

  1. Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated bu CB1 en CB2 receptor coupled pathways

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Korthout, H.A.A.J.; Meeteren-Kreikamp, van A.P.; Ehlert, K.A.; Wang, M.; Greef, de J.; Rodenburg, R.J.T.; Witkamp, R.F.

    2006-01-01

    There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of ¿9-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa

  2. Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways.

    NARCIS (Netherlands)

    Verhoeckx, K.C.; Korthout, H.A.; Meeteren-Kreikamp, A.P. van; Ehlert, K.A.; Wang, M.; Greef, J. van der; Rodenburg, R.J.T.; Witkamp, R.F.

    2006-01-01

    There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa

  3. Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Korthout, H.A.A.J.; Meeteren-Kreikamp, A.P. van; Ehlert, K.A.; Wang, M.; Greef, J. van der; Rodenburg, R.J.T.; Witkamp, R.F.

    2006-01-01

    There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Δ9-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa

  4. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

    Science.gov (United States)

    De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

    2016-06-01

    In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Jelsing, Jacob; van de Wall, Esther H E M

    2009-01-01

    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R...... blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac...... system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia....

  6. Polymorphisms of the dopamine D4 receptor gene (DRD4 VNTR) and cannabinoid CB1 receptor gene (CNR1) are not strongly related to cue-reactivity after alcohol exposure

    NARCIS (Netherlands)

    Wildenberg, E. van den; Janssen, R.G.J.H.; Hutchison, K.E.; Breukelen, G.J.P. van; Wiers, R.W.H.J.

    2007-01-01

    Polymorphisms in the D4 dopamine receptor gene (DRD4) and the CB1 cannabinoid receptor gene (CNR1) have been associated with a differential response to alcohol after consumption. The goal of the present study was to investigate whether heavy drinkers with these polymorphisms would respond with

  7. Shear rate normalization is not essential for removing the dependency of flow-mediated dilation on baseline artery diameter: past research revisited

    International Nuclear Information System (INIS)

    Atkinson, Greg

    2014-01-01

    A ratio index (FMD%) is used ubiquitously to scale (by simple division) brachial artery flow-mediated dilation (D diff ) in direct proportion to baseline diameter (D base ). It is now known that D diff is inversely proportional to D base rendering FMD% wholly inappropriate. Consequently, FMD% is still substantially dependent on D base . Although this problem is grounded in statistics, normalization of FMD% for the change in arterial shear rate (ΔSR) has been proposed to remove this D base -dependency. It was hypothesized that, if the flow-mediated response is scaled properly to D base in the first place, shear rate normalization would not be needed to remove D base -dependency. Dedicated software (Digitizelt) was employed to extract the data from a seminal study on FMD% normalization. The underlying allometric relationship between D base and peak diameter (D peak ) was described. The re-analyses revealed that the absolute change in arterial diameter was strongly inversely proportional to D base (r= − 0.7, P < 0.0005). The allometric exponent for the D base –D peak relationship was 0.82 (95% CI: 0.78–0.86) rather than the value of 1 needed for appropriate use of FMD%. The allometric approach completely eliminated the originally reported dependency on D base without any need for ΔSR normalization (r=0.0, P=0.96). The correlation between ΔSR and FMD% reduced from 0.69 to 0.37, when adjusted for D base . In conclusion, this new re-analysis of data from an influential study demonstrates that the FMD%–D base correlation is caused by the inappropriate size-scaling properties of FMD% itself. Removal of D base -dependency via FMD%/ΔSR normalization is not essential at all if allometric scaling is applied to isolate the flow-mediated response in the first place. Consequently, the influence of ΔSR on this properly scaled response can also be isolated and quantified accurately without the confounding influence of D base . (paper)

  8. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

    Science.gov (United States)

    Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

    2013-03-19

    Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

  9. Baseline rationing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    The standard problem of adjudicating conflicting claims describes a situation in which a given amount of a divisible good has to be allocated among agents who hold claims against it exceeding the available amount. This paper considers more general rationing problems in which, in addition to claims...... to international protocols for the reduction of greenhouse emissions, or water distribution in drought periods. We define a family of allocation methods for such general rationing problems - called baseline rationing rules - and provide an axiomatic characterization for it. Any baseline rationing rule within...... the family is associated with a standard rule and we show that if the latter obeys some properties reflecting principles of impartiality, priority and solidarity, the former obeys them too....

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

    Directory of Open Access Journals (Sweden)

    Miñarro José

    2010-03-01

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

  11. Chronic restraint stress impairs endocannabinoid mediated suppression of GABAergic signaling in the hippocampus of adult male rats.

    Science.gov (United States)

    Hu, Wen; Zhang, Mingyue; Czéh, Boldizsár; Zhang, Weiqi; Flügge, Gabriele

    2011-07-15

    Chronic stress, a risk factor for the development of psychiatric disorders, is known to induce alterations in neuronal networks in many brain areas. Previous studies have shown that chronic stress changes the expression of the cannabinoid receptor 1 (CB1) in the brains of adult rats, but neurophysiological consequences of these changes remained unclear. Here we demonstrate that chronic restraint stress causes a dysfunction in CB1 mediated modulation of GABAergic transmission in the hippocampus. Using an established protocol, adult male Sprague Dawley rats were daily restrained for 21 days and whole-cell voltage clamp was performed at CA1 pyramidal neurons. When recording carbachol-evoked inhibitory postsynaptic currents (IPSCs) which presumably originate from CB1 expressing cholecystokinin (CCK) interneurons, we found that depolarization-induced suppression of inhibition (DSI) was impaired by the stress. DSI is a form of short-term plasticity at GABAergic synapses that is known to be CB1 mediated and has been suggested to be involved in hippocampal information encoding. Chronic stress attenuated the depolarization-induced suppression of the frequency of carbachol-evoked IPSCs. Incubation with a CB1 receptor antagonist prevented this DSI effect in control but not in chronically stressed animals. The stress-induced impairment of CB1-mediated short-term plasticity at GABAergic synapses may underlie cognitive deficits which are commonly observed in animal models of stress as well as in patients with stress-related psychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  13. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

  14. Feeding induced by cannabinoids is mediated independently of the melanocortin system.

    Directory of Open Access Journals (Sweden)

    Puspha Sinnayah

    2008-05-01

    Full Text Available Cannabinoids, the active components of marijuana, stimulate appetite, and cannabinoid receptor-1 (CB1-R antagonists suppress appetite and promote weight loss. Little is known about how CB1-R antagonists affect the central neurocircuitry, specifically the melanocortin system that regulates energy balance.Here, we show that peripherally administered CB1-R antagonist (AM251 or agonist equally suppressed or stimulated feeding respectively in A(y , which lack a functional melanocortin system, and wildtype mice, demonstrating that cannabinoid effects on feeding do not require melanocortin circuitry. CB1-R antagonist or agonist administered into the ventral tegmental area (VTA equally suppressed or stimulated feeding respectively, in both genotypes. In addition, peripheral and central cannabinoid administration similarly induced c-Fos activation in brain sites suggesting mediation via motivational dopaminergic circuitry. Amperometry-detected increases in evoked dopamine (DA release by the CB1-R antagonist in nucleus accumbens slices indicates that AM251 modulates DA release from VTA terminals.Our results demonstrate that the effects of cannabinoids on energy balance are independent of hypothalamic melanocortin circuitry and is primarily driven by the reward system.

  15. Program reference schedule baseline

    International Nuclear Information System (INIS)

    1986-07-01

    This Program Reference Schedule Baseline (PRSB) provides the baseline Program-level milestones and associated schedules for the Civilian Radioactive Waste Management Program. It integrates all Program-level schedule-related activities. This schedule baseline will be used by the Director, Office of Civilian Radioactive Waste Management (OCRWM), and his staff to monitor compliance with Program objectives. Chapter 1 includes brief discussions concerning the relationship of the PRSB to the Program Reference Cost Baseline (PRCB), the Mission Plan, the Project Decision Schedule, the Total System Life Cycle Cost report, the Program Management Information System report, the Program Milestone Review, annual budget preparation, and system element plans. Chapter 2 includes the identification of all Level 0, or Program-level, milestones, while Chapter 3 presents and discusses the critical path schedules that correspond to those Level 0 milestones

  16. Long Baseline Observatory (LBO)

    Data.gov (United States)

    Federal Laboratory Consortium — The Long Baseline Observatory (LBO) comprises ten radio telescopes spanning 5,351 miles. It's the world's largest, sharpest, dedicated telescope array. With an eye...

  17. Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Xiao-Cui Yuan

    2018-04-01

    Full Text Available Knee osteoarthritis (KOA is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA. EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

  18. First Grade Baseline Evaluation

    Science.gov (United States)

    Center for Innovation in Assessment (NJ1), 2013

    2013-01-01

    The First Grade Baseline Evaluation is an optional tool that can be used at the beginning of the school year to help teachers get to know the reading and language skills of each student. The evaluation is composed of seven screenings. Teachers may use the entire evaluation or choose to use those individual screenings that they find most beneficial…

  19. Rationing with baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    2013-01-01

    We introduce a new operator for general rationing problems in which, besides conflicting claims, individual baselines play an important role in the rationing process. The operator builds onto ideas of composition, which are not only frequent in rationing, but also in related problems...... such as bargaining, choice, and queuing. We characterize the operator and show how it preserves some standard axioms in the literature on rationing. We also relate it to recent contributions in such literature....

  20. The TDAQ Baseline Architecture

    CERN Multimedia

    Wickens, F J

    The Trigger-DAQ community is currently busy preparing material for the DAQ, HLT and DCS TDR. Over the last few weeks a very important step has been a series of meetings to complete agreement on the baseline architecture. An overview of the architecture indicating some of the main parameters is shown in figure 1. As reported at the ATLAS Plenary during the February ATLAS week, the main area where the baseline had not yet been agreed was around the Read-Out System (ROS) and details in the DataFlow. The agreed architecture has: Read-Out Links (ROLs) from the RODs using S-Link; Read-Out Buffers (ROB) sited near the RODs, mounted in a chassis - today assumed to be a PC, using PCI bus at least for configuration, control and monitoring. The baseline assumes data aggregation, in the ROB and/or at the output (which could either be over a bus or in the network). Optimization of the data aggregation will be made in the coming months, but the current model has each ROB card receiving input from 4 ROLs, and 3 such c...

  1. 2017 Annual Technology Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hand, M. M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Eberle, Annika [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Beiter, Philipp C [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kurup, Parthiv [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Turchi, Craig S [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Feldman, David J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Margolis, Robert M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Augustine, Chad R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Maness, Michael [Formerly NREL; O' Connor, Patrick [Oak Ridge National Laboratory

    2018-03-26

    Consistent cost and performance data for various electricity generation technologies can be difficult to find and may change frequently for certain technologies. With the Annual Technology Baseline (ATB), the National Renewable Energy Laboratory annually provides an organized and centralized set of such cost and performance data. The ATB uses the best information from the Department of Energy national laboratories' renewable energy analysts as well as information from the Energy Information Administration for fuel-based technologies. The ATB has been reviewed by experts and it includes the following electricity generation technologies: land-based wind, offshore wind, utility-scale solar photovoltaics (PV), commercial-scale solar PV, residential-scale solar PV, concentrating solar power, geothermal power, hydropower, coal, natural gas, nuclear, and conventional biopower. This webinar presentation introduces the 2017 ATB.

  2. Biofuels Baseline 2008

    Energy Technology Data Exchange (ETDEWEB)

    Hamelinck, C.; Koper, M.; Berndes, G.; Englund, O.; Diaz-Chavez, R.; Kunen, E.; Walden, D.

    2011-10-15

    The European Union is promoting the use of biofuels and other renewable energy in transport. In April 2009, the Renewable Energy Directive (2009/28/EC) was adopted that set a 10% target for renewable energy in transport in 2020. The directive sets several requirements to the sustainability of biofuels marketed in the frame of the Directive. The Commission is required to report to the European Parliament on a regular basis on a range of sustainability impacts resulting from the use of biofuels in the EU. This report serves as a baseline of information for regular monitoring on the impacts of the Directive. Chapter 2 discusses the EU biofuels market, the production and consumption of biofuels and international trade. It is derived where the feedstock for EU consumed biofuels originally come from. Chapter 3 discusses the biofuel policy framework in the EU and major third countries of supply. It looks at various policy aspects that are relevant to comply with the EU sustainability requirements. Chapter 4 discusses the environmental and social sustainability aspects associated with EU biofuels and their feedstock. Chapter 5 discusses the macro-economic effects that indirectly result from increased EU biofuels consumption, on commodity prices and land use. Chapter 6 presents country factsheets for main third countries that supplied biofuels to the EU market in 2008.

  3. Baseline conditions at Olkiluoto

    International Nuclear Information System (INIS)

    2003-09-01

    The main purpose of this report is to establish a reference point - defined as the data collected up until the end of year 2002 - for the coming phases of the Finnish spent nuclear fuel disposal programme. The focus is: to define the current surface and underground conditions at the site, both as regards the properties for which a change is expected and for the properties which are of particular interest for long-term safety or environmental impact; to establish, as far as possible, the natural fluctuation of properties that are potentially affected by construction of the underground laboratory, the ONKALO, and to provide references to data on parameters or use in model development and testing and to use models to assist in understanding and interpreting the data. The emphasis of the baseline description is on bedrock characteristics that are relevant to the long-term safety of a spent fuel repository and, hence, to include the hydrogeological, hydrogeochemical, rock mechanical, tectonic and seismic conditions of the site. The construction of the ONKALO will also affect some conditions on the surface, and, therefore, a description of the main characteristics of the nature and the man-made constructions at Olkiluoto is also given. This report is primarily a road map to the available information on the prevailing conditions at the Olkiluoto site and a framework for understanding of data collected. Hence, it refers to numerous available background reports and other archived information produced over the past 20 years or more, and forms a recapitulation and revaluation of the characterisation data of the Olkiluoto site. (orig.)

  4. Performance Measurement Baseline Change Request

    Data.gov (United States)

    Social Security Administration — The Performance Measurement Baseline Change Request template is used to document changes to scope, cost, schedule, or operational performance metrics for SSA's Major...

  5. DairyBISS Baseline report

    NARCIS (Netherlands)

    Buizer, N.N.; Berhanu, Tinsae; Murutse, Girmay; Vugt, van S.M.

    2015-01-01

    This baseline report of the Dairy Business Information Service and Support (DairyBISS) project presents the findings of a baseline survey among 103 commercial farms and 31 firms and advisors working in the dairy value chain. Additional results from the survey among commercial dairy farms are

  6. Program Baseline Change Control Procedure

    International Nuclear Information System (INIS)

    1993-02-01

    This procedure establishes the responsibilities and process for approving initial issues of and changes to the technical, cost, and schedule baselines, and selected management documents developed by the Office of Civilian Radioactive Waste Management (OCRWM) for the Civilian Radioactive Waste Management System. This procedure implements the OCRWM Baseline Management Plan and DOE Order 4700.1, Chg 1. It streamlines the change control process to enhance integration, accountability, and traceability of Level 0 and Level I decisions through standardized Baseline Change Proposal (BCP) forms to be used by the Level 0, 1, 2, and 3 Baseline Change Control Boards (BCCBs) and to be tracked in the OCRWM-wide Configuration Information System (CIS) Database.This procedure applies to all technical, cost, and schedule baselines controlled by the Energy System Acquisition Advisory Board (ESAAB) BCCB (Level 0) and, OCRWM Program Baseline Control Board (PBCCB) (Level 1). All baseline BCPs initiated by Level 2 or lower BCCBs, which require approval from ESAAB or PBCCB, shall be processed in accordance with this procedure. This procedure also applies to all Program-level management documents controlled by the OCRWM PBCCB

  7. Oscillation Baselining and Analysis Tool

    Energy Technology Data Exchange (ETDEWEB)

    2017-03-27

    PNNL developed a new tool for oscillation analysis and baselining. This tool has been developed under a new DOE Grid Modernization Laboratory Consortium (GMLC) Project (GM0072 - “Suite of open-source applications and models for advanced synchrophasor analysis”) and it is based on the open platform for PMU analysis. The Oscillation Baselining and Analysis Tool (OBAT) performs the oscillation analysis and identifies modes of oscillations (frequency, damping, energy, and shape). The tool also does oscillation event baselining (fining correlation between oscillations characteristics and system operating conditions).

  8. 324 Building Baseline Radiological Characterization

    Energy Technology Data Exchange (ETDEWEB)

    R.J. Reeder, J.C. Cooper

    2010-06-24

    This report documents the analysis of radiological data collected as part of the characterization study performed in 1998. The study was performed to create a baseline of the radiological conditions in the 324 Building.

  9. Baseline restoration using current conveyors

    International Nuclear Information System (INIS)

    Morgado, A.M.L.S.; Simoes, J.B.; Correia, C.M.

    1996-01-01

    A good performance of high resolution nuclear spectrometry systems, at high pulse rates, demands restoration of baseline between pulses, in order to remove rate dependent baseline shifts. This restoration is performed by circuits named baseline restorers (BLRs) which also remove low frequency noise, such as power supply hum and detector microphonics. This paper presents simple circuits for baseline restoration based on a commercial current conveyor (CCII01). Tests were performed, on two circuits, with periodic trapezoidal shaped pulses in order to measure the baseline restoration for several pulse rates and restorer duty cycles. For the current conveyor based Robinson restorer, the peak shift was less than 10 mV, for duty cycles up to 60%, at high pulse rates. Duty cycles up to 80% were also tested, being the maximum peak shift 21 mV. The peak shift for the current conveyor based Grubic restorer was also measured. The maximum value found was 30 mV at 82% duty cycle. Keeping the duty cycle below 60% improves greatly the restorer performance. The ability of both baseline restorer architectures to reject low frequency modulation is also measured, with good results on both circuits

  10. Developing RESRAD-BASELINE for environmental baseline risk assessment

    International Nuclear Information System (INIS)

    Cheng, Jing-Jy.

    1995-01-01

    RESRAD-BASELINE is a computer code developed at Argonne developed at Argonne National Laboratory for the US Department of Energy (DOE) to perform both radiological and chemical risk assessments. The code implements the baseline risk assessment guidance of the US Environmental Protection Agency (EPA 1989). The computer code calculates (1) radiation doses and cancer risks from exposure to radioactive materials, and (2) hazard indexes and cancer risks from exposure to noncarcinogenic and carcinogenic chemicals, respectively. The user can enter measured or predicted environmental media concentrations from the graphic interface and can simulate different exposure scenarios by selecting the appropriate pathways and modifying the exposure parameters. The database used by PESRAD-BASELINE includes dose conversion factors and slope factors for radionuclides and toxicity information and properties for chemicals. The user can modify the database for use in the calculation. Sensitivity analysis can be performed while running the computer code to examine the influence of the input parameters. Use of RESRAD-BASELINE for risk analysis is easy, fast, and cost-saving. Furthermore, it ensures in consistency in methodology for both radiological and chemical risk analyses

  11. Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

    OpenAIRE

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-qian; Wu, Yan; Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmaco...

  12. Long baseline neutrino oscillation experiments

    International Nuclear Information System (INIS)

    Gallagher, H.

    2006-01-01

    In this paper I will review briefly the experimental results which established the existence of neutrino mixing, the current generation of long baseline accelerator experiments, and the prospects for the future. In particular I will focus on the recent analysis of the MINOS experiment. (author)

  13. Baseline Report on HB2320

    Science.gov (United States)

    State Council of Higher Education for Virginia, 2015

    2015-01-01

    Staff provides this baseline report as a summary of its preliminary considerations and initial research in fulfillment of the requirements of HB2320 from the 2015 session of the General Assembly. Codified as § 23-7.4:7, this legislation compels the Education Secretary and the State Council of Higher Education for Virginia (SCHEV) Director, in…

  14. Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.

    Science.gov (United States)

    Skosnik, Patrick D; Hajós, Mihály; Cortes-Briones, Jose A; Edwards, Chad R; Pittman, Brian P; Hoffmann, William E; Sewell, Andrew R; D'Souza, Deepak C; Ranganathan, Mohini

    2018-06-01

    Cannabis use has been associated with altered sensory gating and neural oscillations. However, it is unclear which constituent in cannabis is responsible for these effects, or whether these are cannabinoid receptor 1 (CB1R) mediated. Therefore, the present study in humans and rats examined whether cannabinoid administration would disrupt sensory gating and evoked oscillations utilizing electroencephalography (EEG) and local field potentials (LFPs), respectively. Human subjects (n = 15) completed four test days during which they received intravenous delta-9-tetrahydrocannabinol (Δ 9 -THC), cannabidiol (CBD), Δ 9 -THC + CBD, or placebo. Subjects engaged in a dual-click paradigm, and outcome measures included P50 gating ratio (S2/S1) and evoked power to S1 and S2. In order to examine CB1R specificity, rats (n = 6) were administered the CB1R agonist CP-55940, CP-55940+AM-251 (a CB1R antagonist), or vehicle using the same paradigm. LFPs were recorded from CA3 and entorhinal cortex. Both Δ 9 -THC (p < 0.007) and Δ 9 -THC + CBD (p < 0.004) disrupted P50 gating ratio compared to placebo, while CBD alone had no effect. Δ 9 -THC (p < 0.048) and Δ 9 -THC + CBD (p < 0.035) decreased S1 evoked theta power, and in the Δ 9 -THC condition, S1 theta negatively correlated with gating ratios (r = -0.629, p < 0.012 (p < 0.048 adjusted)). In rats, CP-55940 disrupted gating in both brain regions (p < 0.0001), and this was reversed by AM-251. Further, CP-55940 decreased evoked theta (p < 0.0077) and gamma (p < 0.011) power to S1, which was partially blocked by AM-251. These convergent human/animal data suggest that CB1R agonists disrupt sensory gating by altering neural oscillations in the theta-band. Moreover, this suggests that the endocannabinoid system mediates theta oscillations relevant to perception and cognition. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Baseline budgeting for continuous improvement.

    Science.gov (United States)

    Kilty, G L

    1999-05-01

    This article is designed to introduce the techniques used to convert traditionally maintained department budgets to baseline budgets. This entails identifying key activities, evaluating for value-added, and implementing continuous improvement opportunities. Baseline Budgeting for Continuous Improvement was created as a result of a newly named company president's request to implement zero-based budgeting. The president was frustrated with the mind-set of the organization, namely, "Next year's budget should be 10 to 15 percent more than this year's spending." Zero-based budgeting was not the answer, but combining the principles of activity-based costing and the Just-in-Time philosophy of eliminating waste and continuous improvement did provide a solution to the problem.

  16. Integrated Baseline Review (IBR) Handbook

    Science.gov (United States)

    Fleming, Jon F.; Terrell, Stefanie M.

    2018-01-01

    The purpose of this handbook is intended to be a how-to guide to prepare for, conduct, and close-out an Integrated Baseline Review (IBR). It discusses the steps that should be considered, describes roles and responsibilities, tips for tailoring the IBR based on risk, cost, and need for management insight, and provides lessons learned from past IBRs. Appendices contain example documentation typically used in connection with an IBR. Note that these appendices are examples only, and should be tailored to meet the needs of individual projects and contracts.

  17. Environmental Baseline File National Transportation

    International Nuclear Information System (INIS)

    Harris, M.

    1999-01-01

    This Environmental Baseline File summarizes and consolidates information related to the national-level transportation of commercial spent nuclear fuel. Topics addressed include: shipments of commercial spent nuclear fuel based on mostly truck and mostly rail shipping scenarios; transportation routing for commercial spent nuclear fuel sites and DOE sites; radionuclide inventories for various shipping container capacities; transportation routing; populations along transportation routes; urbanized area population densities; the impacts of historical, reasonably foreseeable, and general transportation; state-level food transfer factors; Federal Guidance Report No. 11 and 12 radionuclide dose conversion factors; and national average atmospheric conditions

  18. Baseline atmospheric program Australia 1993

    International Nuclear Information System (INIS)

    Francey, R.J.; Dick, A.L.; Derek, N.

    1996-01-01

    This publication reports activities, program summaries and data from the Cape Grim Baseline Air Pollution Station in Tasmania, during the calendar year 1993. These activities represent Australia's main contribution to the Background Air Pollution Monitoring Network (BAPMoN), part of the World Meteorological Organization's Global Atmosphere Watch (GAW). The report includes 5 research reports covering trace gas sampling, ozone and radon interdependence, analysis of atmospheric dimethylsulfide and carbon-disulfide, sampling of trace gas composition of the troposphere, and sulfur aerosol/CCN relationship in marine air. Summaries of program reports for the calendar year 1993 are also included. Tabs., figs., refs

  19. Baseline LAW Glass Formulation Testing

    International Nuclear Information System (INIS)

    Kruger, Albert A.; Mooers, Cavin; Bazemore, Gina; Pegg, Ian L.; Hight, Kenneth; Lai, Shan Tao; Buechele, Andrew; Rielley, Elizabeth; Gan, Hao; Muller, Isabelle S.; Cecil, Richard

    2013-01-01

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements

  20. FED baseline engineering studies report

    Energy Technology Data Exchange (ETDEWEB)

    Sager, P.H.

    1983-04-01

    Studies were carried out on the FED Baseline to improve design definition, establish feasibility, and reduce cost. Emphasis was placed on cost reduction, but significant feasibility concerns existed in several areas, and better design definition was required to establish feasibility and provide a better basis for cost estimates. Design definition and feasibility studies included the development of a labyrinth shield ring concept to prevent radiation streaming between the torus spool and the TF coil cryostat. The labyrinth shield concept which was developed reduced radiation streaming sufficiently to permit contact maintenance of the inboard EF coils. Various concepts of preventing arcing between adjacent shield sectors were also explored. It was concluded that installation of copper straps with molybdenum thermal radiation shields would provide the most reliable means of preventing arcing. Other design studies included torus spool electrical/structural concepts, test module shielding, torus seismic response, poloidal conditions in the magnets, disruption characteristics, and eddy current effects. These additional studies had no significant impact on cost but did confirm the feasibility of the basic FED Baseline concept.

  1. FED baseline engineering studies report

    International Nuclear Information System (INIS)

    Sager, P.H.

    1983-04-01

    Studies were carried out on the FED Baseline to improve design definition, establish feasibility, and reduce cost. Emphasis was placed on cost reduction, but significant feasibility concerns existed in several areas, and better design definition was required to establish feasibility and provide a better basis for cost estimates. Design definition and feasibility studies included the development of a labyrinth shield ring concept to prevent radiation streaming between the torus spool and the TF coil cryostat. The labyrinth shield concept which was developed reduced radiation streaming sufficiently to permit contact maintenance of the inboard EF coils. Various concepts of preventing arcing between adjacent shield sectors were also explored. It was concluded that installation of copper straps with molybdenum thermal radiation shields would provide the most reliable means of preventing arcing. Other design studies included torus spool electrical/structural concepts, test module shielding, torus seismic response, poloidal conditions in the magnets, disruption characteristics, and eddy current effects. These additional studies had no significant impact on cost but did confirm the feasibility of the basic FED Baseline concept

  2. Pinellas Plant Environmental Baseline Report

    Energy Technology Data Exchange (ETDEWEB)

    1997-06-01

    The Pinellas Plant has been part of the Department of Energy`s (DOE) nuclear weapons complex since the plant opened in 1957. In March 1995, the DOE sold the Pinellas Plant to the Pinellas County Industry Council (PCIC). DOE has leased back a large portion of the plant site to facilitate transition to alternate use and safe shutdown. The current mission is to achieve a safe transition of the facility from defense production and prepare the site for alternative uses as a community resource for economic development. Toward that effort, the Pinellas Plant Environmental Baseline Report (EBR) discusses the current and past environmental conditions of the plant site. Information for the EBR is obtained from plant records. Historical process and chemical usage information for each area is reviewed during area characterizations.

  3. Integrated Baseline Review (IBR) Handbook

    Science.gov (United States)

    Fleming, Jon F.; Kehrer, Kristen C.

    2016-01-01

    The purpose of this handbook is intended to be a how-to guide to prepare for, conduct, and close-out an Integrated Baseline Review (IBR). It discusses the steps that should be considered, describes roles and responsibilities, tips for tailoring the IBR based on risk, cost, and need for management insight, and provides lessons learned from past IBRs. Appendices contain example documentation typically used in connection with an IBR. Note that these appendices are examples only, and should be tailored to meet the needs of individual projects and contracts. Following the guidance in this handbook will help customers and suppliers preparing for an IBR understand the expectations of the IBR, and ensure that the IBR meets the requirements for both in-house and contract efforts.

  4. The California Baseline Methane Survey

    Science.gov (United States)

    Duren, R. M.; Thorpe, A. K.; Hopkins, F. M.; Rafiq, T.; Bue, B. D.; Prasad, K.; Mccubbin, I.; Miller, C. E.

    2017-12-01

    The California Baseline Methane Survey is the first systematic, statewide assessment of methane point source emissions. The objectives are to reduce uncertainty in the state's methane budget and to identify emission mitigation priorities for state and local agencies, utilities and facility owners. The project combines remote sensing of large areas with airborne imaging spectroscopy and spatially resolved bottom-up data sets to detect, quantify and attribute emissions from diverse sectors including agriculture, waste management, oil and gas production and the natural gas supply chain. Phase 1 of the project surveyed nearly 180,000 individual facilities and infrastructure components across California in 2016 - achieving completeness rates ranging from 20% to 100% per emission sector at < 5 meters spatial resolution. Additionally, intensive studies of key areas and sectors were performed to assess source persistence and variability at times scales ranging from minutes to months. Phase 2 of the project continues with additional data collection in Spring and Fall 2017. We describe the survey design and measurement, modeling and analysis methods. We present initial findings regarding the spatial, temporal and sectoral distribution of methane point source emissions in California and their estimated contribution to the state's total methane budget. We provide case-studies and lessons learned about key sectors including examples where super-emitters were identified and mitigated. We summarize challenges and recommendations for future methane research, inventories and mitigation guidance within and beyond California.

  5. Hydrogeology baseline study Aurora Mine

    International Nuclear Information System (INIS)

    1996-01-01

    A baseline hydrogeologic study was conducted in the area of Syncrude's proposed Aurora Mine in order to develop a conceptual regional hydrogeologic model for the area that could be used to understand groundwater flow conditions. Geologic information was obtained from over 2,000 coreholes and from data obtained between 1980 and 1996 regarding water level for the basal aquifer. A 3-D numerical groundwater flow model was developed to provide quantitative estimates of the potential environmental impacts of the proposed mining operations on the groundwater flow system. The information was presented in the context of a regional study area which encompassed much of the Athabasca Oil Sands Region, and a local study area which was defined by the lowlands of the Muskeg River Basin. Characteristics of the topography, hydrology, climate, geology, and hydrogeology of the region are described. The conclusion is that groundwater flow in the aquifer occurs mostly in a westerly direction beneath the Aurora Mine towards its inferred discharge location along the Athabasca River. Baseflow in the Muskeg River is mostly related to discharge from shallow surficial aquifers. Water in the river under baseflow conditions was fresh, of calcium-carbonate type, with very little indication of mineralization associated with deeper groundwater in the Aurora Mine area. 44 refs., 5 tabs., 31 figs

  6. 2016 Annual Technology Baseline (ATB)

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley; Kurup, Parthiv; Hand, Maureen; Feldman, David; Sigrin, Benjamin; Lantz, Eric; Stehly, Tyler; Augustine, Chad; Turchi, Craig; O' Connor, Patrick; Waldoch, Connor

    2016-09-01

    Consistent cost and performance data for various electricity generation technologies can be difficult to find and may change frequently for certain technologies. With the Annual Technology Baseline (ATB), National Renewable Energy Laboratory provides an organized and centralized dataset that was reviewed by internal and external experts. It uses the best information from the Department of Energy laboratory's renewable energy analysts and Energy Information Administration information for conventional technologies. The ATB will be updated annually in order to provide an up-to-date repository of current and future cost and performance data. Going forward, we plan to revise and refine the values using best available information. The ATB includes both a presentation with notes (PDF) and an associated Excel Workbook. The ATB includes the following electricity generation technologies: land-based wind; offshore wind; utility-scale solar PV; concentrating solar power; geothermal power; hydropower plants (upgrades to existing facilities, powering non-powered dams, and new stream-reach development); conventional coal; coal with carbon capture and sequestration; integrated gasification combined cycle coal; natural gas combustion turbines; natural gas combined cycle; conventional biopower. Nuclear laboratory's renewable energy analysts and Energy Information Administration information for conventional technologies. The ATB will be updated annually in order to provide an up-to-date repository of current and future cost and performance data. Going forward, we plan to revise and refine the values using best available information.

  7. Endocannabinoids mediate neuron-astrocyte communication.

    Science.gov (United States)

    Navarrete, Marta; Araque, Alfonso

    2008-03-27

    Cannabinoid receptors play key roles in brain function, and cannabinoid effects in brain physiology and drug-related behavior are thought to be mediated by receptors present in neurons. Neuron-astrocyte communication relies on the expression by astrocytes of neurotransmitter receptors. Yet, the expression of cannabinoid receptors by astrocytes in situ and their involvement in the neuron-astrocyte communication remain largely unknown. We show that hippocampal astrocytes express CB1 receptors that upon activation lead to phospholipase C-dependent Ca2+ mobilization from internal stores. These receptors are activated by endocannabinoids released by neurons, increasing astrocyte Ca2+ levels, which stimulate glutamate release that activates NMDA receptors in pyramidal neurons. These results demonstrate the existence of endocannabinoid-mediated neuron-astrocyte communication, revealing that astrocytes are targets of cannabinoids and might therefore participate in the physiology of cannabinoid-related addiction. They also reveal the existence of an endocannabinoid-glutamate signaling pathway where astrocytes serve as a bridge for nonsynaptic interneuronal communication.

  8. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

  9. 2016 Annual Technology Baseline (ATB) - Webinar Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley; Kurup, Parthiv; Hand, Maureen; Feldman, David; Sigrin, Benjamin; Lantz, Eric; Stehly, Tyler; Augustine, Chad; Turchi, Craig; Porro, Gian; O' Connor, Patrick; Waldoch, Connor

    2016-09-13

    This deck was presented for the 2016 Annual Technology Baseline Webinar. The presentation describes the Annual Technology Baseline, which is a compilation of current and future cost and performance data for electricity generation technologies.

  10. 75 FR 66748 - Notice of Baseline Filings

    Science.gov (United States)

    2010-10-29

    ...- 000] Notice of Baseline Filings October 22, 2010. ONEOK Gas Transportation, L.L.C Docket No. PR11-68... above submitted a revised baseline filing of their Statement of Operating Conditions for services...

  11. 324 Building Baseline Radiological Characterization

    International Nuclear Information System (INIS)

    Reeder, R.J.; Cooper, J.C.

    2010-01-01

    This report documents the analysis of radiological data collected as part of the characterization study performed in 1998. The study was performed to create a baseline of the radiological conditions in the 324 Building. A total of 85 technical (100 square centimeter (cm 2 )) smears were collected from the Room 147 hoods, the Shielded Materials Facility (SMF), and the Radiochemical Engineering Cells (REC). Exposure rate readings (window open and window closed) were taken at a distance of 2.5 centimeters (cm) and 30 cm from the surface of each smear. Gross beta-gamma and alpha counts of each smear were also performed. The smear samples were analyzed by gamma energy analysis (GEA). Alpha energy analysis (AEA) and strontium-90 analysis were also performed on selected smears. GEA results for one or more samples reported the presence of manganese-54, cobalt-60, silver-108m antimony-125, cesium-134, cesium-137, europium-154, europium-155, and americium-241. AEA results reported the presence of plutonium-239/240, plutonium-238/ 241 Am, curium-243/244, curium-242, and americium-243. Tables 5 through 9 present a summary by location of the estimated maximum removable and total contamination levels in the Room 147 hoods, the SMF, and the REC. The smear sample survey data and laboratory analytical results are presented in tabular form by sample in Appendix A. The Appendix A tables combine survey data documented in radiological survey reports found in Appendix B and laboratory analytical results reported in the 324 Building Physical and Radiological Characterization Study (Berk, Hill, and Landsman 1998), supplemented by the laboratory analytical results found in Appendix C.

  12. Program Baseline Change Control Board charter

    International Nuclear Information System (INIS)

    1993-02-01

    The purpose of this Charter is to establish the Program Baseline Change Control Board (PBCCB) for the Office of Civilian Radioactive Waste Management (OCRWM) Program, and to describe its organization, responsibilities, and basic methods of operation. Guidance for implementing this Charter is provided by the OCRWM Baseline Management Plan (BMP) and OCRWM Program Baseline Change Control Procedure

  13. 40 CFR 1042.825 - Baseline determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Baseline determination. 1042.825... Provisions for Remanufactured Marine Engines § 1042.825 Baseline determination. (a) For the purpose of this... not valid. (f) Use good engineering judgment for all aspects of the baseline determination. We may...

  14. 40 CFR 74.20 - Data for baseline and alternative baseline.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Data for baseline and alternative baseline. 74.20 Section 74.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... baseline and alternative baseline. (a) Acceptable data. (1) The designated representative of a combustion...

  15. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  16. Hazard Baseline Downgrade Effluent Treatment Facility

    International Nuclear Information System (INIS)

    Blanchard, A.

    1998-01-01

    This Hazard Baseline Downgrade reviews the Effluent Treatment Facility, in accordance with Department of Energy Order 5480.23, WSRC11Q Facility Safety Document Manual, DOE-STD-1027-92, and DOE-EM-STD-5502-94. It provides a baseline grouping based on the chemical and radiological hazards associated with the facility. The Determination of the baseline grouping for ETF will aid in establishing the appropriate set of standards for the facility

  17. Integrated planning: A baseline development perspective

    International Nuclear Information System (INIS)

    Clauss, L.; Chang, D.

    1994-01-01

    The FEMP Baseline establishes the basis for integrating environmental activity technical requirements with their cost and schedule elements. The result is a path forward to successfully achieving the FERMCO mission. Specific to cost management, the FEMP Baseline has been incorporate into the FERMCO Project Control System (PCS) to provide a time-phased budget plan against which contractor performance is measured with an earned value management system. The result is the Performance Measurement Baseline (PMB), an important tool for keeping cost under control

  18. IPCC Socio-Economic Baseline Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — The Intergovernmental Panel on Climate Change (IPCC) Socio-Economic Baseline Dataset consists of population, human development, economic, water resources, land...

  19. TAPIR--Finnish national geochemical baseline database.

    Science.gov (United States)

    Jarva, Jaana; Tarvainen, Timo; Reinikainen, Jussi; Eklund, Mikael

    2010-09-15

    In Finland, a Government Decree on the Assessment of Soil Contamination and Remediation Needs has generated a need for reliable and readily accessible data on geochemical baseline concentrations in Finnish soils. According to the Decree, baseline concentrations, referring both to the natural geological background concentrations and the diffuse anthropogenic input of substances, shall be taken into account in the soil contamination assessment process. This baseline information is provided in a national geochemical baseline database, TAPIR, that is publicly available via the Internet. Geochemical provinces with elevated baseline concentrations were delineated to provide regional geochemical baseline values. The nationwide geochemical datasets were used to divide Finland into geochemical provinces. Several metals (Co, Cr, Cu, Ni, V, and Zn) showed anomalous concentrations in seven regions that were defined as metal provinces. Arsenic did not follow a similar distribution to any other elements, and four arsenic provinces were separately determined. Nationwide geochemical datasets were not available for some other important elements such as Cd and Pb. Although these elements are included in the TAPIR system, their distribution does not necessarily follow the ones pre-defined for metal and arsenic provinces. Regional geochemical baseline values, presented as upper limit of geochemical variation within the region, can be used as trigger values to assess potential soil contamination. Baseline values have also been used to determine upper and lower guideline values that must be taken into account as a tool in basic risk assessment. If regional geochemical baseline values are available, the national guideline values prescribed in the Decree based on ecological risks can be modified accordingly. The national geochemical baseline database provides scientifically sound, easily accessible and generally accepted information on the baseline values, and it can be used in various

  20. FAQs about Baseline Testing among Young Athletes

    Science.gov (United States)

    ... a similar exam conducted by a health care professional during the season if an athlete has a suspected concussion. Baseline testing generally takes place during the pre-season—ideally prior to the first practice. It is important to note that some baseline ...

  1. 75 FR 74706 - Notice of Baseline Filings

    Science.gov (United States)

    2010-12-01

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Baseline Filings November 24, 2010. Centana Intrastate Pipeline, LLC. Docket No. PR10-84-001. Centana Intrastate Pipeline, LLC... applicants listed above submitted a revised baseline filing of their Statement of Operating Conditions for...

  2. 76 FR 8725 - Notice of Baseline Filings

    Science.gov (United States)

    2011-02-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Baseline Filings Enstor Grama Ridge Storage and Docket No. PR10-97-002. Transportation, L.L.C.. EasTrans, LLC Docket No. PR10-30-001... revised baseline filing of their Statement of Operating Conditions for services provided under section 311...

  3. 75 FR 57268 - Notice of Baseline Filings

    Science.gov (United States)

    2010-09-20

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-103-000; Docket No. PR10-104-000; Docket No. PR10-105- 000 (Not Consolidated)] Notice of Baseline Filings September 13..., 2010, and September 10, 2010, respectively the applicants listed above submitted their baseline filing...

  4. 75 FR 65010 - Notice of Baseline Filings

    Science.gov (United States)

    2010-10-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR11-1-000; Docket No. PR11-2-000; Docket No. PR11-3-000] Notice of Baseline Filings October 14, 2010. Cranberry Pipeline Docket..., 2010, respectively the applicants listed above submitted their baseline filing of its Statement of...

  5. 76 FR 5797 - Notice of Baseline Filings

    Science.gov (United States)

    2011-02-02

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-114-001; Docket No. PR10-129-001; Docket No. PR10-131- 001; Docket No. PR10-68-002 Not Consolidated] Notice of Baseline... applicants listed above submitted a revised baseline filing of their Statement of Operating Conditions for...

  6. 75 FR 70732 - Notice of Baseline Filings

    Science.gov (United States)

    2010-11-18

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR11-71-000; Docket No. PR11-72-000; Docket No. PR11-73- 000] Notice of Baseline Filings November 10, 2010. Docket No. PR11-71-000..., 2010, the applicants listed above submitted their baseline filing of their Statement of Operating...

  7. Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

    Science.gov (United States)

    Sideris, Alexandra; Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

    2016-01-01

    The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. At baseline, CB1R-/- mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R-/- mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R-/- mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/-) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R-/- mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. Cold allodynia and

  8. TWRS technical baseline database manager definition document

    International Nuclear Information System (INIS)

    Acree, C.D.

    1997-01-01

    This document serves as a guide for using the TWRS Technical Baseline Database Management Systems Engineering (SE) support tool in performing SE activities for the Tank Waste Remediation System (TWRS). This document will provide a consistent interpretation of the relationships between the TWRS Technical Baseline Database Management software and the present TWRS SE practices. The Database Manager currently utilized is the RDD-1000 System manufactured by the Ascent Logic Corporation. In other documents, the term RDD-1000 may be used interchangeably with TWRS Technical Baseline Database Manager

  9. Life Support Baseline Values and Assumptions Document

    Science.gov (United States)

    Anderson, Molly S.; Ewert, Michael K.; Keener, John F.

    2018-01-01

    The Baseline Values and Assumptions Document (BVAD) provides analysts, modelers, and other life support researchers with a common set of values and assumptions which can be used as a baseline in their studies. This baseline, in turn, provides a common point of origin from which many studies in the community may depart, making research results easier to compare and providing researchers with reasonable values to assume for areas outside their experience. This document identifies many specific physical quantities that define life support systems, serving as a general reference for spacecraft life support system technology developers.

  10. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  11. Hanford Site technical baseline database. Revision 1

    International Nuclear Information System (INIS)

    Porter, P.E.

    1995-01-01

    This report lists the Hanford specific files (Table 1) that make up the Hanford Site Technical Baseline Database. Table 2 includes the delta files that delineate the differences between this revision and revision 0 of the Hanford Site Technical Baseline Database. This information is being managed and maintained on the Hanford RDD-100 System, which uses the capabilities of RDD-100, a systems engineering software system of Ascent Logic Corporation (ALC). This revision of the Hanford Site Technical Baseline Database uses RDD-100 version 3.0.2.2 (see Table 3). Directories reflect those controlled by the Hanford RDD-100 System Administrator. Table 4 provides information regarding the platform. A cassette tape containing the Hanford Site Technical Baseline Database is available

  12. THE US LONG BASELINE NEUTRINO EXPERIMENT STUDY.

    Energy Technology Data Exchange (ETDEWEB)

    BISHAI,M.

    2007-08-06

    The US Long Baseline Neutrino Experiment Study was commissioned jointly by Brookhaven National Laboratory (BNL)and Fermi National Accelerator Laboratory (FNAL) to investigate the potential for future U.S. based long baseline neutrino oscillation experiments using MW class conventional neutrino beams that can be produced at FNAL. The experimental baselines are based on two possible detector locations: (1) off-axis to the existing FNAL NuMI beamline at baselines of 700 to 810 km and (2) NSF's proposed future Deep Underground Science and Engineering Laboratory (DUSEL) at baselines greater than 1000km. Two detector technologies are considered: a megaton class Water Cherenkov detector deployed deep underground at a DUSEL site, or a 100kT Liquid Argon Time-Projection Chamber (TPC) deployed on the surface at any of the proposed sites. The physics sensitivities of the proposed experiments are summarized. We find that conventional horn focused wide-band neutrino beam options from FNAL aimed at a massive detector with a baseline of > 1000km have the best sensitivity to CP violation and the neutrino mass hierarchy for values of the mixing angle {theta}{sub 13} down to 2{sup o}.

  13. The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

    Science.gov (United States)

    Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

    2007-08-15

    Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

  14. A long baseline global stereo matching based upon short baseline estimation

    Science.gov (United States)

    Li, Jing; Zhao, Hong; Li, Zigang; Gu, Feifei; Zhao, Zixin; Ma, Yueyang; Fang, Meiqi

    2018-05-01

    In global stereo vision, balancing the matching efficiency and computing accuracy seems to be impossible because they contradict each other. In the case of a long baseline, this contradiction becomes more prominent. In order to solve this difficult problem, this paper proposes a novel idea to improve both the efficiency and accuracy in global stereo matching for a long baseline. In this way, the reference images located between the long baseline image pairs are firstly chosen to form the new image pairs with short baselines. The relationship between the disparities of pixels in the image pairs with different baselines is revealed by considering the quantized error so that the disparity search range under the long baseline can be reduced by guidance of the short baseline to gain matching efficiency. Then, the novel idea is integrated into the graph cuts (GCs) to form a multi-step GC algorithm based on the short baseline estimation, by which the disparity map under the long baseline can be calculated iteratively on the basis of the previous matching. Furthermore, the image information from the pixels that are non-occluded under the short baseline but are occluded for the long baseline can be employed to improve the matching accuracy. Although the time complexity of the proposed method depends on the locations of the chosen reference images, it is usually much lower for a long baseline stereo matching than when using the traditional GC algorithm. Finally, the validity of the proposed method is examined by experiments based on benchmark datasets. The results show that the proposed method is superior to the traditional GC method in terms of efficiency and accuracy, and thus it is suitable for long baseline stereo matching.

  15. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  16. Associations between baseline allergens and polysensitization

    DEFF Research Database (Denmark)

    Carlsen, B.C.; Menne, T.; Johansen, J.D.

    2008-01-01

    Background: Identification of patients at risk of developing polysensitization is not possible at present. An association between weak sensitizers and polysensitization has been hypothesized. Objectives: To examine associations of 21 allergens in the European baseline series to polysensitization....... Patients/Methods: From a database-based study with 14 998 patients patch tested with the European baseline series between 1985 and 2005, a group of 759 (5.1%) patients were polysensitized. Odds ratios were calculated to determine the relative contribution of each allergen to polysensitization. Results...... denominator for the association between the allergens and the polysensitization was apparent, and any association, whether positive or negative, was relatively low. Based on these results, sensitization to specific baseline allergens cannot be used as risk indicators for polysensitization Udgivelsesdato: 2008...

  17. Associations between baseline allergens and polysensitization

    DEFF Research Database (Denmark)

    Carlsen, Berit Christina; Menné, Torkil; Johansen, Jeanne Duus

    2008-01-01

    BACKGROUND: Identification of patients at risk of developing polysensitization is not possible at present. An association between weak sensitizers and polysensitization has been hypothesized. OBJECTIVES: To examine associations of 21 allergens in the European baseline series to polysensitization....... PATIENTS/METHODS: From a database-based study with 14 998 patients patch tested with the European baseline series between 1985 and 2005, a group of 759 (5.1%) patients were polysensitized. Odds ratios were calculated to determine the relative contribution of each allergen to polysensitization. RESULTS...... denominator for the association between the allergens and the polysensitization was apparent, and any association, whether positive or negative, was relatively low. Based on these results, sensitization to specific baseline allergens cannot be used as risk indicators for polysensitization....

  18. CA1 Pyramidal Cell Theta-Burst Firing Triggers Endocannabinoid-Mediated Long-Term Depression at Both Somatic and Dendritic Inhibitory Synapses

    Science.gov (United States)

    Younts, Thomas J.; Chevaleyre, Vivien

    2013-01-01

    Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons' axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner. PMID:23966696

  19. Baseline methodologies for clean development mechanism projects

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.K. (ed.); Shrestha, R.M.; Sharma, S.; Timilsina, G.R.; Kumar, S.

    2005-11-15

    The Kyoto Protocol and the Clean Development Mechanism (CDM) came into force on 16th February 2005 with its ratification by Russia. The increasing momentum of this process is reflected in more than 100 projects having been submitted to the CDM Executive Board (CDM-EB) for approval of the baselines and monitoring methodologies, which is the first step in developing and implementing CDM projects. A CDM project should result in a net decrease of GHG emissions below any level that would have resulted from other activities implemented in the absence of that CDM project. The 'baseline' defines the GHG emissions of activities that would have been implemented in the absence of a CDM project. The baseline methodology is the process/algorithm for establishing that baseline. The baseline, along with the baseline methodology, are thus the most critical element of any CDM project towards meeting the important criteria of CDM, which are that a CDM should result in 'real, measurable, and long term benefits related to the mitigation of climate change'. This guidebook is produced within the frame work of the United Nations Environment Programme (UNEP) facilitated 'Capacity Development for the Clean Development Mechanism (CD4CDM)' Project. This document is published as part of the projects effort to develop guidebooks that cover important issues such as project finance, sustainability impacts, legal framework and institutional framework. These materials are aimed to help stakeholders better understand the CDM and are believed to eventually contribute to maximize the effect of the CDM in achieving the ultimate goal of UNFCCC and its Kyoto Protocol. This Guidebook should be read in conjunction with the information provided in the two other guidebooks entitled, 'Clean Development Mechanism: Introduction to the CDM' and 'CDM Information and Guidebook' developed under the CD4CDM project. (BA)

  20. Geochemical baseline studies of soil in Finland

    Science.gov (United States)

    Pihlaja, Jouni

    2017-04-01

    The soil element concentrations regionally vary a lot in Finland. Mostly this is caused by the different bedrock types, which are reflected in the soil qualities. Geological Survey of Finland (GTK) is carrying out geochemical baseline studies in Finland. In the previous phase, the research is focusing on urban areas and mine environments. The information can, for example, be used to determine the need for soil remediation, to assess environmental impacts or to measure the natural state of soil in industrial areas or mine districts. The field work is done by taking soil samples, typically at depth between 0-10 cm. Sampling sites are chosen to represent the most vulnerable areas when thinking of human impacts by possible toxic soil element contents: playgrounds, day-care centers, schools, parks and residential areas. In the mine districts the samples are taken from the areas locating outside the airborne dust effected areas. Element contents of the soil samples are then analyzed with ICP-AES and ICP-MS, Hg with CV-AAS. The results of the geochemical baseline studies are published in the Finnish national geochemical baseline database (TAPIR). The geochemical baseline map service is free for all users via internet browser. Through this map service it is possible to calculate regional soil baseline values using geochemical data stored in the map service database. Baseline data for 17 elements in total is provided in the map service and it can be viewed on the GTK's web pages (http://gtkdata.gtk.fi/Tapir/indexEN.html).

  1. Baseline methodologies for clean development mechanism projects

    International Nuclear Information System (INIS)

    Lee, M.K.; Shrestha, R.M.; Sharma, S.; Timilsina, G.R.; Kumar, S.

    2005-11-01

    The Kyoto Protocol and the Clean Development Mechanism (CDM) came into force on 16th February 2005 with its ratification by Russia. The increasing momentum of this process is reflected in more than 100 projects having been submitted to the CDM Executive Board (CDM-EB) for approval of the baselines and monitoring methodologies, which is the first step in developing and implementing CDM projects. A CDM project should result in a net decrease of GHG emissions below any level that would have resulted from other activities implemented in the absence of that CDM project. The 'baseline' defines the GHG emissions of activities that would have been implemented in the absence of a CDM project. The baseline methodology is the process/algorithm for establishing that baseline. The baseline, along with the baseline methodology, are thus the most critical element of any CDM project towards meeting the important criteria of CDM, which are that a CDM should result in 'real, measurable, and long term benefits related to the mitigation of climate change'. This guidebook is produced within the frame work of the United Nations Environment Programme (UNEP) facilitated 'Capacity Development for the Clean Development Mechanism (CD4CDM)' Project. This document is published as part of the projects effort to develop guidebooks that cover important issues such as project finance, sustainability impacts, legal framework and institutional framework. These materials are aimed to help stakeholders better understand the CDM and are believed to eventually contribute to maximize the effect of the CDM in achieving the ultimate goal of UNFCCC and its Kyoto Protocol. This Guidebook should be read in conjunction with the information provided in the two other guidebooks entitled, 'Clean Development Mechanism: Introduction to the CDM' and 'CDM Information and Guidebook' developed under the CD4CDM project. (BA)

  2. Waste management project technical baseline description

    International Nuclear Information System (INIS)

    Sederburg, J.P.

    1997-01-01

    A systems engineering approach has been taken to describe the technical baseline under which the Waste Management Project is currently operating. The document contains a mission analysis, function analysis, requirement analysis, interface definitions, alternative analysis, system definition, documentation requirements, implementation definitions, and discussion of uncertainties facing the Project

  3. Baseline and Multimodal UAV GCS Interface Design

    Science.gov (United States)

    2013-07-01

    complete a computerized version of the NASA - TLX assessment of perceived mental workload. 2.3 Results The baseline condition ran smoothly and with...System MALE Medium-altitude, Long-endurance NASA - TLX NASA Task Load Index SA Situation Awareness TDT Tucker Davis Technologies UAV Uninhabited Aerial

  4. National Cyberethics, Cybersafety, Cybersecurity Baseline Study

    Science.gov (United States)

    Education Digest: Essential Readings Condensed for Quick Review, 2009

    2009-01-01

    This article presents findings from a study that explores the nature of the Cyberethics, Cybersafety, and Cybersecurity (C3) educational awareness policies, initiatives, curriculum, and practices currently taking place in the U.S. public and private K-12 educational settings. The study establishes baseline data on C3 awareness, which can be used…

  5. Guidance on Port Biological Baseline Surveys (PBBS)

    Digital Repository Service at National Institute of Oceanography (India)

    Awad, A.; Haag, F.; Anil, A.C.; Abdulla, A.

    This publication has been prepared by GBP, IOI, CSIR-NIO and IUCN in order to serve as guidance to those who are planning to carry out a port biological baseline survey, in particular in the context of Ballast Water Management. It has been drafted...

  6. Solid Waste Program technical baseline description

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, A.B.

    1994-07-01

    The system engineering approach has been taken to describe the technical baseline under which the Solid Waste Program is currently operating. The document contains a mission analysis, function analysis, system definition, documentation requirements, facility and project bases, and uncertainties facing the program.

  7. Toward Baseline Software Anomalies in NASA Missions

    Science.gov (United States)

    Layman, Lucas; Zelkowitz, Marvin; Basili, Victor; Nikora, Allen P.

    2012-01-01

    In this fast abstract, we provide preliminary findings an analysis of 14,500 spacecraft anomalies from unmanned NASA missions. We provide some baselines for the distributions of software vs. non-software anomalies in spaceflight systems, the risk ratings of software anomalies, and the corrective actions associated with software anomalies.

  8. Physics Potential of Long-Baseline Experiments

    Directory of Open Access Journals (Sweden)

    Sanjib Kumar Agarwalla

    2014-01-01

    Full Text Available The discovery of neutrino mixing and oscillations over the past decade provides firm evidence for new physics beyond the Standard Model. Recently, θ13 has been determined to be moderately large, quite close to its previous upper bound. This represents a significant milestone in establishing the three-flavor oscillation picture of neutrinos. It has opened up exciting prospects for current and future long-baseline neutrino oscillation experiments towards addressing the remaining fundamental questions, in particular the type of the neutrino mass hierarchy and the possible presence of a CP-violating phase. Another recent and crucial development is the indication of non-maximal 2-3 mixing angle, causing the octant ambiguity of θ23. In this paper, I will review the phenomenology of long-baseline neutrino oscillations with a special emphasis on sub-leading three-flavor effects, which will play a crucial role in resolving these unknowns. First, I will give a brief description of neutrino oscillation phenomenon. Then, I will discuss our present global understanding of the neutrino mass-mixing parameters and will identify the major unknowns in this sector. After that, I will present the physics reach of current generation long-baseline experiments. Finally, I will conclude with a discussion on the physics capabilities of accelerator-driven possible future long-baseline precision oscillation facilities.

  9. Accelerated Best Basis Inventory Baselining Task

    International Nuclear Information System (INIS)

    SASAKI, L.M.

    2001-01-01

    The baselining effort was recently proposed to bring the Best-Basis Inventory (BBI) and Question No.8 of the Tank Interpretive Report (TIR) for all 177 tanks to the current standards and protocols and to prepare a TIR Question No.8 if one is not already available. This plan outlines the objectives and methodology of the accelerated BBI baselining task. BBI baselining meetings held during December 2000 resulted in a revised BBI methodology and an initial set of BBI creation rules to be used in the baselining effort. The objectives of the BBI baselining effort are to: (1) Provide inventories that are consistent with the revised BBI methodology and new BBI creation rules. (2) Split the total tank waste in each tank into six waste phases, as appropriate (Supernatant, saltcake solids, saltcake liquid, sludge solids, sludge liquid, and retained gas). In some tanks, the solids and liquid portions of the sludge and/or saltcake may be combined into a single sludge or saltcake phase. (3) Identify sampling events that are to be used for calculating the BBIs. (4) Update waste volumes for subsequent reconciliation with the Hanlon (2001) waste tank summary. (5) Implement new waste type templates. (6) Include any sample data that might have been unintentionally omitted in the previous BBI and remove any sample data that should not have been included. Sample data to be used in the BBI must be available on TWINS. (7) Ensure that an inventory value for each standard BBI analyte is provided for each waste component. Sample based inventories for supplemental BBI analytes will be included when available. (8) Provide new means and confidence interval reports if one is not already available and include uncertainties in reporting inventory values

  10. Mercury baseline levels in Flemish soils (Belgium)

    International Nuclear Information System (INIS)

    Tack, Filip M.G.; Vanhaesebroeck, Thomas; Verloo, Marc G.; Van Rompaey, Kurt; Ranst, Eric van

    2005-01-01

    It is important to establish contaminant levels that are normally present in soils to provide baseline data for pollution studies. Mercury is a toxic element of concern. This study was aimed at assessing baseline mercury levels in soils in Flanders. In a previous study, mercury contents in soils in Oost-Vlaanderen were found to be significantly above levels reported elsewhere. For the current study, observations were extended over two more provinces, West-Vlaanderen and Antwerpen. Ranges of soil Hg contents were distinctly higher in the province Oost-Vlaanderen (interquartile range from 0.09 to 0.43 mg/kg) than in the other provinces (interquartile ranges from 0.7 to 0.13 and 0.7 to 0.15 mg/kg for West-Vlaanderen and Antwerpen, respectively). The standard threshold method was applied to separate soils containing baseline levels of Hg from the data. Baseline concentrations for Hg were characterised by a median of 0.10 mg Hg/kg dry soil, an interquartile range from 0.07 to 0.14 mg/kg and a 90% percentile value of 0.30 mg/kg. The influence of soil properties such as clay and organic carbon contents, and pH on baseline Hg concentrations was not important. Maps of the spatial distribution of Hg levels showed that the province Oost-Vlaanderen exhibited zones with systematically higher Hg soil contents. This may be related to the former presence of many small-scale industries employing mercury in that region. - Increased mercury levels may reflect human activity

  11. Predicting Baseline for Analysis of Electricity Pricing

    Energy Technology Data Exchange (ETDEWEB)

    Kim, T. [Ulsan National Inst. of Science and Technology (Korea, Republic of); Lee, D. [Ulsan National Inst. of Science and Technology (Korea, Republic of); Choi, J. [Ulsan National Inst. of Science and Technology (Korea, Republic of); Spurlock, A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sim, A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wu, K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-03

    To understand the impact of new pricing structure on residential electricity demands, we need a baseline model that captures every factor other than the new price. The standard baseline is a randomized control group, however, a good control group is hard to design. This motivates us to devlop data-driven approaches. We explored many techniques and designed a strategy, named LTAP, that could predict the hourly usage years ahead. The key challenge in this process is that the daily cycle of electricity demand peaks a few hours after the temperature reaching its peak. Existing methods rely on the lagged variables of recent past usages to enforce this daily cycle. These methods have trouble making predictions years ahead. LTAP avoids this trouble by assuming the daily usage profile is determined by temperature and other factors. In a comparison against a well-designed control group, LTAP is found to produce accurate predictions.

  12. CASA Uno GPS orbit and baseline experiments

    Science.gov (United States)

    Schutz, B. E.; Ho, C. S.; Abusali, P. A. M.; Tapley, B. D.

    1990-01-01

    CASA Uno data from sites distributed in longitude from Australia to Europe have been used to determine orbits of the GPS satellites. The characteristics of the orbits determined from double difference phase have been evaluated through comparisons of two-week solutions with one-week solutions and by comparisons of predicted and estimated orbits. Evidence of unmodeled effects is demonstrated, particularly associated with the orbit planes that experience solar eclipse. The orbit accuracy has been assessed through the repeatability of unconstrained estimated baseline vectors ranging from 245 km to 5400 km. Both the baseline repeatability and the comparison with independent space geodetic methods give results at the level of 1-2 parts in 100,000,000. In addition, the Mojave/Owens Valley (245 km) and Kokee Park/Ft. Davis (5409 km) estimates agree with VLBI and SLR to better than 1 part in 100,000,000.

  13. Baseline composition of solar energetic particles

    International Nuclear Information System (INIS)

    Meyer, J.

    1985-01-01

    We analyze all existing spacecraft observations of the highly variable heavy element composition of solar energetic particles (SEP) during non- 3 He-rich events. All data show the imprint of an ever-present basic composition pattern (dubbed ''mass-unbiased baseline'' SEP composition) that differs from the photospheric composition by a simple bias related to first ionization potential (FIP). In each particular observation, this mass-unbiased baseline composition is being distorted by an additional bias, which is always a monotonic function of mass (or Z). This latter bias varies in amplitude and even sign from observation to observation. To first order, it seems related to differences in the A/Z* ratio between elements (Z* = mean effective charge)

  14. OCRWM baseline management procedure for document identifiers

    International Nuclear Information System (INIS)

    1993-03-01

    This procedure establishes a uniform numbering system (document identifier) for all Program and project technical, cost, and schedule baselines, and selected management and procurement documents developed for and controlled by the Office of Civilian Radioactive Waste Management (OCRWM) for the Civilian Radioactive Waste Management System (CRWMS). The document identifier defined in this procedure is structured to ensure that the relational integrity between configuration items (CIs) and their associated documentation and software is maintained, traceable, categorical, and retrievable for the life of the program

  15. Information Technology Sector Baseline Risk Assessment

    Science.gov (United States)

    2009-08-01

    alternative root be economically advantageous , an actor’s ability to exploit market forces and create an alternative root would be significantly improved...conduct their operations. Therefore, a loss or disruption to Internet services would not be advantageous for the desired outcomes of these syndicates.26... eCommerce Service loss or disruption [C] Traffic Redirection [C] = Undesired consequence Information Technology Sector Baseline Risk Assessment

  16. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  17. Baseline glucocorticoids are drivers of body mass gain in a diving seabird

    Science.gov (United States)

    Hennin, Holly; Berlin, Alicia; Love, Oliver P.

    2016-01-01

    Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic–pituitary–adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

  18. Baseline glucocorticoids are drivers of body mass gain in a diving seabird.

    Science.gov (United States)

    Hennin, Holly L; Wells-Berlin, Alicia M; Love, Oliver P

    2016-03-01

    Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic-pituitary-adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

  19. Base-line studies for DAE establishments

    International Nuclear Information System (INIS)

    Puranik, V.D.

    2012-01-01

    The Department of Atomic Energy has establishments located in various regions of the country and they include front-end fuel cycle facilities, nuclear power stations, back-end fuel cycle facilities and facilities for research and societal applications. These facilities handle naturally occurring radionuclides such as uranium, thorium and a variety of man-made radionuclides. These radionuclides are handled with utmost care so that they do not affect adversely the occupational workers or the members of public residing nearby. There is safety culture of the highest standard existing in all DAE establishments and it matches with the international standards. In addition, there is a perpetual environmental monitoring program carried out by the Environmental Survey Laboratories (ESLs) located at all DAE establishments. The environmental data generated by such program is studied regularly by experts to ensure compliance with the regulatory requirements. The regulatory requirements in the country are of international standards and ensure adequate protection of workers and members of public. In addition to such continued monitoring program and studies being carried out for the ongoing projects, base-line studies are carried out for all the new projects of the DAE. The purpose of the base-line studies is to establish a detailed base-line data set for a new DAE location well before the foundation stone is laid, so that the data collected when there is no departmental activity can be compared with the data generated later by the ESL. The data so generated is site specific and it varies from place to place depending upon the location of the site, e.g., inland or coastal, the presence of water bodies and pattern of irrigation, the geological characteristics of the location, the local culture and habits of the people, population density and urban or rural background. The data to be recorded as base-line data is generated over a period of at least one year covering all the seasons

  20. Pipeline integrity: ILI baseline data for QRA

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Todd R. [Tuboscope Pipeline Services, Houston, TX (United States)]. E-mail: tporter@varco.com; Silva, Jose Augusto Pereira da [Pipeway Engenharia, Rio de Janeiro, RJ (Brazil)]. E-mail: guto@pipeway.com; Marr, James [MARR and Associates, Calgary, AB (Canada)]. E-mail: jmarr@marr-associates.com

    2003-07-01

    The initial phase of a pipeline integrity management program (IMP) is conducting a baseline assessment of the pipeline system and segments as part of Quantitative Risk Assessment (QRA). This gives the operator's integrity team the opportunity to identify critical areas and deficiencies in the protection, maintenance, and mitigation strategies. As a part of data gathering and integration of a wide variety of sources, in-line inspection (ILI) data is a key element. In order to move forward in the integrity program development and execution, the baseline geometry of the pipeline must be determined with accuracy and confidence. From this, all subsequent analysis and conclusions will be derived. Tuboscope Pipeline Services (TPS), in conjunction with Pipeway Engenharia of Brazil, operate ILI inertial navigation system (INS) and Caliper geometry tools, to address this integrity requirement. This INS and Caliper ILI tool data provides pipeline trajectory at centimeter level resolution and sub-metre 3D position accuracy along with internal geometry - ovality, dents, misalignment, and wrinkle/buckle characterization. Global strain can be derived from precise INS curvature measurements and departure from the initial pipeline state. Accurate pipeline elevation profile data is essential in the identification of sag/over bend sections for fluid dynamic and hydrostatic calculations. This data, along with pipeline construction, operations, direct assessment and maintenance data is integrated in LinaViewPRO{sup TM}, a pipeline data management system for decision support functions, and subsequent QRA operations. This technology provides the baseline for an informed, accurate and confident integrity management program. This paper/presentation will detail these aspects of an effective IMP, and experience will be presented, showing the benefits for liquid and gas pipeline systems. (author)

  1. SRP Baseline Hydrogeologic Investigation, Phase 3

    Energy Technology Data Exchange (ETDEWEB)

    Bledsoe, H.W.

    1988-08-01

    The SRP Baseline Hydrogeologic Investigation was implemented for the purpose of updating and improving the knowledge and understanding of the hydrogeologic systems underlying the SRP site. Phase III, which is discussed in this report, includes the drilling of 7 deep coreholes (sites P-24 through P-30) and the installation of 53 observation wells ranging in depth from approximately 50 ft to more than 970 ft below the ground surface. In addition to the collection of geologic cores for lithologic and stratigraphic study, samples were also collected for the determination of physical characteristics of the sediments and for the identification of microorganisms.

  2. Environmental Baseline File for National Transportation

    International Nuclear Information System (INIS)

    1999-01-01

    This Environmental Baseline File summarizes and consolidates information related to the national-level transportation of commercial spent nuclear fuel. Topics address include: shipments of commercial spent nuclear fuel based on mostly truck and mostly rail shipping scenarios; transportation routing for commercial spent nuclear fuel sites and DOE sites; radionuclide inventories for various shipping container capacities; transportation routing; populations along transportation routes; urbanized area population densities; the impacts of historical, reasonably foreseeable, and general transportation; state-level food transfer factors; Federal Guidance Report No. 11 and 12 radionuclide dose conversion factors; and national average atmospheric conditions

  3. Baseline-dependent averaging in radio interferometry

    Science.gov (United States)

    Wijnholds, S. J.; Willis, A. G.; Salvini, S.

    2018-05-01

    This paper presents a detailed analysis of the applicability and benefits of baseline-dependent averaging (BDA) in modern radio interferometers and in particular the Square Kilometre Array. We demonstrate that BDA does not affect the information content of the data other than a well-defined decorrelation loss for which closed form expressions are readily available. We verify these theoretical findings using simulations. We therefore conclude that BDA can be used reliably in modern radio interferometry allowing a reduction of visibility data volume (and hence processing costs for handling visibility data) by more than 80 per cent.

  4. Spectrometer Baseline Control Via Spatial Filtering

    Science.gov (United States)

    Burleigh, M. R.; Richey, C. R.; Rinehart, S. A.; Quijada, M. A.; Wollack, E. J.

    2016-01-01

    An absorptive half-moon aperture mask is experimentally explored as a broad-bandwidth means of eliminating spurious spectral features arising from reprocessed radiation in an infrared Fourier transform spectrometer. In the presence of the spatial filter, an order of magnitude improvement in the fidelity of the spectrometer baseline is observed. The method is readily accommodated within the context of commonly employed instrument configurations and leads to a factor of two reduction in optical throughput. A detailed discussion of the underlying mechanism and limitations of the method are provided.

  5. Neutrino physics with short baseline experiments

    International Nuclear Information System (INIS)

    Zimmerman, E.D.

    2006-01-01

    Neutrino physics with low- to medium-energy beams has progressed steadily over the last several years. Neutrino oscillation searches at short baseline (defined as 2 - -> 0.1eV 2 . One positive signal, from the LSND collaboration, exists and is being tested by the MiniBooNE experiment. Neutrino cross-section measurements are being made by MiniBooNE and K2K, which will be important for reducing systematic errors in present and future oscillation measurements. In the near future, dedicated cross- section experiments will begin operating at Fermilab. (author)

  6. Rationing in the presence of baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter

    2013-01-01

    We analyze a general model of rationing in which agents have baselines, in addition to claims against the (insufficient) endowment of the good to be allocated. Many real-life problems fit this general model (e.g., bankruptcy with prioritized claims, resource allocation in the public health care...... sector, water distribution in drought periods). We introduce (and characterize) a natural class of allocation methods for this model. Any method within the class is associated with a rule in the standard rationing model, and we show that if the latter obeys some focal properties, the former obeys them...

  7. Baseline scenarios of global environmental change

    International Nuclear Information System (INIS)

    Alcamo, J.; Kreileman, G.J.J.; Bollen, J.C.; Born, G.J. van den; Krol, M.S.; Toet, A.M.C.; Vries, H.J.M. de; Gerlagh, R.

    1996-01-01

    This paper presents three baseline scenarios of no policy action computed by the IMAGE2 model. These scenarios cover a wide range of coupled global change indicators, including: energy demand and consumption; food demand, consumption, and production; changes in land cover including changes in extent of agricultural land and forest; emissions of greenhouse gases and ozone precursors; and climate change and its impacts on sea level rise, crop productivity and natural vegetation. Scenario information is available for the entire world with regional and grid scale detail, and covers from 1970 to 2100. (author)

  8. SRP baseline hydrogeologic investigation: Aquifer characterization

    Energy Technology Data Exchange (ETDEWEB)

    Strom, R.N.; Kaback, D.S.

    1992-03-31

    An investigation of the mineralogy and chemistry of the principal hydrogeologic units and the geochemistry of the water in the principal aquifers at Savannah River Site (SRS) was undertaken as part of the Baseline Hydrogeologic Investigation. This investigation was conducted to provide background data for future site studies and reports and to provide a site-wide interpretation of the geology and geochemistry of the Coastal Plain Hydrostratigraphic province. Ground water samples were analyzed for major cations and anions, minor and trace elements, gross alpha and beta, tritium, stable isotopes of hydrogen, oxygen, and carbon, and carbon-14. Sediments from the well borings were analyzed for mineralogy and major and minor elements.

  9. Analysis of baseline gene expression levels from ...

    Science.gov (United States)

    The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in gene expression. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selectiv

  10. Structure of a traditional baseline data system

    Energy Technology Data Exchange (ETDEWEB)

    1976-12-01

    Research was conducted to determine whether appropriate data exist for the development of a comprehensive statistical baseline data system on the human environment in the Athabasca oil sands region of Alberta. The existing data sources pertinent to the target area were first reviewed and discussed. Criteria were selected to assist the evaluation of data, including type of data collected, source, degree of detail, geographic identification, accessibility, and time frame. These criteria allowed assessing whether the data would be amenable to geographically-coded, continuous monitoring systems. It was found that the Statistics Canada Census provided the most detail, the most complete coverage of the target area, the smallest statistical areas, the greatest consistency in data and data collection, and the most regular collection. The local agency collection efforts were generally oriented toward specific goals and the data intended primarily for intra-agency use. The smallest statistical units in these efforts may be too large to be of value to a common small-area system, and data collection agencies did not generally use coterminous boundaries. Recommendations were made to give primary consideration to Statistics Canada data in the initial development of the baseline data system. Further development of such a system depends on the adoption by local agencies of a common small-area system for data collection. 38 refs., 6 figs.

  11. Long-baseline neutrino oscillation experiments

    International Nuclear Information System (INIS)

    Crane, D.; Goodman, M.

    1994-01-01

    There is no unambiguous definition for long baseline neutrino oscillation experiments. The term is generally used for accelerator neutrino oscillation experiments which are sensitive to Δm 2 2 , and for which the detector is not on the accelerator site. The Snowmass N2L working group met to discuss the issues facing such experiments. The Fermilab Program Advisory Committee adopted several recommendations concerning the Fermilab neutrino program at their Aspen meeting immediately prior to the Snowmass Workshop. This heightened the attention for the proposals to use Fermilab for a long-baseline neutrino experiment at the workshop. The plan for a neutrino oscillation program at Brookhaven was also thoroughly discussed. Opportunities at CERN were considered, particularly the use of detectors at the Gran Sasso laboratory. The idea to build a neutrino beam from KEK towards Superkamiokande was not discussed at the Snowmass meeting, but there has been considerable development of this idea since then. Brookhaven and KEK would use low energy neutrino beams, while FNAL and CERN would plan have medium energy beams. This report will summarize a few topics common to LBL proposals and attempt to give a snapshot of where things stand in this fast developing field

  12. Baseline response rates affect resistance to change.

    Science.gov (United States)

    Kuroda, Toshikazu; Cook, James E; Lattal, Kennon A

    2018-01-01

    The effect of response rates on resistance to change, measured as resistance to extinction, was examined in two experiments. In Experiment 1, responding in transition from a variable-ratio schedule and its yoked-interval counterpart to extinction was compared with pigeons. Following training on a multiple variable-ratio yoked-interval schedule of reinforcement, in which response rates were higher in the former component, reinforcement was removed from both components during a single extended extinction session. Resistance to extinction in the yoked-interval component was always either greater or equal to that in the variable-ratio component. In Experiment 2, resistance to extinction was compared for two groups of rats that exhibited either high or low response rates when maintained on identical variable-interval schedules. Resistance to extinction was greater for the lower-response-rate group. These results suggest that baseline response rate can contribute to resistance to change. Such effects, however, can only be revealed when baseline response rate and reinforcement rate are disentangled (Experiments 1 and 2) from the more usual circumstance where the two covary. Furthermore, they are more cleanly revealed when the programmed contingencies controlling high and low response rates are identical, as in Experiment 2. © 2017 Society for the Experimental Analysis of Behavior.

  13. Baseline Estimation and Outlier Identification for Halocarbons

    Science.gov (United States)

    Wang, D.; Schuck, T.; Engel, A.; Gallman, F.

    2017-12-01

    The aim of this paper is to build a baseline model for halocarbons and to statistically identify the outliers under specific conditions. In this paper, time series of regional CFC-11 and Chloromethane measurements was discussed, which taken over the last 4 years at two locations, including a monitoring station at northwest of Frankfurt am Main (Germany) and Mace Head station (Ireland). In addition to analyzing time series of CFC-11 and Chloromethane, more importantly, a statistical approach of outlier identification is also introduced in this paper in order to make a better estimation of baseline. A second-order polynomial plus harmonics are fitted to CFC-11 and chloromethane mixing ratios data. Measurements with large distance to the fitting curve are regard as outliers and flagged. Under specific requirement, the routine is iteratively adopted without the flagged measurements until no additional outliers are found. Both model fitting and the proposed outlier identification method are realized with the help of a programming language, Python. During the period, CFC-11 shows a gradual downward trend. And there is a slightly upward trend in the mixing ratios of Chloromethane. The concentration of chloromethane also has a strong seasonal variation, mostly due to the seasonal cycle of OH. The usage of this statistical method has a considerable effect on the results. This method efficiently identifies a series of outliers according to the standard deviation requirements. After removing the outliers, the fitting curves and trend estimates are more reliable.

  14. Baseline Response Levels Are a Nuisance in Infant Contingency Learning

    Science.gov (United States)

    Millar, W. S.; Weir, Catherine

    2015-01-01

    The impact of differences in level of baseline responding on contingency learning in the first year was examined by considering the response acquisition of infants classified into baseline response quartiles. Whereas the three lower baseline groups showed the predicted increment in responding to a contingency, the highest baseline responders did…

  15. 33 CFR 2.20 - Territorial sea baseline.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Territorial sea baseline. 2.20... JURISDICTION Jurisdictional Terms § 2.20 Territorial sea baseline. Territorial sea baseline means the line.... Normally, the territorial sea baseline is the mean low water line along the coast of the United States...

  16. The WITCH Model. Structure, Baseline, Solutions.

    Energy Technology Data Exchange (ETDEWEB)

    Bosetti, V.; Massetti, E.; Tavoni, M.

    2007-07-01

    WITCH - World Induced Technical Change Hybrid - is a regionally disaggregated hard link hybrid global model with a neoclassical optimal growth structure (top down) and an energy input detail (bottom up). The model endogenously accounts for technological change, both through learning curves affecting prices of new vintages of capital and through R and D investments. The model features the main economic and environmental policies in each world region as the outcome of a dynamic game. WITCH belongs to the class of Integrated Assessment Models as it possesses a climate module that feeds climate changes back into the economy. In this paper we provide a thorough discussion of the model structure and baseline projections. We report detailed information on the evolution of energy demand, technology and CO2 emissions. Finally, we explicitly quantifiy the role of free riding in determining the emissions scenarios. (auth)

  17. Global Nuclear Energy Partnership Waste Treatment Baseline

    International Nuclear Information System (INIS)

    Gombert, Dirk; Ebert, William; Marra, James; Jubin, Robert; Vienna, John

    2008-01-01

    The Global Nuclear Energy Partnership (GNEP) program is designed to demonstrate that a proliferation-resistant and sustainable integrated nuclear fuel cycle can be commercialized and used internationally. Alternative stabilization concepts for byproducts and waste streams generated by fuel recycling processes were evaluated and a baseline set of waste forms was recommended for the safe disposition of waste streams. Specific waste forms are recommended based on the demonstrated or expected commercial practicability and technical maturity of the processes needed to make the waste forms, and expected performance of the waste form materials when disposed. Significant issues remain in developing technologies to process some of the wastes into the recommended waste forms, and a detailed analysis of technology readiness may lead to the choice of a different waste form than what is recommended herein. Evolving regulations could also affect the selection of waste forms. (authors)

  18. In-Space Manufacturing Baseline Property Development

    Science.gov (United States)

    Stockman, Tom; Schneider, Judith; Prater, Tracie; Bean, Quincy; Werkheiser, Nicki

    2016-01-01

    The In-Space Manufacturing (ISM) project at NASA Marshall Space Flight Center currently operates a 3D FDM (fused deposition modeling) printer onboard the International Space Station. In order to enable utilization of this capability by designer, the project needs to establish characteristic material properties for materials produced using the process. This is difficult for additive manufacturing since standards and specifications do not yet exist for these technologies. Due to availability of crew time, there are limitations to the sample size which in turn limits the application of the traditional design allowables approaches to develop a materials property database for designers. In this study, various approaches to development of material databases were evaluated for use by designers of space systems who wish to leverage in-space manufacturing capabilities. This study focuses on alternative statistical techniques for baseline property development to support in-space manufacturing.

  19. Global Nuclear Energy Partnership Waste Treatment Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Gombert, Dirk; Ebert, William; Marra, James; Jubin, Robert; Vienna, John [Idaho National laboratory, 2525 Fremont Ave., Idaho Falls, ID 83402 (United States)

    2008-07-01

    The Global Nuclear Energy Partnership (GNEP) program is designed to demonstrate that a proliferation-resistant and sustainable integrated nuclear fuel cycle can be commercialized and used internationally. Alternative stabilization concepts for byproducts and waste streams generated by fuel recycling processes were evaluated and a baseline set of waste forms was recommended for the safe disposition of waste streams. Specific waste forms are recommended based on the demonstrated or expected commercial practicability and technical maturity of the processes needed to make the waste forms, and expected performance of the waste form materials when disposed. Significant issues remain in developing technologies to process some of the wastes into the recommended waste forms, and a detailed analysis of technology readiness may lead to the choice of a different waste form than what is recommended herein. Evolving regulations could also affect the selection of waste forms. (authors)

  20. Global Nuclear Energy Partnership Waste Treatment Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Dirk Gombert; William Ebert; James Marra; Robert Jubin; John Vienna

    2008-05-01

    The Global Nuclear Energy Partnership program (GNEP) is designed to demonstrate a proliferation-resistant and sustainable integrated nuclear fuel cycle that can be commercialized and used internationally. Alternative stabilization concepts for byproducts and waste streams generated by fuel recycling processes were evaluated and a baseline of waste forms was recommended for the safe disposition of waste streams. Waste forms are recommended based on the demonstrated or expected commercial practicability and technical maturity of the processes needed to make the waste forms, and performance of the waste form materials when disposed. Significant issues remain in developing technologies to process some of the wastes into the recommended waste forms, and a detailed analysis of technology readiness and availability may lead to the choice of a different waste form than what is recommended herein. Evolving regulations could also affect the selection of waste forms.

  1. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  2. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  3. 40 CFR 80.915 - How are the baseline toxics value and baseline toxics volume determined?

    Science.gov (United States)

    2010-07-01

    ... baseline toxics value if it can determine an applicable toxics value for every batch of gasoline produced... of gasoline batch i produced or imported between January 1, 1998 and December 31, 2000, inclusive. i = Individual batch of gasoline produced or imported between January 1, 1998 and December 31, 2000, inclusive. n...

  4. Pakistan, Sindh Province - Baseline Indicators System : Baseline Procurement Performance Assessment Report

    OpenAIRE

    World Bank

    2009-01-01

    This document provides an assessment of the public procurement system in Sindh province using the baseline indicators system developed by the Development Assistance Committee of the Organization for Economic Cooperation and Development (OECD-DAC). This assessment, interviews and discussions were held with stakeholders from the public and private sectors as well as civil society. Developing...

  5. The London low emission zone baseline study.

    Science.gov (United States)

    Kelly, Frank; Armstrong, Ben; Atkinson, Richard; Anderson, H Ross; Barratt, Ben; Beevers, Sean; Cook, Derek; Green, Dave; Derwent, Dick; Mudway, Ian; Wilkinson, Paul

    2011-11-01

    On February 4, 2008, the world's largest low emission zone (LEZ) was established. At 2644 km2, the zone encompasses most of Greater London. It restricts the entry of the oldest and most polluting diesel vehicles, including heavy-goods vehicles (haulage trucks), buses and coaches, larger vans, and minibuses. It does not apply to cars or motorcycles. The LEZ scheme will introduce increasingly stringent Euro emissions standards over time. The creation of this zone presented a unique opportunity to estimate the effects of a stepwise reduction in vehicle emissions on air quality and health. Before undertaking such an investigation, robust baseline data were gathered on air quality and the oxidative activity and metal content of particulate matter (PM) from air pollution monitors located in Greater London. In addition, methods were developed for using databases of electronic primary-care records in order to evaluate the zone's health effects. Our study began in 2007, using information about the planned restrictions in an agreed-upon LEZ scenario and year-on-year changes in the vehicle fleet in models to predict air pollution concentrations in London for the years 2005, 2008, and 2010. Based on this detailed emissions and air pollution modeling, the areas in London were then identified that were expected to show the greatest changes in air pollution concentrations and population exposures after the implementation of the LEZ. Using these predictions, the best placement of a pollution monitoring network was determined and the feasibility of evaluating the health effects using electronic primary-care records was assessed. To measure baseline pollutant concentrations before the implementation of the LEZ, a comprehensive monitoring network was established close to major roadways and intersections. Output-difference plots from statistical modeling for 2010 indicated seven key areas likely to experience the greatest change in concentrations of nitrogen dioxide (NO2) (at least 3

  6. Camera Trajectory fromWide Baseline Images

    Science.gov (United States)

    Havlena, M.; Torii, A.; Pajdla, T.

    2008-09-01

    Camera trajectory estimation, which is closely related to the structure from motion computation, is one of the fundamental tasks in computer vision. Reliable camera trajectory estimation plays an important role in 3D reconstruction, self localization, and object recognition. There are essential issues for a reliable camera trajectory estimation, for instance, choice of the camera and its geometric projection model, camera calibration, image feature detection and description, and robust 3D structure computation. Most of approaches rely on classical perspective cameras because of the simplicity of their projection models and ease of their calibration. However, classical perspective cameras offer only a limited field of view, and thus occlusions and sharp camera turns may cause that consecutive frames look completely different when the baseline becomes longer. This makes the image feature matching very difficult (or impossible) and the camera trajectory estimation fails under such conditions. These problems can be avoided if omnidirectional cameras, e.g. a fish-eye lens convertor, are used. The hardware which we are using in practice is a combination of Nikon FC-E9 mounted via a mechanical adaptor onto a Kyocera Finecam M410R digital camera. Nikon FC-E9 is a megapixel omnidirectional addon convertor with 180° view angle which provides images of photographic quality. Kyocera Finecam M410R delivers 2272×1704 images at 3 frames per second. The resulting combination yields a circular view of diameter 1600 pixels in the image. Since consecutive frames of the omnidirectional camera often share a common region in 3D space, the image feature matching is often feasible. On the other hand, the calibration of these cameras is non-trivial and is crucial for the accuracy of the resulting 3D reconstruction. We calibrate omnidirectional cameras off-line using the state-of-the-art technique and Mičušík's two-parameter model, that links the radius of the image point r to the

  7. Integrating risk management into the baselining process

    International Nuclear Information System (INIS)

    Jennett, N.; Tonkinson, A.

    1994-01-01

    These processes work together in building the project (comprised of the technical, schedule, and cost baselines) against which performance is measured and changes to the scope, schedule and cost of a project are managed and controlled. Risk analysis is often performed as the final element of the scheduling or estimating processes, a precursor to establishing cost and schedule contingency. However, best business practices dictate that information that may be crucial to the success of a project be analyzed and incorporated into project planning as soon as it is available and usable. The purpose or risk management is not to eliminate risk. Neither is it intended to suggest wholesale re-estimating and re-scheduling of a project. Rather, the intent is to make provisions to reduce and control the schedule and/or cost ramifications of risk by anticipating events and conditions that cannot be reliably planned for and which have the potential to negatively impact accomplishment of the technical objectives and requirements of the project

  8. Shifting environmental baselines in the Red Sea.

    Science.gov (United States)

    Price, A R G; Ghazi, S J; Tkaczynski, P J; Venkatachalam, A J; Santillan, A; Pancho, T; Metcalfe, R; Saunders, J

    2014-01-15

    The Red Sea is among the world's top marine biodiversity hotspots. We re-examined coastal ecosystems at sites surveyed during the 1980s using the same methodology. Coral cover increased significantly towards the north, mirroring the reverse pattern for mangroves and other sedimentary ecosystems. Latitudinal patterns are broadly consistent across both surveys and with results from independent studies. Coral cover showed greatest change, declining significantly from a median score of 4 (1000-9999 m(2)) to 2 (10-99m(2)) per quadrat in 2010/11. This may partly reflect impact from coastal construction, which was evident at 40% of sites and has significantly increased in magnitude over 30 years. Beach oil has significantly declined, but shore debris has increased significantly. Although substantial, levels are lower than at some remote ocean atolls. While earlier reports have suggested that the Red Sea is generally healthy, shifting environmental baselines are evident from the current study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Regional geochemical baselines for Portuguese shelf sediments

    International Nuclear Information System (INIS)

    Mil-Homens, M.; Stevens, R.L.; Cato, I.; Abrantes, F.

    2007-01-01

    Metal concentrations (Al, Cr, Cu, Ni, Pb and Zn) from the DGM-INETI archive data set have been examined for sediments collected during the 1970s from 267 sites on the Portuguese shelf. Due to the differences in the oceanographic and sedimentological settings between western and Algarve coasts, the archive data set is split in two segments. For both shelf segments, regional geochemical baselines (RGB) are defined using aluminium as a reference element. Seabed samples recovered in 2002 from four distinct areas of the Portuguese shelf are superimposed on these models to identify and compare possible metal enrichments relative to the natural distribution. Metal enrichments associated with anthropogenic influences are identified in three samples collected nearby the Tejo River and are characterised by the highest enrichment factors (EF; EF Pb Zn < 4). EF values close to 1 suggest a largely natural origin for metal distributions in sediments from the other areas included in the study. - Background metal concentrations and their natural variability must be established before assessing anthropogenic impacts

  10. Arc melter demonstration baseline test results

    International Nuclear Information System (INIS)

    Soelberg, N.R.; Chambers, A.G.; Anderson, G.L.; Oden, L.L.; O'Connor, W.K.; Turner, P.C.

    1994-07-01

    This report describes the test results and evaluation for the Phase 1 (baseline) arc melter vitrification test series conducted for the Buried Waste Integrated Demonstration program (BWID). Phase 1 tests were conducted on surrogate mixtures of as-incinerated wastes and soil. Some buried wastes, soils, and stored wastes at the INEL and other DOE sites, are contaminated with transuranic (TRU) radionuclides and hazardous organics and metals. The high temperature environment in an electric arc furnace may be used to process these wastes to produce materials suitable for final disposal. An electric arc furnace system can treat heterogeneous wastes and contaminated soils by (a) dissolving and retaining TRU elements and selected toxic metals as oxides in the slag phase, (b) destroying organic materials by dissociation, pyrolyzation, and combustion, and (c) capturing separated volatilized metals in the offgas system for further treatment. Structural metals in the waste may be melted and tapped separately for recycle or disposal, or these metals may be oxidized and dissolved into the slag. The molten slag, after cooling, will provide a glass/ceramic final waste form that is homogeneous, highly nonleachable, and extremely durable. These features make this waste form suitable for immobilization of TRU radionuclides and toxic metals for geologic timeframes. Further, the volume of contaminated wastes and soils will be substantially reduced in the process

  11. Cryogenics Testbed Laboratory Flange Baseline Configuration

    Science.gov (United States)

    Acuna, Marie Lei Ysabel D.

    2013-01-01

    As an intern at Kennedy Space Center (KSC), I was involved in research for the Fluids and Propulsion Division of the NASA Engineering (NE) Directorate. I was immersed in the Integrated Ground Operations Demonstration Units (IGODU) project for the majority of my time at KSC, primarily with the Ground Operations Demonstration Unit Liquid Oxygen (GODU L02) branch of IGODU. This project was established to develop advancements in cryogenic systems as a part of KSC's Advanced Exploration Systems (AES) program. The vision of AES is to develop new approaches for human exploration, and operations in and beyond low Earth orbit. Advanced cryogenic systems are crucial to minimize the consumable losses of cryogenic propellants, develop higher performance launch vehicles, and decrease operations cost for future launch programs. During my internship, I conducted a flange torque tracking study that established a baseline configuration for the flanges in the Simulated Propellant Loading System (SPLS) at the KSC Cryogenics Test Laboratory (CTL) - the testing environment for GODU L02.

  12. Gated integrator with signal baseline subtraction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.

    1996-12-17

    An ultrafast, high precision gated integrator includes an opamp having differential inputs. A signal to be integrated is applied to one of the differential inputs through a first input network, and a signal indicative of the DC offset component of the signal to be integrated is applied to the other of the differential inputs through a second input network. A pair of electronic switches in the first and second input networks define an integrating period when they are closed. The first and second input networks are substantially symmetrically constructed of matched components so that error components introduced by the electronic switches appear symmetrically in both input circuits and, hence, are nullified by the common mode rejection of the integrating opamp. The signal indicative of the DC offset component is provided by a sample and hold circuit actuated as the integrating period begins. The symmetrical configuration of the integrating circuit improves accuracy and speed by balancing out common mode errors, by permitting the use of high speed switching elements and high speed opamps and by permitting the use of a small integrating time constant. The sample and hold circuit substantially eliminates the error caused by the input signal baseline offset during a single integrating window. 5 figs.

  13. Gated integrator with signal baseline subtraction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xucheng (Lisle, IL)

    1996-01-01

    An ultrafast, high precision gated integrator includes an opamp having differential inputs. A signal to be integrated is applied to one of the differential inputs through a first input network, and a signal indicative of the DC offset component of the signal to be integrated is applied to the other of the differential inputs through a second input network. A pair of electronic switches in the first and second input networks define an integrating period when they are closed. The first and second input networks are substantially symmetrically constructed of matched components so that error components introduced by the electronic switches appear symmetrically in both input circuits and, hence, are nullified by the common mode rejection of the integrating opamp. The signal indicative of the DC offset component is provided by a sample and hold circuit actuated as the integrating period begins. The symmetrical configuration of the integrating circuit improves accuracy and speed by balancing out common mode errors, by permitting the use of high speed switching elements and high speed opamps and by permitting the use of a small integrating time constant. The sample and hold circuit substantially eliminates the error caused by the input signal baseline offset during a single integrating window.

  14. LTC vacuum blasting machine (concrete): Baseline report

    International Nuclear Information System (INIS)

    1997-01-01

    The LTC shot blast technology was tested and is being evaluated at Florida International University (FIU) as a baseline technology. In conjunction with FIU's evaluation of efficiency and cost, this report covers the evaluation conducted for safety and health issues. It is a commercially available technology and has been used for various projects at locations throughout the country. The LTC 1073 Vacuum Blasting Machine uses a high-capacity, direct-pressure blasting system which incorporates a continuous feed for the blast media. The blast media cleans the surface within the contained brush area of the blast. It incorporates a vacuum system which removes dust and debris from the surface as it is blasted. The safety and health evaluation during the testing demonstration focused on two main areas of exposure: dust and noise. Dust exposure during maintenance activities was minimal, but due to mechanical difficulties dust monitoring could not be conducted during operation. Noise exposure was significant. Further testing for each of these exposures is recommended because of the outdoor environment where the testing demonstration took place. This may cause the results to be inaccurate. It is feasible that the dust and noise levels will be higher in an enclosed environment. In addition, other safety and health issues found were ergonomics, heat stress, tripping hazards, electrical hazards, lockout/tagout, and arm-hand vibration

  15. FAIR - Baseline technical report. Executive summary

    International Nuclear Information System (INIS)

    Gutbrod, H.H.; Augustin, I.; Eickhoff, H.; Gross, K.D.; Henning, W.F.; Kraemer, D.; Walter, G.

    2006-09-01

    This document presents the Executive Summary, the first of six volumes comprising the 2006 Baseline Technical Report (BTR) for the international FAIR project (Facility for Antiproton and Ion Research). The BTR provides the technical description, cost, schedule, and assessments of risk for the proposed new facility. The purpose of the BTR is to provide a reliable basis for the construction, commissioning and operation of FAIR. The BTR is one of the central documents requested by the FAIR International Steering Committee (ISC) and its working groups, in order to prepare the legal process and the decisions on the construction and operation of FAIR in an international framework. It provides the technical basis for legal contracts on contributions to be made by, so far, 13 countries within the international FAIR Consortium. The BTR begins with this extended Executive Summary as Volume 1, which is also intended for use as a stand-alone document. The Executive Summary provides brief summaries of the accelerator facilities, the scientific programs and experimental stations, civil construction and safety, and of the workproject structure, costs and schedule. (orig.)

  16. Pentek metal coating removal system: Baseline report

    International Nuclear Information System (INIS)

    1997-01-01

    The Pentek coating removal technology was tested and is being evaluated at Florida International University (FIU) as a baseline technology. In conjunction with FIU's evaluation of efficiency and cost, this report covers evaluation conducted for safety and health issues. It is a commercially available technology and has been used for various projects at locations throughout the country. The Pentek coating removal system consisted of the ROTO-PEEN Scaler, CORNER-CUTTER reg-sign, and VAC-PAC reg-sign. They are designed to remove coatings from steel, concrete, brick, and wood. The Scaler uses 3M Roto Peen tungsten carbide cutters while the CORNER-CUTTER reg-sign uses solid needles for descaling activities. These hand tools are used with the VAC-PAC reg-sign vacuum system to capture dust and debris as removal of the coating takes place. The safety and health evaluation during the testing demonstration focused on two main areas of exposure: dust and noise. Dust exposure minimal, but noise exposure was significant. Further testing for each exposure is recommended because of the environment where the testing demonstration took place. It is feasible that the dust and noise levels will be higher in an enclosed operating environment of different construction. In addition, other areas of concern found were arm-hand vibration, whole-body, ergonomics, heat stress, tripping hazards, electrical hazards, machine guarding, and lockout/tagout

  17. Nonintrusive methodology for wellness baseline profiling

    Science.gov (United States)

    Chung, Danny Wen-Yaw; Tsai, Yuh-Show; Miaou, Shaou-Gang; Chang, Walter H.; Chang, Yaw-Jen; Chen, Shia-Chung; Hong, Y. Y.; Chyang, C. S.; Chang, Quan-Shong; Hsu, Hon-Yen; Hsu, James; Yao, Wei-Cheng; Hsu, Ming-Sin; Chen, Ming-Chung; Lee, Shi-Chen; Hsu, Charles; Miao, Lidan; Byrd, Kenny; Chouikha, Mohamed F.; Gu, Xin-Bin; Wang, Paul C.; Szu, Harold

    2007-04-01

    We develop an accumulatively effective and affordable set of smart pair devices to save the exuberant expenditure for the healthcare of aging population, which will not be sustainable when all the post-war baby boomers retire (78 millions will cost 1/5~1/4 GDP in US alone). To design an accessible test-bed for distributed points of homecare, we choose two exemplars of the set to demonstrate the possibility of translation of modern military and clinical know-how, because two exemplars share identically the noninvasive algorithm adapted to the Smart Sensor-pairs for the real world persistent surveillance. Currently, the standard diagnoses for malignant tumors and diabetes disorders are blood serum tests, X-ray CAT scan, and biopsy used sometime in the physical checkup by physicians as cohort-average wellness baselines. The loss of the quality of life in making second careers productive may be caused by the missing of timeliness for correct diagnoses and easier treatments, which contributes to the one quarter of human errors generating the lawsuits against physicians and hospitals, which further escalates the insurance cost and wasteful healthcare expenditure. Such a vicious cycle should be entirely eliminated by building an "individual diagnostic aids (IDA)," similar to the trend of personalized drug, developed from daily noninvasive intelligent databases of the "wellness baseline profiling (WBP)". Since our physiology state undulates diurnally, the Nyquist anti-aliasing theory dictates a minimum twice-a-day sampling of the WBP for the IDA, which must be made affordable by means of noninvasive, unsupervised and unbiased methodology at the convenience of homes. Thus, a pair of military infrared (IR) spectral cameras has been demonstrated for the noninvasive spectrogram ratio test of the spontaneously emitted thermal radiation from a normal human body at 37°C temperature. This invisible self-emission spreads from 3 microns to 12 microns of the radiation wavelengths

  18. 100-D Area technical baseline report

    International Nuclear Information System (INIS)

    Carpenter, R.W.

    1993-01-01

    This document is prepared in support of the 100 Area Environmental Restoration activity at the US Department of Energy's Hanford Site near Richland, Washington. It provides a technical baseline of waste sites located at the 100-D Area. The report is based on an environmental investigation undertaken by the Westinghouse Hanford Company (WHC) History Office in support of the Environmental Restoration Engineering Function and on review and evaluation of numerous Hanford Site current and historical reports, drawings, and photographs, supplemented by site inspections and employee interviews. No intrusive field investigation or sampling was conducted. All Hanford coordinate locations are approximate locations taken from several different maps and drawings of the 100-D Area. Every effort was made to derive coordinate locations for the center of each facility or waste site, except where noted, using standard measuring devices. Units of measure are shown as they appear in reference documents. The 100-D Area is made up of three operable units: 100-DR-1, 100-DR-2, and 100-DR-3. All three are addressed in this report. These operable units include liquid and solid waste disposal sites in the vicinity of, and related to, the 100-D and 100-DR Reactors. A fourth operable unit, 100-HR-3, is concerned with groundwater and is not addressed here. This report describes waste sites which include cribs, trenches, pits, french drains, retention basins, solid waste burial grounds, septic tanks, and drain fields. Each waste site is described separately and photographs are provided where available. A complete list of photographs can be found in Appendix A. A comprehensive environmental summary is not provided here but may be found in Hanford Site National Environmental Policy Act Characterization (Cushing 1988), which describes the geology and soils, meteorology, hydrology, land use, population, and air quality of the area

  19. Baseline Architecture of ITER Control System

    Science.gov (United States)

    Wallander, A.; Di Maio, F.; Journeaux, J.-Y.; Klotz, W.-D.; Makijarvi, P.; Yonekawa, I.

    2011-08-01

    The control system of ITER consists of thousands of computers processing hundreds of thousands of signals. The control system, being the primary tool for operating the machine, shall integrate, control and coordinate all these computers and signals and allow a limited number of staff to operate the machine from a central location with minimum human intervention. The primary functions of the ITER control system are plant control, supervision and coordination, both during experimental pulses and 24/7 continuous operation. The former can be split in three phases; preparation of the experiment by defining all parameters; executing the experiment including distributed feed-back control and finally collecting, archiving, analyzing and presenting all data produced by the experiment. We define the control system as a set of hardware and software components with well defined characteristics. The architecture addresses the organization of these components and their relationship to each other. We distinguish between physical and functional architecture, where the former defines the physical connections and the latter the data flow between components. In this paper, we identify the ITER control system based on the plant breakdown structure. Then, the control system is partitioned into a workable set of bounded subsystems. This partition considers at the same time the completeness and the integration of the subsystems. The components making up subsystems are identified and defined, a naming convention is introduced and the physical networks defined. Special attention is given to timing and real-time communication for distributed control. Finally we discuss baseline technologies for implementing the proposed architecture based on analysis, market surveys, prototyping and benchmarking carried out during the last year.

  20. 1993 baseline solid waste management system description

    International Nuclear Information System (INIS)

    Armacost, L.L.; Fowler, R.A.; Konynenbelt, H.S.

    1994-02-01

    Pacific Northwest Laboratory has prepared this report under the direction of Westinghouse Hanford Company. The report provides an integrated description of the system planned for managing Hanford's solid low-level waste, low-level mixed waste, transuranic waste, and transuranic mixed waste. The primary purpose of this document is to illustrate a collective view of the key functions planned at the Hanford Site to handle existing waste inventories, as well as solid wastes that will be generated in the future. By viewing this system as a whole rather than as individual projects, key facility interactions and requirements are identified and a better understanding of the overall system may be gained. The system is described so as to form a basis for modeling the system at various levels of detail. Model results provide insight into issues such as facility capacity requirements, alternative system operating strategies, and impacts of system changes (ie., startup dates). This description of the planned Hanford solid waste processing system: defines a baseline system configuration; identifies the entering waste streams to be managed within the system; identifies basic system functions and waste flows; and highlights system constraints. This system description will evolve and be revised as issues are resolved, planning decisions are made, additional data are collected, and assumptions are tested and changed. Out of necessity, this document will also be revised and updated so that a documented system description, which reflects current system planning, is always available for use by engineers and managers. It does not provide any results generated from the many alternatives that will be modeled in the course of analyzing solid waste disposal options; such results will be provided in separate documents

  1. The very-long-baseline array

    International Nuclear Information System (INIS)

    Kellermann, K.I.; Thompson, A.R.

    1988-01-01

    The development of radio technology in World War II opened a completely new window on the universe. When astronomers turned radio antennas to the heavens, they began to find a previously unknown universe of solar and planetary radio bursts, quasars, pulsars, radio galaxies, giant molecular clouds and cosmic masers. Not only do the radio waves reveal a new world of astronomical phenomena but also-because they are much longer than light waves-they are not as severely distorted by atmospheric turbulence or small imperfections in the telescope. About 25 years ago radio astronomers became aware that they could synthesize a resolution equivalent to that of a large aperture by combining data from smaller radio antennas that are widely separated. The effective aperture size would be about equal to the largest separation between the antennas. The technique is called synthesis imaging and is based on the principles of interferometry. Radio astronomers in the U.S. are now building a synthesis radio telescope called the Very-Long-Baseline Array, or VLBA. With 10 antennas sited across the country from the Virgin Islands to Hawaii, it will synthesize a radio antenna 8,000 kilometers across, nearly the diameter of the earth. The VLBA'S angular resolution will be less than a thousandth of an arc-second-about three orders of magnitude better than that of the largest conventional ground-based optical telescopes. Astronomers eagerly await the completion early in the next decade of the VLBA, which is expected, among other things, to give an unprecedentedly clear view into the cores of quasars and galactic nuclei and to reveal details of the processe-thought to be powered by black holes-that drive them

  2. Drawing a baseline in aesthetic quality assessment

    Science.gov (United States)

    Rubio, Fernando; Flores, M. Julia; Puerta, Jose M.

    2018-04-01

    Aesthetic classification of images is an inherently subjective task. There does not exist a validated collection of images/photographs labeled as having good or bad quality from experts. Nowadays, the closest approximation to that is to use databases of photos where a group of users rate each image. Hence, there is not a unique good/bad label but a rating distribution given by users voting. Due to this peculiarity, it is not possible to state the problem of binary aesthetic supervised classification in such a direct mode as other Computer Vision tasks. Recent literature follows an approach where researchers utilize the average rates from the users for each image, and they establish an arbitrary threshold to determine their class or label. In this way, images above the threshold are considered of good quality, while images below the threshold are seen as bad quality. This paper analyzes current literature, and it reviews those attributes able to represent an image, differentiating into three families: specific, general and deep features. Among those which have been proved more competitive, we have selected a representative subset, being our main goal to establish a clear experimental framework. Finally, once features were selected, we have used them for the full AVA dataset. We have to remark that to perform validation we report not only accuracy values, which is not that informative in this case, but also, metrics able to evaluate classification power within imbalanced datasets. We have conducted a series of experiments so that distinct well-known classifiers are learned from data. Like that, this paper provides what we could consider valuable and valid baseline results for the given problem.

  3. 10 CFR 850.20 - Baseline beryllium inventory.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Baseline beryllium inventory. 850.20 Section 850.20 Energy... Baseline beryllium inventory. (a) The responsible employer must develop a baseline inventory of the... inventory, the responsible employer must: (1) Review current and historical records; (2) Interview workers...

  4. A study of man made radioactivity baseline in dietary materials

    International Nuclear Information System (INIS)

    de la Paz, L.; Estacio, J.; Palattao, M.V.; Anden, A.

    1986-01-01

    This paper describes the radioactivity baseline from literature data coming from various countries where data are available. 1979-1985 were chosen as the baseline years for the following: milk (fresh and powdered), meat and meat products, cereals, fruits, coffee and tea, fish and vegetables. Pre- and post-Chernobyl baseline data are given. (ELC). 21 figs; 17 refs

  5. 40 CFR 80.92 - Baseline auditor requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Baseline auditor requirements. 80.92... (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Anti-Dumping § 80.92 Baseline auditor requirements. (a... determination methodology, resulting baseline fuel parameter, volume and emissions values verified by an auditor...

  6. Physics with a very long neutrino factory baseline

    International Nuclear Information System (INIS)

    Gandhi, Raj; Winter, Walter

    2007-01-01

    We discuss the neutrino oscillation physics of a very long neutrino factory baseline over a broad range of lengths (between 6000 km and 9000 km), centered on the 'magic baseline' (∼7500 km) where correlations with the leptonic CP phase are suppressed by matter effects. Since the magic baseline depends only on the density, we study the impact of matter density profile effects and density uncertainties over this range, and the impact of detector locations off the optimal baseline. We find that the optimal constant density describing the physics over this entire baseline range is about 5% higher than the average matter density. This implies that the magic baseline is significantly shorter than previously inferred. However, while a single detector optimization requires fine-tuning of the (very long) baseline length, its combination with a near detector at a shorter baseline is much less sensitive to the far detector location and to uncertainties in the matter density. In addition, we point out different applications of this baseline which go beyond its excellent correlation and degeneracy resolution potential. We demonstrate that such a long baseline assists in the improvement of the θ 13 precision and in the resolution of the octant degeneracy. Moreover, we show that the neutrino data from such a baseline could be used to extract the matter density along the profile up to 0.24% at 1σ for large sin 2 2θ 13 , providing a useful discriminator between different geophysical models

  7. Intrafractional baseline drift during free breathing breast cancer radiation therapy.

    Science.gov (United States)

    Jensen, Christer Andre; Acosta Roa, Ana María; Lund, Jo-Åsmund; Frengen, Jomar

    2017-06-01

    Intrafraction motion in breast cancer radiation therapy (BCRT) has not yet been thoroughly described in the literature. It has been observed that baseline drift occurs as part of the intrafraction motion. This study aims to measure baseline drift and its incidence in free-breathing BCRT patients using an in-house developed laser system for tracking the position of the sternum. Baseline drift was monitored in 20 right-sided breast cancer patients receiving free breathing 3D-conformal RT by using an in-house developed laser system which measures one-dimensional distance in the AP direction. A total of 357 patient respiratory traces from treatment sessions were logged and analysed. Baseline drift was compared to patient positioning error measured from in-field portal imaging. The mean overall baseline drift at end of treatment sessions was -1.3 mm for the patient population. Relatively small baseline drift was observed during the first fraction; however it was clearly detected already at the second fraction. Over 90% of the baseline drift occurs during the first 3 min of each treatment session. The baseline drift rate for the population was -0.5 ± 0.2 mm/min in the posterior direction the first minute after localization. Only 4% of the treatment sessions had a 5 mm or larger baseline drift at 5 min, all towards the posterior direction. Mean baseline drift in the posterior direction in free breathing BCRT was observed in 18 of 20 patients over all treatment sessions. This study shows that there is a substantial baseline drift in free breathing BCRT patients. No clear baseline drift was observed during the first treatment session; however, baseline drift was markedly present at the rest of the sessions. Intrafraction motion due to baseline drift should be accounted for in margin calculations.

  8. Spent Nuclear Fuel Project technical baseline document. Fiscal year 1995: Volume 1, Baseline description

    International Nuclear Information System (INIS)

    Womack, J.C.; Cramond, R.; Paedon, R.J.

    1995-01-01

    This document is a revision to WHC-SD-SNF-SD-002, and is issued to support the individual projects that make up the Spent Nuclear Fuel Project in the lower-tier functions, requirements, interfaces, and technical baseline items. It presents results of engineering analyses since Sept. 1994. The mission of the SNFP on the Hanford site is to provide safety, economic, environmentally sound management of Hanford SNF in a manner that stages it to final disposition. This particularly involves K Basin fuel, although other SNF is involved also

  9. Time-Dependent Vascular Effects of Endocannabinoids Mediated by Peroxisome Proliferator-Activated Receptor Gamma (PPAR

    Directory of Open Access Journals (Sweden)

    Saoirse E. O'Sullivan

    2009-01-01

    Full Text Available The aim of the present study was to examine whether endocannabinoids cause PPAR-mediated vascular actions. Functional vascular studies were carried out in rat aortae. Anandamide and N-arachidonoyl-dopamine (NADA, but not palmitoylethanolamide, caused significant vasorelaxation over time (2 hours. Vasorelaxation to NADA, but not anandamide, was inhibited by CB1 receptor antagonism (AM251, 1 M, and vasorelaxation to both anandamide and NADA was inhibited by PPAR antagonism (GW9662, 1 M. Pharmacological inhibition of de novo protein synthesis, nitric oxide synthase, and super oxide dismutase abolished the responses to anandamide and NADA. Removal of the endothelium partly inhibited the vasorelaxant responses to anandamide and NADA. Inhibition of fatty acid amide hydrolase (URB597, 1 M inhibited the vasorelaxant response to NADA, but not anandamide. These data indicate that endocannabinoids cause time-dependent, PPAR-mediated vasorelaxation. Activation of PPAR in the vasculature may represent a novel mechanism by which endocannabinoids are involved in vascular regulation.

  10. Large short-baseline νμ disappearance

    International Nuclear Information System (INIS)

    Giunti, Carlo; Laveder, Marco

    2011-01-01

    We analyze the LSND, KARMEN, and MiniBooNE data on short-baseline ν μ →ν e oscillations and the data on short-baseline ν e disappearance obtained in the Bugey-3 and CHOOZ reactor experiments in the framework of 3+1 antineutrino mixing, taking into account the MINOS observation of long-baseline ν μ disappearance and the KamLAND observation of very-long-baseline ν e disappearance. We show that the fit of the data implies that the short-baseline disappearance of ν μ is relatively large. We obtain a prediction of an effective amplitude sin 2 2θ μμ > or approx. 0.1 for short-baseline ν μ disappearance generated by 0.2 2 2 , which could be measured in future experiments.

  11. Overgeneral autobiographical memory at baseline predicts depressive symptoms at follow-up in patients with first-episode depression.

    Science.gov (United States)

    Liu, Yansong; Zhang, Fuquan; Wang, Zhiqiang; Cao, Leiming; Wang, Jun; Na, Aiguo; Sun, Yujun; Zhao, Xudong

    2016-09-30

    Previous studies have shown that overgeneral autobiographical memory (OGM) is a characteristic of depression. However, there are no studies to explore the association between baseline OGM and depressive symptoms at follow-up in patients with first-episode depression (FE). This study investigated whether baseline OGM predicts depressive symptoms at follow-up in patients with FE. We recruited 125 patients with FE. The participants were divided into remitted group and non-remitted group according to the severity of their depression at 12 months follow-up. The measures consisted of the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Hierarchical linear regression analyses and bootstrap mediation analyses were conducted. The results showed that non-remitted patients had more OGM at baseline. Baseline OGM predicted depressive symptoms at follow-up in patients with FE. Rumination mediated the relationship between baseline OGM and depressive symptoms at follow-up. Our findings highlight OGM as a vulnerability factor involved in the maintenance of depression in patients with FE. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Baseline inventory data recommendations for National Wildlife Refuges

    Data.gov (United States)

    Department of the Interior — The Baseline Inventory Team recommends that each refuge have available abiotic “data layers” for topography, aerial photography, hydrography, soils, boundaries, and...

  13. Site Outcomes Baseline Multi Year Work Plan Volume 1, River Corridor Restoration Baseline

    International Nuclear Information System (INIS)

    Wintczak, T.M.

    2001-01-01

    The River Corridor Restoration volume is a compilation of Hanford Site scope, which excludes the approximately 194 km 2 Central Plateau. The River Corridor scope is currently contractually assigned to Fluor Hanford, Bechtel Hanford, inc., DynCorp, and Pacific Northwest National Laboratory, and others. The purpose of this project specification is to provide an overall scoping document for the River Corridor Restoration volume, and to provide a link with the overall Hanford Site River Corridor scope. Additionally, this specification provides an integrated and consolidated source of information for the various scopes, by current contract, for the River Corridor Restoration Baseline. It identifies the vision, mission, and goals, as well as the operational history of the Hanford Site, along with environmental setting and hazards

  14. Business-as-Unusual: Existing policies in energy model baselines

    International Nuclear Information System (INIS)

    Strachan, Neil

    2011-01-01

    Baselines are generally accepted as a key input assumption in long-term energy modelling, but energy models have traditionally been poor on identifying baselines assumptions. Notably, transparency on the current policy content of model baselines is now especially critical as long-term climate mitigation policies have been underway for a number of years. This paper argues that the range of existing energy and emissions policies are an integral part of any long-term baseline, and hence already represent a 'with-policy' baseline, termed here a Business-as-Unusual (BAuU). Crucially, existing energy policies are not a sunk effort; as impacts of existing policy initiatives are targeted at future years, they may be revised through iterative policy making, and their quantitative effectiveness requires ex-post verification. To assess the long-term role of existing policies in energy modelling, currently identified UK policies are explicitly stripped out of the UK MARKAL Elastic Demand (MED) optimisation energy system model, to generate a BAuU (with-policy) and a REF (without policy) baseline. In terms of long-term mitigation costs, policy-baseline assumptions are comparable to another key exogenous modelling assumption - that of global fossil fuel prices. Therefore, best practice in energy modelling would be to have both a no-policy reference baseline, and a current policy reference baseline (BAuU). At a minimum, energy modelling studies should have a transparent assessment of the current policy contained within the baseline. Clearly identifying and comparing policy-baseline assumptions are required for cost effective and objective policy making, otherwise energy models will underestimate the true cost of long-term emissions reductions.

  15. Study on the calibration and optimization of double theodolites baseline

    Science.gov (United States)

    Ma, Jing-yi; Ni, Jin-ping; Wu, Zhi-chao

    2018-01-01

    For the double theodolites measurement system baseline as the benchmark of the scale of the measurement system and affect the accuracy of the system, this paper puts forward a method for calibration and optimization of the double theodolites baseline. Using double theodolites to measure the known length of the reference ruler, and then reverse the baseline formula. Based on the error propagation law, the analyses show that the baseline error function is an important index to measure the accuracy of the system, and the reference ruler position, posture and so on have an impact on the baseline error. The optimization model is established and the baseline error function is used as the objective function, and optimizes the position and posture of the reference ruler. The simulation results show that the height of the reference ruler has no effect on the baseline error; the posture is not uniform; when the reference ruler is placed at x=500mm and y=1000mm in the measurement space, the baseline error is the smallest. The experimental results show that the experimental results are consistent with the theoretical analyses in the measurement space. In this paper, based on the study of the placement of the reference ruler, for improving the accuracy of the double theodolites measurement system has a reference value.

  16. 75 FR 30014 - Consumers Energy Company; Notice of Baseline Filing

    Science.gov (United States)

    2010-05-28

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-25-000] Consumers Energy Company; Notice of Baseline Filing May 21, 2010. Take notice that on May 17, 2010, Consumers Energy Company (Consumers) submitted a baseline filing of its Statement of Operating Conditions for the...

  17. 77 FR 31841 - Hope Gas, Inc.; Notice of Baseline Filing

    Science.gov (United States)

    2012-05-30

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR12-23-001] Hope Gas, Inc.; Notice of Baseline Filing Take notice that on May 16, 2012, Hope Gas, Inc. (Hope Gas) submitted a revised baseline filing of their Statement of Operating Conditions for services provided under Section 311 of the...

  18. 77 FR 26535 - Hope Gas, Inc.; Notice of Baseline Filing

    Science.gov (United States)

    2012-05-04

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR12-23-000] Hope Gas, Inc.; Notice of Baseline Filing Take notice that on April 26, 2012, Hope Gas, Inc. (Hope Gas) submitted a baseline filing of their Statement of Operating Conditions for services provided under Section 311 of the...

  19. Esophageal acid exposure decreases intraluminal baseline impedance levels

    NARCIS (Netherlands)

    Kessing, Boudewijn F.; Bredenoord, Albert J.; Weijenborg, Pim W.; Hemmink, Gerrit J. M.; Loots, Clara M.; Smout, A. J. P. M.

    2011-01-01

    Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in

  20. Tank waste remediation system technical baseline summary description

    International Nuclear Information System (INIS)

    Raymond, R.E.

    1998-01-01

    This document is one of the tools used to develop and control the mission work as depicted in the included figure. This Technical Baseline Summary Description document is the top-level tool for management of the Technical Baseline for waste storage operations

  1. Vegetation Parameter Extraction Using Dual Baseline Polarimetric SAR Interferometry Data

    Science.gov (United States)

    Zhang, H.; Wang, C.; Chen, X.; Tang, Y.

    2009-04-01

    For vegetation parameter inversion, the single baseline polarimetric SAR interferometry (POLinSAR) technique, such as the three-stage method and the ESPRIT algorithm, is limited by the observed data with the minimum ground to volume amplitude ration, which effects the estimation of the effective phase center for the vegetation canopy or the surface, and thus results in the underestimated vegetation height. In order to remove this effect of the single baseline inversion techniques in some extend, another baseline POLinSAR data is added on vegetation parameter estimation in this paper, and a dual baseline POLinSAR technique for the extraction of the vegetation parameter is investigated and improved to reduce the dynamic bias for the vegetation parameter estimation. Finally, the simulated data and real data are used to validate this dual baseline technique.

  2. Establishing a store baseline during interim storage of waste packages and a review of potential technologies for base-lining

    Energy Technology Data Exchange (ETDEWEB)

    McTeer, Jennifer; Morris, Jenny; Wickham, Stephen [Galson Sciences Ltd. Oakham, Rutland (United Kingdom); Bolton, Gary [National Nuclear Laboratory Risley, Warrington (United Kingdom); McKinney, James; Morris, Darrell [Nuclear Decommissioning Authority Moor Row, Cumbria (United Kingdom); Angus, Mike [National Nuclear Laboratory Risley, Warrington (United Kingdom); Cann, Gavin; Binks, Tracey [National Nuclear Laboratory Sellafield (United Kingdom)

    2013-07-01

    Interim storage is an essential component of the waste management lifecycle, providing a safe, secure environment for waste packages awaiting final disposal. In order to be able to monitor and detect change or degradation of the waste packages, storage building or equipment, it is necessary to know the original condition of these components (the 'waste storage system'). This paper presents an approach to establishing the baseline for a waste-storage system, and provides guidance on the selection and implementation of potential base-lining technologies. The approach is made up of two sections; assessment of base-lining needs and definition of base-lining approach. During the assessment of base-lining needs a review of available monitoring data and store/package records should be undertaken (if the store is operational). Evolutionary processes (affecting safety functions), and their corresponding indicators, that can be measured to provide a baseline for the waste-storage system should then be identified in order for the most suitable indicators to be selected for base-lining. In defining the approach, identification of opportunities to collect data and constraints is undertaken before selecting the techniques for base-lining and developing a base-lining plan. Base-lining data may be used to establish that the state of the packages is consistent with the waste acceptance criteria for the storage facility and to support the interpretation of monitoring and inspection data collected during store operations. Opportunities and constraints are identified for different store and package types. Technologies that could potentially be used to measure baseline indicators are also reviewed. (authors)

  3. High Baseline Postconcussion Symptom Scores and Concussion Outcomes in Athletes.

    Science.gov (United States)

    Custer, Aimee; Sufrinko, Alicia; Elbin, R J; Covassin, Tracey; Collins, Micky; Kontos, Anthony

    2016-02-01

    Some healthy athletes report high levels of baseline concussion symptoms, which may be attributable to several factors (eg, illness, personality, somaticizing). However, the role of baseline symptoms in outcomes after sport-related concussion (SRC) has not been empirically examined. To determine if athletes with high symptom scores at baseline performed worse than athletes without baseline symptoms on neurocognitive testing after SRC. Cohort study. High school and collegiate athletic programs. A total of 670 high school and collegiate athletes participated in the study. Participants were divided into groups with either no baseline symptoms (Postconcussion Symptom Scale [PCSS] score = 0, n = 247) or a high level of baseline symptoms (PCSS score > 18 [top 10% of sample], n = 68). Participants were evaluated at baseline and 2 to 7 days after SRC with the Immediate Post-concussion Assessment and Cognitive Test and PCSS. Outcome measures were Immediate Post-concussion Assessment and Cognitive Test composite scores (verbal memory, visual memory, visual motor processing speed, and reaction time) and total symptom score on the PCSS. The groups were compared using repeated-measures analyses of variance with Bonferroni correction to assess interactions between group and time for symptoms and neurocognitive impairment. The no-symptoms group represented 38% of the original sample, whereas the high-symptoms group represented 11% of the sample. The high-symptoms group experienced a larger decline from preinjury to postinjury than the no-symptoms group in verbal (P = .03) and visual memory (P = .05). However, total concussion-symptom scores increased from preinjury to postinjury for the no-symptoms group (P = .001) but remained stable for the high-symptoms group. Reported baseline symptoms may help identify athletes at risk for worse outcomes after SRC. Clinicians should examine baseline symptom levels to better identify patients for earlier referral and treatment for their

  4. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  5. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  6. An Automated Baseline Correction Method Based on Iterative Morphological Operations.

    Science.gov (United States)

    Chen, Yunliang; Dai, Liankui

    2018-05-01

    Raman spectra usually suffer from baseline drift caused by fluorescence or other reasons. Therefore, baseline correction is a necessary and crucial step that must be performed before subsequent processing and analysis of Raman spectra. An automated baseline correction method based on iterative morphological operations is proposed in this work. The method can adaptively determine the structuring element first and then gradually remove the spectral peaks during iteration to get an estimated baseline. Experiments on simulated data and real-world Raman data show that the proposed method is accurate, fast, and flexible for handling different kinds of baselines in various practical situations. The comparison of the proposed method with some state-of-the-art baseline correction methods demonstrates its advantages over the existing methods in terms of accuracy, adaptability, and flexibility. Although only Raman spectra are investigated in this paper, the proposed method is hopefully to be used for the baseline correction of other analytical instrumental signals, such as IR spectra and chromatograms.

  7. Extracting Baseline Electricity Usage Using Gradient Tree Boosting

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taehoon [Ulsan Nat. Inst. of Sci. & Tech., Ulsan (South Korea); Lee, Dongeun [Ulsan Nat. Inst. of Sci. & Tech., Ulsan (South Korea); Choi, Jaesik [Ulsan Nat. Inst. of Sci. & Tech., Ulsan (South Korea); Spurlock, Anna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sim, Alex [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, Annika [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wu, Kesheng [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-05

    To understand how specific interventions affect a process observed over time, we need to control for the other factors that influence outcomes. Such a model that captures all factors other than the one of interest is generally known as a baseline. In our study of how different pricing schemes affect residential electricity consumption, the baseline would need to capture the impact of outdoor temperature along with many other factors. In this work, we examine a number of different data mining techniques and demonstrate Gradient Tree Boosting (GTB) to be an effective method to build the baseline. We train GTB on data prior to the introduction of new pricing schemes, and apply the known temperature following the introduction of new pricing schemes to predict electricity usage with the expected temperature correction. Our experiments and analyses show that the baseline models generated by GTB capture the core characteristics over the two years with the new pricing schemes. In contrast to the majority of regression based techniques which fail to capture the lag between the peak of daily temperature and the peak of electricity usage, the GTB generated baselines are able to correctly capture the delay between the temperature peak and the electricity peak. Furthermore, subtracting this temperature-adjusted baseline from the observed electricity usage, we find that the resulting values are more amenable to interpretation, which demonstrates that the temperature-adjusted baseline is indeed effective.

  8. Baseline frontostriatal-limbic connectivity predicts reward-based memory formation.

    Science.gov (United States)

    Hamann, Janne M; Dayan, Eran; Hummel, Friedhelm C; Cohen, Leonardo G

    2014-12-01

    Reward mediates the acquisition and long-term retention of procedural skills in humans. Yet, learning under rewarded conditions is highly variable across individuals and the mechanisms that determine interindividual variability in rewarded learning are not known. We postulated that baseline functional connectivity in a large-scale frontostriatal-limbic network could predict subsequent interindividual variability in rewarded learning. Resting-state functional MRI was acquired in two groups of subjects (n = 30) who then trained on a visuomotor procedural learning task with or without reward feedback. We then tested whether baseline functional connectivity within the frontostriatal-limbic network predicted memory strength measured immediately, 24 h and 1 month after training in both groups. We found that connectivity in the frontostriatal-limbic network predicted interindividual variability in the rewarded but not in the unrewarded learning group. Prediction was strongest for long-term memory. Similar links between connectivity and reward-based memory were absent in two control networks, a fronto-parieto-temporal language network and the dorsal attention network. The results indicate that baseline functional connectivity within the frontostriatal-limbic network successfully predicts long-term retention of rewarded learning. © 2014 Wiley Periodicals, Inc.

  9. Skin conductance at baseline and postheel lance reflects sympathetic activation in neonatal opiate withdrawal.

    Science.gov (United States)

    Oji-Mmuo, Christiana N; Michael, Eric J; McLatchy, Jacqueline; Lewis, Mary M; Becker, Julie E; Doheny, Kim Kopenhaver

    2016-03-01

    Skin conductance (SC) provides an objective measure of autonomic system regulation through sympathetic-mediated filling of sweat glands. This study aimed to test the utility of SC to detect sympathetic activation in neonatal abstinence syndrome (NAS). Fourteen term (mean, SE: 38.8 ± 0.35 weeks gestational age) neonates with chronic prenatal opiate exposure were enrolled. SC (peaks/seconds and mean of peaks) was measured at baseline, during heel lance/squeeze (HLS) and recovery from HLS at 24-48 (mean 38) hours of life prior to treatment for NAS. Blinded coders with established reliability assessed neonates using the Modified Finnegan Neonatal Scoring System (MFNSS). Nonparametric tests were used to determine group differences, phase differences from baseline to HLS and HLS to recovery, and associations between MFNSS and SC measures. Neonates that would later require morphine treatment for NAS (n = 6) had higher baseline SC mean of peaks than those that did not require treatment (n = 8) (p < 0.05). Moreover, there were unique phase differences between groups and SC positively correlated with MFNSS (p < 0.05). SC provides early identification of NAS severity. However, a larger sample is needed to determine sensitivity and specificity of SC for early identification of NAS and treatment effectiveness. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  10. Cortisol and politics: variance in voting behavior is predicted by baseline cortisol levels.

    Science.gov (United States)

    French, Jeffrey A; Smith, Kevin B; Alford, John R; Guck, Adam; Birnie, Andrew K; Hibbing, John R

    2014-06-22

    Participation in electoral politics is affected by a host of social and demographics variables, but there is growing evidence that biological predispositions may also play a role in behavior related to political involvement. We examined the role of individual variation in hypothalamic-pituitary-adrenal (HPA) stress axis parameters in explaining differences in self-reported and actual participation in political activities. Self-reported political activity, religious participation, and verified voting activity in U.S. national elections were collected from 105 participants, who were subsequently exposed to a standardized (nonpolitical) psychosocial stressor. We demonstrated that lower baseline salivary cortisol in the late afternoon was significantly associated with increased actual voting frequency in six national elections, but not with self-reported non-voting political activity. Baseline cortisol predicted significant variation in voting behavior above and beyond variation accounted for by traditional demographic variables (particularly age of participant in our sample). Participation in religious activity was weakly (and negatively) associated with baseline cortisol. Our results suggest that HPA-mediated characteristics of social, cognitive, and emotional processes may exert an influence on a trait as complex as voting behavior, and that cortisol is a better predictor of actual voting behavior, as opposed to self-reported political activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

    Science.gov (United States)

    Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

    2015-07-01

    The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

  12. Cortisol and Politics: Variance in Voting Behavior is Predicted by Baseline Cortisol Levels

    Science.gov (United States)

    French, Jeffrey A.; Smith, Kevin B.; Alford, John R.; Guck, Adam; Birnie, Andrew K.; Hibbing, John R.

    2014-01-01

    Participation in electoral politics is affected by a host of social and demographics variables, but there is growing evidence that biological predispositions may also play a role in behavior related to political involvement. We examined the role of individual variation in hypothalamic-pituitary-adrenal (HPA) stress axis parameters in explaining differences in self-reported and actual participation in political activities. Self-reported political activity, religious participation, and verified voting activity in U.S. national elections were collected from 105 participants, who were subsequently exposed to a standardized (nonpolitical) psychosocial stressor. We demonstrated that lower baseline salivary cortisol in the late afternoon was significantly associated with increased actual voting frequency in six national elections, but not with self-reported non-voting political activity. Baseline cortisol predicted significant variation in voting behavior above and beyond variation accounted for by traditional demographic variables (particularly age of participant in our sample). Participation in religious activity was weakly (and negatively) associated with baseline cortisol. Our results suggest that HPA-mediated characteristics of social, cognitive, and emotional processes may exert an influence on a trait as complex as voting behavior, and that cortisol is a better predictor of actual voting behavior, as opposed to self-reported political activity. PMID:24835544

  13. Dynamic baseline detection method for power data network service

    Science.gov (United States)

    Chen, Wei

    2017-08-01

    This paper proposes a dynamic baseline Traffic detection Method which is based on the historical traffic data for the Power data network. The method uses Cisco's NetFlow acquisition tool to collect the original historical traffic data from network element at fixed intervals. This method uses three dimensions information including the communication port, time, traffic (number of bytes or number of packets) t. By filtering, removing the deviation value, calculating the dynamic baseline value, comparing the actual value with the baseline value, the method can detect whether the current network traffic is abnormal.

  14. CryoSat SAR/SARin Level1b products: assessment of BaselineC and improvements towards BaselineD

    Science.gov (United States)

    Scagliola, Michele; Fornari, Marco; Bouffard, Jerome; Parrinello, Tommaso

    2017-04-01

    CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. Cryosat carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. This allows to reach a significantly improved along track resolution with respect to traditional pulse-width limited altimeters. CryoSat is the first altimetry mission operating in SAR mode and continuous improvements in the Level1 Instrument Processing Facility (IPF1) are being identified, tested and validated in order to improve the quality of the Level1b products. The current IPF, Baseline C, was released in operation in April 2015 and the second CryoSat reprocessing campaign was jointly initiated, taking benefit of the upgrade implemented in the IPF1 processing chain but also of some specific configurations for the calibration corrections. In particular, the CryoSat Level1b BaselineC products generated in the framework of the second reprocessing campaign include refined information for what concerns the mispointing angles and the calibration corrections. This poster will thus detail thus the evolutions that are currently planned for the CryoSat BaselineD SAR/SARin Level1b products and the corresponding quality improvements that are expected.

  15. Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab

    NARCIS (Netherlands)

    Weide, Benjamin; Martens, Alexander; Hassel, Jessica C.; Berking, Carola; Postow, Michael A.; Bisschop, Kees; Simeone, Ester; Mangana, Johanna; Schilling, Bastian; Di Giacomo, Anna Maria; Brenner, Nicole; Kaehler, Katharina; Heinzerling, Lucie; Gutzmer, Ralf; Bender, Armin; Gebhardt, Christoffer; Romano, Emanuela; Meier, Friedegund; Martus, Peter; Maio, Michele; Blank, Christian; Schadendorf, Dirk; Dummer, Reinhard; Ascierto, Paolo A.; Hospers, Geke; Garbe, Claus; Wolchok, Jedd D.

    2016-01-01

    Purpose: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients. Experimental Design:

  16. Baseline assessment of fish communities of the Flower Garden Banks

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The work developed baseline information on fish and benthic communities within the Flower Garden Banks National Marine Sanctuary (FGBNMS). Surveys employed diving,...

  17. Information architecture. Volume 2, Part 1: Baseline analysis summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    The Department of Energy (DOE) Information Architecture, Volume 2, Baseline Analysis, is a collaborative and logical next-step effort in the processes required to produce a Departmentwide information architecture. The baseline analysis serves a diverse audience of program management and technical personnel and provides an organized way to examine the Department`s existing or de facto information architecture. A companion document to Volume 1, The Foundations, it furnishes the rationale for establishing a Departmentwide information architecture. This volume, consisting of the Baseline Analysis Summary (part 1), Baseline Analysis (part 2), and Reference Data (part 3), is of interest to readers who wish to understand how the Department`s current information architecture technologies are employed. The analysis identifies how and where current technologies support business areas, programs, sites, and corporate systems.

  18. Magical properties of a 2540 km baseline superbeam experiment

    International Nuclear Information System (INIS)

    Raut, Sushant K.; Singh, Ravi Shanker; Uma Sankar, S.

    2011-01-01

    Lack of any information on the CP violating phase δ CP weakens our ability to determine neutrino mass hierarchy. Magic baseline of 7500 km was proposed to overcome this problem. However, to obtain large enough fluxes, at this very long baseline, one needs new techniques of generating high intensity neutrino beams. In this Letter, we highlight the magical properties of a 2540 km baseline. At such a baseline, using a narrow band neutrino superbeam whose no oscillation event rate peaks around the energy 3.5 GeV, we can determine neutrino mass hierarchy independently of the CP phase. For sin 2 2θ 13 ≥0.05, a very modest exposure of 10 Kiloton-years is sufficient to determine the hierarchy. For 0.02≤sin 2 2θ 13 ≤0.05, an exposure of about 100 Kiloton-years is needed.

  19. Parametric estimation of time varying baselines in airborne interferometric SAR

    DEFF Research Database (Denmark)

    Mohr, Johan Jacob; Madsen, Søren Nørvang

    1996-01-01

    A method for estimation of time varying spatial baselines in airborne interferometric synthetic aperture radar (SAR) is described. The range and azimuth distortions between two images acquired with a non-linear baseline are derived. A parametric model of the baseline is then, in a least square...... sense, estimated from image shifts obtained by cross correlation of numerous small patches throughout the image. The method has been applied to airborne EMISAR imagery from the 1995 campaign over the Storstrommen Glacier in North East Greenland conducted by the Danish Center for Remote Sensing. This has...... reduced the baseline uncertainties from several meters to the centimeter level in a 36 km scene. Though developed for airborne SAR the method can easily be adopted to satellite data...

  20. Validity and Reliability of Baseline Testing in a Standardized Environment.

    Science.gov (United States)

    Higgins, Kathryn L; Caze, Todd; Maerlender, Arthur

    2017-08-11

    The Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) is a computerized neuropsychological test battery commonly used to determine cognitive recovery from concussion based on comparing post-injury scores to baseline scores. This model is based on the premise that ImPACT baseline test scores are a valid and reliable measure of optimal cognitive function at baseline. Growing evidence suggests that this premise may not be accurate and a large contributor to invalid and unreliable baseline test scores may be the protocol and environment in which baseline tests are administered. This study examined the effects of a standardized environment and administration protocol on the reliability and performance validity of athletes' baseline test scores on ImPACT by comparing scores obtained in two different group-testing settings. Three hundred-sixty one Division 1 cohort-matched collegiate athletes' baseline data were assessed using a variety of indicators of potential performance invalidity; internal reliability was also examined. Thirty-one to thirty-nine percent of the baseline cases had at least one indicator of low performance validity, but there were no significant differences in validity indicators based on environment in which the testing was conducted. Internal consistency reliability scores were in the acceptable to good range, with no significant differences between administration conditions. These results suggest that athletes may be reliably performing at levels lower than their best effort would produce. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling

    Science.gov (United States)

    Yang, Hongwei; Tang, Ya-ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-01-01

    SUMMARY Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. PMID:24267894

  2. Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

    Science.gov (United States)

    Chen, Rongqing; Zhang, Jian; Fan, Ni; Teng, Zhao-Qian; Wu, Yan; Yang, Hongwei; Tang, Ya-Ping; Sun, Hao; Song, Yunping; Chen, Chu

    2013-11-21

    Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW

    Energy Technology Data Exchange (ETDEWEB)

    Partnership, ALMA [Astrophysics Research Institute, Liverpool John Moores University, IC2, Liverpool Science Park, 146 Brownlow Hill, Liverpool L3 5RF (United Kingdom); Fomalont, E. B.; Vlahakis, C.; Corder, S.; Remijan, A.; Barkats, D.; Dent, W. R. F.; Phillips, N.; Cox, P.; Hales, A. S. [Joint ALMA Observatory, Alonso de Córdova 3107, Vitacura, Santiago (Chile); Lucas, R. [Institut de Planétologie et d’Astrophysique de Grenoble (UMR 5274), BP 53, F-38041 Grenoble Cedex 9 (France); Hunter, T. R.; Brogan, C. L.; Amestica, R.; Cotton, W. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Asaki, Y. [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Matsushita, S. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 106, Taiwan (China); Hills, R. E. [Astrophysics Group, Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Richards, A. M. S. [Jodrell Bank Centre for Astrophysics, School of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Broguiere, D., E-mail: efomalon@nrao.edu [Institut de Radioastronomie Millime´trique (IRAM), 300 rue de la Piscine, Domaine Universitaire, F-38406 Saint Martin d’Hères (France); and others

    2015-07-20

    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ∼15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ∼350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.

  4. STATUS OF THE US LONG BASELINE NEUTRINO EXPERIMENT STUDY.

    Energy Technology Data Exchange (ETDEWEB)

    BISHAI,M.

    2006-09-21

    The US Long Baseline Neutrino Experiment Study was commissioned jointly by Brookhaven National Laboratory and Fermi National Accelerator Laboratory to investigate the potential for future U.S. based long baseline neutrino oscillation experiments beyond the currently planned program. The Study focused on MW class convention at neutrino beams that can be produced at Fermilab or BNL. The experimental baselines are based on two possible detector locations: (1) off-axis to the existing Fermilab NuMI beamline at baselines of 700 to 810 km and (2) NSF's proposed future Deep Underground Science and Engineering Laboratory (DUSEL) at baselines greater than 1000 km. Two detector technologies are considered: a megaton class Water Cherenkov detector deployed deep underground at a DUSEL site, or a 100kT Liquid Argon Time-Projection Chamber (TPC) deployed on the surface at any of the proposed sites. The physics sensitivities of the proposed experiments are summarized. We find that conventional horn focused wide-band neutrino beam options from Fermilab or BNL aimed at a massive detector with a baseline of > 1000 km have the best sensitivity to CP violation and the neutrino mass hierarchy for values of the mixing angle {theta}{sub 13} down to 2.2{sup o}.

  5. MALDI-TOF Baseline Drift Removal Using Stochastic Bernstein Approximation

    Directory of Open Access Journals (Sweden)

    Howard Daniel

    2006-01-01

    Full Text Available Stochastic Bernstein (SB approximation can tackle the problem of baseline drift correction of instrumentation data. This is demonstrated for spectral data: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF data. Two SB schemes for removing the baseline drift are presented: iterative and direct. Following an explanation of the origin of the MALDI-TOF baseline drift that sheds light on the inherent difficulty of its removal by chemical means, SB baseline drift removal is illustrated for both proteomics and genomics MALDI-TOF data sets. SB is an elegant signal processing method to obtain a numerically straightforward baseline shift removal method as it includes a free parameter that can be optimized for different baseline drift removal applications. Therefore, research that determines putative biomarkers from the spectral data might benefit from a sensitivity analysis to the underlying spectral measurement that is made possible by varying the SB free parameter. This can be manually tuned (for constant or tuned with evolutionary computation (for .

  6. A Fully Customized Baseline Removal Framework for Spectroscopic Applications.

    Science.gov (United States)

    Giguere, Stephen; Boucher, Thomas; Carey, C J; Mahadevan, Sridhar; Dyar, M Darby

    2017-07-01

    The task of proper baseline or continuum removal is common to nearly all types of spectroscopy. Its goal is to remove any portion of a signal that is irrelevant to features of interest while preserving any predictive information. Despite the importance of baseline removal, median or guessed default parameters are commonly employed, often using commercially available software supplied with instruments. Several published baseline removal algorithms have been shown to be useful for particular spectroscopic applications but their generalizability is ambiguous. The new Custom Baseline Removal (Custom BLR) method presented here generalizes the problem of baseline removal by combining operations from previously proposed methods to synthesize new correction algorithms. It creates novel methods for each technique, application, and training set, discovering new algorithms that maximize the predictive accuracy of the resulting spectroscopic models. In most cases, these learned methods either match or improve on the performance of the best alternative. Examples of these advantages are shown for three different scenarios: quantification of components in near-infrared spectra of corn and laser-induced breakdown spectroscopy data of rocks, and classification/matching of minerals using Raman spectroscopy. Software to implement this optimization is available from the authors. By removing subjectivity from this commonly encountered task, Custom BLR is a significant step toward completely automatic and general baseline removal in spectroscopic and other applications.

  7. THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW

    International Nuclear Information System (INIS)

    Partnership, ALMA; Fomalont, E. B.; Vlahakis, C.; Corder, S.; Remijan, A.; Barkats, D.; Dent, W. R. F.; Phillips, N.; Cox, P.; Hales, A. S.; Lucas, R.; Hunter, T. R.; Brogan, C. L.; Amestica, R.; Cotton, W.; Asaki, Y.; Matsushita, S.; Hills, R. E.; Richards, A. M. S.; Broguiere, D.

    2015-01-01

    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ∼15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ∼350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy

  8. Novel time-dependent vascular actions of Δ9-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

    International Nuclear Information System (INIS)

    O'Sullivan, Saoirse E.; Tarling, Elizabeth J.; Bennett, Andrew J.; Kendall, David A.; Randall, Michael D.

    2005-01-01

    Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, Δ 9 -tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPARγ). In vitro, THC (10 μM) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPARγ agonist rosiglitazone and was inhibited by the PPARγ antagonist GW9662 (1 μM), but not the cannabinoid CB 1 receptor antagonist AM251 (1 μM). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPARγ, transiently expressed in combination with retinoid X receptor α and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 μM). In vitro incubation with THC (1 or 10 μM, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPARγ ligands. The present results provide strong evidence that THC is a PPARγ ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors

  9. Precise baseline determination for the TanDEM-X mission

    Science.gov (United States)

    Koenig, Rolf; Moon, Yongjin; Neumayer, Hans; Wermuth, Martin; Montenbruck, Oliver; Jäggi, Adrian

    The TanDEM-X mission will strive for generating a global precise Digital Elevation Model (DEM) by way of bi-static SAR in a close formation of the TerraSAR-X satellite, already launched on June 15, 2007, and the TanDEM-X satellite to be launched in May 2010. Both satellites carry the Tracking, Occultation and Ranging (TOR) payload supplied by the GFZ German Research Centre for Geosciences. The TOR consists of a high-precision dual-frequency GPS receiver, called Integrated GPS Occultation Receiver (IGOR), and a Laser retro-reflector (LRR) for precise orbit determination (POD) and atmospheric sounding. The IGOR is of vital importance for the TanDEM-X mission objectives as the millimeter level determination of the baseline or distance between the two spacecrafts is needed to derive meter level accurate DEMs. Within the TanDEM-X ground segment GFZ is responsible for the operational provision of precise baselines. For this GFZ uses two software chains, first its Earth Parameter and Orbit System (EPOS) software and second the BERNESE software, for backup purposes and quality control. In a concerted effort also the German Aerospace Center (DLR) generates precise baselines independently with a dedicated Kalman filter approach realized in its FRNS software. By the example of GRACE the generation of baselines with millimeter accuracy from on-board GPS data can be validated directly by way of comparing them to the intersatellite K-band range measurements. The K-band ranges are accurate down to the micrometer-level and therefore may be considered as truth. Both TanDEM-X baseline providers are able to generate GRACE baselines with sub-millimeter accuracy. By merging the independent baselines by GFZ and DLR, the accuracy can even be increased. The K-band validation however covers solely the along-track component as the K-band data measure just the distance between the two GRACE satellites. In addition they inhibit an un-known bias which must be modelled in the comparison, so the

  10. Effect of biliary cirrhosis on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum: Role of nitric oxide pathway and endocannabinoid system

    Directory of Open Access Journals (Sweden)

    Dehpour A.R.

    2008-06-01

    Full Text Available Background: Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide (NO is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic (NANC nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic (NANC-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems.Methods: Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 µM and atropine (1 µM to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride (7.5 µM and electrical field stimulation was applied at different frequencies (2, 5, 10, 15 Hz to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside (10 nM-1mM, as an NO donor, were assessed.  Results: The NANC-mediated relaxation was significantly enhanced in cirrhotic animals (P<0.01. Anandamide potentiated the relaxations in both groups (P<0.05. The cannabinoid CB1 receptor antagonist AM251 (10 µM and the vanilloid receptor antagonist capsazepine (10 µM each significantly prevented the enhanced relaxations in cirrhotic rats (P<0.01. The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME (30-1000 nM inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside (10 nM-1 mM was similar in the two groups.Conclusions: Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and

  11. Placental baseline conditions modulate the hyperoxic BOLD-MRI response.

    Science.gov (United States)

    Sinding, Marianne; Peters, David A; Poulsen, Sofie S; Frøkjær, Jens B; Christiansen, Ole B; Petersen, Astrid; Uldbjerg, Niels; Sørensen, Anne

    2018-01-01

    Human pregnancies complicated by placental dysfunction may be characterized by a high hyperoxic Blood oxygen level-dependent (BOLD) MRI response. The pathophysiology behind this phenomenon remains to be established. The aim of this study was to evaluate whether it is associated with altered placental baseline conditions, including a lower oxygenation and altered tissue morphology, as estimated by the placental transverse relaxation time (T2*). We included 49 normal pregnancies (controls) and 13 pregnancies complicated by placental dysfunction (cases), defined by a birth weight baseline BOLD)/baseline BOLD) from a dynamic single-echo gradient-recalled echo (GRE) MRI sequence and the absolute ΔT2* (hyperoxic T2*- baseline T2*) from breath-hold multi-echo GRE sequences. In the control group, the relative ΔBOLD response increased during gestation from 5% in gestational week 20 to 20% in week 40. In the case group, the relative ΔBOLD response was significantly higher (mean Z-score 4.94; 95% CI 2.41, 7.47). The absolute ΔT2*, however, did not differ between controls and cases (p = 0.37), whereas the baseline T2* was lower among cases (mean Z-score -3.13; 95% CI -3.94, -2.32). Furthermore, we demonstrated a strong negative linear correlation between the Log 10 ΔBOLD response and the baseline T2* (r = -0.88, p baseline conditions, as the absolute increase in placental oxygenation (ΔT2*) does not differ between groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Atmospheric pressure loading parameters from very long baseline interferometry observations

    Science.gov (United States)

    Macmillan, D. S.; Gipson, John M.

    1994-01-01

    Atmospheric mass loading produces a primarily vertical displacement of the Earth's crust. This displacement is correlated with surface pressure and is large enough to be detected by very long baseline interferometry (VLBI) measurements. Using the measured surface pressure at VLBI stations, we have estimated the atmospheric loading term for each station location directly from VLBI data acquired from 1979 to 1992. Our estimates of the vertical sensitivity to change in pressure range from 0 to -0.6 mm/mbar depending on the station. These estimates agree with inverted barometer model calculations (Manabe et al., 1991; vanDam and Herring, 1994) of the vertical displacement sensitivity computed by convolving actual pressure distributions with loading Green's functions. The pressure sensitivity tends to be smaller for stations near the coast, which is consistent with the inverted barometer hypothesis. Applying this estimated pressure loading correction in standard VLBI geodetic analysis improves the repeatability of estimated lengths of 25 out of 37 baselines that were measured at least 50 times. In a root-sum-square (rss) sense, the improvement generally increases with baseline length at a rate of about 0.3 to 0.6 ppb depending on whether the baseline stations are close to the coast. For the 5998-km baseline from Westford, Massachusetts, to Wettzell, Germany, the rss improvement is about 3.6 mm out of 11.0 mm. The average rss reduction of the vertical scatter for inland stations ranges from 2.7 to 5.4 mm.

  13. Baseline development, economic risk, and schedule risk: An integrated approach

    International Nuclear Information System (INIS)

    Tonkinson, J.A.

    1994-01-01

    The economic and schedule risks of Environmental Restoration (ER) projects are commonly analyzed toward the end of the baseline development process. Risk analysis is usually performed as the final element of the scheduling or estimating processes for the purpose of establishing cost and schedule contingency. However, there is an opportunity for earlier assessment of risks, during development of the technical scope and Work Breakdown Structure (WBS). Integrating the processes of risk management and baselining provides for early incorporation of feedback regarding schedule and cost risk into the proposed scope of work. Much of the information necessary to perform risk analysis becomes available during development of the technical baseline, as the scope of work and WBS are being defined. The analysis of risk can actually be initiated early on during development of the technical baseline and continue throughout development of the complete project baseline. Indeed, best business practices suggest that information crucial to the success of a project be analyzed and incorporated into project planning as soon as it is available and usable

  14. Is CP violation observable in long baseline neutrino oscillation experiments?

    International Nuclear Information System (INIS)

    Tanimoto, M.

    1997-01-01

    We have studied CP violation originating from the phase of the neutrino-mixing matrix in the long baseline neutrino oscillation experiments. The direct measurement of CP violation is the difference of the transition probabilities between CP-conjugate channels. In those experiments, the CP-violating effect is not suppressed if the highest neutrino mass scale is taken to be 1 endash 5 eV, which is appropriate for the cosmological hot dark matter. Assuming the hierarchy for the neutrino masses, the upper bounds of CP violation have been calculated for three cases, in which mixings are constrained by the recent short baseline ones. The calculated upper bounds are larger than 10 -2 , which will be observable in the long baseline accelerator experiments. The matter effect, which is not CP invariant, has been also estimated in those experiments. copyright 1997 The American Physical Society

  15. A publication database for optical long baseline interferometry

    Science.gov (United States)

    Malbet, Fabien; Mella, Guillaume; Lawson, Peter; Taillifet, Esther; Lafrasse, Sylvain

    2010-07-01

    Optical long baseline interferometry is a technique that has generated almost 850 refereed papers to date. The targets span a large variety of objects from planetary systems to extragalactic studies and all branches of stellar physics. We have created a database hosted by the JMMC and connected to the Optical Long Baseline Interferometry Newsletter (OLBIN) web site using MySQL and a collection of XML or PHP scripts in order to store and classify these publications. Each entry is defined by its ADS bibcode, includes basic ADS informations and metadata. The metadata are specified by tags sorted in categories: interferometric facilities, instrumentation, wavelength of operation, spectral resolution, type of measurement, target type, and paper category, for example. The whole OLBIN publication list has been processed and we present how the database is organized and can be accessed. We use this tool to generate statistical plots of interest for the community in optical long baseline interferometry.

  16. Functional Testing Protocols for Commercial Building Efficiency Baseline Modeling Software

    Energy Technology Data Exchange (ETDEWEB)

    Jump, David; Price, Phillip N.; Granderson, Jessica; Sohn, Michael

    2013-09-06

    This document describes procedures for testing and validating proprietary baseline energy modeling software accuracy in predicting energy use over the period of interest, such as a month or a year. The procedures are designed according to the methodology used for public domain baselining software in another LBNL report that was (like the present report) prepared for Pacific Gas and Electric Company: ?Commercial Building Energy Baseline Modeling Software: Performance Metrics and Method Testing with Open Source Models and Implications for Proprietary Software Testing Protocols? (referred to here as the ?Model Analysis Report?). The test procedure focuses on the quality of the software?s predictions rather than on the specific algorithms used to predict energy use. In this way the software vendor is not required to divulge or share proprietary information about how their software works, while enabling stakeholders to assess its performance.

  17. Carbon tetrachloride ERA soil-gas baseline monitoring

    International Nuclear Information System (INIS)

    Fancher, J.D.

    1994-01-01

    From December 1991 through December 1993, Westinghouse Hanford Company performed routine baseline monitoring of selected wells ad soil-gas points twice weekly in the 200 West Area of the Hanford Site. This work supported the carbon Tetrachloride Expedited Response Action (ERA) and provided a solid baseline of volatile organic compound (VOC) concentrations in wells and in the subsurface at the ERA site. As site remediation continues, comparisons to this baseline can be one means of measuring the success of carbon tetrachloride vapor extraction. This report contains observations of the patterns and trends associated with data obtained during soil-gas monitoring at the 200 West Area: Monitoring performed since late 1991 includes monitoring soil-gas probes ad wellheads for volatile organic compounds (VOCs). This report reflects monitoring data collected from December 1991 through December 1993

  18. Environmental baselines: preparing for shale gas in the UK

    Science.gov (United States)

    Bloomfield, John; Manamsa, Katya; Bell, Rachel; Darling, George; Dochartaigh, Brighid O.; Stuart, Marianne; Ward, Rob

    2014-05-01

    Groundwater is a vital source of freshwater in the UK. It provides almost 30% of public water supply on average, but locally, for example in south-east England, it is constitutes nearly 90% of public supply. In addition to public supply, groundwater has a number of other uses including agriculture, industry, and food and drink production. It is also vital for maintaining river flows especially during dry periods and so is essential for maintaining ecosystem health. Recently, there have been concerns expressed about the potential impacts of shale gas development on groundwater. The UK has abundant shales and clays which are currently the focus of considerable interest and there is active research into their characterisation, resource evaluation and exploitation risks. The British Geological Survey (BGS) is undertaking research to provide information to address some of the environmental concerns related to the potential impacts of shale gas development on groundwater resources and quality. The aim of much of this initial work is to establish environmental baselines, such as a baseline survey of methane occurrence in groundwater (National methane baseline study) and the spatial relationships between potential sources and groundwater receptors (iHydrogeology project), prior to any shale gas exploration and development. The poster describes these two baseline studies and presents preliminary findings. BGS are currently undertaking a national survey of baseline methane concentrations in groundwater across the UK. This work will enable any potential future changes in methane in groundwater associated with shale gas development to be assessed. Measurements of methane in potable water from the Cretaceous, Jurassic and Triassic carbonate and sandstone aquifers are variable and reveal methane concentrations of up to 500 micrograms per litre, but the mean value is relatively low at documented in the range 2km. The geological modelling process will be presented and discussed

  19. Evidence of the shifting baseline syndrome in ethnobotanical research.

    Science.gov (United States)

    Hanazaki, Natalia; Herbst, Dannieli Firme; Marques, Mel Simionato; Vandebroek, Ina

    2013-11-14

    The shifting baseline syndrome is a concept from ecology that can be analyzed in the context of ethnobotanical research. Evidence of shifting baseline syndrome can be found in studies dealing with intracultural variation of knowledge, when knowledge from different generations is compared and combined with information about changes in the environment and/or natural resources. We reviewed 84 studies published between 1993 and 2012 that made comparisons of ethnobotanical knowledge according to different age classes. After analyzing these studies for evidence of the shifting baseline syndrome (lower knowledge levels in younger generations and mention of declining abundance of local natural resources), we searched within these studies for the use of the expressions "cultural erosion", "loss of knowledge", or "acculturation". The studies focused on different groups of plants (e.g. medicinal plants, foods, plants used for general purposes, or the uses of specific important species). More than half of all 84 studies (57%) mentioned a concern towards cultural erosion or knowledge loss; 54% of the studies showed evidence of the shifting baseline syndrome; and 37% of the studies did not provide any evidence of shifting baselines (intergenerational knowledge differences but no information available about the abundance of natural resources). The general perception of knowledge loss among young people when comparing ethnobotanical repertoires among different age groups should be analyzed with caution. Changes in the landscape or in the abundance of plant resources may be associated with changes in ethnobotanical repertoires held by people of different age groups. Also, the relationship between the availability of resources and current plant use practices rely on a complexity of factors. Fluctuations in these variables can cause changes in the reference (baseline) of different generations and consequently be responsible for differences in intergenerational knowledge. Unraveling

  20. 200-BP-5 operable unit Technical Baseline report

    International Nuclear Information System (INIS)

    Jacques, I.D.; Kent, S.K.

    1991-10-01

    This report supports development of a remedial investigation/feasibility study work plan for the 200-BP-5 operable unit. The report summarizes baseline information for waste sites and unplanned release sites located in the 200-BP-5 operable unit. The sites were investigated by the Technical Baseline Section of the Environmental Engineering Group, Westinghouse Hanford Company (Westinghouse Hanford). The investigation consisted of review and evaluation of current and historical Hanford Site reports, drawings, and photographs, and was supplemented with recent inspections of the Hanford Site and employee interviews. No field investigations or sampling were conducted

  1. Way to increase the user access at the LCLS baseline

    Energy Technology Data Exchange (ETDEWEB)

    Geloni, Gianluca [European XFEL GmbH, Hamburg; Kocharyan, Vitali; Saldin, Evgeni [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2010-10-15

    Although the LCLS photon beam is meant for a single user, the baseline undulator is long enough to serve two users simultaneously. To this end, we propose a setup composed of two simple elements: an X-ray mirror pair for X-ray beam deflection, and a short (4 m-long) magnetic chicane, which creates an offset for mirror pair installation in the middle of the baseline undulator. The insertable mirror pair can be used for spatial separation of the X-ray beams generated in the first and in the second half of the baseline undulator. The method of deactivating one half and activating another half of the undulator is based on the rapid switching of the FEL amplification process. As proposed elsewhere, using a kicker installed upstream of the LCLS baseline undulator and an already existing corrector in the first half of the undulator, it is possible to rapidly switch the X-ray beam from one user to another, thus providing two active beamlines at any time. We present simulation results dealing with the LCLS baseline, and show that it is possible to generate two saturated SASE X-ray beams in the whole 0.8-8 keV photon energy range in the same baseline undulator. These can be exploited to serve two users. Implementation of the proposed technique does not perturb the baseline mode of operation of the LCLS undulator. Moreover, the magnetic chicane setup is very flexible, and can be used as a self-seeding setup too. We present simulation results for the LCLS baseline undulator with SHAB (second harmonic afterburner) and show that one can produce monochromatic radiation at the 2nd harmonic as well as at the 1st. We describe an efficient way for obtaining multi-user operation at the LCLS hard X-ray FEL. To this end, a photon beam distribution system based on the use of crystals in the Bragg reflection geometry is proposed. The reflectivity of crystal deflectors can be switched fast enough by flipping the crystals with piezoelectric devices similar to those for X-ray phase retarders

  2. Addendum to the 2015 Eastern Interconnect Baselining and Analysis Report

    Energy Technology Data Exchange (ETDEWEB)

    Amidan, Brett G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Follum, James D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-06-30

    This report serves as an addendum to the report 2015 Eastern Interconnect Baselining and Analysis Report (Amidan, Follum, and Freeman, 2015). This addendum report investigates the following: the impact of shorter record lengths and of adding a daily regularization term to the date/time models for angle pair measurements, additional development of a method to monitor the trend in phase angle pairs, the effect of changing the length of time to determine a baseline, when calculating atypical events, and a comparison between quantitatively discovered atypical events and actual events.

  3. Pediatric Heart Transplantation: Transitioning to Adult Care (TRANSIT): Baseline Findings.

    Science.gov (United States)

    Grady, Kathleen L; Hof, Kathleen Van't; Andrei, Adin-Cristian; Shankel, Tamara; Chinnock, Richard; Miyamoto, Shelley; Ambardekar, Amrut V; Anderson, Allen; Addonizio, Linda; Latif, Farhana; Lefkowitz, Debra; Goldberg, Lee; Hollander, Seth A; Pham, Michael; Weissberg-Benchell, Jill; Cool, Nichole; Yancy, Clyde; Pahl, Elfriede

    2018-02-01

    Young adult solid organ transplant recipients who transfer from pediatric to adult care experience poor outcomes related to decreased adherence to the medical regimen. Our pilot trial for young adults who had heart transplant (HT) who transfer to adult care tests an intervention focused on increasing HT knowledge, self-management and self-advocacy skills, and enhancing support, as compared to usual care. We report baseline findings between groups regarding (1) patient-level outcomes and (2) components of the intervention. From 3/14 to 9/16, 88 subjects enrolled and randomized to intervention (n = 43) or usual care (n = 45) at six pediatric HT centers. Patient self-report questionnaires and medical records data were collected at baseline, and 3 and 6 months after transfer. For this report, baseline findings (at enrollment and prior to transfer to adult care) were analyzed using Chi-square and t-tests. Level of significance was p Baseline demographics were similar in the intervention and usual care arms: age 21.3 ± 3.2 vs 21.5 ± 3.3 years and female 44% vs 49%, respectively. At baseline, there were no differences between intervention and usual care for use of tacrolimus (70 vs 62%); tacrolimus level (mean ± SD = 6.5 ± 2.3 ng/ml vs 5.6 ± 2.3 ng/ml); average of the within patient standard deviation of the baseline mean tacrolimus levels (1.6 vs 1.3); and adherence to the medical regimen [3.6 ± 0.4 vs 3.5 ± 0.5 (1 = hardly ever to 4 = all of the time)], respectively. At baseline, both groups had a modest amount of HT knowledge, were learning self-management and self-advocacy, and perceived they were adequately supported. Baseline findings indicate that transitioning HT recipients lack essential knowledge about HT and have incomplete self-management and self-advocacy skills.

  4. Nordic Mediation Reseach

    DEFF Research Database (Denmark)

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  5. Development of a Soil Organic Carbon Baseline for Otjozondjupa, Namibia

    NARCIS (Netherlands)

    Nijbroek, R.; Kempen, B.; Mutua, J.; Soderstrom, M.; Piikki, K.; Hengari, S.; Andreas, A.

    2017-01-01

    Land Degradation Neutrality (LDN) has been piloted in 14 countries and will be scaled up to over 120 countries. As a LDN pilot country, Namibia developed sub-national LDN baselines in Otjozondjupa Region. In addition to the three LDN indicators (soil organic carbon, land productivity and land cover

  6. Automated baseline change detection phase I. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    The Automated Baseline Change Detection (ABCD) project is supported by the DOE Morgantown Energy Technology Center (METC) as part of its ER&WM cross-cutting technology program in robotics. Phase 1 of the Automated Baseline Change Detection project is summarized in this topical report. The primary objective of this project is to apply robotic and optical sensor technology to the operational inspection of mixed toxic and radioactive waste stored in barrels, using Automated Baseline Change Detection (ABCD), based on image subtraction. Absolute change detection is based on detecting any visible physical changes, regardless of cause, between a current inspection image of a barrel and an archived baseline image of the same barrel. Thus, in addition to rust, the ABCD system can also detect corrosion, leaks, dents, and bulges. The ABCD approach and method rely on precise camera positioning and repositioning relative to the barrel and on feature recognition in images. In support of this primary objective, there are secondary objectives to determine DOE operational inspection requirements and DOE system fielding requirements.

  7. Abstract: Notes from the Field: Establishing Baseline Data for ...

    African Journals Online (AJOL)

    Abstract: Notes from the Field: Establishing Baseline Data for Pressure Ulcers in a Rwandan Intensive Care Unit. Gedeon Mutabazi, Jessie Silver. Abstract. Abstract. Background Pressure ulcers are a common iatrogenic medical problem. Pressure ulcers increase the morbidity and mortality of hospitalized patients as well as ...

  8. Effect of computer game playing on baseline laparoscopic simulator skills.

    Science.gov (United States)

    Halvorsen, Fredrik H; Cvancarova, Milada; Fosse, Erik; Mjåland, Odd

    2013-08-01

    Studies examining the possible association between computer game playing and laparoscopic performance in general have yielded conflicting results and neither has a relationship between computer game playing and baseline performance on laparoscopic simulators been established. The aim of this study was to examine the possible association between previous and present computer game playing and baseline performance on a virtual reality laparoscopic performance in a sample of potential future medical students. The participating students completed a questionnaire covering the weekly amount and type of computer game playing activity during the previous year and 3 years ago. They then performed 2 repetitions of 2 tasks ("gallbladder dissection" and "traverse tube") on a virtual reality laparoscopic simulator. Performance on the simulator were then analyzed for association to their computer game experience. Local high school, Norway. Forty-eight students from 2 high school classes volunteered to participate in the study. No association between prior and present computer game playing and baseline performance was found. The results were similar both for prior and present action game playing and prior and present computer game playing in general. Our results indicate that prior and present computer game playing may not affect baseline performance in a virtual reality simulator.

  9. Baselining PMU Data to Find Patterns and Anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Amidan, Brett G.; Follum, James D.; Freeman, Kimberly A.; Dagle, Jeffery E.

    2016-10-25

    This paper looks at the application of situational awareness methodologies with respect to power grid data. These methodologies establish baselines that look for typical patterns and atypical behavior in the data. The objectives of the baselining analyses are to provide: real-time analytics, the capability to look at historical trends and events, and reliable predictions of the near future state of the grid. Multivariate algorithms were created to establish normal baseline behavior and then score each moment in time according to its variance from the baseline. Detailed multivariate analytical techniques are described in this paper that produced ways to identify typical patterns and atypical behavior. In this case, atypical behavior is behavior that is unenvisioned. Visualizations were also produced to help explain the behavior that was identified mathematically. Examples are shown to help describe how to read and interpret the analyses and visualizations. Preliminary work has been performed on PMU data sets from BPA (Bonneville Power Administration) and EI (Eastern Interconnect). Actual results are not fully shown here because of confidentiality issues. Comparisons between atypical events found mathematically and actual events showed that many of the actual events are also atypical events; however there are many atypical events that do not correlate to any actual events. Additional work needs to be done to help classify the atypical events into actual events, so that the importance of the events can be better understood.

  10. ecotaxonomic baseline evaluation of the plant species in a ...

    African Journals Online (AJOL)

    Admin

    plant species of medicinal and other economic values. The investigation was ... A total of 41 and 24 representative ... INTRODUCTION. Baseline .... at 100m interval, involving a total of 15 sampling locations .... explained by factors such as climate, productivity and ... encouraging the: Maintenance of traditional tree species.

  11. Baseline design of an OTEC pilot plantship. Volume C. Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Glosten, L. R.; Bringloe, Thomas; Soracco, Dave; Fenstermacher, Earl; Magura, Donald; Sander, Olof; Richards, Dennis; Seward, Jerry

    1979-05-01

    Volume C is part of a three-volume report that presents a baseline engineering design of an Ocean Thermal Energy Conversion (OTEC) plantship. This volume provides the specifications for the hull, cold-water pipe, ship outfitting and machinery, OTEC power system, electrical system, and folded-tube heat exchangers.

  12. Technical Baseline Summary Description for the Tank Farm Contractor

    International Nuclear Information System (INIS)

    TEDESCHI, A.R.

    2000-01-01

    This document is a revision of the document titled above, summarizing the technical baseline of the Tank Farm Contractor. It is one of several documents prepared by CH2M HILL Hanford Group, Inc. to support the U.S. Department of Energy Office of River Protection Tank Waste Retrieval and Disposal Mission at Hanford

  13. Delta Healthy Sprouts: Participants' Diet and Food Environment at Baseline

    Science.gov (United States)

    Local food environments influence the nutrition and health of area residents. This baseline analysis focuses on the food environments of women who participated in the Delta Healthy Sprouts project, a randomized, controlled, comparative trial designed to test the efficacy of two Maternal, Infant, an...

  14. 48 CFR 34.202 - Integrated Baseline Reviews.

    Science.gov (United States)

    2010-10-01

    ... or contractor, and the Government, of the— (1) Ability of the project's technical plan to achieve the... successfully achieve the project schedule objectives; (3) Ability of the Performance Measurement Baseline (PMB... SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 34.202...

  15. Baseline Radioactivity Measurements In The Vicinity Of A Gold ...

    African Journals Online (AJOL)

    Western Region, Ghana) to obtain baseline radioactivity data prior to the installation of Cs-137 nuclear density gauges for quality control measure-ment of the density of slurry in the pipelines at the plant. A survey meter, gamma spectrometry and ...

  16. Automated baseline change detection phase I. Final report

    International Nuclear Information System (INIS)

    1995-12-01

    The Automated Baseline Change Detection (ABCD) project is supported by the DOE Morgantown Energy Technology Center (METC) as part of its ER ampersand WM cross-cutting technology program in robotics. Phase 1 of the Automated Baseline Change Detection project is summarized in this topical report. The primary objective of this project is to apply robotic and optical sensor technology to the operational inspection of mixed toxic and radioactive waste stored in barrels, using Automated Baseline Change Detection (ABCD), based on image subtraction. Absolute change detection is based on detecting any visible physical changes, regardless of cause, between a current inspection image of a barrel and an archived baseline image of the same barrel. Thus, in addition to rust, the ABCD system can also detect corrosion, leaks, dents, and bulges. The ABCD approach and method rely on precise camera positioning and repositioning relative to the barrel and on feature recognition in images. In support of this primary objective, there are secondary objectives to determine DOE operational inspection requirements and DOE system fielding requirements

  17. Ecotaxonmic baseline evaluation of the plant species in a ...

    African Journals Online (AJOL)

    The survey of the flora composition of an ecosystem is important in several environmental baseline studies. An ecotaxonomic assessment was carried out in Ase-Ndoni proposed Rivgas Refinery project site in other to find out the plant species of medicinal and other economic values. The investigation was carried out to ...

  18. How to deal with cost differences at baseline

    NARCIS (Netherlands)

    Van Asselt, Antoinette D.I.; Van Mastrigt, Ghislaine A.P.G.; Dirksen, Carmen D.; Arntz, Arnoud; Severens, Johan L.; Kessels, Alfons G.H.

    BACKGROUND: To our knowledge, adjustment for baseline imbalances in costs has never been performed in trial-based cost-effectiveness analyses. METHODS: We used data from a clinical trial performed in the Netherlands comparing two outpatient psychotherapies: schema-focused therapy (SFT) versus

  19. The Dutch CAFE baseline: In or out of line?

    NARCIS (Netherlands)

    Jimmink BA; Folkert RJM; Thomas R; Beck JP; Eerdt MM van; Elzenga HE; Hoek KW van der; Hoen A; Peek CJ; LED; KMD; NMD; LVM; RIM; LDL

    2004-01-01

    The European Commission is constructing a strategy on air pollution within the Clean Air For Europe (CAFE) programme. This strategy will be based on assessments using the RAINS model for different policy ambitions where the CAFE baseline scenario and control strategies are employed. The Netherlands

  20. Emergency Response Capability Baseline Needs Assessment - Requirements Document

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, J A

    2016-10-04

    This document was prepared by John A. Sharry, LLNL Fire Marshal and LLNL Division Leader for Fire Protection and reviewed by LLNL Emergency Management Department Head James Colson. The document follows and expands upon the format and contents of the DOE Model Fire Protection Baseline Capabilities Assessment document contained on the DOE Fire Protection Web Site, but only addresses emergency response.

  1. IEA Wind Task 26: Offshore Wind Farm Baseline Documentation

    Energy Technology Data Exchange (ETDEWEB)

    Smart, Gavin [Offshore Renewable Energy Catapult, Blyth, Northumberland (United Kingdom); Smith, Aaron [National Renewable Energy Lab. (NREL), Golden, CO (United States); Warner, Ethan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sperstad, Iver Bakken [SINTEF Energy Research, Trondheim (Norway); Prinsen, Bob [Ecofys, Utrecht (Netherlands). TKI Wind Op Zee; Lacal-Arantegui, Roberto [European Commission Joint Research Centre (JRC), Brussels (Belgium)

    2016-06-02

    This document has been produced to provide the definition and rationale for the Baseline Offshore Wind Farm established within IEA Wind Task 26--Cost of Wind Energy. The Baseline has been developed to provide a common starting point for country comparisons and sensitivity analysis on key offshore wind cost and value drivers. The baseline project reflects an approximate average of the characteristics of projects installed between 2012 and 2014, with the project life assumed to be 20 years. The baseline wind farm is located 40 kilometres (km) from construction and operations and maintenance (O&M) ports and from export cable landfall. The wind farm consists of 100 4-megawatt (MW) wind turbines mounted on monopile foundations in an average water depth of 25 metres (m), connected by 33-kilovolt (kV) inter-array cables. The arrays are connected to a single offshore substation (33kV/220kV) mounted on a jacket foundation, with the substation connected via a single 220kV export cable to an onshore substation, 10km from landfall. The wind farm employs a port-based O&M strategy using crew-transfer vessels.

  2. Shifted Baselines Reduce Willingness to Pay for Conservation

    Directory of Open Access Journals (Sweden)

    Loren McClenachan

    2018-02-01

    Full Text Available A loss of memory of past environmental degradation has resulted in shifted baselines, which may result in conservation and restoration goals that are less ambitious than if stakeholders had a full knowledge of ecosystem potential. However, the link between perception of baseline states and support for conservation planning has not been tested empirically. Here, we investigate how perceptions of change in coral reef ecosystems affect stakeholders' willingness to pay (WTP for the establishment of protected areas. Coral reefs are experiencing rapid, global change that is observable by the public, and therefore provide an ideal ecosystem to test links between beliefs about baseline states and willingness to support conservation. Our survey respondents perceived change to coral reef communities across six variables: coral abundance, fish abundance, fish diversity, fish size, sedimentation, and water pollution. Respondants who accurately perceived declines in reef health had significantly higher WTP for protected areas (US $256.80 vs. $102.50 per year, suggesting that shifted baselines may reduce engagement with conservation efforts. If WTP translates to engagement, this suggests that goals for restoration and recovery are likely to be more ambitious if the public is aware of long term change. Therefore, communicating the scope and depth of environmental problems is essential in engaging the public in conservation.

  3. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  4. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  5. Baseline series fragrance markers fail to predict contact allergy.

    Science.gov (United States)

    Mann, Jack; McFadden, John P; White, Jonathan M L; White, Ian R; Banerjee, Piu

    2014-05-01

    Negative patch test results with fragrance allergy markers in the European baseline series do not always predict a negative reaction to individual fragrance substances. To determine the frequencies of positive test reactions to the 26 fragrance substances for which labelling is mandatory in the EU, and how effectively reactions to fragrance markers in the baseline series predict positive reactions to the fragrance substances that are labelled. The records of 1951 eczema patients, routinely tested with the labelled fragrance substances and with an extended European baseline series in 2011 and 2012, were retrospectively reviewed. Two hundred and eighty-one (14.4%) (71.2% females) reacted to one or more allergens from the labelled-fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were cinnamyl alcohol (48; 2.46%), Evernia furfuracea (44; 2.26%), and isoeugenol (40; 2.05%). Of the 203 patients who reacted to any of the 26 fragrances in the labelled-fragrance substance series, only 117 (57.6%) also reacted to a fragrance marker in the baseline series. One hundred and seven (52.7%) reacted to either fragrance mix I or fragrance mix II, 28 (13.8%) reacted to Myroxylon pereirae, and 13 (6.4%) reacted to hydroxyisohexyl 3-cyclohexene carboxaldehyde. These findings confirm that the standard fragrance markers fail to identify patients with contact allergies to the 26 fragrances. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  7. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  8. General gauge mediation

    International Nuclear Information System (INIS)

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  9. Bayesian dynamic mediation analysis.

    Science.gov (United States)

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. S Plant Aggregate Area Management study technical baseline report

    International Nuclear Information System (INIS)

    DeFord, D.H.; Carpenter, R.W.

    1995-05-01

    This document is prepared in support of an Aggregate Area Management Study of S Plant, 200 West Area, at the US Department of Energy's (DOE) Hanford Site near Richland, Washington. It provides a technical baseline of the aggregate area and the results from an environmental investigation undertaken by the Technical Baseline Section of the Environmental Engineering Group, Westinghouse Hanford Company (WHC). This document is based on review and evaluation of numerous Hanford Site current and historical reports, drawings and photographs, supplemented with site inspections and employee interviews. This report describes the REDOX facility and its waste sites, including cribs, french drains, septic tanks and drain fields, trenches, catch tanks, settling tanks, diversion boxes, underground tank farms designed for high-level liquid wastes, and the lines and encasements that connect them

  11. Baseline ecological risk assessment Salmon Site, Lamar County, Mississippi

    International Nuclear Information System (INIS)

    1995-04-01

    The Salmon Site (SS), formerly the Tatum Dome Test Site, located in Mississippi was the site of two nuclear and two gas explosion tests conducted between 1964 and 1970. A consequence of these testing activities is that radionuclides were released into the salt dome, where they are presently contained. During reentry drilling and other site activities, incidental liquid and solid wastes that contained radioactivity were generated, resulting in some soil, ground water and equipment contamination. As part of the remedial investigation effort, a Baseline Ecological Risk Assessment was conducted at the SS. The purpose is to gauge ecological and other environmental impacts attributable to past activities at the former test facility. The results of this facility-specific baseline risk assessment are presented in this document

  12. U-10Mo Baseline Fuel Fabrication Process Description

    Energy Technology Data Exchange (ETDEWEB)

    Hubbard, Lance R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Arendt, Christina L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dye, Daniel F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clayton, Christopher K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lerchen, Megan E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lombardo, Nicholas J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lavender, Curt A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zacher, Alan H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2017-09-27

    This document provides a description of the U.S. High Power Research Reactor (USHPRR) low-enriched uranium (LEU) fuel fabrication process. This document is intended to be used in conjunction with the baseline process flow diagram (PFD) presented in Appendix A. The baseline PFD is used to document the fabrication process, communicate gaps in technology or manufacturing capabilities, convey alternatives under consideration, and as the basis for a dynamic simulation model of the fabrication process. The simulation model allows for the assessment of production rates, costs, and manufacturing requirements (manpower, fabrication space, numbers and types of equipment, etc.) throughout the lifecycle of the USHPRR program. This document, along with the accompanying PFD, is updated regularly

  13. NA61/SHINE Data For Long Baseline Neutrino Experiments

    CERN Document Server

    Hälser, Alexis

    2015-01-01

    Accelerator based long baseline neutrino experiments require precise neutrino fl ux predictions to reach their physics goals. These experiments are commonly based on a set of two detectors. At the near detector, cross section measurements are performed and the neutrino fl ux can be observed before oscillation, while at the far detector the signal for neutrino oscillations is studied. An accurate knowledge on hadron production is mandatory in order to predict the neutrino fluxes. The NA61/SHINE facility at the CERN SPS has proven its ability to deliver high quality measurements of hadron production for the long baseline neutrino experiments. In this paper, the latest results from N A61 /SHINE for the neutrino physics programme are reviewed and future plans are presented.

  14. Overview of the Long-Baseline Neutrino Facility cryogenic system

    CERN Document Server

    Montanari, David; Bremer, Johan; Delaney, Michael; Aurelien, Diaz; Doubnik, Roza; Haaf, Kevin; Hentschel, Steve; Norris, Barry; Voirin, Erik

    2017-01-01

    The Deep Underground Neutrino Experiment (DUNE) collaboration is developing a multi-kiloton Long-Baseline neutrino experiment that will be located one mile underground at the Sanford Underground Research Facility (SURF) in Lead, SD. In the present design, detectors will be located inside four cryostats filled with a total of 68,400 ton of ultrapure liquid argon, at the level of impurities lower than 100 parts per trillion of oxygen equivalent contamination. The Long-Baseline Neutrino Facility (LBNF) is developing the conventional facilities and cryogenics infrastructure supporting this experiment. The cryogenics system is composed of several sub-systems: External/Infrastructure, Proximity, and Internal cryogenics. It will be engineered, manufactured, commissioned, and qualified by an international engineering team. This contribution highlights the main features of the LBNF cryogenic system. It presents its performance, functional requirements and modes of operations. It also details the status of the design, ...

  15. Hepatitis C treatment response kinetics and impact of baseline predictors

    DEFF Research Database (Denmark)

    Lindh, M; Arnholm, B; Eilard, A

    2011-01-01

    Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics...... above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected...... by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks....

  16. Measurement of baseline and orientation between distributed aerospace platforms.

    Science.gov (United States)

    Wang, Wen-Qin

    2013-01-01

    Distributed platforms play an important role in aerospace remote sensing, radar navigation, and wireless communication applications. However, besides the requirement of high accurate time and frequency synchronization for coherent signal processing, the baseline between the transmitting platform and receiving platform and the orientation of platform towards each other during data recording must be measured in real time. In this paper, we propose an improved pulsed duplex microwave ranging approach, which allows determining the spatial baseline and orientation between distributed aerospace platforms by the proposed high-precision time-interval estimation method. This approach is novel in the sense that it cancels the effect of oscillator frequency synchronization errors due to separate oscillators that are used in the platforms. Several performance specifications are also discussed. The effectiveness of the approach is verified by simulation results.

  17. Mercury exposure may suppress baseline corticosterone levels in juvenile birds.

    Science.gov (United States)

    Herring, Garth; Ackerman, Joshua T; Herzog, Mark P

    2012-06-05

    Mercury exposure has been associated with a wide variety of negative reproductive responses in birds, however few studies have examined the potential for chick impairment via the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis regulates corticosterone levels during periods of stress. We examined the relationship between baseline fecal corticosterone metabolite concentrations and mercury concentrations in down feathers of recently hatched (feathers (decreasing by 45% across the range of observed mercury concentrations) while accounting for stronger positive correlations between corticosterone concentrations and colony nest abundance and date. These results indicate that chronic mercury exposure may suppress baseline corticosterone concentrations in tern chicks and suggests that a juvenile bird's ability to respond to stress may be reduced via the downregulation of the HPA axis.

  18. Decomposition for emission baseline setting in China's electricity sector

    International Nuclear Information System (INIS)

    Steenhof, Paul A.

    2007-01-01

    Decomposition analysis is used to generate carbon dioxide emission baselines in China's electricity sector to the year 2020. This is undertaken from the vantage point of the final consumer of electricity, and therefore considers factors influencing electricity demand, efficiency of generation, sources of energy used for generation purposes, and the effectiveness of transmission and distribution. It is found that since 1980, gains in efficiency of generation have been the most important factor affecting change in the emission intensity of electricity generated. Based upon known energy and economic policy, efficiency gains will continue to contribute to reductions in the emission intensity of electricity generated, however, fuel shifts to natural gas and increases in nuclear generation will further these trends into the future. The analysis confirms other sources in the literature that decomposition is an appropriate technique available for baseline construction, thereby suitable for the emerging carbon market and its related mechanisms

  19. Baseline ecological risk assessment Salmon Site, Lamar County, Mississippi

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

    The Salmon Site (SS), formerly the Tatum Dome Test Site, located in Mississippi was the site of two nuclear and two gas explosion tests conducted between 1964 and 1970. A consequence of these testing activities is that radionuclides were released into the salt dome, where they are presently contained. During reentry drilling and other site activities, incidental liquid and solid wastes that contained radioactivity were generated, resulting in some soil, ground water and equipment contamination. As part of the remedial investigation effort, a Baseline Ecological Risk Assessment was conducted at the SS. The purpose is to gauge ecological and other environmental impacts attributable to past activities at the former test facility. The results of this facility-specific baseline risk assessment are presented in this document.

  20. Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

    Science.gov (United States)

    Beaton, K. H.; Bloomberg, J. J.

    2016-01-01

    One of the greatest challenges for sensorimotor adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. This information could guide individually customized countermeasures, which would enable more efficient use of crew time and provide better outcomes. The principal aim of this work is to look for baseline performance metrics that relate to locomotor adaptability. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations ("noise") in motor performance, as a predictor of individual adaptive capabilities.

  1. Technical baseline description for in situ vitrification laboratory test equipment

    International Nuclear Information System (INIS)

    Beard, K.V.; Bonnenberg, R.W.; Watson, L.R.

    1991-09-01

    IN situ vitrification (ISV) has been identified as possible waste treatment technology. ISV was developed by Pacific Northwest Laboratory (PNL), Richland, Washington, as a thermal treatment process to treat contaminated soils in place. The process, which electrically melts and dissolves soils and associated inorganic materials, simultaneously destroys and/or removes organic contaminants while incorporating inorganic contaminants into a stable, glass-like residual product. This Technical Baseline Description has been prepared to provide high level descriptions of the design of the Laboratory Test model, including all design modifications and safety improvements made to data. Furthermore, the Technical Baseline Description provides a basic overview of the interface documents for configuration management, program management interfaces, safety, quality, and security requirements. 8 figs

  2. Development of a Soil Organic Carbon Baseline for Otjozondjupa, Namibia

    OpenAIRE

    Nijbroek, R.; Kempen, B.; Mutua, J.; Soderstrom, M.; Piikki, K.; Hengari, S.; Andreas, A.

    2017-01-01

    Land Degradation Neutrality (LDN) has been piloted in 14 countries and will be scaled up to over 120 countries. As a LDN pilot country, Namibia developed sub-national LDN baselines in Otjozondjupa Region. In addition to the three LDN indicators (soil organic carbon, land productivity and land cover change), Namibia also regards bush encroachment as an important form of land degradation. We collected 219 soil profiles and used Random Forest modelling to develop the soil organic carbon stock ba...

  3. Logistics Operations Management Center: Maintenance Support Baseline (LOMC-MSB)

    Science.gov (United States)

    Kurrus, R.; Stump, F.

    1995-01-01

    The Logistics Operations Management Center Maintenance Support Baseline is defined. A historical record of systems, applied to and deleted from, designs in support of future management and/or technical analysis is provided. All Flight elements, Ground Support Equipment, Facility Systems and Equipment and Test Support Equipment for which LOMC has responsibilities at Kennedy Space Center and other locations are listed. International Space Station Alpha Program documentation is supplemented. The responsibility of the Space Station Launch Site Support Office is established.

  4. Baseline descriptions for LWR spent fuel storage, handling, and transportation

    International Nuclear Information System (INIS)

    Moyer, J.W.; Sonnier, C.S.

    1978-04-01

    Baseline descriptions for the storage, handling, and transportation of reactor spent fuel are provided. The storage modes described include light water reactor (LWR) pools, away-from-reactor basins, dry surface storage, reprocessing-facility interim storage pools, and deep geologic storage. Land and water transportation are also discussed. This work was sponsored by the Department of Energy/Office of Safeguards and Security as part of the Sandia Laboratories Fixed Facility Physical Protection Program. 45 figs, 4 tables

  5. A novel type of very long baseline astronomical intensity interferometer

    Science.gov (United States)

    Borra, Ermanno F.

    2013-12-01

    This article presents a novel type of very long baseline astronomical interferometer that uses the fluctuations, as a function of time, of the intensity measured by a quadratic detector, which is a common type of astronomical detector. The theory on which the technique is based is validated by laboratory experiments. Its outstanding principal advantages comes from the fact that the angular structure of an astronomical object is simply determined from the visibility of the minima of the spectrum of the intensity fluctuations measured by the detector, as a function of the frequency of the fluctuations, while keeping the spacing between mirrors constant. This would allow a simple setup capable of high angular resolutions because it could use an extremely large baseline. Another major interest is that it allows for a more efficient use of telescope time because observations at a single baseline are sufficient, while amplitude and intensity interferometers need several observations at different baselines. The fact that one does not have to move the telescopes would also allow detecting faster time variations because having to move the telescopes sets a lower limit to the time variations that can be detected. The technique uses wave interaction effects and thus has some characteristics in common with intensity interferometry. A disadvantage of the technique, like in intensity interferometry, is that it needs strong sources if observing at high frequencies (e.g. the visible). This is a minor disadvantage in the radio region. At high frequencies, this disadvantage is mitigated by the fact that, like in intensity interferometry, the requirements of the optical quality of the mirrors used are far less severe than in amplitude interferometry so that poor quality large reflectors (e.g. Cherenkov telescopes) can be used in the optical region.

  6. The optimized baseline project: Reinventing environmental restoration at Hanford

    International Nuclear Information System (INIS)

    Goodenough, J.D.; Janaskie, M.T.; Kleinen, P.J.

    1994-01-01

    The U.S. Department of Energy Richland Operations Office (DOE-RL) is using a strategic planning effort (termed the Optimized Baseline Project) to develop a new approach to the Hanford Environmental Restoration program. This effort seeks to achieve a quantum leap improvement in performance through results oriented prioritization of activities. This effort was conducted in parallel with the renegotiation of the Tri-Party Agreement and provided DOE with an opportunity to propose innovative initiatives to promote cost effectiveness, accelerate progress in the Hanford Environmental Restoration Program and involve stakeholders in the decision-making process. The Optimized Baseline project is an innovative approach to program planning and decision-making in several respects. First, the process is a top down, value driven effort that responds to values held by DOE, the regulatory community and the public. Second, planning is conducted in a way that reinforces the technical management process at Richland, involves the regulatory community in substantive decisions, and includes the public. Third, the Optimized Baseline Project is being conducted as part of a sitewide Hanford initiative to reinvent Government. The planning process used for the Optimized Baseline Project has many potential applications at other sites and in other programs where there is a need to build consensus among diverse, independent groups of stakeholders and decisionmakers. The project has successfully developed and demonstrated an innovative approach to program planning that accelerates the pace of cleanup, involves the regulators as partners with DOE in priority setting, and builds public understanding and support for the program through meaningful opportunities for involvement

  7. Baseline descriptions for LWR spent fuel storage, handling, and transportation

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, J.W.; Sonnier, C.S.

    1978-04-01

    Baseline descriptions for the storage, handling, and transportation of reactor spent fuel are provided. The storage modes described include light water reactor (LWR) pools, away-from-reactor basins, dry surface storage, reprocessing-facility interim storage pools, and deep geologic storage. Land and water transportation are also discussed. This work was sponsored by the Department of Energy/Office of Safeguards and Security as part of the Sandia Laboratories Fixed Facility Physical Protection Program. 45 figs, 4 tables.

  8. Baseline and cognition activated brain SPECT imaging in depression

    International Nuclear Information System (INIS)

    Zhao Jinhua; Lin Xiangtong; Jiang Kaida; Liu Yongchang; Xu Lianqin

    1998-01-01

    Purpose: To evaluate the regional cerebral blood flow (rCBF) abnormalities through the semiquantitative analysis of the baseline and cognition activated rCBF imaging in unmedicated depressed patients. Methods: 27 depressed patients unmedicated by anti-depressants were enrolled. The diagnosis (depression of moderate degree with somatization) was confirmed by the ICD-10 criteria. 15 age matched normal controls were studied under identical conditions. Baseline and cognition activated 99m Tc-ECD SPECT were performed on 21 of the 27 patients with depression and 13 of the 15 normal controls. Baseline 99m Tc-ECD SPECT alone were performed on the rest 6 patients with depression and 2 normal controls. The cognitive activation is achieved by Wisconsin Card Sorting Test (WCST). 1110 MBq of 99m Tc-ECD was administered by intravenous bolus injection 5 minutes after the onset of the WCST. Semi-quantitative analysis was conducted with the 7th, 8th, 9th, 10th, 11th slices of the transaxial imaging. rCBF ratios of every ROI were calculated using the average tissue activity in the region divided by the maximum activity in the cerebellum. Results: 1) The baseline rCBF of left frontal (0.720) and left temporal lobe (0.720) were decreased significantly in depressed patients comparing with those of the control subjects. 2) The activated rCBF of left frontal lobe (0.719) and left temporal lobe (0.690), left parietal lobe (0.701) were decreased evidently than those of the controls. Conclusions: 1) Hypoperfusions of left frontal and left temporal cortexes were identified in patients with depression. 2) The hypoperfusion of left frontal and left temporal cortexes may be the cause of cognition disorder and depressed mood in patients with depression. 3) Cognition activated brain perfusion imaging is helpful for making a more accurate diagnosis of depression

  9. Robotics Collaborative Technology Alliance (RCTA) 2011 Baseline Assessment Experimental Strategy

    Science.gov (United States)

    2011-09-01

    Traversal over different surfaces— climbing stairs , negotiating ditches, etc.—is an inherent mobility concern. The platform capability of moving over...2 design, not run in a factorial manner. a. Goal: To establish a baseline for the height and type of stairs the SUGV is willing to climb . b...bricks to adjust heights of platforms)? (GDRS will handle this.) • Do we want to add something like bags of mulch as steps for the robot to climb or

  10. Baseline Gas Turbine Development Program. Fourteenth quarterly progress report

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, F W; Wagner, C E

    1976-04-30

    Progress is reported for a Baseline Gas Turbine Development Program sponsored by the Heat Engine Systems Branch, Division of Transportation Energy Conservation (TEC) of the Energy Research and Development Administration (ERDA). Structurally, this program is made up of three parts: (1) documentation of the existing automotive gas turbine state-of-the-art; (2) conduction of an extensive component improvement program; and (3) utilization of the improvements in the design, and building of an Upgraded Engine capable of demonstrating program goals.

  11. Vascular Function at Baseline in the Hemodialysis Fistula Maturation Study

    OpenAIRE

    Dember, Laura M.; Imrey, Peter B.; Duess, Mai?Ann; Hamburg, Naomi M.; Larive, Brett; Radeva, Milena; Himmelfarb, Jonathan; Kraiss, Larry W.; Kusek, John W.; Roy?Chaudhury, Prabir; Terry, Christi M.; Vazquez, Miguel A.; Vongpatanasin, Wanpen; Beck, Gerald J.; Vita, Joseph A.

    2016-01-01

    Background End?stage renal disease is accompanied by functional and structural vascular abnormalities. The objective of this study was to characterize vascular function in a large cohort of patients with end?stage renal disease, using noninvasive physiological measurements, and to correlate function with demographic and clinical factors. Methods and Results We analyzed cross?sectional baseline data from the Hemodialysis Fistula Maturation Study, a multicenter prospective observational cohort ...

  12. Wide baseline stereo matching based on double topological relationship consistency

    Science.gov (United States)

    Zou, Xiaohong; Liu, Bin; Song, Xiaoxue; Liu, Yang

    2009-07-01

    Stereo matching is one of the most important branches in computer vision. In this paper, an algorithm is proposed for wide-baseline stereo vision matching. Here, a novel scheme is presented called double topological relationship consistency (DCTR). The combination of double topological configuration includes the consistency of first topological relationship (CFTR) and the consistency of second topological relationship (CSTR). It not only sets up a more advanced model on matching, but discards mismatches by iteratively computing the fitness of the feature matches and overcomes many problems of traditional methods depending on the powerful invariance to changes in the scale, rotation or illumination across large view changes and even occlusions. Experimental examples are shown where the two cameras have been located in very different orientations. Also, epipolar geometry can be recovered using RANSAC by far the most widely method adopted possibly. By the method, we can obtain correspondences with high precision on wide baseline matching problems. Finally, the effectiveness and reliability of this method are demonstrated in wide-baseline experiments on the image pairs.

  13. Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

    Science.gov (United States)

    Beaton, K. H.; Bloomberg, J. J.

    2014-01-01

    One of the greatest challenges surrounding adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. Such knowledge could guide individually customized countermeasures, which would enable more efficient use of crew time, both preflight and inflight, and provide better outcomes. The primary goal of this project is to look for a baseline performance metric that can forecast sensorimotor adaptability without exposure to an adaptive stimulus. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations in motor performance, as a predictor of individual sensorimotor adaptive capabilities. To-date, a strong relationship has been found between baseline inter-trial correlations and adaptability in two oculomotor systems. For this project, we will explore an analogous predictive mechanism in the locomotion system. METHODS: Baseline Inter-trial Correlations: Inter-trial correlations specify the relationships among repeated trials of a given task that transpire as a consequence of correcting for previous performance errors over multiple timescales. We can quantify the strength of inter-trial correlations by measuring the decay of the autocorrelation function (ACF), which describes how rapidly information from past trials is "forgotten." Processes whose ACFs decay more slowly exhibit longer-term inter-trial correlations (longer memory processes), while processes whose ACFs decay more rapidly exhibit shorterterm inter-trial correlations (shorter memory processes). Longer-term correlations reflect low-frequency activity, which is more easily

  14. Assessment of local GNSS baselines at co-location sites

    Science.gov (United States)

    Herrera Pinzón, Iván; Rothacher, Markus

    2018-01-01

    As one of the major contributors to the realisation of the International Terrestrial Reference System (ITRS), the Global Navigation Satellite Systems (GNSS) are prone to suffer from irregularities and discontinuities in time series. While often associated with hardware/software changes and the influence of the local environment, these discrepancies constitute a major threat for ITRS realisations. Co-located GNSS at fundamental sites, with two or more available instruments, provide the opportunity to mitigate their influence while improving the accuracy of estimated positions by examining data breaks, local biases, deformations, time-dependent variations and the comparison of GNSS baselines with existing local tie measurements. With the use of co-located GNSS data from a subset sites of the International GNSS Service network, this paper discusses a global multi-year analysis with the aim of delivering homogeneous time series of coordinates to analyse system-specific error sources in the local baselines. Results based on the comparison of different GNSS-based solutions with the local survey ties show discrepancies of up to 10 mm despite GNSS coordinate repeatabilities at the sub-mm level. The discrepancies are especially large for the solutions using the ionosphere-free linear combination and estimating tropospheric zenith delays, thus corresponding to the processing strategy used for global solutions. Snow on the antennas causes further problems and seasonal variations of the station coordinates. These demonstrate the need for a permanent high-quality monitoring of the effects present in the short GNSS baselines at fundamental sites.

  15. Item response theory analysis of the mechanics baseline test

    Science.gov (United States)

    Cardamone, Caroline N.; Abbott, Jonathan E.; Rayyan, Saif; Seaton, Daniel T.; Pawl, Andrew; Pritchard, David E.

    2012-02-01

    Item response theory is useful in both the development and evaluation of assessments and in computing standardized measures of student performance. In item response theory, individual parameters (difficulty, discrimination) for each item or question are fit by item response models. These parameters provide a means for evaluating a test and offer a better measure of student skill than a raw test score, because each skill calculation considers not only the number of questions answered correctly, but the individual properties of all questions answered. Here, we present the results from an analysis of the Mechanics Baseline Test given at MIT during 2005-2010. Using the item parameters, we identify questions on the Mechanics Baseline Test that are not effective in discriminating between MIT students of different abilities. We show that a limited subset of the highest quality questions on the Mechanics Baseline Test returns accurate measures of student skill. We compare student skills as determined by item response theory to the more traditional measurement of the raw score and show that a comparable measure of learning gain can be computed.

  16. Localizing gravitational wave sources with single-baseline atom interferometers

    Science.gov (United States)

    Graham, Peter W.; Jung, Sunghoon

    2018-02-01

    Localizing sources on the sky is crucial for realizing the full potential of gravitational waves for astronomy, astrophysics, and cosmology. We show that the midfrequency band, roughly 0.03 to 10 Hz, has significant potential for angular localization. The angular location is measured through the changing Doppler shift as the detector orbits the Sun. This band maximizes the effect since these are the highest frequencies in which sources live for several months. Atom interferometer detectors can observe in the midfrequency band, and even with just a single baseline they can exploit this effect for sensitive angular localization. The single-baseline orbits around the Earth and the Sun, causing it to reorient and change position significantly during the lifetime of the source, and making it similar to having multiple baselines/detectors. For example, atomic detectors could predict the location of upcoming black hole or neutron star merger events with sufficient accuracy to allow optical and other electromagnetic telescopes to observe these events simultaneously. Thus, midband atomic detectors are complementary to other gravitational wave detectors and will help complete the observation of a broad range of the gravitational spectrum.

  17. Rutin as a Mediator of Lipid Metabolism and Cellular Signaling Pathways Interactions in Fibroblasts Altered by UVA and UVB Radiation

    Directory of Open Access Journals (Sweden)

    Agnieszka Gęgotek

    2017-01-01

    Full Text Available Background. Rutin is a natural nutraceutical that is a promising compound for the prevention of UV-induced metabolic changes in skin cells. The aim of this study was to examine the effects of rutin on redox and endocannabinoid systems, as well as proinflammatory and proapoptotic processes, in UV-irradiated fibroblasts. Methods. Fibroblasts exposed to UVA and UVB radiation were treated with rutin. The activities and levels of oxidants/antioxidants and endocannabinoid system components, as well as lipid, DNA, and protein oxidation products, and the proinflammatory and pro/antiapoptotic proteins expression were measured. Results. Rutin reduced UV-induced proinflammatory response and ROS generation and enhanced the activity/levels of antioxidants (SOD, GSH-Px, vitamin E, GSH, and Trx. Rutin also normalized UV-induced Nrf2 expression. Its biological activity prevented changes in the levels of the lipid mediators: MDA, 4-HNE, and endocannabinoids, as well as the endocannabinoid receptors CB1/2, VR1, and GPR55 expression. Furthermore, rutin prevented the protein modifications (tyrosine derivatives formation in particular and decreased the levels of the proapoptotic markers—caspase-3 and cytochrome c. Conclusion. Rutin prevents UV-induced inflammation and redox imbalance at protein and transcriptional level which favors lipid, protein, and DNA protection. In consequence rutin regulates endocannabinoid system and apoptotic balance.

  18. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  19. Flexible Mediation Analysis With Multiple Mediators.

    Science.gov (United States)

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....

  1. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

  2. Applied mediation analyses

    DEFF Research Database (Denmark)

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  3. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  4. Implementing general gauge mediation

    International Nuclear Information System (INIS)

    Carpenter, Linda M.; Dine, Michael; Festuccia, Guido; Mason, John D.

    2009-01-01

    Recently there has been much progress in building models of gauge mediation, often with predictions different than those of minimal gauge mediation. Meade, Seiberg, and Shih have characterized the most general spectrum which can arise in gauge-mediated models. We discuss some of the challenges of building models of general gauge mediation, especially the problem of messenger parity and issues connected with R symmetry breaking and CP violation. We build a variety of viable, weakly coupled models which exhibit some or all of the possible low energy parameters.

  5. Baseline requirements for assessment of mining impact using biological monitoring

    International Nuclear Information System (INIS)

    Humphrey, C.L.; Dostine, P.L.

    1995-01-01

    Biological monitoring programmes for environmental protection should provide for both early detection of possible adverse effects, and assessment of the ecological significance of these effects. Monitoring techniques are required that include responses sensitive to the impact, that can be subjected to rigorous statistical analysis and for which statistical power is high. Such issues in baseline research of 'what and how to measure?' and 'for how long?' have been the focus of a programme being developed to monitor and assess effects of mining operations on the essentially pristine, freshwater ecosystems of the Alligator Rivers Region (ARR) in tropical northern Australia. Application of the BACIP (Before, After, Control, Impact, Paired differences) design, utilizing a form of temporal replication, to univariate (single species) and multivariate (community) data is described. The BACIP design incorporates data from single control and impact sites. We argue for modification of the design for particular studies conducted in streams, to incorporate additional independent control sites from adjacent catchment. Inferential power, by way of (i) more confidently attributing cause to an observed change and (ii) providing information about the ecological significance of the change, will be enhanced using a modified BACIP design. In highly valued environments such as the ARR, monitoring programmes require application of statistical tests with high power to guarantee that an impact no greater than a prescribed amount has gone undetected. A minimum number of baseline years using the BACIP approach would therefore be required in order to achieve some desired level of statistical power. This paper describes the results of power analyses conducted on 2-5 years (depending upon the technique) of baseline data from streams of the ARR and discuss the implications of these results for management. 44 refs., 1 tab., 3 figs

  6. 200-UP-2 Operable Unit technical baseline report

    International Nuclear Information System (INIS)

    Deford, D.H.

    1991-02-01

    This report is prepared in support of the development of a Remedial Investigation/Feasibility Study (RI/FS) Work Plan for the 200-UP-2 Operable Unit by EBASCO Environmental, Incorporated. It provides a technical baseline of the 200-UP-2 Operable Unit and results from an environmental investigation undertaken by the Technical Baseline Section of the Environmental Engineering Group, Westinghouse Hanford Company (Westinghouse Hanford). The 200-UP-2 Operable Unit Technical Baseline Report is based on review and evaluation of numerous Hanford Site current and historical reports, Hanford Site drawings and photographs and is supplemented with Hanford Site inspections and employee interviews. No field investigations or sampling were conducted. Each waste site in the 200-UP-2 Operable Unit is described separately. Close relationships between waste units, such as overflow from one to another, are also discussed. The 200-UP-2 Operable Unit consists of liquid-waste disposal sites in the vicinity of, and related to, U Plant operations in the 200 West Area of the Hanford Site. The ''U Plant'' refers to the 221-U Process Canyon Building, a chemical separations facility constructed during World War 2. It also includes the Uranium Oxide (UO 3 ) Plant, which was constructed at the same time and, like the 221-U Process Canyon Building, was later converted for other missions. Waste sites in the 200-UP-2 Operable Unit are associated with the U Plant Uranium Metal Recovery Program mission that occurred between 1952 and 1958 and the UO 3 Plant's ongoing uranium oxide mission and include one or more cribs, reverse wells, french drains, septic tanks and drain fields, trenches, catch tanks, settling tanks, diversion boxes, waste vaults, and the lines and encasements that connect them. 11 refs., 1 tab

  7. Re-creating missing population baselines for Pacific reef sharks.

    Science.gov (United States)

    Nadon, Marc O; Baum, Julia K; Williams, Ivor D; McPherson, Jana M; Zgliczynski, Brian J; Richards, Benjamin L; Schroeder, Robert E; Brainard, Russell E

    2012-06-01

    Sharks and other large predators are scarce on most coral reefs, but studies of their historical ecology provide qualitative evidence that predators were once numerous in these ecosystems. Quantifying density of sharks in the absence of humans (baseline) is, however, hindered by a paucity of pertinent time-series data. Recently researchers have used underwater visual surveys, primarily of limited spatial extent or nonstandard design, to infer negative associations between reef shark abundance and human populations. We analyzed data from 1607 towed-diver surveys (>1 ha transects surveyed by observers towed behind a boat) conducted at 46 reefs in the central-western Pacific Ocean, reefs that included some of the world's most pristine coral reefs. Estimates of shark density from towed-diver surveys were substantially lower (sharks observed in towed-diver surveys and human population in models that accounted for the influence of oceanic primary productivity, sea surface temperature, reef area, and reef physical complexity. We used these models to estimate the density of sharks in the absence of humans. Densities of gray reef sharks (Carcharhinus amblyrhynchos), whitetip reef sharks (Triaenodon obesus), and the group "all reef sharks" increased substantially as human population decreased and as primary productivity and minimum sea surface temperature (or reef area, which was highly correlated with temperature) increased. Simulated baseline densities of reef sharks under the absence of humans were 1.1-2.4/ha for the main Hawaiian Islands, 1.2-2.4/ha for inhabited islands of American Samoa, and 0.9-2.1/ha for inhabited islands in the Mariana Archipelago, which suggests that density of reef sharks has declined to 3-10% of baseline levels in these areas. ©2012 Society for Conservation Biology No claim to original US government works.

  8. Baseline Predictors of Missed Visits in the Look AHEAD Study

    Science.gov (United States)

    Fitzpatrick, Stephanie L.; Jeffery, Robert; Johnson, Karen C.; Roche, Cathy C.; Van Dorsten, Brent; Gee, Molly; Johnson, Ruby Ann; Charleston, Jeanne; Dotson, Kathy; Walkup, Michael P.; Hill-Briggs, Felicia; Brancati, Frederick L.

    2013-01-01

    Objective To identify baseline attributes associated with consecutively missed data collection visits during the first 48 months of Look AHEAD—a randomized, controlled trial in 5145 overweight/obese adults with type 2 diabetes designed to determine the long-term health benefits of weight loss achieved by lifestyle change. Design and Methods The analyzed sample consisted of 5016 participants who were alive at month 48 and enrolled at Look AHEAD sites. Demographic, baseline behavior, psychosocial factors, and treatment randomization were included as predictors of missed consecutive visits in proportional hazard models. Results In multivariate Cox proportional hazard models, baseline attributes of participants who missed consecutive visits (n=222) included: younger age ( Hazard Ratio [HR] 1.18 per 5 years younger; 95% Confidence Interval 1.05, 1.30), higher depression score (HR 1.04; 1.01, 1.06), non-married status (HR 1.37; 1.04, 1.82), never self-weighing prior to enrollment (HR 2.01; 1.25, 3.23), and randomization to minimal vs. intensive lifestyle intervention (HR 1.46; 1.11, 1.91). Conclusions Younger age, symptoms of depression, non-married status, never self-weighing, and randomization to minimal intervention were associated with a higher likelihood of missing consecutive data collection visits, even in a high-retention trial like Look AHEAD. Whether modifications to screening or retention efforts targeted to these attributes might enhance long-term retention in behavioral trials requires further investigation. PMID:23996977

  9. The LIFE Cognition Study: design and baseline characteristics

    Science.gov (United States)

    Sink, Kaycee M; Espeland, Mark A; Rushing, Julia; Castro, Cynthia M; Church, Timothy S; Cohen, Ronald; Gill, Thomas M; Henkin, Leora; Jennings, Janine M; Kerwin, Diana R; Manini, Todd M; Myers, Valerie; Pahor, Marco; Reid, Kieran F; Woolard, Nancy; Rapp, Stephen R; Williamson, Jeff D

    2014-01-01

    Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate–high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey–Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7) had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P<0.001). The LIFE Study will contribute important information on the effects of a structured physical activity program on cognitive outcomes in sedentary older adults at particular risk for mobility impairment. In addition to its importance in the

  10. TWRS phase I privatization site environmental baseline and characterization plan

    International Nuclear Information System (INIS)

    Shade, J.W.

    1997-01-01

    This document provides a plan to characterize and develop an environmental baseline for the TWRS Phase I Privatization Site before construction begins. A site evaluation study selected the former Grout Disposal Area of the Grout Treatment Facility in the 200 East Area as the TWRS Phase I Demonstration Site. The site is generally clean and has not been used for previous activities other than the GTF. A DQO process was used to develop a Sampling and Analysis Plan that would allow comparison of site conditions during operations and after Phase I ends to the presently existing conditions and provide data for the development of a preoperational monitoring plan

  11. Spectrum from the Proposed BNL Very Long Baseline Neutrino Facility

    CERN Document Server

    Kahn, S A

    2005-01-01

    This paper calculates the neutrino flux that would be seen at the far detector location from the proposed BNL Very Long Baseline Neutrino Facility. The far detector is assumed to be located at an underground facility in South Dakota 2540 km from BNL. The neutrino beam facility uses a 1 MW upgraded AGS to provide an intense proton beam on the target and a magnetic horn to focus the secondary pion beam. The paper will examine the sensitivity of the neutrino flux at the far detector to the positioning of the horn and target so as to establish alignment tolerances for the neutrino system.

  12. Integrated Baseline System (IBS) Version 1.03: Utilities guide

    Energy Technology Data Exchange (ETDEWEB)

    Burford, M.J.; Downing, T.R.; Pottier, M.C.; Schrank, E.E.; Williams, J.R.

    1993-01-01

    The Integrated Baseline System (IBS) is an emergency management planning and analysis tool that was developed under the direction of the Federal Emergency Management Agency (FEMA). This Utilities Guide explains how to operate utility programs that are supplied as a part of the IBS. These utility programs are chiefly for managing and manipulating various kinds of IBS data and system administration files. Many of the utilities are for creating, editing, converting, or displaying map data and other data that are related to geographic location.

  13. Integrated Baseline System (IBS) Version 2.0: Utilities Guide

    Energy Technology Data Exchange (ETDEWEB)

    Burford, M.J.; Downing, T.R.; Williams, J.R. [Pacific Northwest Lab., Richland, WA (United States); Bower, J.C. [Bower Software Services, Kennewick, WA (United States)

    1994-03-01

    The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the US Army Nuclear and Chemical Agency. This Utilities Guide explains how you can use the IBS utility programs to manage and manipulate various kinds of IBS data. These programs include utilities for creating, editing, and displaying maps and other data that are referenced to geographic location. The intended audience for this document are chiefly data managers but also system managers and some emergency management planners and analysts.

  14. Baseline review of the U.S. LHC Accelerator project

    International Nuclear Information System (INIS)

    1998-02-01

    The Department of Energy (DOE) Review of the U.S. Large Hadron Collider (LHC) Accelerator project was conducted February 23--26, 1998, at the request of Dr. John R. O'Fallon, Director, Division of High Energy Physics, Office of Energy Research, U.S. DOE. This is the first review of the U.S. LHC Accelerator project. Overall, the Committee found that the U.S. LHC Accelerator project effort is off to a good start and that the proposed scope is very conservative for the funding available. The Committee recommends that the project be initially baselined at a total cost of $110 million, with a scheduled completion data of 2005. The U.S. LHC Accelerator project will supply high technology superconducting magnets for the interaction regions (IRs) and the radio frequency (rf) straight section of the LHC intersecting storage rings. In addition, the project provides the cryogenic support interface boxes to service the magnets and radiation absorbers to protect the IR dipoles and the inner triplet quadrupoles. US scientists will provide support in analyzing some of the detailed aspects of accelerator physics in the two rings. The three laboratories participating in this project are Brookhaven National Laboratory, Fermi National Accelerator Laboratory (Fermilab), and Lawrence Berkeley National Laboratory. The Committee was very impressed by the technical capabilities of the US LHC Accelerator project team. Cost estimates for each subsystem of the US LHC Accelerator project were presented to the Review Committee, with a total cost including contingency of $110 million (then year dollars). The cost estimates were deemed to be conservative. A re-examination of the funding profile, costs, and schedules on a centralized project basis should lead to an increased list of deliverables. The Committee concluded that the proposed scope of US deliverables to CERN can be readily accomplished with the $110 million total cost baseline for the project. The current deliverables should serve as

  15. Organic Contamination Baseline Study on NASA JSC Astromaterial Curation Gloveboxes

    Science.gov (United States)

    Calaway, Michael J.; Allton, J. H.; Allen, C. C.; Burkett, P. J.

    2013-01-01

    Future planned sample return missions to carbon-rich asteroids and Mars in the next two decades will require strict handling and curation protocols as well as new procedures for reducing organic contamination. After the Apollo program, astromaterial collections have mainly been concerned with inorganic contamination [1-4]. However, future isolation containment systems for astromaterials, possibly nitrogen enriched gloveboxes, must be able to reduce organic and inorganic cross-contamination. In 2012, a baseline study was orchestrated to establish the current state of organic cleanliness in gloveboxes used by NASA JSC astromaterials curation labs that could be used as a benchmark for future mission designs.

  16. Scanner baseliner monitoring and control in high volume manufacturing

    Science.gov (United States)

    Samudrala, Pavan; Chung, Woong Jae; Aung, Nyan; Subramany, Lokesh; Gao, Haiyong; Gomez, Juan-Manuel

    2016-03-01

    We analyze performance of different customized models on baseliner overlay data and demonstrate the reduction in overlay residuals by ~10%. Smart Sampling sets were assessed and compared with the full wafer measurements. We found that performance of the grid can still be maintained by going to one-third of total sampling points, while reducing metrology time by 60%. We also demonstrate the feasibility of achieving time to time matching using scanner fleet manager and thus identify the tool drifts even when the tool monitoring controls are within spec limits. We also explore the scanner feedback constant variation with illumination sources.

  17. Environmental surveys of the Heidrun field. Supplementary baseline survey 1992

    International Nuclear Information System (INIS)

    Oug, E.; Konieczny, R.M.; Bakke, T.; Lind, K.

    1993-02-01

    The present survey is a re-investigation of the sea bottom sediments at six sites in the Heidrun oil and gas field, May 1992. Petroleum hydrocarbons and heavy metals were at background levels. Compared to the baseline survey in 1988 values of hydrocarbons and barium were decreased. The sediment fauna was sparse with low numbers of species and individuals. Densities were strongly reduced and diversity decreased compared to 1988. There is no indication of anthropogenic factors or other large scale disturbances in the area to explain the faunal changes, which may reflect a large natural variation in the sediment fauna. 22 refs., 16 figs., 35 tabs

  18. Integrated Baseline System (IBS) Version 2.0: Models guide

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    The Integrated Baseline System (IBS) is an emergency management planning and analysis tool being developed under the direction of the US Army Nuclear and Chemical Agency. This Models Guide summarizes the IBS use of several computer models for predicting the results of emergency situations. These include models for predicting dispersion/doses of airborne contaminants, traffic evacuation, explosion effects, heat radiation from a fire, and siren sound transmission. The guide references additional technical documentation on the models when such documentation is available from other sources. The audience for this manual is chiefly emergency management planners and analysts, but also data managers and system managers.

  19. Exploring the potential of short-baseline physics at Fermilab

    Science.gov (United States)

    Miranda, O. G.; Pasquini, Pedro; Tórtola, M.; Valle, J. W. F.

    2018-05-01

    We study the capabilities of the short-baseline neutrino program at Fermilab to probe the unitarity of the lepton mixing matrix. We find the sensitivity to be slightly better than the current one. Motivated by the future DUNE experiment, we have also analyzed the potential of an extra liquid Argon near detector in the LBNF beamline. Adding such a near detector to the DUNE setup will substantially improve the current sensitivity on nonunitarity. This would help to remove C P degeneracies due to the new complex phase present in the neutrino mixing matrix. We also study the sensitivity of our proposed setup to light sterile neutrinos for various configurations.

  20. Project W-320 thermal hydraulic model benchmarking and baselining

    International Nuclear Information System (INIS)

    Sathyanarayana, K.

    1998-01-01

    Project W-320 will be retrieving waste from Tank 241-C-106 and transferring the waste to Tank 241-AY-102. Waste in both tanks must be maintained below applicable thermal limits during and following the waste transfer. Thermal hydraulic process control models will be used for process control of the thermal limits. This report documents the process control models and presents a benchmarking of the models with data from Tanks 241-C-106 and 241-AY-102. Revision 1 of this report will provide a baselining of the models in preparation for the initiation of sluicing

  1. Emergency Response Capability Baseline Needs Assessment Compliance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-09-16

    This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2013 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2009 BNA, the 2012 BNA document, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures.

  2. The Baseline Positron Production and Capture Scheme for CLIC

    CERN Document Server

    Dadoun, Olivier; Lepercq, Pierre; Poirier, Freddy; Variola, Alessandro; Chehab, Robert; Rinolfi, Louis; Vivoli, Alessandro; Strakhovenko, Vladimir; Xu, Chengai

    2010-01-01

    The CLIC study considers the hybrid source using channeling as the baseline for unpolarised positron production. The hybrid source uses a few GeV electron beam impinging on a tungsten crystal target. With the crystal oriented on its axis it results an intense relatively low energy photon beam. The later is then impinging on an amorphous tungsten target producing positrons by e+e− pair creation. Downstream the amorphous target, a capture section based on an adiabatic matching device followed by a 2 GHz Pre- Injector Linac focuses and accelerates the positron beam up to around 200 MeV

  3. Developing models of how cognitive improvements change functioning: Mediation, moderation and moderated mediation

    Science.gov (United States)

    Wykes, Til; Reeder, Clare; Huddy, Vyv; Taylor, Rumina; Wood, Helen; Ghirasim, Natalia; Kontis, Dimitrios; Landau, Sabine

    2012-01-01

    Background Cognitive remediation (CRT) affects functioning but the extent and type of cognitive improvements necessary are unknown. Aim To develop and test models of how cognitive improvement transfers to work behaviour using the data from a current service. Method Participants (N49) with a support worker and a paid or voluntary job were offered CRT in a Phase 2 single group design with three assessments: baseline, post therapy and follow-up. Working memory, cognitive flexibility, planning and work outcomes were assessed. Results Three models were tested (mediation — cognitive improvements drive functioning improvement; moderation — post treatment cognitive level affects the impact of CRT on functioning; moderated mediation — cognition drives functioning improvements only after a certain level is achieved). There was evidence of mediation (planning improvement associated with improved work quality). There was no evidence that cognitive flexibility (total Wisconsin Card Sorting Test errors) and working memory (Wechsler Adult Intelligence Scale III digit span) mediated work functioning despite significant effects. There was some evidence of moderated mediation for planning improvement if participants had poorer memory and/or made fewer WCST errors. The total CRT effect on work quality was d = 0.55, but the indirect (planning-mediated CRT effect) was d = 0.082 Conclusion Planning improvements led to better work quality but only accounted for a small proportion of the total effect on work outcome. Other specific and non-specific effects of CRT and the work programme are likely to account for some of the remaining effect. This is the first time complex models have been tested and future Phase 3 studies need to further test mediation and moderated mediation models. PMID:22503640

  4. A baseline for the multivariate comparison of resting state networks

    Directory of Open Access Journals (Sweden)

    Elena A Allen

    2011-02-01

    Full Text Available As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting state networks of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12 to 71 years. Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. Resting state networks were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

  5. The IUGS/IAGC Task Group on Global Geochemical Baselines

    Science.gov (United States)

    Smith, David B.; Wang, Xueqiu; Reeder, Shaun; Demetriades, Alecos

    2012-01-01

    The Task Group on Global Geochemical Baselines, operating under the auspices of both the International Union of Geological Sciences (IUGS) and the International Association of Geochemistry (IAGC), has the long-term goal of establishing a global geochemical database to document the concentration and distribution of chemical elements in the Earth’s surface or near-surface environment. The database and accompanying element distribution maps represent a geochemical baseline against which future human-induced or natural changes to the chemistry of the land surface may be recognized and quantified. In order to accomplish this long-term goal, the activities of the Task Group include: (1) developing partnerships with countries conducting broad-scale geochemical mapping studies; (2) providing consultation and training in the form of workshops and short courses; (3) organizing periodic international symposia to foster communication among the geochemical mapping community; (4) developing criteria for certifying those projects whose data are acceptable in a global geochemical database; (5) acting as a repository for data collected by those projects meeting the criteria for standardization; (6) preparing complete metadata for the certified projects; and (7) preparing, ultimately, a global geochemical database. This paper summarizes the history and accomplishments of the Task Group since its first predecessor project was established in 1988.

  6. Baseline metal concentrations in Paramoera walkeri from East Antarctica

    International Nuclear Information System (INIS)

    Palmer, Anne S. . E-mail Anne.Palmer@utas.edu.au; Snape, Ian; Stark, Jonathan S.; Johnstone, Glenn J.; Townsend, Ashley T.

    2006-01-01

    Remediation of the Thala Valley waste disposal site near Casey Station, East Antarctica was conducted in the austral summer of 2003/2004. Biomonitoring of the adjacent marine environment was undertaken using the gammaridean amphipod Paramoera walkeri as a sentinel species [Stark, J.S., Johnstone, G.J., Palmer, A.S., Snape, I., Larner, B.L., Riddle, M.J., in press, doi:10.1016/j.marpolbul.2006.05.020. Monitoring the remediation of a near shore waste disposal site in Antarctica using the amphipod Paramoera walkeri and diffusive gradients in thin films (DGTs). Marine Pollution Bulletin and references therein]. Determination of uptake of metals and hypothesis testing for differences that could be attributed to contamination required the establishment of baseline metal concentrations in P. walkeri. Baseline metal concentrations from two reference locations in the Windmill Islands are presented here. P. walkeri was a found to be a sensitive bioaccumulating organism that recorded spatial and temporal variability at the reference sites. Measurement of metals in P. walkeri required the development of a simple digestion procedure that used concentrated nitric acid. For the first time, rare earth metals were determined with additional clean procedures required to measure ultra low concentrations using magnetic sector ICP-MS. Certified and in-house reference materials were employed to ensure method reliability

  7. On the baseline evolution of automobile fuel economy in Europe

    International Nuclear Information System (INIS)

    Zachariadis, Theodoros

    2006-01-01

    'Business as usual' scenarios in long-term energy forecasts are crucial for scenario-based policy analyses. This article focuses on fuel economy of passenger cars and light trucks, a long-disputed issue with serious implications for worldwide energy use and CO 2 emissions. The current status in Europe is explained and future developments are analysed with the aid of historical data of the last three decades from the United States and Europe. As a result of this analysis, fuel economy values are proposed for use as assumptions in baseline energy/transport scenarios in the 15 'old' European Union Member States. Proposed values are given for new gasoline and diesel cars and for the years 2010, 2020 and 2030. The increasing discrepancy between vehicle fuel consumption measured under test conditions and that in the real world is also considered. One main conclusion is that the European Commission's voluntary agreement with the automobile industry should not be assumed to fully achieve its target under baseline conditions, nor should it be regarded as a major stimulus for autonomous vehicle efficiency improvements after 2010. A second conclusion is that three very recent studies enjoying authority across the EU tend to be overly optimistic as regards the technical progress for conventional and alternative vehicle propulsion technologies under 'business as usual' conditions

  8. U Plant Aggregate Area Management study technical baseline report

    International Nuclear Information System (INIS)

    DeFord, D.H.; Carpenter, R.W.

    1995-05-01

    This document was prepared in support of an Aggregate Area Management Study of U Plant. It provides a technical baseline of the aggregate area and results from an environmental investigation that was undertaken by the Technical Baseline Section of the Environmental Engineering Group, Westinghouse Hanford Company (WHC), which is currently the Waste Site and Facility Research Office, Natural Resources, Bechtel Hanford, Inc. (BHI). It is based upon review and evaluation of numerous Hanford Site current and historical reports, drawings and photographs, supplemented with site inspections and employee interviews. U Plant refers to the 221-U Process Canyon Building, a chemical separation facility constructed during World War II. It also includes the Uranium Oxide (UO 3 ) Plant constructed at the same time as 221-U as an adjunct to the original plutonium separation process but which, like 221-U, was converted for other missions. Waste sites are associated primarily with U Plant's 1952 through 1958 Uranium Metal Recovery Program mission and the U0 3 Plant's ongoing U0 3 mission. Waste sites include cribs, reverse wells, french drains, septic tanks and drain fields, trenches, catch tanks, settling tanks, diversion boxes, a waste vault, and the lines and encasements that connect them. It also includes the U Pond and its feed ditches and an underground tank farm designed for high-level liquid wastes

  9. NOvA Short-Baseline Tau Neutrino Appearance Search

    Energy Technology Data Exchange (ETDEWEB)

    Keloth, Rijeesh [Cochin U.; Aurisano, Adam [Cincinnati U.; Sousa, Alexander [Cincinnati U.; Davies, Gavin S [Indiana U.; Suter, Louise [Fermilab; Plunkett, Robert K [Fermilab

    2017-10-01

    Standard three-flavor neutrino oscillations have well explained by a wide range of neutrino experiments. However, the anomalous results, such as electron-antineutrino excess seen by LSND and MiniBooNE do not fit the three-flavor paradigm. This can be explained by an additional fourth flavor sterile neutrino at a larger scale than the existing three flavor neutrinos. The NOvA experiment consists of two finely segmented, liquid scintillator detectors operating 14 .6 mrad off-axis from the NuMI muon-neutrino beam. The Near Detector is located on the Fermilab campus, 1 km from the NuMI target, while the Far Detector is located at Ash River, MN, 810 km from the NuMI target. The NOvA experiment is primarily designed to measure electron-neutrino appearance at the Far Detector using the Near Detector to control systematic uncertainties; however, the Near Detector is well suited for searching for anomalous short-baseline oscillations. This poster will present a novel method for selecting tau neutrino interactions with high purity at the Near Detector using a convolutional neural network. Using this method, the sensitivity to anomalous short-baseline tau-neutrino appearance due to sterile neutrino oscillations will be presented.

  10. Moderate Baseline Vagal Tone Predicts Greater Prosociality in Children

    Science.gov (United States)

    Miller, Jonas G.; Kahle, Sarah; Hastings, Paul D.

    2016-01-01

    Vagal tone is widely believed to be an important physiological aspect of emotion regulation and associated positive behaviors. However, there is inconsistent evidence for relations between children’s baseline vagal tone and their helpful or prosocial responses to others (Hastings & Miller, 2014). Recent work in adults suggests a quadratic association (inverted U-shape curve) between baseline vagal tone and prosociality (Kogan et al., 2014). The present research examined whether this nonlinear association was evident in children. We found consistent evidence for a quadratic relation between vagal tone and prosociality across 3 samples of children using 6 different measures. Compared to low and high vagal tone, moderate vagal tone in early childhood concurrently predicted greater self-reported prosociality (Study 1), observed empathic concern in response to the distress of others and greater generosity toward less fortunate peers (Study 2), and longitudinally predicted greater self-, mother-, and teacher-reported prosociality 5.5 years later in middle childhood (Study 3). Taken together, our findings suggest that moderate vagal tone at rest represents a physiological preparedness or tendency to engage in different forms of prosociality across different contexts. Early moderate vagal tone may reflect an optimal balance of regulation and arousal that helps prepare children to sympathize, comfort, and share with others. PMID:27819463

  11. Baseline Glass Development for Combined Fission Products Waste Streams

    International Nuclear Information System (INIS)

    Crum, Jarrod V.; Billings, Amanda Y.; Lang, Jesse B.; Marra, James C.; Rodriguez, Carmen P.; Ryan, Joseph V.; Vienna, John D.

    2009-01-01

    Borosilicate glass was selected as the baseline technology for immobilization of the Cs/Sr/Ba/Rb (Cs), lanthanide (Ln) and transition metal fission product (TM) waste steams as part of a cost benefit analysis study.(1) Vitrification of the combined waste streams have several advantages, minimization of the number of waste forms, a proven technology, and similarity to waste forms currently accepted for repository disposal. A joint study was undertaken by Pacific Northwest National Laboratory (PNNL) and Savannah River National Laboratory (SRNL) to develop acceptable glasses for the combined Cs + Ln + TM waste streams (Option 1) and Cs + Ln combined waste streams (Option 2) generated by the AFCI UREX+ set of processes. This study is aimed to develop baseline glasses for both combined waste stream options and identify key waste components and their impact on waste loading. The elemental compositions of the four-corners study were used along with the available separations data to determine the effect of burnup, decay, and separations variability on estimated waste stream compositions.(2-5) Two different components/scenarios were identified that could limit waste loading of the combined Cs + LN + TM waste streams, where as the combined Cs + LN waste stream has no single component that is perceived to limit waste loading. Combined Cs + LN waste stream in a glass waste form will most likely be limited by heat due to the high activity of Cs and Sr isotopes.

  12. New light Higgs boson and short-baseline neutrino anomalies

    Science.gov (United States)

    Asaadi, J.; Church, E.; Guenette, R.; Jones, B. J. P.; Szelc, A. M.

    2018-04-01

    The low-energy excesses observed by the MiniBooNE experiment have, to date, defied a convincing explanation under the standard model even with accommodation for nonzero neutrino mass. In this paper we explore a new oscillation mechanism to explain these anomalies, invoking a light neutrinophilic Higgs boson, conceived to induce a low Dirac neutrino mass in accord with experimental limits. Beam neutrinos forward scattering off of a locally overdense relic neutrino background give rise to a novel matter effect with an energy-specific resonance. An enhanced oscillation around this resonance peak produces flavor transitions which are highly consistent with the MiniBooNE neutrino- and antineutrino-mode data sets. The model provides substantially improved χ2 values beyond either the no-oscillation hypothesis or the more commonly explored 3 +1 sterile neutrino hypothesis. This mechanism would introduce distinctive signatures at each baseline in the upcoming short-baseline neutrino program at Fermilab, presenting opportunities for further exploration.

  13. Gravity sensing using Very Long Baseline Atom Interferometry

    Science.gov (United States)

    Schlippert, D.; Wodey, E.; Meiners, C.; Tell, D.; Schubert, C.; Ertmer, W.; Rasel, E. M.

    2017-12-01

    Very Long Baseline Atom Interferometry (VLBAI) has applications in high-accuracy absolute gravimetry, gravity-gradiometry, and for tests of fundamental physics. Thanks to the quadratic scaling of the phase shift with increasing free evolution time, extending the baseline of atomic gravimeters from tens of centimeters to meters puts resolutions of 10-13g and beyond in reach.We present the design and progress of key elements of the VLBAI-test stand: a dual-species source of Rb and Yb, a high-performance two-layer magnetic shield, and an active vibration isolation system allowing for unprecedented stability of the mirror acting as an inertial reference. We envisage a vibration-limited short-term sensitivity to gravitational acceleration of 1x10-8 m/s-2Hz-1/2 and up to a factor of 25 improvement when including additional correlation with a broadband seismometer. Here, the supreme long-term stability of atomic gravity sensors opens the route towards competition with superconducting gravimeters. The operation of VLBAI as a differential dual-species gravimeter using ultracold mixtures of Yb and Rb atoms enables quantum tests of the universality of free fall (UFF) at an unprecedented level of <10-13, potentially surpassing the best experiments to date.

  14. Elevating Baseline Activation Does Not Facilitate Reading of Unattended Words

    Science.gov (United States)

    Lien, Mei-Ching; Kouchi, Scott; Ruthruff, Eric; Lachter, Joel B.

    2009-01-01

    Previous studies have disagreed the extent to which people extract meaning from words presented outside the focus of spatial attention. The present study, examined a possible explanation for such discrepancies, inspired by attenuation theory: unattended words can be read more automatically when they have a high baseline level of activation (e.g., due to frequent repetition or due to being expected in a given context). We presented a brief prime word in lowercase, followed by a target word in uppercase. Participants indicated whether the target word belonged to a particular category (e.g., "sport"). When we drew attention to the prime word using a visual cue, the prime produced substantial priming effects on target responses (i.e., faster responses when the prime and target words were identical or from the same category than when they belonged to different categories). When prime words were not attended, however, they produced no priming effects. This finding replicated even when there were only 4 words, each repeated 160 times during the experiment. Even with a very high baseline level of activation, it appears that very little word processing is possible without spatial attention.

  15. Eielson Air Force Base OU-1 baseline risk assessment

    International Nuclear Information System (INIS)

    Jarvis, M.T.; Jarvis, T.T.; Van Houten, N.C.; Lewis, R.E.

    1993-09-01

    This Baseline Risk Assessment report is the second volume in a set of three volumes for operable Unit 1 (OU-1). The companion documents contain the Remedial Investigation and the Feasibility Study. Operable Unit 1 (OU-1) is one of several groups of hazardous waste sites located at Eielson Air Force Base (AFB) near Fairbanks, Alaska. The operable units at Eielson are typically characterized by petroleum, oil, lubricant/solvent contamination, and by the presence of organics floating at the water table. In 1989 and 1990, firms under contract to the Air Force conducted field studies to gather information about the extent of chemical contamination in soil, groundwater, and soil air pore space (soil gas) at the site. This report documents the results of a baseline risk assessment, which uses the 1989 and 1991 site characterization database to quantify the potential human health risk associated with past Base industrial activities in the vicinity of OU-1. Background data collected in 1992 were also used in the preparation of this report

  16. DGEMP-OE (2008) Energy Baseline Scenario. Synthesis report

    International Nuclear Information System (INIS)

    2008-01-01

    A 'Business as usual' or 'Baseline' scenario of energy trends to 2020-2030 is produced by France every four years, as requested by the International Energy Agency in order to update the global scenarios published in its World Energy Outlook. Since the most recent scenario of this type was drawn up in 2003-2004, the time has come to renew the effort for the IEA's next in-depth review of French energy policy. Specifically, the DGEMP seeks to predict the future of France's energy situation assuming that no policies or new measures are taken affecting (i.e. improving or deteriorating) the situation other than those already in place or adopted as of 1 January 2008 (in other words, before measures such as those stemming from the Grenelle Environment Forum). On the other hand, it is assumed that change in the energy system is guided by 'conventional wisdom' according to which political options and behaviours by economic units are expected to be 'reasonable'. As a result, even should its projections prove inappropriate, this cannot be considered a 'worst-case' scenario. Indeed, beyond the IEA, this scenario can be used to establish an MEA (Multilateral Environment Agreement) scenario (based on existing measures) for national communications submitted under the U.N. Climate Convention. The scenarios by the 'Energy' Commission, part of the Centre d'Analyse Strategique (CAS), could have been used, particularly since the consultant who worked with the CAS to develop its scenarios was also commissioned by the DGEMP. However, several considerations argued in favour of proceeding separately: - The CAS scenarios drew on the DGEMP's 2004 baseline scenario, even though certain parameters were updated (in particular energy prices). - Moreover, the concept underpinning the DGEMP baseline scenario is that it should to every extent possible remain constant over time to secure continued consensus on this 'reference' at national level. - Finally, the MEDEE energy demand model applied in

  17. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function

    NARCIS (Netherlands)

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CBI

  18. Endocannabinoids shape accumbal encoding of cue-motivated behavior via CB1 receptor activation in the ventral tegmentum.

    Science.gov (United States)

    Oleson, Erik B; Beckert, Michael V; Morra, Joshua T; Lansink, Carien S; Cachope, Roger; Abdullah, Rehab A; Loriaux, Amy L; Schetters, Dustin; Pattij, Tommy; Roitman, Mitchell F; Lichtman, Aron H; Cheer, Joseph F

    2012-01-26

    Transient increases in nucleus accumbens (NAc) dopamine concentration are observed when animals are presented with motivationally salient stimuli and are theorized to energize reward seeking. They arise from high-frequency firing of dopamine neurons in the ventral tegmental area (VTA), which also results in the release of endocannabinoids from dopamine cell bodies. In this context, endocannabinoids are thought to regulate reward seeking by modulating dopamine signaling, although a direct link has never been demonstrated. To test this, we pharmacologically manipulated endocannabinoid neurotransmission in the VTA while measuring transient changes in dopamine concentration in the NAc during reward seeking. Disrupting endocannabinoid signaling dramatically reduced, whereas augmenting levels of the endocannabinoid 2-arachidonoylglycerol (2AG) increased, cue-evoked dopamine concentrations and reward seeking. These data suggest that 2AG in the VTA regulates reward seeking by sculpting ethologically relevant patterns of dopamine release during reward-directed behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Cannabinoid CB1 receptor agonists do not decrease, but may increase, acoustic trauma-induced tinnitus in rats

    Directory of Open Access Journals (Sweden)

    Yiwen eZheng

    2015-03-01

    Full Text Available Tinnitus has been suggested to arise from neuronal hyperactivity in auditory areas of the brain and anti-epileptic drugs are sometimes used to provide relief from tinnitus. Recently, the anti-epileptic properties of the cannabinoid drugs have gained increasing interest; however, the use of cannabinoids as a form of treatment for tinnitus is controversial. In the present study, we tested whether a combination of delta-9-tetrahydrocannabinol (delta-9-THC and cannabidiol (CBD, delivered in a 1:1 ratio, could affect tinnitus perception in a rat model of acoustic trauma-induced tinnitus. Following sham treatment or acoustic trauma, the animals were divided into the following groups: 1 sham (i.e. no acoustic trauma with vehicle treatment; 2 sham with drug treatment (i.e. delta-9-THC + CBD; 3 acoustic trauma-exposed exhibiting tinnitus, with drug treatment; and 4 acoustic trauma-exposed exhibiting no tinnitus, with drug treatment. The animals received either the vehicle or the cannabinoid drugs every day, 30 min before the tinnitus behavioural testing. Acoustic trauma caused a significant increase in the auditory brainstem response (ABR thresholds in the exposed animals, indicating hearing loss; however, there was a partial recovery over 6 months. Acoustic trauma did not always result in tinnitus; however among those that did exhibit tinnitus, some of them had tinnitus at multiple frequencies while others had it only at a single frequency. The cannabinoids significantly increased the number of tinnitus animals in the exposed-tinnitus group, but not in the sham group. The results suggest that cannabinoids may promote the development of tinnitus, especially when there is pre-existing hearing damage.

  20. Preparation of iodine-123 labeled AM251: a potential SPECT radioligand for the brain cannabinoid CB1 receptor

    International Nuclear Information System (INIS)

    Lan, Ruoxi; Makriyannis, Alexandros; Gatley, S.J.

    1996-01-01

    We report the synthesis and labeling with iodine-123 of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). This compound is an analog of the recently described cannabinoid receptor antagonist, SR141716A, in which a 4-chlorophenyl group is replaced by 4-iodophenyl. Labeling in good yield (62%) and radiochemical purity (> 95%), and high specific activity (> 2500 Ci/mmol) was achieved by an iododestannylation reaction using the tributyltin precursor, no carrier added I-123 iodide, and chloramine-T. (author)

  1. Preparation of iodine-123 labeled AM251: a potential SPECT radioligand for the brain cannabinoid CB1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Ruoxi; Makriyannis, Alexandros [Connecticut Univ., Molecular and Cell Biology Dept., Storrs, CT (United States); Gatley, S.J. [Brookhaven National Lab., Medical Dept., Upton, NY (United States)

    1996-10-01

    We report the synthesis and labeling with iodine-123 of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). This compound is an analog of the recently described cannabinoid receptor antagonist, SR141716A, in which a 4-chlorophenyl group is replaced by 4-iodophenyl. Labeling in good yield (62%) and radiochemical purity (> 95%), and high specific activity (> 2500 Ci/mmol) was achieved by an iododestannylation reaction using the tributyltin precursor, no carrier added I-123 iodide, and chloramine-T. (author).

  2. Structural basis for vinyl sulfone inhibition of the SmCB1 drug target from the human blood fluke

    Czech Academy of Sciences Publication Activity Database

    Jílková, Adéla; Marešová, Lucie; Rubešová, Petra; Fajtová, Pavla; Horn, Martin; Řezáčová, Pavlína; Brynda, Jiří; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael

    2017-01-01

    Roč. 284, Suppl 1 (2017), s. 191 ISSN 1742-464X. [FEBS Congress /42./ From Molecules to Cells and Back. 10.09.2017-14.09.2017, Jerusalem] Institutional support: RVO:61388963 Keywords : schistosomiasis * cathepsin B1 * inhibitor Subject RIV: CE - Biochemistry

  3. CB1 and CB2 Receptors are Novel Molecular Targets for Tamoxifen and 4OH-Tamoxifen

    OpenAIRE

    Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; Greer, Aleksandra K.; Bratton, Stacie M.; Ford, Benjamin M.; Franks, Lirit N.; Radominska-Pandya, Anna

    2013-01-01

    Tamoxifen (Tam) is classified as a selective estrogen receptor modulator (SERM) and is used for treatment of patients with ER-positive breast cancer. However, it has been shown that Tam and its cytochrome P450-generated metabolite 4-hydroxy-Tam (4OH-Tam) also exhibit cytotoxic effects in ER-negative breast cancer cells. These observations suggest that Tam and 4OH-Tam can produce cytotoxicity via estrogen receptor (ER)-independent mechanism(s) of action. The molecular targets responsible for t...

  4. SIR-C/X-SAR data calibration and ground truth campaign over the NASA-CB1 test-site

    International Nuclear Information System (INIS)

    Notarnicola, C.; Posa, F.; Refice, A.; Sergi, R.; Smacchia, P.; Casarano, D.; De Carolis, G.; Mattia, F.; Schena, V.D.

    2001-01-01

    During the Space Shuttle Endeavour mission in October 1994, a remote-sensing campaign was carried out with the objectives of both radiometric and polarimetric calibration and ground truth data acquisition of bare soils. This paper presents the results obtained in the experiment. Polarimetric cross-talk and channel imbalance values, as well as radiometric calibration parameters, have been found to be within the science requirements for SAR images. Regarding ground truth measurements, a wide spread in the height rms values and correlation lengths has been observed, which was motivated a critical revisiting of surface parameters descriptors

  5. Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation

    NARCIS (Netherlands)

    Kleijn, J.; Wiskerke, J.; Cremers, T.I.F.H.; Schoffelmeer, A.N.M.; Westerink, B.H.C.; Pattij, T.

    2012-01-01

    The psychostimulant drug amphetamine is often prescribed to treat Attention-Deficit/Hyperactivity Disorder. The behavioral effects of the psychostimulant drug amphetamine depend on its ability to increase monoamine neurotransmission in brain regions such as the nucleus accumbens (NAC) and medial

  6. Is Baseline Cardiac Autonomic Modulation Related to Performance and Physiological Responses Following a Supramaximal Judo Test?

    Science.gov (United States)

    Blasco-Lafarga, Cristina; Martínez-Navarro, Ignacio; Mateo-March, Manuel

    2013-01-01

    Little research exists concerning Heart Rate (HR) Variability (HRV) following supramaximal efforts focused on upper-body explosive strength-endurance. Since they may be very demanding, it seems of interest to analyse the relationship among performance, lactate and HR dynamics (i.e. HR, HRV and complexity) following them; as well as to know how baseline cardiac autonomic modulation mediates these relationships. The present study aimed to analyse associations between baseline and post-exercise HR dynamics following a supramaximal Judo test, and their relationship with lactate, in a sample of 22 highly-trained male judoists (20.70±4.56 years). A large association between the increase in HR from resting to exercise condition and performance suggests that individuals exerted a greater sympathetic response to achieve a better performance (Rating of Perceived Exertion: 20; post-exercise peak lactate: 11.57±2.24 mmol/L; 95.76±4.13 % of age-predicted HRmax). Athletes with higher vagal modulation and lower sympathetic modulation at rest achieved both a significant larger ∆HR and a faster post-exercise lactate removal. A enhanced resting parasympathetic modulation might be therefore related to a further usage of autonomic resources and a better immediate metabolic recovery during supramaximal exertions. Furthermore, analyses of variance displayed a persistent increase in α1 and a decrease in lnRMSSD along the 15 min of recovery, which are indicative of a diminished vagal modulation together with a sympathovagal balance leaning to sympathetic domination. Eventually, time-domain indices (lnRMSSD) showed no lactate correlations, while nonlinear indices (α1 and lnSaEn) appeared to be moderate to strongly correlated with it, thus pointing to shared mechanisms between neuroautonomic and metabolic regulation. PMID:24205273

  7. 40 CFR 80.1285 - How does a refiner apply for a benzene baseline?

    Science.gov (United States)

    2010-07-01

    ... baseline? 80.1285 Section 80.1285 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... (abt) Program § 80.1285 How does a refiner apply for a benzene baseline? (a) A benzene baseline... credits. (b) For U.S. Postal delivery, the benzene baseline application shall be sent to: Attn: MSAT2...

  8. Teaching Mediated Public Relations.

    Science.gov (United States)

    Kent, Michael L.

    2001-01-01

    Discusses approaches to teaching a mediated public relations course, emphasizing the World Wide Web. Outlines five course objectives, assignments and activities, evaluation, texts, and lecture topics. Argues that students mastering these course objectives will understand ethical issues relating to media use, using mediated technology in public…

  9. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

  10. The Mediated Transparent Society

    DEFF Research Database (Denmark)

    Backer, Lise

    2001-01-01

    in the mediated transparent society. The paper concludes that, based on these analyses, the mediated panopticism working on the business segment is not an effective disciplinary apparatus, which can guarantee that business corporations are carrying out important ecological or ethical improvements....

  11. Laccase/Mediator Systems

    NARCIS (Netherlands)

    Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

    2018-01-01

    Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

  12. The multitalented Mediator complex.

    Science.gov (United States)

    Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

    2013-11-01

    The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Music, radio and mediatization

    DEFF Research Database (Denmark)

    Michelsen, Morten; Krogh, Mads

    2016-01-01

    of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex nonlinearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life.......Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music–radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...

  14. Exhaled Breath Condensate Detects Baseline Reductions in Chloride and Increases in Response to Albuterol in Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    Courtney M. Wheatley

    2013-01-01

    Full Text Available Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF lung disease. A potential application of exhaled breath condensate (EBC collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl − , DLCO and SpO 2 were lower in CF (n = 16 compared to healthy participants (n = 16. EBC Cl − increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO 2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl − in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.

  15. Very Long Baseline Interferometry: Dependencies on Frequency Stability

    Science.gov (United States)

    Nothnagel, Axel; Nilsson, Tobias; Schuh, Harald

    2018-04-01

    Very Long Baseline Interferometry (VLBI) is a differential technique observing radiation of compact extra-galactic radio sources with pairs of radio telescopes. For these observations, the frequency standards at the telescopes need to have very high stability. In this article we discuss why this is, and we investigate exactly how precise the frequency standards need to be. Four areas where good clock performance is needed are considered: coherence, geodetic parameter estimation, correlator synchronization, and UT1 determination. We show that in order to ensure the highest accuracy of VLBI, stability similar to that of a hydrogen maser is needed for time-scales up to a few hours. In the article, we are considering both traditional VLBI where extra-galactic radio sources are observed, as well as observation of man-made artificial radio sources emitted by satellites or spacecrafts.

  16. Sandia National Laboratories, California proposed CREATE facility environmental baseline survey.

    Energy Technology Data Exchange (ETDEWEB)

    Catechis, Christopher Spyros

    2013-10-01

    Sandia National Laboratories, Environmental Programs completed an environmental baseline survey (EBS) of 12.6 acres located at Sandia National Laboratories/California (SNL/CA) in support of the proposed Collaboration in Research and Engineering for Advanced Technology and Education (CREATE) Facility. The survey area is comprised of several parcels of land within SNL/CA, County of Alameda, California. The survey area is located within T 3S, R 2E, Section 13. The purpose of this EBS is to document the nature, magnitude, and extent of any environmental contamination of the property; identify potential environmental contamination liabilities associated with the property; develop sufficient information to assess the health and safety risks; and ensure adequate protection for human health and the environment related to a specific property.

  17. PUREX Plant aggregate area management study technical baseline report

    International Nuclear Information System (INIS)

    DeFord, D.H.; Carpenter, R.W.

    1995-05-01

    The PUREX aggregate area is made up of six operable units; 200-PO-1 through 200-PO-6 and consists of liquid and solid waste disposal sites in the vicinity of, and related to, PUREX Plant operations. This report describes PUREX and its waste sites, including cribs, french drains, septic tanks and drain fields, trenches and ditches, ponds, catch tanks, settling tanks, diversion boxes, underground tank farms, and the lines and encasements that connect them. Each waste site in the aggregate area is described separately. Close relationships between waste units, such as overflow from one to another, are also discussed. This document provides a technical baseline of the aggregate area and results from an environmental investigation. This document is based upon review and evaluation of numerous Hanford Site current and historical reports, drawings and photographs, supplemented with site inspections and employee interviews. No intrusive field investigations or sampling were conducted

  18. Z plant aggregate area management study technical baseline report

    International Nuclear Information System (INIS)

    DeFord, D.H.; Carpenter, R.W.

    1995-05-01

    This document was prepared in support of the development of a Aggregate Area Management Study of Z Plant, 200 West Area, at the US Department of Energy (DOE) Hanford Site near Richland, Washington. It provides a technical description and operational history of the aggregate area and results from an environmental investigation undertaken by the Technical Baseline Section of the Environmental Engineering Group, Westinghouse Hanford Company (WHC) which is currently the Waste Site and Facility Research Office, Natural Resources, Bechtel Hanford, Inc. (BHI). It is based upon review and evaluation of numerous Hanford Site current and historical reports, drawings and photographs, supplemented with site inspections and employee interviews. No intrusive field investigations or sampling were conducted in support of this report

  19. Baselines and test data for cross-lingual inference

    DEFF Research Database (Denmark)

    Agic, Zeljko; Schluter, Natalie

    2018-01-01

    The recent years have seen a revival of interest in textual entailment, sparked by i) the emergence of powerful deep neural network learners for natural language processing and ii) the timely development of large-scale evaluation datasets such as SNLI. Recast as natural language inference......, the problem now amounts to detecting the relation between pairs of statements: they either contradict or entail one another, or they are mutually neutral. Current research in natural language inference is effectively exclusive to English. In this paper, we propose to advance the research in SNLI-style natural...... language inference toward multilingual evaluation. To that end, we provide test data for four major languages: Arabic, French, Spanish, and Russian. We experiment with a set of baselines. Our systems are based on cross-lingual word embeddings and machine translation. While our best system scores an average...

  20. Emergency Response Capability Baseline Needs Assessment - Compliance Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Sharry, John A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-09-01

    This document was prepared by John A. Sharry, LLNL Fire Marshal and Division Leader for Fire Protection and was reviewed by LLNL Emergency Management Department Head, James Colson. This document is the second of a two-part analysis on Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2016 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2016 BNA, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, fire department training records, and fire department policies and procedures. The 2013 BNA was approved by NNSA’s Livermore Field Office on January 22, 2014.

  1. Electricity End Uses, Energy Efficiency, and Distributed Energy Resources Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, Lisa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Morrow, William [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Deason, Jeff [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schiller, Steven R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Leventis, Greg [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Smith, Sarah [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Leow, Woei Ling [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Levin, Todd [Argonne National Lab. (ANL), Argonne, IL (United States); Plotkin, Steven [Argonne National Lab. (ANL), Argonne, IL (United States); Zhou, Yan [Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)

    2017-01-01

    This report was developed by a team of analysts at Lawrence Berkeley National Laboratory, with Argonne National Laboratory contributing the transportation section, and is a DOE EPSA product and part of a series of “baseline” reports intended to inform the second installment of the Quadrennial Energy Review (QER 1.2). QER 1.2 provides a comprehensive review of the nation’s electricity system and cover the current state and key trends related to the electricity system, including generation, transmission, distribution, grid operations and planning, and end use. The baseline reports provide an overview of elements of the electricity system. This report focuses on end uses, electricity consumption, electric energy efficiency, distributed energy resources (DERs) (such as demand response, distributed generation, and distributed storage), and evaluation, measurement, and verification (EM&V) methods for energy efficiency and DERs.

  2. 1st DeepWind 5 MW Baseline design

    DEFF Research Database (Denmark)

    Schmidt Paulsen, Uwe; Vita, Luca; Aagaard Madsen, Helge

    2012-01-01

    The first 5MW baseline design of the DeepWind concept is presented for a Darrieus type floating wind turbine system for water depths of more than 150 m. This design will be used as design reference to test the next technological improvements of sub-component level, being based as much as possible...... trajectory on the water plane. The generator is placed at the bottom of the platform and uses 5MW direct drive technology.The conceptual design is evaluated with numerical simulations in the time domain using the aero-elastic code HAWC2. In order to investigate the concept, a double-disc blade element....... A site has been chosen for the floating turbine off Norway as representative for external conditions. The structure is verified according to an ultimate strength analysis, including loads from wind, waves and currents. The stability of the platform is investigated, considering the displacements...

  3. The OPERA Long Baseline Experiment: Status and First Results

    CERN Document Server

    Duchesneau, Dominique

    2008-01-01

    OPERA (Oscillation Project with Emulsion tRacking Apparatus)is an international collaboration between Europe and Asia, aiming to give the first direct proof of tau neutrino appearance in a pure muon neutrino beam, in order to validate the hypothesis for atmospheric neutrino oscillations. The first european long baseline neutrino beam called CNGS is produced at CERN and sent in the direction of the Gran Sasso underground laboratory 730 km away, where the OPERA detector is located. Since 2006 the electronic detector part is fully commissioned and running. Cosmic ray events have been recorded on a regular basis and the first neutrino beam events have been observed in the target elements made of very precise emulsion films and lead sheets during the last run in autumn 2007. This paper reviews the status of the detector, the beam performances, the first results from the neutrino event analysis and the prospects.

  4. OCRWM procedure for reporting software baseline change information

    International Nuclear Information System (INIS)

    1994-07-01

    The purpose of this procedure is to establish a requirement and method for participant organizations to report software baseline change information to the M ampersand O Configuration Management (CM) organization for inclusion in the OCRWM Configuration Information System (CIS). (The requirements for performing software configuration management (SCM) are found in the OCRWM Quality Assurance Requirements and Description (QARD) document and in applicable DOE orders, and not in this procedure.) This procedure provides a linkage between each participant's SCM system and the CIS, which may be accessed for identification, descriptive, and contact information pertaining to software released by a participant. Such information from the CIS will enable retrieval of details and copies of software code and documentation from the participant SCM system

  5. Nonlinear Dynamic Inversion Baseline Control Law: Architecture and Performance Predictions

    Science.gov (United States)

    Miller, Christopher J.

    2011-01-01

    A model reference dynamic inversion control law has been developed to provide a baseline control law for research into adaptive elements and other advanced flight control law components. This controller has been implemented and tested in a hardware-in-the-loop simulation; the simulation results show excellent handling qualities throughout the limited flight envelope. A simple angular momentum formulation was chosen because it can be included in the stability proofs for many basic adaptive theories, such as model reference adaptive control. Many design choices and implementation details reflect the requirements placed on the system by the nonlinear flight environment and the desire to keep the system as basic as possible to simplify the addition of the adaptive elements. Those design choices are explained, along with their predicted impact on the handling qualities.

  6. Detectors for the MINOS long-baseline neutrino oscillation experiment

    International Nuclear Information System (INIS)

    Ayres, D.S.

    1996-01-01

    The MINOS long-baseline experiment will use an intense neutrino beam, generated by Fermilab''s Main Injector accelerator, and 730 km flight path to search for neutrino oscillations. The 10,000 ton MINOS far detector will utilize toroidally magnetized steel plates interleaved with track chambers to reconstruct event topologies and to measure the energies of the muons, hadrons and electromagnetic showers produced by neutrino interactions. The MINOS collaboration is currently developing three alternative technologies for the track chambers: ''Iarocci'' tubes (operated in either limited streamer or saturated proportional mode), RPC''s (with either glass or ABS plates), and scintillator (either liquid or plastic) with wavelength shifting fiber readout. The technology choice will be made in mid 1997 based on the projected performance and cost of the 32,000 m 2 active detector system

  7. Integrated Baseline Bystem (IBS) Version 1.03: Models guide

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The Integrated Baseline System)(IBS), operated by the Federal Emergency Management Agency (FEMA), is a system of computerized tools for emergency planning and analysis. This document is the models guide for the IBS and explains how to use the emergency related computer models. This document provides information for the experienced system user, and is the primary reference for the computer modeling software supplied with the system. It is designed for emergency managers and planners, and others familiar with the concepts of computer modeling. Although the IBS manual set covers basic and advanced operations, it is not a complete reference document set. Emergency situation modeling software in the IBS is supported by additional technical documents. Some of the other IBS software is commercial software for which more complete documentation is available. The IBS manuals reference such documentation where necessary.

  8. Baseline projections of transportation energy consumption by mode: 1981 update

    Energy Technology Data Exchange (ETDEWEB)

    Millar, M; Bunch, J; Vyas, A; Kaplan, M; Knorr, R; Mendiratta, V; Saricks, C

    1982-04-01

    A comprehensive set of activity and energy-demand projections for each of the major transportation modes and submodes is presented. Projections are developed for a business-as-usual scenario, which provides a benchmark for assessing the effects of potential conservation strategies. This baseline scenario assumes a continuation of present trends, including fuel-efficiency improvements likely to result from current efforts of vehicle manufacturers. Because of anticipated changes in fuel efficiency, fuel price, modal shifts, and a lower-than-historic rate of economic growth, projected growth rates in transportation activity and energy consumption depart from historic patterns. The text discusses the factors responsible for this departure, documents the assumptions and methodologies used to develop the modal projections, and compares the projections with other efforts.

  9. C-018H Pre-Operational Baseline Sampling Plan

    International Nuclear Information System (INIS)

    Guzek, S.J.

    1993-01-01

    The objective of this task is to field characterize and sample the soil at selected locations along the proposed effluent line routes for Project C-018H. The overall purpose of this effort is to meet the proposed plan to discontinue the disposal of contaminated liquids into the Hanford soil column as described by DOE (1987). Detailed information describing proposed transport pipeline route and associated Kaiser Engineers Hanford Company (KEH) preliminary drawings (H288746...755) all inclusive, have been prepared by KEH (1992). The information developed from field monitoring and sampling will be utilized to characterize surface and subsurface soil along the proposed C-018H effluent pipeline and it's associated facilities. Potentially existing contaminant levels may be encountered therefore, soil characterization will provide a construction preoperational baseline reference, develop personnel safety requirements, and determine the need for any changes in the proposed routes prior to construction of the pipeline

  10. Energy reconstruction in the long-baseline neutrino experiment.

    Science.gov (United States)

    Mosel, U; Lalakulich, O; Gallmeister, K

    2014-04-18

    The Long-Baseline Neutrino Experiment aims at measuring fundamental physical parameters to high precision and exploring physics beyond the standard model. Nuclear targets introduce complications towards that aim. We investigate the uncertainties in the energy reconstruction, based on quasielastic scattering relations, due to nuclear effects. The reconstructed event distributions as a function of energy tend to be smeared out and shifted by several 100 MeV in their oscillatory structure if standard event selection is used. We show that a more restrictive experimental event selection offers the possibility to reach the accuracy needed for a determination of the mass ordering and the CP-violating phase. Quasielastic-based energy reconstruction could thus be a viable alternative to the calorimetric reconstruction also at higher energies.

  11. Waste Assessment Baseline for the IPOC Second Floor, West Wing

    Energy Technology Data Exchange (ETDEWEB)

    McCord, Samuel A [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Waste Management and Pollution Prevention

    2015-04-01

    Following a building-wide waste assessment in September, 2014, and subsequent presentation to Sandia leadership regarding the goal of Zero Waste by 2025, the occupants of the IPOC Second Floor, West Wing contacted the Materials Sustainability and Pollution Prevention (MSP2) team to guide them to Zero Waste in advance of the rest of the site. The occupants are from Center 3600, Public Relations and Communications , and Center 800, Independent Audit, Ethics and Business Conduct . To accomplish this, MSP2 conducted a new limited waste assessment from March 2-6, 2015 to compare the second floor, west wing to the building as a whole. The assessment also serves as a baseline with which to mark improvements in diversion in approximately 6 months.

  12. Effects of triplet Higgs bosons in long baseline neutrino experiments

    Science.gov (United States)

    Huitu, K.; Kärkkäinen, T. J.; Maalampi, J.; Vihonen, S.

    2018-05-01

    The triplet scalars (Δ =Δ++,Δ+,Δ0) utilized in the so-called type-II seesaw model to explain the lightness of neutrinos, would generate nonstandard interactions (NSI) for a neutrino propagating in matter. We investigate the prospects to probe these interactions in long baseline neutrino oscillation experiments. We analyze the upper bounds that the proposed DUNE experiment might set on the nonstandard parameters and numerically derive upper bounds, as a function of the lightest neutrino mass, on the ratio the mass MΔ of the triplet scalars, and the strength |λϕ| of the coupling ϕ ϕ Δ of the triplet Δ and conventional Higgs doublet ϕ . We also discuss the possible misinterpretation of these effects as effects arising from a nonunitarity of the neutrino mixing matrix and compare the results with the bounds that arise from the charged lepton flavor violating processes.

  13. The NuMAX Long Baseline Neutrino Factory Concept

    Energy Technology Data Exchange (ETDEWEB)

    Delahaye, J-P. [SLAC; Ankenbrandt, C. [MUONS Inc., Batavia; Bogacz, A. [Jefferson Lab; Huber, P. [Virginia Tech.; Kirk, H. [Brookhaven; Neuffer, D. [Fermilab; Palmer, M. A. [Fermilab; Ryne, R. [LBL, Berkeley; Snopok, P. [IIT, Chicago

    2018-03-19

    A Neutrino Factory where neutrinos of all species are produced in equal quantities by muon decay is described as a facility at the intensity frontier for exquisite precision providing ideal conditions for ultimate neutrino studies and the ideal complement to Long Baseline Facilities like LBNF at Fermilab. It is foreseen to be built in stages with progressively increasing complexity and performance, taking advantage of existing or proposed facilities at an existing laboratory like Fermilab. A tentative layout based on a recirculating linac providing opportunities for considerable saving is discussed as well as its possible evolution toward a muon collider if and when requested by Physics. Tentative parameters of the various stages are presented as well as the necessary R&D to address the technological issues and demonstrate their feasibility.

  14. Determination of the Territorial Sea Baseline - Measurement Aspect

    Science.gov (United States)

    Specht, Cezary; Weintrit, Adam; Specht, Mariusz; Dabrowski, Pawel

    2017-12-01

    Determining the course of the territorial sea baseline (TSB) of the coastal state is the basis for establishing its maritime boundaries, thus becoming indirect part of maritime policy of the state. Besides the following aspects: legal and methodological as described in the conventions, acts, standards and regulations, equally important is the issue of measurement methodology with respect to the boundaries of the territorial sea. The publication discussed accuracy requirements of the TSB measurement implementation, the relationship of sea level with a choice of the method of its determination, and discussed the implementation of such a measurement on a selected example. As the test reservoir was used the 400-meter stretch of the public beach in Gdynia. During the measurements they used the GNSS geodetic receiver operating in real time based on the geodetic network - VRSnet.pl. Additionally, a comparison was made of the applied method with analogous measurements of the TSB performed in 1999.

  15. Long baseline Super-Beam experiments in Europe within LAGUNA

    CERN Document Server

    Coloma, Pilar; Pascoli, Silvia

    2011-01-01

    We explore the physics reach of several possible configurations for a Super-Beam experiment in Europe, focusing on the possibilities of discovering $\\theta_{13}$, CP violation in the leptonic sector and the ordering of neutrino mass eigenstates. We consider the three different detector technologies: Water \\v{C}erenkov, Liquid Argon and Liquid Scintillator, and seven possible sites in Europe which would be able to host such a detector underground. The distances to these sites from CERN, where the beam would be originated, go from 130 km to 2300 km. The neutrino flux is optimized in each case as to match the first oscillation peak for each of the baselines under consideration. We also study the impact of several experimental factors in the performance of each detector technology. These include the reconstruction efficiencies for quasi-elastic events, the rejection efficiencies for the neutral-current backgrounds, the ratio between running times in neutrino and antineutrino modes and the systematic uncertainties...

  16. Probing Neutrino Properties with Long-Baseline Neutrino Beams

    International Nuclear Information System (INIS)

    Marino, Alysia

    2015-01-01

    This final report on an Early Career Award grant began in April 15, 2010 and concluded on April 14, 2015. Alysia Marino's research is focussed on making precise measurements of neutrino properties using intense accelerator-generated neutrino beams. As a part of this grant, she is collaborating on the Tokai-to-Kamioka (T2K) long-baseline neutrino experiment, currently taking data in Japan, and on the Deep Underground Neutrino Experiment (DUNE) design effort for a future Long-Baseline Neutrino Facility (LBNF) in the US. She is also a member of the NA61/SHINE particle production experiment at CERN, but as that effort is supported by other funds, it will not be discussed further here. T2K was designed to search for the disappearance of muon neutrinos (?_?) and the appearance of electron neutrinos (?_e), using a beam of muon neutrino beam that travels 295 km across Japan towards the Super-Kamiokande detector. In 2011 T2K first reported indications of ?_e appearance, a previously unobserved mode of neutrino oscillations. In the past year, T2K has published a combined analysis of ?_? disappearance and ?_e appearance, and began collecting taking data with a beam of anti-neutrinos, instead of neutrinos, to search for hints of violation of the CP symmetry of the universe. The proposed DUNE experiment has similar physics goals to T2K, but will be much more sensitive due to its more massive detectors and new higher-intensity neutrino beam. This effort will be very high-priority particle physics project in the US over the next decade.

  17. Automated baseline change detection - Phases 1 and 2. Final report

    International Nuclear Information System (INIS)

    Byler, E.

    1997-01-01

    The primary objective of this project is to apply robotic and optical sensor technology to the operational inspection of mixed toxic and radioactive waste stored in barrels, using Automated Baseline Change Detection (ABCD), based on image subtraction. Absolute change detection is based on detecting any visible physical changes, regardless of cause, between a current inspection image of a barrel and an archived baseline image of the same barrel. Thus, in addition to rust, the ABCD system can also detect corrosion, leaks, dents, and bulges. The ABCD approach and method rely on precise camera positioning and repositioning relative to the barrel and on feature recognition in images. The ABCD image processing software was installed on a robotic vehicle developed under a related DOE/FETC contract DE-AC21-92MC29112 Intelligent Mobile Sensor System (IMSS) and integrated with the electronics and software. This vehicle was designed especially to navigate in DOE Waste Storage Facilities. Initial system testing was performed at Fernald in June 1996. After some further development and more extensive integration the prototype integrated system was installed and tested at the Radioactive Waste Management Facility (RWMC) at INEEL beginning in April 1997 through the present (November 1997). The integrated system, composed of ABCD imaging software and IMSS mobility base, is called MISS EVE (Mobile Intelligent Sensor System--Environmental Validation Expert). Evaluation of the integrated system in RWMC Building 628, containing approximately 10,000 drums, demonstrated an easy to use system with the ability to properly navigate through the facility, image all the defined drums, and process the results into a report delivered to the operator on a GUI interface and on hard copy. Further work is needed to make the brassboard system more operationally robust

  18. General resonance mediation

    International Nuclear Information System (INIS)

    McGarrie, Moritz

    2012-07-01

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for σ(visible → hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  19. General resonance mediation

    Energy Technology Data Exchange (ETDEWEB)

    McGarrie, Moritz

    2012-07-15

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for {sigma}(visible {yields} hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  20. Positively deflected anomaly mediation

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2002-01-01

    We generalize the so-called 'deflected anomaly mediation' scenario to the case where threshold corrections of heavy messengers to the sparticle squared masses are positive. A concrete model realizing this scenario is also presented. The tachyonic slepton problem can be fixed with only a pair of messengers. The resultant sparticle mass spectrum is quite different from that in the conventional deflected anomaly mediation scenario, but is similar to the one in the gauge mediation scenario. The lightest sparticle is mostly B-ino

  1. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  2. Safe and sensible preprocessing and baseline correction of pupil-size data.

    Science.gov (United States)

    Mathôt, Sebastiaan; Fabius, Jasper; Van Heusden, Elle; Van der Stigchel, Stefan

    2018-02-01

    Measurement of pupil size (pupillometry) has recently gained renewed interest from psychologists, but there is little agreement on how pupil-size data is best analyzed. Here we focus on one aspect of pupillometric analyses: baseline correction, i.e., analyzing changes in pupil size relative to a baseline period. Baseline correction is useful in experiments that investigate the effect of some experimental manipulation on pupil size. In such experiments, baseline correction improves statistical power by taking into account random fluctuations in pupil size over time. However, we show that baseline correction can also distort data if unrealistically small pupil sizes are recorded during the baseline period, which can easily occur due to eye blinks, data loss, or other distortions. Divisive baseline correction (corrected pupil size = pupil size/baseline) is affected more strongly by such distortions than subtractive baseline correction (corrected pupil size = pupil size - baseline). We discuss the role of baseline correction as a part of preprocessing of pupillometric data, and make five recommendations: (1) before baseline correction, perform data preprocessing to mark missing and invalid data, but assume that some distortions will remain in the data; (2) use subtractive baseline correction; (3) visually compare your corrected and uncorrected data; (4) be wary of pupil-size effects that emerge faster than the latency of the pupillary response allows (within ±220 ms after the manipulation that induces the effect); and (5) remove trials on which baseline pupil size is unrealistically small (indicative of blinks and other distortions).

  3. Reinforced Carbon Carbon (RCC) oxidation resistant material samples - Baseline coated, and baseline coated with tetraethyl orthosilicate (TEOS) impregnation

    Science.gov (United States)

    Gantz, E. E.

    1977-01-01

    Reinforced carbon-carbon material specimens were machined from 19 and 33 ply flat panels which were fabricated and processed in accordance with the specifications and procedures accepted for the fabrication and processing of the leading edge structural subsystem (LESS) elements for the space shuttle orbiter. The specimens were then baseline coated and tetraethyl orthosilicate impregnated, as applicable, in accordance with the procedures and requirements of the appropriate LESS production specifications. Three heater bars were ATJ graphite silicon carbide coated with the Vought 'pack cementation' coating process, and three were stackpole grade 2020 graphite silicon carbide coated with the chemical vapor deposition process utilized by Vought in coating the LESS shell development program entry heater elements. Nondestructive test results are reported.

  4. Single-baseline RTK GNSS Positioning for Hydrographic Surveying

    Science.gov (United States)

    Metin Alkan, Reha; Murat Ozulu, I.; Ilçi, Veli; Kahveci, Muzaffer

    2015-04-01

    Positioning with GNSS technique can be carried out in two ways, absolute and relative. It has been possible to reach a few meters absolute point positioning accuracies in real time after disabling SA permanently in May 2000. Today, accuracies obtainable from absolute point positioning using code observations are not sufficient for most surveying applications. Thus to meet higher accuracy requirements, differential methods using single or dual frequency geodetic-grade GNSS receivers that measure carrier phase have to be used. However, this method requires time-cost field and office works and if the measurement is not carried out with conventional RTK method, user needs a GNSS data processing software to estimate the coordinates. If RTK is used, at least two or more GNSS receivers are required, one as a reference and the other as a rover. Moreover, the distance between the receivers must not exceed 15-20 km in order to be able to rapidly and reliably resolve the carrier phase ambiguities. On the other hand, based on the innovations and improvements in satellite geodesy and GNSS modernization studies occurred within the last decade, many new positioning methods and new approaches have been developed. One of them is Network-RTK (or commonly known as CORS) and the other is Single-baseline RTK. These methods are widely used for many surveying applications in many countries. The user of the system can obtain his/her position within a few cm level of accuracy in real-time with only a single GNSS receiver that has Network RTK (CORS) capability. When compared with the conventional differential and RTK methods, this technique has several significant advantages as it is easy to use and it produces accurate, cost-effective and rapid solutions. In Turkey, establishment of a multi-base RTK network was completed and opened for civilian use in 2009. This network is called CORS-TR and consists of 146 reference stations having about 80-100 km interstation distances. It is possible

  5. Making mediation work.

    Science.gov (United States)

    Arif, Zeba

    2016-10-26

    Mediation can be an effective way of solving conflict between staff members. It signifies a willingness for people to work together to discuss their differences in a constructive way, before going down the official grievance route.

  6. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2004-01-01

    Implementation of new computer-mediated communication (CMC) systems in organizations is a complex socio-technical endeavour, involving the mutual adaptation of technology and organization over time. Drawing on the analytic concept of sensemaking, this paper provides a theoretical perspective...... that deepens our understanding of how organizations appropriate new electronic communication media. The paper analyzes how a group of mediators in a large, multinational company adapted a new web-based CMC technology (a virtual workspace) to the local organizational context (and vice versa) by modifying...... features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. We found that these mediators exerted considerable influence on how the technology was established and used in the organization. The mediators were not neutral facilitators of a well...

  7. The LIFE Cognition Study: design and baseline characteristics

    Directory of Open Access Journals (Sweden)

    Sink KM

    2014-08-01

    adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey–Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7 had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P<0.001. The LIFE Study will contribute important information on the effects of a structured physical activity program on cognitive outcomes in sedentary older adults at particular risk for mobility impairment. In addition to its importance in the area of prevention of cognitive decline, the LIFE Study will also likely serve as a model for exercise and other behavioral intervention trials in older adults. Keywords: exercise, physical activity, older adults, dementia

  8. Idaho National Laboratory’s Greenhouse Gas FY08 Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer D. Morton

    2010-09-01

    A greenhouse gas (GHG) inventory is a systematic attempt to account for the production and release of certain gasses generated by an institution from various emission sources. The gasses of interest are those which have become identified by climate science as related to anthropogenic global climate change. This document presents an inventory of GHGs generated during fiscal year (FY) 2008 by Idaho National Laboratory (INL), a Department of Energy (DOE)-sponsored entity, located in southeastern Idaho. Concern about the environmental impact of GHGs has grown in recent years. This, together with a desire to decrease harmful environmental impacts, would be enough to encourage the calculation of a baseline estimate of total GHGs generated at the INL. Additionally, the INL has a desire to see how its emissions compare with similar institutions, including other DOE-sponsored national laboratories. Executive Order 13514 requires that federally-sponsored agencies and institutions document reductions in GHG emissions in the future, and such documentation will require knowledge of a baseline against which reductions can be measured. INL’s FY08 GHG inventory was calculated according to methodologies identified in Federal recommendations and an as-yet-unpublished Technical and Support Document (TSD) using operational control boundary. It measures emissions generated in three Scopes: (1) INL emissions produced directly by stationary or mobile combustion and by fugitive emissions, (2) the share of emissions generated by entities from which INL purchased electrical power, and (3) indirect or shared emissions generated by outsourced activities that benefit INL (occur outside INL’s organizational boundaries but are a consequence of INL’s activities). This inventory found that INL generated a total of 114,256 MT of CO2-equivalent emissions during fiscal year 2008 (FY08). The following conclusions were made from looking at the results of the individual contributors to INL

  9. Idaho National Laboratory’s Greenhouse Gas FY08 Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer D. Morton

    2011-06-01

    A greenhouse gas (GHG) inventory is a systematic attempt to account for the production and release of certain gasses generated by an institution from various emission sources. The gasses of interest are those which have become identified by climate science as related to anthropogenic global climate change. This document presents an inventory of GHGs generated during fiscal year (FY) 2008 by Idaho National Laboratory (INL), a Department of Energy (DOE)-sponsored entity, located in southeastern Idaho. Concern about the environmental impact of GHGs has grown in recent years. This, together with a desire to decrease harmful environmental impacts, would be enough to encourage the calculation of a baseline estimate of total GHGs generated at INL. Additionally, INL has a desire to see how its emissions compare with similar institutions, including other DOE national laboratories. Executive Order 13514 requires that federal agencies and institutions document reductions in GHG emissions in the future, and such documentation will require knowledge of a baseline against which reductions can be measured. INL's FY08 GHG inventory was calculated according to methodologies identified in federal GHG guidance documents using operational control boundaries. It measures emissions generated in three Scopes: (1) INL emissions produced directly by stationary or mobile combustion and by fugitive emissions, (2) the share of emissions generated by entities from which INL purchased electrical power, and (3) indirect or shared emissions generated by outsourced activities that benefit INL (occur outside INL's organizational boundaries but are a consequence of INL's activities). This inventory found that INL generated a total of 113,049 MT of CO2-equivalent emissions during FY08. The following conclusions were made from looking at the results of the individual contributors to INL's baseline GHG inventory: (1) Electricity (including the associated transmission and

  10. Understanding Mediation Support

    OpenAIRE

    Lanz, David; Pring, Jamie; von Burg, Corinne; Zeller, Mathias

    2017-01-01

    Recent decades have witnessed increasing institutionalization of mediation support through the establishment of mediation support structures (MSS) within foreign ministries and secretariats of multilateral organizations. This study sheds light on this trend and aims to better understand the emergence, design and development of different MSS. This study analyzes six MSS, namely those established in the United Nations (UN), the Organization for Security and Co-operation in Europe (OSCE), the Eu...

  11. ENVIRONMENTAL CONFLICT MEDIATION

    Directory of Open Access Journals (Sweden)

    GABRIELA G. MIHUT

    2011-04-01

    Full Text Available At a time of global economic crisis followed by resource crisis, a period in which the world seeks alternative resources through eco-investment, environmental conflicts are inevitable. Romania is among the few countries that do not pay enough attention to environmental conflicts and to the advantages to of solving them through mediation procedure. The present paper deals with areas in which conflicts can be applied in environmental mediation and its benefits.

  12. Comparison of CFD Predictions of the TCA Baseline

    Science.gov (United States)

    Cappuccio, Gelsomina

    1999-01-01

    The computational fluid dynamics (CFD) comparisons being presented are compared to each other and to wind tunnel (WT) data on the baseline TCA. Some of the CFD computations were done prior to the tests and others later. Only force data (CL vs CD) from CFD will be presented as part of this report. The WT data presented comes from the testing of the baseline TCA in the Langley Unitary Plan Wind Tunnel (UPWT), Test Section #2. There are 2 sets of wind tunnel data being presented: one from test 1671 of model 2a (flapped wing) and the other from test 1679 of model 2b (solid wing). Most of the plots show only one run from each of the WT tests per configuration. But many repeat runs were taken during the tests. The WT repeat runs showed an uncertainty in the drag of +/- 0.5 count. There were times when the uncertainty in drag was better, +/- 0.25 count. Test 1671 data was of forces and pressures measured from model 2a. The wing had cutouts for installing various leading and trailing edge flaps at lower Mach numbers. The internal duct of the nacelles are not designed and fabricated as defined in the outer mold lines (OML) iges file. The internal duct was fabricated such that a linear transition occurs from the inlet to exhaust. Whereas, the iges definition has a constant area internal duct that quickly transitions from the inlet to exhaust cross sectional shape. The nacelle internal duct was fabricated, the way described, to save time and money. The variation in the cross sectional area is less than 1% from the iges definition. The nacelles were also installed with and without fairings. Fairings are defined as the build up of the nacelles on the upper wing surface so that the nacelles poke through the upper surface as defined in the OML iges file. Test 1679 data was of forces measured from model 2a and 2b. The wing for model 2b was a solid wing. The nacelles were built the same way as for model 2a, except for the nacelle base pressure installation. The nacelles were only

  13. Baseline Geochemical Data for Medical Researchers in Kentucky

    Science.gov (United States)

    Anderson, W.

    2017-12-01

    According to the Centers for Disease Control, Kentucky has the highest cancer incidence and death rates in the country. New efforts by geochemists and medical researchers are examining ways to diagnose the origin and sources of carcinogenesis. In an effort to determine if naturally occurring geochemical or mineral elements contributes to the cancer causation, the Kentucky Geological Survey has established a Minerals and Geochemical Database that is available to medical researchers for examination of baseline geochemistry and determine if naturally occurring mineral or chemical elements contribute to the high rate of cancers in the state. Cancer causation is complex, so if natural sources can be accounted for, then researchers can focus on the true causation. Naturally occurring minerals, metals and elements occur in many parts of the state, and their presence is valuable for evaluating causation. For example, some data in the database contain maps showing (a) statewide elemental geochemistry, (b) areas of black shale oxidation occurrence, which releases metals in soil and surface waters, (c) some clay deposits in the state that can contain high content of rare earth elements, and (d) site-specific uranium occurrences. Knowing the locations of major ore deposits in the state can also provide information related to mineral and chemical anomalies, such as for base metals and mercury. Radionuclide data in soil and water analyses are limited, so future research may involve obtaining more analyses to determine radon potential. This database also contains information on faulting and geology in the state. Although the metals content of trees may not seem relevant, the ash and humus content of degraded trees affects soil, stream sediment and water geochemistry. Many rural homes heat with wood, releasing metals into the surrounding biosphere. Stressed vegetation techniques can be used to explore for ore deposits and look for high metal contents in soils and rocks. These

  14. Positive emotional change: mediating effects of forgiveness and spirituality.

    Science.gov (United States)

    Levenson, Michael R; Aldwin, Carolyn M; Yancura, Loriena

    2006-01-01

    We evaluated the efficacy of an emotional education program that seeks to reduce the intergenerational transmission of negative interaction patterns by increasing forgiveness and spirituality. We examined both reduction of psychological symptoms and increase in positive psychological outcomes over the course of a year, as well as the mediators of this change. At baseline, the sample consisted of 99 participants and 47 waiting list controls. Comparisons of scores from baseline (Time 1) to one week after the Hoffman Quadrinity Process (Time 2) showed large declines in negative affect (depressive symptoms) and increases in both positive outcomes (mastery, empathy, emotional intelligence, life satisfaction, forgiveness, and spiritual experience) and health and well-being. Over the course of a year, most of these gains were sustained, in comparison with the control group. Further, increases in forgiveness and spirituality mediated the effect of program participation on depressive symptoms.

  15. A sampling strategy to establish existing plant configuration baselines

    International Nuclear Information System (INIS)

    Buchanan, L.P.

    1995-01-01

    The Department of Energy's Gaseous Diffusion Plants (DOEGDP) are undergoing a Safety Analysis Update Program. As part of this program, critical existing structures are being reevaluated for Natural Phenomena Hazards (NPH) based on the recommendations of UCRL-15910. The Department of Energy has specified that current plant configurations be used in the performance of these reevaluations. This paper presents the process and results of a walkdown program implemented at DOEGDP to establish the current configuration baseline for these existing critical structures for use in subsequent NPH evaluations. These structures are classified as moderate hazard facilities and were constructed in the early 1950's. The process involved a statistical sampling strategy to determine the validity of critical design information as represented on the original design drawings such as member sizes, orientation, connection details and anchorage. A floor load inventory of the dead load of the equipment, both permanently attached and spare, was also performed as well as a walkthrough inspection of the overall structure to identify any other significant anomalies

  16. A SURVEY OF ASTRONOMICAL RESEARCH: A BASELINE FOR ASTRONOMICAL DEVELOPMENT

    International Nuclear Information System (INIS)

    Ribeiro, V. A. R. M.; Russo, P.; Cárdenas-Avendaño, A.

    2013-01-01

    Measuring scientific development is a difficult task. Different metrics have been put forward to evaluate scientific development; in this paper we explore a metric that uses the number of peer-reviewed, and when available non-peer-reviewed, research articles as an indicator of development in the field of astronomy. We analyzed the available publication record, using the Smithsonian Astrophysical Observatory/NASA Astrophysics Database System, by country affiliation in the time span between 1950 and 2011 for countries with a gross national income of less than 14,365 USD in 2010. This represents 149 countries. We propose that this metric identifies countries in ''astronomical development'' with a culture of research publishing. We also propose that for a country to develop in astronomy, it should invest in outside expert visits, send its staff abroad to study, and establish a culture of scientific publishing. Furthermore, we propose that this paper may be used as a baseline to measure the success of major international projects, such as the International Year of Astronomy 2009

  17. Control advances for achieving the ITER baseline scenario on KSTAR

    Science.gov (United States)

    Eidietis, N. W.; Barr, J.; Hahn, S. H.; Humphreys, D. A.; in, Y. K.; Jeon, Y. M.; Lanctot, M. J.; Mueller, D.; Walker, M. L.

    2017-10-01

    Control methodologies developed to enable successful production of ITER baseline scenario (IBS) plasmas on the superconducting KSTAR tokamak are presented: decoupled vertical control (DVC), real-time feedforward (rtFF) calculation, and multi-input multi-output (MIMO) X-point control. DVC provides fast vertical control with the in-vessel control coils (IVCC) while sharing slow vertical control with the poloidal field (PF) coils to avoid IVCC saturation. rtFF compensates for inaccuracies in offline PF current feedforward programming, allowing reduction or removal of integral gain (and its detrimental phase lag) from the shape controller. Finally, MIMO X-point control provides accurate positioning of the X-point despite low controllability due to the large distance between coils and plasma. Combined, these techniques enabled achievement of IBS parameters (q95 = 3.2, βN = 2) with a scaled ITER shape on KSTAR. n =2 RMP response displays a strong dependence upon this shaping. Work supported by the US DOE under Award DE-SC0010685 and the KSTAR project.

  18. B Plant aggregate area management study technical baseline report

    International Nuclear Information System (INIS)

    DeFord, D.H.; Carpenter, R.W.

    1995-05-01

    The B aggregate area is made up of 13 operable units; 200-BP 1 through 200-BP 1 1, 200-IU-6, and 200-SS-1 that consist of liquid and solid waste disposal sites in the vicinity of, and related to, B Plant operations. This report describes B Plant and its waste sites, including cribs, french drains, septic tanks and drain fields, trenches and ditches, ponds, catch tanks, settling tanks, diversion boxes, underground tank farms designed for high-level liquid wastes, and the lines and encasements that connect them. Each waste site in the aggregate area is described separately. Close relationships between waste units, such as overflow from one to another, are also discussed. This document provides a technical baseline of the aggregate area and results from an environmental investigation. This document is based upon review and evaluation of numerous Hanford Site current and historical reports, drawings and photographs, supplemented with site inspections and employee interviews. No intrusive field investigations or sampling were conducted

  19. Energy conservation on Nova Scotia farms: Baseline energy data

    International Nuclear Information System (INIS)

    Bailey, J.A.; Gordon, R.; Burton, D.; Yiridoe, E.K.

    2008-01-01

    Direct energy use is a small but essential component of the farm greenhouse gas (GHG) budget. Improvements in energy efficiency and renewable energy can help reduce farm operating costs, improve air quality and reduce GHG emission levels. Energy conservation is especially important in Nova Scotia (NS), Canada, where fossil fuels, particularly coal, remain the primary source of electrical generation. Responses from mail surveys were used to establish baseline data on a cross-section of NS farms with respect to direct energy costs and usage to demonstrate differences in farm type and size. A 32% (N=224) response rate was achieved. Based on this survey, the average energy bill for a NS farm in 2004 was $11,228, with most (61.7%) of their energy cost attributable to the purchase of petroleum products. Almost all farmers (96.4%) indicated that their energy cost was a primary concern. Farmers identified the operation of vehicles and mobile equipment, as well as lighting and heating as having the greatest energy requirements in their operations. Energy usage varied with farm type and size. NS farms consumed 1.2 petajoules of energy equivalent to 127 kilotonnes of CO 2 with 52.7% of emissions from electricity use in 2004

  20. Future Long-Baseline Neutrino Facilities and Detectors

    Directory of Open Access Journals (Sweden)

    Milind Diwan

    2013-01-01

    Full Text Available We review the ongoing effort in the US, Japan, and Europe of the scientific community to study the location and the detector performance of the next-generation long-baseline neutrino facility. For many decades, research on the properties of neutrinos and the use of neutrinos to study the fundamental building blocks of matter has unveiled new, unexpected laws of nature. Results of neutrino experiments have triggered a tremendous amount of development in theory: theories beyond the standard model or at least extensions of it and development of the standard solar model and modeling of supernova explosions as well as the development of theories to explain the matter-antimatter asymmetry in the universe. Neutrino physics is one of the most dynamic and exciting fields of research in fundamental particle physics and astrophysics. The next-generation neutrino detector will address two aspects: fundamental properties of the neutrino like mass hierarchy, mixing angles, and the CP phase, and low-energy neutrino astronomy with solar, atmospheric, and supernova neutrinos. Such a new detector naturally allows for major improvements in the search for nucleon decay. A next-generation neutrino observatory needs a huge, megaton scale detector which in turn has to be installed in a new, international underground laboratory, capable of hosting such a huge detector.