Sample records for central phencyclidine pcp

  1. Substance use -- phencyclidine (PCP) (United States)

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  2. Central phencyclidine (PCP) receptor binding is glutamate dependent: evidence for a PCP/excitatory amino acid receptor (EAAR) complex

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    Loo, P.; Braunwalder, A.; Lehmann, J.; Williams, M.


    PCP and other dissociative anesthetica block the increase in neuronal firing rate evoked by the EAAR agonist, N-methyl-Daspartate. NMDA and other EAAs such as glutamate (glu) have not been previously shown to affect PCP ligand binding. In the present study, using once washed rat forebrain membranes, 10 was found to increase the binding of (/sup 3/H)TCP, a PCP analog, to defined PCP recognition sites by 20%. Removal of glu and aspartate (asp) by extensive washing decreased TCP binding by 75-90%. In these membranes, 10 L-glu increased TCP binding 3-fold. This effect was stereospecific and evoked by other EAAs with the order of activity, L-glu > D-asp > L- asp > NMDA > D-glu > quisqualate. Kainate, GABA, NE, DA, 5-HT, 2-chloroadenosine, oxotremorine and histamine had no effect on TCP binding at concentrations up to 100 The effects of L-glu were attenuated by the NMDA-type receptor antagonist, 2-amino-7--phosphonoheptanoate (AP7; 10 mM). These findings indicate that EAAS facilitate TCP binding, possibly through NMDA-type receptors. The observed interaction between the PCP receptor and EAARs may reflect the existence of a macromolecular receptor complex similar to that demonstrated for the benzodiazepines and GABA.

  3. Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review. (United States)

    Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C


    Cognitive dysfunction and negative symptoms of schizophrenia remain an unmet clinical need. Therefore, it is essential that new treatments and approaches are developed to recover the cognitive and social impairments that are seen in patients with schizophrenia. These may only be discovered through the use of carefully validated, aetiologically relevant and translational animal models. With recent renewed interest in the neurodevelopmental hypothesis of schizophrenia, postnatal administration of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) has been proposed as a model that can mimic aspects of schizophrenia pathophysiology. The purpose of the current review is to examine the validity of this model and compare it with the adult subchronic PCP model. We review the ability of postnatal PCP administration to produce behaviours (specifically cognitive deficits) and neuropathology of relevance to schizophrenia and their subsequent reversal by pharmacological treatments. We review studies investigating effects of postnatal PCP on cognitive domains in schizophrenia in rats. Morris water maze and delayed spontaneous alternation tasks have been used for working memory, attentional set-shifting for executive function, social novelty discrimination for selective attention and prepulse inhibition of acoustic startle for sensorimotor gating. In addition, we review studies on locomotor activity and neuropathology. We also include two studies using dual hit models incorporating postnatal PCP and two studies on social behaviour deficits following postnatal PCP. Overall, the evidence we provide supports the use of postnatal PCP to model cognitive and neuropathological disturbances of relevance to schizophrenia. To date, there is a lack of evidence to support a significant advantage of postnatal PCP over the adult subchronic PCP model and full advantage has not been taken of its neurodevelopmental component. When thoroughly characterised, it is likely

  4. Brief exposure to methamphetamine (METH) and phencyclidine (PCP) during late development leads to long-term learning deficits in rats. (United States)

    White, Ilsun M; Minamoto, Takehiro; Odell, Joseph R; Mayhorn, Joseph; White, Wesley


    Exposure to methamphetamine (METH) and phencyclidine (PCP) during early development is thought to produce later behavioral deficits. We postulated that exposure to METH and PCP during later development would produce similar behavioral deficits, particularly learning deficits in adulthood. Wistar rats were treated with METH (9 mg/kg), PCP (9 mg/kg), or saline during later development, postnatal days (PD) 50-51, and subsequent behavioral changes were examined including: locomotor activity during the acute drug state (PD 50-51) and the post-drug phase (PD 50-80); social interaction on PD 54-80; and spatial discrimination and reversal in adulthood (after PD 90). METH and PCP differentially affected locomotion during the acute state, but not during the post-drug phase. METH decreased social interaction throughout tests two weeks after drug treatment, whereas PCP decreased social interaction only during the first 8 min of tests. Neither METH nor PCP impaired initial acquisition of spatial discrimination. However, reversal was significantly impaired by PCP, whereas METH produced a mild deficit, compared to controls. Our data provide evidence that exposure to PCP and METH during later development lead to enduring cognitive deficits in adulthood. Selective impairment of reversal may reflect neurological damage in the prefrontal cortex due to early exposure to drugs.

  5. Effects of subchronic phencyclidine (PCP treatment on social behaviors, and operant discrimination and reversal learning in C57BL/6J mice

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    Jonathan L Brigman


    Full Text Available Subchronic treatment with the psychotomimetic phencyclidine (PCP has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily x 7 days, followed by 7 days withdrawal in C57BL/6J mice on 1 social behaviors using a sociability/social novelty-preference paradigm, and 2 pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains that produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice.

  6. Comparative effects of phencyclidine (PCP) and. delta. /sup 9/-tetrahydrocannabinol (THC) on glucose oxidation in the rat testis

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    Husain, S.; Bauer, V.


    Glucose and fructose are important fuels of cellular energetics in organs like testis and brain. The previous in-vitro studies indicated that THC may disrupt many gonadal functions by inhibiting energy metabolism in the testis. PCP is sold on the street as any one of a variety of psychoactive drugs. Most commonly it is misrepresented as THC. Therefore, to compare the effects of PCP and THC on glucose utilization, in-vitro radiorespirometric experiments were conducted in rat testicular tissues. The /sup 14/CO/sub 2/ production from 5.5 mM radiolabelled glucose was followed in the presence and absence of 0.2, 0.1, 0.05, 0.01, 0.005, 0.0025 mM PCP. PCP produced a dose-dependent biphasic effect, stimulating /sup 14/CO/sub 2/ production by 6.2, 17 and 5.8% and then inhibiting it by 13.2, 15.4 and 8.9% with respective concentrations of PCP. This is in contrast to THC which produced a dose-related inhibition of 15.2, 18.1, 20.1 and 25.3% in /sup 14/CO/sub 2/ production with 0.1, 0.2, 0.3 and 0.4 mM THC. These observations are significant due to the possible abuse of PCP together with THC either deliberately or by misrepresentation.

  7. The effects of phencyclidine (PCP) on anxiety-like behavior in the elevated plus maze and the light-dark exploration test are age dependent, sexually dimorphic, and task dependent. (United States)

    Turgeon, Sarah M; Kim, Daniel; Pritchard, Melissa; Salgado, Sanjay; Thaler, Alison


    Previous research in our laboratory revealed sexually dimorphic effects of prior exposure to phencyclidine (PCP) on elevated plus maze behavior. In an attempt to examine the developmental time course of this effect and determine the extent to which it generalizes to other anxiety paradigms, young adult (61-64 days old) and adult (96-107 days old) male and female rats were treated with PCP (15 mg/kg) or saline. Following a two week withdrawal period, animals were tested in either the elevated plus maze (EPM) or a light-dark exploration (LD) test. In adults, both tests revealed a sexually dimorphic effect driven by PCP-induced decreases in anxiety in females as indicated by increased time spent in the open arms of the EPM and in the lit compartment of the LD test and increased anxiety in males as indicated by decreased time spent in the lit compartment of the LD. In young animals, PCP pretreatment decreased open arm exploration in the elevated plus maze, indicating increased anxiety. However, PCP increased time spent in the light compartment in the light-dark exploration test, indicating decreased anxiety. Corticosterone levels measured 15 min after the onset of the EPM failed to reveal an association between the behavioral effects of PCP and corticosterone levels. The results in adults substantiate the previously observed sexually dimorphic effect of PCP on elevated plus maze behavior in adults and indicate that the effect generalizes to another anxiety paradigm. The results in the younger animals suggest an age dependent effect of PCP on anxiety in general and indicate that behaviors in the elevated plus maze and the light-dark exploration test reflect dissociable psychobiological states.

  8. Metabolism of phencyclidine

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    Hoag, M.K.P.


    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s).

  9. Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP: effects of modafinil and relevance to cognitive deficits in schizophrenia?

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    John P Redrobe


    Full Text Available Phencyclidine (PCP induces a behavioural syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p. or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP-treatment. Acute treatment with modafinil (64 mg/kg, p.o. ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c., risperidone (0.2 mg/kg, i.p. and donepezil (3 mg/kg, p.o. were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP-NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS.

  10. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

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    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O' Donohue, T.L.


    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with (/sup 14/C)-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.

  11. Treatment of PCP addiction and PCP addiction-related behavior

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    Dewey, Stephen L. (Manorville, NY); Brodie, Jonathan D. (Cos Cob, CT); Ashby, Jr., Charles R. (Miller Place, NY)


    The present invention provides a method for changing addiction-related behavior of a mammal suffering from addiction to phencyclidine (PCP). The method includes administering to the mammal an effective amount of gamma vinylGABA (GVG) or a pharmaceutically acceptable salt thereof, or an enantiomer or a racemic mixture thereof, wherein the effective amount is sufficient to diminish, inhibit or eliminate behavior associated with craving or use of PCP.

  12. Simulation of psychosis by continuous delivery of phencyclidine from controlled-release polymer implants. (United States)

    Schroeder, U; Schroeder, H; Darius, J; Grecksch, G; Sabel, B A


    To simulate psychosis in rats we have developed a method for the continuous delivery of phencyclidine (PCP) using implantable controlled-release polymers. PCP polymer implants produced deficits in latent inhibition which do not occur after repeated bolus injections. PCP implanted rats were also devoid of any anxiogenic signs, motoric hyperactivity and learning acquisition which can be seen in rats receiving daily bolus injections of a comparable PCP dose. This behavioral double-dissociation of the two modes of PCP application was accompanied by respective neurochemical changes. PCP binding sites were reduced in both striatum and hippocampus, but in the hippocampus, loss of PCP binding sites was more severe following pulsatile PCP administration. Morphological assessment revealed a significant shrinkage of the CA3 region in hippocampus in both groups. Pharmacokinetic analysis showed that the maximum PCP concentration in the brain after bolus injections was 10-fold above the PCP implants.

  13. Disposition of phencyclidine in mice after smoke exposure

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    Freeman, A.S.; Martin, B.R.

    Mice were exposed to the smoke from placebo marihuana cigarettes treated with phencyclidine hydrochloride (PCP . HCl). A dose-related decrement in motor performance was observed after exposure to the smoke from cigarettes containing 10-15 mg of PCP . HCl. Tissue levels of /sup 3/H-PCP, /sup 3/H-PC (pyrolysis product), and /sup 3/H-metabolites were measured in several tissues up to 7 days after exposure to 50 mg of /sup 3/H-PCP . HCl. /sup 3/H-PCP levels were highest in liver followed by lung, brain, fat, and plasma for the first 10 min after exposure. The /sup 3/H-PCP concentration in all tissues, except fat, declined during the subsequent 50 min. Liver and lung contained the highest levels of /sup 3/H-metabolites during this hour, followed by plasma, fat, and brain. Brain levels of /sup 3/H-PCP correlated well with the magnitude and duration of behavioral effects observed (r . 0.98). /sup 3/H-PC was also well absorbed from smoke as evidenced by initial tissue levels comparable to those of /sup 3/H-PCP, but they declined more rapidly than /sup 3/H-PCP levels. Excellent correlations were obtained between /sup 3/H-PCP and /sup 3/H-PC concentrations in plasma and those in liver, lung, and brain. /sup 3/H-PCP was not detected in any tissue 3 days after smoke exposure. At 1 and 3 days, radioactivity corresponding to metabolites persisted in liver and lung, but had largely disappeared by 7 days.

  14. Evaluation of a neurodevelopmental model of schizophrenia--early postnatal PCP treatment in attentional set-shifting

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    Broberg, Brian Villumsen; Dias, Rebecca; Glenthøj, Birte Yding;


    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel finding...

  15. Tetrahydrocannabinol interactions with phencyclidine and methaqualone

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    Lame, M.W.


    To determine the effects of 9/-tetrahydrocannabinol (THC) on the pharmacokinetics and metabolism of phencyclidine (PCP) or methaqualone (MTQ), both in vivo and in vitro studies were conducted using Sprague Dawley rats. In the in vivo studies, plasma levels of /sup 3/H-PCP.HCl equivalents were significantly altered by the administration of THC, with the test curve elevated and parallel to the control. Tissue data followed the same pattern as plasma. The urinary, fecal, and biliary excretion of /sup 3/H-PCP.HCl equivalents for the most part did not show significant perturbation with the coadministration of THC. With respect of MTQ, plasma studies indicated that THC could significantly elevate /sup 14/C-MTQ equivalents for the first 4.5 hours, reduce these levels from approximately 6.5 to 16.5 hours, and again elevate the levels above controls for the period from 19.5 to 22.5 hours. All significant changes in tissue levels mirrored plasma value differences seen between test and control animals. Biliary excretion data indicated that THC showed a trend towards altering the active excretion of /sup 14/C-MTQ equivalents. In vitro microsomal metabolism studies indicated that THC production of phenylcyclohexylamine, 1-(1-phenyl-4-hydroxycyclohexyl)piperidine, and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine. Similar studies conducted with MTQ revealed that THC at the 0.05, 0.025, and 0.0125 mM levels also inhibited the metabolism of this compound.

  16. Synthesis and characterization of phencyclidine and his derivatives

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    Ilić Nataša C.


    Full Text Available Phencyclidine (PCP or 1-phenyl-cyclohexylpiperidine is the best known representative drug from the compound class of arylcyclohexylamines. On an account of pharmacological activities it belongs to the family of drugs known as a dissociative anesthetics. In recent years, great attention has been paid to the investigation of the substances that have been abused, including PCP. PCP is the synthetic drug with stimulant and hallucinogens effects (street name “angel dust” and it's situated on the Schedule Substances List, in Serbia and worldwide. In the beginning, PCP has been sold in pharmacies as local anesthetic, but very quickly it was pulled from sale because of the unwanted effects on consumer´s health causing psychoactive addiction. Taking into the account that today a great attention has been given to the substances that are subject of abuse, in this paper, biological and pharmacological effect of PCP and it's derivative is described. It is shown that PCP is antagonist of N-methyl-D-aspartate (NMDA and that it causes antiglutamateric hallucinations. Unlike BTCP which agonist is NMDA receptor and is obtained by modifying the structure of PCP. This paper presents a PCP metabolism and provides an overview of the methods for their identification and quantification in the biological samples. Immunological tests of PCP in the biological samples can provide a quick but wrong result because of the possible interference with the other substances of abuse as opposed to instrumental methods. Based on the presented method and the results it was concluded that the method of choice for the examinations of biological samples for the presence of PCP is gas chromatography in combination with mass spectroscopy.

  17. Phencyclidine in the social interaction test: an animal model of schizophrenia with face and predictive validity. (United States)

    Sams-Dodd, F


    Phencyclidine (PCP) is a hallucinogenic drug that can mimic several aspects of the schizophrenic symptomatology in healthy volunteers. In a series of studies PCP was administered to rats to determine whether it was possible to develop an animal model of the positive and negative symptoms of schizophrenia. The rats were tested in the social interaction test and it was found that PCP dose-dependently induces stereotyped behaviour and social withdrawal, which may correspond to certain aspects of the positive and negative symptoms, respectively. The effects of PCP could be reduced selectively by antipsychotic drug treatment, whereas drugs lacking antipsychotic effects did not alleviate the PCP-induced behaviours. Together these findings indicate that PCP effects in the rat social interaction test may be a model of the positive and negative symptoms of schizophrenia with face and predictive validity and that it may be useful for the evaluation of novel antipsychotic compounds.

  18. Evaluation of a neurodevelopmental model of schizophrenia--early postnatal PCP treatment in attentional set-shifting

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    Broberg, Brian Villumsen; Dias, Rebecca; Glenthøj, Birte Yding;


    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel findin...... is reminiscent of the impairment observed in schizophrenia patients, and supports the validity of the early postnatal PCP regimen as a disease-like model....

  19. Differential expression of parvalbumin interneurons in neonatal phencyclidine treated rats and socially isolated rats

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    Kaalund, Sanne Simone; Riise, Jesper; Broberg, Brian;


    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration...... of parvalbumin-positive interneurons (PV(+) interneurons). In this study we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia, the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical...... phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment...

  20. Acute phencyclidine treatment induces extensive and distinct protein phosphorylation in rat frontal cortex

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    Palmowski, Pawel; Rogowska-Wrzesinska, Adelina; Williamson, James


    assessment of the regulated proteins biological function revealed that PCP perturbs key processes in the frontal cortex including calcium homeostasis, organization of cytoskeleton, endo/exocytosis, and energy metabolism. This study on acute PCP treatment provides the largest proteomics and phosphoproteomics......Phencyclidine (PCP), a noncompetitive N-methyl-d-aspartate receptor antagonist, induces psychotomimetic effects in humans and animals. Administration of PCP to rodents is used as a preclinical model for schizophrenia; however, the molecular mechanisms underlying the symptoms remain largely unknown....... Acute PCP treatment rapidly induces behavioral and cognitive deficits; therefore, post-translational regulation of protein activity is expected to play a role at early time points. We performed mass-spectrometry- driven quantitative analysis of rat frontal cortex 15, 30, or 240 min after...

  1. alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

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    Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H;


    , and administration of the NMDA-antagonist phencyclidine (PCP) in rodents is a well validated model of such cognitive deficits. Here we show that repeated PCP treatment (10 mg/kg/day for 10 days) decreased the expression of parvalbumin and synaptophysin mRNA in the mouse PFC, which corresponds to changes seen...... in patients with schizophrenia. In addition, PCP increased the basal mRNA expression in the PFC of the activity-regulated cytoskeleton-associated protein (Arc), a molecule involved in synaptic plasticity. These molecular changes produced by PCP were accompanied by a behavioral impairment as determined...... in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

  2. The gut microbiota influence behavior in the subchronic PCP-induced model of schizophrenia

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    Jørgensen, Bettina Merete Pyndt; Redrobe, John Paul; Pedersen, Tina Brønnum;

    Introduction: Evidence is accumulating that the gut microbiota (GM) impact on the individual to a degree, which were not previously believed. We investigated the impact of the GM on behavior in the subchronic phencyclidine (PCP) induced model of Schizophrenia. Materials and methods: Three batches...... microbiota in the analysis of studies using this model....

  3. Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats

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    Secher, Thomas; Berezin, Vladimir; Bock, Elisabeth


    The FGL peptide is a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist. FGL has both neurotrophic and memory enhancing properties. Neonatal phencyclidine (PCP) treatment on postnatal days 7, 9, and 11 has been shown to result in long-lasting behavioral abnormalities...

  4. Phencyclidine Induced Oculogyric Crisis Responding Well to Conventional Treatment

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    Hassan Tahir


    Full Text Available Background. Oculogyric crisis is a form of acute dystonic reaction characterized by involuntary upward deviation of eye ball. Its causes are broad with antipsychotics and antiemetics as the most common causes. Case Presentation. A 25-year-old man with the past medical history of marijuana use presented to ED with involuntary upward deviation of eye 1 day after using phencyclidine (PCP for the first time. He did not have any other symptoms and was hemodynamically stable. All laboratory investigations were normal except urine drug screen which was positive for PCP. Patient was treated with IV diphenhydramine which improved his symptoms. Conclusion. Illicit drug abuse is a growing problem in our society with increasingly more patients presenting to ED with its complications. The differential diagnosis of acute dystonic reactions should be extended to include illicit drugs as the potential cause of reversible acute dystonias especially in high risk patients.

  5. Evaluation of a neurodevelopmental model of schizophrenia - Early postnatal PCP treatment in attentional set-shifting

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    Broberg, B.V.; Dias, R.; Olsen, C.K.;


    Phencyclidine (PCP) was administered to male and female Lister hooded rats on postnatal days (PND) 7, 9 and 11. All PCP animals tested in adulthood (PND 53-93) showed deficits in cognitive flexibility, specifically in their ability to shift attentional set, compared to controls. This novel findin...... is reminiscent of the impairment observed in schizophrenia patients, and supports the validity of the early postnatal PCP regimen as a disease-like model. (c) 2008 Elsevier B.V. All rights reserved Udgivelsesdato: 2008...

  6. Differential expression of parvalbumin in neonatal phencyclidine-treated rats and socially isolated rats. (United States)

    Kaalund, Sanne S; Riise, Jesper; Broberg, Brian V; Fabricius, Katrine; Karlsen, Anna S; Secher, Thomas; Plath, Niels; Pakkenberg, Bente


    Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin-positive interneurons (PV(+) interneurons). In this study, we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical fractionator, we counted neurons, PV(+) interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV(+) interneurons (p = 0.021) and glial cells (p = 0.024) in the mPFC of neonatal phencyclidine rats, but not in SI rats. We observed no alterations in the total number of neurons, hippocampal PV(+) interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV(+) interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations.

  7. The Effect of Phencyclidine New Derivatives on Anxiety Behaviors in Rats

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    Ramin Hajkhani


    Full Text Available Objective(s Anxiety is a common disorder which afflicts many people in any society and is often accompanied by physiological sensations such as tachycardia, chest pain, shortness of breath, insensitivity, etc. The purpose of present study was to evaluate the putative anxiolytic-like effects of phencyclidine (1-(1-phenylcyclohexyl piperidine, CAS 956-90-1, PCP, I and its methyl and methoxy hydroxyl derivatives (II, III using elevated plus maze test of anxiety. Materials and Methods Phencyclidine as well as its methyl and methoxy hydroxyl derivatives (I, II, III (hydrochloride, 1, 2, 5 mg/kg were synthesized and administrated intraperitoneally (IP on adult male Wistar rats.ResultsThe results of this study demonstrated that, intraperitoneal (IP administration of PCP analogues (I, II, III hydrochloride (1, 2, 5 mg/kg increases the percentage of open arm time (OAT% and percentage of open arm entries (OAE%.ConclusionThis study revealed that both derivatives of phencyclidine (II, III were more effective than PCP (I itself in modulation of anxiety behavior in rats.

  8. Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology. (United States)

    Kyzar, Evan J; Collins, Christopher; Gaikwad, Siddharth; Green, Jeremy; Roth, Andrew; Monnig, Louie; El-Ounsi, Mohamed; Davis, Ari; Freeman, Andrew; Capezio, Nicholas; Stewart, Adam Michael; Kalueff, Allan V


    Mescaline and phencyclidine (PCP) are potent hallucinogenic agents affecting human and animal behavior. As their psychotropic effects remain poorly understood, further research is necessary to characterize phenotypes they evoke in various animal models. Zebrafish (Danio rerio) are rapidly emerging as a new model organism for neuroscience research. Here, we examine the effects of mescaline (5-20mg/l) and PCP (0.5-3mg/l) in several zebrafish paradigms, including the novel tank, open field and shoaling tests. Mescaline and PCP dose-dependently increased top activity in the novel tank test, also reducing immobility and disrupting the patterning of zebrafish swimming, as assessed by ethograms. PCP, but not mescaline, evoked circling behavior in the open field test. At the highest doses tested, mescaline markedly increased, while PCP did not affect, zebrafish shoaling behavior. Finally, 20mg/l mescaline did not alter, and 3mg/l PCP elevated, whole-body cortisol levels. Overall, our studies indicate high sensitivity of zebrafish models to hallucinogenic compounds with complex behavioral and physiological effects.

  9. Relation between hippocampal gamma waves and behavioral disturbances induced by phencyclidine and methamphetamine. (United States)

    Ma, J; Leung, L S


    The relationship between hippocampal electrical activity and behavioral hyperactivity induced by either phencyclidine (PCP) or methamphetamine (MAP) was examined in freely behaving rats. The EEGs at the hippocampal CA1 region were simultaneously recorded with the animal's behavior for 2 h after administration of either PCP or MAP. PCP (10 mg/kg, intraperitoneal (i.p.)) significantly increased locomotor activity including rearing, walking, head-weaving and circling. Spectral analysis of the EEG showed that hippocampal gamma waves (30-70 Hz), but not other frequency bands, were significantly increased from 5 to 120 min after systemic injection of PCP. Inactivation of the medial septum with muscimol, a gamma-aminobutyric acid receptor A agonist, 15 min prior to injection of PCP, suppressed both hippocampal gamma waves and locomotor activity. MAP (1.5 mg/kg, i.p.) also increased locomotor activity for longer than 2 h. During the behavioral hyperactivity induced by MAP, hippocampal EEG showed θ and gamma rhythms that were not significantly different from those during walking before MAP. However, MAP-induced behavioral activity was suppressed by pre-injection of muscimol in the medial septum, which also decreased hippocampal gamma activity. It is suggested that the medial septum plays a role in mediating behavioral disturbances induced by both PCP and MAP through control of the hippocampal electrical activity, and that hippocampal gamma waves may play a permissible role in the expression of behaviors.

  10. Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

    Directory of Open Access Journals (Sweden)

    Yumi Shirai

    Full Text Available Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA neurons expressing parvalbumin (PV, which is also involved in cognitive impairment. Sulforaphane (SFN, an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP. Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

  11. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice


    Xu, Jian; Kurup, Pradeep; Baguley, Tyler D.; Foscue, Ethan; Ellman, Jonathan A.; Nairn, Angus C.; Lombroso, Paul J.


    Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we ch...

  12. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice. (United States)

    Xu, Jian; Kurup, Pradeep; Baguley, Tyler D; Foscue, Ethan; Ellman, Jonathan A; Nairn, Angus C; Lombroso, Paul J


    Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we characterize the regulation of BDNF expression by STEP61, utilizing PCP-treated cortical culture and PCP-treated mice. PCP-treated cortical neurons showed both an increase in STEP61 levels and a decrease in BDNF expression. The reduction in BDNF expression was prevented by STEP61 knockdown or use of the STEP inhibitor, TC-2153. The PCP-induced increase in STEP61 expression was associated with the inhibition of CREB-dependent BDNF transcription. Similarly, both genetic and pharmacologic inhibition of STEP prevented the PCP-induced reduction in BDNF expression in vivo and normalized PCP-induced hyperlocomotion and cognitive deficits. These results suggest a mechanism by which STEP61 regulates BDNF expression, with implications for cognitive functioning in CNS disorders.

  13. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

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    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  14. Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats. (United States)

    Katayama, T; Okamoto, M; Suzuki, Y; Hoshino, K-Y; Jodo, E


    Patients with schizophrenia exhibit deficits in motivation and affect, which suggests an impairment in the reward system. The psychotomimetic drug, phencyclidine (PCP), also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect, and social withdrawal in both humans and animals. Previous studies have indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. However, how PCP affects the activity of VTA neurons during performance of a reward-related task and social interaction with others in unanesthetized animals remains unclear. Here, we recorded the unit activity of VTA neurons in freely moving rats before and after systemic administration of PCP in a classical conditioning paradigm, and during social interaction with an unfamiliar partner. In the classical conditioning task, two different tones were sequentially presented, one of which accompanied electrical stimulation of the medial forebrain bundle as an unconditioned stimulus. After identifying the response properties of recorded neurons in the classical conditioning task and social interaction, animals received an intraperitoneal injection of PCP. Our study demonstrated that most VTA neurons responsive to reward-associated stimuli were also activated during social interaction. Such activation of neurons was considerably suppressed by systemic administration of PCP, thus, PCP may affect the firing activity of VTA neurons that are involved in motivation, learning, and social interaction. Disruption of the response of VTA neurons to reward stimuli and socially interactive situations may be involved in PCP-induced impairments similar to the negative symptoms of schizophrenia.

  15. Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behaviour and social isolation in the rat social interaction test. (United States)

    Sams-Dodd, F


    Phencyclidine (PCP) induces stereotyped behaviour and social isolation in rats; comparisons with clinical observations have suggested that these behaviours may mimic certain aspects of the positive and the negative symptoms, respectively, of an acute schizophrenic episode. Novel antipsychotics are effective in treating the positive symptoms in schizophrenic patients and have also shown some promise in treating the negative symptoms. In the present study the effects of the novel antipsychotics remoxipride (2.5-20 mg/kg), risperidone (0.02-0.63 mg/kg), sertindole (0.01-2.5 mg/kg), olanzapine (0.16-2.5 mg/kg) and quetiapine (0.16-10 mg/kg) on PCP-induced behaviours were determined. The drugs were administered daily for 3 or 21 days in combination with vehicle or 2.0 mg/kg of PCP for the last 3 days of the administration regime, and the rats were tested using the social interaction test. The antipsychotic drugs all reliably reduced the level of PCP-induced stereotyped behaviour and had distinct effects on PCP-induced social isolation. Comparison with clinical findings suggests that the PCP-induced behaviours respond to treatment with antipsychotic drugs in a manner that correlates well with clinical observations, and that this animal model of schizophrenia may be useful for evaluating novel drug candidates. However, the study also showed that additional experiments are required to determine the specificity by which antipsychotic drugs alleviate PCP-induced behaviours because most of the drugs also affected considerably the behaviour of the control animals.

  16. Effects of dopamine agonists and antagonists on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test. (United States)

    Sams-Dodd, F


    Phencyclidine (PCP) can induce a model psychosis in humans that resembles an acute schizophrenic psychosis. In animal models of schizophrenia, PCP induces locomotor hyperactivity, stereotyped behaviour and social isolation, and the purpose of the present study was to describe the ability of dopamine agonists and antagonists to mimic or interact with these PCP-induced behaviours in rats. The compounds were administered daily for 3 days in combination with vehicle or 2.0 mg/kg PCP and the rats were tested in the social interaction test on the last day of drug administration. The study showed that D1-agonists with relative differences in efficacy at the DA-stimulated adenylate cyclase had limited effects on the PCP-induced behaviours, whereas the D1-antagonist SCH 23391 could alleviate the PCP-induce social isolation following daily treatment for 3 days. However, following long-term treatment for 21 days, the rats develop tolerance to this effect. These data thus suggested that the D1-receptor system only had a modulatory effect on PCP. In contrast, the D2-receptor family may be more directly involved, because the D2/D3/D4-agonist quinpirole could mimic and potentiate the PCP-induced deficits in social behaviour, and the D2/D3-antagonist (-)sulpiride could alleviate the PCP-induced stereotyped behaviour and social isolation. However, a D4-antagonist did not affect the behaviour of vehicle- and PCP-treated rats, suggesting that this system plays a less direct role in the behavioural effects of PCP. In general, however, the effects of SCH 23391, quinpirole and (-)sulpiride on the PCP-induced behaviours were mirrored in the vehicle-treated control groups and it is therefore possible that non-specific effects may have been important.

  17. Impaired GABAergic Inhibition in the Prefrontal Cortex of Early Postnatal Phencyclidine (PCP)-Treated Rats

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe;


    A compromised ¿-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-d-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmissio...

  18. Differential effects of subchronic phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests. (United States)

    Enkel, Thomas; Thomas, Mara; Bartsch, Dusan


    Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents. We addressed the question whether subchronic PCP (scPCP) treatment (5 mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light-dark exploration test (LDT) and in an open field environment (OFT). The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity. Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm.

  19. Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia. (United States)

    Deng, Xiangdong; Takaki, Hiromi; Wang, Lixiang; Kuroki, Tosihide; Nakahara, Tatsuo; Hashimoto, Kijiro; Ninomiya, Hideaki; Arinami, Tadao; Inada, Toshiya; Ujike, Hiroshi; Itokawa, Masanari; Tochigi, Mamoru; Watanabe, Yuichiro; Someya, Toshiyuki; Kunugi, Hiroshi; Iwata, Nakao; Ozaki, Norio; Shibata, Hiroki; Fukumaki, Yasuyuki


    As schizophrenia-like symptoms are produced by administration of phencyclidine (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP-responsive genes could be involved in the pathophysiology of schizophrenia. We injected PCP to Wistar rats and isolated five different parts of the brain in 1 and 4 hr after the injection. We analyzed the gene expression induced by the PCP treatment of these tissues using the AGILENT rat cDNA microarray system. We observed changes in expression level in 90 genes and 21 ESTs after the treatment. Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we selected 7 genes as subjects for the locus-wide association study to identify susceptibility genes for schizophrenia in the Japanese population. In haplotype analysis, significant associations were detected in combinations of two SNPs of BTG2 (P = 1.4 × 10(-6) ), PDE4A (P = 1.4 × 10(-6) ), and PLAT (P = 1 × 10(-3) ), after false discovery rate (FDR) correction. Additionally, we not only successfully replicated the haplotype associations in PDE4A (P = 6.8 × 10(-12) ) and PLAT (P = 0.015), but also detected single-point associations of one SNP in PDE4A (P = 0.0068) and two SNPs in PLAT (P = 0.0260 and 0.0104) in another larger sample set consisting of 2,224 cases and 2,250 controls. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population.

  20. Application of solvent microextraction to the analysis of amphetamines and phencyclidine in urine. (United States)

    Casari, C; Andrews, A R


    A fast and simple method to detect some commonly abused illicit drugs, amphetamine, methamphetamine, 3,4-methylendioxy-amphetamine (MDA), 3,4-methylendioxy-methamphetamine (MDMA), 3,4-methylendioxy-N-ethylamphetamine (MDEA) and phencyclidine (PCP) in urine using solvent microextraction (SME) combined with gas chromatography (GC) analysis has been developed. The extraction is conducted by suspending a 2 microl drop of chloroform in a 2 ml urine sample. Following 8 min of extraction, the organic solvent is withdrawn into the syringe and injected into a GC with a pulsed discharge helium ionization detector (PDHID). The effects of different extraction solvents and times, pH and sample preparation were studied. The optimized method was capable of detecting drugs in urine at concentrations below Substance Abuse and Mental Health Services Administration (SAMHSA) established cut-off values for preliminary testing. Good linearity and reproducibility of extraction were obtained. The limits of detection were 0.5 microg/ml for amphetamine, 0.1 microg/ml for methamphetamine and MDA, 0.05 microg/ml for MDMA, 0.025 microg/ml for MDEA and 0.015 microg/ml for PCP. Relative standard deviation (R.S.D.) values ranged between 5 and 20% for the studied drugs.

  1. Prolonged reversal of the phencyclidine-induced impairment in novel object recognition by a serotonin (5-HT)1A-dependent mechanism. (United States)

    Horiguchi, Masakuni; Miyauchi, Masanori; Neugebauer, Nichole M; Oyamada, Yoshihiro; Meltzer, Herbert Y


    Many acute treatments transiently reverse the deficit in novel object recognition (NOR) produced by subchronic treatment with the N-methyl-d-aspartate receptor non-competitive antagonist, phencyclidine (PCP), in rodents. Treatments which restore NOR for prolonged periods after subchronic PCP treatment may have greater relevance for treating the cognitive impairment in schizophrenia than those which restore NOR transiently. We examined the ability of post-PCP subchronic lurasidone, an atypical APD with potent serotonin (5-HT)1A partial agonism and subchronic tandospirone, a selective 5-HT1A partial agonist, to enable prolonged reversal of the subchronic PCP-induced NOR deficit. Rats treated with subchronic PCP (2mg/kg, twice daily for 7 days) or vehicle, followed by a 7day washout period were subsequently administered lurasidone or tandospirone twice daily for 7 days (day 15-21), and tested for NOR weekly for up to two additional weeks. Subchronic lurasidone (1, but not 0.1mg/kg) or tandospirone (5, but not 0.6mg/kg) significantly reversed the PCP-induced NOR deficit at 24h and 7days after the last injection, respectively. The effect of lurasidone persisted for one more week (day 36, 14 days after the last lurasidone dose), while tandospirone-treated rats were able to perform NOR at 7, but not 14, days after the last tandospirone dose. Co-administration of WAY100635 (0.6mg/kg), a 5-HT1A antagonist, with lurasidone, blocked the ability of lurasidone to restore NOR, suggesting that 5-HT1A receptor stimulation is necessary for lurasidone to reverse the effects of PCP. The role of dopamine, GABA and the MAPK/ERK signalling pathway in the persistent, but not indefinite, restoration of NOR is discussed.

  2. Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro. (United States)

    Shukla, V K; Bansinath, M; Dumont, M; Lemaire, S


    Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.

  3. Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia. (United States)

    Pyndt Jørgensen, B; Krych, L; Pedersen, T B; Plath, N; Redrobe, J P; Hansen, A K; Nielsen, D S; Pedersen, C S; Larsen, C; Sørensen, D B


    Subchronic phencyclidine (subPCP) treatment induces schizophrenic-like behavior in rodents, including cognitive deficits and increased locomotor sensitivity towards acute administration of PCP. Evidence is accumulating that the gut microbiota (GM) influences behavior through modulation of the microbiota-gut-brain axis, and hence, part of the variation within this animal model may derive from variation in the GM. The aims of this study was to investigate first, the duration of subPCP-induced cognitive impairment in the novel object recognition test, and second, the possible effect of subchronic PCP-treatment on the GM, and the association between the GM and the behavioral parameters. The association was further investigated by antibiotic reduction of the GM. Male Lister Hooded rats were dosed twice daily i.p. with either 5mg/kg PCP or sterile isotonic saline for seven days followed by a seven-day washout period. Rats were tested in the novel object recognition and the locomotor activity assays immediately after, three weeks after, or six weeks after washout, and the fecal GM was analyzed by high throughput sequencing. Antibiotic- and control-treated rats were tested in the same manner following washout. In conclusion, subPCP-treatment impaired novel object recognition up to three weeks after washout, whereas locomotor sensitivity was increased for at least six weeks after washout. Differences in the core gut microbiome immediately after washout suggested subPCP treatment to alter the GM. GM profiles correlated to memory performance. Administration of ampicillin abolished the subPCP-induced memory deficit. It thus seems reasonable to speculate that the GM influences memory performance, contributing to variation within the model.

  4. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia. (United States)

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J


    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach.

  5. Validation of analysis of amphetamines, opiates, phencyclidine, cocaine, and benzoylecgonine in oral fluids by liquid chromatography-tandem mass spectrometry. (United States)

    Kala, Subbarao V; Harris, Steve E; Freijo, Tom D; Gerlich, Stan


    The aim of the present study was to develop and validate a method for the detection and quantitation of drugs of abuse in oral fluids. Fortified oral fluid samples (made in-house) and samples from donors collected with Quantasil oral fluid collection kits from Immunalysis were screened on an Olympus 5400 using reagents purchased from Immunalysis. Amphetamines (AMPs), opiates, phencyclidine (PCP), and cocaine and its metabolite benzoylecgonine (BE) in oral fluids were quantitated by an Applied Biosystems 3200 QTRAP liquid chromatograph-tandem mass spectrometer (LC-MS-MS). AMPs, opiates, PCP, cocaine, and BE were extracted from samples using liquid-liquid or solid-phase extractions and the extracts were separated on a Shimadzu high-performance liquid chromatograph prior to the MS-MS analysis. For each drug, two multiple reaction mode transitions were monitored using positive electrospray ionization coupled to an MS-MS detector. Corresponding d3, d5, d6, and d11 internal standards were used to quantitate the results. The limit of detection/quantitation for AMPs, opiates, PCP, cocaine, and its metabolite BE were 10, 10, 2, 2, and 2 ng/mL of oral fluid, respectively, on a signal-to-noise ratio > 4. This corresponded to 25, 25, 5, 5, and 5 pg on column. The method was verified by participating in the North America Oral Fluid Proficiency Testing administered by Research Triangle Institute and by analyzing real samples from donors. In conclusion, LC-MS-MS provided a simple way to analyze and quantitate drugs of abuse in oral fluids.

  6. Effects of diazepam, citalopram, methadone and naloxone on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test. (United States)

    Sams-Dodd, F


    Phencyclidine (PCP) can induce a model psychosis in humans that mimics the positive and negative symptoms of schizophrenia. In the social interaction test PCP induces stereotyped behaviour and social isolation in rats, and these behaviours can be inhibited by antipsychotic drugs. In order to further evaluate the predictive validity of this model of schizophrenia the anxiolytic diazepam (0.02-17.5 micromol/kg; 0.005-5.0 mg/kg), the antidepressant citalopram (0.62-19.8 micromol/kg; 0.3-4.0 mg/kg), the opioid agonist methadone (0.36-5.8 micromol/kg; 0.13-2.0 mg/kg) and the opioid antagonist naloxone (0.34-22.0 micromol/kg; 0.13-8.0 mg/kg) were tested as examples of drugs without antipsychotic activity. The experiments demonstrated that these compounds did not specifically inhibit the behavioural effects of PCP. So far only antipsychotic drugs have been able to specifically inhibit the PCP-induced behaviours.

  7. A schizophrenia rat model induced by early postnatal phencyclidine treatment and characterized by Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Broberg, Brian V; Madsen, Kristoffer H; Plath, Niels


    PCP), compared to saline (neoVeh), were hypersensitive to acute PCP administration in adulthood (acutePCP). Intravenous administration of 0.5mg/kg acutePCP produced robust and sustained relative cerebral blood volume (rCBV) increase in discrete frontal, neocortical, hippocampal, thalamic, and limbic brain...... structures in both neoPCP:acutePCP and neoVeh:acutePCP rats compared to acute saline treatment (Vehicle control group). AcutePCP injection significantly increased the rCBV response in the medial prefrontal cortex and nucleus accumbens compared to the Vehicle control group, without distinguishing neo......PCP and neoVeh animals. However, at late time points (25-33min post acutePCP injection), neoPCP animals showed significantly higher rCBV values compared to the Vehicle control group, suggesting an altered sensitivity towards NMDAR blockade in adult rats subjected to this neurodevelopmental procedure...

  8. Identification of developmentally regulated PCP-responsive non-coding RNA, prt6, in the rat thalamus.

    Directory of Open Access Journals (Sweden)

    Hironao Takebayashi

    Full Text Available Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor antagonists, such as phencyclidine (PCP and ketamine, usually develop after adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor antagonist application in rodents is observed after a critical period at around 3 postnatal weeks. These observations suggest that the schizophrenic symptoms caused by and psychotomimetic effects of NMDA antagonists require the maturation of certain brain neuron circuits and molecular networks, which differentially respond to NMDA receptor antagonists across adolescence and the critical period. From this viewpoint, we have identified a novel developmentally regulated phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as a candidate molecule involved in the above schizophrenia-related systems using a DNA microarray technique. The transcript is a non-coding RNA that includes sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly in the brain and testis, with trace or non-detectable levels in the spleen, heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c. significantly elevated the expression of prt6 mRNA in the thalamus at postnatal days (PD 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg, s.c., and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg, s.c., mimicked a significant increase in the levels of thalamic prt6 mRNAs, while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the increasing influence of PCP on thalamic prt6 expression without its own effects. These data indicate that prt6 may be involved in the pathophysiology of the onset of drug-induced schizophrenia-like symptoms and schizophrenia through the possible

  9. Structural basis of interaction between protein tyrosine phosphatase PCP-2 and β-catenin

    Institute of Scientific and Technical Information of China (English)

    HE; Yaqin; YAN; Hexin; DONG; Hui; ZHANG; Peng; TANG; Liang


    PCP-2 is a member of receptor-like protein tyrosine phosphatase of the MAM domain family. To investigate which part of PCP-2 was involved in its interaction with β-catenin, we constructed various deletion mutants of PCP-2. These PCP-2 mutants and wild-type PCP-2 were co-transfected into BHK-21 cells with β-catenin individually. An in vivo binding assay revealed that the expression of wild-type PCP-2, PCP-2△C1C2 (deleted PCP-2 without both PTP domains) and PCP-2△C2 (deleted PCP-2 without the second PTP domain) could be immunoprecipitated by anti-catenin antibody in every co-transfection, but PCP-2 EXT (deleted PCP-2 without the juxtamembrane region and both PTP domains) was missing, which implied that PCP-2 and β-catenin could associate directly and the juxtamembrane region in PCP-2 was sufficient for the process.

  10. Radiolysis of pentachlorophenol (PCP) in aqueous solution by gamma radiation

    Institute of Scientific and Technical Information of China (English)

    XUE Jun; WANG Jianlong


    Steady-state radiolysis experiments were performed to investigate the y-irradiation treatment of pentachlorophenol (PCP) in aqueoussolution. The effect of initial concentration on the PCP degradation was also investigated. The experimental results showed that γ-irradiation was able to degrade PCP in aqueous solution successfully, and the radiolytical degradation process of PCP could be describedby the first-order kinetic model. When the initial concentration of PCP was 25 and 50 mg/L and the radiation dose was 4 and 6 kGy,respectively, the degradation efficiency was 100%. A luminescence bacterial test was used for evaluating the toxicity of the radiolyticintermediate products. Total detoxification of a 75 mg/L PCP solution could be achieved by carrying out the irradiation procedure at the dose of 15 kGy.

  11. Neonatal administration of phencyclidine decreases the number of putative inhibitory interneurons and increases neural excitability to auditory paired clicks in the hippocampal CA3 region of freely moving adult mice. (United States)

    Okamoto, M; Katayama, T; Suzuki, Y; Hoshino, K-Y; Yamada, H; Matsuoka, N; Jodo, E


    Animals exposed to phencyclidine (PCP) during the neonatal period have fewer GABAergic interneurons in the corticolimbic area, including the hippocampus, and exhibit abnormal behaviors after attaining maturation that correspond with schizophrenic symptoms. Since a lack of inhibitory interneurons in the hippocampus has also been reported in postmortem studies of patients with schizophrenia, the deficit may induce abnormal activity of hippocampal neurons that underlies pathological states in schizophrenia. However, it remains unclear how PCP treatment during the neonatal period affects the discharge activity of hippocampal neurons in adulthood. In the current study, single unit responses of hippocampal CA3 neurons to paired auditory clicks were recorded in freely moving mice repeatedly injected with PCP or saline during the neonatal period. The recorded neurons were classified into two subpopulations, narrow-spike neurons and broad-spike neurons, based on the spike width. The spontaneous discharge rate was higher in the narrow-spike neurons than in the broad-spike neurons, indicating that the narrow-spike neurons correspond with hippocampal inhibitory neurons. The proportion of narrow-spike neurons was significantly smaller in neonatally PCP-treated mice than in saline-treated mice. The broad-spike neurons that exhibited a response magnitude to the second click as large as that to the first click (E/E-type response) showed longer response duration to the paired clicks in PCP-treated mice than in the saline-treated mice. Further, the number of neurons with E/E-type response was higher in the PCP-treated mice than in the saline-treated mice. Finally, the attenuation of an auditory-evoked potential component, N40, to the second click (sensory gating) was blunted in the PCP-treated mice when compared with that in the saline-treated mice. These results suggest that the neonatal administration of PCP induced a deficit of inhibitory interneurons and altered discharge

  12. Dinuclear PCP pincer complexes from Lewis acidic [Pd(OTf)(PCP)] and basic [Pd(4-Spy)(PCP)] (OTf = triflate; 4-Spy = 4-pyridinethiolate; PCP = (-)CH(CH(2)CH(2)PPh(2))(2)). (United States)

    Neo, Kian Eang; Huynh, Han Vinh; Koh, Lip Lin; Henderson, William; Hor, T S Andy


    The Lewis acidic pincer with a labile triflate ligand, viz. [Pd(OTf)(PCP)] (PCP = (-)CH(CH(2)CH(2)PPh(2))(2)) was prepared from [PdCl(PCP)] with AgOTf. It reacts readily with neutral bidentate ligands [L = 4,4'-bipyridine (4,4'-bpy) and 1,1'-bis(diphenylphosphino)ferrocene (dppf)] to give dinuclear PCP pincers [{Pd(PCP)}(2)(micro-L)][OTf](2) (L = 4,4'-bpy, 2; dppf,3). [PdCl(PCP)] also reacts with 4-mercaptopyridine in the presence of KOH to give a Lewis basic pincer with a free pyridine functional group [Pd(4-Spy)(PCP)]4. Its metalloligand character is exemplified by the isolation of an asymmetric dinuclear double-pincer complex [{Pd(PCP)}(2)(micro-4-Spy)][PF(6)] 6 bridged by an ambidentate pyridinethiolato ligand. Complexes 1, 2, 3, 4 and 6 have been characterized by single-crystal X-ray diffraction analyses.

  13. The immunotoxic effects of dual exposure to PCP and TCDD. (United States)

    Chen, Hsiu-Min; Lee, Yu-Hsuan; Chen, Rong-Jane; Chiu, Hui-Wen; Wang, Bour-Jr; Wang, Ying-Jan


    Pentachlorophenol (PCP) was a commonly used fungicide, herbicide, insecticide, and bactericide in industrial, agricultural, and domestic settings; however, it was also contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). It has been reported that technical grade PCP had immunosuppressive effects and that the immune system was the major target of PCDD/PCDFs toxicity. Although the immune response after exposure to PCP or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied, the toxic effects of exposure to both PCP and TCDD have not yet been reported. The aim of this study was to evaluate the effects on immune cells from mice intraperitoneally immunized with OVA and subsequently treated with PCP or TCDD alone or in combination by gavage. The animals were terminated on day 7 and 14, and the spleen and plasma samples were collected for immunotoxicity evaluation. The numbers and populations of splenocytes, T cell-derived cytokines produced by splenocytes, splenocyte-generated cytotoxicity and OVA-specific antibodies in plasma were investigated. Our results indicate that the spleen/body weight ratio and splenocyte number was reduced by TCDD alone; in addition, this reduction was enhanced when TCDD was combined with PCP. Exposure to TCDD alone or in conjunction with PCP suppressed many ovalbumin (OVA)-stimulated cytokines, including IL-2, IFN-γ, IL-4, IL-5, and IL-10. Furthermore, the immunoglobulins IgG and IgM were suppressed in mice administered by PCP alone, but the suppressive effects were greater in mice treated with TCDD alone or in combination with PCP. Co-exposure to PCP and TCDD resulted in an antagonistic effect on TCDD-induced suppression of IFN-γ and IL-10. Our results demonstrate that PCP alone is immunotoxic, regardless of the presence of TCDD. PCP led to mild changes in cytokine secretion, and it compromised splenocyte-generated cytotoxicity and IgM and IgG antibody production on day 7. The finding

  14. Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model (United States)

    Sershen, Henry; Hashim, Audrey; Dunlop, David S.; Suckow, Raymond F.; Cooper, Tom B.; Javitt, Daniel C.


    Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol®) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor sodium benzoate (NaB) (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level

  15. Choosing a Primary Health Care Provider (PCP): A Guide for Young Women (United States)

    ... Gynecology Medical Conditions Nutrition & Fitness Emotional Health Choosing a Primary Health Care Provider (PCP): General Information Posted ... taking care of yourself. Why do I need a PCP? You need a PCP so that your ...

  16. Choosing a Primary Health Care Provider (PCP): A Guide for Young Men (United States)

    ... Health Medical Conditions Nutrition & Fitness Emotional Health Choosing a Primary Health Care Provider (PCP): General Information Posted ... help address your problems. Why do I need a PCP? You need a PCP so that your ...

  17. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    Energy Technology Data Exchange (ETDEWEB)

    Temma, K.; Akera, T.; Ng, Y.C.


    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific (/sup 3/H)phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca/sup 2 +/ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K/sup +/ currents.

  18. Exploring metabolic pathway disruption in the subchronic phencyclidine model of schizophrenia with the Generalized Singular Value Decomposition

    Directory of Open Access Journals (Sweden)

    Morris Brian J


    Full Text Available Abstract Background The quantification of experimentally-induced alterations in biological pathways remains a major challenge in systems biology. One example of this is the quantitative characterization of alterations in defined, established metabolic pathways from complex metabolomic data. At present, the disruption of a given metabolic pathway is inferred from metabolomic data by observing an alteration in the level of one or more individual metabolites present within that pathway. Not only is this approach open to subjectivity, as metabolites participate in multiple pathways, but it also ignores useful information available through the pairwise correlations between metabolites. This extra information may be incorporated using a higher-level approach that looks for alterations between a pair of correlation networks. In this way experimentally-induced alterations in metabolic pathways can be quantitatively defined by characterizing group differences in metabolite clustering. Taking this approach increases the objectivity of interpreting alterations in metabolic pathways from metabolomic data. Results We present and justify a new technique for comparing pairs of networks--in our case these networks are based on the same set of nodes and there are two distinct types of weighted edges. The algorithm is based on the Generalized Singular Value Decomposition (GSVD, which may be regarded as an extension of Principle Components Analysis to the case of two data sets. We show how the GSVD can be interpreted as a technique for reordering the two networks in order to reveal clusters that are exclusive to only one. Here we apply this algorithm to a new set of metabolomic data from the prefrontal cortex (PFC of a translational model relevant to schizophrenia, rats treated subchronically with the N-methyl-D-Aspartic acid (NMDA receptor antagonist phencyclidine (PCP. This provides us with a means to quantify which predefined metabolic pathways (Kyoto

  19. Optimization of enrichment processes of pentachlorophenol (PCP) from water samples

    Institute of Scientific and Technical Information of China (English)

    LI Ping; LIU Jun-xin


    The method of enriching PCP (pentachlorophenol) from aquatic environment by solid phase extraction (SPE) was studied.Several factors affecting the recoveries of PCP, including sample pH, eluting solvent, eluting volume and flow rate of water sample, were optimized by orthogonal array design(OAD). The optimized results were sample pH 4; eluting solvent, 100% methanol; eluting solvent volume, 2 mi and flow rate of water sample, 4 mi/min. A comparison is made between SPE and liquid-liquid extraction(LLE) method. The recoveries of PCP were in the range of 87.6 % 133.6 % and 79 %- 120.3 % for S PE and LLE, respectively. Important advantages of the SPE compared with the LLE include the short extraction time and reduced consumption of organic solvents. SPE can replace LLE for isolating and concentrating PCP from water samples.

  20. The plane facts of PCP in the CNS



    Planar Cell Polarity (PCP) pathways have been defined by their ability to direct the development of obviously polarized cellular architectures, such as the asymmetric localization of the stereociliary bundle in cochlear hair cells. Recent studies indicate that PCP pathways converge on the actin skeleton to regulate additional aspects of cell morphology that are not restricted to the plane of the epithelium. In the developing nervous system, these changes in the cytoskeleton are fundamental to...

  1. Phencyclidine prevents spatial navigation and passive avoidance deficits in ibotenate lesioned rats. (United States)

    O'Connell, A; Earley, B; Leonard, B E


    The potential neuroprotective effects of phencyclidine (5 mg/kg i.p.) were assessed in rats which had been treated with the excitotoxin, ibotenic acid (IBO) (0.015 M) to lesion the nucleus basalis magnocellularis. IBO treated rats showed a significant impairment in 13 of the 25 test trials in the spatial navigation Morris water maze task and deficits in passive avoidance learning. Phencyclidine was found to prevent the IBO-induced impairment in 4 of the 13 test trials in which the IBO Morris maze deficit was observed and also successfully prevented the passive avoidance learning deficits. Neurochemically, IBO was shown to reduce the levels of gamma amino-n-butyric acid (GABA) in the cortex. This effect of IBO on the inhibitory GABAergic system may contribute to the direct toxic effects of IBO which is mediated through excitatory amino acid receptors. Phencyclidine had no effect on the changes in GABA produced by IBO. The effect of phencyclidine treatment on IBO behavioural toxicity observed in this study demonstrates that antagonism of the phencyclidine receptor site on the N-methyl-D-aspartate receptor complex may be partially protective against the excitotoxic damage induced by IBO.

  2. Pentachlorophenol (PCP) degradation microorganism community structure under microaeration condition

    Institute of Scientific and Technical Information of China (English)

    Chen Yuancai; Hao Yuan; Fu Shiyu; Zhan Huaiyu


    The comparison of pentachlorophenol (PCP)degradation was conducted under micro-aeration and anaerobic condition with three series of batch experiment,results of which indicated that during micro-aeration condition co-immobilized of anaerobic granular sludge and isolated aerobic bacterial species could enhance the efficiency of PCP reduction through the synergism of aerobes and anaerobes reductive dechlorination and exchange of metabolites within the co-immobilized granular sludge.While during anaerobic condition,there was no great difference in the three series.The specific activities experiment further confirmed that strict anaerobes were not affected over the presence of micro aeration environment.Microorganism community construction of co-immobilized anaerobic granular sludge and the mixed isolated aerobic community was also deduced.By the efficient cooperation of aerobes and anaerobes,the high efficiency removal rate of PCP was implemented.

  3. Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Bundgaard, Christoffer; Fejgin, Kim;


    treatment, pyramidal neurons displayed a reduced mIPSC frequency and up-regulation of extrasynaptic THIP-induced current. ADX47273 treatment restored this up-regulation of THIP-induced current. Reduced receptor function seems to be the underlying cause of the reported changes, since repeated treatment...

  4. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice. (United States)

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves


    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

  5. Adaptive response of trivial activated sludge towards toxic effect of oNP, PCP and combination oNP/PCP

    Energy Technology Data Exchange (ETDEWEB)

    Topalova, Y.; Dimkov, R. (Sofia Univ. (Bulgaria). Faculty of Biology); Kozuharov, D. (Bulgarian Academy of Science, Sofia (Bulgaria))


    The reaction of the real aerobic activated sludge taken from the Sofia Waste Water Treatment Plant (SWWTP) and treated with the xenobiotics pentachlorphenol (PCP) (0.16 mMol), ortho-nitrophenol (oNP) (0.58 mMol) and with a combination of PCP (0.08 mMol), oNP (0.29 mMol) has been investigated in a model detoxification process. The adaptive changes are studied in the microbial structure level and at the level of changes in the qualitative and quantitative parameters of the macro-organisms in the activated sludge (consuments of 1 and 2 level). The presence of several different taxonomic groups has been shown by other researchers to be essential in the detoxification process. The quantitative changes in these taxonomic and physiological groups of micro-organisms are studied. The number of micro-organisms from Pseudomonas, Acinetobacter and the bacteria from the xenobiotic-catabolizing complex considerably increased with the individual and the combined effect of the xenobiotics oNP, PCP and oNP PCP. At the same time the toxic shock leads to a remarkable reduction of NH[sub 3] releasing, nitrifying bacteria and those from family Enterobacteriaceae. It is ascertained that the number of Ciliata, Flagellata apochromata, Oligochaeta and Rotatoria is strongly decreased in the series of samples treated with xenobiotics. The leading role of micro-organisms in the real detoxification of hazardous pollutants was experimentally confirmed by research.

  6. Hippocampal serotonin depletion unmasks differences in the hyperlocomotor effects of phencyclidine and MK-801: quantitative versus qualitative analyses

    Directory of Open Access Journals (Sweden)

    Wendy K Adams


    Full Text Available Antagonism of N-methyl-D-aspartate (NMDA receptors by phencyclidine is thought to underlie its ability to induce a schizophrenia-like syndrome in humans, yet evidence indicates it has a broader pharmacological profile. Our previous lesion studies highlighted a role for serotonergic projections from the median, but not dorsal, raphe nucleus in mediating the hyperlocomotor effects of phencyclidine, without changing the action of the more selective NMDA receptor antagonist, MK-801. Here we compared locomotor responses to phencyclidine and MK 801 in rats that were administered 5,7 dihydroxytryptamine (5,7-DHT into either the dorsal or ventral hippocampus, which are preferentially innervated by median and dorsal raphe, respectively. Dorsal hippocampus lesions potentiated phencyclidine-induced hyperlocomotion (0.5, 2.5 mg/kg, but not the effect of MK-801 (0.1 mg/kg. Ventral hippocampus lesions did not alter the hyperlocomotion elicited by either compound. Given that phencyclidine and MK-801 may induce different spatiotemporal patterns of locomotor behavior, together with the known role of the dorsal hippocampus in spatial processing, we also assessed whether the 5,7-DHT-lesions caused any qualitative differences in locomotor responses. Treatment with phencyclidine or MK-801 increased the smoothness of the path travelled (reduced spatial d and decreased the predictability of locomotor patterns within the chambers (increased entropy. 5,7-DHT-lesions of the dorsal hippocampus did not alter the effects of phencyclidine on spatial d or entropy—despite potentiating total distance moved—but caused a slight reduction in levels of MK-801-induced entropy. Taken together, serotonergic lesions targeting the dorsal hippocampus unmask a functional differentiation of the hyperlocomotor effects of phencyclidine and MK 801. These findings have implications for studies utilising NMDA receptor antagonists in modeling glutamatergic dysfunction in schizophrenia.

  7. Health risk assessment of pentachlorophenol (pcp) in California drinking water. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Reed, N.R.; Reed, W.A.; Encomienda, I.; Beltran, L.; Araba-Owoyele, L.


    The purpose of the document is to review the toxicology of PCP and to estimate the exposure of California residents to PCP found in drinking water. The information provided will help the California Dept. of Health Services develop drinking water standards for PCP.

  8. Constraining PCP Violating Varying Alpha Theory through Laboratory Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Maity, Debaprasad; /NCTS, Taipei /Taiwan, Natl. Taiwan U.; Chen, Pisin; /NCTS, Taipei /Taiwan, Natl. Taiwan U. /KIPAC, Menlo Park /SLAC


    In this report we have studied the implication of a parity and charge-parity (PCP) violating interaction in varying alpha theory. Due to this interaction, the state of photon polarization can change when it passes through a strong background magnetic field. We have calculated the optical rotation and ellipticity of the plane of polarization of an electromagnetic wave and tested our results against different laboratory experiments. Our model contains a PCP violating parameter {beta} and a scale of alpha variation {omega}. By analyzing the laboratory experimental data, we found the most stringent constraints on our model parameters to be 1 {le} {omega} {le} 10{sup 13} GeV{sup 2} and -0.5 {le} {beta} {le} 0.5. We also found that with the existing experimental input parameters it is very difficult to detect the ellipticity in the near future.

  9. Response of compost maturity and microbial community composition to pentachlorophenol (PCP)-contaminated soil during composting. (United States)

    Zeng, Guangming; Yu, Zhen; Chen, Yaoning; Zhang, Jiachao; Li, Hui; Yu, Man; Zhao, Mingjie


    Two composting piles were prepared by adding to a mixture of rice straw, vegetables and bran: (i) raw soil free from pentachlorophenol (PCP) contamination (pile A) and (ii) PCP-contaminated soil (pile B). It was shown by the results that compost maturity characterized by water soluble carbon (WSC), TOC/TN ratio, germination index (GI) and dehydrogenase activity (DA) was significantly affected by PCP exposure, which resulted in an inferior degree of maturity for pile B. DGGE analysis revealed an inhibited effect of PCP on compost microbial abundance. The bacteria community shifts were mainly consistent with composting factors such as temperature, pH, moisture content and substrates. By contrast, the fungal communities were more sensitive to PCP contamination due to the significant correlation between fungal community shifts and PCP removal. Therefore, the different microbial community compositions for properly evaluating the degree of maturity and PCP contamination were suggested.

  10. Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway. (United States)

    Wang, Jianbo; Mark, Sharayne; Zhang, Xiaohui; Qian, Dong; Yoo, Seung-Jong; Radde-Gallwitz, Kristen; Zhang, Yanping; Lin, Xi; Collazo, Andres; Wynshaw-Boris, Anthony; Chen, Ping


    The mammalian auditory sensory organ, the organ of Corti, consists of sensory hair cells with uniformly oriented stereocilia on the apical surfaces and has a distinct planar cell polarity (PCP) parallel to the sensory epithelium. It is not certain how this polarity is achieved during differentiation. Here we show that the organ of Corti is formed from a thicker and shorter postmitotic primordium through unidirectional extension, characteristic of cellular intercalation known as convergent extension. Mutations in the PCP pathway interfere with this extension, resulting a shorter and wider cochlea as well as misorientation of stereocilia. Furthermore, parallel to the homologous pathway in Drosophila melanogaster, a mammalian PCP component Dishevelled2 shows PCP-dependent polarized subcellular localization across the organ of Corti. Taken together, these data suggest that there is a conserved molecular mechanism for PCP pathways in invertebrates and vertebrates and indicate that the mammalian PCP pathway might directly couple cellular intercalations to PCP establishment in the cochlea.

  11. Imaging the PCP site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail:


    The N-methyl-D-aspartate (NMDA) ion channel plays a role in neuroprotection, neurodegeneration, long-term potentiation, memory, and cognition. It is implicated in the pathophysiology of several neurological and neuropsychiatric disorders including Parkinson's Disease, Huntington's Chorea, schizophrenia, alcoholism and stroke. The development of effective radiotracers for the study of NMDA receptors is critical for our understanding of their function, and their modulation by endogenousr substances or therapeutic drugs. Since the NMDA/PCP receptor lies within the channel, it is a unique target and is theoretically accessible only when the channel is in the active and 'open' state, but not when it is in the inactive or 'closed' state. The physical location of the NMDA/PCP receptor not only makes it an important imaging target but also complicates the development of suitable PET and SPECT radiotracers for this site. An intimate understanding of the biochemical, pharmacological, physiological and behavioral processes associated with the NMDA ion channel is essential to develop improved imaging agents. This review outlines progress made towards the development of radiolabeled agents for PCP sites of the NMDA ion channel. In addition, the animal and pharmacological models used for in vitro and in vivo assessment of NMDA receptor targeted agents are discussed.

  12. Bioremediation of PCP by Trichoderma and Cunninghamella Strains Isolated from Sawdust

    Directory of Open Access Journals (Sweden)

    Ngieng Ngui Sing


    Full Text Available Four fungal isolates, SD12, SD14, SD19 and SD20 isolated from the aged sawdust grew on agar plates supplemented with PCP up to a concentration of 100 mg L-1. At high PCP concentration, isolate SD12 showed the highest radial growth rate of 10 mm day-1, followed by SD14 and SD19 both with 4.5 mm day-1 and SD20 with 4.2 mm day-1. Ultrastructural study on the effect of PCP on the PCP tolerant fungi using scanning electron microscope showed that high concentration of PCP caused the collapse of both fungal hyphae and spores. Among the four PCP tolerant fungi examined, isolate SD12 showed the least structural damage at high PCP concentration of 100 mg L-1. This fungal isolate was further characterized and identified as Cunninghamella sp. UMAS SD12. Preliminary PCP biodegradation trial performed in liquid minimal medium supplemented with 20 mg L-1 of PCP using Cunninghamella sp. UMAS SD12 showed that the degradation up to 51.7% of PCP in 15 days under static growth condition.

  13. Appetite for danger - genetic potential for PCP degradation at historically polluted groundwater sites (United States)

    Mikkonen, Anu; Yläranta, Kati; Tiirola, Marja; Romantschuk, Martin; Sinkkonen, Aki


    Pentachlorophenol (PCP) is a priority pollutant of exclusively anthropogenic origin. Formerly used commonly in timber preservatives, PCP has persisted at polluted groundwater sites decades after its use was banned, typically as the last detectable contaminant component. Notorious for its toxicity and poor biodegradability, little is known about the genetic potential and pathways for PCP degradation in the environment. The only fully characterized mineralization pathway is initiated by the enzyme coded by chromosomal pcpB gene, previously detected in PCP degrading Sphingomonadaceae bacteria isolated at two continents. However, there is no information about the abundance or diversity of any PCP degradation related gene at contaminated sites in situ. Our aim was to assess whether pcpB and/or sphingomonads seem to play a role in in situ degradation of PCP, by studying whether pcpB i) is detectable at chlorophenol-polluted groundwater sediments, ii) responds to PCP concentration changes, and iii) shows correlation with the abundance of sphingomonads or a specific sphingomonad genus. Novel protocols for quantification and profiling of pcpB, with primers covering full known diversity, were developed and tested at two sites in Finland with well-documented long-term chlorophenol contamination history: Kärkölä and Pursiala. High throughput sequencing complemented characterization of the total bacterial community and pcpB gene pool. The relative abundance of pcpB in bacterial community was associated with spatial variability in groundwater PCP concentration in Pursiala, and with temporal differences in groundwater PCP concentration in Kärkölä. T-RFLP fingerprinting results indicated and Ion Torrent PGM and Sanger sequencing confirmed the presence of a single phylotype of pcpB at both geographically distant, historically contaminated sites, matching the one detected previously in Canadian bioreactor clones and Kärkölä bioreactor isolates. Sphingomonad abundance

  14. Polyphasic characterization of a PCP-to-phenol dechlorinating microbial community enriched from paddy soil

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Naoko [EcoTopia Science Institute, Nagoya University Nagoya 464-8603 (Japan)]. E-mail:; Yoshida, Yukina [Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Handa, Yuko [Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Kim, Hyo-Keun [Korea Ginseng and Tobacco Research Institute, Taejon 305-345 (Korea, Republic of); Ichihara, Shigeyuki [Faculty of Agriculture, Meijo University, Nagoya 468-8502 (Japan); Katayama, Arata [EcoTopia Science Institute, Nagoya University Nagoya 464-8603 (Japan); Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan)


    Dechlorination of PCP has been observed previously under anaerobic condition in paddy soil. However, there is poor information about the dechlorination pathway of PCP and the microbial community associated with the PCP dechlorination in paddy soil. In this study, an anaerobic microbial community dechlorinating PCP was enriched by serial transfers from a paddy soil using a medium containing PCP, lactate and the steam-sterilized paddy soil. The enriched microbial community dechlorinated PCP completely to phenol under the anaerobic condition by a dechlorinating pathway as follows; PCP {sup {yields}} 2,3,4,5-tetrachlorophenol {sup {yields}} 3,4,5-trichlorophenol {sup {yields}} 3,5-dichlorophenol {sup {yields}} 3-chlorophenol {sup {yields}} phenol. Intermediate products such as 3-chlorophenol were not accumulated, which were immediately dechlorinated to phenol. The enriched microbial community was characterized physiologically by testing the effects of electron donors and electron acceptors on the dechlorinating activity. The dechlorinating activity was promoted with lactate, pyruvate, and hydrogen as electron donors but not with acetate. Electron acceptors, nitrate and sulphate, inhibited the dechlorinating activity competitively but not iron (III). The microbial group associated with the anaerobic dechlorination was characterized by the effect of specific inhibitors on the PCP dechlorination. Effects of specific metabolic inhibitors and antibiotics indicated the involvement of Gram-positive spore-forming bacteria with the PCP dechlorinating activity, which was represented as bacteria of phylum Firmicutes. The structure of the microbial community was characterized by fluorescence in situ hybridization, quinone profiling, and PCR-DGGE (denaturing gel gradient electrophoresis). The combined results indicated the predominance of Clostridium species of phylum Firmicutes in the microbial community. Desulfitobacterium spp. known as anaerobic Gram-positive spore

  15. Assessment of the ability of sludge to degrade PCP under anaerobic conditions

    Directory of Open Access Journals (Sweden)

    R. M. L. Bolaños


    Full Text Available The capacity of sludge from different sources to degrade pentachlorophenol (PCP was evaluated. Three 2.5 liter reactors (R1, R2, and R3 were inoculated with different anaerobic sludges, semi continuously fed and maintained in orbital motion at 30±1°C. R1 was inoculated with aerobic sludge and river sediment collected downstream from a pulp and paper plant. R2 received sludge from an anaerobic reactor treating effluents from a paper recycling plant and R3 received anaerobic sludge from a biodigestor treating industrial and domestic effluents. The sludges were first acclimatized to a culture medium generally recommended for organochloride anaerobic degradation studies. The reactors were then subjected to increasing concentrations of PCP from 0.05 to 10.0 mg.l-1. PCP degradation and metabolite formation were monitored using gas chromatography, and the effects of PCP on the anaerobic process were verified by monitoring pH, volatile fatty acids, alkalinity, total suspended solids, and chemical oxygen demand. It was found that PCP did not affect reactor performance. All the sludges displayed the best PCP degradation capacity at a concentration of 0.2 mg.l-1, producing fewer chlorinated metabolites than when higher PCP concentrations were applied. R1 consistently produced fewer chlorinated metabolites, confirming the hypothesis that pre exposure to chlorinated compounds improves the sludge's capacity to degrade PCP.

  16. The gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia

    DEFF Research Database (Denmark)

    Jørgensen, Bettina Merete Pyndt; Redrobe, Paul; Brønnum Pedersen, Tina

    The gut microbiota has major impact on the individual. Here we show that the gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gut microbiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...

  17. Roles of noncanonical Wnt/PCP pathway genes in neuronal migration and neurulation in zebrafish. (United States)

    Wada, Hironori; Okamoto, Hitoshi


    Noncanonical Wnt/planar cell polarity (PCP) pathways regulate oriented cell movement during development in both Drosophila and vertebrates. Recent studies have revealed similarities and differences between these pathways in the tissues on which they act. In zebrafish, PCP pathway genes regulate the directional migration of a specific population of motor neurons in the hindbrain, as well as morphogenesis of the neuroepithelium. In the present review, neuronal and neuroepithelial defects in zebrafish PCP pathway mutants are compared, and the possible cellular and molecular mechanisms underlying these phenotypes are discussed. Future analyses of zebrafish PCP mutants will reveal the general mechanisms underlying the development of the neuroepithelium and provide novel insights into both conserved and diverse functions of PCP pathway genes in vertebrate development.

  18. Massive venlafaxine overdose resulted in a false positive Abbott AxSYM (R) urine immunoassay for phencyclidine

    NARCIS (Netherlands)

    Bond, GR; Steele, PE; Uges, DRA


    Case report: A 13-yr-old girl overdosed on 48 x 150 mg venlafaxine (Effexor XR(R)). She was taking venlafaxine regularly for depression. Her only other medications included topical Benzamycin and pyridoxine 50 mg daily for acne. The Abbott AxSYM(R) assay was positive only for phencyclidine, but GC/M

  19. Acute phencyclidine administration induces c-Fos-immunoreactivity in interneurons in cortical and subcortical regions

    DEFF Research Database (Denmark)

    Hervig, Mona E.; Thomsen, Morten S; Kalló, Imre;


    ) field of hippocampus and mediodorsal thalamus (MD); (2) PV-IR cells in the ventrolateral orbitofrontal and retrosplenial cortices and CA1 field of hippocampus; and (3) CB-IR cells in the motor cortex. Overall, our data indicate that PCP activates a wide range of cortical and subcortical brain regions...

  20. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP? (United States)


    ... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... results involving marijuana, cocaine, amphetamines, or PCP? (a) As the MRO, you must verify a confirmed positive test result for marijuana, cocaine, amphetamines, and/or PCP unless the employee presents...

  1. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking. (United States)

    Gault, William J; Olguin, Patricio; Weber, Ursula; Mlodzik, Marek


    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes.

  2. The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling.

    Directory of Open Access Journals (Sweden)

    Alessia Soldano

    Full Text Available Wnt Planar Cell Polarity (PCP signaling is a universal regulator of polarity in epithelial cells, but it regulates axon outgrowth in neurons, suggesting the existence of axonal modulators of Wnt-PCP activity. The Amyloid precursor proteins (APPs are intensely investigated because of their link to Alzheimer's disease (AD. APP's in vivo function in the brain and the mechanisms underlying it remain unclear and controversial. Drosophila possesses a single APP homologue called APP Like, or APPL. APPL is expressed in all neurons throughout development, but has no established function in neuronal development. We therefore investigated the role of Drosophila APPL during brain development. We find that APPL is involved in the development of the Mushroom Body αβ neurons and, in particular, is required cell-autonomously for the β-axons and non-cell autonomously for the α-axons growth. Moreover, we find that APPL is a modulator of the Wnt-PCP pathway required for axonal outgrowth, but not cell polarity. Molecularly, both human APP and fly APPL form complexes with PCP receptors, thus suggesting that APPs are part of the membrane protein complex upstream of PCP signaling. Moreover, we show that APPL regulates PCP pathway activation by modulating the phosphorylation of the Wnt adaptor protein Dishevelled (Dsh by Abelson kinase (Abl. Taken together our data suggest that APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth.

  3. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. (United States)

    Wang, Jianbo; Hamblet, Natasha S; Mark, Sharayne; Dickinson, Mary E; Brinkman, Brendan C; Segil, Neil; Fraser, Scott E; Chen, Ping; Wallingford, John B; Wynshaw-Boris, Anthony


    The planar cell polarity (PCP) pathway is conserved throughout evolution, but it mediates distinct developmental processes. In Drosophila, members of the PCP pathway localize in a polarized fashion to specify the cellular polarity within the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In Xenopus and zebrafish, several homologs of the components of the fly PCP pathway control convergent extension. We have shown previously that mammalian PCP homologs regulate both cell polarity and polarized extension in the cochlea in the mouse. Here we show, using mice with null mutations in two mammalian Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous mammalian PCP pathway regulates concomitant lengthening and narrowing of the neural plate, a morphogenetic process defined as convergent extension. Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial chromosome) transgenes and introducing different domain deletions and a point mutation identical to the dsh1 allele in fly, we further demonstrated a high degree of conservation between Dvl function in mammalian convergent extension and the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows DEP domain-dependent membrane localization, a pre-requisite for its involvement in convergent extension. Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea. These results are discussed in light of recent models on PCP and convergent extension.

  4. The PCP pathway regulates Baz planar distribution in epithelial cells (United States)

    Aigouy, Benoit; Le Bivic, André


    The localisation of apico-basal polarity proteins along the Z-axis of epithelial cells is well understood while their distribution in the plane of the epithelium is poorly characterised. Here we provide a systematic description of the planar localisation of apico-basal polarity proteins in the Drosophila ommatidial epithelium. We show that the adherens junction proteins Shotgun and Armadillo, as well as the baso-lateral complexes, are bilateral, i.e. present on both sides of cell interfaces. In contrast, we report that other key adherens junction proteins, Bazooka and the myosin regulatory light chain (Spaghetti squash) are unilateral, i.e. present on one side of cell interfaces. Furthermore, we demonstrate that planar cell polarity (PCP) and not the apical determinants Crumbs and Par-6 control Bazooka unilaterality in cone cells. Altogether, our work unravels an unexpected organisation and combination of apico-basal, cytoskeletal and planar polarity proteins that is different on either side of cell-cell interfaces and unique for the different contacts of the same cell. PMID:27624969

  5. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. (United States)

    Luga, Valbona; Zhang, Liang; Viloria-Petit, Alicia M; Ogunjimi, Abiodun A; Inanlou, Mohammad R; Chiu, Elaine; Buchanan, Marguerite; Hosein, Abdel Nasser; Basik, Mark; Wrana, Jeffrey L


    Stroma in the tumor microenvironment plays a critical role in cancer progression, but how it promotes metastasis is poorly understood. Exosomes are small vesicles secreted by many cell types and enable a potent mode of intercellular communication. Here, we report that fibroblast-secreted exosomes promote breast cancer cell (BCC) protrusive activity and motility via Wnt-planar cell polarity (PCP) signaling. We show that exosome-stimulated BCC protrusions display mutually exclusive localization of the core PCP complexes, Fzd-Dvl and Vangl-Pk. In orthotopic mouse models of breast cancer, coinjection of BCCs with fibroblasts dramatically enhances metastasis that is dependent on PCP signaling in BCCs and the exosome component, Cd81 in fibroblasts. Moreover, we demonstrate that trafficking in BCCs promotes tethering of autocrine Wnt11 to fibroblast-derived exosomes. This work reveals an intercellular communication pathway whereby fibroblast exosomes mobilize autocrine Wnt-PCP signaling to drive BCC invasive behavior.

  6. Combover/CG10732, a novel PCP effector for Drosophila wing hair formation.

    Directory of Open Access Journals (Sweden)

    Jeremy K Fagan

    Full Text Available The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP, the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh and Rho Kinase (Rok are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC, similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh.

  7. Identifying Drugs (United States)

    ... Oxycodone PCP (Phencyclidine) Peyote and Mescaline Psilocybin Rohypnol Salvia Divinorum Spice/ K2, Synthetic Marijuana Steroids U-47700 Flakka ( ... Oxycodone PCP (Phencyclidine) Peyote and Mescaline Psilocybin Rohypnol Salvia Divinorum Spice/ K2, Synthetic Marijuana Steroids U-47700 Aerosol ...

  8. Synthesis of PCP-supported nickel complexes and their reactivity with carbon dioxide. (United States)

    Schmeier, Timothy J; Nova, Ainara; Hazari, Nilay; Maseras, Feliu


    The Ni amide and hydroxide complexes [(PCP)Ni(NH(2))] (2; PCP=bis-2,6-di-tert-butylphosphinomethylbenzene) and [(PCP)Ni(OH)] (3) were prepared by treatment of [(PCP)NiCl] (1) with NaNH(2) or NaOH, respectively. The conditions for the formation of 3 from 1 and NaOH were harsh (2 weeks in THF at reflux) and a more facile synthetic route involved protonation of 2 with H(2)O, to generate 3 and ammonia. Similarly the basic amide in 2 was protonated with a variety of other weak acids to form the complexes [(PCP)Ni(2-Me-imidazole)] (4), [(PCP)Ni(dimethylmalonate)] (5), [(PCP)Ni(oxazole)] (6), and [(PCP)Ni(CCPh)] (7), respectively. The hydroxide compound 3, could also be used as a Ni precursor and treatment of 3 with TMSCN (TMS=trimethylsilyl) or TMSN(3) generated [(PCP)Ni(CN)] (8) or [(PCP)Ni(N(3))] (9), respectively. Compounds 3-7, and 9 were characterized by X-ray crystallography. Although 3, 4, 6, 7, and 9 are all four-coordinate complexes with a square-planar geometry around Ni, 5 is a pseudo-five-coordinate complex, with the dimethylmalonate ligand coordinated in an X-type fashion through one oxygen atom, and weakly as an L-type ligand through another oxygen atom. Complexes 2-9 were all reacted with carbon dioxide. Compounds 2-4 underwent facile reaction at low temperature to form the κ(1)-O carboxylate products [(PCP)Ni{OC(O)NH(2)}] (10), [(PCP)Ni{OC(O)OH}] (11), and [(PCP)Ni{OC(O)-2-Me-imidazole}] (12), respectively. Compounds 10 and 11 were characterized by X-ray crystallography. No reaction was observed between 5-9 and carbon dioxide, even at elevated temperatures. DFT calculations were performed to model the thermodynamics for the insertion of carbon dioxide into 2-9 to form a κ(1)-O carboxylate product and understand the pathways for carbon dioxide insertion into 2, 3, 6, and 7. The computed free energies indicate that carbon dioxide insertion into 2 and 3 is thermodynamically favorable, insertion into 8 and 9 is significantly uphill, insertion into 5 and 7

  9. Application of LPME/GC-ECD for determination of PCP in water

    Institute of Scientific and Technical Information of China (English)

    李萍; 刘俊新


    Liquid-phase microextraction (LPME) followed by gas chromatography (GC) coupled with an electron capture detector (ECD) was applied for the analysis of pentachlorophenol (PCP) in aqueous samples. After alkalization with Na2CO3 solution, PCP was acetylated with acetic anhydride. The pentachlorophenyl acetate derivative was then extracted with n-hexane by LPME. 1.5 μL organic drop exposed to the aqueous sample solution at 15℃ for 5 min, stirring rate at 100 r/min was chosen as the optimum extraction condition. Under this condition, LPME provided a very simple, fast and solvent-less procedure to collect PCP from aqueous sample for GC determination. The linearity of LPME/GC-ECD for PCP in distilled water was investigated at the range of 2-200 μg/L with a coefficient of correlation 0.998. The repeatability of this method was determined at the level of 50 μg/L with the average of relative standard deviations (RSDs) 7%. Detection limit was obtained at less than 0.5 μg/L levels. When LPME/GC-ECD was applied to the determination of PCP in municipal sewage, the average of relative recoveries and RSDs were 70% and 6.5%, respectively.

  10. Anti-apoptotic Effects of PCP4/PEP19 in Human Breast Cancer Cell Lines: A Novel Oncotarget


    HAMADA, Taiji; Souda, Masakazu; Yoshimura, Takuya; Sasaguri, Shoko; Hatanaka, Kazuhito; Tasaki, Takashi; Yoshioka, Takako; Ohi, Yasuyo; Yamada, Sohsuke; Tsutsui, Masato; Umekita, Yoshihisa; TANIMOTO, Akihide


    The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines...

  11. Accelerated Mineralization of Pentachlorophenol in Soil upon Inoculation with Mycobacterium chlorophenolicum PCP1 and Sphingomonas chlorophenolica RA2


    Miethling, R.; Karlson, U.


    Mineralization of pentachlorophenol (PCP) was studied in nonsterile soil from a PCP-contaminated site upon inoculation with two PCP-degrading bacterial strains. At spiked [(sup14)C]PCP concentrations of 30 and 100 mg/kg, the effects of organism type, different inoculation techniques, including structural amendment with sawdust and cell attachment to polyurethane (PU), as well as the effect of different inoculum sizes of 10(sup4) to 10(sup8) cells per g (dry weight) of soil were compared with ...

  12. The emerging role of Wnt/PCP signaling in organ formation. (United States)

    Dale, Rodney M; Sisson, Barbara E; Topczewski, Jacek


    Over the last two decades zebrafish has been an excellent model organism to study vertebrate development. Mutant analysis combined with gene knockdown and other manipulations revealed an essential role of Wnt signaling, independent of beta-catenin, during development. Especially well characterized is the function of Wnt/planar cell polarity (PCP) signaling in the regulation of gastrulation movements and neurulation, described in other reviews within this special issue. Here, we set out to highlight some of the new and exciting research that is being carried out in zebrafish to elucidate the role that Wnt/PCP signaling plays in the formation of specific organs, including the lateral line, craniofacial development, and regeneration. We also summarized the emerging connection of the Wnt/PCP pathway with primary cilia function, an essential organelle in several organ activities.

  13. Accelerated Mineralization of Pentachlorophenol in Soil upon Inoculation with Mycobacterium chlorophenolicum PCP1 and Sphingomonas chlorophenolica RA2. (United States)

    Miethling, R; Karlson, U


    Mineralization of pentachlorophenol (PCP) was studied in nonsterile soil from a PCP-contaminated site upon inoculation with two PCP-degrading bacterial strains. At spiked [(sup14)C]PCP concentrations of 30 and 100 mg/kg, the effects of organism type, different inoculation techniques, including structural amendment with sawdust and cell attachment to polyurethane (PU), as well as the effect of different inoculum sizes of 10(sup4) to 10(sup8) cells per g (dry weight) of soil were compared with PCP mineralization by indigenous bacteria. Gas chromatographic analysis was used to monitor PCP disappearance and to check mass balances. The survival and activity of the released bacteria were examined by immunofluorescence microscopy and respiking experiments. Noninoculated soil completely mineralized 30 mg of PCP per kg within 7 months but showed no or only low degradation activity at 100 mg/kg in the same period. Structural amendment with PU or sawdust initiated slow mineralization after half a year. Soil inoculation with Sphingomonas chlorophenolica RA2 shortened the mineralization time drastically to 1 month at 30 mg of PCP per kg using 10(sup8) cells per g, with approximately 80% of the added radioactivity being converted to CO(inf2). The inoculated cells disappeared rapidly, with a count of 2 x 10(sup6) cells per g after 2.3 months and nondetectability after 7 months. At 100 mg/kg, mineralization was slower because of PCP toxicity but approached completion within 7.5 months. The inhibition could be overcome by addition of sawdust (1 g/kg of soil), resulting in a mineralization rate of 3 to 4 mg/kg(middot)d. PU had the opposite effect. Lower inoculum densities resulted in prolonged lag phases and lower rates, although mineralization was still enhanced over the background level. At 30 mg of PCP per kg, inoculation with Mycobacterium chlorophenolicum PCP1 increased mineralization slightly over the indigenous bacterial activity, regardless of inoculum size, but only when

  14. The role of P2X7 receptors in a rodent PCP-induced schizophrenia model


    Bence Koványi; Cecilia Csölle; Stefano Calovi; Adrienn Hanuska; Erzsébet Kató; László Köles; Anindya Bhattacharya; József Haller; Beáta Sperlágh


    P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the soc...

  15. The gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia

    DEFF Research Database (Denmark)

    Pyndt, Bettina Merete; Redrobe, Paul; Brønnum Pedersen, Tina;

    The gut microbiota has major impact on the individual. Here we show that the gut microbiota influence behavior in the subchronic PCP induced animal model of schizophrenia. The gut microbiota were changed in the group treated subchronic with PCP, and restoration coincided with normalisation...... of memory performance in lister hooded rats. Furthermore the individual gut microbiota correlated to the individual behavior abserved in the tests conducted. In conclusion results show an influence of the gut microbiota on behavior in this model, and therefore it might be relavant to include the information...

  16. Anti-apoptotic effects of PCP4/PEP19 in human breast cancer cell lines: a novel oncotarget. (United States)

    Hamada, Taiji; Souda, Masakazu; Yoshimura, Takuya; Sasaguri, Shoko; Hatanaka, Kazuhito; Tasaki, Takashi; Yoshioka, Takako; Ohi, Yasuyo; Yamada, Sohsuke; Tsutsui, Masato; Umekita, Yoshihisa; Tanimoto, Akihide


    The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-Akt(Thr308), enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-Akt(Thr308) and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression.

  17. A PCP-Pincer RuII-Terpyridine Building Block as a Potential "Antenna Unit" for Intramolecular Sensitization

    NARCIS (Netherlands)

    Gagliardo, M.; Rizzo, F.; Lutz, M.; Spek, A.L.; van Klink, G.P.M.; Merbach, A.E.; De Cola, L.; van Koten, G.


    The redox- and photoactive mononuclear complex [Ru(PCP)(tpy-DTTANa4)]Cl {PCP = [C6H3(CH2PPh2)2-2,6]-; tpy-DTTA4- = 4'-(2,2':6',2''-terpyridine)-diethylenetriamine-N,N,N",N"-tetraacetate} possesses an externally directed, vacant N3O4 polyaminocarboxylate-type binding site that coordinates to lanthani

  18. Dissecting the PCP pathway: one or more pathways?: Does a separate Wnt-Fz-Rho pathway drive morphogenesis? (United States)

    Lapébie, Pascal; Borchiellini, Carole; Houliston, Evelyn


    Planar cell polarity (PCP), the alignment of cells within 2D tissue planes, involves a set of core molecular regulators highly conserved between animals and cell types. These include the transmembrane proteins Frizzled (Fz) and VanGogh and the cytoplasmic regulators Dishevelled (Dsh) and Prickle. It is widely accepted that this core forms part of a 'PCP pathway' for signal transduction, which can affect cell morphology through activation of an evolutionary ancient regulatory module involving Rho family GTPases and Myosin II, and/or the JNK kinase cascade. We have re-examined the evidence for interactions between the proposed PCP pathway components, and question the placing of the cell morphology regulators in the same pathway as the PCP core. While Fz and Dsh are clearly involved in both PCP and Rho-based cell morphology regulation, available evidence cannot currently discriminate whether these processes are linked mechanistically by a shared Fz/Dsh population, or pass by two distinct pathways.

  19. IFT88 plays a cilia- and PCP-independent role in controlling oriented cell divisions during vertebrate embryonic development. (United States)

    Borovina, Antonia; Ciruna, Brian


    The role for cilia in establishing planar cell polarity (PCP) is contentious. Although knockdown of genes known to function in ciliogenesis has been reported to cause PCP-related morphogenesis defects in zebrafish, genetic mutations affecting intraflagellar transport (IFT) do not show PCP phenotypes despite the requirement for IFT in cilia formation. This discrepancy has been attributed to off-target effects of antisense morpholino oligonucleotide (MO) injection, confounding maternal effects in zygotic mutant embryos, or an inability to distinguish between cilia-dependent versus cilia-independent protein functions. To determine the role of cilia in PCP, we generated maternal + zygotic IFT88 (MZift88) mutant zebrafish embryos, which never form cilia. We clearly demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Our results have important implications for the interpretation of cilia gene function in normal development and in disease.

  20. 非典型钙粘蛋白Celsr1-3在神经系统发育和PCP中的功能%Role of atypical cadherins Celsr1-3 in neural development and PCP

    Institute of Scientific and Technical Information of China (English)

    曲宜波; 周立兵


    Celsrl-3 (for Cadherin EGF laminin seven pass receptor), the mammalian orthologs of Drosophila Flamingo/starry night, encode proteins of the cadherin superfamily. Celsrl-3 belong to a group named ' core PCP ( planar cell polarity) genes'. All three Celsr genes are expressed in the developing central nervous system (CNS) in mice. Here, we summari2e some work on Celsrl-3 in PCP and neural development. Celsrl is a major player in vertebrate PCP and it plays important roles in classic PCP events. Celsr2 and Celsr3 regulate ciliogenesis and are involved in ependymal cilia development probably via PCP signaling. Celsrl-3 differentially regulate FBM neuron migration. Celsrl helps to specify the direction of facial branchiomotor(FBM) neuron migration, whereas Celsr2 and 3 control its ability to migrate. More evidence has accumulated for crucial and" different roles of Celsrl-3 in PCP and brain development and maintenance.%Celsr1-3(Cadherin EGF Laninin Seven Pass Receptor 1-3)是果蝇Flamingo/starry night的哺乳动物同源基因,其编码属于钙粘蛋白家族的非典型钙粘蛋白.Celsr1-3是“核心平面细胞极性(PCP)基因”组的成员.3个Cekr基因在小鼠中枢神经系统发育过程中都有表达.总结有关Celsr1-3在神经系统发育和PCP中的工作.Celsr1是在脊椎动物PCP的主要参与者,在许多典型PCP事件中发挥着重要作用.Celsr2和Celsr3可调节纤毛生成,并很可能是通过PCP信号参与调控脑室管膜纤毛发生.Celsr1-3在FBM神经元迁移过程中扮演着不同的重要角色.Celsr1决定FBM神经元迁移的方向,而Celsr2和3则控制其迁移能力.越来越多的证据证明Celsr1-3在神经系统的发育、维持以及PCP中发挥着多种不同的重要作用.

  1. Changes in dopamine D2 and GluR-1 glutamate receptor mRNAs in the rat brain after treatment with phencyclidine.

    Directory of Open Access Journals (Sweden)



    Full Text Available In situ hybridization of slide-mounted brain sections from rats subjected to acute and chronic phencyclidine treatment was carried out using synthetic oligonucleotides complementary to dopamine D2-receptor and non-N-methyl-D-aspartate (NMDA glutamate-receptor-subunit (GluR-1 mRNAs. There was no significant difference in either the D2-receptor or the GluR-1 mRNA levels in any brain region of the acute phencyclidine (10 mg/kg-treated and control groups. However, chronic administration of phencyclidine (10 mg/kg/day, 14 days significantly decreased the dopamine D2-receptor mRNA level in the caudate-putamen (by 27%, P < 0.01 and significantly increased the GluR-1 mRNA level in the prefrontal cortex (by 29%, P < 0.001. These results suggest that the chronic pharmaco-behavioral effects of phencyclidine may involve expression of both dopamine- and non-NMDA glutamate-receptor mRNAs.

  2. Receptor site topographies for phencyclidine-like and sigma drugs: predictions from quantitative conformational, electrostatic potential, and radioreceptor analyses. (United States)

    Manallack, D T; Wong, M G; Costa, M; Andrews, P R; Beart, P M


    Computer-assisted molecular modelling techniques and electrostatic analyses of a wide range of phenycyclidine (PCP) and sigma ligands, in conjunction with radioreceptor studies, were used to determine the topographies of the PCP and sigma receptors. The PCP receptor model was defined using key molecules from the arylcyclohexylamine, benzomorphan, bridged benz[f]isoquinoline, and dibenzocycloalkenimine drug classes. Hypothetical receptor points (R1, R2) were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor, along with an additional receptor point (R3) representing a hydrogen bond between the nitrogen atom and the receptor. The superimposition of these key molecules gave the coordinates of the receptor points and nitrogen defining the primary PCP pharmacophore as follows: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (6.66, -1.13, 0.00), and N (3.90, -1.46, -0.32). Additional analyses were used to describe secondary binding sites for an additional hydrogen bonding site and two lipophilic clefts. Similarly, the sigma receptor model was constructed from ligands of the benzomorphan, octahydrobenzo[f]quinoline, phenylpiperidine, and diphenylguanidine drug classes. Coordinates for the primary sigma pharmacophore are as follows: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (6.09, 2.09, 0.00), and N (4.9, -0.12, -1.25). Secondary binding sites for sigma ligands were proposed for the interaction of aromatic ring substituents and large N-substituted lipophilic groups with the receptor. The sigma receptor model differs from the PCP model in the position of nitrogen atom, direction of the nitrogen lone pair vector, and secondary sigma binding sites. This study has thus demonstrated that the differing quantitative structure-activity relationships of PCP and sigma ligands allow the definition of discrete receptors. These models may be used in conjunction with rational drug design techniques to design novel PCP

  3. a7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D


    (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  4. α7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D


    (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  5. PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration.

    Directory of Open Access Journals (Sweden)

    Crystal F Davey


    Full Text Available The planar cell polarity (PCP pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP "core components" (Vangl, Fz, Pk, Dsh, and Celsr are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia.

  6. Cultivation and characters of aerobic granules for pentachlorophenol (PCP) degradation under microaerobic condition

    Institute of Scientific and Technical Information of China (English)

    LAN Hui-xia; CHEN Yuan-cai; CHEN Zhong-hao; CHEN Rong


    Cultivation of aerobic granular sludge for pentachlorophenol (PCP) degradation under microaerobic condition ( DO concentration was controlled at 0.2-0.7 mg/L) was studied in this paper. Anaerobic granules were selected as inoculum. The changes of appearance were observed and the variations of SVI, VSS/TSS, PN/PS and the size of sludge were measured during cultivating. The capabilities for degradation of PCP, AOX and CODcr were also studied. Observations on mature granules were carried out by scanning electron microscope, and the results indicated bacillus was dominant on the surface of granules while in the inner of granules both bacillus and coccus were the dominant microorganisms. K, Na, Fe, Ca, Mg, Ni, Co, Mn, Cu and Zn were detected in the granules by element analysis.

  7. Simplifying complex sequence information: a PCP-consensus protein binds antibodies against all four Dengue serotypes. (United States)

    Bowen, David M; Lewis, Jessica A; Lu, Wenzhe; Schein, Catherine H


    Designing proteins that reflect the natural variability of a pathogen is essential for developing novel vaccines and drugs. Flaviviruses, including Dengue (DENV) and West Nile (WNV), evolve rapidly and can "escape" neutralizing monoclonal antibodies by mutation. Designing antigens that represent many distinct strains is important for DENV, where infection with a strain from one of the four serotypes may lead to severe hemorrhagic disease on subsequent infection with a strain from another serotype. Here, a DENV physicochemical property (PCP)-consensus sequence was derived from 671 unique sequences from the Flavitrack database. PCP-consensus proteins for domain 3 of the envelope protein (EdomIII) were expressed from synthetic genes in Escherichia coli. The ability of the purified consensus proteins to bind polyclonal antibodies generated in response to infection with strains from each of the four DENV serotypes was determined. The initial consensus protein bound antibodies from DENV-1-3 in ELISA and Western blot assays. This sequence was altered in 3 steps to incorporate regions of maximum variability, identified as significant changes in the PCPs, characteristic of DENV-4 strains. The final protein was recognized by antibodies against all four serotypes. Two amino acids essential for efficient binding to all DENV antibodies are part of a discontinuous epitope previously defined for a neutralizing monoclonal antibody. The PCP-consensus method can significantly reduce the number of experiments required to define a multivalent antigen, which is particularly important when dealing with pathogens that must be tested at higher biosafety levels.

  8. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    Energy Technology Data Exchange (ETDEWEB)

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd [Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg (Germany); Schaefer, Tobias, E-mail: [Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg (Germany)


    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  9. Automation of the social interaction test by a video-tracking system: behavioural effects of repeated phencyclidine treatment. (United States)

    Sams-Dodd, F


    The social interaction test is a valuable behavioural model for testing anxiolytic and neuroleptic drugs. The test quantifies the level of social behaviour between pairs of rats and it is usually based on manual analysis of behaviour. Advances in computer technology have made it possible to track the movements of pairs of rats in an arena, and the present paper describes the automation of the social interaction test by the commercial video-tracking programme, the EthoVision system. The ability of the automated system to correctly measure the social behaviour of rats is demonstrated by determining a dose-response relationship in the social interaction test for phencyclidine, a psychotomimetic drug that reduces social behaviour between pairs of rats. These data are subsequently analysed by the manual and automated data-acquisition methods and the results are compared. The study shows that the automated data-acquisition method best describes the behavioural effects of phencyclidine in the social interaction test by the locomotor activity of the rats, how much time the rats spend in different sections of the testing arena, and the level of social behaviour. Correlation analysis of the results from the manual and automated data-acquisition methods shows that the social behaviour measured by the automated system corresponds correctly to the social behaviour measured by the manual analysis. The present study has shown that the automated data-acquisition method can quantify locomotor activity, how rats use a testing arena and the level of social behaviour between rats in the social interaction test. The system cannot distinguish between social and aggressive behaviours, and therefore the rats should be tested in an unfamiliar arena to reduce territorial behaviour. Taking this limitation into consideration, the social interaction test can be automated by this computer-based video-tracking system and can be used as a routine test for quantifying the effects of drugs on the

  10. Characterization of pPCP1 Plasmids in Yersinia pestis Strains Isolated from the Former Soviet Union

    Directory of Open Access Journals (Sweden)

    Chythanya Rajanna


    Full Text Available Complete sequences of 9.5-kb pPCP1 plasmids in three Yersinia pestis strains from the former Soviet Union (FSU were determined and compared with those of pPCP1 plasmids in three well-characterized, non-FSU Y. pestis strains (KIM, CO92, and 91001. Two of the FSU plasmids were from strains C2614 and C2944, isolated from plague foci in Russia, and one plasmid was from strain C790 from Kyrgyzstan. Sequence analyses identified four sequence types among the six plasmids. The pPCP1 plasmids in the FSU strains were most genetically related to the pPCP1 plasmid in the KIM strain and least related to the pPCP1 plasmid in Y. pestis 91001. The FSU strains generally had larger pPCP1 plasmid copy numbers compared to strain CO92. Expression of the plasmid's pla gene was significantly (P≤.05 higher in strain C2944 than in strain CO92. Given pla's role in Y. pestis virulence, this difference may have important implications for the strain's virulence.

  11. Opposite effect of phencyclidine on activity-regulated cytoskeleton-associated protein (Arc) in juvenile and adult limbic rat brain regions

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D


    animals. However, schizophrenia is believed to develop in part due to neurodevelopmental dysfunction during adolescence. Therefore, the effects of PCP in juvenile animals may better reflect the pathophysiology of schizophrenia. Here, we compare the effect of PCP (5mg/kg/day for 5 days) on activity......-regulated cytoskeleton-associated protein (Arc) and parvalbumin mRNA expression in juvenile and adult rats. Arc is a marker for excitatory neurotransmission. Parvalbumin is a marker for GABAergic neurotransmission, known to be reduced in postmortem brains of schizophrenics. PCP reduced parvalbumin mRNA expression...

  12. Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP (United States)

    Wang, Ying; Naturale, Victor F.; Adler, Paul N.


    The Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled. PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild overexpression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (inPD). We found that mild overexpression of Fritz partially rescued inPD, indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritzmNeonGreen provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains (“puncta”). Surprisingly, we found it in stripes in developing bristles. PMID:28258110

  13. Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia (PCP.

    Directory of Open Access Journals (Sweden)

    Julie R Harris

    Full Text Available BACKGROUND: Diagnosis of Pneumocystis jirovecii pneumonia (PCP is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. METHODS AND FINDINGS: We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients. Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained compared with several molecular diagnostic options. CONCLUSIONS: For diagnosis of PCP, use of PCR technologies, when

  14. Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila

    Directory of Open Access Journals (Sweden)

    Lindsay K. Kelly


    Full Text Available Epithelial tissues are polarized along two axes. In addition to apical-basal polarity, they are often polarized within the plane of the epithelium, so-called Planar Cell Polarity (PCP. PCP depends upon Wnt/Frizzled (Fz signaling factors, including Fz itself and Van Gogh (Vang/Vangl. We sought to understand how Vang interaction with other core PCP factors affects Vang function. We find that Fz induces Vang phosphorylation in a cell-autonomous manner. Vang phosphorylation occurs on conserved N-terminal serine/threonine residues, is mediated by CK1ε/Dco, and is critical for polarized membrane localization of Vang and other PCP proteins. This regulatory mechanism does not require Fz signaling through Dishevelled and thus represents a cell-autonomous upstream interaction between Fz and Vang. Furthermore, this signaling event appears to be related to Wnt5a-mediated Vangl2 phosphorylation during mouse limb patterning and may thus be a general mechanism underlying Wnt-regulated PCP establishment.

  15. IFT88 Plays a Cilia- and PCP-Independent Role in Controlling Oriented Cell Divisions during Vertebrate Embryonic Development

    Directory of Open Access Journals (Sweden)

    Antonia Borovina


    Full Text Available The role for cilia in establishing planar cell polarity (PCP is contentious. Although knockdown of genes known to function in ciliogenesis has been reported to cause PCP-related morphogenesis defects in zebrafish, genetic mutations affecting intraflagellar transport (IFT do not show PCP phenotypes despite the requirement for IFT in cilia formation. This discrepancy has been attributed to off-target effects of antisense morpholino oligonucleotide (MO injection, confounding maternal effects in zygotic mutant embryos, or an inability to distinguish between cilia-dependent versus cilia-independent protein functions. To determine the role of cilia in PCP, we generated maternal + zygotic IFT88 (MZift88 mutant zebrafish embryos, which never form cilia. We clearly demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Our results have important implications for the interpretation of cilia gene function in normal development and in disease.

  16. A Systematic Review and Meta-Analysis of the Data Behind Current Recommendations for Corticosteroids in Non–HIV-Related PCP: Knowing When You Are on Shaky Foundations (United States)

    Injean, Patil; Eells, Samantha J.; Wu, Hoover; McElroy, Imani; Gregson, Aric L.; McKinnell, James A.


    Background Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related Pneumocystis jiroveci pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic review and meta-analysis characterizing adjunctive corticosteroids for NH-PCP. Methods We searched MEDLINE from 1966 through 2015. Data on clinical outcomes from NH-PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I2 index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. Results Our search yielded 5044 abstracts, 277 articles were chosen for full review, and 6 articles described outcomes in moderate to severe NH-PCP. Studies were limited by variable definitions, treatment selection bias, concomitant infections and small sample size. Individual studies reported shorter intensive care unit stay and duration of mechanical ventilation of patients given adjunctive corticosteroids. There was no association between corticosteroids and survival in NH-PCP (odds ratio, 0.66; 95% confidence interval, 0.38-1.15; P = 0.14). Conclusions The literature does not support an association between adjunctive corticosteroids and survival from NH-PCP but data are limited and findings should not be considered conclusive. Further research with improved methodology is needed to better understand the role of adjunctive corticosteroids for NH-PCP. PMID:28361121

  17. CAFET algorithm reveals Wnt/PCP signature in lung squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Yue Hu

    Full Text Available We analyzed the gene expression patterns of 138 Non-Small Cell Lung Cancer (NSCLC samples and developed a new algorithm called Coverage Analysis with Fisher's Exact Test (CAFET to identify molecular pathways that are differentially activated in squamous cell carcinoma (SCC and adenocarcinoma (AC subtypes. Analysis of the lung cancer samples demonstrated hierarchical clustering according to the histological subtype and revealed a strong enrichment for the Wnt signaling pathway components in the cluster consisting predominantly of SCC samples. The specific gene expression pattern observed correlated with enhanced activation of the Wnt Planar Cell Polarity (PCP pathway and inhibition of the canonical Wnt signaling branch. Further real time RT-PCR follow-up with additional primary tumor samples and lung cancer cell lines confirmed enrichment of Wnt/PCP pathway associated genes in the SCC subtype. Dysregulation of the canonical Wnt pathway, characterized by increased levels of β-catenin and epigenetic silencing of negative regulators, has been reported in adenocarcinoma of the lung. Our results suggest that SCC and AC utilize different branches of the Wnt pathway during oncogenesis.

  18. Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors. (United States)

    Waks, Adrienne G; Tolaney, Sara M; Galar, Alicia; Arnaout, Amal; Porter, Julie B; Marty, Francisco M; Winer, Eric P; Hammond, Sarah P; Baden, Lindsey R


    Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been recognized as a significant complication of early-stage breast cancer treatment. However, we have observed an increase in PCP incidence among patients receiving chemotherapy for early-stage breast cancer. Herein we identify risk factors for and calculate incidence of PCP in this population. We identified all cases of PCP at Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH) from 1/1/2000 to 12/31/2013 in patients with stage I-III breast cancer treated with an adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non-metastatic breast cancer patients were identified. All patients with PCP were diagnosed after receipt of either three or four cycles of AC chemotherapy on a dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg prednisone equivalents/day as nausea prophylaxis for a median 64 days. The overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3-1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC. There was one death from PCP. Women receiving dose-dense AC chemotherapy for early-stage breast cancer are at risk for PCP. Administering the same chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense schedule appears to have created a novel infectious vulnerability. Replacing dexamethasone with alternative anti-emetics may mitigate this risk.

  19. Kinetics and thermodynamics of small molecule binding to pincer-PCP rhodium(I) complexes

    KAUST Repository

    Doherty, Mark D.


    The kinetics and thermodynamics of the binding of several small molecules, L (L = N2, H2, D2, and C2H 4), to the coordinatively unsaturated pincer-PCP rhodium(I) complexes Rh[tBu2PCH2(C6H3)CH 2PtBu2] (1) and Rh[tBu 2P(CH2)2(CH)(CH2)2P tBu2] (2) in organic solvents (n-heptane, toluene, THF, and cyclohexane-d12) have been investigated by a combination of kinetic flash photolysis methods, NMR equilibrium studies, and density functional theory (DFT) calculations. Using various gas mixtures and monitoring by NMR until equilibrium was established, the relative free energies of binding of N2, H2, and C2H4 in cyclohexane-d12 were found to increase in the order C 2H4 < N2 < H2. Time-resolved infrared (TRIR) and UV-vis transient absorption spectroscopy revealed that 355 nm excitation of 1-L and 2-L results in the photoejection of ligand L. The subsequent mechanism of binding of L to 1 and 2 to regenerate 1-L and 2-L is determined by the structure of the PCP ligand framework and the nature of the solvent. In both cases, the primary transient is a long-lived, unsolvated species (τ = 50-800 ns, depending on L and its concentration in solution). For 2, this so-called less-reactive form (LRF) is in equilibrium with a more-reactive form (MRF), which reacts with L at diffusion-controlled rates to regenerate 2-L. These two intermediates are proposed to be different conformers of the three-coordinate (PCP)Rh fragment. For 1, a similar mechanism is proposed to occur, but the LRF to MRF step is irreversible. In addition, a parallel reaction pathway was observed that involves the direct reaction of the LRF of 1 with L, with second-order rate constants that vary by almost 3 orders of magnitude, depending on the nature of L (in n-heptane, k = 6.7 × 10 5 M-1 s-1 for L = C2H4; 4.0 × 106 M-1 s-1 for L = N2; 5.5 × 108 M-1 s-1 for L = H2). Experiments in the more coordinating solvent, THF, revealed the binding of THF to 1 to generate 1-THF, and its subsequent reaction with L, as a

  20. Involvement of β3A Subunit of Adaptor Protein-3 in Intracellular Trafficking of Receptor-like Protein Tyrosine Phosphatase PCP-2

    Institute of Scientific and Technical Information of China (English)

    Hui DONG; Hong YUAN; Weirong JIN; Yan SHEN; Xiaojing XU; Hongyang WANG


    PCP-2 is a human receptor-like protein tyrosine phosphatase and a member of the MAM domain family cloned in human pancreatic adenocarcinoma cells. Previous studies showed that PCP-2 directly interacted with β-catenin through the juxtamembrane domain, dephosphorylated β-catenin and played an important role in the regulation of cell adhesion. Recent study showed that PCP-2 was also involved in the repression of β-catenin-induced transcriptional activity. Here we describe the interactions of PCP-2 with the β3A subunit of adaptor protein (AP)-3 and sorting nexin (SNX) 3. These protein complexes were detected using the yeast two-hybrid assay with the juxtamembrane and membrane-proximal catalytic domain of PCP-2 as "bait". Both AP-3 and SNX3 are molecules involved in intracellular trafficking of membrane receptors. The association between the β3A subunit of AP-3 and PCP-2 was further confirmed in mammalian cells. Our results suggested a possible mechanism of intracellular trafficking of PCP-2 mediated by AP-3 and SNX3 which might participate in the regulation of PCP-2 functions.

  1. Complete DNA sequence and gene analysis of the virulence plasmid pCP301 of Shigella flexneri 2a

    Institute of Scientific and Technical Information of China (English)

    张继瑜; 刘红; 张笑兵; 杨剑; 杨帆; 杨国威; 沈岩; 侯云德; 金奇


    The complete nucleotide sequence and organization of the large virulence plasmid pCP301 (termed by us) of Shigella flexneri 2a strain 301 were determined and analyzed. The result showed that the entire DNA sequence of pCP301 is composed of 221618 bp which form a circular plasmid. Sequence analysis identified 272 open reading frames (ORFs), among which, 194 correspond to the proteins described previously, 61 have low identity (<60%) to known proteins and the rest 17 have no regions of significant homology with proteins in database. The genes of pCP301 mainly include the genes associated with bacterial virulence, the genes associated with regulation and the genes relating to plasmid maintenance, stability and DNA metabolism. Insertion sequence (IS) elements are 68 kb in length and account for 30 percent of complete sequence of the plasmid which indicates that gene multiple rearrangements of the pCP301 have taken place in Shigella flexneri evolution history. The research result is helpful for interpreting the pathogenesis of Shigella, as well as the genetics and evolution of the plasmid.

  2. A density functional theory for vapor-liquid interfaces using the PCP-SAFT equation of state

    NARCIS (Netherlands)

    Gross, J.


    A Helmholtz energy functional for inhomogeneous fluid phases based on the perturbed-chain polar statistical associating fluid theory (PCP-SAFT) equation of state is proposed. The model is supplemented with a capillary wave contribution to the surface tension to account for long-wavelength fluctuatio


    This case study describes the development of solidification/stabilization (S/S) formulas and their application to rededicate the American Creosote site in Jackson, Tennessee. During 1998 and 1999, 45,000 cubic yards of soil contaminated with Creosote, PCP, and Dioxins were treat...

  4. The effect of rhizosphere on growth of Sphingomonas chlorophenolica ATCC 39723 during pentachlorophenol (PCP biodegradation in batch culture and soil

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    Ken Killhan


    Full Text Available Studies on the influence of the rhizosphere on the growth of Sphingomonas chlorophenolica during Pentacholophenol (PCP degradation in batch culture and in soil were carried out. In batch culture, a basal minimal medium with or without rhizosphere exudates extracted from winter wheat was used. In soil systems, degradation experiments were performed in the presence and absence of plants. Measurements of PCP concentrations were made using high performance liquid chromatography analysis (HPLC. Bacterial analyses of S. chlorophenolica were carried out by plating on MSM medium. The results showed that the rhizosphere exudates stimulated the growth of the cells of S. chlorophenolica at concentrations of 50 and 80mg kg dry wt soil –1 as well as stimulating the ability of S. chlorophenolica to degrade PCP at a concentration of 80mg Kg dry wt soil -1. In addition, pentachlorophenol had an adverse effect on the growth of S. chlorophenolica. The introduction of S.chlorophenolica into the loamy soil with plants showed a faster degradation when compared to the inoculated soil without plants. There was a significant increase of S. chlorophenolica in the roots in comparison to those in the soil. This study showed that the presence of the inoculum S. chlorophenolica enhanced the PCP degradation in a loamy soil and it indicates the potential for a treatment process under a appropriate environmental conditions such as there present in soil systems.

  5. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

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    Cheng Cui


    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin


    Directory of Open Access Journals (Sweden)

    Hessy Novita


    Full Text Available Penanggulangan penyakit ikan dapat dilakukan dengan cara meningkatkan kekebalan tubuh ikan melalui program vaksinasi. Namun vaksinasi tidak tepat untuk udang, karena udang tidak mempunyai immunological memory seperti ikan. Oleh karena itu, perlindungan udang terhadap serangan penyakit viral dengan menggunakan RNA interference (RNAi. Teknologi RNAi digunakan untuk menghalangi (interfere proses replikasi infectious myonecrosis virus (IMNV pada udang vaname dengan cara menon-aktifkan gen putative cleavage protein 1 (PCP-1, yang berfungsi dalam pembentukan capsid dan proses transkripsi RNA IMNV. Penelitian ini bertujuan untuk melakukan kloning gen putative cleavage protein 1 dalam rangka perakitan teknologi RNAi untuk pengendalian penyakit IMNV pada udang vaname. Tahapan penelitian meliputi koleksi sampel, isolasi RNA, sintesis cDNA, amplifikasi PCR, purifikasi DNA, transformasi, isolasi plasmid, serta sekuensing dan analisis data. Hasil isolasi plasmid cDNA PCP-1 memperlihatkan semua koloni bakteri terseleksi ternyata membawa plasmid hasil insersi DNA gen PCP–1, hasil sekuen dengan nilai homologinya mencapai 100% dan 99% yang dibandingkan dengan sekuen di Genebank. Hasil penelitian menunjukkan bahwa kloning gen putative cleavage protein 1 (PCP-1 dari udang vaname yang terserang Infectious Myonecrosis Virus berhasil dikloning yang nantinya digunakan untuk perakitan RNAi. The prevention of fish diseases can be done by increasing of the fish immune through vaccination programs. However, the vaccination can not be done for the shrimp,due to the absence of  immunological memory. Therefore, the protection of shrimp against viral diseases was done by using of RNA interference (RNAi. RNAi technology is used to interfere infectious myonecrosis virus (IMNV replication process on white shrimp by disabling of putative cleavage protein 1 (PCP-1gene, which functions in capsid formation and RNA transcription process. The study was conducted to perform putative

  7. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye (United States)

    López-Escobar, Beatriz; Cano, David A.; Rojas, Anabel; de Felipe, Beatriz; Palma, Francisco; Sánchez-Alcázar, José A.; Henderson, Deborah; Ybot-González, Patricia


    Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos. PMID:25540130

  8. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

    Directory of Open Access Journals (Sweden)

    Beatriz López-Escobar


    Full Text Available Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1 and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.

  9. Identification and quantitation of amphetamines, cocaine, opiates, and phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry. (United States)

    Fritch, Dean; Blum, Kristen; Nonnemacher, Sheena; Haggerty, Brenda J; Sullivan, Matthew P; Cone, Edward J


    Analytical methods for measuring multiple licit and illicit drugs and metabolites in oral fluid require high sensitivity, specificity, and accuracy. With the limited volume available for testing, comprehensive methodology is needed for simultaneous measurement of multiple analytes in a single aliquot. This report describes the validation of a semi-automated method for the simultaneous extraction, identification, and quantitation of 21 analytes in a single oral fluid aliquot. The target compounds included are amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4-methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine, codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone, oxymorphone, and phencyclidine. Oral fluid specimens were collected with the Intercept device and extracted by solid-phase extraction (SPE). Drug recovery from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged 91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography-tandem mass spectrometry in the positive electrospray mode using ratios of qualifying product ions within +/-25% of calibration standards. Matrix ion suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5 ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was demonstrated by testing oral fluid specimens from drug abuse treatment patients. Thirty-nine patients tested positive for various combinations of licit and illicit drugs and metabolites. In conclusion, this validated method is suitable for simultaneous measurement of 21 licit and illicit drugs and metabolites in oral fluid.

  10. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites. (United States)


    ... cutoff levels. Otherwise, the following cutoff levels must be used for initial testing of urine specimens... Cocaine metabolites 300 Opiate metabolites 2000 Phencyclidine (PCP) 25 Amphetamines 1000...

  11. Opposite effect of phencyclidine on activity-regulated cytoskeleton-associated protein (Arc) in juvenile and adult limbic rat brain regions

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D


    in the medial prefrontal cortex (mPFC), ventrolateral orbitofrontal cortex (VLO) and shell of the nucleus accumbens (ACCshell) in both juvenile and adult rats. Contrarily, PCP produced opposite effects on Arc mRNA expression in the mPFC, VLO and ACCshell, leading to decreased expression in juvenile...

  12. Photocatalytic degradation of PCP-Na with TiO2 photocatalysis loaded with platinum

    Institute of Scientific and Technical Information of China (English)


    Titanium dioxide(TiO2 ) samples of different crystal forms were prepared by hydrolysis tetrabutyl titanate in various water to alkoxide ratios and sintering the hydrolysis product at different temperatures.The photocatalysts coated on hollow glass beads and loaded with platinum varying from 0.2% to 2.4% by weight.The photecatalytic degradation rate of sodium pentachlorophenolate (PCP- Na) depends on the preparing conditions such as.:sintering temperatures,water to alkoxide ratios(R),platinum content and the size.The proper conditions of preparation photoeatalysts are as follows:the ratio of TiO2:sodium silicate :hollow glass beads :platinum is 10:5:20:0.15(w/w),R is 100,sintering temperature is 650℃,and the size of hollow glass is 0.5 - 1 mm.Under these conditions,the ratio between aeatase and rutile of the photocatalyst is 2:1,and the photocatalytie activity is high.

  13. Mitotic Spindle Asymmetry: A Wnt/PCP-Regulated Mechanism Generating Asymmetrical Division in Cortical Precursors

    Directory of Open Access Journals (Sweden)

    Delphine Delaunay


    Full Text Available The regulation of asymmetric cell division (ACD during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis. Imaging of spindle behavior and division outcome reveals that neurons preferentially arise from the larger-spindle pole. Mechanistically, SSA magnitude is controlled by Wnt7a and Vangl2, both members of the Wnt/planar cell polarity (PCP-signaling pathway, and relayed to the cell cortex by P-ERM proteins. In vivo, Vangl2 and P-ERM downregulation promotes early cell-cycle exit and prevents the proper generation of late-born neurons. Thus, SSA is a core component of ACD that is conserved in invertebrates and vertebrates and plays a key role in the tight spatiotemporal control of self-renewal and differentiation during mammalian corticogenesis.

  14. Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B. (United States)

    Wang, Bing; Sinha, Tanvi; Jiao, Kai; Serra, Rosa; Wang, Jianbo


    Brachydactyly type B (BDB1) and Robinow syndrome (RRS) are two skeletal disorders caused by mutations in ROR2, a co-receptor of Wnt5a. Wnt5a/Ror2 can activate multiple branches of non-canonical Wnt signaling, but it is unclear which branch(es) mediates Wnt5a/Ror2 function in limb skeletal development. Here, we provide evidence implicating the planar cell polarity (PCP) pathway as the downstream component of Wnt5a in the limb. We show that a mutation in the mouse PCP gene Vangl2 causes digit defects resembling the clinical phenotypes in BDB1, including loss of phalanges. Halving the dosage of Wnt5a in Vangl2 mutants enhances the severity and penetrance of the digit defects and causes long bone defects reminiscent of RRS, suggesting that Wnt5a and Vangl2 function in the same pathway and disruption of PCP signaling may underlie both BDB1 and RRS. Consistent with a role for PCP signaling in tissue morphogenesis, mutation of Vangl2 alters the shape and dimensions of early limb buds: the width and thickness are increased, whereas the length is decreased. The digit pre-chondrogenic condensates also become wider, thicker and shorter. Interestingly, altered limb bud dimensions in Vangl2 mutants also affect limb growth by perturbing the signaling network that regulates the balance between Fgf and Bmp signaling. Halving the dosage of Bmp4 partially suppresses the loss of phalanges in Vangl2 mutants, supporting the hypothesis that an aberrant increase in Bmp signaling is the cause of the brachydactyly defect. These findings provide novel insight into the signaling mechanisms of Wnt5a/Ror2 and the pathogenesis in BDB1 and RRS.

  15. Wnt activity guides facial branchiomotor neuron migration, and involves the PCP pathway and JNK and ROCK kinases

    Directory of Open Access Journals (Sweden)

    Kelley Matthew


    Full Text Available Abstract Background Wnt proteins play roles in many biological processes, including axon guidance and cell migration. In the mammalian hindbrain, facial branchiomotor (FBM neurons undergo a striking rostral to caudal migration, yet little is known of the underlying molecular mechanisms. In this study, we investigated a possible role of Wnts and the planar cell polarity (PCP pathway in this process. Results Here we demonstrate a novel role for Wnt proteins in guiding FBM neurons during their rostral to caudal migration in the hindbrain. We found that Wnt5a is expressed in a caudalhigh to rostrallow gradient in the hindbrain. Wnt-coated beads chemoattracted FBM neurons to ectopic positions in an explant migration assay. The rostrocaudal FBM migration was moderately perturbed in Wnt5a mutant embryos and severely disrupted in Frizzled3 mutant mouse embryos, and was aberrant following inhibition of Wnt function by secreted Frizzled-related proteins. We also show the involvement of the Wnt/PCP pathway in mammalian FBM neuron migration. Thus, mutations in two PCP genes, Vangl2 and Scribble, caused severe defects in FBM migration. Inhibition of JNK and ROCK kinases strongly and specifically reduced the FBM migration, as well as blocked the chemoattractant effects of ectopic Wnt proteins. Conclusion These results provide in vivo evidence that Wnts chemoattract mammalian FBM neurons and that Wnt5a is a candidate to mediate this process. Molecules of the PCP pathway and the JNK and ROCK kinases also play a role in the FBM migration and are likely mediators of Wnt signalling.

  16. PLD1 regulates Xenopus convergent extension movements by mediating Frizzled7 endocytosis for Wnt/PCP signal activation. (United States)

    Lee, Hyeyoon; Lee, Seung Joon; Kim, Gun-Hwa; Yeo, Inchul; Han, Jin-Kwan


    Phospholipase D (PLD) is involved in the regulation of receptor-associated signaling, cell movement, cell adhesion and endocytosis. However, its physiological role in vertebrate development remains poorly understood. In this study, we show that PLD1 is required for the convergent extension (CE) movements during Xenopus gastrulation by activating Wnt/PCP signaling. Xenopus PLD1 protein is specifically enriched in the dorsal region of Xenopus gastrula embryo and loss or gain-of-function of PLD1 induce defects in gastrulation and CE movements. These defective phenotypes are due to impaired regulation of Wnt/PCP signaling pathway. Biochemical and imaging analysis using Xenopus tissues reveal that PLD1 is required for Fz7 receptor endocytosis upon Wnt11 stimulation. Moreover, we show that Fz7 endocytosis depends on dynamin and regulation of GAP activity of dynamin by PLD1 via its PX domain is crucial for this process. Taken together, our results suggest that PLD1 acts as a new positive mediator of Wnt/PCP signaling by promoting Wnt11-induced Fz7 endocytosis for precise regulation of Xenopus CE movements.

  17. The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway. (United States)

    Martinez, Sébastien; Scerbo, Pierluigi; Giordano, Marilyn; Daulat, Avais M; Lhoumeau, Anne-Catherine; Thomé, Virginie; Kodjabachian, Laurent; Borg, Jean-Paul


    The non-canonical WNT/planar cell polarity (WNT/PCP) pathway plays important roles in morphogenetic processes in vertebrates. Among WNT/PCP components, protein tyrosine kinase 7 (PTK7) is a tyrosine kinase receptor with poorly defined functions lacking catalytic activity. Here we show that PTK7 associates with receptor tyrosine kinase-like orphan receptor 2 (ROR2) to form a heterodimeric complex in mammalian cells. We demonstrate that PTK7 and ROR2 physically and functionally interact with the non-canonical WNT5A ligand, leading to JNK activation and cell movements. In the Xenopus embryo, Ptk7 functionally interacts with Ror2 to regulate protocadherin papc expression and morphogenesis. Furthermore, we show that Ptk7 is required for papc activation induced by Wnt5a. Interestingly, we find that Wnt5a stimulates the release of the tagged Ptk7 intracellular domain, which can translocate into the nucleus and activate papc expression. This study reveals novel molecular mechanisms of action of PTK7 in non-canonical WNT/PCP signaling that may promote cell and tissue movements.

  18. Synthesis, Structure, and Reactivity of Co(II) and Ni(II) PCP Pincer Borohydride Complexes (United States)


    The 15e square-planar complexes [Co(PCPMe-iPr)Cl] (2a) and [Co(PCP-tBu)Cl] (2b), respectively, react readily with NaBH4 to afford complexes [Co(PCPMe-iPr)(η2-BH4)] (4a) and [Co(PCP-tBu)(η2-BH4)] (4b) in high yields, as confirmed by IR spectroscopy, X-ray crystallography, and elemental analysis. The borohydride ligand is symmetrically bound to the cobalt center in η2-fashion. These compounds are paramagnetic with effective magnetic moments of 2.0(1) and 2.1(1) μB consistent with a d7 low-spin system corresponding to one unpaired electron. None of these complexes reacted with CO2 to give formate complexes. For structural and reactivity comparisons, we prepared the analogous Ni(II) borohydride complex [Ni(PCPMe-iPr)(η2-BH4)] (5) via two different synthetic routes. One utilizes [Ni(PCPMe-iPr)Cl] (3) and NaBH4, the second one makes use of the hydride complex [Ni(PCPMe-iPr)H] (6) and BH3·THF. In both cases, 5 is obtained in high yields. In contrast to 4a and 4b, the borohydride ligand is asymmetrically bound to the nickel center but still in an η2-mode. [Ni(PCPMe-iPr)(η2-BH4)] (5) loses readily BH3 at elevated temperatures in the presence of NEt3 to form 6. Complexes 5 and 6 are both diamagnetic and were characterized by a combination of 1H, 13C{1H}, and 31P{1H} NMR, IR spectroscopy, and elemental analysis. Additionally, the structure of these compounds was established by X-ray crystallography. Complexes 5 and 6 react with CO2 to give the formate complex [Ni(PCPMe-iPr)(OC(C=O)H] (7). The extrusion of BH3 from [Co(PCPMe-iPr)(η2-BH4)] (4a) and [Ni(PCPMe-iPr)(η2-BH4)] (5) with the aid of NH3 to yield the respective hydride complexes [Co(PCPMe-iPr)H] and [Ni(PCPMe-iPr)H] (6) and BH3NH3 was investigated by DFT calculations showing that formation of the Ni hydride is thermodynamically favorable, whereas the formation of the Co(II) hydride, in agreement with the experiment, is unfavorable. The electronic structures and the bonding of the borohydride ligand in [Co

  19. Differential responses to Wnt and PCP disruption predict expression and developmental function of conserved and novel genes in a cnidarian.

    Directory of Open Access Journals (Sweden)

    Pascal Lapébie


    Full Text Available We have used Digital Gene Expression analysis to identify, without bilaterian bias, regulators of cnidarian embryonic patterning. Transcriptome comparison between un-manipulated Clytia early gastrula embryos and ones in which the key polarity regulator Wnt3 was inhibited using morpholino antisense oligonucleotides (Wnt3-MO identified a set of significantly over and under-expressed transcripts. These code for candidate Wnt signaling modulators, orthologs of other transcription factors, secreted and transmembrane proteins known as developmental regulators in bilaterian models or previously uncharacterized, and also many cnidarian-restricted proteins. Comparisons between embryos injected with morpholinos targeting Wnt3 and its receptor Fz1 defined four transcript classes showing remarkable correlation with spatiotemporal expression profiles. Class 1 and 3 transcripts tended to show sustained expression at "oral" and "aboral" poles respectively of the developing planula larva, class 2 transcripts in cells ingressing into the endodermal region during gastrulation, while class 4 gene expression was repressed at the early gastrula stage. The preferential effect of Fz1-MO on expression of class 2 and 4 transcripts can be attributed to Planar Cell Polarity (PCP disruption, since it was closely matched by morpholino knockdown of the specific PCP protein Strabismus. We conclude that endoderm and post gastrula-specific gene expression is particularly sensitive to PCP disruption while Wnt-/β-catenin signaling dominates gene regulation along the oral-aboral axis. Phenotype analysis using morpholinos targeting a subset of transcripts indicated developmental roles consistent with expression profiles for both conserved and cnidarian-restricted genes. Overall our unbiased screen allowed systematic identification of regionally expressed genes and provided functional support for a shared eumetazoan developmental regulatory gene set with both predicted and

  20. Long-term changes in brain following continuous phencyclidine administration: An autoradiographic study using flunitrazepam, ketanserin, mazindol, quinuclidinyl benzilate, piperidyl-3,4-{sup 3}H(N)-TCP, and AMPA receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Ellison, Gaylord; Keys, Alan; Noguchi, Kevin [Univ. of California Los Angeles, Dept. of Psychology, Los Angeles, CA (United States)


    Phencyclidine induces a model psychosis which can persist for prolonged periods and presents a strong drug model of schizophrenia. When given continuously for several days to rats, phencyclidine and other N-methyl-D-aspartate (NMDA) antagonists induce neural degeneration in a variety of limbic structures, including retrosplenial cortex, hippocampus, septohippocampal projections, and piriform cortex. In an attempt to further clarify the mechanisms underlying these degeneration patterns, autoradiographic studies using a variety of receptor ligands were conducted in animals 21 days after an identical dosage of the continuous phencyclidine administration employed in the previous degeneration studies. The results indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-{sup 3}H(N)-TCP (TCP), flunitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously. Quinuclidinyl benzilate and (AMPA) binding were decreased in anterior cingulate and piriform cortex, and in accumbens and striatum. Piperidyl-3,4-{sup 3}H(N)-TCP binding was decreased in most hippocampal regions. Many of these long-term alterations would not have been predicted by prior studies of the neurotoxic effects of continuous phencyclidine, and these results do not suggest a unitary source for the neurotoxicity. Whereas retrosplenial cortex, the structure which degenerates earliest, showed minimal alterations, some of the most consistent, long term alterations were in structures which evidence no immediate signs of neural degeneration, such as anterior cingulate cortex and caudate nucleus. In these structures, some of the receptor changes appeared to develop gradually (they were not present immediately after cessation of drug administration), and thus were perhaps due to changed input from regions evidencing neurotoxicity. Some of these findings, particularly in anterior cingulate, may have implications for models of

  1. The primary care provider (PCP)-cancer specialist relationship: A systematic review and mixed-methods meta-synthesis. (United States)

    Dossett, Lesly A; Hudson, Janella N; Morris, Arden M; Lee, M Catherine; Roetzheim, Richard G; Fetters, Michael D; Quinn, Gwendolyn P


    Although they are critical to models of coordinated care, the relationship and communication between primary care providers (PCPs) and cancer specialists throughout the cancer continuum are poorly understood. By using predefined search terms, the authors conducted a systematic review of the literature in 3 databases to examine the relationship and communication between PCPs and cancer specialists. Among 301 articles identified, 35 met all inclusion criteria and were reviewed in-depth. Findings from qualitative, quantitative, and disaggregated mixed-methods studies were integrated using meta-synthesis. Six themes were identified and incorporated into a preliminary conceptual model of the PCP-cancer specialist relationship: 1) poor and delayed communication between PCPs and cancer specialists, 2) cancer specialists' endorsement of a specialist-based model of care, 3) PCPs' belief that they play an important role in the cancer continuum, 4) PCPs' willingness to participate in the cancer continuum, 5) cancer specialists' and PCPs' uncertainty regarding the PCP's oncology knowledge/experience, and 6) discrepancies between PCPs and cancer specialists regarding roles. These data indicate a pervasive need for improved communication, delineation, and coordination of responsibilities between PCPs and cancer specialists. Future interventions aimed at these deficiencies may improve patient and physician satisfaction and cancer care coordination. CA Cancer J Clin 2017;67:156-169. © 2016 American Cancer Society.

  2. Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development

    Directory of Open Access Journals (Sweden)

    David Landeira


    Full Text Available Jarid2 is part of the Polycomb Repressor complex 2 (PRC2 responsible for genome-wide H3K27me3 deposition. Unlike other PRC2-deficient embryonic stem cells (ESCs, however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2−/− ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered β-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2−/− with wild-type ESCs restores variable Nanog expression and β-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development.


    Energy Technology Data Exchange (ETDEWEB)

    Nathan, S.


    The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials, are significantly less hazardous than large amounts of the same materials. This study describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package compliant with 10 CFR Part 71 external radiation level limits regulations. These regulations require packaging for the shipment of radioactive materials perform, under both normal and accident conditions, the essential functions of material containment, subcriticality, and maintain external radiation levels within regulatory limits. 10 CFR 71.33(b)(1)(2)&(3) state radioactive and fissile materials must be identified and their maximum quantity, chemical and physical forms be included in an application. Furthermore, the U.S. Federal Regulations require application contain an evaluation demonstrating the package (i.e., the packaging and its contents) satisfies the external radiation standards for all packages (10 CFR 71.31(2), 71.35(a), & 71.47). By placing the contents in a He leak-tight containment vessel, and limiting the mass to ensure subcriticality, the first two essential functions are readily met. Some isotopes emit sufficiently strong photon radiation that small amounts of material can yield a large external dose rate. Quantifying of the dose rate for a proposed content is a challenging issue for the SGQ approach. It is essential to quantify external radiation levels from several common gamma and neutron sources that can be safely placed in a specific packaging, to ensure compliance with federal regulations. The Packaging Certification Program (PCP) Methodology for Determining Dose Rate for Small Gram Quantities in Shipping Packagings described in this report provides bounding mass limits for a set of proposed SGQ isotopes. Methodology calculations were performed to estimate external radiation levels

  4. Ag/AgO Nanoparticles Grown via Time Dependent Double Mechanism in a 2D Layered Ni-PCP and Their Antibacterial Efficacy (United States)

    Agarwal, Rashmi A.; Gupta, Neeraj K.; Singh, Rajan; Nigam, Shivansh; Ateeq, Bushra


    A simple synthesis route for growth of Ag/AgO nanoparticles (NPs) in large quantitative yields with narrow size distribution from a functional, non-activated, Ni (II) based highly flexible porous coordination polymer (PCP) as a template has been demonstrated. This template is a stable storage media for the NPs larger than the pore diameters of the PCP. From EPR study it was concluded that NPs were synthesized via two mechanisms i.e. acid formation and the redox activity of the framework. Size range of Ag/AgO NPs is sensitive to choice of solvent and reaction time. Direct use of Ag/AgO@Ni-PCP shows influential growth inhibition towards Escherichia coli and the pathogen Salmonella typhimurium at extremely low concentrations. The pristine template shows no cytotoxic activity, even though it contains Ni nodes in the framework.

  5. High average daily intake of PCDD/Fs and serum levels in residents living near a deserted factory producing pentachlorophenol (PCP) in Taiwan: influence of contaminated fish consumption

    Energy Technology Data Exchange (ETDEWEB)

    Lee Ching-Chang; Lin Wu-Ting; Liao Po-Chi; Su Huey-Jen [Dept. of Environmental and Occupational Health/Research Center of Environmental Trace Toxic substances, Medical Coll., National Cheng Kung Univ., Tainan (Taiwan); Chen Hsiu-Lin [Inst. of Basic Medical Sciences, Medical Coll., National Cheng Kung Univ., Tainan (Taiwan)


    Many reports have suggested that PCDD/Fs (polychlorinated dibenzo-p-dioxins and dibenzofurans) contribute to immune deficiency, liver damage, human carcinogenesis, and neuromotor maturation in children. Therefore, beginning in 1999, the Taiwan Environmental Protection Agency (EPA) conducted a survey to determine serum levels of PCDD/Fs in the general populations living around 19 incinerators in Taiwan. Relatively high average serum PCDD/F levels were unexpectedly found in Tainan city, a less industrialized area in southwestern Taiwan, than in other urban areas. We therefore reviewed the usage history of the land and found that a factory situated between Hsien-Gong Li and Lu-Erh Li, two administrative units of Tainan city, had been manufacturing pentachlorophenol (PCP) between 1967 and 1982. PCDD/Fs are formed as byproducts in the PCP manufacturing process. Exposure to PCP and its derivatives via the food chain is the most significant intake route of PCDD/Fs in consumers in the European Union (EU). In Japan, in addition to combustion processes, PCP and chlornitrofen (CNP) have also been identified as the major sources of PCDD/Fs in Tokyo Bay7. A preliminary investigation showed that the soil in the PCP factory and sediments in the sea reservoir (13 hectares) near the deserted factory were seriously contaminated with PCDD/Fs (260-184,000 and 20-6220 pg I-TEQ/g, respectively), levels higher than those in other countries. Therefore, the aim of this study was to compare the PCDD/F levels of fish meat in the sea reservoir and the serum in inhabitants living in the vicinity of the closed PCP plant and other nearby areas. The data from human and other biota samples might clarify the transmission pathway of the PCDD/F contaminants from the PCP factory to local residents, provide information about the exposure status of those living in the vicinity of the deserted PCP factory, and also lead to useful suggestions for controlling PCDD/F accumulation in those living near such

  6. Enhancement of social novelty discrimination by positive allosteric modulators at metabotropic glutamate 5 receptors: adolescent administration prevents adult-onset deficits induced by neonatal treatment with phencyclidine. (United States)

    Clifton, Nicholas E; Morisot, Nadège; Girardon, Sylvie; Millan, Mark J; Loiseau, Florence


    Metabotropic glutamate-5 receptors (mGluR5), which physically and functionally interact with N-methyl-D-Aspartate (NMDA) receptors, likewise control cognitive processes and have been proposed as targets for novel classes of antipsychotic agent. Since social cognition is impaired in schizophrenia and disrupted by NMDA receptor antagonists like dizocilpine, we evaluated its potential modulation by mGluR5. Acute administration (0.63-40 mg/kg) of the mGluR5 positive allosteric modulators (PAMs), 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) and ADX47273, reversed a delay-induced impairment in social novelty discrimination (SND) in adult rats. The action of CDPPB was blocked by the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (2.5-10 mg/kg), and was also expressed upon microinjection into frontal cortex (0.63-10 μg/side), but not striatum. Supporting an interrelationship between mGluR5 and NMDA receptors, enhancement of SND by CDPPB was blocked by dizocilpine (0.08 mg/kg) while, reciprocally, dizocilpine-induced impairment in SND was attenuated by CDPPB (10 mg/kg). The SND deficit elicited by post-natal administration of phencyclidine (10 mg/kg, days 7-11) was reversed by CDPPB or ADX47273 in adults at week 8. This phencyclidine-induced impairment in cognition emerged in adult rats from week 7 on, and chronic, pre-symptomatic treatment of adolescent rats with CDPPB over weeks 5-6 (10 mg/kg per day) prevented the appearance of SND deficits in adults until at least week 13. In conclusion, as evaluated by a SND procedure, mGluR5 PAMs promote social cognition via actions expressed in interaction with NMDA receptors and exerted in frontal cortex. MGluR5 PAMs not only reverse but also (when given during adolescence) prevent the emergence of cognitive impairment associated with a developmental model of schizophrenia.

  7. Onderzoek naar de concentraties in bloed van pentachloorfenol (PCP) en gamma-hexachloorcyclohexaan (gamma-HCH) van bewoners en toekomstige bewoners van een gerenoveerd pakhuis te Amsterdam

    NARCIS (Netherlands)

    Remmert HP; van den Doel R; Hofstee AWM; Meulenbelt J; Greve PA; Slob W; Meyer HHP; van den Boogert ALF; Savelkoul TJF


    Bij huidige en toekomstige bewoners van een gerenoveerd pakhuis te Amsterdam waarvan houten balken bewerkt waren met PCP en gamma-HCH, werd een onderzoek verricht naar de concentraties van deze stoffen in het bloed als maat voor de lichaamsbelasting. Tussen de beide groepen werd geen statistisch si

  8. PCP-induced deficits in murine nest building activity: employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia. (United States)

    Pedersen, Christian Spang; Sørensen, Dorte Bratbo; Parachikova, Anna I; Plath, Niels


    Schizophrenia is a severe psychiatric disorder characterized by three symptom domains, positive (hallucinations, obsession), negative (social withdrawal, apathy, self-neglect) and cognitive (impairment in attention, memory and executive function). Whereas current medication ameliorates positive symptomatology, negative symptoms as well as cognitive dysfunctions remain untreated. The development of improved therapies for negative symptoms has proven particularly difficult, in part due to the inability of mimicking these in rodents. Here, we address the predictive validity of combining an ethologically well preserved behavior in rodents, namely nest building activity, with an established animal model of schizophrenia, the sub-chronic PCP model, for negative symptoms. Decline in rodent nesting activity has been suggested to mirror domains of negative symptoms of schizophrenia, including social withdrawal, anhedonia and self-neglect, whereas repeated treatment with the NMDAR antagonist PCP induces and exacerbates schizophrenia-like symptoms in rodents and human subjects. Using a back-translational approach of pharmacological validation, we tested the effects of two agents targeting the nicotinic α7 receptor (EVP-6124 and TC-5619) that were reported to exert some beneficial effect on negative symptoms in schizophrenic patients. Sub-chronic PCP treatment resulted in a significant nest building deficit in mice and treatment with EVP-6124 and TC-5619 reversed this PCP-induced deficit. In contrast, the atypical antipsychotic drug risperidone remained ineffective in this assay. In addition, EVP-6124, TC-5619 and risperidone were tested in the Social Interaction Test (SIT), an assay suggested to address negative-like symptoms. Results obtained in SIT were comparable to results in the nest building test (NEST). Based on these findings, we propose nest building in combination with the sub-chronic PCP model as a novel approach to assess negative-like symptoms of schizophrenia

  9. Reflections on production planning and control (PPC Reflexões sobre o planejamento e controle da produção (PCP

    Directory of Open Access Journals (Sweden)

    Maurice Bonney


    Full Text Available The paper examines the current state of Production Planning and Control (PPC, identifies some technical and systems changes that have occurred over recent years and links these with the requirements being placed on companies by the market. PPC is being asked to respond effectively to these internal and external changes by being more dynamic and providing better control of resources and delivery performance. Some of the requirements to be satisfied by the new PPC systems are identified. To meet these requirements it is suggested that better understanding is required of how different factors affect PPC systems performance and that administrative systems need improving. The quantitative, administrative and behavioural aspects of PPC are discussed. A framework for developing an agenda for action and research is provided.O artigo examina o estado da arte do Planejamento e Controle da Produção (PCP, identifica algumas mudanças técnicas e nos sistemas que têm ocorrido em anos recentes, e as relaciona com as necessidades que estão sendo colocadas nas companhias pelo mercado. O PCP está sendo solicitado para responder efetivamente a essas mudanças internas e externas, para ser mais dinâmico e fornecer um melhor controle dos recursos e desempenho nas entregas. Algumas das necessidades a serem satisfeitas pelos novos sistemas de PCP são identificadas. Para atender essas necessidades é sugerido que é preciso um melhor entendimento de como diferentes fatores afetam o desempenho dos sistemas de PCP, e que os sistemas administrativos precisam melhorar. Os aspectos quantitativos, administrativos e comportamentais do PCP são discutidos. Uma estrutura para desenvolver uma agenda de ação e pesquisa é proposta.

  10. New designed device allows significant savings in PCP completions, in the Zuata Field, Junin block of the Orinoco oil belt, Venezuela

    Energy Technology Data Exchange (ETDEWEB)

    Busto, T.; Brunings, C. [PDVSA (Venezuela); Grisoni, J. [TIET, C.A. (Venezuela)


    In the Zuata principal field in the Orinoco oil belt, PDVSA has implemented a new device named FMB-TIET. This device is a retrievable mechanically activated tool designed with a torque anchor which converts a tubular PCP into an insertable PCP. In the Zuata principal field, the insertable PCPs have been used since 2001 but, given the intent of PDVSA to increase its oil production rates and decrease its operational expenditure, the FMB-TIET device was tried in well ZPZ0047 in February, 2010. This implementation along with Flush by unit resulted in a considerable saving: the operational expenditure for replacement service was reduced by 63%, rig time was reduced by two days and production delays were also reduced by two days. The test of the FMB-TIET device in one well of the Orinoco oil belt has proved to be successful and PDVSA is planning to install twenty devices in the short term.

  11. Planar Cell Polarity (PCP) Protein Vangl2 Regulates Ectoplasmic Specialization Dynamics via Its Effects on Actin Microfilaments in the Testes of Male Rats. (United States)

    Chen, Haiqi; Mruk, Dolores D; Lee, Will M; Cheng, C Yan


    Planar cell polarity (PCP) proteins confer polarization of a field of cells (eg, elongating/elongated spermatids) within the plane of an epithelium such as the seminiferous epithelium of the tubule during spermatogenesis. In adult rat testes, Sertoli and germ cells were found to express PCP core proteins (eg, Van Gogh-like 2 [Vangl2]), effectors, ligands, and signaling proteins. Vangl2 expressed predominantly by Sertoli cells was localized at the testis-specific, actin-rich ectoplasmic specialization (ES) at the Sertoli-spermatid interface in the adluminal compartment and also Sertoli-Sertoli interface at the blood-testis barrier (BTB) and structurally interacted with actin, N-cadherin, and another PCP/polarity protein Scribble. Vangl2 knockdown (KD) by RNA interference in Sertoli cells cultured in vitro with an established tight junction-permeability barrier led to BTB tightening, whereas its overexpression using a full-length cDNA construct perturbed the barrier function. These changes were mediated through an alteration on the organization actin microfilaments at the ES in Sertoli cells, involving actin-regulatory proteins, epidermal growth factor receptor pathway substrate 8, actin-related protein 3, and Scribble, which in turn affected the function of adhesion protein complexes at the ES during the epithelial cycle of spermatogenesis. Using Polyplus in vivo-jetPEI reagent as a transfection medium to silence Vangl2 in the testis in vivo by RNA interference with high efficacy, Vangl2 KD led to changes in F-actin organization at the ES in the epithelium, impeding spermatid and phagosome transport and spermatid polarity, meiosis, and BTB dynamics. For instance, step 19 spermatids remained embedded in the epithelium alongside with step 9 and 10 spermatids in stages IX-X tubules. In summary, the PCP protein Vangl2 is an ES regulator through its effects on actin microfilaments in the testis.

  12. CTHRC1 Acts as a Prognostic Factor and Promotes Invasiveness of Gastrointestinal Stromal Tumors by Activating Wnt/PCP-Rho Signaling

    Directory of Open Access Journals (Sweden)

    Ming-Ze Ma


    Full Text Available Gastrointestinal stromal tumors (GISTs are the major gastrointestinal mesenchymal tumors with a variable malignancy ranging from a curable disorder to highly malignant sarcomas. Metastasis and recurrence are the main causes of death in GIST patients. To further explore the mechanism of metastasis and to more accurately estimate the recurrence risk of GISTs after surgery, the clinical significance and functional role of collagen triple helix repeat containing-1 (CTHRC1 in GIST were investigated. We found that CTHRC1 expression was gradually elevated as the risk grade of NIH classification increased, and was closely correlated with disease-free survival and overall survival in 412 GIST patients. In vitro experiments showed that recombinant CTHRC1 protein promoted the migration and invasion capacities of primary GIST cells. A luciferase reporter assay and pull down assay demonstrated that recombinant CTHRC1 protein activated noncanonical Wnt/PCP-Rho signaling but inhibited canonical Wnt signaling. The pro-motility effect of CTHRC1 on GIST cells was reversed by using a Wnt5a neutralizing antibody and inhibitors of Rac1 or ROCK. Taken together, these data indicate that CTHRC1 may serve as a new predictor of recurrence risk and prognosis in post-operative GIST patients and may play an important role in facilitating GIST progression. Furthermore, CTHRC1 promotes GIST cell migration and invasion by activating Wnt/PCP-Rho signaling, suggesting that the CTHRC1-Wnt/PCP-Rho axis may be a new therapeutic target for interventions against GIST invasion and metastasis.

  13. The analysis of PCP in renal transplantation recipients and HIV-infected patients%HIV阳性PCP及肾移植术后PCP患者诊治分析

    Institute of Scientific and Technical Information of China (English)

    焦洋; 董宇超; 黄怡; 李强; 周道银


    目的 探讨HIV阳性PCP及肾移植术后PCP患者的临床特点.方法 对我院呼吸科收治的4例HIV阳性PCP及4例肾移植术后PCP患者的临床症状、影像学、治疗经过进行总结分析.结果 7例患者为男性,1例为女性,发热、无痰性咳嗽及气促是常见的临床表现.影像学主要表现为两肺弥漫性磨玻璃影.肾移植术后PCP患者的确诊时间小于HIV阳性PCP患者(P<0.05)、CRP及CD+4T淋巴细胞绝对值均高于HIV阳性PCP患者(P>0.05).结论 肾移植患者在术后半年内容易发生PCP.早期诊断,及时TMP-SMZ治疗,对疾病的预防和控制有重要作用.%Objective To investigate the clinical characteristics of pneumocystis carinii pneumonia ( PCP ) alter HIV-infected and renal transplantation patients. Methods The clinical data of four HIV-infected PCP and four renal transplantal PCP were analyzed, inclu ding the clinical profiles, immunological status, and chest radiological characteristics. Results Seven of the patients were men, and one was women. The most common clinical symptoms were level', cough without sputum and breathless, and the typical imaging finding was bi lateral diffuse ground glass opacities distributing in perihilar regions. Compared with HIV-infected patients, the number of white blood cell, neumophila and CD4+ T cell were higher in renal tiansplantal patients than that of HIV-infected ones with significant difference. Con clusion More and more PCP happens in HIV-negative patients because of the use of glucocorticoid and immunosuppressive agents. Early diagnosis and timely treatment of TMP-SMZ are important in treating the disease.

  14. Brainstem respiratory oscillators develop independently of neuronal migration defects in the Wnt/PCP mouse mutant looptail.

    Directory of Open Access Journals (Sweden)

    Muriel Thoby-Brisson

    Full Text Available The proper development and maturation of neuronal circuits require precise migration of component neurons from their birthplace (germinal zone to their final positions. Little is known about the effects of aberrant neuronal position on the functioning of organized neuronal groups, especially in mammals. Here, we investigated the formation and properties of brainstem respiratory neurons in looptail (Lp mutant mice in which facial motor neurons closely apposed to some respiratory neurons fail to migrate due to loss of function of the Wnt/Planar Cell Polarity (PCP protein Vangl2. Using calcium imaging and immunostaining on embryonic hindbrain preparations, we found that respiratory neurons constituting the embryonic parafacial oscillator (e-pF settled at the ventral surface of the medulla in Vangl2(Lp/+ and Vangl2(Lp/Lp embryos despite the failure of tangential migration of its normally adjacent facial motor nucleus. Anatomically, the e-pF neurons were displaced medially in Lp/+ embryos and rostro-medially Lp/Lp embryos. Pharmacological treatments showed that the e-pF oscillator exhibited characteristic network properties in both Lp/+ and Lp/Lp embryos. Furthermore, using hindbrain slices, we found that the other respiratory oscillator, the preBötzinger complex, was also anatomically and functionally established in Lp mutants. Importantly, the displaced e-pF oscillator established functional connections with the preBötC oscillator in Lp/+ mutants. Our data highlight the robustness of the developmental processes that assemble the neuronal networks mediating an essential physiological function.

  15. 纺织品中五氯酚残留量检测方法的研究%Study on determination of pentachlorophenol(PCP)residues in textiles

    Institute of Scientific and Technical Information of China (English)




  16. 49 CFR 199.3 - Definitions. (United States)


    ... Schedule II of the Controlled Substances Act (21 U.S.C. 812): marijuana, cocaine, opiates, amphetamines, and phencyclidine (PCP). Refuse to submit, refuse, or refuse to take means behavior consistent...

  17. Lpp is involved in Wnt/PCP signaling and acts together with Scrib to mediate convergence and extension movements during zebrafish gastrulation. (United States)

    Vervenne, Hilke B V K; Crombez, Koen R M O; Lambaerts, Kathleen; Carvalho, Lara; Köppen, Mathias; Heisenberg, Carl-Philipp; Van de Ven, Wim J M; Petit, Marleen M R


    The zyxin-related LPP protein is localized at focal adhesions and cell-cell contacts and is involved in the regulation of smooth muscle cell migration. A known interaction partner of LPP in human is the tumor suppressor protein SCRIB. Knocking down scrib expression during zebrafish embryonic development results in defects of convergence and extension (C&E) movements, which occur during gastrulation and mediate elongation of the anterior-posterior body axis. Mediolateral cell polarization underlying C&E is regulated by a noncanonical Wnt signaling pathway constituting the vertebrate planar cell polarity (PCP) pathway. Here, we investigated the role of Lpp during early zebrafish development. We show that morpholino knockdown of lpp results in defects of C&E, phenocopying noncanonical Wnt signaling mutants. Time-lapse analysis associates the defective dorsal convergence movements with a reduced ability to migrate along straight paths. In addition, expression of Lpp is significantly reduced in Wnt11 morphants and in embryos overexpressing Wnt11 or a dominant-negative form of Rho kinase 2, which is a downstream effector of Wnt11, suggesting that Lpp expression is dependent on noncanonical Wnt signaling. Finally, we demonstrate that Lpp interacts with the PCP protein Scrib in zebrafish, and that Lpp and Scrib cooperate for the mediation of C&E.

  18. Catalytic amine-borane dehydrogenation by a PCP-pincer palladium complex: a combined experimental and DFT analysis of the reaction mechanism. (United States)

    Rossin, Andrea; Bottari, Giovanni; Lozano-Vila, Ana M; Paneque, Margarita; Peruzzini, Maurizio; Rossi, Andrea; Zanobini, Fabrizio


    Catalytic dehydrogenation of ammonia-borane (NH(3)·BH(3), AB) and dimethylamine borane (NHMe(2)·BH(3), DMAB) by the Pd(II) complex [((tBu)PCP)Pd(H(2)O)]PF(6) [(tBu)PCP = 2,6-C(6)H(3)(CH(2)P(t)Bu(2))(2)] leads to oligomerization and formation of spent fuels of general formula cyclo-[BH(2)-NR(2)](n) (n = 2,3; R = H, Me) as reaction byproducts, while one equivalent of H(2) is released per amine-borane equivalent. The processes were followed through multinuclear ((31)P, (1)H, (11)B) variable temperature NMR spectroscopy; kinetic measurements on the hydrogen production rate and the relative rate constants were also carried out. One non-hydridic intermediate could be detected at low temperature, whose chemical nature was explored through a DFT modeling of the reaction mechanism, at the M06//6-31+G(d,p) computational level. The computational output was of help to propose a reliable mechanistic picture of the process.

  19. The comparative photodegradation activities of pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs) using UV alone and TiO2-derived photocatalysts in methanol soil washing solution. (United States)

    Zhou, Zeyu; Zhang, Yaxin; Wang, Hongtao; Chen, Tan; Lu, Wenjing


    Photochemical treatment is increasingly being applied to remedy environmental problems. TiO2-derived catalysts are efficiently and widely used in photodegradation applications. The efficiency of various photochemical treatments, namely, the use of UV irradiation without catalyst or with TiO2/graphene-TiO2 photodegradation methods was determined by comparing the photodegadation of two main types of hydrophobic chlorinated aromatic pollutants, namely, pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs). Results show that photodegradation in methanol solution under pure UV irradiation was more efficient than that with either one of the catalysts tested, contrary to previous results in which photodegradation rates were enhanced using TiO2-derived catalysts. The effects of various factors, such as UV light illumination, addition of methanol to the solution, catalyst dosage, and the pH of the reaction mixture, were examined. The degradation pathway was deduced. The photochemical treatment in methanol soil washing solution did not benefit from the use of the catalysts tested. Pure UV irradiation was sufficient for the dechlorination and degradation of the PCP and PCBs.

  20. Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death. (United States)

    Schuenemann, Verena J; Bos, Kirsten; DeWitte, Sharon; Schmedes, Sarah; Jamieson, Joslyn; Mittnik, Alissa; Forrest, Stephen; Coombes, Brian K; Wood, James W; Earn, David J D; White, William; Krause, Johannes; Poinar, Hendrik N


    Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348-1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.

  1. A PCP Pincer Ligand for Coordination Polymers with Versatile Chemical Reactivity: Selective Activation of CO2 Gas over CO Gas in the Solid State. (United States)

    He, Junpeng; Waggoner, Nolan W; Dunning, Samuel G; Steiner, Alexander; Lynch, Vincent M; Humphrey, Simon M


    A tetra(carboxylated) PCP pincer ligand has been synthesized as a building block for porous coordination polymers (PCPs). The air- and moisture-stable PCP metalloligands are rigid tetratopic linkers that are geometrically akin to ligands used in the synthesis of robust metal-organic frameworks (MOFs). Here, the design principle is demonstrated by cyclometalation with Pd(II) Cl and subsequent use of the metalloligand to prepare a crystalline 3D MOF by direct reaction with Co(II) ions and structural resolution by single crystal X-ray diffraction. The Pd-Cl groups inside the pores are accessible to post-synthetic modifications that facilitate chemical reactions previously unobserved in MOFs: a Pd-CH3 activated material undergoes rapid insertion of CO2 gas to give Pd-OC(O)CH3 at 1 atm and 298 K. However, since the material is highly selective for the adsorption of CO2 over CO, a Pd-N3 modified version resists CO insertion under the same conditions.

  2. The comparative photodegradation activities of pentachlorophenol (PCP and polychlorinated biphenyls (PCBs using UV alone and TiO2-derived photocatalysts in methanol soil washing solution.

    Directory of Open Access Journals (Sweden)

    Zeyu Zhou

    Full Text Available Photochemical treatment is increasingly being applied to remedy environmental problems. TiO2-derived catalysts are efficiently and widely used in photodegradation applications. The efficiency of various photochemical treatments, namely, the use of UV irradiation without catalyst or with TiO2/graphene-TiO2 photodegradation methods was determined by comparing the photodegadation of two main types of hydrophobic chlorinated aromatic pollutants, namely, pentachlorophenol (PCP and polychlorinated biphenyls (PCBs. Results show that photodegradation in methanol solution under pure UV irradiation was more efficient than that with either one of the catalysts tested, contrary to previous results in which photodegradation rates were enhanced using TiO2-derived catalysts. The effects of various factors, such as UV light illumination, addition of methanol to the solution, catalyst dosage, and the pH of the reaction mixture, were examined. The degradation pathway was deduced. The photochemical treatment in methanol soil washing solution did not benefit from the use of the catalysts tested. Pure UV irradiation was sufficient for the dechlorination and degradation of the PCP and PCBs.

  3. High average daily intake of PCDD/Fs and serum levels in residents living near a deserted factory producing pentachlorophenol (PCP) in Taiwan: Influence of contaminated fish consumption

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.C. [Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Research Center of Environmental Trace Toxic Substances, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Lin, W.T. [Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Liao, P.C. [Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Research Center of Environmental Trace Toxic Substances, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Su, H.J. [Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Research Center of Environmental Trace Toxic Substances, Medical College, National Cheng Kung University, Tainan, Taiwan (China); Chen, H.L. [Department of Industrial Safety and Health, Hung Kuang University, Taichung, 34 Chung Chie Rd. Sha Lu, Taichung 433, Taiwan (China)]. E-mail:


    An abandoned pentachlorophenol plant and nearby area in southern Taiwan was heavily contaminated by dioxins, impurities formed in the PCP production process. The investigation showed that the average serum PCDD/Fs of residents living nearby area (62.5 pg WHO-TEQ/g lipid) was higher than those living in the non-polluted area (22.5 and 18.2 pg WHO-TEQ/g lipid) (P < 0.05). In biota samples, average PCDD/F of milkfish in sea reservoir (28.3 pg WHO-TEQ/g) was higher than those in the nearby fish farm (0.15 pg WHO-TEQ/g), and Tilapia and shrimp showed the similar trend. The average daily PCDD/Fs intake of 38% participants was higher than 4 pg WHO-TEQ/kg/day suggested by the world health organization. Serum PCDD/F was positively associated with average daily intake (ADI) after adjustment for age, sex, BMI, and smoking status. In addition, a prospective cohort study is suggested to determine the long-term health effects on the people living near factory. - Inhabitants living near a deserted PCP factory are exposed to high PCDD/F levels.

  4. Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Marta Vitorino

    Full Text Available Protein Kinase Domain Containing, Cytoplasmic (PKDCC is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.

  5. Physical-constraint-preserving Central Discontinuous Galerkin Methods for Special Relativistic Hydrodynamics with a General Equation of State (United States)

    Wu, Kailiang; Tang, Huazhong


    The ideal gas equation of state (EOS) with a constant adiabatic index is a poor approximation for most relativistic astrophysical flows, although it is commonly used in relativistic hydrodynamics (RHD). This paper develops high-order accurate, physical-constraints-preserving (PCP), central, discontinuous Galerkin (DG) methods for the one- and two-dimensional special RHD equations with a general EOS. It is built on our theoretical analysis of the admissible states for RHD and the PCP limiting procedure that enforce the admissibility of central DG solutions. The convexity, scaling invariance, orthogonal invariance, and Lax–Friedrichs splitting property of the admissible state set are first proved with the aid of its equivalent form. Then, the high-order central DG methods with the PCP limiting procedure and strong stability-preserving time discretization are proved, to preserve the positivity of the density, pressure, specific internal energy, and the bound of the fluid velocity, maintain high-order accuracy, and be L1-stable. The accuracy, robustness, and effectiveness of the proposed methods are demonstrated by several 1D and 2D numerical examples involving large Lorentz factor, strong discontinuities, or low density/pressure, etc.

  6. Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses subcronic PCP-induced deficits in the novel object recognition task in rats

    DEFF Research Database (Denmark)

    Nielsen, Trine Damgaard; Larsen, Dorrit Bjerg; Hansen, Suzanne Lisbet;


    deficit in female Lister hooded rats in teh novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub......-cbronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this diruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment...

  7. In-situ generated H{sub 2}O{sub 2} induced efficient visible light photo-electrochemical catalytic oxidation of PCP-Na with TiO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wei; Liu, Huichao; Ai, Zhihui, E-mail:


    Graphical abstract: We demonstrate a novel PEC system where the cathodic in-situ generated H{sub 2}O{sub 2} interacts with TiO{sub 2} particles to form interfacial Ti{sup IV}−OOH species which endow TiO{sub 2} with visible light photocatalytic activity for efficient PCP-Na degradation for the first time. - Highlights: • We demonstrate a novel visible light driven PEC system for efficient PCP-Na degradation. • The in-situ generated H{sub 2}O{sub 2} reacts with TiO{sub 2} suspensions to form interfacial Ti{sup IV}−OOH species. • Ti{sup IV}−OOH species endow TiO{sub 2} with visible light photocatalytic activity. • ·O{sub 2}{sup −} and ·OH are responsible for the dechlorination and mineralization of PCP-Na, respectively. - Abstract: In this study, we developed a novel photo-electrochemical catalytic oxidation wastewater treatment system by interacting the cathodic in-situ generated H{sub 2}O{sub 2} with TiO{sub 2} suspension to form interfacial ≡Ti{sup IV}−OOH species, which endowed the PEC system with superior efficiency for degrading sodium pentachlorophenate (PCP-Na) under visible light irradiation at neutral pH. The apparent PCP-Na degradation rate constant of the PEC system was more than 10 times that of the electrochemical oxidation counterpart. In the PEC system, the interfacial ≡Ti{sup IV}−OOH species injected electrons to the conduction band of TiO{sub 2} to initiate the activation of O{sub 2} and the in-situ generated H{sub 2}O{sub 2} adsorbed on the surface of TiO{sub 2}, lead to producing reactive oxygen species of superoxide anions and hydroxyl radicals, which were responsible for the dechlorination and mineralization of PCP-Na during the PEC process, respectively. The dosage of TiO{sub 2} catalyst and the current intensity applied on PCP-Na degradation were optimized. This study develops a high efficient PEC oxidation system for wastewater treatment and provides new insight into the role of cathodic in-situ generated H{sub 2}O

  8. Effect of Se-PCP-B and ketamine on enduration of oxygen deficiency in mice%板党硒多糖与氯氨酮对小鼠低氧耐受性的影响

    Institute of Scientific and Technical Information of China (English)



    Objective To study the effect of Se-Polysaccharides in Codonopsis Pilosula from Banqiao(Se-PCP-B) on enduration of oxygen deficiency and amino acid in the brain tissue. Methods The mice were divided into four groups:control group, ketamine group,Se-PCP-B group and ketamine+Se-PCP-B group,respectively treated with 0.9% Nacl,ketamine,Se-PCP-B and ketamine+Se-PCP-B,then the endurance of oxygen deficiency experiment model was established. To observe the time of the endurance of oxygen deficiency, to measured the content of Glu, Asp, GABA and Gly in brain tissue. Results Compared with control group: the time of the endurance of oxygen deficiency obviously extended in the Se-PCP-B group, ketamine group and ketamine+ Se-PCP-B group mice(P<0.05); The content of Glu and Asp obviously decreased in the Se-PCP-B group and ketamine+Se-PCP-B group mice(P<0.05). Conclusion Se-PCP-B and ketamine can increase the enduration of oxygen deficiency in mice; Se PCP B can decrease the content of Glu and Asp also.%目的 探讨板党硒多糖对小鼠低氧耐受性和脑内氨基酸类递质含量的影响.方法 将小鼠随机分为4组:生理盐水对照组、氯氨酮组、板党硒多糖组和氯氨酮加板党硒多糖组,分别用生理盐水、氯氨酮、板党硒多糖和氯氨酮加板党硒多糖处理后,建立小鼠急性重复低氧耐受模型,观察各组小鼠低氧耐受时间和脑组织中谷氨酸(Glu)、天冬氨酸(Asp)、γ-氨基丁酸(GABA)和甘氨酸(Gly)含量的变化.结果 与生理盐水对照组比较,板党硒多糖组小鼠各次低氧耐受时间明显延长(P<0.05),脑组织中Glu和Asp含量明显减少(P<0.05),GABA和Gly无明显变化;氯氨酮组小鼠各次低氧耐受时间明显延长(P<0.01),脑组织中氨基酸无明显变化;氯氨酮加板党硒多糖组小鼠各次低氧耐受时间明显延长(P<0.01),且明显长于氯氨酮组和板党硒多糖组,脑组织中Glu和Asp含量明显减少(P<0.05),GABA

  9. 三苯基锡和五氯酚对斑马鱼急性毒性作用和过氧化物酶活性的影响%Effects of TPT and PCP on Acute Toadcity and POD Activity of Zebrafish

    Institute of Scientific and Technical Information of China (English)

    宋志慧; 王庆伟; 杨鲁娜; 丛林


    [Objective] The effect of TPT and PCP on peroxidase ( POD) activity in zebra fish was studied, and the toxic effect of TPT and PCP on zebra fish was discussed. [ Method ] The LC50 of TPT and PCP and the joint action of TPT-PCP to zebra fish were studied using zebra fish by semi-static method test. The toxic effects of TPT and PCP on peroxidase (POD) were discussed. [ Result] The results showed that the 96 h-LC50 of TPT and PCP were 12.313 and 61. 195 (μg/L, respectively. The toxicity order of them was TPT > PCP. Effects of TPT and PCP stress on POD in zebra fish were induction-inhibition at 1 d, effects of TPT and PCP stress on POD in zebra fish were inhibition at 7d. The enzyme activities were changed markedly significantly at from 1 d to 7 d. [ Conclusion] TPT and PCP were high toxic substances. The type of joint effect of TPT-PCP had synergistic effect. TPT and PCP single stress on POD enzyme activities in zebra fish changed significantly. The study could provide the reference for the organic pollution on the aquatic organisms' toxicity mechanism.%[目的]研究三苯基锡(TPT)和五氯酚 (PCP)对斑马鱼过氧化物酶(POD)活性的影响,探讨TPT和PCP对斑马鱼的毒性作用.[方法]以斑马鱼为受试生物,采用半静态法对斑马鱼进行驯养和试验,测定TPT和PCP对斑马鱼的LC50、联合毒性作用类型和对POD活性的影响.[结果]TPT和PCP对斑马鱼的96h LC50分别为12.313和61.195 μg/L,毒性顺序为TPT>PCP,TPT和PCP暴露1d胁迫斑马鱼POD为诱导-抑制效应,暴露7d胁迫斑马鱼POD为抑制效应.且暴露1d和暴露7d酶活性变化均显著.[结论]TPT和PCP为剧毒物质,TPT和PCP联合作用类型为协同作用;TPT和PCP单一胁迫斑马鱼POD活性变化显著,可为有机物污染对水生生物毒性机理研究提供参考.

  10. Recent advances in visible-light-responsive photocatalysts for hydrogen production and solar energy conversion--from semiconducting TiO2 to MOF/PCP photocatalysts. (United States)

    Horiuchi, Yu; Toyao, Takashi; Takeuchi, Masato; Matsuoka, Masaya; Anpo, Masakazu


    The present perspective describes recent advances in visible-light-responsive photocatalysts intended to develop novel and efficient solar energy conversion technologies, including water splitting and photofuel cells. Water splitting is recognized as one of the most promising techniques to convert solar energy as a clean and abundant energy resource into chemical energy in the form of hydrogen. In recent years, increasing concern is directed to not only the development of new photocatalytic materials but also the importance of technologies to produce hydrogen and oxygen separately. Photofuel cells can convert solar energy into electrical energy by decomposing bio-related compounds and livestock waste as fuels. The advances of photocatalysts enabling these solar energy conversion technologies have been going on since the discovery of semiconducting titanium dioxide materials and have extended to organic-inorganic hybrid materials, such as metal-organic frameworks and porous coordination polymers (MOF/PCP).

  11. Evaluation of the information and support services in the voluntary sector using a new P-C-P (pivotal-core-peripheral) attributes model. (United States)

    Philip, G; Stewart, J


    This paper describes the development and use of a modified SERVQUAL research instrument for measuring the service quality of voluntary organizations from the perspective of their 'customers'. A series of focus group meetings were run with providers and users of the services to identify the appropriate dimensions of service quality. These were structured meetings led by the researchers addressing set questions in a group setting. The meeting enabled the identification of six different dimensions of service quality which neatly mapped on to the pivotal-core-peripheral (P-C-P attributes model [Philip and Hazlett, 1997]), which was developed after extensive research of existing models such as SERVQUAL. These dimensions were used to develop a questionnaire to assess service quality within the voluntary sector. The questionnaire was distributed to 2005 service users, representing eight voluntary organizations from across Northern Ireland. The research resulted in the development of a methodology and research instrument suitable for measuring service quality in the voluntary sector.

  12. Deployable centralizers

    Energy Technology Data Exchange (ETDEWEB)

    Grubelich, Mark C.; Su, Jiann-Cherng; Knudsen, Steven D.


    A centralizer assembly is disclosed that allows for the assembly to be deployed in-situ. The centralizer assembly includes flexible members that can be extended into the well bore in situ by the initiation of a gas generating device. The centralizer assembly can support a large load carrying capability compared to a traditional bow spring with little or no installation drag. Additionally, larger displacements can be produced to centralize an extremely deviated casing.

  13. E6/E7-P53-POU2F1-CTHRC1 axis promotes cervical cancer metastasis and activates Wnt/PCP pathway (United States)

    Zhang, Rong; Lu, Huan; Lyu, Yuan-yuan; Yang, Xiao-mei; Zhu, Lin-yan; Yang, Guang-dong; Jiang, Peng-cheng; Re, Yuan; Song, Wei-wei; Wang, Jin-hao; Zhang, Can-can; Gu, Fei; Luo, Tian-jiao; Wu, Zhi-yong; Xu, Cong-jian


    Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis. PMID:28303973

  14. Formation of a “Pre-mouth Array” from the Extreme Anterior Domain Is Directed by Neural Crest and Wnt/PCP Signaling

    Directory of Open Access Journals (Sweden)

    Laura Jacox


    Full Text Available The mouth arises from the extreme anterior domain (EAD, a region where the ectoderm and endoderm are directly juxtaposed. Here, we identify a “pre-mouth array” in Xenopus that forms soon after the cranial neural crest has migrated to lie on either side of the EAD. Initially, EAD ectoderm comprises a wide and short epithelial mass that becomes narrow and tall with cells and nuclei changing shape, a characteristic of convergent extension. The resulting two rows of cells—the pre-mouth array—later split down the midline to surround the mouth opening. Neural crest is essential for convergent extension and likely signals to the EAD through the Wnt/planar cell polarity (PCP pathway. Fzl7 receptor is locally required in EAD ectoderm, while Wnt11 ligand is required more globally. Indeed, heterologous cells expressing Wnt11 can elicit EAD convergent extension. The study reveals a precise cellular mechanism that positions and contributes to the future mouth.

  15. Vaccination with a Streptococcus pneumoniae trivalent recombinant PcpA, PhtD and PlyD1 protein vaccine candidate protects against lethal pneumonia in an infant murine model. (United States)

    Verhoeven, David; Xu, Qingfu; Pichichero, Michael E


    Streptococcus pneumoniae infections continue to cause significant worldwide morbidity and mortality despite the availability of efficacious serotype-dependent vaccines. The need to incorporate emergent strains expressing additional serotypes into pneumococcal polysaccharide conjugate vaccines has led to an identified need for a pneumococcal protein-based vaccine effective against a broad scope of serotypes. A vaccine consisting of several conserved proteins with different functions during pathogenesis would be preferred. Here, we investigated the efficacy of a trivalent recombinant protein vaccine containing pneumococcal choline-binding protein A (PcpA), pneumococcal histidine triad D (PhtD), and genetically detoxified pneumolysin (PlyD1) in an infant mouse model. We found the trivalent vaccine conferred protection from lethal pneumonia challenges using serotypes 6A and 3. The observed protection with trivalent PcpA, PhtD, and PlyD1 vaccine in infant mice supports the ongoing study of this candidate vaccine in human infant clinical trials.

  16. SEC14 and Spectrin Domains 1 (Sestd1), Dishevelled 2 (Dvl2) and Dapper Antagonist of Catenin-1 (Dact1) co-regulate the Wnt/Planar Cell Polarity (PCP) pathway during mammalian development. (United States)

    Yang, Xiaoyong; Fisher, Daniel A; Cheyette, Benjamin Nr


    We previously reported that Sestd1 KO phenocopies Dact1 KO in mice, consistent with a model in which Sestd1 and Dact1 act together to form a crucial functional complex that regulates Vangl2 in the Wnt/Planar Cell Polarity (PCP) pathway. Here, we show that Dvl2, a binding partner of Dact1, also forms complexes with Sestd1, and does so independently of both Dact1 and Vangl2. In cell-based assays, whereas Sestd1 does not alter Dvl2 activation of the Wnt/β-catenin signaling pathway, Dvl2 enhances activation of Rho family GTPases by Dact1 and Sestd1, consistent with a role in the PCP pathway. In mice, although Dvl2 KO is recessive in an otherwise wild type background, it leads to dominant embryonic lethality in either the Sestd1 or Dact1 KO background. This genetic synergy stands in contrast to the epistasis we have previously reported between Sestd1 and Dact1 KO, and suggests independent or semi-independent functions for Dvl2 vs. Sestd1/Dact1 in the regulation of the PCP pathway during development. In conclusion, biochemical and genetic interactions between Dvl2, Sestd1, and Dact1, in addition to prior reported interactions between these same molecules and Vangl2, suggest that all these gene products can form complexes together and regulate the PCP pathway during mammalian development. However, Sestd1 and Dact1 have a closely allied function in the post-translational regulation of Vangl2 that is at least partially distinct from the functions of Dvl2 in this pathway.

  17. A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling.

    Directory of Open Access Journals (Sweden)

    Evelien Gebruers

    Full Text Available Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen - Jasminum gilgianum, an Oleaceae species native to Papua New Guinea - induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125 phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME's mechanism of action will help determine this compound's pharmacological utility.

  18. In vivo evaluation of [{sup 11}C]N-(2-chloro-5-thiomethylphenyl)-N'- (3-methoxy-phenyl)-N'-methylguanidine ([{sup 11}C]GMOM) as a potential PET radiotracer for the PCP/NMDA receptor

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail:; Slifstein, Mark; Dumont, Filip; Zhao Jun; Chang, Raymond C.; Sudo, Yasuhiko; Sultana, Abida; Balter, Andrew; Laruelle, Marc


    The development of imaging methods to measure changes in NMDA ion channel activation would provide a powerful means to probe the mechanisms of drugs and device based treatments (e.g., ECT) thought to alter glutamate neurotransmission. To provide a potential NMDA/PCP receptor PET tracer, we synthesized the radioligand [{sup 11}C]GMOM (K{sub i} = 5.2 {+-}0.3 nM; log P = 2.34) and evaluated this ligand in vivo in awake male rats and isoflurane anesthetized baboons. In rats, the regional brain uptake of [{sup 11}C]GMOM ranged from 0.75{+-}0.13% ID/g in the medulla and pons to 1.15{+-}0.17% ID/g in the occipital cortex. MK801 (1 mg/kg i.v.) significantly reduced (24-28%) [{sup 11}C]GMOM uptake in all regions. D-serine (10 mg/kg i.v.) increased [{sup 11}C]GMOM %ID/g values in all regions (10-24%) reaching significance in the frontal cortex and cerebellum only. The NR2B ligand RO 25-6981 (10 mg/kg i.v.) reduced [{sup 11}C]GMOM uptake significantly (24-38%) in all regions except for the cerebellum and striatum. Blood activity was 0.11{+-}0.03 %ID/g in the controls group and did not vary significantly across groups. PET imaging in isoflurane-anesthetized baboons with high specific activity [{sup 11}C]GMOM provided fairly uniform regional brain distribution volume (V{sub T}) values (12.8-17.1 ml g{sup -1}). MK801 (0.5 mg/kg, i.v., n = 1, and 1.0 mg/kg, i.v., n = 1) did not significantly alter regional V{sub T} values, indicating a lack of saturable binding. However, the potential confounding effects associated with ketamine induction of anesthesia along with isoflurane maintenance must be considered because both agents are known to reduce NMDA ion channel activation. Future and carefully designed studies, presumably utilizing an optimized NMDA/PCP site tracer, will be carried out to further explore these hypotheses. We conclude that, even though [{sup 11}C]GMOM is not an optimized PCP site radiotracer, its binding is altered in vivo in awake rats as expected by modulation of

  19. Central line infections - hospitals (United States)

    ... infection; Central venous catheter - infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired ...

  20. Two-phase flow simulation inside a tubing string with artificial lift system PCP based; Simulacao do escoamento bifasico em uma coluna de producao com sistema de elevacao artificial por BCP

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, F.J.T.; Salazar, A.O.; Maitelli, A.L. [Rio Grande do Norte Univ., Natal, RN (Brazil). Programa de Pos-graduacao em Engenharia Eletrica]. E-mail:;;; Assmann, B.W. [PETROBRAS S.A., Natal/Fortaleza, RN/CE (Brazil). Unidade de Negocios]. E-mail:; Lima, J.A. [Rio Grande do Norte Univ., Natal, RN (Brazil). Dept. de Engenharia Mecanica. Programa de Pos-graduacao em Engenharia Mecanica]. E-mail:


    The main goal of the present work is the computational simulation of the vertical two-phase flow within a tubing string in the production of oil equipped with a PCP artificial lift system (Progressive Cavity Pumping). By initially adopting the homogeneous model for the two-phase mixture (oil and gas), the fields of velocity and pressure are evaluated for prediction of pressure loss along the tubing, as well as the spatial and temporal behavior of typical parameters as gas-oil ratio, bubble pressure, solubility ratio, void fraction, gas and oil formation volume factors, among others. Prediction of these properties is an integral part of pressure loss calculations, as well as they constitute essential parameters for optimization of any artificial lift system. The numerical simulation is based on the transport equations (continuity and momentum equations) for a pseudo-fluid through the finite difference method, and the mixture properties are evaluated by employing the black-oil fluid model. Behavior analyses of the main flow variables are made and results for a typical artificial lift system PCP based are discussed. (author)

  1. Central Solenoid

    CERN Multimedia


    The Central Solenoid (CS) is a single layer coil wound internally in a supporting cylinder housed in the cryostat of the Liquid Argon Calorimeter. It was successfully tested at Toshiba in December 2000 and was delivered to CERN in September 2001 ready for integration in the LAr Calorimeter in 2003. An intermediate test of the chimney and proximity cryogenics was successfully performed in June 2002.

  2. Clinical analysis of 45 patients with geratic pancytopenia(PCP)%45例老年的全血细胞减少症的临床分析

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the etiology of the geratic pancytopenia( PCP). Methods Forty-five patients with geratic Pancytopenia collected from January 2009 to January 2013 in our hospital were selected and their clinical data were retrospectively analyzed. Results Among the 45 cases of geratic Pancytopenia, 31cases were non-hematologic systemic diseases, 12 cases were hematologic systemic diseases, and the other 2 cases were of other reasons. The clinical symptoms of the non-hematologic systemic diseases were mild or moderate leucopenia and anaemia, while moderate or severe decreases of three-line blood cells happened in the hematologic systemic diseases. There was a significant difference between the decrease degree of the three-line blood cells in two kinds of diseases(P<0. 05). Conclusion The geratic Pancytopenia should be paid attention to. Both hematologic systemic diseases and non-hematologic systemic diseases might be its causes. The pathogenesis should be analyzed so as to reduce the rate of misdiagnosis and missed diagnosis.%目的:探讨老年全血细胞减少症的病因分析。方法选取2009年1月至2013年1月在江苏省常州市第七人民医院治疗的45例老年全血细胞减少症患者作为研究对象,回顾性分析老年全血细胞减少症患者的的临床资料。结果45例老年全血细胞减少症患者中,非血液系统疾病31例,血液系统疾病12例,不明原因2例。非血液系统疾病白细胞减少和贫血多表现为轻、中度,血液系统疾病的白细胞和红细胞减少多为中、重度,血小板减少为极重度,三系血细胞减少程度差异有统计学意义(P<0.05)。结论应重视老年全血细胞减少的原因,除造血系统疾病的原因以外,非造血系统疾病占相当比例,分析其病因,以便减少其误诊率和漏诊率,进一步提高诊断准确率。

  3. Europa central

    Directory of Open Access Journals (Sweden)

    Karel BARTOSEK


    Full Text Available La investigación francesa continúa interesándose por Europa Central. Desde luego, hay límites a este interés en el ambiente general de mi nueva patria: en la ignorancia, producto del largo desinterés de Francia por este espacio después de la Segunda Guerra Mundial, y en el comportamiento y la reflexión de la clase política y de los medios de comunicación (una anécdota para ilustrar este ambiente: durante la preparación de nuestro coloquio «Refugiados e inmigrantes de Europa Central en el movimiento antifascista y la Resistencia en Francia, 1933-1945», celebrado en París en octubre de 1986, el problema de la definición fue planteado concreta y «prácticamente». ¡Y hubo entonces un historiador eminente, para quién Alemania no formaría parte de Europa Central!.

  4. Central pain. (United States)

    Singh, Supreet


    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  5. central t

    Directory of Open Access Journals (Sweden)

    Manuel R. Piña Monarrez


    Full Text Available Dado que la Regresión Ridge (RR, es una estimación sesgada que parte de la solución de la regresión de Mínimos Cuadrados (MC, es vital establecer las condiciones para las que la distribución central t de Student que se utiliza en la prueba de hipótesis en MC, sea también aplicable a la regresión RR. La prueba de este importante resultado se presenta en este artículo.

  6. Expression of presynaptic markers in a neurodevelopmental animal model with relevance to schizophrenia

    DEFF Research Database (Denmark)

    Karlsen, Anna S; Kaalund, Sanne S; Møller, Morten;


    Administration of N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) to rat pups at postnatal day (PND) 7, 9, and 11 [neonatal PCP (neoPCP) model] induces cognitive deficits similar to those observed in schizophrenia. Expression of presynaptic SNARE protein, synaptosomal-associated prot....... Stereological estimation of the number of neurons and volume was used to exclude potential bias in cell numbers. A significant reduction in the expression of Snap25 in the hippocampal CA4 region was observed in adult neoPCP rats (PND 80, P...

  7. 14 CFR 120.109 - Types of drug testing required. (United States)


    ... the employer's Substance Abuse Professional conducted in accordance with the provisions of 49 CFR part... CFR part 40). (a) Pre-employment drug testing. (1) No employer may hire any individual for a safety..., cocaine, opiates, phencyclidine (PCP), and amphetamines, or a metabolite of those drugs in the...

  8. A chord recognition method based on joint feature of MFCC and PCP%一种基于MFCC与PCP联合特征的和弦识别方法

    Institute of Scientific and Technical Information of China (English)

    李锵; 秦媛媛


    结合乐理理论和信号处理理论,针对传统和弦识别仅考虑音高特性的音级轮廓特征PCP(pitch class profile)造成正确识别率较低的问题,提出一种以反映听觉特性的MFCC(mel frequency cepstral coefficent)与PCP的联合特征和稀疏表示分类器(sparse representation classification,SRC)的和弦识别方法。通过对两特征矢量的叠加构成新的和弦特征,然后利用SRC进行和弦识别。实验结果表明,与传统方法的识别率相比,本方法的识别率大幅提高。%Combined with music and signal process theory, the paper proposes a new chord recognition approach which utilizes the MFCC (Mel Frequency Cepstral Coefficent) reflecting auditory perception properties jointly with the traditional PCP (Pitch Class Profile) as the combined feature and SRC (Sparse Representation classification) to improve the recognition rate. The experimental results show that the recognition rata of the new method is much better in average than that of the traditional methods.

  9. Avian facial morphogenesis is regulated by c-Jun N-terminal kinase/planar cell polarity (JNK/PCP) wingless-related (WNT) signaling. (United States)

    Geetha-Loganathan, Poongodi; Nimmagadda, Suresh; Fu, Katherine; Richman, Joy M


    Wingless-related proteins (WNTs) regulate extension of the central axis of the vertebrate embryo (convergent extension) as well as morphogenesis of organs such as limbs and kidneys. Here, we asked whether WNT signaling directs facial morphogenesis using a targeted approach in chicken embryos. WNT11 is thought to mainly act via β-catenin-independent pathways, and little is known about its role in craniofacial development. RCAS::WNT11 retrovirus was injected into the maxillary prominence, and the majority of embryos developed notches in the upper beak or the equivalent of cleft lip. Three-dimensional morphometric analysis revealed that WNT11 prevented lengthening of the maxillary prominence, which was due in part to decreased proliferation. We next determined, using a series of luciferase reporters, that WNT11 strongly induced JNK/planar cell polarity signaling while repressing the β-catenin-mediated pathway. The activation of the JNK-ATF2 reporter was mediated by the DEP domain of Dishevelled. The impacts of altered signaling on the mesenchyme were assessed by implanted Wnt11- or Wnt3a-expressing cells (activates β-catenin pathway) into the maxillary prominence or by knocking down endogenous WNT11 with RNAi. Host cells were attracted to Wnt11 donor cells. In contrast, cells exposed to Wnt3a or the control cells did not migrate. Cells in which endogenous WNT11 was knocked down were more oriented and shorter than those exposed to exogenous WNT11. The data suggest that JNK/planar cell polarity WNT signaling operates in the face to regulate several morphogenetic events leading to lip fusion.

  10. SEC14 and spectrin domains 1 (Sestd1) and Dapper antagonist of catenin 1 (Dact1) scaffold proteins cooperatively regulate the Van Gogh-like 2 (Vangl2) four-pass transmembrane protein and planar cell polarity (PCP) pathway during embryonic development in mice. (United States)

    Yang, XiaoYong; Cheyette, Benjamin N R


    The planar cell polarity (PCP) pathway is a conserved non-canonical (β-catenin-independent) branch of Wnt signaling crucial to embryogenesis, during which it regulates cell polarity and polarized cell movements. Disruption of PCP components in mice, including Vangl2 and Dact1, results in defective neural tube closure and other developmental defects. Here, we show that Sestd1 is a novel binding partner of Vangl2 and Dact1. The Sestd1-Dact1 interface is formed by circumscribed regions of Sestd1 (the carboxyl-terminal region) and Dact1 (the amino-terminal region). Remarkably, we show that loss of Sestd1 precisely phenocopies loss of Dact1 during embryogenesis in mice, leading to a spectrum of birth malformations, including neural tube defects, a shortened and/or curly tail, no genital tubercle, blind-ended colons, hydronephrotic kidneys, and no bladder. Moreover, as with Dact1, a knock-out mutation at the Sestd1 locus exhibits reciprocal genetic rescue interactions during development with a semidominant mutation at the Vangl2 locus. Consistent with this, examination of Wnt pathway activities in Sestd1 mutant mouse embryonic tissue reveals disrupted PCP pathway biochemistry similar to that characterized in Dact1 mutant embryos. The Sestd1 protein is a divergent member of the Trio family of GTPase regulatory proteins that lacks a guanine nucleotide exchange factor domain. Nonetheless, in cell-based assays the Sestd1-Dact1 interaction can induce Rho GTPase activation. Together, our data indicate that Sestd1 cooperates with Dact1 in Vangl2 regulation and in the PCP pathway during mammalian embryonic development.

  11. Central bank Financial Independence


    J.Ramon Martinez-Resano


    Central bank independence is a multifaceted institutional design. The financial component has been seldom analysed. This paper intends to set a comprehensive conceptual background for central bank financial independence. Quite often central banks are modelled as robot like maximizers of some goal. This perspective neglects the fact that central bank functions are inevitably deployed on its balance sheet and have effects on its income statement. A financially independent central bank exhibits ...

  12. NIDDK Central Repository (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  13. Central Neuropathic Pain Syndromes. (United States)

    Watson, James C; Sandroni, Paola


    Chronic pain is common in patients with neurologic complications of a central nervous system insult such as stroke. The pain is most commonly musculoskeletal or related to obligatory overuse of neurologically unaffected limbs. However, neuropathic pain can result directly from the central nervous system injury. Impaired sensory discrimination can make it challenging to differentiate central neuropathic pain from other pain types or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring recognition of its association with a past neurologic injury. This review focuses on unique clinical features that help distinguish central neuropathic pain. The most common clinical central pain syndromes-central poststroke pain, multiple sclerosis-related pain, and spinal cord injury-related pain-are reviewed in detail. Recent progress in understanding of the pathogenesis of central neuropathic pain is reviewed, and pharmacological, surgical, and neuromodulatory treatments of this notoriously difficult to treat pain syndrome are discussed.

  14. Central venous catheter - flushing (United States)

    ... during cancer treatment Bone marrow transplant - discharge Central venous catheter - dressing change Peripherally inserted central catheter - flushing Sterile technique Surgical wound care - open Review Date 9/22/2016 Updated by: ...

  15. Role of hydrogen bonding in ligand interaction with the N-methyl-D-aspartate receptor ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Leeson, P.D.; Carling, R.W.; James, K.; Smith, J.D.; Moore, K.W.; Wong, E.H.; Baker, R. (Merck Sharp Laboratory, Harlow, Essex (England))


    Displacement of (3H)MK-801 (dizocilpine, 1) binding to rat brain membranes has been used to evaluate the affinities of novel dibenzocycloalkenimines related to 1 for the ion channel binding site (also known as the phencyclidine or PCP receptor) on the N-methyl-D-aspartate (NMDA) subtype of excitory amino acid receptor. In common with many other agents having actions in the central nervous system, these compounds contain a hydrophobic aromatic moiety and a basic nitrogen atom. The conformational rigidity of these ligands provides a unique opportunity to evaluate the importance of specific geometrical properties that influence active-site recognition, in particular the role of the nitrogen atom in hydrogen-bonding interactions. The relative affinities (IC50s) of hydrocarbon-substituted analogues of 1 and ring homologated cyclooctenimines illustrate the importance of size-limited hydrophobic binding of both aryl rings and of the quaternary C-5 methyl group. Analysis of the binding of a series of the 10 available structurally rigid dibenzoazabicyclo(x.y.z)alkanes, by using molecular modeling techniques, uncovered a highly significant correlation between affinity and a proposed ligand-active site hydrogen bonding vector (r = 0.950, p less than 0.001). These results are used to generate a pharmacophore of the MK-801 recognition site/PCP receptor, which accounts for the binding of all of the known ligands.

  16. Central Laboratories Services (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  17. Central Pain Syndrome (United States)

    ... or hands. Central pain syndrome often begins shortly after the causative injury or damage, but may be delayed by months or even years, especially if it is related to post-stroke pain. × Definition Central pain syndrome is a neurological ...

  18. Central centrifugal cicatricial alopecia

    Directory of Open Access Journals (Sweden)

    Collin Blattner


    Full Text Available Central centrifugal cicatricial alopecia is a common cause of progressive permanent apical alopecia. This unique form of alopecia includes entities previously know as "hot comb alopecia," "follicular degeneration syndrome," "pseudopelade" in African Americans and "central elliptical pseudopelade" in Caucasians. The etiology appears to be multifactorial and the condition occurs in all races.

  19. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.


    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the opt

  20. Optimal central bank transparency

    NARCIS (Netherlands)

    van der Cruijsen, C.A.B.; Eijffinger, S.C.W.; Hoogduin, L.H.


    Should central banks increase their degree of transparency any further? We show that there is likely to be an optimal intermediate degree of central bank transparency. Up to this optimum more transparency is desirable: it improves the quality of private sector inflation forecasts. But beyond the opt

  1. The central peak revisited

    Energy Technology Data Exchange (ETDEWEB)

    Shirane, G.


    The central peak in SrTiO{sub 3} was first observed by Riste and his collaborators in 1971. This was one of the key discoveries leading to an understanding of the dynamics of phase transitions. The most recent discovery of two length scales in SrTiO{sub 3} motivated a reinvestigation of the soft phonon and associated central peak by neutron scattering. These recent experiments shed new light on the nature of the central peak. It is now well established to be strongly sample dependent and it originates from defects in bulk crystals.

  2. Imaging central pain syndromes. (United States)

    Veldhuijzen, Dieuwke S; Greenspan, Joel D; Kim, Jong H; Coghill, Robert C; Treede, Rolf-Detlef; Ohara, Shinji; Lenz, Frederick A


    Anatomic, functional, and neurochemical imaging studies have provided new investigative tools in the study of central pain. High-resolution imaging studies allow for precise determination of lesion location, whereas functional neuroimaging studies measure pathophysiologic consequences of injury to the central nervous system. Additionally, magnetic resonance spectroscopy evaluates lesion-induced neurochemical changes in specific brain regions that may be related to central pain. The small number of studies to date precludes definitive conclusions, but the recent findings provide information that either supports or refutes current hypotheses and can serve to generate new ideas.

  3. Reduction transformation and biochemistry mechanisms of PCP in latosol under addition of exogenous nutrients%外加营养源作用下砖红壤中五氯酚还原转化的生物化学作用机制

    Institute of Scientific and Technical Information of China (English)

    陈曼佳; 刘承帅; 吴伟坚; 童辉; 李芳柏


      采用室内培养实验研究外加乳酸和蒽醌-2,6-磺酸钠等营养源条件下,玄武岩砖红壤中五氯酚的还原转化动力学与微生物群落结构变化.结果表明,玄武岩砖红壤中五氯酚的还原转化一级动力学常数为4.5×10−3 d−1;添加乳酸或同时添加乳酸和AQDS,五氯酚的还原转化速率显著提高,其一级动力学常数分别为7.3×10−3 d−1和14.3×10−3 d−1.循环伏安试测结果表明,添加乳酸和 AQDS 促进了砖红壤中活性亚铁的生成,并显著降低体系的氧化半反应峰电位.末端限制性片段长度多态性分析结果表明,添加五氯酚、乳酸和 AQDS 显著影响微生物群落结构,土壤微生物多样性显著下降;添加乳酸时,体系中微生物优势种群为梭菌,存在少量的具有铁还原能力的希瓦氏菌,未发现脱氯菌.因此,玄武岩砖红壤中五氯酚的还原转化主要是通过铁还原菌介导生成吸附态Fe(II)引起的活性亚铁还原脱氯机制.%In this study, we investigated the reductive transformation of PCP and soil bacteria community structures in basalt latosol under addition of lactate and AQDS. Results showed that PCP reductive transformation occurred with k value of 4.5×10−3 d-1 in basalt latosol. The addition of lactate and AQDS led to the enhanced rates of PCP transformation with k value of 7.3×10−3 d−1 and 14.3 × 10−3 d−1, respectively. Cyclic voltammetry test results showed that the addition of lactate and AQDS led to the enhanced rates of active Fe(Ⅱ)species generation in basalt latosol and significantly enhance the reduction potential in the system. T-RFLP analysis results showed that the microbial communities were affected by the addition of PCP, lactate and AQDS and the microbial diversity was significantly decreased. Clostridum was the dominant population in the system after the addition of lactate. There were also small amounts of Shewanella which has iron-reducing ability but

  4. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E;


    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities ...

  5. Central Asian Republic Info (United States)

    US Agency for International Development — CAR Info is designed and managed by the Central Asian Republic Mission to fill in the knowledge and reporting gaps in existing agency systems for that Mission. It...

  6. Central nervous system (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  7. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E


    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  8. "Central Station" Londonis

    Index Scriptorium Estoniae


    Londoni galeriis Milch seitsme läti, leedu ja eesti kunstniku projekt "Central Station". Kuraatorid Lisa Panting, Sally Tallant. Eestist osalevad Hanno Soans (Catarina Campinoga koostöös valminud video), Kiwa, Kai Kaljo

  9. Central Station Design Options

    DEFF Research Database (Denmark)


    The purpose of EDISON Work Package 4.1 is the evaluation of possible Central (charging) Stations design options for making possible the public charging of Electric Vehicles (EVs). A number of scenarios for EVs are assessed, with special emphasis on the options of Fast Charging and Battery Swapping....... The work identifies the architecture, sizing and siting of prospective Central Stations in Denmark, which can be located at shopping centers, large car parking lots or gas stations. Central Stations are planned to be integrated in the Danish distribution grid. The Danish island of Bornholm, where a high.......g. due to vandalism, the charge supply circuit is disconnected. More electrical vehicles on the market are capable today of quick charging up to 50 kW power level. The feasibility of Central Stations with fast charging/swapping option, their capacity, design, costs and grid impact, as well as battery...

  10. Gangs in Central America (United States)


    Citizen Security held in July 2008 indicated that Guatemala now has the second highest murder rate in Central America (roughly 45 per 100,000 regional security forces.48 In recent years, the U.S. Southern Command has taken a leading role in discussing the problem of citizen security in...the results CRS-19 51 “Memo: The Merida Initiative and Citizen Security in Mexico and Central America,” Washington Office on Latin America, March 2008

  11. Outsourcing central banking

    DEFF Research Database (Denmark)

    Khoury, Sarkis Joseph; Wihlborg, Clas


    The literature on Currency Boards (CB) stops at the water edge in terms of dealing with the totality of the functions of a central bank. Monetary policy, and banking supervisioncan be "outsourced" in an open economy with substantial foreign direct investment (FDI)in the banking sector if political...... the feasibility of, and constraints on, outsourcing of central bank functions. A brief discussion of the Argentinian experience is used for contrast.Key words: Currency Board, Foreign Banks, Supervision, Regional Integration,outsourcing....


    Energy Technology Data Exchange (ETDEWEB)

    ROMINE, L.D.


    A systematic approach to closure planning is being implemented at the Hanford Site's Central Plateau to help achieve the goal of closure by the year 2035. The overall objective of Central Plateau remediation is to protect human health and the environment from the significant quantity of contaminated material that resulted from decades of plutonium production in support of the nation's defense. This goal will be achieved either by removing contaminants or placing the residual contaminated materials in a secure configuration that minimizes further migration to the groundwater and reduces the potential for inadvertent intrusion into contaminated sites. The approach to Central Plateau cleanup used three key concepts--closure zones, closure elements, and closure process steps--to create an organized picture of actions required to complete remediation. These actions were merged with logic ties, constraints, and required resources to produce an integrated time-phased schedule and cost profile for Central Plateau closure. Programmatic risks associated with implementation of Central Plateau closure were identified and analyzed. Actions to mitigate the most significant risks are underway while high priority remediation projects continue to make progress.

  13. The Naive Central Banker

    Directory of Open Access Journals (Sweden)

    Marcelo de Carvalho Griebeler


    Full Text Available There has been in some countries a trend of assigning other functions to central banks besides price stability. The most suggested function to be added to monetary authority’s obligations is to pursue economic growth or full employment. In this paper we characterize the behavior and analyse the optimal monetary policy of, what we call, a naive central banker. We describe the naive behavior as one that does face the inflation-unemployment trade-off, but it tries to minimize both variables simultaneously. Our findings, both under discretion and commitment, indicate that the naive central banker delivers lower expected inflation and inflation variance than the benchmark behavior whenever the economy is rigid enough. However, the degree of conservativeness also affects this result, such that the less conservative the naive policymaker, the more rigidity is necessary.

  14. SOCRATES Invades Central Europe

    Directory of Open Access Journals (Sweden)

    Joseph Slowinski


    Full Text Available The objective of this article is to explore the current reality faced by higher education students in Central and Eastern Europe and to draw out the implications of this current reality for policy makers in the future. In the article, I explore the influence of transnational corporations' training programs on education as it currently pertains to Central and Eastern European higher education and employment. In addition, multinational corporate entities exercise influence on European Union policy through the role of lobby organizations and activities. I explore the influence of these practices on education with an emphasis on the emerging importance of Western language skills. In addition, I focus on the European Union and its efforts to expand into Central and Eastern Europe in order to provide a focal point for analysis.

  15. Central Bank independence

    Directory of Open Access Journals (Sweden)

    Vasile DEDU


    Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

  16. Several Centuries of Centrality


    Roth, Dana L.


    As Carolyn Bertozzi mentioned in her inaugural editorial, the relationship of “Central Science” to “Chemistry” became popularized over 40 years ago with the publication of the first edition of Brown and LeMay’s Chemistry: The Central Science, now in its 13th edition. Yet as late as 2003, Prof. Sason Shaik at The Hebrew University claimed “popularization of chemistry remains scant.” He goes on to share [his] “own experience of popularizing chemistry by delivering the following universal messag...

  17. Glueballs A central mystery

    CERN Document Server

    Close, Francis Edwin


    Glueball candidates and qqbar mesons have been found to be produced with different momentum and angular dependences in the central region of pp collisions. This talk illustrates this phenomenon and explains the phi and t dependences of mesons with JPC = 0++,0-+, 1++, 2++ and 2-+. For production of 0++ and 2++ mesons the analysis reveals a systematic behaviour in the data that appears to distinguish between qqbar and non-qqbar or glueball candidates. An explanation is given for the absence of 0-+ glueball candidates in central production at present energies and the opportunity for their discovery at RHIC is noted.

  18. Retiring the central executive. (United States)

    Logie, Robert H


    Reasoning, problem solving, comprehension, learning and retrieval, inhibition, switching, updating, or multitasking are often referred to as higher cognition, thought to require control processes or the use of a central executive. However, the concept of an executive controller begs the question of what is controlling the controller and so on, leading to an infinite hierarchy of executives or "homunculi". In what is now a QJEP citation classic, Baddeley [Baddeley, A. D. (1996). Exploring the central executive. Quarterly Journal of Experimental Psychology, 49A, 5-28] referred to the concept of a central executive in cognition as a "conceptual ragbag" that acted as a placeholder umbrella term for aspects of cognition that are complex, were poorly understood at the time, and most likely involve several different cognitive functions working in concert. He suggested that with systematic empirical research, advances in understanding might progress sufficiently to allow the executive concept to be "sacked". This article offers an overview of the 1996 article and of some subsequent systematic research and argues that after two decades of research, there is sufficient advance in understanding to suggest that executive control might arise from the interaction among multiple different functions in cognition that use different, but overlapping, brain networks. The article concludes that the central executive concept might now be offered a dignified retirement.

  19. Central Nervous System Tuberculosis


    Bano, Shahina; Chaudhary, Vikas; Yadav, Sachchidanand


    Central nervous system tuberculosis is a rare presentation of active tuberculosis and accounts for about 1% of cases (1). The three clinical categories include meningitis, intracranial tuberculomas, and spinal tuberculous arachnoiditis. We report a case of a young man who presented with active pulmonary tuberculosis in addition to tuberculous meningitis and the presence of numerous intracranial tuberculomas.

  20. Central venous line - infants (United States)

    A central venous line (CVL) is a long, soft, plastic tube that is put into a large vein in the chest. WHY IS A CVL USED? A CVL is often put in when a baby cannot get a ... (MCC). A CVL can be used to give nutrients or medicines to a ...

  1. CMS Central Hadron Calorimeter


    Budd, Howard S.


    We present a description of the CMS central hadron calorimeter. We describe the production of the 1996 CMS hadron testbeam module. We show the results of the quality control tests of the testbeam module. We present some results of the 1995 CMS hadron testbeam.

  2. Ecodesign in Central America

    NARCIS (Netherlands)

    Crul, M.R.M.


    This PhD thesis describes and analyses the change process started by the Ecodesign project in Central America, executed between 1998 and 2002. The project started using the concept and praxis developed in Europe. Nine ecodesign projects were performed in industry, and ecodesign was introduced to cou

  3. Central nervous system tuberculosis. (United States)

    Torres, Carlos; Riascos, Roy; Figueroa, Ramon; Gupta, Rakesh K


    Tuberculosis (TB) has shown a resurgence in nonendemic populations in recent years and accounts for 8 million deaths annually in the world. Central nervous system involvement is one of the most serious forms of this infection, acting as a prominent cause of morbidity and mortality in developing countries. The rising number of cases in developed countries is mostly attributed to factors such as the pandemic of acquired immunodeficiency syndrome and increased migration in a globalized world. Mycobacterium TB is responsible for almost all cases of tubercular infection in the central nervous system. It can manifest in a variety of forms as tuberculous meningitis, tuberculoma, and tubercular abscess. Spinal infection may result in spondylitis, arachnoiditis, and/or focal intramedullary tuberculomas. Timely diagnosis of central nervous system TB is paramount for the early institution of appropriate therapy, because delayed treatment is associated with severe morbidity and mortality. It is therefore important that physicians and radiologists understand the characteristic patterns, distribution, and imaging manifestations of TB in the central nervous system. Magnetic resonance imaging is considered the imaging modality of choice for the study of patients with suspected TB. Advanced imaging techniques including magnetic resonance perfusion and diffusion tensor imaging may be of value in the objective assessment of therapy and to guide the physician in the modulation of therapy in these patients.

  4. Central Dogma Goes Digital. (United States)

    Lin, Yihan; Elowitz, Michael B


    In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology.

  5. Multicultural Central Asia. (United States)

    Boyle, Eric D.

    This article addresses the multicultural aspect of Central Asia in response to the discussion on diversity in U.S. classrooms. Many areas of the world are more diverse than the U.S., and these areas experience successes and failures with many of the same issues the U.S. is currently struggling with. Comparing the U.S. diversity debate with similar…

  6. Channeling the Central Dogma. (United States)

    Calabrese, Ronald L


    How do neurons and networks achieve their characteristic electrical activity, regulate this activity homeostatically, and yet show population variability in expression? In this issue of Neuron, O'Leary et al. (2014) address some of these thorny questions in this theoretical analysis that starts with the Central Dogma.

  7. Company activities - central region

    Energy Technology Data Exchange (ETDEWEB)

    Ayling, G.


    The first section of the article gives an overview of exploration and new developments in the field of gold, nickel, diamond and opal mining in central Queensland. The second part looks at coal, coal seam gas and petroleum exploration and development projects in the area. 1 fig.

  8. Testing for central symmetry

    NARCIS (Netherlands)

    Einmahl, John; Gan, Zhuojiong


    Omnibus tests for central symmetry of a bivariate probability distribution are proposed. The test statistics compare empirical measures of opposite regions. Under rather weak conditions, we establish the asymptotic distribution of the test statistics under the null hypothesis; it follows that they a

  9. Central areolar choroidal dystrophy.

    NARCIS (Netherlands)

    Boon, C.J.F.; Klevering, B.J.; Cremers, F.P.M.; Zonneveld-Vrieling, M.N.; Theelen, T.; Hollander, A.I. den; Hoyng, C.B.


    OBJECTIVE: To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD). DESIGN: Retrospective case series study. PARTICIPANTS: One hundred three patients with CACD from the Netherlands. METHODS

  10. Induced, endogenous and exogenous centrality


    Everett, Martin G.; Stephen P. Borgatti


    Centrality measures are based upon the structural position an actor has within the network. Induced centrality, sometimes called vitality measures, take graph invariants as an overall measure and derive vertex level measures by deleting individual nodes or edges and examining the overall change. By taking the sum of standard centrality measures as the graph invariant we can obtain measures which examine how much centrality an individual node contributes to the centrality of the other nodes in...

  11. Do Central Banks Need Capital?


    Peter Stella


    Central banks may operate perfectly well without capital as conventionally defined. A large negative net worth, however, is likely to compromise central bank independence and interfere with its ability to attain policy objectives. If society values an independent central bank capable of effectively implementing monetary policy, recapitalization may become essential. Proper accounting practice in determining central bank profit or loss and rules governing the transfer of the central bank’s ope...

  12. Métodos de auxílio multicritério à decisão aplicados a problemas de PCP: mapeamento da produção em periódicos publicados no Brasil Multicriteria decision aid methods applied to PPC problems: a mapping of papers published in Brazilian journals

    Directory of Open Access Journals (Sweden)

    Dey Salvador Sanchez Rodriguez


    Full Text Available O presente trabalho tem por objetivo estabelecer um mapeamento da produção científica divulgada em importantes periódicos publicados no Brasil sobre a aplicação de Métodos de Auxílio Multicritério à Decisão (AMD à modelagem de problemas de Planejamento e Controle da Produção. O mapeamento contemplou 32 artigos, que foram selecionados criteriosamente, tendo como base a lista de periódicos científicos oferecida no Scielo e em importantes sociedades científicas brasileiras no âmbito da Engenharia de Produção. Os resultados permitiram indicar, entre outros aspectos, os periódicos que mais publicam neste contexto, os métodos de AMD mais usados nesta interface, os setores de produção nos quais as aplicações ocorreram e os tópicos de PCP mais abordados. Também foram destacados os aspectos de PCP que ainda carecem de estudos que envolvam métodos multicritério.The objective of this study is to map the Brazilian scientific production based on Brazilian journal publications on the implementation of Multicriteria Decision Aid (MCDA to model Production Planning and Control problems. It consisted of 32 papers that were systematically selected from journals indexed in the Scielo database and also from a list of journals suggested by major Brazilian Industrial Engineering research societies. The results revealed, among other aspects, the journals that publish the most on this topic, the most often used MCDA methods in this interface, the production sectors in which the applications took place, and the most commonly discussed PPC topics. This paper also highlights the PPC aspects that need further research including MCDA methods.

  13. Central simple Poisson algebras

    Institute of Scientific and Technical Information of China (English)

    SU Yucai; XU Xiaoping


    Poisson algebras are fundamental algebraic structures in physics and symplectic geometry. However, the structure theory of Poisson algebras has not been well developed. In this paper, we determine the structure of the central simple Poisson algebras related to locally finite derivations, over an algebraically closed field of characteristic zero.The Lie algebra structures of these Poisson algebras are in general not finitely-graded.

  14. Central corneal abscess. (United States)

    van Bijsterveld, O P


    Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae.

  15. FNAL central email systems

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Jack; Lilianstrom, Al; Pasetes, Ray; Hill, Kevin; /Fermilab


    The FNAL Email System is the primary point of entry for email destined for an employee or user at Fermilab. This centrally supported system is designed for reliability and availability. It uses multiple layers of protection to help ensure that: (1) SPAM messages are tagged properly; (2) All mail is inspected for viruses; and (3) Valid mail gets delivered. This system employs numerous redundant subsystems to accomplish these tasks.

  16. Centrality Measures in Networks

    CERN Document Server

    Bloch, Francis; Tebaldi, Pietro


    We show that although the prominent centrality measures in network analysis make use of different information about nodes' positions, they all process that information in an identical way: they all spring from a common family that are characterized by the same simple axioms. In particular, they are all based on a monotonic and additively separable treatment of a statistic that captures a node's position in the network.

  17. Distributed Assessment of Network Centrality

    CERN Document Server

    Wehmuth, Klaus


    We propose a method for the Distributed Assessment of Network CEntrality (DANCE) in complex networks. DANCE attributes to each node a volume-based centrality computed using only localized information, thus not requiring knowledge of the full network topology. We show DANCE is simple, yet efficient, in assessing node centrality in a distributed way. Our proposal also provides a way for locating the most central nodes, again using only the localized information at each node. We also show that the node rankings based on DANCE's centrality and the traditional closeness centrality correlate very well. This is quite useful given the vast potential applicability of closeness centrality, which is however limited by its high computational costs. We experimentally evaluate DANCE against a state-of-the-art proposal to distributively assess network centrality. Results attest that DANCE achieves similar effectiveness in assessing network centrality, but with a significant reduction in the associated costs for practical ap...

  18. Central core disease

    Directory of Open Access Journals (Sweden)

    Jungbluth Heinz


    Full Text Available Abstract Central core disease (CCD is an inherited neuromuscular disorder characterised by central cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown but the condition is probably more common than other congenital myopathies. CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle; orthopaedic complications are common and malignant hyperthermia susceptibility (MHS is a frequent complication. CCD and MHS are allelic conditions both due to (predominantly dominant mutations in the skeletal muscle ryanodine receptor (RYR1 gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1. Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanism(s. The diagnosis of CCD is based on the presence of suggestive clinical features and central cores on muscle biopsy; muscle MRI may show a characteristic pattern of selective muscle involvement and aid the diagnosis in cases with equivocal histopathological findings. Mutational analysis of the RYR1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to anticipate susceptibility to potentially life-threatening reactions to general anaesthesia. Further evaluation of the underlying molecular mechanisms may provide the basis for future rational pharmacological treatment. In the majority of patients, weakness is static or only slowly progressive, with a favourable long-term outcome.

  19. West and Central Africa. (United States)

    Lydie, N; Robinson, N J


    This article reviews scientific and other literature during the 1990s that links migration and mobility with the spread of sexually transmitted diseases (STDs), including HIV/AIDS. The focus is on key population groups linked to the spread of HIV and STDs in West and Central Africa: migrant laborers, truck drivers, itinerant traders, commercial sex workers (CSWs), and refugees. Countries with high emigration and immigration tend to have high levels of HIV infection, with the exception of Senegal. The main destination of immigrants are Senegal, Nigeria, and Cote d'Ivoire in West Africa and Cameroon, Congo, Gabon, and Congo in Central Africa. The risk of infection and the spread of HIV is variable among migrants. There is little in the literature that substantiates hypotheses about the strong association between migration and HIV-positive status. Information is needed on the duration, frequency of return visits, living conditions, sexual activities with multiple partners, and information before departure, along the routes, at final destination, and at the time of returns. Action-based research in five West African countries (Burkina Faso, Cote d'Ivoire, Mali, Niger, and Senegal) should produce results in late 1998. Comparable studies in Central Africa are unknown. Regional studies should be complemented by local studies. Prevention would benefit from studies on the relative size of these five population groups by geographic location.

  20. Central African Republic. (United States)


    Focus in this discussion of the Central African Republic is on: geography; the people; history and political conditions; government; the economy; foreign relations; and relations with the US. The population of the Central African Republic totaled 2.7 million in 1985 with an annual growth rate of 2.8%. The infant mortality rate is 134/1000 with life expectancy at 49 years. The Central African Republic is at almost the precise center of Africa, about 640 km from the nearest ocean. More than 70% of the population live in rural areas. There are more than 80 ethnic groups, each with its own language. The precolonial history of the area was marked by successive waves of migration, of which little is known. These migrations are responsible for the complex ethnic and linguistic patterns today. United with Chad in 1906, it formed the Oubangui-Chari-Chad colony. In 1910, it became 1 of the 4 territories of the Federation of French Equatorial Africa, along with Chad, Congo, and Gabon. After World War II, the French Constitution of 1946 inaugurated the first of a series of reforms that led eventually to complete independence for all French territories in western and equatorial Africa. The nation became an autonomous republic within the newly established French Community on December 1, 1958, and acceded to complete independence as the Central Africa Republic on August 13, 1960. The government is made up of the executive and the judicial branches. The constitution and legislature remain suspended. All executive and legislative powers, as well as judicial oversight, are vested in the chief of state. The Central African Republic is 1 of the world's least developed countries, with an annual per capita income of $310. 85% of the population is engaged in subsistence farming. Diamonds account for nearly 1/3 of export earnings; the industrial sector is limited. The US terminated bilateral assistance programs in 1979, due to the human rights violations of the Bokassa regime, but modest

  1. Sweat Collecting Device and Methods for Use and Detection of Tampering (United States)


    Cocaine Metabolite, Amphetamines , Opiates, Cannabinoid and Cannabinoid Metabolites, and 18 Phencyclidine (PCP) Through the Skin. PharmChem...Laboratories, Inc. Menlo Park, CA. 1999. 19 An article by P. Kintz , Drug Testing in Addicts: a Comparison between Urine , Sweat, 20 and Hair, Therapeutic Drug...Enzyme Immunoassay Validation for Qualitative Detection of Cocaine in Sweat, 7 Clinical Chemistry, 42(1) (1996) 34-38 states that the transparent film

  2. Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias.



    Quantitative receptor autoradiography was used to measure muscarinic cholinergic, benzodiazepine, kainate, phencyclidine (PCP), N-methyl-D-aspartate (NMDA) (measured in Tris acetate), quisqualate-sensitive, non-quisqualate-sensitive and total glutamate (measured in Tris chloride buffer) binding sites in adjacent sections of the hippocampal region of 10 Alzheimer's disease, nine control, and six demented, non-Alzheimer's disease postmortem human brains. The measurements were compared to the nu...

  3. Central venous catheter - dressing change (United States)

    ... during cancer treatment Bone marrow transplant - discharge Central venous catheter - flushing Peripherally inserted central catheter - flushing Sterile technique Surgical wound care - open Review Date 9/17/2016 Updated by: ...

  4. Central effects of fingolimod. (United States)

    Cruz, Vítor T; Fonseca, Joaquim


    Introduccion. El fingolimod, un modulador del receptor de la esfingosina-1-fosfato (S1P) dotado de un mecanismo de accion novedoso, fue el primer tratamiento oral aprobado para la esclerosis multiple remitente recurrente. Su union a los receptores S1P1 de los linfocitos promueve la retencion selectiva de los linfocitos T virgenes y de memoria central en los tejidos linfoides secundarios, lo que impide su salida hacia el sistema nervioso central (SNC). Asimismo, el fingolimod atraviesa con facilidad la barrera hematoencefalica, y diversos estudios le atribuyen un efecto neuroprotector directo en el SNC. Objetivo. Revisar la informacion disponible acerca de los efectos centrales del fingolimod. Desarrollo. El desequilibrio entre los procesos lesivos y reparadores constituye un reflejo de la desmielinizacion cronica, la degeneracion axonal y la gliosis, y parece contribuir a la discapacidad que la esclerosis multiple acarrea. La facilidad con la que el fingolimod atraviesa la barrera hematoencefalica le permite actuar directamente sobre los receptores S1P localizados en las celulas del SNC. Una vez en el interior del SNC, ocupa los receptores S1P de los oligodendrocitos y de sus celulas precursoras, de los astrocitos, los microgliocitos y las neuronas, fomentando la remielinizacion, la neuroproteccion y los procesos endogenos de regeneracion. La eficacia evidenciada en los ensayos clinicos concuerda con un mecanismo de accion que incluiria efectos directos sobre las celulas del SNC. Conclusiones. Los datos disponibles indican que la eficacia del fingolimod en el tratamiento de la esclerosis multiple se debe a su ambivalencia como molecula inmunomoduladora y moduladora directa de los receptores S1P del SNC. Tanto es asi que estudios recientes le atribuyen efectos neuroprotectores en varios modelos que suscitan expectativas en torno a su posible aplicacion terapeutica en la enfermedad de Alzheimer, el paludismo cerebral y el neuroblastoma, asi como en la neuroproteccion

  5. [Central anticholinergic syndrome]. (United States)

    Fernández Urretavizcaya, P; Cenoz Osinaga, J C; Jáuregui Garía, M L; Gállego Culleré, J


    Two new cases of anticolinergic central syndrome are described. The first case, a 8 year old girl, suffered a severe encefalopathy after topical application of mydriatic cholirio as an aid in a rutine study of ocular refraction. The second case, 67 year old man presented a severe neurological picture after accidental intake of a silvester plantground (Atropa belladonna). His neurological condition returned quickly to normal whith administration of physostigmine. Differents aspects of the etiology, clinical picture and diagnosis are discussed with special emphasis in patients with delirium or acute confusional states. Finally, attention is drawn in the necessity of a properly use of anticholinergic drugs overcoat in aged or children.

  6. Central osteosclerosis with trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Wakeling, Emma L.; Brady, Angela F. [North West Thames Regional Genetics Service, Kennedy-Galton Centre, Level 8 V, North West London Hospitals NHS Trust, Watford Road, HAI 3UJ, Harrow, Middlesex (United Kingdom); Cruwys, Michele [Department of Paediatrics, Hillingdon Hospital, Hillingdon, Middlesex (United Kingdom); Suri, Mohnish [Clinical Genetics Service, City Hospital, Nottingham (United Kingdom); Aylett, Sarah E. [Neurosciences Unit, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom); Hall, Christine [Department of Radiology, Great Ormond Street Hospital for Children NHS Trust, London (United Kingdom)


    Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder associated with defects in nucleotide excision repair. We report a 7-year-old boy with TTD due to mutation in the XPD gene. The patient has classic features of this condition, including brittle, sulphur-deficient hair, ichthyosis, growth retardation and developmental delay. In addition, he has radiological evidence of progressive central osteosclerosis. Although similar radiological findings have previously been reported in a small number of patients, this association is not widely recognised. We review the radiological findings in this and other similar cases and discuss the natural history of these bony changes. (orig.)

  7. Centralized vs. De-centralized Multinationals and Taxes

    DEFF Research Database (Denmark)

    Nielsen, Søren Bo; Raimondos-Møller, Pascalis; Schjelderup, Guttorm


    The paper examines how country tax differences affect a multinational enterprise's choice to centralize or de-centralize its decision structure. Within a simple model that emphasizes the multiple conflicting roles of transfer prices in MNEs - here, as a strategic pre-commitment device and a tax...... manipulation instrument -, we show that (de-)centralized decisions are more profitable when tax differentials are (small) large.Keywords: Centralized vs. de-centralized decisions, taxes, MNEs.JEL-Classification: H25, F23, L23....

  8. The role of the central histaminergic system on schizophrenia. (United States)

    Ito, Chihiro


    Schizophrenia resistant to treatments with D(2) antagonists is thought to have the changes of extradopaminergic systems. In addition, histamine has been suggested to be a neurotransmitter in the mammalian brain that regulates many brain functions. We have recently found evidence of the role of brain histamine in schizophrenia in basic and clinical studies. Methamphetamine-induced behavioral sensitization, which has been well established as the animal model of schizophrenia, induced the enhanced histamine release, and histamine agonists inhibited the development of behavioral sensitization. As another animal model of schizophrenia, phencyclidine also increased the histamine release. In clinical studies, the levels of N-tele-methylhistamine, a major brain histamine metabolite, were elevated in the cerebrospinal fluid of schizophrenics. Moreover, H(1) receptor binding sites decreased in schizophrenics. Many atypical antipsychotics also increased histamine turnovers. Therefore, the dysfunction of the histamine neuron system may participate in the extradopaminergic brain dysfunction of schizophrenia, and histamine agents may improve the refractory schizophrenia.

  9. Central centrifugal cicatricial alopecia. (United States)

    Whiting, David A; Olsen, Elise A


    A progressive scarring alopecia of the central scalp is commonly seen in young to middle-aged females of African descent. It usually starts at the vertex or mid top of the scalp and gradually spreads centrifugally, hence, the unifying term of central centrifugal cicatricial alopecia. The clinical pattern is suggestive of female pattern alopecia, but a lack of follicular pores indicative of scarring is present. It can progress for years before slowly burning out. The etiology is unknown but genetic factors may be important. It is often associated with a history of traumatic hairstyling involving heat, traction, and chemicals. However, most patients of African descent without this disorder have similar styling habits. Nonetheless, avoidance of physical and chemical trauma to the scalp hair, the use of suitable shampoos and conditioners, and the encouragement of natural hairstyles may be helpful. Any infection should be treated. Topical or intralesional corticosteroids and systemic antibiotics may be useful and topical minoxidil should be tried with the hope of preventing further scarring and encouraging regrowth of recovering follicles. Current research into the etiology of this disorder will help to foster much-needed clinical trials of therapeutic agents.

  10. Central Sumatra enjoys success

    Energy Technology Data Exchange (ETDEWEB)

    Wongsosantiko, A.


    The Sihapas group contains the most prolific oil producing zones in the Central Sumatra Basin. It represents the transgressive, coarse clastic sequence deposited during the early Miocene. Some of these sandstone grade laterally into siltstones and shales of the Telisa Formation, believed to be a major source of rock for Central Sumatra oil. Recent exploratory wells drilled between the mountain front and coastal plain areas have provided more data for stratigraphic studies. These have resulted in subdivision of the lower Miocene transgressive sequence into discrete rock-stratigraphic units. The former Sihapas Formation has subsequently been elevated to group rank and now consists of several formations with the Duri Formation as the uppermost sand unit. This study covers Caltex's areas of operation, which includes the area between the Kampar River of the south, the Barumum River to the north, the Malacca Straits to the east, and the Barisan Mt. to the west. A basic map shows the regional scene, while a stratigraphic chart shows the lithology.

  11. en los pivotes centrales

    Directory of Open Access Journals (Sweden)

    Reynaldo Roque Rodés


    Full Text Available Se hace una revisión y comentarios sobre las ventajas y limitantes del empleo del LEPA (Low Enery Precision Aplication en los sistemas de riego de pivotes centrales. Estos sistemas o filosofía de manejo del agua para condiciones de escasez o mala calidad del líquido es una alternativa viable para la producción de alimentos. Introducida en la década del 80 en las planicies del sur de Texas, donde la alta evaporación del agua y la necesidad de regar grandes áreas con pivotes centrales obligaba a la búsqueda de una alternativa para incrementar al máximo la eficiencia de aplicación del riego. Aún en fase de estudio e introducción en Cuba para áreas específicas, puede ser una solución de incremento de los rendimientos de los cultivos, empleando menos agua y aguas con calidad limitada

  12. Centrality Measures in Urban Networks

    CERN Document Server

    Crucitti, P; Porta, S; Crucitti, Paolo; Latora, Vito; Porta, Sergio


    Centrality has revealed crucial for understanding the structural order of complex relational networks. Centrality is also relevant for various spatial factors affecting human life and behaviors in cities. We present a comprehensive study of centrality distributions over geographic networks of urban streets. Four different measures of centrality, namely closeness, betweenness, straightness and information, are compared over eighteen 1-square-mile samples of different world cities. Samples are represented by primal geographic graphs, i.e. valued graphs defined by metric rather than topologic distance where intersections are turned into nodes and streets into edges. The spatial behavior of centrality indexes over the networks is investigated graphically by means of colour-coded maps. The results indicate that a spatial analysis, that we term Multiple Centrality Assessment(MCA), grounded not a single but on a set of different centrality indices, allows an extended comprehension of the city structure, nicely captu...

  13. Orden monetario y bancos centrales Monetary order and Central Banks

    Directory of Open Access Journals (Sweden)

    Aglietta Michel


    Full Text Available Con el enfoque evolucionista e institucionalista de la economía de las convenciones francesa, este trabajo analiza el surgimiento histórico de la banca central y la creación institucional del 'arte de la banca central'. El artículo estudia los modelos formales del orden monetario, la banca libre y la banca central, y analiza los eventos históricos que llevaron a que el Banco de Inglaterra inventara el arte de manejar los bancos centrales en conjunción con el aprendizaje colectivo e institucional que lo hizo posible. Aglietta muestra que la banca central no es una creación del Estado sino una creación institucional endógena al sistema de mercado.With the evolutionist and institutionalist focus of the economics of the French conventions, this paper analyzes the historical rise of the central bank and the institutional creation of the 'art of the central bank'. The article studies formal models of the monetary order, free banking and the central bank, and analyzes the historie events that led to the Bank of England inventing the art of managing the central banks, in conjunction with the collective and institutional learning that made it possible. Aglietta shows that the central bank is not a creation of the State, but rather aninstitutional creation endogenous to the market system.

  14. UA1 central detector

    CERN Multimedia

    The UA1 central detector was crucial to understanding the complex topology of proton-antiproton events. It played a most important role in identifying a handful of Ws and Zs among billions of collisions. The detector was a 6-chamber cylindrical assembly 5.8 m long and 2.3 m in diameter, the largest imaging drift chamber of its day. It recorded the tracks of charged particles curving in a 0.7 Tesla magnetic field, measuring their momentum, the sign of their electric charge and their rate of energy loss (dE/dx). Atoms in the argon-ethane gas mixture filling the chambers were ionised by the passage of charged particles. The electrons which were released drifted along an electric field shaped by field wires and were collected on sense wires. The geometrical arrangement of the 17000 field wires and 6125 sense wires allowed a spectacular 3-D interactive display of reconstructed physics events to be produced.

  15. UA2 central calorimeter

    CERN Multimedia

    The UA2 central calorimeter measured the energy of individual particles created in proton-antiproton collisions. Accurate calibration allowed the W and Z masses to be measured with a precision of about 1%. The calorimeter had 24 slices like this one, each weighing 4 tons. The slices were arranged like orange segments around the collision point. Incoming particles produced showers of secondary particles in the layers of heavy material. These showers passed through the layers of plastic scintillator, generating light which was taken by light guides (green) to the data collection electronics. The amount of light was proportional to the energy of the original particle. The inner 23 cm of lead and plastic sandwiches measured electrons and photons; the outer 80 cm of iron and plastic sandwiches measured strongly interacting hadrons. The detector was calibrated by injecting light through optical fibres or by placing a radioactive source in the tube on the bottom edge.

  16. Central Disorders of Hypersomnolence (United States)

    Khan, Zeeshan


    The central disorders of hypersomnolence are characterized by severe daytime sleepiness, which is present despite normal quality and timing of nocturnal sleep. Recent reclassification distinguishes three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are the focus of this review. Narcolepsy type 1 results from loss of hypothalamic hypocretin neurons, while the pathophysiology underlying narcolepsy type 2 and IH remains to be fully elucidated. Treatment of all three disorders focuses on the management of sleepiness, with additional treatment of cataplexy in those patients with narcolepsy type 1. Sleepiness can be treated with modafinil/armodafinil or sympathomimetic CNS stimulants, which have been shown to be beneficial in randomized controlled trials of narcolepsy and, quite recently, IH. In those patients with narcolepsy type 1, sodium oxybate is effective for the treatment of both sleepiness and cataplexy. Despite these treatments, there remains a subset of hypersomnolent patients with persistent sleepiness, in whom alternate therapies are needed. Emerging treatments for sleepiness include histamine H3 antagonists (eg, pitolisant) and possibly negative allosteric modulators of the gamma-aminobutyric acid-A receptor (eg, clarithromycin and flumazenil). PMID:26149554


    Dauvilliers, Yves; Lopez, Régis


    Central hypersomnias include narcolepsy type 1, type 2 and idiopathic hypersomnia with daytime sleepiness excessive in the foreground of the clinical symptoms. Despite major advances in our understanding of the mechanisms of the narcolepsy type 1 with a low level of hypocretin-1 in cerebrospinal fluid, its current management is only symptomatic. The current management is also only symptomatic for type 2 narcolepsy and idiopathic hypersomnia with an unknown pathophysiology. Treatment options may vary from a single drug targeting several symptoms or several drugs treating a specific symptom. The treatment of daytime sleepiness is based on modafinil in first intention. Other psychostimulants such as methylphenidate, pitolisant and exceptionally dextro-amfetamine may be considered. In narcolepsy type 1, antidepressants such as inhibitors of the reuptake of serotonin and noradrenaline will be considered to improve cataplexy. Sodium oxybate is an effective treatment on sleepiness, cataplexy and bad night sleep in narcolepsy. The management for other symptoms or comorbidities should be considered it necessary such as hallucinations, sleep paralysis, the disturbed nighttime sleep, unpleasant dreams, parasomnias, depressive symptoms, overweight/obesity, cardiovascular disease and obstructive sleep apnea syndrome. Important therapeutic perspectives are to be expected concerning new psychostimulant and anticataplectiques, but mainly on immune-based therapies administered as early as possible after disease onset and on hypocretin replacement therapy for patients with severe symptoms.

  18. Spatiotemporal analysis of precipitation trends during 1961-2010 in Hubei province, central China (United States)

    Wang, Ranghui; Li, Cheng


    Precipitation is an important climatic parameter, and its variability severely affects regional hydrological processes and water resource management. In order to explore the changing spatial and temporal characteristics of precipitation-related indices, including precipitation amounts indices, extreme precipitation indices, and precipitation concentration indices, in Hubei province, central China during 1961-2010, several precipitation-related indices series were analyzed using the Mann-Kendall test, Pettitt test, and inverse distance weighted interpolation method in this paper. The results are as follows: (1) A clear south-north gradient is apparent in the spatial distribution of the majority of precipitation-related indices, while the distribution of other indices (i.e., CDD, PCD, and PCP) is just the opposite. Most part of Hubei province can experience mixed positive and negative trends in precipitation-related indices. (2) The majority of precipitation-related indices exhibit an increasing trend, but most of which are not significant. July has the largest positive trend, with a regional average of 14.76 mm/decade. As for extreme precipitation indices, there exist large variations in Hubei, especially in R95pTOT. Besides, no obvious trends are shown in precipitation concentration indices. (3) With the exception of consecutive dry days (CDD), most of extreme precipitation indices are strongly correlated with annual mean precipitation (AMP) in Hubei. And the extreme precipitation indices are well correlated with each other except CDD and consecutive wet days (CWD). For six precipitation-related indices (i.e., SDII, RX1day, RX5day, R95pTOT R99pTOT, and PCD), there are significant positive relationships with Northern Hemisphere Subtropical High (NHSH) but significant negative relationships with Northern Hemisphere Polar Vortex (NHPV). Furthermore, the majority of precipitation-related indices have significant negative correlations with East Asian summer monsoon

  19. y Banca Central

    Directory of Open Access Journals (Sweden)

    Ángel García Banchs


    Full Text Available Las teorías monetarias modernas, ortodoxas y heterodoxas, han pasado por alto el hecho de que posterior a la Segunda Guerra Mundial el mundo quedó dividido entre economías emisoras y receptoras de reservas, pasando el sistema monetario internacional desde entonces a ser completamente asimétrico. De allí que, desde el punto de vista teórico, señalemos la necesidad de tomar en cuenta si las economías emiten o no una moneda de reserva internacional, pues ello explicaría la existencia de diversas prácticas monetarias a nivel mundial. Este trabajo propone, y calcula, indicadores basados en datos provenientes de los balances de activos y pasivos de quince bancos centrales pertenecientes a Norteamérica, Suramérica, Europa y Asia. Los hallazgos con respecto a las diversas estructuras de activos y pasivos confirman la hipótesis acerca de la presencia de tales asimetrías. Se infiere en consecuencia que la política monetaria es menos flexible pero más influyente en las economías receptoras de reservas, y a la vez más flexible pero menos influyente en las economías emisoras. En pocas palabras, la exogeneidad de la tasa de interés de corto plazo es más débil en el caso de las economías receptoras de reservas las cuales se ven obligadas a acumular divisas y a procurar la estabilidad del tipo de cambio, debido a que sus monedas locales no son aceptadas en el exterior. Así, aunque la oferta crediticia es endógena en esas economías, las mismas no han sido capaces de librarse aún de la necesidad de mantener reservas monetarias en divisas extranjeras

  20. Dublin South Central (DSC)

    LENUS (Irish Health Repository)

    O'Gorman, Clodagh S M


    Children who appear healthy, even if they have one or more recognized cardiovascular risk factors, do not generally have outcomes of cardiovascular or other vascular disease during childhood. Historically, pediatric medicine has not aggressively screened for or treated cardiovascular risk factors in otherwise healthy children. However, studies such as the P-Day Study (Pathobiological Determinants of Atherosclerosis in Youth), and the Bogalusa Heart Study, indicate that healthy children at remarkably young ages can have evidence of significant atherosclerosis. With the increasing prevalence of pediatric obesity, can we expect more health problems related to the consequences of pediatric dyslipidemia, hypertriglyceridemia, and atherosclerosis in the future? For many years, medications have been available and used in adult populations to treat dyslipidemia. In recent years, reports of short-term safety of some of these medications in children have been published. However, none of these studies have detailed long-term follow-up, and therefore none have described potential late side-effects of early cholesterol-lowering therapy, or potential benefits in terms of reduction of or delay in cardiovascular or other vascular end-points. In 2007, the American Heart Association published a scientific statement on the use of cholesterol-lowering therapy in pediatric patients. In this review paper, we discuss some of the current literature on cholesterol-lowering therapy in children, including the statins that are currently available for use in children, and some of the cautions with using these and other cholesterol-lowering medications. A central tenet of this review is that medications are not a substitute for dietary and lifestyle interventions, and that even in children on cholesterol-lowering medications, physicians should take every opportunity to encourage children and their parents to make healthy diet and lifestyle choices.

  1. Central African Republic. (United States)


    The Central African Republic contains 242,000 square miles, which rolling terrain almost 2000 feet above sea level. The climate is tropical, and it has a population of 2.8 million people with a 2.5% growth rate. There are more than 80 ethnic groups including Baya 34%, Banda 28%, Sara 10%, Mandja 9%, Mboum 9%, and M'Baka 7%. The religions are traditional African 35%, protestant 25%, Roman Catholic 25%, and Muslim 15%, and the languages are French and Sangho. The infant mortality rate is 143/1000, with expectancy at 49 years and a 40% literacy rate. The work force of 1 million is 70% agricultural, industry 6% and commerce and service 6% and government 3%. The government consists of a president assisted by cabinet ministers and a single party. Natural resources include diamonds, uranium, timber, gold, and oil, and major industries are beverages, textiles, and soap. Agricultural products feature coffee, cotton, peanuts, tobacco, food crops and livestock. Most of the population live in rural areas and most of the 80 ethnic groups have their own language. This is one of the world's least developed countries, with a per capita income of $375/year. The main problems with development are the poor transportation infrastructure, and the weak internal and international marketing systems. The US and various international organizations have aided in agriculture development, health programs, and family planning. US investment is mainly in diamond and gold mining, and although oil drilling has been successful it is not economically feasible at current prices.

  2. Central Hypothyroidism in Miniature Schnauzers

    NARCIS (Netherlands)

    Voorbij, Annemarie M W Y; Leegwater, Peter A J; Buijtels, Jenny J C W M; Daminet, Sylvie; Kooistra, Hans S


    BACKGROUND: Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species. OBJECTIVES: The objective of this article is to describe the occurrence and clinical presentation of central hypothyroidism in Miniature Schnauzers. Additionally, the p

  3. Central presbycusis: an emerging view. (United States)

    Gates, George A


    Age-related dysfunction of the central auditory system (central presbycusis) is common but rarely looked for by those who provide aural rehabilitation. Patients who complain of difficulty hearing in noise--the key symptom of central presbycusis--are generally disadvantaged with conventional rehabilitation. This symptom should be documented with commercially available speech-in-noise tests, which use materials that are uncomplicated to administer. Those patients who perform poorly on such tests should have a customized rehabilitation program aimed at optimizing their remaining communication abilities. Otolaryngologists who provide auditory rehabilitation may wish to consider expanding their practices to meet the communication needs of older patients with central presbycusis. Central presbycusis is an emerging area for basic and clinical research in auditory neurotology, particularly in the relation of cognitive dysfunction to impaired auditory processing.

  4. Pharmacological Investigations of the Dissociative ‘Legal Highs’ Diphenidine, Methoxphenidine and Analogues (United States)

    Colestock, Tristan; Morris, Hamilton; Bortolotto, Zuner A.; Lodge, David; Halberstadt, Adam L.; Brandt, Simon D.


    1,2-Diarylethylamines including lanicemine, lefetamine, and remacemide have clinical relevance in a range of therapeutic areas including pain management, epilepsy, neurodegenerative disease and depression. More recently 1,2-diarylethylamines have been sold as ‘legal highs’ in a number of different forms including powders and tablets. These compounds are sold to circumvent governmental legislation regulating psychoactive drugs. Examples include the opioid MT-45 and the dissociative agents diphenidine (DPH) and 2-methoxy-diphenidine (2-MXP). A number of fatal and non-fatal overdoses have been linked to abuse of these compounds. As with many ‘legal highs’, little is known about their pharmacology. To obtain a better understanding, the effects of DPH, 2-MXP and its 3- and 4-MeO- isomers, and 2-Cl-diphenidine (2-Cl-DPH) were investigated using binding studies at 46 central nervous system receptors including the N-methyl-D-aspartate receptor (NMDAR), serotonin, dopamine, norepinephrine, histamine, and sigma receptors as well as the reuptake transporters for serotonin, dopamine and norepinephrine. Reuptake inhibition potencies were measured at serotonin, norepinephrine and dopamine transporters. NMDAR antagonism was established in vitro using NMDAR-induced field excitatory postsynaptic potential (fEPSP) experiments. Finally, DPH and 2-MXP were investigated using tests of pre-pulse inhibition of startle (PPI) in rats to determine whether they reduce sensorimotor gating, an effect observed with known dissociative drugs such as phencyclidine (PCP) and ketamine. The results suggest that these 1,2-diarylethylamines are relatively selective NMDAR antagonists with weak off-target inhibitory effects on dopamine and norepinephrine reuptake. DPH and 2-MXP significantly inhibited PPI. DPH showed greater potency than 2-MXP, acting with a median effective dose (ED50) of 9.5 mg/kg, which is less potent than values reported for other commonly abused dissociative drugs such as

  5. Centralized versus Decentralized Information Systems (United States)

    Hugoson, Mats-Åke

    This paper brings into question whether information systems should be centralized or decentralized in order to provide greater support for different business processes. During the last century companies and organizations have used different approaches for centralization and decentralization; a simple answer to the question does not exist. This paper provides a survey of the evolution of centralized and decentralized approaches, mainly in a Nordic perspective. Based on critical reflections on the situation in the end of the century we can discuss what we can learn from history to achieve alignment between centralized and decentralized systems and the business structure. The conclusion is that theories, management and practice for decisions on centralization or decentralization of information systems must be improved. A conscious management and control of centralization /decentralization of IT support is a vital question in the company or the organization, and this is not a task that can be handled only by IT-specialists. There is a need for business oriented IT management of centralization/decentralization.

  6. Betweenness centrality profiles in trees

    CERN Document Server

    Fish, Benjamin; Turan, Gyorgy


    Betweenness centrality of a vertex in a graph measures the fraction of shortest paths going through the vertex. This is a basic notion for determining the importance of a vertex in a network. The k-betweenness centrality of a vertex is defined similarly, but only considers shortest paths of length at most k. The sequence of k-betweenness centralities for all possible values of k forms the betweenness centrality profile of a vertex. We study properties of betweenness centrality profiles in trees. We show that for scale-free random trees, for fixed k, the expectation of k-betweenness centrality strictly decreases as the index of the vertex increases. We also analyze worst-case properties of profiles in terms of the distance of profiles from being monotone, and the number of times pairs of profiles can cross. This is related to whether k-betweenness centrality, for small values of k, may be used instead of having to consider all shortest paths. Bounds are given that are optimal in order of magnitude. We also pre...

  7. Nonnatural deaths among users of illicit drugs: pathological findings and illicit drug abuse stigmata. (United States)

    Delaveris, Gerd Jorunn Møller; Hoff-Olsen, Per; Rogde, Sidsel


    The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (γ-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions. Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative.

  8. Inmunoterapias para las adicciones a las drogas Immunotherapies for Drug Addictions (United States)

    Montoya, Iván D.


    Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders. PMID:18551223

  9. Demographic tensions in Central America. (United States)


    This discussion of Central America focuses on the rapid growth of its population, its stagnating economy, and those countries that are socioeconomically advanced. Between 1950-85 the population of Central America tripled, from 9.1 million to 26. 4 million, due to marked mortality declines and the absence of off-setting fertility declines. The distribution of Central Americas's growing populations sets its population growth apart from that of other developing regions. Currently, almost half of all Central Americans live in cities. Although the average growth rate for Central American countries has fallen and is expected to drop further, the decline does not counterbalance the effect of the absolute rise in population numbers. The average annual growth rate of more than 3% annually in the 1960s fell to about 2.6% in recent years, but this decline is due primarily to socioeconomically advanced Costa Rica and Panama. Central America's age structure further complicates the population crisis. About 43% of Central Americans are under the age of 15. When the increasingly larger young population group enters it reproductive years, the potential for future growth (albeit the falling rate of population increase) is unparalleled. UN population projections show the region's population at 40 million by the year 2000. The 1973 oil crisis began a downward spiral for the buoyant post World War II Central American economy. Between 1950-79, real per capita income growth in Central America doubled, with Central American economies growing an average of 5.3% annually. By the early 1980s, overseas markets of the trade-dependent countries of Central America had dried up due to protectionism abroad and slumping basic commodity prices. These and other factors plunged Central America into its current economic malaise of falling real per capita income, rising unemployment, curtailed export led economic growth, and a rising cost of living. In general, economic growth in Central America

  10. The Central Trigger Processor (CTP)

    CERN Multimedia

    Franchini, Matteo


    The Central Trigger Processor (CTP) receives trigger information from the calorimeter and muon trigger processors, as well as from other sources of trigger. It makes the Level-1 decision (L1A) based on a trigger menu.

  11. Payments and Central Bank Policy

    DEFF Research Database (Denmark)

    Korsgaard, Søren

    This thesis consists of three chapters. The rst, "Paying for Payments", examines the role of interchange fees in payment card networks. The second, "Bank Liquidity and the Interbank Market" (co-authored with Mikael Reimer Jensen), investigates how banks' liquidity holdings at the central bank a ect...... outcomes in the money market. The third, "Collateralized Lending and Central Bank Collateral Policy", considers the emergence of credit constraints under collateralized lending, and how central banks use collateral policy to mitigate these constraints. While the chapters can be read independently......, they share common themes. Each chapter is concerned with payments in one way or another, each is concerned with the e ciency of market outcomes, and, to the extent that there is scope for improving these outcomes, each discusses the appropriate role for policy, in particular central bank policy....

  12. Central cementifying fibroma of mandible

    Directory of Open Access Journals (Sweden)

    Joseph Edward


    Full Text Available Central cementifying fibroma is a rare non odontogenic tumor coming in the group of fibro osseouslesion, arising from periodontal ligament and is usually seen in tooth bearing area. It can affect boththe mandible and the maxilla, particularly the mandible. This bone tumour consists of highly cellular,fibrous tissue that contains varying amounts of calcified tissue resembling bone, cementum or both.Here we present a case of Central cementifying fibroma (recurrent in a 34 year old female.

  13. Inferring Centrality from Network Snapshots


    Haibin Shao; Mehran Mesbahi; Dewei Li; Yugeng Xi


    The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagati...


    Energy Technology Data Exchange (ETDEWEB)




  15. Controlling centrality in complex networks

    CERN Document Server

    Nicosia, Vincenzo; Romance, Miguel; Russo, Giovanni; Latora, Vito


    Spectral centrality measures allow to identify influential individuals in social groups, to rank Web pages by their popularity, and even to determine the impact of scientific researches. The centrality score of a node within a network crucially depends on the entire pattern of connections, so that the usual approach is to compute the node centralities once the network structure is assigned. We face here with the inverse problem, that is, we study how to modify the centrality scores of the nodes by acting on the structure of a given network. We prove that there exist particular subsets of nodes, called controlling sets, which can assign any prescribed set of centrality values to all the nodes of a graph, by cooperatively tuning the weights of their out-going links. We show that many large networks from the real world have surprisingly small controlling sets, containing even less than 5-10% of the nodes. These results suggest that rankings obtained from spectral centrality measures have to be considered with ex...

  16. Redução do lead time e entregas no prazo em pequenas e médias empresas que fabricam sob encomenda: a abordagem Worload Control (WLC para o Planejamento e Controle da Produção (PCP Lead time reduction and improved tardiness performance in small and medium sized Make-to-Order Companies: the Workload Control (WLC approach, a solution for Production Planning and Control (PPC

    Directory of Open Access Journals (Sweden)

    Matthias Thurer


    Full Text Available A maior parte da literatura a respeito de Planejamento e Controle da Produção (PCP é focada em estudar e desenvolver aplicativos para grandes empresas, principalmente de ambiente repetitivo. Nesse contexto, são as poucas as alternativas para o PCP para pequenas e médias empresas que fabricam sob encomenda, as quais têm papel fundamental na atual economia brasileira. Em resposta a essa demanda, o presente trabalho objetiva apresentar uma abordagem para o PCP denominada Controle de Carga (Workload Control - WLC. Essa abordagem é reconhecidamente um método com potencial para trazer melhorias no lead time, no estoque em processo e na pontualidade de entregas em ambientes que fabricam sob encomenda (Make-To-Order - MTO. Primeiramente, o artigo apresenta a abordagem WLC, revisando e discutindo os principais assuntos tratados pela literatura internacional na área. Após isso, o desempenho do WLC é avaliado por meio de simulação. Os resultados mostram o potencial de melhorias no lead time e nas ordens em atraso que o WLC pode trazer a pequenas e médias empresas que fabricam sob encomenda. Dessa forma, o presente trabalho pretende contribuir tanto para a teoria a respeito de tal abordagem, praticamente introduzindo tal assunto na literatura brasileira, como para a prática, fornecendo e demonstrando, por meio de simulação, aos gerentes de PCP, uma alternativa para suas empresas trabalharem rumo a baixos lead times e de acordo com modernos paradigmas de produção, tais como o Lean Manufacturing e o Quick Response Manufacturing.The majority of Production Planning and Control (PPC literature is focused on the study and development of solutions for large companies, especially in repetitive environments. Therefore, there are few specific PPC solutions available in the literature for small and medium sized companies (SMC operating in a Make -to-Order (MTO environment. This paper presents the Workload Control (WLC, which is a useful PPC approach

  17. Rosette Central Configurations, Degenerate central configurations and bifurcations

    CERN Document Server

    Lei, Jinzhi


    In this paper we find a class of new degenerate central configurations and bifurcations in the Newtonian $n$-body problem. In particular we analyze the Rosette central configurations, namely a coplanar configuration where $n$ particles of mass $m_1$ lie at the vertices of a regular $n$-gon, $n$ particles of mass $m_2$ lie at the vertices of another $n$-gon concentric with the first, but rotated of an angle $\\pi/n$, and an additional particle of mass $m_0$ lies at the center of mass of the system. This system admits two mass parameters $\\mu=m_0/m_1$ and $\\ep=m_2/m_1$. We show that, as $\\mu$ varies, if $n> 3$, there is a degenerate central configuration and a bifurcation for every $\\ep>0$, while if $n=3$ there is a bifurcations only for some values of $\\epsilon$.

  18. Spatial and Temporal Distributions of Soil Organic Matter in the Mixed Plantations of Alder and Cypress in the Hilly Areas of Central Sichuan Basin

    Institute of Scientific and Technical Information of China (English)

    WU Pengfei; ZHU Bo; YANG Yuanli; WANG Xiaoguo


    The investigation was conducted on the spatial and temporal distributions of soil organic mater (SOM) in the mixed plantations of alder (Aluns cremastogyne) and cypress (Cupressus funebris) (MPAC),which distributed in the hilly areas of central Sichuan Basin (HACSB). The results show that:① the spatial distribution of SOM among different sites at the same age are not significant before 15-year-old, but significant at 20-year-old, and not significant again after 25-year-old; ② the SOM contents in 0-15 cm and 15-30 cm layers increase sharply from 10- to 15-year-old, and decline gradually from 15- to 30-year-old; the SOM contents of the 30-year-old PCP were 80.38% and 78.42% higher than that of the 10-year-old, but 29.16% and 53.37% lower than that of 15-year-old in the 0-15 cm and 15-30 cm layers, respectively. The decrease of SOM contents would lead to the degradation of soil fertility and the decline of forest productivity.

  19. Coverage centralities for temporal networks

    CERN Document Server

    Takaguchi, Taro; Yoshida, Yuichi


    Structure of real networked systems, such as social relationship, can be modeled as temporal networks in which each edge appears only at the prescribed time. Understanding the structure of temporal networks requires quantifying the importance of a temporal vertex, which is a pair of vertex index and time. In this paper, we define two centrality measures of a temporal vertex by the proportion of (normal) vertex pairs, the quickest routes between which can (or should) use the temporal vertex. The definition is free from parameters and robust against the change in time scale on which we focus. In addition, we can efficiently compute these centrality values for all temporal vertices. Using the two centrality measures, we reveal that distributions of these centrality values of real-world temporal networks are heterogeneous. For various datasets, we also demonstrate that a majority of the highly central temporal vertices are located within a narrow time window around a particular time. In other words, there is a bo...

  20. Coverage centralities for temporal networks* (United States)

    Takaguchi, Taro; Yano, Yosuke; Yoshida, Yuichi


    Structure of real networked systems, such as social relationship, can be modeled as temporal networks in which each edge appears only at the prescribed time. Understanding the structure of temporal networks requires quantifying the importance of a temporal vertex, which is a pair of vertex index and time. In this paper, we define two centrality measures of a temporal vertex based on the fastest temporal paths which use the temporal vertex. The definition is free from parameters and robust against the change in time scale on which we focus. In addition, we can efficiently compute these centrality values for all temporal vertices. Using the two centrality measures, we reveal that distributions of these centrality values of real-world temporal networks are heterogeneous. For various datasets, we also demonstrate that a majority of the highly central temporal vertices are located within a narrow time window around a particular time. In other words, there is a bottleneck time at which most information sent in the temporal network passes through a small number of temporal vertices, which suggests an important role of these temporal vertices in spreading phenomena. Contribution to the Topical Issue "Temporal Network Theory and Applications", edited by Petter Holme.Supplementary material in the form of one pdf file available from the Journal web page at

  1. Inferring Centrality from Network Snapshots (United States)

    Shao, Haibin; Mesbahi, Mehran; Li, Dewei; Xi, Yugeng


    The topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data. PMID:28098166


    Directory of Open Access Journals (Sweden)

    Eman S. Mansour


    Full Text Available Background: Acupuncture is an component of traditional Chinese medicine (TCM that has been used for three thousand years to treat diseases and relieve pain. Pain is found to be the most common reason for people to use acupuncture. Due to recent scientific findings, acupuncture treatment has been accepted worldwide. Numerous trials have been conducted especially in analgesia. The mechanisms of acupuncture analgesia has been widely investigated, however, the underlying mechanism still not clear. This article summarizes the central mechanisms of acupuncture analgesia and reviews recent studies on the topic. Method: We have focused on examining the recent literature on acupuncture analgesia. The central mechanisms of acupuncture analgesia and reviews recent studies on the topic. We focused on the studies related to central mechanisms of acupuncture analgesia from these aspects: (neurophysiology, neurochemistry and neuroanatomy. Result: The result revealed that acupuncture act on various parts of the central nervous system, including the spinal cord, brain stem, cerebral ganglia and cerebral cortex to alleviate pain. The central mechanisms underlying the effects of acupuncture include neurohumors and neurotransmitters, which are involved in analgesia. At spinal level, Spinal opioids, glutamate, norepinephrine and serotonin are the key elements acupuncture-induced analgesia. At brain level, Endogenous opioid peptides, limbic system play essential roles in mediating the analgesia. Conclusion: Acupuncture is an effective approach to pain management. There is good evidence in both experimental and clinical research that supports acupuncture efficacy in management of chronic pain through central nervous system. Acupuncture should be strongly used as a part of pain management plans. This work helps in improving our understanding of the scientific basis underlying acupuncture analgesia.

  3. Central Stars of Planetary Nebulae

    CERN Document Server

    Jones, David


    In this brief invited review, I will attempt to summarise some of the key areas of interest in the study of central stars of planetary nebulae which (probably) won't be covered by other speakers' proceedings. The main focus will, inevitably, be on the subject of multiplicity, with special emphasis on recent results regarding triple central star systems as well as wide binaries which avoid a common-envelope phase. Furthermore, in light of the upcoming release of Kepler's Campaign 11 data, I will discuss a few of the prospects from that data including the unique possibility to detect merger products.

  4. N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro. (United States)

    Yavas, Ersin; Young, Andrew M J


    The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.

  5. Central Libraries in Uncertain Times. (United States)

    Kenney, Brian J.


    Discusses security and safety issues for public libraries, especially high-profile central facilities, in light of the September 11 terrorist attacks. Highlights include inspecting bags as patrons enter as well as exit; the need for security guidelines for any type of disaster or emergency; building design; and the importance of communication.…

  6. New Economy, Old Central Banks?

    NARCIS (Netherlands)

    Berk, Jan Marc


    Proponents of the so-called New Economy claim that it entails a structural change of the economy. Such a change, in turn, would require the central bank to rethink its monetary policy to the extent that traditional relationships between inf1ation and economic growth are no longer valid. But such a r

  7. Vulnerability in north- central Vietnam

    DEFF Research Database (Denmark)

    Casse, Thorkil; Milhøj, Anders; Nguyen, Thao Phuong


    This article examines changes in livelihood strategies in response to flooding. It does so on the basis of a household survey which was undertaken in three provinces in north central Vietnam. All households in the survey were regularly affected by flooding, but only poor households experience...

  8. Water Governance in Central Asia

    NARCIS (Netherlands)

    Djanibekov, Nodir; Assche, Van Kristof; Valentinov, Vladislav


    We develop a social systems theory perspective on Central Asian post-Socialist transition, placing particular emphasis on the coordination problems in transboundary water governance. The extensive Soviet water-energy infrastructure around the Amudarya and Syrdarya rivers required coordination, bu

  9. The Centrality of Ethical Leadership (United States)

    Ehrich, Lisa C.; Harris, Jessica; Klenowski, Val; Smeed, Judy; Spina, Nerida


    Purpose: The central argument in this paper is that ethical school leadership is imperative in a context of increasing performance-driven accountability. The purpose of this paper is to focus on school principals' perceptions of how they understand ethical leadership and how they lead the ethical use of data. Design/Methodology/Approach: This…

  10. Learning and the central bank


    Charles T. Carlstrom; Timothy S. Fuerst


    It is well known that sunspot equilibria may arise under an interest-rate operating procedure in which the central bank varies the nominal rate with movements in future inflation (a forward-looking Taylor rule). This paper demonstrates that these sunspot equilibria may be learnable in the sense of E-stability.

  11. The MEANING multilingual central repository

    NARCIS (Netherlands)

    Atserias, J.; Villarejo, L.; Rigau, G.; Agirre, E.; Carroll, J.; Magnini, B.; Vossen, P.


    This paper describes the first version of the Multilingual Central Repository, a lexical knowledge base developed in the framework of the MEANING project. Currently the MCR integrates into the EuroWordNet framework five local wordnets (including four versions of the English WordNet from Princeton),

  12. Copycats of the Central Himalayas

    NARCIS (Netherlands)

    P.A. Arora (Payal)


    textabstractThis case study highlights practices of a rarely documented group of neo-users of the Internet or newbies from Central Himalayas, serving as a catalyst for delving deeply into the act of ‘plagiarism’ in online learning By looking at such ‘learning’ practices away from schools, namely at

  13. Reduced central blood volume in cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Bendtsen, Flemming; Sørensen, T I


    for measuring the central blood volume. We have developed a method that enables us to determine directly the central blood volume, i.e., the blood volume in the heart cavities, lungs, and central arterial tree. In 60 patients with cirrhosis and 16 control subjects the central blood volume was assessed according...

  14. 27 CFR 9.75 - Central Coast. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Central Coast. 9.75... Central Coast. (a) Name. The name of the viticultural area described in this section is “Central Coast.” (b) Approved maps. The approved maps for determining the boundary of the Central Coast...

  15. Noncanonical Wnt/PCP signaling during vertebrate gastrulation. (United States)

    Tada, Masazumi; Kai, Masatake


    The branch of the Wnt pathway, related to planar cell polarity signaling in Drosophila, is fundamental not only to the establishment of tissue polarity but also to a variety of morphogenetic processes in vertebrates. The genetic pathway has been noted for its similarity as well as divergence of between vertebrates and Drosophila. This review focuses on issues related to the complexity of the output of the planar cell polarity pathway during gastrulation in zebrafish and Xenopus and, to a lesser extent, during gastrulation/neurulation in mice.

  16. Resource Letter PCP-1: Pre-college Physics Curriculum Materials (United States)

    Paldy, Lester G.; Swartz, Clifford E.


    Presents a guide to 101 physics curriculum materials including improvement projects and related articles, reference books, commonly used textbooks, teaching aids, and science education periodicals. (CC)

  17. The PCP pathway regulates Baz planar distribution in epithelial cells



    The localisation of apico-basal polarity proteins along the Z-axis of epithelial cells is well understood while their distribution in the plane of the epithelium is poorly characterised. Here we provide a systematic description of the planar localisation of apico-basal polarity proteins in the Drosophila ommatidial epithelium. We show that the adherens junction proteins Shotgun and Armadillo, as well as the baso-lateral complexes, are bilateral, i.e. present on both sides of cell interfaces. ...

  18. Central venous line complications and tip detection


    Ameneh Rezaee Gheshlaghi; Hamid Zamani Moghadam Dolu; Elham Pishbin; Maryam Salehi


    Central venous line is one of a creative instrument that saves human’s life in critical medical situation. Central venous line access is frequently involved in the disease management. It is used for rapid fluid therapy, transvenous pacemakers, infusion of some medications, hemodialysis or plasmapheresis and etc. Most of the emergency departments have some staffs that are trained for central venous line insertion but related complications occur during central venous line placement.Central veno...

  19. Is Central Asia really exsiccating? (United States)

    Aizen, V. B.; Aizen, E. M.; Surazakov, A. B.


    At the end of 20th and the beginning of 21st century central Asia oases suffered from serious drought caused lack of water for agriculture, economy growth and population increase. However, people of this region always experienced lack of water for irrigation and fought a war over the rights to control river streams. The drying up of central Asian rivers is not a new phenomenon according to the ancient manuscripts. Thus, lets see about what has happened with the past century climate and water resources of central Asia using the long-term observational data. We analyzed data from more than 200 meteorological stations and stream gauges over the central Asia in elevation range from 25 m. b.s.l. to 4,000 m. a.s.l. to understand the last 100 years variability in climate and water resources, examining changes in the extreme and mean monthly air temperatures, precipitation and river runoff. The evaluation of seasonal snow and glacier's covered areas between 1970th and 2007th in central Asia derived from AVHRR, MODIS, Hexagon KH-9, Landsat ETM and ASTER data exhibit 15% reduction of the seasonal snow covered area and 10.1% of the glacier area. It has been found that during last twenty years the duration of snowmelt, from the date of maximum snow cover to date of its disappearance, reduced by 30 days and in 2007 was equal to 138 days in the central Asian mountains. The decrease of seasonal snow cover is not a linear process. The further decrease may be accelerated due to increase of rainfall instead of snowfall in early spring months at high elevations, and consequently a lesser heat expenditure for the snowmelt. The growth in summer air temperatures, especially observable since the 1970th, accompanied by increase of evapotranspiration and precipitation, notably in summer and autumn, and at high elevations over 3,000 m, and at the western peripheral mountain ridges. Average difference in the means of annual air temperatures for the two thirty-year periods before and after

  20. SAR110894, a potent histamine H₃-receptor antagonist, displays procognitive effects in rodents. (United States)

    Griebel, Guy; Pichat, Philippe; Pruniaux, Marie-Pierre; Beeské, Sandra; Lopez-Grancha, Mati; Genet, Elisabeth; Terranova, Jean-Paul; Castro, Antonio; Sánchez, Juan Antonio; Black, Mark; Varty, Geoffrey B; Weiner, Ina; Arad, Michal; Barak, Segev; De Levie, Amaya; Guillot, Etienne


    SAR110894 is a novel histamine H₃-R ligand, displaying high and selective affinity for human, rat or mouse H₃-Rs. SAR110894 is a potent H₃-R antagonist at native receptors, reversing R-α-methylhistamine-induced inhibition of electrical field stimulation contraction in the guinea-pig ileum. Additionally, SAR110894 inhibited constitutive GTPγS binding at human H₃-Rs demonstrating inverse agonist properties. In behavioral models addressing certain aspects of cognitive impairment associated with schizophrenia (CIAS) and attention deficit/hyperactivity disorder (ADHD), SAR110894 improved memory performances in several variants of the object recognition task in mice (0.3-3 mg/kg, p.o.) or rats (0.3-1 mg/kg, p.o.). Moreover, SAR110894 (1 mg/kg, p.o.) reversed a deficit in working memory in the Y-maze test, following an acute low dose of phencyclidine (PCP) (0.5 mg/kg, i.p.) in mice sensitized by repeated treatment with a high dose of PCP (10 mg/kg, i.p.). In the latent inhibition (LI) model, SAR110894 potentiated LI in saline-treated rats (1 and 3 mg/kg, i.p.) and reversed abnormally persistent LI induced by neonatal nitric oxide synthase (NOS) inhibition in rodents (0.3-3 mg/kg, i.p.). In a social novelty discrimination task in rats, SAR110894 attenuated selective attention deficit induced by neonatal PCP treatment (3 and 10 mg/kg, p.o.) or a parametric modification of the procedure (3 and 10 mg/kg, p.o.). SAR110894 showed efficacy in several animal models related to the cognitive deficits in Alzheimer's disease (AD). It prevented the occurrence of episodic memory deficit induced by scopolamine in rats (0.01-10 mg/kg, p.o.) or by the central infusion of the toxic amyloid fragment β₂₅₋₃₅ in the object recognition test in mice (1 and 3 mg/kg, p.o.). Altogether, these findings suggest that SAR110894 may be of therapeutic interest for the treatment of the cognitive symptoms of AD, schizophrenia and certain aspects of ADHD.

  1. The Central Valley Hydrologic Model (United States)

    Faunt, C.; Belitz, K.; Hanson, R. T.


    Historically, California’s Central Valley has been one of the most productive agricultural regions in the world. The Central Valley also is rapidly becoming an important area for California’s expanding urban population. In response to this competition for water, a number of water-related issues have gained prominence: conjunctive use, artificial recharge, hydrologic implications of land-use change, subsidence, and effects of climate variability. To provide information to stakeholders addressing these issues, the USGS made a detailed assessment of the Central Valley aquifer system that includes the present status of water resources and how these resources have changed over time. The principal product of this assessment is a tool, referred to as the Central Valley Hydrologic Model (CVHM), that simulates surface-water flows, groundwater flows, and land subsidence in response to stresses from human uses and from climate variability throughout the entire Central Valley. The CVHM utilizes MODFLOW combined with a new tool called “Farm Process” to simulate groundwater and surface-water flow, irrigated agriculture, land subsidence, and other key processes in the Central Valley on a monthly basis. This model was discretized horizontally into 20,000 1-mi2 cells and vertically into 10 layers ranging in thickness from 50 feet at the land surface to 750 feet at depth. A texture model constructed by using data from more than 8,500 drillers’ logs was used to estimate hydraulic properties. Unmetered pumpage and surface-water deliveries for 21 water-balance regions were simulated with the Farm Process. Model results indicate that human activities, predominately surface-water deliveries and groundwater pumping for irrigated agriculture, have dramatically influenced the hydrology of the Central Valley. These human activities have increased flow though the aquifer system by about a factor of six compared to pre-development conditions. The simulated hydrology reflects spatial

  2. Centrality in Interconnected Multilayer Networks

    CERN Document Server

    De Domenico, Manlio; Omodei, Elisa; Gómez, Sergio; Arenas, Alex


    Real-world complex systems exhibit multiple levels of relationships. In many cases, they require to be modeled by interconnected multilayer networks, characterizing interactions on several levels simultaneously. It is of crucial importance in many fields, from economics to biology, from urban planning to social sciences, to identify the most (or the less) influent nodes in a network. However, defining the centrality of actors in an interconnected structure is not trivial. In this paper, we capitalize on the tensorial formalism, recently proposed to characterize and investigate this kind of complex topologies, to show how several centrality measures -- well-known in the case of standard ("monoplex") networks -- can be extended naturally to the realm of interconnected multiplexes. We consider diagnostics widely used in different fields, e.g., computer science, biology, communication and social sciences, to cite only some of them. We show, both theoretically and numerically, that using the weighted monoplex obta...

  3. Centralized versus Decentralized Infrastructure Networks

    CERN Document Server

    Hines, Paul D H; Schläpfer, Markus


    While many large infrastructure networks, such as power, water, and natural gas systems, have similar physical properties governing flows, these systems tend to have distinctly different sizes and topological structures. This paper seeks to understand how these different size-scales and topological features can emerge from relatively simple design principles. Specifically, we seek to describe the conditions under which it is optimal to build decentralized network infrastructures, such as a microgrid, rather than centralized ones, such as a large high-voltage power system. While our method is simple it is useful in explaining why sometimes, but not always, it is economical to build large, interconnected networks and in other cases it is preferable to use smaller, distributed systems. The results indicate that there is not a single set of infrastructure cost conditions under which optimally-designed networks will have highly centralized architectures. Instead, as costs increase we find that average network size...

  4. A centralized audio presentation manager

    Energy Technology Data Exchange (ETDEWEB)

    Papp, A.L. III; Blattner, M.M.


    The centralized audio presentation manager addresses the problems which occur when multiple programs running simultaneously attempt to use the audio output of a computer system. Time dependence of sound means that certain auditory messages must be scheduled simultaneously, which can lead to perceptual problems due to psychoacoustic phenomena. Furthermore, the combination of speech and nonspeech audio is examined; each presents its own problems of perceptibility in an acoustic environment composed of multiple auditory streams. The centralized audio presentation manager receives abstract parameterized message requests from the currently running programs, and attempts to create and present a sonic representation in the most perceptible manner through the use of a theoretically and empirically designed rule set.

  5. The CDF Central Analysis Farm

    Energy Technology Data Exchange (ETDEWEB)

    Kim, T.H.; /MIT; Neubauer, M.; /UC, San Diego; Sfiligoi, I.; /Frascati; Weems, L.; /Fermilab; Wurthwein, F.; /UC, San Diego


    With Run II of the Fermilab Tevatron well underway, many computing challenges inherent to analyzing large volumes of data produced in particle physics research need to be met. We present the computing model within CDF designed to address the physics needs of the collaboration. Particular emphasis is placed on current development of a large O(1000) processor PC cluster at Fermilab serving as the Central Analysis Farm for CDF. Future plans leading toward distributed computing and GRID within CDF are also discussed.

  6. Central Nucleon-Nucleon Potential (United States)

    Robilotta, M. R.


    The outer region of the NN interactions is dominated by the one pion exchange potential (OPEP), followed by the two-pion exchange potential (TPEP). Chiral calculations of the TPEP have been performed using either heavy baryon1 (HB) or relativistic2 perturbation theories. We compare the predictions from these two approaches for the dominant central interaction and show that they fail to agree by 25% ...

  7. Celtic Sites of Central Iberia (United States)

    Pérez Gutiérrez, Manuel

    This chapter concerns the astronomy practiced by Celtic peoples in some parts of central Iberia, specifically the Vetton and Celtiberian peoples, inhabitants of the so-called Late Iron Age. The construction of some elements of religion or worship was perfectly determined by geometry, topography, and especially astronomy, because their spatial orientation occurs in locations of great interest for maintaining the local calendar. The maintenance of this calendar was probably the primary objective of some of the elements studied.

  8. Information from the central stores

    CERN Multimedia

    GS Department


    All items sold in the CERN shop (Bldg. 33) are now available in the central stores (Bldg. 73) and can be purchased on-line via EDH “Material Request” or at the “Emergency Desk” of the stores on the ground floor of Bldg. 73. These items are visible in the CERN catalogue under the “SCEM” codes beginning with 92. Department of General Infrastructure Services (GS) GS-SEM Group

  9. Central Asia, Physical Geography Handbook. (United States)


    over 2,000 m) is not applicable to Central Asia, partly because the general hypsometric level of this region is high and unstable, as a consequence fossils in them, gastropods have been discovered. On the main territory of the Tarim massif, which evidently represented a weakly elevated...places seams of gypsum and rock salt, and, in a part to the west of the town of Aksu, also a bed of gray limestone with small fresh- water gastropods

  10. Central charges in regular mechanics

    CERN Document Server

    Cabo-Montes de Oca, Alejandro; Villanueva, V M


    We consider the algebra associated to a group of transformations which are symmetries of a regular mechanical system (i.e. system free of constraints). For time dependent coordinate transformations we show that a central extension may appear at the classical level which is coordinate and momentum independent. A cochain formalism naturally arises in the argument and extends the usual configuration space cochain concepts to phase space.

  11. Central hypersensitivity in chronic musculoskeletal pain. (United States)

    Curatolo, Michele; Arendt-Nielsen, Lars


    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity.

  12. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars


    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold...... standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...... level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity....



    Guang, Pan


    This paper is divided into three parts: China’s energy policy and energy development strategy; Central Asia’s significance for China’s overseas energy development strategy; and Central Asia’s energy security and energy development.

  14. [Historical demography in the Central American isthmus]. (United States)

    Perez Brignoli, H


    The author reviews and evaluates sources of information on the demographic history of Central America. Past and present administrative, state, ecclesiastical, and genealogical sources are examined, and recent studies of various Central American countries are cited. A bibliography is provided

  15. Puente del Pedrido, tramo central

    Directory of Open Access Journals (Sweden)

    Torroja, Eduardo


    Full Text Available Planteada la necesidad de proceder a la ejecución del tramo central del puente en el Pasaje del Pedrido sobre la ría de Betanzos, y encontrándonos con que las armaduras para el mismo, que ya estaban acopiadas a pie de obra antes de la guerra, estaban totalmente no tuvimos inconveniente, puesto que habían de adquirirse de nuevo, en introducir algunas ligeras modificaciones sobre el proyecto anterior, a fin de reducir en lo posible el coste de la obra.

  16. Nonlocally Centralized Simultaneous Sparse Coding

    Institute of Scientific and Technical Information of China (English)

    雷阳; 宋占杰


    The concept of structured sparse coding noise is introduced to exploit the spatial correlations and nonlo-cal constraint of the local structure. Then the model of nonlocally centralized simultaneous sparse coding(NC-SSC)is proposed for reconstructing the original image, and an algorithm is proposed to transform the simultaneous sparse coding into reweighted low-rank approximation. Experimental results on image denoisng, deblurring and super-resolution demonstrate the advantage of the proposed NC-SSC method over the state-of-the-art image resto-ration methods.

  17. Inverting the central limit theorem

    CERN Document Server

    Navascues, Miguel; Villanueva, Ignacio


    The central limit theorem states that the sum of N independently distributed n-tuples of real variables (subject to appropriate normalization) tends to a multivariate gaussian distribution for large N. Here we propose to invert this argument: given a set of n correlated gaussian variables, we try to infer information about the structure of the discrete microscopic probability distributions whose convolution generated such a macroscopic behavior. The techniques developed along the article are applied to prove that the classical description of certain macroscopic optical experiments is infinitely more complex than the quantum one.

  18. Kalmanovitz y la banca central.


    Maya M, Guillermo


    Salomón Kalmanovitz, Codirector del Banco de la República (B de la R) hasta enero de 2005, uno de los economistas colombianos más brillantes, publicó un libro titulado Ensayos sobre Banca Central, Comportamiento, Independencia e Historia (Norma, 2003). Si los estudiantes de economía de los años 70 y 80 estudiaron a un Kalmanovitz marxista, los estudiantes de hoy estudian a un economista ortodoxo y liberal, igualmente brillante. Kalmanovitz es un partidario de la independencia de la BC para la...

  19. Distributed trace using central performance counter memory (United States)

    Satterfield, David L.; Sexton, James C.


    A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

  20. Capitalizing Central Banks: A Net Worth Approach


    Alain Ize


    This paper provides a simple, quantitative, net worth-based, approach to assessing the need for central bank capital. It derives a concept of "core capital" (a function of the central bank's operating expenditures and the carrying cost of its international reserves) as the minimum capital needed by a central bank to ensure the credibility of its inflation target. The approach is illustrated with the published accounts of three loss-making central banks and selected accounting entries for a br...

  1. The European Central Bank and the Eurosystem


    Carol C. Bertaut


    The Eurosystem comprises the European Central Bank at its center as well as the national central banks of the twelve countries currently participating in monetary union. The European Central Bank was established in July 1998, six months before the beginning of Stage Three of economic and monetary union. Although decisions regarding monetary policy are made centrally by the Governing Council of the Eurosystem, the operational aspects of monetary policy-including open market operations, adminis...

  2. Legal and actual central bank independence


    Artha, I.K.D.S.; de Haan, J.


    Indicators of central bank independence (CBI) based on the interpretation central bank laws in place may not capture the actual independence of the central bank. This paper develops an indicator of actual independence of the Bank Indonesia (BI), the central bank of Indonesia, for the period 1953-2008 and compares it with a new legal CBI indicator based on Cukierman (1992). The indicator of actual independence captures institutional and economic factors that affect CBI. We find that before 199...

  3. Central Pontine Myelinolysis: Report of Four Cases

    Directory of Open Access Journals (Sweden)

    Handan Akar


    Full Text Available Central pontine myelinolysis is a neurological disorder characterized by loss of myelin in the central pons as well as in the other parts of the brain like basal ganglia, lateral geniculate bodies, external and internal capsules, and cerebellum. We report the clinical and radiological findings of three patients with central pontine myelinolysis and one patient with both pontine and extrapontine myelinolysis.

  4. Central bank independence and inflation revisited

    NARCIS (Netherlands)

    Klomp, Jeroen; de Haan, Jakob


    We re-examine the relationship between central bank independence (CBI), proxied by the central bank governor's turnover rate and an indicator based on central bank laws in place, and inflation using a random coefficient model with the Hildreth-Houck estimator for more than 100 countries in the perio

  5. "Christofest" New Yorgi Central Parkis / Rael Artel

    Index Scriptorium Estoniae

    Artel, Rael, 1980-


    12. II 2005. a. avatakse Christo ja Jeanne-Claude'i keskkonnainstallatsioon "The Gates" New Yorgi Central Parkis. Paralleelselt toimub Metropolitan Muuseumis näitus "Christo and Jeanne-Claude : The Gates, Central Park, New York", kus eksponeeritakse Central Parki installatsiooni ettevalmistavaid materjale: joonistusi, diagramme, fotosid jne

  6. Precipitation chemistry in central Amazonia (United States)

    Andreae, M. O.; Talbot, R. W.; Berresheim, H.; Beecher, K. M.


    Rain samples from three sites in central Amazonia were collected over a period of 6 weeks during the 1987 wet season and analyzed for ionic species and dissolved organic carbon. A continuous record of precipitation chemistry and amount was obtained at two of these sites, which were free from local or regional pollution, for a time period of over 1 month. The volume-weighted mean concentrations of most species were found to be about a factor of 5 lower during the wet season compared with previous results from the dry season. Only sodium, potassium, and chloride showed similar concentrations in both seasons. When the seasonal difference in rainfall amount is taken into consideration, the deposition fluxes are only slightly lower for most species during the wet season than during the dry season, again with the exception of chloride, potassium, and sodium. Sodium and chloride are present in the same ratio as in sea salt; rapid advection of air masses of marine origin to the central Amazon Basin during the wet season may be responsible for the observed higher deposition flux of these species. Statistical analysis suggests that sulfate is, to a large extent, of marine (sea salt and biogenic) origin, but that long-range transport of combustion-derived aerosols also makes a significant contribution to sulfate and nitrate levels in Amazonian rain. Organic acid concentrations in rain were responsible for a large fraction of the observed precipitation acidity; their concentration was strongly influenced by gas/liquid interactions.

  7. Glial involvement in trigeminal central sensitization

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE


    Recent studies have indicated that trigeminal neurons exhibit central sensitization, an increase in the excitability of neurons within the central nervous system to the extent that a normally innocuous stimulus begins to produce pain after inflamma-tion or injury, and that glial activities play a vital role in this central sensitization. The involvement of glial cells in trigeminal central sensitization contains multiple mechanisms, including interaction with glutamatergic and purinergic receptors. A better understanding of the trigeminal central sensitization mediated by glial cells will help to find potential therapeutic targets and lead to developing new analge-sics for orofacial-specific pain with higher efficiency and fewer side-effects.

  8. Central Solenoid Insert Technical Specification

    Energy Technology Data Exchange (ETDEWEB)

    Martovetsky, Nicolai N [ORNL; Smirnov, Alexandre [ORNL


    The US ITER Project Office (USIPO) is responsible for the ITER central solenoid (CS) contribution to the ITER project. The Central Solenoid Insert (CSI) project will allow ITER validation the appropriate lengths of the conductors to be used in the full-scale CS coils under relevant conditions. The ITER Program plans to build and test a CSI to verify the performance of the CS conductor. The CSI is a one-layer solenoid with an inner diameter of 1.48 m and a height of 4.45 m between electric terminal ends. The coil weight with the terminals is approximately 820 kg without insulation. The major goal of the CSI is to measure the temperature margin of the CS under the ITER direct current (DC) operating conditions, including determining sensitivity to load cycles. Performance of the joints, ramp rate sensitivity, and stability against thermal or electromagnetic disturbances, electrical insulation, losses, and instrumentation are addressed separately and therefore are not major goals in this project. However, losses and joint performance will be tested during the CSI testing campaign. The USIPO will build the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at the Japan Atomic Energy Agency (JAEA), Naka, Japan. The industrial vendors (the Suppliers) will report to the USIPO (the Company). All approvals to proceed will be issued by the Company, which in some cases, as specified in this document, will also require the approval of the ITER Organization. Responsibilities and obligations will be covered by respective contracts between the USIPO, called Company interchangeably, and the industrial Prime Contractors, called Suppliers. Different stages of work may be performed by more than one Prime Contractor, as described in this specification. Technical requirements of the contract between the Company and the Prime Contractor will be covered by the Fabrication Specifications developed by the Prime Contractor based on this document and approved by

  9. 76 FR 22746 - Wiregrass Central Railway, LLC-Acquisition and Operation Exemption-Wiregrass Central Railroad... (United States)


    ... Surface Transportation Board Wiregrass Central Railway, LLC--Acquisition and Operation Exemption--Wiregrass Central Railroad Company, Inc. Wiregrass Central Railway, LLC (WCR), a noncarrier, has filed a verified notice of exemption under 49 CFR 1150.31 to acquire from Wiregrass Central Railroad Company,...

  10. Central Exclusive Production at LHCb

    CERN Document Server

    McNulty, Ronan


    Central Exclusive Production (CEP) is a unique process at hadron machines in which particles are produced via colourless propagators. LHCb have measured the cross-sections for the CEP of vector mesons, $J/\\psi,\\psi(2S),\\Upsilon(1S),\\Upsilon(2S)$ and $\\Upsilon(3S)$, which are photo-produced. In the double pomeron exchange process, preliminary measurements have been made of $\\chi_{c0},\\chi_{c1}, \\chi_{c2}$ meson production while the first observations of the CEP of pairs of charmonia, $J/\\psi J/\\psi$ and $J/\\psi \\psi(2S)$, have been made and limits obtained on the pair production of other charmonia.

  11. Centralized Allocation in Multiple Markets

    DEFF Research Database (Denmark)

    Monte, Daniel; Tumennasan, Norovsambuu

    The problem of allocating indivisible objects to different agents, where each indi vidual is assigned at most one object, has been widely studied. Pápai (2000) shows that the set of strategy-proof, nonbossy, Pareto optimal and reallocation-proof rules are hierarchical exchange rules | generalizat......The problem of allocating indivisible objects to different agents, where each indi vidual is assigned at most one object, has been widely studied. Pápai (2000) shows that the set of strategy-proof, nonbossy, Pareto optimal and reallocation-proof rules are hierarchical exchange rules...... | generalizations of Gale's Top Trading Cycles mechanism. We study the centralized allocation that takes place in multiple markets. For example, the assignment of multiple types of indivisible objects; or the assignment of objects in successive periods. We show that the set of strategy-proof, Pareto efficient...

  12. CST-01-Central Standard Timing

    Institute of Scientific and Technical Information of China (English)



  13. Banco Central de Costa Rica

    Directory of Open Access Journals (Sweden)

    Sauter, Franz


    Full Text Available This new building is intended to house the various services of the Central Bank of Costa Rica. It has a prestressed concrete structure, and consists of a basement parking space for 105 vehicles, and nine storeys, providing altogether a floor surface of 12,000 ms2. The building rests on a ground area of 40 by 60 ms, and the main structure occupies 22 by 45 ms. This Bank is located in a district of narrow streets, but its main side overlooks a green open space, which will improve its visibility and appearance. The building structure is made up of a framework of prestressed beams and columns. The beams have been concreted at the site, and the joists, which are also prestressed, are factory made. This framework, at each floor level, constitutes the basis of a continuous slab, which renders the total structure exceedingly stiff. The main continuous girders span 11.22 ms spaces, and vary in cross section. The prestressing reinforcements consist of 6 Loeba type cables. This is an original design by Dr. Leonhardt, in which the cables are placed on three horizontal layers, of parabolic outline. Each cable is made up of 12 x 5.4 mm wires, with a breaking stress of 180 kg/mm2 The tensioning stress was 108 kg/mm2, and the total prestress load is 29,700 kgs. The cables run in corrugated metal tubes, and these were kept in precise position with the aid of distance pieces.El nuevo edificio, destinado a agrupar los servicios del Banco Central de Costa Rica, está constituido por una estructura de hormigón pretensado. El inmueble dispone de un sótano, estacionamiento propio para 105 vehículos y nueve plantas, con una superficie total de 12.000 metros cuadrados. Se asienta sobre una base de 40x60 m, donde se levanta un núcleo central de 22x45 metros. Está situado en un barrio de calles estrechas, pero tiene su fachada, principal frente a una zona verde que le proporcionará mayor categoría y visibilidad. La estructura se compone de una retícula de vigas

  14. ITER Central Solenoid Module Fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Smith, John [General Atomics, San Diego, CA (United States)


    The fabrication of the modules for the ITER Central Solenoid (CS) has started in a dedicated production facility located in Poway, California, USA. The necessary tools have been designed, built, installed, and tested in the facility to enable the start of production. The current schedule has first module fabrication completed in 2017, followed by testing and subsequent shipment to ITER. The Central Solenoid is a key component of the ITER tokamak providing the inductive voltage to initiate and sustain the plasma current and to position and shape the plasma. The design of the CS has been a collaborative effort between the US ITER Project Office (US ITER), the international ITER Organization (IO) and General Atomics (GA). GA’s responsibility includes: completing the fabrication design, developing and qualifying the fabrication processes and tools, and then completing the fabrication of the seven 110 tonne CS modules. The modules will be shipped separately to the ITER site, and then stacked and aligned in the Assembly Hall prior to insertion in the core of the ITER tokamak. A dedicated facility in Poway, California, USA has been established by GA to complete the fabrication of the seven modules. Infrastructure improvements included thick reinforced concrete floors, a diesel generator for backup power, along with, cranes for moving the tooling within the facility. The fabrication process for a single module requires approximately 22 months followed by five months of testing, which includes preliminary electrical testing followed by high current (48.5 kA) tests at 4.7K. The production of the seven modules is completed in a parallel fashion through ten process stations. The process stations have been designed and built with most stations having completed testing and qualification for carrying out the required fabrication processes. The final qualification step for each process station is achieved by the successful production of a prototype coil. Fabrication of the first

  15. Performance contracting in central government in Denmark

    DEFF Research Database (Denmark)

    Kristiansen, Mads Bøge


    in organisational structure, tasks, culture and time with performance contracts is expected to affect the contract content, hypotheses on variation across agencies are deduced. The empirical basis of the paper is a study of all performance contracts between parent ministries and subordinate agencies in Danish......This paper looks into performance contracting in Danish central government. Management by Objectives and Results (MBOR) was adopted in central government in Denmark during the 1980s and early 1990s. In 1991, performance contracts between parent ministries and their agencies were introduced...... in Danish central government. Since their introduction, performance contracts have become central elements in the steering and management of agencies in central government in Denmark, and today they are nearly universally adopted in central government. In Denmark, the Ministry of Finance is responsible...

  16. Hirsch index as a network centrality measure

    CERN Document Server

    Campiteli, Monica G; Soles, Paulo R C; Soares, Leonardo H D; Kinouchi, Osame


    We study the h Hirsch index as a local node centrality measure for complex networks in general. The h index is compared with the Degree centrality (a local measure), the Betweenness and Eigenvector centralities (two non-local measures) in the case of a biological network (Yeast interaction protein-protein network) and a linguistic network (Moby Thesaurus II) as test environments. In both networks, the Hirsch index has poor correlation with Betweenness centrality but correlates well with Eigenvector centrality, specially for the more important nodes that are relevant for ranking purposes, say in Search Machine Optimization. In the thesaurus network, the h index seems even to outperform the Eigenvector centrality measure as evaluated by simple linguistic criteria.

  17. A matrix analysis of different centrality measures

    CERN Document Server

    Benzi, Michele


    Node centrality measures including degree, eigenvector, Katz and subgraph centralities are analyzed for both undirected and directed networks. We show how parameter-dependent measures, such as Katz and subgraph centrality, can be "tuned" to interpolate between degree and eigenvector centrality, which appear as limiting cases of the other measures. We interpret our finding in terms of the local and global influence of a given node in the graph as measured by graph walks of different length through that node. Our analysis gives some guidance for the choice of parameters in Katz and subgraph centrality, and provides an explanation for the observed correlations between different centrality measures and for the stability exhibited by the ranking vectors for certain parameter ranges. The important role played by the spectral gap of the adjacency matrix is also highlighted.

  18. Reduced central blood volume in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Sørensen, T I


    for measuring the central blood volume. We have developed a method that enables us to determine directly the central blood volume, i.e., the blood volume in the heart cavities, lungs, and central arterial tree. In 60 patients with cirrhosis and 16 control subjects the central blood volume was assessed according......The pathogenesis of ascites formation in cirrhosis is uncertain. It is still under debate whether the effective blood volume is reduced (underfilling theory) or whether the intravascular compartment is expanded (overflow theory). This problem has not yet been solved because of insufficient tools...... to the kinetic theory as the product of cardiac output and mean transit time of the central vascular bed. Central blood volume was significantly smaller in patients with cirrhosis than in controls (mean 21 vs. 27 ml/kg estimated ideal body weight, p less than 0.001; 25% vs. 33% of the total blood volume, p less...

  19. Market strategies for Central American dry beans.


    Mertínez, Lourdes; Bernsten, Richard; Zamora, Miguel


    In the past few years, the dry bean sub-sector in CentralAmerica has witnessed many dynamic changes. Unless wefind ways to increase the competitiveness of the regionalbean sub-sector, Central American countries will likelyexperience significant negative social and economic impacts,especially since these countries are facing the challenge ofadjusting to new open markets, such as the Central AmericanFree Trade Agreement (CAFTA). Bean traders, retailers, andknowledgeable government official in C...

  20. Transpleural central venous catheter discovered during thoracotomy

    Directory of Open Access Journals (Sweden)

    Ashima Malhotra


    Full Text Available We report an uncommon complication of subclavian central venous catheterization, discovered at thoracotomy. The central venous catheter (CVC was placed by left infraclavicular route after induction of general anesthesia. CVC was secured after aspiration of blood and satisfactory central venous tracing. On thoracotomy, CVC was noticed to traverse the pleural cavity while the tracing was normal. CVC was thus removed consequent to which bleeding from each puncture site was noticed, that were secured surgically.

  1. The Centrality of Organization Design

    Directory of Open Access Journals (Sweden)

    Raymond E. Miles


    Full Text Available I am excited about this new journal focused on the subject of organization design. In my view, organization design is a central issue in the field of management. Designing an organization requires an understanding of strategy, as we pointed out some time ago (Miles & Snow, 1978. For example, if you want to be a prospector (a first-mover strategy, you have to design your firm to move quickly in new directions, which is likely to require that it be arranged so that various kinds of teams can interact across organizational units and levels. Designing an organization to follow a first-mover strategy also requires both an understanding of leadership and a commitment to the free flow of information throughout the organization. Leaders must understand how cross-functional teams pursue ideas and opportunities, and they must facilitate collaborative knowledge sharing to drive innovations that help the firm operate entrepreneurially. Because an organization is a complex, dynamic system, perhaps no other single topic is so deeply implanted at the core of management, organization theory, and organizational behavior as organization design. Moreover, organization design once was, and could be again, the topic of an ongoing dialogue between managers and academics focused on business organizations.

  2. Maximal switchability of centralized networks (United States)

    Vakulenko, Sergei; Morozov, Ivan; Radulescu, Ovidiu


    We consider continuous time Hopfield-like recurrent networks as dynamical models for gene regulation and neural networks. We are interested in networks that contain n high-degree nodes preferably connected to a large number of N s weakly connected satellites, a property that we call n/N s -centrality. If the hub dynamics is slow, we obtain that the large time network dynamics is completely defined by the hub dynamics. Moreover, such networks are maximally flexible and switchable, in the sense that they can switch from a globally attractive rest state to any structurally stable dynamics when the response time of a special controller hub is changed. In particular, we show that a decrease of the controller hub response time can lead to a sharp variation in the network attractor structure: we can obtain a set of new local attractors, whose number can increase exponentially with N, the total number of nodes of the nework. These new attractors can be periodic or even chaotic. We provide an algorithm, which allows us to design networks with the desired switching properties, or to learn them from time series, by adjusting the interactions between hubs and satellites. Such switchable networks could be used as models for context dependent adaptation in functional genetics or as models for cognitive functions in neuroscience.

  3. Central nervous system tuberculosis: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kioumehr, F.; Dadsetan, M.R.; Rooholamini, S.A.; Au, A.


    The MRI findings of 18 proven cases of central nervous system (CNS) tuberculosis were reviewed; 10 patients were seropositive for HIV. All had medical, laboratory, or surgical proof of CNS tuberculosis. Eleven patients had meningitis, of whom two also had arachnoiditis. Five patients had focal intra-axial tuberculomas: four brain masses and one an intramedullary spinal lesion. Two patients had focal extra-axial tuberculomas: one in the pontine cistern, and one in the spine. In all 11 patients with meningitis MRI showed diffuse, thick, meningeal enhancement. All intraparenchymal tuberculomas showed low signal intensity on T2-weighted images and ring or nodular enhancement. The extra-axial tuberculomas had areas isointense or hypointense relative to normal brain and spinal cord on T2-weighted images. Although tuberculous meningitis cannot be differentiated from other meningitides on the basis of MR findings, intraparenchymal tuberculomas show characteristic T2 shortening, not found in most other space-occupying lesions. In the appropriate clinical setting, tuberculoma should be considered. (orig.)

  4. Towards a centralized Grid Speedometer

    Energy Technology Data Exchange (ETDEWEB)

    Dzhunov, I. [CERN; Andreeva, J. [CERN; Fajardo, E.; Gutsche, O.; Luyckx, S.; Saiz, P. [CERN


    Given the distributed nature of the Worldwide LHC Computing Grid and the way CPU resources are pledged and shared around the globe, Virtual Organizations (VOs) face the challenge of monitoring the use of these resources. For CMS and the operation of centralized workflows, the monitoring of how many production jobs are running and pending in the Glidein WMS production pools is very important. The Dashboard Site Status Board (SSB) provides a very flexible framework to collect, aggregate and visualize data. The CMS production monitoring team uses the SSB to define the metrics that have to be monitored and the alarms that have to be raised. During the integration of CMS production monitoring into the SSB, several enhancements to the core functionality of the SSB were required, They were implemented in a generic way, so that other VOs using the SSB can exploit them. Alongside these enhancements, there were a number of changes to the core of the SSB framework. This paper presents the details of the implementation and the advantages for current and future usage of the new features in SSB.

  5. Towards a centralized Grid Speedometer

    CERN Document Server

    Gutsche, Oliver


    Given the distributed nature of the grid and the way CPU resources are pledged and scared around the globe, VOs are facing the challenge to monitor the use of these resources. For CMS and the operation of centralized workflows the monitoring of how many production jobs are running and pending in the Glidein WMS production pools is very important. The Dashboard SSB (Site Status Board) provides a very flexible framework to collect, aggregate and visualize data. The CMS production monitoring team uses the SSB to define the metrics that have to be monitored and the alarms that have to be set. During the integration of the CMS production monitoring into the SSB, several enhancements to the core functionality of the SSB were implemented; all in a generic way, so that other VOs using the SSB can use them as well. Alongside these enhancements, there were a few changes to the core of the SSB framework from which the CMS production team was able to benefit. We will present the details of the implementation and the adva...

  6. [Aniseikonia of central serous chorioretinopathy]. (United States)

    Hisada, H; Awaya, S


    Central serous chorioretinopathy (CRS) is one of the typical diseases that accompany micropsia. However very little is known about micropsia of CRS, because of the difficulty to measure "aniseikonia" in terms of micropsia. Aniseikonia in 65 cases of CRS was measured quantitatively by Awaya's New Aniseikonia Tests (NAT). The tests were performed at two different distances of 40 cm (visual angle: 6 degrees) and 20 cm (12 degrees) and under 4 meridians of the halfmoon on NAT, horizontal, 45 degrees, vertical and 135 degrees, respectively. The mean value of aniseikonia under each testing condition was as follows: 6 degrees horizontal -3.13%, 45 degrees -2.56%, vertical -2.13%, 135 degrees -2.57%, 12 degrees; horizontal -1.38%, 45 degrees -1.69%, vertical -1.84%, 135 degrees -1.50%. At 6 degrees aniseikonia is larger in the horizontal meridian than in the vertical with statistical significance (t-test, p less than 0.05), while at 12 degrees aniseikonia is smaller than at 6 degrees and shows no particular tendency in terms of meridian. The phenomenon observed at 6 degrees may be what is called "oriented metamorphopsia".

  7. Concept of the central clip

    DEFF Research Database (Denmark)

    Alegria-Barrero, Eduardo; Chan, Pak Hei; Foin, Nicolas


    -risk surgical population with severe mitral regurgitation (MR). METHODS AND RESULTS: Patients with severe MR (3 or 4+) and high operative risk (as defined by logistic EuroSCORE) refused for conventional mitral valve repair were considered for MitraClip(®). The procedure was performed under general anaesthesia...... with transoesophageal echocardiographic (TOE) guidance. Device success was defined as placement of one or more MitraClips(®) with a reduction of MR to ≤2+. Patients were followed up clinically and with TOE at one month and one year. From September 2009 to March 2012, 43 patients with severe MR with a mean age of 74.......8±10.7 years (30 males, 13 females; mean logistic EuroSCORE 24.1±11, mean LVEF 47.5±18.5%; mean±SD) were treated. Median follow-up was 385 days (104-630; Q1-Q3). Device implantation success was 93%. All patients were treated following the central clip concept: 52.5% of MR was degenerative in aetiology and 47...

  8. Central venous line complications and tip detection

    Directory of Open Access Journals (Sweden)

    Ameneh Rezaee Gheshlaghi


    Full Text Available Central venous line is one of a creative instrument that saves human’s life in critical medical situation. Central venous line access is frequently involved in the disease management. It is used for rapid fluid therapy, transvenous pacemakers, infusion of some medications, hemodialysis or plasmapheresis and etc. Most of the emergency departments have some staffs that are trained for central venous line insertion but related complications occur during central venous line placement.Central venous line might have some complications and complication follow-up should be considered. Thromboembolism and infection are two important medical complications. Arterial puncture, hematoma, pneumothorax and hemothorax are mechanical Central venous line complications. Chest X-ray and some other techniques should be used for detecting these complications.Central venous line tip misplace is a considerable problem for emergency department staffs, previously chest X-ray has been used for central venous line misplace detection. In some recent studies, contrast-enhanced ultrasonography and intravascular electrocardiography have been used for central venous line misplace.

  9. A global central banker competency model

    Directory of Open Access Journals (Sweden)

    David W. Brits


    Full Text Available Orientation: No comprehensive, integrated competency model exists for central bankers. Due to the importance of central banks in the context of the ongoing global financial crisis, it was deemed necessary to design and validate such a model.Research purpose: To craft and validate a comprehensive, integrated global central banker competency model (GCBCM and to assess whether central banks using the GCBCM for training have a higher global influence.Motivation for the study: Limited consensus exists globally about what constitutes a ‘competent’ central banker. A quantitatively validated GCBCM would make a significant contribution to enhancing central banker effectiveness, and also provide a solid foundation for effective people management.Research approach, design and method: A blended quantitative and qualitative research approach was taken. Two sets of hypotheses were tested regarding the relationships between the GCBCM and the training offered, using the model on the one hand, and a central bank’s global influence on the other.Main findings: The GCBCM was generally accepted across all participating central banks globally, although some differences were found between central banks with higher and lower global influence. The actual training offered by central banks in terms of the model, however, is generally limited to technical-functional skills. The GCBCM is therefore at present predominantly aspirational. Significant differences were found regarding the training offered.Practical/managerial implications: By adopting the GCBCM, central banks would be able to develop organisation-specific competency models in order to enhance their organisational capabilities and play their increasingly important global role more effectively.Contribution: A generic conceptual framework for the crafting of a competency model with evaluation criteria was developed. A GCBCM was quantitatively validated.

  10. Haemangiopericytoma of central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Borg, M.F.; Benjamin, C.S. [Auckland Hospital, Auckland (New Zealand). Dept. of Clinical Oncology


    The records of four patients presenting with a histological diagnosis of haemangiopericytoma of the central nervous system, in Auckland, New Zealand, between 1970 and 1990 were reviewed retrospectively, with the aim of determining the natural history of the disease and response to various treatment modalities. Three out of the four patients reviewed presented with primary cerebral disease and the fourth with a primary spinal cord tumour. All three cerebral primary patients were initially treated with local surgical excision. All three patients received radical radiotherapy following local recurrence. The first two patients remained disease-free locally although one patient developed a solitary liver metastasis 5 years after radiotherapy. The third patient was referred with multiple cerebral metastases and failed to respond to radiotherapy. The patient with the primary lesion in the spinal cord was treated with local excision followed by postoperative radiotherapy and remains disease-free 17 years after treatment. One patient failed to respond to chemotherapy, prescribed to treat a local recurrence adjacent to the previous radiotherapy field. This was successfully excised subsequently. The patient presenting with multiple cerebral metastases was the only patient to die of this disease. Results suggest that local recurrence is avoidable with adequate wide excision of the primary tumour followed by local radical radiotherapy. The role of chemotherapy remains controversial and no conclusion could be drawn regarding the role of palliative radiotherapy from this study. Active treatment and long-term follow-up are necessary because of the relative aggressiveness of this disease and the propensity for late relapses. 22 refs., 2 tabs., 6 figs.

  11. Tethyan evolution of central Asia

    Energy Technology Data Exchange (ETDEWEB)

    Sengor, A.M.C. (Instanbul Technical Univ. (Turkey))


    The study area extends from the eastern shores of the Caspian Sea in the west to the Helan Shan and Longmen Shan in the east and from about 40{degree}N parallel in the north to the neo-Tethyan sutures in the south, thus including what is called Middle Asia in the Soviet literature. In the region thus delineated lies the boundary between the largely late Paleozoic core of Asia (Altaids) and the Tethyside superorogenic complex. This boundary passes through continental objects that collided with nuclear Asia in the late Paleozoic to terminate its Altaid evolution. Subduction to the south of some of these had commenced before they collided (e.g., Tarim in the Kuen-Lun), in others later (e.g., South Ghissar area west of Pamirs). This subduction 1ed, in the late Paleozoic, to the opening of marginal basins, at least one of which may be partly extant (Tarim). Giant subduction accretion complexes of Paleozoic to earliest Triassic age dominate farther south in the basement of Turan (mainly in Turkmenian SSR) and in the Kuen-Lun/Nan Shan ranges. No discrete continental collisions or any continental basement in these regions could be unequivocally recognized contrary to most current interpretations. Magmatic arcs that developed along the southern margin of Asia in the late Paleozoic to early Mesozoic grew atop these subduction-accretion complexes and record a gradual southerly migration of magmatism through time. Subduction also dominated the northern margin of Gondwanaland between Iran and China in late Paleozoic time, although the record in Afghanistan and northwest Tibet is scrappy. It led to back-arc basin formation, which in Iran and Oman became neo-Tethys and, in at least parts of central Asia, the Waser-Mushan-Pshart/Banggong Co-Nu Jiang ocean. This ocean was probably connected with the Omani part of the neo-Tethys via the Sistan region.

  12. Digital data sets that describe aquifer characteristics of the Central Oklahoma aquifer in central Oklahoma (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized polygons of a constant hydraulic conductivity value for the Central Oklahoma aquifer in central Oklahoma. This area encompasses...

  13. Digital data sets that describe aquifer characteristics of the Central Oklahoma aquifer in central Oklahoma (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized water-level elevation contours for the Central Oklahoma aquifer in central Oklahoma. This area encompasses all or part of...

  14. Digital data sets that describe aquifer characteristics of the Central Oklahoma aquifer in central Oklahoma (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized aquifer boundaries created for a previously published report about the Central Oklahoma aquifer in central Oklahoma. This area...

  15. Digital data sets that describe aquifer characteristics of the Central Oklahoma aquifer in central Oklahoma (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized polygons of a constant recharge value for the Central Oklahoma aquifer in central Oklahoma. This area encompasses all or part of...

  16. Novel central nervous system drug delivery systems. (United States)

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz


    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  17. Central Life Interests and Job Satisfaction. (United States)

    Dubin, Robert; And Others

    Data on central life interests (CLI) and five aspects of job satisfaction were obtained in a sample of bluecollar males and two samples of clerical females. Both a multiple discriminant analysis and a bivariate analysis were performed. The results of these analyses showed that central life interest was significantly related to the total set of job…

  18. International Regulation of Central Arctic Ocean Fisheries

    NARCIS (Netherlands)

    Molenaar, E.J.


    Due in particular to the impacts of climate change, the adequacy of the international regulation of Central Arctic Ocean fisheries has come under increasing scrutiny in recent years. As shown in this article, however, international regulation of Central Arctic Ocean fisheries is by no means entirely

  19. An unusual Complication of Central Venous Cannulation

    Directory of Open Access Journals (Sweden)

    Ashvini Kumar


    Full Text Available Central venous catheter (CVC hub fracture is a rare complication of central venous cannulation. We report a case where catheter hub fracture was detected immediately after CVC insertion. Causes of catheter hub fracture and its complications are discussed.

  20. The Latino Experience in Central Falls (United States)

    Holland, William R.


    Central Falls is, by far, the poorest community in Rhode Island. More than 40 percent of the children under 18 live in poverty, and 40 percent of that group live in severe poverty. At Central Falls High School, low-income Latino students have fallen behind their white counterparts, with shockingly low graduation, poor literacy, and low…

  1. Computing betweenness centrality in external memory

    DEFF Research Database (Denmark)

    Arge, Lars; Goodrich, Michael T.; Walderveen, Freek van


    Betweenness centrality is one of the most well-known measures of the importance of nodes in a social-network graph. In this paper we describe the first known external-memory and cache-oblivious algorithms for computing betweenness centrality. We present four different external-memory algorithms...

  2. Traveling Policies: Hijacked in Central Asia (United States)

    Silova, Iveta


    Since the collapse of the Soviet Union, Central Asian education reform discourses have become increasingly similar to distinctive Western policy discourses traveling globally across national boundaries. Tracing the trajectory of "traveling policies" in Central Asia, this article discusses the way Western education discourses have been…

  3. China-Central Asia Power Cooperation Outlook

    Institute of Scientific and Technical Information of China (English)



    After analyzing the basic information,distribution of energy resources and condition of power industry in Central Asia, the high feasibility for China to cooperate closely with Central Asia in transnational power interconnection, power investment and technology exchanges, etc. is studied. Furthermore, the forms, mechanisms, existing problems and suggestions for the improvement of current policies related to the power cooperation are proposed.

  4. An overview of CMS central hadron calorimeter

    CERN Document Server

    Katta, S


    The central hadron calorimeter for CMS detector is a sampling calorimeter with active medium as scintillator plates interleaved with brass absorber plates. It covers the central pseudorapidity region (¿ eta ¿<3.0). The design and construction aspects are reported. The status of construction and assembly of various subdetectors of HCAL are presented. (5 refs).

  5. The Cartan Matrix of a Centralizer Algebra

    Indian Academy of Sciences (India)

    Umesh V Dubey; Amritanshu Prasad; Pooja Singla


    The centralizer algebra of a matrix consists of those matrices that commute with it. We investigate the basic representation-theoretic invariants of centralizer algebras, namely their radicals, projective indecomposable modules, injective indecomposable modules, simple modules and Cartan matrices. With the help of our Cartan matrix calculations we determine their global dimensions. Many of these algebras are of infinite global dimension.

  6. Central bank independence and financial instability

    NARCIS (Netherlands)

    Klomp, J.G.; de Haan, J.


    It has been argued that central bank independence (CBI) may not only be beneficial for reaching the objective of price stability, but also for maintaining financial stability. Greater independence from external pressure implies that central banks are less politically constrained in acting to prevent


    Institute of Scientific and Technical Information of China (English)

    Ya-xiang Yuan


    Interior point methods are very efficient methods for solving large scale linear programming problems. The central path plays a very important role in interior point methods. In this paper we propose a new central path, which scales the variables. Thus it has the advantage of forcing the path to have roughly the same distance from each active constraint boundary near the solution.

  8. Traveling Policies: Hijacked in Central Asia (United States)

    Silova, Iveta


    Since the collapse of the Soviet Union, Central Asian education reform discourses have become increasingly similar to distinctive Western policy discourses traveling globally across national boundaries. Tracing the trajectory of "traveling policies" in Central Asia, this article discusses the way Western education discourses have been hybridized…

  9. Central registry in psychiatry: A structured review

    Directory of Open Access Journals (Sweden)

    Jyoti Prakash


    Full Text Available Background: Central registry in psychiatry is being practiced in few countries and has been found useful in research and clinical management. Role of central registry has also expanded over the years. Materials and Methods: All accessible internet database Medline, Scopus, Embase were accessed from 1990 till date. Available data were systematically reviewed in structured manner and analyzed. Results: Central registry was found useful in epidemiological analysis, association studies, outcome studies, comorbidity studies, forensic issue, effective of medication, qualitative analysis etc., Conclusion: Central registry proves to be effective tool in quantitative and qualitative understanding of psychiatry practice. Findings of studies from central registry can be useful in modifying best practice and evidence based treatment in psychiatry.

  10. Central differences, Euler numbers and symbolic methods

    CERN Document Server

    Dowker, J S


    I relate some coefficients encountered when computing the functional determinants on spheres to the central differentials of nothing. In doing this I use some historic works, in particular transcribing the elegant symbolic formalism of Jeffery (1861) into central difference form which has computational advantages for Euler numbers, as discovered by Shovelton (1915). I derive sum rules for these, and for the central differentials, the proof of which involves an interesting expression for powers of sech x as multiple derivatives. I present a more general, symbolic treatment of central difference calculus which allows known, and unknown, things to be obtained in an elegant and compact fashion gaining, at no cost, the expansion of the powers of the inverse sinh, a basic central function. Systematic use is made of the operator 2 asinh(D/2). Umbral calculus is employed to compress the operator formalism. For example the orthogonality/completeness of the factorial numbers, of the first and second kinds, translates, ...

  11. Central station market development strategies for photovoltaics (United States)


    Federal market development strategies designed to accelerate the market penetration of central station applications of photovoltaic energy system are analyzed. Since no specific goals were set for the commercialization of central station applications, strategic principles are explored which, when coupled with specific objectives for central stations, can produce a market development implementation plan. The study includes (1) background information on the National Photovoltaic Program, photovoltaic technology, and central stations; (2) a brief market assessment; (3) a discussion of the viewpoints of the electric utility industry with respect to solar energy; (4) a discussion of commercialization issues; and (5) strategy principles. It is recommended that a set of specific goals and objectives be defined for the photovoltaic central station program, and that these goals and objectives evolve into an implementation plan that identifies the appropriate federal role.

  12. Centrality and economic development in the Rijnland region: social and spatial concepts of centrality

    NARCIS (Netherlands)

    Van Nes, A.


    In urban research, spatial and social concepts of centrality are being distinguished. From a spatial point of view, metrical centrality implies that something is located in the middle of an area. However, metrical and topological centrality are not equivalent. In research where space syntax methods

  13. XNAT Central: Open sourcing imaging research data. (United States)

    Herrick, Rick; Horton, William; Olsen, Timothy; McKay, Michael; Archie, Kevin A; Marcus, Daniel S


    XNAT Central is a publicly accessible medical imaging data repository based on the XNAT open-source imaging informatics platform. It hosts a wide variety of research imaging data sets. The primary motivation for creating XNAT Central was to provide a central repository to host and provide access to a wide variety of neuroimaging data. In this capacity, XNAT Central hosts a number of data sets from research labs and investigative efforts from around the world, including the OASIS Brains imaging studies, the NUSDAST study of schizophrenia, and more. Over time, XNAT Central has expanded to include imaging data from many different fields of research, including oncology, orthopedics, cardiology, and animal studies, but continues to emphasize neuroimaging data. Through the use of XNAT's DICOM metadata extraction capabilities, XNAT Central provides a searchable repository of imaging data that can be referenced by groups, labs, or individuals working in many different areas of research. The future development of XNAT Central will be geared towards greater ease of use as a reference library of heterogeneous neuroimaging data and associated synthetic data. It will also become a tool for making data available supporting published research and academic articles.

  14. Betweenness Centrality in Some Classes of Graphs

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Raghavan Unnithan


    Full Text Available There are several centrality measures that have been introduced and studied for real-world networks. They account for the different vertex characteristics that permit them to be ranked in order of importance in the network. Betweenness centrality is a measure of the influence of a vertex over the flow of information between every pair of vertices under the assumption that information primarily flows over the shortest paths between them. In this paper we present betweenness centrality of some important classes of graphs.

  15. Central Serous Chorioretinopathy after Solar Eclipse Viewing

    Directory of Open Access Journals (Sweden)

    Allie Lee


    Full Text Available Purpose: To report a case of central serous chorioretinopathy after solar eclipse viewing. Case Report: A middle-age man developed a sudden-onset unilateral scotoma after viewing a partial solar eclipse in Hong Kong. Fundus examination, fluorescein angiography, and optical coherence tomography showed features compatible with central serous chorioretinopathy. The patient was managed conservatively and reevaluated periodically. Serial optical coherence tomographic evaluations demonstrated an initial increase in the amount of subretinal fluid which spontaneously resolved 10 weeks after the onset of symptoms. Conclusion: This case demonstrates the possibility of development of central serous chorioretinopathy following solar eclipse viewing.

  16. [Functional anatomy of the central nervous system]. (United States)

    Krainik, A; Feydy, A; Colombani, J M; Hélias, A; Menu, Y


    The central nervous system (CNS) has a particular regional functional anatomy. The morphological support of cognitive functions can now be depicted using functional imaging. Lesions of the central nervous system may be responsible of specific symptoms based on their location. Current neuroimaging techniques are able to show and locate precisely macroscopic lesions. Therefore, the knowledge of functional anatomy of the central nervous system is useful to link clinical disorders to symptomatic lesions. Using radio-clinical cases, we present the functional neuro-anatomy related to common cognitive impairments.

  17. Central black hole masses of galaxies

    Institute of Scientific and Technical Information of China (English)



    In this paper, the stellar velocity dispersions in the host galaxies are used to estimate the central black hole masses for a sample of elliptical galaxies. We find that the central black hole masses are in the range of 10(5.5-9.5) M(○). Based on the estimated masses in this paper and those by Woo & Urry (2002) and the measured host galaxy absolute magnitude,a relation, log(MBH/M(○)) = -(0.25 ± 4.3 × 10-3)MR + (2.98 4 0.208) is found for central black hole mass and the host galaxy magnitude. Some discussions are presented.

  18. Erroneous laboratory values obtained from central catheters. (United States)

    Johnston, J B; Messina, M


    Serious analytic errors in potassium measurements have been identified in blood specimens obtained from newly inserted central catheters. Erroneous elevated readings have been related to interactions of chemistry analyzer electrodes and substances fixed to external and intraluminal walls of the central catheter. Anecdotal summaries of this phenomenon are presented to enable the nurse to recognize potential problems when sampling blood from central catheters. Studies were performed to determine the amount of flush necessary to clear the catheter of interfering residue. To eliminate this potentially hazardous occurrence, recommended flush volumes, nursing implications, and actions are described.

  19. Genetics Home Reference: central precocious puberty (United States)

    ... difference in gene activation is caused by a phenomenon called genomic imprinting. Because only the copy of ... cause the disorder. When passed from parent to child, the condition is known as familial central precocious ...

  20. 1999 Yellow River Aerial Photos, Central Wisconsin (United States)

    U.S. Geological Survey, Department of the Interior — The 25-mile stretch of the Yellow River adjacent to the Necedah National Wildlife Refuge in Central Wisconsin provides valuable habitat to numerous species of...

  1. Red wine, arterial stiffness and central hemodynamics. (United States)

    Karatzi, Kalliopi; Papaioannou, Theodore G; Papamichael, Christos; Lekakis, John; Stefanadis, Christodoulos; Zampelas, Antonis


    Red wine is considered to reduce cardiovascular risk and decrease peripheral systolic and diastolic blood pressure. Central aortic pressures are often more sensitive clinical and prognostic factors than peripheral pressures, while arterial stiffness is an independent prognostic factor for cardiovascular events. Great efforts are being made to find natural sources of improving health. In order to clarify the mechanisms under which a widely used drink, like red wine, is affecting heart and vessels, we aimed to review the available data regarding the effects of red wine on arterial stiffness, wave reflections and central blood pressures. The effect of red wine on central hemodynamics has been poorly explored with divergent results. Possible consequences of acute and long-term intake on arterial stiffness, wave reflections and central pressures are not clear. This might make someone skeptical when suggesting the consumption of a glass of red wine, although its cardioprotective actions (when moderately consumed) are already shown from epidemiological studies.

  2. NCI Central Review Board Receives Accreditation (United States)

    The Association for the Accreditation of Human Research Protection Programs has awarded the NCI Central Institutional Review Board full accreditation. AAHRPP awards accreditation to organizations demonstrating the highest ethical standards in clinical res

  3. Random walk centrality in interconnected multilayer networks

    CERN Document Server

    Solé-Ribalta, Albert; Gómez, Sergio; Arenas, Alex


    Real-world complex systems exhibit multiple levels of relationships. In many cases they require to be modeled as interconnected multilayer networks, characterizing interactions of several types simultaneously. It is of crucial importance in many fields, from economics to biology and from urban planning to social sciences, to identify the most (or the less) influential nodes in a network using centrality measures. However, defining the centrality of actors in interconnected complex networks is not trivial. In this paper, we rely on the tensorial formalism recently proposed to characterize and investigate this kind of complex topologies, and extend two well known random walk centrality measures, the random walk betweenness and closeness centrality, to interconnected multilayer networks. For each of the measures we provide analytical expressions that completely agree with numerically results.

  4. Central Gulf of Alaska Rockfish Permit Program (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The North Pacific Fishery Management Council adopted the Central Gulf of Alaska Rockfish Program (Rockfish Program) on June 14, 2010, to replace the expiring Pilot...

  5. California Black Rail - Central Delta [ds17 (United States)

    California Department of Resources — Results of taped-call black rail surveys of in-stream habitat within certain waterways in the central Sacramento / San Joaquin Delta during 1992 and 1993. TIME...

  6. Central Asian Snow Cover from Hydrometeorological Surveys (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Central Asian Snow Cover from Hydrometeorological Surveys data are based on observations made by personnel for three river basins: Amu Darya, Sir Darya, and...

  7. Legume Diversity Patterns in West Central Africa

    NARCIS (Netherlands)

    Estrella, de la M.; Mateo, M.A.; Wieringa, J.J.; Mackinder, B.; Munoz, J.


    Objectives - Species Distribution Models (SDMs) are used to produce predictions of potential Leguminosae diversity in West Central Africa. Those predictions are evaluated subsequently using expert opinion. The established methodology of combining all SDMs is refined to assess species diversity withi

  8. Childhood Central Nervous System Embryonal Tumors Treatment (United States)

    ... Cord Tumors Treatment Childhood Astrocytomas Treatment Childhood Brain Stem Glioma ... Central nervous system (CNS) embryonal tumors may begin in embryonic (fetal) cells that remain in the brain after birth. ...

  9. NCPC Central Files Information System (CFIS) (United States)

    National Capital Planning Commission — This dataset contains records from NCPC's Central Files Information System (CFIS), which is a comprehensive database of projects submitted to NCPC for design review...

  10. Central respiratory failure during acute organophosphate poisoning. (United States)

    Carey, Jennifer L; Dunn, Courtney; Gaspari, Romolo J


    Organophosphate (OP) pesticide poisoning is a global health problem with over 250,000 deaths per year. OPs affect neuronal signaling through acetylcholine (Ach) neurotransmission via inhibition of acetylcholinesterase (AChE), leading to accumulation of Ach at the synaptic cleft and excessive stimulation at post-synaptic receptors. Mortality due to OP agents is attributed to respiratory dysfunction, including central apnea. Cholinergic circuits are integral to many aspects of the central control of respiration, however it is unclear which mechanisms predominate during acute OP intoxication. A more complete understanding of the cholinergic aspects of both respiratory control as well as neural modification of pulmonary function is needed to better understand OP-induced respiratory dysfunction. In this article, we review the physiologic mechanisms of acute OP exposure in the context of the known cholinergic contributions to the central control of respiration. We also discuss the potential central cholinergic contributions to the known peripheral physiologic effects of OP intoxication.

  11. Alluvial Boundary of California's Central Valley (United States)

    U.S. Geological Survey, Department of the Interior — This digital dataset defines the extent of the alluvial deposits in the Central Valley of California and encompasses the contiguous Sacramento, San Joaquin, and...

  12. Shattering and Compressing Networks for Centrality Analysis

    CERN Document Server

    Sarıyüce, Ahmet Erdem; Kaya, Kamer; Çatalyürek, Ümit V


    Who is more important in a network? Who controls the flow between the nodes or whose contribution is significant for connections? Centrality metrics play an important role while answering these questions. The betweenness metric is useful for network analysis and implemented in various tools. Since it is one of the most computationally expensive kernels in graph mining, several techniques have been proposed for fast computation of betweenness centrality. In this work, we propose and investigate techniques which compress a network and shatter it into pieces so that the rest of the computation can be handled independently for each piece. Although we designed and tuned the shattering process for betweenness, it can be adapted for other centrality metrics in a straightforward manner. Experimental results show that the proposed techniques can be a great arsenal to reduce the centrality computation time for various types of networks.

  13. Earthquakes in Central California, 1980-1984 (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — There have been many earthquake occurrences in central California. This set of slides shows earthquake damage from the following events: Livermore, 1980, Coalinga,...

  14. Veterans Affairs Central Cancer Registry (VACCR) (United States)

    Department of Veterans Affairs — The Veterans Affairs Central Cancer Registry (VACCR) receives and stores information on cancer diagnosis and treatment constraints compiled and sent in by the local...

  15. Miniaturized Airborne Imaging Central Server System Project (United States)

    National Aeronautics and Space Administration — The innovation is a miniaturized airborne imaging central server system (MAICSS). MAICSS is designed as a high-performance-computer-based electronic backend that...

  16. Miniaturized Airborne Imaging Central Server System Project (United States)

    National Aeronautics and Space Administration — The innovation is a miniaturized airborne imaging central server system (MAICSS). MAICSS is designed as a high-performance computer-based electronic backend that...

  17. Central Bank Transparency: Causes, Consequences and Updates


    Nergiz Dincer; Barry Eichengreen


    We present updated estimates of central bank for 100 countries up through 2006 and use them to analyze both the determinants and consequences of monetary policy transparency in an integrated econometric framework. We establish that there has been significant movement in the direction of greater central bank transparency in recent years. Transparent monetary policy arrangements are more likely in countries with strong and stable political institutions. They are more likely in democracies, with...

  18. Economic Dimensions of Security in Central Asia (United States)


    dollars worth of illegal or unregistered cash, most of it associated with narcotics trafficking and unreported remittances from migrant labor , is...Economic Dimensions of Security in Central Asia month on some construction sites.32 Remittances from legal migrant labor are part of the Central Asian...farms and construction sites,36 since they rarely have any le- gal standing. Also, income from migrant labor is usually barely suffi- cient to cover

  19. "Shadow Banking: Policy Challenges for Central Banks"


    Moe, Thorvald Grung


    Central banks responded with exceptional liquidity support during the financial crisis to prevent a systemic meltdown. They broadened their tool kit and extended liquidity support to nonbanks and key financial markets. Many want central banks to embrace this expanded role as "market maker of last resort" going forward. This would provide a liquidity backstop for systemically important markets and the shadow banking system that is deeply integrated with these markets. But how much liquidity su...

  20. Central odontogenic fibroma of the simple type

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Eui Hwan; Lee, Sang Rae [Department of Oral and Maxillofacial Radiology, College of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)


    The central odontogenic fibroma is a rare benign neoplasm, and considered to be derived from the mesenchymal tissue of dental origin. It is a poorly defined tumor of the jawbones which has only been infrequently reported in the literature. We report a histologically proven case of simple-type central odontogenic fibroma, which affected the left canine-premolar region of the maxilla in a 52-year-old woman.

  1. Entrapment of guidewire during central venous catheterization

    Directory of Open Access Journals (Sweden)

    Tarun S.


    Full Text Available Central venous catheterization (CVC is common in the setting of ICU for various reasons like monitoring of CVP, fluid administration and vasopressor or drug infusions. Guidewires are routinely used in the Seldinger technique during central venous catheter placement CVC placement is not innocuous as numerous complications may occur, with varying frequency and severity. [Int J Res Med Sci 2016; 4(7.000: 3080-3081

  2. A handbook for solar central receiver design

    Energy Technology Data Exchange (ETDEWEB)

    Falcone, P.K.


    This Handbook describes central receiver technology for solar thermal power plants. It contains a description and assessment of the major components in a central receiver system configured for utility scale production of electricity using Rankine-cycle steam turbines. It also describes procedures to size and optimize a plant and discussed examples from recent system analyses. Information concerning site selection criteria, cost estimation, construction, and operation and maintenance is also included, which should enable readers to perform design analyses for specific applications.

  3. Midwifery education in Central-Eastern Europe. (United States)

    Mivšek, Polona; Baškova, Martina; Wilhelmova, Radka


    Problems in midwifery in many Central-Eastern European countries are very similar; it is possible to speak about the evolving Central-Eastern model of midwifery care. The educational models of this region have a relatively strong theoretical part; however, there is an insufficient practical dimension. Theoretical part of midwifery education in the universities is relatively autonomous and is slowly changing the professional identity of graduates.

  4. Central Hemodynamics and Microcirculation in Critical Conditions

    Directory of Open Access Journals (Sweden)

    A. A. Kosovskikh


    Full Text Available Objective: to compare central hemodynamic and microcirculatory changes in critical conditions caused by different factors and to reveal their possible differences for a further differentiated approach to intensive therapy. Subjects and methods. The study covered 16 subjects with severe concomitant injury (mean age 41.96±2.83 years and 19 patients with general purulent peritonitis (mean age 45.34±2.16 years. Their follow-up was 7 days. The central hemodynamics was estimated by transpulmonary thermodilution using a Pulsion PiCCO Plus system (Pulsion Medical Systems, Germany. The microcirculatory bed was evaluated by cutaneous laser Doppler flowmetry using a LAKK-02 capillary blood flow laser analyzer (LAZMA Research-and-Production Association, Russian Federation. Results. The pattern of central hemodynamic and microcirculatory disorders varies with the trigger that has led to a critical condition. Central hemodynamics should be stabilized to ensure the average level of tissue perfusion in victims with severe concomitant injury. In general purulent peritonitis, microcirculatory disorders may persist even if the macrohemodynamic parameters are normal. Conclusion. The macrohemodynamic and microcirculatory differences obtained during the study suggest that a complex of intensive therapy should be differentiated and, if the latter is used, it is necessary not only to be based on the central hemodynamics, but also to take into consideration functional changes in microcirculation. Key words: severe concomitant injury, general purulent peritonitis, micro-circulation, central hemodynamics, type of circulation.

  5. Fast network centrality analysis using GPUs

    Directory of Open Access Journals (Sweden)

    Shi Zhiao


    Full Text Available Abstract Background With the exploding volume of data generated by continuously evolving high-throughput technologies, biological network analysis problems are growing larger in scale and craving for more computational power. General Purpose computation on Graphics Processing Units (GPGPU provides a cost-effective technology for the study of large-scale biological networks. Designing algorithms that maximize data parallelism is the key in leveraging the power of GPUs. Results We proposed an efficient data parallel formulation of the All-Pairs Shortest Path problem, which is the key component for shortest path-based centrality computation. A betweenness centrality algorithm built upon this formulation was developed and benchmarked against the most recent GPU-based algorithm. Speedup between 11 to 19% was observed in various simulated scale-free networks. We further designed three algorithms based on this core component to compute closeness centrality, eccentricity centrality and stress centrality. To make all these algorithms available to the research community, we developed a software package gpu-fan (GPU-based Fast Analysis of Networks for CUDA enabled GPUs. Speedup of 10-50× compared with CPU implementations was observed for simulated scale-free networks and real world biological networks. Conclusions gpu-fan provides a significant performance improvement for centrality computation in large-scale networks. Source code is available under the GNU Public License (GPL at

  6. Central auditory function of deafness genes. (United States)

    Willaredt, Marc A; Ebbers, Lena; Nothwang, Hans Gerd


    The highly variable benefit of hearing devices is a serious challenge in auditory rehabilitation. Various factors contribute to this phenomenon such as the diversity in ear defects, the different extent of auditory nerve hypoplasia, the age of intervention, and cognitive abilities. Recent analyses indicate that, in addition, central auditory functions of deafness genes have to be considered in this context. Since reduced neuronal activity acts as the common denominator in deafness, it is widely assumed that peripheral deafness influences development and function of the central auditory system in a stereotypical manner. However, functional characterization of transgenic mice with mutated deafness genes demonstrated gene-specific abnormalities in the central auditory system as well. A frequent function of deafness genes in the central auditory system is supported by a genome-wide expression study that revealed significant enrichment of these genes in the transcriptome of the auditory brainstem compared to the entire brain. Here, we will summarize current knowledge of the diverse central auditory functions of deafness genes. We furthermore propose the intimately interwoven gene regulatory networks governing development of the otic placode and the hindbrain as a mechanistic explanation for the widespread expression of these genes beyond the cochlea. We conclude that better knowledge of central auditory dysfunction caused by genetic alterations in deafness genes is required. In combination with improved genetic diagnostics becoming currently available through novel sequencing technologies, this information will likely contribute to better outcome prediction of hearing devices.

  7. Dynamics-based centrality for directed networks (United States)

    Masuda, Naoki; Kori, Hiroshi


    Determining the relative importance of nodes in directed networks is important in, for example, ranking websites, publications, and sports teams, and for understanding signal flows in systems biology. A prevailing centrality measure in this respect is the PageRank. In this work, we focus on another class of centrality derived from the Laplacian of the network. We extend the Laplacian-based centrality, which has mainly been applied to strongly connected networks, to the case of general directed networks such that we can quantitatively compare arbitrary nodes. Toward this end, we adopt the idea used in the PageRank to introduce global connectivity between all the pairs of nodes with a certain strength. Numerical simulations are carried out on some networks. We also offer interpretations of the Laplacian-based centrality for general directed networks in terms of various dynamical and structural properties of networks. Importantly, the Laplacian-based centrality defined as the stationary density of the continuous-time random walk with random jumps is shown to be equivalent to the absorption probability of the random walk with sinks at each node but without random jumps. Similarly, the proposed centrality represents the importance of nodes in dynamics on the original network supplied with sinks but not with random jumps.

  8. Community centrality and social science research. (United States)

    Allman, Dan


    Community centrality is a growing requirement of social science. The field's research practices are increasingly expected to conform to prescribed relationships with the people studied. Expectations about community centrality influence scholarly activities. These expectations can pressure social scientists to adhere to models of community involvement that are immediate and that include community-based co-investigators, advisory boards, and liaisons. In this context, disregarding community centrality can be interpreted as failure. This paper considers evolving norms about the centrality of community in social science. It problematises community inclusion and discusses concerns about the impact of community centrality on incremental theory development, academic integrity, freedom of speech, and the value of liberal versus communitarian knowledge. Through the application of a constructivist approach, this paper argues that social science in which community is omitted or on the periphery is not failed science, because not all social science requires a community base to make a genuine and valuable contribution. The utility of community centrality is not necessarily universal across all social science pursuits. The practices of knowing within social science disciplines may be difficult to transfer to a community. These practices of knowing require degrees of specialisation and interest that not all communities may want or have.

  9. Making Central Banks Serve The Real Economy

    Directory of Open Access Journals (Sweden)

    Suleika Reiners


    Full Text Available The challenge is to redirect central bank money into the real economy and to the needs of society. If new money is issued to expand the productive capacity, there is no reason for inflation. Long-term financing could become available at an affordable price. Central bank money must not replace a sound tax system and the distribution of income and wealth, but complement them. The remaining task, apart from the financing of real needs, is the prevention of speculative asset price inflation. For this, central banks and regulators should install debt brakes for the financial sector. Furthermore, independent monetary policy calls for capital account management. It enables national central banks to find space for the conduct of their own policies in an interdependent global economy. Coordination between central banks and governments might increase as policies combine monetary, fiscal and regulatory facets. The future role of central banks should particularly lie in their insights regarding capital flows and leverage cycles and in their ability to create and withdraw money, depend­ing on economic conditions.

  10. Health challenges in Kazakhstan and Central Asia. (United States)

    Adambekov, Shalkar; Kaiyrlykyzy, Aiym; Igissinov, Nurbek; Linkov, Faina


    The Central Asian region, which encompasses Kazakhstan, Uzbekistan, Tajikistan, Turkmenistan and Kyrgyzstan, is an interesting geographic region with a rich history dating back to the Silk Road, Mongol conquests and expansion of the Russian Empire. However, from a public health viewpoint, the Central Asian region is under-investigated, and many public health challenges exist, as countries of Central Asia inherited the centralised medical systems practiced in the Soviet Union, and are currently undergoing rapid transitions. A large number of low and middle-income countries around the world, including countries of Central Asia, face a double burden of chronic and infectious disease. This essay focuses on the exploration of the most important public health challenges in the Central Asian region, including limited scientific productivity, the double burden of chronic and infectious disease, the need for healthcare reform and the reduction in care variation. Central Asia has a large number of medical schools, medical centres, and emerging research institutes that can be used to foster a change in medical and public health practice in the region.

  11. Determinants of Central Adiposity among Iranian Population

    Directory of Open Access Journals (Sweden)

    Leila Azadbakht


    Full Text Available Background: Central obesity is one of the major public health problems. Recent studies have indicated that body fat distribution would be important in general health. Materials and Methods: The present study is a review of several studies which discuss the contributing factors of abdominal obesity, particulary in Iran. This study reviews 34 cross-sectional and interventional studies, which have been comducted during 1995-2012 and issued in English language. PubMed search engine and the related keywords were used to search the papers.Results: Breakfast skipping and also the sleep duration as well as the quality of diet are also associated with central adiposity. Dietary diversity score among Iranians can be related to abdominal adiposity. Fastfood consumption can increase the risk of central adiposity among young Iranian population. Red meat intake and food source of trans fat can increase the risk of central adiposity. Low quality diet with low amount of nutrients can increase the risk of central adiposity. Conclusion: Some behaviours such as sleep duration and eating breakfast can be associated with central adiposity among Iranians. Diet quality and dietary diversity score is also associated with this problem among Iranians.

  12. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia

    DEFF Research Database (Denmark)

    Santini, Martin A; Ratner, Cecilia Friis; Aznar, Susana


    Prefrontal serotonin 2A receptors (5-HT2A Rs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5-HT2A R at clinical relevant doses, and activation of 5-HT2A receptors by lysergic acid diethylamide (LSD) and LSD-like drugs induces a schizophrenia...

  13. Market Information and Signaling in Central Bank Operations, or, How Often Should a Central Bank Intervene?


    International Monetary Fund


    A central bank must decide on the frequency with which it will conduct open market operations and the variability in short-term money market that it will allow. The paper shows how the optimal operating procedure balances the value of attaining an immediate target and broadcasting the central bank's intentions against the informational advantages to the central bank of allowing the free play of market forces to reveal more of the information available to market participants.

  14. Determination of designer drug cross-reactivity on five commercial immunoassay screening kits. (United States)

    Regester, Laura E; Chmiel, Jeffrey D; Holler, Justin M; Vorce, Shawn P; Levine, Barry; Bosy, Thomas Z


    The detection of new designer drugs is often a difficult issue in forensic urine drug testing as immunoassays are the primary screening methodology for drugs of abuse in many of these laboratories. Cross-reactivity of compounds with immunoassay kits can either aid or complicate the detection of a variety of drug and drug metabolites. For instance, emerging designer drugs that share structural similarities to amphetamines and phencyclidine (PCP) have the potential to cross-react with assays designed to detect these compounds. This study evaluates the cross-reactivity of five commercially available immunoassay reagent kits for 94 designer drugs on a Roche/Hitachi Modular P automated screening instrument. The compounds used in this study are grouped by structural class as follows: 2,5-dimethoxyamphetamines, 2C (2,5-dimethoxyphenethylamines), β-keto amphetamines, substituted amphetamines, piperazines, α-pyrrolidinopropiophenones, tryptamines and PCP analogs. A drug concentration of 100 µg/mL was used to determine cross-reactivity for each assay and resulted in the following positive rates: Microgenics DRI(®) Ecstasy enzyme assay (19%), Microgenics DRI(®) Phencyclidine enzyme assay (20%), Lin-Zhi Methamphetamine enzyme immunoassay (39%), Siemens/Syva(®) EMIT(®)II Plus Amphetamines assay (43%) and CEDIA(®) DAU Amphetamine/Ecstasy assay (57%). Of the 94 designer drugs tested, 14% produced a negative response for all five kits. No designer drug used in this study generated a positive result for all five immunoassay kits.

  15. Central nervous system complications after liver transplantation. (United States)

    Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu


    We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology.

  16. Dry needling - peripheral and central considerations. (United States)

    Dommerholt, Jan


    Dry needling is a common treatment technique in orthopedic manual physical therapy. Although various dry needling approaches exist, the more common and best supported approach targets myofascial trigger points. This article aims to place trigger point dry needling within the context of pain sciences. From a pain science perspective, trigger points are constant sources of peripheral nociceptive input leading to peripheral and central sensitization. Dry needling cannot only reverse some aspects of central sensitization, it reduces local and referred pain, improves range of motion and muscle activation pattern, and alters the chemical environment of trigger points. Trigger point dry needling should be based on a thorough understanding of the scientific background of trigger points, the differences and similarities between active and latent trigger points, motor adaptation, and central sensitize application. Several outcome studies are included, as well as comments on dry needling and acupuncture.

  17. Retail Market Structure Development in Central Europe

    Directory of Open Access Journals (Sweden)

    Martin Machek


    Full Text Available This article is analyzing the trends and development in the retailing sector in Central Europe, namely in the Czech Republic, Hungary, Poland and Slovakia. These markets serve about 63 million inhabitants. The retail industry in Central Europe has changed dramatically in the last two decades, and has become a model for successful transformation of emerging markets. The retail market is highly concentrated and dominated by Western European retail chains. International retail chains are using all formats of modern distribution. This article is focusing on the development of hypermarkets, supermarkets and discount stores. Due to the international retail chains, Central European countries benefit from a dense network of modern shopping places; the intense competition of highly productive retailers contributes to the lower level of inflation rate because of the so-called Wal-Mart Effect. The constant pressure on prices influences the marketing strategies of both retailers and suppliers.

  18. Centralized rehabilitation after servere traumatic brain injury

    DEFF Research Database (Denmark)

    Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk


    OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... an uptake area of 2.4 million in Denmark were included at admission to a regional brain injury unit (BIU), on average 19 days after injury. Patients in the retrospective study used for comparison were randomly chosen from the national hospital register. RESULTS AND CONCLUSIONS: Out of 117 patients...... post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge...

  19. Angiotensin II during Experimentally Simulated Central Hypovolemia

    DEFF Research Database (Denmark)

    Jensen, Theo Walther; Olsen, Niels Vidiendal


    Central hypovolemia, defined as diminished blood volume in the heart and pulmonary vascular bed, is still an unresolved problem from a therapeutic point of view. The development of pharmaceutical agents targeted at specific angiotensin II receptors, such as the non-peptidergic AT2-receptor agonist...... of these agents in a hypovolemic setting. We argue that the latest debates on the effect of angiotensin II during hypovolemia might guide for future studies, investigating the effect of such agents during experimentally simulated central hypovolemia. The purpose of this review is to examine the role...... of angiotensin II during episodes of central hypovolemia. To examine this, we reviewed results from studies with three experimental models of simulated hypovolemia: head up tilt table test, lower body negative pressure, and hemorrhage of animals. A systemic literature search was made with the use of Pub...

  20. Central pain: definition, phisiopathology and therapy

    Directory of Open Access Journals (Sweden)

    Vincenzo Moschini


    Full Text Available Central pain is the expression of an injury and/or a primary or secondary dysfunction of the central nervous system.1 It is based on total or partial damage along the spinal-thalamic-cortical pathways and it may have cerebral or spinal origin. It has variable incidence according to its etiology: 8-10% in stroke patients, 30% in multiple sclerosis patients, 30-60% in paraplegic patients.2-3 At the spinal level, the most frequent causes are: traumatic injuries, cancer, plaques from multiple sclerosis, syringomyelia. In this review, we examine the main symptoms that contribute to confirm the diagnosis of central pain, neuropathic or thalamic. The presence of nerve injury, evaluated by neuroimaging and neurophysiological tests, allows us to complete the diagnostic picture.

  1. Generation of central exclusive final states

    CERN Document Server

    Lönnblad, Leif


    We present a scheme for the generation of central exclusive final states in the Pythia 8 program. The implementation allows for the investigation of higher order corrections to such exclusive processes as approximated by the initial-state parton shower in Pythia 8. To achieve this, the spin and colour decomposition of the initial-state shower has been worked out, in order to determine the probability that a partonic state generated from an inclusive sub-process followed by a series of initial-state parton splittings can be considered as an approximation of an exclusive colour- and spin-singlet process. We use our implementation to investigate effects of parton showers on some examples of central exclusive processes, and find sizeable effects on di-jet production, while the effects on e.g. central exclusive Higgs production are minor.

  2. Smart electromechanical systems the central nervous system

    CERN Document Server

    Kurbanov, Vugar


    This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

  3. Centralized rehabilitation after servere traumatic brain injury

    DEFF Research Database (Denmark)

    Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk


    post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge......OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... an uptake area of 2.4 million in Denmark were included at admission to a regional brain injury unit (BIU), on average 19 days after injury. Patients in the retrospective study used for comparison were randomly chosen from the national hospital register. RESULTS AND CONCLUSIONS: Out of 117 patients...

  4. Central Venous Catheter-Related Hydrothorax

    Directory of Open Access Journals (Sweden)

    Se Hun Kim


    Full Text Available This report describes a case of 88-year-old women who developed central venous catheter-related bilateral hydrothorax, in which left pleural effusion, while right pleural effusion was being drained. The drainage prevented accumulation of fluid in the right pleural space, indicating that there was neither extravasation of infusion fluid nor connection between the two pleural cavities. The only explanation for bilateral hydrothorax in this case is lymphatic connections. Although vascular injuries by central venous catheter can cause catheter-related hydrothorax, it is most likely that the positioning of the tip of central venous catheter within the lymphatic duct opening in the right sub-clavian-jugular confluence or superior vena cava causes the catheter-related hydrothorax. Pericardial effusion can also result from retrograde lymphatic flow through the pulmonary lymphatic chains.

  5. Hydrogels for central nervous system therapeutic strategies. (United States)

    Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi


    The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described.

  6. Central functions of the orexinergic system

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yang Zhang; Lei Yu; Qian-Xing Zhuang; Jing-Ning Zhu; Jian-Jun Wang


    The neuropeptide orexin is synthesized by neurons exclusively located in the hypothalamus.However,these neurons send axons over virtually the entire brain and spinal cord and therefore constitute a unique central orexinergic system.It is well known that central orexin plays a crucial role in the regulation of various basic non-somatic and somatic physiological functions,including feeding,energy homeostasis,the sleep/wake cycle,reward,addiction,and neuroendocrine,as well as motor control.Moreover,the absence of orexin results in narcolepsy-cataplexy,a simultaneous somatic and non-somatic dysfunction.In this review,we summarize these central functions of the orexinergic system and associated diseases,and suggest that this system may hold a key position in somatic-non-somatic integration.

  7. 75 FR 14436 - Ameren Corporation, Illinois Power Company, Central Illinois Light Company, Central Illinois... (United States)


    ... Energy Regulatory Commission Ameren Corporation, Illinois Power Company, Central Illinois Light Company, Central Illinois Public Service Company, Ameren Energy Resources Company, LLC, AmerenEnergy Resources Generating Company; Notice of Filing March 18, 2010. Take notice that on March 15, 2010, Ameren...

  8. The primary Maxillary Central Incisor in the Solitary Median Maxillary Central Incisor syndrome

    DEFF Research Database (Denmark)

    Kjaer, I; Balslev-Olesen, M


    Solitary Median Maxillary Central Incisor (SMMCI) is a developmental anomaly in the permanent dentition with one single central incisor in the maxilla, positioned exactly in the midline. This condition has been associated with extra- and intraoral malformations in the frontonasal segment of the c...

  9. Actual versus perceived central bank transparency: the case of the European Central Bank

    NARCIS (Netherlands)

    van der Cruijsen, C.; Eijffinger, S.


    Central banks have become more and more transparent about their monetary policy making process. In the central bank transparency literature the distinction between actual and perceived transparency is often lacking. However, as perceptions are crucial for the actions of economic agents this distinct

  10. What Can We Learn from 15,000 Teachers in Central Europe and Central Asia? (United States)

    Temple, Charles


    Describes the "Reading and Writing for Critical Thinking Project" which has now sent more than 70 volunteer teacher educators into 20 countries across Central Europe and Central Asia to help teachers to try out methods that foster active learning and critical thinking. Discusses support for the project, teaching strategies introduced,…

  11. Central Bank Independence, Centralization of Wage Bargaining, Inflation and Unemployment - Theory and Some Evidence

    NARCIS (Netherlands)

    Cukierman, A.; Lippi, F.


    This paper proposes a conceptual framework to investigate the effects of central bank independence, of the degree of centralization of wage bargaining and of the interaction between those institutional variables, on real wages, unemployment and inflation, in a framework in which unions are averse to

  12. A History of the Central Limit Theorem

    CERN Document Server

    Fischer, Hans


    This study discusses the history of the central limit theorem and related probabilistic limit theorems from about 1810 through 1950. In this context the book also describes the historical development of analytical probability theory and its tools, such as characteristic functions or moments. The central limit theorem was originally deduced by Laplace as a statement about approximations for the distributions of sums of independent random variables within the framework of classical probability, which focused upon specific problems and applications. Making this theorem an autonomous mathematical

  13. Central nervous system involvement in diabetic neuropathy. (United States)

    Selvarajah, Dinesh; Wilkinson, Iain D; Davies, Jennifer; Gandhi, Rajiv; Tesfaye, Solomon


    Diabetic neuropathy is a chronic and often disabling condition that affects a significant number of individuals with diabetes. Long considered a disease of the peripheral nervous system, there is now increasing evidence of central nervous system involvement. Recent advances in neuroimaging methods detailed in this review have led to a better understanding and refinement of how diabetic neuropathy affects the central nervous system. Recognition that diabetic neuropathy is, in part, a disease that affects the whole nervous system is resulting in a critical rethinking of this disorder, opening a new direction for further research.

  14. Simulating central forces in the classroom

    CERN Document Server

    Aguirregabiria, Juan M


    We describe the easy to customize and extend open source Java program Central force workbench that can be used in the classroom to simulate the motion of a particle (or a two-body system) under central forces. It may be useful to illustrate problems in which the analytical solution is not available as well as to help students to grasp a more intuitive understanding of the main features of this kind of problem and to realize the exceptional nature of the particular case of Newtonian (and harmonic) forces. We also include some suggestions on how to use the program as a pedagogical tool.

  15. Peripheral and central mechanisms of stress resilience

    Directory of Open Access Journals (Sweden)

    Madeline L. Pfau


    Full Text Available Viable new treatments for depression and anxiety have been slow to emerge, likely owing to the complex and incompletely understood etiology of these disorders. A budding area of research with great therapeutic promise involves the study of resilience, the adaptive maintenance of normal physiology and behavior despite exposure to marked psychological stress. This phenomenon, documented in both humans and animal models, involves coordinated biological mechanisms in numerous bodily systems, both peripheral and central. In this review, we provide an overview of resilience mechanisms throughout the body, discussing current research in animal models investigating the roles of the neuroendocrine, immune, and central nervous systems in behavioral resilience to stress.

  16. Betweenness Centrality : Algorithms and Lower Bounds

    CERN Document Server

    Kintali, Shiva


    One of the most fundamental problems in large scale network analysis is to determine the importance of a particular node in a network. Betweenness centrality is the most widely used metric to measure the importance of a node in a network. In this paper, we present a randomized parallel algorithm, lower bounds and an algebraic method for computing betweenness centrality of all nodes in a network. We prove that any path comparison based algorithm cannot compute betweenness of all nodes in less than O(nm) time.

  17. Central odontogenic fibroma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Nah, Kyung Soo [School of Dentistry, Busan National University, Busan (Korea, Republic of)


    Central odontogenic fibroma is a rare odontogenic neoplasm that originates from odontogenic ectomesenchyme. Here, a case of central odontogenic fibroma in a 17-year-old male is reported. Since the present case showed a multilocular radiolucency with partially ill-defined border between the right mandibular condyle and the distal root of the right mandibular third molar, differential diagnosis involved a wide range of pathosis from benign lesions like ameoloblastic fibroma and odontogenic myxoma to more aggressive lesions such as desmoplastic fibroma, juvenile aggressive fibromatosis, or fibrosarcoma.

  18. Incoerenza temporale e indipendenza della banca centrale

    Directory of Open Access Journals (Sweden)

    Bruno Jossa


    Full Text Available According to the author, the emphasis authors currently tend to place on the 'surprise effect' in order to argue for the independence of central banks is to a large extent unjustified. The main arguments for the independence of a cen-tral bank are others: firstly, the opinion that governments are induced to in-cur excessive expenditure due to reasons highlighted by public choice theo-rists and, secondly, the idea that inflation arises in connection with social conflict. Additionally, this study makes it clear that 'time inconsistency' theory is far from being a new way of stating old ideas.  JEL Codes: E58Keywords:

  19. [Centralization in obstetrics: pros and cons]. (United States)

    Roemer, V M; Ramb, S


    Possible advantages and disadvantages of a general centralization of German obstetric facilities are analysed in the study. The need for centralization of risk cases, especially premature births (regionalization) is pointed out. Centralization appears appropriate, since every fifth maternity unit in Germany (19.78%) has 300 or fewer deliveries per year. This one fifth of perinatal clinics accounts for 6.3% of all deliveries (N = 49450). There are appreciable differences between the old and new federal states (Bundesländer): in the recently acceded federal states, 48.7% of all perinatal clinics have deliveries of 300 and less per year. This group of perinatal clinics accounts for 29% of all deliveries in the new federal states. We have carried out a survey of the mother's attitude to centralization: out of 416 patients in the Detmold women's hospital whose mean age was 29.0 +/- 4.2 years, 90.4% were not in favor of general centralization of obstetrics. 43% were also against a centralization of risk cases (regionalization). 75% of the women surveyed objected to centralized obstetrics because of the 'possible absence of the family', the 'possible absence of students and trainees' (44.9%), the 'unfamiliarity with staff and premises' (41.8%) and 'fear of anonymity' (44.5%). The majority of all women (84.1%) did not want to have a drive more than 20 km to an obstetrics center. Fear of 'delivery in a taxi'(78.6%), the 'fear that the husband will come too late to the delivery' (65.4%) and that the 'overall course of the delivery might not be adequate for reasons of time'. The presence of a pediatrics department in conjunction with the perinatal clinic was rated very positively (93%). It is concluded from the data and further juridical considerations that centralization of risk cases (regionalization) is indispensable in the near future and that somewhat more further into the future decentralization should be carried out by closing obstetrics departments with substantially

  20. The Boolean algebra and central Galois algebras

    Directory of Open Access Journals (Sweden)

    George Szeto


    Full Text Available Let B be a Galois algebra with Galois group G, Jg={b∈B∣bx=g(xb   for all   x∈B} for g∈G, and BJg=Beg for a central idempotent eg. Then a relation is given between the set of elements in the Boolean algebra (Ba,≤ generated by {0,eg∣g∈G} and a set of subgroups of G, and a central Galois algebra Be with a Galois subgroup of G is characterized for an e∈Ba.

  1. MRI of central nervous system anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Izawa, M.; Oikawa, A.; Matoba, A.


    MRI was very useful in the evaluation of congenital anomalies of central nervous system as well as other nervous system disease with three-dimensional spatial resolution. We had experienced MRI of central nervous system anomalies, demonstrated characterisitic findings in each anomaly. MRI is useful to observe the coronal, horizontal and sagittal images of the brain and spinal cord in order to discuss the etiological mechanisms of spinal dysraphysm and its associated anomalies. In case of spina bifida cystica MRI was available to decide operative indication for radical operation and tetherd cord developed from postoperative scar or accompanied intraspinal lesions.

  2. China-Central Asia Friendship Association Founded

    Institute of Scientific and Technical Information of China (English)


    <正>The China-Central Asia Friendship Association(CCAFA) held its inaugural meeting in Beijing on December 18,2007. The CCAFA,founded at the initiation of the CPAFFC,is a national non-profit social organization with legal person status.It aims to further expand people-to-people contact between China and the five Central Asian countries,namely Kazakhstan,Kirghizstan,Tajikistan,Turkmenistan and Uzbekistan,enhance regional cooperation and deepen good-neighbourly relations so as to consolidate the social foundation for lasting friendship between China and these countries and promote common development.

  3. Ichthyofauna of the reservoirs of Central Vietnam

    Directory of Open Access Journals (Sweden)

    I. A. Stolbunov


    Full Text Available Species composition, distribution and abundance of fish in the pelagic and littoral zone of four reservoirs of Central Vietnam (Suoi Chau, Kam Lam, Da Ban and Suoi Dau were studied first. According to the research data the fish community of the reservoirs is represented by 43 species of 19 fish families.

  4. Central Asia: A New Great Game? (United States)


    southward from civil war, or of revolutionary slogans hitting a chord with Iran’s own ethnic minorities, can only be met by economic investment and reliance...concern, both public and private, over the impact of radiation drifting into Kazakhstan has also been quite vocal .108 Chinese concerns about Central

  5. Quantum Central Processing Unit and Quantum Algorithm

    Institute of Scientific and Technical Information of China (English)



    Based on a scalable and universal quantum network, quantum central processing unit, proposed in our previous paper [Chin. Phys. Left. 18 (2001)166], the whole quantum network for the known quantum algorithms,including quantum Fourier transformation, Shor's algorithm and Grover's algorithm, is obtained in a unitied way.

  6. Intracranial calcification in central diabetes insipidus. (United States)

    Al-Kandari, Salwa Ramadan; Pandey, Tarun; Badawi, Mona H


    Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification.

  7. Intracranial calcification in central diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Al-Kandari, Salwa R. [Al Razi Hospital, Department of Clinical Radiology, Kuwait (Kuwait); Pandey, Tarun [Al Razi Hospital, Department of Clinical Radiology, Kuwait (Kuwait); University of Arkansas for Medical Sciences, Radiology Department, Little Rock, AR (United States); Badawi, Mona H. [Al-Adan Hospital, Department of Paediatrics, Kuwait (Kuwait)


    Intracranial calcification is a known but extremely rare complication of diabetes insipidus. To date, only 16 patients have been reported and all had the peripheral (nephrogenic) type of diabetes insipidus. We report a child with intracranial calcification complicating central diabetes insipidus. We also report a child with nephrogenic diabetes insipidus, and compare the patterns of intracranial calcification. (orig.)

  8. Workers' Central Life Interests and Job Performance. (United States)

    Dubin, Robert; Champoux, Joseph E.

    Supervisors' ratings of individual industrial workers appear to be related to the central life interests (CLI) of the workers. The group of workers who had a job-oriented CLI received the highest ratings from their superivsors among the three CLI groups on Initiative and Application, Cooperation and Quantity of Work and were rated low on…

  9. Dust on UA1 central detector

    CERN Multimedia


    In March 1982 the central derector of UA1 was contaminated by dirt in the compressed air used for cooling during the bakeout of the beam pipe. The lengthy cleaning imposed a change of the collider schedule (Annual Report 1982 p. 114).

  10. Central serotonin metabolism and frequency of depression

    NARCIS (Netherlands)

    Praag, H.M. van; Haan, S. de


    Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement i

  11. Betweenness centrality patterns in random planar graphs

    CERN Document Server

    Lion, Benjamin


    Random planar graphs appear in a variety of context and it is important for many different applications to be able to characterize their structure. Local quantities fail to give interesting information and it seems that path-related measures are able to convey relevant information about the organization of these structures. In particular, nodes with a large betweenness centrality (BC) display non-trivial patterns, such as loops of very central nodes. We discuss briefly empirical results for different random planar graphs and we propose a toy model which allows us to discuss the condition for the emergence of non-trivial patterns such as central loops. This toy model is made of a star network with $N_b$ branches of size $n$ and links of weight $1$, superimposed to a loop at distance $\\ell$ from the center and with links of weight $w$. We estimate for this model the BC at the center and on the loop and we show that the loop can be more central than the origin if $w

  12. Gabapentin inhibits central sensitization during migraine

    Institute of Scientific and Technical Information of China (English)

    Yanbo Zhang; Guo Shao; Wei Zhang; Sijie Li; Jingzhong Niu; Dongmei Hu; Mingfeng Yang; Xunming Ji


    Peripheral and central sensitizations are phenomena that occur during migraine. The role of pentin, a migraine preventive drug, on central sensitization remains unclear. In this study, a rat model of migraine was established by electrical stimulation of the trigeminal ganglion, and the an-imals were given intragastric gabapentin. Changes in amino acid content in the cerebrospinal fluid and protein kinase C membrane translocation in the spinal trigeminal nucleus were examined to clarify the mechanisms underlying the efficacy of gabapentin in the treatment of central sensitization during migraine. Electrophysiology, liquid chromatography-mass spectrometry and western blot analysis results revealed that gabapentin reduces neuronal excitability in the spinal nucleus in the trigeminal nerve, decreases excitatory amino acid content and inhibits the activation of protein ki-nase C. This provides evidence that excitatory amino acids and protein kinase C are involved in the formation and maintenance of central sensitization during migraine. Gabapentin inhibits migraine by reducing excitatory amino acid content in the cerebrospinal fluid and inhibiting protein kinase C ac-tivation.

  13. Ferrobasalts from the Central Indian Ocean Basin

    Digital Repository Service at National Institute of Oceanography (India)

    Iyer, S.D.; Mukhopadhyay, R.; Popko, D.C.

    The occurrence of ferrobasalts recovered from the Central Indian Ocean Basin crust generated at the Southeast Indian Ridge during a phase of moderate to fast spreading accretion (approx 110-190 mm/yr, full rate) is reported. FeO (13-19%), and Ti...

  14. Universities and Knowledge Production in Central Europe (United States)

    Kwiek, Marek


    The article discusses an East/West divide in Europe in university knowledge production. It argues that the communist and post-communist legacies in the four major Central European economies studied (Poland, Hungary, the Czech Republic and the Slovak Republic) matter substantially for educational and research systems. The differences in university…

  15. The central limit theorem and chaos

    Institute of Scientific and Technical Information of China (English)

    NIU Ying-xuan


    Let X be a compact metric space and f : X → X be a continuous map. This paper studies some relationships between stochastic and topological properties of dynamical systems.It is shown that if f satisfies the central limit theorem, then f is topologically ergodic and f is sensitively dependent on initial conditions if and only if f is neither minimal nor equicontinuous.

  16. Award Winning Communication Programs: Centrality or Confusion? (United States)

    Beadle, Mary E.; Schmidt, Jacqueline J.


    Presents a post hoc analysis of peer-identified excellent departments at small colleges (5,000 or fewer undergraduates) to discover if they suffer from a lack of centrality. Hopes that this information may be used to help departments plan curriculum, develop evaluation methods, or write mission statements to strengthen existing programs or defend…

  17. Central Pontine and Extrapontine Myelinolysis in Encephalitis

    Directory of Open Access Journals (Sweden)

    Suvrendu Sankar Kar


    Full Text Available A 15 years male presented with fever, convulsion, unconsciousness and dystonia of acute onset. He was investigated and treated. MRI brain shows central pontine and extrapontine myelinolysis. Osmotic injury, Wilson's disease and other possibilities were excluded by clinical findings with supportive investigations. Patient was improved satisfactorily with treatment. [Natl J Med Res 2013; 3(4.000: 420-421

  18. Central African Security: Conflict in the Congo (United States)


    Alliances mouvantes et conflits extraterritoriaux en Afrique Centrale. Paris: L’Hamarttan. Jean-Claude Willame, Banyarwanda et Banyamulenge: Violence...ethnique et gestion de l’identitaire au Kivu. Paris; L’Harmattan, 1997. Crawford Young, “Zaire: The Anatomy of a Failed State,” in David Birmingham & Phyllis

  19. Performance Management in Dutch Central Government

    NARCIS (Netherlands)

    Mol, Nico P.; Kruijf, de Johan A.M.


    This article investigates how and to what extent performance indicators in Dutch central government are actually embedded in performance management. In a case study encompassing 12 government organizations, the relevance of the indicators presented is analysed in three stages: (1) with respect to th

  20. Imaging of the fetal central nervous system

    NARCIS (Netherlands)

    Pistorius, L.R.


    Introduction : Ultrasound and MR imaging of the fetal central nervous system (CNS) develop at an ever-increasing rate. Theoretically, the two modalities should be synergistic, but a literature review revealed the difficulties of determining the merit of either technique and revealed gaps in our know

  1. Superficial siderosis in the central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Pythinen, J. [Oulu Univ. (Finland). Dept. of Diagnostic Radiology; Paeaekkoe, E. [Oulu Univ. (Finland). Dept. of Diagnostic Radiology; Ilkko, E. [Oulu Univ. (Finland). Dept. of Diagnostic Radiology


    We describe a rare entity, superficial siderosis of the central nervous system, due to multiple small episodes of subarachnoid haemorrhage from any source. Non-specific neurological findings are associated with deposition of iron-containing pigments in the leptomeninges and superficial layers of the cortex. T2-weighted magnetic resonance imaging demonstrates characteristic low signal in the meninges. (orig.)

  2. Ablated tektite from the central Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Glass, B.P.; Chapman, D.R.; ShyamPrasad, M.

    , if it originated in Southeast Asia, it must have had a very shallow trajectory (only a few degrees) and a velocity on the order of 7 km/s as it re-entered the atmosphere. The central Indian Ocean tektite is compositionally similar to high-magnesium (HMg...

  3. The ultimate determinants of central bank independence

    NARCIS (Netherlands)

    Eijffinger, S.C.W.; Schaling, E.


    Using a graphical method, a new way of determining the optimal degree of central bank conservativeness is developed in this paper. Unlike Lohmann (1992) and Rogoff (1985), we are able to express the upper and lower bounds of the interval containing the optimal degree of conservativeness in terms of

  4. Stochastic modelling of central heating systems

    DEFF Research Database (Denmark)

    Hansen, Lars Henrik


    and the degree Erhvervsforsker (a special Danish degree, equivalent to ``Industrial Ph.D.''). The thesis is mainly concerned with experimental design and system identification for individual components in water based central heating systems. The main contribution to this field is on the nonlinear dynamic...

  5. The Marstal Central Solar Heating Plant

    DEFF Research Database (Denmark)

    Heller, Alfred; Jochen, Dahm


    The central solar heating plant in Marstal is running since 1996 and has been monitored since. The resulting data from the plant is analysed and the plant performance evaluated. A TRNSYS-model (computersimulation) id prepared and validated based on the measured data from the plant. Acceptable good...

  6. Central Computer IMS Processing System (CIMS). (United States)

    Wolfe, Howard

    As part of the IMS Version 3 tryout in 1971-72, software was developed to enable data submitted by IMS users to be transmitted to the central computer, which acted on the data to create IMS reports and to update the Pupil Data Base with criterion exercise and class roster information. The program logic is described, and the subroutines and…

  7. Radiologic placement of tunneled central venous catheter

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Seong Tae; Yang, Po Song; Yang, Dong Hunn; Kim, Ki Tae; Kim, Choon Yul; Shinn, Kyung Sub [The Catholic Univ. College of Medicine, Seoul (Korea, Republic of); Yun, Eun Joo [Korea Veterans Hospital, Seoul (Korea, Republic of)


    To evaluate the efficacy and safety of fluoroscopy-guided, radiologic placement of a tunneled central venous catheter into the superior vena cava (SVC). Thirty five patients underwent tunneled central venous catheter placement to facilitate long-term chemotherapy. They included 33 leukemic patients, one colon cancer patient, and one multiple myeloma patient. After confirming central venous patency with a injection of contrast media via the peripheral cephalic or basilic vein in the wrist joint, the subclavian vein was punctured under fluoroscopic guidance. A 7F double lumen TPN catheter was placed into the SVC through a subcutaneous tunnel in the anterior chest wall. Catheter placements were successful in all patients. The mean procedure time was 17.2minutes, mean fluooscopy time was 1.3minutes, mean number of punctures was 1.4, and mean volume of injhected contrast media was 43.5cc. Only two of all leukemic patients developed mild hematomas at the puncture site, but these soon resolved themselves. None of the patients developed pneumothorax or hemothorax. But late complications included local infection in two patients (6%) and thrombotic occlusion of the catheter in one (3%). The occluded catheter was successfully recanalized with Urokinase infusion. Fluoroscopy-guided, radiologic placement of a tunneled central venous catheter is an easy and safe method, and useful for patients requiring long-term venous access.

  8. Central Limit Theorem for Coloured Hard Dimers

    Directory of Open Access Journals (Sweden)

    Maria Simonetta Bernabei


    Full Text Available We study the central limit theorem for a class of coloured graphs. This means that we investigate the limit behavior of certain random variables whose values are combinatorial parameters associated to these graphs. The techniques used at arriving this result comprise combinatorics, generating functions, and conditional expectations.

  9. The quantum human central neural system. (United States)

    Alexiou, Athanasios; Rekkas, John


    In this chapter we present Excess Entropy Production for human aging system as the sum of their respective subsystems and electrophysiological status. Additionally, we support the hypothesis of human brain and central neural system quantumness and we strongly suggest the theoretical and philosophical status of human brain as one of the unknown natural Dirac magnetic monopoles placed in the center of a Riemann sphere.

  10. Gravimetric maps of the Central African Republic (United States)

    Albouy, J.; Godivier, R. (Principal Investigator)


    Gravimetric maps of the Central African Republic are described including a map of Bouguer anomalies at 1/1,000,000 in two sections (eastern sheet, western sheet) and a map, in color, of Bouguer anomalies at 1/2,000,000. Instrumentation, data acquisition, calibration, and data correction procedures are discussed.

  11. Primary Angiitis Of The Central Nervous System

    Directory of Open Access Journals (Sweden)

    Sundaram Meenakshi


    Full Text Available An unusual case of primary angiitis of central nervous system (PACNS presenting with headache, seizures and focal deficits is presented. Despite multiple lesions noted on brain MRI, definitive diagnosis required a brain biopsy. A high index of clinical suspicious and the utility of brain biopsy for diagnosis are emphasized.

  12. Hypersensitivity Responses in the Central Nervous System

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen


    of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals...

  13. Interferons in the central nervous system

    DEFF Research Database (Denmark)

    Owens, Trevor; Khorooshi, Reza M. H.; Wlodarczyk, Agnieszka


    Interferons (IFNs) are implicated as an important component of the innate immune system influencing viral infections, inflammation, and immune surveillance. We review here the complex biological activity of IFNs in the central nervous system (CNS) and associated glial–immune interactions...


    Directory of Open Access Journals (Sweden)



    Full Text Available Over 1,000 specimens of lichens were collected at 78 collecting stations in 11 counties of North Central Oklahoma during 1959 and 1960. The objectives were to identify lichens collected in the area; to establish a record of lichen distribution for each county in the area; and to analyze the ecological relationships.

  15. Notes on Central Asian dragonflies (Insecta: Odonata)

    NARCIS (Netherlands)

    Schoorl Jr., J.W.


    New and old material from Central Asia is published. In total 38 species are recorded from various locations in this region. For the more interesting species notes and figures are provided. One probably new Ischnura species is briefly described, but not formally named. For a, possibly new, subspecie

  16. Notes on Central Asian dragonflies (Insecta: Odonata)


    Schoorl Jr., J.W.


    New and old material from Central Asia is published. In total 38 species are recorded from various locations in this region. For the more interesting species notes and figures are provided. One probably new Ischnura species is briefly described, but not formally named. For a, possibly new, subspecies of Sympetrum sinaiticum Dumont, 1977, a short diagnosis with figures is provided.

  17. Larger foraminifera from Central Falcon (Venezuela)

    NARCIS (Netherlands)

    Gorter, Nettie E.; Vlerk, van der I.M.


    Dr. H. G. Kugler, chief geologist of the North Venezuelan Petroleum Company, at Puerto Cabello, entrusted us with the examination of a collection of larger foraminifera, selected from material collected by the geologists of this Company in Central Falcon. Dr. A. Senn kindly added material that had a

  18. Volkswagen Sets up Central Lab in BRICI

    Institute of Scientific and Technical Information of China (English)


    @@ On June 2, Volkswagen Corp of Germany settled its Chinese central laboratory in Sinopec Beijing Research Institute of Chemical Industry (BRICI). This is the top-level lab of Volkswagen in Asia - Pacific region and it marks another close cooperation between Volkswagen Corp of Germany and Sinopec Corp.

  19. The Centrality of Engagement in Higher Education (United States)

    Fitzgerald, Hiram E.; Bruns, Karen; Sonka, Steven T.; Furco, Andrew; Swanson, Louis


    The centrality of engagement is critical to the success of higher education in the future. Engagement is essential to most effectively achieving the overall purpose of the university, which is focused on the knowledge enterprise. Today's engagement is scholarly, is an aspect of learning and discovery, and enhances society and higher education.…

  20. Financial Stability and Central Bank Governance

    NARCIS (Netherlands)

    Koetter, Michael; Roszbach, Kasper; Spagnolo, Giancarlo


    The financial crisis has ignited a debate about the appropriate objectives and the governance structure of Central Banks. We use novel survey data to investigate the relation between these traits and banking system stability focusing in particular on their role in micro-prudential supervision. We fi

  1. Stone age transitions. Neolithisation in central Scandinavia

    Directory of Open Access Journals (Sweden)

    Helena Knutsson


    Full Text Available A summary of a series of individual research projects focused on the processes from the Mesolithic to the Late Neolithic in central Scandinavia. The projects were embeded in the "Coast to Coast project". The historicity in this process was emphasised.

  2. Fat graft myringoplasty in small central perforations

    Directory of Open Access Journals (Sweden)

    Chandni Sharma


    Full Text Available Background: Perforations of the tympanic membrane (TM are treated with various surgical techniques and materials. Although autologous temporalis fascia is the most common material used for the closure of TM perforations, however for a dry, small central perforation the fat graft myringoplasty (FM is a good alternative as it is a simple and cost-effective technique. Objectives: The aim of this study was to determine the efficacy of FM for repair of small central perforations. Suggestions for optimizing the outcome of FM are presented. Material and Methods: Twenty patients (10 males and 10 females who had uncomplicated dry small central perforation, which was confined to one quadrant of the pars tensa underwent FM. The outcome was evaluated after 1-week, 1-month, and 3 months. Results: After 3 months of follow-up, a closure rate of 80% was achieved. Mean preoperative air-bone (AB gap was 22.90 ± 6.54 dB and mean postoperative AB gap was 21.80 ± 6.28 dB. Mean improvement in AB gap postoperatively was 1.1 ± 2.63 dB. Conclusion: Fat graft myringoplasty, with its ease of technique and good graft uptake rate justifies its use in the closure of small dry central TM perforations.

  3. Clinical analysis and treatment of central pain due to headinjury

    Institute of Scientific and Technical Information of China (English)


    @@Central pain is induced by the involvement of the abnormal pain pathway due to diseases of the central nervous system. Central pain after brain trauma is common clinically, but it is often misdiagnosed and neglected because of lack of objective disturbances. We treated 20 cases of central pain after head injury by invigorating blood circulation and satisfactory result was obtained.

  4. A measure of centrality based on modularity matrix

    Institute of Scientific and Technical Information of China (English)


    In this paper, a kind of measure of structural centrality for networks, called modularity centrality, is introduced. This centrality index is based on the eigenvector belonging to the largest magnitude eigenvalue of modularity matrix. The measure is illustrated and compared with the standard centrality measures using a classic dataset. The statistical distribution of modularity centrality is investigated by con- sidering large computer generated graphs and two networks from the real world.

  5. A Climatology of Central American Gyres (United States)

    Papin, P. P.; Griffin, K. S.; Bosart, L. F.; Torn, R. D.


    Monsoon gyres, commonly found over the western Pacific Ocean, are characterized by broad low-level cyclonic circulations that occur at a variety of spatial scales ranging from 1500-3000 km. Low-level cyclonic gyre circulations, while less frequent and occupying a smaller scale, have also been observed over Central America during the tropical cyclone (TC) season. A noteworthy gyre observed during the 2010 PREDICT field project served as a "collector" of TC Matthew and a source for TC Nicole. During October 2011, devastating flooding occurred in Guatemala and El Salvador when TD 12-E, embedded in a gyre circulation, made landfall on the Pacific coast of Central America. These gyre occurrences, their apparent links to TC activity, and their association with high-impact weather motivates this presentation. A preliminary analysis of Central American gyres suggests that their spatial scales vary between 1000-2000 km. These gyres also tend to be co-located with reservoirs of deep moisture that are characterized by high precipitable water values (>50 mm) and embedded deep convection on their southern and eastern sides. Catastrophic flooding can occur when gyre cyclonic circulations interact with the topography of Central America. A Central American gyre climatology including gyre frequency over the TC season and individual gyre duration will be presented. This climatology is then used to craft a gyre composite using previous gyre cases from 1980-2010. Particular attention will be given to the common synoptic and sub-synoptic scale features that precede and take place during gyre formation. This includes the role that intraseasonal and interannual circulations such as the Madden-Julian Oscillation (MJO) and El Nino-Southern Oscillation (ENSO) might play in gyre development. TC genesis events within gyre circulations will also be highlighted and examined further. Finally, the results of a September 2010 case study will be used to illustrate the impact that Central American


    Directory of Open Access Journals (Sweden)



    Full Text Available The therophytic basiphilous vegetation of Central Italy has been generally framed in a single association Trifolio scabri- Hypochoeridetum achyrophori Biondi et al. 1997. We show that a considerable floristic variation exists inside Trifolio-Hypochoeridetum in Central Italy, and that it should be treated as a complex of no less than five different associations: Medicagini rigidulae-Trifolietum scabri Fanelli et al. hoc loco, Trifolio scabri-Hypochoeridetum achyrophori Biondi, Izco. Ballelli & Formica 1997 s.s, Hippocrepido siliquosae- Brachypodietum distachyi Fanelli et al. ad interim, Trigonello gladiatae-Brachypodietum distachyi Fanelli et al. hoc loc, Crucianello latifoliae-Hypochoeridetum achyrophori Filesi, Blasi, Di Marzio 1996. These associations are floristically and ecologically distinct, and show different geographical ranges in Central Italy. The great diversity of Trachynion distachyae in Central Italy is related to the widespread occurrence of limestone and calcareous alluvial rocks and to a climate with abundant winter and autumn rains very favourable to the development of winter annuals.

  7. On Central Extensions of Associative Dialgebras (United States)

    Rakhimov, Isamiddin S.


    The concept of central extensions plays an important in constructing extensions of algebras. This technique has been successfully used in the classification problem of certain classes of algebras. In 1978 Skjelbred and Sund reduced the classification of nilpotent Lie algebras in a given dimension to the study of orbits under the action of automorphism group on the space of second degree cohomology of a smaller Lie algebra with coefficients in a trivial module. Then W. de Graaf applied the Skjelbred and Sund method to the classification problem of low-dimensional nilpotent Lie and associative algebras over some fields. The main purpose of this note is to establish elementary properties of central extensions of associative dialgebras and apply the above mentioned method to the classification of low dimensional nilpotent associative dialgebras.

  8. [Central nervous system malformations: neurosurgery correlates]. (United States)

    Jiménez-León, Juan C; Betancourt-Fursow, Yaline M; Jiménez-Betancourt, Cristina S


    Congenital malformations of the central nervous system are related to alterations in neural tube formation, including most of the neurosurgical management entities, dysraphism and craniosynostosis; alterations of neuronal proliferation; megalencefaly and microcephaly; abnormal neuronal migration, lissencephaly, pachygyria, schizencephaly, agenesis of the corpus callosum, heterotopia and cortical dysplasia, spinal malformations and spinal dysraphism. We expose the classification of different central nervous system malformations that can be corrected by surgery in the shortest possible time and involving genesis mechanisms of these injuries getting better studied from neurogenic and neuroembryological fields, this involves connecting innovative knowledge areas where alteration mechanisms in dorsal induction (neural tube) and ventral induction (telencephalization) with the current way of correction, as well as the anomalies of cell proliferation and differentiation of neuronal migration and finally the complex malformations affecting the posterior fossa and current possibilities of correcting them.

  9. Sheehan's syndrome with central diabetes insipidus. (United States)

    Laway, Bashir Ahmad; Mir, Shahnaz Ahmad; Dar, Mohd Iqbal; Zargar, Abdul Hamid


    Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

  10. Comprehensive management of presbycusis: central and peripheral. (United States)

    Parham, Kourosh; Lin, Frank R; Coelho, Daniel H; Sataloff, Robert T; Gates, George A


    The prevailing otolaryngologic approach to treatment of age-related hearing loss (ARHL), presbycusis, emphasizes compensation of peripheral functional deficits (ie, hearing aids and cochlear implants). This approach does not address adequately the needs of the geriatric population, 1 in 5 of whom is expected to consist of the "old old" in the coming decades. Aging affects both the peripheral and central auditory systems, and disorders of executive function become more prevalent with advancing age. Growing evidence supports an association between age-related hearing loss and cognitive decline. Thus, to facilitate optimal functional capacity in our geriatric patients, a more comprehensive management strategy of ARHL is needed. Diagnostic evaluation should go beyond standard audiometric testing and include measures of central auditory function, including dichotic tasks and speech-in-noise testing. Treatment should include not only appropriate means of peripheral compensation but also auditory rehabilitative training and counseling.

  11. Centralized, Decentralized, and Hybrid Purchasing Organizations

    DEFF Research Database (Denmark)

    Bals, Lydia; Turkulainen, Virpi

    This paper addresses one of the focal issues in purchasing and supply management – global sourcing – from an organizational design perspective. In particular, we elaborate the traditional classification of global sourcing organization designs into centralized, decentralized, and hybrid models. We...... organization we can identify organization designs beyond the classical centralization-decentralization continuum. We also provide explanations for the observed organization design at GCC. The study contributes to research on purchasing and supply management as well as research on organization design....... illustrate with our empirical analysis on global sourcing organization design at Global Chemical Company (GCC, a pseudonym) that revisiting the conventional wisdom about global sourcing organization designs is required; by engaging in a detailed, subfirm level of analysis on the design of the purchasing...

  12. Association and Centrality in Criminal Networks

    DEFF Research Database (Denmark)

    Petersen, Rasmus Rosenqvist

    Network-based techniques are widely used in criminal investigations because patterns of association are actionable and understandable. Existing network models with nodes as first class entities and their related measures (e.g., social networks and centrality measures) are unable to capture...... and analyze the structural richness required to model and investigate criminal network entities and their associations. We demonstrate a need to rethink entity associations with one specific case (inspired by \\textit{The Wire}, a tv series about organized crime in Baltimore, United States) and corroborated...... by similar evidence from other cases. Our goal is to develop centrality measures for fragmented and non-navigational states of criminal network investigations. A network model with three basic first class entities is presented together with a topology of associations between network entities. We implement...

  13. Centralizers in simple locally finite groups

    Directory of Open Access Journals (Sweden)

    Mahmut Kuzucuoğlu


    Full Text Available This is a survey article on centralizers of finitesubgroups in locally finite, simple groups or LFS-groups as wewill call them. We mention some of the open problems aboutcentralizers of subgroups in LFS-groups and applications of theknown information about the centralizers of subgroups to thestructure of the locally finite group. We also prove thefollowing: Let $G$ be a countably infinite non-linear LFS-groupwith a Kegel sequence $mathcal{K}={(G_i,N_i | iinmathbf{N} }$. If there exists an upper bound for ${ |N_i| |iin mathbf{N} }$, then for any finite semisimplesubgroup $F$ in $G$ the subgroup $C_G(F$ has elements oforder $p_i$ for infinitely many distinct prime $p_i$. Inparticular $C_G(F$ is an infinite group. This answers Hartley'squestion provided that there exists a bound on ${ |N_i| | iin mathbf{N}$.

  14. Introduction to FAST central control system (United States)

    Sun, Jinghai; Zhu, Lichun; Jiang, Zhiqian


    FAST is the largest single dish radio telescope in the world. During observation, part of spherical reflector forms paraboloid to the source direction, meanwhile the feed is placed to instant focus. The control of telescope is difficult and complicated. An autonomous central control system is designed and implemented for methodically and efficiently operation. The system connects and coordinates all subsystems including control, measurement and health monitoring for reflector, feed support and receiver respectively. The main functions are managing observation tasks, commanding subsystems, storing operating data, monitoring statuses and providing the uniform time standard. In this paper, the functions, software and hardware of FAST central control system are presented. The relative infrastructures such as power, network and control room arrangement are introduced.

  15. The segetal flora of the Central Poland

    Directory of Open Access Journals (Sweden)

    Aurelia U. Warcholińska


    Full Text Available In the paper a state and general characteristic of segetal flora of Central Poland is given. The segetal flora of the researched area consists 587 taxa. 127 (21,6% of them are on the list of threatened segetal plants. The studied flora was characterized by a high percentage of short-living plants (341 species - 58,1 %. Species of nature origin (apophytes constitute the dominant group (341 species - 58,1 %. Species of the archaeophytes group were frequently recorded (143 species - 24,4%. The most threatened species in the area of Central Poland are: Vaccaria hispanica (CR, Adonis flammea (CR, Coringia orientalis (CR, Thymelaea passerina (CR, Lythrum hyssopifolia (CR, Bupleurum rotundifolium (CR, Kickxia elatine (CR, Isolepis setacea (CR, Bromus arvensis (CR, Lolium temulentum (CR, L. remotum (CR.


    Directory of Open Access Journals (Sweden)

    Veronica MIHALACHE


    Full Text Available The present study highlights the cooperation-competition ratio in the Central Asia region aiming at maintaining a force balance between Russia and China – as main state actors of the Shanghai Cooperation Organization (SCO, and avoiding the dominance of a state over the other member states of the Organization. Our paper attempts to identify the theoretical arguments that might render a better insight in this organization as a framework meant to mutually balance influence between Russia and China, with the purpose of reciprocally monitoring and limiting their power in a region considered the core of SCO – from a geographical point of view and from the point of view of the two powers’ interest. On the other hand, we should take into account that promoting multipolarity in the global politics is a common interest of China and Russia; both countries started to exclude, to various extents, the Western powers’ interests in Central Asia.

  17. Spherical explosion with central energy source

    CERN Document Server

    Masuyama, Miyu; Tsuboki, Yoichiro


    We present a novel semi-analytic solution describing the propagation of a spherical blast wave driven by a central energy source. The initial density profile has a power-law function of the distance from the center and the energy is injected only into the central region at a rate given by a power-law function of time. This solution is composed of three regions separated by the contact surface and the shock front. The innermost region is assumed to be uniform and the outside of the contact surface includes the shocked matter described by self-similar solutions. We analytically derive the applicable range of parameters of this solution from requirements to satisfy boundary conditions. We perform numerical simulations for flows with various values of parameters, some of which reside out of the thus derived applicable range, and compare with the semi-analytic solutions.

  18. Hitherto unreported Agaricus species of Central India

    Directory of Open Access Journals (Sweden)



    Full Text Available Karwa A, Rai MK. 2010. Hitherto unreported Agaricus species of Central India. Nusantara Bioscience 2: 141-145. Melghat forest region from Central India was surveyed for occurrence of medicinal and culinary mushrooms during the years 2005-2008. Out of total 153 species, ten species of Agaricus were recorded from different localities. Of these, seven species namely Agaricus bitorquis, A. subrufescens, A. augustus, A. placomyces, A. essettei, A. basioanolosus and Agaricus sp. nov (a new species are being reported for the first time from the region. The commercial button mushroom Agaricus bisporus lacks good breeding characters due to its bisporic nature. These wild cousins of the button mushroom can definitely prove to be a good source of genetic manipulations to the existing strains and also to develop new strains with improved characters.

  19. Central charge for the Schwarzschild black hole (United States)

    Ropotenko, K.


    Proceeding in exactly the same way as in the derivation of the temperature of a dual CFT for the extremal black hole in the Kerr/CFT correspondence, it is found that the temperature of a chiral, dual CFT for the Schwarzschild black hole is T = 1/2π. Comparing Cardy’s formula with the Bekenstein-Hawking entropy and using T, it is found that the central charge for the Schwarzschild black hole is of the form c = 12Jin, where Jin is the intrinsic angular momentum of the black hole, Jin = A/8πG. It is shown that the central charge for any four-dimensional (4D) extremal black hole is of the same form. The possible universality of this form is briefly discussed.

  20. Expansion of museums in Central Europe?

    Directory of Open Access Journals (Sweden)

    Jagodzińska, Katarzyna


    Full Text Available The paper presents reflections on the specificity of collections and museums of contemporary art in Central Europe and considers a possibility of creating a regional alternative for the West. The analysis is conducted in the context of the expansionist policy of contemporary museums – notably the Louvre, the Guggenheim Foundation, and the Hermitage – whose numerous new development projects gave rise to a number of dilemmas in the museological world. The author discusses global "museum brands" that invest in Central Europe and addresses the possible profits of the expansion of such "concerns" for culture in the region, as well as emphasises the potential of the region itself, which may be used for its development without the avail of the internationally renowned collectors' names.