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Sample records for p4 ht ee

  1. 5-HT system and cognition.

    PubMed

    Meneses, A

    1999-12-01

    The study of 5-hydroxytryptamine (5-HT) system has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT1 to 5-HT7). Growing evidence suggests that 5-HT is important in learning and memory and all its receptors might be implicated in this. Actually, 5-HT pathways, 5-HT reuptake site/transporter complex and 5-HT receptors show regional distribution in brain areas implicated in learning and memory. Likewise, the stimulation or blockade of presynaptic 5-HT1A, 5-HT1B, 5-HT(2A/2C) and 5-HT3 receptors, postsynaptic 5-HT(2B/2C) and 5-HT4 receptors and 5-HT uptake/transporter sites modulate these processes. Available evidence strongly suggests that the 5-HT system may be important in normal function, the treatment and/or pathogenesis of cognitive disorders. Further investigation will help to specify the 5-HT system nature involvement in cognitive processes, pharmacotherapies, their mechanisms and action sites and to determine under which conditions they could operate. In this regard, it is probable that selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties for 5-HT1A, 5-HT(1B/1D), 5-HT(2A/2B/2C), 5-HT4 and 5-HT7 receptors could constitute a new therapeutic opportunity for learning and memory alterations.

  2. Phage P4 DNA replication in vitro.

    PubMed Central

    Díaz Orejas, R; Ziegelin, G; Lurz, R; Lanka, E

    1994-01-01

    Phage P4 DNA is replicated in cell-free extracts of Escherichia coli in the presence of partially purified P4 alpha protein [Krevolin and Calendar (1985), J. Mol. Biol. 182, 507-517]. Using a modified in vitro replication assay, we have further characterized this process. Analysis by agarose gel electrophoresis and autoradiography of in vitro replicated molecules demonstrates that the system yields supercoiled monomeric DNA as the main product. Electron microscopic analysis of in vitro generated intermediates indicates that DNA synthesis initiates in vitro mainly at ori, the origin of replication used in vivo. Replication proceeds from this origin bidirectionally, resulting in theta-type molecules. In contrast to the in vivo situation, no extensive single-stranded regions were found in these intermediates. The initiation proteins of the host, DnaB and DnaG, and the chaperones DnaJ and DnaK are not required for P4 replication, because polyclonal antibodies against those polypeptides do not inhibit the process. The reaction is inhibited by antibodies against the SSB protein, and by ara-CTP, a specific inhibitor of DNA polymerase III holoenzyme. Consistent with previous reports, P4 in vitro replication is independent of transcription by host RNA polymerase. Novobiocin, a DNA gyrase inhibitor, strongly inhibits P4 DNA synthesis, indicating that form I DNA is the required substrate. Images PMID:8029013

  3. Nacnac‐Cobalt‐Mediated P4 Transformations

    PubMed Central

    Spitzer, Fabian; Graßl, Christian; Balázs, Gábor; Mädl, Eric; Keilwerth, Martin; Zolnhofer, Eva M.; Meyer, Karsten

    2017-01-01

    Abstract A comparison of P4 activations mediated by low‐valent β‐diketiminato (L) cobalt complexes is presented. The formal Co0 source [K2(L3Co)2(μ2:η1,η1‐N2)] (1) reacts with P4 to form a mixture of the monoanionic complexes [K(thf)6][(L3Co)2(μ2:η4,η4‐P4)] (2) and [K(thf)6][(L3Co)2(μ2:η3,η3‐P3)] (3). The analogue CoI precursor [L3Co(tol)] (4 a), however, selectively yields the corresponding neutral derivative [(L3Co)2(μ2:η4,η4‐P4)] (5 a). Compound 5 a undergoes thermal P atom loss to form the unprecedented complex [(L3Co)2(μ2:η3,η3‐P3)] (6). The products 2 and 3 can be obtained selectively by an one‐electron reduction of their neutral precursors 5 a and 6, respectively. The electrochemical behaviour of 2, 3, 5 a, and 6 is monitored by cyclic voltammetry and their magnetism is examined by SQUID measurements and the Evans method. The initial CoI‐mediated P4 activation is not influenced by applying the structurally different ligands L1 and L2, which is proven by the formation of the isostructural products [(LCo)2(μ2:η4,η4‐P4)] [L=L3 (5 a), L1 (5 b), L2 (5 c)]. PMID:28032678

  4. FCC-ee: Energy Calibration

    SciTech Connect

    Koratzinos, M.; Blondel, A.; Gianfelice-Wendt, E.; Zimmermann, F.

    2015-06-02

    The FCC-ee aims to improve on electroweak precision measurements, with goals of 100 ke V on the Z mass and width, and a fraction of MeV on the W mass. Compared to LEP, this implies a much improved knowledge of the center-of-mass energy when operating at the Z peak and WW threshold. This can be achieved by making systematic use of resonant depolarization. A number of issues have been identified, due in particular to the long polarization times. However the smaller emittance and energy spread of FCC-ee with respect to LEP should help achieve a much improved performance.

  5. EE-3A Logging Report

    SciTech Connect

    Anderson, David W.

    1993-12-15

    Two logs of EE-3A were performed during the last couple of weeks. The first of which, was a Temperature/Casing-Collar Locator (CCL) log, which took place on Friday, December 10th., 1993. The second log was a Caliper log which was done in cooperation with the Dia-Log Company, of Odessa, TX. on Monday, December, 13th., 1993.

  6. Redrilling Plan for EE-3

    SciTech Connect

    Murphy, Hugh D.

    1984-11-14

    Attached is the 3rd draft copy of the EE-3 redrilling plan. We believe that we have taken the document as far as we can and feel that it is ready for distribution as soon as the trajectory question is resolved and necessary changes in wording that result are made. The figures are presently being redrawn by John Paskiewicz and should be ready in about one week.

  7. Job Prospects for E/E Engineers.

    ERIC Educational Resources Information Center

    Basta, Nicholas

    1987-01-01

    Discusses the trends in employment in the electrical/electronics (E/E) engineering industry. States that although the number of E/E graduates grew at a rate of over 11 percent from 1985 to 1986, the economy continues to be the major determinant in the job outlook in the field. (TW)

  8. Job Prospects for E/E Engineers.

    ERIC Educational Resources Information Center

    Basta, Nicholas

    1986-01-01

    Reviews job prospects for electrical/electronic E/E engineers, indicating that 1985 was not a banner year due to problems in the semiconductor manufacturing industries and in telecommunications. Also indicates that an upturn is expected for 1986 E/E graduates. (JN)

  9. Bacteriophage P2 ogr and P4 delta genes act independently and are essential for P4 multiplication.

    PubMed Central

    Halling, C; Calendar, R

    1990-01-01

    Satellite bacteriophage P4 requires the products of the late genes of a helper phage such as P2 for lytic growth. Expression of the P2 late genes is positively regulated by the P2 ogr gene in a process requiring P2 DNA replication. Transactivation of P2 late gene expression by P4 requires the P4 delta gene product and works even in the absence of P2 DNA replication. We have made null mutants of the P2 ogr and P4 delta genes. In the absence of the P4 delta gene product, P4 multiplication required both the P2 ogr protein and P2 DNA replication. In the absence of the P2 ogr gene product, P4 multiplication required the P4 delta protein. In complementation experiments, we found that the P2 ogr protein was made in the absence of P2 DNA replication but could not function unless P2 DNA replicated. We produced P4 delta protein from a plasmid and found that it complemented the null P4 delta and P2 ogr mutants. Images PMID:2193911

  10. 31 CFR 353.30 - Series EE bonds.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Series EE bonds. 353.30 Section 353... BONDS, SERIES EE AND HH Interest § 353.30 Series EE bonds. Series EE bonds are issued at a discount. The... Department of the Treasury Circular, Public Debt Series No. 1-80 (31 CFR part 351)....

  11. 31 CFR 353.30 - Series EE bonds.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Series EE bonds. 353.30 Section 353.30... BONDS, SERIES EE AND HH Interest § 353.30 Series EE bonds. Series EE bonds are issued at a discount. The... Department of the Treasury Circular, Public Debt Series No. 1-80 (31 CFR part 351)....

  12. 31 CFR 353.30 - Series EE bonds.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Series EE bonds. 353.30 Section 353... SAVINGS BONDS, SERIES EE AND HH Interest § 353.30 Series EE bonds. Definitive Series EE bonds were issued... values is found in Department of the Treasury Circular, Fiscal Service Series No. 1-80 (31 CFR part 351)....

  13. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity.

    PubMed

    Anastasio, Noelle C; Stutz, Sonja J; Fink, Latham H L; Swinford-Jackson, Sarah E; Sears, Robert M; DiLeone, Ralph J; Rice, Kenner C; Moeller, F Gerard; Cunningham, Kathryn A

    2015-07-15

    A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally relevant mechanism underlying motor impulsivity.

  14. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity

    PubMed Central

    Anastasio, Noelle C.; Stutz, Sonja J.; Fink, Latham H. L.; Swinford-Jackson, Sarah E.; Sears, Robert M; DiLeone, Ralph J.; Rice, Kenner C.; Moeller, F. Gerard; Cunningham, Kathryn A.

    2016-01-01

    A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally-relevant mechanism underlying motor impulsivity. PMID:26120876

  15. Separation of e+e- → e+e- and e+e- → π+π- events using SND detector calorimeter

    NASA Astrophysics Data System (ADS)

    Achasov, M. N.; Beloborodov, K. I.; Kupich, A. S.

    2017-01-01

    The technique of discrimination of the e+e- → e+e- and e+e- → π+π- events in energy range 0.5 < √s < 1 GeV by energy deposition in the calorimeter of SND detector was developed by applying machine learning method. Identification efficiency for e+e- → e+e- and e+e- → π+π- events in the range from 99.3 to 99.8% has been achived.

  16. Poly(4-hydroxybutyrate) (P4HB) production in recombinant Escherichia coli: P4HB synthesis is uncoupled with cell growth

    PubMed Central

    2013-01-01

    Background Poly(4-hydroxybutyrate) (P4HB), belonging to the family of bacterial polyhydroxyalkanoates (PHAs), is a strong, flexible and absorbable material which has a large variety of medical applications like tissue engineering and drug delivery. For efficient production of P4HB recombinant Escherichia coli has been employed. It was previously found that the P4HB synthesis is co-related with the cell growth. In this study, we aimed to investigate the physiology of P4HB synthesis, and to reduce the total production cost by using cheap and widely available xylose as the growth substrate and sodium 4-hydroxybutyrate (Na-4HB) as the precursor for P4HB synthesis. Results Six different E. coli strains which are able to utilize xylose as carbon source were compared for their ability to accumulate P4HB. E. coli JM109 was found to be the best strain regarding the specific growth rate and the P4HB content. The effect of growth conditions such as temperature and physiological stage of Na-4HB addition on P4HB synthesis was also studied in E. coli JM109 recombinant in batch culture. Under the tested conditions, a cellular P4HB content in the range of 58 to 70% (w w-1) and P4HB concentrations in the range of 2.76 to 4.33 g L-1 were obtained with a conversion yield (YP4HB/Na-4HB) of 92% w w-1 in single stage batch cultures. Interestingly, three phases were identified during P4HB production: the “growth phase”, in which the cells grew exponentially, the “accumulation phase”, in which the exponential cell growth stopped while P4HB was accumulated exponentially, and the “stagnation phase”, in which the P4HB accumulation stopped and the total biomass remained constant. Conclusions P4HB synthesis was found to be separated from the cell growth, i.e. P4HB synthesis mainly took place after the end of the exponential cell growth. High conversion rate and P4HB contents from xylose and precursor were achieved here by simple batch culture, which was only possible previously

  17. Monitors, messages, and clusters : the p4 parallel programming system.

    SciTech Connect

    Butler, R. M.; Lusk, E. T.; Mathematics and Computer Science; Univ. of North Florida

    1994-01-01

    p4 is a portable library of C and Fortran subroutines for programming parallel computers. It is the current version of a system that has been in use since 1984. It includes features for explicit parallel programming of shared-memory machines, distributed-memory machines (including heterogeneous networks of workstations), and clusters, by which we mean shared-memory multiprocessors communicating via message passing. We discuss here the design goals, history, and system architecture of p4 and describe briefly a diverse collection of applications that have demonstrated the utility of p4.

  18. Failed heart rate recovery at a critical age in 5-HT-deficient mice exposed to episodic anoxia: implications for SIDS

    PubMed Central

    Commons, Kathryn G.; Hewitt, Julie C.; Daubenspeck, John A.; Li, Aihua; Kinney, Hannah C.; Nattie, Eugene E.

    2011-01-01

    Mice deficient in the transcription factor Pet-1−/− have a ∼70% deficiency of brainstem serotonin [5-hydroxytryptamine (5-HT)] neurons and exhibit spontaneous bradycardias in room air at postnatal day (P)5 and P12 and delayed gasping in response to a single episode of anoxia at P4.5 and P9.5 (Cummings KJ, Li A, Deneris ES, Nattie EE. Am J Physiol Regul Integr Comp Physiol 298: R1333–R1342, 2010; and Erickson JT, Sposato BC. J Appl Physiol 106: 1785–1792, 2009). We hypothesized that at a critical age Pet-1−/− mice will fail to autoresuscitate during episodic anoxia, ultimately dying from a failure of gasping to restore heart rate (HR). We exposed P5, P8, and P12 Pet-1−/− mice and wild-type littermates (WT) to four 30-s episodes of anoxia (97% N2-3% CO2), separated by 5 min of room air. We observed excess mortality in Pet-1−/− only at P8: 43% of Pet-1−/− animals survived past the third episode of anoxia while ∼95% of WT survived all four episodes (P = 0.004). No deaths occurred at P5 and at P12, and one of six Pet-1−/− mice died after the fourth episode, while all WT animals survived. At P8, dying Pet-1−/− animals had delayed gasping, recovery of HR, and eupnea after the first two episodes of anoxia (P < 0.001 for each); death ultimately occurred when gasping failed to restore HR. Both high- and low-frequency components of HR variability were abnormally elevated in dying Pet-1−/− animals following the first episode of anoxia. Dying P8 Pet-1−/− animals had significantly fewer 5-HT neurons in the raphe magnus than surviving animals (P < 0.001). Our data indicate a critical developmental window at which a brainstem 5-HT deficiency increases the risk of death during episodes of anoxia. They may apply to the sudden infant death syndrome, which occurs at a critical age and is associated with 5-HT deficiency. PMID:21680874

  19. Serotonin (5-HT) regulates neurite outgrowth through 5-HT1A and 5-HT7 receptors in cultured hippocampal neurons.

    PubMed

    Rojas, Paulina S; Neira, David; Muñoz, Mauricio; Lavandero, Sergio; Fiedler, Jenny L

    2014-08-01

    Serotonin (5-HT) production and expression of 5-HT receptors (5-HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5-HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5-HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development. Signalling mediated by the G-protein-coupled 5-HT1A R and 5-HT7 R, however, has been associated with neuronal plasticity. Thus, we hypothesized that 5-HT promotes neurite outgrowth through 5-HT1A R and 5-HT7 R. The involvement of 5-HT1A R and 5-HT7 R in the morphology of rat hippocampal neurons was evaluated by treating primary cultures at 2 days in vitro with 5-HT and specific antagonists for 5-HT1A R and 5-HT7 R (WAY-100635 and SB269970, respectively). The stimulation of hippocampal neurons with 100 nM 5-HT for 24 hr produced no effect on either the number or the length of primary neurites. Nonetheless, after 5HT7 R was blocked, the addition of 5-HT increased the number of primary neurites, suggesting that 5HT7 R could inhibit neuritogenesis. In contrast, 5-HT induced secondary neurite outgrowth, an effect inhibited by 1 μM WAY-100635 or SB269970. These results suggest that both serotonergic receptors participate in secondary neurite outgrowth. We conclude that 5-HT1A R and 5-HT7 R regulate neuronal morphology in primary hippocampal cultures by promoting secondary neurite outgrowth.

  20. EE Certification: Making Best Practice Standard Practice

    ERIC Educational Resources Information Center

    Glenn, Joanne M. Lozar

    2006-01-01

    Pursuing environmental education certification is difficult, so why do it? What does it mean to be certified? Who benefits? How? These are just a few of the compelling questions addressed in "EE Certification: Making Best Practice Standard Practice," a new article exploring advancements and challenges in state and national EE…

  1. Rhodes University EE and Sustainability Unit

    ERIC Educational Resources Information Center

    Sisitka, Heila Lotz; Schudel, Ingrid

    2007-01-01

    In the early 1990s, in response to the emphasis laid on environment and development issues by the new South African Constitution, Rhodes University undertook several initiatives such as establishing the first Chair of Environmental Education (EE) in Africa. Another important initiative was the introduction of an open-entry participatory course for…

  2. Crystallization of recombinant Haemophilus influenzaee (P4) acid phosphatase

    SciTech Connect

    Ou, Zhonghui; Felts, Richard L.; Reilly, Thomas J.; Nix, Jay C.; Tanner, John J.

    2006-05-01

    Lipoprotein e (P4) is a class C acid phosphatase and a potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. Haemophilus influenzae infects the upper respiratory tract of humans and can cause infections of the middle ear, sinuses and bronchi. The virulence of the pathogen is thought to involve a group of surface-localized macromolecular components that mediate interactions at the host–pathogen interface. One of these components is lipoprotein e (P4), which is a class C acid phosphatase and a potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. The space group is P4{sub 2}2{sub 1}2, with unit-cell parameters a = 65.6, c = 101.4 Å, one protein molecule per asymmetric unit and 37% solvent content. This is the first report of the crystallization of a class C acid phosphatase.

  3. Identification of two replicons in phage-plasmid P4.

    PubMed

    Tocchetti, A; Serina, S; Terzano, S; Dehò, G; Ghisotti, D

    1998-06-05

    DNA replication of phage-plasmid P4 proceeds bidirectionally from the ori1 site (previously named ori), but requires a second cis-acting region, crr. Replication depends on the product of the P4 alpha gene, a protein with primase and helicase activity, that binds both ori1 and crr. A negative regulator of P4 DNA replication, the Cnr protein, is required for copy number control of plasmid P4. Using a plasmid complementation test for replication, we found that two replicons, both dependent on the alpha gene product, coexist in P4. The first replicon is made by the cnr and alpha genes and the ori1 and crr sites. The second is limited to the alpha and crr region. Thus, in the absence of the ori1 region, replication can initiate at a different site. By deletion mapping, a cis-acting region, ori2, essential for replication of the alpha-crr replicon was mapped within a 270-bp fragment in the first half of the alpha gene. The ori2 site was found to be dispensable in a replicon that contains ori1. A construct that besides crr and alpha carries also the cnr gene was unable to replicate, suggesting that Cnr not only controls replication from ori1, but also silences ori2.

  4. Symmetrical P4 cleavage at cobalt: characterization of intermediates on the way from P4 to coordinated P2 units.

    PubMed

    Dürr, Simon; Ertler, Daniel; Radius, Udo

    2012-03-19

    Degradation of white phosphorus (P(4)) in the coordination sphere of transition metals is commonly divided into two major pathways depending on the P(x) ligands obtained. Consecutive metal-assisted P-P bond cleavage of four bonds of the P(4) tetrahedron leads to complexes featuring two P(2) ligands (symmetric cleavage) or one P(3) and one P(1) ligand (asymmetric cleavage). A systematic investigation of the degradation of white phosphorus P(4) to coordinated μ,η(2:2)-bridging diphosphorus ligands in the coordination sphere of cobalt is presented herein as well as isolation of each of the decisive intermediates on the reaction pathway. The olefin complex [Cp*Co((i)Pr(2)Im)(η(2)-C(2)H(4))], 1 (Cp* = η(5)-C(5)Me(5), (i)Pr(2)Im = 1,3-di-isopropylimidazolin-2-ylidene), reacts with P(4) to give [Cp*Co((i)Pr(2)Im)(η(2)-P(4))], 2, the insertion product of [Cp*Co((i)Pr(2)Im)] into one of the P-P bonds. Addition of a further equivalent of the Co(I) complex [Cp*Co((i)Pr(2)Im)(η(2)-C(2)H(4))], 1, induces cleavage of a second P-P bond to yield the dinuclear complex [{Cp*Co((i)Pr(2)Im)}(2)(μ,η(2:2)-P(4))], 3, in which a kinked cyclo-P(4)(4-) ligand bridges two cobalt atoms. Consecutive dissociation of the N-heterocyclic carbene with concomitant rearrangement of the cyclo-P(4) ligand and P-P dissociation leads to complexes [Cp*Co(μ,η(4:2)-P(4))Co((i)Pr(2)Im)Cp*], 4, featuring a P(4) chain, and [{Cp*Co(μ,η(2:2)-P(2))}(2)], 5, in which two isolated P(2)(2-) ligands bridge two [Cp*Co] fragments. Each of these reactions is quantitative if performed on an NMR scale, and each compound can be isolated in high yields and large quantities.

  5. The History of GalaFLEX P4HB Scaffold

    PubMed Central

    Williams, Simon F.; Martin, David P.; Moses, Arikha C.

    2016-01-01

    The GalaFLEX Scaffold (Galatea Surgical, Inc., Lexington, MA) for plastic and reconstructive surgery belongs to a new generation of products for soft tissue reinforcement made from poly-4-hydroxybutyrate (P4HB). Other members of this new family of products include MonoMax Suture (Aesculap AG, Tuttlingen, Germany) for soft tissue approximation, BioFiber Scaffold (Tornier, Inc., Edina, MN) for tendon repair, and Phasix Mesh (C.R. Bard, Inc., Murray Hill, NJ) for hernia repair. Each of these fully resorbable products provides prolonged strength retention, typically 50% to 70% strength retention at 12 weeks, and facilitates remodeling in vivo to provide a strong, lasting repair. P4HB belongs to a naturally occurring class of biopolymers and fibers made from it are uniquely strong, flexible, and biocompatible. GalaFLEX Scaffold is comprised of high-strength, resorbable P4HB monofilament fibers. It is a knitted macroporous scaffold intended to elevate, reinforce, and repair soft tissue. The scaffold acts as a lattice for new tissue growth, which is rapidly vascularized and becomes fully integrated with adjacent tissue as the fibers resorb. In this review, we describe the development of P4HB, its production, properties, safety, and biocompatibility of devices made from P4HB. Early clinical results and current clinical applications of products made from P4HB are also discussed. The results of post-market clinical studies evaluating the GalaFLEX Scaffold in rhytidectomy and cosmetic breast surgery demonstrate that the scaffold can reinforce lifted soft tissue, resulting in persistent surgical results in the face and neck at one year, and provide lower pole stability after breast lift at one year. PMID:27697885

  6. 31 CFR 353.30 - Series EE bonds.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Series EE bonds. 353.30 Section 353.30... BONDS, SERIES EE AND HH Interest § 353.30 Series EE bonds. Definitive Series EE bonds were issued at a... found in Department of the Treasury Circular, Public Debt Series No. 1-80 (31 CFR part 351)....

  7. 31 CFR 353.30 - Series EE bonds.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Series EE bonds. 353.30 Section 353.30... BONDS, SERIES EE AND HH Interest § 353.30 Series EE bonds. Definitive Series EE bonds were issued at a... found in Department of the Treasury Circular, Public Debt Series No. 1-80 (31 CFR part 351)....

  8. Meson-baryon effective chiral Lagrangians at order p4

    NASA Astrophysics Data System (ADS)

    Jiang, Shao-Zhou; Chen, Qing-Sen; Liu, Yan-Rui

    2017-01-01

    We construct the three-flavor Lorentz-invariant meson-baryon chiral Lagrangians at the order p4, with which a full one-loop investigation may be performed. One obtains 540 independent terms. The processes with the minimal number of mesons and photons to which this order of Lagrangians may contribute are also presented.

  9. Tc with AsqTad and p4rhmc

    SciTech Connect

    Soltz, R; Vranas, P; Gupta, R

    2007-06-20

    We present the ongoing analysis of Lattice Quantum Chromodynamics runs on the LLNL BG/L supercomputer. This installment includes the analysis of 12,000 trajectories from the MILC AsqTad code on a 32{sup 3} x 8 lattice and the time histories from the plaquette and {psi} - bar{psi} trajectories from the p4rhmc code.

  10. EE Cep observations requested for upcoming eclipse

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2014-07-01

    The AAVSO requests observations for the upcoming eclipse of EE Cephei, a long-period eclipsing variable. EE Cep has a period of 2,050 days, and shows strong variations in the eclipse light curve from one event to the next. Observations are needed to study the morphology of the upcoming eclipse, which will be used to better understand the shape of the eclipsing disk and how it precesses. Mid-eclipse is predicted to be August 23, 2014, but the early stages of the eclipse may begin as much as a month earlier. EE Cep is being observed by a number of amateur and professional astronomers using multiple telescopes at multiple wavelengths. Among these is a collaboration (see https://sites.google.com/site/eecep2014campaign/) headed by Cezary Galan at the Nicolaus Copernicus Astronomical Center in Poland; several individual AAVSO observers are already participating in this effort. The AAVSO is not currently a partner in that campaign, but all data submitted to the AAVSO will be publicly available. The AAVSO strongly encourages observers to begin following this star now, and to continue observations into October 2014 at least. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details and observations.

  11. Payment for performance (P4P): any future in Italy?

    PubMed Central

    2011-01-01

    Background Pay for Performance (P4P) programs, based on provision of financial incentives for service quality, have been widely adopted to enhance quality of care and to promote a more efficient use of health care resources whilst improving patient outcomes. In Italy, as in other countries, the growing concern over the quality of health services provided and the scarcity of resources would make P4P programs a useful means of improving their performance. The aim of this paper is to evaluate whether it is possible to implement P4P programs in the Lombardy Region, in Italy, based on the existing data set. Methods Thirteen quality measures were identified regarding four clinical conditions (acute myocardial infarction (AMI), heart failure (HF), ischemic stroke and hip and knee replacement) on the basis of an international literature review. Data was collected using the database of three institutions, which included hospital discharge records (Scheda di Dimissione ospedaliera-SDO-) and letters of discharge. The study population was identified using both the Principal ICD-9-CM diagnosis codes and the discharge date. A Statistical Analysis System (SAS) program was used for the text analysis. Results It was possible to calculate almost all the parameters pertaining to the three hospitals as all the data required was available with the exception of inpatient mortality in two hospitals and smoking cessation advice/counseling in one hospital. Conclusions On the ground of this analysis, we believe that it is possible to implement a P4P program in the Lombardy Region. However, for this program to be initiated, all necessary data must be available in electronic format and uniformly collected. Moreover, several other factors must be assessed: which clinical conditions should be included, the threshold for each quality parameter, the amount of financial incentives offered and how they will be provided. PMID:21605472

  12. Systems Biology and P4 Medicine: Past, Present, and Future

    PubMed Central

    Hood, Leroy

    2013-01-01

    Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB) has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes) for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.). The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to detect and treat

  13. Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

    PubMed Central

    Bannerman, David M.

    2017-01-01

    The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10–20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders

  14. The Co-Evolution of ESD and EE

    ERIC Educational Resources Information Center

    Monroe, Martha C.

    2012-01-01

    William B. Stapp, a major author of the founding documents of environmental education (EE), foreshadowed the triple concerns of education for sustainable development (ESD) with environment, social justice and economic health. Yet EE in the USA tended to follow the advocacy orientation of the environmental movement of the 1970s and later, following…

  15. Some Historical Thoughts on the ee-Learning Renaissance

    ERIC Educational Resources Information Center

    Nilles, Jack M.

    2007-01-01

    Jack Nilles surveys the evolution of ee-learning at the University of Southern California, together with the first formal telecommuting demonstration program, from its beginnings in the early 1970s to the relevant trends in 2006. Although the basic technologies of telecommuting and ee-learning were in evidence in the 1970s, subsequent…

  16. 5-HT(1A) receptors and memory.

    PubMed

    Meneses, Alfredo; Perez-Garcia, Georgina

    2007-01-01

    The study of 5-hydroxytryptamine (5-HT) systems has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT(1)-5-HT(7)). Increasing evidence suggests that 5-HT pathways, reuptake site/transporter complex and 5-HT receptors represent a strategic distribution for learning and memory. A key question still remaining is whether 5-HT markers (e.g., receptors) are directly or indirectly contributing to the physiological and pharmacological basis of memory and its pathogenesis or, rather, if they represent protective or adaptable mechanisms (at least in initial stages). In the current paper, the major aim is to revise recent advances regarding mammalian 5-HT(1A) receptors in light of their physiological, pathophysiological and therapeutic implications in memory. An attempt is made to identify and discuss sources of discrepancies by employing an analytic approach to examine the nature and degree of difficulty of behavioral tasks used, as well as implicating other factors (for example, brain areas, training time or duration, and drug administration) which might offer new insights into the understanding and interpretation of these data. In this context, 8-OH-DPAT deserves special attention since for many years it has been the more selective 5-HT drug and, hence, more frequently used. As 5-HT(1A) receptors are key components of serotonergic signaling, investigation of their memory mechanisms and action sites and the conditions under which they might operate, could yield valuable insights. Moreover, selective drugs with agonists, neutral antagonists or inverse agonist properties for 5-HT(1A) (and 5-HT(7)) receptors may constitute a new therapeutic opportunity for learning and memory disorders.

  17. Hydrostatic compaction of Microtherm HT.

    SciTech Connect

    Broome, Scott Thomas; Bauer, Stephen J.

    2010-09-01

    Two samples of jacketed Microtherm{reg_sign}HT were hydrostatically pressurized to maximum pressures of 29,000 psi to evaluate both pressure-volume response and change in bulk modulus as a function of density. During testing, each of the two samples exhibited large irreversible compactive volumetric strains with only small increases in pressure; however at volumetric strains of approximately 50%, the Microtherm{reg_sign}HT stiffened noticeably at ever increasing rates. At the maximum pressure of 29,000 psi, the volumetric strains for both samples were approximately 70%. Bulk modulus, as determined from hydrostatic unload/reload loops, increased by more than two-orders of magnitude (from about 4500 psi to over 500,000 psi) from an initial material density of {approx}0.3 g/cc to a final density of {approx}1.1 g/cc. An empirical fit to the density vs. bulk modulus data is K = 492769{rho}{sup 4.6548}, where K is the bulk modulus in psi, and {rho} is the material density in g/cm{sup 3}. The porosity decreased from 88% to {approx}20% indicating that much higher pressures would be required to compact the material fully.

  18. [5-HT1A/5-HT7 receptor interplay: Chronic activation of 5-HT7 receptors decreases the functional activity of 5-HT1A receptor and its сontent in the mouse brain].

    PubMed

    Kondaurova, E M; Bazovkina, D V; Naumenko, V S

    2017-01-01

    Serotonin receptors 5-HT1A and 5-HT7 are involved in the development of various psychopathologies. Some data indicate that there is an interplay between 5-HT1A 5-HT7 receptors that could be implicated in the regulation of their function. This work analyzed the effects of chronic 5-HT7 activation on the functional activity of 5-HT7 and 5-HT1A receptors, on the corresponding protein levels, and on the expression of genes encoding 5-HT7 and 5-HT1A receptors in the mouse brain. Chronic administration of the 5-HT7 selective agonist LP44 (20.5 nmol, i.c.v., 14 days) produced considerable desensitization of both 5-HT7 and 5-HT1A receptors. In LP44-treated mice, the hypothermic responses mediated by both 5-HT7 and 5-HT1A receptors were attenuated. Moreover, the levels of 5-HT1A receptor protein in the midbrain and the frontal cortex of LP44-treated mice were significantly decreased. However, the brain levels of 5-HT7 receptor protein did not differ between LP44-treated and control mice. Chronic LP44 treatment did not alter the expression of the 5-HT7 and 5-HT1A receptor genes in all investigated brain structure. These data suggest that 5-HT7 receptors participate in the posttranscriptional regulation of the 5-HT1A receptors functioning.

  19. Influence of sodium substitutes on 5-HT-mediated effects at mouse 5-HT3 receptors

    PubMed Central

    Barann, M; Schmidt, K; Göthert, M; Urban, B W; Bönisch, H

    2004-01-01

    The influence of sodium ion substitutes on the 5-hydroxytryptamine (5-HT)-induced flux of the organic cation [14C]guanidinium through the ion channel of the mouse 5-HT3 receptor and on the competition of 5-HT with the selective 5-HT3 receptor antagonist [3H]GR 65630 was studied, unless stated otherwise, in mouse neuroblastoma N1E-115 cells. Under physiological conditions (135 mM sodium), 5-HT induced a concentration-dependent [14C]guanidinium influx with an EC50 (1.3 μM) similar to that in electrophysiological studies. The stepwise replacement of sodium by increasing concentrations of the organic cation hydroxyethyl trimethylammonium (choline) concentration dependently caused both a rightward shift of the 5-HT concentration–response curve and an increase in the maximum effect of 5-HT. Complete replacement of sodium resulted in a 34-fold lower potency of 5-HT and an almost two times higher maximal response. A low potency of 5-HT in choline buffer was also observed in other 5-HT3 receptor-expressing rodent cell lines (NG 108-15 or NCB 20). Replacement of Na+ by Li+ left the potency and maximal effects of 5-HT almost unchanged. Replacement by tris (hydroxymethyl) methylamine (Tris), tetramethylammonium (TMA) or N-methyl-D-glucamine (NMDG) caused an increase in maximal response to 5-HT similar to that caused by choline. The potency of 5-HT was only slightly reduced by Tris, to a high degree decreased by TMA (comparable to the decrease by choline), but not influenced by NMDG. The potency of 5-HT in inhibiting [3H]GR65630 binding to intact cells was 35-fold lower when sodium was completely replaced by choline, but remained unchanged after replacement by NMDG. The results are compatible with the suggestion that choline competes with 5-HT for the 5-HT3 receptor; the increase in maximal response may be partly due to a choline-mediated delay of the 5-HT-induced desensitization. For studies of 5-HT-evoked [14C]guanidinium flux through 5-HT3 receptor channels, NMDG appears

  20. High Energy Polarized e+e- Beams

    NASA Astrophysics Data System (ADS)

    Shatunov, Yu.; Koop, I.; Otboev, A.; Mane, S.

    2016-02-01

    Recently, the wide discussion about Higgs-factory design again returns to problem of high energy polarized electrons and positrons. It’s good known the radiative beam polarization at LEP-collider. It was obtained after spin resonance suppression at Z0 pick, but didn’t appear at energies above 70 GeV due to an enhancement of unavoidable depolarization effects. We examine in this paper various ideas for radiative polarization at TLEP/FCC-ee and formulate some estimates for the polarization buildup time and the asymptotic polarization. Using wigglers, a useful degree of polarization (for energy calibration), with a time constant of about 1 h, may be possible up to the threshold of W pair production. At higher energies such as the threshold of Higgs production, attaining a useful level of polarization may be difficult in a planar ring. With Siberian Snakes, wigglers and some imagination, polarization of reasonable magnitude, with a reasonable time constant (of not more than about 1 h), may be achievable at very high energies.

  1. Pilot Fullerton dons ejection escape suit (EES) on middeck

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Pilot Fullerton dons ejection escape suit (EES) (high altitude pressure garment) life preserver unit (LPU) on forward port side of middeck above potable water tank. Fullerton also adjusts lapbelt fitting and helmet holddown strap.

  2. Role of maternal 5-HT(1A) receptor in programming offspring emotional and physical development.

    PubMed

    van Velzen, A; Toth, M

    2010-11-01

    Serotonin(1A) receptor (5-HT(1A)R) deficiency has been associated with anxiety and depression and mice with genetic receptor inactivation exhibit heightened anxiety. We have reported that 5-HT(1A)R is not only a genetic but also a maternal 'environmental' factor in the development of anxiety in Swiss-Webster mice. Here, we tested whether the emergence of maternal genotype-dependent adult anxiety is preceded by early behavioral abnormalities or whether it is manifested following a normal emotional development. Pups born to null or heterozygote mothers had significantly reduced ultrasonic vocalization (USV) between postnatal day (P) 4 and 12, indicating an influence of the maternal genotype. The offspring's own genotype had an effect limited to P4. Furthermore, we observed reduced weight gain in the null offspring of null but not heterozygote mothers, indicating that a complete maternal receptor deficiency compromises physical development of the offspring. Except a short perinatal deficit during the dark period, heterozygote females displayed normal maternal behavior, which, with the early appearance of USV deficit, suggests a role for 5-HT(1A)R during pre-/perinatal development. Consistent with this notion, adult anxiety in the offspring is determined during the pre-/perinatal period. In contrast to heterozygote females, null mothers exhibited impaired pup retrieval and nest building that may explain the reduced weight gain of their offspring. Taken together, our data indicate an important role for the maternal 5-HT(1A)R in regulating emotional and physical development of their offspring. Because reduced receptor binding has been reported in depression, including postpartum depression, reduced 5-HT(1A)R function in mothers may influence the emotional development of their offspring.

  3. 5-HT induces cAMP production in crypt colonocytes at a 5-HT4 receptor.

    PubMed

    Albuquerque, F C; Smith, E H; Kellum, J M

    1998-07-01

    Previous studies demonstrate that both 5-hydroxytryptamine (5-HT) and cyclic AMP (cAMP) induce chloride efflux from crypt colonocytes in the rat distal colon; antagonist studies suggest that the 5-HT response is mediated primarily by the 5-HT4 receptor. Since this receptor is known to be positively coupled to adenylate cyclase, we postulated that 5-HT should induce generation of cAMP, which should be inhibited by 5-HT4 antagonists. Method. Mucosal cells from rat distal colon were taken by a sequential calcium chelation technique for enrichment of crypt cells. Cytokeratin stains demonstrated that >99% of cells were colonocytes. [3H]Thymidine uptake studies demonstrate a fivefold increased incorporation in this cell preparation compared to earlier fractions. 3-Isobutyl-l-methylxanthine (IBMX, 100 microM) was added to all cell suspensions in order to prevent cAMP metabolism. Cell suspensions were incubated for 2 min at 37 degreesC with different concentrations of 5-HT (n = 7). cAMP was measured by enzyme immunoassay. In another series of experiments, 5-HT (0.3 microM) stimulation of cAMP was similarly measured in the presence and absence of 5-HT receptor antagonists: 10 microM 5-HTP-DP (5-HT1P; n = 4), 0.1 microM ketanserin (5-HT2A; n = 4), 0.3 microM ondansetron (5-HT3; n = 4), 3 microM tropisetron (5-HT3 and 5-HT4; n = 4), and 10 nM GR-113808 (5-HT4; n = 5). Results. 5-HT produced a dose-dependent increase in cAMP. The increase was significant at concentrations >/=0.3 microM when compared to cells incubated with IBMX alone. In the second series of experiment, 5-HT-induced generation of cAMP at a dose of 0.3 microM was significantly inhibited in the presence of GR-113808 and tropisetron. Conclusion. 5-HT acts at a 5-HT4 receptor to induce production of cAMP in rat distal crypt colonocytes.

  4. 5-HT6 receptors and Alzheimer's disease

    PubMed Central

    2013-01-01

    During the past 20 years, the 5-HT6 receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this receptor have come to light, and it is now quite evident that 5-HT6 receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer's disease. PMID:23607787

  5. COMMUNICATION BETWEEN 5-HT AND SMALL GTPases

    PubMed Central

    Mercado, Charles P.; Ziu, Endrit; Kilic, Fusun

    2011-01-01

    Advances over the past decade have improved our understanding of the serotonin (5-HT) biology outside the central nervous system specifically the molecular mechanisms of serotonergic signaling in association with small GTPases. It is now recognized that the communication between 5-HT and GTPases plays important roles in peripheral tissues, vascular cells and are involved in coagulation, hypertension, inflammation, healing and protection. Furthermore, 5-HT receptors as heterotrimeric GTP-binding protein-coupled receptors act as effector protein on the small GTPases. Therefore, the antagonists or agonists of the effector proteins of small GTPases could be useful therapeutic agents for the treatment of several diseases and disorders. PMID:21320798

  6. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... before January 1, 2003. You may redeem your Series EE savings bond at any time beginning six months after... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When may I redeem my Series EE... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings...

  7. 31 CFR 351.41 - When are definitive Series EE savings bonds validly issued?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When are definitive Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.41 When are definitive Series EE savings bonds validly issued? A definitive bond is validly issued when it is...

  8. 31 CFR 351.41 - When are definitive Series EE savings bonds validly issued?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false When are definitive Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.41 When are definitive Series EE savings bonds validly issued? A definitive bond is validly issued when it is...

  9. 31 CFR 351.4 - In what form are Series EE savings bonds issued?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false In what form are Series EE savings... SAVINGS BONDS, SERIES EE General Information § 351.4 In what form are Series EE savings bonds issued? Series EE savings bonds are issued in book-entry form. Effective January 1, 2012, Treasury...

  10. 31 CFR 351.4 - In what form are Series EE savings bonds issued?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false In what form are Series EE savings... SAVINGS BONDS, SERIES EE General Information § 351.4 In what form are Series EE savings bonds issued? Series EE savings bonds are issued in either book-entry or definitive form....

  11. 31 CFR 351.41 - When are definitive Series EE savings bonds validly issued?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false When are definitive Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.41 When are definitive Series EE savings bonds validly issued? A definitive bond is validly issued when it is...

  12. 31 CFR 351.1 - What regulations govern Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What regulations govern Series EE... SAVINGS BONDS, SERIES EE General Information § 351.1 What regulations govern Series EE savings bonds? (a) The regulations in 31 CFR part 353 apply to definitive (paper) Series EE savings bonds that have...

  13. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false When is interest payable on Series EE... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.8 When is interest payable on Series EE savings bonds? Interest on a bond...

  14. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false When may I redeem my Series EE savings... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.6 When may I redeem my Series EE savings bond? (a) Bonds with issue dates on...

  15. 31 CFR 351.41 - When are definitive Series EE savings bonds validly issued?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false When are definitive Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.41 When are definitive Series EE savings bonds validly issued? A definitive bond is validly issued when it is...

  16. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false When may I redeem my Series EE savings... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.6 When may I redeem my Series EE savings bond? (a) Bonds with issue dates on...

  17. 31 CFR 351.1 - What regulations govern Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false What regulations govern Series EE... SAVINGS BONDS, SERIES EE General Information § 351.1 What regulations govern Series EE savings bonds? (a) The regulations in 31 CFR part 353 apply to definitive (paper) Series EE savings bonds that have...

  18. 31 CFR 351.49 - How are definitive Series EE savings bonds delivered?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false How are definitive Series EE savings... UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.49 How are definitive Series EE savings bonds delivered? We deliver definitive bonds by mail to your address. If your...

  19. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false When may I redeem my Series EE... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.6 When may I redeem my Series EE savings bond? (a) Bonds with issue dates on...

  20. 31 CFR 351.4 - In what form are Series EE savings bonds issued?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false In what form are Series EE savings... SAVINGS BONDS, SERIES EE General Information § 351.4 In what form are Series EE savings bonds issued? Series EE savings bonds are issued in book-entry form. Effective January 1, 2012, Treasury...

  1. 31 CFR 351.5 - What is the maturity period of a Series EE savings bond?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Series EE savings bond? 351.5 Section 351.5 Money and Finance: Treasury Regulations Relating to Money and... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.5 What is the maturity period of a Series EE savings bond?...

  2. 31 CFR 351.49 - How are definitive Series EE savings bonds delivered?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false How are definitive Series EE savings... UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.49 How are definitive Series EE savings bonds delivered? We deliver definitive bonds by mail to your address. If your...

  3. 31 CFR 351.5 - What is the maturity period of a Series EE savings bond?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Series EE savings bond? 351.5 Section 351.5 Money and Finance: Treasury Regulations Relating to Money and... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.5 What is the maturity period of a Series EE savings bond?...

  4. 31 CFR 351.49 - How are definitive Series EE savings bonds delivered?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false How are definitive Series EE savings... UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.49 How are definitive Series EE savings bonds delivered? We deliver definitive bonds by mail to your address. If your...

  5. 31 CFR 351.4 - In what form are Series EE savings bonds issued?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false In what form are Series EE savings... SAVINGS BONDS, SERIES EE General Information § 351.4 In what form are Series EE savings bonds issued? Series EE savings bonds are issued in book-entry form. Effective January 1, 2012, Treasury...

  6. 31 CFR 351.1 - What regulations govern Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false What regulations govern Series EE... SAVINGS BONDS, SERIES EE General Information § 351.1 What regulations govern Series EE savings bonds? (a) The regulations in 31 CFR part 353 apply to definitive (paper) Series EE savings bonds that have...

  7. 31 CFR 351.41 - When are definitive Series EE savings bonds validly issued?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false When are definitive Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.41 When are definitive Series EE savings bonds validly issued? A definitive bond is validly issued when it is...

  8. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false When may I redeem my Series EE savings... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.6 When may I redeem my Series EE savings bond? (a) Bonds with issue dates on...

  9. 31 CFR 351.5 - What is the maturity period of a Series EE savings bond?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Series EE savings bond? 351.5 Section 351.5 Money and Finance: Treasury Regulations Relating to Money and... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.5 What is the maturity period of a Series EE savings bond?...

  10. 31 CFR 351.5 - What is the maturity period of a Series EE savings bond?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Series EE savings bond? 351.5 Section 351.5 Money and Finance: Treasury Regulations Relating to Money and... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.5 What is the maturity period of a Series EE savings bond?...

  11. 31 CFR 351.49 - How are definitive Series EE savings bonds delivered?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false How are definitive Series EE savings... UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.49 How are definitive Series EE savings bonds delivered? We deliver definitive bonds by mail to your address. If your...

  12. 31 CFR 351.1 - What regulations govern Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What regulations govern Series EE... SAVINGS BONDS, SERIES EE General Information § 351.1 What regulations govern Series EE savings bonds? (a) The regulations in 31 CFR part 353 apply to definitive (paper) Series EE savings bonds that have...

  13. 31 CFR 351.49 - How are definitive Series EE savings bonds delivered?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false How are definitive Series EE savings... UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.49 How are definitive Series EE savings bonds delivered? We deliver definitive bonds by mail to your address. If your...

  14. 31 CFR 351.5 - What is the maturity period of a Series EE savings bond?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Series EE savings bond? 351.5 Section 351.5 Money and Finance: Treasury Regulations Relating to Money and... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.5 What is the maturity period of a Series EE savings bond?...

  15. 31 CFR 351.1 - What regulations govern Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false What regulations govern Series EE... SAVINGS BONDS, SERIES EE General Information § 351.1 What regulations govern Series EE savings bonds? (a) The regulations in 31 CFR part 353 apply to definitive (paper) Series EE savings bonds that have...

  16. Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory.

    PubMed

    Meneses, Alfredo

    2007-11-22

    In order to determine whether short- (STM) and long-term memory (LTM) function in serial or parallel manner, serotonin (5-hydroxtryptamine, 5-HT) receptor agonists were tested in autoshaping task. Results show that control-vehicle animals were modestly but significantly mastering the autoshaping task as illustrated by memory scores between STM and LTM. Thus, post-training administration of 8-OHDPAT (agonist for 5-HT(1A/7) receptors) only at 0.250 and 0.500 mg/kg impaired both STM and LTM. CGS12066 (agonist for 5-HT(1B)) produced biphasic affects, at 5.0 mg/kg impaired STM but at 1.0 and 10.0 mg/kg, respectively, improved or impaired LTM. DOI (agonist for 5-HT(2A/2C) receptors) dose-dependently impaired STM and, at 10.0 mg/kg only impaired LTM. Both, STM and LTM were impaired by either mCPP (mainly agonist for 5-HT(2C) receptors) or mesulergine (mainly antagonist for 5-HT(2C) receptors) lower dose. The 5-HT(3) agonist mCPBG at 1.0 impaired STM and its higher dose impaired both STM and LTM. RS67333 (partial agonist for 5-HT(4) receptors), at 5.0 and 10.0 mg/kg facilitated both STM and LTM. The higher dose of fluoxetine (a 5-HT uptake inhibitor) improved both STM and LTM. Using as head-pokes during CS as an indirect measure of food-intake showed that of 30 memory changes, 21 of these were unrelated to the former. While some STM or LTM impairments can be attributed to decrements in food-intake, but not memory changes (either increase or decreases) produced by 8-OHDPAT, CGS12066, RS67333 or fluoxetine. Except for animals treated with DOI, mCPBG or fluoxetine, other groups treated with 5-HT agonists 6 h following autoshaping training showed similar LTM and unmodified CS-head-pokes scores.

  17. 5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux.

    PubMed

    Huang, Mei; Horiguchi, Masakuni; Felix, Anna R; Meltzer, Herbert Y

    2012-05-09

    Lurasidone is a novel, atypical antipsychotic drug with serotonin [5-hydroxytryptamine (5-HT)]2A, 5-HT7, dopamine (DA) D2 antagonist, and 5-HT1A receptor partial agonist properties. The ability of lurasidone to reverse the effects of subchronic administration phencyclidine, to impair novel object recognition in rats, an animal model of cognitive impairment in schizophrenia, is dependent, in part, on its 5-HT1A agonist and 5-HT7 receptor antagonist properties. We tested whether 5-HT1A partial agonism or 5-HT7 antagonism, or both, contributed to the ability of lurasidone to enhance cortical and hippocampal DA efflux, which may be related to its ability to improve cognition. Here, we report that lurasidone, 0.25 and 0.5, but not 0.1 mg/kg, subcutaneously, significantly increased DA efflux in the prefrontal cortex and hippocampus in a dose-dependent manner. Lurasidone, 0.5 mg/kg, also produced a smaller increase in DA efflux in the nucleus accumbens. Pretreatment with the 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg, subcutaneously), partially blocked the lurasidone-induced cortical and hippocampal DA efflux. Further, subeffective doses of the 5-HT1A receptor agonist, tandospirone (0.2 mg/kg), or the 5-HT7 antagonist, SB269970 (0.3 mg/kg), potentiated the ability of a subeffective dose of lurasidone (0.1 mg/kg) to increase DA efflux in the prefrontal cortex. These findings suggest that the effects of lurasidone on the prefrontal cortex and hippocampus, DA efflux are dependent, at least partially, on its 5-HT1A agonist and 5-HT7 antagonist properties and may contribute to its efficacy to reverse the effects of subchronic phencyclidine treatment and improve schizophrenia.

  18. The Sun Like Star : HT Vir

    NASA Astrophysics Data System (ADS)

    Tanriver, Mehmet; Özeren, Ferhat Fikri

    2016-12-01

    This study is focused on the photometric (light curve) analysis of the Sun like star HT Vir which is a binary star located in the ASAS catalogue, shows variation in W UMa (EW/KW) type. The solution of light curve was executed using the PHOBE code. We conducted an unspotted solution for the HT Vir binary system. The positions in the HR diagram of the components are also discussed.

  19. Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative.

    PubMed

    Meneses, Alfredo

    2014-01-01

    Agonists and antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) or receptor7 (5-HT7) might improve memory and/or reverse amnesia, although the mechanisms involved are poorly understood. Hence, the current work summarizes recent reviews and findings involving these receptors. Evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effect in conditions, such as memory formation, age-related cognitive impairments and memory deficit in preclinical studies, as well as in diseases such as schizophrenia, Parkinson's, and Alzheimer's disease (AD). Memory, aging, and AD modify 5-HT6 receptors and signaling cascades; likewise, the modulation of 5-HT6 drugs on memory seems to be accompanied with neural changes. Moreover, 5-HT7 receptors are localized in brain areas mediating memory, including the cortex, hippocampus (e.g., Zola-Morgan and Squire, 1993) and raphe nuclei; however, the role of these receptors on memory has yet to be fully explored. Hence, findings and reviews are summarized in this work. Evidence suggests that both 5-HT7 receptor agonists and antagonists might have promnesic and anti-amnesic effects. These effects seem to be dependent on the basal level of performance, i.e., normal or impaired. Available evidence suggests that a potential utility of 5-HT6 and 5-HT7 receptor in mild-to-moderate AD patients and other memory dysfunctions as therapeutic targets.

  20. Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders.

    PubMed

    Naumenko, Vladimir S; Popova, Nina K; Lacivita, Enza; Leopoldo, Marcello; Ponimaskin, Evgeni G

    2014-07-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. Besides the important role of 5-HT receptors in the pathogenesis of depressive disorders and in their clinical medications, underlying mechanisms are far from being completely understood. This review focuses on possible cross talk between two serotonin receptors, 5-HT1A and the 5-HT7 . Although these receptors are highly co-expressed in brain regions implicated in depression, and most agonists developed for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional interaction has not been yet established. It has been recently shown that 5-HT1A and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From the functional point of view, heterodimerization has been shown to play an important role in regulation of receptor-mediated signaling and internalization, suggesting the implication of heterodimerization in the development and maintenance of depression. Interaction between these receptors is also of clinical interest, because both receptors represent an important pharmacological target for the treatment of depression and anxiety.

  1. Serotonergic 5-HT7 receptors and cognition.

    PubMed

    Gasbarri, Antonella; Pompili, Assunta

    2014-01-01

    The abundant distribution of serotonin (5-HT) in different areas of the central nervous system can explain the involvement of this neurotransmitter in the regulation of several functions, such as sleep, pain, feeding, and sexual and emotional behaviors. Moreover, the serotonergic system is also involved in other more complex roles, such as cognition, including learning and memory processes. Recent studies led to the discovery of various types and subtypes of receptors differentially associated to cognitive mechanisms. 5-HT7 is the most recently discovered receptor for 5-HT; therefore, it is also one of the least well characterized. Studies exist hypothesizing the role of 5-HT7 on the modulation of learning and memory processes and other cognitive functions. Moreover, much attention has been devoted to the possible role of 5-HT7 receptors in psychiatric disorders. Therefore, the aim of this review is to clarify the behavioral role of the recently discovered 5-HT7 type receptor and highlight its involvement in the cognitive functions, with particular attention to the modulation of learning and memory processes, thus providing a basis to obtain new therapeutic agents and strategies for the treatment of cognitive disorders.

  2. Memory time-course: mRNA 5-HT1A and 5-HT7 receptors.

    PubMed

    Perez-Garcia, Georgina; Meneses, Alfredo

    2009-08-24

    In an attempt to clarify conflicting results about serotonin (5-hydroxytryptamine, 5-HT) 5-HT(1A) and 5-HT(7) receptors in memory formation, their mRNA expression was determined by RT-PCR in key brain areas for explicit and implicit memory. The time-course (0-120 h) of autoshaped responses was progressive and mRNA 5-HT(1A) or 5-HT(7) receptors expression monotonically augmented or declined in prefrontal cortex, hippocampus and raphe nuclei, respectively. At 24-48 h acutely 8-OH-DPAT (0.062 mg/kg) administration enhanced memory and attenuated mRNA 5-HT(1A)<5-HT(7) receptors expression respect to saline group. WAY100635 (0.3 mg/kg) or SB-269970 (10.0 mg/kg) did not affect the former, partially blocked or reversed the latter, respectively. Furthermore, lower WAY100635 (0.001-0.1 mg/kg) or SB-269970 (1.0-5.0 mg/kg) doses plus 8-OHDPAT not affected memory; however both combinations suppressed or up-regulated mRNA expression 5-HT(1A) or 5-HT(7) receptors. In contrast, AS19 (5.0 mg/kg) facilitated memory consolidation, decreased or increased hippocampal 5-HT(7) and 5-HT(1A) receptors expression. Together these data revealed that, when both 5-HT(1A) and 5-HT(7) receptors were stimulated by 8-OHDPAT under memory consolidation, subtle changes emerged, not evident at behavioral level though detectable at genes expression. Notably, high levels of efficient memory were maintained even when serotonergic tone, via either 5-HT(1A) or 5-HT(7) receptor, was down- or up-regulated. Nevertheless, WAY100635 plus SB-269970 impaired memory consolidation and suppressed their expression. Considering that serotonergic changes are prominent in AD patients with an earlier onset of disease the present approach might be useful in the identification of functional changes associated to memory formation, memory deficits and reversing or even preventing these deficits.

  3. Caspase-3 binds diverse P4 residues in peptides as revealed by crystallography and structural modeling.

    SciTech Connect

    Fang, Bin; Fu, Guoxing; Agniswamy, Johnson; Harrison, Robert W.; Weber, Irene T.

    2009-03-31

    Caspase-3 recognition of various P4 residues in its numerous protein substrates was investigated by crystallography, kinetics, and calculations on model complexes. Asp is the most frequent P4 residue in peptide substrates, although a wide variety of P4 residues are found in the cellular proteins cleaved by caspase-3. The binding of peptidic inhibitors with hydrophobic P4 residues, or no P4 residue, is illustrated by crystal structures of caspase-3 complexes with Ac-IEPD-Cho, Ac-WEHD-Cho, Ac-YVAD-Cho, and Boc-D(OMe)-Fmk at resolutions of 1.9-2.6 {angstrom}. The P4 residues formed favorable hydrophobic interactions in two separate hydrophobic regions of the binding site. The side chains of P4 Ile and Tyr form hydrophobic interactions with caspase-3 residues Trp206 and Trp214 within a non-polar pocket of the S4 subsite, while P4 Trp interacts with Phe250 and Phe252 that can also form the S5 subsite. These interactions of hydrophobic P4 residues are distinct from those for polar P4 Asp, which indicates the adaptability of caspase-3 for binding diverse P4 residues. The predicted trends in peptide binding from molecular models had high correlation with experimental values for peptide inhibitors. Analysis of structural models for the binding of 20 different amino acids at P4 in the aldehyde peptide Ac-XEVD-Cho suggested that the majority of hydrophilic P4 residues interact with Phe250, while hydrophobic residues interact with Trp206, Phe250, and Trp214. Overall, the S4 pocket of caspase-3 exhibits flexible adaptation for different residues and the new structures and models, especially for hydrophobic P4 residues, will be helpful for the design of caspase-3 based drugs.

  4. Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

    PubMed Central

    Morita, Hiroki; Mochiki, Erito; Takahashi, Nobuyuki; Kawamura, Kiyoshi; Watanabe, Akira; Sutou, Toshinaga; Ogawa, Atsushi; Yanai, Mitsuhiro; Ogata, Kyoichi; Fujii, Takaaki; Ohno, Tetsuro; Tsutsumi, Souichi; Asao, Takayuki; Kuwano, Hiroyuki

    2013-01-01

    AIM: To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs. METHODS: Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed. RESULTS: 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. CONCLUSION: The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. PMID:24151388

  5. Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands.

    PubMed

    Ofori, Edward; Zhu, Xue Y; Etukala, Jagan R; Peprah, Kwakye; Jordan, Kamanski R; Adkins, Adia A; Bricker, Barbara A; Kang, Hye J; Huang, Xi-Ping; Roth, Bryan L; Ablordeppey, Seth Y

    2016-08-15

    5-HT1A and 5-HT7 receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT7 receptor ligand culminating in the identification of several dual 5-HT1A and 5-HT7 receptor ligands. Compound 16, a butyrophenone derivative of tetrahydroisoquinoline (THIQ), was identified as the most potent agent with low nanomolar binding affinities to both receptors. Interestingly, compound 16 also displayed moderate affinity to other clinically relevant dopamine receptors. Thus, it is anticipated that compound 16 may serve as a lead for further exploitation in our quest to identify new ligands with the potential to treat diseases of CNS origin.

  6. Proposed Injection into “Thief” Zone in EE-3

    SciTech Connect

    Potter, Robert M.; Grigsby, Charles O.

    1983-08-18

    This report seeks to understand the nature of the "thief" zone inside the EE-3 by pumping 150-200K gallons of heated water into that zone. The questions they seek to answer are; does the thief zone represent a potential danger to future operations in the form of earthquakes, aquifers, damage to equipment or tubulars, or require that it be sealed; is a connection into the the thief zone from EE-2 a disaster point; could the connection into the thief zone provide a low back-pressure condition.

  7. PHP-HT (VitaResc Biotech).

    PubMed

    Baldwin, A; Wiley, E

    2001-04-01

    VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

  8. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Space Station Processing Facility, workers oversee the removal of the P4 truss from the truck that transported it from Tulsa, Okla. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field on the International Space Station, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  9. The Top 10 Things I LOVE about p4c Hawai'i

    ERIC Educational Resources Information Center

    Ikeda, Jolyn

    2012-01-01

    In 2001, Dr. Thomas Jackson, or Dr. J as the author and her colleagues affectionately call him, spoke to the faculty at Waikiki Elementary. He described philosophy for children (p4c) Hawai'i and encouraged them to try P4C if something about it "resonated" with them. In the beginning, Dr. J held a p4t (philosophy for teachers)…

  10. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    In the Space Station Processing Facility, an overhead crane moves the P4 truss to a workstand. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field on the International Space Station, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  11. 31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Series EE savings bond? 351.64 Section 351.64 Money and Finance: Treasury Regulations Relating to Money... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings...

  12. 31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Series EE savings bond? 351.64 Section 351.64 Money and Finance: Treasury Regulations Relating to Money... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings...

  13. 31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-entry Series EE savings bond? 351.64 Section 351.64 Money and Finance: Treasury Regulations Relating to... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings...

  14. Constitutively Active 5-HT Receptors: An Explanation of How 5-HT Antagonists Inhibit Gut Motility in Species Where 5-HT is Not an Enteric Neurotransmitter?

    PubMed Central

    Spencer, Nick J.

    2015-01-01

    Antagonists of 5-Hydroxytryptamine (5-HT) receptors are well known to inhibit gastrointestinal (GI)-motility and transit in a variety of mammals, including humans. Originally, these observations had been interpreted by many investigators (including us) as evidence that endogenous 5-HT plays a major role in GI motility. This seemed a logical assumption. However, the story changed dramatically after recent studies revealed that 5-HT antagonists still blocked major GI motility patterns (peristalsis and colonic migrating motor complexes) in segments of intestine depleted of all 5-HT. Then, these results were further supported by Dr. Gershons' laboratory, which showed that genetic deletion of all genes that synthesizes 5-HT had minor, or no inhibitory effects on GI transit in vivo. If 5-HT was essential for GI motility patterns and transit, then one would expect major disruptions in motility and transit when 5-HT synthesis was genetically ablated. This does not occur. The inhibitory effects of 5-HT antagonists on GI motility clearly occur independently of any 5-HT in the gut. Evidence now suggests that 5-HT antagonists act on 5-HT receptors in the gut which are constitutively active, and don't require 5-HT for their activation. This would explain a long-standing mystery of how 5-HT antagonists inhibit gut motility in species like mice, rats, and humans where 5-HT is not an enteric neurotransmitter. Studies are now increasingly demonstrating that the presence of a neurochemical in enteric neurons does not mean they function as neurotransmitters. Caution should be exercised when interpreting any inhibitory effects of 5-HT antagonists on GI motility. PMID:26732863

  15. The 5-HT1-like receptors mediating inhibition of sympathetic vasopressor outflow in the pithed rat: operational correlation with the 5-HT1A, 5-HT1B and 5-HT1D subtypes

    PubMed Central

    Villalón, Carlos M; Centurión, David; Rabelo, Gonzalo; de Vries, Peter; Saxena, Pramod R; Sánchez-López, Araceli

    1998-01-01

    It has been suggested that the inhibition of sympathetically-induced vasopressor responses produced by 5-hydroxytryptamine (5-HT) in pithed rats is mediated by 5-HT1-like receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors.Intravenous (i.v.) continuous infusions of 5-HT and the 5-HT1 receptor agonists, 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP 93,129 (5-HT1B) and sumatriptan (5-HT1B/1D), resulted in a dose-dependent inhibition of sympathetically-induced vasopressor responses.The sympatho-inhibitory responses induced by 5-HT, 8-OH-DPAT, indorenate, CP 93,129 or sumatriptan were analysed before and after i.v. treatment with blocking doses of the putative 5-HT receptor antagonists, WAY 100635 (5-HT1A), cyanopindolol (5-HT1A/1B) or GR 127935 (5-HT1B/1D). Thus, after WAY 100635, the responses to 5-HT and indorenate, but not to 8-OH-DPAT, CP 93,129 and sumatriptan, were blocked. After cyanopindolol, the responses to 5-HT, indorenate and CP 93,129 were abolished, whilst those to 8-OH-DPAT and sumatriptan (except at the lowest frequency of stimulation) remained unaltered. In contrast, after GR 127935, the responses to 5-HT, CP 93,129 and sumatriptan, but not to 8-OH-DPAT and indorenate, were abolished.In additional experiments, the inhibition induced by 5-HT was not modified after 5-HT7 receptor blocking doses of mesulergine.The above results suggest that the 5-HT1-like receptors, which inhibit the sympathetic vasopressor outflow in pithed rats, display the pharmacological profile of the 5-HT1A, 5-HT1B and 5-HT1D, but not that of 5-HT7, receptors. PMID:9692787

  16. Comparative receptor mapping of serotoninergic 5-HT3 and 5-HT4 binding sites*

    NASA Astrophysics Data System (ADS)

    López-Rodríguez, María L.; Morcillo, María José; Benhamú, Bellinda; Rosado, María Luisa

    1997-11-01

    The clinical use of currently available drugs acting at the5-HT4 receptor has been hampered by their lack of selectivityover 5-HT3 binding sites. For this reason, there is considerableinterest in the medicinal chemistry of these serotonin receptor subtypes, andsignificant effort has been made towards the discovery of potent and selectiveligands. Computer-aided conformational analysis was used to characterizeserotoninergic 5-HT3 and 5-HT4 receptorrecognition. On the basis of the generally accepted model of the5-HT3 antagonist pharmacophore, we have performed a receptormapping of this receptor binding site, following the active analog approach(AAA) defined by Marshall. The receptor excluded volume was calculated as theunion of the van der Waals density maps of nine active ligands(pKi ≥ 8.9), superimposed in pharmacophoric conformations.Six inactive analogs (pKi < 7.0) were subsequently used todefine the essential volume, which in its turn can be used to define theregions of steric intolerance of the 5-HT3 receptor. Five activeligands (pKi ≥ 9.3) at 5-HT4 receptors wereused to construct an antagonist pharmacophore for this receptor, and todetermine its excluded volume by superimposition of pharmacophoricconformations. The volume defined by the superimposition of five inactive5-HT4 receptor analogs that possess the pharmacophoric elements(pKi ≤ 6.6) did not exceed the excluded volume calculated forthis receptor. In this case, the inactivity may be due to the lack of positiveinteraction of the amino moiety with a hypothetical hydrophobic pocket, whichwould interact with the voluminous substituents of the basic nitrogen ofactive ligands. The difference between the excluded volumes of both receptorshas confirmed that the main difference is indeed in the basic moiety. Thus,the 5-HT3 receptor can only accommodate small substituents inthe position of the nitrogen atom, whereas the 5-HT4 receptorrequires more voluminous groups. Also, the basic nitrogen is located at ca

  17. Research Trends in the United States: EE to ESD

    ERIC Educational Resources Information Center

    Heimlich, Joe E.

    2007-01-01

    Research on education for sustainable development (ESD) is not a unified body of work and, much like the literature for environmental education (EE), research is published in many arenas. The trends, however, capture some of the major foci of the research that is emerging on ESD, especially in the early years of the Decade of Education for…

  18. e+e- → charm cross sections via ISR

    NASA Astrophysics Data System (ADS)

    Pakhlova, Galina

    2010-06-01

    We discuss recent measurements of exclusive e+e- cross sections for charmed hadron final states near threshold performed by Belle and BABAR. The results are based on a study of events with initial-state-radiation photons in a large data sample collected with the Belle and BABAR detectors at the γ(4S) resonance and nearby continuum.

  19. EE and ESD: Two Paradigms, One Crucial Goal

    ERIC Educational Resources Information Center

    McKeown, Rosalyn; Hopkins, Chuck

    2005-01-01

    The launch of the United Nations Decade of Education for Sustainable Development (UNDESD) gives the education community opportunity to reflect on and discuss major issues that will affect the future well-being of the world. The goals and dreams of environmental education (EE) are similar to those of educators involved in education for sustainable…

  20. 32. SECTIONS AA, BB, CC, DD, AND EE WASTE CALCINATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. SECTIONS A-A, B-B, C-C, D-D, AND E-E WASTE CALCINATION FACILITY SHOWING RELATIONSHIPS OF DIFFERENT FLOOR LEVELS TO ONE ANOTHER. INEEL DRAWING NUMBER 200-0633-00-287-106353. FLUOR NUMBER 5775-CPP-633-A-3. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

  1. Detection and characterization of a human G9P[4] rotavirus strain in Japan.

    PubMed

    Yamamoto, Seiji P; Kaida, Atsushi; Ono, Atsushi; Kubo, Hideyuki; Iritani, Nobuhiro

    2015-08-01

    In a surveillance system in Osaka City, Japan, 48 sporadic rotavirus A (RVA) infections were detected during 2008/2009-2011/2012 seasons. The G/P-genotypes of detected RVAs were G1P[8], G2P[4], G3P[8], G9P[4], and G9P[8]. Although G9P[4] is a rare genotype that had not been reported in Japan, it was the second most prevalent genotype, following G1P[8], and accounted for 35.3% of RVA cases in the 2011/2012 season. Further genotyping revealed that the G9P[4] strain had genotype 2 internal protein genes except for NSP3: G9-P[4]-I2-R2-C2-M2-A2-N2-T1-E2-H2. Among detected RVA strains, G9P[4] and some G9P[8] strains shared high nucleotide identity in VP7 and NSP3 genes. Phylogenetic and BLAST search analyses showed that the G9P[4] strain in Japan shared high nucleotide identity in genotype 2 genes with common G2P[4] strains circulating globally, but was distinct from other G9P[4] strains circulating worldwide. These results suggest that the G9P[4] strain in Japan may have emerged through an independent reassortment between G9P[8] and G2P[4]. Finally, the role of NSP3 protein in the circulating RVA from an amino acid comparison between T1- and T2-type NSP3 is discussed. These findings provide an important insight into less problematic combinations of circulating RVA genes derived from different genotypes.

  2. Contractile 5-HT1 receptors in human isolated pial arterioles: correlation with 5-HT1D binding sites.

    PubMed Central

    Hamel, E.; Bouchard, D.

    1991-01-01

    1. The 5-hydroxytryptamine (5-HT) receptor responsible for inducing vasoconstriction in human isolated pial arterioles has been pharmacologically characterized. 2. Of several 5-HT agonists tested, 5-carboxamidotryptamine (5-CT) was the most potent and the rank order of agonist potency can be summarized as: 5-CT greater than 5-HT greater than RU 24969 = alpha-methyl-5-HT = methysergide much greater than MDL 72832 = 2-methyl-5-HT much greater than 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT). With few exceptions, the maximal contractile responses of these agonists were comparable to that induced by 5-HT. 3. A correlation analysis performed between the agonists vascular potency (pD2 values) and their affinities (pKD values) published at various subtypes of 5-HT binding sites showed a positive significant correlation with rat cortical 5-HT1B (r = 0.86; P less than 0.01) and human caudate 5-HT1D (r = 0.98; P less than 0.005) subtypes. 4. Selective antagonists at 5-HT2 (ketanserin, mianserin, MDL 11939) and 5-HT3 (MDL 72222) sites were totally devoid of inhibitory activity on the 5-HT-induced contraction, an observation which agreed with the agonist data and further excluded activation of these receptors. In contrast, the 5-HT1-like/5-HT2 antagonist methiothepin and the non-selective 5-HT1D compound metergoline inhibited with high affinity the contraction induced by 5-HT with respective pA2 values of 8.55 +/- 0.16 and 6.88 +/- 0.05. This contractile response was, however, insensitive to 5-HT1B (propranolol) and 5-HT1C (mesulergine, mianserin) antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043924

  3. Pilot Fullerton dons EES anti-gravity suit lower torso on middeck

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Pilot Fullerton dons ejection escape suit (EES) anti-gravity (anti-g) suit lower torso on forward port side middeck above potable water tank. Anti-g suit is an olive drab inner garment that complements EES.

  4. An improved limit for Γee of X (3872) and Γee measurement of ψ (3686)

    NASA Astrophysics Data System (ADS)

    Ablikim, M.; Achasov, M. N.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, H. Y.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Cheng, H. P.; Chu, X. K.; Cibinetto, G.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; De Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Duan, P. F.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Fava, L.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. Y.; Gao, Y.; Gao, Z.; Garzia, I.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, J. F.; Hu, T.; Hu, Y.; Huang, G. M.; Huang, G. S.; Huang, H. P.; Huang, J. S.; Huang, X. T.; Huang, Y.; Hussain, T.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. L.; Jiang, L. W.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Kliemt, R.; Kloss, B.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kühn, W.; Kupsc, A.; Lai, W.; Lange, J. S.; Lara, M.; Larin, P.; Leng, C.; Li, C. H.; Li, Cheng; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, Jin; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. M.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B. J.; Liu, C. X.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, X. X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, R. Q.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. N.; Ma, X. Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Moriya, K.; Muchnoi, N. Yu.; Muramatsu, H.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Patteri, P.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Pu, Y. N.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, N.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ren, H. L.; Ripka, M.; Rong, G.; Ruan, X. D.; Santoro, V.; Sarantsev, A.; Savrié, M.; Schoenning, K.; Schumann, S.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, W. M.; Song, X. Y.; Sosio, S.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Tiemens, M.; Toth, D.; Ullrich, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q. J.; Wang, S. G.; Wang, W.; Wang, X. F.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Weber, T.; Wei, D. H.; Wei, J. B.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, Z.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. X.; Yang, L.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yin, J. H.; Yu, B. X.; Yu, C. X.; Yu, H. W.; Yu, J. S.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J. J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. H.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, Li; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.

    2015-10-01

    Using the data sets taken at center-of-mass energies above 4 GeV by the BESIII detector at the BEPCII storage ring, we search for the reaction e+e- →γISR X (3872) →γISRπ+π- J / ψ via the Initial State Radiation technique. The production of a resonance with quantum numbers JPC =1++ such as the X (3872) via single photon e+e- annihilation is forbidden, but is allowed by a next-to-leading order box diagram. We do not observe a significant signal of X (3872), and therefore give an upper limit for the electronic width times the branching fraction ΓeeX (3872) B (X (3872) →π+π- J / ψ) < 0.13 eV at the 90% confidence level. This measurement improves upon existing limits by a factor of 46. Using the same final state, we also measure the electronic width of the ψ (3686) to be Γeeψ (3686) = 2213 ±18stat ±99sys eV.

  5. 5-Hydroxytryptamine (5-HT) Cellular Sequestration during Chronic Exposure Delays 5-HT3 Receptor Resensitization due to Its Subsequent Release*

    PubMed Central

    Hothersall, J. Daniel; Alexander, Amy; Samson, Andrew J.; Moffat, Christopher; Bollan, Karen A.; Connolly, Christopher N.

    2014-01-01

    The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT3) receptors. We report that recombinantly expressed 5-HT3 receptor binding sites are reduced by chronic exposure to 5-HT (IC50 of 154.0 ± 45.7 μm, t½ = 28.6 min). This is confirmed for 5-HT3 receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC50 of 2.3 ± 1.0 μm, t½ = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization. PMID:25281748

  6. High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

    PubMed

    da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

    2016-04-01

    Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females.

  7. 5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women examined with [(11)C] WAY100635 and [(11)C] MADAM PET.

    PubMed

    Jovanovic, Hristina; Karlsson, Per; Cerin, Asta; Halldin, Christer; Nordström, Anna-Lena

    2009-04-30

    The aim of the present study was to explore the effects of the menstrual cycle phases on 5-HT(1A) receptor and 5-HTT binding potentials (BPs) in healthy women by using positron emission tomography (PET). Women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [(11)C]WAY10035 (n=13) and [(11)C]MADAM (n=8) to study 5-HT(1A) and 5-HTT BPs. The BPs values were quantified using the simplified reference tissue model. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV) and plasma levels of hormones estradiol (E(2)), progesterone (P(4)), follicle stimulating hormone (FSH) and luteinizing hormone (LH).The 5-HT(1A) receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between the change in E(2) or P(4) values with the change in 5-HT(1A) receptor or 5-HTT BPs. The results provide principally a new in vivo finding in human female biology, suggesting the absence of influence of menstrual cycle phase on 5-HT(1A) receptors or 5-HTT. The finding however does not preclude that gonadal hormones differentially influence central serotonin system inwomen and men, which might contribute to gender differences in serotonin-associated disorders.

  8. Antibodies specific for HT.sub.m4

    DOEpatents

    Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel

    1998-01-01

    The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy.

  9. Recombinant HT.sub.m4 gene, protein and assays

    DOEpatents

    Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel

    1996-01-01

    The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy.

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

    PubMed

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

    2013-11-01

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

  11. Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT) neurons in mice with altered 5-HT homeostasis.

    PubMed

    Araragi, Naozumi; Mlinar, Boris; Baccini, Gilda; Gutknecht, Lise; Lesch, Klaus-Peter; Corradetti, Renato

    2013-01-01

    Firing activity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert-/-) and tryptophan hydroxylase-2 knockout (Tph2-/-) mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2-/- mice and Sert-/- mice, respectively. While 5-HT neurons from Tph2-/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert-/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP), neurons from both Tph2-/- and Sert-/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling.

  12. Haemophilus influenzae P4 Interacts With Extracellular Matrix Proteins Promoting Adhesion and Serum Resistance.

    PubMed

    Su, Yu-Ching; Mukherjee, Oindrilla; Singh, Birendra; Hallgren, Oskar; Westergren-Thorsson, Gunilla; Hood, Derek; Riesbeck, Kristian

    2016-01-15

    Interaction with the extracellular matrix (ECM) is one of the successful colonization strategies employed by nontypeable Haemophilus influenzae (NTHi). Here we identified Haemophilus lipoprotein e (P4) as a receptor for ECM proteins. Purified recombinant P4 displayed a high binding affinity for laminin (Kd = 9.26 nM) and fibronectin (Kd = 10.19 nM), but slightly less to vitronectin (Kd = 16.51 nM). A P4-deficient NTHi mutant showed a significantly decreased binding to these ECM components. Vitronectin acquisition conferred serum resistance to both P4-expressing NTHi and Escherichia coli transformants. P4-mediated bacterial adherence to pharynx, type II alveolar, and bronchial epithelial cells was mainly attributed to fibronectin. Importantly, a significantly reduced bacterial infection was observed in the middle ear of the Junbo mouse model when NTHi was devoid of P4. In conclusion, our data provide new insight into the role of P4 as an important factor for Haemophilus colonization and subsequent respiratory tract infection.

  13. The P4 truss is moved to a workstand in the SSPF

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Suspended by an overhead crane in the Space Station Processing Facility, the International Space Station's P4 truss moves toward a workstand. Below and behind it on the floor is the Multi- Purpose Logistics Module Raffaello, another segment of the Space Station. Part of the 10-truss, girder-like structure that will ultimately extend the length of a football field, the P4 is the second port truss segment that will attach to the first port truss segment (P1 truss). The P4 is scheduled for mission 12A in September 2002.

  14. HIF-P4H-2 deficiency protects against skeletal muscle ischemia-reperfusion injury.

    PubMed

    Karsikas, Sara; Myllymäki, Mikko; Heikkilä, Minna; Sormunen, Raija; Kivirikko, Kari I; Myllyharju, Johanna; Serpi, Raisa; Koivunen, Peppi

    2016-03-01

    We show here that mice hypomorphic for hypoxia-inducible factor prolyl 4-hydroxylase-2 (HIF-P4H-2) (Hif-p4h-2 (gt/gt)), the main regulator of the stability of the HIFα subunits, have normoxic stabilization of HIF-1α and HIF-2α in their skeletal muscles. The size of the capillaries, but not their number, was increased in the skeletal muscles of the Hif-p4h-2 (gt/gt) mice, whereas the amount of glycogen was reduced. The expression levels of genes for glycolytic enzymes, glycogen branching enzyme 1 and monocarboxylate transporter 4, were increased in the Hif-p4h-2 (gt/gt) skeletal muscles, whereas no significant increases were detected in the levels of any vasculature-influencing factor studied. Serum lactate levels of the Hif-p4h-2 (gt/gt) mice recovered faster than those of the wild type following exercise. The Hif-p4h-2 (gt/gt) mice had elevated hepatic phosphoenolpyruvate carboxykinase activity, which may have contributed to the faster clearance of lactate. The Hif-p4h-2 (gt/gt) mice had smaller infarct size following limb ischemia-reperfusion injury. The increased capillary size correlated with the reduced infarct size. Following ischemia-reperfusion, glycogen content and ATP/ADP and CrP/Cr levels of the skeletal muscle of the Hif-p4h-2 (gt/gt) mice were higher than in the wild type. The higher glycogen content correlated with increased expression of phosphofructokinase messenger RNA (mRNA) and the increased ATP/ADP and CrP/Cr levels with reduced apoptosis, suggesting that HIF-P4H-2 deficiency supported energy metabolism during ischemia-reperfusion and protection against injury. Key messages: HIF-P4H-2 deficiency protects skeletal muscle from ischemia-reperfusion injury. The mechanisms involved are mediated via normoxic HIF-1α and HIF-2α stabilization. HIF-P4H-2 deficiency increases capillary size but not number. HIF-P4H-2 deficiency maintains energy metabolism during ischemia-reperfusion.

  15. Ultralow thermal conductivity in Electrolessly Etched (EE) Silicon Nanowires

    NASA Astrophysics Data System (ADS)

    Hippalgaonkar, Kedar; Chen, Renkun; Budaev, Bair; Tang, Jinyao; Andrews, Sean; Murphy, Padraig; Mukerjee, Subroto; Moore, Joel; Yang, Peidong; Majumdar, Arun

    2009-03-01

    EE process produces single-crystalline Silicon nanowires with rough walls. We use suspended structures to directly compute the heat transfer through single nanowires. Nanowires with diameters less than the mean free path of phonons impede transport by boundary scattering. The roughness acts as a secondary scattering mechanism to further reduce phonon transport. By controlling the amount of roughness it is possible to push limits to the extent that nanowire conductance close to quanta of thermal conductance,πkB^2 T / πkB^2 T 6 . - 6 is observed. Traditionally, the lower limit of conductivity is amorphous Silicon at 1 W/mK at room temperature. The measured conductivity of our nanostructures challenges even this amorphous limit pointing towards previously unstudied mechanisms of thermal resistance. We measure thermal conductivity of ˜150nm diameter EE wires to be ˜1 W/mK.

  16. EE-3A Logging Report for Feb. 28th., 1994

    SciTech Connect

    Anderson, David W.

    1994-03-14

    A Temperature/Casing-Collar Locator (CCL) log of EE-3A was performed on Monday, February 28th, 1994. This log was the first of two, (the other to be run on March 31st.), in an attempt to investigate a temperature anomaly occurring between 10,000 to 11,435 ft. The thermal recovery of this zone is slower than expected, which is believed to be caused by either; flow through the cemented zone of the 5 1/2" liner, or an upward flow through the reservoir itself. Now that the first log is over, the annulus of EE-3A will be shut-in for a period of approximately one month, at which time the log will be repeated. If the temperature of this zone shows signs of recovery after the shut-in period, the integrity of the cement will be in question. No sign of recovery will point to upward reservoir flow theory.

  17. Role of 5-HT6 receptors in memory formation.

    PubMed

    Meneses, A

    2001-09-01

    Mice lacking the 5-HT(6) receptor presented neither gross anatomical or behavioral abnormalities nor obvious changes in microscopic brain morphology, and their performance in rotarod, open field and novel object testing paradigms revealed no differences compared with wild-type animals. Nevertheless, an association between the 5-HT(6) receptor polymorphism C267T and Alzheimer's disease has been reported. Interestingly, the 5-HT(6) antisense oligonucleotide decreased 5-HT(6) gene expression and enhanced spatial learning acquisition in the water maze. Similarly, injection of the 5-HT(6) receptor antagonist Ro-04-6790 improved learning consolidation in an autoshaping task, while mCPP, scopolamine and dizocilpine decreased performance. The effect induced by scopolamine or dizocilpine, but not that induced by mCPP, was completely or partially reversed by Ro-04-6790. Ro-04-6790 did not modify the 8-OH-DPAT facilitatory effects on learning consolidation. Since Ro-04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A/2B/2C), 5-HT(3), 5-HT(4) or 5-HT(7) receptor blockade, the facilitatory effect induced by Ro-04-6790 involved specifically 5-HT6 receptors. Similarly, the 5-HT(6) receptor antagonist SB-271046 improved retention in the water maze and produced a significant performance improvement in aged rats in an operant-delayed alternation task. A series of Ro-04-6790 analogues that penetrate the brain and specifically bind to 5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive avoidance learning test. Collectively, these data provide further support to the notion that 5-HT systems, via 5-HT(6) receptors, also play a significant role in memory formation under normal and dysfunctional memory conditions.

  18. Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning.

    PubMed

    Meneses, A; Hong, E

    1997-08-01

    The effects of post-training (i.p.) injection of TFMPP, mCPP, DOI or 1-NP in the autoshaping learning task was explored. Furthermore, the post-training effects of these agonists after treatment with the antagonists (+/-)-pindolol, (+/-)-propranolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL-72222 or p-chloroamphetamine (5-HT depleter) were studied. Rats were individually trained with a lever-press response (conditioned response; CR) on the autoshaping task and tested 24 h later. The results showed that the injection of TFMPP (1-10 mg/kg), mCPP (1-10 mg/kg), 1-NP (0.1-1.0 mg/kg) or mesulergine (0.4 mg/kg) decreased the rate of CR, while DOI (0.01-0.1 mg/kg) and ritanserin (0.5 mg/kg) and ketanserin (0.001-0.1 mg/kg) increased it. However, the effect induced by TFMPP was reversed by (+/-)-pindolol, ketanserin, ritanserin and PCA; the mCPP-induced effect was antagonized by (+/-)-propranolol, ketanserin, ritanserin and MDL-72222; and the effect produced by 1-NP was reversed by ketanserin, ritanserin and PCA. In addition, the increment in CR provoked by DOI was enhanced by ketanserin, and reversed by ritanserin, mesulergine and PCA. These findings suggest that TFMPP, 1-NP and DOI exerted their effects via stimulation of presynaptic 5-HT receptors. The effects of mCPP most probably reflect activation of postsynaptic receptors. The present data suggest that both 5-HT1B and 5-HT2A-2C receptors play a significant role in the consolidation of learning.

  19. Experiment 2003 – First Pressurization of EE-2

    SciTech Connect

    Murphy, Hugh D.; Matsunaga, Isao; Kuriyagawa, Michio

    1982-01-07

    Water was pumped into EE-2 at a nominal rate of 9gpm, to a final pressure of 2070 psi. The wellbore was exceptionally tight we might just have well pumped into a steel pressure vessel not only was there no evidence of breakdown, but only a total of about 30 gallons of water permeated the rock during the 2-1/2 hour-long pressurization.

  20. Observation of η'→ω e+e-

    NASA Astrophysics Data System (ADS)

    Ablikim, M.; Achasov, M. N.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Ferroli, R. Baldini; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, H. Y.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Cheng, H. P.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Duan, P. F.; Eren, E. E.; Fan, J. Z.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Fava, L.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. Y.; Gao, Y.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y.; Guo, Y. P.; Haddadi, Z.; Hafner, A.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, J. F.; Hu, T.; Hu, Y.; Huang, G. M.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, Y.; Hussain, T.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, L. W.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Kiese, P.; Kliemt, R.; Kloss, B.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kühn, W.; Kupsc, A.; Lange, J. S.; Lara, M.; Larin, P.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, J. C.; Li, Jin; Li, K.; Li, K.; Li, Lei; Li, P. R.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. M.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B. J.; Liu, C. X.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. H.; Liu, H. H.; Liu, H. M.; Liu, J.; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Loehner, H.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Maas, F. E.; Maggiora, M.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Messchendorp, J. G.; Min, J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales, C. Morales; Moriya, K.; Muchnoi, N. Yu.; Muramatsu, H.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Patteri, P.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Poling, R.; Prasad, V.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, L. Q.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Ripka, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Santoro, V.; Sarantsev, A.; Savrié, M.; Schoenning, K.; Schumann, S.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, W. M.; Song, X. Y.; Sosio, S.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tapan, I.; Thorndike, E. H.; Tiemens, M.; Ullrich, M.; Uman, I.; Varner, G. S.; Wang, B.; Wang, D.; Wang, D. Y.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, S. G.; Wang, W.; Wang, X. F.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Weber, T.; Wei, D. H.; Wei, J. B.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, Z.; Xia, L. G.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, L.; Xu, Q. J.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y.; Yang, Y. X.; Ye, M.; Ye, M. H.; Yin, J. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J. J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. N.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, Q. W.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zotti, L.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

    2015-09-01

    Based on a sample of η' mesons produced in the radiative decay J /ψ →γ η' in 1.31 ×109 J /ψ events collected with the BESIII detector, the decay η'→ω e+e- is observed for the first time, with a statistical significance of 8 σ . The branching fraction is measured to be B (η'→ω e+e-)=(1.97 ±0.34 (stat)±0.17 (syst))×10-4 , which is in agreement with theoretical predictions. The branching fraction of η'→ω γ is also measured to be (2.55 ±0.03 (stat)±0.16 (syst))×10-2 , which is the most precise measurement to date, and the relative branching fraction B/(η'→ω e+e-) B (η'→ω γ ) is determined to be (7.71 ±1.34 (stat)±0.54 (syst))×10-3 .

  1. P4-ATPases as Phospholipid Flippases—Structure, Function, and Enigmas

    PubMed Central

    Andersen, Jens P.; Vestergaard, Anna L.; Mikkelsen, Stine A.; Mogensen, Louise S.; Chalat, Madhavan; Molday, Robert S.

    2016-01-01

    P4-ATPases comprise a family of P-type ATPases that actively transport or flip phospholipids across cell membranes. This generates and maintains membrane lipid asymmetry, a property essential for a wide variety of cellular processes such as vesicle budding and trafficking, cell signaling, blood coagulation, apoptosis, bile and cholesterol homeostasis, and neuronal cell survival. Some P4-ATPases transport phosphatidylserine and phosphatidylethanolamine across the plasma membrane or intracellular membranes whereas other P4-ATPases are specific for phosphatidylcholine. The importance of P4-ATPases is highlighted by the finding that genetic defects in two P4-ATPases ATP8A2 and ATP8B1 are associated with severe human disorders. Recent studies have provided insight into how P4-ATPases translocate phospholipids across membranes. P4-ATPases form a phosphorylated intermediate at the aspartate of the P-type ATPase signature sequence, and dephosphorylation is activated by the lipid substrate being flipped from the exoplasmic to the cytoplasmic leaflet similar to the activation of dephosphorylation of Na+/K+-ATPase by exoplasmic K+. How the phospholipid is translocated can be understood in terms of a peripheral hydrophobic gate pathway between transmembrane helices M1, M3, M4, and M6. This pathway, which partially overlaps with the suggested pathway for migration of Ca2+ in the opposite direction in the Ca2+-ATPase, is wider than the latter, thereby accommodating the phospholipid head group. The head group is propelled along against its concentration gradient with the hydrocarbon chains projecting out into the lipid phase by movement of an isoleucine located at the position corresponding to an ion binding glutamate in the Ca2+- and Na+/K+-ATPases. Hence, the P4-ATPase mechanism is quite similar to the mechanism of these ion pumps, where the glutamate translocates the ions by moving like a pump rod. The accessory subunit CDC50 may be located in close association with the

  2. Selective 5HT2A and 5HT6 Receptor Antagonists Promote Sleep in Rats

    PubMed Central

    Morairty, Stephen R.; Hedley, Linda; Flores, Judith; Martin, Renee; Kilduff, Thomas S.

    2008-01-01

    Study Objectives: Serotonin (5-HT) has long been implicated in the control of sleep and wakefulness. This study evaluated the hypnotic efficacy of the 5-HT6 antagonist RO4368554 (RO) and the 5-HT2A receptor antagonist MDL100907 (MDL) relative to zolpidem. Design: A randomized, repeated-measures design was utilized in which Wistar rats received intraperitoneal injections of RO (1.0, 3.0, and 10 mg/kg), MDL (0.1, 1.0 and 3.0 mg/kg), zolpidem (10 mg/kg), or vehicle in the middle of the dark (active) period. Electroencephalogram, electromyogram, body temperature (Tb) and locomotor activity were analyzed for 6 hours after injection. Measurements and Results: RO, MDL, and zolpidem all produced significant increases in sleep and decreases in waking, compared with vehicle control. All 3 doses of MDL produced more consolidated sleep, increased non-rapid eye movement sleep (NREM) sleep, and increased electroencephalographic delta power during NREM sleep. The highest dose of RO (10.0 mg/kg) produced significant increases in sleep and decreases in waking during hour 2 following dosing. These increases in sleep duration were associated with greater delta power during NREM sleep. ZO Zolpidem induced sleep with the shortest latency and significantly increased NREM sleep and delta power but also suppressed rapid eye movement sleep sleep; in contrast, neither RO nor MDL affected rapid eye movement sleep. Whereas RO did not affect Tb, both zolpidem and MDL reduced Tb relative to vehicle-injected controls. Conclusions: These results support a role for 5-HT2A receptor modulation in NREM sleep and suggest a previously unrecognized role for 5-HT6 receptors in sleep-wake regulation. Citation: Morairty SR; Hedley L; Flores J; Martin R; Kilduff TS. Selective 5HT2A and 5HT6 receptor antagonists promote sleep in rats. SLEEP 2008;31(1):34-44. PMID:18220076

  3. Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors.

    PubMed Central

    Backus, L. I.; Sharp, T.; Grahame-Smith, D. G.

    1990-01-01

    1. The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2. The 5-HT2/5-HTIC antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and gepirone. 3. Pretreatment with the 5-HT2/5-HT1C antagonist ICI 170,809 (0.25-5 mg kg-1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. 4. The 5-HT2/alpha 1-adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg-1) significantly increased the 5-HT behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT, while in a higher dose (2.5 mg kg-1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5-HT behavioural syndrome through blockade of alpha 1-adrenoceptors. 5. Ritanserin and ICI 170,809 had no effect on apomorphine-induced stereotypy or hyperactivity, indicating that these drugs do not produce non-specific behavioural activation. 6. Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. 7. We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT1A agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT1A receptor-mediated function. PMID:2145051

  4. On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor.

    PubMed

    Naumenko, Vladimir S; Kondaurova, Elena M; Popova, Nina K

    2011-12-01

    Intracerebroventricular administration of selective agonist of serotonin 5-HT(7) receptor LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-pyperasinehexanamide hydrochloride; 10.3, 20.5 or 41.0 nmol) produced considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol) hypothermia was significantly attenuated by the selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time, intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0 mg/kg (2.0, 4.0, 20.0 μmol/kg) did not cause considerable hypothermic response. These findings indicate the implication of central, rather than peripheral 5-HT(7) receptors in the regulation of hypothermia. The comparison of LP44-induced (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect of genotype was found. In the same eight mouse strains, functional activity of 5-HT(1A) and 5-HT(3) receptors was studied. The comparison of hypothermic responses produced by 5-HT(7) receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT(1A) receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg), 5-HT(3) receptor agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain correlations between 5-HT(7) and 5-HT(1A) or 5-HT(3) receptor-induced hypothermia. The selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT(7) receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The obtained results suggest that the central 5-HT(7) receptor plays an essential role in the mediation of thermoregulation independent of 5-HT(1A) and 5-HT(3) receptors.

  5. 5-HT spatial distribution imaging with multiphoton excitation of 5-HT correlative visible fluorescence in live cells

    NASA Astrophysics Data System (ADS)

    Zhang, Zhihong; Zeng, Shaoqun; Liu, Yafeng; Zhou, Wei; Chen, Tongsheng; Luo, Qingming

    2002-04-01

    The autofluorescence of 5-Hydroxytryptamine (5-HT) loaded rat mucosal mast cells (RBL-2H3 cells) is imaged with multiphoton excitation laser scanning microscope (MPELSM). 5-HT correlative visible fluorescence (Fco-vis) excited with 740-nm multiphoton excitation is observed in live cells for the first time, and the generating mechanism of 5-HT Fco-vis is studied. The spatial distribution of 5-HT in live cells is imaged at high spatial resolution in our experiment, which provides a new way to study the correlation between 5-HT spatial distribution and content, and the cellular functional state in live tissue or cells.

  6. Effect of Selective 5-HT6R Agonist on Expression of 5-HT Receptor and Neurotransmitter in Vascular Dementia Rats

    PubMed Central

    Yu, Haining; Chen, Tao; Zhou, Li; Tang, Jiyou

    2017-01-01

    Background 5-HT6 receptor (5-HT6R) has pluripotent roles regulating secretion of neurotransmitters. However, whether 5-HT6R is involved in the development of vascular dementia (VD) remains unclear. To evaluate the role and mechanism of 5-HT6R in VD, this study established a rat VD model to evaluate the effect of selective 5-HT6R agonist on the expression of 5-HT6R mRNA and neurotransmitter. Material/Methods Eighty healthy male SD rats (7 weeks old) were randomly assigned to sham, model, 5-HT6R agonist, and placebo groups (N=20 each). A rat VD model was generated by permeant bilateral ligation of the common carotid artery. 5-HT6R agonist, placebo, or saline were given intraperitoneally for 4 weeks. The Morris water maze was utilized to test learning and memory function. Brains were extracted to separate the cortex and hippocampal tissues, in which glutamate and γ-aminobutyric acid (GABA) levels were analyzed. mRNA and protein levels of 5-HT6R were determined by RT-PCR and immunohistochemistry (IHC), respectively. Results Model rats had longer escape latency and fewer crossing platform times. Contents of DA, Glu, GABA, and Ach were lowered in cortical and hippocampal tissues, and 5-HT6R expression was suppressed (p<0.05). The application of 5-HT6R agonist shortened escape latency and increased the number of passing through the platform. It also improved hippocampal CA1 neuronal damage and elevated DA, Glu, GABA, and Ach contents and expression of 5-HT6R. Expression of 5-HT6R was not different from the placebo group. Conclusions Selective 5-HT6R agonist can alleviate learning deficit of VD rats, possibly via improving neurotransmitter levels in brain regions. PMID:28196966

  7. 31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase...

  8. 31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What amount of book-entry Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of...

  9. 31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We will...

  10. 31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds...

  11. 31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held...

  12. 31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What amount of book-entry Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of...

  13. 31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current...

  14. 31 CFR 351.66 - What book-entry Series EE savings bonds are included in the computation?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What book-entry Series EE savings... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.66 What book-entry Series EE savings bonds are included in the computation? (a) We include all bonds...

  15. 31 CFR 351.66 - What book-entry Series EE savings bonds are included in the computation?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What book-entry Series EE savings... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.66 What book-entry Series EE savings bonds are included in the computation? (a) We include all bonds...

  16. 31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We will...

  17. 31 CFR 351.42 - What is the issue date of a definitive series EE savings bond?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... series EE savings bond? 351.42 Section 351.42 Money and Finance: Treasury Regulations Relating to Money... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.42 What is the issue date of a definitive series EE savings bond? The issue date of a definitive bond is the first...

  18. 31 CFR 351.50 - How is payment made when definitive Series EE savings bonds are redeemed?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Series EE savings bonds are redeemed? 351.50 Section 351.50 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.50 How is payment made when definitive Series EE savings bonds are redeemed? (a) Payment in general....

  19. 31 CFR 351.20 - What is the investment yield (interest) during the original maturity period of Series EE savings...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) during the original maturity period of Series EE savings bonds with issue dates from January 1, 1980... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.20 What is...

  20. 31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held...

  1. 31 CFR 351.47 - May I purchase definitive Series EE savings bonds through a payroll savings plan?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false May I purchase definitive Series EE... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.47 May I purchase definitive Series EE savings bonds through a payroll savings plan?...

  2. 31 CFR 351.7 - May Series EE savings bonds be called for redemption prior to final maturity?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false May Series EE savings bonds be called... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.7 May Series EE savings bonds be called...

  3. 31 CFR 351.42 - What is the issue date of a definitive series EE savings bond?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... definitive series EE savings bond? 351.42 Section 351.42 Money and Finance: Treasury Regulations Relating to... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.42 What is the issue date of a definitive series EE savings bond? The issue date of a definitive bond is the first...

  4. 31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held...

  5. 31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds...

  6. 31 CFR 351.42 - What is the issue date of a definitive Series EE savings bond?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Series EE savings bond? 351.42 Section 351.42 Money and Finance: Treasury Regulations Relating to Money... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.42 What is the issue date of a definitive Series EE savings bond? The issue date of a definitive bond is the first...

  7. 31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds...

  8. 31 CFR 351.51 - How can I find out what my definitive Series EE savings bonds are worth?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Series EE savings bonds are worth? 351.51 Section 351.51 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.51 How can I find out what my definitive Series EE savings bonds are worth? (a) Redemption values. We...

  9. 31 CFR 351.50 - How is payment made when definitive Series EE savings bonds are redeemed?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Series EE savings bonds are redeemed? 351.50 Section 351.50 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.50 How is payment made when definitive Series EE savings bonds are redeemed? (a) Payment in general....

  10. 31 CFR 351.40 - What were the denominations and prices of definitive Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... prices of definitive Series EE savings bonds? 351.40 Section 351.40 Money and Finance: Treasury... FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.40 What were the denominations and prices of definitive Series EE savings bonds? Prior to...

  11. 31 CFR 351.46 - May I purchase definitive Series EE savings bonds over-the-counter?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false May I purchase definitive Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.46 May I purchase definitive Series EE savings bonds over-the-counter? You may purchase definitive bonds...

  12. 31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We will...

  13. 31 CFR 351.50 - How is payment made when definitive Series EE savings bonds are redeemed?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Series EE savings bonds are redeemed? 351.50 Section 351.50 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.50 How is payment made when definitive Series EE savings bonds are redeemed? (a) Payment in general....

  14. 31 CFR 351.7 - May Series EE savings bonds be called for redemption prior to final maturity?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false May Series EE savings bonds be called... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.7 May Series EE savings bonds be called...

  15. 31 CFR 351.44 - What amount of definitive Series EE savings bonds may I purchase per year?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What amount of definitive Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.44 What amount of definitive Series EE savings bonds may I purchase per year? The principal amount...

  16. 31 CFR 351.20 - What is the investment yield (interest) during the original maturity period of Series EE savings...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) during the original maturity period of Series EE savings bonds with issue dates from January 1, 1980... UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.20 What is...

  17. 31 CFR 351.46 - May I purchase definitive Series EE savings bonds over-the-counter?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false May I purchase definitive Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.46 May I purchase definitive Series EE savings bonds over-the-counter? You may purchase definitive bonds...

  18. 31 CFR 351.40 - What were the denominations and prices of definitive Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of definitive Series EE savings bonds? 351.40 Section 351.40 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.40 What were the denominations and prices of definitive Series EE savings bonds? Prior to January 1,...

  19. 31 CFR 351.46 - May I purchase definitive Series EE savings bonds over-the-counter?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false May I purchase definitive Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.46 May I purchase definitive Series EE savings bonds over-the-counter? Effective January 1, 2012,...

  20. 31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current...

  1. 31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We will...

  2. 31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held...

  3. 31 CFR 351.50 - How is payment made when definitive Series EE savings bonds are redeemed?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Series EE savings bonds are redeemed? 351.50 Section 351.50 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.50 How is payment made when definitive Series EE savings bonds are redeemed? (a) Payment in general....

  4. 31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false What amount of book-entry Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of...

  5. 31 CFR 351.21 - How are redemption values determined during any extended maturity period of Series EE savings...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? 351... BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series... during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995?...

  6. 31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase...

  7. 31 CFR 351.7 - May Series EE savings bonds be called for redemption prior to final maturity?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false May Series EE savings bonds be called... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.7 May Series EE savings bonds be called...

  8. 31 CFR 351.46 - May I purchase definitive Series EE savings bonds over-the-counter?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false May I purchase definitive Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.46 May I purchase definitive Series EE savings bonds over-the-counter? Effective January 1, 2012,...

  9. 31 CFR 351.47 - May I purchase definitive Series EE savings bonds through a payroll savings plan?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false May I purchase definitive Series EE... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.47 May I purchase definitive Series EE savings bonds through a payroll savings plan? You may...

  10. 31 CFR 351.42 - What is the issue date of a definitive series EE savings bond?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... series EE savings bond? 351.42 Section 351.42 Money and Finance: Treasury Regulations Relating to Money... OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.42 What is the issue date of a definitive series EE savings bond? The issue date of a definitive bond is the first...

  11. 31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current...

  12. 31 CFR 351.42 - What is the issue date of a definitive Series EE savings bond?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... definitive Series EE savings bond? 351.42 Section 351.42 Money and Finance: Treasury Regulations Relating to... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.42 What is the issue date of a definitive Series EE savings bond? The issue date of a definitive bond is the first...

  13. 31 CFR 351.51 - How can I find out what my definitive Series EE savings bonds are worth?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Series EE savings bonds are worth? 351.51 Section 351.51 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.51 How can I find out what my definitive Series EE savings bonds are worth? (a) Redemption values. We...

  14. 31 CFR 351.40 - What were the denominations and prices of definitive Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of definitive Series EE savings bonds? 351.40 Section 351.40 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.40 What were the denominations and prices of definitive Series EE savings bonds? Prior to January 1,...

  15. 31 CFR 351.40 - What are the denominations and prices of definitive Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of definitive Series EE savings bonds? 351.40 Section 351.40 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.40 What are the denominations and prices of definitive Series EE savings bonds? We issue definitive...

  16. 31 CFR 351.51 - How can I find out what my definitive Series EE savings bonds are worth?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Series EE savings bonds are worth? 351.51 Section 351.51 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.51 How can I find out what my definitive Series EE savings bonds are worth? (a) Redemption values. We...

  17. 31 CFR 351.46 - May I purchase definitive Series EE savings bonds over-the-counter?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false May I purchase definitive Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.46 May I purchase definitive Series EE savings bonds over-the-counter? Effective January 1, 2012,...

  18. 31 CFR 351.50 - How is payment made when definitive Series EE savings bonds are redeemed?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Series EE savings bonds are redeemed? 351.50 Section 351.50 Money and Finance: Treasury Regulations... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.50 How is payment made when definitive Series EE savings bonds are redeemed? (a) Payment in general....

  19. 31 CFR 351.47 - May I purchase definitive Series EE savings bonds through a payroll savings plan?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false May I purchase definitive Series EE... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.47 May I purchase definitive Series EE savings bonds through a payroll savings plan?...

  20. 31 CFR 351.51 - How can I find out what my definitive Series EE savings bonds are worth?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Series EE savings bonds are worth? 351.51 Section 351.51 Money and Finance: Treasury Regulations Relating... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.51 How can I find out what my definitive Series EE savings bonds are worth? (a) Redemption values. We...

  1. 31 CFR 351.48 - May I purchase definitive Series EE savings bonds through employee thrift, savings, vacation, and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false May I purchase definitive Series EE... OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.48 May I purchase definitive Series EE savings bonds...

  2. 31 CFR 351.48 - May I purchase definitive Series EE savings bonds through employee thrift, savings, vacation, and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false May I purchase definitive Series EE... OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.48 May I purchase definitive Series EE savings bonds...

  3. 31 CFR 351.21 - How are redemption values determined during any extended maturity period of Series EE savings...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? 351... BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series... during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995?...

  4. 31 CFR 351.7 - May Series EE savings bonds be called for redemption prior to final maturity?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false May Series EE savings bonds be called... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.7 May Series EE savings bonds be called...

  5. 31 CFR 351.63 - How are redemption payments made for my redeemed book-entry Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... my redeemed book-entry Series EE savings bonds? 351.63 Section 351.63 Money and Finance: Treasury... FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.63 How are redemption payments made for my redeemed book-entry Series EE savings bonds? We...

  6. 31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds...

  7. 31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false What amount of book-entry Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of...

  8. 31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current...

  9. 31 CFR 351.40 - What are the denominations and prices of definitive Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of definitive Series EE savings bonds? 351.40 Section 351.40 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.40 What are the denominations and prices of definitive Series EE savings bonds? We issue definitive...

  10. 31 CFR 351.48 - May I purchase definitive Series EE savings bonds through employee thrift, savings, vacation, and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false May I purchase definitive Series EE... OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.48 May I purchase definitive Series EE savings bonds...

  11. 31 CFR 351.65 - What amount of book-entry Series EE savings bonds may I acquire per year?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false What amount of book-entry Series EE... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.65 What amount of book-entry Series EE savings bonds may I acquire per year? The principal amount of...

  12. 31 CFR 351.48 - May I purchase definitive Series EE savings bonds through employee thrift, savings, vacation, and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false May I purchase definitive Series EE... OF THE TREASURY BUREAU OF THE FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.48 May I purchase definitive Series EE savings bonds...

  13. 31 CFR 351.47 - May I purchase definitive Series EE savings bonds through a payroll savings plan?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false May I purchase definitive Series EE... FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.47 May I purchase definitive Series EE savings bonds through a payroll savings plan?...

  14. 31 CFR 351.47 - May I purchase definitive Series EE savings bonds through a payroll savings plan?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false May I purchase definitive Series EE... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.47 May I purchase definitive Series EE savings bonds through a payroll savings plan?...

  15. 31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase...

  16. 31 CFR 351.48 - May I purchase definitive Series EE savings bonds through employee thrift, savings, vacation, and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false May I purchase definitive Series EE... OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.48 May I purchase definitive Series EE savings bonds...

  17. 31 CFR 351.44 - What amount of definitive Series EE savings bonds may I purchase per year?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What amount of definitive Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.44 What amount of definitive Series EE savings bonds may I purchase per year? The principal amount...

  18. 31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase...

  19. 31 CFR 351.70 - How are redemption values calculated for book-entry Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for book-entry Series EE savings bonds? 351.70 Section 351.70 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.70 How are redemption values calculated for book-entry Series EE savings bonds? We base current...

  20. 31 CFR 351.51 - How can I find out what my definitive Series EE savings bonds are worth?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Series EE savings bonds are worth? 351.51 Section 351.51 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.51 How can I find out what my definitive Series EE savings bonds are worth? (a) Redemption values. We...

  1. 31 CFR 351.62 - How is payment made for purchases of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... book-entry Series EE savings bonds? 351.62 Section 351.62 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.62 How is payment made for purchases of book-entry Series EE savings bonds? You may only purchase...

  2. 31 CFR 351.61 - What are the denominations and prices of book-entry Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of book-entry Series EE savings bonds? 351.61 Section 351.61 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.61 What are the denominations and prices of book-entry Series EE savings bonds? Book-entry bonds...

  3. 31 CFR 351.60 - How are book-entry Series EE savings bonds purchased and held?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false How are book-entry Series EE savings... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.60 How are book-entry Series EE savings bonds purchased and held? Book-entry bonds must be purchased and held...

  4. 31 CFR 351.7 - May Series EE savings bonds be called for redemption prior to final maturity?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false May Series EE savings bonds be called... Yields of Series EE Savings Bonds General Provisions § 351.7 May Series EE savings bonds be called for redemption prior to final maturity? The Secretary of the Treasury may not call Series EE bonds for...

  5. The GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5-HT1B, but not to the 5-HT1D or 5-ht1F, receptor subtype

    PubMed Central

    Centurión, David; Sánchez-López, Araceli; De Vries, Peter; Saxena, Pramod R; Villalón, Carlos M

    2001-01-01

    This study has further investigated the pharmacological profile of the GR127935-sensitive 5-HT1 receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs. One-minute intracarotid infusions of the agonists 5-hydroxytryptamine (5-HT; 0.1–10 μg min−1; endogenous ligand) and sumatriptan (0.3–10 μg min−1; 5-HT1B/1D), but not PNU-142633 (1–1000 μg min−1; 5-HT1D) or LY344864 (1–1000 μg min−1; 5-ht1F), produced dose-dependent decreases in internal carotid blood flow without changing blood pressure or heart rate. The responses to 5-HT were apparently resistant to blockade by i.v. administration of the antagonists SB224289 (300 μg kg−1; 5-HT1B), BRL15572 (300 μg kg−1; 5-HT1D) or ritanserin (100 μg kg−1; 5-HT2). In contrast, the responses to sumatriptan were antagonized by SB224289, but not by BRL15572. In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5-HT-induced vasoconstriction and unmasked a vasodilator component. Similarly, in ritanserin-treated animals, the subsequent administration of SB224289, but not BRL15572, completely blocked the 5-HT-induced vasoconstriction, revealing vasodilatation. In animals receiving initially BRL15572, the subsequent administration of SB224289 did not affect (except at 10 μg min−1) the vasoconstrictor responses to 5-HT. Notably, in animals pretreated with 1000 μg kg−1 of mesulergine, a 5-HT2/7 receptor antagonist, 5-HT produced a dose-dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blockade was produced and the subsequent administration of ritanserin was similarly inactive. These results suggest that the GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction resemble the 5-HT1B but not the 5-HT1D or 5-ht1F, receptor subtype. PMID:11226129

  6. Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared with unvaccinated hospitalized cases, despite high vaccine effectiveness against heterotypic G2P[4] rotaviruses.

    PubMed

    Matthijnssens, J; Zeller, M; Heylen, E; De Coster, S; Vercauteren, J; Braeckman, T; Van Herck, K; Meyer, N; Pirçon, J-Y; Soriano-Gabarro, M; Azou, M; Capiau, H; De Koster, J; Maernoudt, A-S; Raes, M; Verdonck, L; Verghote, M; Vergison, A; Van Damme, P; Van Ranst, M

    2014-10-01

    The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher's exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by G1P[8] rotavirus strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was 85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was 90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (p <0.001), whereby G2P[4] strains were proportionally more prevalent in vaccinated cases than in unvaccinated cases. No statistical associations were found between co-infection status and vaccination status, Vesikari severity score or rotavirus genotype. The high vaccine effectiveness against the individual genotypes implies robust protection of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the major human rotavirus genotypes. The prevalence of G2P[4] requires continued monitoring.

  7. Phytosphingosine 1-phosphate: a high affinity ligand for the S1P(4)/Edg-6 receptor.

    PubMed

    Candelore, Mari Rios; Wright, Michael J; Tota, Laurie M; Milligan, James; Shei, Gan-ju; Bergstrom, James D; Mandala, Suzanne M

    2002-09-27

    It has been reported recently that the phosphorylated form of the immunomodulator FTY720 activates sphingosine 1-phosphate G protein-coupled receptors. Therefore, understanding the biology of this new class of receptors will be important in clarifying the immunological function of bioactive lysosphingolipid ligands. The S1P(4) receptor has generated interest due to its lymphoid tissue distribution. While the S1P(4) receptor binds the prototypical ligand, S1P, a survey of other lysosphingolipids demonstrated that 4D-hydroxysphinganine 1-phosphate, more commonly known as phytosphingosine 1-phosphate (PhS1P), binds to S1P(4) with higher affinity. Using radiolabeled S1P (S133P), the affinity of PhS1P for the S1P(4) receptor is 1.6nM, while that of S1P is nearly 50-fold lower (119+/-20nM). Radiolabeled PhS1P proved to be superior to S133P in routine binding assays due to improved signal-to-noise ratio. The present study demonstrates the utility of a novel radiolabeled probe, PhS133P, for in vitro studies of the S1P(4) receptor pharmacology.

  8. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition

    PubMed Central

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-01-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function. PMID:25468940

  9. Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition.

    PubMed

    Naruse, Mie; Ono, Ryuichi; Irie, Masahito; Nakamura, Kenji; Furuse, Tamio; Hino, Toshiaki; Oda, Kanako; Kashimura, Misho; Yamada, Ikuko; Wakana, Shigeharu; Yokoyama, Minesuke; Ishino, Fumitoshi; Kaneko-Ishino, Tomoko

    2014-12-01

    Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus. P4 is an essential hormone in the preparation and maintenance of pregnancy and the determination of the timing of parturition in mammals; however, the biological significance of placental P4 in rodents is not properly recognized. Here, we demonstrate that mouse placentas do produce P4 in mid-gestation, coincident with a temporal reduction in ovarian P4, suggesting that it plays a role in the protection of the conceptuses specifically in this period. Pregnant Sirh7/Ldoc1 knockout females also displayed delayed parturition associated with a low pup weaning rate. All these results suggest that Sirh7/Ldoc1 has undergone positive selection during eutherian evolution as a eutherian-specific acquired gene because it impacts reproductive fitness via the regulation of placental endocrine function.

  10. Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors

    PubMed Central

    Sánchez-López, Araceli; Centurión, David; Vázquez, Erika; Arulmani, Udayasankar; Saxena, Pramod R; Villalón, Carlos M

    2003-01-01

    Continuous infusions of 5-hydroxytryptamine (5-HT) inhibit the tachycardiac responses to preganglionic (C7-T1) sympathetic stimulation in pithed rats pretreated with desipramine. The present study identified the pharmacological profile of this inhibitory action of 5-HT. The inhibition induced by intravenous (i.v.) continuous infusions of 5-HT (5.6 μg kg−1 min−1) on sympathetically induced tachycardiac responses remained unaltered after i.v. treatment with saline or the antagonists GR 127935 (5-HT1B/1D), the combination of WAY 100635 (5-HT1A) plus GR 127935, ritanserin (5-HT2), tropisetron (5-HT3/4), LY215840 (5-HT7) or a cocktail of antagonists/inhibitors consisting of yohimbine (α2), prazosin (α1), ritanserin, GR 127935, WAY 100635 and indomethacin (cyclooxygenase), but was abolished by methiothepin (5-HT1/2/6/7 and recombinant 5-ht5A/5B). These drugs, used in doses high enough to block their respective receptors/mechanisms, did not modify the sympathetically induced tachycardiac responses per se. I.v. continuous infusions of the agonists 5-carboxamidotryptamine (5-CT; 5-HT1/7 and recombinant 5-ht5A/5B), CP 93,129 (r5-HT1B), sumatriptan (5-HT1B/1D), PNU-142633 (5-HT1D) and ergotamine (5-HT1B/1D and recombinant 5-ht5A/5B) mimicked the above sympatho-inhibition to 5-HT. In contrast, the agonists indorenate (5-HT1A) and LY344864 (5-ht1F) were inactive. Interestingly, 5-CT-induced cardiac sympatho-inhibition was abolished by methiothepin, the cocktail of antagonists/inhibitors, GR 127935 or the combination of SB224289 (5-HT1B) plus BRL15572 (5-HT1D), but remained unchanged when SB224289 or BRL15572 were given separately. Therefore, 5-HT-induced cardiac sympatho-inhibition, being unrelated to 5-HT2, 5-HT3, 5-HT4, 5-ht6, 5-HT7 receptors, α1/2-adrenoceptor or prostaglandin synthesis, seems to be primarily mediated by (i) 5-HT1 (probably 5-HT1B/1D) receptors and (ii) a novel mechanism antagonized by methiothepin that, most likely, involves putative 5-ht5A/5B

  11. Application of P4 Polyphase codes pulse compression method to air-coupled ultrasonic testing systems.

    PubMed

    Li, Honggang; Zhou, Zhenggan

    2017-03-03

    Air-coupled ultrasonic testing systems are usually restricted by low signal-to-noise ratios (SNR). The use of pulse compression techniques based on P4 Polyphase codes can improve the ultrasound SNR. This type of codes can generate higher Peak Side Lobe (PSL) ratio and lower noise of compressed signal. This paper proposes the use of P4 Polyphase sequences to code ultrasound with a NDT system based on air-coupled piezoelectric transducer. Furthermore, the principle of selecting parameters of P4 Polyphase sequence for obtaining optimal pulse compression effect is also studied. Successful results are presented in molded composite material. A hybrid signal processing method for improvement in SNR up to 12.11dB and in time domain resolution about 35% are achieved when compared with conventional pulse compression technique.

  12. Constraints on axions from π0 --> e+e- decay

    NASA Astrophysics Data System (ADS)

    Massó, Eduard

    1986-12-01

    The contribution of axions to π0 --> e+e- decay is considered. It is found that a recently proposed short-lived axion with a mass of 1.8 MeV induces a decay rate inconsistent with experimental observations. More generally, upper limits are placed on the mass of an axion that couples to first-generations fermions. On leave of absence from Department de Física Teòrica, Universitat Autònoma de Barcelona, Bellaterra, Spain.

  13. Two-particle distributions in e+e- jets

    NASA Astrophysics Data System (ADS)

    Willen, Dennis E.

    1980-04-01

    We apply the "jet calculus" of Konishi, Ukawa, and Veneziano (KUV) to the two-particle spectra of e+e- jets. This computation uses single-particle fragmentation functions and the KUV analysis of leading logarithms to predict the multiparticle spectra entirely from the single-particle data. The effects of charm and heavier flavors are discussed and a simple prescription for inverting the necessary double moments is given. The double-differential cross section dσdx1dx2 is displayed for various combinations of mesons and the antiproton.

  14. Direct photon production in e+e- annihilation

    NASA Astrophysics Data System (ADS)

    Fernandez, E.; Ford, W. T.; Qi, N.; Read, A. L.; Smith, J. G.; Camporesi, T.; de Sangro, R.; Marini, A.; Peruzzi, I.; Piccolo, M.; Ronga, F.; Blume, H. T.; Hurst, R. B.; Sleeman, J. C.; Venuti, J. P.; Wald, H. B.; Weinstein, Roy; Band, H. R.; Gettner, M. W.; Goderre, G. P.; Meyer, O. A.; Moromisato, J. H.; Shambroom, W. D.; von Goeler, E.; Ash, W. W.; Chadwick, G. B.; Clearwater, S. H.; Coombes, R. W.; Kaye, H. S.; Lau, K. H.; Leedy, R. E.; Lynch, H. L.; Messner, R. L.; Moss, L. J.; Muller, F.; Nelson, H. N.; Ritson, D. M.; Rosenberg, L. J.; Wiser, D. E.; Zdarko, R. W.; Groom, D. E.; Lee, H. Y.; Delfino, M. C.; Heltsley, B. K.; Johnson, J. R.; Lavine, T. L.; Maruyama, T.; Prepost, R.

    1985-01-01

    Direct photon production in hadronic events from e+e- annihilation has been studied at √s =29 GeV with use of the MAC detector at the PEP storage ring. A charge asymmetry A=(-12.3+/-3.5)% is observed in the final-state jets. The cross section and the charge asymmetry are in good agreement with the predictions of the fractionally charged quark-parton model. Both the charge asymmetry and total yield have been used to determine values of quark charges. Limits have been established for anomalous sources of direct photons.

  15. Procedure for an EE-3 Vent Experiment, Experiment No. 2045

    SciTech Connect

    Dash, Zora V.; Cocks, George G.

    1984-07-23

    During Experiment 2042 approximately 2 million gallons of water were injected in the EE-3 wellbore. This caused seismic activity from the bottom of the well to a region well above the casing shoe (3900 m TVD to 2800 m TVD). Thus water was injected into both the lower high pressure zone and the upper low pressure zone just below the casing shoe. Later experiments have shown that these two zones are connected. In the past the upper zone has often been considered to be a water loss zone (thief zone).

  16. Peripheral 5-HT1A and 5-HT7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats

    PubMed Central

    Restrepo, Beatriz; Martín, María Luisa; San Román, Luis; Morán, Asunción

    2010-01-01

    We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels. PMID:21403818

  17. Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft.

    PubMed

    Kodama, Akio; Itoh, Takeo; Komori, Kimihiro

    2014-02-01

    For vascular occlusive disease, an autologous vein graft is the most suitable conduit for arterial reconstruction. Intimal hyperplasia, resulting from the migration and proliferation of vascular smooth muscle cells, is a major obstacle to patency after vein grafting. The degree to which the function of nitric oxide (NO) in the vein graft is preserved has been reported to be associated with the magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in the vascular system and plays physiological roles in controlling the vascular tone. The subtype receptors contributing to the 5-HT-induced mechanical responses vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and so on). Recent studies have demonstrated that 5-HT induces vasoconstriction through the activation of 5-HT2A receptors in smooth muscle cells or vasodilatation through the activation of endothelial 5-HT1B receptors in arteries from various animals. However, the effects of 5-HT have not been clarified in grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins and then autogenous vein grafts. Next, we describe the effects of chronic in vivo administration of Rho-kinase inhibitors and 5-HT2A receptor antagonists, both of which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts. Further studies targeting 5-HT are required to evaluate its possible benefits for autologous vein grafts with respect to vasospasm, function, and patency.

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

    PubMed

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

    2015-05-01

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

  19. The rapid recovery of 5-HT cell firing induced by the antidepressant vortioxetine involves 5-HT(3) receptor antagonism.

    PubMed

    Bétry, Cécile; Pehrson, Alan L; Etiévant, Adeline; Ebert, Bjarke; Sánchez, Connie; Haddjeri, Nasser

    2013-06-01

    The therapeutic effect of current antidepressant drugs appears after several weeks of treatment and a significant number of patients do not respond to treatment. Here, we report the effects of the multi-modal antidepressant vortioxetine (Lu AA21004), a 5-HT(3) and 5-HT(7) receptor antagonist, 5-HT(1B) receptor partial agonist, 5-HT(1A) receptor agonist and 5-HT transporter (SERT) inhibitor, on rat 5-HT neurotransmission. Using in vivo electrophysiological recordings in the dorsal raphe nucleus of anaesthetized rats, we assessed the acute and subchronic effects of vortioxetine and/or the selective 5-HT(3) receptor agonist, SR57227 or the selective 5-HT(1A) receptor agonist flesinoxan, on 5-HT neuronal firing activity. Using ex-vivo autoradiography, we correlated SERT occupancy and presumed 5-HT firing activity. The selective serotonin reuptake inhibitor, fluoxetine, was used as comparator. Importantly, the recovery of 5-HT neuronal firing was achieved after 1 d with vortioxetine and 14 d with fluoxetine. SR57227 delayed this recovery. In contrast, vortioxetine failed to alter the reducing action of 3 d treatment of flesinoxan. Acute dosing of vortioxetine inhibited neuronal firing activity more potently than fluoxetine. SR57227 prevented the suppressant effect of vortioxetine, but not of fluoxetine. In contrast, flesinoxan failed to modify the suppressant effect of vortioxetine acutely administered. Differently to fluoxetine, vortioxetine suppressed neuronal firing without saturating occupancy at the SERT. Vortioxetine produced a markedly faster recovery of 5-HT neuronal firing than fluoxetine. This is at least partly due to 5-HT(3) receptor antagonism of vortioxetine in association with its reduced SERT occupancy.

  20. Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning.

    PubMed

    Meneses, A; Terrón, J A; Hong, E

    1997-12-01

    We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage.

  1. Permitting patients to pay for participation in clinical trials: the advent of the P4 trial.

    PubMed

    Shaw, David; de Wert, Guido; Dondorp, Wybo; Townend, David; Bos, Gerard; van Gelder, Michel

    2016-10-18

    In this article we explore the ethical issues raised by permitting patients to pay for participation (P4) in clinical trials, and discuss whether there are any categorical objections to this practice. We address key considerations concerning payment for participation in trials, including patient autonomy, risk/benefit and justice, taking account of two previous critiques of the ethics of P4. We conclude that such trials could be ethical under certain strict conditions, but only if other potential sources of funding have first been explored or are unavailable.

  2. Antibodies specific for HT{sub m4}

    DOEpatents

    Lim, B.; Adra, C.N.; Lelias, J.M.

    1998-01-06

    The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

  3. Recombinant HT{sub m4} gene, protein and assays

    DOEpatents

    Lim, B.; Adra, C.N.; Lelias, J.M.

    1996-09-03

    The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

  4. Double Higgs Boson Production via WW Fusion in TeV e+e- Collisions

    NASA Astrophysics Data System (ADS)

    Barger, V.; Han, T.

    The production of two standard model Higgs bosons via the WW fusion process e+e- → bar ve ve HH would test the predicted HHH, HWW and HHWW couplings. At TeV energies this fusion cross section dominates over that from e+e- →ZHH and would give significant event rates for mH ≲ 1/2 MZ at high luminosity e+e- colliders. We evaluate the rates and present the dynamical distributions.

  5. The serotonin 5-HT3 receptor: a novel neurodevelopmental target.

    PubMed

    Engel, Mareen; Smidt, Marten P; van Hooft, Johannes A

    2013-01-01

    Serotonin (5-hydroxytryptamine, 5-HT), next to being an important neurotransmitter, recently gained attention as a key-regulator of pre- and postnatal development in the mammalian central nervous system (CNS). Several receptors for 5-HT are expressed in the developing brain including a ligand-gated ion channel, the 5-HT3 receptor. Over the past years, evidence has been accumulating that 5-HT3 receptors are involved in the regulation of neurodevelopment by serotonin. Here, we review the spatial and temporal expression patterns of 5-HT3 receptors in the pre- and early postnatal rodent brain and its functional implications. First, 5-HT3 receptors are expressed on GABAergic interneurons in neocortex and limbic structures derived from the caudal ganglionic eminence. Mature inhibitory GABAergic interneurons fine-tune neuronal excitability and thus are crucial for the physiological function of the brain. Second, 5-HT3 receptors are expressed on specific glutamatergic neurons, Cajal-Retzius cells in the cortex and granule cells in the cerebellum, where they regulate morphology, positioning, and connectivity of the local microcircuitry. Taken together, the 5-HT3 receptor emerges as a potential key-regulator of network formation and function in the CNS, which could have a major impact on our understanding of neurodevelopmental disorders in which 5-HT plays a role.

  6. Orbital period determination in an eclipsing dwarf nova HT Cas

    NASA Astrophysics Data System (ADS)

    Bąkowska, Karolina; Olech, Arkadiusz

    2014-09-01

    HT Cassiopeiae was discovered over seventy years ago (Hoffmeister 1943). Unfortunately, for 35 years this object did not receive any attention, until the eclipses of HT Cas were observed by Bond. After a first analysis, Patterson (1981) called HT Cas "a Rosetta stone among dwarf novae". Since then, the literature on this star is still growing, reaching several dozens of publications. We present an orbital period determination of HT Cas during the November 2010 super-outburst, but also during a longer time span, to check its stability.

  7. A Search for Point Sources of EeV Photons

    NASA Astrophysics Data System (ADS)

    Aab, A.; Abreu, P.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Samarai, I. Al; Albuquerque, I. F. M.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Alves Batista, R.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Aramo, C.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Badescu, A. M.; Barber, K. B.; Bäuml, J.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellido, J. A.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Buchholz, P.; Bueno, A.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, B.; Caccianiga, L.; Candusso, M.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Cester, R.; Chavez, A. G.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Cocciolo, G.; Colalillo, R.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cooper, M. J.; Coutu, S.; Covault, C. E.; Criss, A.; Cronin, J.; Curutiu, A.; Dallier, R.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; de Jong, S. J.; de Mello Neto, J. R. T.; De Mitri, I.; de Oliveira, J.; de Souza, V.; del Peral, L.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Di Matteo, A.; Diaz, J. C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; Dorosti Hasankiadeh, Q.; Dova, M. T.; Ebr, J.; Engel, R.; Erdmann, M.; Erfani, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Fang, K.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fernandes, M.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fox, B. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Fuji, T.; Gaior, R.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Garilli, G.; Gascon Bravo, A.; Gate, F.; Gemmeke, H.; Ghia, P. L.; Giaccari, U.; Giammarchi, M.; Giller, M.; Glaser, C.; Glass, H.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gorham, P.; Gouffon, P.; Grebe, S.; Griffith, N.; Grillo, A. F.; Grubb, T. D.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Heimann, P.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Hollon, N.; Holt, E.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huber, D.; Huege, T.; Insolia, A.; Isar, P. G.; Islo, K.; Jandt, I.; Jansen, S.; Jarne, C.; Josebachuili, M.; Kääpä, A.; Kambeitz, O.; Kampert, K. H.; Kasper, P.; Katkov, I.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Krause, R.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuempel, D.; Kunka, N.; La Rosa, G.; LaHurd, D.; Latronico, L.; Lauer, R.; Lauscher, M.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Malacari, M.; Maldera, S.; Maller, J.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, V.; Mariş, I. C.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Martraire, D.; Masías Meza, J. J.; Mathes, H. J.; Mathys, S.; Matthews, A. J.; Matthews, J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mayotte, E.; Mazur, P. O.; Medina, C.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Messina, S.; Meyhandan, R.; Mićanović, S.; Micheletti, M. I.; Middendorf, L.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morello, C.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Niechciol, M.; Niemietz, L.; Niggemann, T.; Nitz, D.; Nosek, D.; Novotny, V.; Nožka, L.; Ochilo, L.; Olinto, A.; Oliveira, M.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Papenbreer, P.; Parente, G.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Peķala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Peters, C.; Petrera, S.; Petrolini, A.; Petrov, Y.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Porcelli, A.; Porowski, C.; Privitera, P.; Prouza, M.; Purrello, V.; Quel, E. J.; Querchfeld, S.; Quinn, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez Cabo, I.; Rodriguez Fernandez, G.; Rodriguez Rojo, J.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saffi, S. J.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Sanchez-Lucas, P.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarmento, R.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovánek, P.; Schulz, A.; Schulz, J.; Sciutto, S. J.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Sima, O.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Squartini, R.; Srivastava, Y. N.; Stanič, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Taborda, O. A.; Tapia, A.; Tartare, M.; Thao, N. T.; Theodoro, V. M.; Tiffenberg, J.; Timmermans, C.; Todero Peixoto, C. J.; Toma, G.; Tomankova, L.; Tomé, B.; Tonachini, A.; Torralba Elipe, G.; Torres Machado, D.; Travnicek, P.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van den Berg, A. M.; van Velzen, S.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Varner, G.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Vlcek, B.; Vorobiov, S.; Wahlberg, H.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Whelan, B. J.; Widom, A.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wittkowski, D.; Wundheiler, B.; Wykes, S.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhou, J.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.; Auger Collaboration102, The Pierre

    2014-07-01

    Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85° to +20°, in an energy range from 1017.3 eV to 1018.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm-2 s-1, and no celestial direction exceeds 0.25 eV cm-2 s-1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.

  8. Signal of doubly charged Higgs at e+e- colliders

    NASA Astrophysics Data System (ADS)

    Hue, L. T.; Huong, D. T.; Long, H. N.; Hung, H. T.; Thao, N. H.

    2015-11-01

    The masses and signals of the production of doubly charged Higgses (DCH) in the framework of the supersymmetric reduced minimal 3-3-1 model are investigated. In the DCH sector, we prove that there always exists a region of the parameter space where the mass of the lightest DCH is of the order of O(100) GeV even when all other new particles are very heavy. The lightest DCH mainly decays to two same-sign leptons while the dominant decay channels of the heavy DCHs are those decaying to heavy particles. We analyze each production cross section for e^+e^- ⇒ H^{++} H^{-} as a function of a few kinematic variables, which are useful to discuss the creation of DCHs in e^+e^- colliders as an indicator of new physics beyond the Standard Model. A numerical study shows that the cross sections for creating the lightest DCH can reach values of a few pb. The other two DCHs are too heavy, beyond the observable range of experiments. The lightest DCH may be detected by the International Linear Collider or the Compact Linear Collider by searching for its decay to a same-sign charged lepton pair.

  9. A search for point sources of EeV photons

    SciTech Connect

    Aab, A.; Abreu, P.; Andringa, S.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Al Samarai, I.; Albuquerque, I. F. M.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Castillo, J. Alvarez; Alvarez-Muñiz, J.; Batista, R. Alves; Ambrosio, M.; Aramo, C.; Aminaei, A.; Anchordoqui, L.; Arqueros, F.; Collaboration: Pierre Auger Collaboration102; and others

    2014-07-10

    Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from –85° to +20°, in an energy range from 10{sup 17.3} eV to 10{sup 18.5} eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of –2, is 0.06 eV cm{sup –2} s{sup –1}, and no celestial direction exceeds 0.25 eV cm{sup –2} s{sup –1}. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.

  10. Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT2A receptor binding after chronic hypercorticosteronemia, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane administration or neurotoxin-induced depletion of central nervous system 5-HT in the rat.

    PubMed

    Owens, M J; Ballenger, C A; Knight, D L; Nemeroff, C B

    1996-09-01

    There is considerable evidence that the number of platelet 5-hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5-HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I] (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT2A receptor binding. Similarly, 8-week administration of the 5-HT2A/5-HT2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT2A/2C receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT2A receptors. Additionally, para-chloroamphetamine-(11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT2A receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT2A receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status.

  11. FROM "CANAL BRIDGE, F.A.P. 4C, MAR. 1938." SHOWING WAIKELE BRIDGE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FROM "CANAL BRIDGE, F.A.P. 4-C, MAR. 1938." SHOWING WAIKELE BRIDGE PLAN AND ELEVATION. Hawaii Department of Transportation, Design Branch, Project ID 7101-001, drawing 4449.27. - Waikele Canal Bridge and Highway Overpass, Farrington Highway and Waikele Stream, Waipahu, Honolulu County, HI

  12. P4 radiology of hepatobiliary diseases with gadoxetic acid-enhanced MRI as a biomarker.

    PubMed

    Ba-Ssalamah, Ahmed; Qayyum, Aliya; Bastati, Nina; Fakhrai, Negar; Herold, Christian J; Caseiro Alves, Filipe

    2014-02-01

    A recent paradigm shift in radiology has focused on the globalization of so-called P4 radiology. P4 radiology represents delivery of imaging results that are predictive, personalized, pre-emptive and participatory. The combination of the P4 approach and biomarkers is particularly pertinent to MRI, especially with technological advances such as diffusion-weighted imaging. The development of new liver-specific MRI contrast media, particularly gadoxetic acid, demonstrate specific pharmacokinetic properties, which provide combined morphologic and functional information in the same setting. The evaluation of hepatobiliary pathology beyond morphology gives rise to the possibilty of using gadoxetic acid-enhanced MRI as an imaging biomarker of hepatobiliary diseases. The integration of functional imaging with an understanding of complex disease mechanisms forms the basis for P4 radiology, which may ultimately lead to individualized, cost-effective, targeted therapy for patients. This will enable radiologists to determine the prognosis of the disease and estimate early response to treatment, with the participation of all the required medical disciplines.

  13. Influence of the nacnac Ligand in Iron(I)‐Mediated P4 Transformations

    PubMed Central

    Spitzer, Fabian; Graßl, Christian; Balázs, Gábor; Zolnhofer, Eva M.; Meyer, Karsten

    2016-01-01

    Abstract A study of P4 transformations at low‐valent iron is presented using β‐diketiminato (L) FeI complexes [LFe(tol)] (tol=toluene; L=L1 (1 a), L2 (1 b), L3 (1 c)) with different combinations of aromatic and backbone substituents at the ligand. The products [(LFe)4(μ4‐η2:η2:η2:η2‐P8)] (L=L1 (2 a), L2 (2 b)) containing a P8 core were obtained by the reaction of 1 a,b with P4 in toluene at room temperature. Using a slightly more sterically encumbered ligand in 1 c results in the formation of [(L3Fe)2(μ‐η4:η4‐P4)] (2 c), possessing a cyclo‐P4 moiety. Compounds 2 a–c were comprehensively characterized and their electronic structures investigated by SQUID magnetization and 57Fe Mössbauer spectroscopy as well as by DFT methods. PMID:26924606

  14. 77 FR 26014 - Prospective Grant of Exclusive License: P4 Peptide From Streptococcus Pneumoniae

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-02

    ... Prospective Grant of Exclusive License: P4 Peptide From Streptococcus Pneumoniae AGENCY: Technology Transfer... ``Functional Epitopes of Streptococcus Pneumoniae PsaA Antigen and Uses Thereof,'' filed 7/ 18/2008, claiming... Streptococcus pneumoniae. This technology also includes an antibody that can bind to the epitopes of the...

  15. 31P to 77Se cross polarization in beta-P4Se3.

    PubMed

    Pietrass, T; Seydoux, R; Roth, R E; Eckert, H; Pines, A

    1997-08-01

    Cross polarization from 31P to 77Se is demonstrated in beta-P4Se3. This material, an inorganic glass, is readily synthesized from the elements and serves as a convenient sample for setting the Hartmann-Hahn condition.

  16. Cnr interferes with dimerization of the replication protein alpha in phage-plasmid P4.

    PubMed

    Tocchetti, A; Serina, S; Oliva, I; Dehò, G; Ghisotti, D

    2001-01-15

    DNA replication of phage-plasmid P4 in its host Escherichia coli depends on its replication protein alpha. In the plasmid state, P4 copy number is controlled by the regulator protein Cnr (copy number regulation). Mutations in alpha (alpha(cr)) that prevent regulation by Cnr cause P4 over-replication and cell death. Using the two-hybrid system in Saccharomyces cerevisiae and a system based on lambda immunity in E.coli for in vivo detection of protein-protein interactions, we found that (i) alpha protein interacts with Cnr, whereas alpha(cr) proteins do not; (ii) both alpha-alpha and alpha(cr)-alpha(cr) interactions occur and the interaction domain is located within the C-terminal of alpha; (iii) Cnr-Cnr interaction also occurs. Using an in vivo competition assay, we found that Cnr interferes with both alpha-alpha and alpha(cr)-alpha(cr) dimerization. Our data suggest that Cnr and alpha interact in at least two ways, which may have different functional roles in P4 replication control.

  17. Well completion and operations for MHF of Fenton Hill HDR Well EE-2

    SciTech Connect

    Dreesen, D.S.; Nicholson, R.W.

    1985-01-01

    Previous attempts to connect Fenton Hill Hot Dry Rock Geothermal Site Wells EE-2 and EE-3 by pumping 150 thousand to 1.3 million gallons of water had not achieved a detectable hydraulic fracture connection. Therefore, preparations were made to conduct, in December 1983, a 4 to 6 million gallon, 50 BPM water injection in EE-2. The objective was to enlarge the previously created reservoir in EE-2 using massive hydraulic facturing (MHF). The planning, preparations, operations and results of the MHF are presented here. 4 refs., 7 figs.

  18. Cadmium resistance mechanism in Escherichia coli P4 and its potential use to bioremediate environmental cadmium.

    PubMed

    Khan, Zaman; Nisar, Muhammad Atif; Hussain, Syed Zajif; Arshad, Muhammad Nauman; Rehman, Abdul

    2015-12-01

    A cadmium-resistant bacterium was isolated from industrial wastewater and identified as Escherichia coli (dubbed as P4) on the basis of morphological, biochemical tests and 16S rRNA ribotyping. It showed optimum growth at 30 °C and pH 7. E. coli P4 found to resist Cd(+2) (10.6 mM) as well as Zn(+2) (4.4 mM), Pb(+2) (17 mM), Cu(+2) (3.5 mM), Cr(+6) (4.4 mM), As(+2) (10.6 mM), and Hg(+2) (0.53 mM). It could remove 18.8, 37, and 56 % Cd(+2) from aqueous medium after 48, 96, and 144 h, respectively. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and Energy-dispersive X-ray (EDX) analysis also confirmed the biosorption of Cd(+2) by E. coli P4. However, temperature and pH were found to be the most critical factors in biosorption of Cd(+2) by E. coli P4. Cd(+2) stress altered E. coli P4 cell physiology analyzed by measuring glutathione (GSH) and non-protein thiol (cysteine) levels which were increased up to 130 and 48 %, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) showed alteration in the expression levels of ftsZ, mutS, clpB, ef-tu, and dnaK genes in the presence of Cd(+2). Total protein profiles of E. coli P4 in the absence and presence of Cd(+2) were compared by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), which showed remarkable difference in the banding pattern. czcB gene, a component of czcCBA operon, was amplified from genomic DNA which suggested the chromosomal-borne Cd(+2) resistance in E. coli P4. Furthermore, it harbors smtAB gene which plays a significant role in Cd(+2) resistance.

  19. Genomic constellation and evolution of Ghanaian G2P[4] rotavirus strains from a global perspective.

    PubMed

    Agbemabiese, Chantal Ama; Nakagomi, Toyoko; Doan, Yen Hai; Do, Loan Phuong; Damanka, Susan; Armah, George E; Nakagomi, Osamu

    2016-11-01

    Understanding of the genetic diversity and evolution of Rotavirus A (RVA) strains, a common cause of severe diarrhoea in children, needs to be based on the analysis at the whole genome level in the vaccine era. This study sequenced the whole genomes of six representative G2P[4] strains detected in Ghana from 2008 to 2013, and analysed them phylogenetically with a global collection of G2P[4] strains and African non-G2P[4] DS-1-like strains. The genotype constellation of the study strains was G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Strains from the same season were highly identical across the whole genome while strains from different seasons were more divergent from each other. The VP7, VP4, VP2, NSP1, and NSP5 genes belonged to lineage IVa; the VP6, VP1, NSP2, and NSP3 genes belonged to lineage V, and all these genes evolved in the same fashion as the global strains. In the NSP4 gene, lineages V (2008) and X (2009) were replaced by VI (2012/2013) whereas in the VP3 gene, lineage V (2008/2009) was replaced by VII (2012/2013) and these replacements coincided with the vaccine introduction period (2012). The evolutionary rate of the NSP4 gene was 1.2×10(-3) substitutions/site/year and was rather comparable to that of the remaining 10 genes. The multiple NSP4 lineages were explained by intra-genotype reassortment with co-circulating African human DS-1-like strains bearing G2[6], G3P[6], G6[6] and G8. There was no explicit evidence of the contribution of animal RVA strains to the genome of the Ghanaian G2P[4] strains. In summary, this study revealed the dynamic evolution of the G2P[4] strains through intra-genotype reassortment events leading to African specific lineages such IX and X in the NSP4 gene. So far, there was no evidence of a recent direct involvement of animal RVA genes in the genome diversity of African G2P[4] strains.

  20. Shuyu Capsules Relieve Premenstrual Syndrome Depression by Reducing 5-HT3AR and 5-HT3BR Expression in the Rat Brain

    PubMed Central

    Li, Fang; Feng, Jizhen; Gao, Dongmei; Wang, Jieqiong; Song, Chunhong; Wei, Sheng

    2016-01-01

    The effects of the Shuyu capsule on 5-HT3AR and 5-HT3BR expression in a rat model of premenstrual syndrome (PMS) depression and on 5-HT3AR and 5-HT3BR expression and hippocampal neuron 5-HT3 channel current were investigated, to elucidate its mechanism of action against PMS depression. PMS depression model rats were divided into depression and Shuyu- and fluoxetine-treated groups, which were compared to control rats for frontal lobe and hippocampal 5-HT3AR and 5-HT3BR expression and behavior. The depressed model rats displayed symptoms of depression, which were reduced in treated and normal control rats. Frontal lobe and hippocampal 5-HT3AR and 5-HT3BR levels were significantly higher in the model versus the control group and were significantly lower in the Shuyu group. As compared to control rats, the 5-HT3R channel current in the model group was significantly higher; the 5-HT3R channel current in hippocampal neurons treated with serum from Shuyu group rats was significantly lower than that in those treated with model group serum. Thus, PMS depression may be related to 5-HT3AR and 5-HT3BR expression and increased 5-HT3 channel current. Shuyu capsules rectified abnormal 5-HT3AR and 5-HT3BR expression and 5-HT3 channel current changes in a rat model; this finding may provide insight into treating PMS depression. PMID:27725889

  1. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats.

    PubMed

    Albayrak, Abdulmecit; Halici, Zekai; Cadirci, Elif; Polat, Beyzagul; Karakus, Emre; Bayir, Yasin; Unal, Deniz; Atasoy, Mustafa; Dogrul, Ahmet

    2013-09-05

    The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.

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

    PubMed

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

    2016-06-02

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

  3. P3HT-b-PS Copolymers as P3HT/PCBM Interfacial Compatibilizers for High Efficiency Photovoltaics

    SciTech Connect

    Sun, Zhenzhong; Xiao, Kai; Yu, Xiang; Hong, Kunlun; Keum, Jong Kahk; Browning, Jim; Ivanov, Ilia N; Chen, Jihua; Alonzo Calderon, Jose E; Sumpter, Bobby G; Payzant, E Andrew; Rouleau, Christopher M; Geohegan, David B

    2011-01-01

    To control the donor-acceptor phase separation for more efficient organic bulk heterojunction photovoltaic cells, poly(3-hexylthiophene)-block-polystyrene (P3HT-b-PS) diblock copolymer was added to serve as a compatibilizer in a P3HT/ [6,6]-phenyl-C61-butyric acid methyl ester fullerene derivative (PCBM) blend. An addition of 5 wt% of P3HT-b-PS copolymer in the P3HT/PCBM blend improved the power-conversion efficiency from 3.3% to 4.1% due to an enhancement of both the short-circuit current density and fill factor compared to that of a pristine P3HT/PCBM solar cell. Grazing incidence x-ray scattering (GIXS), absorption spectroscopy and carrier mobility studies reveal that the crystallinity and orientation of P3HT were improved, thereby enhancing hole transport in the P3HT polymer, and leading to a better balance between the electron and hole mobilities in the P3HT/PCBM active layer. Neutron reflectometry (NR) experiments demonstrate that a distinct scattering length density profile shows the highest PCBM concentration in the middle layer region and a more compact and homogeneous layer, presumably due to an increase in miscibility of P3HT and PCBM driven by the copolymer compatibilizer, while adding 5 wt% of P3HT-b-PS copolymer in the P3HT/PCBM blend. Quantum density functional theory calculations show that the P3HT-b-PS additive tends to promote microphase segregation, with the PCBM attracted to the PS block, and the P3HT stacking onto the P3HT block, which presumably leads to improvements in long-range crystallinity , consistent with the GIXS findings. Overall, the results for P3HT-b-PS copolymer in a P3HT/PCBM blend demonstrate that tailored block copolymers can act as an effective compatibilizer in blended systems to further improve solar cell performance

  4. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1....

  5. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1....

  6. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1....

  7. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1....

  8. 26 CFR 301.6103(p)(4)-1 - Procedures relating to safeguards for returns or return information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... or return information. 301.6103(p)(4)-1 Section 301.6103(p)(4)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(4)-1 Procedures relating to safeguards for returns..., see § 301.6103(p)(7)-1....

  9. Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

    PubMed

    Meneses, Alfredo

    2002-05-01

    Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the

  10. Spinal 5-HT1A, not the 5-HT1B or 5-HT3 receptors, mediates descending serotonergic inhibition for late-phase mechanical allodynia of carrageenan-induced peripheral inflammation.

    PubMed

    Kim, Joung Min; Jeong, Seong Wook; Yang, Jihoon; Lee, Seong Heon; Kim, Woon Mo; Jeong, Seongtae; Bae, Hong Beom; Yoon, Myung Ha; Choi, Jeong Il

    2015-07-23

    Previous electrophysiological studies demonstrated a limited role of 5-hydroxytryptamine 3 receptor (5-HT3R), but facilitatory role of 5-HT1AR and 5-HT1BR in spinal nociceptive processing of carrageenan-induced inflammatory pain. The release of spinal 5-HT was shown to peak in early-phase and return to baseline in late-phase of carrageenan inflammation. We examined the role of the descending serotonergic projections involving 5-HT1AR, 5-HT1BR, and 5-HT3R in mechanical allodynia of early- (first 4h) and late-phase (24h after) carrageenan-induced inflammation. Intrathecal administration of 5-HT produced a significant anti-allodynic effect in late-phase, but not in early-phase. Similarly, intrathecal 5-HT1AR agonist (8-OH-DPAT) attenuated the intensity of late-phase allodynia in a dose dependent fashion which was antagonized by 5-HT1AR antagonist (WAY-100635), but produced no effect on the early-phase allodynia. However, other agonists or antagonists of 5-HT1BR (CP-93129, SB-224289) and 5-HT3R (m-CPBG, ondansetron) did not produce any anti- or pro-allodynic effect in both early- and late- phase allodynia. These results suggest that spinal 5-HT1A, but not 5-HT1B or 5-HT3 receptors mediate descending serotonergic inhibition on nociceptive processing of late-phase mechanical allodynia in carrageenan-induced inflammation.

  11. 5-HT(1A) and 5-HT(7) receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission.

    PubMed

    Costa, L; Trovato, C; Musumeci, S A; Catania, M V; Ciranna, L

    2012-04-01

    We have studied the effects of 5-HT(1A) and 5-HT(7) serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT(1A)/5-HT(7) receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT(1A) receptor agonist 8-OH PIPAT and blocked by the 5-HT(1A) antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT(7) receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT(7) receptors, we used the compound LP-44, which is considered a selective 5-HT(7) agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT(1A) and 5-HT(7) receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT(1A) receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT(7) receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the

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

    PubMed

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

    1998-11-01

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

  13. Effects of MDMA and related analogs on plasma 5-HT: relevance to 5-HT transporters in blood and brain.

    PubMed

    Yubero-Lahoz, Samanta; Ayestas, Mario A; Blough, Bruce E; Partilla, John S; Rothman, Richard B; de la Torre, Rafael; Baumann, Michael H

    2012-01-15

    (±)-3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that evokes transporter-mediated release of serotonin (5-HT) in the brain. 5-HT transporter (SERT) proteins are also expressed in non-neural tissues (e.g., blood), and evidence suggests that MDMA targets platelet SERT to increase plasma 5-HT. Here we tested two hypotheses related to the effects of MDMA on circulating 5-HT. First, to determine if MDMA metabolites might contribute to actions of the drug in vivo, we used in vitro microdialysis in rat blood specimens to examine the effects of MDMA and its metabolites on plasma 5-HT. Second, to determine whether effects of MDMA on plasma 5-HT might be used as an index of central SERT activity, we carried out in vivo microdialysis in blood and brain after intravenous MDMA administration. The in vitro results show that test drugs evoke dose-related increases in plasma 5-HT ranging from two- to sevenfold above baseline, with MDMA and its metabolite, (±)-3,4-methylenedioxyamphetamine (MDA), producing the largest effects. The ability of MDMA and related analogs to elevate plasma 5-HT is correlated with their potency as SERT substrates in rat brain synaptosomes. The in vivo results reveal that MDMA causes concurrent increases in extracellular 5-HT in blood and brain, but there are substantial individual differences in responsiveness to the drug. Collectively, our findings indicate that MDMA and its metabolites increase plasma 5-HT by a SERT-dependent mechanism, and suggest the possibility that measures of evoked 5-HT release in blood may reflect central SERT activity.

  14. Human 5–HT4 and 5–HT7 Receptor Splice Variants: Are they Important?

    PubMed Central

    Coupar, Ian M; Desmond, Paul V; Irving, Helen R

    2007-01-01

    G-protein-coupled receptors (GPCRs), which are encoded by >300 genes in the human genome, are by far the largest class of targets for modern drugs. These macromolecules display inherent adaptability of function, which is partly due to the production of different forms of the receptor protein. These are commonly called ‘isoforms’ or ‘splice variants’ denoting the molecular process of their production/assembly. Not all GPCRs are expressed as splice variants, but certain subclasses of 5–HT receptors are for example, the 5–HT4 and 5–HT7 receptors. There are at least 11 human 5–HT4 and three h5–HT7 receptor splice variants. This review describestheir discoveries, nomenclature and structures. The discovery that particular splice variants are tissue specific (or prominent) has highlighted their potential as future drug targets. In particular, this review examines the functional relevance of different 5–HT4 and 5–HT7 receptor splice variants. Examples are given to illustrate that splice variants have differential modulatory influences on signalling processes. Differences in agonist potency and efficacies and also differences in desensitisation rates to 5–HT occur with both 5–HT4 and 5–HT7 receptor splice variants. The known and candidate signalling systems that allow for splice variant specific responses include GPCR interacting proteins (GIPs) and GPCR receptor kinases (GRKs) which are examined.Finally, the relevance of 5–HT receptor splice variants to clinical medicine and to the pharmaceutical industry is discussed. PMID:19305739

  15. Experiment 2059: Second Packer Stimulation of EE-3A

    SciTech Connect

    Brown, Donald W.

    1985-05-09

    By late Thursday, 5-9-85, EE-3A should be at a depth of about 12,200 feet. We plan to stop drilling at this point and pressurize the bottom 600 to 700 feet of the open hole using a Lynes packer. The Lynes packer would be set somewhere in the interval of very competent, slow-drilling, and only slightly altered biotite granodiorite from 11,460 ft to 11,590 ft. This would place the packer below the two fractures (at 10,880 ft and 11,000 ft) stimulated during Expt. 2057, and also below the producing fracture at 11,440 ft as reported on 5-2-85.

  16. A Search for Point Sources of EeV Neutrons

    NASA Astrophysics Data System (ADS)

    Pierre Auger Collaboration; Abreu, P.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Alves Batista, R.; Ambrosio, M.; Aminaei, A.; Anchordoqui, L.; Andringa, S.; Antiči'c, T.; Aramo, C.; Arganda, E.; Arqueros, F.; Asorey, H.; Assis, P.; Aublin, J.; Ave, M.; Avenier, M.; Avila, G.; Badescu, A. M.; Balzer, M.; Barber, K. B.; Barbosa, A. F.; Bardenet, R.; Barroso, S. L. C.; Baughman, B.; Bäuml, J.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellétoile, A.; Bellido, J. A.; BenZvi, S.; Berat, C.; Bertou, X.; Biermann, P. L.; Billoir, P.; Blanco, F.; Blanco, M.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Bonino, R.; Borodai, N.; Brack, J.; Brancus, I.; Brogueira, P.; Brown, W. C.; Bruijn, R.; Buchholz, P.; Bueno, A.; Buroker, L.; Burton, R. E.; Caballero-Mora, K. S.; Caccianiga, B.; Caramete, L.; Caruso, R.; Castellina, A.; Catalano, O.; Cataldi, G.; Cazon, L.; Cester, R.; Chauvin, J.; Cheng, S. H.; Chiavassa, A.; Chinellato, J. A.; Chirinos Diaz, J.; Chudoba, J.; Cilmo, M.; Clay, R. W.; Cocciolo, G.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cook, H.; Cooper, M. J.; Coppens, J.; Cordier, A.; Coutu, S.; Covault, C. E.; Creusot, A.; Criss, A.; Cronin, J.; Curutiu, A.; Dagoret-Campagne, S.; Dallier, R.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; De Domenico, M.; De Donato, C.; de Jong, S. J.; De La Vega, G.; de Mello Junior, W. J. M.; de Mello Neto, J. R. T.; De Mitri, I.; de Souza, V.; de Vries, K. D.; del Peral, L.; del Río, M.; Deligny, O.; Dembinski, H.; Dhital, N.; Di Giulio, C.; Díaz Castro, M. L.; Diep, P. N.; Diogo, F.; Dobrigkeit, C.; Docters, W.; D'Olivo, J. C.; Dong, P. N.; Dorofeev, A.; dos Anjos, J. C.; Dova, M. T.; D'Urso, D.; Dutan, I.; Ebr, J.; Engel, R.; Erdmann, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Facal San Luis, P.; Falcke, H.; Farrar, G.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fliescher, S.; Fracchiolla, C. E.; Fraenkel, E. D.; Fratu, O.; Fröhlich, U.; Fuchs, B.; Gaior, R.; Gamarra, R. F.; Gambetta, S.; García, B.; Garcia Roca, S. T.; Garcia-Gamez, D.; Garcia-Pinto, D.; Gascon Bravo, A.; Gemmeke, H.; Ghia, P. L.; Giller, M.; Gitto, J.; Glass, H.; Gold, M. S.; Golup, G.; Gomez Albarracin, F.; Gómez Berisso, M.; Gómez Vitale, P. F.; Gonçalves, P.; Gonzalez, J. G.; Gookin, B.; Gorgi, A.; Gouffon, P.; Grashorn, E.; Grebe, S.; Griffith, N.; Grigat, M.; Grillo, A. F.; Guardincerri, Y.; Guarino, F.; Guedes, G. P.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Haungs, A.; Hebbeker, T.; Heck, D.; Herve, A. E.; Hojvat, C.; Hollon, N.; Holmes, V. C.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huber, D.; Huege, T.; Insolia, A.; Ionita, F.; Italiano, A.; Jansen, S.; Jarne, C.; Jiraskova, S.; Josebachuili, M.; Kadija, K.; Kampert, K. H.; Karhan, P.; Kasper, P.; Katkov, I.; Kégl, B.; Keilhauer, B.; Keivani, A.; Kelley, J. L.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Knapp, J.; Koang, D.-H.; Kotera, K.; Krohm, N.; Krömer, O.; Kruppke-Hansen, D.; Kuempel, D.; Kulbartz, J. K.; Kunka, N.; La Rosa, G.; Lachaud, C.; LaHurd, D.; Latronico, L.; Lauer, R.; Lautridou, P.; Le Coz, S.; Leão, M. S. A. B.; Lebrun, D.; Lebrun, P.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; López, R.; Lopez Agüera, A.; Louedec, K.; Lozano Bahilo, J.; Lu, L.; Lucero, A.; Ludwig, M.; Lyberis, H.; Maccarone, M. C.; Macolino, C.; Maldera, S.; Maller, J.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, J.; Marin, V.; Maris, I. C.; Marquez Falcon, H. R.; Marsella, G.; Martello, D.; Martin, L.; Martinez, H.; Martínez Bravo, O.; Martraire, D.; Masías Meza, J. J.; Mathes, H. J.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurel, D.; Maurizio, D.; Mazur, P. O.; Medina-Tanco, G.; Melissas, M.; Melo, D.; Menichetti, E.; Menshikov, A.; Mertsch, P.; Meurer, C.; Meyhandan, R.; Mi'canovi'c, S.; Micheletti, M. I.; Minaya, I. A.; Miramonti, L.; Molina-Bueno, L.; Mollerach, S.; Monasor, M.; Monnier Ragaigne, D.; Montanet, F.; Morales, B.; Morello, C.; Moreno, E.; Moreno, J. C.; Mostafá, M.; Moura, C. A.; Muller, M. A.; Müller, G.; Münchmeyer, M.; Mussa, R.; Navarra, G.; Navarro, J. L.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nhung, P. T.; Niechciol, M.; Niemietz, L.; Nierstenhoefer, N.; Nitz, D.; Nosek, D.; Nožka, L.; Oehlschläger, J.; Olinto, A.; Ortiz, M.; Pacheco, N.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Palmieri, N.; Parente, G.; Parizot, E.; Parra, A.; Pastor, S.; Paul, T.; Pech, M.; Peķala, J.; Pelayo, R.; Pepe, I. M.; Perrone, L.; Pesce, R.; Petermann, E.; Petrera, S.; Petrolini, A.; Petrov, Y.; Pfendner, C.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Ponce, V. H.; Pontz, M.; Porcelli, A.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Riggi, S.; Risse, M.; Ristori, P.; Rivera, H.; Rizi, V.; Roberts, J.; Rodrigues de Carvalho, W.; Rodriguez, G.; Rodriguez Cabo, I.; Rodriguez Martino, J.; Rodriguez Rojo, J.; Rodríguez-Frías, M. D.; Ros, G.; Rosado, J.; Rossler, T.; Roth, M.; Rouillé-d'Orfeuil, B.; Roulet, E.; Rovero, A. C.; Rühle, C.; Saftoiu, A.; Salamida, F.; Salazar, H.; Salesa Greus, F.; Salina, G.; Sánchez, F.; Santo, C. E.; Santos, E.; Santos, E. M.; Sarazin, F.; Sarkar, B.; Sarkar, S.; Sato, R.; Scharf, N.; Scherini, V.; Schieler, H.; Schiffer, P.; Schmidt, A.; Scholten, O.; Schoorlemmer, H.; Schovancova, J.; Schovánek, P.; Schröder, F.; Schulte, S.; Schuster, D.; Sciutto, S. J.; Scuderi, M.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sidelnik, I.; Sigl, G.; Silva Lopez, H. H.; Sima, O.; 'Smiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sorokin, J.; Spinka, H.; Squartini, R.; Srivastava, Y. N.; Stanic, S.; Stapleton, J.; Stasielak, J.; Stephan, M.; Stutz, A.; Suarez, F.; Suomijärvi, T.; Supanitsky, A. D.; Šuša, T.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Szuba, M.; Tapia, A.; Tartare, M.; Taşcău, O.; Tcaciuc, R.; Thao, N. T.; Thomas, D.; Tiffenberg, J.; Timmermans, C.; Tkaczyk, W.; Todero Peixoto, C. J.; Toma, G.; Tomankova, L.; Tomé, B.; Tonachini, A.; Travnicek, P.; Tridapalli, D. B.; Tristram, G.; Trovato, E.; Tueros, M.; Ulrich, R.; Unger, M.; Urban, M.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van den Berg, A. M.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Wahlberg, H.; Wahrlich, P.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weidenhaupt, K.; Weindl, A.; Werner, F.; Westerhoff, S.; Whelan, B. J.; Widom, A.; Wieczorek, G.; Wiencke, L.; Wilczyńska, B.; Wilczyński, H.; Will, M.; Williams, C.; Winchen, T.; Wommer, M.; Wundheiler, B.; Yamamoto, T.; Yapici, T.; Younk, P.; Yuan, G.; Yushkov, A.; Zamorano Garcia, B.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zaw, I.; Zepeda, A.; Zhou, J.; Zhu, Y.; Zimbres Silva, M.; Ziolkowski, M.

    2012-12-01

    A thorough search of the sky exposed at the Pierre Auger Cosmic Ray Observatory reveals no statistically significant excess of events in any small solid angle that would be indicative of a flux of neutral particles from a discrete source. The search covers from -90° to +15° in declination using four different energy ranges above 1 EeV (1018 eV). The method used in this search is more sensitive to neutrons than to photons. The upper limit on a neutron flux is derived for a dense grid of directions for each of the four energy ranges. These results constrain scenarios for the production of ultrahigh energy cosmic rays in the Galaxy.

  17. The three-jet rate in e+e- annihilation

    NASA Astrophysics Data System (ADS)

    Lovett-Turner, C. N.

    1994-06-01

    Progress has been made on the calculation of R3, the three-jet rate in e+e- annihilation, in the k⊥ (Durham) scheme. Using the coherent branching formalism [A.H. Mueller, Phys. Lett. B 104 (1981) 161; B.I. Ermolaev and V.S. Fadin, JETP Lett. 33 (1981) 285; Yu.L. Dokshitzer, V.S. Fadin and V.A. Khoze, Z. Phys. C 15 (1982) 325; C 18 (1983) 37; A. Bassetto, M. Ciafaloni and G. Marchesini, Phys. Rep. 100 (1983) 202; Yu.L. Dokshitzer and S. Troyan, Leningrad Report LNPI-922 (1984); Yu.L. Dokshitzer, V.A. Khoze and S. Troyan, in: Perturbative QCD, ed. A.H. Mueller (World Scientific, Singapore, 1989)], an explicit expression for R3 is calculated. In this, leading and next-to-leading large logarithms (LL and NLL) are resummed to all orders in QCD perturbation theory. In addition to exponentials an error function is involved.

  18. A SEARCH FOR POINT SOURCES OF EeV NEUTRONS

    SciTech Connect

    Abreu, P.; Andringa, S.; Aglietta, M.; Ahlers, M.; Ahn, E. J.; Albuquerque, I. F. M.; Allard, D.; Allekotte, I.; Allen, J.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muniz, J.; Alves Batista, R.; Ambrosio, M.; Aramo, C.; Aminaei, A.; Anchordoqui, L.; Antici'c, T.; Arganda, E.; Collaboration: Pierre Auger Collaboration; and others

    2012-12-01

    A thorough search of the sky exposed at the Pierre Auger Cosmic Ray Observatory reveals no statistically significant excess of events in any small solid angle that would be indicative of a flux of neutral particles from a discrete source. The search covers from -90 Degree-Sign to +15 Degree-Sign in declination using four different energy ranges above 1 EeV (10{sup 18} eV). The method used in this search is more sensitive to neutrons than to photons. The upper limit on a neutron flux is derived for a dense grid of directions for each of the four energy ranges. These results constrain scenarios for the production of ultrahigh energy cosmic rays in the Galaxy.

  19. SLSF local fault safety experiment P4: summary and conclusions. [Sodium Loop Safety Facility

    SciTech Connect

    Thompson, D.H.; Ragland, W.A.; Holland, J.W.; Dever, D.J.; Braid, T.H.; Baldwin, R.D.; Anderson, T.T.

    1985-01-01

    Sodium Loop Safety Facility (SLSF) experiment P4 in ETR was performed to investigate the consequences of an upper-bound or worse-than-worst case local fault configuration. P4 was intended to bound the consequences of credible subassembly faults by ejecting molten fuel into a 37-pin bundle of full-length Fast Test Reactor (FTR)-type pins and failing fuel with the potential for further cladding and fuel-pin damage. In addition to ejecting a large amount of molten fuel at or near full power, experiment objectives were to evaluate the severity of molten fuel-coolant interactions (MFCIs) and to demonstrate that any resulting blockage could either be tolerated during continued power operation or detected by global monitors in time to prevent significant fuel failure propagation.

  20. Exploration of the ligand binding site of the human 5-HT(4) receptor by site-directed mutagenesis and molecular modeling.

    PubMed

    Mialet, J; Dahmoune, Y; Lezoualc'h, F; Berque-Bestel, I; Eftekhari, P; Hoebeke, J; Sicsic, S; Langlois, M; Fischmeister, R

    2000-06-01

    Among the five human 5-HT(4) (h5-HT(4)) receptor isoforms, the h5-HT(4(a)) receptor was studied with a particular emphasis on the molecular interactions involved in ligand binding. For this purpose, we used site-directed mutagenesis of the transmembrane domain. Twelve mutants were constructed with a special focus on the residue P4.53 of helix IV which substitutes in h5-HT(4) receptors the highly conserved S residue among the rhodopsin family receptors. The mutated receptors were transiently expressed in COS-7 cells. Ligand binding or competition studies with two h5-HT(4) receptor agonists, serotonin and ML10302 and two h5-HT(4) receptor antagonists, [(3)H]-GR113808 and ML10375 were performed on wild type and mutant receptors. Functional activity of the receptors was evaluated by measuring the ability of serotonin to stimulate adenylyl cyclase. Ligand binding experiments revealed that [(3)H]-GR113808 did not bind to mutants P4.53A, S5.43A, F6.51A, Y7.43A and to double mutant F6.52V/N6.55L. On the other hand mutations D3.32N, S5.43A and Y7.43A appeared to promote a dramatic decrease of h5-HT(4(a)) receptor functional activity. From these studies, S5.43 and Y7.43 clearly emerged as common anchoring sites to antagonist [(3)H]-GR113808 and to serotonin. According to these results, we propose ligand-receptor complex models with serotonin and [(3)H]-GR113808. For serotonin, three interaction points were selected including ionic interaction with D3.32, a stabilizing interaction of this ion pair by Y7.43 and a hydrogen bond with S5.43. [(3)H]-GR113808 was also docked, based on the same type of interactions with S5.43 and D3.32: the proposed model suggested a possible role of P4.53 in helix IV structure allowing the involvement of a close hydrophobic residue, W4.50, in a hydrophobic pocket for hydrophobic interactions with the indole ring of [(3)H]-GR113808.

  1. Bivalent Ligands for the Serotonin 5-HT3 Receptor

    PubMed Central

    2011-01-01

    The serotonin 5-HT3 receptor is a ligand-gated ion channel, which by virtue of its pentameric architecture, can be considered to be an intriguing example of intrinsically multivalent biological receptors. This paper describes a general design approach to the study of multivalency in this multimeric ion channel. Bivalent ligands for 5-HT3 receptor have been designed by linking an arylpiperazine moiety to probes showing different functional features. Both homobivalent and heterobivalent ligands have shown 5-HT3 receptor affinity in the nanomolar range, providing evidence for the viability of our design approach. Moreover, the high affinity shown by homobivalent ligands suggests that bivalency is a promising approach in 5-HT3 receptor modulation and provides the rational basis for applying the concepts of multivalency to the study of 5-HT3 receptor function. PMID:24900351

  2. Object-Oriented Version of Glenn-HT Code Released: Glenn-HT2000

    NASA Technical Reports Server (NTRS)

    Heidmann, James D.; Ameri, Ali A.; Rigby, David I.; Garg, Vijay K.; Fabian, John C.; Lucci, Barbara L.; Steinthorsson, Erlendur

    2005-01-01

    NASA Glenn Research Center s General Multi-Block Navier-Stokes Convective Heat Transfer Code (Glenn-HT) has been used extensively to predict heat transfer and fluid flow for a variety of steady gas turbine engine problems. Efforts have focused on turbine heat transfer, where computations have modeled tip clearance, internal coolant, and film cooling flows. Excellent agreement has been achieved for a variety of experimental test cases, and results have been published in over 40 technical publications. The code is available to U.S. industry and has been used by several domestic gas turbine engine companies. The following figure shows a typical flow solution from the Glenn-HT code for a film-cooled turbine blade.

  3. P[8] and P[4] Rotavirus Infection Associated with Secretor Phenotypes Among Children in South China

    PubMed Central

    Zhang, Xu-Fu; Long, Yan; Tan, Ming; Zhang, Ting; Huang, Qiong; Jiang, Xi; Tan, Wen-Fang; Li, Jian-Dong; Hu, Gui-Fang; Tang, Shixing; Dai, Ying-Chun

    2016-01-01

    Rotaviruses are known to recognize human histo-blood group antigens (HBGAs) as a host ligand that is believed to play an important role in rotavirus host susceptibility and host range. In this study, paired fecal and saliva samples collected from children with viral gastroenteritis, as well as paired serum and saliva samples collected from the general population in south China were studied to evaluate potential association between rotavirus infections and human HBGA phenotypes. Rotavirus was detected in 75 (28%) of 266 fecal samples and P[8] rotaviruses were found to be the predominant genotype. The HBGA phenotypes of the rotavirus-infected children were determined through their saliva samples. Secretor statuses were found to correlate with the risk of rotavirus infection and all P[8]/P[4] rotavirus infected children were secretors. Accordingly, recombinant VP8* proteins of the P[8]/P[4] rotaviruses bound saliva samples from secretor individuals. Furthermore, correlation between serum P[8]/P[4]-specific IgG and host Lewis and secretor phenotypes has been found among 206 studied serum samples. Our study supported the association between rotavirus infection and the host HBGA phenotypes, which would help further understanding of rotavirus host range and epidemiology. PMID:27708367

  4. 76 FR 66855 - United States Savings Bonds, Series EE, HH and I

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF THE TREASURY Fiscal Service 31 CFR Parts 351, 353, 359, and 360 United States Savings Bonds, Series EE, HH and I... DEFINITIVE UNITED STATES SAVINGS BONDS, SERIES EE AND HH 0 9. The authority citation for part 353...

  5. Reschooling Society and the Promise of ee-Learning: An Interview with Steve Eskow

    ERIC Educational Resources Information Center

    Trevitte, Chad; Eskow, Steve

    2007-01-01

    In this article, Chad Trevitte interviews "Innovate" guest editor Steve Eskow about the concept of ee-learning and the promise it holds for revitalizing higher education. Eskow defines ee-learning as a combination of the electronic technologies employed in online learning ("e-learning 1") and a pedagogy of experiential learning rooted in real-life…

  6. Improvements to an Electrical Engineering Skill Audit Exam to Improve Student Mastery of Core EE Concepts

    ERIC Educational Resources Information Center

    Parent, D. W.

    2011-01-01

    The San Jose State University Electrical Engineering (EE) Department implemented a skill audit exam for graduating seniors in 1999 with the purpose of assessing the teaching and the students' mastery of core concepts in EE. However, consistent low scores for the first years in which the test was administered suggested that students had little…

  7. Experiment 2018, First Fracturing Attempt Below Casing Shoe in EE-2 (1982-7-19/20)

    SciTech Connect

    Hoffers, Bernard

    1983-03-15

    The purpose of Experiment 2018 was to achieve a hydraulic connection between EE-2 and EE-3 in the region just below their respective casing shoes. To protect the cassing of EE-2, the fracturing fluid had to be pumped down a 3-1/2 inch drill string to an Otis casing packer set 240 ft above the casing shoe of EE-2. Pumping started at 16:23 of July 19, 1982, and was terminated at 2:02 on July 20, 1982, due to hardware failure, after some trouble with the setting of the casing packer had delayed the beginning of the experiment for approximately two days. Prior to the experiment, a sand plug in EE-2 had been set, with its top at 11,910 ft (all depths referenced her are cable depths). A total of 5,698 bbls had been pumped. No hydraulic connection appeared at the end of Experiment 2018.

  8. The research and scheme of RBAC using J2EE security mechanisms

    NASA Astrophysics Data System (ADS)

    Zhang, Fangzhou; Sheng, Xiaoyu; Niu, Yingying; Wang, Fengpin; Zhang, Han

    2006-10-01

    Access control based on RBAC makes the system suitable to the security strategy for special application, relieves burden of system administrators and can adapt itself to the adjustment of the system structure flexibly. But all the existing security mechanisms of the middleware technology can't support the RBAC model very well. The method using J2EE security mechanisms to support RBAC is showed in this paper. First, the configuration of J2EE security systems is given in the paper and the algorithm of J2EE authorization decision is designed. Then, the language of J2EE security description is used to define RBAC, and realization of the requirement of J2EE security service is given. It has achieved the anticipative effect in virtue of deployment and application on the platform of the national science technology infrastructure.

  9. 5-HT1B receptor-mediated contractions in human temporal artery: evidence from selective antagonists and 5-HT receptor mRNA expression

    PubMed Central

    Verheggen, R; Hundeshagen, A G; Brown, A M; Schindler, M; Kaumann, A J

    1998-01-01

    In the human temporal artery both 5-HT1-like and 5-HT2A receptors mediate the contractile effects of 5-hydroxytryptamine (5-HT) and we have suggested that the 5-HT1-like receptors resemble more closely recombinant 5-HT1B than 5-HT1D receptors. To investigate further which subtype is involved, we investigated the blockade of 5-HT-induced contractions by the 5-HT1B-selective antagonist SB-224289 (2,3,6,7-tetrahydro-1′-methyl-5-{2-methyl-4′[(5-methyl-1,2,4-oxadiazole-3-yl) biphenyl-4-yl] carbonyl} furo[2,3-f]indole-3-spiro-4′-piperidine oxalate) and the 5-HT1D-selective antagonist BRL-15572 (1-phenyl-3[4-3-chlorophenyl piperazin-1-yl] phenylpropan-2-ol). We also used RT-PCR to search for the mRNA of 5-HT1B, 5-HT1D and other 5-HT receptors.The contractile effects of 5-HT in temporal artery rings were partially antagonized by SB-224289 (20, 200 nM) (apparent KB=1 nM) and ketanserin (1 μM) but not by BRL-15572 (500 nM).Sumatriptan evoked contractions (EC50, 170 nM) that were resistant to blockade by BRL-15572 (500 nM) but antagonized by SB-224289 (20, 200 nM).The potency of 5-HT (EC50) was estimated to be 94 nM for the ketanserin-sensitive receptor and 34 nM for the SB-224289-sensitive receptor. The fraction of maximal 5-HT response mediated through SB-224289-sensitive receptors was 0.20–0.67, the remainder being mediated through ketanserin-sensitive receptors.We detected arterial receptor mRNA for the following receptors (incidence): 5-HT1B (8/8), 5-HT1D (2/8), 5-HT1F (0/4), 5-HT2A (0/8), 5-HT2B (0/8), 5-HT2C (0/8), 5-HT4 (4/8) and 5-HT7 (4/8).We conclude that the ketanserin-resistant fraction of the 5-HT effects and the effects of sumatriptan are mediated by 5-HT1B receptors. The lack of antagonism by BRL-15572 rules out 5-HT1D receptors as mediators of the contractile effects of 5-HT and sumatriptan. PMID:9723944

  10. New 1-arylindoles based serotonin 5-HT7 antagonists. Synthesis and binding evaluation studies.

    PubMed

    Sagnes, Charlène; Fournet, Guy; Satala, Grzegorz; Bojarski, Andrzej J; Joseph, Benoît

    2014-03-21

    Based on 5-HT1A and 5-HT7 ligand MR25003 scaffold, a new series of 1-aryl indole analogues were prepared and evaluated against 5-HT7 receptors. Modulations of aryl moieties provided a large number of new indolic derivatives. Most of compounds tested have displayed 5-HT7 affinity in the nanomolar range. Among them, 1-(naphthyl)indole derivative 3p (Ki (5-HT7) = 4.5 nM) showed also a good selectivity over 5-HT1A, 5-HT2A and 5-HT6 receptors. This compound was pharmacology characterized as an antagonist.

  11. Physiological, pathophysiological and therapeutic roles of 5-HT systems in learning and memory.

    PubMed

    Meneses, A

    1998-01-01

    Multiple 5-hydroxytryptamine (5-HT) receptors have been identified (5-HT1A/1B/1D/1E/1F, 5-HT2A/2B/2C, 5-HT3A/3B, 5-HT4A/4B, 5-HT5A/5B, 5-HT6 and 5-HT7A/7B/7C/7D) and extensive evidence suggests that 5-HT receptors have a role in learning and memory. Indeed, available evidence strongly supports physiological, pathophysiological and therapeutic roles of 5-HT systems in cognitive processes, although the evidence seems incomplete. Indeed, there has been a clear tendency to use pre-learning administration most frequently, whereas post-learning and pre-retention administration protocols have been utilized in only a few studies, and probably this trend has led to missed relevant information. For instance, when pre- vs post-training administration of 5-HT1A agonist, 5-HT2 antagonists and 5-HT4 agonists have been compared contrasting findings were reported in aversive and appetitive learning tasks. Emerging evidence also indicates that 5-HT1A and 5-HT4 receptor agonists, as well as, 5-HT1A antagonists, 5-HT2 antagonists, 5-HT3 antagonists and 5-HT uptake inhibitors may have therapeutic utility in the treatment of Alzheimer's disease and amnesia. Inasmuch as the activation or blockade of diverse 5-HT receptors is able to modulate cognitive processes, and 5-HT uptake inhibition could have therapeutic applications in the treatment of cognitive disorders, it seems evident that the role of 5-HT in learning and memory is more complex than a simple imbalance. Consequently, the notion that activation of the 5-HT systems impairs performance, whereas reduced serotonergic function may facilitate learning, must be reconsidered.

  12. 5-HT2 receptor blockade exhibits 5-HT vasodilator effects via nitric oxide, prostacyclin and ATP-sensitive potassium channels in rat renal vasculature.

    PubMed

    García-Pedraza, J A; García, M; Martín, M L; Rodríguez-Barbero, A; Morán, A

    2016-04-01

    The aim of this study was to determine whether orally sarpogrelate (selective 5-HT2 antagonist) treatment (30 mg/kg/day; 14 days) could modify 5-HT renal vasoconstrictor responses, characterizing 5-HT receptors and mediator mechanisms involved in serotonergic responses in the in situ autoperfused rat kidney. Intra-arterial (i.a.) injections of 5-HT (0.00000125 to 0.1 μg/kg) decreased renal perfusion pressure (RPP) but did not affect the mean blood pressure (MBP). i.a. agonists 5-CT (5-HT1/7), CGS-12066B (5-HT1B), L-694,247 (5-HT1D) or AS-19 (5-HT7) mimicked renal 5-HT vasodilator effect. However, neither 8-OH-DPAT (5-HT1A) nor 1-phenylbiguanide (5-HT3) modified RPP. Moreover: (i) GR-55562 (5-HT1B antagonist) and L-NAME (nitric oxide synthase [NOS] inhibitor) blocked CGS-12066B-induced vasodilator response, (ii) LY310762 (5-HT1D antagonist) and indomethacin (non-selective cyclooxygenase inhibitor) blocked L-694,247-induced vasodilator response; (iii) SB-258719 (5-HT7 antagonist) and glibenclamide (ATP-sensitive K+ channel blocker) blocked AS-19-induced vasodilator response; and (iv) 5-HT- or 5-CT-elicited renal vasodilation was significantly blocked by the mixture of GR-55562 + LY310762 + SB-258719. Furthermore, eNOS and iNOS proteins and prostacyclin levels are overexpressed in sarpogrelate-treated rats. Our data suggest that 5-HT exerts renal vasodilator effect in the in situ autoperfused sarpogrelate-treated rat kidney, mediated by 5-HT1D, 5-HT1B and 5-HT7 receptors, involving cyclooxygenase-derived prostacyclin, nitric oxide synthesis/release and ATP-sensitive K+ channels, respectively.

  13. 31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false What is the issue date of a book-entry... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings...

  14. 31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false When is a book-entry Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is posted...

  15. 31 CFR 351.64 - What is the issue date of a book-entry Series EE savings bond?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false What is the issue date of a book... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.64 What is the issue date of a book-entry Series EE savings bond? The issue date of a book-entry Series EE savings...

  16. 31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When is a book-entry Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is...

  17. 31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false When is a book-entry Series EE... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is...

  18. 31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false When is a book-entry Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is posted...

  19. 31 CFR 351.69 - When is a book-entry Series EE savings bond validly issued?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false When is a book-entry Series EE savings... OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.69 When is a book-entry Series EE savings bond validly issued? A book-entry bond is validly issued when it is posted...

  20. Important messages in the 'post': recent discoveries in 5-HT neurone feedback control.

    PubMed

    Sharp, Trevor; Boothman, Laura; Raley, Josie; Quérée, Philip

    2007-12-01

    The neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) mediates important brain functions and contributes to the pathophysiology and successful drug treatment of many common psychiatric disorders, especially depression. It is established that a key mechanism involved in the control of 5-HT neurones is feedback inhibition by presynaptic 5-HT autoreceptors, which are located on 5-HT cell bodies and nerve terminals. However, recent experiments have discovered an unexpected complexity of 5-HT neurone control, specifically in the form of postsynaptic 5-HT feedback mechanisms. These mechanisms have the physiological effects of 5-HT autoreceptors but use additional 5-HT receptor subtypes and operate through neural inputs to 5-HT neurones. A postsynaptic feedback system that excites 5-HT neurones has also been reported. This article discusses current knowledge of the pharmacology and physiology of these new found 5-HT feedback mechanisms and considers their possible contribution to depression pathophysiology and utility as a resource of novel antidepressant drug strategies.

  1. 31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of...

  2. 40 CFR Appendix A to Subpart Ee of... - States With Approved State Implementation Plan Revisions Concerning Allocations

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Implementation Plan Revisions Concerning Allocations A Appendix A to Subpart EE of Part 97 Protection of... PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR NOX Allowance Allocations Pt. 97, Subpt. EE, App. A Appendix A to Subpart EE of Part 97—States With Approved State Implementation Plan Revisions...

  3. 31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... apply to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements...

  4. 31 CFR 351.84 - Does Fiscal Service make any reservations as to issue of Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... reservations as to issue of Series EE savings bonds? 351.84 Section 351.84 Money and Finance: Treasury... FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.84 Does Fiscal Service make any reservations as to issue of Series EE savings bonds? We may reject...

  5. 31 CFR 351.9 - When will I receive the redemption value of my Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... value of my Series EE savings bonds? 351.9 Section 351.9 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.9 When will I receive the redemption value...

  6. 31 CFR 351.81 - Is the Education Savings Bond Program available for Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... available for Series EE savings bonds? 351.81 Section 351.81 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.81 Is the Education Savings Bond Program available for Series EE savings bonds? You may be able to exclude from...

  7. 31 CFR 351.81 - Is the Education Savings Bond Program available for Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... available for Series EE savings bonds? 351.81 Section 351.81 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.81 Is the Education Savings Bond Program available for Series EE savings bonds? You may be able to exclude from...

  8. 31 CFR 351.84 - Does Public Debt make any reservations as to issue of Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... as to issue of Series EE savings bonds? 351.84 Section 351.84 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.84 Does Public Debt make any reservations as to issue of Series EE savings bonds? We may reject any application...

  9. 31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... apply to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury... FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements...

  10. 31 CFR 351.83 - May Public Debt issue Series EE savings bonds only in book-entry form?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false May Public Debt issue Series EE... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.83 May Public Debt issue Series EE savings bonds only in book-entry form? We reserve the right to issue bonds only...

  11. 31 CFR 351.9 - When will I receive the redemption value of my Series EE savings bonds?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... value of my Series EE savings bonds? 351.9 Section 351.9 Money and Finance: Treasury Regulations... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.9 When will I receive the redemption value...

  12. 31 CFR 351.9 - When will I receive the redemption value of my Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... value of my Series EE savings bonds? 351.9 Section 351.9 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.9 When will I receive the redemption value...

  13. 31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that apply...

  14. 31 CFR 351.9 - When will I receive the redemption value of my Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... value of my Series EE savings bonds? 351.9 Section 351.9 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.9 When will I receive the redemption value...

  15. 31 CFR 351.9 - When will I receive the redemption value of my Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... value of my Series EE savings bonds? 351.9 Section 351.9 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.9 When will I receive the redemption value...

  16. 31 CFR 351.84 - Does Public Debt make any reservations as to issue of Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... as to issue of Series EE savings bonds? 351.84 Section 351.84 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.84 Does Public Debt make any reservations as to issue of Series EE savings bonds? We may reject any application...

  17. 31 CFR 351.84 - Does Public Debt make any reservations as to issue of Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reservations as to issue of Series EE savings bonds? 351.84 Section 351.84 Money and Finance: Treasury... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.84 Does Public Debt make any reservations as to issue of Series EE savings bonds? We may reject any...

  18. 31 CFR 351.81 - Is the Education Savings Bond Program available for Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... available for Series EE savings bonds? 351.81 Section 351.81 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.81 Is the Education Savings Bond Program available for Series EE savings bonds? You may be able to exclude from...

  19. 31 CFR 351.84 - Does Public Debt make any reservations as to issue of Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... as to issue of Series EE savings bonds? 351.84 Section 351.84 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.84 Does Public Debt make any reservations as to issue of Series EE savings bonds? We may reject any application...

  20. 31 CFR 351.14 - When are rate announcements that apply to Series EE savings bonds announced?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... to Series EE savings bonds announced? 351.14 Section 351.14 Money and Finance: Treasury Regulations... DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds General Provisions § 351.14 When are rate announcements that apply...

  1. 31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... EE Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE savings bonds? The TIN of each person named in the registration is required...

  2. Adaptation of antenna profiles for control of MR guided hyperthermia (HT) in a hybrid MR-HT system

    SciTech Connect

    Weihrauch, Mirko; Wust, Peter; Weiser, Martin; Nadobny, Jacek; Eisenhardt, Steffen; Budach, Volker; Gellermann, Johanna

    2007-12-15

    A combined numerical-experimental iterative procedure, based on the Gauss-Newton algorithm, has been developed for control of magnetic resonance (MR)-guided hyperthermia (HT) applications in a hybrid MR-HT system BSD 2000 3D-MRI. In this MR-HT system, composed of a 3-D HT applicator Sigma-Eye placed inside a tunnel-type MR tomograph Siemens MAGNETOM Symphony (1.5 T), the temperature rise due to the HT radiation can be measured on-line in three dimensions by use of the proton resonance frequency shift (PRFS) method. The basic idea of our iterative procedure is the improvement of the system's characterization by a step-by-step modification of the theoretical HT antenna profiles (electric fields radiated by single antennas). The adaptation of antenna profiles is efficient if the initial estimates are radiation fields calculated from a good a priori electromagnetic model. Throughout the iterative procedure, the calculated antenna fields (FDTD) are step-by-step modified by comparing the calculated and experimental data, the latter obtained using the PRFS method. The procedure has been experimentally tested on homogeneous and inhomogeneous phantoms. It is shown that only few comparison steps are necessary for obtaining a dramatic improvement of the general predictability and quality of the specific absorption rate (SAR) inside the MR-HT hybrid system.

  3. Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration.

    PubMed

    Williams, Simon F; Rizk, Said; Martin, David P

    2013-10-01

    Poly-4-hydroxybutyrate (P4HB) is a thermoplastic, linear polyester, produced by recombinant fermentation, that can be converted into a wide range of resorbable medical devices. P4HB fibers are exceptionally strong, and can be designed to provide prolonged strength retention in vivo. In 2007, the FDA cleared a monofilament suture made from P4HB for general soft tissue approximation and/or ligation. Subsequently, surgical mesh devices for hernia repair, tendon and ligament repair, and plastic and reconstructive surgery have been introduced for clinical use. This review describes the unique properties of P4HB, its clinical applications, and potential uses that are under development.

  4. Cartography of 5-HT1A and 5-HT2A Receptor Subtypes in Prefrontal Cortex and Its Projections.

    PubMed

    Mengod, Guadalupe; Palacios, José M; Cortés, Roser

    2015-07-15

    Since the development of chemical neuroanatomical tools in the 1960s, a tremendous wealth of information has been generated on the anatomical components of the serotonergic system, at the microscopic level in the brain including the prefrontal cortex (PFC). The PFC receives a widespread distribution of serotonin (5-hydroxytryptamine, 5-HT) terminals from the median and dorsal raphe nuclei. 5-HT receptors were first visualized using radioligand autoradiography in the late 1980s and early 1990s and showed, in contrast to 5-HT innervation, a differential distribution of binding sites associated with different 5-HT receptor subtypes. Due to the cloning of the different 5-HT receptor subtype genes in the late 1980s and early 1990s, it was possible, using in situ hybridization histochemistry, to localize cells expressing mRNA for these receptors. Double in situ hybridization histochemistry and immunohistochemistry allowed for the chemical characterization of the phenotype of cells expressing 5-HT receptors. Tract tracing technology allowed a detailed cartography of the neuronal connections of PFC and other brain areas. Based on these data, maps have been constructed that reflect our current understanding of the different circuits where 5-HT receptors can modulate the electrophysiological, pharmacological, and behavioral functions of the PFC. We will review current knowledge regarding the cellular localization of 5-HT1A and 5-HT2A receptors in mammalian PFC and their possible functions in the neuronal circuits of the PFC. We will discuss data generated in our laboratory as well as in others, focusing on localization in the pyramidal and GABAergic neuronal cell populations in different mammalian species using molecular neuroanatomy and on the connections with other brain regions.

  5. Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues

    NASA Astrophysics Data System (ADS)

    Bronowska, Agnieszka; Chilmonczyk, Zdzisław; Leś, Andrzej; Edvardsen, Øyvind; Østensen, Roy; Sylte, Ingebrigt

    2001-11-01

    In the present study experimentally determined ligand selectivity of three methylated buspirone analogues (denoted as MM2, MM5 and P55) towards 5-HT1A and 5-HT2A serotonin receptors was theoretically investigated on a molecular level. The relationships between the ligand structure and 5-HT1A and 5-HT2A receptor affinities were studied and the results were found to be in agreement with the available site-directed mutagenesis and binding affinity data. Molecular dynamics (MD) simulations of ligand-receptor complexes were performed for each investigated analogue, docked twice into the central cavity of 5-HT1A/5-HT2A, each time in a different orientation. Present results were compared with our previous theoretical results, obtained for buspirone and its non-methylated analogues. It was found that due to the presence of the methyl group in the piperazine ring the ligand position alters and the structure of the ligand-receptor complex is modified. Further, the positions of derivatives with pyrimidinyl aromatic moiety and quinolinyl moiety are significantly different at the 5-HT2A receptor. Thus, methylation of such derivatives alters the 3D structures of ligand-receptor complexes in different ways. The ligand-induced changes of the receptor structures were also analysed. The obtained results suggest, that helical domains of both receptors have different dynamical behaviour. Moreover, both location and topography of putative binding sites for buspirone analogues are different at 5-HT1A and 5-HT2A receptors.

  6. Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation.

    PubMed

    Jensen, Jesper Bornø; du Jardin, Kristian Gaarn; Song, Dekun; Budac, David; Smagin, Gennady; Sanchez, Connie; Pehrson, Alan Lars

    2014-01-01

    Depressed patients suffer from cognitive dysfunction, including memory deficits. Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients. The investigational multimodal acting antidepressant vortioxetine is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in normal rats in novel object recognition (NOR) and conditioned fear (Mørk et al., 2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved in its memory effects, and therefore investigated these effects in 5-HT depleted rats. Four injections of the irreversible tryptophan hydroxylase inhibitor 4-chloro-dl-phenylalanine methyl ester hydrochloride (PCPA, 86mg/kg, s.c.) induced 5-HT depletion, as measured in hippocampal homogenate and microdialysate. The effects of acute challenge with vortioxetine or the 5-HT releaser fenfluramine on extracellular 5-HT were measured in PCPA-treated and control rats. PCPA's effects on NOR and spontaneous alternation (SA) performance were assessed along with the effects of acute treatment with 5-hydroxy-l-tryptophan (5-HTP), vortioxetine, the selective 5-HT reuptake inhibitor escitalopram, or the 5-HT norepinephrine reuptake inhibitor duloxetine. SERT occupancies were estimated by ex vivo autoradiography. PCPA depleted central 5-HT by >90% in tissue and microdialysate, and impaired NOR and SA performance. Restoring central 5-HT with 5-HTP reversed these deficits. At similar SERT occupancies (>90%) vortioxetine, but not escitalopram or duloxetine, restored memory performance. Acute fenfluramine significantly increased extracellular 5-HT in control and PCPA-treated rats, while vortioxetine did so only in control rats. Thus, vortioxetine restores 5-HT depletion impaired memory performance in rats through one or more of its receptor activities.

  7. 5-HT1A and 5-HT7 receptor crosstalk in the regulation of emotional memory: implications for effects of selective serotonin reuptake inhibitors.

    PubMed

    Eriksson, Therese M; Holst, Sarah; Stan, Tiberiu L; Hager, Torben; Sjögren, Benita; Ogren, Sven Öve; Svenningsson, Per; Stiedl, Oliver

    2012-11-01

    This study utilized pharmacological manipulations to analyze the role of direct and indirect activation of 5-HT(7) receptors (5-HT(7)Rs) in passive avoidance learning by assessing emotional memory in male C57BL/6J mice. Additionally, 5-HT(7)R binding affinity and 5-HT(7)R-mediated protein phosphorylation of downstream signaling targets were determined. Elevation of 5-HT by the selective serotonin reuptake inhibitor (SSRI) fluoxetine had no effect by itself, but facilitated emotional memory performance when combined with the 5-HT(1A)R antagonist NAD-299. This facilitation was blocked by the selective 5-HT(7)R antagonist SB269970, revealing excitatory effects of the SSRI via 5-HT(7)Rs. The enhanced memory retention by NAD-299 was blocked by SB269970, indicating that reduced activation of 5-HT(1A)Rs results in enhanced 5-HT stimulation of 5-HT(7)Rs. The putative 5-HT(7)R agonists LP-44 when administered systemically and AS19 when administered both systemically and into the dorsal hippocampus failed to facilitate memory. This finding is consistent with the low efficacy of LP-44 and AS19 to stimulate protein phosphorylation of 5-HT(7)R-activated signaling cascades. In contrast, increasing doses of the dual 5-HT(1A)R/5-HT(7)R agonist 8-OH-DPAT impaired memory, while co-administration with NAD-299 facilitated of emotional memory in a dose-dependent manner. This facilitation was blocked by SB269970 indicating 5-HT(7)R activation by 8-OH-DPAT. Dorsohippocampal infusion of 8-OH-DPAT impaired passive avoidance retention through hippocampal 5-HT(1A)R activation, while 5-HT(7)Rs appear to facilitate memory processes in a broader cortico-limbic network and not the hippocampus alone.

  8. Role of spinal 5-HT5A, and 5-HT1A/1B/1D, receptors in neuropathic pain induced by spinal nerve ligation in rats.

    PubMed

    Avila-Rojas, Sabino Hazael; Velázquez-Lagunas, Isabel; Salinas-Abarca, Ana Belen; Barragán-Iglesias, Paulino; Pineda-Farias, Jorge Baruch; Granados-Soto, Vinicio

    2015-10-05

    Serotonin (5-HT) participates in pain modulation by interacting with different 5-HT receptors. The role of 5-HT5A receptor in neuropathic pain has not previously studied. The purpose of this study was to investigate: A) the role of 5-HT5A receptors in rats subjected to spinal nerve injury; B) the expression of 5-HT5A receptors in dorsal spinal cord and dorsal root ganglia (DRG). Neuropathic pain was induced by L5/L6 spinal nerve ligation. Tactile allodynia in neuropathic rats was assessed with von Frey filaments. Western blot methodology was used to determine 5-HT5A receptor protein expression. Intrathecal administration (on day 14th) of 5-HT (10-100 nmol) or 5-carboxamidotryptamine (5-CT, 0.03-0.3 nmol) reversed nerve injury-induced tactile allodynia. Intrathecal non-selective (methiothepin, 0.1-0.8 nmol) and selective (SB-699551, 1-10 nmol) 5-HT5A receptor antagonists reduced, by ~60% and ~25%, respectively, the antiallodynic effect of 5-HT (100 nmol) or 5-CT (0.3 nmol). Moreover, both selective 5-HT1A and 5-HT1B/1D receptor antagonists, WAY-100635 (0.3-1 nmol) and GR-127935 (0.3-1 nmol), respectively, partially diminished the antiallodynic effect of 5-HT or 5-CT by about 30%. Injection of antagonists, by themselves, did not affect allodynia. 5-HT5A receptors were expressed in the ipsilateral dorsal lumbar spinal cord and DRG and L5/L6 spinal nerve ligation did not modify 5-HT5A receptor protein expression in those sites. Results suggest that 5-HT5A receptors reduce pain processing in the spinal cord and that 5-HT and 5-CT reduce neuropathic pain through activation of 5-HT5A and 5-HT1A/1B/1D receptors. These receptors could be an important part of the descending pain inhibitory system.

  9. The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory

    PubMed Central

    Stiedl, Oliver; Pappa, Elpiniki; Konradsson-Geuken, Åsa; Ögren, Sven Ove

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is a multifunctional neurotransmitter innervating cortical and limbic areas involved in cognition and emotional regulation. Dysregulation of serotonergic transmission is associated with emotional and cognitive deficits in psychiatric patients and animal models. Drugs targeting the 5-HT system are widely used to treat mood disorders and anxiety-like behaviors. Among the fourteen 5-HT receptor (5-HTR) subtypes, the 5-HT1AR and 5-HT7R are associated with the development of anxiety, depression and cognitive function linked to mechanisms of emotional learning and memory. In rodents fear conditioning and passive avoidance (PA) are associative learning paradigms to study emotional memory. This review assesses the role of 5-HT1AR and 5-HT7R as well as their interplay at the molecular, neurochemical and behavioral level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces 5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the 5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR transmission. These findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior. Moreover, the results indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and their interaction. Consequently, individual differences due to genetic and/or epigenetic mechanisms play an essential role for the responsiveness to drug treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby activating multiple pre- and postsynaptic 5-HTR subtypes. PMID:26300776

  10. The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory.

    PubMed

    Stiedl, Oliver; Pappa, Elpiniki; Konradsson-Geuken, Åsa; Ögren, Sven Ove

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is a multifunctional neurotransmitter innervating cortical and limbic areas involved in cognition and emotional regulation. Dysregulation of serotonergic transmission is associated with emotional and cognitive deficits in psychiatric patients and animal models. Drugs targeting the 5-HT system are widely used to treat mood disorders and anxiety-like behaviors. Among the fourteen 5-HT receptor (5-HTR) subtypes, the 5-HT1AR and 5-HT7R are associated with the development of anxiety, depression and cognitive function linked to mechanisms of emotional learning and memory. In rodents fear conditioning and passive avoidance (PA) are associative learning paradigms to study emotional memory. This review assesses the role of 5-HT1AR and 5-HT7R as well as their interplay at the molecular, neurochemical and behavioral level. Activation of postsynaptic 5-HT1ARs impairs emotional memory through attenuation of neuronal activity, whereas presynaptic 5-HT1AR activation reduces 5-HT release and exerts pro-cognitive effects on PA retention. Antagonism of the 5-HT1AR facilitates memory retention possibly via 5-HT7R activation and evidence is provided that 5HT7R can facilitate emotional memory upon reduced 5-HT1AR transmission. These findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior. Moreover, the results indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of 5-HT1ARs and 5-HT7Rs and their interaction. Consequently, individual differences due to genetic and/or epigenetic mechanisms play an essential role for the responsiveness to drug treatment, e.g., by SSRIs which increase intrasynaptic 5-HT levels thereby activating multiple pre- and postsynaptic 5-HTR subtypes.

  11. cyclo‐P4 Building Blocks: Achieving Non‐Classical Fullerene Topology and Beyond

    PubMed Central

    Dielmann, Fabian; Peresypkina, Eugenia V.; Krämer, Barbara; Hastreiter, Florian; Johnson, Brian P.; Zabel, Manfred; Heindl, Claudia

    2016-01-01

    Abstract The cyclo‐P4 complexes [CpRTa(CO)2(η4‐P4)] (CpR: Cp′′=1,3‐C5H3tBu2, Cp′′′=1,2,4‐C5H2tBu3) turned out to be predestined for the formation of hollow spherical supramolecules with non‐classical fullerene‐like topology. The resulting assemblies constructed with CuX (X=Cl, Br) showed a highly symmetric 32‐vertex core of solely four‐ and six‐membered rings. In some supramolecules, the inner cavity was occupied by an additional CuX unit. On the other hand, using CuI, two different supramolecules with either peanut‐ or pear‐like shapes and outer diameters in the range of 2–2.5 nm were isolated. Furthermore, the spherical supramolecules containing Cp′′′ ligands at tantalum are soluble in CH2Cl2. NMR spectroscopic investigations in solution revealed the formation of isomeric supramolecules owing to the steric hindrance caused by the third tBu group on the Cp′′′ ligand. In addition, a 2D coordination polymer was obtained and structurally characterized. PMID:27781348

  12. RU 24969-induced emesis in the cat - 5-HT1 sites other than 5-HT1A, 5-HT1B or 5-HT1C implicated

    NASA Technical Reports Server (NTRS)

    Lucot, James B.

    1990-01-01

    RU 24969 was administered s.c. to cats and found to elicit emesis with a maximally effective dose of 1.0 mg/kg 5-Methoxytryptamine was found to have lower efficacy and to produce a higher incidence of nonspecific effects while trifluoromethylphenylpiperizine (TFMPP) was devoid of emetic effects. The emesis elicited by 1.0 mg/kg of RU 24969 was not altered by pretreatment with phentolamine, haloperidol, yohimbine or (-)-propranolol, indicating that catecholamines played no role in this response. The emesis was prevented by metergoline and methysergide but not by ketanserin, cyproheptadine, mesulergine, ICS 205 930, methiothepin, trimethobenzamide or BMY 7378. An indirect argument is presented that implicates a role for 5-HT1D sites. This conclusion must remain tentative until drugs selective for this site are synthesized and tested. The emesis was also prevented by 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT), confirming that this drug has a general antiemetic effect in cats.

  13. Lower bound on e+e- decay of massive neutrinos

    NASA Technical Reports Server (NTRS)

    Cowsik, R.; Schramm, D. N.; Hoflicn, P

    1988-01-01

    Astronomical observations of SN1987A, such as the light curve, spectral intensities of lines, the X-ray emissions, etc., constrain the lifetime for the decay of a heavy neutrino 1 MeV less than or equivalent to m sub nu H less than or equal to 50 MeV through nu sub H yields nu sub 1+e(+)+e(-) exceeds 4 x 10 to the 15th exp(-m sub nuH/5MeV) seconds. Otherwise. resulting ionization energy deposits and stronger X-ray emission would have been observed. This coupled with traditional cosmological considerations argues that the lifetime of tau-neutrinos probably exceeds the age of the universe. This in turn would imply the standard cosmological mass bound does apply to nu sub tau, namely m sub nu sub tau less than or equivalent to 100 h squared eV (where h is the Hubble constant in units of 100 km/sec/mpc). The only significant loophole for these latter arguments would be if nu sub tau primarily decays rapidly into particles having very weak interactions.

  14. Search for EeV protons of galactic origin

    NASA Astrophysics Data System (ADS)

    Abbasi, R. U.; Abe, M.; Abu-Zayyad, T.; Allen, M.; Azuma, R.; Barcikowski, E.; Belz, J. W.; Bergman, D. R.; Blake, S. A.; Cady, R.; Cheon, B. G.; Chiba, J.; Chikawa, M.; Fujii, T.; Fukushima, M.; Goto, T.; Hanlon, W.; Hayashi, Y.; Hayashi, M.; Hayashida, N.; Hibino, K.; Honda, K.; Ikeda, D.; Inoue, N.; Ishii, T.; Ishimori, R.; Ito, H.; Ivanov, D.; Jui, C. C. H.; Kadota, K.; Kakimoto, F.; Kalashev, O.; Kasahara, K.; Kawai, H.; Kawakami, S.; Kawana, S.; Kawata, K.; Kido, E.; Kim, H. B.; Kim, J. H.; Kim, J. H.; Kishigami, S.; Kitamura, S.; Kitamura, Y.; Kuzmin, V.; Kwon, Y. J.; Lan, J.; Lubsandorzhiev, B.; Lundquist, J. P.; Machida, K.; Martens, K.; Matsuda, T.; Matsuyama, T.; Matthews, J. N.; Minamino, M.; Mukai, K.; Myers, I.; Nagasawa, K.; Nagataki, S.; Nakamura, T.; Nonaka, T.; Nozato, A.; Ogio, S.; Ogura, J.; Ohnishi, M.; Ohoka, H.; Oki, K.; Okuda, T.; Ono, M.; Onogi, R.; Oshima, A.; Ozawa, S.; Park, I. H.; Pshirkov, M. S.; Rodriguez, D. C.; Rubtsov, G.; Ryu, D.; Sagawa, H.; Saito, K.; Saito, Y.; Sakaki, N.; Sakurai, N.; Scott, L. M.; Sekino, K.; Shah, P. D.; Shibata, T.; Shibata, F.; Shimodaira, H.; Shin, B. K.; Shin, H. S.; Smith, J. D.; Sokolsky, P.; Stokes, B. T.; Stratton, S. R.; Stroman, T. A.; Suzawa, T.; Takahashi, Y.; Takamura, M.; Takeda, M.; Takeishi, R.; Taketa, A.; Takita, M.; Tameda, Y.; Tanaka, M.; Tanaka, K.; Tanaka, H.; Thomas, S. B.; Thomson, G. B.; Tinyakov, P.; Tirone, A. H.; Tkachev, I.; Tokuno, H.; Tomida, T.; Troitsky, S.; Tsunesada, Y.; Tsutsumi, K.; Uchihori, Y.; Udo, S.; Urban, F.; Wong, T.; Yamane, R.; Yamaoka, H.; Yamazaki, K.; Yang, J.; Yashiro, K.; Yoneda, Y.; Yoshida, S.; Yoshii, H.; Zollinger, R.; Zundel, Z.

    2017-01-01

    Cosmic rays in the energy range 1018.0-1018.5 eV are thought to have a light, probably protonic, composition. To study their origin one can search for anisotropy in their arrival directions. Extragalactic cosmic rays should be isotropic, but galactic cosmic rays of this type should be seen mostly along the galactic plane, and there should be a shortage of events coming from directions near the galactic anticenter. This is due to the fact that, under the influence of the galactic magnetic field, the transition from ballistic to diffusive behavior is well advanced, and this qualitative picture persists over the whole energy range. Guided by models of the galactic magnetic field that indicate that the enhancement along the galactic plane should have a standard deviation of about 20° in galactic latitude, and the deficit in the galactic anticenter direction should have a standard deviation of about 50° in galactic longitude, we use the data of the Telescope Array surface detector in 1018.0 to 1018.5 eV energy range to search for these effects. The data are isotropic. Neither an enhancement along the galactic plane nor a deficit in the galactic anticenter direction is found. Using these data we place an upper limit on the fraction of EeV cosmic rays of galactic origin at 1.3% at 95% confidence level.

  15. Hybrid solar cells from P3HT and silicon nanocrystals.

    PubMed

    Liu, Chin-Yi; Holman, Zachary C; Kortshagen, Uwe R

    2009-01-01

    We are reporting new hybrid solar cells based on blends of silicon nanocrystals (Si NCs) and poly-3(hexylthiophene) (P3HT) polymer in which a percolating network of the nanocrystals acts as the electron-conducting phase. The properties of composite Si NCs/P3HT devices made by spin-coating Si NCs and P3HT from a common solvent were studied as a function of Si NC size and Si NC/P3HT ratio. The open-circuit voltage and short-circuit current are observed to depend on the Si NC size due to changes in the bandgap and surface-area-to-volume ratio. Under simulated one-sun A.M. 1.5 direct illumination (100 mW/cm2), devices made with 35 wt % Si NCs 3-5 nm in size showed 1.15% power conversion efficiency.

  16. Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism.

    PubMed

    du Jardin, Kristian Gaarn; Jensen, Jesper Bornø; Sanchez, Connie; Pehrson, Alan L

    2014-01-01

    We previously reported that the investigational multimodal antidepressant, vortioxetine, reversed 5-HT depletion-induced memory deficits while escitalopram and duloxetine did not. The present report studied the effects of vortioxetine and the potential impact of its 5-HT1A receptor agonist and 5-HT3 receptor antagonist properties on 5-HT depletion-induced memory deficits. Recognition and spatial working memory were assessed in the object recognition (OR) and Y-maze spontaneous alternation (SA) tests, respectively. 5-HT depletion was induced in female Long-Evans rats using 4-cholro-DL-phenylalanine methyl ester HCl (PCPA) and receptor occupancies were determined by ex vivo autoradiography. Rats were acutely dosed with vortioxetine, ondansetron (5-HT3 receptor antagonist) or flesinoxan (5-HT1A receptor agonist). The effects of chronic vortioxetine administration on 5-HT depletion-induced memory deficits were also assessed. 5-HT depletion reliably impaired memory performance in both the tests. Vortioxetine reversed PCPA-induced memory deficits dose-dependently with a minimal effective dose (MED) ≤0.1mg/kg (∼80% 5-HT3 receptor occupancy; OR) and ≤3.0mg/kg (5-HT1A, 5-HT1B, 5-HT3 receptor occupancy: ∼15%, 60%, 95%) in SA. Ondansetron exhibited a MED ≤3.0μg/kg (∼25% 5-HT3 receptor occupancy; OR), but was inactive in the SA test. Flesinoxan had a MED ≤1.0mg/kg (∼25% 5-HT1A receptor occupancy; SA); only 1.0mg/kg ameliorated deficits in the NOR. Chronic p.o. vortioxetine administration significantly improved memory performance in OR and occupied 95%, 66%, and 9.5% of 5-HT3, 5-HT1B, and 5-HT1A receptors, respectively. Vortioxetine's effects on SA performance may involve 5-HT1A receptor agonism, but not 5-HT3 receptor antagonism, whereas the effects on OR performance may involve 5-HT3 receptor antagonism and 5-HT1A receptor agonism.

  17. Peripheral and spinal 5-HT receptors participate in cholestatic itch and antinociception induced by bile duct ligation in rats

    PubMed Central

    Tian, Bin; Wang, Xue-Long; Huang, Ya; Chen, Li-Hua; Cheng, Ruo-Xiao; Zhou, Feng-Ming; Guo, Ran; Li, Jun-Cheng; Liu, Tong

    2016-01-01

    Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7 were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3A were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7 receptor agonists induced scratching in BDL rats, whereas 5-HT3 agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 agonists or antagonists suppressed itch in BDL rats. 5-HT1A agonist attenuated, but 5-HT1A antagonist enhanced antinociception in BDL rats. 5-HT2 and 5-HT3 agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch. PMID:27824106

  18. Methylene blue inhibits function of the 5-HT transporter

    PubMed Central

    Oz, Murat; Isaev, Dmytro; Lorke, Dietrich E; Hasan, Muhammed; Petroianu, Georg; Shippenberg, Toni S

    2012-01-01

    BACKGROUND AND PURPOSE Methylene blue (MB) is commonly employed as a treatment for methaemoglobinaemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause 5-HT toxicity when administered with a 5-HT reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB on SERT. EXPERIMENTAL APPROACH Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP+), [3H]5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function. KEY RESULTS In EM4 cells expressing GFP-tagged human SERT (hSERT), MB concentration-dependently inhibited ASP+ accumulation (IC50: 1.4 ± 0.3 µM). A similar effect was observed in N2A cells. Uptake of [3H]5-HT was decreased by MB pretreatment. Furthermore, patch-clamp studies in hSERT expressing cells indicated that MB significantly inhibited 5-HT-evoked ion currents. Pretreatment with 8-Br-cGMP did not alter the inhibitory effect of MB on hSERT activity, and intracellular Ca2+ levels remained unchanged during MB application. Further experiments revealed that ASP+ binding to cell surface hSERT was reduced after MB treatment. In whole-cell radioligand experiments, exposure to MB (10 µM; 10 min) did not alter surface binding of the SERT ligand [125I]RTI-55. CONCLUSIONS AND IMPLICATIONS MB modulated SERT function and suggested that SERT may be an additional target upon which MB acts to produce 5-HT toxicity. PMID:21542830

  19. Menthol inhibits 5-HT3 receptor-mediated currents.

    PubMed

    Ashoor, Abrar; Nordman, Jacob C; Veltri, Daniel; Yang, Keun-Hang Susan; Shuba, Yaroslav; Al Kury, Lina; Sadek, Bassem; Howarth, Frank C; Shehu, Amarda; Kabbani, Nadine; Oz, Murat

    2013-11-01

    The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT3) receptors expressed in Xenopus laevis oocytes. 5-HT (1 μM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC50 = 163 μM) manner. The effects of menthol developed gradually, reaching a steady-state level within 10-15 minutes and did not involve G-proteins, since GTPγS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (-), (+), and racemic menthol inhibited 5-HT3 receptor-mediated currents to the same extent. Menthol inhibition was not altered by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by increasing concentrations of 5-HT. Furthermore, specific binding of the 5-HT3 antagonist [(3)H]GR65630 was not altered in the presence of menthol (up to 1 mM), indicating that menthol acts as a noncompetitive antagonist of the 5-HT3 receptor. Finally, 5-HT3 receptor-mediated currents in acutely dissociated nodose ganglion neurons were also inhibited by menthol (100 μM). These data demonstrate that menthol, at pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT3 receptors.

  20. The 5-HT[subscript 3A] Receptor Is Essential for Fear Extinction

    ERIC Educational Resources Information Center

    Kondo, Makoto; Nakamura, Yukiko; Ishida, Yusuke; Yamada, Takahiro; Shimada, Shoichi

    2014-01-01

    The 5-HT [subscript 3] receptor, the only ionotropic 5-HT receptor, is expressed in limbic regions, including the hippocampus, amygdala, and cortex. However, it is not known whether it has a role in fear memory processes. Analysis of 5-HT [subscript 3A] receptor knockout mice in fear conditioning paradigms revealed that the 5-HT [subscript 3A]…

  1. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mice lacking 5-HT 2C receptors displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT2CRs only in pro-opiomelanocortin (POMC) neurons. 5-HT2CR deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT2CR agonist); these effects were re...

  2. Multiple 5-HT receptors in the guinea-pig superior cervical ganglion.

    PubMed Central

    Watkins, C. J.; Newberry, N. R.

    1996-01-01

    1. We have studied the pharmacology of the depolarization by 5-hydroxytryptamine (5-HT) of the guinea-pig isolated superior cervical ganglion (SCG) using the grease-gap technique. We studied the effects of selective and non-selective antagonists on the responses to 5-HT and other 5-HT receptor agonists. 2. We have extended the pharmacology of the 5-HT3 receptor in this preparation by studying the effects of granisetron, BRL 46470 and mianserin on the concentration-response curve (CRC) to 2-methyl-5-HT. As with other 5-HT3 receptor antagonists, these compounds exhibited a lower affinity for guinea-pig 5-HT3 receptors than for rat 5-HT3 receptors. 3. We have confirmed that low concentrations of 5-HT (< or = 1 microM) mediate ketanserin-sensitive responses and higher concentrations of 5-HT also recruit 5-HT3 receptors. The responses to low concentrations of 5-HT were antagonized by low concentrations of ketanserin, spiperone, mianserin, DOI and LSD indicating probably mediation by 5-HT2A receptors. At high concentrations, the hallucinogen, DOI, but not LSD, evoked a ketanserin-sensitive depolarization. 4. Although mianserin could bind to the 5-HT2A receptors in this preparation, we could not demonstrate a down-regulation of depolarizations evoked by these receptors after a 10 day oral treatment with mianserin (10 mg kg-1, daily). 5. 5-Carboxamidotryptamine (5-CT) evoked a prolonged depolarization. Although high concentrations of 5-CT (> or = microM) appeared to activate 5-HT2A receptors, lower concentrations of 5-CT evoked a response with a distinct pharmacology. After studying the action of 20 selective and non-selective 5-HT receptor ligands we believe that this response may be mediated by a novel receptor; but its pharmacology is closest to that of receptors in the 5-HT2 receptor family. Like 5-CT, 5-HT (3-300 microM) could evoke an LSD-sensitive response in the presence of the 5-HT2 receptor antagonist, ketanserin and the 5-HT3 receptor antagonist, tropisetron

  3. Asymmetry in the triplet 3p-4s Mg lines in cool DZ white dwarfs

    NASA Astrophysics Data System (ADS)

    Allard, N. F.; Leininger, T.; Gadéa, F. X.; Brousseau-Couture, V.; Dufour, P.

    2016-04-01

    The purpose of the present work is to make an exhaustive study of the line shape of the triplet 3p-4s Mg line (Mgb triplet), which is perturbed by He in the extreme physical conditions found in the cool atmosphere of DZ white dwarfs. This study is undertaken by inferring both a unified theory of spectral line broadening and ab initio potential energies. Cool white dwarfs require a specific treatment for line broadening owing to the high helium densities that are involved. Beyond the conventional symmetrical Lorentzian core at low density, we show that the line profiles are asymmetrical and have significant additional contributions on the short wavelength side. This blue asymmetry is a consequence of low maxima in the corresponding Mg-He potential energy difference curves at short and intermediate internuclear distances. The new profiles are shown to provide a good fit to an SDSS (Sloan Digital Sky Survey) observation.

  4. Pressure-Temperature-Field Phase Diagram in the Ferromagnet U3P4

    NASA Astrophysics Data System (ADS)

    Araki, Shingo; Hayashida, Minami; Nishiumi, Naoto; Manabe, Hiroki; Ikeda, Yoichi; Kobayashi, Tatsuo C.; Murata, Keizo; Inada, Yoshihiko; Wiśniewski, Piotr; Aoki, Dai; Ōnuki, Yoshichika; Yamamoto, Etsuji; Haga, Yoshinori

    2015-02-01

    The pressure-temperature-field phase diagram and quantum fluctuation effect were investigated in the itinerant ferromagnet U3P4 by resistivity, ac susceptibility, and Hall effect measurements under high pressure. The zero-temperature ferromagnetic-to-paramagnetic transition is located at Pc ˜ 4.0 GPa. The tricritical point exists at P* = 3.8 GPa and T* = 32 K, where the ferromagnetic transition changes from second- to first-order. As a quantum fluctuation effect, the low-temperature resistivity at Pc follows T5/3 dependence, which was theoretically described in the case of a three-dimensional ferromagnet. This result indicates that the ferromagnetic-to-paramagnetic transition at Pc may be considered as weakly first-order. Another critical behavior, the huge enhancement of ρ0 observed at Pc, cannot be interpreted as the ferromagnetic fluctuation effect. The Hall effect measurements suggest that the magnetic structure in the ordered state changes under high pressure.

  5. Development of a HT seismic downhole tool.

    SciTech Connect

    Maldonado, Frank P.; Greving, Jeffrey J.; Henfling, Joseph Anthony; Chavira, David J.; Uhl, James Eugene; Polsky, Yarom

    2009-06-01

    Enhanced Geothermal Systems (EGS) require the stimulation of the drilled well, likely through hydraulic fracturing. Whether fracturing of the rock occurs by shear destabilization of natural fractures or by extensional failure of weaker zones, control of the fracture process will be required to create the flow paths necessary for effective heat mining. As such, microseismic monitoring provides one method for real-time mapping of the fractures created during the hydraulic fracturing process. This monitoring is necessary to help assess stimulation effectiveness and provide the information necessary to properly create the reservoir. In addition, reservoir monitoring of the microseismic activity can provide information on reservoir performance and evolution over time. To our knowledge, no seismic tool exists that will operate above 125 C for the long monitoring durations that may be necessary. Replacing failed tools is costly and introduces potential errors such as depth variance, etc. Sandia has designed a high temperature seismic tool for long-term deployment in geothermal applications. It is capable of detecting microseismic events and operating continuously at temperatures up to 240 C. This project includes the design and fabrication of two High Temperature (HT) seismic tools that will have the capability to operate in both temporary and long-term monitoring modes. To ensure the developed tool meets industry requirements for high sampling rates (>2ksps) and high resolution (24-bit Analog-to-Digital Converter) two electronic designs will be implemented. One electronic design will utilize newly developed 200 C electronic components. The other design will use qualified Silicon-on-Insulator (SOI) devices and will have a continuous operating temperature of 240 C.

  6. The P4 Health Spectrum - A Predictive, Preventive, Personalized and Participatory Continuum for Promoting Healthspan.

    PubMed

    Sagner, Michael; McNeil, Amy; Puska, Pekka; Auffray, Charles; Price, Nathan D; Hood, Leroy; Lavie, Carl J; Han, Ze-Guang; Chen, Zhu; Brahmachari, Samir Kumar; McEwen, Bruce S; Soares, Marcelo B; Balling, Rudi; Epel, Elissa; Arena, Ross

    2016-08-18

    Chronic diseases (i.e., noncommunicable diseases), mainly cardiovascular disease, cancer, respiratory diseases and type-2-diabetes, are now the leading cause of death, disability and diminished quality of life on the planet. Moreover, these diseases are also a major financial burden worldwide, significantly impacting the economy of many countries. Healthcare systems and medicine have progressively improved upon the ability to address infectious diseases and react to adverse health events through both surgical interventions and pharmacology; we have become efficient in delivering reactive care (i.e., initiating interventions once an individual is on the verge of or has actually suffered a negative health event). However, with slowly progressing and often 'silent' chronic diseases now being the main cause of illness, healthcare and medicine must evolve into a proactive system, moving away from a merely reactive approach to care. Minimal interactions among the specialists and limited information to the general practitioner and to the individual receiving care lead to a fragmented health approach, non-concerted prescriptions, a scattered follow-up and a suboptimal cost-effectiveness ratio. A new approach in medicine that is predictive, preventive, personalized and participatory, which we label here as "P4" holds great promise to reduce the burden of chronic diseases by harnessing technology and an increasingly better understanding of environment-biology interactions, evidence-based interventions and the underlying mechanisms of chronic diseases. In this concept paper, we propose a 'P4 Health Continuum' model as a framework to promote and facilitate multi-stakeholder collaboration with an orchestrated common language and an integrated care model to increase the healthspan.

  7. Performance evaluation of the microPET P4: a PET system dedicated to animal imaging

    NASA Astrophysics Data System (ADS)

    Tai, Y. C.; Chatziioannou, A.; Siegel, S.; Young, J.; Newport, D.; Goble, R. N.; Nutt, R. E.; Cherry, S. R.

    2001-07-01

    The microPET Primate 4-ring system (P4) is an animal PET tomograph with a 7.8 cm axial extent, a 19 cm diameter transaxial field of view (FOV) and a 22 cm animal port. The system is composed of 168 detector modules, each with an 8×8 array of 2.2×2.2×10 mm3 lutetium oxyorthosilicate crystals, arranged as 32 crystal rings 26 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 PS-PMT via a 10 cm long optical fibre bundle. The detectors have a timing resolution of 3.2 ns, an average energy resolution of 26%, and an average intrinsic spatial resolution of 1.75 mm. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. The reconstructed image spatial resolution ranges from 1.8 mm at the centre to 3 mm at 4 cm radial offset. The tomograph has a peak system sensitivity of 2.25% at the centre of the FOV with a 250-750 keV energy window. The noise equivalent count rate peaks at 100-290 kcps for representative object sizes. Images from two phantoms and three different types of laboratory animal demonstrate the advantage of the P4 system over the original prototype microPET, including its threefold improvement in sensitivity and a large axial FOV sufficient to image an entire mouse in a single bed position.

  8. P-P bond activation of P4 tetrahedron by group 13 carbenoid and its bis molybdenum pentacarbonyl adduct.

    PubMed

    Prabusankar, Ganesan; Doddi, Adinarayana; Gemel, Christian; Winter, Manuela; Fischer, Roland A

    2010-09-06

    Activation of white phosphorus with Ga(DDP) (DDP = 2-diiso-propylphenylamino-4-diiso-propylphenylimino-2-pentene) afforded [(DDP)Ga(P(4))] (1) by insertion of the Ga(I) center at one of the six P-P bonded edges of the P(4) tetrahedron. Further reaction of 1 with three equivalents of Mo(CO)(6) results in the formation of [(DDP)Ga(eta(2:1:1)-P(4)){Mo(CO)(5)}(2)] x 2 toluene (2). Compounds 1 and 2 are characterized by (1)H, (13)C, and (31)P NMR spectroscopy, elemental analysis, and single crystal X-ray structural analysis. The solid-state structure of molecule 1 reveals the first example of a structurally characterized GaP(4) core stabilized by a beta-diketiminate ligand. Compound 2 represents a rare type of coordination mode of a gallium supported P(4) butterfly structure.

  9. The putative α/β-hydrolases of Dietzia cinnamea P4 strain as potential enzymes for biocatalytic applications.

    PubMed

    Procópio, Luciano; Macrae, Andrew; van Elsas, Jan Dirk; Seldin, Lucy

    2013-03-01

    The draft genome of the soil actinomycete Dietzia cinnamea P4 reveals a versatile group of α/β-hydrolase fold enzymes. Phylogenetic and comparative sequence analyses were used to classify the α/β-hydrolases of strain P4 into six different groups: (i) lipases, (ii) esterases, (iii) epoxide hydrolases, (iv) haloacid dehalogenases, (v) C-C breaking enzymes and (vi) serine peptidases. The high number of lipases/esterases (41) and epoxide hydrolase enzymes (14) present in the relatively small (3.6 Mb) P4 genome is unusual; it is likely to be linked to the survival of strain P4 in its natural environment. Strain P4 is thus equipped with a large number of genes which would appear to confer survivability in harsh hot tropical soil. As such, this highly resilient soil bacterial strain provides an interesting genome for enzyme mining for applications in the field of biotransformations of polymeric compounds.

  10. Experiment 2035: Investigation of the EE-2 Casing Shoe and Openhole Interval

    SciTech Connect

    Brown, Donald W.; Dennis, Bert R.; Murphy, Hugh D.

    1983-11-09

    The primary objectives for Expt. 2035 are to determine the amount and distribution of the postulated flow behind the EE-2 casing and determine the flow split between the several openhole fracture entrances.

  11. Precision directional drilling of hot-dry-rock geothermal production well EE-3

    SciTech Connect

    Carden, R.S.; Rowley, J.C.; Helmick, C.

    1982-01-01

    The deviated directional drilling of the hot dry rock (HDR) geothermal production well EE-3 (Energy Extraction No. 3) was successfully completed on August 1981. The injection well, EE-2, previously had been drilled with its lower part at an inclination of 35/sup 0/ to the vertical. It reached an on-line depth of 15,292 feet and its bottom-hole temperature was 608/sup 0/F (320/sup 0/C). The production well EE-3 was required to be drilled 1200 feet (370 m) above and parallel to the injection well. This necessitated high precision, controlled-trajectory directional drilling operations. The directional drilling of EE-3 was accomplished within the required tolerances at a depth of 13,933 feet and a bottom-hole temperature of 580/sup 0/F (280/sup 0/C).

  12. Preferential acceleration and magnetic field enhancement in plasmas with e+/e- beam injection

    NASA Astrophysics Data System (ADS)

    Huynh, Cong Tuan; Ryu, Chang-Mo

    2016-03-01

    A theoretical model of current filaments predicting preferential acceleration/deceleration and magnetic field enhancement in a plasma with e+/e- beam injection is presented. When the e+/e- beams are injected into a plasma, current filaments are formed. The beam particles are accelerated or decelerated depending on the types of current filaments in which they are trapped. It is found that in the electron/ion ambient plasma, the e+ beam particles are preferentially accelerated, while the e- beam particles are preferentially decelerated. The preferential particle acceleration/deceleration is absent when the ambient plasma is the e+/e- plasma. We also find that the particle momentum decrease can explain the magnetic field increase during the development of Weibel/filamentation instability. Supporting simulation results of particle acceleration/deceleration and magnetic field enhancement are presented. Our findings can be applied to a wide range of astrophysical plasmas with the e+/e- beam injection.

  13. Interaction of Pyridostigmine with the 5-HT(3) Receptor Antagonist Ondansetron in Guinea Pigs

    DTIC Science & Technology

    1993-05-13

    5 - HT3 RECEPTOR - ANTAGONIST .ONDANSETRON IN GUINEA PIGS BR. Capacio, CE. Byers...apart. REFERENCES 1. Fozard JR. 5 -HT; The Enigma Variations. =JE, 8, 501-506 (December 1987). 2. Watling KJ. 5 - HT3 Receptor Agonists and Antagonists . In... 5 -HT receptor subtype three antagonists (5HT 3 ) such as the compound ondansetron (OND) have been identified as useful in the treatment of

  14. Evidence for 5-HT1B/1D and 5-HT2A receptors mediating constriction of the canine internal carotid circulation

    PubMed Central

    Centurión, David; Ortiz, Mario I; Sánchez-López, Araceli; De Vries, Peter; Saxena, Pramod R; Villalón, Carlos M

    2001-01-01

    The present study has investigated the preliminary pharmacological profile of the receptors mediating vasoconstriction to 5-hydroxytryptamine (5-HT) in the internal carotid bed of vagosympathectomised dogs. One minute intracarotid infusions of the agonists 5-HT (0.1–10 μg min−1), sumatriptan (0.3–10 μg min−1; 5-HT1B/1D), 5-methoxytryptamine (1–100 μg min−1; 5-HT1, 5-HT2, 5-HT4, 5-ht6 and 5-HT7) or DOI (0.31–10 μg min−1; 5-HT2), but not 5-carboxamidotryptamine (0.01–0.3 μg min−1; 5-HT1, 5-ht5A and 5-HT7), 1-(m-chlorophenyl)-biguanide (mCPBG; 1–1000 μg min−1; 5-HT3) or cisapride (1–1000 μg min−1; 5-HT4), resulted in dose-dependent decreases in internal carotid blood flow, without changing blood pressure or heart rate. The vasoconstrictor responses to 5-HT, which remained unaffected after saline, were resistant to blockade by i.v. administration of the antagonists ritanserin (100 μg kg−1; 5-HT2A/2B/2C) in combination with tropisetron (3000 μg kg−1; 5-HT3/4) or the cyclo-oxygenase inhibitor, indomethacin (5000 μg kg−1), but were abolished by the 5-HT1B/1D receptor antagonist, GR127935 (30 μg kg−1). Interestingly, after administration of GR127935, the subsequent administration of ritanserin unmasked a dose-dependent vasodilator component. GR127935 or saline did not practically modify the vasoconstrictor effects of 5-MeO-T. In animals receiving GR127935, the subsequent administration of ritanserin abolished the vasoconstrictor responses to 5-MeO-T unmasking a dose-dependent vasodilator component. The vasoconstriction induced by sumatriptan was antagonized by GR127935, but not by ritanserin. Furthermore, ritanserin (100 μg kg−1) or ketanserin (100 μg kg−1; 5-HT2A), but not GR127935, abolished DOI-induced vasoconstrictor responses. The above results suggest that 5-HT-induced internal carotid vasoconstriction is predominantly mediated by 5-HT1B/1D and 5-HT2A receptors

  15. Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans.

    PubMed

    Jafari, Gholamali; Xie, Yusu; Kullyev, Andrey; Liang, Bin; Sze, Ji Ying

    2011-06-15

    Serotonin [5-hydroxytryptamine (5-HT)]-absorbing neurons use serotonin reuptake transporter (SERT) to uptake 5-HT from extracellular space but do not synthesize it. While 5-HT-absorbing neurons have been identified in diverse organisms from Caenorhabditis elegans to humans, their function has not been elucidated. Here, we show that SERT in 5-HT-absorbing neurons controls behavioral response to food deprivation in C. elegans. The AIM and RIH interneurons uptake 5-HT released from chemosensory neurons and secretory neurons. Genetic analyses suggest that 5-HT secreted by both synaptic vesicles and dense core vesicles diffuse readily to the extrasynaptic space adjacent to the AIM and RIH neurons. Loss of mod-5/SERT function blocks the 5-HT absorption. mod-5/SERT mutants have been shown to exhibit exaggerated locomotor response to food deprivation. We found that transgenic expression of MOD-5/SERT in the 5-HT-absorbing neurons fully corrected the exaggerated behavior. Experiments of cell-specific inhibition of synaptic transmission suggest that the synaptic release of 5-HT from the 5-HT-absorbing neurons is not required for this behavioral modulation. Our data point to the role of 5-HT-absorbing neurons as temporal-spatial regulators of extrasynaptic 5-HT. Regulation of extrasynaptic 5-HT levels by 5-HT-absorbing neurons may represent a fundamental mechanism of 5-HT homeostasis, integrating the activity of 5-HT-producing neurons with distant targets in the neural circuits, and could be relevant to some actions of selective serotonin reuptake inhibitors in humans.

  16. Serotonin modifies the spontaneous spiking activity of gracile nucleus neurons in rats: role of 5-HT1A and 5-HT2 receptors.

    PubMed

    Grasso, C; Li Volsi, G; Barresi, M

    2016-06-01

    We tested the effects of microiontophoretic application of serotonin (5-HT) on the firing rate of neurons located in the gracile nucleus (GN) of rats. Application of 5-HT1A and 5-HT2 agonists and antagonists respectively mimicked/ modulated and blocked the effects produced by the amine, respectively. Among the tested neurons, 88.2% modified their background firing activity in the presence of 5-HT. Responsive neurons decreased their mean firing activity (MFA) in 56.7% of cases and increased it in the remaining 43.3%. To ascertain the specificity of the effects induced by 5-HT, we utilized 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and alpha-methyl-5-hydroxytryptamine (α-MET-5-HT), agonists for 5-HT1A and 5-HT2 receptors, respectively. The microiontophoresis of 8-OH-DPAT modified the background firing rate of all GN neurons (100% of tested neurons) mimicking the decrease of MFA evoked by 5-HT. The application of a-MET-5-HT modified the MFA in 76.9% of tested neurons, decreasing it in 61.5% of cases and increasing in the remaining 23.1%. The decrease of MFA induced by 8-OH-DPAT was antagonized by application of the 5-HT1A receptor antagonist N-[2-[-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635), while application of 5-HT2 receptor antagonist ketanserine tartrate (KET) antagonized only the increase of MFA induced by a-MET-5-HT. These results indicate that 5-HT is able to modulate the background firing activity of GN neurons by 5-HT1A and 5-HT2 receptors.

  17. Experimental and bioinformatic evidence that raspberry leaf blotch emaravirus P4 is a movement protein of the 30K superfamily.

    PubMed

    Yu, Chulang; Karlin, David G; Lu, Yuwen; Wright, Kathryn; Chen, Jianping; MacFarlane, Stuart

    2013-09-01

    Emaravirus is a recently described genus of negative-strand RNA plant viruses. Emaravirus P4 protein localizes to plasmodesmata, suggesting that it could be a viral movement protein (MP). In the current study, we showed that the P4 protein of raspberry leaf blotch emaravirus (RLBV) rescued the cell-to-cell movement of a defective potato virus X (PVX) that had a deletion mutation in the triple gene block 1 movement-associated protein. This demonstrated that RLBV P4 is a functional MP. Sequence analyses revealed that P4 is a distant member of the 30K superfamily of MPs. All MPs of this family contain two highly conserved regions predicted to form β-strands, namely β1 and β2. We explored by alanine mutagenesis the role of two residues of P4 (Ile106 and Asp127) located in each of these strands. We also made the equivalent substitutions in the 29K MP of tobacco rattle virus, another member of the 30K superfamily. All substitutions abolished the ability to complement PVX movement, except for the I106A substitution in the β1 region of P4. This region has been shown to mediate membrane association of 30K MPs; our results show that it is possible to make non-conservative substitutions of a well-conserved aliphatic residue within β1 without preventing the membrane association or movement function of P4.

  18. Effects of Constant Flickering Light on Refractive Status, 5-HT and 5-HT2A Receptor in Guinea Pigs

    PubMed Central

    Li, Tao; Zheng, Changyue; Ji, Shunmei; Ma, Yuanyuan; Zhang, Shuangshuang; Zhou, Xiaodong

    2016-01-01

    Purpose To investigate the effects of constant flickering light on refractive development, the role of serotonin (i.e.5-hydroxytryptamine, 5-HT)and 5-HT2A receptor in myopia induced by flickering light in guinea pigs. Methods Forty-five guinea pigs were randomly divided into three groups: control, form deprivation myopia (FDM) and flickering light induced myopia (FLM) groups(n = 15 for each group). The right eyes of the FDM group were covered with semitransparent hemispherical plastic shells serving as eye diffusers. Guinea pigs in FLM group were raised with illumination of a duty cycle of 50% at a flash frequency of 0.5Hz. The refractive status, axial length (AL), corneal radius of curvature(CRC) were measured by streak retinoscope, A-scan ultrasonography and keratometer, respectively. Ultramicroscopy images were taken by electron microscopy. The concentrations of 5-HTin the retina, vitreous body and retinal pigment epithelium (RPE) were assessed by high performance liquid chromatography, the retinal 5-HT2A receptor expression was evaluated by immunohistofluorescence and western blot. Results The refraction of FDM and FLM eyes became myopic from some time point (the 4th week and the 6th week, respectively) in the course of the experiment, which was indicated by significantly decreased refraction and longer AL when compared with the controls (p<0.05). The concentrations of 5-HT in the retina, vitreous body and RPE of FDM and FLM eyes were significantly increased in comparison with those of control eyes (both p<0.05). Similar to FDM eyes, the expression of retinal 5-HT2A receptor in FLM eyes was significantly up-regulated compared to that of control eyes (both p<0.05). Western blot analysis showed that retinal 5-HT2A receptor level elevated less in the FLM eyes than that in the FDM eyes. Moreover, the levels of norepinephrine and epinephrine in FDM and FLM groups generally decreased when compared with control groups (all p<0.05). Conclusions Constant flickering

  19. 31 CFR 351.32 - How are redemption values calculated for Series EE bonds with issue dates of May 1, 1997, through...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for Series EE bonds with issue dates of May 1, 1997, through April 1, 2005? 351.32 Section 351.32..., DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds...

  20. 31 CFR 351.19 - What are maturity periods of Series EE savings bonds with issue dates prior to May 1, 1995?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false What are maturity periods of Series EE... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates Prior to May 1,...

  1. 31 CFR 351.34 - What are the maturity periods of Series EE bonds with issue dates of May 1, 2005, or thereafter?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Series EE bonds with issue dates of May 1, 2005, or thereafter? 351.34 Section 351.34 Money and Finance... BUREAU OF THE FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of...

  2. 31 CFR 351.71 - How can I find out what my book-entry Series EE savings bonds are worth?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Series EE savings bonds are worth? 351.71 Section 351.71 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.71 How can I find out what my book-entry Series EE savings bonds are worth? (a) Redemption values. You may...

  3. 31 CFR 351.32 - How are redemption values calculated for Series EE bonds with issue dates of May 1, 1997, through...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for Series EE bonds with issue dates of May 1, 1997, through April 1, 2005? 351.32 Section 351.32..., DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds...

  4. 31 CFR 351.71 - How can I find out what my book-entry Series EE savings bonds are worth?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Series EE savings bonds are worth? 351.71 Section 351.71 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.71 How can I find out what my book-entry Series EE savings bonds are worth? (a) Redemption values. You may...

  5. 31 CFR 351.71 - How can I find out what my book-entry Series EE savings bonds are worth?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Series EE savings bonds are worth? 351.71 Section 351.71 Money and Finance: Treasury Regulations Relating... OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.71 How can I find out what my book-entry Series EE savings bonds are worth? (a) Redemption values. You may...

  6. 31 CFR 351.71 - How can I find out what my book-entry Series EE savings bonds are worth?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Series EE savings bonds are worth? 351.71 Section 351.71 Money and Finance: Treasury Regulations Relating... SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-entry Series EE Savings Bonds § 351.71 How can I find out what my book-entry Series EE savings bonds are worth? (a) Redemption values. You...

  7. 31 CFR 351.34 - What are the maturity periods of Series EE bonds with issue dates of May 1, 2005, or thereafter?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Series EE bonds with issue dates of May 1, 2005, or thereafter? 351.34 Section 351.34 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of...

  8. 31 CFR 351.34 - What are the maturity periods of Series EE bonds with issue dates of May 1, 2005, or thereafter?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Series EE bonds with issue dates of May 1, 2005, or thereafter? 351.34 Section 351.34 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of...

  9. 31 CFR 351.32 - How are redemption values calculated for Series EE bonds with issue dates of May 1, 1997, through...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for Series EE bonds with issue dates of May 1, 1997, through April 1, 2005? 351.32 Section 351.32..., DEPARTMENT OF THE TREASURY BUREAU OF THE FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds...

  10. 31 CFR 351.19 - What are maturity periods of Series EE savings bonds with issue dates prior to May 1, 1995?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false What are maturity periods of Series EE... PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates Prior to May 1,...

  11. Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver

    PubMed Central

    Fu, Jihua; Ma, Shaoxin; Li, Xin; An, Shanshan; Li, Tao; Guo, Keke; Lin, Min; Qu, Wei; Wang, Shanshan; Dong, Xinyue; Han, Xiaoyu; Fu, Ting; Huang, Xinping; Wang, Tianying; He, Siyu

    2016-01-01

    Hepatic triglycerides production and adipose lipolysis are pivotal for long-term stress (LTS) or hyperglucocorticoidemia-induced insulin resistance. 5-hydroxytryptamine (5-HT) has been demonstrated to induce hepatic lipid metabolic abnormality by activating mammalian target of rapamycin (mTOR). In present study, we explored whether 5-HT is involved in LTS effects in liver using restraint stress-exposed rats and cultured primary rat hepatocytes and HepG2 cells. LTS with hyperglucocorticoidemia induced hepatic 5-HT synthetic increase with tryptophan hydroxylase 1 (Tph1) up-regulation, and 5-HT2 receptor (5-HT2R, including 5-HT2A, 2B receptor) up-regulation in liver and visceral adipose, as well as hepatic mTOR activation with triglycerides and VLDL overproduction with steatosis, and visceral adipose lipolytic increase with high blood free fatty acids (FFAs) level. 5-HT exposure exhibited LTS-like effects in both tissues, and both LTS and 5-HT effects could be abolished significantly by blocking 5-HT2R. In HepG2 cells dexamethasone or palmitate-induced mTOR activation with triglycerides and VLDL overproduction were accompanied by up-regulations of 5-HT synthesis and 5-HT2R, which were significantly abolished by gene silencing Tph1 or 5-HT2R and were almost fully abolished by co-silencing of both, especially on VLDL overproduction. Chemical inhibition of Tph1 or/and 5-HT2R in both hepatocytes exhibited similar abolishment with genetic inhibition on dexamethason-induced effects. 5-HT-stimulated effects in both hepatocytes were fully abolished by blocking 5-HT2R, while 5-HT itself also up-regulated 5-HT2R. In conclusion, up-regulated hepatic 5-HT synthesis and 5-HT2R induced by both glucocorticoid and FFAs are crucial for LTS-induced hepatic steatosis with VLDL overproduction, while 5-HT by acting on 5-HT2R mediates mTOR activation in liver. PMID:26884719

  12. Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver.

    PubMed

    Fu, Jihua; Ma, Shaoxin; Li, Xin; An, Shanshan; Li, Tao; Guo, Keke; Lin, Min; Qu, Wei; Wang, Shanshan; Dong, Xinyue; Han, Xiaoyu; Fu, Ting; Huang, Xinping; Wang, Tianying; He, Siyu

    2016-01-01

    Hepatic triglycerides production and adipose lipolysis are pivotal for long-term stress (LTS) or hyperglucocorticoidemia-induced insulin resistance. 5-hydroxytryptamine (5-HT) has been demonstrated to induce hepatic lipid metabolic abnormality by activating mammalian target of rapamycin (mTOR). In present study, we explored whether 5-HT is involved in LTS effects in liver using restraint stress-exposed rats and cultured primary rat hepatocytes and HepG2 cells. LTS with hyperglucocorticoidemia induced hepatic 5-HT synthetic increase with tryptophan hydroxylase 1 (Tph1) up-regulation, and 5-HT2 receptor (5-HT2R, including 5-HT2A, 2B receptor) up-regulation in liver and visceral adipose, as well as hepatic mTOR activation with triglycerides and VLDL overproduction with steatosis, and visceral adipose lipolytic increase with high blood free fatty acids (FFAs) level. 5-HT exposure exhibited LTS-like effects in both tissues, and both LTS and 5-HT effects could be abolished significantly by blocking 5-HT2R. In HepG2 cells dexamethasone or palmitate-induced mTOR activation with triglycerides and VLDL overproduction were accompanied by up-regulations of 5-HT synthesis and 5-HT2R, which were significantly abolished by gene silencing Tph1 or 5-HT2R and were almost fully abolished by co-silencing of both, especially on VLDL overproduction. Chemical inhibition of Tph1 or/and 5-HT2R in both hepatocytes exhibited similar abolishment with genetic inhibition on dexamethason-induced effects. 5-HT-stimulated effects in both hepatocytes were fully abolished by blocking 5-HT2R, while 5-HT itself also up-regulated 5-HT2R. In conclusion, up-regulated hepatic 5-HT synthesis and 5-HT2R induced by both glucocorticoid and FFAs are crucial for LTS-induced hepatic steatosis with VLDL overproduction, while 5-HT by acting on 5-HT2R mediates mTOR activation in liver.

  13. In vitro model for frontal sinus obliteration with bioactive glass S53P4.

    PubMed

    Peltola, M J; Suonpää, J T; Andersson, H; Määttänen, H S; Aitasalo, K M; Yli-Urpo, A; Laippala, P J

    2000-01-01

    An in vitro model was used to investigate the behavior of a massive frontal sinus obliteration with bioactive glass S53P4 (BG) for clinical purposes. Two sizes of granules (0.63-0.8 mm or 0.8-1.0 mm) in 16 separate BG amounts, weight 25 g, were tested both in simulated body fluid (SBF) and a buffer containing trishydroxymethyl aminomethane citric acid (TRIS-c.a) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct current plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG masses were scanned by computer tomography (CT) and the scans analyzed by Region of Interest (ROI) technique. Calcium phosphate (CaP)- and silica (Si)-gel-layers were studied by scanning electron microscopy (SEM) at 1, 3, and 6 months. Cumulative loss of Si and P was stronger in TRIS -c.a than in SBF (p < 0.0001), and it was higher with smaller than with larger granules in both solutions (p < 0.0001). This was shown correspondingly by the decrease in Hounsfield units (HU) by ROI analysis (p < 0.0001). In SBF-soaked BG masses, the CaP-layer occurred on the uppermost granules, and in TRIS-c.a at 3-6 months, on the granules in the center and lower parts. The decrease of HU seems to reveal indirectly the resorption of BG.

  14. n-ZnO/p-4H-SiC diode: Structural, electrical, and photoresponse characteristics

    SciTech Connect

    Guziewicz, M. Jung, W.

    2015-09-07

    Epitaxial n-type ZnO film has been grown, on a commercial 5 μm thick p-type 4H-SiC(00.1) Al doped epilayer, by atomic layer deposition. A full width at half maximum of the ZnO 00.2 diffraction peak rocking curve of 0.34°{sup  }± 0.02° has been measured. Diodes formed on the n-ZnO/p-4H-SiC heterostructure show rectifying behavior with a forward to reverse current ratio at the level of 10{sup 9} at ±4 V, a leakage current density of ∼6 × 10{sup −8} A/cm{sup 2}, and a low ideality factor equal to 1.17 ± 0.04. In addition, the diodes exhibit selective photoresponse with a maximum at 367 nm, and with a current increase of ∼10{sup 3} under illuminations with respect to the dark value, which makes such devices prospective candidates for ultraviolet light sensors.

  15. QED Corrections to the 4p - 4d Transition Energies of Copperlike Heavy Ions

    SciTech Connect

    Chen, M H; Cheng, K T; Johnson, W R; Sapirstein, J

    2006-08-21

    Quantum electrodynamic (QED) corrections to 4p-4d transition energies of several copper-like ions with Z = 70-92 are calculated non-perturbatively in strong external fields to all orders in binding corrections. Dirac-Kohn-Sham potentials are used to account for screening and core-relaxation effects. For the 4p{sub 1/2}-4d{sub 3/2} transition in copperlike bismuth, thorium and uranium, results are in good agreement with empirical QED corrections deduced from differences between transition energies obtained from recent high-precision electron-beam ion-trap (EBIT) measurements and those calculated with the relativistic many-body perturbation theory (RMBPT). These comparisons provide sensitive tests of QED corrections for high angular momentum states in many-electron heavy ions and illustrate the importance of core-relaxation corrections. Comparisons are also made with other theories and with experiment on the 4s-4p transition energies of high-Z Cu-like ions as accuracy checks of the present RMBPT and QED calculations.

  16. QED corrections to the 4p-4d transition energies of copperlike heavy ions

    SciTech Connect

    Chen, M. H.; Cheng, K. T.; Johnson, W. R.; Sapirstein, J.

    2006-10-15

    Quantum electrodynamic (QED) corrections to 4p-4d transition energies of several copperlike ions with Z=70-92 are calculated nonperturbatively in strong external fields to all orders in binding corrections. Dirac-Kohn-Sham potentials are used to account for screening and core-relaxation effects. For the 4p{sub 1/2}-4d{sub 3/2} transition in copperlike bismuth, thorium, and uranium, results are in good agreement with empirical QED corrections deduced from differences between transition energies obtained from recent high-precision electron-beam ion-trap measurements and those calculated with the relativistic many-body perturbation theory (RMBPT). These comparisons provide sensitive tests of QED corrections for high-angular-momentum states in many-electron heavy ions and illustrate the importance of core-relaxation corrections. Comparisons are also made with other theories and with experiments on the 4s-4p transition energies of high-Z Cu-like ions as accuracy checks of the present RMBPT and QED calculations.

  17. Composition dependent mechanical behaviour of S53P4 bioactive glass putty for bone defect grafting.

    PubMed

    van Gestel, N A P; Hulsen, D J W; Geurts, J; Hofmann, S; Ito, K; Arts, J J; van Rietbergen, B

    2017-05-01

    To improve the handling properties of S53P4 bioactive glass granules for clinical applications, bioactive glass putty formulations were developed. These formulations contain both granules and a synthetic binder to form an injectable material that is easy to shape. To explore its applicability in load-bearing bone defect grafting, the relation between the putty composition and its mechanical behaviour was assessed in this study. Five putty formulations with variations in synthetic binder and granule content were mechanically tested in confined compression. The results showed that the impaction strains significantly decreased and the residual strains significantly increased with an increasing binder content. The stiffness of all tested formulations was found to be in the same range as the reported stiffness of cancellous bone. The measured creep strains were low and no significant differences between formulations were observed. The stiffness significantly increased when the samples were subjected to a second loading stage. The residual strains calculated from this second loading stage were also significantly different from the first loading stage, showing an increasing difference with an increasing binder content. Since residual strains are detrimental for graft layer stability in load-bearing defects, putty compositions with a low binder content would be most beneficial for confined, load-bearing bone defect grafting.

  18. 5-HT receptors and reward-related behaviour: a review.

    PubMed

    Hayes, Dave J; Greenshaw, Andrew J

    2011-05-01

    The brain's serotonin (5-HT) system is key in the regulation of reward-related behaviours, from eating and drinking to sexual activity. The complexity of studying this system is due, in part, to the fact that 5-HT acts at many receptor subtypes throughout the brain. The recent development of drugs with greater selectivity for individual receptor subtypes has allowed for rapid advancements in our understanding of this system. Use of these drugs in combination with animal models entailing selective reward measures (i.e. intracranial self-stimulation, drug self-administration, conditioned place preference) have resulted in a greater understanding of the pharmacology of reward-related processing and behaviour (particularly regarding drugs of abuse). The putative roles of each 5-HT receptor subtype in the pharmacology of reward are outlined and discussed here. It is concluded that the actions of 5-HT in reward are receptor subtype-dependent (and thus should not be generalized) and that all studied subtypes appear to have a unique profile which is determined by content (e.g. receptor function, localization - both throughout the brain and within the synapse) and context (e.g. type of behavioural paradigm, type of drug). Given evidence of altered reward-related processing and serotonergic function in numerous neuropsychiatric disorders, such as depression, schizophrenia, and addiction, a clearer understanding of the role of 5-HT receptor subtypes in this context may lead to improved drug development and therapeutic approaches.

  19. A history of atmospheric tritium gas (HT) 1950 2002

    NASA Astrophysics Data System (ADS)

    Happell, James D.; Östlund, Göte; Mason, Allen S.

    2004-07-01

    Data collected as a part of this study from 1968 2002 and data from other studies from 1950 1967 show that the maximum atmospheric concentration of tritium gas (HT) occurred in the early to mid 1970s, which corresponds to the era of frequent, large underground nuclear tests. These data clearly show that the major source of HT to the atmosphere between 1962 and the early 1990s was the underground testing of nuclear weapons. Samples collected at both our Alaska and Miami stations clearly show marked increases in the autumn of each year between 1970 and 1975 that were associated with large underground explosions conducted by the former Soviet Union at the Novaya Zemlya test site. Other significant sources of HT include accidental releases of HT used in the manufacture and maintenance of nuclear weapons stockpiles, the reprocessing of spent nuclear fuel rods and emissions from nuclear power plants. Since the early 1990s, when underground testing largely ceased, emission estimates from our data agree very well with United Nations estimates of worldwide releases from fuel reprocessing and nuclear power plants, suggesting that the nuclear power industry is now the major source of HT to the atmosphere.

  20. Helium-induced weld degradation of HT-9 steel

    SciTech Connect

    Wang, Chin-An; Chin, B.A.; Lin, Hua T.; Grossbeck, M.L.

    1992-12-31

    Helium-bearing Sandvik HT-9 ferritic steel was tested for weldability to simulate the welding of structural components of a fusion reactor after irradiation. Helium was introduced into HT-9 steel to 0.3 and 1 atomic parts per million (appm) by tritium doping and decay. Autogenous single pass full penetration welds were produced using the gas tungsten arc (GTA) welding process under laterally constrained conditions. Macroscopic examination showed no sign of any weld defect in HT-9 steel containing 0.3 appm helium. However, intergranular micro cracks were observed in the HAZ of HT-9 steel containing 1 appm helium. The microcracking was attributed to helium bubble growth at grain boundaries under the influence of high stresses and temperatures that were present during welding. Mechanical test results showed that both yield strength (YS) and ultimate tensile strength (UTS) decreased with increasing temperature, while the total elongation increased with increasing temperature for all control and helium-bearing HT-9 steels.

  1. Characterization of 5-HT receptors mediating constriction of porcine carotid arteriovenous anastomoses; involvement of 5-HT1B/1D and novel receptors

    PubMed Central

    De Vries, Peter; Villalón, Carlos M; Heiligers, Jan P C; Saxena, Pramod R

    1998-01-01

    It was previously shown that porcine cranial arteriovenous anastomoses (AVAs) constrict to 5-hydroxytryptamine (5-HT), ergotamine, dihydroergotamine, as well as sumatriptan and that sumatriptan acts exclusively via 5-HT1B/1D receptors. The present study was devoted to establish the contribution of 5-HT1B/1D receptors in the constriction of AVAs elicited by 5-HT (in presence of 0.5 mg kg−1 ketanserin), ergotamine and dihydroergotamine in anaesthetized pigs.Intracarotid infusion of 5-HT (2 μg kg−1 min−1) and intravenous doses of ergotamine (2.5–20 μg kg−1) and dihydroergotamine (3–100 μg kg−1) reduced AVA and increased nutrient blood flows and vascular conductances. The vasodilator response to 5-HT, observed mainly in the skin and ear, was much more prominent than that of the ergot alkaloids.Treatment with the 5-HT1B/1D receptor antagonist GR127935 (0.5 mg kg−1, i.v.) significantly attenuated both ergot-induced AVA constriction and arteriolar dilatation, whereas GR127935 only slightly affected the carotid vascular effects of 5-HT.The results suggest that 5-HT constricts carotid AVAs primarily via receptors, which seem to differ from those (5-HT1B/1D) stimulated by sumatriptan. The ergot alkaloids produce AVA constriction for a substantial part via 5-HT1B/1D receptors, but also stimulate unidentified receptors. Both these non-5-HT1B/1D receptors may be targets for the development of novel antimigraine drugs.The moderate vasodilator response to the ergot derivatives seems to be mediated, at least in part, by 5-HT1B/1D receptors, whereas the arteriolar dilatation caused by 5-HT may be mediated by other, possibly 5-HT7 receptors. PMID:9605562

  2. 5-HT1A and 5-HT1B receptors differentially modulate rate and timing of auditory responses in the mouse inferior colliculus

    PubMed Central

    Ramsey, Lissandra Castellan Baldan; Sinha, Shiva R.; Hurley, Laura M.

    2010-01-01

    Serotonin is a physiological signal that translates both internal and external information about behavioral context into changes in sensory processing through a diverse array of receptors. The details of this process, particularly how receptors interact to shape sensory encoding, are poorly understood. In the inferior colliculus, a midbrain auditory nucleus, serotonin (5-HT) 1A receptors have suppressive and 5-HT1B receptors have facilitatory effects on evoked responses of neurons. We explored how these two receptor classes interact by testing three hypotheses: that they 1) affect separate neuron populations, 2) affect different response properties, or 3) have different endogenous patterns of activation. The first two hypotheses were tested by iontophoretic application of 5-HT1A and 5-HT1B receptor agonists individually and together to neurons in vivo. 5-HT1A and 5-HT1B agonists affected overlapping populations of neurons. During co-application, 5-HT1A and 5-HT1B agonists influenced spike rate and frequency bandwidth additively, with each moderating the effect of the other. In contrast, although both agonists individually influenced latencies and interspike intervals, the 5-HT1A agonist dominated these measurements during co-application. The third hypothesis was tested by applying antagonists of the 5-HT1A and 5-HT1B receptors. Blocking 5-HT1B receptors was complementary to activation of the receptor, but blocking 5-HT1A receptors was not, suggesting the endogenous activation of additional receptor types. These results suggest that cooperative interactions between 5-HT1A and 5-HT1B receptors shape auditory encoding in the IC, and that the effects of neuromodulators within sensory systems may depend nonlinearly on the specific profile of receptors that are activated. PMID:20646059

  3. 5-HT manipulation and dietary choice: variable carbohydrate (Polycose) suppression demonstrated only under specific experimental conditions.

    PubMed

    Lawton, C L; Blundell, J E

    1993-01-01

    The effects of six 5-HT anorectic agents, d-fenfluramine (5-HT releaser and reuptake inhibitor), fluoxetine (5-HT reuptake inhibitor), mCPP (5-HT1B/5-HT1C receptor agonist), RU24969 (5-HT1A/5-HT1B receptor agonist), MK212 (5-HT1C receptor agonist) and DOI (5-HT2/5-HT1C receptor agonist), and two non-5-HT anorectic agents, salbutamol (beta 2-adrenergic agonist) and d-amphetamine (catecholaminergic agonist), were examined in an experimental procedure designed to disclose selective effects on carbohydrate consumption. In this procedure, a revised version of what we have termed "The Classic Sclafani Paradigm", animals are presented with powdered Polycose as an optional carbohydrate supplement to hydrated chow (nutritionally complete diet). All drugs produced significant reductions in total (hydrated chow plus powdered Polycose) intake. However, only the 5-HT drugs DOI and fluoxetine exerted significantly stronger anorectic effects on intake of powdered Polycose than on intake of hydrated chow. d-Fenfluramine also showed a tendency to selectively suppress Polycose intake but this effect marginally failed to reach significance. These results suggest that when experimental conditions are favourable, what appears to be selective carbohydrate (Polycose) suppression can be demonstrated with certain 5-HT drugs. They also suggest that a selective effect on carbohydrate intake is not the most prominent feeding response to 5-HT drugs.

  4. Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase

    PubMed Central

    Graham, Todd R.

    2016-01-01

    Phospholipid flippases in the type IV P-type ATPase (P4-ATPases) family establish membrane asymmetry and play critical roles in vesicular transport, cell polarity, signal transduction, and neurologic development. All characterized P4-ATPases flip glycerophospholipids across the bilayer to the cytosolic leaflet of the membrane, but how these enzymes distinguish glycerophospholipids from sphingolipids is not known. We used a directed evolution approach to examine the molecular mechanisms through which P4-ATPases discriminate substrate backbone. A mutagenesis screen in the yeast Saccharomyces cerevisiae has identified several gain-of-function mutations in the P4-ATPase Dnf1 that facilitate the transport of a novel lipid substrate, sphingomyelin. We found that a highly conserved asparagine (N220) in the first transmembrane segment is a key enforcer of glycerophospholipid selection, and specific substitutions at this site allow transport of sphingomyelin. PMID:27432949

  5. The lipid kinase PI5P4Kβ is an intracellular GTP sensor for metabolism and tumorigenesis

    PubMed Central

    Sumita, Kazutaka; Lo, Yu-Hua; Takeuchi, Koh; Senda, Miki; Kofuji, Satoshi; Ikeda, Yoshiki; Terakawa, Jumpei; Sasaki, Mika; Yoshino, Hirofumi; Majd, Nazanin; Zheng, Yuxiang; Kahoud, Emily Rose; Yokota, Takehiro; Emerling, Brooke M.; Asara, John M.; Ishida, Tetsuo; Locasale, Jason W.; Daikoku, Takiko; Anastasiou, Dimitrios; Senda, Toshiya; Sasaki, Atsuo T.

    2016-01-01

    Summary While cellular GTP concentration dramatically changes in response to an organism’s cellular status, whether it serves as a metabolic cue for biological signaling remains elusive due to the lack of molecular identification of GTP sensors. Here we report that PI5P4Kβ, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kβ preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration. Structural and biological analyses reveal that the GTP-sensing activity of PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer therapeutic target. PMID:26774281

  6. Cerebral 5-HT release correlates with [(11)C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain.

    PubMed

    Jørgensen, Louise M; Weikop, Pia; Villadsen, Jonas; Visnapuu, Tanel; Ettrup, Anders; Hansen, Hanne D; Baandrup, Anders O; Andersen, Flemming L; Bjarkam, Carsten R; Thomsen, Carsten; Jespersen, Bo; Knudsen, Gitte M

    2017-02-01

    Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [(11)C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [(11)C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [(11)C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2-11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in [(11)C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [(11)C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high.

  7. Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

    PubMed Central

    Dudok, Jacobus J.; Groffen, Alexander J. A.; Toonen, Ruud F. T.; Verhage, Matthijs

    2011-01-01

    The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT) promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival. PMID:22140524

  8. Clinical follow-up method for frontal sinus obliteration with bioactive glass S53P4.

    PubMed

    Peltola, M J; Suonpää, J T; Määttänen, H S; Varpula, M J; Aitasalo, K M; Yli-Urpo, A; Laippala, P J

    2001-01-01

    A clinical follow-up method was developed to investigate the behavior of a massive amount of bioactive glass S53P4 (BG) clinically used in frontal sinus obliteration. Two sizes of granules (0.63-0.8 mm or 0.8-1.0 mm) in 16 separate BG amounts, weight 25 g, were tested both in simulated body fluid (SBF) and in a buffer containing tris-hydroxymethyl aminomethane citric acid (TRIS-c.a) in standard conditions. The dissolution of silicon (Si) and phosphate (P) was detected with direct current plasma atom emission spectroscopy (DCP-AES) monthly up to 6 months. The BG masses were scanned both wet in the solutions and dried by computer tomography (CT), and the scans were analyzed by Region of Interest (ROI) technique. Calcium phosphate (CaP)- and silica (Si)-gel-layers were studied by scanning electron microscopy (SEM) at 1, 3, and 6 months. Cumulative loss of Si and P was stronger in TRIS-c.a than in SBF (p < 0.0001), and it was higher with smaller than with larger granules in both solutions (p < 0.0001). This was shown correspondingly by the decrease of Hounsfield units (HUs) in ROI analysis (p < 0.0001). The level of HUs was lower with dried than with wet BG (p < 0.0001). The results were compared for clinical ROI analysis of patients with obliterated frontal sinuses up to 48 months and they were parallel. The follow-up method seems to indirectly reveal the behavior of BG and the healing process in the obliterated cavity.

  9. SLSF in-reactor local fault safety experiment P4. Final report

    SciTech Connect

    Thompson, D. H.; Holland, J. W.; Braid, T. H.; Ragland, W. A.

    1985-09-01

    The Sodium Loop Safety Facility (SLSF), a major facility in the US fast-reactor safety program, has been used to simulate a variety of sodium-cooled fast reactor accidents. SLSF experiment P4 was conducted to investigate the behavior of a "worse-than-case" local fault configuration. Objectives of this experiment were to eject molten fuel into a 37-pin bundle of full-length Fast-Test-Reactor-type fuel pins form heat-generating fuel canisters, to characterize the severity of any molten fuel-coolant interaction, and to demonstrate that any resulting blockage could either be tolerated during continued power operation or detected by global monitors to prevent fuel failure propagation. The design goal for molten fuel release was 10 to 30 g. Explusion of molten fuel from fuel canisters caused failure of adjacent pins and a partial flow channel blockage in the fuel bundle during full-power operation. Molten fuel and fuel debris also lodged against the inner surface of the test subassembly hex-can wall. The total fuel disruption of 310 g evaluated from posttest examination data was in excellent agreement with results from the SLSF delayed neutron detection system, but exceeded the target molten fuel release by an order of magnitude. This report contains a summary description of the SLSF in-reactor loop and support systems and the experiment operations. results of the detailed macro- and microexamination of disrupted fuel and metal and results from the analysis of the on-line experimental data are described, as are the interpretations and conclusions drawn from the posttest evaluations. 60 refs., 74 figs.

  10. 5-HT2 receptors facilitate JC polyomavirus entry.

    PubMed

    Assetta, Benedetta; Maginnis, Melissa S; Gracia Ahufinger, Irene; Haley, Sheila A; Gee, Gretchen V; Nelson, Christian D S; O'Hara, Bethany A; Allen Ramdial, Stacy-ann A; Atwood, Walter J

    2013-12-01

    The human JC polyomavirus (JCPyV) causes the rapidly progressing demyelinating disease progressive multifocal leukoencephalopathy (PML). The disease occurs most often in individuals with AIDS but also occurs in individuals receiving immunomodulatory therapies for immune-related diseases such as multiple sclerosis. JCPyV infection of host cells requires the pentasaccharide lactoseries tetrasaccharide c (LSTc) and the serotonin receptor 5-hydroxytryptamine (5-HT) receptor 5-HT2AR. While LSTc is involved in the initial attachment of virus to cells via interactions with VP1, the mechanism by which 5-HT2AR contributes to infection is not clear. To further define the roles of serotonin receptors in infection, HEK293A cells, which are poorly permissive to JCPyV, were transfected with 14 different isoforms of serotonin receptor. Only 5-HT2 receptors were found to support infection by JCPyV. None of the other 11 isoforms of serotonin receptor supported JCPyV infection. Expression of 5-HT2 receptors did not increase binding of JCPyV to cells, but this was not unexpected, given that the cells uniformly expressed the major attachment receptor, LSTc. Infection of these cells remained sensitive to inhibition with soluble LSTc, confirming that LSTc recognition is required for JCPyV infection. Virus internalization into HEK293A cells was significantly and specifically enhanced when 5HT2 receptors were expressed. Taken together, these data confirm that the carbohydrate LSTc is the attachment receptor for JCPyV and that the type 2 serotonin receptors contribute to JCPyV infection by facilitating entry.

  11. Role of 5-HT2 receptors in diabetes: Swertiamarin seco-iridoid glycoside might be a possible 5-HT2 receptor modulator.

    PubMed

    Sonawane, Rakesh Deelip; Deore, Vijaykumar B; Patil, Savita D; Patil, Chandragouda R; Surana, Sanjay J; Goyal, Ramesh K

    2015-05-15

    In the present review, we are focusing on modulators of 5-HT2 receptors, swertiamarin and their role in diabetes. These drugs possess both central and peripheral actions in various animal models of depression, diabetes and obesity. Swertiamarin and 5-HT2 antagonist are reported antidepressant, hypolipidemic and beneficial in peripheral vasculopathy. In contrast to this, 5-HT2C selective agonist decreases hyperglycemia, hyperlipidemia and insulin secretogogue by action. Selective serotonin reuptake inhibitors (SSRIs) are known antidepressant having weight gain as an adverse effect. Swertiamarin has similar pharmacological actions as 5-HT2 antagonist and 5-HT2C selective agonist. This warrants that swertiamarin might modulate 5-HT2 receptors rather than affecting the uptake of serotonin. In the light of present investigation, the mechanism of these drugs can correlate the role of central and peripheral 5-HT2 receptors in diabetes.

  12. Synthesis and structure-activity relationships of new carbonyl guanidine derivatives as novel dual 5-HT2B and 5-HT7 receptor antagonists.

    PubMed

    Moritomo, Ayako; Yamada, Hiroyoshi; Watanabe, Toshihiro; Itahana, Hirotsune; Akuzawa, Shinobu; Okada, Minoru; Ohta, Mitsuaki

    2013-12-15

    To identify potent dual 5-HT2B and 5-HT7 receptor antagonists, we synthesized a series of novel carbonyl guanidine derivatives and examined their structure-activity relationships. Among these compounds, N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine (10) had a good in vitro profile, that is, potent affinity for human 5-HT2B and 5-HT7 receptor subtypes (Ki=1.8 nM and Ki=17.6 nM, respectively) and high selectivity over 5-HT2A, 5-HT2C, α1, D2 and M1 receptors. Compound 10 also showed a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs when orally administered.

  13. 5-HT is a potent relaxant in rat superior mesenteric veins.

    PubMed

    Watts, Stephanie W; Darios, Emma S; Seitz, Bridget M; Thompson, Janice M

    2015-02-01

    Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (∼2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT1/5-HT7)>5-HT = LP-44 (5-HT7)>PNU109291 (5-HT1D) = BW723C86 (5-HT2B). 8-OH-DPAT (5-HT1A/7), CP93129 (5-HT1B), mCPBG (5-HT3/4), AS19 (5-HT7) and TCB-2 (5-HT2A) did not relax the isolated vein. Consistent with these findings, two different 5-HT7 receptor antagonists SB 269970 and LY215840 but not the 5-HT2B receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg(-1) min(-1), sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT7 receptor.

  14. GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: are 5-HT5B receptors involved?

    PubMed

    Sánchez-Maldonado, Carolina; López-Sánchez, Pedro; Anguiano-Robledo, Liliana; Leopoldo, Marcello; Lacivita, Enza; Terrón, José A

    2015-04-01

    The 5-HT1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT1A, 5-HT1B/1D and 5-HT7 receptor agonist, and 5-HT5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT1B and 5-HT1D receptor antagonists. Also, expression of 5-HT5A and 5-HT5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction. Decreases in diastolic blood pressure induced by 5-CT (0.001-10 μg/kg, intravenously) were analyzed in anesthetized rats that had received intravenous vehicle (1 mL/kg), SB-224289 (5-HT1B antagonist; 0.3 and 1.0 mg/kg), BRL15572 (5-HT1D antagonist; 0.3 and 1.0 mg/kg), SB-224289 + BRL15572 (0.3 mg/kg, each), or SB-224289 + BRL15572 (0.3 mg/kg, each) + GR-127935 (1 mg/kg). Because only the latter treatment inhibited 5-CT-induced hypotension, suggestive of a mechanism unrelated to 5-HT1B/1D receptors, the effects of antagonists/ligands at 5-HT5A (SB-699551, 1 mg/kg), 5-HT6 (SB-399885, 1 mg/kg), and 5-HT1B/1D/5A/5B/7 receptors (ergotamine, 0.1 mg/kg) on 5-CT-induced hypotension were tested. Interestingly, only ergotamine blocked 5-CT-induced responses; this effect closely paralleled that of SB-224289 + BRL-15572 + GR-127935. Neither did ergotamine nor GR-127935 inhibit hypotensive responses induced by the 5-HT7 receptor agonist, LP-44. Faint but clear bands corresponding to 5-HT5A and 5-HT5B receptor mRNAs in aorta and mesenteric arteries were detected. Results suggest that the GR-127935-sensitive mechanism mediating hypotension in rats is unrelated to 5-HT1B, 5-HT1D, 5-HT5A, 5-HT6, and 5-HT7 receptors. This mechanism, however, resembles putative 5-HT5B receptors.

  15. 5-HT is a potent relaxant in rat superior mesenteric veins

    PubMed Central

    Watts, Stephanie W; Darios, Emma S; Seitz, Bridget M; Thompson, Janice M

    2015-01-01

    Serotonin (5-HT, 5-hydroxytryptamine) reduces blood pressure of the conscious rat when administered chronically (1 week). 5-HT does not directly relax isolated arteries, and microsphere experiments in 5-HT-infused rats suggested that 5-HT increased flow to the splanchnic bed. We hypothesized that 5-HT increased splanchnic flow because of direct venous relaxation; our focus was thus on the superior mesenteric vein (SMV) as an important vein in splanchnic circulation. Real-time RT-PCR, immunohistochemistry and Western analyses supported the predominant expression of the 5-HT2B and 5-HT7 receptor in the SMV. The SMV was mounted in tissue baths for measurement of isometric contraction. 5-HT caused a concentration-dependent relaxation of the endothelin-1 (ET-1)-contracted vein. The threshold of 5-HT-induced venous relaxation was significantly lower than for 5-HT-induced venous contraction (∼2 vs. 700 nmol/L, respectively). A series of serotonergic agonists established in their use of receptor characterization was tested, and the following rank order of potency found for agonist-induced relaxation (receptor selectivity): 5-CT (5-HT1/5-HT7)>5-HT = LP-44 (5-HT7)>PNU109291 (5-HT1D) = BW723C86 (5-HT2B). 8-OH-DPAT (5-HT1A/7), CP93129 (5-HT1B), mCPBG (5-HT3/4), AS19 (5-HT7) and TCB-2 (5-HT2A) did not relax the isolated vein. Consistent with these findings, two different 5-HT7 receptor antagonists SB 269970 and LY215840 but not the 5-HT2B receptor antagonist LY272015 nor the nitric oxide synthase inhibitor LNNA abolished 5-CT-induced relaxation of the isolated SMV. 5-CT (1 μg kg−1 min−1, sc) also reduced blood pressure over 7 days. These findings suggest that 5-HT directly relaxes the SMV primarily through activation of the 5-HT7 receptor. PMID:25692021

  16. Control System of Neutral Beam Injection on HT-7

    NASA Astrophysics Data System (ADS)

    Wang, Yongjun; Hu, Chundong; Liu, Zhimin; Liu, Sheng; Song, Shihua; Yang, Daoye

    2005-06-01

    Neutral Beam Injection control system (NBICS) is constructed to measure the plasma current, Magnet current, vacuum pressure, cryopump temperature, control water cooling, filament voltage, and power supply, etc. The NBICS, consisting mainly of a Programmable Logic Controller (PLC) subsystem, data acquisition and processing subsystem and cryopump and vacuum pressure monitoring subsystem, has successfully been used on a NBI device. In this article, the design of NBICS on HT-7 is discussed and each subsystem is described in particular. In addition, some experimental results are reported which are very important data for further research related to the HT-7 tokamak.

  17. The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation.

    PubMed

    Meneses, A; Perez-Garcia, G; Liy-Salmeron, G; Flores-Galvez, D; Castillo, C; Castillo, E

    2008-12-16

    Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.

  18. The 5-HT1-like receptor mediating the increase in canine external carotid blood flow: close resemblance to the 5-HT1D subtype.

    PubMed Central

    Villalón, C M; Terrón, J A

    1994-01-01

    1. It has recently been shown that the increase in external carotid blood flow induced by 5-hydroxy-tryptamine (5-HT) in the anaesthetized dog, being mimicked by 5-carboxamidotryptamine (5-CT), inhibited by methiothepin, vagosympathectomy and sympatho-inhibitory drugs, and resistant to blockade by ritanserin and MDL 72222, is mediated by stimulation of prejunctional 5-HT1-like receptors leading to an inhibitory action on carotid sympathetic nerves; these 5-HT1-like receptors are unrelated to either the 5-HT1A, 5-HT1B or 5-HT1C (now 5-HT2C) receptor subtypes. Inasmuch as 5-CT, 5-methoxytryptamine, sumatriptan and metergoline display high affinity, amongst other 5-HT binding sites, for the 5-HT1D subtype, in the present study we have used these drugs in an attempt to determine whether the above inhibitory prejunctional 5-HT1-like receptors correlate with the 5-HT1D subtype. 2. One-minute intracarotid (i.c.) infusions of 5-HT (0.3, 1, 3 and 10 micrograms), 5-CT (0.01, 0.03, 0.1 and 0.3 micrograms), 5-methoxytryptamine (1, 3, 10 and 30 micrograms) and sumatriptan (1, 3, 10, 30 and 100 micrograms) resulted in dose-dependent increases in external carotid blood flow (without changes in mean arterial blood pressure or heart rate) with the following rank order of agonist potency: 5-CT >> 5-HT > 5-methoxytryptamine > or = sumatriptan. Interestingly, sumatriptan-induced vasodilatation was followed by a more pronounced vasoconstriction. 3. The external carotid vasodilator effects of 5-HT, 5-CT, 5-methoxytryptamine and sumatriptan were dose-dependently and specifically antagonized by metergoline (10, 30 and/or 100 micrograms kg-1, i.v.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812603

  19. Probing the Higgs with angular observables at future e+e- colliders

    NASA Astrophysics Data System (ADS)

    Liu, Zhen

    2016-10-01

    I summarize our recent works on using differential observables to explore the physics potential of future e+e- colliders in the framework of Higgs effective field theory. This proceeding is based upon Refs. 1 and 2. We study angular observables in the e+e-→ ZHℓ+ℓ-bb¯ channel at future circular e+e- colliders such as CEPC and FCC-ee. Taking into account the impact of realistic cut acceptance and detector effects, we forecast the precision of six angular asymmetries at CEPC (FCC-ee) with center-of-mass energy s = 240 GeV and 5 (30) ab-1 integrated luminosity. We then determine the projected sensitivity to a range of operators relevant for the Higgsstrahlung process in the dimension-6 Higgs EFT. Our results show that angular observables provide complementary sensitivity to rate measurements when constraining various tensor structures arising from new physics. We further find that angular asymmetries provide a novel means of constraining the “blind spot” in indirect limits on supersymmetric scalar top partners. We also discuss the possibility of using ZZ-fusion at e+e- machines at different energies to probe new operators.

  20. The atypical 5-HT2 receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT2A receptor subtype

    PubMed Central

    Centurión, David; Ortiz, Mario I; Saxena, Pramod R; Villalón, Carlos M

    2002-01-01

    In pithed rats, 5-HT mediates tachycardia both directly (by 5-HT2 receptors) and indirectly (by a tyramine-like effect). The receptor mediating tachycardia directly has been classified as an ‘atypical' 5-HT2 receptor since it was ‘weakly' blocked by ketanserin. Moreover, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, failed to mimic 5-HT-induced tachycardia. Since 5-HT2 receptors consist of 5-HT2A, 5-HT2B and 5-HT2C subtypes, this study investigated if these subtypes mediate the above response. In pithed rats, intraperitoneally (i.p.) pre-treated with reserpine (5 mg kg−1), intravenous (i.v.) administration of 5-HT, 5-methoxytryptamine (5-MeO-T), 1-(3-chlorophenyl) piperazine (mCPP) and 5-carboxamidotryptamine (5-CT) (10, 30, 100 and 300 μg kg−1 each), produced dose-dependent tachycardic responses. Interestingly, DOI (10 – 1000 μg kg−1, i.v.) induced only slight, dose-unrelated, tachycardic responses, whilst the 5-HT2C agonist, Ro 60-0175 (10 – 1000 μg kg−1, i.v.), produced a slight tachycardia only at 300 and 1000 μg kg−1. In contrast, sumatriptan and 1-(m-trifluoromethylphenyl)- piperazine (TFMPP) were inactive. The rank order of potency was: 5-HT⩾5-MeO-T> mCPP⩾5-CT⩾DOI>Ro 60-0175. The tachycardic responses to 5-HT, which remained unaffected after i.v. saline (0.3 and 1 ml kg−1) or propranolol (3 mg kg−1), were selectively blocked by the 5-HT2A antagonists ketanserin (30 and 100 μg kg−1) or spiperone (10 and 30 μg kg−1) as well as by the non-selective 5-HT2 antagonists, ritanserin (10 and 30 μg kg−1) or mesulergine (100 μg kg−1). Remarkably, these responses were unaffected by the antagonists rauwolscine (5-HT2B), SB204741 (5-HT2B/2C) or Ro 04-6790 (5-ht6) (300 and 1000 μg kg−1 each). These results suggest that the ‘atypical' 5-HT2 receptors mediating tachycardia in reserpinized pithed rats are pharmacologically similar to the 5-HT2A

  1. Bi-directional modulation of BNST neurons by 5-HT: Molecular expression and functional properties of excitatory 5-HT receptor subtypes

    PubMed Central

    Guo, Ji-Dong; Hammack, Sayamwong E.; Hazra, Rimi; Levita, Liat; Rainnie, Donald G.

    2009-01-01

    Activation of neurons in the anterolateral bed nucleus of the stria terminalis (BNSTALG) plays an important role in mediating the behavioral response to stressful and anxiogenic stimuli. Application of 5-HT elicits complex postsynaptic responses in BNSTALG neurons, which includes 1) membrane hyperpolarization (5-HTHyp), 2) hyperpolarization followed by depolarization (5-HTHyp-Dep), 3) depolarization (5-HTDep) or 4) no response (5-HTNR). We have shown that the inhibitory response is mediated by activation of postsynaptic 5-HT1A receptors. Here, we used a combination of in vitro whole-cell patch-clamp recording and single cell reverse transcriptase polymerase chain reaction (RT-PCR) to determine the pharmacological properties and molecular profile of 5-HT receptor subtypes mediating the excitatory response to 5-HT in BNSTALG neurons. We show that the depolarizing component of both the 5-HTHyp/Dep and the 5-HTDep response was mediated by activation of 5-HT2A, 5-HT2C and/or 5-HT7 receptors. Single cell RT-PCR data revealed that 5-HT7 receptors (46%) and 5-HT1A receptors (41%) are the most prevalent receptor subtypes expressed in BNSTALG neurons. Moreover, 5-HT receptor subtypes are differentially expressed in Type I – III BNSTALG neurons. Hence, 5-HT2C receptors are almost exclusively expressed by Type III neurons, whereas 5-HT7 receptors are expressed by Type I and II neurons, but not Type III neurons. Conversely, 5-HT2A receptors are found predominantly in Type II neurons. Finally, bi-directional modulation of individual neurons occurs only in Type I and II neurons. Significantly the distribution of 5-HT receptor subtypes in BNSTALG neurons predicted the observed expression pattern of 5-HT responses determined pharmacologically. Together, these results suggest that 5-HT can differentially modulate the excitability of Type I – III neurons, and further suggest that bi-directional modulation of BNSTALG neurons occurs primarily through an interplay between 5-HT1A and

  2. BEopt-CA (Ex): A Tool for Optimal Integration of EE, DR and PV in Existing California Homes

    SciTech Connect

    Christensen, Craig; Horowitz, Scott; Maguire, Jeff; Velasco, Paulo Tabrares; Springer, David; Coates, Peter; Bell, Christy; Price, Snuller; Sreedharan, Priya; Pickrell, Katie

    2014-04-01

    This project targeted the development of a software tool, BEopt-CA (Ex) (Building Energy Optimization Tool for California Existing Homes), that aims to facilitate balanced integration of energy efficiency (EE), demand response (DR), and photovoltaics (PV) in the residential retrofit1 market. The intent is to provide utility program managers and contractors in the EE/DR/PV marketplace with a means of balancing the integration of EE, DR, and PV

  3. 5-HT2A receptor activation is necessary for CO2-induced arousal

    PubMed Central

    Smith, Haleigh R.; MacAskill, Amanda; Richerson, George B.

    2015-01-01

    Hypercapnia-induced arousal from sleep is an important protective mechanism pertinent to a number of diseases. Most notably among these are the sudden infant death syndrome, obstructive sleep apnea and sudden unexpected death in epilepsy. Serotonin (5-HT) plays a significant role in hypercapnia-induced arousal. The mechanism of 5-HT's role in this protective response is unknown. Here we sought to identify the specific 5-HT receptor subtype(s) involved in this response. Wild-type mice were pretreated with antagonists against 5-HT receptor subtypes, as well as antagonists against adrenergic, cholinergic, histaminergic, dopaminergic, and orexinergic receptors before challenge with inspired CO2 or hypoxia. Antagonists of 5-HT2A receptors dose-dependently blocked CO2-induced arousal. The 5-HT2C receptor antagonist, RS-102221, and the 5-HT1A receptor agonist, 8-OH-DPAT, attenuated but did not completely block CO2-induced arousal. Blockade of non-5-HT receptors did not affect CO2-induced arousal. None of these drugs had any effect on hypoxia-induced arousal. 5-HT2 receptor agonists were given to mice in which 5-HT neurons had been genetically eliminated during embryonic life (Lmx1bf/f/p) and which are known to lack CO2-induced arousal. Application of agonists to 5-HT2A, but not 5-HT2C, receptors, dose-dependently restored CO2-induced arousal in these mice. These data identify the 5-HT2A receptor as an important mediator of CO2-induced arousal and suggest that, while 5-HT neurons can be independently activated to drive CO2-induced arousal, in the absence of 5-HT neurons and endogenous 5-HT, 5-HT receptor activation can act in a permissive fashion to facilitate CO2-induced arousal via another as yet unidentified chemosensor system. PMID:25925320

  4. 5-HT7 receptor activation inhibits mechanical hypersensitivity secondary to capsaicin sensitization in mice.

    PubMed

    Brenchat, Alex; Romero, Luz; García, Mónica; Pujol, Marta; Burgueño, Javier; Torrens, Antoni; Hamon, Michel; Baeyens, José Manuel; Buschmann, Helmut; Zamanillo, Daniel; Vela, José Miguel

    2009-02-01

    This work aimed to evaluate the potential role of the 5-HT(7) receptor in nociception secondary to a sensitizing stimulus in mice. For this purpose, the effects of relevant ligands (5-HT(7) receptor agonists: AS-19, MSD-5a, E-55888; 5-HT(7) receptor antagonists: SB-258719, SB-269970; 5-HT(1A) receptor agonist: F-13640; 5-HT(1A) receptor antagonist: WAY-100635) were assessed on capsaicin-induced mechanical hypersensitivity, a pain behavior involving hypersensitivity of dorsal horn neurons (central sensitization). For the 5-HT(7) receptor agonists used, binding profile and intrinsic efficacy to stimulate cAMP formation in HEK-293F cells expressing the human 5-HT(7) receptor were also evaluated. AS-19 and E-55888 were selective for 5-HT(7) receptors. E-55888 was a full agonist whereas AS-19 and MSD-5a behaved as partial agonists, with maximal effects corresponding to 77% and 61%, respectively, of the cAMP response evoked by the full agonist 5-HT. Our in vivo results revealed that systemic administration of 5-HT(7) receptor agonists exerted a clear-cut dose-dependent antinociceptive effect that was prevented by 5-HT(7) receptor antagonists, but not by the 5-HT(1A) receptor antagonist. The order of efficacy (E-55888>AS-19>MSD-5a) matched their in vitro efficacy as 5-HT(7) receptor agonists. Contrary to agonists, a dose-dependent promotion of mechanical hypersensitivity was observed after administration of 5-HT(7) receptor antagonists, substantiating the involvement of the 5-HT(7) receptor in the control of capsaicin-induced mechanical hypersensitivity. These findings suggest that serotonin exerts an inhibitory role in the control of nociception through activation of 5-HT(7) receptors, and point to a new potential therapeutic use of 5-HT(7) receptor agonists in the field of analgesia.

  5. 5-HT1B autoreceptor regulation of serotonin transporter activity in synaptosomes

    PubMed Central

    Hagan, Catherine E.; McDevitt, Ross A.; Liu, Yusha; Furay, Amy R.; Neumaier, John F.

    2012-01-01

    Serotonin-1B (5-HT1B) autoreceptors are located in serotonin (5-HT) terminals along with serotonin transporters (SERT), and play a critical role in autoregulation of serotonergic neurotransmission, and are implicated in disorders of serotonergic function, particularly emotional regulation. SERT modulates serotonergic neurotransmission by high-affinity reuptake of 5-HT. Alterations in SERT activity are associated with increased risk for depression and anxiety. Several neurotransmitter receptors are known to regulate SERT Km and Vmax, and previous work suggests that 5-HT1B autoreceptors may regulate 5-HT reuptake, in addition to modulating 5-HT release and synthesis. We used rotating disk electrode voltammetry to investigate 5-HT1B autoreceptor regulation of SERT-mediated 5-HT uptake into synaptosomes. The selective 5-HT1B antagonist SB224289 decreased SERT activity in synaptosomes prepared from wild-type but not 5-HT1B knockout mice, whereas SERT uptake was enhanced after pre-treatment with the selective 5-HT1B agonist CP94253. Furthermore, SERT activity varies as a function of 5-HT1B receptor expression—specifically, genetic deletion of 5-HT1B decreased SERT function, while viral-mediated overexpression of 5-HT1B autoreceptors in rat raphe neurons increased SERT activity in rat hippocampal synaptosomes. Considered collectively, these results provide evidence that 5-HT1B autoreceptors regulate SERT activity. Since SERT clearance rate varies as a function of 5-HT1B autoreceptor expression levels and is modulated by both activation and inhibition of 5-HT1B autoreceptors, this dynamic interaction may be an important mechanism of serotonin autoregulation with therapeutic implications. PMID:22961814

  6. Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors.

    PubMed

    Müller, Christian P; Carey, Robert J; Huston, Joseph P; De Souza Silva, Maria A

    2007-02-01

    Serotonin(1A)-receptors (5-HT(1A)-Rs) are important components of the 5-HT system in the brain. As somatodendritic autoreceptors they control the activity of 5-HT neurons, and, as postsynaptic receptors, the activity in terminal areas. Cocaine (COC), amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine ("Ecstasy", MDMA) are psychostimulant drugs that can lead to addiction-related behavior in humans and in animals. At the neurochemical level, these psychostimulant drugs interact with monoamine transporters and increase extracellular 5-HT, dopamine and noradrenalin activity in the brain. The increase in 5-HT, which, in addition to dopamine, is a core mechanism of action for drug addiction, hyperactivates 5-HT(1A)-Rs. Here, we first review the role of the various 5-HT(1A)-R populations in spontaneous behavior to provide a background to elucidate the contribution of the 5-HT(1A)-Rs to the organization of psychostimulant-induced addiction behavior. The progress achieved in this field shows the fundamental contribution of brain 5-HT(1A)-Rs to virtually all behaviors associated with psychostimulant addiction. Importantly, the contribution of pre- and postsynaptic 5-HT(1A)-Rs can be dissociated and frequently act in opposite directions. We conclude that 5-HT(1A)-autoreceptors mainly facilitate psychostimulant addiction-related behaviors by a limitation of the 5-HT response in terminal areas. Postsynaptic 5-HT(1A)-Rs, in contrast, predominantly inhibit the expression of various addiction-related behaviors directly. In addition, they may also influence the local 5-HT response by feedback mechanisms. The reviewed findings do not only show a crucial role of 5-HT(1A)-Rs in the control of brain 5-HT activity and spontaneous behavior, but also their complex role in the regulation of the psychostimulant-induced 5-HT response and subsequent addiction-related behaviors.

  7. Hippocampal 5-HT1A Receptor and Spatial Learning and Memory

    PubMed Central

    Glikmann-Johnston, Yifat; Saling, Michael M.; Reutens, David C.; Stout, Julie C.

    2015-01-01

    Spatial cognition is fundamental for survival in the topographically complex environments inhabited by humans and other animals. The hippocampus, which has a central role in spatial cognition, is characterized by high concentration of serotonin (5-hydroxytryptamine; 5-HT) receptor binding sites, particularly of the 1A receptor (5-HT1A) subtype. This review highlights converging evidence for the role of hippocampal 5-HT1A receptors in spatial learning and memory. We consider studies showing that activation or blockade of the 5-HT1A receptors using agonists or antagonists, respectively, lead to changes in spatial learning and memory. For example, pharmacological manipulation to induce 5-HT release, or to block 5-HT uptake, have indicated that increased extracellular 5-HT concentrations maintain or improve memory performance. In contrast, reduced levels of 5-HT have been shown to impair spatial memory. Furthermore, the lack of 5-HT1A receptor subtype in single gene knockout mice is specifically associated with spatial memory impairments. These findings, along with evidence from recent cognitive imaging studies using positron emission tomography (PET) with 5-HT1A receptor ligands, and studies of individual genetic variance in 5-HT1A receptor availability, strongly suggests that 5-HT, mediated by the 5-HT1A receptor subtype, plays a key role in spatial learning and memory. PMID:26696889

  8. Evaluation and improvement of the properties of the novel cystine-knot microprotein McoEeTI for oral administration.

    PubMed

    Werle, M; Kafedjiiski, K; Kolmar, H; Bernkop-Schnürch, A

    2007-03-06

    Cystine-knot microproteins exhibit several properties that make them highly interesting as scaffolds for oral peptide drug delivery. It was therefore the aim of the study to evaluate the novel clinically relevant cystine-knot microprotein McoEeTI regarding its potential for oral delivery. Additionally, based on the gained results, important features of McoEeTI were improved. Enzymatic degradation was caused by chymotrypsin, trypsin and porcine small intestinal juice whereas McoEeTI was stable towards elastase, membrane bound proteases, pepsin and porcine gastric juice. Only minor McoEeTI degradation was observed during a 24h incubation period in rat plasma. In the presence of various physiological ions about 50% of McoEeTI formed di- and/or trimers. P(app) value of McoEeTI was determined to be (7.4+/-0.4)x10(-6)cm/s. Sodium caprate and polycarbophil-cysteine (PCP-Cys) had no beneficial effect on McoEeTI permeation, whereas the utilization of a chitosan-thiobutylamidine (Chito-TBA) system improved McoEeTI permeation 3-fold. Enzymatic stability could be strongly improved by the utilization of Bowman-Birk-Inhibitor (BBI) as well as PCP-Cys. In conclusion, this study indicates that McoEeTI represents a promising candidate as a novel scaffold for oral peptide drug delivery.

  9. Occurrence of 17α-ethynylestradiol (EE2) in the environment and effect on exposed biota: a review.

    PubMed

    Aris, Ahmad Zaharin; Shamsuddin, Aida Soraya; Praveena, Sarva Mangala

    2014-08-01

    17α-ethynylestradiol (EE2) is a synthetic hormone, which is a derivative of the natural hormone, estradiol (E2). EE2 is an orally bio-active estrogen, and is one of the most commonly used medications for humans as well as livestock and aquaculture activity. EE2 has become a widespread problem in the environment due to its high resistance to the process of degradation and its tendency to (i) absorb organic matter, (ii) accumulate in sediment and (iii) concentrate in biota. Numerous studies have reported the ability of EE2 to alter sex determination, delay sexual maturity, and decrease the secondary sexual characteristics of exposed organisms even at a low concentration (ng/L) by mimicking its natural analogue, 17β-estradiol (E2). Thus, the aim of this review is to provide an overview of the science regarding EE2, the concentration levels in the environment (water, sediment and biota) and summarize the effects of this compound on exposed biota at various concentrations, stage life, sex, and species. The challenges in respect of EE2 include the extension of the limited database on the EE2 pollution profile in the environment, its fate and transport mechanism, as well as the exposure level of EE2 for better prediction and definition revision of EE2 toxicity end points, notably for the purpose of environmental risk assessment.

  10. Synthesis in the Melt and Characterization of Condensed Binary Phosphates BaNH 4(PO 3) 3, BiNH 4P 4O 12, and Ti(NH 4) 2P 4O 13

    NASA Astrophysics Data System (ADS)

    Selevich, Anatoly F.; Levchik, Sergei V.; Lyakhov, Alexander S.; Levchik, Galina F.; Lesnikovich, Anatoly I.; Catala, Jean-Marie

    1996-08-01

    Barium-ammonium polyphosphate (BaNH4(PO3)3), bismuth-ammonium cyclotetraphosphate (BiNH4P4O12), and titanium-ammonium tetraphosphate (Ti(NH4)2P4O13) have been synthesized in the melt of ammonium polyphosphate (NH4PO3). The prepared phosphates were characterized by chemical analysis, thin layer chromatography, and X-ray diffraction of powders. BiNH4P4O12was found to crystallize in the cubic system, space groupI43dwith the unit-cell parametera= 15.105(2) Å. Thermal decomposition behavior of the phosphates was studied by thermogravimetry and crystalline products of degradation were identified.

  11. Identification and expression analyses of a novel serotonin receptor gene, 5-HT2β, in the field cricket, Gryllus bimaculatus.

    PubMed

    Watanabe, T; Aonuma, H

    2012-01-01

    Biogenic amine serotonin (5-HT) modulates various aspects of behaviors such as aggressive behavior and circadian behavior in the cricket. In our previous report, in order to elucidate the molecular basis of the cricket 5-HT system, we identified three genes involved in 5-HT biosynthesis, as well as four 5-HT receptor genes (5-HT1A, 5-HT1B, 5-HT2α, and 5-HT7) expressed in the brain of the field cricket Gryllus bimaculatus DeGeer [7]. In the present study, we identified Gryllus 5-HT2β gene, an additional 5-HT receptor gene expressed in the cricket brain, and examined its tissue-specific distribution and embryonic stage-dependent expression. Gryllus 5-HT2β gene was ubiquitously expressed in the all examined adult tissues, and was expressed during early embryonic development, as well as during later stages. This study suggests functional differences between two 5-HT2 receptors in the cricket.

  12. Discovering the mechanisms underlying serotonin (5-HT)2A and 5-HT2C receptor regulation following nicotine withdrawal in rats.

    PubMed

    Zaniewska, Magdalena; Alenina, Natalia; Wydra, Karolina; Fröhler, Sebastian; Kuśmider, Maciej; McCreary, Andrew C; Chen, Wei; Bader, Michael; Filip, Małgorzata

    2015-08-01

    We have previously demonstrated that nicotine withdrawal produces depression-like behavior and that serotonin (5-HT)2A/2C receptor ligands modulate that mood-like state. In the present study we aimed to identify the mechanisms (changes in radioligand binding, transcription or RNA-editing) related to such a behavioral outcome. Rats received vehicle or nicotine (0.4 mg/kg, s.c.) for 5 days in home cages. Brain 5-HT2A/2C receptors were analyzed on day 3 of nicotine withdrawal. Nicotine withdrawal increased [(3)H]ketanserin binding to 5-HT2A receptors in the ventral tegmental area and ventral dentate gyrus, yet decreased binding in the nucleus accumbens shell. Reduction in [(3)H]mesulergine binding to 5-HT2C receptors was seen in the ventral dentate gyrus. Profound decrease in the 5-HT2A receptor transcript level was noted in the hippocampus and ventral tegmental area. Out of five 5-HT2C receptor mRNA editing sites, deep sequencing data showed a reduction in editing at the E site and a trend toward reduction at the C site in the hippocampus. In the ventral tegmental area, a reduction for the frequency of CD 5-HT2C receptor transcript was seen. These results show that the reduction in the 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor density in the hippocampus and ventral tegmental area during nicotine withdrawal, while decreased 5-HT2C receptor mRNA editing may explain the reduction in receptor labeling in the hippocampus. Serotonin (5-HT)2A/2C receptor ligands alleviate depression-like state in nicotine-withdrawn rats. Here, we show that the reduction in 5-HT2A receptor transcript level may be an auto-regulatory response to the increased receptor number in the hippocampus and ventral tegmental area during nicotine withdrawal, while attenuated 5-HT2C receptor mRNA editing in the hippocampus might explain reduced inverse agonist binding to 5-HT2C receptor and suggest a shift toward a population of more active receptors. 5

  13. Signalling pathways activated by 5-HT(1B)/5-HT(1D) receptors in native smooth muscle and primary cultures of rabbit renal artery smooth muscle cells.

    PubMed

    Hinton, J M; Hill, P; Jeremy, J; Garland, C

    2000-01-01

    The potential of primary cultures of rabbit renal artery vascular smooth muscle cells (VSMCs) was assessed as a means to investigate the signalling pathways linked to 5-hydroxytryptamine (5-HT) 5-HT(1B)/5-HT(1D) receptors in native arteries. In renal artery segments denuded of endothelium, incubated with ketanserin and prazosin (each 1 microM), and prestimulated with 20 mM K(+) Krebs buffer, 5-HT and CP 93,129, a 5-HT(1B) receptor agonist, evoked concentration-dependent contractions. GR 127935, a 5-HT(1B)/5-HT(1D) receptor antagonist, significantly antagonised 5-HT-evoked contractions at nanomolar concentrations. Reverse transcription polymerase chain reaction (RT-PCR) of mRNA from smooth muscle cells from the isolated renal artery and from primary cultures of VSMCs from the same artery expressed mRNA transcripts for the 5-HT(1B) receptor and the 5-HT(1D) receptor in both preparations. The sequence of the PCR fragments corresponded to the known sequence for these receptors. Application of 5-HT evoked a concentration-dependent, pertussis toxin (PTx)-sensitive reduction in cyclic AMP in both cultured cells and intact artery (cyclic AMP concentration reduced by 65.53 +/- 3.33 and 52.65 +/- 5.34% from basal with 10 microM 5-HT, respectively). The effect of 10 microM 5-HT on cAMP was increased in the presence of 20 mM K(+) (reduced by 82.50 +/- 2.50 and 87.54 +/- 3.97%, respectively). In intact arteries, contraction through 5-HT(1B)/5-HT(1D) receptors was significantly attenuated by inhibitors of phosphatidylinositol 3-kinase (wortmannin) and activated mitogen-activated protein kinase (MAPK), MEK (U0126). In the cultured VSMCs, activated MAPK was identified by immunocytochemistry and immunoblotting after stimulation with 5-HT, but only if 20 mM K(+) was present at the onset of stimulation. These data provide the first direct evidence that 5-HT(1B)/5-HT(1B) receptors are linked to the activation of MAPK and indicate that primary cultures of renal VSMCs could provide a

  14. eeDAP: an evaluation environment for digital and analog pathology

    NASA Astrophysics Data System (ADS)

    Gallas, Brandon D.; Cheng, Wei-Chung; Gavrielides, Marios A.; Ivansky, Adam; Keay, Tyler; Wunderlich, Adam; Hipp, Jason; Hewitt, Stephen M.

    2014-03-01

    Purpose: The purpose of this work is to present a platform for designing and executing studies that compare pathologists interpreting histopathology of whole slide images (WSI) on a computer display to pathologists interpreting glass slides on an optical microscope. Methods: Here we present eeDAP, an evaluation environment for digital and analog pathology. The key element in eeDAP is the registration of theWSI to the glass slide. Registration is accomplished through computer control of the microscope stage and a camera mounted on the microscope that acquires images of the real time microscope view. Registration allows for the evaluation of the same regions of interest (ROIs) in both domains. This can reduce or eliminate disagreements that arise from pathologists interpreting different areas and focuses the comparison on image quality. Results: We reduced the pathologist interpretation area from an entire glass slide (≈10-30 mm)2 to small ROIs <(50 um)2. We also made possible the evaluation of individual cells. Conclusions: We summarize eeDAP's software and hardware and provide calculations and corresponding images of the microscope field of view and the ROIs extracted from the WSIs. These calculations help provide a sense of eeDAP's functionality and operating principles, while the images provide a sense of the look and feel of studies that can be conducted in the digital and analog domains. The eeDAP software can be downloaded from code.google.com (project: eeDAP) as Matlab source or as a precompiled stand-alone license-free application.

  15. e+e- collisions in the multi-TeV region

    SciTech Connect

    Ellis, J.

    1983-05-01

    A leading role in the elucidation of the Standard Model during the last few years has been played by e+e- colliding beam experiments. The e+e- discoveries have been made possible by the cleanliness of the experimental conditions and the ability to tune the centre-of-mass energy with precision to the desired value, thus avoiding less interesting background events. We expect history to repeat itself in the next step of elucidating physics beyond the Standard Model. Just as past e+e- machines such as SPEAR, DORIS and CESR have uncovered physics inaccessible to hadron-hadron collisions with a centre-of-mass energy several times higher, so we feel that future e+e- colliders will provide information that could not be duplicated by hadron colliders with much larger centre-of-mass energies. There is a general consensus that the next interesting energy range is likely to be in the TeV range. It is in this energy range that whatever physics provides and stabilizes the masses of the intermediate vector bosons must be revealed. Unravelling this mass generation mechanism takes us beyond the gauge principle of the Standard Model which has been so triumphantly vindicated in recent months. Therefore we discuss here the capabilities and attributes of an e+e- collider with at least 1 TeV energy per beam. We believe that by enabling an important new energy domain to be explored in detail, such an e+e- collider provides physics opportunities which cannot be paralled by hadron-hadron colliding rings with centre-of-mass energies several times higher. (WHK)

  16. The 2009 Eclipse of EE Cephei: An Educational and Collaborative Journey

    NASA Astrophysics Data System (ADS)

    Pye, John; Elder, Lauren; Hopkins, Jeff

    2009-05-01

    In December 2008 Jeff Hopkins of the Hopkins Phoenix Observatory (HPO) put out a request for assistance in extracting data from images taken by the AAVSO SRO (Sonoita Research Observatory) of EE Cephei, an 11th magnitude (V) long period (5.6 years) eclipsing binary star system that was due to eclipse in January of 2009. The Hopkins Phoenix Observatory originally planned to do BVRI CCD photometry of EE Cephei for the 2009 eclipse, but equipment and logistical changes at HPO meant the EE Cephei project would not be possible. However, in the fall of 2008 Arne Henden of the AAVSO announced the availability of a remote robotic 16" telescope (the Sonoita Research Observatory) in southern Arizona for use by members of the AAVSO. Jeff Hopkins contacted Arne Henden and arrangements were made to have the EE Cephei star system imaged with BVRI filters beginning in November 2008 and running through February 2009. Image files were archived on the AAVSO web site. Soon after his initial request went out, Jeff Hopkins was contacted by John Pye from Maui Community College, who agreed to help with the project by having one of his students, Lauren Elder, examine the image files and extract EE Cephei and 3 comparison stars flux (ADU) counts for each band. The resulting data were then sent to the Hopkins Phoenix Observatory for data reduction and analysis. The project was a successful joint collaboration with 40 nights of observations for over 300 BVRI data points from 20 November 2008 to 17 February 2009. Light curves for each band as well as color indices were plotted and eclipse contact points were determined. The data were also contributed to the EE Cephei Campaign organized by Cezary Galan at the Centre for Astronomy at Nicolaus Copernicus University in Torun (Poland). Our results are plotted along with those of several dozen other observers from around the world.

  17. 5-HT 1A/1B receptor-mediated effects of the selective serotonin reuptake inhibitor, citalopram, on sleep: studies in 5-HT 1A and 5-HT 1B knockout mice.

    PubMed

    Monaca, Christelle; Boutrel, Benjamin; Hen, René; Hamon, Michel; Adrien, Joëlle

    2003-05-01

    Selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of depression. Aside from their antidepressant properties, they provoke a deficit in paradoxical sleep (PS) that is most probably mediated by the transporter blockade-induced increase in serotonin concentration in the extracellular space. Such an effect can be accounted for by the action of serotonin at various types of serotonergic receptors involved in PS regulation, among which the 5-HT(1A) and 5-HT(1B) types are the best candidates. According to this hypothesis, we examined the effects of citalopram, the most selective SSRI available to date, on sleep in the mouse after inactivation of 5-HT(1A) or 5-HT(1B) receptors, either by homologous recombination of their encoding genes, or pharmacological blockade with selective antagonists. For this purpose, sleep parameters of knockout mice that do not express these receptors and their wild-type counterparts were monitored during 8 h after injection of citalopram alone or in association with 5-HT(1A) or 5-HT(1B) receptor antagonists. Citalopram induced mainly a dose-dependent inhibition of PS during 2-6 h after injection, which was observed in wild-type and 5-HT(1B)-/- mice, but not in 5-HT(1A)-/- mutants. This PS inhibition was fully antagonized by pretreatment with the 5-HT(1A) antagonist WAY 100635, but only partially with the 5-HT(1B) antagonist GR 127935. These data indicate that the action of the SSRI citalopram on sleep in the mouse is essentially mediated by 5-HT(1A) receptors. Such a mechanism of action provides further support to the clinical strategy of antidepressant augmentation by 5-HT(1A) antagonists, because the latter would also counteract the direct sleep-inhibitory side-effects of SSRIs.

  18. Anxiolytic-like effects observed in rats exposed to the elevated zero-maze following treatment with 5-HT2/5-HT3/5-HT4 ligands

    PubMed Central

    Bell, Rob; Duke, Aaron A.; Gilmore, Paula E.; Page, Deaglan; Bègue, Laurent

    2014-01-01

    The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT2C antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT2C agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT3 antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT3 agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg), and in the third experiment, we administered the 5-HT4 antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT4 agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT2/3/4 subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT2 and 5-HT3 agonists, the 5-HT4 agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT4 antagonist RS 39604. We conclude by discussing the implications of these findings. PMID:24457553

  19. [Medical economics evaluation of 5-HT3 receptor antagonist drugs].

    PubMed

    Utsunomiya, Junpei; Hirano, Shigeki; Fukui, Aiko; Funabashi, Kazuaki; Deguchi, Yuko; Yamada, Susumu; Naito, Kazuyuki

    2010-10-01

    At Komaki City Hospital, the drug cost in connection with cancer chemotherapy was re-examined as part of improved management along with the introduction of DPC in July 2008. With due attention to the 5-HT3 receptor antagonists, both the change from injections to oral drugs and the change from brand-name drugs to generic drugs were tried between July 2008 and June 2009. After that, in order to examine the economic impact of these changes, we investigated and analyzed the number of medications, the cost of medicine purchased, and the average drug cost per medication of the 5-HT3 receptor antagonists between April 2008 and September 2009. As a result, the cost of 5-HT3 receptor antagonists purchased decreased greatly, and the impact of the improvement was mainly due to the change to oral drugs, and partially to the change to generic drugs. Therefore, from the viewpoint of hospital economic improvement in DPC, it was thought that the change to oral drugs(5-HT3 receptor antagonists)is given top priority.

  20. Study of the Process e+e- → K+K-π+π- With the CMD-3 Detector at the VEPP-2000 e+e- Collider

    NASA Astrophysics Data System (ADS)

    Akhmetshin, R. R.; Anisenkov, A. V.; Aulchenko, V. M.; Banzarov, V. S.; Barkov, L. M.; Bashtovoy, N. S.; Berkaev, D. E.; Bragin, A. V.; Eidelman, S. I.; Epifanov, D. A.; Epshteyn, L. B.; Erofeev, A. L.; Fedotovich, G. V.; Gayazov, S. E.; Grebenuk, A. A.; Grigoriev, D. N.; Gromov, E. M.; Ignatov, F. V.; Karpov, S. V.; Kazanin, V. F.; Khazin, B. I.; Kirpotin, A. N.; Koop, I. A.; Kovalenko, O. A.; Kozyrev, A. N.; Kozyrev, E. A.; Krokovny, P. P.; Kuzmenko, A. E.; Kuzmin, A. S.; Logashenko, I. B.; Lukin, P. A.; Lysenko, A. P.; Mikhailov, K. Yu.; Okhapkin, V. S.; Pestov, Yu. N.; Perevedentsev, E. A.; Popov, A. S.; Popov, Yu. S.; Razuvaev, G. P.; Rogovsky, Yu. A.; Romanov, A. L.; Ruban, A. A.; Ryskulov, N. M.; Ryzhenenkov, A. E.; Shebalin, V. E.; Shemyakin, D. N.; Shwartz, B. A.; Shwartz, D. B.; Sibidanov, A. L.; Shatunov, P. Yu.; Shatunov, Yu. M.; Solodov, E. P.; Titov, V. M.; Talyshev, A. A.; Vorobiov, A. I.; Yudin, Yu. V.; Zharinov, Yu. M.

    2014-12-01

    We report preliminary results on the measurement of the cross section of the process e+e- → K+K-π+π- in the c.m. energy range from 1.5 GeV to 2 GeV. It is shown that the cross section is dominated by the contributions of several intermediate states K+K-ρ, K*Kπ, ϕπ+π- and K*K*.

  1. Growth, Structure, Thermal Properties and Spectroscopic Characteristics of Nd3+-Doped KGdP4O12 Crystal

    PubMed Central

    Sun, Tongqing; Zhang, Yu; Shan, Pai; Zhang, Zichang; Chen, Shaolin; Kong, Yongfa; Xu, Jingjun

    2014-01-01

    A single crystal of Nd3+-doped KGdP4O12 was successfully grown with the top-seeded solution growth and slow cooling (TSSG−SC) technique. It crystallizes in space group C2/c with cell parameters a = 7.812(2) Å, b = 12.307(3) Å, c = 10.474(2) Å, β = 110.84(3)° and Z = 4. The IR and Raman spectra also indicated that the phosphoric polyhedra of Nd:KGdP4O12 has a cyclic symmetry. The chemical composition of the crystal was analyzed and the distribution coefficient of Nd3+ was calculated. The crystal morphology of KGdP4O12 was identified using X-ray diffraction. The compound has good thermal stability to 920°C. Its specific heat and thermal conductivity were determined for potential applications. The spectral properties of Nd:KGdP4O12 indicates that it exhibits broad absorption and emission bands, which are attributed to low symmetry of the crystal. The broad absorption band around 798 nm has a full-width at half-maximum (FWHM) of 14.8 nm and is suitable for AlGaAs laser diode pumping. Moreover, 5 at% Nd3+-doped KGdP4O12 crystal has a long luminescence lifetime of 300 μs and a high quantum efficiency of 96%. PMID:24968165

  2. Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.

    PubMed

    Borroto-Escuela, Dasiel O; Narvaez, Manuel; Pérez-Alea, Mileidys; Tarakanov, Alexander O; Jiménez-Beristain, Antonio; Mudó, Giuseppa; Agnati, Luigi F; Ciruela, Francisco; Belluardo, Natale; Fuxe, Kjell

    2015-01-02

    The ascending midbrain 5-HT neurons known to contain 5-HT1A autoreceptors may be dysregulated in depression due to a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by co-location of the FGFR1 and 5-HT1A immunoreactivities in midbrain raphe 5-HT cells, evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague-Dawley rat. Their existence in the rat medullary raphe RN33B cell cultures was also established. After combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA positive clusters was found in the RN33B cells. Similar results were reached upon coactivation by agonists in HEK293T cells using the Fluorescent Resonance Energy Transfer (FRET) technique resulting in increased FRETmax and reduced FRET50 values. The heteroreceptor complex formation was dependent on TMV of the 5-HT1A receptor since it was blocked by incubation with TMV but not with TMII. Taken together, the 5-HT1A autoreceptors by being recruited into a FGFR1-5-HT1A heteroreceptor complex in the midbrain raphe 5-HT nerve cells may develop a novel function, namely a trophic role in many midbrain 5-HT neuron systems originating from the dorsal and medianus raphe nuclei.

  3. Linking the HOMO-LUMO gap to torsional disorder in P3HT/PCBM blends

    NASA Astrophysics Data System (ADS)

    McLeod, John A.; Pitman, Amy L.; Kurmaev, Ernst Z.; Finkelstein, Larisa D.; Zhidkov, Ivan S.; Savva, Achilleas; Moewes, Alexander

    2015-12-01

    The electronic structure of [6,6]-phenyl C61 butyric acid methyl ester (PCBM), poly(3-hexylthiophene) (P3HT), and P3HT/PCBM blends is studied using soft X-ray emission and absorption spectroscopy and density functional theory calculations. We find that annealing reduces the HOMO-LUMO gap of P3HT and P3HT/PCBM blends, whereas annealing has little effect on the HOMO-LUMO gap of PCBM. We propose a model connecting torsional disorder in a P3HT polymer to the HOMO-LUMO gap, which suggests that annealing helps to decrease the torsional disorder in the P3HT polymers. Our model is used to predict the characteristic length scales of the flat P3TH polymer segments in P3HT and P3HT/PCBM blends before and after annealing. Our approach may prove useful in characterizing organic photovoltaic devices in situ or even in operando.

  4. 5-HT7 receptor signaling: improved therapeutic strategy in gut disorders.

    PubMed

    Kim, Janice J; Khan, Waliul I

    2014-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) is most commonly known for its role as a neurotransmitter in the central nervous system (CNS). However, the majority of the body's 5-HT is produced in the gut by enterochromaffin (EC) cells. Alterations in 5-HT signaling have been associated with various gut disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and enteric infections. Recently, our studies have identified a key role for 5-HT in the pathogenesis of experimental colitis. 5-HT7 receptors are expressed in the gut and very recently, we have shown evidence of 5-HT7 receptor expression on intestinal immune cells and demonstrated a key role for 5-HT7 receptors in generation of experimental colitis. This review summarizes the key findings of these studies and provides a comprehensive overview of our current knowledge of the 5-HT7 receptor in terms of its pathophysiological relevance and therapeutic potential in intestinal inflammatory conditions, such as IBD.

  5. Beam-beam and electron cloud effects in CEPC/FCC-ee

    NASA Astrophysics Data System (ADS)

    Ohmi, Kazuhito

    2016-11-01

    We discuss beam dynamics issues in CEPC/FCC-ee, especially focusing on the beam-beam and electron cloud effects. Beamstrahlung is strong in extreme high energy collision such as Higgs and top factory. Beam-beam simulations considering beamstrahlung are now ready. Several points of beam-beam effects for FCC-ee are presented. Electron cloud effects are serious for high current positron machine, especially in Z factory that many bunches are stored. Analytical estimate for threshold of electron density and electron build-up for CEPC are presented.

  6. Are “normal hips” being labeled as femoroacetabular impingement due to EE angle?

    PubMed Central

    You, Tian; Yang, Bei; Zhang, Xin-tao; Jiang, Xiao-cheng; Wang, Shuang; Zhang, Wen-tao

    2017-01-01

    Abstract Gluteal muscle contracture (GMC) is a clinical syndrome characterized by gait abnormality and limb dysfunction, as well as secondary deformities of pelvis and femur. Femoroacetabular impingement (FAI) typically could be diagnosed on the basis of computed tomography (CT) such as the equatorial-edge angle (EE angle), but it did not work well in GMC patients. In this study, we retrospected all image data and found small EE angles in GMCs, which meant retroverted acetabulum; however, none of them showed no symptoms and signs of FAI. Therefore, we had reasons to think that, some normal hips with unbalanced hip myodynamia as same as GMCs, may be incorrectly diagnosed as FAI through measuring EE angle only. In consequence, the paper was designed to assess the use of the EE angle in the assessment of FAI in the diagnosis, as described by Werner. Twenty-three patients (46 hips) were collected and calculated with the “equatorial-edge angle” (EE angle) by CT scans. All of them were excluded from FAI. Review of the hips showed a mean EE angle was 12.93°, with a minimum of -3.42° and a maximum of 24.08°. The mean value for males and females were 13.52° and 12.40°, respectively, without statistical significance, although the mean value of left hips and right sides reached 13.32° and 12.54° individually, not having statistical differences neither. There were not any symptoms or signs of FAI in all patients. Thus, the reduced EE angle could suggest the local excessive coverage of the femoral head by the anterior acetabular edge, but might not be a reasonably good predictor of FAI. GMC patient's acetabular deformity mainly manifests as increased retroversion, which may be the anatomical basis for FAI and lead to high risks of the acetabular impingement. However, all patients in this study showed no symptoms and signs of FAI, suggesting that the measurement of EE angle can only be applied to assessing those people with normal hip myodynamia, and the bone

  7. Ethanol and Mesolimbic Serotonin/Dopamine Interactions Via 5-HT1B Receptors

    DTIC Science & Technology

    2006-03-01

    5 - HT3 receptor antagonist antagonized systemic ethanol- induced increases of DA release in the VTA [10] or the NACC [9]. Moreover, the...experiments with a selective 5 -HT1B receptor antagonist such as SB 216641 are required to strengthen this conclusion. The future experiments will be... receptor antagonist ), but not BRL 15572 (a 5 -HT1D/1A receptor antagonist ) or WAY 100635 (a 5 -HT1A receptor antagonist ). Administration

  8. The Psu protein of bacteriophage P4 is an antitermination factor for rho-dependent transcription termination.

    PubMed Central

    Linderoth, N A; Calendar, R L

    1991-01-01

    A 0.7-kbp DNA fragment from bacteriophage P4 that contained the polarity suppression (psu) gene was cloned in an expression plasmid. Induction of the plasmid-borne psu gene resulted in the overproduction of a protein having the biological properties of the P4-induced polarity suppressor. In vivo, Psu protein acted in trans to suppress rho-dependent polarity in the late genes of an infecting P2 phage, in plasmid operons, and in the host chromosome. Psu action did not require the presence of other P2 or P4 phage genes. Psu caused efficient readthrough (antitermination) by Escherichia coli RNA polymerase at the rho-dependent terminators tR1 and TIS2, individually and in tandem, but did not affect termination at rho-independent sites. Neither the conserved antitermination sequence boxA nor any unique promoter or utilization sequence was required for Psu activity. Images FIG. 2 PMID:1938879

  9. An excellent reduction in sidelobe level for P4 code by using of a new pulse compression scheme

    NASA Astrophysics Data System (ADS)

    Alighale, S.; Zakeri, B.

    2014-10-01

    P4 polyphase code is well known in pulse compression technique. For P4 code with length 1000, peak sidelobe level (PSL) and integrated sidelobe level (ISL) are -36dB and -16dB, respectively. In order to increase the performance, there are different reduction techniques to reduce the sidelobes of P4 code. This paper presents a novel sidelobe reduction technique that reduces the PSL and ISL to -127dB and -104dB, respectively. Also, other sidelobe reduction techniques such as Woo filter are investigated and compared with the novel proposed technique. Simulations and results show that the proposed technique produces a better peak side lobe ratio (PSL) and integrated side lobe ratio (ISL) than other techniques.

  10. Monovalent rotavirus vaccine provides protection against an emerging fully heterotypic G9P[4] rotavirus strain in Mexico.

    PubMed

    Yen, Catherine; Figueroa, Jesùs Reyna; Uribe, Edgar Sánchez; Carmen-Hernández, Luz Del; Tate, Jacqueline E; Parashar, Umesh D; Patel, Manish M; Richardson López-Collado, Vesta

    2011-09-01

    After the introduction of monovalent rotavirus vaccine (RV1) in Mexico in 2006-2007, diarrhea mortality and morbidity declined substantially among Mexican children under 5 years of age. In January 2010, surveillance identified the emergence of a novel G9P[4] rotavirus strain nationwide. We conducted a case-control study to assess the field effectiveness of RV1 against severe rotavirus gastroenteritis caused by this unusual strain and to determine whether the G9P[4] emergence was related to vaccine failure or failure to vaccinate. RV1 was 94% effective (95% confidence interval, 16%-100%) against G9P[4] rotavirus-related hospitalization, indicating that its emergence was likely unrelated to vaccine pressure.

  11. Neuronal localization of the 5-HT2 receptor family in the amygdaloid complex.

    PubMed

    Bombardi, Cristiano

    2014-01-01

    The amygdaloid complex (or amygdala), a heterogeneous structure located in the medial portion of the temporal lobe, is composed of deep, superficial, and "remaining" nuclei. This structure is involved in the generation of emotional behavior, in the formation of emotional memories and in the modulation of the consolidation of explicit memories for emotionally arousing events. The serotoninergic fibers originating in the dorsal and medial raphe nuclei are critically involved in amygdalar functions. Serotonin (5-hydroxytryptamine, 5-HT) regulates amygdalar activity through the activation of the 5-HT2 receptor family, which includes three receptor subtypes: 5-HT2A, 5-HT2B, and 5-HT2C. The distribution and the functional activity of the 5-HT2 receptor family has been studied more extensively than that of the 5-HT2A receptor subtypes, especially in the deep nuclei. In these nuclei, the 5-HT2A receptor is expressed on both pyramidal and non-pyramidal neurons, and could play a critical role in the formation of emotional memories. However, the exact role of the 5-HT2A receptor subtypes, as well as that of the 5-HT2B and 5-HT2C receptor subtypes, in the modulation of the amygdalar microcircuits requires additional study. The present review reports data concerning the distribution and the functional roles of the 5-HT2 receptor family in the amygdala.

  12. Evidence that the anorexia induced by lipopolysaccharide is mediated by the 5-HT2C receptor.

    PubMed

    von Meyenburg, Claudia; Langhans, Wolfgang; Hrupka, Brian J

    2003-01-01

    Rats consistently reduce their food intake following injections of bacterial lipopolysaccharides (LPS). Because inhibition of serotonergic (5-HT) activity by 8-OH-DPAT (5-HT(1A) activation) attenuates LPS-induced anorexia, we conducted a series of studies to examine whether other 5-HT-receptors are involved in the mediation of peripheral LPS-induced anorexia. In all experiments, rats were injected with LPS (100 microg/kg body weight [BW] ip) at lights out (hour 0). Antagonists were administered peripherally at hour 4, shortly after the onset of anorexia, which presumably follows the enhanced cytokine production after LPS. Food intake was then recorded during the subsequent 2 h or longer. 5-HT receptor antagonists cyanopindolol and SB 224289 (5-HT(1B)), ketanserin (5-HT(2A)), RS-102221 (5-HT(2C)), and metoclopramide (5-HT(3)) failed to attenuate LPS-induced anorexia. In contrast, both ritanserin (5-HT(2A/C)-receptor antagonist) (0.5 mg/kg BW) and SB 242084 (5-HT(2C)) (0.3 mg/kg BW) attenuated LPS-induced anorexia at doses that did not alter food intake in non-LPS-treated rats (all P<.01). Our results suggest that at least part of the anorexia following peripheral LPS administration is mediated through an enhanced 5-HT-ergic activity and the 5-HT(2C) receptor.

  13. The role of serotonin 5-HT2A receptors in memory and cognition

    PubMed Central

    Zhang, Gongliang; Stackman, Robert W.

    2015-01-01

    Serotonin 5-HT2A receptors (5-HT2ARs) are widely distributed in the central nervous system, especially in brain region essential for learning and cognition. In addition to endogenous 5-HT, several hallucinogens, antipsychotics, and antidepressants function by targeting 5-HT2ARs. Preclinical studies show that 5-HT2AR antagonists have antipsychotic and antidepressant properties, whereas agonist ligands possess cognition-enhancing and hallucinogenic properties. Abnormal 5-HT2AR activity is associated with a number of psychiatric disorders and conditions, including depression, schizophrenia, and drug addiction. In addition to its traditional activity as a G protein-coupled receptor (GPCR), recent studies have defined novel operations of 5-HT2ARs. Here we review progress in the (1) receptor anatomy and biology: distribution, signaling, polymerization and allosteric modulation; and (2) receptor functions: learning and memory, hallucination and spatial cognition, and mental disorders. Based on the recent progress in basic research on the 5-HT2AR, it appears that post-training 5-HT2AR activation enhances non-spatial memory consolidation, while pre-training 5-HT2AR activation facilitates fear extinction. Further, the potential influence that 5-HT2AR-elicited visual hallucinations may have on visual cue (i.e., landmark) guided spatial cognition is discussed. We conclude that the development of selective 5-HT2AR modulators to target distinct signaling pathways and neural circuits represents a new possibility for treating emotional, neuropsychiatric, and neurodegenerative disorders. PMID:26500553

  14. 5-HT systems: emergent targets for memory formation and memory alterations.

    PubMed

    Meneses, Alfredo

    2013-01-01

    Drugs acting through 5-hydroxytryptamine (serotonin or 5-HT) systems modulate memory and its alterations, although the mechanisms involved are poorly understood. 5-HT drugs may present promnesic and/or antiamnesic (or even being amnesic) effects. Key questions regarding 5-HT markers include whether receptors directly or indirectly participate and/or contribute to the physiological and pharmacological basis of memory and its pathogenesis; hence, the major aim of this article was to examine recent advances in emergent targets of the 5-HT systems for memory formation and memory alterations. Recent reviews and findings are summarized, mainly in the context of the growing notion of memory deficits in brain disorders (e.g., posttraumatic stress disorder, mild cognitive impairment, consumption of drugs, poststroke cognitive dysfunctions, schizophrenia, Parkinson disease, and infection-induced memory impairments). Mainly, mammalian and (some) human data were the focus. At least agonists and antagonists for 5-HT1A/1B, 5-HT2A/2B/2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors as well as serotonin uptake inhibitors seem to have a promnesic and/or antiamnesic effect in different conditions and 5-HT markers seem to be associated to neural changes. Available evidence offers clues about the possibilities, but the exact mechanisms remain unclear. For instance, 5-HT transporter expression seems to be a reliable neural marker related to memory mechanisms and its alterations.

  15. Transcriptional regulation of the 5-HT1A receptor: implications for mental illness.

    PubMed

    Albert, Paul R

    2012-09-05

    The serotonin-1A (5-HT(1A)) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT(1A) receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre- versus post-synaptic 5-HT(1A) receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT(1A) receptor gene (Htr1a). A functional polymorphism, rs6295 in the Htr1a promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT(1A) autoreceptor expression in animal models and humans. Its association with altered 5-HT(1A) expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene × environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT(1A) heteroreceptors, and rs6295-induced upregulation of 5-HT(1A) autoreceptors. Targeted therapeutics to inhibit 5-HT(1A) autoreceptor expression and induce 5-HT(1A) heteroreceptor expression may ameliorate treatment of anxiety and major depression.

  16. 49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Specification 3HT seamless steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.44 Specification 3HT seamless steel cylinders for aircraft use. (a) Type, size and service pressure. A DOT 3HT cylinder is a seamless steel...

  17. 49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 3HT seamless steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.44 Specification 3HT seamless steel cylinders for aircraft use. (a) Type, size and service pressure. A DOT 3HT cylinder is a seamless steel...

  18. 49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 3HT seamless steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.44 Specification 3HT seamless steel cylinders for aircraft use. (a) Type, size and service pressure. A DOT 3HT cylinder is a seamless steel...

  19. 49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Specification 3HT seamless steel cylinders for...) SPECIFICATIONS FOR PACKAGINGS Specifications for Cylinders § 178.44 Specification 3HT seamless steel cylinders for aircraft use. (a) Type, size and service pressure. A DOT 3HT cylinder is a seamless steel...

  20. HT.sub.m4 methods of treatment and assays, agonists and antagonists

    DOEpatents

    Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel

    1999-01-01

    The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy.

  1. Immunohistological localization of 5-HT in the CNS and feeding system of the Stable Fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    5-HT immunoreactive neurons were detected in the CNS of the stable fly. The finding of strong innervations of the cibarial pump muscles and the foregut by 5-HT IR neurons in the feeding-related systems suggests that 5-HT may play a crucial role in the control of the feeding behavior in both the larv...

  2. Purification in an active form of the phage phi 29 protein p4 that controls the viral late transcription.

    PubMed Central

    Barthelemy, I; Lázaro, J M; Méndez, E; Mellado, R P; Salas, M

    1987-01-01

    The phage phi 29 protein p4, that controls viral late transcription, was highly purified from Escherichia coli cells harbouring a gene 4-containing plasmid. This protein, representing about 6% of the total cellular protein, was obtained in a highly purified form. The protein was characterized as p4 by amino acid analysis and NH2-terminal sequence determination. The purified protein was active in an in vitro transcription assay, allowing specific initiation of transcription at the phi 29 A3 late promoter in the presence of Bacillus subtilis sigma 43-RNA polymerase holoenzyme. Images PMID:3671066

  3. Studies on the site and mode of TMPyP4 interactions with Bcl-2 promoter sequence G-Quadruplexes.

    PubMed

    Nagesh, Narayana; Buscaglia, Robert; Dettler, Jamie M; Lewis, Edwin A

    2010-06-02

    TMPyP4 (Mesotetra(N-methyl-4-pyridyl)porphine) is known to have a high affinity for G-quadruplex DNA. However, there is still some controversy over the exact site(s) and mode(s) of TMPyP4 binding to G-quadruplex DNA. We examined TMPyP4 interactions with seven G-quadruplex forming oligonucleotides. The parent oligonucleotide is a 27-mer with a wild-type (WT) G-rich sequence of the Bcl-2 P1 promoter mid-region (5'-d(CGG GCG CGG GAG GAA GGG GGC GGG AGC-3')). This sequence folds into at least three unique loop isomer quadruplexes. The two mutant oligonucleotides used in this study are shorter (23-mer) sequences in which nonquadruplex core bases were eliminated and two different (-G-G-) --> (-T-T-) substitutions were made to restrict the folding complexity. The four additional mutant oligonucleotides were labeled by substituting a 2-aminopurine (2-AP) base for an A or G in either the first three-base lateral loop or the second five- or seven-base lateral loop (depending on the G-->T mutation positions). Spectroscopic and microcalorimetric studies indicate that four molecules of TMPyP4 can be bound to a single G-quadruplex. Binding of the first two moles of TMPyP4 appears to occur by an end or exterior mode (K approximately 1 x 10(7) M(-1)), whereas binding of the third and fourth moles of TMPyP4 appears to occur by a weaker, intercalative binding mode (K approximately 1 x 10(5) M(-1)). As the mid-loop size decreases from seven to five bases, end binding occurs with significantly increased affinity. 2-AP-labeled Bcl-2 promoter region quadruplexes show increased fluorescence of the 2-AP base on addition of TMPyP4. The change in fluorescence for 2-AP bases in the second half of the TMPyP4 titration lends support to our previous speculation regarding the intercalative nature of the weaker binding mode.

  4. Impaired effect of activation of rat hippocampal 5-HT7 receptors, induced by treatment with the 5-HT7 receptor antagonist SB 269970.

    PubMed

    Kusek, M; Sowa, J; Tokarski, K; Hess, G

    2015-04-01

    Effects of the 5-HT(7) receptor antagonist SB 269970, administered for 14 days (1.25 mg/kg), were studied in ex vivo slices of rat hippocampus. To activate the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT, 200 nM) was applied in the presence of WAY 100635 (2 μM), a 5-HT(1A) receptor antagonist. In contrast to control preparations, no 5-HT(7) receptor-mediated increase in excitability nor depolarization and an increase in the input resistance of CA1 and CA3 pyramidal neurons were present in slices prepared from rats treated with SB 269970. The treatment also abolished the stimulatory effect of 5-HT(7) receptor activation on spontaneous excitatory postsynaptic currents recorded from CA1 stratum radiatum/lacunosum-moleculare interneurons. These data demonstrate that repeated administration of SB 269970 impairs the reactivity of the CA1 hippocampal neuronal network to 5-HT(7) receptor activation.

  5. Rational Drug Design Leading to the Identification of a Potent 5-HT(2C) Agonist Lacking 5-HT(2B) Activity.

    PubMed

    Chen, Gang; Cho, Sung Jin; Huang, Xi-Ping; Jensen, Niels H; Svennebring, Andreas; Sassano, Maria F; Roth, Bryan L; Kozikowski, Alan P

    2011-12-08

    The 5-HT(2C) receptor is an attractive drug target in the quest for new therapeutics to treat a variety of human disorders. We have previously undertaken a structural optimization campaign that has led to some potent and moderately selective 5-HT(2C) receptor agonists. After expanding our structure-function library, we were able to combine our datasets so as to allow the design of compounds of improved selectivity and potency. We disclose herein the structural optimization of our previously reported 5-HT(2B)/5-HT(2C) agonists, which has led to the identification of a highly selective 5-HT(2C) agonist, (+)-trans-[2-(2-cyclopropylmethoxyphenyl)cyclopropyl]methylamine hydrochloride, with an EC(50) of 55 nM and no detectable agonism at the 5-HT(2B) receptor.

  6. A Pharmacological Analysis of an Associative Learning Task: 5-HT1 to 5-HT7 Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory

    PubMed Central

    Meneses, Alfredo

    2003-01-01

    Recent studies using both invertebrates and mammals have revealed that endogenous serotonin (5-hydroxytryptamine [5-HT]) modulates plasticity processes, including learning and memory. However, little is currently known about the mechanisms, loci, or time window of the actions of 5-HT. The aim of this review is to discuss some recent results on the effects of systemic administration of selective agonists and antagonists of 5-HT on associative learning in a Pavlovian/instrumental autoshaping (P/I-A) task in rats. The results indicate that pharmacological manipulation of 5-HT1-7 receptors or 5-HT reuptake sites might modulate memory consolidation, which is consistent with the emerging notion that 5-HT plays a key role in memory formation. PMID:14557609

  7. A pharmacological analysis of an associative learning task: 5-HT(1) to 5-HT(7) receptor subtypes function on a pavlovian/instrumental autoshaped memory.

    PubMed

    Meneses, Alfredo

    2003-01-01

    Recent studies using both invertebrates and mammals have revealed that endogenous serotonin (5-hydroxytryptamine [5-HT]) modulates plasticity processes, including learning and memory. However, little is currently known about the mechanisms, loci, or time window of the actions of 5-HT. The aim of this review is to discuss some recent results on the effects of systemic administration of selective agonists and antagonists of 5-HT on associative learning in a Pavlovian/instrumental autoshaping (P/I-A) task in rats. The results indicate that pharmacological manipulation of 5-HT1-7 receptors or 5-HT reuptake sites might modulate memory consolidation, which is consistent with the emerging notion that 5-HT plays a key role in memory formation.

  8. 31 CFR 321.8 - Redemption-exchange of Series E and EE savings bonds and savings notes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... exchange are: (1) Series EE bonds bearing issue dates of January 1, 2003, or earlier, presented no earlier than six months from their issue dates; (2) Series EE bonds bearing issue dates of February 1, 2003, or... redemption-exchange. An agent shall not accept and redeem eligible securities on exchange unless: (1)...

  9. 31 CFR 321.8 - Redemption-exchange of Series E and EE savings bonds and savings notes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Redemption-exchange of Series E and EE... STATES SAVINGS NOTES (FREEDOM SHARES) Scope of Authority § 321.8 Redemption-exchange of Series E and EE... payment of eligible securities presented for redemption in exchange for Series HH bonds....

  10. 31 CFR 321.8 - Redemption-exchange of Series E and EE savings bonds and savings notes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Redemption-exchange of Series E and EE... STATES SAVINGS NOTES (FREEDOM SHARES) Scope of Authority § 321.8 Redemption-exchange of Series E and EE... payment of eligible securities presented for redemption in exchange for Series HH bonds....

  11. A coordinated set of ecosystem research platforms open to international research in ecotoxicology, AnaEE-France.

    PubMed

    Mougin, Christian; Azam, Didier; Caquet, Thierry; Cheviron, Nathalie; Dequiedt, Samuel; Le Galliard, Jean-François; Guillaume, Olivier; Houot, Sabine; Lacroix, Gérard; Lafolie, François; Maron, Pierre-Alain; Michniewicz, Radika; Pichot, Christian; Ranjard, Lionel; Roy, Jacques; Zeller, Bernd; Clobert, Jean; Chanzy, André

    2015-10-01

    The infrastructure for Analysis and Experimentation on Ecosystems (AnaEE-France) is an integrated network of the major French experimental, analytical, and modeling platforms dedicated to the biological study of continental ecosystems (aquatic and terrestrial). This infrastructure aims at understanding and predicting ecosystem dynamics under global change. AnaEE-France comprises complementary nodes offering access to the best experimental facilities and associated biological resources and data: Ecotrons, seminatural experimental platforms to manipulate terrestrial and aquatic ecosystems, in natura sites equipped for large-scale and long-term experiments. AnaEE-France also provides shared instruments and analytical platforms dedicated to environmental (micro) biology. Finally, AnaEE-France provides users with data bases and modeling tools designed to represent ecosystem dynamics and to go further in coupling ecological, agronomical, and evolutionary approaches. In particular, AnaEE-France offers adequate services to tackle the new challenges of research in ecotoxicology, positioning its various types of platforms in an ecologically advanced ecotoxicology approach. AnaEE-France is a leading international infrastructure, and it is pioneering the construction of AnaEE (Europe) infrastructure in the field of ecosystem research. AnaEE-France infrastructure is already open to the international community of scientists in the field of continental ecotoxicology.

  12. 31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE savings bonds? The TIN of each person named in the registration is required to purchase a...

  13. 31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE savings bonds? The TIN of each person named in the registration is required to purchase a...

  14. 31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE savings bonds? The TIN of each person named in the registration is required to purchase a...

  15. Adult AMPA GLUA1 receptor subunit loss in 5-HT neurons results in a specific anxiety-phenotype with evidence for dysregulation of 5-HT neuronal activity.

    PubMed

    Weber, Tillmann; Vogt, Miriam A; Gartside, Sarah E; Berger, Stefan M; Lujan, Rafael; Lau, Thorsten; Herrmann, Elke; Sprengel, Rolf; Bartsch, Dusan; Gass, Peter

    2015-05-01

    Both the glutamatergic and serotonergic (5-HT) systems are implicated in the modulation of mood and anxiety. Descending cortical glutamatergic neurons regulate 5-HT neuronal activity in the midbrain raphe nuclei through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. To analyze the functional role of GLUA1-containing AMPA receptors in serotonergic neurons, we used the Cre-ERT2/loxP-system for the conditional inactivation of the GLUA1-encoding Gria1 gene selectively in 5-HT neurons of adult mice. These Gria1(5-HT-/-) mice exhibited a distinct anxiety phenotype but showed no alterations in locomotion, depression-like behavior, or learning and memory. Increased anxiety-related behavior was associated with significant decreases in tryptophan hydroxylase 2 (TPH2) expression and activity, and subsequent reductions in tissue levels of 5-HT, its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine in the raphe nuclei. However, TPH2 expression and activity as well as monoamine levels were unchanged in the projection areas of 5-HT neurons. Extracellular electrophysiological recordings of 5-HT neurons revealed that, while α1-adrenoceptor-mediated excitation was unchanged, excitatory responses to AMPA were enhanced and the 5-HT1A autoreceptor-mediated inhibitory response to 5-HT was attenuated in Gria1(5-HT-/-) mice. Our data show that a loss of GLUA1 protein in 5-HT neurons enhances AMPA receptor function and leads to multiple local molecular and neurochemical changes in the raphe nuclei that dysregulate 5-HT neuronal activity and induce anxiety-like behavior.

  16. Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats.

    PubMed Central

    Fone, K. C.; Robinson, A. J.; Marsden, C. A.

    1991-01-01

    1. The motor behavioural effects of intrathecal injections of 5-hydroxytryptamine (5-HT) and a variety of 5-HT receptor agonists were examined in adult Wistar rats to establish; (a) which 5-HT receptor subtype/s elicit each behaviour and (b) whether these receptors are located within the spinal cord. 2. Intrathecal injection of 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) or 2,5-dimethoxy-alpha,4-dimethylbenzene ethamine hydrochloride (DOM) produced dose-related back muscle contractions (BMC) and wet dog shakes (WDS) which were both markedly attenuated by intraperitoneal pretreatment with either ritanserin (1 mg kg-1), ketanserin (0.16 mg kg-1) or mianserin (0.6 mg kg-1) indicating the involvement of 5-HT2 receptors in both these motor behaviours. Both fluoxetine (1-20 mg kg-1, i.p.) and high doses of 5-HT (50 micrograms) following fluoxetine (5 mg kg-1, i.p.) also elicited BMC, further confirming the involvement of 5-HT in this behaviour. 3. Intrathecal 5-carboxamidotryptamine (5-CT) evoked a marked wet-dog shake response without producing any BMC. Intrathecal pretreatment with 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) enhanced, while in contrast 2-methyl-5-HT pretreatment attenuated, 5-HT agonist-induced BMC without affecting WDS. These data suggest that the spinal 5-HT2 receptors mediating BMC are positively modulated by 5-HT1A but negatively influenced by 5-HT3 receptor activation and may be of a different subtype to the supra-spinal 5-HT2 receptors which elicit WDS.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 5 PMID:1832068

  17. Novel Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications

    PubMed Central

    Solstad, Runar Gjerp; Li, Chun; Isaksson, Johan; Johansen, Jostein; Svenson, Johan; Stensvåg, Klara; Haug, Tor

    2016-01-01

    The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635) was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring. PMID:27007817

  18. Novel Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications.

    PubMed

    Solstad, Runar Gjerp; Li, Chun; Isaksson, Johan; Johansen, Jostein; Svenson, Johan; Stensvåg, Klara; Haug, Tor

    2016-01-01

    The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635) was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring.

  19. Lamotrigine, an antiepileptic drug, inhibits 5-HT3 receptor currents in NCB-20 neuroblastoma cells

    PubMed Central

    Kim, Ki Jung; Jeun, Seung Hyun

    2017-01-01

    Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC50 value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT3-mediated currents evoked by 1 mM dopamine, a partial 5-HT3 receptor agonist, were inhibited by lamotrigine co-application. The EC50 of 5-HT for 5-HT3 receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT3 receptor desensitization, inhibited 5-HT3 receptor currents in a concentration-dependent manner. The deactivation of 5-HT3 receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT3 receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT3-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization. PMID:28280410

  20. The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

    PubMed

    Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

    2015-12-02

    Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response.

  1. Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-HT1A receptors.

    PubMed

    Millan, M J; Colpaert, F C

    1991-02-07

    In rats lightly restrained in horizontal cylinders, (+/-)-3,4-methylenedioxymethamphetamine (MDMA) dose dependently (0.16-10.0 mg/kg, s.c.) elicited spontaneous tail-flicks; that is, tail-flicks in the absence of extraneous stimulation. In contrast, amphetamine over a similar dose-range was inactive. Selective inhibitors of 5-hydroxytryptamine (5-HT) uptake and carrier-mediated 5-HT release, paroxetine and citalopram, did not induce spontaneous tail-flicks themselves and blocked those induced by MDMA. In distinction, maprotiline and bupropion, selective inhibitors of noradrenaline and dopamine uptake, respectively, failed to modify the action of MDMA. Spontaneous tail-flicks elicited by MDMA were unaffected by the selective 5-HT3 receptor antagonists, ICS 205,930 and GR 38032F. They were attenuated by the mixed 5-HT1/5-HT2 receptor antagonist, methiotepin, the mixed 5-HT1A/5-HT1B receptor antagonist, (-)-alprenolol and the mixed 5-HT1A/5-HT2 receptor antagonist, spiperone, but not by the selective 5-HT1C/5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ketanserin. The novel 5-HT1A receptor antagonists, BMY 7378 and NAN-190, each abolished MDMA-evoked spontaneous tail-flicks. Selective D1, D2, alpha 1, alpha 2, beta 1 and beta 2 antagonists had little influence upon induction of spontaneous tail-flicks by MDMA. These data indicate that MDMA evokes spontaneous tail-flicks in the rat via a release of 5-HT which acts at 5-HT1A receptors. Thus, 5-HT1A receptors appear to be involved in the acute functional actions of MDMA.

  2. Lamotrigine, an antiepileptic drug, inhibits 5-HT3 receptor currents in NCB-20 neuroblastoma cells.

    PubMed

    Kim, Ki Jung; Jeun, Seung Hyun; Sung, Ki-Wug

    2017-03-01

    Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)3 receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC50 value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT3-mediated currents evoked by 1 mM dopamine, a partial 5-HT3 receptor agonist, were inhibited by lamotrigine co-application. The EC50 of 5-HT for 5-HT3 receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT3 receptor desensitization, inhibited 5-HT3 receptor currents in a concentration-dependent manner. The deactivation of 5-HT3 receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT3 receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT3-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

  3. Correction to ATel 10128: Spectral Comparison Object SN 1999em -> SN 1999ee

    NASA Astrophysics Data System (ADS)

    Wang, Xiaofeng

    2017-02-01

    We report a correction to the spectroscopic classification announced in ATel #10128. The spectral comparison shows that SN 2017bke is similar to type Ia supernova SN 1999ee (which was incorrectly typed as SN 1999em) at t = -7 days from the maximum light. We apologize for any confusion caused by this typo error.

  4. 31 CFR 351.4 - In what form are Series EE savings bonds issued?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false In what form are Series EE savings bonds issued? 351.4 Section 351.4 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED...

  5. Standards Setting and Federal Information Policy: The Escrowed Encryption Standard (EES).

    ERIC Educational Resources Information Center

    Gegner, Karen E.; Veeder, Stacy B.

    1994-01-01

    Examines the standards process used for developing the Escrowed Encryption Standard (EES) and its possible impact on national communication and information policies. Discusses the balance between national security and law enforcement concerns versus privacy rights and economic competitiveness in the area of foreign trade and export controls. (67…

  6. Perspectives from Emerging Researchers: What Next in EE/SE Research?

    ERIC Educational Resources Information Center

    Aguayo, Claudio; Higgins, Blanche; Field, Ellen; Nicholls, Jennifer; Pudin, Susan; Tiu, Sangion Appiee; Osborn, Maia; Hashemzadeh, Farshad; Lubuulwa, Kevin Kezabu; Boulet, Mark; Christie, Belinda A.; Mah, Jeremy

    2016-01-01

    Following the inaugural Australian Association for Environmental Education (AAEE) research symposium in November 2014, we--a group of emerging researchers in Environmental Education/Sustainability Education (EE/SE)--commenced an online collaboration to identify and articulate our responses to the main themes of the symposium. Identifying as…

  7. Transforming e-Learning into ee-Learning: The Centrality of Sociocultural Participation

    ERIC Educational Resources Information Center

    Schneider, Sandra B.; Evans, Michael A.

    2008-01-01

    Traditional e-learning efforts use information communication technologies to create and support educational opportunities that are not constrained by temporal and spatial considerations. The focus of ee-learning is to couple e-learning's approach with experiential education models that employ service-learning methodologies and with…

  8. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false When is interest payable on Series EE savings bonds? 351.8 Section 351.8 Money and Finance: Treasury Regulations Relating to Money and Finance... and becomes part of the redemption value. Interest earnings are payable upon redemption....

  9. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false When is interest payable on Series EE savings bonds? 351.8 Section 351.8 Money and Finance: Treasury Regulations Relating to Money and Finance... and becomes part of the redemption value. Interest earnings are payable upon redemption....

  10. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false When is interest payable on Series EE savings bonds? 351.8 Section 351.8 Money and Finance: Treasury Regulations Relating to Money and Finance... and becomes part of the redemption value. Interest earnings are payable upon redemption....

  11. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false When is interest payable on Series EE savings bonds? 351.8 Section 351.8 Money and Finance: Treasury Regulations Relating to Money and Finance... and becomes part of the redemption value. Interest earnings are payable upon redemption....

  12. 77 FR 213 - United States Savings Bonds, Series EE and I

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... Federal Regulations is sold by the Superintendent of Documents. #0;Prices of new books are listed in the..., Fiscal Service, Treasury. ACTION: Final rule. SUMMARY: This rule increases the amount of book-entry... the amount of book- entry Series EE and Series I savings bonds a person may acquire each year....

  13. Resource Materials To Support Your Environmental Education Efforts. EE-TIPS (Environmental Education Technical Information Packages).

    ERIC Educational Resources Information Center

    North American Association for Environmental Education, Troy, OH.

    This collection gathers together over 50 high-quality materials to support environmental education (EE) curricula. Because each community has unique environmental and educational needs, the guide includes a broad set of educational materials that can be adapted to a variety of settings. The materials can be used to supplement educational…

  14. Polysynaptic excitatory postsynaptic potentials that trigger spasms after spinal cord injury in rats are inhibited by 5-HT1B and 5-HT1F receptors.

    PubMed

    Murray, Katherine C; Stephens, Marilee J; Rank, Michelle; D'Amico, Jessica; Gorassini, Monica A; Bennett, David J

    2011-08-01

    Sensory afferent transmission and associated spinal reflexes are normally inhibited by serotonin (5-HT) derived from the brain stem. Spinal cord injury (SCI) that eliminates this 5-HT innervation leads to a disinhibition of sensory transmission and a consequent emergence of unusually long polysynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons. These EPSPs play a critical role in triggering long polysynaptic reflexes (LPRs) that initiate muscles spasms. In the present study we examined which 5-HT receptors modulate the EPSPs and whether these receptors adapt to a loss of 5-HT after chronic spinal transection in rats. The EPSPs and associated LPRs recorded in vitro in spinal cords from chronic spinal rats were consistently inhibited by 5-HT(1B) or 5-HT(1F) receptor agonists, including zolmitriptan (5-HT(1B/1D/1F)) and LY344864 (5-HT(1F)), with a sigmoidal dose-response relation, from which we computed the 50% inhibition (EC(50)) and potency (-log EC(50)). The potencies of 5-HT receptor agonists were highly correlated with their binding affinity to 5-HT(1B) and 5-HT(1F) receptors, and not to other 5-HT receptors. Zolmitriptan also inhibited the LPRs and general muscle spasms recorded in vivo in the awake chronic spinal rat. The 5-HT(1B) receptor antagonists SB216641 and GR127935 and the inverse agonist SB224289 reduced the inhibition of LPRs by 5-HT(1B) agonists (zolmitriptan). However, when applied alone, SB224289, SB216641, and GR127935 had no effect on the LPRs, indicating that 5-HT(1B) receptors do not adapt to chronic injury, remaining silent, without constitutive activity. The reduction in EPSPs with zolmitriptan unmasked a large glycine-mediated inhibitory postsynaptic current (IPSC) after SCI. This IPSC and associated chloride current reversed at -73 mV, slightly below the resting membrane potential. Zolmitriptan did not change motoneuron properties. Our results demonstrate that 5-HT(1B/1F) agonists, such as zolmitriptan, can restore inhibition

  15. Role of dorsal raphe nucleus 5-HT(1A) and 5-HT(2) receptors in tonic immobility modulation in guinea pigs.

    PubMed

    Ferreira, Mateus Dalbem; Menescal-de-Oliveira, Leda

    2009-08-18

    Tonic immobility (TI) is an innate defensive behavior characterized by a state of physical inactivity and diminished responsiveness to environmental stimuli. Behavioral adaptations to changes in the external and internal milieu involve complex neuronal network activity and a large number of chemical neurotransmitters. The TI response is thought to be influenced by serotonin (5-HT) activity in the central nervous system (CNS) of vertebrates, but the neuronal groups involved in the mechanisms underlying this behavior are poorly understood. Owing to its extensive afferents and efferents, the dorsal raphe nucleus (DRN) has been implicated in a great variety of physiological and behavioral functions. In the current study, we investigated the influence of serotonergic 5-HT(1A) and 5-HT(2) receptor activity within the DRN on the modulation of TI behavior in the guinea pig. Microinjection of a 5-HT(1A) receptor agonist (8-OH-DPAT, 0.01 and 0.1 microg) decreased TI behavior, an effect blocked by pretreatment with WAY-100635 (0.033 microg), a 5-HT(1A) antagonist. In contrast, activation of 5-HT(2) receptors within the DRN (alpha-methyl-5-HT, 0.5 microg) increased the TI duration, and this effect could be reversed by pretreatment with an ineffective dose (0.01 microg) of ketanserine. Since the 5-HT(1A) and 5-HT(2) agonists decreased and increased, respectively, the duration of TI, different serotonin receptor subtypes may play distinct roles in the modulation of TI in the guinea pig.

  16. Structure-activity relationships of quinoxaline-based 5-HT3A and 5-HT3AB receptor-selective ligands.

    PubMed

    Thompson, Andrew J; Verheij, Mark H P; van Muijlwijk-Koezen, Jacqueline E; Lummis, Sarah C R; Leurs, Rob; de Esch, Iwan J P

    2013-06-01

    Until recently, discriminating between homomeric 5-HT3A and heteromeric 5-HT3AB receptors was only possible with ligands that bind in the receptor pore. This study describes the first series of ligands that can discriminate between these receptor types at the level of the orthosteric binding site. During a recent fragment screen, 2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline (VUF10166) was identified as a ligand that displays an 83-fold difference in [(3)H]granisetron binding affinity between 5-HT3A and 5-HT3AB receptors. Fragment hit exploration, initiated from VUF10166 and 3-(4-methylpiperazin-1-yl)quinoxalin-2-ol, resulted in a series of compounds with higher affinity at either 5-HT3A or 5-HT3AB receptors. These ligands reveal that a single atom is sufficient to change the selectivity profile of a compound. At the extremes of the new compounds were 2-amino-3-(4-methylpiperazin-1-yl)quinoxaline, which showed 11-fold selectivity for the 5-HT3A receptor, and 2-(4-methylpiperazin-1-yl)quinoxaline, which showed an 8.3-fold selectivity for the 5-HT3AB receptor. These compounds represent novel molecular tools for studying 5-HT3 receptor subtypes and could help elucidate their physiological roles.

  17. The Cobalt cyclo‐P4 Sandwich Complex and Its Role in the Formation of Polyphosphorus Compounds

    PubMed Central

    Dielmann, Fabian; Timoshkin, Alexey; Piesch, Martin; Balázs, Gábor

    2017-01-01

    Abstract A synthetic approach to the sandwich complex [Cp′′′Co(η4‐P4)] (2) containing a cyclo‐P4 ligand as an end‐deck was developed. Complex 2 is the missing homologue in the series of first‐row cyclo‐Pn sandwich complexes, and shows a unique tendency to dimerize in solution to form two isomeric P8 complexes [(Cp′′′Co)2(μ,η4:η2:η1‐P8)] (3 and 4). Reactivity studies indicate that 2 and 3 react with further [Cp′′′Co] fragments to give [(Cp′′′Co)2(μ,η2:η2‐P2)2] (5) and [(Cp′′′Co)3P8] (6), respectively. Furthermore, complexes 2, 3, and 4 thermally decompose forming 5, 6, and the P12 complex [(Cp′′′Co)3P12] (7). DFT calculations on the P4 activation process suggest a η3‐P4 Co complex as the key intermediate in the synthesis of 2 as well as in the formation of larger polyphosphorus complexes via a unique oligomerization pathway. PMID:28078794

  18. Activation of organozinc reagents with t-Bu-P4 base for transition metal-free catalytic SN2' reaction.

    PubMed

    Kobayashi, Koji; Ueno, Masahiro; Naka, Hiroshi; Kondo, Yoshinori

    2008-08-28

    The t-Bu-P4 base was found to be an excellent catalyst for activating organozinc reagents and was used to promote the S(N)2' reaction of alpha,beta-unsaturated esters bearing a gamma-chloride using various organozinc reagents: these reactions proceeded in high yields with excellent chemo-and regioselectivity.

  19. EPA, U.S. Department of Justice settle with P4 Production LLC, over hazardous chemical reporting requirements

    EPA Pesticide Factsheets

    (Seattle, WA - March 26, 2015) The U.S. Environmental Protection Agency Region 10 and the U.S. Department of Justice have settled with P4 Productions LLC, for violations of federal Emergency Planning and Community-Right-to-Know Act (EPCRA) and Comprehensiv

  20. Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era

    PubMed Central

    Matthijnssens, Jelle; Nuyts, Valerie; Heylen, Elisabeth; De Coster, Sarah; Conceição-Neto, Nádia; Van Ranst, Marc; Matthijnssens, Jelle

    2016-01-01

    The introduction of Rotarix into the Belgian immunization program in June 2006 coincided with an increase of the relative prevalence of G2P[4] strains. However, the genetic composition of these persistent G2P[4] strains has not been investigated. Therefore, we have investigated the NSP4 gene of 89 Belgian G2P[4] strains detected between 1999 and 2013, covering both pre- and post-vaccination periods. The NSP4 genes were divided over seven separate clusters of which six were more closely related to animal than to human strains. The NSP4 genes that clustered more closely to animal DS-1-like strains were isolated after 2004–2005 and were found throughout multiple seasons. Complete genome sequencing of 28 strains identified several other gene segments that clustered more closely to animal than to human DS-1-like strains. These findings suggest that frequent interspecies reassortments may have played a role in the spread of G2P[4] rotaviruses in the post-vaccination period in Belgium. PMID:27841357

  1. Stepwise Self-Assembly of P3HT/CdSe Hybrid Nanowires with Enhanced Photoconductivity.

    PubMed

    Xu, Jingjing; Hu, Jianchen; Liu, Xinfeng; Qiu, Xiaohui; Wei, Zhixiang

    2009-08-18

    A facile approach to prepare poly(3-hexylthiophene) (P3HT)/cadmium selenide quantum dot (CdSe QD) hybrid coaxial nanowires by a stepwise self-assembly process is reported. P3HT nanowires of ≈20 nm diameter are first prepared by self-assembly in a poor solvent such as cyclohexanone, and then as-prepared CdSe QDs are deposited compactly onto the P3HT nanowires by non-covalent interactions between P3HT and CdSe. When illuminated with white light, the hybrid nanowires show enhanced photoconductivity compared with the pristine P3HT nanowires and the blended nanocomposites.

  2. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

    PubMed

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  3. Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens.

    PubMed

    Titeler, M; Lyon, R A; Glennon, R A

    1988-01-01

    Alterations in brain serotonergic function have been implicated in the mechanism of action of LSD, mescaline, and other similarly acting hallucinogenic drugs of abuse such as STP (2,5-dimethoxyphenylisopropylamine; DOM). In order to test the hypothesis that the mechanism of action of LSD and phenylisopropylamine hallucinogens is through stimulation of a specific brain serotonin receptor sub-type, the affinities of these compounds for radiolabelled 5-HT2, 5-HT1A, 5-HT1B, and 5-HT1C receptors have been determined using recently developed in vitro radioligand binding methodologies. The 5-HT2 receptor was labelled with the agonist/hallucinogen radioligand 3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine). The 5-HT1A, 5-HT1B, and 5-HT1C receptors were labelled with 3H-OH-DPAT, 3H-5-HT, and 3H-mesulergine, respectively. In general, the phenylisopropylamines displayed 10-100 fold higher affinities for the 5-HT2 receptor than for the 5-HT1C receptor and 100-1000 fold higher affinities for the 5-HT2 receptor than for the 5-HT1A or 5-HT1B receptor. There was a strong correlation between hallucinogenic potencies and 5-HT2 receptor affinities of the phenylisopropylamines (r = 0.90); the correlation coefficients for the 5-HT1A, 5-HT1B, and 5-HT1C were 0.73, 0.85, and 0.78, respectively. Because there is no evidence that 5-HT1A-selective or 5-HT1B-selective agonists are hallucinogenic and because the phenylisopropylamines are potent hallucinogens, a 5-HT2 receptor interaction is implicated and supports our previous suggestions to this effect. A secondary role for 5-HT1C receptors cannot be discounted at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee

    SciTech Connect

    d'Enterria, David; Skands, Peter Z.

    2015-01-01

    This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\\alpha_s(m_Z)$ = 0.1177 $\\pm$ 0.0013, is about 1\\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.

  5. Arabidopsis HT1 kinase controls stomatal movements in response to CO2.

    PubMed

    Hashimoto, Mimi; Negi, Juntaro; Young, Jared; Israelsson, Maria; Schroeder, Julian I; Iba, Koh

    2006-04-01

    Guard cells, which form stomata in leaf epidermes, sense a multitude of environmental signals and integrate this information to regulate stomatal movements. Compared with the advanced understanding of light and water stress responses in guard cells, the molecular mechanisms that underlie stomatal CO(2) signalling have remained relatively obscure. With a high-throughput leaf thermal imaging CO(2) screen, we report the isolation of two allelic Arabidopsis mutants (high leaf temperature 1; ht1-1 and ht1-2) that are altered in their ability to control stomatal movements in response to CO(2). The strong allele, ht1-2, exhibits a markedly impaired CO(2) response but shows functional responses to blue light, fusicoccin and abscisic acid (ABA), indicating a role for HT1 in stomatal CO(2) signalling. HT1 encodes a protein kinase that is expressed mainly in guard cells. Phosphorylation assays demonstrate that the activity of the HT1 protein carrying the ht1-1 or ht1-2 mutation is greatly impaired or abolished, respectively. Furthermore, dominant-negative HT1(K113W) transgenic plants, which lack HT1 kinase activity, show a disrupted CO(2) response. These findings indicate that the HT1 kinase is important for regulation of stomatal movements and its function is more pronounced in response to CO(2) than it is to ABA or light.

  6. Electroacupuncture Restores 5-HT System Deficit in Chronic Mild Stress-Induced Depressed Rats

    PubMed Central

    Tu, Ya; Yang, Xiuyan; Liu, Ping

    2016-01-01

    Objective. The current study is designed to investigate the antidepressant efficacy of electroacupuncture (EA) treatment by evaluating its effect on the synthesis, metabolism, reuptake, and receptors of 5-hydroxytryptamine (5-HT), so as to clarify the molecular mechanisms of EA for antidepression. Materials and Methods. Solitary combined with the chronic unpredictable mild stress (CUMS) was used to establish the rat model with depression. The depressed rats were supplied with EA treatment for 4 weeks, and the behavior change and the following indices including 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), monoamine oxidase A (MAO-A), tryptophan hydroxylase (TPH), 5-HT transporter (SERT), 5-HT1A, and 5-HT2A in hippocampus and prefrontal cortex were examined. Results. EA treatment significantly improved the behavior of rats and increased 5-HT level in hippocampus of depressed rats. Similarly, EA treatment could significantly increase protein and mRNA expression of TPH and 5-HT1A during 5-HT synthesis process in hippocampus of depressed rats. However, EA treatment had no effect on the activity of MAO-A and the expression of SERT protein and mRNA. Conclusion. Antidepressant efficacy of EA treatment can be accomplished through enhancing 5-HT synthesis, upregulating 5-HT1A level, and improving 5-HT content in brain and synaptic gaps. PMID:27994633

  7. What Do We Really Know About 5-HT1A Receptor Signaling in Neuronal Cells?

    PubMed Central

    Rojas, Paulina S.; Fiedler, Jenny L.

    2016-01-01

    Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of 5-HT receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT1A receptor (5-HT1AR), specially contrasting with those findings obtained in neuronal cells. The 5-HT1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT1AR differs from other 5-HT receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by Gα isoforms and some cascades involve βγ signaling. The activity of 5-HT1AR usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca2+, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT1AR induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and phosphoinositide-3-kinase (PI3K)-Akt signaling pathways. Advances in understanding the actions of 5-HT1AR and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease. PMID:27932955

  8. Building a 5-HT3A Receptor Expression Map in the Mouse Brain

    PubMed Central

    Koyama, Yoshihisa; Kondo, Makoto; Shimada, Shoichi

    2017-01-01

    Of the many serotonin receptors, the type 3 receptors (5-HT3R) are the only ionotropic ones, playing a key role in fast synaptic transmission and cognitive and emotional brain function through controlled neuronal excitation. To better understand the various functions of 5-HT3Rs, it is very important to know their expression pattern in the central nervous system (CNS). To date, many distributional studies have shown localized 5-HT3R expression in the brain and spinal cord. However, an accurate pattern of 5-HT3R expression in the CNS remains to be elucidated. To investigate the distribution of 5-HT3R in the mouse brain in detail, we performed immunofluorescent staining using 5-HT3AR-GFP transgenic mice. We found strong 5-HT3AR expression in the olfactory bulb, cerebral cortex, hippocampus, and amygdala; and partial expression in the pons, medulla, and spinal cord. Meanwhile, the thalamus, hypothalamus, and midbrain exhibited a few 5-HT3AR-expressing cells, and no expression was detected in the cerebellum. Further, double-immunostaining using neural markers confirmed that 5-HT3AR is expressed in GABAergic interneurons containing somatostatin or calretinin. In the present study, we built a 5-HT3AR expression map in the mouse brain. Our findings make significant contributions in elucidating the novel functions of 5-HT3R in the CNS. PMID:28276429

  9. Quantitation of 5HT3 receptors in forebrain of serotonin transporter deficient mice.

    PubMed

    Mössner, R; Schmitt, A; Hennig, T; Benninghoff, J; Gerlach, M; Riederer, P; Deckert, J; Lesch, K P

    2004-01-01

    Mice deficient in the serotonin transporter (5HTT) display highly elevated extracellular 5HT levels. 5HT exerts ist effects via at least fourteen different cloned 5HT receptors located pre- and postsynaptically. In contrast to the other 5HT receptors, the 5HT3 receptor is a ionotropic receptor with ligand-gated cation channel function. Since G-protein-coupled 5HT receptors show extensive adaptive changes in 5HTT-deficient mice, we investigated whether 5HT3 receptors are also altered in these mice. Using quantitative autoradiography, we found that 5HT3 receptors are upregulated in frontal cortex (+46%), parietal cortex (+42%), and in stratum oriens of the CA3 region of the hippocampus (+18%) of 5HTT knockout mice. Changes in 5HT3 receptor mRNA expression, as determined by quantitative in situ hybridisation, were less pronounced. The adaptive changes of 5HT3 receptor expression constitute a part of the complex regulatory pattern of 5HT receptors in 5HTT knockout mice.

  10. Cellular mechanisms of the 5-HT7 receptor-mediated signaling

    PubMed Central

    Guseva, Daria; Wirth, Alexander; Ponimaskin, Evgeni

    2014-01-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. The 5-HT7 receptor is one of the most recently described members of the 5-HT receptor family. Functionally, 5-HT7 receptor is associated with a number of physiological and pathological responses, including serotonin-induced phase shifting of the circadian rhythm, control of memory as well as locomotor and exploratory activity. A large body of evidence indicates involvement of the 5-HT7 receptor in anxiety and depression, and recent studies suggest that 5-HT7 receptor can be highly relevant for the treatment of major depressive disorders. The 5-HT7 receptor is coupled to the stimulatory Gs-protein, and receptor stimulation results in activation of adenylyl cyclase (AC) leading to a rise of cAMP concentration. In addition, this receptor is coupled to the G12-protein to activate small GTPases of the Rho family. This review focuses on molecular mechanisms responsible for the 5-HT7 receptor-mediated signaling. We provide detailed overview of signaling cascades controlled and regulated by the 5-HT7 receptor and discuss the functional impact of 5-HT7 receptor for the regulation of different cellular and subcellular processes. PMID:25324743

  11. Cellular mechanisms of the 5-HT7 receptor-mediated signaling.

    PubMed

    Guseva, Daria; Wirth, Alexander; Ponimaskin, Evgeni

    2014-01-01

    Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. The 5-HT7 receptor is one of the most recently described members of the 5-HT receptor family. Functionally, 5-HT7 receptor is associated with a number of physiological and pathological responses, including serotonin-induced phase shifting of the circadian rhythm, control of memory as well as locomotor and exploratory activity. A large body of evidence indicates involvement of the 5-HT7 receptor in anxiety and depression, and recent studies suggest that 5-HT7 receptor can be highly relevant for the treatment of major depressive disorders. The 5-HT7 receptor is coupled to the stimulatory Gs-protein, and receptor stimulation results in activation of adenylyl cyclase (AC) leading to a rise of cAMP concentration. In addition, this receptor is coupled to the G12-protein to activate small GTPases of the Rho family. This review focuses on molecular mechanisms responsible for the 5-HT7 receptor-mediated signaling. We provide detailed overview of signaling cascades controlled and regulated by the 5-HT7 receptor and discuss the functional impact of 5-HT7 receptor for the regulation of different cellular and subcellular processes.

  12. Functions of 5-HT2A receptor and its antagonists in the cardiovascular system.

    PubMed

    Nagatomo, Takafumi; Rashid, Mamunur; Abul Muntasir, Habib; Komiyama, Tadazumi

    2004-10-01

    The serotonin (5-hydroxytryptamine, 5-HT) receptors have conventionally been divided into seven subfamilies, most of which have several subtypes. Among them, 5-HT(2A) receptor is associated with the contraction of vascular smooth muscle, platelet aggregation and thrombus formation and coronary artery spasms. Accordingly, selective 5-HT(2A) antagonists may have potential in the treatment of cardiovascular diseases. Sarpogrelate, a selective 5-HT(2A) antagonist, has been introduced clinically as a therapeutic agent for the treatment of ischemic diseases associated with thrombosis. Molecular modeling studies also suggest that sarpogrelate is a 5-HT(2A) selective antagonist and is likely to have pharmacological effects beneficial in the treatment of cardiovascular diseases. This review describes the above findings as well as the signaling linkages of the 5-HT(2A) receptors and the mode of agonist binding to 5-HT(2A) receptor using data derived from molecular modeling and site-directed mutagenesis.

  13. NASA Rotor 37 CFD Code Validation: Glenn-HT Code

    NASA Technical Reports Server (NTRS)

    Ameri, Ali A.

    2010-01-01

    In order to advance the goals of NASA aeronautics programs, it is necessary to continuously evaluate and improve the computational tools used for research and design at NASA. One such code is the Glenn-HT code which is used at NASA Glenn Research Center (GRC) for turbomachinery computations. Although the code has been thoroughly validated for turbine heat transfer computations, it has not been utilized for compressors. In this work, Glenn-HT was used to compute the flow in a transonic compressor and comparisons were made to experimental data. The results presented here are in good agreement with this data. Most of the measures of performance are well within the measurement uncertainties and the exit profiles of interest agree with the experimental measurements.

  14. The 5-HT1A receptor in Major Depressive Disorder

    PubMed Central

    Kaufman, Joshua; DeLorenzo, Christine; Choudhury, Sunia; Parsey, Ramin V.

    2016-01-01

    Major Depressive Disorder (MDD) is a highly prevalent psychiatric diagnosis that is associated with a high degree of morbidity and mortality. This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030. A large body of previous research has theorized that serotonergic dysfunction, specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD. The purpose of this review is to describe the evolution of our current understanding of the serotonin 1A (5-HT1A) receptor and its role in the pathophysiology MDD through the discussion of animal, post-mortem, positron emission tomography (PET), pharmacologic and genetic studies. PMID:26851834

  15. The 5-HT1A receptor in Major Depressive Disorder.

    PubMed

    Kaufman, Joshua; DeLorenzo, Christine; Choudhury, Sunia; Parsey, Ramin V

    2016-03-01

    Major Depressive Disorder (MDD) is a highly prevalent psychiatric diagnosis that is associated with a high degree of morbidity and mortality. This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030. A large body of previous research has theorized that serotonergic dysfunction, specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD. The purpose of this review is to describe the evolution of our current understanding of the serotonin 1A (5-HT1A) receptor and its role in the pathophysiology MDD through the discussion of animal, post-mortem, positron emission tomography (PET), pharmacologic and genetic studies.

  16. Nonswelling behavior of HT9 alloy irradiated to high exposure

    SciTech Connect

    Pitner, A.L.; Hecht, S.L.; Trenchard, R.G.

    1993-10-01

    In-reactor monitoring of assembly axial growths in the Fast Flux Test Facility (FFTF) has shown the ferritic/martensitic alloy HT9 to be essentially swelling free out to a fast neutron fluence of at least 37 {times} 10{sup 22} n/cm{sup 2}. This superior performance directly contributes to the ability to achieve high fuel burnup levels necessary for the ultimate viability of an economical Liquid Metal Reactor (LMR) fuel system.

  17. Brown adipose tissue sympathetic nerve activity is potentiated by activation of 5-hydroxytryptamine (5-HT)1A/5-HT7 receptors in the rat spinal cord

    PubMed Central

    Madden, C. J.; Morrison, S. F.

    2008-01-01

    In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats, microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4) spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control), expired CO2 (+0.1%) heart rate (+48 beats min−1) and arterial pressure (+8 mmHg). The increase in BAT SNA evoked by T4 IML microinjection of NMDA was potentiated when it was administered immediately following a T4 IML microinjection of 5-hydroxytryptamine (5-HT, 100 pmol) or the 5-HT1A/5-HT7 receptor agonist, 8-OH-DPAT (600 pmol), (area under the curve: 184%, and 259% of the NMDA-only response, respectively). In contrast, T4 IML microinjection of the 5-HT2 receptor agonist, DOI (28 pmol) did not potentiate the NMDA-evoked increase in BAT SNA (101% of NMDA-only response). Microinjection into the T4 IML of the selective 5-HT1A antagonist, WAY-100635 (500 pmol), plus the 5-HT7 antagonist, SB-269970 (500 pmol), prevented the 5-HT-induced potentiation of the NMDA-evoked increase in BAT SNA. When administered separately, WAY-100635 (800 pmol) and SB-269970 (800 pmol) attenuated the 8-OH-DPAT-induced potentiation of the NMDA-evoked increase in BAT SNA through effects on the amplitude and duration of the response, respectively. The selective 5-HT2 receptor antagonist, ketanserin (100 pmol), did not attenuate the potentiations of the NMDA-evoked increase in BAT SNA induced by either 5-HT or 8-OH-DPAT. These results demonstrate that activation of 5-HT1A/5-HT7 receptors can act synergistically with NMDA receptor activation within the IML to markedly increase BAT SNA. PMID:18082230

  18. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

    PubMed

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

    2014-01-03

    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists.

  19. Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test.

    PubMed

    Vidal-Cantú, Guadalupe C; Jiménez-Hernández, Mildred; Rocha-González, Héctor I; Villalón, Carlos M; Granados-Soto, Vinicio; Muñoz-Islas, Enriqueta

    2016-06-15

    Sumatriptan, dihydroergotamine and methysergide inhibit 1% formalin-induced nociception by activation of peripheral 5-HT1B/1D receptors. This study set out to investigate the pharmacological profile of the antinociception produced by intrathecal and intraplantar administration of ergotamine (a 5-HT1B/1D and 5-HT5A/5B receptor agonist) and valerenic acid (a partial agonist at 5-HT5A receptors). Intraplantar injection of 1% formalin in the right hind paw resulted in spontaneous flinching behavior of the injected hindpaw of female Wistar rats. Intrathecal ergotamine (15nmol) or valerenic acid (1 nmol) blocked in a dose dependent manner formalin-induced nociception. The antinociception by intrathecal ergotamine (15nmol) or valerenic acid (1nmol) was partly or completely blocked by intrathecal administration of the antagonists: (i) methiothepin (non-selective 5-HT5A/5B; 0.01-0.1nmol); (ii) SB-699551 (selective 5-HT5A; up to 10nmol); (iii) anti-5-HT5A antibody; (iv) SB-224289 (selective 5-HT1B; 0.1-1nmol); or (v) BRL-15572 (selective 5-HT1D; 0.1-1nmol). Likewise, antinociception by intraplantar ergotamine (15nmol) and valerenic acid (10nmol) was: (i) partially blocked by methiothepin (1nmol), SB-699551 (10nmol) or SB-224289 (1nmol); and (ii) abolished by BRL-15572 (1nmol). The above doses of antagonists (which did not affect per se the formalin-induced nociception) were high enough to completely block their respective receptors. Our results suggest that ergotamine and valerenic acid produce antinociception via 5-HT5A and 5-HT1B/1D receptors located at both spinal and peripheral sites. This provides new evidence for understanding the modulation of nociceptive pathways in inflammatory pain.

  20. 5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats.

    PubMed

    García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

    2015-09-01

    Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3±1.0, 43.7±2.7 and 66.7±4.0 for 2, 4 and 6Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT1/7 agonist) (0.00000125-0.1μg/kg each) or l-694,247 (5-HT1D agonist; 0.0125μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT2), 1-PBG (5-HT3), cisapride (5-HT4), AS-19 (5-HT7), CGS-12066B (5-HT1B) or 8-OH-DPAT (5-HT1A) (0.0125μg/kg each). The effect of l-694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT1D; 1mg/kg) or l-NAME (nitric oxide; 10mg/kg), but not by indomethacin (COX1/2; 2mg/kg) or glibenclamide (ATP-dependent K(+) channel; 20mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT1D receptors via nitric oxide release.

  1. Evidence for excitatory 5-HT2-receptors on rat brainstem neurones.

    PubMed Central

    Davie, M.; Wilkinson, L. S.; Roberts, M. H.

    1988-01-01

    1. The technique of microiontophoresis was used to investigate the identity of the receptor mediating the excitatory effects of 5-hydroxytryptamine (5-HT) upon neurones in the midline of the medullary brainstem of the rat in vivo. 2. The 5-HT1-like receptor agonists 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) failed to excite the majority of neurones excited by 5-HT. The mobilities of 5-CT and 8-OH-DPAT when tested in vitro were found not to differ significantly from that of 5-HT, suggesting that the lack of effect of these agonists was not due to a lower rate of release from the microelectrodes. 3. The excitatory responses to 5-HT were attenuated by the 5-HT 2-receptor antagonists ketanserin and methysergide when applied microiontophoretically or administered intravenously (0.3 and 1 mg kg-1 respectively). Excitatory responses to glutamate and noradrenaline were not reduced. 4. The 5-HT3-receptor antagonist MDL 72222 failed to attenuate selectively the excitatory response to 5-HT when applied either by microiontophoresis or administered intravenously (1 mg kg-1). 5. Microiontophoretic application of the alpha 1-adrenoceptor antagonist prazosin did not attenuate excitatory responses to either 5-HT or noradrenaline. Intravenously administered prazosin (0.8 mg kg-1) also failed to attenuate excitatory responses to 5-HT, but did block excitatory responses to noradrenaline. 6. These results suggest that 5-HT2-receptors, but not 5-HT1-like receptors, 5-HT3-receptors or alpha 1-adrenoceptors, are involved in the excitatory response of midline medullary neurones to 5-HT. PMID:3395786

  2. Development of the 5-HT2CR-Tango System Combined with an EGFP Reporter Gene.

    PubMed

    Watanabe, Yoshihisa; Tsujimura, Atsushi; Aoki, Miku; Taguchi, Katsutoshi; Tanaka, Masaki

    2016-02-01

    The serotonin 2C receptor (5-HT2CR) is a G-protein-coupled receptor implicated in emotion, feeding, reward, and cognition. 5-HT2CRs are pharmacological targets for mental disorders and metabolic and reward system abnormalities, as alterations in 5-HT2CR expression, RNA editing, and SNPs are involved in these disturbances. To date, 5-HT2CR activity has mainly been measured by quantifying inositol phosphate production and intracellular Ca(2+) release, but these assays are not suitable for in vivo analysis. Here, we developed a 5-HT2CR-Tango assay system, a novel analysis tool of 5-HT2CR activity based on the G-protein-coupled receptor (GPCR)-arrestin interaction. With desensitization of activated 5-HT2CR by arrestin, this system converts the 5-HT2CR-arrestin interaction into EGFP reporter gene signal via the LexA transcriptional activation system. For validation of our system, we measured activity of two 5-HT2CR RNA-editing isoforms (INI and VGV) in HEK293 cells transfected with EGFP reporter gene. The INI isoform displayed both higher basal- and 5-HT-stimulated activities than the VGV isoform. Moreover, an inhibitory effect of 5-HT2CR antagonist SB242084 was also detected by 5-HT2CR-Tango system. This novel tool is useful for in vitro high-throughput targeted 5-HT2CR drug screening and can be applied to future in vivo brain function studies associated with 5-HT2CRs in transgenic animal models.

  3. Identification and functional characterisation of 5-HT4 receptor in sea cucumber Apostichopus japonicus (Selenka)

    PubMed Central

    Wang, Tianming; Yang, Zhen; Zhou, Naiming; Sun, Lina; Lv, Zhenming; Wu, Changwen

    2017-01-01

    Serotonin (5-HT) is an important neurotransmitter and neuromodulator that controls a variety of sensory and motor functions through 5-HT receptors (5-HTRs). The 5-HT4R subfamily is linked to Gs proteins, which activate adenylyl cyclases (ACs), and is involved in many responses in peripheral organs. In this study, the 5-HT4R from Apostichopus japonicus (Aj5-HT4R) was identified and characterised. The cloned full-length Aj5-HT4R cDNA is 1,544 bp long and contains an open reading frame 1,011 bp in length encoding 336 amino acid proteins. Bioinformatics analysis of the Aj5-HT4R protein indicated this receptor was a member of class A G protein coupled receptor (GPCR) family. Further experiments using Aj5-HT4R-transfected HEK293 cells demonstrated that treatment with 5-HT triggered a significant increase in intracellular cAMP level in a dose-dependent manner and induced a rapid internalisation of Aj5-HT4R fused with enhanced green fluorescent protein (Aj5-HT4R-EGFP) from the cell surface into the cytoplasm. In addition, the transcriptional profiles of Aj5-HT4R in aestivating A. japonicas and phosphofructokinase (AjPFK) in 5-HT administrated A. japonicus have been analysed by real-time PCR assays. Results have led to a basic understanding of Aj5-HT4R in A. japonicus, and provide a foundation for further exploration of the cell signaling and regulatory functions of this receptor. PMID:28059140

  4. [5-HT3 receptor antagonist als analgetics in rheumatic diseases].

    PubMed

    Müller, W; Fiebich, B L; Stratz, T

    2006-10-01

    Various rheumatic diseases like fibromyalgia, systemic inflammatory rheumatic disorders and localized diseases, such as arthritides and activated arthroses, tendinopathies and periarthropathies, as well as trigger points can be improved considerably by treatment with the 5-HT3 receptor antagonist tropisetron. Particularly in the latter group of diseases, local injections have done surprisingly rapid analgesic action. This effect matches that of local anesthetics, but lasts considerably longer and is comparable to local injections of local anesthetics combined with corticosteroids. The action of the 5-HT3 receptor antagonists can be attributed to an antinociceptive effect that occurs at the same time as an antiphlogistic and probably also an immunosuppressive effect. Whereas an inhibited release of substance P from the nociceptors, and possibly some other neurokins as well, seems to be the most likely explanation for the antinociceptive action, the antiphlogistic effect is primarily due to an inhibited formation of various different phlogistic substances; in some conditions, like systemic inflammatory rheumatic diseases, for example, the 5-HT3 receptor antagonists may exert an immunosuppressive effect in addition to this.

  5. HT-7 Multipoint Nd Laser Thomson Scattering Apparatus

    NASA Astrophysics Data System (ADS)

    Mao, Jian-shan; Zhao, Jun-yu; Li, Ya-dong; Xie, Ai-gen; Fang, Zhi-sheng; V, Sannikov; A, Gorshkov

    2001-04-01

    A compact, low cost, multipoint Thomson scattering diagnostic system for HT-7 superconducting tokamak has been in operation since 1999. Its capability of measuring electron temperatures is in the range of 200 eV to 2 keV at a density of a few times 1012 cm-3, with a spatial resolution of 2.4 cm for 5 spatial points and a temporal resolution of 1 ms similar 1 s for 8 time points. The main components of the diagnostic system include a 20-25 J Nd:glass laser with 35 ns pulse width (8 pulses per burst), a KDP frequency-doubling unit, spherical mirrors of multipass input optical system, a wide-angle collection objective, a bandpass glass filter for reducing the stray light to zero, a f/2.5 polychromator, a fiberglass collimator, a photomultiplier's box with electronic preamplifier, high gain and high signal/noise ratio, CAMAC data acquisition and so on. The multipass optical system has been successful at increasing the quantity of scattered photons by passing the probing laser beam 10 times through the plasma under investigation. The HT-7 Thomson scattering diagnostic has provided successfully the information on two-dimensional electron temperature in the plasma of HT-7 tokamak with LHCD and IBW.

  6. The serotonin 5-HT7 receptors: two decades of research.

    PubMed

    Gellynck, Evelien; Heyninck, Karen; Andressen, Kjetil W; Haegeman, Guy; Levy, Finn Olav; Vanhoenacker, Peter; Van Craenenbroeck, Kathleen

    2013-10-01

    Like most neurotransmitters, serotonin possesses a simple structure. However, the pharmacological consequences are more complex and diverse. Serotonin is involved in numerous functions in the human body including the control of appetite, sleep, memory and learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation, and depression. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, Parkinson's disease, obsessive-compulsive disorder, eating disorders, migraine, irritable bowel syndrome, tinnitus, and bipolar disease. These effects are mediated via different serotonin (5-HT) receptors. In this review, we will focus on the last discovered member of this serotonin receptor family, the 5-HT7 receptor. This receptor belongs to the G protein-coupled receptor superfamily and was cloned two decades ago. Later, different splice variants were described but no major functional differences have been described so far. All 5-HT7 receptor variants are coupled to Gαs proteins and stimulate cAMP formation. Recently, several interacting proteins have been reported, which can influence receptor signaling and trafficking.

  7. The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves

    PubMed Central

    Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C.; Finger, Thomas E.

    2015-01-01

    Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT3A promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT3A mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μm 5-HT and this response is blocked by 1 μm ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μm m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response. SIGNIFICANCE STATEMENT Historically, serotonin (5-hydroxytryptamine; 5-HT) has been described as a candidate neurotransmitter in the gustatory system and recent studies show that type III taste receptor cells release 5-HT in response to various taste stimuli. In the present study, we demonstrate that a subset of gustatory sensory neurons express functional

  8. 40 CFR 180.1126 - Codlure, (E,E)-8,10-Dodecadien-1-ol; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Codlure, (E,E)-8,10-Dodecadien-1-ol... RESIDUES IN FOOD Exemptions From Tolerances § 180.1126 Codlure, (E,E)-8,10-Dodecadien-1-ol; exemption from... the insect pheromone codlure, (E,E)-8,10-dodecadien-1-ol, on all raw agricultural commodities...

  9. 31 CFR 351.19 - What are maturity periods of Series EE savings bonds with issue dates prior to May 1, 1995?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false What are maturity periods of Series... BUREAU OF THE FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates...

  10. 31 CFR 351.82 - Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... issuance of Series EE savings bonds in a chain letter scheme? 351.82 Section 351.82 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.82 Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?...

  11. 31 CFR 363.52 - What is the principal amount of book-entry Series EE and Series I savings bonds that I may...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-entry Series EE and Series I savings bonds that I may acquire in one year? 363.52 Section 363.52 Money... of book-entry Series EE and Series I savings bonds that I may acquire in one year? (a) The principal... Series EE savings bonds and $10,000 for Series I savings bonds. (b) Bonds purchased or transferred...

  12. 31 CFR 363.52 - What is the principal amount of book-entry Series EE and Series I savings bonds that I may...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-entry Series EE and Series I savings bonds that I may acquire in one year? 363.52 Section 363.52 Money... of book-entry Series EE and Series I savings bonds that I may acquire in one year? (a) The principal... Series EE savings bonds and $10,000 for Series I savings bonds. (b) Bonds purchased or transferred...

  13. 31 CFR 351.82 - Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of Series EE savings bonds in a chain letter scheme? 351.82 Section 351.82 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.82 Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?...

  14. 31 CFR 363.52 - What is the principal amount of book-entry Series EE and Series I savings bonds that I may...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-entry Series EE and Series I savings bonds that I may acquire in one year? 363.52 Section 363.52 Money... of book-entry Series EE and Series I savings bonds that I may acquire in one year? (a) The principal... Series EE savings bonds and $10,000 for Series I savings bonds. (b) Bonds purchased or transferred...

  15. 31 CFR 351.82 - Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of Series EE savings bonds in a chain letter scheme? 351.82 Section 351.82 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.82 Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?...

  16. 31 CFR 351.82 - Does Fiscal Service prohibit the issuance of Series EE savings bonds in a chain letter scheme?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... issuance of Series EE savings bonds in a chain letter scheme? 351.82 Section 351.82 Money and Finance... BUREAU OF THE FISCAL SERVICE OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.82 Does Fiscal Service prohibit the issuance of Series EE savings bonds in a chain letter...

  17. 31 CFR 351.82 - Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of Series EE savings bonds in a chain letter scheme? 351.82 Section 351.82 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Miscellaneous Provisions § 351.82 Does Public Debt prohibit the issuance of Series EE savings bonds in a chain letter scheme?...

  18. Differences in agonist dissociation constant estimates for 5-HT at 5-HT2-receptors: a problem of acute desensitization?

    PubMed Central

    Leff, P.; Martin, G. R.

    1988-01-01

    1. The agonist dissociation constant for 5-hydroxytryptamine (5-HT) was estimated in the guinea-pig isolated trachea by the method of receptor inactivation. The value obtained (pKA = 6.45) was significantly lower than estimates previously obtained in the rabbit aorta and rat jugular vein, although all three tissues are supposed to contain the same 5-HT2 class of receptor. 2. The antagonist dissociation constant for alpha,alpha-dimethyltryptamine was also estimated in the guinea-pig trachea. The pKB value (5.43) was not significantly different from previous estimates in the rabbit aorta and rat jugular vein, consistent with receptor homogeneity between the three tissues. 3. The effect-time profiles corresponding to individual 5-HT applications were more transient in the guinea-pig trachea than in the rabbit aorta. This difference could be accounted for using a simple model of acute receptor desensitization (Leff, 1986), assuming that the conversion of active agonist-receptor complexes into inactive ones was faster in the guinea-pig trachea than in the rabbit aorta. 4. Computer simulation of the desensitization model showed that the discrepancy of pKA estimates for 5-HT between the rabbit aorta and guinea-pig trachea could also be explained using the same rate constant difference that accounted for the difference in effect-time profiles. This analysis indicated that the estimate made in the trachea was erroneously low, whereas that made in the aorta was concluded to be correct. 5. The apparent association between transience of response and pKA estimates is discussed with particular attention to the reliability of agonist affinity estimates in receptor classification. PMID:3228675

  19. Molecular and functional characterization of proteins interacting with the C-terminal domains of 5-HT2 receptors: emergence of 5-HT2 "receptosomes".

    PubMed

    Gavarini, Sophie; Bécamel, Carine; Chanrion, Benjamin; Bockaert, Joël; Marin, Philippe

    2004-06-01

    Many cellular functions are carried out by multiprotein complexes. The last five years of research have revealed that many G-protein coupled receptor (GPCR) functions that are not mediated by G proteins involve protein networks, which interact with their intracellular domains. This review focuses on one family of GPCRs activated by serotonin, the 5-HT(2) receptor family, which comprises three closely related subtypes, the 5-HT(2A), the 5-HT(2B) and the 5-HT(2c) receptors. These receptors still raise particular interest, because a large number of psychoactive drugs including hallucinogens, anti-psychotics, anxiolytics and anti-depressants, mediate their action, at least in part, through activation of 5-HT(2) receptors. Recent studies based on two-hybrid screens, proteomic, biochemical and cell biology approaches, have shown that the C-terminal domains of 5-HT(2) receptors interact with intracellular proteins. To date, the protein network associated with the C-terminus of the 5-HT(2C) receptor has been the most extensively characterized, using a proteomic approach combining affinity chromatography, mass spectrometry and immunoblotting. It includes scaffolding proteins containing one or several PDZ domains, signalling proteins and proteins of the cytoskeleton. Data indicating that the protein complexes interacting with 5-HT(2) receptor C-termini tightly control receptor trafficking and receptor-mediated signalling will also be reviewed.

  20. Fluvoxamine, a selective serotonin reuptake inhibitor, and 5-HT2C receptor inactivation induce appetite-suppressing effects in mice via 5-HT1B receptors.

    PubMed

    Nonogaki, Katsunori; Nozue, Kana; Takahashi, Yukiko; Yamashita, Nobuyuki; Hiraoka, Shuichi; Kumano, Hiroaki; Kuboki, Tomifusa; Oka, Yohsitomo

    2007-10-01

    Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream melanocortin pathway are suggested to mediate the appetite-suppressing effects of 5-HT drugs such as m-chlorophenylpiperazine (mCPP) and fenfluramine. Here, we report that fluvoxamine (3-30 mg/kg), a selective serotonin reuptake inhibitor (SSRI), in the presence of SB 242084 (1-2 mg/kg), a selective 5-HT2C receptor antagonist, exerts appetite-suppressing effects while fluvoxamine or SB 242084 alone has no effect. The appetite-suppressing effects were attenuated in the presence of SB 224289 (5 mg/kg), a selective 5-HT1B receptor antagonist. Moreover, CP 94253 (5-10 mg/kg), a selective 5-HT1B receptor agonist, exerted appetite-suppressing effects and significantly increased hypothalamic pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) gene expression and decreased hypothalamic orexin gene expression. These results suggest that fluvoxamine and inactivation of 5-HT2C receptors exert feeding suppression through activation of 5-HT1B receptors, and that 5-HT1B receptors up-regulate hypothalamic POMC and CART gene expression and down-regulate hypothalamic orexin gene expression in mice.