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Sample records for p4 ht ee

  1. P4 medicine needs P4 education.

    PubMed

    Cesario, Alfredo; Auffray, Charles; Russo, Patrizia; Hood, Leroy

    2014-01-01

    This monographic issue of Current Pharmacological Design discusses extensively on the innovative paradigms for disease control in Active and Healthy Ageing. Wellness, as a status to be achieved and maintained in our lives, getting longer and hopefully healtier, is the new and comprehensive declination of "health" itself, leading the shaping of research and research policy in the health domain worldwide. Many of the contributions describe the state of the art -and beyond- approaches for the most common diseases based on the available medical knowledge; two, in particular (Bousquet J et al., Cesario A, et al.), extend to the innovative approaches defined in the framework of the holistic and integrative philosophy of the Predictive, Preventive, Personalized and Participatory (P4) Systems Medicine. The availability of more and more powerful technologies to extract data coupled with the inclusion of information coming from the nonstrictly-medical sphere of the patient/individual and his/her lifestyle along with the increase in computational power, will definitely set the stage for a paradigm-shift in bio-medicine with deep ethical and societal impact. The brief comment that follows speculates about the implications of this transition from the educational perspective taking stock of the direct experience of the Authors in the consultation process active in the scientific community.

  2. P4 Medicine versus Hippocrates.

    PubMed

    Pulciani, Simonetta; Di Lonardo, Anna; Fagnani, Corrado; Taruscio, Domenica

    2017-01-01

    Hippocrates was the first to raise awareness of medicine as a science. He asserted the body being a unified whole and emphasized the importance of preventive and predictive medicine, spurring physicians to foster patient collaboration. Recent achievements today have permitted a new approach "P4 medicine" - Predictive, Preventive, Personalized and Participatory - with the aim of depicting an individual's health history and molecular profile in determining the best medical intervention in maintaining or restoring wellbeing. There is a link, which brings together Hippocrates and P4 Medicine. This review will elaborate further this statement, considering the scientific achievements that paved the way for recent medical approaches. Emphasis will be given to the social impact of new diagnostic and therapeutic protocols, considering their costs and their success probabilities.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Preparative parallel protein purification (P4).

    PubMed

    Strömberg, Patrik; Rotticci-Mulder, Joke; Björnestedt, Robert; Schmidt, Stefan R

    2005-04-15

    In state of the art drug discovery, it is essential to gain structural information of pharmacologically relevant proteins. Increasing the output of novel protein structures requires improved preparative methods for high throughput (HT) protein purification. Currently, most HT platforms are limited to small-scale and available technology for increasing throughput at larger scales is scarce. We have adapted a 10-channel parallel flash chromatography system for protein purification applications. The system enables us to perform 10 different purifications in parallel with individual gradients and UV monitoring. Typical protein purification applications were set up. Methods for ion exchange chromatography were developed for different sample proteins and columns. Affinity chromatography was optimized for His-tagged proteins using metal chelating media and buffer exchange by gel filtration was also tested. The results from the present system were comparable, with respect to resolution and reproducibility, with those from control experiments on an AKTA purifier system. Finally, lysates from 10 E. coli cultures expressing different His-tagged proteins were subjected to a three-step parallel purification procedure, combining the above-mentioned procedures. Nine proteins were successfully purified whereas one failed probably due to lack of expression.

  8. 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.

  9. 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.

  10. 40 CFR Table 1 to Subpart Ee of... - Applicability of General Provisions to Subpart EE

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Reference Applies to subpart EE Comment 63.1(a)(1) Yes Additional terms defined in § 63.702(a); when overlap between subparts A and EE occurs, subpart EE takes precedence. 63.1(a)(2)-(14) Yes. 63.1(b)(1)-(3) Yes. 63.1(c)(1) Yes Subpart EE specifies the applicability of each paragraph in subpart A to sources subject...

  11. 40 CFR Table 1 to Subpart Ee of... - Applicability of General Provisions to Subpart EE

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Reference Applies to subpart EE Comment 63.1(a)(1) Yes Additional terms defined in § 63.702(a); when overlap between subparts A and EE occurs, subpart EE takes precedence. 63.1(a)(2)-(14) Yes. 63.1(b)(1)-(3) Yes. 63.1(c)(1) Yes Subpart EE specifies the applicability of each paragraph in subpart A to sources subject...

  12. 40 CFR Table 1 to Subpart Ee of... - Applicability of General Provisions to Subpart EE

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Reference Applies to subpart EE Comment 63.1(a)(1) Yes Additional terms defined in § 63.702(a); when overlap between subparts A and EE occurs, subpart EE takes precedence. 63.1(a)(2)-(14) Yes. 63.1(b)(1)-(3) Yes. 63.1(c)(1) Yes Subpart EE specifies the applicability of each paragraph in subpart A to sources subject...

  13. 40 CFR Table 1 to Subpart Ee of... - Applicability of General Provisions to Subpart EE

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Reference Applies to subpart EE Comment 63.1(a)(1) Yes Additional terms defined in § 63.702(a); when overlap between subparts A and EE occurs, subpart EE takes precedence. 63.1(a)(2)-(14) Yes. 63.1(b)(1)-(3) Yes. 63.1(c)(1) Yes Subpart EE specifies the applicability of each paragraph in subpart A to sources subject...

  14. 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)

  15. 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)

  16. 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)

  17. 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)

  18. P4P4P: An Agenda for Research on Pay for Performance for Patients

    PubMed Central

    Volpp, Kevin G.; Pauly, Mark V.; Loewenstein, George; Bangsberg, David

    2012-01-01

    Unhealthy behaviors are a major cause of poor health outcomes and high health care costs. In this Commentary, we describe an agenda for research to guide broader use of patient-targeted financial incentives either in conjunction with provider-targeted financial incentives (P4P) or in clinical contexts where provider-targeted approaches are unlikely to be effective. We discuss evidence of proven effectiveness and limitations of the existing evidence, reasons for underutilization of these approaches, and options for operationalizing wider use. Patient-targeted incentives have great potential, and systematic testing will help determine how they can best be used to improve population health. PMID:19124872

  19. Extending the coordination chemistry of molecular P(4)S(3): the polymeric Ag(P(4)S(3))(+) and Ag(P(4)S(3))(2)(+) cations.

    PubMed

    Adolf, Ariane; Gonsior, Marcin; Krossing, Ingo

    2002-06-19

    Upon reacting P(4)S(3) with AgAl(hfip)(4) and AgAl(pftb)(4) [hfip = OC(H)(CF(3))(2); pftb = OC(CF(3))(3)], the compounds Ag(P(4)S(3))Al(hfip)(4) 1 and Ag(P(4)S(3))(2)(+)[Al(pftb)(4)](-) 2 formed in CS(2) (1) or CS(2)/CH(2)Cl(2) (2) solution. Compounds 1 and 2 were characterized by single-crystal X-ray structure determinations, Raman and solution NMR spectroscopy, and elemental analyses. One-dimensional chains of [Ag(P(4)S(3))(x)](infinity) (x = 1, 1; x = 2, 2) formed in the solid state with P(4)S(3) ligands that bridge through a 1,3-P,S, a 2,4-P,S, or a 3,4-P,P eta(1) coordination to the silver ions. Compound 2 with the least basic anion contains the first homoleptic metal(P(4)S(3)) complex. Compounds 1 and 2 also include the long sought sulfur coordination of P(4)S(3). Raman spectra of 1 and 2 were assigned on the basis of DFT calculations of related species. The influence of the silver coordination on the geometry of the P(4)S(3) cage is discussed, additionally aided by DFT calculations. Consequences for the frequently observed degradation of the cage are suggested. An experimental silver ion affinity scale based on the solid-state structures of several weak Lewis acid base adducts of type (L)AgAl(hfip)(4) is given. The affinity of the ligand L to the silver ion increases according to P(4) < CH(2)Cl(2) < P(4)S(3) < S(8) < 1,2-C(2)H(4)Cl(2) < toluene.

  20. 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)....

  1. 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)....

  2. 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)....

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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…

  10. 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…

  11. 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.

  12. 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

  13. 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)....

  14. 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)....

  15. 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.

  16. 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.

  17. Case for an EeV Gravitino

    NASA Astrophysics Data System (ADS)

    Dudas, Emilian; Mambrini, Yann; Olive, Keith A.

    2017-08-01

    We consider the possibility that supersymmetry is broken above the inflationary mass scale and that the only "low" energy remnant of supersymmetry is the gravitino with a mass of the order of the EeV scale. The gravitino in this class of models becomes a candidate for the dark matter of the Universe. To avoid the overproduction of gravitinos from the decays of the next-to-lightest supersymmetric particle we argue that the supersymmetric spectrum must lie above the inflationary mass scale (MSUSY>10-5MP˜1 013 GeV ). Since m3 /2≃MSUSY2/MP , we expect m3 /2≳0.2 EeV . Cosmological constraints then predict a relatively large reheating temperature between 1 010 and 1 012 GeV .

  18. 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.

  19. 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.

  20. 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

  1. The History of GalaFLEX P4HB Scaffold.

    PubMed

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

    2016-11-01

    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. © 2016 The American Society for Aesthetic Plastic Surgery, Inc.

  2. 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.

  3. 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.

  4. First LQCD Physics Runs with MILC and P4RHMC

    SciTech Connect

    Soltz, R; Gupta, R

    2007-01-18

    An initial series of physics LQCD runs were submitted to the BG/L science bank with the milc and p4rhmc. Both runs were for lattice dimensions of 32{sup 2} x 8. The p4 calculation was performed with v2.0 QMP{_}MPI.X (semioptomized p4 code using qmp over mpi) and milc v7.2, also using RHMC, but not specifically optimized for BlueGene. Calculations were performed along lines of constant physics, with the light quark masses 2-3 times their physics values and the strange quark mass set by m{sub ud} = 0.1m{sub s}. Job submissions was performed using the standard milc and p4 scripts provided on the ubgl cluster. Initial thermalized lattices for each code were also provided in this way. The only modifications for running on BG/L were to the directory names and the mT parameter which determines job durations (24 hrs on BG/L vs. 4 hrs on ubgl). The milc scripts were set to resubmit themselves 10 times, and the p4 scripts were submitted serially using the ''psub -d'' job dependency option. The runp4rhmc.tcsh could not be used to resubmit due to the 30m time limit imposed on interactive jobs. Most jobs were submitted to the smallest, 512 node partitions, but both codes could also run on the 1024 node partitions with a gain of only 30-50%. The majority of jobs ran without error. Stalled jobs were often indicative of a communication gap within a partition that LC was able to fix quickly. On some occasion a zero-length lattice file was deleted to allow jobs to restart successfully. Approximately 1000 trajectories were calculated for each beta value, see Table . The analysis was performed with the standard analysis scripts for each code, make{_}summary.pl for milc and analysis.tcsh for p4rhmc. All lattices, log files, and job submission scripts have been archived to permanent storage for subsequent analysis.

  5. 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

  6. EE Cep Winks in Full Color (Abstract)

    NASA Astrophysics Data System (ADS)

    Walker, G.

    2015-06-01

    (Abstract only) We observe the long period (5.6 years) Eclipsing Binary Variable Star EE Cep during its 2014 eclipse. It was observed on every clear night from the Maria Mitchell Observatory as well as remote sites for a total of 25 nights. Each night consisted of a detailed time series in BVRI looking for short term variations for a total of >10,000 observations. The data was transformed to the Standard System. In addition, a time series was captured during the night of the eclipse. This data provides an alternate method to determine Time of Minimum than traditionally performed. The TOM varied with color. Several strong correlations are seen between colors substantiating the detection of variations on a time scale of hours. The long term light curve shows five interesting and different Phases with different characteristics.

  7. Systems biology and p4 medicine: past, present, and future.

    PubMed

    Hood, Leroy

    2013-04-01

    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 perturbations in

  8. 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

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. Effect of electron irradiation on P4VP/PTSA complex and P4VP/Phthalocyanine composites

    NASA Astrophysics Data System (ADS)

    Vijayalakshmi Rao, R.; Mohan Rao, P.; Shridhar, M. H.

    2002-03-01

    Effect of electron irradiation on the optical and electrical properties of poly(4vinyl pyridine) (P4VP) complexed with P-toluene sulfonic acid (PTSA) and composites of P4VP with copper phthalocyanine (CuPc) and nickel phthalocyanine (NiPc) have been studied. In the optical spectra of the complex and composites, there is a shift in the absorption peak towards lower energy side and broadening of the peaks in case of composites after irradiation indicating the possibility of unsaturation. The FTIR analysis after irradiation shows the shift of number of peaks towards higher and lower energy sides. Shift in typical major peaks like CN, C-H are interpreted as due to the crosslinking or creation of unsaturated bonds. From electrical studies, it is seen that for lower dose of irradiation (1 kGy) there is no significant change but for higher doses the current conduction increases substantially. The permanent and temporary defects produced in the polymer matrix seems to affect the I/V characteristics of the complex and composites.

  14. 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

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

    PubMed

    Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2017-02-15

    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

  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. 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.

  18. 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.

  19. Micro-canonical pentaquark production in ee and pp collisions

    NASA Astrophysics Data System (ADS)

    Liu, Fu-Ming; Werner, Klaus

    2008-01-01

    The existence of pentaquarks became questionable, because the Θ peak is observed in some p+p collisions, but not in ee annihilations. People think initial baryon number is necessary to produce pentaquarks. In this paper, we estimate and compare the production of Θ(1540) and Ξ(1860) in ee and pp collisions at different energies using Fermi statistical model as originally proposed in its microcanonical form. We find that both Θ(1540) and Ξ(1860) yield more in ee at LEP energies than in pp collisions at SPS and RHIC energies, if pentaquarks do exist. Initial baryon number is not necessary for pentaquark production.

  20. [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.

  1. 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

  2. 8. Site Section EE Aquatic Park, Area bounded by ...

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

    8. Site Section E-E - Aquatic Park, Area bounded by Hyde Street and Van Ness Avenue on the East and West and the Aquatic Cove and Beach Street on the North and South, San Francisco, San Francisco County, CA

  3. 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.

  4. Experiment 2039 – Diagnostic Logging in EE-3

    SciTech Connect

    Dash, Zora V.; Grigsby, Charles O.; Murphy, Hugh D.

    1984-06-19

    Experiment 2039, diagnostic logging in EE-3, was conducted in two parts. Part A, temperature and collar locator surveys while injecting water was run from ~16:00, 4-Apr-84 through ~11:00, 5-Apr-84. Part B, tracer surveys, run from ~8:15 - 21:00, 6-Apr-84. The purpose of the surveys was to determine fluid entry locations in the open hole sections of EE-3

  5. A racemate-rules effect supramolecular polymer for ee determination of malic acid in the high ee region.

    PubMed

    Chen, Xuan-Xuan; Jiang, Yun-Bao; Anslyn, Eric V

    2016-10-18

    A supramolecular polymeric system that shows an unusual "racemate-rules" chiroptical property, an effect opposite to the well-known "majority-rules", has been utilized for accurate determination of malic acid enantiopurity at high ee values.

  6. 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...

  7. 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...

  8. 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...

  9. 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....

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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?...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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?...

  6. 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...

  7. 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...

  8. 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...

  9. 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?...

  10. 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...

  11. 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...

  12. 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

  13. 5-HT6 receptors and Alzheimer's disease.

    PubMed

    Ramírez, María Javier

    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.

  14. Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors.

    PubMed

    Delgado, Mercedes; Caicoya, Anne G; Greciano, Virginia; Benhamú, Bellinda; López-Rodríguez, María Luz; Fernández-Alfonso, María Soledad; Pozo, Miguel A; Manzanares, Jorge; Fuentes, José A

    2005-03-21

    S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety.

  15. 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

  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. 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.

  18. Existence of Brain 5-HT1A-5-HT2A Isoreceptor Complexes with Antagonistic Allosteric Receptor-Receptor Interactions Regulating 5-HT1A Receptor Recognition.

    PubMed

    Borroto-Escuela, Dasiel O; Li, Xiang; Tarakanov, Alexander O; Savelli, David; Narváez, Manuel; Shumilov, Kirill; Andrade-Talavera, Yuniesky; Jimenez-Beristain, Antonio; Pomierny, Bartosz; Díaz-Cabiale, Zaida; Cuppini, Riccardo; Ambrogini, Patrizia; Lindskog, Maria; Fuxe, Kjell

    2017-08-31

    Studies on serotonin-selective reuptake inhibitors have established that disturbances in the ascending 5-HT neuron systems and their 5-HT receptor subtypes and collateral networks to the forebrain contribute to the etiology of major depression and are targets for treatment. The therapeutic action of serotonin-selective reuptake inhibitors is of proven effectiveness, but the mechanisms underlying their effect are still unclear. There are many 5-HT subtypes involved; some need to be blocked (e.g., 5-HT2A, 5-HT3, and 5-HT7), whereas others need to be activated (e.g., postjunctional 5-HT1A and 5-HT4). These state-of-the-art developments are in line with the hypothesis that the development of major depression can involve an imbalance of the activity between different types of 5-HT isoreceptors. In the current study, using in situ proximity ligation assay (PLA), we report evidence for the existence of brain 5-HT1A-5-HT2A isoreceptor complexes validated in cellular models with bioluminescence resonance energy transfer (BRET(2)) assay. A high density of PLA-positive clusters visualizing 5-HT1A-5-HT2A isoreceptor complexes was demonstrated in the pyramidal cell layer of the CA1-CA3 regions of the dorsal hippocampus. A marked reduction in the density of PLA-positive clusters was observed in the CA1 and CA2 regions 24 h after a forced swim test session, indicating the dynamics of this 5-HT isoreceptor complex. Using a bioinformatic approach, previous work indicates that receptors forming heterodimers demonstrate triplet amino acid homologies. The receptor interface of the 5-HT1A-5-HT2A isoreceptor dimer was shown to contain the LLG and QNA protriplets in the transmembrane and intracellular domain, respectively. The 5-HT2A agonist TCB2 markedly reduced the affinity of the 5-HT1A agonist ipsapirone for the 5-HT1A agonist binding sites in the frontal lobe using the 5-HT1A radioligand binding assay. This action was blocked by the 5-HT2A antagonist ketanserin. It is proposed that

  19. 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.

  20. Separation of e+e- → e+e- and e+e- → π+π- events based on the difference in the energy deposition profiles in SND detector calorimeter.

    NASA Astrophysics Data System (ADS)

    Achasov, M. N.; Kupich, A. S.

    2017-06-01

    The technique of discrimination of the e+e- → e+e- and e+e- → π+π- events in energy range 0.5 < √s < 1 GeV based on the difference in the energy deposition in calorimeter of SND detector was developed by applying machine learning method. Identification efficiency for e+e- → e+e- and e+e- → π+π- events is estimated to be in the range from 99.3 to 99.8%. Contribution of the identification efficiencies errors to the total error of e+e- → π+π- cross section is less than 0.2% for the most energy points.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Expressed emotion, human agency, and schizophrenia: toward a new model for the EE-relapse association.

    PubMed

    Breitborde, Nicholas J K; López, Steven R; Nuechterlein, Keith H

    2009-03-01

    Although there is a clear statistical association between expressed emotion (EE) and schizophrenic relapse, our understanding of the mechanisms underlying this relationship is underdeveloped. This study tested a theoretical model in which caregivers' perceptions of their ill relative's agency underlie the EE-relapse association. To evaluate this model, we completed qualitative and quantitative analyses of narratives provided by individuals caring for a relative with schizophrenia. The results indicate that high-EE caregivers perceive the expression of symptoms as stemming from their ill relative's agency more frequently than low-EE caregivers. This was true for both high-EE-criticism and high-EE-emotional overinvolvement caregivers. High-EE and low-EE caregivers did not differ in their perceptions of the role of their ill relative's agency with regard to the control of symptoms. The findings suggest that EE may be a proxy risk factor for caregivers' perceptions of their ill relative's agency.

  7. 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.

  8. Involvement of 5-HT1, 5-HT2, and 5-HT3 receptors in the mediation of the prolactin response to serotonin and 5-hydroxytryptophan.

    PubMed

    Jørgensen, H; Knigge, U; Warberg, J

    1992-03-01

    Serotonin (5-HT) is involved in the neuroendocrine regulation of prolactin (PRL) secretion as a stimulator. Within the last decade several 5-HT receptor types have been identified, but their individual role in the mediation of the PRL response to 5-HT is only partly understood. We investigated in conscious male rats the effect of different 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytrytophan (5-HTP) which was administered in combination with the 5-HT reuptake inhibitor fluoxetine. 5-HT (0.5-5.0 mg/kg BW i.v.) or 5-HTP (25-100 mg/kg i.p.) in combination with saline or fluoxetine (10 mg/kg i.p.) increased the plasma PRL concentration dose-dependently. Pretreatment with the 5-HT1+2 receptor antagonist methysergide (2.5 mg/kg i.p.) prevented the stimulatory effect of 5-HT or 5-HTP + fluoxetine. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (2.5 mg/kg i.p.) inhibited the PRL response to 5-HT by approximately 80% and to 5-HTP + fluoxetine approximately 100%. A higher dose (10 mg/kg) of the 5-HT2 receptor antagonists possessed only 50% inhibitory effect. Pretreatment with the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the PRL response induced by 5-HT or by 5-HTP + fluoxetine. The maximal inhibitory effect (approximately 80%) was obtained by a dose of 0.1 mg/kg of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 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

  10. Simulated transient behavior of HT9 cladding

    SciTech Connect

    Cannon, N.S.; Huang, F.H.; Hamilton, M.L.

    1988-09-01

    Simulated transient tests were performed on sections of HT9 fast- reactor fuel pin cladding irradiated to a fast fluence of nearly 16 /times/ 10/sup 22/ n/cm/sup 2/ at temperatures ranging from 370 to 620/degree/C. After removing fuel, these specimens were internally pressurized and heated at one of several constant rates (0.56, 5.6, or 110/degree/C/s) until specimen failure occurred. A slight reduction of strength was observed in irradiated cladding, particularly at 110/degree/C/s, when compared with transient results from unirradiated HT9 control specimens; however, this strength reduction did not correlate with either fluence or irradiation temperature. A small reduction of ductility was also observed for irradiated cladding failing at temperatures above 800/degree/C at the lower heating rates (0.56 or 5.6/degree/C/s); irradiated cladding was generally more ductile at 110/degree/C/s than unirradiated HT9 cladding. The HT9 cladding results were compared with similar transient data obtained previously from 20% Cold-Worked Type 316 Stainless Steel (316 SS) cladding. In the unirradiated state, this austenitic cladding is stronger and less ductile than HT9 cladding. However, the 316 SS cladding undergoes a significant loss of strength and ductility during irradiation when in contact with oxide fuel, by a mechanism labeled the fuel adjacency effect (FAE). The FAE is believed to be liquid metal embrittlement from fission products. The HT9 fuel pin cladding remained as strong or stronger than the 316 SS cladding when irradiated in contact with fuel, showing no evidence of the FAE up to the high fluences reported here. The ductility of the irradiated HT9 fuel pin cladding remained significantly greater than that of irradiated 316 SS cladding. 14 refs., 11 figs., 1 tab.

  11. 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.

  12. Superweak complexes of tetrahedral P4 molecules with the silver cation of weakly coordinating anions.

    PubMed

    Krossing, Ingo; van, Wüllen Leo

    2002-02-02

    The silver aluminates AgAl[OC(CF3)2(R)]4 (R = H, CH3, CF3) react with solutions of white phosphorus P4 to give complexes that bind one or two almost undistorted tetrahedral P4 molecules in an fashion: [Ag(P4)2]+[Al(OC(CF3)3)4]+ (1) containing the first homoleptic metal-phosphorus cation, the molecular species (P4)AgAl[OC(CH3)(CF3)2]4 (2), and the dimeric Ag(mu,eta2-P4)Ag bridged [(P4)AgAl[OC(H)(CF3)2]4]2 (3). Compounds 1-3 were characterized by variable-temperature (VT) 31P NMR spectroscopy (1 also by VT 32P MAS-NMR spectroscopy), Raman spectroscopy, and single-crystal X-ray crystallography. Other Ag:P4 ratios did not lead to new species, and this observation was rationalized on thermodynamic grounds. The Ag(P4)2+ ion has an almost planar coordination environment around the Ag+ ion due to d(x2 - y2)(Ag) --> sigma*(P-P) backbonding. Calculations (HF-DFT) on six Ag(P4)2+ isomers 4a-f showed that the planar eta2 form 4a is only slightly favored by 5.2 kJ mol(-1) over the tetrahedral eta2 species 4b; eta1-P4 and eta3-P4 complexes are less favorable (27-76 kJ mol(-1)). The bonding of the P4 moiety in [RhCl(eta2-P4)(PPh3)2], the only compound in which an eta2 bonding mode of a tetrahedral P4 molecule has been claimed, must be regarded as a tetraphosphabicyclobutane, and not as a tetrahedro-P4 complex, on the basis of the published NMR and vibrational spectra, the calculated geometry of [RhCl(P4)(PH3)2] (10), the highly endothermic (385 kJ mol(-1)) calculated dissociation enthalpy of 10 into P4 and RhCl(PH3)2 (11), as well as atoms in molecules (AIM) and natural bond orbital (NBO) population analyses of 10 and the Ag(P4)2+ ion. Therefore, 1-3 are the first examples of species containing eta2-coordinated tetrahedral P4 molecules.

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  17. Measuring Preferences for a Diabetes Pay-for-Performance for Patient (P4P4P) Program using a Discrete Choice Experiment.

    PubMed

    Chen, Tsung-Tai; Tung, Tao-Hsin; Hsueh, Ya-Seng Arthur; Tsai, Ming-Han; Liang, Hsiu-Mei; Li, Kay-Lun; Chung, Kuo-Piao; Tang, Chao-Hsiun

    2015-07-01

    To elicit a patient's willingness to participate in a diabetes pay-for-performance for patient (P4P4P) program using a discrete choice experiment method. The survey was conducted in March 2013. Our sample was drawn from patients with diabetes at five hospitals in Taiwan (International Classification of Diseases, Ninth Revision, Clinical Modification code 250). The sample size was 838 patients. The discrete choice experiment questionnaire included the attributes monthly cash rewards, exercise time, diet control, and program duration. We estimated a bivariate probit model to derive willingness-to-accept levels after accounting for the characteristics (e.g., severity and comorbidity) of patients with diabetes. The preferred program was a 3-year program involving 30 minutes of exercise per day and flexible diet control. Offering an incentive of approximately US $67 in cash per month appears to increase the likelihood that patients with diabetes will participate in the preferred P4P4P program by approximately 50%. Patients with more disadvantageous characteristics (e.g., elderly, low income, greater comorbidity, and severity) could have less to gain from participating in the program and thus require a higher monetary incentive to compensate for the disutility caused by participating in the program's activities. Our result demonstrates that a modest financial incentive could increase the likelihood of program participation after accounting for the attributes of the P4P4P program and patients' characteristics. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  18. 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

  19. Designing ee-Learning Environments: Lessons from an Online Workshop

    ERIC Educational Resources Information Center

    Godwin, Lindsey; Kaplan, Soren

    2008-01-01

    Based on their work leading three experiential, online workshops with over 180 participants from around the world, Lindsey Godwin and Soren Kaplan share reflections on designing and conducting successful ee-learning courses. The workshops sought to translate a popular face-to-face seminar in appreciative inquiry, an increasingly popular…

  20. 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.

  1. Designing ee-Learning Environments: Lessons from an Online Workshop

    ERIC Educational Resources Information Center

    Godwin, Lindsey; Kaplan, Soren

    2008-01-01

    Based on their work leading three experiential, online workshops with over 180 participants from around the world, Lindsey Godwin and Soren Kaplan share reflections on designing and conducting successful ee-learning courses. The workshops sought to translate a popular face-to-face seminar in appreciative inquiry, an increasingly popular…

  2. 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…

  3. 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…

  4. 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…

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

    NASA Image and Video Library

    1982-03-30

    STS003-23-165 (22-30 March 1982) --- Astronaut Gordon Fullerton, STS-3 pilot, 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. Photo credit: NASA

  6. 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].

  7. Edema of the interarytenoid mucosa seen on endoscopy is related to endoscopic-positive esophagitis (EE) and is an independent predictor of EE.

    PubMed

    Kondo, Yoshihiro; Ogasawara, Naotaka; Sasaki, Makoto; Arimoto, Mariko; Yanamoto, Kenichiro; Nishimura, Kunihiro; Noda, Hisatsugu; Okaniwa, Noriko; Ogawa, Tetsuya; Kasugai, Kunio

    2013-11-01

    Laryngopharyngeal reflux (LPR) is defined as the retrograde flow of gastric contents up through the esophagus to the larynx and hypopharynx; this is an extra-esophageal manifestation of gastroesophageal reflux disease (GERD). Although both LPR and GERD are caused by reflux of stomach contents, their clinical presentations and treatments differ. In the present study, we assessed esophago-gastroendoscopic findings related to GERD, specifically endoscopic-positive esophagitis (EE), laryngopharyngeal findings, and GERD symptoms on the 12-question frequency scale for the symptoms of gastroesophageal reflux disease (FSSG). Then, independent predictors of EE were analyzed, and relationships among EE, laryngopharyngeal findings, and patients' symptoms and characteristics were investigated. Hiatal hernia (odds ratio [OR]: 2.70; 95% confidence interval [CI]: 1.17-6.23, P-value 0.019) and edema of theinterarytenoid mucosa (OR, 3.77; 95% CI, 1.26-16.3; P-value 0.035) were significantly related with EE and independent predictors of EE. However, patients' characteristics and the FSSG score had no significant relationship with EE; there was no relationship between patients' characteristics and EE, regardless of its severity. Although LPR symptoms had no significant relationship with the findings of EE, hiatal hernia and edema of the interarytenoid mucosa were significantly related with EE and were considered to be independent predictors of EE. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

  8. 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.

  9. 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

  10. 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.

  11. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (Continued) FISCAL SERVICE, 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...

  12. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (Continued) FISCAL SERVICE, 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...

  13. 31 CFR 351.6 - When may I redeem my Series EE savings bond?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (Continued) FISCAL SERVICE, 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...

  14. 31 CFR 351.8 - When is interest payable on Series EE savings bonds?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (Continued) FISCAL SERVICE, 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...

  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. 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.

  18. 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.

  19. 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)…

  20. 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 get ready to lower the International Space Station's P4 truss onto a workstand. 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.

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

    NASA Technical Reports Server (NTRS)

    2000-01-01

    After its move across the Space Station Processing Facility, the International Space Station's P4 truss rests in its workstand. 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.

  2. 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.

  3. 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.

  4. Validation of the emotional eating scale adapted for use in children and adolescents (EES-C).

    PubMed

    Tanofsky-Kraff, Marian; Theim, Kelly R; Yanovski, Susan Z; Bassett, Allison M; Burns, Noel P; Ranzenhofer, Lisa M; Glasofer, Deborah R; Yanovski, Jack A

    2007-04-01

    Eating in response to negative emotions is associated with binge or loss of control (LOC) eating in adults. Although children report engaging in LOC eating, data on emotional eating among youth are limited. We adapted the adult Emotional Eating Scale (Arnow et al., Int J Eat Disord, 18, 79-90, 1995) to be used with children and adolescents (EES-C). Fifty-nine overweight (BMI > or = 95th percentile for age and sex) and 100 non-overweight (BMI 5th-94th percentile) participants (mean age +/- SD 14.3 +/- 2.4 years) completed the EES-C, and measures of recent LOC eating and general psychopathology. Test-retest reliability was assessed in 64 children over a 3.4 +/- 2.6 month interval. A factor analysis generated three subscales: eating in response to anxiety, anger, and frustration (EES-C-AAF), depressive symptoms (EES-C-DEP), and feeling unsettled (EES-C-UNS). Internal consistency for the subscales was established; Cronbach's alphas for the EES-C-AAF, EES-C-DEP, and EES-C-UNS were 0.95, 0.92, and 0.83, respectively. The EES-C had good convergent validity: children reporting recent LOC eating episodes scored higher on all subscales (p's < 0.05). The EES-C-AAF and EES-C-UNS subscales demonstrated good discriminant validity and the EES-C-DEP revealed adequate discriminant validity. Intra-class correlation coefficients revealed good temporal stability for each subscale (EES-C-AAF = 0.59, EES-C-DEP = 0.74, EES-C-UNS = 0.66; p's < 0.001). The EES-C has good convergent and discriminant validity, and test-retest reliability for assessing emotional eating in children. Further investigation is required to clarify the role emotional eating may play in children's energy intake and body weight.

  5. 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

  6. 31 CFR 351.5 - What is the maturity period of a 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 What is the maturity period of a... 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? Series...

  7. 31 CFR 351.5 - What is the maturity period of a 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 What is the maturity period of a... 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? Series...

  8. The clinical utility of fetal cell sorting to determine prenatally fetal E/e or e/e Rh genotype from peripheral maternal blood.

    PubMed

    Geifman-Holtzman, O; Makhlouf, F; Kaufman, L; Gonchoroff, N J; Holtzman, E J

    2000-08-01

    This study was undertaken to determine the fetal E/e or e/e Rh genotype prenatally from peripheral maternal blood by examining sorted fetal cells from alloimmunized and nonalloimmunized pregnancies. Eighteen maternal peripheral venous blood samples were obtained before amniocentesis from 15 pregnant women who were homozygous for the e allele. Five were not alloimmunized and 10 were alloimmunized. The mononuclear cell layer was isolated from the maternal blood and enriched for fetal nucleated red blood cells by flow cytometry with monoclonal antibodies to CD36 or CD71 and to glycophorin A. Eight samples were treated with CD45 monoclonal antibody-coated magnetic beads before they were sorted to deplete the maternal sample of leukocytes (CD45(+) cells). We defined the positive fetal cell fractions as the monoclonal antibody positive-sorted cells derived from the maternal samples. These included sorted cells that were CD36(+)/glycophorin A(+), CD71(+)/glycophorin A(+) and CD45(-) cells that were sorted to become CD45(-)/CD36(+)/glycophorin A(+) or CD45(-)/CD71(+)/glycophorin A(+). The negative fractions were the cells that were negative for either CD36/glycophorin A or CD71/glycophorin A or were the CD45(+) cells. Deoxyribonucleic acid was isolated from all fractions and amplified by polymerase chain reaction with allele-specific primers for the E or e Rh genes. Gel electrophoresis was performed to detect fetal E/e or e/e Rh genotype. The fetal E/e or e/e Rh genotype was confirmed by serologic and deoxyribonucleic acid testing. The accuracy of E/e or e/e Rh genotype determination from the positive cell fractions was compared with that of E/e or e/e Rh genotype determination from the negative fractions. Fetal E/e or e/e Rh genotype was determined correctly in 17 of 18 of the fetal cell enriched positive fractions (94%). Fetal E/e or e/e Rh genotype was determined correctly in 11 of 14 of the maternal samples in the negative unselected cell fractions (79%). Fetal E/e or

  9. CDC50 Proteins Are Critical Components of the Human Class-1 P4-ATPase Transport Machinery*

    PubMed Central

    Bryde, Susanne; Hennrich, Hanka; Verhulst, Patricia M.; Devaux, Philippe F.; Lenoir, Guillaume; Holthuis, Joost C. M.

    2010-01-01

    Members of the P4 subfamily of P-type ATPases catalyze phospholipid transport and create membrane lipid asymmetry in late secretory and endocytic compartments. P-type ATPases usually pump small cations and the transport mechanism involved appears conserved throughout the family. How this mechanism is adapted to flip phospholipids remains to be established. P4-ATPases form heteromeric complexes with CDC50 proteins. Dissociation of the yeast P4-ATPase Drs2p from its binding partner Cdc50p disrupts catalytic activity (Lenoir, G., Williamson, P., Puts, C. F., and Holthuis, J. C. (2009) J. Biol. Chem. 284, 17956–17967), suggesting that CDC50 subunits play an intimate role in the mechanism of transport by P4-ATPases. The human genome encodes 14 P4-ATPases while only three human CDC50 homologues have been identified. This implies that each human CDC50 protein interacts with multiple P4-ATPases or, alternatively, that some human P4-ATPases function without a CDC50 binding partner. Here we show that human CDC50 proteins each bind multiple class-1 P4-ATPases, and that in all cases examined, association with a CDC50 subunit is required for P4-ATPase export from the ER. Moreover, we find that phosphorylation of the catalytically important Asp residue in human P4-ATPases ATP8B1 and ATP8B2 is critically dependent on their CDC50 subunit. These results indicate that CDC50 proteins are integral part of the P4-ATPase flippase machinery. PMID:20961850

  10. 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. © 2015 Wiley Periodicals, Inc.

  11. 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.

  12. 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.

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

    PubMed Central

    Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

    2016-01-01

    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 [11C]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. PMID:26772668

  14. 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

  15. SiW ECAL for future e+e- collider

    NASA Astrophysics Data System (ADS)

    Balagura, V.; Bilokin, S.; Bonis, J.; Boudry, V.; Brient, J.-C.; Callier, S.; Cheng, T.; Cornat, R.; De La Taille, C.; Doan, T. H.; Frotin, M.; Gastaldi, F.; Hirai, H.; Jain, S.; Jain, Sh.; Lacour, D.; Lavergne, L.; Lleres, A.; Magniette, F.; Mastrolorenzo, L.; Nanni, J.; Poeschl, R.; Pozdnyakov, A.; Psallidas, A.; Ruan, M.; Rubio-Roy, M.; Seguin-Moreau, N.; Shpak, K.; Suehara, T.; Thiebault, A.; Wright, J.; Yu, D.

    2017-07-01

    Calorimeters with silicon detectors have many unique features and are proposed for several world-leading experiments. We discuss the tests of the first three 18×18 cm2 layers segmented into 1024 pixels of the technological prototype of the silicon-tungsten electromagnetic calorimeter for a future e+e- collider. The tests have beem performed in November 2015 at CERN SPS beam line.

  16. 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.

  17. 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 .

  18. Dark photon search at a circular e+e- collider

    NASA Astrophysics Data System (ADS)

    He, Min; He, Xiao-Gang; Huang, Cheng-Kai

    2017-08-01

    One of the interesting portals linking a dark sector and the Standard Model (SM) is the kinetic mixing between the SM U(1)Y field with a new dark photon A‧ from a U(1)A‧ gauge interaction. Stringent limits have been obtained for the kinetic mixing parameter 𝜖 through various processes. In this work, we study the possibility of searching for a dark photon interaction at a circular e+e- collider through the process e+e-→ γA‧→ γμ+μ-. We find that the constraint on 𝜖2 for dark photon mass in the few tens of GeV range, assuming that the μ+μ- invariant mass can be measured to an accuracy of 0.5% mA‧, can be better than 3 × 10-6 for the proposed CEPC with a 10-year running at 3σ (statistic) level, and better than 2 × 10-6 for FCC-ee with even just one-year running at s = 240GeV, better than the LHCb, ATLAS, CMS experiments and other facilities can do in a similar dark photon mass range. For FCC-ee, running at s = 160GeV, the constraint can be even better.

  19. p-(4-Azipentyl)-propofol: A Potent Photoreactive General Anesthetic Derivative of Propofol

    PubMed Central

    Stewart, Deirdre S.; Savechenkov, Pavel Y.; Dostalova, Zuzana; Chiara, David C.; Ge, Rile; Raines, Douglas E.; Cohne, Jonathan B.; Forman, Stuart A.; Bruzik, Karol S.; Miller, Keith W.

    2013-01-01

    We synthesized 2,6-Diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)-propyl]-phenol (p-(4-azipentyl)-propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to propofol. Like propofol, the compound potentiates inhibitory GABAA receptor current responses and allosterically modulates binding to both agonist and benzodiazepine sites, assayed on heterologously expressed GABAA receptors. p-4-AziC5-Pro inhibits excitatory current responses of nACh receptors expressed in Xenopus oocytes and photoincorporates into native nACh receptor-enriched Torpedo membranes. Thus p-4-AziC5-Pro is a functional general anesthetic that both modulates and photoincorporates into Cys-loop ligand-gated ion channels, making it an excellent candidate for use in identifying propofol binding sites. PMID:22029276

  20. p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol.

    PubMed

    Stewart, Deirdre S; Savechenkov, Pavel Y; Dostalova, Zuzana; Chiara, David C; Ge, Rile; Raines, Douglas E; Cohen, Jonathan B; Forman, Stuart A; Bruzik, Karol S; Miller, Keith W

    2011-12-08

    We synthesized 2,6-diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)propyl]phenol (p-(4-azipentyl)propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to that of propofol. Like propofol, the compound potentiates inhibitory GABA(A) receptor current responses and allosterically modulates binding to both agonist and benzodiazepine sites, assayed on heterologously expressed GABA(A) receptors. p-4-AziC5-Pro inhibits excitatory current responses of nACh receptors expressed in Xenopus oocytes and photoincorporates into native nACh receptor-enriched Torpedo membranes. Thus, p-4-AziC5-Pro is a functional general anesthetic that both modulates and photoincorporates into Cys-loop ligand-gated ion channels, making it an excellent candidate for use in identifying propofol binding sites.

  1. Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists.

    PubMed

    Berg, K A; Maayani, S; Goldfarb, J; Clarke, W P

    1998-12-15

    There is now considerable evidence that a single receptor subtype can couple to multiple effector pathways within a cell. Recently, Kenakin proposed a new concept, termed "agonist-directed trafficking of receptor stimulus", that suggests that agonists may be able to selectively activate a subset of multiple signaling pathways coupled to a single receptor subtype. 5-HT2A and 5-HT2C receptors couple to phospholipase C-(PLC) mediated inositol phosphate (IP) accumulation and PLA2-mediated arachidonic acid (AA) release. Relative efficacies of agonists (referenced to 5-HT) differed depending upon whether IP accumulation or AA release was measured. For the 5-HT2C receptor system, some agonists (e.g. TFMPP) preferentially activated the PLC-IP pathway, whereas others (e.g. LSD) favored PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT2A receptor system, all agonists tested had greater relative efficacy for PLA2-AA than for PLC-IP. In contrast, relative efficacies were not different for 5-HT2A agonists when sequential effects in a pathway were measured (IP accumulation vs. calcium mobilization). These data strongly support the agonist-directed trafficking hypothesis.

  2. 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.

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

    SciTech Connect

    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.

  4. 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.

  5. 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.

  6. The effect of ethinylestradiol (EE)/cyproterone acetate (CA) and EE/CA plus metformin treatment on adhesion molecules in cases with polycystic ovary syndrome (PCOS).

    PubMed

    Bilgir, Oktay; Kebapcilar, Levent; Taner, Cuneyt; Bilgir, Ferda; Kebapcilar, Ayse; Bozkaya, Giray; Yildiz, Yasar; Yuksel, Arif; Sari, Ismail

    2009-01-01

    To determine if EE/CA and EE/CA plus metformin treatment have any effect on adhesion molecules in cases with PCOS. Among 40 patients diagnosed with PCOS, one study arm was administered EE/CA (n=20, cyproterone acetate 2 mg, ethinylestradiol 35 microg) and the other was administered metformin (1,700 mg) combined with EE/CA (n=20, cyproterone acetate 2 mg, ethinylestradiol 35 microg). Soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte endothelial cell adhesion molecule-3 (sP-selectin), lipid profile, androgens, insulin, and HOMA-IR values were assessed prior to treatment and after 3 months of therapy. The comparison of the groups receiving EE/CA and EE/CA+metformin revealed a significant reduction in sVCAM (1,445+/-614 vs 1,167+/-482, p<0.05) and sICAM (442+/-141 vs 345+/-118, p<0.05) values relative to pre-treatment values while no significant changes were detected in sE-selectin and sP-selectin levels relative to pre-treatment levels in the EE/CA+metformin group (p>0.05). In the post-treatment period, sVCAM, sICAM, sE-selectin values did not significantly change compared to the pre-treatment values in EE/CA group (p>0.05). sP-selectin levels were also decreased but missed the significance in EE/CA group (229.4+/-68.0 vs 189.6+/-65.0, p=0.08). These results demonstrate that EE/CA+metformin treatment reduced inflammation markers in cases with PCOS compared to EE/CA treatment. The clinical relevance of this conclusion may be clarified by longer metformin treatment and clinical follow-up.

  7. 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.

  8. Review: 5-Ht1, 5-Ht2, 5-Ht3, And 5-Ht7 Receptors And Their Role In The Modulation Of Pain Response In The Central Nervous System.

    PubMed

    Cortes-Altamirano, José Luis; Olmos-Hernández, Adriana; Bonilla-Jaime, Herlinda; Carrillo-Mora, Paul; Bandala, Cindy; Reyes-Long, S; Alfaro-Rodríguez, Alfonso

    2017-09-11

    The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physiological, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional experience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. Serotonin [5-HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1–5-HT7) and approximately 15 receptor subtypes. Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS). In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain. Conclusions We concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration to order to inhibit, to excite, or even maintain the nociceptive response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. 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.

  10. Pentose phosphate pathway function affects tolerance to the G-quadruplex binder TMPyP4.

    PubMed

    Andrew, Elizabeth J; Merchan, Stephanie; Lawless, Conor; Banks, A Peter; Wilkinson, Darren J; Lydall, David

    2013-01-01

    G-quadruplexes form in guanine-rich regions of DNA and the presence of these structures at telomeres prevents the activity of telomerase in vitro. Ligands such as the cationic porphyrin TMPyP4 stabilise G-quadruplexes and are therefore under investigation for their potential use as anti-cancer drugs. In order to investigate the mechanism of action of TMPyP4 in vivo, we carried out a genome-wide screen in the budding yeast Saccharomyces cerevisiae. We found that deletion of key pentose phosphate pathway (PPP) genes increased the sensitivity of yeast to the presence of TMPyP4. The PPP plays an important role in the oxidative stress response and sensitivity to TMPyP4 also increased when genes involved in the oxidative stress response, CCS1 and YAP1, were deleted. For comparison we also report genome wide-screens using hydrogen peroxide, which causes oxidative stress, RHPS4, another G-quadruplex binder and hydroxyurea, an S phase poison. We found that a number of TMPyP4-sensitive strains are also sensitive to hydrogen peroxide in a genome-wide screen. Overall our results suggest that treatment with TMPyP4 results in light-dependent oxidative stress response in budding yeast, and that this, rather than G-quadruplex binding, is the major route to cytotoxicity. Our results have implications for the usefulness and mechanism of action of TMPyP4.

  11. 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.

  12. Guided crystallization of P3HT in ternary blend solar cell based on P3HT:PCPDTBT:PCBM

    SciTech Connect

    Gu, Yu; Wang, Cheng; Liu, Feng; Chen, Jihua; Dyck, Ondrej E.; Duscher, Gerd; Russell, Thomas P.

    2014-01-01

    In ternary blend of P3HT:PCPDTBT:PC61BM, bundles of well-defined P3HT fibrils formed a network in a matrix comprised of a mixture of P3HT, PCPDTBT and PCBM yielding a 27% improvement in device efficiency.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT

    PubMed Central

    Sia, Tiong C.; Whiting, Malcolm; Kyloh, Melinda; Nicholas, Sarah J.; Oliver, John; Brookes, Simon J.; Dinning, Phil G.; Wattchow, David A.; Spencer, Nick J.

    2013-01-01

    Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI) transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT) receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT). In control animals, peristaltic contractions were blocked temporarily by ondansetron (1–10 μM) and SDZ-205–557 (1–10 μM) in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis. PMID:23935564

  18. Structural, electronic and optical properties of SrHfO 3 (I4/mcm, Imma, Cmcm, P4/mbm and P4mm) phases

    NASA Astrophysics Data System (ADS)

    Cherrad, D.; Maouche, D.

    2010-09-01

    The structural, electronic and optical properties of SrHfO 3 phases have been investigated, employing first-principles method, using the plane wave pseudo-potential calculations (PP-PW), based on the density functional theory (DFT) within the local density approximation (LDA). Band structures reveal that I4/mcm, Imma, Cmcm and P4/mbm phases are indirect energy band gap (G-G) semiconductors while P4mm phase is (R-G), a direct band gap material. The analysis of the site and momentum projected densities, valence charge density, bond length, bond population and Milliken charges transfer shows that bonding is of covalent-ionic nature. The optical constants, including the dielectric function, optical reflectivity, refractive index and electron energy loss, are calculated for radiation up to 20 eV.

  19. Estimating the dose from atmospheric releases of HT

    SciTech Connect

    Murphy, C.E. Jr.

    1990-11-13

    Measurements of uptake of tritium by humans and laboratory animals following exposure to tritiated hydrogen gas, HT, suggest that the radiotoxicity of HT is four orders of magnitude less than that of tritiated water, HTO. However, this analysis does not take into account the conversion of HT into HTO following release into the environment. Experimental releases of HT have demonstrated that HT release to the environment is converted to HTO by soil microorganisms. In this report two methods are used to estimate the effect of HT to HTO conversion on the inhalation dose of individuals exposed to tritium downwind of a release of HT. From this analysis it is predicted that the ratio of dose from inhalation of tritium following an atmospheric release of HT, as compared to inhalation of HTO, is closer to 0.01 than the 0.0001 attributed to simple HT inhalation. Under meteorologic conditions which keep the HT release near the surface and promote optimum soil microbial activity, the analysis suggests that the ratio of dose from an atmospheric HT release could be as high as 25% of that from an atmospheric HTO release.

  20. Diet-induced alterations in hepatic progesterone (P4) catabolic enzyme activity and P4 clearance rate in lactating dairy cows.

    PubMed

    Lemley, C O; Vonnahme, K A; Tager, L R; Krause, K M; Wilson, M E

    2010-06-01

    Elevated rates of steroid clearance may lead to lower reproductive success in several mammalian species. Cytochrome P450 (EC 1.14.14.1) and aldo-keto reductases (AKR; EC 1.1.1.145-151) are involved in the first phase of steroid inactivation, before second phase conjugation and excretion of the steroid metabolite. The current objectives were to determine liver blood flow (LBF), hepatic enzyme activity, and metabolic clearance rate (MCR) of progesterone (P(4)) in dairy cows consuming isoenergetic and isonitrogenous diets formulated to cause divergent insulin secretion. Insulin concentrations increased by 22% in cows fed the high cornstarch diet, and both cytochrome P450 2C and cytochrome P450 3A activities were decreased (P<0.05) by approximately 50%, while AKR1C tended (P<0.10) to be lower in cows fed the high cornstarch diet. LBF was similar between the two diets (1891+/-91 l/h). MCR of P(4) tended (P<0.10) to be lower in cows fed the high cornstarch diet (25+/-5 l/hxBW(0.75)) versus the high fiber diet (40+/-6 l/hxBW(0.75)). The half-life of P(4) was increased (P<0.05) in cows fed the high cornstarch diet (73+/-10 min) versus the high fiber diet (24+/-10 min). In summary, cows with elevated insulin concentrations and lower enzyme activity showed a decrease in P(4) clearance without any changes in LBF. This dietary relationship with hepatic enzyme activity may explain some of the observed alterations in steroid profiles during the estrous cycle or gestation of the high producing dairy cow.

  1. Spinal 5-HT4 and 5-HT6 receptors contribute to the maintenance of neuropathic pain in rats.

    PubMed

    Pineda-Farias, Jorge Baruch; Barragán-Iglesias, Paulino; Valdivieso-Sánchez, Alann; Rodríguez-Silverio, Juan; Flores-Murrieta, Francisco Javier; Granados-Soto, Vinicio; Rocha-González, Héctor Isaac

    2017-04-04

    Nerve injury promotes release of 5-HT at the spinal cord. Once released, 5-HT may produce antinociceptive or pronociceptive effects depending of the nature of 5-HT receptors. The purpose of this study was to investigate the participation of spinal 5-HT4 and 5-HT6 receptors in the maintenance of neuropathic pain in rats. Tactile allodynia was measured using von Frey hairs in male Wistar rats subjected to L5-L6 spinal nerve injury. Selective 5-HT4 (GR-113808, 0.01-10nmol/rat) and 5-HT6 (SB-258585, 1-1000nmol/rat) receptor antagonists were administered intrathecally to nerve injured rats. Likewise, the most effective dose of 5-HT4 (1nmol/rat) and 5-HT6 (100 nmol/rat) antagonists were co-administered with their respective agonists (ML-10302, 10-100nmol/rat and WAY-208466, 100-1000nmol/rat, respectively). Spinal cord protein expression of both receptors was determined by western blot. Intrathecal administration of 5-HT4 or 5-HT6 receptor antagonists, but not vehicle, decreased in a dose-dependent manner tactile allodynia in neuropathic rats. Moreover, intrathecal co-administration with the agonists prevented in a dose-dependent manner the antagonists-induced antiallodynic effect. Both 5-HT4 and 5-HT6 receptors were expressed in the spinal cord of naïve, sham and neuropathic rats. Nerve injury did not modify expression of any receptor. Data suggests that spinal 5-HT4 and 5-HT6 receptors are expressed in dorsal spinal cord and they participate in the maintenance of neuropathic pain in rats. In this regard, blockade of these receptors could be a useful strategy to treat neuropathic pain states. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. 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

  3. Role of 5-HT3 Receptors in the Antidepressant Response

    PubMed Central

    Bétry, Cécile; Etiévant, Adeline; Oosterhof, Chris; Ebert, Bjarke; Sanchez, Connie; Haddjeri, Nasser

    2011-01-01

    Serotonin (5-HT)3 receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they are involved in regulation of neurotransmitter systems implicated in the pathophysiology of major depression (e.g., dopamine or GABA). Clinical and preclinical studies have suggested that 5-HT3 receptors may be a relevant target in the treatment of affective disorders. 5-HT3 receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT3 receptor antagonists, such as ondansetron, present antidepressant-like activities. In addition, several antidepressants, such as mirtazapine, also target 5-HT3 receptors. In this review, we will report major advances in the research of 5-HT3 receptor's roles in neuropsychiatric disorders, with special emphasis on mood and anxiety disorders.

  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. T-2 toxin and its metabolite HT-2 toxin combined with insulin-like growth factor-I modify progesterone secretion by porcine ovarian granulosa cells.

    PubMed

    Maruniakova, Nora; Kadasi, Attila; Sirotkin, Alexander V; Bulla, Jozef; Kolesarova, Adriana

    2014-01-01

    The aim of this study was to examine the effect of A-trichothecenes T-2 and HT-2 toxins combined with insulin-like growth factor I (IGF-I) on the release of steroid hormone progesterone (P4) by porcine ovarian granulosa cells (GCs). The cells were incubated without (control) or with treatments of A-trichothecenes T-2 (100 and 1000 ng/mL)/ HT-2 (100 and 1000 ng/mL) combined with IGF-I (1, 10 and 100 ng/mL) for 24 h. Progesterone secretion was determined by RIA. The release of P4 by GCs after addition of T-2 toxin (at 100 ng/mL) combined with IGF-I (at 10 but not at 1 and 100 ng/mL) and HT-2 toxin (at 100 ng/mL) combined with IGF-I (at all doses) was significantly (P < 0.05) inhibited. On the other hand the release of P4 after addition of T-2/ HT-2 toxin (at 1000 ng/mL) combined with IGF-I (at all doses) was significantly (P < 0.05) stimulated. Alone IGF-I addition (at 10, 100 but not at 1 ng/mL) significantly (P < 0.05) stimulated P4 release by GCs. The results of our in vitro study indicate the T-2 and HT-2 toxins combined with IGF-I could modify progesterone secretion by porcine ovarian granulosa cells and potentially regulate process of steroidogenesis in the ovaries. Currently, occurrence of mycotoxins in food and feed is a worldwide problem and therefore study of these toxins as well as their interaction with different substances such as growth factors could be beneficial for better understanding of mechanism of their toxic effects in organism.

  6. 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...

  7. 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....

  8. 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...

  9. 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?...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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....

  18. 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...

  19. 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...

  20. 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...

  1. 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....

  2. 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...

  3. 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...

  4. 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...

  5. 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,...

  6. 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,...

  7. 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...

  8. 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...

  9. 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...

  10. 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....

  11. 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...

  12. 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...

  13. 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,...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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,...

  20. 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...

  1. 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...

  2. 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,...

  3. 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....

  4. 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?...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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?...

  17. 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?...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 31 CFR 351.21 - How are redemption values determined during any extended maturity period of Series EE savings...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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 Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.21 How are redemption values determined...

  11. 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 make...

  12. 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 are...

  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 redemption...

  14. 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 that...

  15. 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 book-entry...

  16. 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 book...

  17. 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...

  18. 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.

  19. 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

  20. Merging P4P and disease management: how do you know which one is working?

    PubMed

    Smith, Allen L

    2007-03-01

    An intervention movement in managed care, disease management (DM), is a system of coordinated health care interventions and communication for populations with conditions in which patient self-care efforts are significant. Another managed care intervention movement, pay for performance (P4P), involves an incentive component in which payment is defined based on meeting specific, previously agreed-upon process or outcomes targets. To explore the various characteristics of DM and P4P interventions, determine how they differ, and explore the differences in results of programs in current practice. In DM, regular ongoing evaluation of clinical, humanistic, and economic outcomes plays a crucial role in reducing costs and improving quality of care. The goal of improving overall patient health in DM is also accomplished by supporting the physician or practitioner/patient relationship and plan of care. P4P initiatives vary more according to the needs and preferences of local providers and plans than do DM initiatives. While DM programs can be implemented without necessarily changing how providers deliver health care, P4P requires new programs and/or systems within the provider sector to improve patient care quality and/or efficiency. P4P initiatives also typically involve the upside or downside risk by physicians/hospitals. Partners HealthCare, based in Boston, features P4P initiatives for inpatient admissions, diabetes, and radiology that have all been met with success. Both DM and P4P initiatives have been successful in managed care. However, in terms of determining whether DM or P4P initiatives are more effective in improving the quality and efficiency of health care delivery, it is simply too early to tell at this time.

  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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

  6. 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

  7. The pharmacology of the 5-HT4 receptor.

    PubMed

    Costall, B; Naylor, R J

    1993-11-01

    Dumuis and colleagues (1988) in their investigation of a 5-HT receptor positively linked to adenylate cyclase in the central nervous system, concluded that the receptor was not 5-HT1, 5-HT2 or 5-HT3-like and suggested that it belonged to a new class of 5-HT receptor called 5-HT4. A similar, if not identical receptor was located by Craig and Clark (1990) in the guinea pig ileum and a functional role for the peripheral 5-HT4 receptor has since been established in many species to mediate muscle contraction or relaxation within the gut and positive inotropic effects in the heart. In contrast, a functional role for central 5-HT4 receptors has remained obscure. Using measurements of rodent behaviour in the mouse light and dark test box and rat social interaction, anxiolytic agents such as diazepam and putative anxiolytic agents such as the 5-HT1A and 5-HT3 receptor ligands 8-OH-DPAT and low doses of tropisetron release behaviour suppressed by the aversive situation. 5-Hydroxytryptophan has the opposite effect exacerbating the behavioural response to the aversive situation. But an anxiolytic profile is revealed by co-treatment with ritanserin plus 5-hydroxytryptophan. The drug-induced anxiolytic profiles are inhibited by SDZ205-557 and a high dose of tropisetron. Both compounds are 5-HT3/5-HT4 receptor antagonists yet the selective 5-HT3 receptor antagonist ondansetron fails to inhibit the drug-induced anxiolytic profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Improved synthesis of mestranol and ethinyl estradiol (EE) related degradation products as authentic references.

    PubMed

    Li, Hongqi; Song, Yanxi; Peng, Xianfu

    2008-05-01

    Preparative chemical methods for the synthesis of 10 degradation or photodecomposition products of mestranol and ethinyl estradiol (EE) are described. The synthesized compounds are useful as reference materials and standards for pharmaceutical analysis of mestranol and EE as bulk chemical or in formulated product. New synthetic methods were presented and the known synthetic procedures were improved. Detailed structural characterization of the degradation or photodecomposition products of mestranol and EE and related compounds was reported.

  14. 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.

  15. 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.

  16. 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

  17. 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. © 2014. Published by The Company of Biologists Ltd.

  18. P4P: a peptidome-based strain-level genome comparison web tool.

    PubMed

    Blanco-Míguez, Aitor; Fdez-Riverola, Florentino; Lourenço, Anália; Sánchez, Borja

    2017-05-08

    Peptidome similarity analysis enables researchers to gain insights into differential peptide profiles, providing a robust tool to discriminate strain-specific peptides, true intra-species differences among biological replicates or even microorganism-phenotype variations. However, no in silico peptide fingerprinting software existed to facilitate such phylogeny inference. Hence, we developed the Peptidomes for Phylogenies (P4P) web tool, which enables the survey of similarities between microbial proteomes and simplifies the process of obtaining new biological insights into their phylogeny. P4P can be used to analyze different peptide datasets, i.e. bacteria, viruses, eukaryotic species or even metaproteomes. Also, it is able to work with whole proteome datasets and experimental mass-to-charge lists originated from mass spectrometers. The ultimate aim is to generate a valid and manageable list of peptides that have phylogenetic signal and are potentially sample-specific. Sample-to-sample comparison is based on a consensus peak set matrix, which can be further submitted to phylogenetic analysis. P4P holds great potential for improving phylogenetic analyses in challenging taxonomic groups, biomarker identification or epidemiologic studies. Notably, P4P can be of interest for applications handling large proteomic datasets, which it is able to reduce to small matrices while maintaining high phylogenetic resolution. The web server is available at http://sing-group.org/p4p. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Convergence of Melatonin and Serotonin (5-HT) Signaling at MT2/5-HT2C Receptor Heteromers*

    PubMed Central

    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

    2015-01-01

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

  20. 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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. 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

  2. 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.

  3. The involvement of 5-HT3 and 5-HT4 receptors in two models of gastrointestinal transit in mice.

    PubMed

    Pascual, D; Alsasua, A; Goicoechea, C; Martín, M I

    2002-07-05

    Our aim was to study the involvement of 5-hydroxytryptamine (5-HT)(3) and 5-HT(4) receptors in two models of gastrointestinal transit (GIT) in mice: the 5-hydroxytryptophan (5-HTP)-induced diarrhea and intestinal inflammation produced by an irritant agent, croton oil (CO). 5-HTP (10 mg/kg) produced diarrhea that was significantly inhibited after pretreatment with ondansetron (5-HT(3) antagonist) or RS 39604 (5-HT(4) antagonist) (1-5 mg/kg). The GIT speed was increased after CO and 5-HTP administration. 5-HT(3-4) antagonists decreased GIT after 5-HTP-treatment but not after CO-treatment. Our results show that 5-HT(3) and 5-HT(4) receptors are involved in 5-HTP-induced diarrhea. This may be the reason why 5-HT(3-4) antagonists could be useful in the treatment of carcinoid syndrome diarrhea. 5-HT(3-4) antagonists were not effective in the modifications of GIT; nevertheless, they could be useful in the treatment of inflammatory bowel diseases because some symptoms as abdominal pain, discomfort or abnormal bowel function are modulated via 5-HT(3).

  4. Validation of the Emotional Eating Scale Adapted for Use in Children and Adolescents (EES-C)

    PubMed Central

    Tanofsky-Kraff, Marian; Theim, Kelly R.; Yanovski, Susan Z.; Bassett, Allison M.; Burns, Noel P.; Ranzenhofer, Lisa M.; Glasofer, Deborah R.; Yanovski, Jack A.

    2007-01-01

    Objective Eating in response to negative emotions is associated with binge or loss of control (LOC) eating in adults. Although children report engaging in LOC eating, data on emotional eating among youth are limited. Method We adapted the adult Emotional Eating Scale (Arnow et al., Int J Eat Disord, 18, 79–90, 1995) to be used with children and adolescents (EES-C). Fifty-nine overweight (BMI ≥ 95th percentile for age and sex) and 100 non-overweight (BMI 5th–94th percentile) participants (mean age ± SD 14.3 ± 2.4 years) completed the EES-C, and measures of recent LOC eating and general psychopathology. Test-retest reliability was assessed in 64 children over a 3.4 ± 2.6 month interval. Results A factor analysis generated three subscales: eating in response to anxiety, anger, and frustration (EES-C-AAF), depressive symptoms (EES-C-DEP), and feeling unsettled (EES-C-UNS). Internal consistency for the subscales was established; Cronbach’s alphas for the EES-C-AAF, EES-C-DEP, and EES-C-UNS were 0.95, 0.92, and 0.83, respectively. The EES-C had good convergent validity: children reporting recent LOC eating episodes scored higher on all subscales (p’s < 0.05). The EES-C-AAF and EES-CUNS subscales demonstrated good discriminant validity and the EES-C-DEP revealed adequate discriminant validity. Intra-class correlation coefficients revealed good temporal stability for each subscale (EES-C-AAF = 0.59, EES-C-DEP = 0.74, EES-C-UNS = 0.66; p’s < 0.001). Conclusion The EES-C has good convergent and discriminant validity, and test-retest reliability for assessing emotional eating in children. Further investigation is required to clarify the role emotional eating may play in children’s energy intake and body weight. PMID:17262813

  5. 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.

  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. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  7. Serotonin 5-HT2 and 5-HT1A-like receptors differentially modulate aggressive behaviors in Drosophila melanogaster

    PubMed Central

    Johnson, Oralee; Becnel, Jaime; Nichols, Charles D.

    2009-01-01

    Aggressive behavior is widespread throughout the animal kingdom, and is a complex social behavior influenced by both genetics and environment. Animals typically fight over resources that include food, territory, and sexual partners. Of all the neurotransmitters, serotonin has been the most implicated in modulating aggressive behaviors in mammalian systems. In the fruit fly, Drosophila melanogaster, the involvement of serotonin itself in aggressive behaviors has been recently established, however, the underlying mechanisms have largely remained elusive. Here we describe the influence of different serotonin receptor subtypes on aggressive behaviors in Drosophila. Drosophila express homologs of three mammalian serotonin receptors: the 5-HT1A, 5-HT2, and 5-HT7 receptors. Significantly, these receptors mediate important behaviors in mammalian systems ranging from feeding, aggression, and sleep, to cognition. To examine the role of the 5-HT2Dro receptor, we utilized the selective 5-HT2 receptor agonist (R)-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), and the 5-HT2 receptor antagonist, ketanserin. To examine the role of 5-HT1A-like receptors we used the 5-HT1A receptor agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT), and the 5-HT1A receptor antagonist WAY100635. We find that activation of 5-HT2 receptors with (R)-DOI appears to decrease overall aggression, whereas activation of 5-HT1A-like receptors with 8-OH-DPAT increases overall aggression. Furthermore, the different serotonin receptor circuitries appear to mediate different aspects of aggression: 5-HT2 receptor manipulation primarily alters lunging and boxing, whereas 5-HT1A-like receptor manipulation primarily affects wing threats and fencing. Elucidating the effects of serotonergic systems on aggression in the fly is a significant advancement not only in establishing the fly as a system to study aggression, but as a system relevant to elucidating molecular mechanisms underlying aggression

  8. 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.

  9. 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.

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

    PubMed

    Li, Honggang; Zhou, Zhenggan

    2017-07-01

    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. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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.

  12. 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.

  13. Crystal structure and immunologic characterization of the major grass pollen allergen Phl p 4.

    PubMed

    Zafred, Domen; Nandy, Andreas; Pump, Linda; Kahlert, Helga; Keller, Walter

    2013-09-01

    Phl p 4 is a major pollen allergen but exhibits lower allergenicity than other major allergens. The natural protein is glycosylated and shows cross-reactivity with related and structurally unrelated allergens. We sought to determine the high-resolution crystal structure of Phl p 4 and to evaluate the immunologic properties of the recombinant allergen in comparison with natural Phl p 4. Different isoallergens of Phl p 4 were expressed, and the nonglycosylated mutant was crystallized. The specific role of protein and carbohydrate epitopes for allergenicity was studied by using IgE inhibition and basophil release assays. The 3-dimensional structure was determined by using x-ray crystallography at a resolution of 1.9 Å. The allergen is a glucose dehydrogenase with a bicovalently attached flavin adenine dinucleotide. Glycosylated and nonglycosylated recombinant Phl p 4 showed identical inhibition of IgE binding, but compared with natural Phl p 4, all recombinant isoforms displayed a reduced IgE-binding inhibition. However, the recombinant protein exhibited an approximately 10-fold higher potency in basophil release assays than the natural protein. The crystal structure reveals the compact globular nature of the protein, and the observed binding pocket implies the size of the natural substrate. Plant-derived cross-reactive carbohydrate determinants (CCDs) appear to reduce the allergenicity of the natural allergen, whereas the Pichia pastoris-derived glycosylation does not. Our results imply yet undescribed mechanism of how CCDs dampen the immune response, leading to a novel understanding of the role of CCDs. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  14. P4 Truss FWD SAW during Expedition 13 and STS-115 EVA Joint Operations

    NASA Image and Video Library

    2006-09-14

    S115-E-05999 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m CDT. The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Tuesday, and the deployment of the arrays set the stage for future expansion of the station.

  15. Deployment of the P4 Truss SAW during Expedition 13 / STS-115 Joint Operations

    NASA Image and Video Library

    2006-09-15

    S115-E-06184 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Sept. 12 and the deployment of the arrays set the stage for future expansion of the station.

  16. Deployment of the P4 Truss SAW during Expedition 13 / STS-115 Joint Operations

    NASA Image and Video Library

    2006-09-15

    S115-E-06186 (14 Sept. 2006) --- Space Shuttle Atlantis astronauts spread a second set of wings for the International Space Station today. The new solar arrays were fully extended at 7:44 a.m. (CDT). The new arrays span a total of 240 feet and have a width of 38 feet. They are attached to the station's newest component, the P3/P4 integrated truss segment. The installation of the P3/P4, which occurred Sept. 12 and the deployment of the arrays set the stage for future expansion of the station.

  17. Selective P4 Activation by a Highly Reduced Cobaltate: Synthesis of Dicobalt Tetraphosphido Complexes.

    PubMed

    Pelties, Stefan; Maier, Thomas; Herrmann, Dirk; de Bruin, Bas; Rebreyend, Christophe; Gärtner, Stefanie; Shenderovich, Ilya G; Wolf, Robert

    2017-05-02

    Although the chemistry of transition metal polyphosphide anions has attracted significant attention, there are few reports of studies in which such species have been synthesized directly from white phosphorus. [K(OEt2 )2 {Co(BIAN)(cod)}] (1, BIAN=1,2-bis(2,6-diisopropylphenylimino)acenaphthene, cod=1,5-cyclooctadiene), which is readily prepared by ligand exchange from [K(thf)x {Co(cod)2 }], reacts with P4 to afford [{K(thf)}2 {(BIAN)Co}2 (μ-η(4) :η(4) -P4 )] (2 a) in 61 % yield (isolated product). [{K(OEt2 )}2 {(BIAN)Co}2 (μ-η(4) :η(4) -P4 )] (2 b) and [K([18]crown-6)(MeCN)]2 [{(BIAN)Co}2 (μ-η(4) :η(4) -P4 )] (2 c) were obtained by recrystallizing 2 a from diethyl ether and acetonitrile (and using [18]crown-6 in case of 2 c). Oxidation of 2 a with [Cp2 Fe]BAr(F)4 (one equivalent) and subsequent recrystallization of the product from different solvents gave [K(OEt2 ){(BIAN)Co}2 (μ-η(4) :η(4) -P4 )] (3 a) and [K(dme)4 ][{(BIAN)Co}2 (μ-η(4) :η(4) -P4 )] (3 b; dme=1,2-dimethoxyethane). Neutral [{(BIAN)Co}2 (μ-η(4) :η(4) -P4 )] (4) was obtained in moderate yield by oxidizing 2 a with two equivalents of [Cp2 Fe]BAr(F)4 . The new complexes were characterized by NMR, EPR (in the case of 3 a), and UV/Vis spectroscopy, and elemental analysis. The molecular structures revealed by X-ray crystallography display planar cyclic or open-chain P4(4-) units sandwiched between {(BIAN)Co} fragments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. 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.

  19. 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.

  20. 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.

  1. Understanding and controlling morphology formation in Langmuir-Blodgett block copolymer films using PS-P4VP and PS-P4VP/PDP.

    PubMed

    Perepichka, Iryna I; Lu, Qing; Badia, Antonella; Bazuin, C Geraldine

    2013-04-09

    This contribution offers a comprehensive understanding of the factors that govern the morphologies of Langmuir-Blodgett (LB) monolayers of amphiphilic diblock copolymers (BCs). This is achieved by a detailed investigation of a wide range of polystyrene-poly(4-vinyl pyridine) (PS-P4VP) block copolymers, in contrast to much more limited ranges in previous studies. Parameters that are varied include the block ratios (mainly for similar total molecular weights, occasionally other total molecular weights), the presence or not of 3-n-pentadecylphenol (PDP, usually equimolar with VP, with which it hydrogen bonds), the spreading solution concentration ("low" and "high"), and the LB technique (standard vs "solvent-assisted"). Our observations are compared with previously published results on other amphiphilic diblock copolymers, which had given rise to contradictory interpretations of morphology formation. Based on the accumulated results, we re-establish early literature conclusions that three main categories of LB block copolymer morphologies are obtained depending on the block ratio, termed planar, strand, and dot regimes. The block composition boundaries in terms of mol % block content are shown to be similar for all BCs having alkyl chain substituents on the hydrophilic block (such as PS-P4VP/PDP) and are shifted to higher values for BCs with no alkyl chain substituents (such as PS-P4VP). This is attributed to the higher surface area per repeat unit of the hydrophilic block monolayer on the water surface for the former, as supported by the onset and limiting areas of the Langmuir isotherms for the BCs in the dot regime. 2D phase diagrams are discussed in terms of relative effective surface areas of the two blocks. We identify and discuss how kinetic effects on morphology formation, which have been highlighted in more recent literature, are superposed on the compositional effects. The kinetic effects are shown to depend on the morphology regime, most strongly

  2. 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.

  3. 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.

  4. 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.

  5. Collins Effect from Polarized SIDIS and e+e- Data

    SciTech Connect

    Prokudin, A.; Tuerk, C.

    2007-06-13

    The recent data on the transverse single spin asymmetry A{sub UT}{sup sin({phi}{sub h}+{phi}{sub S})} from HERMES and COMPASS Collaborations are analysed within LO parton model with unintegrated parton distribution and fragmentation functions. A fit of SIDIS data from HERMES Collaboration is performed leading to the extraction of favoured and unfavoured Collins fragmentation functions. A very good description of COMPASS data is obtained. BELLE e+e- data are shown to be compatible with our estimates based on the extracted Collins fragmentation functions. Predictions for A{sub UT}{sup sin({phi}{sub h}+{phi}{sub S})} asymmetries at JLab and COMPASS operating on a proton target are given.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Preliminary design of FCC-ee pre-injector complex

    NASA Astrophysics Data System (ADS)

    Ogur, S.; Barnyakov, A.; Furukawa, K.; Iida, N.; Levichev, A.; Miyahara, F.; Nikiforov, D.; Oide, K.; Papaphilippou, Y.; Zimmermann, F.

    2017-07-01

    The design of a 100 km circular e + e - collider with extremely high luminosity is an important component of the global Future Circular Collider (FCC) study hosted by CERN. FCC-ee is being designed to serve as Z, W, H and top factory, covering beam energies from 45.6 to 175 GeV. For the injectors, the Z-operation is the most challenging mode, due to the high total charge and low equilibrium emittance in the collider at this energy. Thus, fulfilling the Z-mode will also meet the demands for all other modes of FCC-ee. This goal can be achieved by using a 6 GeV NC linac with an S-band RF frequency of 2.856 GHz and a repetition rate of 100 Hz. This linac will accelerate two bunches per RF pulse, each with a charge of 6.5 nC. Positrons will be generated by sending 4.46 GeV e - onto a hybrid target so that the e + created can still be accelerated to 1.54 GeV in the remaining part of the same linac. The emittance of the e + beam will then shrink to the nm level in a 1.54 GeV damping ring. After damping, the e + will be reinjected into the linac and accelerated to 6 GeV. The e - and e + will then be accelerated alternately to 45.6 GeV in the booster, before they are injected into the collider.

  11. EE-drospirenone-levomefolate calcium versus EE-drospirenone + folic acid: folate status during 24 weeks of treatment and over 20 weeks following treatment cessation.

    PubMed

    Diefenbach, Konstanze; Trummer, Dietmar; Ebert, Frank; Lissy, Michael; Koch, Manuela; Rohde, Beate; Blode, Hartmut

    2013-01-01

    Adequate folate supplementation in the periconceptional phase is recommended to reduce the risk of neural tube defects. Oral contraceptives may provide a reasonable delivery vehicle for folate supplementation before conception in women of childbearing potential. This study aimed to demonstrate that a fixed-dose combination of an oral contraceptive and levomefolate calcium leads to sustainable improvements in folate status compared with an oral contraceptive + folic acid. This was a double-blind, randomized, parallel-group study in which 172 healthy women aged 18-40 years received ethinylestradiol (EE)-drospirenone-levomefolate calcium or EE-drospirenone + folic acid for 24 weeks (invasion phase), and EE-drospirenone for an additional 20 weeks (folate elimination phase). The main objective of the invasion phase was to examine the area under the folate concentration time-curve for plasma and red blood cell (RBC) folate, while the main objective of the elimination phase was to determine the duration of time for which RBC folate concentration remained ≥ 906 nmol/L after cessation of EE-drospirenone-levomefolate calcium. Mean concentration-time curves for plasma folate, RBC folate, and homocysteine were comparable between treatment groups during both study phases. During the invasion phase, plasma and RBC folate concentrations increased and approached steady-state after about 8 weeks (plasma) or 24 weeks (RBC). After cessation of treatment with levomefolate calcium, folate concentrations decreased slowly. The median time to RBC folate concentrations falling below 906 nmol/L was 10 weeks (95% confidence interval 8-12 weeks) after cessation of EE-drospirenone-levomefolate calcium treatment. Plasma and RBC folate levels remained above baseline values in 41.3% and 89.3% of women, respectively, at the end of the 20-week elimination phase. Improvements in folate status were comparable between EE-drospirenone-levomefolate calcium and EE-drospirenone + folic acid. Plasma and

  12. 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. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. 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...

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

    PubMed

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

    2016-04-01

    Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. © 2016. Published by The Company of Biologists Ltd.

  20. 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

  1. 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.

  2. 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.

  3. 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…

  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. 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…

  6. 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…

  7. Analysis of the EE-3A Temperature Logs Following the Expt. 2064 Pre-Pump

    SciTech Connect

    Brown, Donald W.

    1985-12-24

    From Nov. 25 to Dec. 1, 1985, 189,700 gallons of Fenton Hill well water were injected into EE-2 using the big Kobe pump (at 34 gpm). Temperature logs were run in EE-3A on Dec. 3 and 5 to assess the results of this reservoir reinflation.

  8. Redrilling of well EE-3 at the Los Alamos National Laboratory HDR (Hot Dry Rock) project

    SciTech Connect

    Schillo, J.C.; Nicholson, R.W.; Hendron, R.H.; Thomson, J.C.

    1987-01-01

    The successful sidetracking of well EE-3 and the drilling of well EE-3A proved that with detailed planning and by adjusting techniques based on previous experience at Fenton Hill, drilling can be accomplished with reduced risk. The primary drilling problems associated with drilling of hot, crystalline basement rock, are (a) abrasiveness between the downhole tools and the formations and (b) a crooked wellbore path. These were essentially eliminated by a specially designed drilling fluid and careful pre-planning of the directional drilling operations. These improvements have taken much of the risk out of drilling at the Fenton Hill Hot Dry Rock (HDR) Geothermal Test Site. The sidetracking of EE-3 and drilling of EE-3A were undertaken to complete the hydraulic connection between boreholes. Drilling through fractured regions indicated by the dense zones of microseismic activity increased the probability of success. EE-3 was sidetracked at 9373' and redrilled to a depth of 13,182'.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats.

    PubMed

    Hayashi, Y; Jacob-Vadakot, S; Dugan, E A; McBride, S; Olexa, R; Simansky, K; Murray, M; Shumsky, J S

    2010-01-01

    Serotonergic (5-HT) receptors are upregulated following spinal cord transection. Stimulation by administration of serotonergic receptor agonists has been successful in improving hindlimb function. We tested whether this strategy would be successful in incomplete injury models (moderate or severe thoracic contusion) where descending projections are partially spared which should produce less denervation-induced receptor upregulation. Adult rats received midthoracic moderate (MOD: 25 mm drop) or severe (SEV: 50 mm drop) contusion injuries. Distribution of 5-HT and its transporter and expression of 5-HT(2C) receptors were evaluated in lumbar spinal cord and motor response to 5-HT receptor activation was assessed using open field locomotion (BBB) score, percent weight supported treadmill stepping (%WS) and evaluation of hindlimb muscle activation (tremor and serotonin syndrome). 5-HT immunostaining 3 months post-contusion revealed few 5-HT fibers caudal to the severe contusion, and more spared caudal to the moderate contusion. The distribution of 5-HT transporter paralleled 5-HT staining, but was more greatly reduced. Thus serotonin reuptake may be less efficient in the injured spinal cord. Immunostaining for the 5-HT(2C) receptor in the dorsal and ventral horns at L5 showed significant upregulation in SEV, compared to sham or MOD rats. Neither 5-HT(2C) nor 5-HT(1A) receptor agonists, alone or in combination, nor the serotonin transporter inhibitor d-fenfluramine modified BBB scores or %WS in either group. Despite the increased sensitivity of post-synaptic targets, agonist treatment did not improve function in SEV rats. We conclude that selective 5-HT(2C) or 5-HT(1A) receptor activation was not effective in improving hindlimb function after incomplete lesions. In contrast, the 5-HT precursor 5-hydroxytryptophan (L-5-HTP), which leads to activation of all classes of 5-HT receptors, increased both %WS and hindlimb activity in the MOD group. While no side effects were

  15. 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.

  16. 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.

  17. 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

  18. Possible involvement of 5-HT and 5-HT2 receptors in acceleration of gastrointestinal transit by escin Ib in mice.

    PubMed

    Matsuda, H; Li, Y; Yoshikawa, M

    2000-01-01

    We have reported previously that escin Ib accelerated gastrointestinal transit (GIT) in mice, and that its effect may be mediated by the release of endogenous prostaglandins (PGs) and nitric oxide (NO). In this study, the possible involvement of 5-HT and 5-HT receptors in the GIT acceleration of escin Ib was investigated in mice. The acceleration of GIT by escin Ib (25 or 50 mg/kg, p.o.) was attenuated by pretreatment with ritanserin (0.5-5 mg/kg, s.c., a 5-HT(2A/2C/2B) receptor antagonist), but not with MDL 72222 (1 and 5 mg/kg, s.c.) and metoclopramide (10 mg/kg, s.c.) (5-HT3 receptor antagonists) or tropisetron (1 and 10 mg/kg, s.c., a 5-HT(3/4) receptor antagonist). Furthermore, pretreatment with ketanserin (0.05-5 mg/kg, s.c.), haloperidol (1-5 mg/kg, s.c.) and spiperone (0.5-5 mg/kg, s.c.) (5-HT2A receptor antagonists), as well as a bolus of dl-p-chlorophenylalanine methyl ester (PCPA, 1000 mg/kg, p.o., 1, 6 or 24 h before administration of the sample) (an inhibitor of 5-HT synthesizing enzyme tryptophan hydroxylase) and reserpine (5 mg/kg, p.o.) (a 5-HT depletor), but not 6-hydroxydopamine (80 mg/kg, i.p., a dopamine depletor) or repeated PCPA (300 mg/kg x2, p.o., 72 and 48 h before administration of the sample), also attenuated the effects of escin Ib. It is postulated that escin Ib accelerates GIT, at least in part, by stimulating the synthesis of 5-HT to act through 5-HT2, possibly 5-HT2A receptors, which in turn causes the release of NO and PGs.

  19. Incorporation of scaffolding protein gpO in bacteriophages P2 and P4.

    PubMed

    Chang, Jenny R; Poliakov, Anton; Prevelige, Peter E; Mobley, James A; Dokland, Terje

    2008-01-20

    Scaffolding proteins act as chaperones for the assembly of numerous viruses, including most double-stranded DNA bacteriophages. In bacteriophage P2, an internal scaffolding protein, gpO, is required for the assembly of correctly formed viral capsids. Bacteriophage P4 is a satellite phage that has acquired the ability to take control of the P2 genome and use the P2 capsid protein gpN to assemble a capsid that is smaller than the normal P2 capsid. This size determination is dependent on the P4 external scaffolding protein Sid. Although Sid is sufficient to form morphologically correct P4-size capsids, the P2 internal scaffolding protein gpO is required for the formation of viable capsids of both P2 and P4. In most bacteriophages, the scaffolding protein is either proteolytically degraded or exits intact from the capsid after assembly. In the P2/P4 system, however, gpO is cleaved to an N-terminal fragment, O(*), that remains inside the mature capsid after DNA packaging. We previously showed that gpO exhibits autoproteolytic activity, which is abolished by removal of the first 25 amino acids. Co-expression of gpN with this N-terminally truncated version of gpO leads to the production of immature P2 procapsid shells. Here, we use protein analysis and mass spectroscopy to show that P2 and P4 virions as well as procapsids isolated from viral infections contain O(*) and that cleavage occurs between residues 141 and 142 of gpO. By co-expression of gpN with truncated gpO proteins, we show that O(*) binds to gpN and retains the proteolytic activity of gpO and that the C-terminal 90 residues of gpO (residues 195-284) are sufficient to promote the formation of P2-size procapsids. Using mass spectrometry, we have also identified the head completion protein gpL in the virions.

  20. Incorporation of scaffolding protein gpO in bacteriophages P2 and P4

    PubMed Central

    Chang, Jenny R.; Poliakov, Anton; Prevelige, Peter E.; Mobley, James A.; Dokland, Terje

    2008-01-01

    Scaffolding proteins act as chaperones for the assembly of numerous viruses, including most double-stranded DNA bacteriophages. In bacteriophage P2, an internal scaffolding protein, gpO, is required for the assembly of correctly formed viral capsids. Bacteriophage P4 is a satellite phage that has acquired the ability to take control of the P2 genome and use the P2 capsid protein gpN to assemble a capsid that is smaller than the normal P2 capsid. This size determination is dependent on the P4 external scaffolding protein Sid. Although Sid is sufficient to form morphologically correct P4-size capsids, the P2 internal scaffolding protein gpO is required for the formation of viable capsids of both P2 and P4. In most bacteriophages, the scaffolding protein is either proteolytically degraded or exits intact from the capsid after assembly. In the P2/P4 system, however, gpO is cleaved to an N-terminal fragment, O*, that remains inside the mature capsid after DNA packaging. We previously showed that gpO exhibits autoproteolytic activity, which is abolished by removal of the first 25 amino acids. Co-expression of gpN with this N-terminally truncated version of gpO leads to the production of immature P2 procapsid shells. Here, we use protein analysis and mass spectroscopy to show that P2 and P4 virions as well as procapsids isolated from viral infections contain O* and that cleavage occurs between residues 141 and 142 of gpO. By co-expression of gpN with truncated gpO proteins, we show that O* binds to gpN and retains the proteolytic activity of gpO and that the C-terminal 90 residues of gpO (residues 195–284) are sufficient to promote the formation of P2-size procapsids. Using mass spectrometry we have also identified the head completion protein gpL in the virions. PMID:17931675

  1. 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....

  2. 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....

  3. 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....

  4. 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....

  5. 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....

  6. 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

  7. 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.

  8. Stabilization and Transfer of the Transient [Mes*P4](-) Butterfly Anion Using BPh3.

    PubMed

    Borger, Jaap E; Ehlers, Andreas W; Lutz, Martin; Slootweg, J Chris; Lammertsma, Koop

    2016-01-11

    The transient bicyclo[1.1.0]tetraphosphabutane anion, generated from white phosphorus (P4) and Mes*Li (Mes*=2,4,6-tBu3C6H2), can be trapped by BPh3 in THF. This Lewis acid stabilized anion can be used as an [RP4](-) transfer agent, reacting cleanly with neutral Lewis acids (B(C6F5)3, BH3, and W(CO)5) to afford unique singly and doubly coordinated butterfly anions, and with the trityl cation to form a neutral, nonsymmetrical, all-carbon-substituted P4  derivative. This reaction path enables a simple, stepwise functionalization of white phosphorus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. Ferrenberg Swendsen Analysis of LLNL and NYBlue BG/L p4rhms Data

    SciTech Connect

    Soltz, R

    2007-12-05

    These results are from the continuing Lattice Quantum Chromodynamics runs on BG/L. These results are from the Ferrenberg-Swendsen analysis [?] of the combined data from LLNL and NYBlue BG/L runs for 32{sup 3} x 8 runs with the p4rhmc v2.0 QMP-MPI.X (semi-optimized p4 code using qmp over mpi). The jobs include beta values ranging from 3.525 to 3.535 with an alternate analysis extending to 3.540. The NYBlue data sets are from 9k trajectories from Oct 2007, and the LLNL data are from two independent streams of {approx}5k each, taking from the July 2007 runs. The following outputs are produced by the fs-2+1-chiub.c program. All outputs have had checksums produced by addCks.pl and checked by the checkCks.pl perl script after scanning.

  11. P3 and P4 position analysis of vinyl ester pseudopeptide proteasome inhibitors.

    PubMed

    Marastoni, Mauro; Baldisserotto, Anna; Trapella, Claudio; Gavioli, Riccardo; Tomatis, Roberto

    2006-06-15

    Two small libraries of tripeptidic-based vinyl ester derivative proteasome inhibitors were synthesized and tested, starting with the Hmb-Val-Gln-Leu-VE prototype. The P3 and P4 positions were investigated with a complete set of amino acid residues, some of which showed remarkable selective inhibition of the trypsin-like (beta2) subunit. In both positions, aromatic and hydrophobic residues were preferred.

  12. Variational principle for the P(4) affine theory of gravitation and electromagnetism

    SciTech Connect

    Chilton, J.H.; Norris, L.K.

    1992-07-01

    We propose a Lagrangian for the P(4) theory of gravitation and electromagnetism which is a straightforward generalization of the Einstein Lagrangian. A constrained Palatini variation of this Lagrangian yields the geometrical Einstein-Maxwell affine field equations. We show that these results can be extended easily to include both electric and magnetic charges. Finally, we consider conservation laws arising from the invariance properties of the Lagrangian. 14 refs.

  13. 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

  14. Antibacterial Bioactive Glass, S53P4, for Chronic Bone Infections - A Multinational Study.

    PubMed

    Lindfors, Nina; Geurts, Jan; Drago, Lorenzo; Arts, J J; Juutilainen, Vesa; Hyvönen, Pekka; Suda, Arnold J; Domenico, Aloj; Artiaco, Stefano; Alizadeh, Chingiz; Brychcy, Adrian; Bialecki, Jertzy; Romanò, Carlo L

    2017-01-01

    Osteomyelitis is an infectious process in bone that occasionally leads to bone destruction. Traditionally, the surgical treatment procedure is performed in combination with systemic and local antibiotics as a two-stage procedure that uses autograft or allograft bone for filling of the cavitary defect. Bioactive glass (BAG-S53P4) is a bone substitute with proven antibacterial and bone bonding properties.One hundred and sixteen patients who had verified chronic osteomyelitis was treated using BAG-S53P4 as part of the treatment. Most of the patients had previously undergone numerous procedures, sometimes for decades. A register of patient data obtained from 11 centers from Finland, Italy, the Netherlands, Germany, Azerbaijan and Poland was set-up and continuously maintained at Helsinki University Central Hospital.The location of the osteomyelitis was mainly in the tibia followed by the femur and then the calcaneus. The median age of the patients was 48 years (15-87). The patients were either treated according to a one-stage procedure without local antibiotics (85 %) or by a two-stage procedure using antibiotic beads in the first procedure (15 %). The minimum follow-up was 1 year (12-95 months, median 31).The cure rate was 104/116, the total success rate 90 % and most of the patients showed a rapid recovery.The study shows that (BAG-S53P4) can be used in a one-stage procedure in treatment of osteomyelitis with excellent results.

  15. Mammalian P4-ATPases and ABC Transporters And Their Role in Phospholipid Transport

    PubMed Central

    Coleman, Jonathan A.; Quazi, Faraz; Molday, Robert S.

    2012-01-01

    Transport of phospholipids across cell membranes plays a key role in a wide variety of biological processes. These include membrane biosynthesis, generation and maintenance of membrane asymmetry, cell and organelle shape determination, phagocytosis, vesicle tranfficking, blood coagulation, lipid homeostasis, regulation of membrane protein function, apoptosis among others. P4-ATPases and ATP binding cassette (ABC) transporters are the two principal classes of membranes proteins that actively transport phospholipids across cellular membranes. P4-ATPases utilize the energy from ATP hydrolysis to flip aminophospholipids from the exocytoplasmic (extracellular/lumen) to the cytoplasmic leaflet of cell membranes generating membrane lipid asymmetry and lipid imbalance which can induce membrane curvature. Many ABC transporters play crucial roles in lipid homeostasis by actively transporting phospholipids from the cytoplasmic to the exocytoplasmic leaflet of cell membranes or exporting phospholipids to protein acceptors or micelles. Recent studies indicate that some ABC proteins can also transport phospholipids in the opposite direction. The importance of P4-ATPases and ABC transporters is evident from the findings that mutations in many of these transporters are responsible for severe human genetic diseases linked to defective phospholipid transport. PMID:23103747

  16. 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

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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 to...

  3. 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 online...

  4. 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 bond...

  5. 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.

  6. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects.

    PubMed

    Lee, Go-Eun; Yun, Jong-Min; Yang, Seung-Bum; Kang, Yeonseok; Kang, Hyung-Won; Choi, Kwang-Ho; Kim, Junbeom; Kwon, O Sang; Park, Ji-Eun; Kim, Jae-Hyo

    2017-01-01

    The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the "closed-eye" state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS).

  7. Deqi Induction by HT7 Acupuncture Alters Theta and Alpha Band Coherence in Human Healthy Subjects

    PubMed Central

    Choi, Kwang-Ho

    2017-01-01

    The aim of this preliminary study is to investigate the changes in phase synchronization in the theta and alpha bands before and during the performance of classical acupuncture on the Sinmun (HT7). The electroencephalogram (EEG) signals from nine healthy young subjects were recorded before and during acupuncture in the “closed-eye” state. The EEG signals were acquired from 19 surface scalp electrodes (FP1, FP2, F7, F3, Fz F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1, and O2). Needles were inserted into the HT7 bilaterally and were then manipulated to induce deqi and retained for 15 minutes. Phase synchronization was measured by phase coherence. In the theta band, coherence significantly increased between the temporal (T5, T6) and occipital areas (O1, O2) during the acupuncture stimulation. In the alpha band, coherence significantly increased between the left temporal area (T5) and other areas (frontal, parietal, and occipital). Phase coherence in the theta and alpha bands tended to increase during the retention of the acupuncture needles after deqi. Therefore, it can be concluded that acupuncture stimulation with deqi is clinically effective via the central nervous system (CNS). PMID:28484506

  8. 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.

  9. Signatures of rocky planet engulfment in HAT-P-4. Implications for chemical tagging studies

    NASA Astrophysics Data System (ADS)

    Saffe, C.; Jofré, E.; Martioli, E.; Flores, M.; Petrucci, R.; Jaque Arancibia, M.

    2017-07-01

    Aims: We aim to explore the possible chemical signature of planet formation in the binary system HAT-P-4 by studying the trends of abundance vs. condensation temperature Tc. The star HAT-P-4 hosts a planet detected by transits, while its stellar companion does not have any detected planet. We also study the lithium content, which might shed light on the problem of Li depletion in exoplanet host stars. Methods: We derived for the first time both stellar parameters and high-precision chemical abundances by applying a line-by-line full differential approach. The stellar parameters were determined by imposing ionization and excitation equilibrium of Fe lines, with an updated version of the FUNDPAR program, together with ATLAS9 model atmospheres and the MOOG code. We derived detailed abundances of different species with equivalent widths and spectral synthesis with the MOOG program. Results: The exoplanet host star HAT-P-4 is found to be 0.1 dex more metal rich than its companion, which is one of the highest differences in metallicity observed in similar systems. This could have important implications for chemical tagging studies. We rule out a possible peculiar composition for each star, such as is the case for λ Boötis and δ Scuti, and neither is this binary a blue straggler. The star HAT-P-4 is enhanced in refractory elements relative to volatile when compared to its stellar companion. Notably, the Li abundance in HAT-P-4 is greater than that of its companion by 0.3 dex, which is contrary to the model that explains the Li depletion by the presence of planets. We propose a scenario where at the time of planet formation, the star HAT-P-4 locked the inner refractory material in planetesimals and rocky planets, and formed the outer gas giant planet at a greater distance. The refractories were then accreted onto the star, possibly as a result of the migration of the giant planet. This explains the higher metallicity, the higher Li content, and the negative Tc trend we

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 40 CFR Appendix A to Subpart Ee of... - States With Approved State Implementation Plan Revisions Concerning Allocations

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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 Concerning...

  5. 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...

  6. 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 book-entry...

  7. 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...

  8. 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... Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.21 How are redemption values determined during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? The...

  9. 31 CFR 351.21 - How are redemption values determined during any extended maturity period of Series EE savings...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? 351... Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.21 How are redemption values determined during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? The...

  10. 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... Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.21 How are redemption values determined during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? The...

  11. 31 CFR 351.21 - How are redemption values determined during any extended maturity period of Series EE savings...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? 351... Ee Savings Bonds with Issue Dates Prior to May 1, 1995 § 351.21 How are redemption values determined during any extended maturity period of Series EE savings bonds with issue dates prior to May 1, 1995? The...

  12. [Homozygous hemoglobin-E (Hb-EE) disease].

    PubMed

    Amendola, G; Danise, P; Di Palma, A; Franzese, M; Avino, D; D'Arco, A M

    2004-01-01

    The Authors report on a 16 year-old girl, of Cambodian descent, who was admitted to the hospital for hematuria. She showed a mild microcytic, hypochromic anemia with a normal iron balance; clinical examination was normal with neither pallor nor icterus nor splenomegaly; electrophoresis of hemoglobin yielded no hemoglobin A, a sligtly increased amount of HbF and a single band with a mobility similar to that of HbA2; the patient showed no evidence of overt increased hemolysis. With the DNA technology a final diagnosis of homozygous hemoglobin E was made. Hemoglobin E is the most common Hb variant among Southeast Asian populations. The Authors discuss on the benign nature of Hb-EE disease, pointing out that the presence of a single HbE gene in combination with that for beta-thalassemia leads generally to a disorder often comparable in severity to that of homozygous beta-thalassemia. With the recent migration of a high number of people from the countries, where HbE is extremely frequent, to the Western world (including Italy), this thalassemia syndrome is now a global health problem; therefore its knowledge is an important diagnostic challenge to all the experts involved in the care of thalassemic patients.

  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. CAFE: aCcelerated Alignment-FrEe sequence analysis.

    PubMed

    Lu, Yang Young; Tang, Kujin; Ren, Jie; Fuhrman, Jed A; Waterman, Michael S; Sun, Fengzhu

    2017-05-03

    Alignment-free genome and metagenome comparisons are increasingly important with the development of next generation sequencing (NGS) technologies. Recently developed state-of-the-art k-mer based alignment-free dissimilarity measures including CVTree, $d_2^*$ and $d_2^S$ are more computationally expensive than measures based solely on the k-mer frequencies. Here, we report a standalone software, aCcelerated Alignment-FrEe sequence analysis (CAFE), for efficient calculation of 28 alignment-free dissimilarity measures. CAFE allows for both assembled genome sequences and unassembled NGS shotgun reads as input, and wraps the output in a standard PHYLIP format. In downstream analyses, CAFE can also be used to visualize the pairwise dissimilarity measures, including dendrograms, heatmap, principal coordinate analysis and network display. CAFE serves as a general k-mer based alignment-free analysis platform for studying the relationships among genomes and metagenomes, and is freely available at https://github.com/younglululu/CAFE. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. 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.

  16. 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.

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

    PubMed Central

    Swinford-Jackson, Sarah E.; Anastasio, Noelle C.; Fox, Robert G.; Stutz, Sonja J.; Cunningham, Kathryn A.

    2016-01-01

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

  18. 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.

  19. Cross section of 3He( 3He,2p) 4He measured near the Gamow peak

    NASA Astrophysics Data System (ADS)

    Itahashi, T.; Kudomi, N.; Yoshida, S.; Kume, K.; Komori, M.; Ohsumi, H.

    2003-06-01

    We measured the cross section of 3He( 3He,2p) 4He in the energy region of 30-50 keV center of mass energy by using the OCEAN facility. The resulting astrophysical S-factors are in agreement with the existing data and their total errors are as good as those of the previous experiment. For further study we tried the measurements at lower energies than E cm = 30 keV. It will require running times of one month with more improvements such as background reduction and steady operation of the detection system.

  20. THE SEROTONIN (5-HT) 5-HT2A RECEPTOR: ASSOCIATION WITH INHERENT AND COCAINE-EVOKED BEHAVIORAL DISINHIBITION IN RATS

    PubMed Central

    Anastasio, Noelle C.; Stoffel, Erin C.; Fox, Robert G.; Bubar, Marcy J.; Rice, Kenner C.; Moeller, F. Gerard; Cunningham, Kathryn A.

    2011-01-01

    Alterations in the balance of functional activity within the serotonin (5-HT) system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently demonstrate greater impulsivity relative to non-drug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT2AR as an important regulatory substrate in impulse control. PMID:21499079

  1. 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.

  2. Guided Crystallization of P3HT in Ternary Blend Solar Cell Based on P3HT:PCPDTBT:PCBM

    SciTech Connect

    Gu, Yu; Wang, Cheng; Liu, Feng; Chen, Jihua; Dyck, Ondrej E.; Duscher, Gerd; Russell, Thomas P.

    2014-09-08

    To mimic the performance of the tandem solar cells, ternary blend solar cells with a single active layer of P3HT:PCPDTBT:PC61BM were cast from chlorobenzene and thermally annealed. By varying blending ratio, thermal annealing time and P3HT molecular weight, the device performance was enhanced relative to the binary references.For further understanding, the morphology of the active layer was studied using hard and soft X-ray scattering methods in concert with bright field and energy resolved transmission electron microscopies. We found that the phase separation of the amorphous PCPDTBT and P3HT guided the formation of P3HT fibrils, resulting in a unique multi-length-scale morphology. This morphology consisted of bundles of well-defined P3HT fibrils, forming a network, imbedded in an amorphous mixture of the PCBM, PCPDTBT and P3HT. The two polymers acted independently in their specific photoactive ranges, and the sensitization of PCPDTBT benefited the cascade charge transfer. In addition, this multi-length-scale morphology was linked to the improved device performance of P3HT:PCPDTBT:PC61BM and the photophysics of the active layer.

  3. 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.

  4. Discriminative stimulus properties of indorenate, a 5-HT1A, 5-HT1B and 5-HT2C agonist: a study in rats.

    PubMed

    Sánchez, H; Velázquez-Martínez, D N

    2001-03-01

    Indorenate (INDO), initially described as an antihypertensive agent, also has some effects on behaviour, with anxiolytic and anorectic actions being reported. The aim of the present experiment was to examine the activity of INDO at the behavioural level at various serotonin (5-hydroxytryptamine, 5-HT) receptor sites by comparing its stimulus properties with those of other 5-HT receptor agonists and by examining its interactions with some 5-HT antagonists. Rats were trained to discriminate between 10.0 mg/kg INDO (administered intraperitoneally (90 min before the start of the session) from saline. A Fixed Ratio 10 (FR10) schedule of reinforcement was in effect in each drug condition. During generalization test sessions, the discrimination index (DI, responses to drug lever/responses to drug + saline lever) was calculated from the responses emitted before the first reinforcer of the session. DI was a function of the dose of INDO employed. Generalization to the discriminative stimulus properties of INDO was observed with the 5-HT1A receptor agonist 8-OH-DPAT (1.0 mg/kg produced 90% generalization) and the 5-HT(1B/2C) receptor agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) (3.0 mg/kg produced up to 75% generalization). Yohimbine (5.6 mg/kg), buspirone (1.0 mg/kg), 6-chloro-2-(1-piperaziny)pyrazine (1.0 mg/kg) and m-chlorophenylpiperazine (mCPP) (1.0 mg/kg) induced a DI of 70%, 50% and 48% and 55%, respectively. In generalization tests, ritanserin (0.01-1.0 mg/kg) induced saline-like responding. NAN-190 (3.0 mg/kg), a 5-HT1A receptor antagonist, was able to reduce the DI of INDO to 50%. Although the 5-HT(2C/2A) receptor antagonists cinanserin (10.0 mg/kg) and metergoline (0.3 mg/kg) were able to reduce the stimulus properties of INDO to 60% and 30%, respectively, only ritanserin (1.0 mg/kg) reduced the stimulus properties of INDO to 25% with a clear dose-response relationship. The results suggest that INDO acts as an agonist at 5-HT1A receptor sites, but its

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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. © 2013 Published by Elsevier B.V. and ECNP.

  10. 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.

  11. 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.

  12. Interactions of metoclopramide and ergotamine with human 5-HT3A receptors and human 5-HT reuptake carriers

    PubMed Central

    Walkembach, Jan; Brüss, Michael; Urban, Bernd W; Barann, Martin

    2005-01-01

    The actions of metoclopramide and ergotamine, drugs which are used as a combined migraine medication, on human (h)5-HT3A receptors and 5-HT reuptake carriers, stably expressed in HEK-293 cells, were studied with patch-clamp- and ([3H]5-HT)-uptake techniques. At clinical concentrations, metoclopramide inhibited peak and integrated currents through h5-HT3A receptors concentration-dependently (IC50=0.064 and 0.076 μM, respectively) when it was applied in equilibrium (60 s before and during 5-HT (30 μM) exposure). The onset and offset time constants of metoclopramide action were 1.3 and 2.1 s, respectively. The potency of metoclopramide when exclusively applied during the agonist pulse decreased more than 200-fold (IC50=19.0 μM, peak current suppression). Metoclopramide (0.10 μM) did not alter the EC50 of 5-HT-induced peak currents. In contrast to the lack of competitive interaction between metoclopramide and 5-HT in this functional assay, metoclopramide inhibited specific [3H]GR65630 binding to human h5-HT3A receptors in a surmountable manner. This seeming discrepancy between functional studies and radioligand binding experiments may be accounted for by (1) the slow kinetics of inhibition of peak currents by metoclopramide compared with the fast onset and offset kinetics of 5-HT-induced currents and (2) the low efficacy of metoclopramide in inhibiting radioligand binding (e.g. only 20% binding inhibition compared to 79% peak current suppression by 200 nM metoclopramide). At low concentrations (1–10 nM), ergotamine had no effect on 5-HT (30 μM)-induced peak currents. Above clinical concentrations, ergotamine (>3 μM) inhibited them. When both drugs were applied together (0.10 μM metoclopramide+0.001 to 0.01 μM ergotamine), an inhibition of both, peak and integrated current responses was observed. Neither metoclopramide (⩽30 μM) nor ergotamine (⩽30 μM) had an effect on the 5-HT reuptake carrier as they did not alter the

  13. 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.

  14. 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).

  15. 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.

  16. cyclo-P4 Building Blocks: Achieving Non-Classical Fullerene Topology and Beyond.

    PubMed

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

    2016-11-14

    The cyclo-P4 complexes [Cp(R) Ta(CO)2 (η(4) -P4 )] (Cp(R) : Cp''=1,3-C5 H3 tBu2 , Cp'''=1,2,4-C5 H2 tBu3 ) 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 CH2 Cl2 . 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. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  17. Assembly of bacteriophage P2 and P4 procapsids with internal scaffolding protein.

    PubMed

    Wang, Sifang; Chang, Jenny R; Dokland, Terje

    2006-04-25

    Assembly of the E. coli bacteriophage P2 into an icosahedral capsid with T = 7 symmetry is dependent on the gpN capsid protein, the gpQ connector protein and the gpO internal scaffolding protein. In the presence of the P4-encoded protein Sid, the same proteins are assembled into a smaller capsid with T = 4 symmetry. Although gpO has long been expected to act as an internal scaffolding protein, it has not been possible to produce P2 procapsids efficiently in vitro or in vivo due to a failure to express gpO at high levels. In this study, we find that full-length gpO undergoes proteolytic degradation within 1 h of induction of expression. However, a truncated version of gpO lacking the N-terminal 25 amino acids (Odelta25) is stably expressed at high levels and is able to direct the formation of P2 size procapsids. In the presence of Sid, Odelta25 is incorporated into P4 procapsids, showing that Sid overrides the effect of gpO on capsid size determination.

  18. Postmodification of PS-b-P4VP diblock copolymer membranes by ARGET ATRP.

    PubMed

    Keskin, Damla; Clodt, Juliana I; Hahn, Janina; Abetz, Volker; Filiz, Volkan

    2014-07-29

    The surfaces of polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymer membranes were modified in order to obtain polymer brushes by using surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). Isoporous membranes were prepared by the combination of self-assembly of PS-b-P4VP diblock copolymers and the nonsolvent induced phase separation process, also known as "phase inversion". In order to allow further functionalization, the membranes were modified with an ATRP initiator, 2-bromoisobutyryl bromide (BIBB). Therefore, the mussel-inspired poly(dopamine) coating was used to attach BIBB on the membranes surface. In the next step the coated membranes were postmodified by using surface-initiated ARGET ATRP with the hydrophilic monomer 2-hydroxyethyl methacrylate (HEMA). HEMA as a hydrophilic methacrylate was chosen for the modification in order to enhance the membrane characteristics and to obtain a surface with antifouling properties. The surface-initiated ARGET ATRP reaction was carried out using different reaction times and environments. PHEMA could successfully incorporate on the membrane surface as confirmed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), (1)H nuclear magnetic resonance spectroscopy ((1)H NMR), scanning electron microscopy (SEM), and contact angle measurements. Furthermore, stability tests against heat and solvents were performed, and water flux was measured for the raw and modified membranes. Stability against heat and hydrophilicity could be increased with this type of modification for diblock copolymer membranes.

  19. The new holism: P4 systems medicine and the medicalization of health and life itself.

    PubMed

    Vogt, Henrik; Hofmann, Bjørn; Getz, Linn

    2016-06-01

    The emerging concept of systems medicine (or 'P4 medicine'-predictive, preventive, personalized and participatory) is at the vanguard of the post-genomic movement towards 'precision medicine'. It is the medical application of systems biology, the biological study of wholes. Of particular interest, P4 systems medicine is currently promised as a revolutionary new biomedical approach that is holistic rather than reductionist. This article analyzes its concept of holism, both with regard to methods and conceptualization of health and disease. Rather than representing a medical holism associated with basic humanistic ideas, we find a technoscientific holism resulting from altered technological and theoretical circumstances in biology. We argue that this holism, which is aimed at disease prevention and health optimization, points towards an expanded form of medicalization, which we call 'holistic medicalization': Each person's whole life process is defined in biomedical, technoscientific terms as quantifiable and controllable and underlain a regime of medical control that is holistic in that it is all-encompassing. It is directed at all levels of functioning, from the molecular to the social, continual throughout life and aimed at managing the whole continuum from cure of disease to optimization of health. We argue that this medicalization is a very concrete materialization of a broader trend in medicine and society, which we call 'the medicalization of health and life itself'. We explicate this holistic medicalization, discuss potential harms and conclude by calling for preventive measures aimed at avoiding eventual harmful effects of overmedicalization in systems medicine (quaternary prevention).

  20. Rotavirus G2P[4] detection in fresh vegetables and oysters in Mexico City.

    PubMed

    Quiroz-Santiago, Carolina; Vázquez-Salinas, Carlos; Natividad-Bonifacio, Ivan; Barrón-Romero, Blanca Lilia; Quiñones-Ramírez, Elsa Irma

    2014-11-01

    Rotaviruses are the principal cause of dehydration caused by diarrhea in children younger than 2 years of age. Although these viral infections have mainly been associated with ingestion of fecally contaminated food and water, few studies have addressed the presence of the virus in food that is consumed raw or slightly cooked. In this work, 30 oyster samples and 33 vegetable samples were examined for the presence of rotavirus genotypes to evaluate their potential to produce gastrointestinal infections. The rotaviruses were identified by reverse transcriptase PCR amplification of the VP7 gene. G and P genotyping was also performed by reverse transcriptase PCR, with a detection sensitivity of up to 15 PFU/ml. Rotaviruses were found in 17 (26.9%) of 63 samples (10 oysters and 7 vegetables). The G2 genotype was found in 11 (64.7%) of 17 of the rotavirus strains, and 16 (94.1%) of 17 had the P[4] genotype. The combined genotypes found most frequently were G2P[4] (10 [58.82%] of 17), GNTP[4] (6 [35.29%] of 17), and G2P[NT] (1 [5.8%] of 17).

  1. 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

  2. Performance of HT9 clad metallic fuel at high temperature

    SciTech Connect

    Pahl, R.G.; Lahm, C.E.; Hayes, S.L.

    1992-12-01

    Steady-state testing of HT9 clad metallic fuel at high temperatures was initiated in EBR-II in November of 1987. At that time U-10 wt. % Zr fuel clad with the low-swelling ferritic/martensitic alloy HT9 was being considered as driver fuel options for both EBR-II and FFTF. The objective of the X447 test described here was to determine the lifetime of HT9 cladding when operated with metallic fuel at beginning of life inside wall temperatures approaching {approximately}660{degree}C. Though stress-temperature design limits for HT9 preclude its use for high burnup applications under these conditions due to excessive thermal creep, the X447 test was carried out to obtain data on high temperature breach phenomena involving metallic fuel since little data existed in that area.

  3. 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.

  4. Performance of HT9 clad metallic fuel at high temperature

    SciTech Connect

    Pahl, R.G.; Lahm, C.E.; Hayes, S.L.

    1992-01-01

    Steady-state testing of HT9 clad metallic fuel at high temperatures was initiated in EBR-II in November of 1987. At that time U-10 wt. % Zr fuel clad with the low-swelling ferritic/martensitic alloy HT9 was being considered as driver fuel options for both EBR-II and FFTF. The objective of the X447 test described here was to determine the lifetime of HT9 cladding when operated with metallic fuel at beginning of life inside wall temperatures approaching [approximately]660[degree]C. Though stress-temperature design limits for HT9 preclude its use for high burnup applications under these conditions due to excessive thermal creep, the X447 test was carried out to obtain data on high temperature breach phenomena involving metallic fuel since little data existed in that area.

  5. Environmental exposure assessment of ethinyl estradiol (EE) from a combined hormonal vaginal contraceptive ring after disposal; leaching from landfills.

    PubMed

    Geurts, M G J; de Boer, W; de Graaf, J S; van Ginkel, C G

    2007-05-15

    In this study an environmental exposure assessment and experiments were carried out to identify the leaching potential of ethinyl estradiol (EE) present in a vaginal contraceptive (NuvaRing) when disposed of in landfills. Landfill material and a sandy soil were used to investigate the mobility of EE. Log K(oc) values determined in the range of 3 to 4 indicate that EE does not have a high mobility in landfills and soils. Column experiments were used to estimate that it takes approximately 40 years before EE leaches from a column of 1 m of landfill material or sandy soil. This column experiment, which was performed with an EE concentration based on worst-case assumptions, demonstrates that the emission of EE from landfills is negligible. Sandy soils below landfills also act as a strong sorbent of EE, thereby further reducing the potential for groundwater contamination.

  6. Reprogramming of fetal cells by avian EE for generation of pluripotent stem cell like cells in caprine.

    PubMed

    Bharadwaj, Parul; Kumar, Kuldeep; Singh, Renu; Puri, Gopal; Yasotha, T; Kumar, Manish; Bhure, Sanjeev; Das, B C; Sarkar, M; Bag, Sadhan

    2013-10-01

    The present work was carried out to study the ability of avian "Extract Egg" (EE) for reprogramming caprine fetal cells. The isolated caprine fetal cells were cultured in stem cell media supplemented with different percentages of either EE or FBS. The results indicated that the supplementation of 2-4% EE formed lesser but larger size stem cell like cell colonies as compared to 6% or 10% EE. The expression of pluripotent genes were comparatively higher in colonies developed in 2% or 4% as compared to 6% or 10% EE. Further, immunocytochemistry revealed that the colonies developed in all percentage of EE expressed pluripotent markers like Oct4, Nanog, TRA-1-60 and TRA-1-81. Our findings indicated that avian EE has the potentiality to reprogram caprine fetal cells into embryonic state which may help in generation of pluripotent stem cells without using viral vector. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The predictive validity of expressed emotions (EE) in schizophrenia. A 20-year prospective study.

    PubMed

    Cechnicki, Andrzej; Bielańska, Anna; Hanuszkiewicz, Igor; Daren, Artur

    2013-02-01

    The level of expressed emotions in the family (EE) and components thereof (emotional over-involvement EOI, and critical comments CC) have been found to be related to treatment outcomes in psychotic patients. One point of interest is the dynamic of various outcomes in relation to initial EE, CC and EOI levels. 43 individuals with diagnosis of schizophrenia were assessed at 1, 3, 7, 12 and 20-year follow-ups. The EE indicator was evaluated during the index hospitalization. Outcome indicators included: number of relapses, number and duration of in-patient rehospitalizations, and severity of psychopathological symptoms. 1) A high EE indicator was associated with a higher number of relapses in every follow-up and differences between the groups with low and high EE indicators proved significant after 3, 7, 12 and 20 years of the illness. 2) A high EE indicator was associated with a higher number of rehospitalizations after 3 and 7 years, and showed as a clear trend after 12 and 20 years. 3) A high level of CC was associated with a higher number of relapses. 4) The severity of positive symptoms increased only in the group with high CC. 5) The negative syndrome was not associated with EE, EOI or CC. The EE indicator may be considered a valid prolonged predictor of relapses and rehospitalizations. A high level of CC was associated with a higher number of relapses and intensification of the positive syndrome in both the short-term and long-term course of the illness. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  10. 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

  11. 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.

  12. Hot Spot Manifestation in Eclipsing Dwarf Nova HT Cassiopeiae

    NASA Astrophysics Data System (ADS)

    Bąkowska, K.; Olech, A.

    2014-09-01

    We report the detection of a hot spot in the light curves of the eclipsing dwarf nova HT Cas during its superoutburst in 2010 November. Analysis of the eight reconstructed light curves of the hot spot eclipses showed directly that the brightness of the hot spot was changing significantly during the superoutburst. Thereby, detected hot spot manifestation in HT Cas is the newest observational evidence for the EMT model for dwarf novae.

  13. 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

  14. 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]…

  15. 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]…

  16. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

    USDA-ARS?s Scientific Manuscript database

    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...

  17. 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.

  18. Further pharmacological characterization of 5-HT2C receptor agonist-induced inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo

    PubMed Central

    Quérée, P; Peters, S; Sharp, T

    2009-01-01

    Background and purpose: Recent experiments using non-selective 5-hydroxytryptamine (5-HT)2C receptor agonists including WAY 161503 suggested that midbrain 5-HT neurones are under the inhibitory control of 5-HT2C receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The present study extended this pharmacological characterization by comparing the actions of WAY 161503 with the 5-HT2C receptor agonists, Ro 60-0275 and 1-(3-chlorophenyl) piperazine (mCPP), as well as the non-selective 5-HT agonist lysergic acid diethylamide (LSD) and the 5-HT releasing agent 3,4-methylenedioxymethamphetamine (MDMA). Experimental approach: 5-HT neuronal activity was measured in the dorsal raphe nucleus (DRN) using extracellular recordings in anaesthetized rats. The activity of DRN GABA neurones was assessed using double-label immunohistochemical measurements of Fos and glutamate decarboxylase (GAD). Key results: Ro 60-0175, like WAY 161503, inhibited 5-HT neurone firing, and the 5-HT2C antagonist SB 242084 reversed this effect. mCPP also inhibited 5-HT neurone firing (∼60% neurones) in a SB 242084-reversible manner. LSD inhibited 5-HT neurone firing; however, this effect was not altered by either SB 242084 or the 5-HT2A/C receptor antagonist ritanserin but was reversed by the 5-HT1A receptor antagonist WAY 100635. Similarly, MDMA inhibited 5-HT neurone firing in a manner reversible by WAY 100635, but not SB 242084 or ritanserin. Finally, both Ro 60-0275 and mCPP, like WAY 161503, increased Fos expression in GAD-positive DRN neurones. Conclusions and implications: These data strengthen the hypothesis that midbrain 5-HT neurones are under the inhibitory control of 5-HT2C receptors, and suggest that the 5-HT2C agonists Ro 60-0175, mCPP and WAY 161503, but not LSD or MDMA, are useful probes of the mechanism(s) involved. PMID:19845681

  19. The cyclo-tetra-phosphate Cd(2)P(4)O(12), a member of the isotypic series M(2)P(4)O(12) (M = Mg, Mn, Fe, Co, Ni, Cu).

    PubMed

    Weil, Matthias

    2010-10-13

    The title compound, Cd(2)P(4)O(12), dicadmium cyclo-tetra-phosphate, crystallizes isotypically with the members of the series M(II) (2)P(4)O(12), where M = Mg, Mn, Fe, Co, Ni or Cu. Two CdO(6) octa-hedra, one with 2 and one with symmetry, share corners with the centrosymmetric P(4)O(12) (4-) ring anion that is built up from four corner-sharing PO(4) tetra-hedra. The isolated ring anions are arranged in layers parallel to (10) with the CdO(6) octa-hedra situated between these layers. The main difference between the individual M(II) (2)P(4)O(12) structures pertains to the different sizes of the MO(6) octa-hedra whereas the geometric parameters of all cyclo-P(4)O(12) (4-) anions are very similar.

  20. 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

  1. Preclinical profile of the mixed 5-HT1A/5-HT2A receptor antagonist S 21,357.

    PubMed

    Griebel, G; Blanchard, D C; Rettori, M C; Guardiola-Lemaître, B; Blanchard, R J

    1996-06-01

    This study evaluated the pharmacological and behavioral effects of S 21,357, a drug with high affinity for both 5-HT1A and 5-HT2A receptors. The drug behaved as antagonist at both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors, as it prevented the inhibitory effect of lesopitron on the electrical discharge of the dorsal raphé nucleus (DRN) 5-HT neurons and the activity of forskolin-stimulated adenylate cyclase in hippocampal homogenates. In addition, S 21,357 (4 and 128 mg/kg, PO) inhibited 5-HTP-induced head-twitch responses in mice, indicating that it possesses 5-HT2A antagonistic properties. In a test battery designed to assess defensive behaviors of Swiss-Webster mice to the presence of, or situations associated with, a natural threat stimulus (i.e., rat), S 21,357 (0.12-2 mg/kg, IP) reduced contextual defense reactions after the rat was removed, risk assessment activities when the subject was chased, and finally, defensive attack behavior. These behavioral changes are consistent with fear/anxiety reduction. Furthermore, the drug strongly reduced flight reactions in response to the approaching rat. This last finding, taken together with recent results with panic-modulating drugs, suggest that S 21,357 may have potential efficacy against panic attack. Finally, our results suggest that compounds sharing high affinities for both 5-HT1A and 5-HT2A receptors may directly or synergistically increase the range of defensive behaviors affected.

  2. Effects of dominance status on conditioned defeat and expression of 5-HT1A and 5-HT2A receptors

    PubMed Central

    Morrison, Kathleen E.; Swallows, Cody L.; Cooper, Matthew A.

    2011-01-01

    Past experience can alter how individuals respond to stressful events. The brain serotonin system is a key factor modulating stress-related behavior and may contribute to individual variation in coping styles. In this study we investigated whether dominant and subordinate hamsters respond differently to social defeat and whether their behavioral responses are associated with changes in 5-HT1A and 5-HT2A receptor immunoreactivity in several limbic brain regions. We paired weight-matched hamsters in daily aggressive encounters for two weeks so that they formed a stable dominance relationship. We also included controls that were exposed to an empty cage each day for two weeks. Twenty-four hours after the final pairing or empty cage exposure, subjects were socially defeated in 3, 5-min encounters with a more aggressive hamster. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains following conditioned defeat testing and performed immunohistochemistry for 5-HT1A and 5-HT2A receptors. We found that dominants showed less submissive and defensive behavior at conditioned defeat testing compared to both subordinates and controls. Additionally, both dominants and subordinates had an increased number of 5-HT1A immunopositive cells in the basolateral amygdala compared to controls. Subordinates also had more 5-HT1A immunopositive cells in the dorsal medial amygdala than did controls. Finally, dominants had fewer 5-HT1A immunopositive cells in the paraventricular nucleus of the hypothalamus compared to controls. Our results indicate that dominant social status results in a blunted conditioned defeat response and a distinct pattern of 5-HT1A receptor expression, which may contribute to resistance to conditioned defeat. PMID:21362435

  3. Architecture and characterization of the P4DI CMOS hybrid pixel sensor

    NASA Astrophysics Data System (ADS)

    Chatzistratis, D.; Theodoratos, G.; Kazas, I.; Zervakis, E.; Loukas, D.; Lambropoulos, C. P.

    2017-09-01

    Gamma ray imaging can be used for the extraction either of the activity map of a source or of the attenuation map of an object or both, as well as for the identification of the material composition of the emitting source or the object. All these imaging modalities can benefit from instruments giving the information of the energy of the converted photons and also the spatial and time coordinates of the conversion. The P4DI CMOS and hybrid provides the core technology for this task being a 2-D array based on Cd(Zn)Te material for the sensing layer. It consists of 1250 pixels with 400 μ m pitch. The energy resolution of the 241Am photopeak is 3.5 keV, time resolution is less than 12 μ s and power consumption is less than 100 mW. Architecture and characterization are described.

  4. 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.

  5. 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.

  6. P4 medicine and osteoporosis: a systematic review.

    PubMed

    Kodrič, Klemen; Čamernik, Klemen; Černe, Darko; Komadina, Radko; Marc, Janja

    2016-12-01

    Osteoporosis is the most frequent bone metabolic disease. In order to improve early detection, prediction, prevention, diagnosis, and treatment of the disease, a new model of P4 medicine (personalized, predictive, preventive, and participatory medicine) could be applied. The aim of this work was to systematically review the publications of four different types of "omics" studies related to osteoporosis, in order to discover novel predictive, preventive, diagnostic, and therapeutic targets for better management of the geriatric population. To systematically search the PubMed database, we created specific groups of criteria for four different types of "omics" information on osteoporosis: genomic, transcriptomic, proteomic, and metabolomic. We then analyzed the intersections between them in order to find correlations and common pathways or molecules with important roles in osteoporosis, and with a potential application in disease prediction, prevention, diagnosis, or treatment. Altogether, 180 publications of "omics" studies in the field of osteoporosis were found and reviewed at first selection. After introducing the inclusion and exclusion criteria (the secondary selection), 46 papers were included in the systematic review. The intersection of reviewed papers identified five genes (ESR1, IBSP, CTNNB1, SOX4, and IDUA) and processes like the Wnt pathway, JAK/STAT signaling, and ERK/MAPK, which should be further validated for their predictive, diagnostic, or other clinical value in osteoporosis. Such molecular insights will enable us to fit osteoporosis into the P4 strategy and could increase the effectiveness of disease prediction and prevention, with a decrease in morbidity in the geriatric population.

  7. 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

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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.

  9. N-arylsulfonyl-2-vinyltryptamines as new 5-HT6 serotonin receptor ligands.

    PubMed

    Raoul, Marion; Patigny, Dominique; Fabis, Frédréic; Dauphin, Françis; Rault, Sylvain; Sapi, Janos; Laronze, Jean-Yves

    2006-06-01

    Several new 2-vinyl-Nb,Nb-dimethyltryptamines were prepared using Fischer indole synthesis followed by simple functional group transformations and evaluated on 5-HT4, 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. It was found that 2-vinyl substitution conferred a potent and selective 5-HT6 binding activity to these molecules which could be enhanced by Na-arylsulfonyl substituents.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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, 2010 CFR

    2010-07-01

    ... 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 with...

  17. 31 CFR 351.67 - What happens if any person purchases book-entry Series EE savings bonds in excess of the maximum...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... book-entry Series EE savings bonds in excess of the maximum annual amount? 351.67 Section 351.67 Money... OF THE TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.67 What happens if any person purchases book-entry Series EE savings...

  18. 31 CFR 351.45 - What happens if I purchase definitive Series EE savings bonds in excess of the maximum annual...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Series EE savings bonds in excess of the maximum annual amount? 351.45 Section 351.45 Money and Finance... BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Definitive Series EE Savings Bonds § 351.45 What happens if I purchase definitive Series EE savings bonds in excess of the maximum...

  19. 31 CFR 351.35 - What do I need to know about interest rates, penalties, and redemption values for Series EE bonds...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... rates, penalties, and redemption values for Series EE bonds with issue dates of May 1, 2005, or... SAVINGS BONDS, SERIES EE Maturities, Redemption Values, and Investment Yields of Series EE Savings Bonds Series Ee Savings Bonds with Issue Dates of May 1, 2005, Or Thereafter § 351.35 What do I need to know...

  20. 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, 2010 CFR

    2010-07-01

    ... 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 May...

  1. 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

  2. Insulin-like growth factor 1 (IGF-1) mediates the effects of enriched environment (EE) on visual cortical development.

    PubMed

    Ciucci, Francesca; Putignano, Elena; Baroncelli, Laura; Landi, Silvia; Berardi, Nicoletta; Maffei, Lamberto

    2007-05-30

    Enriched environment (EE) has been recently shown to affect visual cortex development and plasticity, and to prevent dark rearing effects. The factors mediating EE effects on visual cortical development and plasticity are still unclear. We have investigated whether IGF-1 is involved in mediating EE effects on the developing visual cortex. We show that EE increases the number of IGF-1 positive neurons in the visual cortex at P18. Increasing IGF-1 in the visual cortex of non-EE rats by means of osmotic minipumps implanted at P18 mimics EE effects, accelerating visual acuity development, assessed with Visual Evoked Potentials (VEPs). Blocking IGF-1 action in the visual cortex of EE rats by means of the IGF-1 receptor antagonist JB1 from P18 completely blocks EE action on visual acuity development. These results show that IGF-1 is a key factor mediating EE effects on visual cortical development. We then show that IGF-1 affects GAD65 immunoreactivity in perisomatic innervation and the condensation of Chondroitin Sulphate Proteoglycans (CSPGs) in perineuronal nets (PNNs) in the visual cortex. This suggests that IGF-1 action in mediating EE effects could be exerted through the modulation of intracortical inhibitory circuitry and PNN development.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Rearrangement of a P4 Butterfly Complex-The Formation of a Homoleptic Phosphorus-Iron Sandwich Complex.

    PubMed

    Müller, Julian; Heinl, Sebastian; Schwarzmaier, Christoph; Balázs, Gábor; Keilwerth, Martin; Meyer, Karsten; Scheer, Manfred

    2017-06-12

    The versatile coordination behavior of the P4 butterfly complex [{Cp'''Fe(CO)2 }2 (μ,η(1:1) -P4 )] (1, Cp'''=η(5) -C5 H2(t) Bu3 ) towards different iron(II) compounds is presented. The reaction of 1 with [FeBr2 ⋅dme] (dme=dimethoxyethane) leads to the chelate complex [{Cp'''Fe(CO)2 }2 (μ3 ,η(1:1:2) -P4 ){FeBr2 }] (2), whereas, in the reaction with [Fe(CH3 CN)6 ][PF6 ]2 , an unprecedented rearrangement of the P4 butterfly structural motif leads to the cyclo-P4 moiety in {(Cp'''Fe(CO)2 )2 (μ3 ,η(1:1:4) -P4 )}2 Fe][PF6 ]2 (3). Complex 3 represents the first fully characterized "carbon-free" sandwich complex containing cyclo-P4 R2 ligands in a homoleptic-like iron-phosphorus-containing molecule. Alternatively, 2 can be transformed into 3 by halogen abstraction and subsequent coordination of 1. The additional isolated side products, [{Cp'''Fe(CO)2 }2 (μ3 ,η(1:1:2) -P4 ){Cp'''Fe(CO)}][PF6 ] (4) and [{Cp'''Fe(CO)2 }2 (μ3 ,η(1:1:4) -P4 ){Cp'''Fe}][PF6 ] (5), give insight into the stepwise activation of the P4 butterfly moiety in 1. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

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

    2016-01-01

    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. 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. 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). Constant flickering light could cause progressive myopia in

  9. 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

  10. Immobilization of metalloporphyrins on P(4VP-co-St)/SiO 2 by the quaternarization reaction

    NASA Astrophysics Data System (ADS)

    Wang, Ruixin; Jiao, Weizhou; Gao, Baojiao

    2010-08-01

    Poly(4vinylpyridine-co-styrene) (P(4VP-co-St)) was grafted on silica gel particles in the manner of "grafting from", and the grafting particle P(4VP-co-St)/SiO 2 was gained. The chloromethylation reaction for the tetraphenylporphyrin (TPP) was performed using a chloromethylation reagent, 1,4-bis(chloromethyoxy)butane which was uncarcinogenic, and the tetra-chloromethylphenyl-porphyrin (TMCPP) was prepared. Then, the quaternization reaction between the benzyl chloride groups on TMCPP and pyridine groups of the grafted P(4VP-co-St) macromolecules occurred and the bonding of TMCPP on the particles P(4VP-co-St)/SiO 2 was realized, resulting in the functional composite-type particles TMCPP-P(4VP-co-St)/SiO 2. Subsequently, the metallation of the bonded particles TMCPP-P(4VP-co-St)/SiO 2 was carried out via the coordination reaction between TMCPP-P(4VP-co-St)/SiO 2 and metal salt, resulting in the supported metalloporphyrin (MP) catalysts MP-P(4VP-co-St)/SiO 2. The supported catalysts were characterized by UV-Vis spectra. The effects of various factors on the bonding process of TMCPP on P(4VP-co-St)/SiO 2 were studied in detail. In addition, the catalytic activity of the supported catalysts MP-P(4VP-co-St)/SiO 2 have been studied in oxidation process of ethyl benzene with molecular oxygen to acetophenone without the use of sacrificial co-reductant. The experimental results showed that the tetra-chloromethylphenyl-porphyrin (TMCPP) could be successfully bonded onto the P(4VP-co-St)/SiO 2 surfaces by means of the quaternization reaction between TMCPP and the pyridine groups on grafted P(4VP-co-St) macromolecules. The supported catalysts MP-P(4VP-co-St)/SiO 2 exhibited the fine catalytic activity. Moreover, the supported cobalt porphyrin was more active than the supported iron and manganese porphyrins.

  11. Cluster structure of 8p-4h states in /sup 20/Ne

    SciTech Connect

    Hindi, M.M.; Thomas, J.H.; Radford, D.C.; Parker, P.D.

    1983-06-01

    The structure of high-lying states in /sup 20/Ne has been studied using the /sup 12/C(/sup 12/C, ..cap alpha..)/sup 20/Ne reaction at E( /sup 12/C) = 64 and 80 MeV. The spins and branching ratios to the ..cap alpha..+ /sup 16/O channel were determined by measuring double (..cap alpha..-..cap alpha..) and triple (..cap alpha..-..cap alpha..-..gamma..) angular correlations. The branching ratios for decay to the /sup 12/C+ /sup 8/Be channel were obtained from an ..cap alpha..-/sup 12/C coincidence experiment. In addition to confirming the spins of several lower-lying states, we have made a spin assignment of 8/sup +/ for the state at 18.538 MeV and also suggest assignments to states at 17.259 MeV (7/sup -/), 20.478 MeV (8/sup +/), and 24.378 MeV (7/sup -/). The 13.927-MeV (6/sup +/) state is assigned to the K/sup ..pi../ = 0/sub 2//sup +/ band, and it is suggested that this band also includes the 8/sup +/ state at 20.478 MeV. The 18.538-MeV (8/sup +/) state was found to have a large reduced width for decay into /sup 12/C + /sup 8/Be which, together with its small reduced width for decay to ..cap alpha..+ /sup 16/O/sub g.s./, suggests that it has a large /sup 12/C + /sup 8/Be cluster parentage. This state appears to be the 8/sup +/ member of a new 8p-4h band which has the 12.436-MeV (0/sub 6//sup +/) state as its band head and the state at 15.159 MeV as its 6/sup +/ member. The discovery of such a rotational band in /sup 20/Ne with a large /sup 12/C + /sup 8/Be cluster parentage and a large moment of inertia provides the first direct indication of correlations between the ..cap alpha.. clusters in 8p-4h states.

  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. 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

  14. 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.

  15. 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.

  16. Structural basis of ligand recognition in 5-HT3 receptors

    PubMed Central

    Kesters, Divya; Thompson, Andrew J; Brams, Marijke; van Elk, René; Spurny, Radovan; Geitmann, Matthis; Villalgordo, Jose M; Guskov, Albert; Helena Danielson, U; Lummis, Sarah C R; Smit, August B; Ulens, Chris

    2013-01-01

    The 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation–π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. PMID:23196367

  17. SHEDS-HT: An Integrated Probabilistic Exposure Model for ...

    EPA Pesticide Factsheets

    United States Environmental Protection Agency (USEPA) researchers are developing a strategy for highthroughput (HT) exposure-based prioritization of chemicals under the ExpoCast program. These novel modeling approaches for evaluating chemicals based on their potential for biologically relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. Based on probabilistic methods and algorithms developed for The Stochastic Human Exposure and Dose Simulation Model for Multimedia, Multipathway Chemicals (SHEDS-MM), a new mechanistic modeling approach has been developed to accommodate high-throughput (HT) assessment of exposure potential. In this SHEDS-HT model, the residential and dietary modules of SHEDS-MM have been operationally modified to reduce the user burden, input data demands, and run times of the higher-tier model, while maintaining critical features and inputs that influence exposure. The model has been implemented in R; the modeling framework links chemicals to consumer product categories or food groups (and thus exposure scenarios) to predict HT exposures and intake doses. Initially, SHEDS-HT has been applied to 2507 organic chemicals associated with consumer products and agricultural pesticides. These evaluations employ data from recent USEPA efforts to characterize usage (prevalence, frequency, and magnitude), chemical composition, and exposure scenarios for a wide range of consumer products. In modeling indirec

  18. 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.

  19. 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.

  20. Pay for performance in the inpatient sector: A review of 34 P4P programs in 14 OECD countries.

    PubMed

    Milstein, Ricarda; Schreyoegg, Jonas

    2016-10-01

    Across the member countries of the Organisation for Economic Co-operation and Development (OECD), pay-for-performance (P4P) programs have been implemented in the inpatient sector to improve the quality of care provided by hospitals. This paper provides an overview of 34 existing P4P programs in the inpatient sector in 14 OECD countries based on a structured literature search in five databases to identify relevant sources in Danish, English, French, German, Hebrew, Italian, Japanese, Korean, Norwegian, Spanish, Swedish and Turkish. It assembles information on the design and effects of these P4P systems and discusses whether evaluations of such programs allow preliminary conclusions to be drawn about the effects of P4P. The programs are very heterogeneous in their aim, the selection of indicators and the design of financial rewards. The impact of P4P is unclear and it may be that the moderately positive effects seen for some programs can be attributed to side effects, such as public reporting and increased awareness of data recording. Policy makers must decide whether the potential benefits of introducing a P4P program outweigh the potential risks within their particular national or regional context, and should be aware that P4P programs have yet not lived up to expectations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Synthesis of cubic zirconium and hafnium nitride having Th3P4 structure.

    PubMed

    Zerr, Andreas; Miehe, Gerhard; Riedel, Ralf

    2003-03-01

    High-pressure synthesis is a powerful method for the preparation of novel materials with high elastic moduli and hardness. Additionally, such materials may exhibit interesting thermal, optoelectronic, semiconductuing, magnetic or superconducting properties. Here, we report on the high-pressure synthesis of zirconium and hafnium nitrides with the stoichiometry M3N4, where M = Zr, Hf. Synthesis experiments were performed in a laser-heated diamond anvil cell at pressures up to 18 GPa and temperatures up to 3,000 K. We observed formation of cubic Zr3N4 and Hf3N4 (c-M3N4) with a Th3P4-structure, where M-cations are eightfold coordinated by N anions. The c-M3N4 phases are the first binary nitrides with such a high coordination number. Both compounds exhibit high bulk moduli around 250 GPa, which indicates high hardness. Moreover, the new nitrides, c-Zr3N4 and c-Hf3N4, may be the first members of a larger group of transition metal and/or lanthanide nitrides with interesting ferromagnetic or superconducting behaviour.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Working with women prisoners who seriously harm themselves: ratings of staff expressed emotion (EE).

    PubMed

    Moore, Estelle; Andargachew, Sara; Taylor, Pamela J

    2011-02-01

    Prison staff are repeatedly exposed to prisoners' suicidal behaviours; this may impair their capacity to care. Expressed emotion (EE), as a descriptor of the 'emotional climate' between people, has been associated with challenging behaviour in closed environments, but not previously applied to working alliances in a prison. To investigate the feasibility of rating EE between staff and suicidal women in prison; to test the hypothesis that most such staff-inmate alliances would be rated high EE. All regular staff on two small UK prison units with high suicidal behaviour rates were invited to participate. An audiotaped five-minute speech sample (FMSS) about work with one nominated suicidal prisoner was embedded in a longer research interview, then rated by two trained raters, independent of the interview process and the prison. Seven prison officers and 8 clinically qualified staff completed interviews; 3 refused, but 17 others were not interviewed, reasons including not having worked long enough with any one such prisoner. Participants and non-participants had similar relevant backgrounds. Contrary to our hypothesis, EE ratings were generally 'low'. As predicted, critical comments were directed at high frequency oppositional behaviour. EE assessments with prison staff are feasible, but our sample was small and turnover of prisoners high, so the study needs replication. Attributions about problem behaviour to illness, and/or traumatic life experience, tend to confirm generally supportive working relationships in this sample. Copyright © 2010 John Wiley & Sons, Ltd.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. The relaxant 5-HT receptor in the dog coronary artery smooth muscle: pharmacological resemblance to the cloned 5-ht7 receptor subtype.

    PubMed Central

    Terrón, J. A.

    1996-01-01

    1. The relaxant effect of 5-hydroxytryptamine (5-HT) in the dog isolated coronary artery deprived of endothelium is mediated by a receptor unrelated to the 5-HT1, 5-HT2, 5-HT3 or 5-HT4 types. Based upon the pharmacological characteristics of this relaxant 5-HT receptor and those reported for the new members of the 5-HT receptor family, the present study explored the possibility that the relaxant 5-HT receptor referred to above, corresponds to the cloned 5-ht7 subtype. Thus, the relaxing and/or blocking effects of several 5-HT receptor drugs as well as some typical and atypical antipsychotic drugs with high affinity for the cloned 5-ht7 receptor in precontracted ring segments were analyzed. 2. 5-HT, 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine, but not 8-OH-DPAT or sumatriptan, produced concentration-dependent relaxations in endothelium-denuded canine coronary artery rings precontracted with prostaglandin F2a (2 microM). Clozapine (1 microM) produced in some cases a small relaxing effect and antagonized 5-HT- and 5-CT-induced relaxation suggesting a partial agonist effect. In the presence of the 5-HT1D receptor antagonist, GR127935 (100 nM), the rank order of agonist potency was 5-CT > 5-HT > clozapine > or = 5-methoxytryptamine. 8-OH-DPAT and sumatriptan remained inactive as agonists. 3. In GR127935-treated preparations, methiothepin (3 nM) and mianserin (1 microM), as well as the antipsychotics, clozapine (1 microM), pimozide (300 nM), risperidone (3 nM) and spiperone (1 microM), failed to induce a significant relaxation in prostaglandin F2x-precontracted vessels, but produced significant rightward displacements of the concentration-response curves to 5-HT and 5-CT without significantly reducing the Emax. In a final set of experiments with 5-CT, metergoline (100 nM) and mesulergine (300 nM) behaved as competitive antagonists. In contrast, lisuride (3 nM) noncompetitively antagonized 5-CT-induced relaxation. The estimated affinity (apparent pKa values) of

  13. Study of dielectric phenomenon for P3HT: PCBM blend

    NASA Astrophysics Data System (ADS)

    Kumar, Sunil; Kumar, Manoj; Rathi, Sonika; Singh, Amarjeet

    2017-05-01

    In this present work we prepared the film sample of blend (P3HT (poly (3-hexylthiophene-2, 5-diyl)): PCBM ([6,6]-phenyl C61-butyric acid methyl ester)), P3HT and PCBM solution on ITO substrate by drop cast method. Capacitance and tangent loss (tan δ) were measured and dielectric constants έ and dielectric loss ɛ″ were deduced from them as function frequency at room temperature. Blend samples show strong frequency dependence as compared to pristine P3HT and pristine PCBM sample. The high dielectric constant in blend films at low frequency was attributed to characteristic slow relaxation process in polymers along with polarization of isolated grains in the blend sample.

  14. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Effects of LSD on Ca++ currents in central 5-HT-containing neurons: 5-HT1A receptors may play a role in hallucinogenesis.

    PubMed

    Penington, N J; Fox, A P

    1994-06-01

    Drugs that influence the activity of central serotonergic neurons by activating a 5-hydroxytryptamine subtype of receptor (5-HT1A) alter mood and perception. Previously, we demonstrated with whole-cell recordings from acutely isolated 5-HT-containing dorsal raphe (DR) neurons from the adult rat that 5-HT inhibited Ca++ current and activated K+ current in DR neurons. We now show that D-lysergic acid diethylamide (LSD) mimics the actions of 5-HT; it dramatically suppresses Ca++ current in a dose-dependent manner and activates an inwardly rectifying K+ conductance. Spiperone (0.2 microM), a 5-HT1A/5-HT2 antagonist, blocks the effect of both LSD and 5-HT. The nonhallucinogenic structural analog 2-bromo-LSD (2-Bol) at 10 microM has no effect on either Ca++ or K+ current by itself, but it competitively antagonizes both effects of LSD. Inhibition of 5-HT release resulting from 5-HT1A receptor activation may play an integral role in the hallucinogenic actions of LSD by reducing competition between 5-HT and LSD for the postsynaptic 5-HT receptors.

  20. 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.