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Sample records for volume 2-c havre

  1. La geografia come monumento. Il progetto di Auguste Perret per Le Havre / Geography as a monument. The Auguste Perret’s project for Le Havre

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    Antonio Nitti

    2014-11-01

    Full Text Available Nel progetto di Auguste Perret per Le Havre una forma chiaramente compatta ed evocativa dell’urbanità della città storica si definisce a partire dalle relazioni stabilite con quegli elementi della geografia fisica che costituiscono l’identità del luogo nel quale questa si colloca, e costruisce una significativa relazione con gli spazi aperti e vasti della natura, acquisendo in questo modo quella ‘dimensione’ e quei caratteri propri della città contemporanea. Nei suoi spazi collettivi, che rimandano a una cultura dell’abitare che affonda le proprie radici nella più generale storia della città francese, Le Havre rappresenta sé stessa e traduce nella Place de l’Hôtel de Ville le ripide pendici della falesia, nella Porte Océane l’orizzonte lontano dell’Oceano, nel Front-de-mer Sud l’altra riva della foce della Senna, e fa di questi i veri ‘monumenti’ della città. / In the Auguste Perret’s project for Le Havre a clearly compact form, evocative of urbanity of the historical city, is defined starting from the relations established with those elements of physical geography which constitute the identity of the place where the city is located, and builds a significant relationship with the open and vast spaces of nature, thus acquiring the ‘size’ and those features of the contemporary city. In its public spaces, which refer to a culture of inhabiting that is rooted in the more general history of the French city, Le Havre represents itself and translates in the Place de l'Hôtel de Ville, the steep slopes of the cliff, in the Porte Oceane the distant horizon of the ocean, in the Front-de-mer South the other bank of the mouth of the Seine, and defines these as the real 'monuments' of the city.

  2. Le Havre, Berlim, Jersalém: a cartografia do mundo

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    Sylvaine Bulle

    2005-07-01

    Full Text Available Por ocasião de uma exposição de fotos de três cidades (Le Havre, Berlim e Jerusalém, o artigo discute as culturas urbanas e os modos de representação e exposição de fatos urbanos modernos. Como vincular séries de imagens para que se tornem legíveis os enunciados políticos e a memória das cidades diante desses fatos? A análise das imagens de cidades no contexto da guerra (Jerusalém e da reconstrução (Berlim, Le Havre remete à produção de culturas urbanas e de arquiteturas entre uma memória local e os fluxos internacionais.Taking an exhibition of photos of three cities (Le Havre, Berlin and Jerusalém as a guideline, the article discusses urban cultures and possibilities of representation and exhibition of modern urban events. How to associate series of images in order to clarify political propositions and the memory of cities in face of these events? The analysis of images of cities in context of war (Jerusalém and of reconstruction (Berlin, Le Havre refers to the production of urban cultures and architectures between local memory and international flows.

  3. Quatre générations de lazarets au Havre

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    Claire Etienne-Steiner

    2012-04-01

    Full Text Available Fondés en 1517 par François Ier pour remplacer le port souverain de Normandie, Harfleur, irrémédiablement envasé par les alluvions de la Seine, la ville et le port du Havre sont implantés à l'extrême pointe de l'estuaire, sur un terrain à peu près stabilisé derrière un amas de galets. La nouvelle fondation est reliée à la terre ferme par le cordon ombilical que constitue une route en chaussée qui traverse des terrains marécageux, sillonnés de ruisseaux issus de la falaise calcaire qui borde l...

  4. Port Competition in the Northern Range from Le Havre to Hamburg

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    Pierre Thorez

    2006-03-01

    Full Text Available The main European ports of the Northern Range facingstrong competition develop various strategies. Rotterdam andLe Havre, fast transit, Antwe1p, logistic activities with storage,Hamburg, hub for central and eastem Europe. These strategieswill be described in the paper.All of them are building new container terminals and usenew tools in technology of communications to increase trafficand to enable shipping lines to achieve their own strategies. Thenew equipments will also b.: analysed.In the last years, the competition is mainly on the links withthe hinterland. Major ports t1y to enlarge their hinterlands bytransshipment, railway con"idors, waterway connections andhighways. The importance of ports and inland intermodalnodes is growing.Nowadays, port competition in the Northern Range is locatednot only in the ports.

  5. How to prioritize numerous environmental issues? Case study of the Havre-Saint-Pierre spill

    Energy Technology Data Exchange (ETDEWEB)

    Grenon, S. [Environment Canada, Montreal, PQ (Canada). Environmental Emergencies Div

    2000-07-01

    While docking at the QIT facility at Havre St. Pierre, Quebec, on March 23, 1999, the cargo ship M/V Gordon C. Leitch collided with the dock, ruptured a fuel tank, and spilled 49 metric tons of light bunker oil (IFO-180) in the Gulf of St. Lawrence. The situation seemed under control at the beginning since the ice cover contained the migration of oil, but it quickly degenerated when the whole picture became clear. The spill occurred in a remote location where wildlife is abundant and diversified. The economy was largely dependant on ecotourism and several environmental and social factors had to be considered when devising the clean up procedure. Oil was found on 120 km of shoreline in the vicinity of the Mingan Archipelago National Park, a wildlife sanctuary protected by the government of Canada. There were oil-covered birds, a native hunting ground, several fishing zones and the National Park. The spill was cleaned up in two months. The authors described the different factors to be considered and the appropriateness and effectiveness of the Regional Environmental Emergency Team in setting priorities and choosing the best course of action to deal with each set of circumstances. 1 tab., 2 figs.

  6. The (p, {rho}, T) properties and apparent molar volumes V{sub {phi}} of (ZnBr{sub 2} + C{sub 2}H{sub 5}OH)

    Energy Technology Data Exchange (ETDEWEB)

    Guliyev, Tavakkul [Department of Heat and Refrigeration Techniques, Azerbaijan Technical University, H. Javid Avn. 25, AZ1073 Baku (Azerbaijan); Safarov, Javid [Department of Heat and Refrigeration Techniques, Azerbaijan Technical University, H. Javid Avn. 25, AZ1073 Baku (Azerbaijan); Lehrstuhl fuer Technische Thermodynamik, Universitaet Rostock, 18059 Rostock (Germany)], E-mail: javid.safarov@uni-rostock.de; Shahverdiyev, Astan [Department of Heat and Refrigeration Techniques, Azerbaijan Technical University, H. Javid Avn. 25, AZ1073 Baku (Azerbaijan); Hassel, Egon [Lehrstuhl fuer Technische Thermodynamik, Universitaet Rostock, 18059 Rostock (Germany)

    2009-10-15

    The (p, {rho}, T) properties and apparent molar volumes V{sub {phi}} of ZnBr{sub 2} in ethanol at temperatures (293.15 to 393.15) K and pressures up to p = 40 MPa are reported. The measurements were made with a recently developed vibration-tube densimeter. The system was calibrated using double-distilled water, methanol, ethanol, and aqueous NaCl solutions. The experiments were carried out at molalities of m = (0.05681, 0.16958, 0.30426, 0.43835, 0.93055, 1.49016, and 1.88723) mol . kg{sup -1} using zinc bromide. An empirical correlation for the density of (ZnBr{sub 2} + C{sub 2}H{sub 5}OH) with pressure, temperature, and molality has been derived. This equation of state was used to calculate other volumetric properties such as isothermal compressibility, isobaric thermal expansibility, the differences in specific heat capacities at constant pressures and volumes, apparent molar volumes of ZnBr{sub 2} in ethanol, and partial molar volumes of both components.

  7. Backarc rifting, constructional volcanism and nascent disorganised spreading in the southern Havre Trough backarc rifts (SW Pacific)

    Science.gov (United States)

    Wysoczanski, R. J.; Todd, E.; Wright, I. C.; Leybourne, M. I.; Hergt, J. M.; Adam, C.; Mackay, K.

    2010-02-01

    High resolution multibeam (EM300 and SEABEAM) data of the Southern Havre Trough (SHT), combined with observations and sample collections from the submersible Shinkai6500 and deep-tow camera, are used to develop a model for the evolution and magmatism of this backarc system. The Havre Trough and the associated Kermadec Arc are the product of westward subduction at the Pacific-Australian plate boundary. Detailed studies focus on newly discovered features including a seamount (Saito Seamount) and a deep graben (Ngatoroirangi Rift, > 4000 m water depth floored with a constructional axial volcanic ridge > 5 km in length and in excess of 200 m high), both of which are characterised by pillow and lobate flows estimated at Mass balance modelling indicates a maximum crustal thickness of ~ 11 km to magmatism within deep SHT rifts, we propose that the SHT is in an incipient phase of distributed and "disorganised" oceanic crustal accretion in multiple, ephemeral, and short but deep (> 4000 m) spreading systems. These discontinuous spreading systems are characterised by failed rifts, rift segmentation, and propagation. Successive episodes of magmatic intrusion into thinned faulted arc basement results in defocused asymmetrical accretion. Cross-arc volcanic chains, isolated volcanoes and underlying basement plateaus are interpreted to represent a "cap" of recent extrusives. However, they may also be composed entirely of newly accreted crust and the spatially extensive basement fabric of elongated volcanic ridges may be the surface expression of pervasive dike intrusion that has thoroughly penetrated and essentially replaced the original arc crust with newly accreted intrusives.

  8. Proceedings of the Third NRC/ASME Symposium on Valve and Pump Testing. Session 1A--Session 2C: Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    The 1994 Symposium on Valve and Pump Testing, jointly sponsored by the Board of Nuclear Codes and Standards of the American Society of Mechanical Engineers and by the Nuclear Regulatory Commission, provides a forum for the discussion of current programs and methods for inservice testing and motor-operated valve testing at nuclear power plants. The symposium also provides an opportunity to discuss the need to improve that testing in order to help ensure the reliable performance of pumps and valves. The participation of industry representatives, regulators, and consultants results in the discussion of a broad spectrum of ideas and perspectives regarding the improvement of inservice testing of pumps and valves at nuclear power plants. This document, Volume 1, covers sessions 1A through session 2C. The individual papers have been cataloged separately.

  9. From rifting to active spreading in the Lau Basin - Havre Trough backarc system (SW Pacific): Locking/unlocking induced by seamount chain subduction

    Science.gov (United States)

    Ruellan, E.; Delteil, J.; Wright, I.; Matsumoto, T.

    2003-05-01

    Associated with Pacific-Australia plate convergence, the Lau Basin - Havre Trough is an active back-arc basin that has been opened since ˜5.5 Ma by rifting and southward propagating oceanic spreading. Current back-arc opening rates decrease from 159 mm yr-1 in the northern Lau Basin to 15 mm y-1 in the southern Havre Trough. Major tectonic changes occur at the transition between Havre Trough rifting and full oceanic spreading of the Eastern Lau Spreading Center (ELSC), where the oblique-to-trench, westward subducting Louisville Seamount Chain (LSC) sweeps southwards along the Tonga trench. New swath bathymetry, seismic reflection data, and limited rock sampling in this area constrain a tectonic and kinematic back-arc model that incorporates the effects of LSC subduction. The ELSC, which extends southward to 24°55'S, forms a deep rift valley propagating southward through older, rifted arc basement. Present-day seismicity and fresh and fractured pillow lavas at 23°42'S are consistent with rift valley neovolcanism. Conversely, the northern Havre Trough has low seismicity and rifted volcanic basement ridges trending 25-45° oblique to the basin axis consistent with low levels of extensional tectonism and volcanism. This latter structural fabric is interpreted as an early stage of rifting that is now "locked" due to compression on the arc exerted by LSC subduction, while in the Lau Basin such effects have passed as the LSC swept along the Tonga Trench. It is proposed that the Lau-Havre back-arc opening is controlled by tectonic constraints exerted at the limits of the system by the LSC subduction, which determines the southward migration of the Tonga Arc pole of rotation and associated Lau Basin opening. A discrete three-stage back-arc opening evolution is proposed, comprising: (1) an initial phase of back-arc rifting along the whole length of the plate boundary, beginning at ˜6-5 Ma; (2) a subsequent phase, mostly present in the southern part of the back-arc domain

  10. Investigating syn- vs. post-eruption hydration mechanisms of the 2012 Havre submarine explosive eruption: Water speciation analysis of pumiceous rhyolitic glass

    Science.gov (United States)

    Mitchell, S. J.; McIntosh, I. M.; Houghton, B. F.; Shea, T.; Carey, R.

    2016-12-01

    Volatiles preserved in volcanic glass can record the quenching, fragmentation and solubility conditions during an explosive eruption. The VEI-5 2012 eruption of Havre volcano, which produced >1.5 km3 of rhyolite, provides exciting new insight into deep-submarine explosive eruptions. With no direct observations of the eruption at the 900 mbsl vent, the analysis and interpretation of volatile concentrations and speciation within pyroclasts is essential to constraining the eruption style and quenching mechanisms in this understudied environment. We present here the first detailed water speciation data for a large submarine explosive eruption. Water concentrations were measured in pyroclasts from known deposit localities across the Havre stratigraphic succession after ROV collection in 2015. Variations in total water concentration (H2OT) within pyroclasts were determined using high spatial resolution (1 - 2 µm) micro-Raman spectroscopy and water speciation (molecular water (H2Om) and OH) concentrations were measured using Fourier-transform infrared spectroscopy. H2OT concentrations are consistent between Raman and FTIR analysis, ranging from 0.1 - 1.5 wt % H2OT over different stratigraphic units. Comparison of water speciation data with speciation models suggests the Havre pyroclasts experienced secondary, non-magmatic hydration. Since OH is unaltered by secondary hydration, OH concentrations aid in the interpretation of quench depths and inferring of eruption mechanisms. The variability of excess H2Om across units suggests a more complex glass-hydration mechanism during the eruption instead of exclusively post-eruption, low-temperature secondary rehydration. The young sample ages are inconsistent with our current understanding of low-temperature H2O-diffusivity timescales, implying faster secondary rehydration in a higher-temperature submarine setting. We here explore potentially novel syn-eruptive, higher-temperature hydration mechanisms for deep-submarine pumice.

  11. Les villégiatures familiales de la côte d’Albâtre (du Tréport au Havre

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    Viviane Manase

    2012-04-01

    Full Text Available Du Tréport au Havre, la côte d’Albâtre a été particulièrement précoce en matière de pratiques balnéaires, avec notamment l’émergence et l’épanouissement de la station de Dieppe, la plus ancienne de France. Pourtant, force est de constater que son histoire balnéaire demeure méconnue. Ainsi cette contribution a-t-elle pour ambition d’évoquer à la fois les processus d’installation et de développement de ses sites balnéaires, souvent modestes, mais aussi les différents modes d’habiter des villégiateurs, qu’il s’agisse de villas privées, de lotissements, de locations ou d’hôtels de voyageurs. Enfin, à travers la naissance et l’évolution du hameau des Petites-Dalles transparaissent toute la dimension humaine et le mode de vie des estivants au sein d’une villégiature dite familiale, entre constitution d’un maillage humain et affirmation d’une vocation balnéaire.

  12. Pasarela en Le Havre Francia

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    Gillet, Guillaume

    1975-03-01

    Full Text Available The longitudinal profile of this is a cubic parabola with a 6 m rise and a length of 105 m. Essentially this footbridge consists of a metal pier —that supports two unequal spans— situated at 3/10 of the length so as to utilize the pier of an old bridge; it has the shape of a capital A, the posts of which are pyramids with triangular section and which are formed by sheet plates joined together by welding. The spans, however, consist of: two lateral metal welded beams; a series of bridge ties also of metal, at a distance of 2.50 m from each other and joined to the beams by means of bolts; and resting upon these, a 10 cm thick reinforced concrete slab, protected by a greatly adhesive covering due to the strong slope of the accesses. The suspended solution does not allow any greater thickness of the footbridge and thus the views of the harbour are hardly obstructed. Its assymmetric shape along with the slender form of the pier contributes to making its location in the centre of the city very suitable.El perfil longitudinal de esta pasarela es el de una parábola cúbica con 6 m de flecha y 105 m de longitud. Esencialmente está constituida por una pila metálica —que soporta dos tramos desiguales— situada a 3/10 de la longitud con el fin de reutilizar, para su cimentación, la pila de un antiguo puente; tiene la forma de una gran A, cuyos montantes son pirámides de sección triangular formados por palastros soldados entre sí. Los tramos, a su vez, están formados por: dos vigas laterales metálicas, soldadas; una serie de traviesas, también metálicas, distanciadas 2,50 m y unidas a las vigas mediante bulones; y, apoyando sobre estas últimas, una losa de hormigón armado de 10 cm de espesor, protegida por un revestimiento de gran adherencia motivado por la fuerte pendiente de los accesos. La solución suspendida ha permitido dar un espesor muy pequeño a la pasarela, con lo que apenas se obstaculizan las perspectivas de la dársena. Su forma asimétrica, unida a la gran esbeltez de la pila, la hacen muy adecuada a su emplazamiento en pleno centro de la ciudad.

  13. Ti2C80 is more likely a titanium carbide endohedral metallofullerene (Ti2C2)@C78.

    Science.gov (United States)

    Tan, Kai; Lu, Xin

    2005-09-21

    We show by means of density functional calculations that the previously synthesized metallofullerene Ti2C80 does not take the form of Ti2@C80, but is a titanium carbide endohedral metallofullerene, Ti2C2@C78, that has a C78(6-)(D3h) cage which follows faithfully the stable closed-shell electronic rule.

  14. Le latin de Thomas d’Aquin et l’intellectualisation de Havránek. Entre lexicographie computationnelle et histoire des idées sémiotiques

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    Raynaud Savina

    2015-09-01

    Full Text Available The paper aims to evaluate the semantic - terminological effect on the use of the Latin lexicon that are shaped by a particular author, given the complete documentation of the occurrences of his lemmata (Index Thomisticus, further supplied by on-going syntactic annotation, but nevertheless requiring proper, theoretically well-founded semantic analysis and lexicographic production. We propose linking the rich theoretical tradition which has produced the Prague Dependency Treebank (PDT and the correlated Tectogrammatical Annotation (TGA to the objectives of the Bicultural Thomistic Lexicon (LTB. To do this, we will examine and discuss Havránek’s contribution to the shaping of standard language, especially through the distinctive, creative procedure he calls intellectualisation. At the same time, we will outline the effect determined by the use – established in all its extensions – of an expression (lexical item or noun phrase. Given that the user – Thomas Aquinas – was an author who profoundly influenced subsequent thought, the creation or codification of a terminological value of the item will be investigated.

  15. GENETIC POLYMORPHISM OF CYTOCHROMES P450 2C9 AND 2C19 IN SLOVENIAN POPULATION

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    Darja Herman

    2003-06-01

    Full Text Available Background. Cytochrome P450 2C9 (CYP2C9 and 2C19 (CYP2C19 participate in metabolism of many clinically important drugs. Genetic polymorphisms of the CYP2C9 and CYP2C19 genes are described which may affect drug treatment. The aim of this study was to determine the frequencies of polymorphic CYP2C9 and CYP2C19 alleles in Slovenian population in order to estimate the proportion of the population that might experience adverse drug reaction.Methods. The polymorphism of CYP2C9 and CYP2C19 was analysed by a genotyping technique, based on polymerase chain reaction (PCR followed by restriction enzyme analysis. DNA samples from 129 unrelated healthy subjects were obtained from the Blood Transfusion Centre of Slovenia and University Children’s Hospital in Ljubljana.Results. In the analysed group of samples one-third of individuals carried at least one of the defective CYP2C9 alleles while among them 3.2% of individuals had both alleles affected. The frequencies of CYP2C9*2 and CYP2C9*3 were 0.122 and 0.063, respectively. Almost one-third of Slovenian individuals analysed carried at least one of the CYP2C19 polymorphic allele. The frequencies of CYP2C19*2 and CYP2C19*3 were 0.159 and 0.004, respectively.Conclusions. The results of our study indicate that approximately one-third of the patients from Slovenian population may require either adjustments of dose or increased monitoring when initiating treatment with CYP2C9 and CYP2C19 substrates having a narrow therapeutic index. High risk of adverse drug reaction may be expected in 1–3% of eventual patients.

  16. Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

    Science.gov (United States)

    Jukić, M M; Opel, N; Ström, J; Carrillo-Roa, T; Miksys, S; Novalen, M; Renblom, A; Sim, S C; Peñas-Lledó, E M; Courtet, P; Llerena, A; Baune, B T; de Quervain, D J; Papassotiropoulos, A; Tyndale, R F; Binder, E B; Dannlowski, U; Ingelman-Sundberg, M

    2016-11-29

    The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype. In humans, we found that the absence of CYP2C19 was associated with a bilateral hippocampal volume increase in two independent healthy cohorts (N=386 and 1032) and a lower prevalence of major depressive disorder and depression severity in African-Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic capacity was associated with higher suicidality in depressed suicide attempters (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf homeostasis in stress, and more despair-like behavior in the forced swim test (FST). After the treatment with citalopram and 5-HT1A receptor agonist 8OH-DPAT, the reduction in immobility time in the FST was more pronounced in 2C19TG mice compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of serotonin was reduced, whereas ERK1/2 and GSK3β phosphorylation was increased. Altogether, this study indicates that elevated CYP2C19 expression is associated with depressive symptoms, reduced hippocampal volume and impairment of hippocampal serotonin and BDNF homeostasis.Molecular Psychiatry advance online publication, 29 November 2016; doi:10.1038/mp.2016.204.

  17. Developing 2 C-compatible investment criteria

    Energy Technology Data Exchange (ETDEWEB)

    Roeser, Frauke [NewClimate - Institute for Climate Policy and Global Sustainability gGmbH, Bonn (Germany); Weischer, Lutz [Germanwatch e.V., Koeln (Germany); Thomae, Jakob [2degrees Investing Initiative, New York, NY (United States); Hoehne, Niklas; Hagemann, Markus; El Alaoui, Alexander; Bals, Christoph; Eckstein, David; Kreft, Soenke; Rosse, Morten

    2015-11-30

    This report studies the development of criteria for assessing the compatibility of financial investments with the international goal to limit global temperature increase to below 2 C above pre-industrial levels. The findings are intended as a starting point and a key input for a longer term process to develop consensus-based 2 C investing criteria. The focus here is placed on investments in projects and physical assets, in particular of development and climate finance organisations. In order to limit global temperature increase to 2 C, global greenhouse gas (GHG) emissions will have to be reduced significantly, eventually to zero, during the course of this century. This requires shifting capital from high to low carbon investments as well as significant capital mobilisation for investments in 2 C-compatible infrastructure. Given the long lifetime of physical assets, and the urgency of decarbonisation over the coming decades, this needs to begin today. Public financial institutions can play a prominent role in contributing to aligning investment flows with the 2 C limit, as well as in closing the current infrastructure investment gap, responding to their explicit or implicit climate mandates and leadership role in the finance sector. The majority of international financial institutions integrate climate considerations into their finance decisions to some degree, and are familiar with different types of criteria, including positive and negative lists, qualitative and quantitative benchmarks, and the use of shadow carbon pricing. However, current approaches do not link to the 2 C limit. 2 C investment criteria are therefore needed to guide investors in this regard. Such criteria may also support other purposes, including an understanding of climate risks and improved reporting and accountability.

  18. LM-2C Series Launch Vehicles

    Institute of Scientific and Technical Information of China (English)

    XueFuxing

    2004-01-01

    On December 30, 2003, a LM-2C/SM launch vehicle was launched from Xichang Satellite Launch Center (XSLC), successfully sending TC-1 satellite into orbit. The satellite is the first one of the two scientific satellites known as Double Star. The operation orbit of the satellite is the highest compared with China's other satellites ever launched.

  19. Far infrared transmittance of Sc2@C84 and Er2@C82

    NARCIS (Netherlands)

    Grannan, S.M.; Birmingham, J.T.; Richards, P.L.; Bethune, D.S.; Vries, M.S. de; Loosdrecht, P.H.M. van; Dorn, H.C.; Burbank, P.; Bailey, J.; Stevenson, S.

    1997-01-01

    We have measured the far infrared transmittance of Sc2@C84 and Er2@C82 at 1.5 K between 30 and 200 cm-1. Both materials are observed to have a large primary absorption feature centered at 95 cm-1 with a width of approximately 50 cm-1, as well as a number of secondary absorption features which are di

  20. Surface reconstruction of W2C(0001)

    Science.gov (United States)

    Aizawa, Takashi; Hishita, Shunichi; Tanaka, Takaho; Otani, Shigeki

    2011-08-01

    A single crystal surface of ditungsten carbide, W2C(0001) was investigated using low-energy (LEED) and high-energy electron diffraction, Auger electron spectroscopy, x-ray photoelectron spectroscopy (XPS), and high-resolution electron energy loss spectroscopy (HREELS). A new reconstruction, \\sqrt {13} \\times \\sqrt {13} {R}+/- 13.9^{\\circ } , was found as a clean surface structure after annealing the W2C at > 1900 K. The surface carbon content is shown as larger than that in the bulk. Our preliminary results showed that the same structure is realized also on WC(0001). The same surface periodicity is described for an Mo2C(0001) LEED pattern in the literature. This reconstruction phase is presumably common on the (0001) surface of hexagonal group-6 transition-metal carbides. In the off-specular HREELS, an atomic vibration of 44.8 meV (361 cm - 1) appeared within the gap energy region of the bulk phonon bands, which was assigned to a surface carbon vibration perpendicular to the surface. One possible explanation of the low vibrational frequency is very low adsorption height of the surface carbon atoms.

  1. Experimental Electronic Structure of Be_2C

    Science.gov (United States)

    Tsuei, K.-D.; Tzeng, C.-T.; Lo, W.-S.; Yuh, J.-Y.; Chu, R.-Y.

    1998-03-01

    The insulating Be_2C thin films have been successfully prepared on a Be surface. LEED pattern shows that the films have (100) orientation along the surface normal. We have used angle-resolved photoemission to map out the occupied bulk band dispersion along Γ-X direction. The band gap edges at X point are 6.5 and 11.7 eV below the valence band maximum which is located at Γ point. These values are in good agreement with theoretical calculations. [1,2] In addition two surface states are observed. One is 0.5 eV above VBM. The other is located at 9.5 eV below VBM in the middle of the band gap at X point. The unoccupied bulk electronic structure is measured using C 1s near edge x-ray absorption spectroscopy. The spectrum is similar in shape to an energy loss spectrum [3] and p-PDOS from the calculation, [2] while the relative peak positions are different. [1] J.L. Corkill and M.L. Cohen, Phy. Rev. B 48, 17138 (1993). [2] C.H. Lee, W.R. Lambrecht, and B. Segall, Phys. Rev. B 51, 10392 (1995). [3] M.M. Disko, J.C.H. Spence, O.F. Sankey, and D. Saldin, Phys. Rev. B 33, 5642 (1986).

  2. Isolation and characterization of canine parvovirus type 2C (CPV-2C) from symptomatic puppies.

    Science.gov (United States)

    Puentes, R; Eliopulos, N; Pérez, R; Franco, G; Sosa, K; Bianchi, P; Furtado, A; Hübner, S O; Esteves, P A

    2012-07-01

    Canine parvovirus type 2 (CPV-2) is a leading cause of diarrhea in puppies in several parts of the world. In this study CPV-2 was detected and recovered from puppies showing clinical disease from Montevideo, Uruguay. Samples were processed and used to infect CRFK and MDCK cells in order to isolate the virus. Out of twelve, two samples were positive for CPV-2. A genomic region of 583 bp was amplified and the molecular characterization was performed by sequencing, phylogenetic analysis and Restriction Fragment Length Polymorphism (RFLP). Two isolated viruses (UY1 and UY2) were CPV-2c-like viruses. The comparison between the cytophatic effect (CPE) of CPV-2 (vaccinal virus) and CPV-2c (isolated virus) on primary canine cells cultures and on CRFK line cells, demonstrated that CPV-2c is less citopathogenic in CRFK than in primary cultures. Our study represents the first report on isolation and characterization of canine parvovirus type 2c (CPV-2c) in cell cultures from South American dogs.

  3. Isolation and characterization of canine parvovirus type 2c (CPV-2c from symptomatic puppies

    Directory of Open Access Journals (Sweden)

    R Puentes

    2012-09-01

    Full Text Available Canine parvovirus type 2 (CPV-2 is a leading cause of diarrhea in puppies in several parts of the world. In this study CPV-2 was detected and recovered from puppies showing clinical disease from Montevideo, Uruguay. Samples were processed and used to infect CRFK and MDCK cells in order to isolate the virus. Out of twelve, two samples were positive for CPV-2. A genomic region of 583 bp was amplified and the molecular characterization was performed by sequencing, phylogenetic analysis and Restriction Fragment Length Polymorphism (RFLP. Two isolated viruses (UY1 and UY2 were CPV-2c-like viruses. The comparison between the cytophatic effect (CPE of CPV-2 (vaccinal virus and CPV-2c (isolated virus on primary canine cells cultures and on CRFK line cells, demonstrated that CPV-2c is less citopathogenic in CRFK than in primary cultures. Our study represents the first report on isolation and characterization of canine parvovirus type 2c (CPV-2c in cell cultures from South American dogs.

  4. Crystal Structures and Mechanical Properties of Ca2C at High Pressure

    Directory of Open Access Journals (Sweden)

    Qun Wei

    2016-07-01

    Full Text Available Recently, a new high-pressure semiconductor phase of Ca2C (space group Pnma was successfully synthesized, it has a low-pressure metallic phase (space group C2/m. In this paper, a systematic investigation of the pressure-induced phase transition of Ca2C is studied on the basis of first-principles calculations. The calculated enthalpy reveals that the phase transition which transforms from C2/m-Ca2C to Pnma-Ca2C occurs at 7.8 GPa, and it is a first-order phase transition with a volume drop of 26.7%. The calculated elastic constants show that C2/m-Ca2C is mechanically unstable above 6.4 GPa, indicating that the structural phase transition is due to mechanical instability. Both of the two phases exhibit the elastic anisotropy. The semiconductivity of Pnma-Ca2C and the metallicity of C2/m-Ca2C have been demonstrated by the electronic band structure calculations. The quasi-direct band gap of Pnma-Ca2C at 0 GPa is 0.86 eV. Furthermore, the detailed analysis of the total and partial density of states is performed to show the specific contribution to the Fermi level.

  5. Design and Discovery of Functionally Selective Serotonin 2C (5-HT2C) Receptor Agonists.

    Science.gov (United States)

    Cheng, Jianjun; McCorvy, John D; Giguere, Patrick M; Zhu, Hu; Kenakin, Terry; Roth, Bryan L; Kozikowski, Alan P

    2016-11-10

    On the basis of the structural similarity of our previous 5-HT2C agonists with the melatonin receptor agonist tasimelteon and the putative biological cross-talk between serotonergic and melatonergic systems, a series of new (2,3-dihydro)benzofuran-based compounds were designed and synthesized. The compounds were evaluated for their selectivity toward 5-HT2A, 5-HT2B, and 5-HT2C receptors in the calcium flux assay with the ultimate goal to generate selective 5-HT2C agonists. Selected compounds were studied for their functional selectivity by comparing their transduction efficiency at the G protein signaling pathway versus β-arrestin recruitment. The most functionally selective compound (+)-7e produced weak β-arrestin recruitment and also demonstrated less receptor desensitization compared to serotonin in both calcium flux and phosphoinositide (PI) hydrolysis assays. We report for the first time that selective 5-HT2C agonists possessing weak β-arrestin recruitment can produce distinct receptor desensitization properties.

  6. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  7. Analysis list: Tfap2c [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Tfap2c Breast,Pluripotent stem cell + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Tfap2...c.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Tfap2c.5.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/mm9/target/Tfap2c.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Tfap2...c.Breast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Tfap2c.Pluripo

  8. Submillimeter spectroscopy of H$_2$C$^{17}$O and a revisit of the rotational spectra of H$_2$C$^{18}$O and H$_2$C$^{16}$O

    CERN Document Server

    Müller, Holger S P

    2016-01-01

    The rotational spectrum of the formaldehyde isotopologue H2C(17)O was investigated between 0.56 and 1.50 THz using a sample of natural isotopic composition. In addition, transition frequencies were determined for H2C(18)O and H2C(16)O between 1.37 and 1.50 THz. The data were combined with critically evaluated literature data to derive improved sets of spectroscopic parameters which include (17)O or H nuclear hyperfine structure parameters.

  9. GUCY2C: at the intersection of obesity and cancer

    OpenAIRE

    Kim, Gilbert W.; Lin, Jieru E.; Waldman, Scott A.

    2013-01-01

    Guanylyl cyclase C (GUCY2C) has canonical centrality in defense of key intestinal homeostatic mechanisms, encompassing fluid and electrolyte balance, epithelial dynamics, antitumorigenesis, and intestinal barrier function. Recent discoveries expand the homeostatic role of GUCY2C to reveal a novel gut-brain endocrine axis regulating appetite, anchored by hypothalamic GUCY2C which is responsive to intestine-derived uroguanylin. Thus, GUCY2C may represent a new target for anti-obesity pharmacoth...

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

    Science.gov (United States)

    Cheng, Jianjun; Kozikowski, Alan P

    2015-12-01

    The serotonin 2C (5-HT2C ) receptor has been identified as a potential drug target for the treatment of a variety of central nervous system (CNS) disorders, such as obesity, substance abuse, and schizophrenia. In this Viewpoint article, recent progress in developing selective 5-HT2C agonists for use in treating these disorders is summarized, including the work of our group. Challenges in this field and the possible future directions are described. Homology modeling as a method to predict the binding modes of 5-HT2C ligands to the receptor is also discussed. Compared to known ligands, the improved pharmacological profiles of the 2-phenylcyclopropylmethylamine-based 5-HT2C agonists make them preferred candidates for further studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Analysis list: TFAP2C [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available TFAP2C Breast,Epidermis,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TFA...P2C.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TFAP2C.5.tsv http://dbarchive....biosciencedbc.jp/kyushu-u/hg19/target/TFAP2C.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TFA...P2C.Breast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TFAP2C.Epider...mis.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TFAP2C.Uterus.tsv http://dbarchive.biosciencedb

  12. Analysis list: Kmt2c [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Kmt2c Embryonic fibroblast,Liver,Muscle + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Kmt...2c.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Kmt2c.5.tsv http://dbarch...ive.biosciencedbc.jp/kyushu-u/mm9/target/Kmt2c.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Kmt...2c.Embryonic_fibroblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Kmt...2c.Liver.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Kmt2c.Muscle.tsv http://dbarchive.biosci

  13. Main: 1I2C [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1I2C シロイヌナズナ Arabidopsis Arabidopsis thaliana (L.) Heynh. Udp-Sulfoquinovose Syntha... AAM47379.1; -.|PIR; T05311; T05311.|PDB; 1I24; X-ray; A=74-477.|PDB; 1I2B; X-ray; A=74-477.|PDB; 1I2C; X-ra...FCVQAAVGHPLTVYGKGGQTRGYLDIRDTVQCVEIAIANPAKAGEFRVFNQFTEQFSVNELASLVTKAGSKLGLDVKKMTVPNPRVEAEEHYYNAKHTKLMELGLEPHYLSDSLLDSLLNFAVQFKDRVDTKQIMPSVSWKKIGVKTKSMTT arabi_1I2C.jpg ...

  14. Quantifying the reliability of image replication studies: the image intraclass correlation coefficient (I2C2).

    Science.gov (United States)

    Shou, H; Eloyan, A; Lee, S; Zipunnikov, V; Crainiceanu, A N; Nebel, N B; Caffo, B; Lindquist, M A; Crainiceanu, C M

    2013-12-01

    This article proposes the image intraclass correlation (I2C2) coefficient as a global measure of reliability for imaging studies. The I2C2 generalizes the classic intraclass correlation (ICC) coefficient to the case when the data of interest are images, thereby providing a measure that is both intuitive and convenient. Drawing a connection with classical measurement error models for replication experiments, the I2C2 can be computed quickly, even in high-dimensional imaging studies. A nonparametric bootstrap procedure is introduced to quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo permutation is utilized to test reproducibility versus a zero I2C2, representing complete lack of reproducibility. Methodologies are applied to three replication studies arising from different brain imaging modalities and settings: regional analysis of volumes in normalized space imaging for characterizing brain morphology, seed-voxel brain activation maps based on resting-state functional magnetic resonance imaging (fMRI), and fractional anisotropy in an area surrounding the corpus callosum via diffusion tensor imaging. Notably, resting-state fMRI brain activation maps are found to have low reliability, ranging from .2 to .4. Software and data are available to provide easy access to the proposed methods.

  15. NOAA-CIRES 20th Century Reanalysis (V2c)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The 20th Century Reanalysis version 2c (20CRV2c)is an effort led by PSD and the CIRES at the University of Colorado to produce a reanalysis dataset spanning the...

  16. Dephosphorylation of Centrins by Protein Phosphatase 2C and

    Directory of Open Access Journals (Sweden)

    Marie-Christin Thissen

    2009-01-01

    Full Text Available In the present study, we identified protein phosphatases dephosphorylating centrins previously phosphorylated by protein kinase CK2. The following phosphatases known to be present in the retina were tested: PP1, PP2A, PP2B, PP2C, PP5, and alkaline phosphatase. PP2C and were capable of dephosphorylating P-Thr138-centrin1 most efficiently. PP2C was inactive and the other retinal phosphatases also had much less or no effect. Similar results were observed for centrins 2 and 4. Centrin3 was not a substrate for CK2. The results suggest PP2C and to play a significant role in regulating the phosphorylation status of centrins in vivo.

  17. The interstellar chemistry of H2C3O isomers

    Science.gov (United States)

    Loison, Jean-Christophe; Agúndez, Marcelino; Marcelino, Núria; Wakelam, Valentine; Hickson, Kevin M.; Cernicharo, José; Gerin, Maryvonne; Roueff, Evelyne; Guélin, Michel

    2016-01-01

    We present the detection of two H2C3O isomers, propynal and cyclopropenone, toward various starless cores and molecular clouds, together with upper limits for the third isomer propadienone. We review the processes controlling the abundances of H2C3O isomers in interstellar media showing that the reactions involved are gas-phase ones. We show that the abundances of these species are controlled by kinetic rather than thermodynamic effects. PMID:27013768

  18. Evaluation of P2-C2 bias estimation

    Science.gov (United States)

    Santos, M. C.; van der Bree, R.; van der Marel, H.; Verhagen, S.; Garcia, C. A.

    2010-12-01

    The availability of the second civilian code C2 created a new issue to be considered: the bias relating P2 and C2 signals. Such an issue is important when merging C2-capable and legacy receivers and when processing data collected by a C2-capable receiver with satellite clock values generated using a legacy receiver network. The P2-C2 bias is essentially a consequence from the fact that receiver and satellite hardware delays for C2 measurements may not be necessarily the same of those for P2. Knowing this bias makes possible the use of C2 as an observable for positioning using IGS clock products. We are using the PPP-based approach for P2-C2 bias estimation developed at the University of New Brunswick. For that purpose, we use GAPS, the GPS Analysis and Positioning Software. We also determine P2-C2 bias directly from the code observations. This poster presents and discusses the evaluation of P2-C2 values estimated from a sub-set of the IGS L2C Test Network. The values are applied to observations collected by C2-capable receivers in the point positioning mode. Coordinate repeatability indicate an improvement of up to 50% when using the P2-C2 bias.

  19. Character algebras of decorated SL_2(C)-local systems

    CERN Document Server

    Muller, Greg

    2011-01-01

    Let S be a path-connected, locally-compact CW-complex, and let M be a subcomplex with finitely-many components. A `decorated SL_2(C)-local system' is an SL_2(C)-local system on S, together with a choice of `decoration' at each component of M (a section of the stalk of an associated vector bundle). We study the (decorated SL_2(C)-)character algebra of (S,M), those functions on the space of decorated SL_2(C)-local systems on (S,M) which are regular with respect to the monodromy. The character algebra is presented explicitly. The character algebra is then shown to correspond to the algebra spanned by collections of oriented curves in S modulo simple graphical rules. As an intermediate step, we obtain an invariant-theory result of independent interest: a presentation of the algebra of SL_2(C)-invariant functions on End(V)^m + V^n, where V is the tautological representation of SL_2(C).

  20. Serotonin2C receptors and drug addiction: focus on cocaine.

    Science.gov (United States)

    Devroye, Céline; Filip, Malgorzata; Przegaliński, Edmund; McCreary, Andrew C; Spampinato, Umberto

    2013-10-01

    This review provides an overview of the role of central serotonin2C (5-HT2C) receptors in drug addiction, specifically focusing on their impact on the neurochemical and behavioral effects of cocaine, one of the most worldwide abused drug. First, we described the neurochemical and electrophysiological mechanisms underlying the interaction between 5-HT2C receptors and the mesocorticolimbic dopaminergic network, in keeping with the key role of this system in drug abuse and dependence. Thereafter, we focused on the role of 5-HT2C receptors in the effects of cocaine in various preclinical behavioral models used in drug addiction research, such as locomotor hyperactivity, locomotor sensitization, drug discrimination, and self-administration, to end with an overview of the neurochemical mechanisms underlying the interactions between 5-HT2C receptors, mesocorticolimbic dopamine system, and cocaine. On their whole, the presented data provide compelling preclinical evidence that 5-HT2C receptor agonists may have efficacy in the treatment of cocaine abuse and dependence, thereby underlying the need for additional clinical studies to ascertain whether preclinical data translate to the human.

  1. Implementation of I 2C Master Bus Protocol on FPGA

    Directory of Open Access Journals (Sweden)

    Regu Archana

    2014-10-01

    Full Text Available The focus of this paper is on I 2C (Inter-Integrated Circuit protocol interface between Master Bus protocol and slave. Here we are interfacing between micro-controller and DS1307. I 2C bus protocol sends 8 bit data from micro-controller to DS1307. This module was designed in VHDL and simulated and synthesized using Xilinx ISE Design Suite 14.2. I 2C and optimized for area and power. This concept is widely applicable from any high speed device or low speed device to any low speed device or high speed device. This module acts as a slave for the DS1307 at the same time acts like a master for the micro-controller device which can be considered as a slave. . It can be used to interface low speed peripherals like motherboard, embedded system, mobile phones, set top boxes, DVD, PDA’s or other electronic devices.

  2. Thermoelectric performance of functionalized Sc2C MXenes

    KAUST Repository

    Kumar, S.

    2016-07-05

    Functionalization of the MXene Sc2C, which has the rare property to realize semiconducting states for various functionalizations including O, F, and OH, is studied with respect to the electronic and thermal behavior. The lowest lattice thermal conductivity is obtained for OH functionalization and an additional 30% decrease can be achieved by confining the phonon mean free path to 100 nm. Despite a relatively low Seebeck coefficient, Sc2C(OH)2 is a candidate for intermediate-temperature thermoelectric applications due to compensation by a high electrical conductivity and very low lattice thermal conductivity.

  3. Risk Analysis and Consumer Protection in B2C Transactions

    Institute of Scientific and Technical Information of China (English)

    YANG Jian-zheng; SHI Qi-liang; Gary Millar; Ruhul A. Sarker

    2005-01-01

    Recent studies have shown that the perceived lack of security is a major obstacle to the wider acceptance of e-commerce. To overcome this barrier, businesses need to implement comprehensive consumer protection systems that protect consumers during every stage of the purchasing process. This paper used the consumer behaviour model as the basis for analysing risks in Bussiness-to-Consumer (B2C) transactions. Four categories of risks were identified: information, agreement, payment and delivery risk. By combining these risk categories with the three dimensions of management, technology and legislation, a comprehensive B2C consumer protection framework is developed.

  4. Theoretical Investigations of La2C2 Cluster

    Institute of Scientific and Technical Information of China (English)

    武志坚; 周誓红; 张思远

    2003-01-01

    Possible structures of La2C2 were studied and proposed by use of density functional theory. All proposed isomers are planar. The results indicate that the structure with the lowest symmetry (C1) is the most stable. Linear isomers are not favored.

  5. LM-2C Sent Yaogan 13 into Space

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The Yaogan 13 remote sensing satellite was launched into orbit from the Taiyuan Satellite Launch Center on November 30 on a LM-2C launch vehicle.Developed by SAST,the satellite will be used for scientific experiments,land survey,crop yield assessment and disaster monitoring.

  6. Therapeutic Potential of 5-HT2C Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Nanna H. Jensen

    2010-01-01

    Full Text Available Serotonin 2C receptors are G protein-coupled receptors expressed by GABAergic, glutamatergic, and dopaminergic neurons. Anatomically, they are present in various brain regions, including cortical areas, hippocampus, ventral midbrain, striatum, nucleus accumbens, hypothalamus, and amygdala. A large body of evidence supports a critical role of serotonin 2C receptors in mediating the interaction between serotonergic and dopaminergic systems, which is at the basis of their proposed involvement in the regulation of mood, affective behavior, and memory. In addition, their expression in specific neuronal populations in the hypothalamus would be critical for their role in the regulation of feeding behavior. Modulation of these receptors has therefore been proposed to be of interest in the search for novel pharmacological strategies for the treatment of various pathological conditions, including schizophrenia and mood disorders, as well as obesity. More precisely, blockade of serotonin 2C receptors has been suggested to provide antidepressant and anxiolytic benefit, while stimulation of these receptors may offer therapeutic benefit for the treatment of psychotic symptoms in schizophrenia and obesity. In addition, modulation of serotonin 2C receptors may offer cognitive-enhancing potential, albeit still a matter of debate. In the present review, the most compelling evidence from the literature is presented and tentative hypotheses with respect to existing controversies are outlined.

  7. THE NUCLEOTIDE RECEPTORS ON MOUSE C2C12 MYOTUBES

    NARCIS (Netherlands)

    HENNING, RH; NELEMANS, A; VANDENAKKER, J; DENHERTOG, A

    1992-01-01

    1 The response of C2C12 mouse myotubes to stimulation with adenosine triphosphate (ATP) and other nucleotides was studied by measuring changes in membrane potential. 2 A transient hyperpolarization followed by a slowly declining depolarization of the cells was observed in the presence of ATP (10-mu-

  8. THE NUCLEOTIDE RECEPTORS ON MOUSE C2C12 MYOTUBES

    NARCIS (Netherlands)

    HENNING, RH; NELEMANS, A; VANDENAKKER, J; DENHERTOG, A

    1 The response of C2C12 mouse myotubes to stimulation with adenosine triphosphate (ATP) and other nucleotides was studied by measuring changes in membrane potential. 2 A transient hyperpolarization followed by a slowly declining depolarization of the cells was observed in the presence of ATP

  9. E-2C Loads Calibration in DFRC Flight Loads Lab

    Science.gov (United States)

    Schuster, Lawrence S.

    2008-01-01

    Objectives: a) Safely and efficiently perform structural load tests on NAVAIR E-2C aircraft to calibrate strain gage instrumentation installed by NAVAIR; b) Collect load test data and derive loads equations for use in NAVAIR flight tests; and c) Assist flight test team with use of loads equations measurements at PAX River.

  10. Units in Z_2(C_2 × D_infinity

    Directory of Open Access Journals (Sweden)

    Kanchan Joshi

    2012-12-01

    Full Text Available In this paper we consider the group algebra R(C_2 ×D_infinity. It is shown that R(C_2 ×D_infinity can be represented by a 4 × 4 block circulant matrix. It is also shown that U(Z_2(C_2 × D_infinity isinfinitely generated

  11. High-throughput screening assays for the assessment of CYP2C9*1, CYP2C9*2, and CYP2C9*3 metabolism using fluorogenic Vivid substrates.

    Science.gov (United States)

    Marks, Bryan D; Thompson, David V; Goossens, Tony A; Trubetskoy, Olga V

    2004-08-01

    CYP2C9 is a genetically polymorphic human cytochrome P450 isozyme involved in the oxidative metabolism of many drugs, including nonsteroidal anti-inflammatory compounds. Individuals genotyped heterozygous or homozygous for CYP2C9 allelic variants have demonstrated altered metabolism of some drugs primarily metabolized by CYP2C9. The ability to expand screening of CYP2C9 allelic variants to a larger set of drugs and pharmaceutical agents would contribute to a better understanding of the significance of CYP2C9 polymorphisms in the population and to predictions of possible outcomes. The authors report the development of an in vitro fluorescence-based assay employing recombinant CYP2C9 variants (CYP2C9*1, CYP2C9*2, and CYP2C9*3) and fluorogenic Vivid(R) CYP2C9 substrates to explore the effects of CYP2C9 polymorphisms on drug metabolism, using drugs primarily metabolized by CYP2C9. Several chemically diverse fluorogenic substrates (Vivid(R) CYP2C9 blue, green, and red substrates) were used as prototypic probes to obtain in vitro CYP2C9 metabolic rates and kinetic parameters, such as apparent K(m), V(max), and V(max)/K(m) ratios for each allelic variant. In addition, a diverse panel of drugs was screened as assay modifiers with CYP2C9*1, CYP2C9*2, CYP2C9*3, and the fluorogenic Vivid(R) CYP2C9 substrates. The inhibitory potential of this large group of chemically diverse drugs and compounds has been assessed on the basis of their ability to compete with Vivid(R) CYP2C9 substrates in fluorescent reporter assays, thus providing a sensitive and quick assessment of polymorphism-dependent changes in CYP2C9 metabolism.

  12. Effect of Additives on Properties of MgO-ZrO2-C Material

    Institute of Scientific and Technical Information of China (English)

    TIAN Shouxin; LIU Shanlin; XIE Mengqin

    2002-01-01

    The paper describes the effect of additives Al, Si,SiC and B4 C on the expansion of MgO-ZrO2-C material after being coked . The results indicate that Al and Si can not increase its hot and cold strength. Al and Si were oxidized to form Al2 O3 and SiO2 respectively, and then reacted with CaZrO3 or stabilizer in c-ZrO2 to form calcium aluminate , spinel ( MA ), dicalcium silicate ( C2 S ) and forsterite (M2S). Meanwhile, α-C2S was transformed to γ-C2S and c-ZrO2 to m-ZrO2 when temperature changed.All the above reactions resulted in the decrease of the amount of Al4 C3 and SiC and the increase in bulk volume ,which caused the structure of MgO-ZrO2-C material destroyed. Hence, contrary to the MgO-C material, when adding Al. and Si, the MgO-ZrO2-C material would be structurally deteriorated after heat-treatment and its strength and corrosion resistance decreased.

  13. SL(2,C) Chern-Simons Theory and Quantum Gravity with a Cosmological Constant

    Science.gov (United States)

    Haggard, Hal; Han, Muxin; Kaminski, Wojciech; Riello, Aldo

    2015-04-01

    We show a relation between 4-dimensional quantum gravity with a cosmological constant and SL(2,C) Chern-Simons theory in 3-dimensions with knotted graph defects. In particular, we study the expectation value of a non-planar Wilson graph operator in SL(2,C) Chern-Simons theory on S3. We analyze its asymptotic behavior in the double-scaling limit in which both the representation labels and the Chern-Simons coupling are taken to be large, but with fixed ratio. We find that a class of flat connections in the graph complement manifold are in correspondence with the geometries of constant curvature 4-simplices. We show that the asymptotic behavior of the amplitude contains an oscillatory part proportional to the Regge action for the single 4-simplex in the presence of a cosmological constant. In particular, the cosmological term contains the full-fledged curved volume of the 4-simplex. Interestingly, the volume term stems from the asymptotics of the Chern-Simons action. Another peculiarity of our approach is that the sign of the curvature of the reconstructed geometry, and hence of the cosmological constant in the Regge action, is not fixed a priori, but rather emerges semiclassically and dynamically from the solution of the equations of motion. This work was supported by the U.S. National Science Foundation, the European Marie Curie actions, and the Perimeter Institute.

  14. A generalized stoichiometric model of C3, C2, C2+C4, and C4 photosynthetic metabolism.

    Science.gov (United States)

    Bellasio, Chandra

    2017-01-01

    The goal of suppressing photorespiration in crops to maximize assimilation and yield is stimulating considerable interest among researchers looking to bioengineer carbon-concentrating mechanisms into C3 plants. However, detailed quantification of the biochemical activities in the bundle sheath is lacking. This work presents a general stoichiometric model for C3, C2, C2+C4, and C4 assimilation (SMA) in which energetics, metabolite traffic, and the different decarboxylating enzymes (NAD-dependent malic enzyme, NADP-dependent malic enzyme, or phosphoenolpyruvate carboxykinase) are explicitly included. The SMA can be used to refine experimental data analysis or formulate hypothetical scenarios, and is coded in a freely available Microsoft Excel workbook. The theoretical underpinnings and general model behaviour are analysed with a range of simulations, including (i) an analysis of C3, C2, C2+C4, and C4 in operational conditions; (ii) manipulating photorespiration in a C3 plant; (iii) progressively upregulating a C2 shuttle in C3 photosynthesis; (iv) progressively upregulating a C4 cycle in C2 photosynthesis; and (v) manipulating processes that are hypothesized to respond to transient environmental inputs. Results quantify the functional trade-offs, such as the electron transport needed to meet ATP/NADPH demand, as well as metabolite traffic, inherent to different subtypes. The SMA refines our understanding of the stoichiometry of photosynthesis, which is of paramount importance for basic and applied research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. Predicting drug metabolism by cytochrome P450 2C9

    DEFF Research Database (Denmark)

    Rydberg, Patrik; Olsen, Lars

    2012-01-01

    By the use of knowledge gained through modeling of drug metabolism mediated by the cytochrome P450 2D6 and 3A4 isoforms, we constructed a 2D-based model for site-of-metabolism prediction for the cytochrome P450 2C9 isoform. The similarities and differences between the models for the 2C9 and 2D6...... isoforms are discussed through structural knowledge from the X-ray crystal structures and trends in experimental data. The final model was validated on an independent test set, resulting in an area under the curve value of 0.92, and a site of metabolism was found among the top two ranked atoms for 77...

  16. Online Trading C2C Operators Fight for Number One

    Institute of Scientific and Technical Information of China (English)

    DAVID HENDRICKSON

    2006-01-01

    @@ Whether shopping casually or searching for some obscure, hard to find item, more and more Chinese are logging online and turning to customer-to-customer (C2C) network operators for their trading needs rather than bother with the hassles of conventional buying and selling. Proof is in the numbers. A leading technology, new media, and telecom watchdog, Analysys International reports that China's C2C market users more than doubled in 2005 to 37.87 million, while the sector's total transaction value increased from 4.16 billion yuan in 2004, to 13.9billion yuan (US$1.74 billion). Supplanted by a web surfing pool of 100 million and counting, they are trends that Analysys and other industry groups expect will continue in China for some time, fundamentally transforming how the country's independent traders do business.

  17. Robotic Range Clearance Competition (R2C2)

    Science.gov (United States)

    2011-10-01

    Paddock. Meals—Breakfast, Lunch and Dinner will be available in the mess tent (See Schedule, Section 2.1). Snacks – Snack foods and bottled water...ROBOTIC RANGE CLEARANCE COMPETITION (R2C2) Final Report DISTRIBUTION A: AIR FORCE RESEARCH LABORATORY MATERIALS AND MANUFACTURING DIRECTORATE Air...other person or corporation; or convey any rights or permission to manufacture , use, or sell any patented invention that may relate to them. This

  18. Field emission from Mo2C coated carbon nanosheets

    Science.gov (United States)

    Bagge-Hansen, M.; Outlaw, R. A.; Miraldo, P.; Zhu, M. Y.; Hou, K.; Theodore, N. D.; Zhao, X.; Manos, D. M.

    2008-01-01

    Carbon nanosheets have recently evolved into useful edge emitters with high emission current densities, low threshold electric fields, and long lifetimes. In addition to further improvement in these characteristics, good stability and repeatability are also essential for these materials to be suitable for high vacuum applications such as microwave tubes and flat panel displays. Since the work function of graphite, carbon nanotubes, and amorphous carbon is relatively high, 4.6-4.8eV, selective thin film coatings may offer significant advantages. Carbides are a good film choice for their corrosive resistance, chemical stability, and substantially lower work function. Approximately 3 ML (monolayer) (˜1nm) of molybdenum were deposited on carbon nanosheets by physical vapor deposition and the carbide (Mo2C) formed by heating to >200°C at 1×10-8Torr. The carbide stoichiometry was confirmed in situ by the characteristic Auger triple peak at 272eV. A stoichiometric Mo2C calibration sample was used to acquire the Auger electron spectroscopy asymmetric ratio of 0.7 and this was used to determine the carbide growth as a function of temperature (from room temperature to 1000°C). Field emission currents of up to 400μA were compared with uncoated CNS at a given electric field. The Mo2C/CNS cathodes were shown to have greater than a factor of 100 increase in current and greater than 2V/μm decrease in threshold. The Fowler-Nordheim plots were exceptionally linear and quite repeatable (correlation coefficient R2=0.999+). Using the slope and vertical intercept, an emission area for the 0.07cm2 Mo2C/CNS dot sample was determined to be ˜3×10-9cm2 and the field enhancement factor was found to be β ˜530.

  19. Optical characterization of polished Mo2C foil.

    Science.gov (United States)

    Grimes, Jacob; Geerts, W.; Bandyopadhyay, A.; Gutierrez; Radican, K.; Rivera, N.; Holland, P.; Givens, J.; Oyama, Ted

    2003-03-01

    Mo_2C has been in use by industry for a number of years, however its optical properties are previously uncharacterized with no reports of experimentally obtained values for the refraction index(n) and extinction coefficient(k). Toward the goal of identifying the values for these properties several tests are performed on a Molybdenum foil carburized in a stream of 20 molar CH4 in H2 at 1373K. The surface of the sample is polished to an optically flat finish using several diamond disks in an Allied High Tech polisher. X-ray data shows that the remaining surface material is Mo_2C. Ψ and Δ are measured with a Variable Angle Spectroscopic Ellipsometer from 190 to 1700nm. Then n, k, and reflectance are calculated using FilmWizard. The spectra for refraction, extinction, and reflectance of Mo_2C differ greatly from those reported for Mo. Generally they exhibit a quasi-linear character increasing with wavelength with structures in the red and blue parts of the spectra.

  20. Similar substrate specificity of cynomolgus monkey cytochrome P450 2C19 to reported human P450 2C counterpart enzymes by evaluation of 89 drug clearances.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-12-01

    Cynomolgus monkeys are used widely in preclinical studies as non-human primate species. The amino acid sequence of cynomolgus monkey cytochrome P450 (P450 or CYP) 2C19 is reportedly highly correlated to that of human CYP2C19 (92%) and CYP2C9 (93%). In the present study, 89 commercially available compounds were screened to find potential substrates for cynomolgus monkey CYP2C19. Of 89 drugs, 34 were metabolically depleted by cynomolgus monkey CYP2C19 with relatively high rates. Among them, 30 compounds have been reported as substrates or inhibitors of, either or both, human CYP2C19 and CYP2C9. Several compounds, including loratadine, showed high selectivity to cynomolgus monkey CYP2C19, and all of these have been reported as human CYP2C19 and/or CYP2C9 substrates. In addition, cynomolgus monkey CYP2C19 formed the same loratadine metabolite as human CYP2C19, descarboethoxyloratadine. These results suggest that cynomolgus monkey CYP2C19 is generally similar to human CYP2C19 and CYP2C9 in its substrate recognition functionality.

  1. Global structure search and physical properties of Os2C

    Science.gov (United States)

    Hong, Feng; Lu, Jian; Gao, Heng; Ren, Wei; Xu, Run; Xu, Fei; Ma, Zhongquan; Yan, Yanfa

    2016-09-01

    The crystal structures of Os2C were extensively investigated using the structure search method from the first-principles calculations. In contrast to the P6 3 /mmc phase previously proposed as the ground state at ambient pressure, an energetically favorable structure with space group P-6m2 was found more stable at ambient condition. The structural stabilities of the new phase are confirmed by the phonon dispersion and elastic constants. Further calculations indicate that the newly predicted P-6m2 phase is ultra-incompressible with a high bulk modulus of 387 GPa and has a larger ideal shear strength than the P6 3 /mmc phase.

  2. Interactions between CYP2C9 and CYP2C19 in reconstituted binary systems influence their catalytic activity: possible rationale for the inability of CYP2C19 to catalyze methoxychlor demethylation in human liver microsomes.

    Science.gov (United States)

    Hazai, Eszter; Kupfer, David

    2005-01-01

    Previous studies in our laboratory showed that among cDNA-expressed human cytochrome P450 (P450) supersomes, CYP2C19 was the most active in methoxychlor-O-demethylation. However, based on the lack of inhibition of methoxychlor-O-demethylation by monoclonal anti-CYP2C19 antibodies in human liver microsomes (HLM), CYP2C19 did not seem to catalyze that reaction in HLM. By contrast, CYP2C9, much less active than CYP2C19 in supersomes, was the most active in HLM. The current study examines whether the lack of methoxychlor-O-demethylation by CYP2C19 in HLM was due to CYP2C19 exhibiting inferior competition for the NADPH-cytochrome P450 reductase (CPR) versus CYP2C9 and explores the interactions between CYP2C9 and CYP2C19 in a singular and binary complex of a reconstituted system. When reconstituted with CPR, cytochrome b(5), and lipid, purified CYP2C19 and CYP2C9 catalyzed methoxychlor-O-demethylation. However, whereas equimolar CPR to CYP2C9 supported maximal rates of methoxychlor demethylation and diclofenac hydroxylation, the rate of methoxychlor demethylation by CYP2C19 was not fully saturated, even with a 9-fold molar excess of CPR over CYP2C19. This behavior of CYP2C19 was also observed with S-mephenytoin as the substrate. When a binary reconstitution system was prepared by mixing CYP2C9 and CYP2C19 enzymes, methoxychlor-O-demethylation and S-mephenytoin hydroxylation by CYP2C19 were dramatically inhibited. Inhibition depended on the amount of CPR and substrate used. By contrast, in the incubation containing CYP2C9, diclofenac hydroxylation was activated by the presence of CYP2C19. These results show that interactions among P450 enzymes can modulate their catalytic rates, which depend on the substrate undergoing metabolism.

  3. The 2 C scenario - A sustainable world energy perspective

    Energy Technology Data Exchange (ETDEWEB)

    Krewitt, Wolfram; Simon, Sonja [German Aerospace Center (DLR), Institute of Technical Thermodynamics, Department of Systems Analysis and Technology Assessment, Pfaffenwaldring 38-40, 70565 Stuttgart (Germany); Graus, Wina [Ecofys, Kanaalweg 16G, 3526 KL Utrecht (Netherlands); Teske, Sven [Greenpeace International, Ottho Heldringstraat 5, 1066 AZ Amsterdam (Netherlands); Zervos, Arthouros; Schaefer, Oliver [European Renewable Energy Council, 63-65, rue d' Arlon, 1040 Brussels (Belgium)

    2007-10-15

    A target-oriented scenario of future energy demand and supply is developed in a backcasting process. The main target is to reduce global CO{sub 2} emissions to around 10 Gt/a in 2050, thus limiting global average temperature increase to 2 C and preventing dangerous anthropogenic interference with the climate system. A 10-region energy system model is used for simulating global energy supply strategies. A review of sector and region-specific energy efficiency measures resulted in the specification of a global energy demand scenario incorporating strong energy efficiency measures. The corresponding supply scenario has been developed in an iterative process in close cooperation with stakeholders and regional counterparts from academia, NGOs and the renewable energy industry. The 2 C scenario shows that renewable energy could provide as much as half of the world's energy needs by 2050. Developing countries can virtually stabilise their CO{sub 2} emissions, while at the same time increasing energy consumption through economic growth. OECD countries will be able to reduce their emissions by up to 80%. (author)

  4. Esters with water esters 2-c to 6-c

    CERN Document Server

    Getzen, F W; Hefter, G T; Maczynski, Andrzej

    1992-01-01

    This volume is the first of two devoted to esters and water. It includes solubility data for binary systems containing an ester and water up to the end of 1988. The critical evaluations were all prepared by one author and an introductory section has been included to elaborate the philosophy and methodology followed in the evaluations.

  5. NCEP/DOE Reanalysis II in HDF-EOS5, for GSSTF2c, 1x1 deg Daily grid V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are the Goddard Satellite-based Surface Turbulent Fluxes Version-2c (GSSTF2c) Dataset recently produced through a MEaSURES funded project led by Dr....

  6. Vortex lattice transitions in YNi2B2C

    Indian Academy of Sciences (India)

    S J Levett; C D Dewhurst; D McK Paul

    2002-05-01

    We have performed extensive small-angle neutron scattering (SANS) diffraction studies of the vortex lattice in single crystal YNi2B2C for $B||c$. High-resolution SANS, combined with a field-oscillation vortex lattice preparation technique, allows us to separate Bragg scattered intensities from two orthogonal domains and accurately determine the unit cell angle, . The data suggest that upon increasing field there is a finite transition width where both low- and high-field distorted hexagonal vortex lattice phases, mutually rotated by 45°, coexist. The smooth variation of diffracted intensity from each phase through the transition corresponds to a redistribution of populations between the two types of domains.

  7. A rare Cervical Nerve Root, C2-C3 Schwannoma

    Directory of Open Access Journals (Sweden)

    Nilesh Chordia

    2014-04-01

    Full Text Available Schwannomas, neurilemmomas or neurinomas are benign nerve sheath tumors deriving from Schwann cells that occur in the head and neck region in 25-45% of cases 1 .About 10% of schwannoma that occur in the head and neck region generally originate from the vagus or sympathetic nervous system, those arising from C2 nerve root are extremely rare. 2 Preoperative imaging studies such as magnetic resonance imaging (MRI and computed tomography (CT are used to distinguish its location and origin. The treatment of schwannoma is surgical resection, with several surgical modalities have been introduced to preserve the neurological function. We present a rare case of Cervical nerve (C2-C3 root schwannoma of 70 years old male who presented with lateral neck swelling with no neurological deficit ,swelling which also had intervertebral part was removed successfully through neck incision with no post-operative neurological symptoms

  8. Exactly solvable models of scattering with SL(2, C) symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Levay, P. [School of Physics, University of Melbourne, Parkville (Australia); Department of Theoretical Physics, Institute of Physics, Technical University, Budapest (Hungary)

    2002-08-02

    Using the theory of induced representations two exactly solvable models of non-relativistic scattering with SL(2, C) symmetry are presented. The first describes the scattering of a charged particle moving on the Poincare upper half space H under the influence of an SU(2) non-Abelian gauge potential with isospin s. The second deals with a one-dimensional coupled-channel scattering problem for a charged particle in a matrix-valued scalar potential containing Morse-like interaction terms. The coupled channel wavefunctions and the corresponding scattering matrices are calculated. A detailed description of the underlying geometric structures is also given and a generalization for restricting the motion to fundamental domains of H (three manifolds of constant negative sectional curvature) is outlined. Such models provide an interesting generalization to the known ones of multichannel scattering, quantum chaos and chaotic cosmology. (author)

  9. Volume Entropy

    CERN Document Server

    Astuti, Valerio; Rovelli, Carlo

    2016-01-01

    Building on a technical result by Brunnemann and Rideout on the spectrum of the Volume operator in Loop Quantum Gravity, we show that the dimension of the space of the quadrivalent states --with finite-volume individual nodes-- describing a region with total volume smaller than $V$, has \\emph{finite} dimension, bounded by $V \\log V$. This allows us to introduce the notion of "volume entropy": the von Neumann entropy associated to the measurement of volume.

  10. Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes.

    Science.gov (United States)

    Wang, Zhe; Sun, Wei; Huang, Cheng-Ke; Wang, Li; Xia, Meng-Ming; Cui, Xiao; Hu, Guo-Xin; Wang, Zeng-Shou

    2015-04-01

    Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4'-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug-drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10 µmol L(-1) diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25 µmol L(-1) and Ki = 4.473 µmol L(-1) in human liver microsomes. Curcumin's mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100 µmol L(-1). The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These in vitro findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment.

  11. Preparation and characterization of Pt–CeO{sub 2}/C and Pt–TiO{sub 2}/C electrocatalysts with improved electrocatalytic activity for methanol oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Hameed, R.M. Abdel [Chemistry Department, Faculty of Science, Cairo University, Giza (Egypt); Amin, R.S. [Chemical Engineering Department, National Research Center, Dokki, Giza (Egypt); El-Khatib, K.M., E-mail: Kamelced@hotmail.com [Chemical Engineering Department, National Research Center, Dokki, Giza (Egypt); Fetohi, Amani E. [Chemical Engineering Department, National Research Center, Dokki, Giza (Egypt)

    2016-03-30

    Graphical abstract: - Highlights: • Adding TiO{sub 2} or CeO{sub 2} to Pt/C reduced its Pt particle size. • Methanol oxidation current density decreased as Pt–CeO{sub 2}/C > Pt–TiO{sub 2}/C > Pt/C. • Decreased R{sub ct} values were observed at Pt–TiO{sub 2}/C and Pt–CeO{sub 2}/C. - Abstract: Pt–TiO{sub 2}/C and Pt–CeO{sub 2}/C electrocatalysts were synthesized by solid state reaction of TiO{sub 2}/C and CeO{sub 2}/C powders using intermittent microwave heating, followed by chemical reduction of platinum ions using mixed reducing agents of ethylene glycol and sodium borohydride. The crystal structure, surface morphology and chemical composition of prepared electrocatalysts were investigated using X-ray diffraction (XRD), transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDX). The phase angle values of different Pt diffraction planes in Pt–TiO{sub 2}/C and Pt–CeO{sub 2}/C were shifted in the positive direction relative to those in Pt/C. Pt particles with diameter values of 3.06 and 2.78 nm were formed in Pt–TiO{sub 2}/C and Pt–CeO{sub 2}/C, respectively. The electrochemical performance of prepared electrocatalysts was examined using cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy. Pt–CeO{sub 2}/C showed an enhanced oxidation current density when compared to Pt/C. Long time oxidation test at Pt–TiO{sub 2}/C and Pt–CeO{sub 2}/C revealed their improved stability. Lower charge transfer resistance values were estimated at Pt–metal oxide/C electrocatalysts.

  12. Study on Cytochrome P450 2C19 (CYP2C19) Genetic Polymorphism in Qinghai Sala Population%青海撒拉族人群CYP2C19基因多态性研究

    Institute of Scientific and Technical Information of China (English)

    李永芳; 杨梅; 寇毅英

    2012-01-01

    目的 调查青海撒拉族健康人群中CYP2C19基因型及等位基因的分布特征.方法 采用聚合酶链式反应与限制性内切酶片段长度多态性技术(PCR-RFLP),对99例健康撒拉族人群CYP2C19基因多态性进行分析.结果 撒拉族人群的CYP2C19*1、CYP2C19*2和CYP2C19*3 3种等位基因的发生频率分别为56.6%、29.8%和13.6%;CYP2C19*1/*1、CYP2C19* 1/*2、CYP2C19*1/*3、CYP2C19* 2/*2和CYP2C19*2/*3基因型出现频率分别为30.3%、36.4%、16.2%、6.1%和11.1%,CYP2C19* 3/*3的纯合子基因型在本试验中未发现.结论 青海撒拉族人群CYP2C19基因分布明显不同于维族、黎族、傣族、白族、畲族、回族和爱尔兰人,而相似于土族、独龙族、苗族、藏族和汉族.%OBJECTIVE To identify the genotype and allele distribution feature of cytochrome P450 2C19(CYP2C19)in Qinghai Sala population. METHODS The CYP2C19 genotypes of 99 healthy Sala population were detected by polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) technology. RESULTS In Qinghai Sala population, CYP2C19 * 1, CYP2C19 * 2 and CYP2C19 * 3 allele frequencies were 56. 6% ,29. 8% and 13. 6% , respectively; CYP2C19 * 1/ * 1, CYP2C19 * 1/ * 2, CYP2C19 * 1/ * 3, CYP2C19 * 2/ * 2 and CYP2C19 * 2/ * 3 genotype frequencies were 30. 3% , 36.4% , 16. 2% , 6. 1 % and 11. 1 % , respectively ;CYP2C19 * 3 / * 3 homozygous genotype was not found in this study. CONCLUSION The genotype distribution of CYP2C19 in Qinghai Sala population is significantly different to Uigu,Lj,Bai,Dai,She,Hui and Iran population,but similar to Tu.Dulong, Miao, Zang and Han population.

  13. A mild route to mesoporous Mo2C-C hybrid nanospheres for high performance lithium-ion batteries

    Science.gov (United States)

    Gao, Qing; Zhao, Xinyu; Xiao, Ying; Zhao, Di; Cao, Minhua

    2014-05-01

    In this work, we have developed a mild route to fabricate typically mesoporous Mo2C-C hybrid nanospheres based on a solvothermal synthesis and reduction-carbonization process. This work opens a low-temperature route to synthesize valuable carbides. The resultant Mo2C-C hybrid, for the first time, is used as an anode material in lithium ion batteries (LIBs). Compared with bulk Mo2C, the Mo2C-C hybrid exhibits much better electrochemical performance. Remarkably, the hybrid electrode can deliver a specific capacity of over 670 mA h g-1 after 50 cycles at 100 mA g-1, which is much higher than that of the bulk material (113 mA h g-1). Even cycled at a high current density of 1000 mA g-1, high capacities of around 400-470 mA h g-1 can still be retained for the Mo2C-C hybrid. It might benefit from the synergistic effect of the nanohybridization, effectively relieving the volume change during the repeated lithium insertion-extraction reactions and maintaining the integrity of the electrical connections. It is expected that the present synthesis strategy for the Mo2C-C hybrid can be extended to other nanostructured carbides with good energy storage performance.In this work, we have developed a mild route to fabricate typically mesoporous Mo2C-C hybrid nanospheres based on a solvothermal synthesis and reduction-carbonization process. This work opens a low-temperature route to synthesize valuable carbides. The resultant Mo2C-C hybrid, for the first time, is used as an anode material in lithium ion batteries (LIBs). Compared with bulk Mo2C, the Mo2C-C hybrid exhibits much better electrochemical performance. Remarkably, the hybrid electrode can deliver a specific capacity of over 670 mA h g-1 after 50 cycles at 100 mA g-1, which is much higher than that of the bulk material (113 mA h g-1). Even cycled at a high current density of 1000 mA g-1, high capacities of around 400-470 mA h g-1 can still be retained for the Mo2C-C hybrid. It might benefit from the synergistic effect of

  14. Preparation and characterization of Pt-CeO2/C and Pt-TiO2/C electrocatalysts with improved electrocatalytic activity for methanol oxidation

    Science.gov (United States)

    Hameed, R. M. Abdel; Amin, R. S.; El-Khatib, K. M.; Fetohi, Amani E.

    2016-03-01

    Pt-TiO2/C and Pt-CeO2/C electrocatalysts were synthesized by solid state reaction of TiO2/C and CeO2/C powders using intermittent microwave heating, followed by chemical reduction of platinum ions using mixed reducing agents of ethylene glycol and sodium borohydride. The crystal structure, surface morphology and chemical composition of prepared electrocatalysts were investigated using X-ray diffraction (XRD), transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDX). The phase angle values of different Pt diffraction planes in Pt-TiO2/C and Pt-CeO2/C were shifted in the positive direction relative to those in Pt/C. Pt particles with diameter values of 3.06 and 2.78 nm were formed in Pt-TiO2/C and Pt-CeO2/C, respectively. The electrochemical performance of prepared electrocatalysts was examined using cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy. Pt-CeO2/C showed an enhanced oxidation current density when compared to Pt/C. Long time oxidation test at Pt-TiO2/C and Pt-CeO2/C revealed their improved stability. Lower charge transfer resistance values were estimated at Pt-metal oxide/C electrocatalysts.

  15. Structural and functional insights into CYP2C8.3:A genetic polymorph of cytochrome P450 2C8

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The cytochrome P450 (CYP) superfamily plays a key role in the oxidative metabolism of a wide range of exogenous chemicals. CYP2C8 is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel in the human liver, and carries out the oxidative metabolism of at least 5% of clinical drugs. Polymorphisms in CYP2C8 have been closely implicated in individualized medication. CYP2C8.3, a common polymorph of CYP2C8 with dual amino acid substitutions R139K and K399R, is found primarily in Caucasians. In this study, CYP2C8.3 and its wild type (WT) CYP2C8 were expressed in E. coli, and their purified proteins were characterized by UV-visible spectroscopy, mass spectrometry, and circular dichroism. Their thermal stability, substrate binding ability, and metabolic activity against paclitaxel were investigated. The electron transfer kinetics during paclitaxel metabolism by WT CYP2C8 or CYP2C8.3 was studied by stopped-flow kinetics. The results revealed that mutations in CYP2C8.3 did not greatly influence the heme active site or protein thermal stability and paclitaxel binding ability, but the metabolic activity against paclitaxel was significantly depressed to just 11% of that of WT CYP2C8. Electron transfer from CYP reductase to CYP2C8.3 was found to be significantly slower than that to WT CYP2C8 during catalysis, and this might be the main reason for the depressed metabolic activity. Since the polymorph CYP2C8.3 is defective in catalyzing substrates of CYP2C8 in vitro, it might be expected to have important clinical and pathophysiological consequences in homozygous individuals, and this study provides valuable information in this aspect.

  16. C-2-C market relations and word of mouth

    Directory of Open Access Journals (Sweden)

    Grubor Aleksandar

    2015-01-01

    Full Text Available Most market research focuses on business-to-business and business- to-consumer interactions to explain the structure and dynamics of the market. Meanwhile, negligible effort has been invested in researching consumer-to-consumer interaction and its impact on companies’ behaviour and purchase decision-making, which determines business performance. The greatest challenge for marketers at the beginning of the 21st century is this third relationship dimension, consumer-to-consumer interaction: how consumers influence each other’s attitudes, expectations, perceptions, preferences, satisfaction, loyalty, and purchasing decisions, and, importantly, the possibility of incorporating consumers into businesses’ marketing programmes. Despite the existence of a multitude of media and different forms of communication between businesses and the market, such as newspapers, periodicals, billboards, television etc., a considerable portion of information is communicated to consumers informally, mostly in the form of word-of-mouth. The information received by consumers through this communication form - from family and similar individuals -is very often accepted as more reliable and certain than information transmitted through formal communication channels. What is often neglected when studying the phenomenon of word-of-mouth communication is the fact that its efficiency and effect also depend on the type and character of the interaction between the consumers themselves. This paper aims to investigate the extent to which the nature of customer to-customer (C2C interaction influences the effect of word-of-mouth communication.

  17. Phonon linewidths in YNi2B2C

    Indian Academy of Sciences (India)

    L Pintschovius; F Weber; W Reichardt; A Kreyssig; R Heid; D Reznik; O Stockert; K Hradil

    2008-10-01

    Phonons in a metal interact with conduction electrons which give rise to a finite linewidth. In the normal state, this leads to a Lorentzian shape of the phonon line. Density functional theory is able to predict the phonon linewidths as a function of wave vector for each branch of the phonon dispersion. An experimental verification of such predictions is feasible only for compounds with very strong electron–phonon coupling. YN2B2C was chosen as a test example because it is a conventional superconductor with a fairly high c (15.2 K). Inelastic neutron scattering experiments did largely confirm the theoretical predictions. Moreover, they revealed a strong temperature dependence of the linewidths of some phonons with particularly strong electron–phonon coupling which can as yet only qualitatively be accounted for by theory. For such phonons, marked changes of the phonon frequencies and linewidths were observed from room temperature down to 15 K. Further changes were observed on entering into the superconducting state. These changes can, however, not be described simply by a change of the phonon linewidth.

  18. Severe α-thalassemia intermedia due to a compound heterozygosity for the highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A) mutation.

    Science.gov (United States)

    Megawati, Dewi; Nainggolan, Ita M; Swastika, Maria; Susanah, Susi; Mose, Johanes C; Harahap, Alida R; Setianingsih, Iswari

    2014-01-01

    We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

  19. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    Science.gov (United States)

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  20. Establishment of a transgenic cell line stably expressing human cytochrome P450 2C18 and identification of a CYP2C18 clone with exon 5 missing

    Institute of Scientific and Technical Information of China (English)

    Jian Zhu-Ge; Ying-Nian Yu; Yu-Li Qian; Xin Li

    2002-01-01

    AIM: The human cytochrome P-450 2C18(CYP2C18) hasbeen characterized. However, the protein has not beenpurified from liver and very little is known regarding thespecific substrate of CYP2C18. In order to study its enzymaticactivity for drug metabolism, the CYP2C18cDNA was clonedand a stable CHL cell line expressing recombinant CYP 2C18was established.METHODS: The human CYP2C18cDNA was amplified withreverse transcription-polymerase chain reaction (RT-PCR)from total RNAs extracted from human liver and cloned intopGEM-T vector. The cDNA segment was identified by DNAsequencing and subcloned into a mammalian expressionvector pREP9. A transgenic cell line was established bytransfecting the recombinant plasmid of pREPg-CYP2C18toChinese hamster lung (CHL) cell. The enzyme activity ofCYP2C18 catalyzing oxidation of tolbutamide tohydroxytolbutamide in postmitochondrial supernant(Sg)fraction of the cell was determined by high performanceliquid chromatography(HPLC).RESULTS: The amino acid sequence predicted from thecloned cDNA segment was identical to that of reported byRomkes et al(GenBank accession number: M61856,J05326).The S9 fraction of the established cell line metabolizestolbutamide to hydroxytolbutamide. Tolbutamide hydroxylaseactivity was found to be 0.509±0.052 μmol.min-1.g-1 S9protein or 8.82±0.90 mol.min-1.mol-1 CYP, but wasundetectable in parental CHL cell. In addition, we haveidentified a CYP2C18cDNA clone with exon 5 missing.CONCLUSION: The cDNA of human CYP2C18 wassuccessfully cloned and a cell line, CHL-CYP2C18, efficientlyexpressing the protein of CYP2C18, was established. Aspliced variant of CYP2C18 with exon 5 missing was identifiedin the cloning process.

  1. Basic Data Report for Drillhole SNL-2 (C-2948)

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Dennis W. [Washington Regulatory and Environmental Services (United States)

    2005-01-19

    SNL-2 was drilled in the northwest quarter of Section 12, T22S, R30E, in eastern Eddy County, New Mexico (Figure 2-1). It is located 574 ft from the north line (fnl) and 859 ft from the west line (fwl) of the section (Figure 2-2). This location places the drillhole east of the Livingston Ridge escarpment among oil wells of the Cabin Lake field. SNL-2 will be used to test hydraulic properties and to monitor ground water levels of the Culebra Dolomite Member of the Permian Rustler Formation. SNL-2 was permitted by the New Mexico State Engineer as C-2948. [Official correspondence regarding permitting and regulatory information must reference this permit number.] In the plan describing the integrated groundwater hydrology program (Sandia National Laboratories, 2003), SNL-2 is also codesignated WTS-1 because the location also satisfies needs for long-term monitoring of water quality and movement in the Culebra Dolomite for RCRA permitting; this program is under the management of Washington TRU Solutions LLC (WTS). In the event that additional wells are established on the SNL-2 drillpad to monitor other hydrological units (e.g., the Magenta Dolomite Member of the Permian Rustler Formation), the current drillhole will likely be referred to as SNL-2C because it is completed in the Culebra. Most drillholes at WIPP have been described after completion to provide an account of the geology, hydrology, or other basic data acquired during drilling and immediate completion of the drillhole. In addition, the basic data report provides an account of the drilling procedures and activities that may be helpful to later interpretations of data or for further work in the drillhole, including test activities and eventual plugging and abandoning activities. The basic data report also provides a convenient means of reporting information about administrative activities necessary to drill the hole.

  2. Changes at the CYP2C locus and disruption of CYP2C8/9 linkage disequilibrium in patients with essential tremor.

    Science.gov (United States)

    Martínez, Carmen; García-Martín, Elena; Alonso-Navarro, Hortensia; Jiménez-Jiménez, Félix Javier; Benito-León, Julián; García-Ferrer, Isabel; Vázquez-Torres, Pilar; Puertas, Inmaculada; Zurdo, José M; López-Alburquerque, Tomás; Agúndez, José A G

    2007-01-01

    To identify low-penetrance genes related to sporadic essential tremor (ET) at the CYP2C locus, located in chromosome 10 q23.33. Leukocytary DNA from 200 ET patients and a control group of 300 unrelated healthy individuals with known CYP2C19 genotypes was studied for common CYP2C8 and CYP2C9 allelic variants by using amplification-restriction analyses. Patients with ET showed the following differences compared with healthy subjects: a 1.6-fold reduction in the frequency for CYP2C8*3 (p=0.006), a 1.35-fold reduction of CYP2C9*2 (p=0.05) and a 1.52-fold reduction in the frequency for CYP2C9*3 (p=0.07). The frequency for patients with ET carrying at least one defective allele was 1.33-fold reduced as compared with healthy subjects (p=0.002). In addition, a disruption of the CYP2C8*3/CYP2C9*2 linkage disequilibrium was observed in ET patients, with a 2.1-fold reduction in the percentage for carriers of the haplotype CYP2C8*3 plus CYP2C9*2 in ET patients (p=0.0001). These findings were independent of gender, age, age of onset, or clinical symptoms. These results suggest that alterations at the CYP2C gene locus are associated with the risk for ET.

  3. Genetic Polymorphism of Cytochrome p450 (2C19) Enzyme in Iranian Turkman Ethnic Group.

    Science.gov (United States)

    Tabari, Robabeh Ghiyas; Marjani, Abdoljalal; Ataby, Ogholdondy Agh; Mansourian, Azad Reza; Samai, Nader Mansour

    2013-07-01

    Different findings indicate that CYP2C plays a clinical role in determining interindividual and interethnic differences in drug effectiveness. The ethnic differences in the frequency of CYP2C19 mutant alleles continue to be a significant study topic. The aim of the present study was to assess the frequency of allelic variants of CYP2C19 in Turkman ethnic groups and compare them with the frequencies in other ethnic populations. The study group included 140 unrelated healthy ethnic Turkman subject referred to the Health Center. Genotyping of CYP2C19 alleles (CYP2C19*1, CYP2C19*2, and CYP2C19*3 alleles) was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. The allele frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 56.43%, 23.57% and 20%, respectively. The result also showed that 39.7% of subjects expressed the CYP2C19*1/*1 genotype. While 42.1%, 9.3%, 9.3% and 1.4% expressed CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2 and CYP2C19*3/*3 genotypes, respectively. The genotype CYP2C19*2/*3 was not expressed in this study population. The findings suggested that 10% of subjects were poor metabolizers by expressing CYP2C19*2/*2 and CYP2C19*3/*3 genotypes. Fifty one percent of subjects were intermediate metabolizers having CYP2C19*1/*2, CYP2C19*2/*3 and CYP2C19*1/*3 genotypes and 37.86% were found to be extensive metabolizers expressing CYP2C19*1/*1 genotype. The frequency of intermediate metabolizers genotype was high (51%) in Turkman ethnic groups. This study showed that the determined allelic variants of CYP2C19 (CYP2C19*2 and CYP2C19*3 mutations) in Turkman ethnic group are comparable to other populations. These findings could be useful for the clinicians in different country to determine optimal dosage and effectiveness of drugs metabolized by this polymorphic enzyme.

  4. Facile fabrication of transparent TiO2-C@TiO2-C free-standing film for visible-light photocatalytic application

    Science.gov (United States)

    Hu, Luyang; Zhang, Yumin; Zhang, Shanmei; Li, Benxia

    2017-02-01

    A transparent TiO2-C@TiO2-C free-standing film has been synthesized by two-step hydrothermal method and subsequent thermal annealing. The chemical composition and morphological features of the TiO2-C@TiO2-C film are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy and N2 adsorption-desorption measurement. The results indicate that the flower-like micro/nanostructure TiO2-C particle layers are intimately inhered to porous TiO2-C fibers. The fibers in film are interconnected each other to form a three-dimensional reticulate microstructure, and exhibit intense visible light absorption and high adsorptivity of dye molecules. The interaction between TiO2 and its surface carbon layer in TiO2-C particle promotes the generation of Ti-O-C bonds, which leads to effective charge transfer. Under visible-light irradiation, TiO2-C@TiO2-C film presents enhanced photocatalytic activity for degradation of methylene blue. This work may provide a new viewpoint for designing transparent photocatalytic film for promising applications in heterogeneous photocatalysis.

  5. Heat treatment effects on the microstructure and mechanical properties of a medium manganese steel (0.2C-5Mn)

    Energy Technology Data Exchange (ETDEWEB)

    Xu, H.F., E-mail: xuhaifeng228@163.com [School of Materials Science and Engineering, State Key Laboratory of Material Processing and Die and Mould Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China) and National Engineering Research Center of Advanced Steel Technology NERCAST, Central Iron and Steel Research Institute CISRI, Beijing 100081 (China); Zhao, J. [School of Materials Science and Engineering, State Key Laboratory of Material Processing and Die and Mould Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); National Engineering Research Center of Advanced Steel Technology (NERCAST), Central Iron and Steel Research Institute (CISRI), Beijing 100081 (China); Cao, W.Q.; Shi, J.; Wang, C.Y.; Wang, C. [National Engineering Research Center of Advanced Steel Technology NERCAST, Central Iron and Steel Research Institute (CISRI), Beijing 100081 (China); Li, J. [School of Materials Science and Engineering, State Key Laboratory of Material Processing and Die and Mould Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Dong, H. [National Engineering Research Center of Advanced Steel Technology NERCAST, Central Iron and Steel Research Institute (CISRI), Beijing 100081 (China)

    2012-01-15

    Highlights: Black-Right-Pointing-Pointer Substantially improved mechanical properties of 0.2C-5Mn steels. Black-Right-Pointing-Pointer Intercritical austenization followed by short time annealing. Black-Right-Pointing-Pointer Phase transformation induced plasticity of the large volume fractioned austenite. Black-Right-Pointing-Pointer Dependence of yield stress on austenite grain size accords with Hall-Petch equation. - Abstract: Microstructures and mechanical properties of 0.2C-5Mn steel processed under different heat treatment conditions were examined by scanning electron microscopy (SEM), Transmission electron microscopy (TEM) and X-ray diffraction (XRD). It was found that high temperature austenization (above Ac3) resulted in a full martensite structure after quenching, which gradually transformed into the ferrite/austenite duplex structure during the following annealing process. However, austenization in the intercritical region (between Ac1 and Ac3) gave a duplex structure after quenching, which was nearly not affected by followed annealing process. The ultrahigh strength {approx}1000 MPa and total elongation {approx}40% were only obtained in the specimens with 6 h annealing at 650 Degree-Sign C under both heat treatment conditions. However, the excellent mechanical properties could be obtained in the intercritically austenitized samples with only 10 min annealing at 650 Degree-Sign C. Based on the analysis on the relationship between microstructure and mechanical properties, it was found that the total elongation was strongly dependent on the austenite fraction, which was ascribed to the phase transformation induced plasticity of the large volume fraction of austenite. Otherwise, the dependence of the yield stress on the austenite grain size accords with Hall-Petch equation, which implies that the austenite is soft phase. It was concluded that 10 min annealing at 650 Degree-Sign C was enough to obtain a large volume fraction of austenite ({approx}30%) in 0.2

  6. Induced differentiation of C2C12 to osteoblast via adenovirus-mediated Cbfa1 in vitro%体外诱导C2C12细胞向成骨细胞的分化

    Institute of Scientific and Technical Information of China (English)

    张勇; 杨彤涛; 胡运生; 廖博; 文艳华; 范清宇

    2013-01-01

    目的 成骨细胞特异性转录因子a1(core binding factor a1,Cbfa1)通过调节生长因子和骨特异性细胞外基质蛋白的基因表达而参与成骨细胞的分化和骨发育过程.文中构建成Cbfa1,以腺病毒载体转染成肌细胞C2C12,为种子细胞构建组织工程化骨.方法 体外培养小鼠成肌细胞C2C12,用重组腺病毒质粒pAd-IL-31介导Cbfa1/Osf2基因瞬时转染小鼠成肌C2C12细胞,Western blot检测Cbfa1蛋白表达.结果 Cbfa1蛋白表达、碱性磷酸酶(alkaline phosphatase,ALP)活性测定、骨钙素(osteocalcin,OCN)分泌量以及茜素红染色感染组明显高于对照组.结论 成肌细胞C2C12可以作为种子细胞构建组织工程化骨.%Objective Osteoblast core binding factor a 1 ( Cbfal) plays a role in osteoblast differentiation and development by regulating the gene of growth factor and extracellular matrix proteins . Recombinant adenovirus vector mediated Cbfa 1 was transferred to myoblast C2C12 to construct the tissue-engineered bone. Methods The myoblast C2C12 was cultured in vitro, and then transiently transfected with recombinant adenovirus vector pAd -IL-31 mediated-Cbfal/Osf2. Western blot was used to detect the expression of Cbfal. Results Compared with the control group , the expression of Cbfal, activity of alkaline phosphtase (ALP) , secretory volume of osteocalcin (OCN) and staining via alizarin bordeaux were higher in the transfection group . Conclusion Myoblast C2C12 acts as a seed cell for constructing tissue -engineered bone.

  7. 23. Establishment of two transgenic cells stable expression of human cytochrome P450 2C

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To clone the human cytochrome P450 2C9 (CYP2C9) and CYP2C18 cDNA and establish two transgenic CHL cell line stable expressing human CYP2C9 and CYP2C18. METHODS:Extracting total RNA from human liver tissue, the human CYP2C9 and CYP2C18 cDNA was amplified with reverse transcription polymerase chain reaction (RT-PCR), and cloned into cloning vector pGEM-T. The cDNA segment was identified by DNA sequencing and subcloned into a mammalian expression vector pREP9. Two transgenic cell line were established by transfecting the recombinant vectors of pREP9-CYP2C9 and pREP9-CYP2C18 to Chinese hamster lung cell CHL. The enzyme activity of CYP2C9 and CYP2C18 catalyze tolbutamide to 4-hydroxy tolbutamide in S9 protein of the cells were determinated by HPLC. RESULTS: The sequence of the two cDNA segments cloned, which were 1540 bp and 1671 bp in length, were identical to those reported by Romkes et al(GenBank accession number: M61855, M61856, J05326) in coding amino acids. The S9 fraction of the established cell lines can metabolize tolbutamide to 4-hydroxy tolbutamide, the tolbutamide-4-hydroxylase activity was found to be 0.465±0.109 and 0.509±0.052 nmol*min-1*(mg S9 protein)-1 (n=3), but was not detectable in parental CHL cell. CONCLUSION: The cDNA of CYP2C9 and CYP2C18 were successfolly cloned and cell lines of CHL-CYP2C9 and CHL-CYP2C18 which efficiently expressed the protein of CYP2C9 and CYP2C18 were established.

  8. Enhanced tolerance to low temperature in tobacco by over-expression of a new maize protein phosphatase 2C, ZmPP2C2.

    Science.gov (United States)

    Hu, Xiaoli; Liu, Lixia; Xiao, Beilei; Li, Dapeng; Xing, Xin; Kong, Xiangpei; Li, Dequan

    2010-10-15

    Low temperature is one of the most common environmental stresses affecting plant growth and agricultural production. Serine/threonine protein phosphatases 2C (PP2Cs) have been suggested to play an important role in stress signaling. To identify potential new member of the PP2C proteins in maize and investigate its functions for stress responses, the ZmPP2C2 gene, encoding a new PP2C protein from maize roots, was cloned by RT-PCR and RACE-PCR. Its constitutive expression in roots, stems and leaves of maize seedlings was detected by RNA gel blot, and its regulation in response to cold stress was also examined. To further evaluate its function in the cold stress response, we over-expressed the ZmPP2C2 gene in tobacco under the control of the Cauliflower Mosaic Virus (CaMV) 35S promoter, and assessed a series of physiological changes in wild type and transgenic plants under low temperatures. Compared with wild type tobacco under cold stress, plants that over-expressed ZmPP2C2 displayed higher germination speed and rate, higher antioxidant enzyme (SOD, POD, CAT) activities, with lower cold-induced electrolyte leakage and malondialdehyde (MDA) contents. These results show that over-expression of ZmPP2C2 in tobacco enhanced tolerance to cold stress, suggesting that this new gene, ZmPP2C2, may act as a positive regulator of cold resistance in plants.

  9. Frequencies of two CYP2C19 defective alleles (CYP2C19*2, and *3 among Iranian population in Mazandaran Province

    Directory of Open Access Journals (Sweden)

    Naghi Shahabi-Majd

    2013-02-01

    Conclusion: The result of the present study showed that the two inactive alleles of CYP2C19 accounted for 9.0% of CYP2C19 alleles in our sample versus 8.8 - 40.1% reported in other populations. The frequencies of the studied alleles resulted significant differences between our sample and African and Eastern Asian populations.

  10. Synthesis of furo[3,2-c ]- and pyrano[ 3,2-c ] quinolines by lanthanide triflate catalyzed imino-Diels-Alder reaction

    Institute of Scientific and Technical Information of China (English)

    MA, Yun(马云); QIAN, Chang-Tao(钱长涛); SUN, Jie(孙杰); XIE, Mei-Hua(谢美华)

    2000-01-01

    Imino Diels-Alder reaction of imines witth 2,3-dihydrofuran or 3,4-dihydro-2H-pyran proceeded smothly in the presence of a catalytic amount (0.5 mol %) of ytterbium triflate to afford furo[3,2-c]- and pyrano[3,2-c] quinolines conveniently in high yield.

  11. Session 6: Decomposition of NO over {beta}-Mo{sub 2}C and {beta}-Mo{sub 2}C/Al{sub 2}O{sub 3} catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Shengfu, Ji; Chengyue, Li [Beijing University of Chemical Technology, Key Lab. of Science and Technology of Controllable Chemical Reactions, Ministry of Education (China); Shengfu, Ji; Jiaxin, Wang; Jian, Yang; Shuben, Li [State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou (China)

    2004-07-01

    In this study, for the first time it has been found that the the bulk {beta}-Mo{sub 2}C and an alumina-supported {beta}-Mo{sub 2}C catalysts are very active for the direct NO decomposition at low temperature. The obtained experimental results are presented. (authors)

  12. Surface Turbulent Fluxes, 1x1 deg Daily Grid, Satellite F10 V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are part of the Goddard Satellite-based Surface Turbulent Fluxes Version-2c (GSSTF 2c) Dataset recently produced through a MEaSURES funded project led by...

  13. Surface Turbulent Fluxes, 1x1 deg Daily Grid, Satellite F15 V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are part of the Goddard Satellite-based Surface Turbulent Fluxes Version-2c (GSSTF 2c) Dataset recently produced through a MEaSURES funded project led by...

  14. Surface Turbulent Fluxes, 1x1 deg Daily Grid, Satellite F13 V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are part of the Goddard Satellite-based Surface Turbulent Fluxes Version-2c (GSSTF 2c) Dataset recently produced through a MEaSURES funded project led by...

  15. Surface Turbulent Fluxes, 1x1 deg Daily Grid, Satellite F11 V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are part of the Goddard Satellite-based Surface Turbulent Fluxes Version-2c (GSSTF 2c) Dataset recently produced through a MEaSURES funded project led by...

  16. Surface Turbulent Fluxes, 1x1 deg Daily Grid, Satellite F08 V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are part of the Goddard Satellite-based Surface Turbulent Fluxes Version-2c (GSSTF 2c) Dataset recently produced through a MEaSURES funded project led by...

  17. Data of evolutionary structure change: 1ACLA-2C0QA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACLA-2C0QA 1ACL 2C0Q A A -----SELLVNTKSGKVMGTRVPVLSSHISAFLGIPFAE...AFGGDPMSVTLFGESAGAASVGMHILSLPSRSLFHRAVLQSGTPNGPWATVSAGEARRRATLLARLVGC---NDTELIACLRTRPAQDLVDHEWHVLPQESIFRFSFV.../ss_2> 0 1ACL A 1ACLA SPRPK-STTVM 1ACL A 1ACLA

  18. Data of evolutionary structure change: 1ACLA-2C0QB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACLA-2C0QB 1ACL 2C0Q A B --SELLVNTKSGKVMGTRVPVLSSHISAFLGIPFAEPPV...PMSVTLFGESAGAASVGMHILSLPSRSLFHRAVLQSGTPNGPWATVSAGEARRRATLLARLVGC---NDTELIACLRTRPAQDLVDHEWHVLPQESIFRFSFVPVVDG.../alignment> 0 1ACL A 1ACL.../line> LEU CA 297 1ACL A 1ACL

  19. Data of evolutionary structure change: 1ACLA-2C0PA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACLA-2C0PA 1ACL 2C0P A A -----SELLVNTKSGKVMGTRVPVLSSHISAFLGIPFAE...AFGGDPMSVTLFGESAGAASVGMHILSLPSRSLFHRAVLQSGTPNGPWATVSAGEARRRATLLARLVGC---NDTELIACLRTRPAQDLVDHEWHVLPQESIFRFSFV...IHHHH - 0 1ACL ...A 1ACLA SPRPK-STTVM 1ACL A 1ACLA

  20. Data of evolutionary structure change: 1ACLA-2C0PB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ACLA-2C0PB 1ACL 2C0P A B --SELLVNTKSGKVMGTRVPVLSSHISAFLGIPFAEPPV...PMSVTLFGESAGAASVGMHILSLPSRSLFHRAVLQSGTPNGPWATVSAGEARRRATLLARLVGC---NDTELIACLRTRPAQDLVDHEWHVLPQESIFRFSFVPVVDG... 0 1ACL AGLU CA 218 LEU CA 292 1ACL A 1ACLA RNLNCNLNSDEEL

  1. Genetic polymorphisms of CYP2C9%药物代谢酶CYP2C9基因多态性

    Institute of Scientific and Technical Information of China (English)

    李树春; 王桂萍

    2011-01-01

    Human cytochrome P450 2C9 (CYP2C9) accounts for -20% of hepatic total cytochrome P450 content and metabolizes~15% clinical drugs, especially the drugs with a narrow therapeutic index. CYP2C9 is highly polymorphism. Many results have shown that the genetic polymorphisms of CYP2C9 have close relationship with drug metabolism and adverse drug reaction. According to CYP2C9 enzyme activity, CYP2C9 could be classified as extensive metabolizers, intermedia metabolizers and poor metabolizers. The relationship between genetic polymorphisms and phenotypes, have become the prevalent research topics in the area of pharmacogenetics. In this paper, we reviewed the genetic polymorphisms of CYP2C9 in four areas: the mechanism, metabolic phenotype, drug metabolism and disease susceptibility.%细胞色素氧化酶P450 2C9(CYP2C9)是人类肝脏中一类重要的药物代谢酶,负责约15%临床上常用药物(特别是一些治疗安全范围较窄的药物)的代谢.CYP2C9基因具有高度多态性,研究表明该多态性与药物代谢和药物不良反应的产生关系密切.根据CYP2C9突变基因对CYP2C9酶活性的影响结果,一般可将CYP2C9的代谢表型划分为泛代谢型、中间代谢型和弱代谢型.近年来对该基因多态性及其与表型关系的研究再次成为遗传药理学研究的热点.本文从发生机制、代谢表型、药物代谢以及疾病的易感性等四个方面对CYP2C9基因多态性进行综述.

  2. Vortex phase diagram studies in the weakly pinned single crystals of YNi2B2C and LuNi2B2C

    Indian Academy of Sciences (India)

    D Jaiswal-Nagar; D Pal; M R Eskildsen; P C Canfield; H Takeya; S Ramakrishnan; A K Grover

    2006-01-01

    We present a study of magnetization measurements performed on the single crystals of YNi2B2C and LuNi2B2C. For both the compounds, we find flux jumps in magnetisation values in the respective field regions, where the structural transitions in the flux line lattice symmetry have been reported in these systems via the small angle neutron scattering experiments. The magnetisation hysteresis loops and the AC susceptibility measurements show pronounced peak effect as well as second magnetisation peak anomaly for both YNi2B2C and LuNi2B2C. Based on these results, a vortex phase diagram has been constructed for YNi2B2C for $H \\Arrowvert c$ depicting different glassy phases of the vortex matter.

  3. Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9

    Directory of Open Access Journals (Sweden)

    Calvo AM

    2017-07-01

    Full Text Available Adriana Maria Calvo, Paulo Zupelari-Gonçalves, Thiago José Dionísio, Daniel Thomas Brozoski, Flávio Augusto Faria, Carlos Ferreira Santos Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, São Paulo, Brazil Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs are metabolized by the cytochrome P450 enzymes (CYPs, predominantly CYP2C8 and CYP2C9. The aim of this study was to evaluate the possible association of polymorphisms in the CYP2C8*3 and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4 days after lower third molar surgeries with regard to postoperative pain, swelling, trismus, adverse reactions, need for rescue medication and the volunteer’s overall satisfaction. Materials and methods: For this purpose, 102 volunteers were genotyped for CYP2C8*3 and CYP2C9 polymorphisms. Briefly, genomic DNA was isolated from saliva collected from volunteers subjected to invasive lower third molar surgeries, and the preoperative, intraoperative and postoperative parameters were collected and analyzed. Results: An equal amount of piroxicam sufficiently managed postoperative pain and inflammatory symptoms, with visual analog pain scores typically <40 mm for all genotypes investigated. Furthermore, only two out of 102 volunteers heterozygous for CYP2C8*3 and CYP2C9*3 reported adverse side effects. Conclusion: In general, slow metabolizers of piroxicam, who were volunteers with mutant alleles, were indifferent from normal metabolizers with the wild-type alleles and therefore did not require specialized piroxicam doses to manage postoperative pain and inflammation. Keywords: piroxicam, lower third molar surgery, P450, CYP2C8, CYP2C9, pharmacogenetics 

  4. Molecular genetic analyses of human NKG2C (KLRC2) gene deletion

    NARCIS (Netherlands)

    Miyashita, R; Tsuchiya, N; Hikami, K; Kuroki, K; Fukazawa, T; Bijl, M; Kallenberg, CGM; Hashimoto, H; Yabe, T; Tokunaga, K

    Human NKG2A, NKG2C and NKG2E genes are located on 12p13 in the NK gene complex. We recently identified deletion of NKG2C in a Japanese population. This study was performed to identify the breakpoint, and to examine the association of NKG2C deletion with susceptibility to rheumatoid arthritis and

  5. File list: Oth.Brs.50.TFAP2C.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.50.TFAP2C.AllCell hg19 TFs and others TFAP2C Breast SRX128102,SRX128099,SRX...128100,SRX018833,SRX128101,SRX028632,SRX028633,SRX673728,SRX673727 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.50.TFAP2C.AllCell.bed ...

  6. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  7. Sea urchin-likeNiCoO2@C nanocompositesforLi-ionbatteries and supercapacitors

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Jin; Xi, Kai; Tan, Guoqiang; Chen, Sheng; Zhao, Teng; Coxon, Paul R.; Kim, Hyun-Kyung; Ding, Shujiang; Yang, Yuan; Kumar, R. Vasant; Lu, Jun

    2016-09-01

    The rational construction of battery electrode architecture that offers both high energy and power densities on a gravimetric and volumetric basis is a critical concern but achieving this aim is beset by many fundamental and practical challenges. Here we report a new sea urchin-like NiCoO2@C composite electrode architecture composed of NiCoO2 nanosheets grown on hollow concave carbon disks. Such a unique structural design not only preserves all the advantages of hollow structures but also increases the packing density of the active materials. NiCoO2 nanosheets grown on carbon disks promote a high utilization of active materials in redox reactions by reducing the path length for Li+ ions and for electron transfer. Meanwhile, the hollow concave carbon not only reduces the volume change, but also improves the volumetric energy density of the entire composite electrode. As a result, the nanocomposites exhibit superior electrochemical performance measured in terms of high capacity/capacitance, stable cycling performance and good rate capability in both Li-ion battery and supercapacitor applications. Such nanostructured composite electrode may also have great potential for application in other electrochemical devices.

  8. Novel SiO2-C composite adsorptive material

    Directory of Open Access Journals (Sweden)

    Volzone, C.

    2001-08-01

    Full Text Available The present work is about the development of a Novel Composite that has several properties in only one material. This material is composed by a silica network with a sharpened pore size distribution - diameter near 1000 Å - intercrossed with another carbon network that has carbonaceous microdomains of high activity. The first network facilitates the entrance of big molecules to the interior of the material grains so they quickly reach the active sites of the carbonous network, minimizing the diffusional resistance observed when high performance activated carbons are used in adsorption processes or catalytic applications. These two intercrossed structures are self-supporting and independent among them, so one from the other can be isolated without losing the original shape and volume of the starting composite, then, their possible uses may be multiplied. The Novel Composite is stable with respect to other support or adsorbent materials due to its high obtention temperature (1550 ºC. The obtention methods of the composite and its isolated structures are described. The material was characterized by different techniques (XRD, IR, Loss on ignition, pore size distribution, specific surface area, adsorption desorption isotherms, methylene blue adsorption and SEM.En el presente trabajo se describe el desarrollo de un nuevo material compuesto que reúne distintas propiedades en un solo material. Dicho material está formado por una red de sílice con distribución de tamaño de poro estrecha - diámetro cercano a los 1000 Å - entrecruzada con otra red de carbón pseudografítica donde los microdominios carbonosos son de alta actividad. La primer red facilita la entrada de grandes moléculas al interior de los granos del material permitiendo su rápido acceso a los sitios activos de la red carbonosa, esto minimiza la resistencia difusional observada cuando se utilizan carbones activados de alto rendimiento en los procesos de adsorción o aplicaciones

  9. Impact of RNA editing on functions of the serotonin 2C receptor in vivo

    Directory of Open Access Journals (Sweden)

    Uade B Olaghere Da Silva

    2010-03-01

    Full Text Available Transcripts encoding 5-HT2C receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms. In recombinant cells, the fully edited isoform, 5-HT2C-VGV, exhibits blunted G-protein coupling and reduced constitutive activity. The present studies examine the signal transduction properties of 5-HT2C-VGV receptors in brain to determine the in vivo consequences of altered editing. Using mice solely expressing the 5-HT2C-VGV receptor (VGV/Y, we demonstrate reduced G-protein coupling efficiency and high-affinity agonist binding of brain 5-HT2C-VGV receptors. However, enhanced behavioral sensitivity to a 5-HT2C receptor agonist was also seen in mice expressing 5-HT2C-VGV receptors, an unexpected finding given the blunted G-protein coupling. In addition, mice expressing 5-HT2C-VGV receptors had greater sensitivity to a 5-HT2C inverse agonist/antagonist enhancement of dopamine turnover relative to wild-type mice. These behavioral and biochemical results are most likely explained by increases in 5-HT2C receptor binding sites in the brains of mice solely expressing -5HT2C-VGV receptors. We conclude that 5-HT2C-VGV receptor signaling in brain is blunted, but this deficiency is masked by a marked increase in 5HT2C receptor binding site density in mice solely expressing the VGV isoform. These findings suggest that RNA editing may regulate the density of 5-HT2C receptor binding sites in brain. We further caution that the pattern of 5-HT2C receptor RNA isoforms may not reflect the pattern of protein isoforms, and hence the inferred overall function of the receptor.

  10. Pressure-induced phase transition and electronic properties of MgB2C2

    Science.gov (United States)

    Zheng, Baobing

    2017-05-01

    Two thermodynamically stable new high-pressure phases of MgB2C2 with P-3m1 and I4 cm structure were uncovered through first principles crystal structure search based on unbiased evolutionary simulations. Compared with oC80-MgB2C2 and oP10-MgB2C2 phases, the theoretically predicted hP5-MgB2C2 and tI20-MgB2C2 phases show an intriguing three-dimensional (3D) sp3 B-C bonded network, instead of original 2D sp2 B-C layers, which has been confirmed with the analysis of their structures and partial densities of states. The phase transitions of oC80-MgB2C2 → oP10-MgB2C2, oP10-MgB2C2 → hP5-MgB2C2, and hP5-MgB2C2 → tI20-MgB2C2 occur at 4.6 GPa, 18.9 GPa, and 247.5 GPa, respectively, which have been determined according to the examination of enthalpy differences curves. Electronic band structure calculations suggest that the oC80-MgB2C2, oP10-MgB2C2 and hP5-MgB2C2 phases are indirect band gap semiconductor, while the tI20-MgB2C2 phase changes to direct band gap semiconductor.

  11. Reduced Toxicity of Shiga Toxin (Stx Type 2c in Mice Compared to Stx2d Is Associated with Instability of Stx2c Holotoxin

    Directory of Open Access Journals (Sweden)

    Joshua C. Bunger

    2015-06-01

    Full Text Available Shiga toxin (Stx is an AB5 ribotoxin made by Stx-producing Escherichia coli (STEC. These organisms cause diarrhea, hemorrhagic colitis and the hemolytic uremic syndrome. STEC make two types of Stxs, Stx1 and/or Stx2. Stx2 has one prototype (a and six subtypes (b–g, but only STEC that make Stx2a, and/or Stx2c, or Stx2d are associated with severe disease. However, Stx2c is about 10-fold less toxic than Stx2d in vivo despite only two amino acid differences in the A subunit at positions 291 and 297. We made mutations at these two sites to create intermediate toxins between Stx2c and Stx2d, and determined the 50% cytotoxic dose on Vero cells before and after heat treatment, and the 50% lethal dose in mice of the toxins. We found that serine 291 was associated with increased toxicity in vivo and that either amino acid change from that in Stx2c to that in Stx2d increased heat stability. We also assessed the secondary structure of Stx2c and Stx2d by circular dichroism (CD spectroscopy. The CD studies suggest that Stx2c has a less-ordered secondary structure than Stx2d. We conclude that both amino acids at positions 291 and 297 in Stx2c contribute to its decreased stability and in vivo toxicity compared to Stx2d.

  12. Genetic variability of CYP2C9*2 and CYP2C9*3 in seven indigenous groups from Mexico.

    Science.gov (United States)

    Sánchez-Pozos, Katy; Rivera-Santiago, Carolina; García-Rodríguez, María Helena; Ortiz-López, María Guadalupe; Peña-Espinoza, Barbara Itzel; Granados-Silvestre, María de Los Ángeles; Llerena, Adrian; Menjívar, Marta

    2016-10-28

    CYP2C9 is one of the major drug metabolizing enzymes, however, little is known about polymorphisms in CYP2C9 gene and pharmacological implications in Mexican indigenous populations. Thus, frequencies of CYP2C9*2 and CYP2C9*3 alleles were evaluated in indigenous groups located in northwest (Cora), center (Mazahua and Teenek), south (Chatino and Mixteco) and southeast (Chontal and Maya) regions Mexico. Allelic discrimination was performed by real-time PCR. CYP2C9*2 allele was found only in Chontal and Maya groups, despite the low contribution of Caucasian component in these populations. CYP2C9*3 allele was present in all populations except in Mazahua, showing a wide genetic variability in the studied populations. Interestingly, we found significant differences between indigenous groups in CYP2C9*3 allele, even in groups located at the same region and belonging to the same linguistic family. These results contribute to laying the pharmacogenetic bases in Mexico, in addition to improving treatment, taking into account the genetic interethnic differences.

  13. First detection of canine parvovirus type 2c in Brazil Detecção de parvovírus canino tipo 2c no Brasil

    OpenAIRE

    André Felipe Streck; Carine Kunzler Souza; Karla Rathje Gonçalves; Luciana Zang; Luciane Dubina Pinto; Cláudio Wageck Canal

    2009-01-01

    The presence of canine parvovirus type 2 (CPV-2), 2a and 2b has been described in Brazil, however, the type 2c had not been reported until now. In the current study, seven out of nine samples from dogs with diarrhea were characterized as CPV-2c, indicating that this virus is already circulating in the Brazilian canine population.No Brasil, a presença do parvovírus canino do tipo 2 (CPV-2), 2a e 2b já havia sido descrita, contudo, ainda não havia sido verificada a presença do tipo 2c. No prese...

  14. Genetic Polymorphism of Cytochrome p450 (2C9) Enzyme in Iranian Baluch Ethnic Group.

    Science.gov (United States)

    Tabari, Mojdeh Ghiyas; Naseri, Fatemeh; Ataby, Maryam Agh; Marjani, Abdoljalal

    2015-01-01

    The aim of the present study is to assess and compare the frequencies of the cytochrome P450 CYP2C9 variations in the Baluch ethnic group (n=110) with other ethnic groups. The allele frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 were 80.90%, 11.82% and 7.27%, respectively. 70.90%, 11.82%, 8.18%, 4.55%, 2.73% and 1.82% of subjects were with CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes, respectively. Different mutants may effect on prediction of drug dose requirements in different ethnic groups. Thus, CYP2C9 variants to be determined for findings high risk groups use optimal dosage of drugs metabolized by this polymorphic enzyme.

  15. Genotype and allele frequency of CYP2C19*17 in a healthy Iranian population.

    Science.gov (United States)

    Payan, Maryam; Tajik, Nader; Rouini, Mohammad Reza; Ghahremani, Mohammad Hossein

    2015-01-01

    Cytochrome P450 2C19 (CYP2C19) is important in metabolism of wide range of drugs. CYP2C19*17 is a novel variant allele which increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (URM). Distribution of this variant allele has not been well studied worldwide. The aim of present study was to investigate allele and genotype frequencies of CYP2C19*17 in a healthy Iranian population and compare them with other ethnic groups. One hundred eighty healthy unrelated Iranian volunteer took part in this study and were genotyped for CYP2C19 *2, *3, *17 (-3402) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and CYP2C19*17 (-806) by a nested-PCR assays. The distribution of CYP2C19*17 polymorphism in Iranian population was then compared with other ethnic groups. The CYP2C19*17 allele frequency was 21.6% in Iranian population. Among studied subjects 5.5% were homozygous for CYP2C19*17 and phenotyped as ultra-rapid metabolizers; 28.8% were genotyped as CYP2C19*1*17 (extensive metabolizers) and 3.3% as CYP2C19*2*17 (intermediate metabolizers). The CYP2C19*17 genetic distribution in Iranian population is similar to Middle East or European countries. The high frequency of CYP2C19*17 in Iranian population highlights the importance of this new variant allele in metabolism of CYP2C19 substrates. Thus, future association studies are required to reveal clinical consequence of this genetic polymorphism in carrier individuals.

  16. First detection of canine parvovirus type 2c in Brazil Detecção de parvovírus canino tipo 2c no Brasil

    Directory of Open Access Journals (Sweden)

    André Felipe Streck

    2009-09-01

    Full Text Available The presence of canine parvovirus type 2 (CPV-2, 2a and 2b has been described in Brazil, however, the type 2c had not been reported until now. In the current study, seven out of nine samples from dogs with diarrhea were characterized as CPV-2c, indicating that this virus is already circulating in the Brazilian canine population.No Brasil, a presença do parvovírus canino do tipo 2 (CPV-2, 2a e 2b já havia sido descrita, contudo, ainda não havia sido verificada a presença do tipo 2c. No presente trabalho, sete de nove amostras de cães com diarréia foram caracterizadas como CPV-2c, indicando que este vírus já está circulando na população canina no Brasil.

  17. Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Sarmistha; Das, Rajat Kumar; Giffear, Kelly A.; Shapiro, Bernard H., E-mail: shapirob@vet.upenn.edu

    2015-04-01

    Perinatal exposure of rats and mice to the typically reported 4 mg/g bd wt dose of monosodium glutamate (MSG) results in a complete block in GH secretion as well as obesity, growth retardation and a profound suppression of several cytochrome P450s, including CYP2C11, the predominant male-specific isoform — all irreversible effects. In contrast, we have found that a lower dose of the food additive, 2 mg/g bd wt on alternate days for the first 9 days of life results in a transient neonatal depletion of plasma GH, a subsequent permanent overexpression of CYP2C11 as well as subnormal (mini) GH pulse amplitudes in an otherwise normal adult masculine episodic GH profile. The overexpressed CYP2C11 was characterized by a 250% increase in mRNA, but only a 40 to 50% increase in CYP2C11 protein and its catalytic activity. Using freshly isolated hepatocytes as well as primary cultures exposed to the masculine-like episodic GH profile, we observed normal induction, activation, nuclear translocation and binding to the CYP2C11 promoter of the GH-dependent signal transducers required for CYP2C11 transcription. The disproportionately lower expression levels of CYP2C11 protein were associated with dramatically high expression levels of an aberrant, presumably nontranslated CYP2C11 mRNA, a 200% increase in CYP2C11 ubiquitination and a 70–80% decline in miRNAs associated, at normal levels, with a suppression of CYP2C expression. Whereas the GH-responsiveness of CYP2C7 and CYP2C6 as well as albumin was normal in the MSG-derived hepatocytes, the abnormal expression of CYP2C11 was permanent and irreversible. - Highlights: • A “low” neonatal dose of MSG causes an immediate but transient growth hormone depletion. • Adult circulating growth hormone contains mini pulses in an otherwise male profile. • CYP2C11 is permanently overexpressed > 250%; CYP2C6, 2C7 and albumin remain normal. • The bulk of the overexpressed CYP2C11 mRNA consists of an intron-retained form. • SOCS2

  18. Molecular Mimicry Regulates ABA Signaling by SnRK2 Kinases and PP2C Phosphatases

    Energy Technology Data Exchange (ETDEWEB)

    Soon, Fen-Fen; Ng, Ley-Moy; Zhou, X. Edward; West, Graham M.; Kovach, Amanda; Tan, M.H. Eileen; Suino-Powell, Kelly M.; He, Yuanzheng; Xu, Yong; Chalmers, Michael J.; Brunzelle, Joseph S.; Zhang, Huiming; Yang, Huaiyu; Jiang, Hualiang; Li, Jun; Yong, Eu-Leong; Cutler, Sean; Zhu, Jian-Kang; Griffin, Patrick R.; Melcher, Karsten; Xu, H. Eric (Van Andel); (Scripps); (NWU); (Purdue); (UCR); (Chinese Aca. Sci.); (NU Singapore)

    2014-10-02

    Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.

  19. Identification of a cys-ser substitution in the 5-HT{sub 2C} (HTR2C) receptor gene and allelic association to violent behavior and alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Lappalainen, J.; Ozaki, N.; Goldman, D. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

    1994-09-01

    Several lines of evidence suggest that brain serotonergic functions, including behavioral and neurochemical responses to 5-HT{sub 2C} agonist, are abnormal in some individuals with alcoholism and aggressive behaviors. The aim of the present study was to identify coding sequence variants in the human 5-HT{sub 2C} receptor gene which may cause abnormal or variant function of this receptor. Using SSCP analysis, a non-conservative cys-ser substitution was found in the 5-HT{sub 2C} receptor (designated 5-HT{sub 2Ccys} and 5-HT{sub 2Cser}). The polymorphism was typed in CEPH families to genetically map the gene. To test for association of the variant to alcoholism, violent behavior and serotonin function, the 5-HT{sub 2C} genotypes of 151 non-related Finnish male alcoholic violent offenders and impulsive fire setters and 127 Finnish psychiatrically interviewed healthy male volunteers were determined. CSF 5-HIAA concentrations were available for 74 alcoholic violent offenders and 25 healthy volunteers. Linkage analysis placed the 5-HT{sub 2C} gene on Xq21, a region that has been previously shown to contain genes for several mental retardation syndromes. The 5-HT{sub 2Ccys}/5-HT{sub 2Cser} genotype frequencies in alcoholic violent offenders and controls differed significantly (0.90/0.10 and 0.82/0.18, respectively, P=0.048). The association was found to be strongest in the violent offenders who did not fulfill the criteria for antisocial personality disorder (5-HT{sub 2Ccys}/5-HT{sub 2Cser} 0.93/0.07, p=0.021). No association was found between CSF 5-HIAA concentrations and 5-HT{sub 2C} genotype. These results implicate a 5-HT{sub 2C} receptor amino acid substitution in predisposition to alcohol abuse and violent behavior in a subgroup of alcoholics.

  20. File list: Oth.ALL.05.TFAP2C.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.TFAP2C.AllCell hg19 TFs and others TFAP2C All cell types SRX673727,SRX67...3728,SRX150450,SRX190406,SRX018833,SRX128099,SRX128102,SRX028632,SRX128100,SRX028633,SRX128101 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.05.TFAP2C.AllCell.bed ...

  1. Synergistic Impairment of Glucose Homeostasis in ob/ob Mice Lacking Functional Serotonin 2C Receptors

    OpenAIRE

    Wade, Jennifer M.; Juneja, Punita; Mackay, Adrienne W.; Graham, James; Havel, Peter J.; Tecott, Laurence H.; Goulding, Evan H.

    2007-01-01

    To investigate how serotonin and leptin interact in the regulation of energy balance and glucose homeostasis, we generated a genetic mouse model, the OB2C mouse, which lacks functional serotonin 2C receptors and the adipocyte hormone leptin. The OB2C mice exhibited a dramatic diabetes phenotype, evidenced by a synergistic increase in serum glucose levels and water intake. The severity of the animals’ diabetes phenotype would not have been predicted from the phenotypic characterization of mice...

  2. Volumetric Properties of the Mixture Ethane-1,2-diol C2H6O2 + C6H10O Cyclohexanone (VMSD1212, LB4988_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume A 'Binary Liquid Systems of Nonelectrolytes I' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Ethane-1,2-diol C2H6O2 + C6H10O Cyclohexanone (VMSD1212, LB4988_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  3. Volumetric Properties of the Mixture 2-Ethoxyethanol C4H10O2 + C5H10O3 Diethyl carbonate (VMSD1212, LB4692_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture 2-Ethoxyethanol C4H10O2 + C5H10O3 Diethyl carbonate (VMSD1212, LB4692_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  4. Volumetric Properties of the Mixture 2-Methoxyethanol C3H8O2 + C5H10O3 Diethyl carbonate (VMSD1212, LB4691_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture 2-Methoxyethanol C3H8O2 + C5H10O3 Diethyl carbonate (VMSD1212, LB4691_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  5. Frequency of CYP2C9 alleles in Koreans and their effects on Iosartan pharmacokinetics

    Institute of Scientific and Technical Information of China (English)

    Jung-woo BAE; Byung-sung KANG; Hye-in LEE; Yun-jeong LEE; Hyun-joo PARK; Ji-hey HA; Hee-jung SHIN; Young-hoon KIM; Han-sung NA; Myeon-woo CHUNG; Soon-young HAN; Chang-ik CHOI; Seung-hee KIM; Choon-gon JANG; Seok-yong LEE; Mi-jeong KIM; Da-hee OH; Seul-ki KEUM; Jung-in PARK; Bo-hye KIM; Hye-kyoung BANG; Sung-gon OH

    2011-01-01

    Aim:CYP2C9 enzyme metabolizes numerous clinically important drugs.The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on Iosartan pharmacokinetics in a large sample of the Korean population.Methods:The CYP2C9 gene was genotyped in 1796 healthy Korean subjects.CYP2C9 alleles (CYP2C9*1,*2,*3,and *13 alleles)were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and direct sequencing assay.The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate.Results:The frequencies of CYP2C9*1,*3,and *13 allele were 0.952 (95% confidence interval 0.945-0.959),0.044 (95% CI 0.037-0.051),and 0.005 (95% CI 0.003-0.007),respectively.The frequencies of the CYP2C9*1/*1,*1/*3,*1/*13,and *3/*3 genotypes were 0.904 (95% CI 0.890-0.918),0.085 (95% CI 0.072-0.098),0.009 (95% CI 0.005-0.013),and 0.001 (95% CI 0.000-0.002),respectively.In the pharmacokinetics studies,the AUC0-∞ of losartan in CYP2C9*3/*3 subject was 1.42-fold larger than that in CYP2C9*1/*1 subjects,and the AUC0-∞ of E-3174,a more active metaboiite of Iosartan,in CYP2C9*3/*3 subject was only 12% of that in CYP2C9*1/*1 subjects.Conclusion:The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans,and detected the CYP2C9*3/*3 genotype.CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects.

  6. Metabolism of R- and S-Warfarin by CYP2C19 into Four Hydroxywarfarins

    Science.gov (United States)

    Kim, So-Young; Kang, Ji-Yeon; Hartman, Jessica H.; Park, Sun-Ha; Jones, Drew R.; Yun, Chul-Ho; Boysen, Gunnar; Miller, Grover P.

    2013-01-01

    Coumadin (R/S-warfarin) is a highly efficacious and widely used anticoagulant; however, its highly variable metabolism remains an important contributor to uncertainties in therapeutic responses. Pharmacogenetic studies report conflicting findings on the clinical relevance of CYP2C19. A resolution to this controversy is impeded by a lack of detail on the potential role of CYP2C19 in warfarin metabolism. Consequently, we assessed the efficiency of CYP2C19 metabolism of R- and S-warfarin and explored possible contributions in the liver using in vitro methods. Recombinant CYP2C19 metabolized R- and S-warfarin mainly to 6-, 7-, and 8-hydroxywarfarin, while 4′-hydroxywarfarin was a minor metabolite. Overall R-warfarin metabolism was slightly more efficient than that for S-warfarin. Metabolic pathways that produce R-6-, 7-, and 8-hydroxywarfarin in human liver microsomal reactions correlated strongly with CYP2C19 S-mephenytoin hydroxylase activity. Similarly, CYP1A2 activity toward phenacetin correlated with formation of R-6 and 7-hydroxywarfarin such that R-8-hydroxywarfarin seems unique to CYP2C19 and possibly a biomarker. In following, CYP2C19 likely impacts R-warfarin metabolism and patient response to therapy. Intriguingly, CYP2C19 may contribute to S-warfarin metabolism in patients, especially when CYP2C9 activity is compromised due to drug interactions or genetic polymorphisms. PMID:23331088

  7. CYP2C9 polymorphism in patients with epilepsy: genotypic frequency analyzes andphenytoin adverse reactions correlation

    Directory of Open Access Journals (Sweden)

    Carlos Alexandre Twardowschy

    2011-04-01

    Full Text Available OBJECTIVE: CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect therapeutic outcome during treatment. The distribution of variant CYP2C9 alleles and prevalence of phenytoin adverse reactions were hereby investigated in a population of patients diagnosed with epilepsy. METHOD: Allele-specific PCR analysis was carried out in order to determine frequencies of the two most common variant alleles, CYP2C9*2 and CYP2C9*3 in genomic DNA isolated from 100 epileptic patients. We also analyzed the frequency of phenytoin adverse reactions among those different genotypes groups. The data was presented as mean±standard deviation. RESULTS: The mean age at enrollment was 39.6±10.3 years (range, 17-72 years and duration of epilepsy was 26.5±11.9 years (range 3-48 years. The mean age at epilepsy onset was 13.1±12.4 years (range, 1 month-62 years. Frequencies of CYP2C9*1 (84%, CYP2C9*2 (9% and CYP2C9*3 (7% were similar to other published reports. Phenytoin adverse reactions were usually mild and occurred in 15% patients, without correlation with the CYP2C9 polymorphism (p=0.34. CONCLUSION: Our findings indicate an overall similar distribution of the CYP2C9 alleles in a population of patients diagnosed with epilepsy in the South of Brazil, compared to other samples. This sample of phenytoin users showed no drug related adverse reactions and CYP2C9 allele type correlation. The role of CYP2C9 polymorphism influence on phenytoin adverse reaction remains to be determined since some literature evidence and our data found negative results.

  8. Association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and activity of P-glycoprotein with response to anti-epileptic drugs

    Directory of Open Access Journals (Sweden)

    S R Taur

    2014-01-01

    Full Text Available Background and Objective: Epilepsy, the most common neurological disorder, has treatment failure rate of 20 to 25%. Inter-individual variability in drug response can be attributed to genetic polymorphism in genes encoding different drug metabolizing enzymes, drug transporters (P-gp, and enzymes involved in sodium channel biosynthesis. The present study attempted to evaluate association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and P-gp activity with treatment response in patients with epilepsy. Materials and Methods: Patients with epilepsy on phenytoin and/or phenobarbital and/or carbamazepine were categorized into responders and non-responders as per the International League Against Epilepsy. Plasma drug concentration was estimated by high-performance liquid chromatography. P-gp activity was measured by flow cytometry using rhodamine efflux. The polymerase chain reaction (PCR-RFLP was used to study polymorphisms of ABCB1 (C3435T, CYP2C9 (416 C > T, and 1061 A > T, and CYP2C19 (681 G > A and 636 G > A. Results: Of total 117 patients enrolled in this study, genotype data was available for 115 patients. P-gp activity was higher in non-responders (n = 68 compared to responders (n = 47 (P T and 1061 A > T in CYP2C9 or 681 G > A and 636 G > A in CYP2C19 was observed with response phenotype in genotypic analysis. Significant genotypic (odds ratio, OR = 4.5; 95% CI, 1.04 to 20.99 and allelic association (OR = 1.73; 95% CI, 1.02 to 2.95 was observed with ABCB1 C3435T and response phenotype. Conclusions: The response to antiepileptics seems to be modulated by C3435T in ABCB1 or P-gp activity. At present, role of other genetic factors in treatment responsiveness in epilepsy appears limited, warranting analysis in a larger cohort.

  9. Interferon signaling is dependent on specific tyrosines located within the intracellular domain of IFNAR2c. Expression of IFNAR2c tyrosine mutants in U5A cells.

    Science.gov (United States)

    Wagner, T Charis; Velichko, Sharlene; Vogel, David; Rani, M R Sandhya; Leung, Stewart; Ransohoff, Richard M; Stark, George R; Perez, H Daniel; Croze, Ed

    2002-01-11

    Type I interferons (IFNs) are cytokines that play a central role in mediating antiviral, antiproliferative, and immunomodulatory activities in virtually all cells. These activities are entirely dependent on the interaction of IFNs with their particular cell surface receptor. In this report, we identify two specific tyrosine residues located within the cytoplasmic domain of IFNAR2c that are obligatory for IFN-dependent signaling. Various IFNAR2c tyrosine mutants were expressed in a human lung fibroscarcoma cell line lacking IFNAR2c (U5A). Stable clones expressing these mutants were analyzed for their ability to induce STAT1 and STAT2 activation, ISGF3 transcriptional complex formation, gene expression, and cell growth regulation in response to stimulation with type I IFNs. The replacement of all seven cytoplasmic tyrosine residues of IFNAR2c with phenylalanine resulted in a receptor unable to respond to IFN stimulation. Substitution of single tyrosines at amino acid residue 269, 316, 318, 337, or 512 with phenylalanine had no effect on IFN-dependent signaling, suggesting that no single tyrosine is essential for IFN receptor-mediated signaling. In addition, IFNAR2c retaining five proximal tyrosines residues (269, 306, 316, 318, and 337) or either two distal tyrosine residues (411 or 512) continued to be responsive to IFN stimulation. Surprisingly, the presence of only a single tyrosine at either position 337 or 512 was sufficient to restore a complete IFN response. These results indicate that IFN-dependent signaling proceeds through the redundant usage of two tyrosine residues in the cytoplasmic domain of IFNAR2c.

  10. Renormalized Volume

    Science.gov (United States)

    Gover, A. Rod; Waldron, Andrew

    2017-09-01

    We develop a universal distributional calculus for regulated volumes of metrics that are suitably singular along hypersurfaces. When the hypersurface is a conformal infinity we give simple integrated distribution expressions for the divergences and anomaly of the regulated volume functional valid for any choice of regulator. For closed hypersurfaces or conformally compact geometries, methods from a previously developed boundary calculus for conformally compact manifolds can be applied to give explicit holographic formulæ for the divergences and anomaly expressed as hypersurface integrals over local quantities (the method also extends to non-closed hypersurfaces). The resulting anomaly does not depend on any particular choice of regulator, while the regulator dependence of the divergences is precisely captured by these formulæ. Conformal hypersurface invariants can be studied by demanding that the singular metric obey, smoothly and formally to a suitable order, a Yamabe type problem with boundary data along the conformal infinity. We prove that the volume anomaly for these singular Yamabe solutions is a conformally invariant integral of a local Q-curvature that generalizes the Branson Q-curvature by including data of the embedding. In each dimension this canonically defines a higher dimensional generalization of the Willmore energy/rigid string action. Recently, Graham proved that the first variation of the volume anomaly recovers the density obstructing smooth solutions to this singular Yamabe problem; we give a new proof of this result employing our boundary calculus. Physical applications of our results include studies of quantum corrections to entanglement entropies.

  11. Draft genome sequence of the antagonistic rhizosphere bacterium Serratia plymuthica strain PRI-2C.

    Science.gov (United States)

    Garbeva, P; van Elsas, J D; de Boer, W

    2012-08-01

    Serratia plymuthica strain PRI-2C is a rhizosphere bacterial strain with antagonistic activity against different plant pathogens. Here we present the 5.39-Mb (G+C content, 55.67%) draft genome sequence of S. plymuthica strain PRI-2C with the aim of providing insight into the genomic basis of its antagonistic activity.

  12. Structural and electronic studies of metal carbide clusterfullerene Sc2C2@Cs-C72

    Science.gov (United States)

    Feng, Yongqiang; Wang, Taishan; Wu, Jingyi; Feng, Lai; Xiang, Junfeng; Ma, Yihan; Zhang, Zhuxia; Jiang, Li; Shu, Chunying; Wang, Chunru

    2013-07-01

    We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed.We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed. Electronic supplementary information (ESI) available: Experimental details, HPLC chromatogram, and DFT calculations. CCDC 917712. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3nr01739g

  13. Genotype of cytochrome-450 2C9 in patients with tuberculosis

    Directory of Open Access Journals (Sweden)

    Kresyun V.I.

    2013-06-01

    Full Text Available The aim of present work was to investigate CYP2С9 polymorphism in the south of Ukraine in TB-patients and comparing with the same data of control group by the example of Odessa region. Gene CYP2С9 polymorphism was studied with the help of PCR (polymerase chain reaction and endonuclease analysis. The blood samples were obtained from patients with new cases of pulmonary TB from Odessa regional antituberculous dispensary and healthy donors in Odessa district station of blood transfusion in the year 2010-12. According to genotype of CYP2C9 of 55 TB-patients, 67,3% persons were the carriers of homozygote wild gene CYP2C9*1/*1, 21,8 and 3,6% - heterozygote genes CYP2C9*1/*2 and CYP2C9*1/*3. Only 7,2% individuals belonged to carriers of slow metabolizers genotype - CYP2C9*2/*2, *2/*3, *3/*3. In general, the mutated alleles CYP2C9*2 and CYP2C9*3 in TB-males were observed by 1,8 times more frequently than among healthy donors of the same gender. TB-patients older than 30 years more frequently had mutated allele CYP2C9*2, almost by 3 times than individuals from control group.

  14. Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

    Directory of Open Access Journals (Sweden)

    Débora González

    2015-01-01

    Full Text Available Background. 2C-B (Nexus is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. Objectives. To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. Methods. Twenty healthy recreational 2C-B users (12 women self-administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech, subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires, and cardiovascular effects (blood pressure and heart rate. Results. Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and well-being, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed. Conclusions. The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties.

  15. Data of evolutionary structure change: 1MRUA-2C3KA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1MRUA-2C3KA 1MRU 2C3K A A TPSHLSDRYELGEILGFGGMSEVHLARDLRLHRDVAVKV...HHHHHHHHHHHHH HHHH -----HHHH -- 0 1MRU... A 1MRUA GDSVD-ARSDV 1MRU A 1MRU...ILE CA 362 ASP CA 288 SER CA 245 1MRU

  16. Data of evolutionary structure change: 1MRUB-2C3KA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1MRUB-2C3KA 1MRU 2C3K B A MTTPSHLSDRYELGEILGFGGMSEVHLARDLRLHRDVAV...HH ---HHHHHHHHHHHHHH -------HHHH HHHH -- 0 1MRU... B 1MRUB GDSVD-A.../rmsd> 3.5074009895324707 1 1MRU... B 1MRUB

  17. Data of evolutionary structure change: 1CRLA-2C0PA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CRLA-2C0PA 1CRL 2C0P A A ------APTATLANGDTITGLNAI----INEAFLGIPFA...VYDGRFLAQV---EG--AVLVSMNYRVGTFGFLALPGS-REAPGNVGLLDQRLALQWVQENIAAFGGDPMSVTLFGESAGAASVGMHILS--------LPSRSLFHRA...DTPEALINTGDFQDLQVLVGVVKDEGSYFLVYGVPGFSKDNESLISRAQFLAGVRIGVPQASDLAAEAVVLHYT-----------DWLHPEDPTHLRDAMSAVVGDHNVVCPVAQLAGRLA...ment> 0 1CRL A 1CRLA...>LEU CA 304 1CRL A 1CRLA

  18. La2@C72 : Metal-Mediated Stabilization of a Carbon Cage

    NARCIS (Netherlands)

    Stevenson, S.; Burbank, P.; Harich, K.; Dorn, H.C.; Loosdrecht, P.H.M. van; Vries, M.S. de; Salem, J.R.; Kiang, C.-H.; Johnson, R.D.; Bethune, D.S.

    1998-01-01

    In this study, we report production, isolation, and characterization for the relatively small endohedral metallofullerene, La2@C72. As described, La2@C72 is readily isolated from conventional electric-arc-generated carbon/metal soot. This new species was purified by HPLC chromatography and

  19. 40 CFR Table 2c to Subpart E of... - Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Reactivity Factors for Aromatic Hydrocarbon Solvent Mixtures 2C Table 2C to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Boiling range (degrees F) Criteria Reactivityfactor 21 280-290...

  20. First-Principle Calculations of Hardness and Melting Point of Mo2C

    Institute of Scientific and Technical Information of China (English)

    X.R.Wang; M.F.Yan; H.T.Chen

    2009-01-01

    This paper has constructed two kinds of atomic and electronic models for hexagonal β-Mo2C and orthorhombic α-Mo2C.The optimized lattice parameters, elastic constant matrixes and overlap population for Mo2C crystal cells have been obtained to realize the characterization of the hardness and melting point of the two structures by the first-principles plane wave pseudo potential method based on the density functional theory. The results reveal that the calculated lattice parameters of the Mo2C crystal cells agree with the experimental and other calculated data.The calculated melting point/hardness are 2715 K/11.38 GPa for β-Mo2C and 2699 K/10.57~12.67 GPa for α-Mo2C, respectively.The calculated results from the density of states (DOS)demonstrate that the hybridization effect between Mo-3d and C-2p states in α-Mo2C crystal cell is much stronger than that in β-Mo2C one.

  1. Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis

    Directory of Open Access Journals (Sweden)

    Yan Gong

    2016-11-01

    Full Text Available Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPARα agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs. While ω-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both ω-3 and ω-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C ω-3 LCPUFA (and ω-6 LCPUFA pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPARα-/-mice and augmented ω-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic ω-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPARα. Fenofibrate augmented the overall protective effects of ω-3 LCPUFAs on neovascular eye diseases.

  2. Hydrogenation of Benzene over Mo2C/Al2O3 Catalyst

    Institute of Scientific and Technical Information of China (English)

    Zhang Jing; Wu Weicheng

    2008-01-01

    The process of benzene hydrogenation over Mo2C catalyst has been studied.Mo2C was the active phase in benzene hydrogenation.The major problem with the metal carbides was their poor stability due to deactivation by carbon deposition.

  3. Polyclonal Expansion of NKG2C+ NK Cells in TAP-deficient Patients

    Directory of Open Access Journals (Sweden)

    vivien eBeziat

    2015-10-01

    Full Text Available Adaptive natural killer (NK cell responses to human cytomegalovirus (CMV infection are characterized by the expansion of NKG2C+ NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs. Here, we set out to study the HLA class I-dependency of such NKG2C+ NK cell expansions. We demonstrate expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP-deficiency, whom express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C+ NK cell populations in TAP-deficient patients display a polyclonal KIR-profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR-repertoire of expanding NKG2C+ NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C+ NK cell expansions to occur. Thus, the emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to anti-viral immunity and potentially explain these patients’ low incidence of severe viral infections.

  4. Polyclonal Expansion of NKG2C+ NK Cells in TAP-Deficient Patients

    Science.gov (United States)

    Béziat, Vivien; Sleiman, Marwan; Goodridge, Jodie P.; Kaarbø, Mari; Liu, Lisa L.; Rollag, Halvor; Ljunggren, Hans-Gustaf; Zimmer, Jacques; Malmberg, Karl-Johan

    2015-01-01

    Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C+ NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C+ NK cell expansions. We demonstrate the expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C+ NK cell populations in TAP-deficient patients display a polyclonal KIR profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR repertoire of expanding NKG2C+ NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C+ NK cell expansions to occur. The emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to antiviral immunity and potentially explain these patients’ low incidence of severe viral infections. PMID:26500647

  5. Cytoprotective Effect of Hispidin against Palmitate-Induced Lipotoxicity in C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    Jun Myoung Park

    2015-03-01

    Full Text Available It is well known that Phellinus linteus, which produces hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in C2C12 myotubes increased ROS generation and cell death as compared with the control. However, pretreatment of hispidin for 8 h improved the survival of C2C12 myotubes against palmitate-induced oxidative stress via inhibition of intracellular ROS production. Hispidin also inhibited palmitate-induced apoptotic nuclear condensation in C2C12 myotubes. In addition, we found that hispidin can suppress cleavage of caspase-3, expression of Bax, and NF-κB translocation. Therefore, these results suggest that hispidin is capable of protecting C2C12 myotubes against palmitate-induced oxidative stress.

  6. Relative Copy Number Variations of CYP2C19 in South Indian Population

    Directory of Open Access Journals (Sweden)

    Anichavezhi Devendran

    2012-01-01

    Full Text Available CYP2C19 is a polymorphic enzyme involved in the metabolism of clinically important drugs. Genotype-phenotype association studies of CYP2C19 have reported wide ranges in the metabolic ratios of its substrates. These discrepancies could be attributed to the variations in the promoter region and this aspect has been reported recently. The observations in the recent reports on the influence of promoter region variants on the metabolism of CYP2C19 substrates might also have been influenced by the copy number variations of CYP2C19. In this paper, we describe copy number variations of CYP2C19 using real-time polymerase chain reaction by comparative Ct method. No copy number variations were observed in the south Indian population indicating the observed discrepancies in genotype-phenotype association studies might be due to the regulatory region polymorphisms as reported earlier.

  7. High specific surface area Mo2C nanoparticles as an efficient electrocatalyst for hydrogen evolution

    Science.gov (United States)

    Tang, Chaoyun; Sun, Aokui; Xu, Yushuai; Wu, Zhuangzhi; Wang, Dezhi

    2015-11-01

    Mo2C nanoparticles with high specific surface area (120 m2 g-1) are successfully synthesized using a typical and low-cost monosaccharide of glucose via a facile calcination and subsequent reduction process. The HER functions of the obtained Mo2C nanoparticles are investigated and the effect of reduction time in hydrogen is also discussed. It is found that η-MoC can be obtained at 800 °C with a reduction time of 10 min, but the formation of β-Mo2C phase requires more than 20 min. Moreover, the β-Mo2C obtained with a reduction time of 20 min exhibits the best HER activity with a small Tafel slope of 55 mV dec-1 and a large current density of 60 mA cm-2 at -200 mV, which is among the best records over Mo2C-based HER catalysts.

  8. CO2-C emissions associated to soil tillage, liming and gypsum applications in sugarcane areas under green and burned harvest

    Science.gov (United States)

    Figueiredo, E. B.; Panosso, A. R.; La Scala, N., Jr.

    2012-04-01

    Debate regarding the potential of bioenergy crops to substitute fossil fuel in an efficient way is still opened. New management strategies from agricultural crops should be identified to increase their potential contributing to avoid the climate changes. This study quantified the impact of sugarcane harvest systems and other management practices on CO2-C fluxes following crop replanting. Two agricultural systems were considered: burned and green harvest, in plots where residues were left or removed from soil surface, from no till and after conventional tillage, with or without dolomite and agricultural gypsum applications. Soil CO2 emission, moisture and soil temperature were taken since 24 hours after tillage, totalizing 25 days after tillage with 18 measuring days. NT plots emissions were kept lower than others during the whole period studied, presenting in some cases fluctuations which were mostly related to changes in soil moisture associated to the occurrence of rain precipitations. Changes in CO2-C emission, in each of the harvest systems can be clearly seen when tillage, dolomite or gypsum were applied. The removal of sugarcane residues from soil surface resulted in almost immediate reduction of soil moisture (6% in volume) following an increase in soil NT CO2 emission of + 64%. The additional soil carbon emission due to the simple operation of removing the crop residues from soil surface was 252.4 kg CO2-C ha-1, as higher as the soil CO2 losses induced by tillage operation. Dolomite and agricultural gypsum applications did not always result in higher emissions, especially when applied at the presence of crop residues on soil surface. Reducing tillage frequency in green harvested sugarcane areas could reduce CO2 emissions and probably increasing the soil carbon stock considering long-term period crop system, while maintaining the sugarcane crop residues on soil surface has shown to be also a GHG mitigation option.

  9. Pharmacological evaluation of selective α2c-adrenergic agonists in experimental animal models of nasal congestion.

    Science.gov (United States)

    Jia, Yanlin; Mingo, Garfield G; Hunter, John C; Lieber, Gissela B; Palamanda, Jairam R; Mei, Hong; Boyce, Christopher W; Koss, Michael C; Yu, Yongxin; Cicmil, Milenko; Hey, John A; McLeod, Robbie L

    2014-04-01

    Nasal congestion is one of the most troublesome symptoms of many upper airways diseases. We characterized the effect of selective α2c-adrenergic agonists in animal models of nasal congestion. In porcine mucosa tissue, compound A and compound B contracted nasal veins with only modest effects on arteries. In in vivo experiments, we examined the nasal decongestant dose-response characteristics, pharmacokinetic/pharmacodynamic relationship, duration of action, potential development of tolerance, and topical efficacy of α2c-adrenergic agonists. Acoustic rhinometry was used to determine nasal cavity dimensions following intranasal compound 48/80 (1%, 75 µl). In feline experiments, compound 48/80 decreased nasal cavity volume and minimum cross-sectional areas by 77% and 40%, respectively. Oral administration of compound A (0.1-3.0 mg/kg), compound B (0.3-5.0 mg/kg), and d-pseudoephedrine (0.3 and 1.0 mg/kg) produced dose-dependent decongestion. Unlike d-pseudoephedrine, compounds A and B did not alter systolic blood pressure. The plasma exposure of compound A to produce a robust decongestion (EC(80)) was 500 nM, which related well to the duration of action of approximately 4.0 hours. No tolerance to the decongestant effect of compound A (1.0 mg/kg p.o.) was observed. To study the topical efficacies of compounds A and B, the drugs were given topically 30 minutes after compound 48/80 (a therapeutic paradigm) where both agents reversed nasal congestion. Finally, nasal-decongestive activity was confirmed in the dog. We demonstrate that α2c-adrenergic agonists behave as nasal decongestants without cardiovascular actions in animal models of upper airway congestion.

  10. The alpha2C-adrenoceptor modulates GABA release in mouse striatum.

    Science.gov (United States)

    Zhang, Weilie; Ordway, Gregory A

    2003-04-10

    The alpha(2C)-adrenoceptor occurs in high density in the striatum relative to other brain regions, but its biological role in striatal physiology is perplexing because of the paucity of noradrenergic terminals in this region. In this study, mice with a targeted inactivation of the alpha(2C)-adrenoceptor gene (alpha(2C)-KO mice), and genetically related mice (WT mice), were used to study the potential role of the striatal alpha(2C)-adrenoceptor in modulating GABA release. Perfused brain slices were pre-loaded with [(3)H]GABA and were stimulated electrically. In WT mice, the alpha(2)-adrenoceptor agonist, UK14304 (brimonidine), significantly enhanced [(3)H]GABA release from striatal slices, while the alpha(2)-adrenoceptor antagonist, RX821002, alone evoked a significant decrease in [(3)H]GABA release. In alpha(2C)-KO mice, the effect of RX821002 was absent, while UK14304 retained its ability to enhance [(3)H]GABA release. Pharmacological depletion of monoamines in WT mice also abolished the effect of RX821002 on [(3)H]GABA release. In hippocampal slices, RX821002-induced reduction in [(3)H]GABA release was present in WT and alpha(2C)-KO mice. In the presence of tetrodotoxin, RX821002 increased [(3)H]GABA release in striatal slices from both WT and alpha(2C)-KO mice. Together, these data imply that alpha(2A)- and alpha(2C)-adrenoceptors are located on different neurons in the striatum, that alpha(2C)-adrenoceptor-mediated effects on striatal GABA release are mediated by an endogenous catecholamine that could be dopamine, and that the alpha(2C)-adrenoceptor effect of RX821002 does not occur at the GABAergic terminal.

  11. Pressure-structure relationships in the 10 K layered carbide halide superconductor Y2C2I2

    Science.gov (United States)

    Ahn, Kyungsoo; Kremer, Reinhard K.; Simon, Arndt; Marshall, William G.; Muñoz, Alfonso

    2016-09-01

    The electronic structures of the 10 K layered yttrium carbide halide superconductor Y2C2I2 is characterized by bands of low dispersion and narrow peak-valley features in the electronic density of states at the Fermi level. In order to investigate to what extent the superconducting properties can be modified by external pressure we have studied the pressure dependence of the superconducting critical temperature and the crystal structure of Y2C2I2 to pressures of 7.4 GPa. Up to ~2.5 GPa we observe an increase of T c from 10 K to about 12 K. A structural phase transition from a 1s to a 3s stacking variant occurs at about 2.5 GPa above which T c rapidly decreases to a value of ~7.5 K at 7.5 GPa. Density functional calculations corroborate the structural phase transition to occur at a critical cell volume of ~270 Å3 corresponding to a pressure of ~2.4 GPa, in good agreement with the experimental findings. The pressure dependence of T c and inter-atomic distances and angles are discussed with respect to the results of density functional calculations of the electronic and crystal structure.

  12. Pressure-structure relationships in the 10 K layered carbide halide superconductor Y2C2I2.

    Science.gov (United States)

    Ahn, Kyungsoo; Kremer, Reinhard K; Simon, Arndt; Marshall, William G; Muñoz, Alfonso

    2016-09-21

    The electronic structures of the 10 K layered yttrium carbide halide superconductor Y2C2I2 is characterized by bands of low dispersion and narrow peak-valley features in the electronic density of states at the Fermi level. In order to investigate to what extent the superconducting properties can be modified by external pressure we have studied the pressure dependence of the superconducting critical temperature and the crystal structure of Y2C2I2 to pressures of 7.4 GPa. Up to ~2.5 GPa we observe an increase of T c from 10 K to about 12 K. A structural phase transition from a 1s to a 3s stacking variant occurs at about 2.5 GPa above which T c rapidly decreases to a value of ~7.5 K at 7.5 GPa. Density functional calculations corroborate the structural phase transition to occur at a critical cell volume of ~270 Å(3) corresponding to a pressure of ~2.4 GPa, in good agreement with the experimental findings. The pressure dependence of T c and inter-atomic distances and angles are discussed with respect to the results of density functional calculations of the electronic and crystal structure.

  13. Neutron diffraction studies of magnetic ordering in superconducting ErNi2B2C and TmNi2B2C in an applied magnetic field

    DEFF Research Database (Denmark)

    Toft, Katrine Nørgaard

    along [110], the magnetic structure rotates a small angle of 0.5 degrees away from the symmetrydirection. TmNi2B2C: A magnetic field applied in the [100] direction suppresses the zero field magnetic structure QF = (0.094,0.094,0) (TN = 1.6 K), in favor of the Fermi surface nesting structure QN = (0......The field-induced magnetic structures of ErNi2B2C and TmNi2B2C in are especially interesting because the field suppresses the superconducting order parameter and therefore the magnetic properties can be studied while varying the strength ofsuperconductivity. ErNi2B2C: For magnetic fields along all...... three symmetry directions, the observed magnetic structures have a period corresponding to the Fermi surface nesting structure. The phase diagrams present all the observed magnetic structures.Two results remain unresolved: 1. When applying the magnetic field along [010], the minority domain (QNB = (0,Q...

  14. Role of cytochrome P450 2C8*3 (CYP2C8*3) in paclitaxel metabolism and paclitaxel-induced neurotoxicity

    DEFF Research Database (Denmark)

    Lee, Mi-Young; Apellániz-Ruiz, María; Johansson, Inger

    2015-01-01

    AIM: The CYP2C8*3 allele has been suggested as a risk factor for paclitaxel-induced neuropathy but the data hitherto published are conflicting. MATERIALS & METHODS: In total 435 patients were investigated with respect to maximum neuropathy grade and accumulated paclitaxel dose. The enzymatic prop...

  15. Structural and functional characterization of the coxsackievirus B3 CRE(2C): role of CRE(2C) in negative- and positive-strand RNA synthesis.

    NARCIS (Netherlands)

    Ooij, M.J. van; Vogt, D.A.; Paul, A.; Castro, C.; Kuijpers, J.M.; Kuppeveld, F.J.M. van; Cameron, C.E.; Wimmer, E.; Andino, R.; Melchers, W.J.G.

    2006-01-01

    A stem-loop element located within the 2C-coding region of the coxsackievirus B3 (CVB3) genome has been proposed to function as a cis-acting replication element (CRE). It is shown here that disruption of this structure indeed interfered with viral RNA replication in vivo and abolished uridylylation

  16. Cytochrome P450 2C24: expression, tissue distribution, high-throughput assay, and pharmacological inhibition

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2012-04-01

    Full Text Available Cytochrome P450 (CYP-mediated epoxidation of arachidonic acid (AA contributes to important biological functions, including the pain-relieving responses produced by analgesic drugs. However, the relevant epoxygenase(s remain unidentified. Presently, we describe the tissue distribution, high-throughput assay, and pharmacological characteristics of the rat epoxygenase CYP2C24. Following cloning from male rat liver, recombinant baculovirus containing the C-terminal His-tagged cDNA was constructed and used to express the protein in Spodoptera frugiperda (Sf9 cells. Enzymatic activity was detected with membranes, NADPH regenerating system and CYP reductase, and optimized for high throughput screening by use of the Vivid Blue© BOMCC fluorescence substrate. Quantitative real-time PCR identified CYP2C24 m-RNA in liver, kidney, heart, lung, gonad and brain. Screening of CYP2C24 activity against a panel of inhibitors showed a very strong correlation with activity against the human homologue CYP2C19. In agreement with recent findings on CYP2C19, the epoxygenase blockers PPOH and MS-PPOH inhibited CYP2C24 only weakly, confirming that these drugs are not universal epoxygenase inhibitors. Finally, comparisons of the CYP2C24 inhibitor profile with anti-analgesic activity suggests that this isoform does not contribute to brain analgesic drug action. The present methods and pharmacological data will aid in study of the biological significance of this CYP isoform.

  17. The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro.

    Science.gov (United States)

    Pan, Pei-Pei; Weng, Qing-Hua; Zhou, Chen-Jian; Wei, Yan-Li; Wang, Li; Dai, Da-Peng; Cai, Jian-Ping; Hu, Guo-Xin

    2016-02-01

    We aimed at investigating the role of CYP2C9 in carvedilol O-desmethylation and identifying the effect of 35 CYP2C9 allelic variants we found in Chinese Han population on the in vitro metabolism of carvedilol. Recombinant CYP2C9 and CYP2D6 microsomes of the wild type were used to test and verify the enzymes involved in carvedilol O-desmethylation. Recombinant CYP2C9 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity toward carvedilol. 2-100 μM carvedilol was incubated for 30 min at 37 °C. The products were detected using high-performance liquid chromatography. CYP2C9 plays a certain role in carvedilol metabolism. Compared with wild-type CYP2C9*1, the intrinsic clearance (V max/K m) values of all variants toward carvedilol O-desmethylation were significantly altered. The variants exhibited significantly decreased values (from 30 to 99.8 %) due to increased K m and/or decreased V max values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings complement the database where CYP2C9 polymorphism interacts with biotransformation of exogenous substances like drugs and toxins.

  18. In silico description of differential enantioselectivity in methoxychlor O-demethylation by CYP2C enzymes.

    Science.gov (United States)

    Bikádi, Zsolt; Hazai, Eszter

    2008-09-01

    Methoxychlor undergoes metabolism by cytochrome P450 (CYP) enzymes forming a chiral mono-phenolic derivative (Mono-OH-M) as main metabolite. In the current study, members of the CYP2C family were examined for their chiral preference in Mono-OH-M formation. CYP2C9 and CYP2C19 possessed high enantioselectivity favoring the formation of S-Mono-OH-M; CYP2C3 showed no enantioselectivity, whereas CYP2C5 slightly favored the formation of R-Mono-OH-M. Molecular modeling calculations were utilized in order to explain the observed differences in chiral preference of CYP2C enzymes. Molecular docking calculations could describe neither the existence of chiral preference in metabolism, nor the enantiomer which is preferentially formed. Molecular dynamic calculations were also carried out and were found to be useful for accurate description of chiral preference in biotransformation of methoxychlor by CYP2C enzymes. An in silico model capable of predicting chiral preference in cytochrome P450 enzymes in general can be developed based on the analysis of the stability and rigidity parameters of interacting partners during molecular dynamic simulation.

  19. MEF2C mediates the effect of microRNA-214 on inhibiting cardiomyocyte hypertrophy

    Institute of Scientific and Technical Information of China (English)

    TANG Chun-mei; ZHU Jie-ning; ZHU Wen-si; LIN Qiu-xiong; HU Zhi-qin; FU Yong-heng; ZHANG Meng-zhen; SHAN Zhi-xin

    2016-01-01

    AIM:To investigate the effect of miR-214 on cardiomyocyte hypertrophy and the expression of the potential target genes . METHODS:A cell model of hypertrophy was established based on angiotensin-Ⅱ( Ang-Ⅱ)-induced neonatal mouse ventricular car-diomyocytes (NMVCs).Dual luciferase reporter assay was performed to verify the interaction between miR-214 and the 3’ UTR of MEF2C.The expression of MEF2C and hypertrophy-related genes at mRNA and protein levels was determined by RT-qPCR and Wes-tern blotting, respectively.RESULTS:The expression of ANP, ACTA1,β-MHC and miR-214 was markedly increased in Ang-Ⅱ-in-duced hypertrophic cardiomyocytes .Dual luciferase reporter assay revealed that miR-214 interacted with the 3’ UTR of MEF2C, and miR-214 was verified to inhibit MEF2C expression at the transcriptional level .The protein expression of MEF2C was markedly in-creased in the hypertrophic cardiomyocytes .Moreover, miR-214 mimic, in parallel to MEF2C siRNA, inhibited the expression of hy-pertrophy-related genes in Ang-Ⅱ-induced NMVCs.CONCLUSION:MEF2C is a target gene of miR-214, which mediates the effect of miR-214 on attenuating cardiomyocyte hypertrophy .

  20. Regulation of adipogenesis by nucelar receptor PPARγ is modulated by the histone demethylase JMJD2C

    Directory of Open Access Journals (Sweden)

    Lizcano Fernando

    2011-01-01

    Full Text Available A potential strategy to combat obesity and its associated complications involves modifying gene expression in adipose cells to reduce lipid accumulation. The nuclear receptor Peroxisome Proliferator-activated receptor gamma (PPARγ is the master regulator of adipose cell differentiation and its functional activation is currently used as a therapeutic approach for Diabetes Mellitus type 2. However, total activation of PPARγ induces undesirable secondary effects that might be set with a partial activation. A group of proteins that produce histone demethylation has been shown to modify the transcriptional activity of nuclear receptors. Here we describe the repressive action of the jumonji domain containing 2C/lysine demethylase 4 C (JMJD2C/KDM4C on PPARγ transcriptional activation. JMJD2C significantly reduced the rosiglitazone stimulated PPARγ activation. This effect was mainly observed in experiments performed using the Tudor domains that may interact with histone deacetylase class 1 (HDAC and this interaction probably reduces the mediated activation of PPARγ. Trichostatin A, a HDAC inhibitor, reduces the repressive effect of JMJD2C. When JMJD2C was over-expressed in 3T3-L1 cells, a reduction of differentiation was observed with the Tudor domain. In summary, we herein describe JMJD2C-mediated reduction of PPARgamma transcriptional activation as well as preadipocyte differentiation. This novel action of JMJD2C might have an important role in new therapeutic approaches to treat obesity and its complications.

  1. Growth hormone-regulated periportal expression of CYP2C7 in rat liver.

    Science.gov (United States)

    Oinonen, T; Ronis, M; Wigell, T; Tohmo, K; Badger, T; Lindros, K O

    2000-03-01

    Most drug- and steroid-metabolizing cytochrome P450 (CYP) enzymes are expressed in the mammalian liver in a characteristic zonated pattern, with high expression in the downstream perivenous (centrilobular) region. Here, we report that CYP2C7, a member of the rat CYP2 family, is expressed preferentially in the opposite, periportal region. CYP2C7 mRNA, as detected by reverse transcription-polymerase chain reaction, was detected almost exclusively in cell lysates obtained from the periportal region, indicating a very steep acinar gradient. The amount of immunoreactive CYP2C7 protein in periportal cell lysates was also higher than in samples from the perivenous region. This gradient was reversed by hypophysectomy, which markedly and selectively reduced the periportal CYP2C7 protein content. Subsequent growth hormone infusion by osmotic minipumps restored the zonation by selectively increasing the amount of periportal CYP2C7 protein. Although hypophysectomy suppressed CYP2C7 mRNA and growth hormone counteracted it, regulation at this level did not appear to occur in a zone-specific fashion. This indicates that growth hormone-mediated zonal regulation of CYP2C7 protein has additional translational or posttranslational components. Ethanol treatment, which has been shown to affect growth hormone levels, significantly induced CYP2C7 mRNA, but not zone specifically. Our results demonstrate that growth hormone up-regulates the CYP2C7 gene by enhancing the expression of the protein specifically in the periportal liver region. Growth hormone may up-regulate other periportally expressed liver genes in a similar fashion.

  2. Strategies for purifying variants of human rhinovirus 14 2C protein.

    Science.gov (United States)

    Sára, Tomáš; Konrat, Robert; Skern, Tim

    2014-03-01

    The positive strand RNA genome of picornaviruses, including human rhinovirus (HRV), poliovirus (PV) and foot-and-mouth disease virus, is translated immediately into a polyprotein that is cleaved by virally encoded proteinases into 10-13 mature proteins. These include the four proteins required to assemble the viral particle as well as 3D(pol) (the viral RNA polymerase) and 2C, an ATPase and putative helicase. 2C is a protein which is responsible, together with 2B and 3A, for anchoring the replication complexes to membranous structures in the infected cell on which RNA replication takes place. Additionally, expression of 2C and its precursor 2BC in mammalian cells leads to vesicle formation observed in infected cells. 2C is encoded by all picornaviruses; nevertheless, its exact role in viral replication remains unclear. A contributing factor is the absence of structural data for this hydrophobic protein the generation of which has been hampered by an inability to produce soluble and stable material. Here, we compare 2C from several genera and show that the 2C protein has considerable heterogeneity. Using protein structure meta-analysis, we developed models of HRV14 2C that should be useful for mutational analysis. Based on these analyses, we expressed and purified two domains of HRV14 2C using three different protocols and examined the folding by thermal denaturation or (1)H NMR. Both domains were concentrated sufficiently to allow crystal screens or NMR pilot experiments to be performed. This work provides a platform to explore 2C proteins from all picornaviral genera to generate candidates for structural analysis.

  3. High energy factorization predictions for the charm structure function $F_{2}^{c}$ at HERA

    CERN Document Server

    Munier, S

    1998-01-01

    High energy factorization predictions for F2^c are derived using BFKL descriptions of the proton structure function F2 at HERA. The model parameters are fixed by a fit of F2 at small x. Two different approaches of the non perturbative proton input are shown to correspond to the factorization at the gluon or quark level, respectively. The predictions for F2^c are in agreement with the data within the present error bars. However, the photon wave-function formulation (factorization at quark level) predicts significantly higher F2^c than both gluon factorization and a next-leading order DGLAP model.

  4. Clinically significant CYP2C inhibition by noscapine but not by glucosamine.

    Science.gov (United States)

    Rosenborg, S; Stenberg, M; Otto, S; Ostervall, J; Masquelier, M; Yue, Q-Y; Bertilsson, L; Eliasson, E

    2010-09-01

    Noscapine and glucosamine reportedly interact with warfarin. We investigated the effects of these drugs on various cytochrome P450 (CYP) activity markers. Twelve healthy subjects were phenotyped at baseline and during separate treatments with noscapine and glucosamine. Whereas glucosamine had no significant effect on CYP activity, noscapine caused marked inhibition of CYP2C9 (4.9-fold increase in urinary losartan/E3174 ratio) and CYP2C19 (3.6-fold increase in the plasma omeprazole/5-hydroxyomeprazole ratio). Noscapine-dependent inhibition of CYP2C9 may explain the interaction with warfarin.

  5. Electrochemical Synthesis of Mo2C Catalytical Coatings for the Water-Gas Shift Reaction

    Science.gov (United States)

    Kuznetsov, Sergey A.; Dubrovskiy, Anton R.; Rebrov, Evgeny V.; Schouten, Jaap C.

    2007-11-01

    The electroreduction of CO32- ions on a molybdenum cathode in a NaCl-KCl-Li2CO3 melt was studied by cyclic voltammetry. The electrochemical synthesis of Mo2C on molybdenum substrates has been performed at 1123 K for 7 h with a cathodic current density of 5 mA cm-2. If molybdenum carbide is present as a thin (ca. 500 nm) film on a molybdenum substrate (Mo2C/Mo), its catalytic activity in the water gas-shift reaction is enhanced by at least an order of magnitude compared to that of the bulk Mo2C phase.

  6. CYP2C9 genotype does not affect risk of tobacco-related cancer in the general population

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Nordestgaard, B.G.; Bojesen, S.E.

    2010-01-01

    Background: CYP2C9 enzymes are important in the metabolism of procarcinogenic chemicals such as polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke. Two functional variants in the CYP2C9 gene (CYP2C9*2 and CYP2C9*3) are known to be associated with decreased enzyme activity towards tolb...

  7. Graphene-Based Patterning and Differentiation of C2C12 Myoblasts

    DEFF Research Database (Denmark)

    Bajaj, Piyush; Rivera, Jose A; Marchwiany, Daniel

    2014-01-01

    This study aims at generating highly aligned functional myotubes using graphene as the underlying scaffold. Graphene not only supports the growth of C2C12 muscle cells but also enhances its differentiation and leads to spontaneous patterning of myotubes....

  8. Northwestern Hawaiian Islands (NWHI) photo-quadrat monitoring data table : Site number MID P2c

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This spreadsheet summarizes the number of corals photographed along a 26-meter transect line at Underwater Site P2-C at Midway Atoll in the Northwestern Hawaiian...

  9. Possible coexistence of superconductivity and magnetic order in NdPt2B2C

    Indian Academy of Sciences (India)

    S K Dhar; A D Chinchure; E Alleno; C Godart; L C Gupta; R Nagarajan

    2002-05-01

    Coexistence of superconductivity and magnetic order has been one of the exciting aspects of the quaternary borocarbide superconductors. So far, RNi2B2C (R=Tm, Er, Ho and Dy) are the only known magnetic superconductors in this family. Here, we present our resistivity, magnetization and heat capacity studies on NdPt2B2C (nominal composition, NdPt1.5Au0.6B2C and NdPt2.1B2.4C1.2). We find superconductivity in both samples with c,onset∼ 3 K. Bulk magnetic order is found to occur below 1.7 K. We suggest that NdPt2B2C is a possible magnetic superconductor.

  10. Surface Turbulent Fluxes, 1x1 deg Yearly Climatology, Set1 and NCEP V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are the Goddard Satellite-based Surface Turbulent Fluxes Version-2c Dataset recently produced through a MEaSURES funded project led by Dr. Chung-Lin Shie...

  11. Surface Turbulent Fluxes, 1x1 deg Seasonal Climatology, Set1 and NCEP V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are the Goddard Satellite-based Surface Turbulent Fluxes Version-2c Dataset recently produced through a MEaSUREs funded project led by Dr. Chung-Lin Shie...

  12. Ultra-rapid processing of refractory carbides; 20 s synthesis of molybdenum carbide, Mo2C.

    Science.gov (United States)

    Vallance, Simon R; Kingman, Sam; Gregory, Duncan H

    2007-02-21

    The microwave synthesis of molybdenum carbide, Mo(2)C, from carbon and either molybdenum metal or the trioxide has been achieved on unprecedented timescales; Ex- and in-situ characterisation reveals key information as to how the reaction proceeds.

  13. Detection of ATP2C1 Gene Mutation in Familial Benign Chronic Pemphigus

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The ATP2C1 gene mutation in one case of familial benign chronic pemphigus was investigated.One patient was diagnosed as familial benign chronic pemphigus by pathology, ultrastructral examination and clinical features. Genomic DNA was extracted from blood samples. Mutation of ATP2C1 gene was detected by polymerase chain reaction (PCR) and DNA sequencing. The results showed that deletion mutation was detected in ATP2C1 gene in this patient, which was 2374delTTTG. No mutation was found in the family members and normal individuals. It was concluded that the 2374delTTTG mutation in ATP2C1 gene was the specific mutation for the clinical phenotype for this patient and was a de novo mutation.

  14. Classification of gradient space of dimension 8 by a reducible sl(2,C)action

    Institute of Scientific and Technical Information of China (English)

    YAU; Stephen; S.-T.

    2009-01-01

    This paper deals with a reducible sl(2,C)action on the formal power series ring.The purpose of this paper is to confirm a special case of the Yau conjecture:Suppose that sl(2,C)acts on the formal power series ring via(1.1).Then I(f)=(li 1 )⊕(il2 )⊕···⊕(lis)modulo some one dimensional sl(2,C)representations where(i)is an irreducible sl(2,C)representation of i dimension and{li1 ,li2 ,...,lis }{ll1,ll2,...,lr}.Unlike classical invariant theory which deals only with irreducible action and 1-dimensional representations,we treat the reducible action and higher dimensional representations successively.

  15. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Neutron scattering study of Na2C60 in the pressure-temperature plane

    Science.gov (United States)

    Yildirim, T.; Neumann, D. A.; Trevino, S. F.; Fischer, J. E.

    1999-10-01

    Na2C60 is the only known fulleride with divalent C60 and orientational order (Pa3¯ symmetry). We investigated the phase behavior of Na2C60 for 0200 K and P>1 kbar, the structure is transformed into a low-symmetry distorted phase. Here the peaks at low Q are significantly broadened while the high Q peaks are almost completely smeared out. This transformation is reversible; releasing pressure above 200 K recovers the cubic Pa3¯ structure.

  17. Synthesis and Performance of Tungsten Disulfide/Carbon (WS2/C) Composite as Anode Material

    Science.gov (United States)

    Yuan, Zhengyong; Jiang, Qiang; Feng, Chuanqi; Chen, Xiao; Guo, Zaiping

    2017-09-01

    The precursors of an amorphous WS2/C composite were synthesized by a simple hydrothermal method using Na2WO4·2H2O and CH3CSNH2 as raw materials, polyethylene glycol as dispersant, and glucose as the carbon source. The as-synthesized precursors were further annealed at a low temperature in flowing argon to obtain the final materials (WS2/C composite). The structure and morphology of the WS2/C composite were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, and scanning electron microscopy. The electrochemical properties were tested by galvanostatic charge/discharge testing and alternating current (AC) impedance measurements. The results show that the as-prepared amorphous WS2/C composite features both high specific capacity and good cycling performance at room temperature within the potential window from 3.0 V to 0.01 V (versus Li+/Li) at current density of 100 mAg-1. The achieved initial discharge capacity was 1080 mAhg-1, and 786 mAhg-1 was retained after 170 cycles. Furthermore, the amorphous WS2/C composite exhibited a lower charge/discharge plateau than bare WS2, which is more beneficial for use as an anode. The cyclic voltammetry and AC impedance testing further confirmed the change in the plateau and the decrease in the charge transfer resistance in the WS2/C composite. The chemical formation process and the electrochemical mechanism of the WS2/C composite are also presented. The amorphous WS2/C composite can be used as a new anode material for future applications.

  18. Estradiol increases the anorexia associated with increased 5-HT2C receptor activation in ovariectomized rats

    OpenAIRE

    Rivera, Heidi M.; Santollo, Jessica; Nikonova, Larissa V.; Eckel, Lisa A.

    2011-01-01

    Estradiol’s inhibitory effect on food intake is mediated, in part, by its ability to increase the activity of meal-related signals, including serotonin (5-HT), which hasten satiation. The important role that postsynaptic 5-HT2C receptors play in mediating 5-HT’s anorexigenic effect prompted us to investigate whether a regimen of acute estradiol treatment increases the anorexia associated with increased 5-HT2C receptor activation in ovariectomized (OVX) rats. We demonstrated that intraperitone...

  19. Optical and structural characterization of the Co/Mo2C/Y system

    Science.gov (United States)

    Yuan, Yanyan; Le Guen, Karine; André, Jean-Michel; Wang, Zhanshan; Zhu, Jingtao; Mény, Christian; Jonnard, Philippe

    2014-10-01

    We study the thermal behaviour of a tri-layer multilayer, designed by inserting a third material, yttrium, into the previously studied Co/Mo2C system. The system is designed to work at near-normal incidence at the wavelength of 14.1 nm. The theoretical reflectivity of Co-based multilayer (Co/Mo2C/Y system) is improved up to 54% after the addition of yttrium. Two types of multilayers with different orders of yttrium layer are deposited: Co/Mo2C/Y and Co/Y/Mo2C. The samples are annealed up to 600 °C. The multilayers were characterized using hard x-ray and extreme ultraviolet reflectivity, nuclear magnetic resonance (NMR) spectroscopy and x-ray diffraction (XRD). The results show that the reflectivity of the Co/Mo2C/Y multilayer is 27.5% at near normal incidence around 14.6 nm for as-deposited sample, and then it decreases gradually after annealing up to 600 °C. A significant period compression is observed from 300 °C annealing and above. The Co/Y/Mo2C multilayer shows low reflectivity, less than 2.5%. NMR spectra reveal that the pure Co layers are completely mixed with other elements since there is no signal from ferromagnetic Co in the annealing samples of the Co/Mo2C/Y multilayer and all Co/Y/Mo2C samples. Based on the NMR and XRD results, we fit the EUV data for both multilayers with two different models in one period taking into account the formation of the interfacial compounds.

  20. M2C Precipitate in Isothermal Tempering of High Co-Ni Alloy Steel

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The ultra-strength alloy steel with high content of Co and Ni is typical tempering martensite steel, and the secondary hardening is accomplished by the precipitation of fine scale alloy carbides with black-white contrast until peak-hardening. The crystal structure of precipitates was well determined as M2C with hexagonal by micro-beam diffraction. Observing in HREM, M2C carbides were shown coherent with the ferrite matrix completely and have their own structure.

  1. SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist.

    Science.gov (United States)

    Sard, Howard; Kumaran, Govindaraj; Morency, Cynthia; Roth, Bryan L; Toth, Beth Ann; He, Ping; Shuster, Louis

    2005-10-15

    An SAR study of psilocybin and psilocin derivatives reveals that 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor. The corresponding phosphate derivative, 1-methylpsilocybin, shows efficacy in an animal model for obsessive-compulsive disorder, as does 4-fluoro-N,N-dimethyltryptamine. These results suggest a new area for development of novel 5-HT(2C) agonists with applications for drug discovery.

  2. An ANFIS-based on B2C electronic commerce transaction

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Juan, E-mail: linjuanliucaihong@qq.com [Department of Mathematics and Computer Science, Fuqing Branch of Fujian Normal University, Fuqing 350300 (China); Liu, Chenlian, E-mail: chenglian.liu@gmail.com [School of Mathematics and Computer Science, Long Yan University, Longyan 364012 (China); Guo, Yongning, E-mail: guoyn@163.com [Fuqing Branch of Fujian Normal University, Fuqing 350300 (China)

    2014-10-06

    The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion.

  3. An ANFIS-based on B2C electronic commerce transaction

    Science.gov (United States)

    Lin, Juan; Liu, Chenlian; Guo, Yongning

    2014-10-01

    The purpose of this study is to use an adaptive-network-based fuzzy inference system to model a fuzzy logic-based system (FIS) for supporting decision-making process in B2C electronic commerce transaction. Firstly we introduce FIS in B2C electronic commerce transaction and ANFIS. Then we use ANFIS to model FIS with different membership functions(MF). Lastly we give a conclusion.

  4. Phylodynamics of hepatitis C virus subtype 2c in the province of Cordoba, Argentina.

    Directory of Open Access Journals (Sweden)

    Viviana E Ré

    Full Text Available The Hepatitis C Virus Genotype 2 subtype 2c (HCV-2c is detected as a low prevalence subtype in many countries, except in Southern Europe and Western Africa. The current epidemiology of HCV in Argentina, a low-prevalence country, shows the expected low prevalence for this subtype. However, this subtype is the most prevalent in the central province of Córdoba. Cruz del Eje (CdE, a small rural city of this province, shows a prevalence for HCV infections of 5%, being 90% of the samples classified as HCV-2c. In other locations of Córdoba Province (OLC with lower prevalence for HCV, HCV-2c was recorded in about 50% of the samples. The phylogenetic analysis of samples from Córdoba Province consistently conformed a monophyletic group with HCV-2c sequences from all the countries where HCV-2c has been sequenced. The phylogeographic analysis showed an overall association between geographical traits and phylogeny, being these associations significant (α = 0.05 for Italy, France, Argentina (places other than Córdoba, Martinique, CdE and OLC. The coalescence analysis for samples from CdE, OLC and France yielded a Time for the Most Common Recent Ancestor of about 140 years, whereas its demographic reconstruction showed a "lag" phase in the viral population until 1880 and then an exponential growth until 1940. These results were also obtained when each geographical area was analyzed separately, suggesting that HCV-2c came into Córdoba province during the migration process, mainly from Europe, which is compatible with the history of Argentina of the early 20th century. This also suggests that the spread of HCV-2c occurred in Europe and South America almost simultaneously, possibly as a result of the advances in medicine technology of the first half of the 20th century.

  5. Heat and charge transport in YNi{sub 2}B{sub 2}C and HoNi{sub 2}B{sub 2}C single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M; Gladun, A; Kreyssig, A [Institut fuer Festkoerperphysik, Technische Universitaet Dresden, D-01062 Dresden (Germany); Wosnitza, J [Hochfeld-Magnetlabor Dresden (HLD), Forschungszentrum Dresden-Rossendorf, D-01314 Dresden (Germany); Petzold, V; Rosner, H [Max-Planck-Institut fuer Chemische Physik fester Stoffe, D-01187 Dresden (Germany); Behr, G; Souptel, D; Mueller, K-H; Drechsler, S-L; Fuchs, G [Leibniz-Institut fuer Festkoerper- und Werkstoffforschung Dresden (IFW), D-01171 Dresden (Germany)], E-mail: M.Schneider@ifw-dresden.de, E-mail: G.Fuchs@ifw-dresden.de

    2008-04-30

    For a systematic investigation of the heat- and charge-transport properties of YNi{sub 2}B{sub 2}C and HoNi{sub 2}B{sub 2}C, single-crystal measurements of the electrical resistivity, the thermal conductivity, and the thermoelectric power were performed on the same samples. For HoNi{sub 2}B{sub 2}C, a local maximum of the Lorenz number at 20 K is evidently connected with the occurrence of magnetic fluctuations well above the ordering temperature. For the in-plane thermal conductivity, a kink near the superconducting transition was observed, consistent with an anisotropic gap or a multiband description. For both investigated borocarbides, the electrical resistance is isotropic. In contrast, the thermal conductivity shows a pronounced anisotropy. The thermoelectric power exhibits a minor anisotropy and can be well described by electron-diffusion and phonon-drag contributions over a wide temperature range. Based on an analysis of full-potential local-orbital calculations, a strong influence of the boron z position on the thermoelectric power has been revealed.

  6. New polymorphisms in human MEF2C gene as potential modifier of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Alonso-Montes, Cristina; Naves-Diaz, Manuel; Fernandez-Martin, Jose Luis; Rodriguez-Reguero, Julian; Moris, Cesar; Coto, Eliecer; Cannata-Andia, Jorge B; Rodriguez, Isabel

    2012-09-01

    Hypertrophic cardiomyopathy is caused by mutations in genes encoding sarcomeric proteins. Its variable phenotype suggests the existence of modifier genes. Myocyte enhancer factor (MEF) 2C could be important in this process given its role as transcriptional regulator of several cardiac genes. Any variant affecting MEF2C expression and/or function may impact on hypertrophic cardiomyopathy clinical manifestations. In this candidate gene approach, we screened 209 Caucasian hypertrophic cardiomyopathy patients and 313 healthy controls for genetic variants in MEF2C gene by single-strand conformation polymorphism analysis and direct sequencing. Functional analyses were performed with transient transfections of luciferase reporter constructions. Three new variants in non-coding exon 1 were found both in patients and controls with similar frequencies. One-way ANOVA analyses showed a greater left ventricular outflow tract obstruction (p = 0.011) in patients with 10C+10C genotype of the c.-450C(8_10) variant. Moreover, one patient was heterozygous for two rare variants simultaneously. This patient presented thicker left ventricular wall than her relatives carrying the same sarcomeric mutation. In vitro assays additionally showed a slightly increased transcriptional activity for both rare MEF2C alleles. In conclusion, our data suggest that 15 bp-deletion and C-insertion in the 5'UTR region of MEF2C could affect hypertrophic cardiomyopathy, potentially by affecting expression of MEF2C and therefore, the expression of their target cardiac proteins that are implicated in the hypertrophic process.

  7. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; Maldonado, Carola; Adasme, Tatiana; Carrasco, Loreto; Ocaranza, Paula; Bravo, Roberto; Gonzalez, Leticia; Diaz-Araya, Guillermo [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Hidalgo, Cecilia [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Lavandero, Sergio, E-mail: slavander@uchile.cl [Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile); Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)

    2009-10-09

    Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

  8. Decreased serotonin2C receptor responses in male patients with schizophrenia.

    Science.gov (United States)

    Lee, Myung Ae; Jayathilake, Karuna; Sim, Min Young; Meltzer, Herbert Y

    2015-03-30

    Serotonin (5-HT)2C receptors in brain affect psychosis, reward, substance abuse, anxiety, other behaviors, appetite, body temperature, and other physiological measures. They also have been implicated in antipsychotic drug efficacy and side effects. We previously reported that the hyperthermia following administration of MK-212, a predominantly 5-HT(2C) receptor agonist, was diminished in a small sample of patients with schizophrenia (SCH), suggesting decreased 5-HT(2C) receptor responsiveness. We have now studied the responses to oral MK-212 and placebo in a larger sample of unmedicated male SCH (n = 69) and normal controls (CON) (n = 33), and assessed the influence of comorbid substance abuse (SA) on oral body temperature, behavioral responses, etc. The placebo-adjusted oral body temperature response to MK-212 was significantly lower in SCH compared to CON and not significantly different between the SCH with or without SA. Some behavioral responses to MK-212, e.g. self-rated feelings of increased anxiety, depression and decreased calmness, or good overall feeling, were significantly lower in the SCH patients compared to CON. These results add to the evidence for diminished 5-HT(2C) receptor responsiveness in SCH patients compared to CON and are consistent with reported association of HTR(2C) polymorphisms, leading to decreased expression or function of the HTR(2C) in patients with SCH.

  9. TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling.

    Science.gov (United States)

    Woodfield, George W; Horan, Annamarie D; Chen, Yizhen; Weigel, Ronald J

    2007-09-15

    Breast cancers expressing estrogen receptor-alpha (ERalpha) are associated with a favorable biology and are more likely to respond to hormonal therapy. In addition to ERalpha, other pathways of estrogen response have been identified including ERbeta and GPR30, a membrane receptor for estrogen, and the key mechanisms regulating expression of ERs and hormone response remain controversial. Herein, we show that TFAP2C is the key regulator of hormone responsiveness in breast carcinoma cells through the control of multiple pathways of estrogen signaling. TFAP2C regulates the expression of ERalpha directly by binding to the ERalpha promoter and indirectly via regulation of FoxM1. In so doing, TFAP2C controls the expression of ERalpha target genes, including pS2, MYB, and RERG. Furthermore, TFAP2C controlled the expression of GPR30. In distinct contrast, TFAP2A, a related factor expressed in breast cancer, was not involved in estrogen-mediated pathways but regulated expression of genes controlling cell cycle arrest and apoptosis including p21(CIP1) and IGFBP-3. Knockdown of TFAP2C abrogated the mitogenic response to estrogen exposure and decreased hormone-responsive tumor growth of breast cancer xenografts. We conclude that TFAP2C is a central control gene of hormone response and is a novel therapeutic target in the design of new drug treatments for breast cancer.

  10. A new 2D monolayer BiXene, M2C (M = Mo, Tc, Os).

    Science.gov (United States)

    Sun, Weiwei; Li, Yunguo; Wang, Baotian; Jiang, Xue; Katsnelson, Mikhail I; Korzhavyi, Pavel; Eriksson, Olle; Di Marco, Igor

    2016-08-25

    The existence of BiXenes, a new family of 2D monolayers, is hereby predicted. Theoretically, BiXenes have 1H symmetry (P6[combining macron]m2) and can be formed from the 4d/5d binary carbides. As the name suggests, they are close relatives of MXenes, which instead have 1T symmetry (P3[combining macron]m1). The newly found BiXenes, as well as some new MXenes, are shown to have formation energies close to that of germanene, which suggests that these materials should be possible to be synthesised. Among them, we illustrate that 1H-Tc2C and 1T-Mo2C are dynamically stable at 0 K, while 1H-Mo2C, 1T-Tc2C, 1H-Os2C, and 1T-Rh2C are likely to be stabilised via strain or temperature. In addition, the nature of the chemical bonding is analysed, emphasizing that the covalency between the transition metal ions and carbon is much stronger in BiXenes than in MXenes. The emergence of BiXenes can not only open up a new era of conducting 2D monolayers, but also provide good candidates for carrier materials aimed at energy storage and spintronic devices that have already been unveiled in MXenes.

  11. Evidence for conventional superconducting behavior in noncentrosymmetric Mo3Al2C

    Science.gov (United States)

    Bonalde, I.; Kim, H.; Prozorov, R.; Rojas, C.; Rogl, P.; Bauer, E.

    2011-10-01

    We report on measurements of the magnetic penetration depth of polycrystalline samples of nonmagnetic Mo3Al2C (Tc=9 K) without inversion symmetry. Two previous specific-heat measurements in this compound found different anomalous peaks in the low-temperature limit. One of these peaks was attributed to the superconducting transition at 3 K of the impurity phase Mo2C. We argue here that the second anomalous peak may be caused by the superconducting transition of SiC:Al at 1.45 K, another impurity phase possibly present in Mo3Al2C samples. The temperature-independent behavior of the penetration depth observed below 0.5 K is taken as firm evidence for the presence of a nodeless superconducting gap in Mo3Al2C. Numerical calculations using the BCS expression for the penetration depth give qualitative support for an isotropic energy gap in Mo3Al2C. The present results suggest that Mo3Al2C is a conventional s-wave superconductor, although two-gap or anisotropic-gap superconductivity cannot be ruled out.

  12. Nickel and potassium co-modified β-Mo2C catalyst for CO conversion

    Institute of Scientific and Technical Information of China (English)

    Minglin Xiang; Juan Zou; Debao Li; Wenhuai Li; Yuhan Sun; Xichun She

    2009-01-01

    Nickel and potassium co-medified β-Mo2C catalysts were prepared and used for CO hydrogenation reaction. The major products over β-Mo2C were C1-C4 hydrocarbons, only few alcohols were obtained. Addition of potassium resulted in remarkable selectivity shift from hydrocarbons to alcohols at the expense of CO conversion over β-Mo2C. Moreover, it was found that potassium enhanced the ability of chain propagation with a higher C2+OH production. Modified by nickel, β-Mo-2C showed a relatively high CO conversion, however, the products were similar to those of pure β-Mo2C. When co-modified by nickel and potassium,β-Mo2C exhibited high activity and selectivity towards mixed alcohols synthesis, and also the whole chain propagation to produce alcohols especially for the stage of C1OH to C2OH was remarkably enhanced. It was concluded that the Ni and K had, to some extent, synergistic effect on CO conversion.

  13. Selective deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo{sub 2}C) surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Ke [Catalysis Center for Energy Innovation, Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716 (United States); Yu, Weiting [Chemical Engineering, Columbia University, New York, NY 10027 (United States); Chen, Jingguang G., E-mail: jgchen@columbia.edu [Chemical Engineering, Columbia University, New York, NY 10027 (United States)

    2014-12-30

    Highlights: • Mo{sub 2}C surface can deoxygenate propanal and 1-propanol to produce propene through a similar intermediate (propoxide or η{sup 2}(C,O)-propanal). • Mo{sub 2}C surface can deoxygenate furfural and furfuryl alcohol to make 2-methylfuran through a 2-methylfuran-like intermediate. • The presence of furan ring modifies the selectivity between deoxygenation and hydrogenation/dehydrogenation pathways. - Abstract: The selective deoxygenation of aldehydes and alcohols without cleaving the C-C bond is crucial for upgrading bio-oil and other biomass-derived molecules to useful fuels and chemicals. In this work, propanal, 1-propanol, furfural and furfuryl alcohol were selected as probe molecules to study the deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo{sub 2}C) prepared over a Mo(1 1 0) surface. The reaction pathways were investigated using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS). The deoxygenation of propanal and 1-propanol went through a similar intermediate (propoxide or η{sup 2}(C,O)-propanal) to produce propene. The deoxygenation of furfural and furfuryl alcohol produced a surface intermediate similar to adsorbed 2-methylfuran. The comparison of these results revealed the promising deoxygenation performance of Mo{sub 2}C, as well as the effect of the furan ring on the selective deoxygenation of the C=O and C-OH bonds.

  14. Dynamic 5-HT2C receptor editing in a mouse model of obesity.

    Directory of Open Access Journals (Sweden)

    Harriët Schellekens

    Full Text Available The central serotonergic signalling system has been shown to play an important role in appetite control and the regulation of food intake. Serotonin exerts its anorectic effects mainly through the 5-HT(1B, 5-HT(2C and 5-HT(6 receptors and these are therefore receiving increasing attention as principal pharmacotherapeutic targets for the treatment of obesity. The 5-HT(2C receptor has the distinctive ability to be modified by posttranscriptional RNA editing on 5 nucleotide positions (A, B, C, D, E, having an overall decreased receptor function. Recently, it has been shown that feeding behaviour and fat mass are altered when the 5-HT(2C receptor RNA is fully edited, suggesting a potential role for 5-HT(2C editing in obesity. The present studies investigate the expression of serotonin receptors involved in central regulation of food intake, appetite and energy expenditure, with particular focus on the level of 5-HT(2C receptor editing. Using a leptin-deficient mouse model of obesity (ob/ob, we show increased hypothalamic 5-HT(1A receptor expression as well as increased hippocampal 5-HT(1A, 5-HT(1B, and 5-HT(6 receptor mRNA expression in obese mice compared to lean control mice. An increase in full-length 5-HT(2C expression, depending on time of day, as well as differences in 5-HT(2C receptor editing were found, independent of changes in total 5-HT(2C receptor mRNA expression. This suggests that a dynamic regulation exists of the appetite-suppressing effects of the 5-HT(2C receptor in both the hypothalamus and the hippocampus in the ob/ob mice model of obesity. The differential 5-HT(1A, 5-HT(1B and 5-HT(6 receptor expression and altered 5-HT(2C receptor editing profile reported here is poised to have important consequences for the development of novel anti-obesity therapies.

  15. Genome-wide and expression analysis of protein phosphatase 2C in rice and Arabidopsis

    Directory of Open Access Journals (Sweden)

    Jakab Stephen

    2008-11-01

    Full Text Available Abstract Background The protein phosphatase 2Cs (PP2Cs from various organisms have been implicated to act as negative modulators of protein kinase pathways involved in diverse environmental stress responses and developmental processes. A genome-wide overview of the PP2C gene family in plants is not yet available. Results A comprehensive computational analysis identified 80 and 78 PP2C genes in Arabidopsis thaliana (AtPP2Cs and Oryza sativa (OsPP2Cs, respectively, which denotes the PP2C gene family as one of the largest families identified in plants. Phylogenic analysis divided PP2Cs in Arabidopsis and rice into 13 and 11 subfamilies, respectively, which are supported by the analyses of gene structures and protein motifs. Comparative analysis between the PP2C genes in Arabidopsis and rice identified common and lineage-specific subfamilies and potential 'gene birth-and-death' events. Gene duplication analysis reveals that whole genome and chromosomal segment duplications mainly contributed to the expansion of both OsPP2Cs and AtPP2Cs, but tandem or local duplication occurred less frequently in Arabidopsis than rice. Some protein motifs are widespread among the PP2C proteins, whereas some other motifs are specific to only one or two subfamilies. Expression pattern analysis suggests that 1 most PP2C genes play functional roles in multiple tissues in both species, 2 the induced expression of most genes in subfamily A by diverse stimuli indicates their primary role in stress tolerance, especially ABA response, and 3 the expression pattern of subfamily D members suggests that they may constitute positive regulators in ABA-mediated signaling pathways. The analyses of putative upstream regulatory elements by two approaches further support the functions of subfamily A in ABA signaling, and provide insights into the shared and different transcriptional regulation machineries in dicots and monocots. Conclusion This comparative genome-wide overview of the PP

  16. Renormalized Volume

    CERN Document Server

    Gover, A Rod

    2016-01-01

    For any conformally compact manifold with hypersurface boundary we define a canonical renormalized volume functional and compute an explicit, holographic formula for the corresponding anomaly. For the special case of asymptotically Einstein manifolds, our method recovers the known results. The anomaly does not depend on any particular choice of regulator, but the coefficients of divergences do. We give explicit formulae for these divergences valid for any choice of regulating hypersurface; these should be relevant to recent studies of quantum corrections to entanglement entropies. The anomaly is expressed as a conformally invariant integral of a local Q-curvature that generalizes the Branson Q-curvature by including data of the embedding. In each dimension this canonically defines a higher dimensional generalization of the Willmore energy/rigid string action. We show that the variation of these energy functionals is exactly the obstruction to solving a singular Yamabe type problem with boundary data along the...

  17. Photoelectron spectroscopy of the hydroxymethoxide anion, H2C(OH)O-

    Science.gov (United States)

    Oliveira, Allan M.; Lehman, Julia H.; McCoy, Anne B.; Lineberger, W. Carl

    2016-09-01

    We report the negative ion photoelectron spectroscopy of the hydroxymethoxide anion, H2C(OH)O-. The photoelectron spectra show that 3.49 eV photodetachment produces two distinct electronic states of the neutral hydroxymethoxy radical (H2C(OH)Oṡ). The H2C(OH)Oṡ ground state (X ˜ 2A) photoelectron spectrum exhibits a vibrational progression consisting primarily of the OCO symmetric and asymmetric stretches, the OCO bend, as well as combination bands involving these modes with other, lower frequency modes. A high-resolution photoelectron spectrum aids in the assignment of several vibrational frequencies of the neutral H2C(OH)Oṡ radical, including an experimental determination of the H2C(OH)Oṡ 2ν12 overtone of the H-OCO torsional vibration as 220(10) cm-1. The electron affinity of H2C(OH)Oṡ is determined to be 2.220(2) eV. The low-lying A ˜ 2A excited state is also observed, with a spectrum that peaks ˜0.8 eV above the X ˜ 2A state origin. The A ˜ 2A state photoelectron spectrum is a broad, partially resolved band. Quantum chemical calculations and photoelectron simulations aid in the interpretation of the photoelectron spectra. In addition, the gas phase acidity of methanediol is calculated to be 366(2) kcal mol-1, which results in an OH bond dissociation energy, D0(H2C(OH)O-H), of 104(2) kcal mol-1, using the experimentally determined electron affinity of the hydroxymethoxy radical.

  18. CYP2C19 polymorphisms in acute coronary syndrome patients undergoing clopidogrel therapy in Zhengzhou population.

    Science.gov (United States)

    Guo, Y M; Zhao, Z C; Zhang, L; Li, H Z; Li, Z; Sun, H L

    2016-05-25

    The goal of this study was to explore the polymorphisms of CYP2C19 (CYP2C19*2, CYP2C19*3) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on clopidogrel therapy in Zhengzhou city for guidance on clinical medication and reduction in the incidence of thromboembolic events. Two hundred and thirty-four ACS patients undergoing PCI were included in the study, including 171 males (average age = 64.13 ± 12 years) and 63 females (average age = 67.86 ± 10.20 years). Pyrosequencing analysis detected CYP2C19*2/*3 genotypes, which were divided into wild-type homozygous C/C, mutant heterozygous C/T, and mutant homozygous T/T. This study further explored the relationship between CYP2C19 polymorphisms and clopidogrel resistance in ACS patients. Gene frequencies of C/C, C/T, and T/T for CYP2C19*2 were 39.74, 50, and 10.26%, respectively, while the frequencies of C/C, C/T, and T/T for CYP2C19*3 were 94.02, 5.55, and 0.43%, respectively. According to platelet aggregation analysis, 203 cases normally responded to clopidogrel (86.8%) and 31 cases were clopidogrel resistant (13.2%). There was a correlation between gender and genotype distribution but none between age and genotype. In addition, patients with clopidogrel resistance were treated with ticagrelor antiplatelet therapy instead of clopidogrel, and only 1 case in all patients suffered thrombotic events during a 3-12 month follow-up. In conclusion, CYP2C19*2/*3 polymorphisms may be associated with clopidogrel resistance. Wild-type homozygote and single mutant heterozygote of CYP2C19*2/*3 can be given a normal dose of clopidogrel, while carriers with single mutant homozygote or double mutant heterozygote require ticagrelor antiplatelet therapy as an alternative.

  19. Ultrasmall and phase-pure W2C nanoparticles for efficient electrocatalytic and photoelectrochemical hydrogen evolution

    Science.gov (United States)

    Gong, Qiufang; Wang, Yu; Hu, Qi; Zhou, Jigang; Feng, Renfei; Duchesne, Paul N.; Zhang, Peng; Chen, Fengjiao; Han, Na; Li, Yafei; Jin, Chuanhong; Li, Yanguang; Lee, Shuit-Tong

    2016-01-01

    Earlier research has been primarily focused on WC as one of the most promising earth-abundant electrocatalysts for hydrogen evolution reaction (HER), whereas the other compound in this carbide family—W2C—has received far less attention. Our theoretical calculations suggest that such a focus is misplaced and W2C is potentially more HER-active than WC. Nevertheless, the preparation of phase pure and sintering-free W2C nanostructures represents a formidable challenge. Here we develop an improved carburization method and successfully prepare ultrasmall and phase-pure W2C nanoparticles. When evaluated for HER electrocatalysis, W2C nanoparticles exhibit a small onset overpotential of 50 mV, a Tafel slope of 45 mV dec−1 and outstanding long-term cycling stability, which are dramatically improved over all existing WC-based materials. In addition, the integration of W2C nanoparticles with p-type Si nanowires enables highly active and sustainable solar-driven hydrogen production. Our results highlight the great potential of this traditionally non-popular material in HER electrocatalysis. PMID:27752046

  20. Re-engineering of CYP2C9 to probe acid-base substrate selectivity.

    Science.gov (United States)

    Tai, Guoying; Dickmann, Leslie J; Matovic, Nicholas; DeVoss, James J; Gillam, Elizabeth M J; Rettie, Allan E

    2008-10-01

    A common feature of many CYP2C9 ligands is their weak acidity. As revealed by crystallography, the structural basis for this behavior involves a charge-pairing interaction between an anionic moiety on the substrate and an active site R108 residue. In the present study we attempted to re-engineer CYP2C9 to better accept basic ligands by charge reversal at this key residue. We expressed and purified the R108E and R108E/D293N mutants and compared their ability with that of native CYP2C9 to interact with (S)-warfarin, diclofenac, pyrene, propranolol, and ibuprofen amine. As expected, the R108E mutant maintained all the native enzyme's pyrene 1-hydroxylation activity, but catalytic activity toward diclofenac and (S)-warfarin was abrogated. In contrast, the double mutant displayed much less selectivity in its behavior toward these control ligands. Neither of the mutants displayed significant enhancement of propranolol metabolism, and all three preparations exhibited a type II (inhibitor) rather than type I (substrate) spectrum with ibuprofen amine, although binding became progressively weaker with the single and double mutants. Collectively, these data underscore the importance of the amino acid at position 108 in the acid substrate selectivity of CYP2C9, highlight the accommodating nature of the CYP2C9 active site, and provide a cautionary note regarding facile re-engineering of these complex cytochrome P450 active sites.

  1. HDAC5 controls MEF2C-driven sclerostin expression in osteocytes.

    Science.gov (United States)

    Wein, Marc N; Spatz, Jordan; Nishimori, Shigeki; Doench, John; Root, David; Babij, Philip; Nagano, Kenichi; Baron, Roland; Brooks, Daniel; Bouxsein, Mary; Pajevic, Paola Divieti; Kronenberg, Henry M

    2015-03-01

    Osteocytes secrete paracrine factors that regulate the balance between bone formation and destruction. Among these molecules, sclerostin (encoded by the gene SOST) inhibits osteoblastic bone formation and is an osteoporosis drug target. The molecular mechanisms underlying SOST expression remain largely unexplored. Here, we report that histone deacetylase 5 (HDAC5) negatively regulates sclerostin levels in osteocytes in vitro and in vivo. HDAC5 shRNA increases, whereas HDAC5 overexpression decreases SOST expression in the novel murine Ocy454 osteocytic cell line. HDAC5 knockout mice show increased levels of SOST mRNA, more sclerostin-positive osteocytes, decreased Wnt activity, low trabecular bone density, and reduced bone formation by osteoblasts. In osteocytes, HDAC5 binds and inhibits the function of MEF2C, a crucial transcription factor for SOST expression. Using chromatin immunoprecipitation, we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic enhancer 45 kB downstream from the transcription start site. HDAC5 deficiency increases SOST enhancer MEF2C chromatin association and H3K27 acetylation and decreases recruitment of corepressors NCoR and HDAC3. HDAC5 associates with and regulates the transcriptional activity of this enhancer, suggesting direct regulation of SOST gene expression by HDAC5 in osteocytes. Finally, increased sclerostin production achieved by HDAC5 shRNA is abrogated by simultaneous knockdown of MEF2C, indicating that MEF2C is a major target of HDAC5 in osteocytes.

  2. Preparation of the flexible ZrO{sub 2}/C composite nanofibrous film via electrospinning

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Xin; Song, Lixin; Xie, Xueyao; Zhou, Yangyang; Guan, Yingli; Xiong, Jie [Zhejiang Sci-Tech University, College of Materials and Textiles, Hangzhou (China); Zhejiang Sci-Tech University, Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, Hangzhou (China)

    2016-07-15

    The flexible ZrO{sub 2}/C composite nanofibrous film was fabricated by electrospinning and thermal treatment. Field-emission scanning electron microscopy, transmission electron microscopy, X-ray diffractometer, and Fourier transform infrared spectra were used to characterize the morphology and microstructure of the ZrO{sub 2}/C composite nanofibrous film. The ZrO{sub 2}/C nanofibers exhibited rough surface and had the average diameter of about 230 ± 35 nm. And the ZrO{sub 2} nanoparticles were incorporated in carbon matrix and in tetragonal and monoclinic. The flexural property of the ZrO{sub 2}/C composite nanofibrous film was investigated in detail. The results showed that the flexural property of the nanofibrous film was greatly improved with addition of the ZrO{sub 2} nanoparticles. Besides, with the increase of the contents of ZrO{sub 2} nanoparticles, the flexural modulus of the nanofibrous film decreased, reached a lowest value, and then increased. The lowest flexural modulus of the ZrO{sub 2}/C composite nanofibrous film in precursor concentration of 7.0 wt% was 8.55 ± 0.06 MPa. (orig.)

  3. Notch pathway activation contributes to inhibition of C2C12 myoblast differentiation by ethanol.

    Directory of Open Access Journals (Sweden)

    Michelle A Arya

    Full Text Available The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of myogenic cell differentiation into myotubes. Here, using a high content imaging system we show that ethanol inhibits C2C12 myoblast differentiation by reducing myogenic fusion, creating smaller and less complex myotubes compared with controls. Ethanol administration during C2C12 differentiation reduced MyoD and myogenin expression, and microarray analysis identified ethanol activation of the Notch signaling pathway target genes Hes1 and Hey1. A reporter plasmid regulated by the Hes1 proximal promoter was activated by alcohol treatment in C2C12 cells. Treatment of differentiating C2C12 cells with a gamma secretase inhibitor (GSI abrogated induction of Hes1. On a morphological level GSI treatment completely rescued myogenic fusion defects and partially restored other myotube parameters in response to alcohol. We conclude that alcohol inhibits C2C12 myoblast differentiation and the inhibition of myogenic fusion is mediated by Notch pathway activation.

  4. Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats.

    Science.gov (United States)

    Rivera, Heidi M; Santollo, Jessica; Nikonova, Larissa V; Eckel, Lisa A

    2012-01-18

    Estradiol's inhibitory effect on food intake is mediated, in part, by its ability to increase the activity of meal-related signals, including serotonin (5-HT), which hastens satiation. The important role that postsynaptic 5-HT(2C) receptors play in mediating 5-HT's anorexigenic effect prompted us to investigate whether a regimen of acute estradiol treatment increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized (OVX) rats. We demonstrated that intraperitoneal and intracerebroventricular (i.c.v.) administration of low doses of the 5-HT(2C) receptor agonist meta-chlorophenylpiperazine (mCPP) decreased 1-h dark-phase food intake in estradiol-treated, but not oil-treated, OVX rats. During a longer feeding test, we demonstrated that i.c.v. administration of mCPP decreased 22-h food intake in oil-treated and, to a greater extent, estradiol-treated OVX rats. In a second study, we demonstrated that estradiol increased 5-HT(2C) receptor protein content in the caudal brainstem, but not hypothalamus, of OVX rats. We conclude that a physiologically-relevant regimen of acute estradiol treatment increases sensitivity to mCPP's anorexigenic effect. Our demonstration that this same regimen of estradiol treatment increases 5-HT(2C) receptor protein content in the caudal hindbrain of OVX rats provides a possible mechanism to explain our behavioral findings.

  5. Canine parvovirus type 2c infection in a kitten associated with intracranial abscess and convulsions.

    Science.gov (United States)

    Decaro, Nicola; Desario, Costantina; Amorisco, Francesca; Losurdo, Michele; Colaianni, Maria Loredana; Greco, Maria Fiorella; Buonavoglia, Canio

    2011-04-01

    A case of canine parvovirus type 2c (CPV-2c) infection in a 3-month-old feral kitten with a cerebral abscess and neurological disease is reported. The cat displayed ataxia and convulsions together with signs of gastroenteritis and profound alteration of the total and differential white blood cell counts. A parvovirus strain was detected by a TaqMan assay in the blood and faeces of the affected kitten, which was characterised as CPV by means of molecular assays but did not react with any of the CPV type-specific probes. By sequence and phylogenetic analyses of the VP2-protein gene, the CPV-2c strain displayed a non-coding mutation in the probe-binding region. Although the role of CPV-2c in this particular case is unclear, it is possible that it predisposed the kitten to the clinical signs seen. Continuous surveillance is needed to monitor future spreading of this CPV-2c mutant, and any associated clinical signs, in the dog and cat population.

  6. Lrrc75b is a novel negative regulator of C2C12 myogenic differentiation

    Science.gov (United States)

    Zhong, Yuechun; Zou, Liyi; Wang, Zonggui; Pan, Yaqiong; Dai, Zhong; Liu, Xinguang; Cui, Liao; Zuo, Changqing

    2016-01-01

    Many transcription factors and signaling molecules involved in the guidance of myogenic differentiation have been investigated in previous studies. However, the precise molecular mechanisms of myogenic differentiation remain largely unknown. In the present study, by performing a meta-analysis of C2C12 myogenic differentiation microarray data, we found that leucine-rich repeat-containing 75B (Lrrc75b), also known as AI646023, a molecule of unknown biological function, was downregulated during C2C12 myogenic differentiation. The knockdown of Lrrc75b using specific siRNA in C2C12 myoblasts markedly enhanced the expression of muscle-specific myogenin and increased myoblast fusion and the myotube diameter. By contrast, the adenovirus-mediated overexpression of Lrrc75b in C2C12 cells markedly inhibited myoblast differentiation accompanied by a decrease in myogenin expression. In addition, the phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) was suppressed in the cells in which Lrrc75b was silenced. Taken together, our results demonstrate that Lrrc75b is a novel suppressor of C2C12 myogenic differentiation by modulating myogenin and Erk1/2 signaling. PMID:27633041

  7. Mo2C Nanoparticles Dispersed on Hierarchical Carbon Microflowers for Efficient Electrocatalytic Hydrogen Evolution.

    Science.gov (United States)

    Huang, Yang; Gong, Qiufang; Song, Xuening; Feng, Kun; Nie, Kaiqi; Zhao, Feipeng; Wang, Yeyun; Zeng, Min; Zhong, Jun; Li, Yanguang

    2016-12-27

    The development of nonprecious metal based electrocatalysts for hydrogen evolution reaction (HER) has received increasing attention over recent years. Previous studies have established Mo2C as a promising candidate. Nevertheless, its preparation requires high reaction temperature, which more than often causes particle sintering and results in low surface areas. In this study, we show supporting Mo2C nanoparticles on the three-dimensional scaffold as a possible solution to this challenge and develop a facile two-step preparation method for ∼3 nm Mo2C nanoparticles uniformly dispersed on carbon microflowers (Mo2C/NCF) via the self-polymerization of dopamine. The resulting hybrid material possesses large surface areas and a fully open and accessible structure with hierarchical order at different levels. MoO4(2-) was found to play an important role in inducing the formation of this morphology presumably via its strong chelating interaction with the catechol groups of dopamine. Our electrochemical evaluation demonstrates that Mo2C/NCF exhibits excellent HER electrocatalytic performance with low onset overpotentials, small Tafel slopes, and excellent cycling stability in both acidic and alkaline solutions.

  8. Controlled growth of ultrathin Mo2C superconducting crystals on liquid Cu surface

    Science.gov (United States)

    Geng, Dechao; Zhao, Xiaoxu; Li, Linjun; Song, Peng; Tian, Bingbing; Liu, Wei; Chen, Jianyi; Shi, Dong; Lin, Ming; Zhou, Wu; Loh, Kian Ping

    2017-03-01

    Exhibiting thickness-dependent change in the critical temperature (T c) for the onset of superconductivity, Mo2C has emerged as an important new member in the family of two-dimensional atomic crystals. Controllable growth in terms of morphology and thickness is necessary to elucidate its intrinsic properties at the 2D limit. Here we demonstrate the chemical vapor deposition of ultrathin Mo2C crystals on liquid Cu surface where the morphology of the crystals can be controlled by tuning the carbon supersaturation. A unique staggered carbon vacancy ordering is discovered in Mo2C crystals having particular geometries. Thickness engineering of the crystal can be achieved by controlling the thickness of the Cu catalyst layer, which affords a facile route to grow ultrathin 2D samples. Ultrathin Mo2C crystals so obtained, have been characterized using aberration corrected scanning transmission electron microscopy annular dark field imaging, where the co-existence of both AA and AB stacking modes is observed. The high crystallinity of the Mo2C crystals synthesized in this work is attested by its characteristic sharp superconducting transition.

  9. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.

    Science.gov (United States)

    Xian, Li; Hou, Siyuan; Huang, Zan; Tang, An; Shi, Peiliang; Wang, Qinghua; Song, Anying; Jiang, Shujun; Lin, Zhaoyu; Guo, Shiying; Gao, Xiang

    2015-04-01

    Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.

  10. Methane Activation by Tantalum Carbide Cluster Anions Ta2C4().

    Science.gov (United States)

    Li, Hai-Fang; Zhao, Yan-Xia; Yuan, Zhen; Liu, Qing-Yu; Li, Zi-Yu; Li, Xiao-Na; Ning, Chuan-Gang; He, Sheng-Gui

    2017-02-02

    Methane activation by transition metals is of fundamental interest and practical importance, as this process is extensively involved in the natural gas conversion to fuels and value-added chemicals. While single-metal centers have been well recognized as active sites for methane activation, the active center composed of two or more metal atoms is rarely addressed and the detailed reaction mechanism remains unclear. Here, by using state-of-the-art time-of-flight mass spectrometry, cryogenic anion photoelectron imaging spectroscopy, and quantum-chemical calculations, the cooperation of the two Ta atoms in a dinuclear carbide cluster Ta2C4(-) for methane activation has been identified. The C-H bond activation takes place predominantly around one Ta atom in the initial stage of the reaction and the second Ta atom accepts the delivered H atom from the C-H bond cleavage. The well-resolved vibrational spectra of the cryogenically cooled anions agree well with theoretical simulations, allowing the clear characterization of the structure of Ta2C4(-) cluster. The reactivity comparison between Ta2C4(-) cluster and the carbon-less analogues (Ta2C3(-) and Ta2C2(-)) demonstrated that the cooperative effect of the two metal atoms can be well tuned by the carbon ligands in terms of methane activation and transformation.

  11. Structural analysis of CYP2C9 and CYP2C5 and an evaluation of commonly used molecular modeling techniques

    DEFF Research Database (Denmark)

    Afzelius, Lovisa; Raubacher, Florian; Karlén, Anders;

    2004-01-01

    This work had two separate aims: to evaluate different modeling techniques and to make a detailed structural characterization of CYP2C9. To achieve these goals, the consensus principal component analysis (CPCA) technique and distance measurements were used to explore available crystal structures...... by the CPCA. Advantages and drawbacks are presented for the different modeling techniques. Despite the varying modeling success, the models give insight and understanding by the mutual forming and discarding of hypotheses. This is a dynamic process since the crystal structures are improving with time and...

  12. Immunization of Bos taurus steers with Babesia bovis recombinant antigens MSA-1, MSA-2c and 12D3.

    Science.gov (United States)

    Antonio Alvarez, J; Lopez, U; Rojas, C; Borgonio, V M; Sanchez, V; Castañeda, R; Vargas, P; Figueroa, J V

    2010-04-01

    The purpose of this research was to evaluate the recombinant proteins MSA-1, MSA-2c and 12D3 as a combined immunogen for cattle. Fifteen steers were randomly assigned into three groups of five animals each (I, II and III). On day 0, cattle in group I were injected with 50 microg each of rMSA-1, rMSA-2c and r12D3 with the adjuvant Montanide 75; cattle in Group II received adjuvant-PBS, and Group III were untreated controls. On day 14, cattle in Group I received a second injection of the three recombinant proteins in adjuvant and cattle in Group II again received adjuvant alone. On day 28, all groups of cattle were challenged with a field strain of Babesia bovis. After challenge, the experimental cattle were clinically and serologically monitored. Three of the five steers immunized with the combined recombinant B. bovis proteins seroconverted on day 14 post-immunization (P.I.) and the maximum titre was 1 : 1600. All five immunized steers presented strong seropositivity to B. bovis antigens at day 21 P.I. The prepatent periods of vaccinated cattle were delayed until day 10 post-challenge exposure versus 8 and 7 days in Groups II and III, respectively. Cattle in all groups had fever above 41 degrees C; the reduction in packed cell volume was not significantly different (P > 0.05) in vaccinated group I compared with Groups II and III (29% versus 26% and 31%, respectively). Treatment was required for one steer in the control group. During the period of the study, the weight of cattle in Groups I and II increased an average of 9 and 7 kg, whereas the weight of the control cattle was reduced on average 4 kg. Immunization with rMSA-1-rMSA-2c-r12D3 proteins was not sufficient to prevent clinical symptoms against challenge, but the immunologic response was sufficient to protect steers against a mild virulent strain of B. bovis.

  13. Molecular mechanisms of genetic variation and transcriptional regulation of CYP2C19

    Directory of Open Access Journals (Sweden)

    Nuala Ann Helsby

    2012-10-01

    Full Text Available Inherited variation in the function of the drug metabolising enzyme CYP2C19 was first observed 40 years ago. The SNP variants which underpin loss of CYP2C19 function have been elucidated and extensively studied in healthy populations. However, there has been relatively meagre translation of this information into the clinic. The presence of genotype-phenotype discordance in certain patients suggests that changes in the regulation of this gene, as well as loss of function SNPs, could play a role in deficient activity of this enzyme. Knowledge of the molecular mechanisms which control transcription of this gene, reviewed in this article, may aid the challenge of delivering CYP2C19 pharmacogenetics into clinical use.

  14. Transport properties of carbide superconductor La{sub 2}C{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. S. [Dept. of Physics, Pohang University of Science and Technology, Pohang (Korea, Republic of); Kremer, R. K. [Max-Planck-Institut fuer Festkoerperforschung, Stuttgart (Korea, Republic of)

    2013-03-15

    We investigate the electrical and thermal transport properties of a sesquicarbide superconductor La{sub 2}C{sub 3}, including electrical resistivity, thermoelectric power, and thermal conductivity. The electrical resistivity exhibits a typical metallic character with a saturation behavior at high temperatures. The thermoelectric power shows a metallic behavior with pronounced phonon-drag effect, comparable with pure metals. The broad peak of the thermal conductivity is observed in the superconducting state, which is rapidly suppressed by magnetic fields. These observations suggest that the electron-phonon scattering is significant in La{sub 2}C{sub 3}, which is relevant with the relatively high-T{sub c} in La{sub 2}C{sub 3} through strong electron-phonon coupling with low frequency phonon modes.

  15. Magnetic properties of Y1- xGdxCo2B2C series of borocarbides

    Science.gov (United States)

    Bud'ko, S. L.; Giordanengo, B.; Sulpice, A.; Fontes, M. B.; Baggio-Saitovitch, E. M.

    1995-04-01

    Magnetic properties of Y1- xGdxCo2B2C series of compounds were studied. Two magnetically ordered phases were observed for 0.7 ≤ x ≤ 1. Change of the magnetic ordering temperatures T 1 and T 2 with the Gd concentration is argued to be related to the dilution of magnetic Gd by nonmagnetic Y and to the reduction of the distance between ( Y1- xGdx) C planes. However, significant contribution to the changes in T 1 between pure GdNi2B2C and GdCo2B2C samples is suggested to be due to the different 3 d band filling in these compounds.

  16. Catalytic performance of Fe modified K/Mo2C catalyst for CO hydrogenation

    Institute of Scientific and Technical Information of China (English)

    Minglin Xiang; Dudu Wu; Juan Zou; Debao Li; Yuhan Sun; Xichun She

    2011-01-01

    Fe modified and un-modified K/Mo2C were prepared and investigated as catalysts for CO hydrogenation reaction.Compared with K/Mo2C catalyst,the addition of Fe increased the production of alcohols,especially the C2+OH.Meanwhile,considerable amounts of C5+ hydrocarbons and C=2-C=4 were formed,whereas methane selectivity greatly decreased.Also,the activity and selectivity of the catalyst were readily affected by the reaction pressure and temperature employed.According to the XPS results,Mo4+ might be responsible for the production of alcohols,whereas the low valence state of Mo species such as Moo and/or Mo2+ might be account for the high activity and selectivity toward hydrocarbons.

  17. Selective deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo2C) surfaces

    Science.gov (United States)

    Xiong, Ke; Yu, Weiting; Chen, Jingguang G.

    2014-12-01

    The selective deoxygenation of aldehydes and alcohols without cleaving the Csbnd C bond is crucial for upgrading bio-oil and other biomass-derived molecules to useful fuels and chemicals. In this work, propanal, 1-propanol, furfural and furfuryl alcohol were selected as probe molecules to study the deoxygenation of aldehydes and alcohols on molybdenum carbide (Mo2C) prepared over a Mo(1 1 0) surface. The reaction pathways were investigated using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS). The deoxygenation of propanal and 1-propanol went through a similar intermediate (propoxide or η2(C,O)-propanal) to produce propene. The deoxygenation of furfural and furfuryl alcohol produced a surface intermediate similar to adsorbed 2-methylfuran. The comparison of these results revealed the promising deoxygenation performance of Mo2C, as well as the effect of the furan ring on the selective deoxygenation of the Cdbnd O and Csbnd OH bonds.

  18. CO Hydrogenation over Transition Metals (Fe, Co, or Ni Modified K/Mo2C Catalysts

    Directory of Open Access Journals (Sweden)

    Minglin Xiang

    2013-01-01

    Full Text Available Transition metals (Fe, Co, or Ni modified K/Mo2C catalysts were prepared and investigated as catalysts for CO hydrogenation. The addition of Fe, Co, or Ni to K/Mo2C catalyst led to a sharp increase in both the activity and selectivity of C2+OH, but the promotion effects were quite different and followed the sequence: Ni > Co > Fe for the activity and Fe > Co > Ni for the alcohol selectivity. For the products distributions, it also displayed some differences; Co promoter showed much higher C5+ hydrocarbon selectivity than Fe or Ni promoter, but Fe or Co promoter gave lower methane selectivity than Ni promoter, and Fe promoter showed the highest C2=-C4= selectivity.

  19. Empirical Study of Consumers' Purchase Intentions in C2C Electronic Commerce

    Institute of Scientific and Technical Information of China (English)

    HE Dehua; LU Yaobin; ZHOU Deyi

    2008-01-01

    Electronic commerce is becoming increasingly important in business, but lack of intention to purchase has become a main barrier in the development of electronic commerce. Thus, effective measures are needed to promote consumers' intentions to purchase in online consumer to consumer (C2C) stores. This paper postulates that five factors, the perceived ease of use of the website, perceived usefulness of the website, vendor competence, introduction and recommendations of third parties, and vendors' attitude toward customers, influence consumers' intentions to purchase in online C2C stores and this intention directly leads to their action to purchase from online C2C stores. The structural equation modeling (SEM) method was used to analyze empirical data, supporting these hypotheses except for the effect of vendor competence.

  20. Volumetric Properties of the Mixture Ethane-1,2-diol C2H6O2 + C6H10O Cyclohexanone (VMSD1111, LB4980_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume A 'Binary Liquid Systems of Nonelectrolytes I' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Ethane-1,2-diol C2H6O2 + C6H10O Cyclohexanone (VMSD1111, LB4980_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  1. Heat of Mixing and Solution of 1,2-Dichloroethane C2H4Cl2 + C6H10O Cyclohexanone (HMSD1111, LB3663_H)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'heat of Mixing and Solution of 1,2-Dichloroethane C2H4Cl2 + C6H10O Cyclohexanone (HMSD1111, LB3663_H)' providing data from direct low-pressure calorimetric measurement of molar excess enthalpy at variable mole fraction and constant temperature.

  2. Vapor-Liquid Equilibrium in the Mixture 1,2-Dichloroethane C2H4Cl2 + C6H10O Cyclohexanone (EVLM1111, LB5653_E)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'vapor-Liquid Equilibrium in the Mixture 1,2-Dichloroethane C2H4Cl2 + C6H10O Cyclohexanone (EVLM1111, LB5653_E)' providing data from direct measurement of pressure at variable mole fraction in liquid phase and constant temperature.

  3. Heat of Mixing and Solution of 2-Ethoxyethanol C4H10O2 + C5H10O3 Diethyl carbonate (HMSD1111, LB4209_H)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'heat of Mixing and Solution of 2-Ethoxyethanol C4H10O2 + C5H10O3 Diethyl carbonate (HMSD1111, LB4209_H)' providing data from direct low-pressure calorimetric measurement of molar excess enthalpy at variable mole fraction and constant temperature.

  4. Volumetric Properties of the Mixture 2-Methoxyethanol C3H8O2 + C5H10O3 Diethyl carbonate (VMSD1111, LB4682_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture 2-Methoxyethanol C3H8O2 + C5H10O3 Diethyl carbonate (VMSD1111, LB4682_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  5. Heat of Mixing and Solution of 2-Methoxyethanol C3H8O2 + C5H10O3 Diethyl carbonate (HMSD1111, LB4208_H)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'heat of Mixing and Solution of 2-Methoxyethanol C3H8O2 + C5H10O3 Diethyl carbonate (HMSD1111, LB4208_H)' providing data from direct low-pressure calorimetric measurement of molar excess enthalpy at variable mole fraction and constant temperature.

  6. Volumetric Properties of the Mixture 2-Ethoxyethanol C4H10O2 + C5H10O3 Diethyl carbonate (VMSD1111, LB4686_V)

    Science.gov (United States)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture 2-Ethoxyethanol C4H10O2 + C5H10O3 Diethyl carbonate (VMSD1111, LB4686_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  7. CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP.

    Science.gov (United States)

    Huezo-Diaz, Patricia; Perroud, Nader; Spencer, Edgar P; Smith, Rebecca; Sim, Sarah; Virding, Susanne; Uher, Rudolf; Gunasinghe, Cerisse; Gray, Jo; Campbell, Desmond; Hauser, Joanna; Maier, Wolfgang; Marusic, Andrej; Rietschel, Marcella; Perez, Jorge; Giovannini, Caterina; Mors, Ole; Mendlewicz, Julien; McGuffin, Peter; Farmer, Anne E; Ingelman-Sundberg, Magnus; Craig, Ian W; Aitchison, Katherine J

    2012-03-01

    In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

  8. The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia.

    Science.gov (United States)

    Mulder, Hans; Franke, Barbara; van der-Beek van der, Annemarie Aart; Arends, Johan; Wilmink, Frederik W; Scheffer, Hans; Egberts, Antoine C G

    2007-08-01

    The use of antipsychotics is associated with metabolic side effects, which put patients with schizophrenia or related disorders at risk for cardiovascular morbidity. The high interindividual variability in antipsychotic-induced metabolic abnormalities suggests that genetic makeup is a possible determinant. In this cross-sectional study, we investigated whether genotypes of the HTR2C receptor are associated with the metabolic syndrome in patients using antipsychotics. Patients were identified from a schizophrenia disease management program. In this program, patients' blood pressure, triglycerides, high-density lipoprotein-cholesterol, and waist circumference are measured regularly during follow-up. The primary end point of our study was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the HTR2C receptor gene (HTR2C:c.1-142948[GT]n, rs3813928 [-997 G/A], rs3813929 [-759 C/T], rs518147 [-697 G/C], and rs1414334 [C > G]). The included patients (n = 112) mainly (>80%) used atypical antipsychotics (clozapine, olanzapine, and risperidone). Carriership of the variant alleles of the HTR2C polymorphisms rs518147, rs1414334, and HTR2C:c.1-142948(GT)n was associated with an increased risk of the metabolic syndrome (adjusted odds ratio [OR], 2.62 [95% confidence interval {CI}, 1.00-6.85]; OR, 4.09 [95% CI, 1.41-11.89]; and OR, 3.12 [95% CI, 1.13-8.16]), respectively. Our findings suggest that HTR2C genotypes are associated with antincreased risk of metabolic syndrome in patients taking antipsychotics.

  9. D2d(23)-C84 versus Sc2C2@D2d(23)-C84: Impact of Endohedral Sc2C2 Doping on Chemical Reactivity in the Photolysis of Diazirine.

    Science.gov (United States)

    Yamada, Michio; Tanabe, Yukiko; Dang, Jing-Shuang; Sato, Satoru; Mizorogi, Naomi; Hachiya, Makoto; Suzuki, Mitsuaki; Abe, Tsuneyuki; Kurihara, Hiroki; Maeda, Yutaka; Zhao, Xiang; Lian, Yongfu; Nagase, Shigeru; Akasaka, Takeshi

    2016-12-21

    We compared the chemical reactivity of D2d(23)-C84 and that of Sc2C2@D2d(23)-C84, both having the same carbon cage geometry, in the photolysis of 2-adamantane-2,3'-[3H]-diazirine, to clarify metal-atom doping effects on the chemical reactivity of the carbon cage. Experimental and computational studies have revealed that the chemical reactivity of the D2d(23)-C84 carbon cage is altered drastically by endohedral Sc2C2 doping. The reaction of empty D2d(23)-C84 with the diazirine under photoirradiation yields two adamantylidene (Ad) adducts. NMR spectroscopic studies revealed that the major Ad monoadduct (C84(Ad)-A) has a fulleroid structure and that the minor Ad monoadduct (C84(Ad)-B) has a methanofullerene structure. The latter was also characterized using X-ray crystallography. C84(Ad)-A is stable under photoirradiation, but it interconverted to C84(Ad)-B by heating at 80 °C. In contrast, the reaction of endohedral Sc2C2@D2d(23)-C84 with diazirine under photoirradiation affords four Ad monoadducts (Sc2C2@C84(Ad)-A, Sc2C2@C84(Ad)-B, Sc2C2@C84(Ad)-C, and Sc2C2@C84(Ad)-D). The structure of Sc2C2@C84(Ad)-C was characterized using X-ray crystallography. Thermal interconversion of Sc2C2@C84(Ad)-A and Sc2C2@C84(Ad)-B to Sc2C2@C84(Ad)-C was also observed. The reaction mechanisms of the Ad addition and thermal interconversion were elucidated from theoretical calculations. Calculation results suggest that C84(Ad)-B and Sc2C2@C84(Ad)-C are thermodynamically favorable products. Their different chemical reactivities derive from Sc2C2 doping, which raises the HOMO and LUMO levels of the D2d(23)-C84 carbon cage.

  10. Evaluation of the abuse potential of lorcaserin, a serotonin 2C (5-HT2C) receptor agonist, in recreational polydrug users.

    Science.gov (United States)

    Shram, M J; Schoedel, K A; Bartlett, C; Shazer, R L; Anderson, C M; Sellers, E M

    2011-05-01

    Lorcaserin is a selective and potent serotonin 2C receptor subtype (5-HT(2C)) agonist under development for the treatment of obesity. This study assessed the drug's abuse potential on the basis of its pharmacological profile. For this purpose, a double-blind, double-dummy, placebo-controlled, randomized seven-way crossover study with single oral doses of lorcaserin (20, 40, and 60 mg), zolpidem (15 and 30 mg), ketamine (100 mg), and placebo was conducted in recreational polydrug users (N = 35). Subjective and objective measures were assessed up to 24 h after the dose. We found that zolpidem and ketamine had significantly higher peak scores relative to placebo on the primary measures as well as on most of the secondary measures. The subjective effects of a 20-mg dose of lorcaserin were similar to those of placebo, whereas supratherapeutic doses of lorcaserin were associated with significant levels of dislike by users as compared with placebo, zolpidem, and ketamine. Perceptual effects were minimal after administration of lorcaserin and significantly lower than after administration of either ketamine or zolpidem. The findings suggest that, at supratherapeutic doses, lorcaserin is associated with distinct, primarily negative, subjective effects and has low abuse potential.

  11. Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain.

    Science.gov (United States)

    Booth Depaz, Iris M; Toselli, Francesca; Wilce, Peter A; Gillam, Elizabeth M J

    2015-03-01

    Cytochrome P450 enzymes from the CYP2C subfamily play a prominent role in the metabolic clearance of many drugs. CYP2C enzymes have also been implicated in the metabolism of arachidonic acid to vasoactive epoxyeicosatrienoic acids. CYP2C8, CYP2C9, and CYP2C19 are expressed in the adult liver at significant levels; however, the expression of CYP2C enzymes in extrahepatic tissues such as the brain is less well characterized. Form-specific antibodies to CYP2C9 and CYP2C19 were prepared by affinity purification of antibodies raised to unique peptides. CYP2C9 and CYP2C19 were located in microsomal fractions of all five human brain regions examined, namely the frontal cortex, hippocampus, basal ganglia, amygdala, and cerebellum. Both CYP2C9 and CYP2C19 were detected predominantly within the neuronal soma but with expression extending down axons and dendrites in certain regions. Finally, a comparison of cortex samples from alcoholics and age-matched controls suggested that CYP2C9 expression was increased in alcoholics.

  12. CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: use of inhibitory monoclonal antibodies in P450 identification.

    Science.gov (United States)

    Hu, Y; Krausz, K; Gelboin, H V; Kupfer, D

    2004-02-01

    1. The endocrine disruptor pesticide methoxychlor undergoes O-demethylation by mammalian liver microsomes forming chiral mono-phenolic (1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane, i.e. mono-OH-M) and achiral bis-phenolic oestrogenic metabolites. Human liver microsomes (HLM) generated primarily the S-mono-OH-M. 2. Inhibitory monoclonal antibodies (MAb) identified those P450s catalysing the enantioselective O-demethylation of methoxychlor. In HLM, O-demethylation was inhibited by MAb anti-2C9 (30-40%), diminishing the per cent of S-mono-OH-M from about 80 to 55-60%. MAb anti-CYP1A2, 2A6, 2B6, 2C8, 2C19, 2D6 and 3A4 did not affect the demethylation rate in HLM. Nevertheless, MAb anti-CYP1A2 decreased the formation of R-mono-OH-M from 21-23 to 10-17%, indicating that CYP1A2 exhibits a role in generating the R-enantiomer. 3. Among cDNA-expressed human P450s (supersomes), CYP2C19 was the most active in demethylation, but in HLM, CYP2C19 appeared inactive (no inhibition by MAb anti-CYP2C19). There was a substantial difference in the per cent inhibition of demethylation by MAb anti-CYP2C9 and anti-rat CYP2C (MAb inhibiting all human CYP2C forms) and in altering the enantioselectivity, suggesting that demethylation by combined CYP2C8, 2C18 and 2C19 was significant (20-30%). 4. Polymorphism of methoxychlor demethylation was examined with supersomes and HLM-expressing CYP2C9 allelic variants. CYP2C9*1 and 2C9*2 were highly active; however, CYP2C9*3 appeared inactive.

  13. Impact of CYP2C8*3 on paclitaxel clearance

    DEFF Research Database (Denmark)

    Bergmann, T K; Brasch-Andersen, C; Gréen, H

    2011-01-01

    The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the in...... associations found for CYP2C8*4 (P=0.04) and ABCC1 g.7356253C>G (P=0.04).The Pharmacogenomics Journal advance online publication, 6 April 2010; doi:10.1038/tpj.2010.19....

  14. Modelling the B2C Marketplace: Evaluation of a Reputation Metric for e-Commerce

    Science.gov (United States)

    Gutowska, Anna; Sloane, Andrew

    This paper evaluates recently developed novel and comprehensive reputation metric designed for the distributed multi-agent reputation system for the Business-to-Consumer (B2C) E-commerce applications. To do that an agent-based simulation framework was implemented which models different types of behaviours in the marketplace. The trustworthiness of different types of providers is investigated to establish whether the simulation models behaviour of B2C e-Commerce systems as they are expected to behave in real life.

  15. China's B2C e-commerce development and its future prospects

    OpenAIRE

    Jin, Guming

    2012-01-01

    China’s E-commerce environment is improving all the time. Consumers are getting more and more habituated to this form of consumption mode. The recent trend shows that China’s e- commerce market is booming mainly because of major enterprises’ fierce competition within Business To Customer E-commerce market. People are optimistic about B2C E-commerce which strengthens the China’s B2C E-commerce market. Even though E-commerce business in China is soaring, there still persists a problem, too. ...

  16. Sc3N and Sc2C2 encapsulated B40: Smarter than its carbon analogue

    Science.gov (United States)

    Shah, Esha V.; Roy, Debesh R.

    2016-10-01

    A detailed comparative investigation on the recently synthesised B40 and C40 along with their metal nitride (Sc3N)and carbide (Sc2C2) encapsulated endohedral fullerenes, is performed under density functional theory for the first time. The structures, electronic, thermodynamic and magnetic properties of all the considered compounds are explored in detail. The present study identifies borospherene (B40) and its encapsulated nitride (Sc3N@B40) and carbide (Sc2C2@B40) endohedral borofullerenes as the better candidates for future novel nano-applications compared to their carbon bucky ball analogues.

  17. Anisotropic Multiband Many-Body Interactions in LuNi2B2C

    Energy Technology Data Exchange (ETDEWEB)

    Bergk, B.; Petzold, V.; Rosner, H.; Drechsler, S.-L.; Bartkowiak, M.; Ignatchik, O.; Bianchi, A. D.; Sheikin, I.; Canfield, P. C.; Wosnitza, J.

    2008-06-27

    We present a comprehensive de Haas-van Alphen study on the nonmagnetic borocarbide superconductor LuNi{sub 2}B{sub 2}C. The analysis of the angular-dependent effective masses for different bands in combination with full-potential density functional calculations allowed us to determine the mass-enhancement factors, {lambda}, for the different electronic bands and their wave-vector dependences. Our data clearly show the anisotropic multiband character of the superconductivity in LuNi{sub 2}B{sub 2}C.

  18. China's B2C e-commerce development and its future prospects

    OpenAIRE

    2012-01-01

    China’s E-commerce environment is improving all the time. Consumers are getting more and more habituated to this form of consumption mode. The recent trend shows that China’s e- commerce market is booming mainly because of major enterprises’ fierce competition within Business To Customer E-commerce market. People are optimistic about B2C E-commerce which strengthens the China’s B2C E-commerce market. Even though E-commerce business in China is soaring, there still persists a problem, too. ...

  19. Preparation of SnO2/C biomorphic materials by biotemplating from ramie fibres

    Indian Academy of Sciences (India)

    Xin-Hai He; Le-Hua Qi; Jun-Bo Wang; Ming-Qian Shen; Wei Chang; Chong Fu; Min-Ge Yang; Xiao-Lei Su

    2011-08-01

    A new SnO2/C biomorphic material has been prepared by molding into a composite billet and carbothermal-reduction under vacuum from ramie fibres/Sn(OH)4 precursors. The phase composition and microstructure of the prepared materials were characterized. The effects of the carbonization temperature, holding time and other factors on the crystal structure, morphology and ingredients of the prepared samples were discussed. The results showed that the sintering temperature and holding time have significant effects on the final products. When the sintering temperature reached 480°C, the SnO2/C biomorphic materials were synthesized successfully.

  20. E2C(R2) Periodic Benefit-Risk Evaluation Report and E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and Answers; International Council for Harmonisation; Guidances for Industry; Availability. Notice.

    Science.gov (United States)

    2016-07-19

    The Food and Drug Administration (FDA or Agency) is announcing the availability of guidances for industry entitled ``E2C(R2) Periodic Benefit-Risk Evaluation'' (E2C(R2) guidance) and ``E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and Answers'' (E2C(R2) Q&A guidance). These guidances were prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The E2C(R2) draft guidance, issued April 11, 2012, updated and combined two ICH guidances, ``E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs'' (addendum to the E2C guidance). The E2C(R2) guidance is intended to describe the format, content, and timing of a Periodic Benefit-Risk Evaluation Report (PBRER) for an approved drug or biologic, and it finalizes the draft guidance. The E2C(R2) Q&A guidance is a supplementary guidance that is intended to clarify key issues in the E2C(R2) guidance.

  1. Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Rafael Linden

    2009-09-01

    Full Text Available The CYP2C19 gene presents polymorphism affecting the pharmacokinetics of several drugs of clinical importance. The purpose of this study was to investigate the correlation between CYP2C19 genotype and metabolic phenotype in a group of 38 Brazilian volunteers, evaluating the phenotype prediction capacity of the genotyping procedure. For CYP2C19 phenotyping, omeprazole was used as the probe drug, using the hydroxylation metabolic ratio as the phenotypic indicator. Venous blood samples were drawn before and three hours after an oral administration of 20 mg omeprazole. The plasma concentrations of omeprazole and hydroxy-omeprazole were determined by high performance liquid chromatography. The genotyping assay was carried out using a Real-Time-PCR-based assay, identifying the alleles *1 (completely functional, *2, *3 and *4 (null. The phenotyping procedure estimated the presence of 4 poor, 34 extensive and 1 ultra-extensive metabolizer. The genotyping identified 4 poor, 23 extensive and 11 intensive metabolizers. The groups of volunteers classified according to the number of active alleles of CYP2C19 had significant differences in the metabolic ratios of omeprazole hydroxylation. However, volunteers exhibiting the same number of active alleles presented different phenotypes. Therefore, the phenotyping of CYP2C19 is a more promising alternative to dose individualization of CYP2C19 substrate drugs.O gene CYP2C19 apresenta polimorfismo genético, com impacto importante na farmacocinética de diversos fármacos de importância clínica. O objetivo deste estudo foi avaliar a correlação entre genótipo e fenótipo de CYP2C19 em um grupo de 38 voluntários brasileiros, avaliando a capacidade de predição do fenótipo a partir de testes de genotipagem. Para a fenotipagem, utilizou-se omeprazol (OME como fármaco-sonda para CYP2C19, empregando sua razão metabólica de hidroxilação como indicador fenotípico. Amostras de sangue foram coletadas antes e tr

  2. Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

    Science.gov (United States)

    Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

    2015-07-01

    Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans.

  3. Menthol reduces the anticoagulant effect of warfarin by inducing cytochrome P450 2C expression.

    Science.gov (United States)

    Hoshino, Motohiro; Ikarashi, Nobutomo; Tsukui, Makoto; Kurokawa, Asako; Naito, Rina; Suzuki, Midori; Yokobori, Kohsuke; Ochiai, Takumi; Ishii, Makoto; Kusunoki, Yoshiki; Kon, Risako; Ochiai, Wataru; Wakui, Nobuyuki; Machida, Yoshiaki; Sugiyama, Kiyoshi

    2014-06-02

    Recently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally administered to mice 24h after the administration of menthol for 2 days, and the plasma warfarin concentration was measured. In the menthol administration group, the area under the blood concentration time curve of warfarin was decreased by approximately 25%, while total clearance was increased to 1.3-fold compared to the control group. The hepatic cytochrome P450 (CYP) 2C protein expression level in the menthol administration group was significantly increased compared to that in the control group. An increase in the nuclear translocation of constitutive androstane receptor (CAR) was also observed. The addition of menthol to human hepatic cells, HepaRG cells, caused an increase in the mRNA expression level of CYP2C9. The results of this study revealed that menthol causes an increase in CYP2C expression levels in the liver, which leads to an enhancement of warfarin metabolism, resulting in a decreased anticoagulant effect of warfarin. It was also suggested that menthol acted directly on the liver and increased the expression level of CYP2C by enhancing the nuclear translocation of CAR.

  4. The Development of B2C E-Commerce in Greece: Current Situation and Future Potential.

    Science.gov (United States)

    Kardaras, Dimitris; Papathanassiou, Eleutherios

    2000-01-01

    Reports on the results of a survey of 120 companies in Greece that evaluated the potential of business to customer (B2C) Internet applications and investigated how the Internet and e-commerce can offer new opportunities for businesses to improve their customers' satisfaction. Discusses electronic commerce problems and future technology. (Contains…

  5. B2C social media value gap-model: a study of the Dutch online retailing

    NARCIS (Netherlands)

    Constantinides, Efthymios; Schepers, Lonieke; Vries, de Sjoerd

    2015-01-01

    Social media are extensively used by customers and businesses in the B2C domain but the objectives and the way the two parties use them are different. Based on the uses and gratifications theory, the article identifies similarities and differences in motives and use of social media in retailing. The

  6. Hysteresis in the field-induced magnetic structure in TmNi2B2C

    DEFF Research Database (Denmark)

    Eskildsen, M.R.; Harada, K.; Gammel, P.L:

    1999-01-01

    Using small-angle neutron scattering we have studied the flux line lattice and the magnetic structure in TmNi2B2C. With an applied field parallel to the crystalline c-axis several magnetic and flux line lattice symmetry transitions have been reported. The subject of this paper is the held-induced...

  7. B2C social media value gap-model: a study of the Dutch online retailing

    NARCIS (Netherlands)

    Constantinides, Efthymios; Schepers, Lonieke; de Vries, Sjoerd A.

    2015-01-01

    Social media are extensively used by customers and businesses in the B2C domain but the objectives and the way the two parties use them are different. Based on the uses and gratifications theory, the article identifies similarities and differences in motives and use of social media in retailing. The

  8. Midway Atoll Site P2C 9/21/2002 21-22M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Midway Atoll, site P2C (28.260 N, 177.345 W), between 21 and 22 meters along a permanent transect.

  9. Midway Atoll Site P2C 9/21/2002 13-14M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Midway Atoll, site P2C (28.260 N, 177.345 W), between 13 and 14 meters along a permanent transect.

  10. The Development of B2C E-Commerce in Greece: Current Situation and Future Potential.

    Science.gov (United States)

    Kardaras, Dimitris; Papathanassiou, Eleutherios

    2000-01-01

    Reports on the results of a survey of 120 companies in Greece that evaluated the potential of business to customer (B2C) Internet applications and investigated how the Internet and e-commerce can offer new opportunities for businesses to improve their customers' satisfaction. Discusses electronic commerce problems and future technology. (Contains…

  11. Thermal ramp tritium release in COBRA-1A2 C03 beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, D.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-03-01

    Tritium release kinetics, using the method of thermal ramp heating at three linear ramp rates, were measured on the COBRA-1A2 C03 1-mm beryllium pebbles. This report includes a brief discussion of the test, and the test data in graph format.

  12. Accelerating MP2C dispersion corrections for dimers and molecular crystals

    Science.gov (United States)

    Huang, Yuanhang; Shao, Yihan; Beran, Gregory J. O.

    2013-06-01

    The MP2C dispersion correction of Pitonak and Hesselmann [J. Chem. Theory Comput. 6, 168 (2010)], 10.1021/ct9005882 substantially improves the performance of second-order Møller-Plesset perturbation theory for non-covalent interactions, albeit with non-trivial computational cost. Here, the MP2C correction is computed in a monomer-centered basis instead of a dimer-centered one. When applied to a single dimer MP2 calculation, this change accelerates the MP2C dispersion correction several-fold while introducing only trivial new errors. More significantly, in the context of fragment-based molecular crystal studies, combination of the new monomer basis algorithm and the periodic symmetry of the crystal reduces the cost of computing the dispersion correction by two orders of magnitude. This speed-up reduces the MP2C dispersion correction calculation from a significant computational expense to a negligible one in crystals like aspirin or oxalyl dihydrazide, without compromising accuracy.

  13. PRODUCTION, ISOLATION AND SPECTROSCOPIC STUDIES OF THE ENDOHEDRAL FULLERENE Sc2@C80 (Ⅰ-Ⅲ)

    Institute of Scientific and Technical Information of China (English)

    Chunru Wang; Lihua Gan; Chunli Bai; Hisanori Shinohara

    2004-01-01

    The isolation of multiple-isomers of Sc2@C80 (Ⅰ, Ⅱ, Ⅲ) endohedral metallofullerenes is reported for the first time. The new C80-based Sc-metallofullerenes are characterized by UV-Vis-NIR absorption spectroscopy and detailed chromatographic retention time data. A close relationship between the isomer structure and the corresponding HPLC retention time of the metallofullerenes is presented.

  14. L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death

    Science.gov (United States)

    Le Borgne, Françoise; Ravaut, Gaétan; Bernard, Arnaud; Demarquoy, Jean

    2017-01-01

    AIM To identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells. METHODS Myoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine (a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death. RESULTS Associated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species (ROS), especially under pathological conditions. High levels of ROS are known to induce injuries in cell structure as they interact at many levels in cell function. In C2C12 cells, a treatment with menadione induced a loss of transmembrane mitochondrial potential, an increase in mitochondrial production of ROS; it also induces autophagy and was able to provoke cell death. Pre-treatment of the cells with L-carnitine reduced ROS production, diminished autophagy and protected C2C12 cells against menadione-induced deleterious effects. CONCLUSION In conclusion, L-carnitine limits the oxidative stress in these cells and prevents cell death.

  15. Midway Atoll Site P2C 9/21/2002 18-19M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Midway Atoll, site P2C (28.260 N, 177.345 W), between 18 and 19 meters along a permanent transect.

  16. Midway Atoll Site P2C 9/21/2002 24-25M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Midway Atoll, site P2C (28.260 N, 177.345 W), between 24 and 25 meters along a permanent transect.

  17. The High-Pressure Phase of MgB2C2

    NARCIS (Netherlands)

    Woerle, Michael; Fischbach, Urs; Widmer, Daniel; Krumeich, Frank; Nesper, Reinhard; Evers, Juergen; Stalder, Roland; Ulmer, Peter

    2010-01-01

    A high-pressure modification of MgB2C2 was synthesized and structurally characterized. The compound crystallizes in the orthorhombic space group Pnnm, with the lattice parameters a = 7.19633(3) angstrom, b = 4.61791(13) angstrom and c = 2.77714(8) angstrom. The compound contains heterographene B-C n

  18. "Expectations to Change" ((E2C): A Participatory Method for Facilitating Stakeholder Engagement with Evaluation Findings

    Science.gov (United States)

    Adams, Adrienne E.; Nnawulezi, Nkiru A.; Vandenberg, Lela

    2015-01-01

    From a utilization-focused evaluation perspective, the success of an evaluation is rooted in the extent to which the evaluation was used by stakeholders. This paper details the "Expectations to Change" (E2C) process, an interactive, workshop-based method designed to engage primary users with their evaluation findings as a means of…

  19. Dynamical Trust and Reputation Computation Model for B2C E-Commerce

    Directory of Open Access Journals (Sweden)

    Bo Tian

    2015-10-01

    Full Text Available Trust is one of the most important factors that influence the successful application of network service environments, such as e-commerce, wireless sensor networks, and online social networks. Computation models associated with trust and reputation have been paid special attention in both computer societies and service science in recent years. In this paper, a dynamical computation model of reputation for B2C e-commerce is proposed. Firstly, conceptions associated with trust and reputation are introduced, and the mathematical formula of trust for B2C e-commerce is given. Then a dynamical computation model of reputation is further proposed based on the conception of trust and the relationship between trust and reputation. In the proposed model, classical varying processes of reputation of B2C e-commerce are discussed. Furthermore, the iterative trust and reputation computation models are formulated via a set of difference equations based on the closed-loop feedback mechanism. Finally, a group of numerical simulation experiments are performed to illustrate the proposed model of trust and reputation. Experimental results show that the proposed model is effective in simulating the dynamical processes of trust and reputation for B2C e-commerce.

  20. Effect of Carbon Sources on the Catalytic Performance of Ni/β-Mo2C.

    Science.gov (United States)

    Zeng, Li-Zhen; Zhao, Shao-Fei; Li, Wei-Shan

    2015-06-01

    In this paper, Ni/β-Mo2C(S) and Ni/β-Mo2C(G) were prepared from solution-derived precursor with two different carbon sources (starch and glucose) and tested as anodic noble-metal-free catalysts in air-cathode microbial fuel cells (MFCs). The carburized catalyst samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET). The activity of the electrocatalyst towards the oxidation of several common microbial fermentation products (formate, lactate, and ethanol) was studied for MFC based on Klebsiella pneumoniae conditions. The composite MFC anodes were fabricated, and their catalytic behavior was investigated. With different carbon sources, the crystalline structure does not change and the crystallinity and surface area increase. The electrocatalytic experiments show that the Ni/β-Mo2C(G) gives the better bio- and electrocatalytic performance than Ni/β-Mo2C(S) due to its higher crystallinity and BET surface area.

  1. Deoxygenation of glycolaldehyde and furfural on Mo2C/Mo(100)

    Science.gov (United States)

    McManus, Jesse R.; Vohs, John M.

    2014-12-01

    The desire to produce fuels and chemicals in an energy conscious, environmentally sympathetic approach has motivated considerable research on the use of cellulosic biomass feedstocks. One of the major challenges facing the utilization of biomass is finding effective catalysts for the efficient and selective removal of oxygen from the highly-oxygenated, biomass-derived platform molecules. Herein, a study of the reaction pathways for the biomass-derived platform molecule furfural and biomass-derived sugar model compound glycolaldehyde provides insight into the mechanisms of hydrodeoxygenation (HDO) on a model molybdenum carbide catalyst, Mo2C/Mo(100). Using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS), it was found that the Mo2C/Mo(100) catalyst was active for selective deoxygenation of the aldehyde carbonyl by facilitating adsorption of the aldehyde in an η2(C,O) bonding configuration. Furthermore, the catalyst showed no appreciable activity for furanic ring hydrogenation, highlighting the promise of relatively inexpensive Mo2C catalysts for selective HDO chemistry.

  2. Magnetotransport Properties in High-Quality Ultrathin Two-Dimensional Superconducting Mo2C Crystals.

    Science.gov (United States)

    Wang, Libin; Xu, Chuan; Liu, Zhibo; Chen, Long; Ma, Xiuliang; Cheng, Hui-Ming; Ren, Wencai; Kang, Ning

    2016-04-26

    Ultrathin transition metal carbides are a class of developing two-dimensional (2D) materials with superconductivity and show great potentials for electrical energy storage and other applications. Here, we report low-temperature magnetotransport measurements on high-quality ultrathin 2D superconducting α-Mo2C crystals synthesized by a chemical vapor deposition method. The magnetoresistance curves exhibit reproducible oscillations at low magnetic fields for temperature far below the superconducting transition temperature of the crystals. We interpret the oscillatory magnetoresistance as a consequence of screening currents circling around the boundary of triangle-shaped terraces found on the surface of ultrathin Mo2C crystals. As the sample thickness decreases, the Mo2C crystals exhibit negative magnetoresistance deep in the superconducting transition regime, which reveals strong phase fluctuations of the superconducting order parameters associated with the superconductor-insulator transition. Our results demonstrate that the ultrathin superconducting Mo2C crystals provide an interesting system for studying rich transport phenomena in a 2D crystalline superconductor with enhanced quantum fluctuations.

  3. Surface morphology of orthorhombic Mo2C catalyst and high coverage hydrogen adsorption

    Science.gov (United States)

    Wang, Tao; Tian, Xinxin; Yang, Yong; Li, Yong-Wang; Wang, Jianguo; Beller, Matthias; Jiao, Haijun

    2016-09-01

    High coverage hydrogen adsorption on twenty two terminations of orthorhombic Mo2C has been systematically studied by using density functional theory and ab initio thermodynamics. Hydrogen stable coverage on the surfaces highly depends on temperatures and H2 partial pressure. The estimated hydrogen desorption temperatures under ultra-high vacuum condition on Mo2C are in reasonable agreement with the available temperature-programmed desorption data. Obviously, hydrogen adsorption can affect the surface stability and therefore modify the surface morphology of Mo2C. Upon increasing the chemical potential of hydrogen which can be achieved by increasing the H2 partial pressure and/or decreasing the temperature, the proportions of the (001), (010), (011) and (100) surfaces increase, while those of the (101), (110) and (111) surfaces decrease. Among these surfaces, the (100) surface is most sensitive upon hydrogen adsorption and the (111) surface is most exposed under a wide range of conditions. Our study clearly reveals the role of hydrogen on the morphology of orthorhombic Mo2C catalyst in conjugation with hydro-treating activity.

  4. High reflectance and low stress Mo2C/Be multilayers

    Science.gov (United States)

    Bajt, Sasa; Barbee, Jr., Troy W.

    2001-01-01

    A material for extreme ultraviolet (EUV) multilayers that will reflect at about 11.3 nm, have a high reflectance, low stress, and high thermal and radiation stability. The material consists of alternating layers of Mo.sub.2 C and Be deposited by DC magnetron sputtering on a substrate, such as silicon. In one example a Mo.sub.2 C/Be multilayer gave 65.2% reflectance at 11.25 nm measured at 5 degrees off normal incidence angle, and consisted of 70 bilayers with a deposition period of 5.78 nm, and was deposited at 0.83 mTorr argon (Ar) sputtering pressure, with the first and last layers being Be. The stress of the multilayer is tensile and only +88 MPa, compared to +330 MPa of a Mo/Be multilayers of the same thickness. The Mo.sub.2 C/Be multilayer was capped with carbon which produced an increase in reflectivity of about 7% over a similar multilayer with no carbon capping material, thus raising the reflectivity from 58.3% to over 65%. The multilayers were formed using either Mo.sub.2 C or Be as the first and last layers, and initial testing has shown the formation of beryllium carbide at the interfaces between the layers which both stabilizes and has a smoothing effect, and appear to be smoother than the interfaces in Mo/Be multilayers.

  5. Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

    NARCIS (Netherlands)

    Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M

    1995-01-01

    Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

  6. The pharmacogenetic control of antiplatelet response: candidate genes and CYP2C19.

    Science.gov (United States)

    Yang, Yao; Lewis, Joshua P; Hulot, Jean-Sébastien; Scott, Stuart A

    2015-01-01

    Aspirin, clopidogrel, prasugrel and ticagrelor are antiplatelet agents for the prevention of ischemic events in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) and other indications. Variability in response is observed to different degrees with these agents, which can translate to increased risks for adverse cardiovascular events. As such, potential pharmacogenetic determinants of antiplatelet pharmacokinetics, pharmacodynamics and clinical outcomes have been actively studied. This article provides an overview of the available antiplatelet pharmacogenetics literature. Evidence supporting the significance of candidate genes and their potential influence on antiplatelet response and clinical outcomes are summarized and evaluated. Additional focus is directed at CYP2C19 and clopidogrel response, including the availability of clinical testing and genotype-directed antiplatelet therapy. The reported aspirin response candidate genes have not been adequately replicated and few candidate genes have thus far been implicated in prasugrel or ticagrelor response. However, abundant data support the clinical validity of CYP2C19 and clopidogrel response variability among ACS/PCI patients. Although limited prospective trial data are available to support the utility of routine CYP2C19 testing, the increased risks for reduced clopidogrel efficacy among ACS/PCI patients that carry CYP2C19 loss-of-function alleles should be considered when genotype results are available.

  7. ABA Inducible Rice Protein Phosphatase 2C Confers ABA Insensitivity and Abiotic Stress Tolerance in Arabidopsis

    Science.gov (United States)

    Singh, Amarjeet; Jha, Saroj K.; Bagri, Jayram; Pandey, Girdhar K.

    2015-01-01

    Arabidopsis PP2C belonging to group A have been extensively worked out and known to negatively regulate ABA signaling. However, rice (Oryza sativa) orthologs of Arabidopsis group A PP2C are scarcely characterized functionally. We have identified a group A PP2C from rice (OsPP108), which is highly inducible under ABA, salt and drought stresses and localized predominantly in the nucleus. Genetic analysis revealed that Arabidopsis plants overexpressing OsPP108 are highly insensitive to ABA and tolerant to high salt and mannitol stresses during seed germination, root growth and overall seedling growth. At adult stage, OsPP108 overexpression leads to high tolerance to salt, mannitol and drought stresses with far better physiological parameters such as water loss, fresh weight, chlorophyll content and photosynthetic potential (Fv/Fm) in transgenic Arabidopsis plants. Expression profile of various stress marker genes in OsPP108 overexpressing plants revealed interplay of ABA dependent and independent pathway for abiotic stress tolerance. Overall, this study has identified a potential rice group A PP2C, which regulates ABA signaling negatively and abiotic stress signaling positively. Transgenic rice plants overexpressing this gene might provide an answer to the problem of low crop yield and productivity during adverse environmental conditions. PMID:25886365

  8. 76 FR 77833 - Scientific Information Request on CYP2C19 Variants and Platelet Reactivity Tests

    Science.gov (United States)

    2011-12-14

    ... Variants and Platelet Reactivity Tests AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS... platelet reactivity tests. Scientific information is being solicited to inform our Comparative... for studies that report on CYP2C19 variants and platelet reactivity tests, including those...

  9. BAMBI Promotes C2C12 Myogenic Differentiation by Enhancing Wnt/β-Catenin Signaling

    Directory of Open Access Journals (Sweden)

    Qiangling Zhang

    2015-08-01

    Full Text Available Bone morphogenic protein and activin membrane-bound inhibitor (BAMBI is regarded as an essential regulator of cell proliferation and differentiation that represses transforming growth factor-β and enhances Wnt/β-catenin signaling in various cell types. However, its role in skeletal muscle remains largely unknown. In the current study, we found that the expression level of BAMBI peaked in the early differentiation phase of the C2C12 rodent myoblast cell line. Knockdown of BAMBI via siRNA inhibited C2C12 differentiation, indicated by repressed MyoD, MyoG, and MyHC expression as well as reductions in the differentiation and fusion indices. BAMBI knockdown reduced the activity of Wnt/β-catenin signaling, as characterized by the decreased nuclear translocation of β-catenin and the lowered transcription of Axin2, which is a well-documented target gene of the Wnt/β-catenin signaling pathway. Furthermore, treatment with LiCl, an activator of Wnt/β-catenin signaling, rescued the reduction in C2C12 differentiation caused by BAMBI siRNA. Taken together, our data suggest that BAMBI is required for normal C2C12 differentiation, and that its role in myogenesis is mediated by the Wnt/β-catenin pathway.

  10. Activation of serotonin 2C receptors in dopamine neurons inhibits binge-like eating in mice

    Science.gov (United States)

    Neural networks that regulate binge eating remain to be identified, and effective treatments for binge eating are limited. We combined neuroanatomic, pharmacologic, electrophysiological, Cre-lox, and chemogenetic approaches to investigate the functions of 5-hydroxytryptamine (5-HT) 2C receptor (5-HT...

  11. Electron Affinity of trans-2-C4F8 from Electron Attachment-Detachment Kinetics

    Science.gov (United States)

    2009-09-04

    either isomer. This attachment rate constant agrees well with other values measured only at 300 K for “2-C4F8” by Bansal and Fessenden (4.9 × 10-8...Grajower, R. Int. J. Mass Spectrom. Ion Phys. 1973, 10, 11. (5) Bansal, K. M.; Fessenden , R. W. J. Chem. Phys. 1973, 59, 1760. (6) Sauers, I

  12. User-Interface Design Characteristics of Fortune 500 B2C E-Commerce Sites and Industry Differences

    Science.gov (United States)

    Zhao, Jensen J.; Truell, Allen D.; Alexander, Melody W.

    2006-01-01

    This study examined the user-interface design characteristics of 107 Fortune 500 B2C e-commerce Web sites and industry differences. Data were collected from corporate homepages, B2C product/service pages, B2C interactive shopping pages, as well as customer satisfaction of 321 online shoppers. The findings indicate that (a) to attract online…

  13. The in-vitro effect of complementary and alternative medicines on cytochrome P450 2C9 activity

    NARCIS (Netherlands)

    Mooiman, Kim D; Goey, Andrew K L; Huijbregts, Tomy J; Maas-Bakker, Roel F; Beijnen, Jos H; Schellens, Jan H M; Meijerman, Irma

    OBJECTIVES: The aim of this study is to establish the inhibitory effects of 14 commonly used complementary and alternative medicines (CAM) on the metabolism of cytochrome P450 2C9 (CYP2C9) substrates 7-methoxy-4-trifluoromethyl coumarine (MFC) and tolbutamide. CYP2C9 is important for the metabolism

  14. User-Interface Design Characteristics of Fortune 500 B2C E-Commerce Sites and Industry Differences

    Science.gov (United States)

    Zhao, Jensen J.; Truell, Allen D.; Alexander, Melody W.

    2006-01-01

    This study examined the user-interface design characteristics of 107 Fortune 500 B2C e-commerce Web sites and industry differences. Data were collected from corporate homepages, B2C product/service pages, B2C interactive shopping pages, as well as customer satisfaction of 321 online shoppers. The findings indicate that (a) to attract online…

  15. 77 FR 2573 - International Product Change-Global Plus 1C and 2C Negotiated Service Agreements

    Science.gov (United States)

    2012-01-18

    ... International Product Change--Global Plus 1C and 2C Negotiated Service Agreements AGENCY: Postal Service TM... Regulatory Commission to add Global Plus 1C and 2C Negotiated Service Agreements to the Competitive Products... of United States Postal Service to Add Global Plus 1C and 2C Negotiated Service Agreements to the...

  16. Role of 5-HT2C receptor gene variants in antipsychotic-induced weight gain

    Directory of Open Access Journals (Sweden)

    Brandl EJ

    2011-08-01

    Full Text Available Tessa JM Wallace, Clement C Zai, Eva J Brandl, Daniel J MüllerNeurogenetics Section, Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, CanadaAbstract: Antipsychotic-induced weight gain is a serious side effect of antipsychotic medication that can lead to increased morbidity, mortality, and non-compliance in patients. Numerous single nucleotide polymorphisms have been studied for association with antipsychotic-induced weight gain in an attempt to find genetic predictors of this side effect. An ability to predict this side effect could lead to personalized treatment plans for predisposed individuals, which could significantly decrease the prevalence and severity of weight gain. Variations in the serotonin receptor 2c gene (HTR2C have emerged as promising candidates for prediction of antipsychotic-induced weight gain. Specifically, the well-studied -759C/T promoter polymorphism has been associated with weight gain in diverse populations, although some studies have reported no association. This discrepancy is likely due to heterogeneity in study design with respect to ethnicity, treatment duration, and other variables. Notably, the association between HTR2C and antipsychotic-induced weight gain appears strongest in short-term studies on patients with limited or no previous antipsychotic treatment. Other, less extensively studied promoter polymorphisms (-697C/G, -997G/A, and -1165A/G have also emerged as potential predictors of antipsychotic-induced weight gain. Conversely, the well-studied intronic polymorphism Cys23Ser does not appear to be associated. With further research on both HTR2C and other genetic and environmental predictors of antipsychotic-induced weight gain, a predictive test could one day be created to screen patients and provide preventative or alternative treatment for those who are predisposed to this serious side effect.Keywords: HTR2C, pharmacogenomics, promoter polymorphism

  17. First-principles study of He trapping in η-Fe2C

    Science.gov (United States)

    He, Bing-Ling; Wang, Jin-Long; Tian, Zhi-Xue; Jiang, Li-Juan; Song, Wei; Wang, Bin

    2016-11-01

    The distribution of He in η-Fe2C has been studied by first-principles calculations. The formation energies of interstitial He and substitutional He (replacing Fe) are 3.76 eV and 3.49 eV, respectively, which are remarkably smaller than those in bcc Fe, indicating that He is more soluble in η-Fe2C than in bcc Fe. The binding potencies of both a substitutional-interstitial He pair (1.28 eV) and a substitutional-substitutional He pair (0.76 eV) are significantly weaker than those in bcc Fe. The binding energy between the two He atoms in an interstitial-interstitial He pair (0.31 eV) is the same as that in bcc Fe, but the diffusion barrier of interstitial He (0.35 eV) is much larger than that in bcc Fe, suggesting that it is more difficult for the interstitial He atom to agglomerate in η-Fe2C than in bcc Fe. Thus, self-trapping of He in η-Fe2C is less powerful than that in bcc Fe. As a consequence, small and dense η-Fe2C particles in ferritic steels might serve as scattered trapping centers for He, slow down He bubble growth at the initial stage, and make the steel more swelling resistant. Project supported by the Research Key Project of Science and Technology of Education Bureau of Henan Province, China (Grant Nos. 14A140030, 15A140032, 15B150010, and 15A430037) and the Innovation Talents Program of Science and Technology of Institution of Higher Education of Henan Province, China (Grant No. 14HASTIT044).

  18. Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2-deficient myotubes.

    Science.gov (United States)

    Schöneich, Christian; Dremina, Elena; Galeva, Nadezhda; Sharov, Victor

    2014-01-01

    Muscle cell apoptosis accompanies normal muscle development and regeneration, as well as degenerative diseases and aging. C2C12 murine myoblast cells represent a common model to study muscle differentiation. Though it was already shown that myogenic differentiation of C2C12 cells is accompanied by enhanced apoptosis in a fraction of cells, either the cell population sensitive to apoptosis or regulatory mechanisms for the apoptotic response are unclear so far. In the current study we characterize apoptotic phenotypes of different types of C2C12 cells at all stages of differentiation, and report here that myotubes of differentiated C2C12 cells with low levels of anti-apoptotic Bcl-2 expression are particularly vulnerable to apoptosis even though they are displaying low levels of pro-apoptotic proteins Bax, Bak and Bad. In contrast, reserve cells exhibit higher levels of Bcl-2 and high resistance to apoptosis. The transfection of proliferating myoblasts with Bcl-2 prior to differentiation did not protect against spontaneous apoptosis accompanying differentiation of C2C12 cells but led to Bcl-2 overexpression in myotubes and to significant protection from apoptotic cell loss caused by exposure to hydrogen peroxide. Overall, our data advocate for a Bcl-2-dependent mechanism of apoptosis in differentiated muscle cells. However, downstream processes for spontaneous and hydrogen peroxide induced apoptosis are not completely similar. Apoptosis in differentiating myoblasts and myotubes is regulated not through interaction of Bcl-2 with pro-apoptotic Bcl-2 family proteins such as Bax, Bak, and Bad.

  19. Pharmacokinetics of lansoprazole in Chinese healthy subjects in relation to CYP2C19 genotypes

    Institute of Scientific and Technical Information of China (English)

    Yu-rong HU; Hai-ling QIAO; Quan-cheng KAN

    2004-01-01

    AIM: To study the kinetic characteristics of lansoprazole in healthy Chinese subjects in relation to CYP2C19 genotype status for the individualized dose regimen of lansoprazole. METHODS: Nine homozygous extensive metabolizers (homo EMs) and 9 poor metabolizers (PMs) were recruited for the study from a total of 70 healthy Chinese volunteers, whose CYP2C19 genotype status was determined by the PCR-RFLP techniques. After a single oral dose of 30 mg lansoprazole capsule, plasma concentrations of lansoprazole were determined with HPLC method. RESULTS: In Chinese subjects, the allele frequencies of the CYP2C19ml and CYP2C19m2 mutation were 0.35 and 0.07, respectively. The concentration-time curves in the two groups were best fitted to a one-compartment model. In the homo EMs and the PMs groups, the main kinetic parameters were as follows: Tmax(2.44±0.85)and (2.33±0.94) h, Cmax (1.10±0.34) and (1.73±0.56) mg/L, Cl/F (16.55±6.38) and (3.58± 1) L/h, T1/2ke (1.96±0.51)Cmax values existed between the two groups (P<0.01). CONCLUSION: CYP2C19 genotype is the major factor to influence the interindividual kinetic variability of lansoprazole. Individualized dose regimen of lansoprazole, based on identification of genotype, can be of great benefit for the reasonable use of this drug.

  20. Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

    Directory of Open Access Journals (Sweden)

    Case Karen L

    2008-10-01

    Full Text Available Abstract Background Persistent stimulation of cardiac β1-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively on the risk of death/transplant in heart failure patients. Methods Sixteen sequence variations in ADRA2C and 17 sequence variations in ADRB1 were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation. Results Three polymorphisms in ADRA2C and five polymorphisms in ADRB1 were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18 relative to all other genotype classes. Conclusion Multiple polymorphisms act synergistically between the ADRA2C and ADRB1 genes to increase risk of death or cardiac transplant in heart failure patients.

  1. cis-Dichlorido(1,3-dimesitylimidazolidin-2-ylidene(2-formylbenzylidene-κ2C,Oruthenium diethyl ether solvate

    Directory of Open Access Journals (Sweden)

    Christian Slugovc

    2010-02-01

    Full Text Available The title compound, [RuCl2(C8H6O(C21H26N2]·C4H10O, contains a catalytically active ruthenium carbene complex of the `second-generation Grubbs/Hoveyda' type with Ru in a square-pyramidal coordination, the apex of which is formed by the benzylidene carbene atom with Ru=C 1.827 (2 Å. The complex shows the uncommon cis, rather than the usual trans, arrangement of the two chloride ligands, with Ru—Cl bond lengths of 2.3548 (6 and 2.3600 (6 Å, and a Cl—Ru—Cl angle of 89.76 (2°. This cis configuration is desirable for certain applications of ring-opening metathesis polymerization (ROMP of strained cyclic olefins. The crystalline solid is a diethyl ether solvate, which is built up from a porous framework of Ru complexes held together by π–π stacking and C—H...Cl and C—H...O interactions. The disordered diethyl ether solvent molecules are contained in two independent infinite channels, which extend parallel to the c axis at x,y = 0,0 and x,y = {1over 2},{1over 2} and have solvent-accessible void volumes of 695 and 464 Å3 per unit cell.

  2. FeS2@C nanowires derived from organic-inorganic hybrid nanowires for high-rate and long-life lithium-ion batteries

    Science.gov (United States)

    Zhang, Feifei; Wang, Chunli; Huang, Gang; Yin, Dongming; Wang, Limin

    2016-10-01

    One-dimensional (1D) porous FeS2@C nanowires as a high cathode material for lithium-ion batteries (LIBs) are synthesized on a large-scale from an organic-inorganic hybrid nanowire precursor. The FeS2@C nanowires not only provide a continuous and fast electron transport pathway, favorable diffusion kinetics, but also provide the protection buffer the volume expansion and effectively prevent the polysulfides from dissolving in the electrolyte during cycling. Attributing to the synergistic advantages of both 1D porous nanostructure and the encapsulation of thin amorphous carbon layers, the FeS2@C nanowires exhibit remarkable lithium storage performance with a high specific capacity of 889 mA h g-1 at 0.1 A g-1 and 521 mA h g-1 at 10 A g-1. Moreover, a discharge energy density of 1225 Wh kg-1 is obtained at 2 A g-1 and remains as high as 637 Wh kg-1 after 1000 cycles, which is even higher than the LiCoO2 cathode. The results demonstrate that the potential for applications in LIBs with high power density and long cycling life.

  3. Toward reduction in animal sacrifice for drugs: molecular modeling of Macaca fascicularis P450 2C20 for virtual screening of Homo sapiens P450 2C8 substrates.

    Science.gov (United States)

    Rua, Francesco; Di Nardo, Giovanna; Sadeghi, Sheila J; Gilardi, Gianfranco

    2012-01-01

    Macaca fascicularis P450 2C20 shares 92% identity with human cytochrome P450 2C8, which is involved in the metabolism of more than 8% of all prescribed drugs. To date, only paclitaxel and amodiaquine, two substrate markers of the human P450 2C8, have been experimentally confirmed as M. fascicularis P450 2C20 drugs. To bridge the lack of information on the ligands recognized by M. fascicularis P450 2C20, in this study, a three-dimensional homology model of this enzyme was generated on the basis of the available crystal structure of the human homologue P450 2C8 using YASARA. The results indicated that 90.0%, 9.0%, 0.5%, and 0.5% of the residues of the P450 2C20 model were located in the most favorable, allowed, generously allowed, and disallowed regions, respectively. The root-mean-square deviation of the C-alpha superposition of the M. fascicularis P450 2C20 model with the Homo sapiens P450 2C8 was 0.074 Å, indicating a very high similarity of the two structures. Subsequently, the 2C20 model was used for in silico screening of 58 known P450 2C8 substrates and 62 inhibitors. These were also docked in the active site of the crystal structure of the human P450 2C8. The affinity of each compound for the active site of both cytochromes proved to be very similar, meaning that the few key residues that are mutated in the active site of the M. fascicularis P450 do not prevent the P450 2C20 from recognizing the same substrates as the human P450 2C8.

  4. Effect of Mo{sub 2}C/(Mo{sub 2}C + WC) weight ratio on the microstructure and mechanical properties of Ti(C,N)-based cermet tool materials

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qingzhong; Zhao, Jun, E-mail: zhaojun@sdu.edu.cn; Ai, Xing; Qin, Wenzhen; Wang, Dawei; Huang, Weimin

    2015-11-15

    To optimize the Mo{sub 2}C content in Ti(C,N)-based cermet tool materials used for cutting the high-strength steel of 42CrMo (AISI 4140/4142 steel), the cermets with different Mo{sub 2}C/(Mo{sub 2}C + WC) weight ratios were prepared. And the microstructure and mechanical properties of cermets were investigated by scanning electron microscope (SEM), X-ray diffraction (XRD) and measurements of transverse rupture strength (TRS), Vickers hardness (HV) and fracture toughness (K{sub IC}). The results indicate that the Mo{sub 2}C/(Mo{sub 2}C + WC) ratios have great influences on the microstructure features and mechanical properties of Ti(C,N)-based cermets. When the Mo{sub 2}C/(Mo{sub 2}C + WC) ratio increases, the Ti(C,N) grains become finer with smaller black cores surrounded by thinner rims, and the structure of cermets tends to be more compact with smaller binder mean free path. Owing to the medium grains and moderate rims, the cermets with a Mo{sub 2}C/(Mo{sub 2}C + WC) ratio of 0.4 exhibit better mechanical properties, and can be chosen as the tool material for machining 42CrMo steel due to the lower Mo content. - Highlights: • Mo{sub 2}C/(Mo{sub 2}C + WC) ratios affect microstructure and mechanical properties of cermets. • Grains become fine and structure of cermets tends to be compact with raised Mo{sub 2}C. • The cermets with a Mo{sub 2}C/(Mo{sub 2}C + WC) ratio of 0.4 can be used to machine 42CrMo steel.

  5. Lack of α2C-Adrenoceptor Results in Contrasting Phenotypes of Long Bones and Vertebra and Prevents the Thyrotoxicosis-Induced Osteopenia.

    Directory of Open Access Journals (Sweden)

    Marilia Bianca Cruz Grecco Teixeira

    Full Text Available A series of studies have demonstrated that activation of the sympathetic nervous system (SNS causes osteopenia via β2-adrenoceptor (β2-AR signaling. However, in a recent study, we found an unexpected and generalized phenotype of high bone mass in female mice with chronic sympathetic hyperactivity, due to double gene inactivation of adrenoceptors that negatively regulate norepinephrine release, α2A-and α2C-AR (α2A/2C-AR-/-. These findings suggest that β2-AR is not the single adrenoceptor involved in bone turnover regulation and show that α2-AR signaling may also mediate the SNS actions in the skeleton. In addition, we found that α2A/2C-AR-/- animals are resistant to the thyrotoxicosis-induced osteopenia, suggesting that thyroid hormone (TH, when in supraphysiological levels, interacts with the SNS to control bone mass and structure, and that this interaction may also involve α2-AR signaling. In the present study, to further investigate these hypotheses and to discriminate the roles of α2-AR subtypes, we have evaluated the bone phenotype of mice with the single gene inactivation of α2C-AR subtype, which mRNA expression was previously shown to be down regulated by triiodothyronine (T3. A cohort of 30 day-old female α2CAR-/- mice and their wild-type (WT controls were treated with a supraphysiological dose of T3 for 30 or 90 days, which induced a thyrotoxic state in both mouse lineages. The micro-computed tomographic (μCT analysis showed that α2C-AR-/- mice present lower trabecular bone volume (BV/TV and number (Tb.N, and increased trabecular separation (Tb.Sp in the femur compared with WT mice; which was accompanied by decreased bone strength (determined by the three-point bending test in the femur and tibia. The opposite was observed in the vertebra, where α2C-AR-/- mice show increased BV/TV, Tb.N and trabecular thickness (Tb.Th, and decreased Tb.Sp, compared with WT animals. In spite of the contrasting bone phenotypes of the femur

  6. Development of gas chromatography-flame ionization detection system with a single column and liquid nitrogen-free for measuring atmospheric C2-C12 hydrocarbons.

    Science.gov (United States)

    Liu, Chengtang; Mu, Yujing; Zhang, Chenglong; Zhang, Zhibo; Zhang, Yuanyuan; Liu, Junfeng; Sheng, Jiujiang; Quan, Jiannong

    2016-01-04

    A liquid nitrogen-free GC-FID system equipped with a single column has been developed for measuring atmospheric C2-C12 hydrocarbons. The system is consisted of a cooling unit, a sampling unit and a separation unit. The cooling unit is used to meet the temperature needs of the sampling unit and the separation unit. The sampling unit includes a dehydration tube and an enrichment tube. No breakthrough of the hydrocarbons was detected when the temperature of the enrichment tube was kept at -90 °C and sampling volume was 400 mL. The separation unit is a small round oven attached on the cooling column. A single capillary column (OV-1, 30 m × 0.32 mm I.D.) was used to separate the hydrocarbons. An optimal program temperature (-60 ∼ 170 °C) of the oven was achieved to efficiently separate C2-C12 hydrocarbons. There were good linear correlations (R(2)=0.993-0.999) between the signals of the hydrocarbons and the enrichment amount of hydrocarbons, and the relative standard deviation (RSD) was less than 5%, and the method detection limits (MDLs) for the hydrocarbons were in the range of 0.02-0.10 ppbv for sampling volume of 400 mL. Field measurements were also conducted and more than 50 hydrocarbons from C2 to C12 were detected in Beijing city.

  7. Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Rovetta, Francesca [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Stacchiotti, Alessandra [Institute of Human Anatomy, Department of Clinical and Experimental Sciences, University of Brescia, Brescia I-25123 (Italy); Faggi, Fiorella [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Catalani, Simona; Apostoli, Pietro [Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia I-25123 (Italy); Fanzani, Alessandro, E-mail: fanzani@med.unibs.it [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Aleo, Maria Francesca, E-mail: aleo@med.unibs.it [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy)

    2013-09-01

    Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl{sub 2} doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl{sub 2} doses for prolonged time points. Furthermore, CoCl{sub 2} treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes.

  8. Dissolution and electrochemical properties of molybdenum carbide (Mo{sub 2}C) in basic solutions

    Energy Technology Data Exchange (ETDEWEB)

    Maslennikov, A.; Boudanova, N. [Academy of Sciences, Moscow (Russian Federation). A.N. Frumkin Inst. of Physical Chemistry and Electrochemistry; Cannes, C.; Fourest, B. [Institut de Physique Nucleaire (INP), 91 - Orsay (France); Vivier, V. [Lab. Interfaces et Systemes Electrochimiques, 75 - Paris (France); Moisy, P. [CEA VALRHO DEN/DRCP/SCPS, 30 - Bagnols sur Ceze (France)

    2007-07-01

    The dissolution and electrochemical properties of molybdenum carbide were investigated using a number of electrochemical techniques, including general corrosion tests (GCT), linear voltammetry (LV), potential controlled electrolysis (PCE) and Scanning Electrochemical Microscopy (SECM), in basic media (0.5-4 M NaOH and 1 M NaHCO{sub 3}/Na{sub 2}CO{sub 3}, pH 9.1-11.3). It was shown that the Mo2C corrosion potential (E{sub corr}) shifted towards negative values from -0.39 to -0.96 V/SCE with an increase of the OH{sup -} concentration and did not depend on the CO{sub 3}{sup 2-} concentration in the electrolyte. LV measurements in carbonate buffer (pH 9.2), evidenced three potential regions: passivation from E{sub corr} to -0.2 V/SCE, pseudopassivation from -0.25 to 0 V/SCE and anodic dissolution (transpassivation) at E > 0.1 V/SCE. The potentials delimiting the mentioned regions decreased with the increase of the OH{sup -} concentration, becoming undistinguished in 2 M NaOH. The Mo{sub 2}C dissolution rate (k{sub diss}) in the transpassive state was estimated using LV data. In 4 M NaOH at -0.1 V/SCE, k{sub diss} reached 430 mg cm{sup -2}h{sup -1} and decreased with the decrease of the OH{sup -} concentration and the electrolysis potential. The Mo{sub 2}C dissolution current efficiency varied between 12 and 13Fmol{sup -1} Mo{sub 2}C, proving the formation of the intermediate products of a carbon oxidative degradation during PCE. The presence of C{sub 2}O{sub 4}{sup 2-} and non-identified aromatic compounds in the electrolytes after Mo{sub 2}C dissolution was ascertained, using capillary zone electrophoresis. Scanning electrochemical microscopy (SECM) confirmed the formation of a pseudopassive film and demonstrated the increase of its thickness with the increase of the applied potential. The effect of the presence of Mo{sub 2}C on the irradiated UC fuel dissolution rate and the mechanisms involved are discussed. (orig.)

  9. Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52,000 individuals

    DEFF Research Database (Denmark)

    Kaur-Knudsen, D; Bojesen, S E; Nordestgaard, B G

    2009-01-01

    Cytochrome P450 2C9 (CYP2C9) enzymes metabolize warfarin and arachidonic acid. We hypothesized that the CYP2C9(*)2 (rs.1799853) and CYP2C9(*)3 (rs.1057910) polymorphisms with decreased enzyme activity affect risk of subclinical atherosclerosis (reduced ankle brachial index and increased C...... of follow-up; the Copenhagen General Population Study, a cross-sectional study including 21 629 participants; and the Copenhagen Ischemic Heart Disease Study, a case-control study including 5082 cases and 14 904 controls. CYP2C9 carriers versus noncarriers did not associate with subclinical atherosclerosis......% power. In conclusion, in three independent studies totaling more than 52 000 individuals, we found no association between CYP2C9(*)2 and CYP2C9(*)3 polymorphisms and risk of subclinical atherosclerosis, ischemic vascular disease or death after ischemic heart disease....

  10. Impact of CYP2C8*3 polymorphism on in vitro metabolism of imatinib to N-desmethyl imatinib.

    Science.gov (United States)

    Khan, Muhammad Suleman; Barratt, Daniel T; Somogyi, Andrew A

    2016-01-01

    1. Imatinib is metabolized to N-desmethyl imatinib by CYPs 3A4 and 2C8. The effect of CYP2C8*3 genotype on N-desmethyl imatinib formation was unknown. 2. We examined imatinib N-demethylation in human liver microsomes (HLMs) genotyped for CYP2C8*3, in CYP2C8*3/*3 pooled HLMs and in recombinant CYP2C8 and CYP3A4 enzymes. Effects of CYP-selective inhibitors on N-demethylation were also determined. 3. A single-enzyme Michaelis-Menten model with autoinhibition best fitted CYP2C8*1/*1 HLM (n = 5) and recombinant CYP2C8 kinetic data (median ± SD Ki = 139 ± 61 µM and 149 µM, respectively). Recombinant CYP3A4 showed two-site enzyme kinetics with no autoinhibition. Three of four CYP2C8*1/*3 HLMs showed single-enzyme kinetics with no autoinhibition. Binding affinity was higher in CYP2C8*1/*3 than CYP2C8*1/*1 HLM (median ± SD Km = 6 ± 2 versus 11 ± 2 µM, P=0.04). CYP2C8*3/*3 (pooled HLM) also showed high binding affinity (Km = 4 µM) and single-enzyme weak autoinhibition (Ki = 449 µM) kinetics. CYP2C8 inhibitors reduced HLM N-demethylation by 47-75%, compared to 0-30% for CYP3A4 inhibitors. 4. In conclusion, CYP2C8*3 is a gain-of-function polymorphism for imatinib N-demethylation, which appears to be mainly mediated by CYP2C8 and not CYP3A4 in vitro in HLM.

  11. Synthesis, crystal structure, growth, optical and third order nonlinear optical studies of 8HQ2C5N single crystal - An efficient third-order nonlinear optical material

    Energy Technology Data Exchange (ETDEWEB)

    Divya Bharathi, M.; Ahila, G.; Mohana, J. [Department of Physics, Presidency College, Chennai 600005 (India); Chakkaravarthi, G. [Department of Physics, CPCL Polytechnic College, Chennai 600068 (India); Anbalagan, G., E-mail: anbu24663@yahoo.co.in [Department of Nuclear Physics, University of Madras, Chennai 600025 (India)

    2017-05-01

    A neoteric organic third order nonlinear optical material 8-hydroxyquinolinium 2-chloro-5-nitrobenzoate dihydrate (8HQ2C5N) was grown by slow cooling technique using ethanol: water (1:1) mixed solvent. The calculated low value of average etch pit solidity (4.12 × 10{sup 3} cm{sup −2}) indicated that the title crystal contain less defects. From the single crystal X-ray diffraction data, it was endowed that 8HQ2C5N crystal belongs to the monoclinic system with centrosymmetric space group P2{sub 1}/c and the cell parameters values, a = 9.6546 (4) Ǻ, b = 7.1637(3) Ǻ, c = 24.3606 (12) Ǻ, α = γ = 90°, β = 92.458(2)° and volume = 1683.29(13) Ǻ{sup 3}. The FT-IR and FT-Raman spectrum were used to affirm the functional group of the title compound. The chemical structure of 8HQ2C5N was scrutinized by {sup 13}C and {sup 1}H NMR spectral analysis and thermal stability through the differential scanning calorimetry study. Using optical studies the lower cut-off wavelength and optical band gap of 8HQ2C5N were found to be 364 nm and 3.17 eV respectively. Using the single oscillator model suggested by Wemple – Didomenico, the oscillator energy (E{sub o}), the dispersion energy (E{sub d}) and static dielectric constant (ε{sub o}) were estimated. The third-order susceptibility were determined as Im χ{sup (3)} = 2.51 × 10{sup −5} esu and Re χ{sup (3)} = 4.46 × 10{sup −7} esu. The theoretical third-order nonlinear optical susceptibility χ{sup (3)} was calculated and the results were compared with experimental value. Photoluminescence spectrum of 8HQ2C5N crystal showed the yellow emission. The crystal had the single shot laser damage threshold of 5.562 GW/cm{sup 2}. Microhardness measurement showed that 8HQ2C5N belongs to a soft material category. - Highlights: • A new organic single crystals were grown and the crystal structure was reported. • Crystal possess, good transmittance, thermal and mechanical stability. • Single shot LDT value is found to be

  12. A phylogenetic study of canine parvovirus type 2c in midwestern Brazil

    Directory of Open Access Journals (Sweden)

    Danúbia S. Fontana

    2013-02-01

    Full Text Available Since the late 1970s, canine parvovirus type 2 (CPV-2 has emerged as a causative agent of fatal severe acute hemorrhagic enteritis in dogs. To date, three antigenic types of CPV-2 were described worldwide (CPV-2a/b/c. This study was conducted to determine the variants of CPV-2 circulating in dogs from the Cuiabá Municipality in Midwestern Brazil. Out of 50 fecal samples, collected between 2009 and 2011, 27 tested positive for CPV-2. A 583 bp fragment of the VP2 gene was amplified by PCR, 13 representative samples were analyzed further by DNA sequencing. All strains were characterized as CPV-2c, displayed a low genetic variability although observed several amino acid substitution. These findings indicated that CPV-2c has been circulating in dogs from the Cuiabá Municipality in Midwestern Brazil.

  13. Establishing Efficient C2C E-alliance Based on Mobile Agent

    Institute of Scientific and Technical Information of China (English)

    YU Xiao-bing; GUO Shun-sheng; GUO Jun

    2010-01-01

    In order to alleviate difficulties of conducting consumer-to-consumer(C2C)e-commerce transaction,establishing efficient e-alliance was proposed.E-alliance is the union of e-commerce sites.It is constructed by mobile agents.The mobile agent architecture was discussed.The process of selecting suitable e-commerce site to e-alliance was presented based on support vector machine(SVM)and fuzzy method.A prototype of the proposed system is implemented on a web platform.To enable data exchange between e-alliance and e-commerce,the system employs XML as data format.The prototype has demonstrated that the efficient C2C e-alliance is reasonable.

  14. Be{sub 2}C formation in beryllium-carbon binary system by vacuum heating

    Energy Technology Data Exchange (ETDEWEB)

    Ashida, Kan; Watanabe, Kuniaki [Toyama Univ. (Japan). Hydrogen Isotope Research Center

    1998-01-01

    The surface chemical states of beryllium and carbon binary systems at elevated temperature were investigated by means of x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS). The XPS measurements revealed that the mixed subsurface layers containing Be and C readily yield Be{sub 2}C layers by vacuum heating and ion bombardment. The SIMS measurements showed that hydrogen isotope atoms are trapped by three distinct sites; namely Be, C, and O-sites on the sample surface. The SIMS measurements also showed that carbon atoms lose its ability to bind with hydrogen isotope atoms on forming Be{sub 2}C. It would be a key to control hydrogen inventory when Be and C are used together as PFM. (author)

  15. Neutron Scattering Study of Na_2C_60 in (P,T)-Plane

    Science.gov (United States)

    Trevino, S. F.; Yildirim, T.; Neumann, D. A.; Fischer, J. E.

    1996-03-01

    Na_2C_60 forms the simplest system to investigate various intermolecular interactions. Therefore, we have studied Na_2C_60 for 0 250 K and P > 1 kbar, the structure is distorted, qualitatively similar to suggested pressure induced polymer phase of Na_2RbC_60[1]. Here the peaks at low Q are significantly broaden while the higher Q peaks are almost completely smeared out. Inelastic neutron scattering measurements performed at T=150 K and with P=0 and 4 kbar did not show any new lattice modes in the range 100-200 cm-1, inconsistent with C_60 polymerization. Instead, we observed an excess of low energy states in the distorted phase, reminiscent of what is observed in glassy solids. fˇill [1] Q.Zhu, Phys. Rev. B 52, R723 (1995).

  16. Occurrence of canine parvovirus type 2c in the dogs with haemorrhagic enteritis in India.

    Science.gov (United States)

    Nandi, S; Chidri, S; Kumar, Manoj; Chauhan, R S

    2010-02-01

    Canine parvovirus 2 (CPV-2) causes a highly contagious and often fatal disease in dogs. Since its sudden emergence in the early 1970s, CPV-2 has been evolving through the generation of novel genetic and antigenic variants (CPV-2a/b/c) that are unevenly distributed throughout the world. In the present study we have examined 36 clinical cases of dogs suspected of CPV collected during year 2006. A fragment of the VP2 gene of the virus was analyzed using polymerase chain reaction (PCR), restriction endonuclease (RE) and DNA sequence analysis. Out of the 36 samples analyzed, 16 were found positive for CPV-2a/2b by conventional PCR. DNA sequencing was done for 6 PCR positive samples, out of which three were characterized as CPV-2c, indicating that this CPV type 2c is currently circulating in India.

  17. SPECIAL LINEAR GROUP SL(2, C AND GENERATING FUNCTIONS FOR ULTRASPHERICAL POLYNOMIALS

    Directory of Open Access Journals (Sweden)

    I.K.Khanna

    2011-11-01

    Full Text Available In this paper, the generating functions for ultraspherical polynomials Cα n (x (Gegenbaur polynomials are obtained by using the representa- tion theory of the Lie group SL(2, C (the complex special linear group giving a suitable interpretation to the index 0 n0 . Further, linearly inde- pendent differential J-operators derived, which generate a Lie algebra isomorphic to sl(2, C. The principle interest in our results lies in the fact that, how thecomplex special linear group can be applied suitably to the Gegenbaur polynomials in order to derive six bilinear/bilateral generating functions. The generating functions, in turn yield, Legendre polynomials as special cases. Many results obtained are well known but some of them are believed to be new in the theory of specialfunctions.

  18. Silencing myotubularin related protein 7 enhances proliferation and early differentiation of C2C12 myoblast.

    Science.gov (United States)

    Yuan, Zhuning; Chen, Yaosheng; Zhang, Xumeng; Zhou, Xingyu; Li, Mingsen; Chen, Hu; Wu, Ming; Zhang, Ying; Mo, Delin

    2017-03-11

    Myotubularin related protein 7 (MTMR7) is a key member of the highly conserved myotubularin related proteins (MTMRs) family, which has phosphatase activity. MTMR7 was increased during myoblast differentiation and exhibited high expression level at primary fibers formation stages in pigs. This suggests that MTMR7 may be involved in myogenesis. In our study, we investigated the roles of MTMR7 on proliferation and differentiation of C2C12 myoblasts. Knocking down MTMR7 not only enhanced myoblast early differentiation via altering the expression of Myf5, but also promoted myoblast proliferation through increasing cyclinA2 expression. The improved proliferation capacity was related to the increased phosphorylation of AKT. Taken together, our research demonstrates that MTMR7 plays an important role in proliferation and early differentiation of C2C12 myoblast.

  19. Degradation of triclocarban by a triclosan-degrading Sphingomonas sp. strain YL-JM2C.

    Science.gov (United States)

    Mulla, Sikandar I; Hu, Anyi; Wang, Yuwen; Sun, Qian; Huang, Shir-Ly; Wang, Han; Yu, Chang-Ping

    2016-02-01

    Bacterial degradation plays a vital role in determining the environmental fate of micropollutants like triclocarban. The mechanism of triclocarban degradation by pure bacterium is not yet explored. The purpose of this study was to identify metabolic pathway that might be involved in bacterial degradation of triclocarban. Triclosan-degrading Sphingomonas sp. strain YL-JM2C was first found to degrade up to 35% of triclocarban (4 mg L(-1)) within 5 d. Gas chromatography-mass spectrometry detected 3,4-dichloroaniline, 4-chloroaniline and 4-chlorocatechol as the major metabolites of the triclocarban degradation. Furthermore, total organic carbon results confirmed that the intermediates, 3,4-dichloroaniline (4 mg L(-1)) and 4-chloroaniline (4 mg L(-1)) could be degraded up to 77% and 80% by strain YL-JM2C within 5 d.

  20. Carbon-nitrogen place exchange on NO exposed beta-Mo2C.

    Science.gov (United States)

    Siaj, Mohamed; Maltais, Carl; Zahidi, El Mamoune; Oudghiri-Hassani, Hicham; Wang, Jiqing; Rosei, Federico; McBreen, Peter H

    2005-08-18

    Atomic nitrogen and oxygen were deposited on beta-Mo(2)C through dissociative adsorption of NO. Reflectance absorbance infrared spectroscopy (RAIRS), thermal desorption, and synchrotron X-ray photoelectron spectroscopy (XPS) measurements were used to investigate the interplay between atomic nitrogen, carbon, and oxygen in the 400-1250 K region. The combination of the high resolution and high surface sensitivity offered by the synchrotron XPS technique was used to show that atomic nitrogen displaces interstitial carbon onto the carbide surface. Thermal desorption measurements show that the burnoff of the displaced carbon occurs at approximately 890 K. The incorporation of nitrogen into interstitial sites inhibits oxygen dissolution into the bulk. RAIRS spectroscopy was used to identify surface oxo, terminal oxygen, species formed from O(2) and NO on beta-Mo(2)C.

  1. Rab8A regulates insulin-stimulated GLUT4 translocation in C2C12 myoblasts.

    Science.gov (United States)

    Li, Hanbing; Ou, Liting; Fan, Jiannan; Xiao, Mei; Kuang, Cuifang; Liu, Xu; Sun, Yonghong; Xu, Yingke

    2017-02-01

    Rab proteins are important regulators of GLUT4 trafficking in muscle and adipose cells. It is still unclear which Rabs are involved in insulin-stimulated GLUT4 translocation in C2C12 myoblasts. In this study, we detect the colocalization of Rab8A with GLUT4 and the presence of Rab8A at vesicle exocytic sites by TIRFM imaging. Overexpression of dominant-negative Rab8A (T22N) diminishes insulin-stimulated GLUT4 translocation, while constitutively active Rab8A (Q67L) augments it. In addition, knockdown of Rab8A inhibits insulin-stimulated GLUT4 translocation, which is rescued by replenishment of RNAi-resistant Rab8A. Together, these results indicate an indispensable role for Rab8A in insulin-regulated GLUT4 trafficking in C2C12 cells.

  2. Type II collagen C2C epitope in human synovial fluid and serum after knee injury

    DEFF Research Database (Denmark)

    Kumahashi, N; Swärd, P; Larsson, S

    2015-01-01

    PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235...... = 0.403, P collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P ... with an immediate and sustained local degradation of type II collagen....

  3. Effect of the Ni site substitution on superconducting properties of YNi 2B 2C

    Science.gov (United States)

    Bud'ko, S. L.; Elmassalami, M.; Fontes, M. B.; Mondragon, J.; Vanoni, W.; Giordanengo, B.; Baggio-Saitovitch, E. M.

    1995-02-01

    Structural and superconducting properties of Y(Ni 1- xM x) 2B 2C compounds with MCo, Fe and Ru have been studied. A fast decrease of Tc with the concentration of the dopants was found. This effect can be attributed to the shift of the Fermi level induced by the dopant concentration with the additional contributions from the chemical-pressure effects and from the decrease of the electronic mean free path.

  4. Interdependence of magnetism and superconductivity in the borocarbide TmNi2B2C

    DEFF Research Database (Denmark)

    Nørgaard, K.; Eskildsen, M.R.; Andersen, N.H.

    2000-01-01

    We have discovered anew antiferromagnetic phase in TmNi2B2C by neutron diffraction. The ordering vector is Q(A) = (0.48,0,0) and the phase appears shove a critical in-plans magnetic field of 0.9 T. The field was applied in order to test the assumption that the zero-field magnetic structure at Q...

  5. Floating zone growth and magnetic properties of Y2C two-dimensional electride

    Science.gov (United States)

    Otani, Shigeki; Hirata, Kazuto; Adachi, Yutaka; Ohashi, Naoki

    2016-11-01

    The floating zone method was used to obtain single crystals several mm in size of the low-temperature rhombohedral form of Y2C rather than its typical rocksalt-type cubic form. This was achieved through optimization of the chemical compositions of the starting materials with the aim of producing a two-dimensional electride material. The crystals obtained exhibited a paramagnetic temperature-dependence at 1.8-300 K, with no trace of any obvious magnetic ordering.

  6. 3,4-O-Isopropylidene-2-C-methyl-d-galactonolactone

    Directory of Open Access Journals (Sweden)

    N. Dai

    2010-02-01

    Full Text Available X-ray crystallography unequivocally confirmed the stereochemistry of the 2-C-methyl group in the title molecule, C10H16O6, in which the 1,5-lactone ring exists in a boat conformation. The use of d-galactose in the synthesis determined the absolute stereochemistry. The crystal exists as O—H...O hydrogen-bonded layers in the ab plane, with each molecule acting as a donor and acceptor for two hydrogen bonds.

  7. Rabeprazole can overcome the impact of CYP2C19 polymorphism on quadruple therapy.

    Science.gov (United States)

    Kuo, Chao-Hung; Wang, Sophie S W; Hsu, Wen-Hung; Kuo, Fu-Chen; Weng, Bi-Chuang; Li, Chia-Jung; Hsu, Ping-I; Chen, Angela; Hung, Wen-Chun; Yang, Yuan-Chieh; Wang, Wen-Ming; Wu, Deng-Chyang

    2010-08-01

    The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole-based quadruple therapy for Helicobacter pylori infection after failure of standard triple therapies. From January 2007 to March 2009, 1055 H. pylori-infected patients received standard triple regimens (proton-pump inhibitor (PPI), clarithromycin, and amoxicillin). Helicobacter pylori eradication was achieved in 865 (81.9%) subjects. One hundred ninety eradication-failure patients were enrolled and randomly assigned to receive a 7-day eradication therapy. Ninety-six patients were treated with esomeprazole-based quadruple rescue therapies (EB), while 94 patients were treated with rabeprazole-based quadruple rescue therapies (RB). Follow-up endoscopy was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes, and antibiotics resistances were also examined. Intention-to-treat analysis revealed that RB had better eradication rates than EB (EB: 72.9%; 95% CI: 64.9-80.9% and RB: 78.7%; 95% CI 72.5-84.9%) (p value = .543). Per-protocol results were EB = 75.3%; 95% CI: 70.3-80.3% and RB = 85.1%; 95% CI: 80.6-89.6% (p value = .0401). Both regimens had similar compliance (p value = 0.155) and adverse events (p value = 0.219). We also surveyed those patients without resistance of any antibiotics. RB still showed better outcome than EB. Our data showed that esomeprazole-based regimen and CYP2C19 Hom EM genotype were important predictors for eradication failure. In quadruple therapy, rabeprazole-based regimens had better efficacy than esomeprazole-based regimens. CYP2C19 polymorphism also played an important role in quadruple therapy. It seems advisable to change PPI to rabeprazole in second-line quadruple therapy.

  8. GDF11 does not improve the palmitate induced insulin resistance in C2C12.

    Science.gov (United States)

    Jing, Y-Y; Li, D; Wu, F; Gong, L-L; Li, R

    2017-04-01

    GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro. The mRNA expression of GDF11, GLUT4, IRS-1 (insulin receptor substrate-1) and PGC-1α (peroxisome proliferator-activated receptor-gamma coactivator 1) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein level of GDF11 and PGC-1α were detected by Western blot. The glucose uptake was measured by 2NBDG uptake assay. In high fat diet induced obese mice, both serum level of GDF11 and the expression of GDF11 in skeletal muscle decreased. Similarly, the expression of GDF11 also reduced in palmitate-treated C2C12 myotubes. In vitro, the glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α significantly decreased after palmitate intervention, but GDF11 treatment did not reverse the reduction of glucose uptake and the expression of GLUT4, IRS-1 and PGC-1α in C2C12 myotubes. We firstly confirmed that the expression of GDF11 decreased both in the skeletal muscle of obese mice and palmitate-treated myotubes, but supplementation GDF11 does not ameliorate the palmitate-induced insulin resistance in C2C12 myotubes.

  9. Lysine suppresses protein degradation through autophagic-lysosomal system in C2C12 myotubes.

    Science.gov (United States)

    Sato, Tomonori; Ito, Yoshiaki; Nedachi, Taku; Nagasawa, Takashi

    2014-06-01

    Muscle mass is determined between protein synthesis and protein degradation. Reduction of muscle mass leads to bedridden condition and attenuation of resistance to diseases. Moreover, bedridden condition leads to additional muscle loss due to disuse muscle atrophy. In our previous study (Sato et al. 2013), we showed that administered lysine (Lys), one of essential amino acid, suppressed protein degradation in skeletal muscle. In this study, we investigated that the mechanism of the suppressive effects of Lys on skeletal muscle proteolysis in C2C12 cell line. C2C12 myotubes were incubated in the serum-free medium containing 10 mM Lys or 20 mM Lys, and myofibrillar protein degradation was determined by the rates of 3-methylhistidine (MeHis) release from the cells. The mammalian target of rapamycin (mTOR) activity from the phosphorylation levels of p70-ribosormal protein S6 kinase 1 and eIF4E-binding protein 1 and the autophagic-lysosomal system activity from the ratio of LC3-II/I in C2C12 myotubes stimulated by 10 mM Lys for 0-3 h were measured. The rates of MeHis release were markedly reduced by addition of Lys. The autophagic-lysosomal system activity was inhibited upon 30 min of Lys supplementation. The activity of mTOR was significantly increased upon 30 min of Lys supplementation. The suppressive effect of Lys on the proteolysis by the autophagic-lysosomal system was maintained partially when mTOR activity was inhibited by 100 nM rapamycin, suggesting that some regulator other than mTOR signaling, for example, Akt, might also suppress the autophagic-lysosomal system. From these results, we suggested that Lys suppressed the activity of the autophagic-lysosomal system in part through activation of mTOR and reduced myofibrillar protein degradation in C2C12 myotubes.

  10. Diameter-Specific Growth of Semiconducting SWNT Arrays Using Uniform Mo2C Solid Catalyst.

    Science.gov (United States)

    Zhang, Shuchen; Tong, Lianming; Hu, Yue; Kang, Lixing; Zhang, Jin

    2015-07-22

    Semiconducting single-walled nanotube (s-SWNT) arrays with specific diameters are urgently demanded in the applications in nanoelectronic devices. Herein, we reported that by using uniform Mo2C solid catalyst, aligned s-SWNT (∼90%) arrays with narrow-diameter distribution (∼85% between 1.0 and 1.3 nm) on quartz substrate can be obtained. Mo2C nanoparticles with monodisperse sizes were prepared by using molybdenum oxide-based giant clusters, (NH4)42[Mo132O372(H3CCOO)30(H2O)72]·10H3CCOONH4·300H2O(Mo132), as the precursor that was carburized by a gas mixture of C2H5OH/H2 during a temperature-programmed reduction. In this approach, the formation of volatile MoO3 was inhibited due to the annealing and reduction at a low temperature. As a result, uniform Mo2C nanoparticles are formed, and their narrow size-dispersion strictly determines the diameter distribution of SWNTs. During the growth process, Mo2C selectively catalyzes the scission of C-O bonds of ethanol molecules, and the resultant absorbed oxygen (Oads) preferentially etches metallic SWNTs (m-SWNTs), leading to the high-yield of s-SWNTs. Raman spectroscopic analysis showed that most of the s-SWNTs can be identified as (14, 4), (13, 6), or (10, 9) tubes. Our findings open up the possibility of the chirality-controlled growth of aligned-SWNTs using uniform carbide nanoparticles as solid catalysts for practical nanoelectronics applications.

  11. Harvesting and preparation of cadaveric osseoligamentous lower cervical spine (C2-C7) for biomechanical testing

    OpenAIRE

    Yeh, J; Jackowski, A

    1998-01-01

    Cadaveric osseoligamentous lower cervical spines (C2-C7) are often used in the investigation of spinal biomechanics in vitro. Surprisingly, however, the techniques of harvesting at postmortem and preparation of cadaveric osseoligamentous lower cervical spine for biomechanical testing have not been described in detail. We describe a simple and effective method that can be readily integrated into the routine autopsy procedure. Points on the avoidance of disfiguring the cadaver and damaging the ...

  12. Intercomparison of an improved 20th Century reanalysis version 2c dataset spanning 1850 to 2012

    Science.gov (United States)

    Compo, G. P.; Whitaker, J. S.; Sardeshmukh, P. D.; Giese, B. S.; Brohan, P.

    2014-12-01

    The historical reanalysis dataset generated by NOAA ESRL and the University of Colorado CIRES, the Twentieth Century Reanalysis version 2 (20CRv2), is a comprehensive global atmospheric circulation dataset spanning 1871-2012, assimilating only surface pressure and using monthly Hadley Centre SST and sea ice distributions (HadISST1.1) as boundary conditions. It has been made possible through collaboration with GCOS, WCRP, and the ACRE initiative. It is chiefly motivated by a need to provide an observational validation dataset, with quantified uncertainties, for assessments of climate model simulations of the 20th century, with emphasis on the statistics of daily weather. It uses, together with an NCEP global numerical weather prediction (NWP) land/atmosphere model to provide background "first guess" fields, an Ensemble Kalman Filter (EnKF) data assimilation method. This yields a global analysis every 6 hours as the most likely state of the atmosphere, and also yields the uncertainty of that analysis. Improvements in the new version ("2c") include an extension back to 1850 and the specification of new boundary conditions. These come from new fields of monthly COBE-SST2 sea ice concentrations and an ensemble of daily Simple Ocean Data Assimilation with Sparse Input (SODAsi.2c) sea surface temperatures. SODAsi.2c itself was forced with 20CR, allowing these boundary conditions to be more consistent with the atmospheric reanalysis. Millions of additional pressure observations contained in the new International Surface Pressure Databank version 3 are also included. These improvements result in 20CR version "2c" having comparable or better analyses, as suggested by improved 24 hour forecast skill, more realistic uncertainty in near-surface air temperature, and a reduction in spurious centennial trends in the tropical and polar regions. An intercomparison with ERA-Interim, MERRA, and JRA-55 reanalyses that assimilate all available upper-air and satellite observations will

  13. I2C: a system for the indexing, storage, and retrieval of medical images by content.

    Science.gov (United States)

    Orphanoudakis, S C; Chronaki, C; Kostomanolakis, S

    1994-01-01

    Image indexing, storage, and retrieval based on pictorial content is a feature of image database systems which is becoming of increasing importance in many application domains. Medical image database systems, which support the retrieval of images generated by different modalities based on their pictorial content, will provide added value to future generation picture archiving and communication systems (PACS), and can be used as a diagnostic decision support tools and as a tool for medical research and training. We present the architecture and features of I2C, a system for the indexing, storage, and retrieval of medical images by content. A unique design feature of this architecture is that it also serves as a platform for the implementation and performance evaluation of image description methods and retrieval strategies. I2C is a modular and extensible system, which has been developed based on object-oriented principles. It consists of a set of cooperating modules which facilitate the addition of new graphical tools, image description and matching algorithms. These can be incorporated into the system at the application level. The core concept of I2C is an image class hierarchy. Image classes encapsulate different segmentation and image content description algorithms. Medical images are assigned to image classes based on a set of user-defined attributes such as imaging modality, type of study, anatomical characteristics, etc. This class-based treatment of images in the I2C system achieves increased accuracy and efficiency of content-based retrievals, by limiting the search space and allowing specific algorithms to be fine-tuned for images acquired by different modalities or representing different parts of the anatomy.

  14. Investigation of encephalopathy caused by Shiga toxin 2c-producing Escherichia coli infection in mice.

    Directory of Open Access Journals (Sweden)

    Muhammad Yunus Amran

    Full Text Available A large outbreak of Shiga toxin (Stx-producing enteroaggregative Escherichia coli (EAEC O104:H4 occurred in northern Germany. From this outbreak, at least 900 patients developed hemolytic uremic syndrome (HUS, resulting in more than 50 deaths. Thirty percent of the HUS patients showed encephalopathy. We previously established a mouse model with encephalopathy associated with blood brain barrier (BBB damage after oral infection with the Shiga toxin (Stx 2c-producing Escherichia coli O157: H- strain E32511 (E32511. In this model, we detected high expression of the Stx receptor synthase enzyme, glycosphingolipid globotriaosylceramide (Gb3 synthase, in endothelial cells (ECs and neurons in the reticular formation of the medulla oblongata by in situ hybridization. Caspase-3 was activated in neurons in the reticular formation of the medulla oblongata and the anterior horn of the spinal cord. Astrocytes (ASTs were activated in the medulla oblongata and spinal cord, and a decrease in aquaporin 4 around the ECs suggested that BBB integrity was compromised directly by Stx2c or through the activation of ASTs. We also report the effectiveness of azithromycin (AZM in our model. Moreover, AZM strongly inhibited the release of Stx2c from E32511 in vitro.

  15. Investigation of Encephalopathy Caused by Shiga Toxin 2c-Producing Escherichia coli Infection in Mice

    Science.gov (United States)

    Amran, Muhammad Yunus; Fujii, Jun; Suzuki, Satoshi O.; Kolling, Glynis L.; Villanueva, Sharon Y. A. M.; Kainuma, Mosaburo; Kobayashi, Hideyuki; Kameyama, Hideko; Yoshida, Shin-ichi

    2013-01-01

    A large outbreak of Shiga toxin (Stx)-producing enteroaggregative Escherichia coli (EAEC) O104:H4 occurred in northern Germany. From this outbreak, at least 900 patients developed hemolytic uremic syndrome (HUS), resulting in more than 50 deaths. Thirty percent of the HUS patients showed encephalopathy. We previously established a mouse model with encephalopathy associated with blood brain barrier (BBB) damage after oral infection with the Shiga toxin (Stx) 2c-producing Escherichia coli O157: H- strain E32511 (E32511). In this model, we detected high expression of the Stx receptor synthase enzyme, glycosphingolipid globotriaosylceramide (Gb3) synthase, in endothelial cells (ECs) and neurons in the reticular formation of the medulla oblongata by in situ hybridization. Caspase-3 was activated in neurons in the reticular formation of the medulla oblongata and the anterior horn of the spinal cord. Astrocytes (ASTs) were activated in the medulla oblongata and spinal cord, and a decrease in aquaporin 4 around the ECs suggested that BBB integrity was compromised directly by Stx2c or through the activation of ASTs. We also report the effectiveness of azithromycin (AZM) in our model. Moreover, AZM strongly inhibited the release of Stx2c from E32511 in vitro. PMID:23516588

  16. DFT study of oxygen adsorption on Mo2C(001) and (201) surfaces at different conditions

    Science.gov (United States)

    Cheng, Lihong; Li, Wenkui; Chen, Zhiqin; Ai, Jianping; Zhou, Zehua; Liu, Jianwen

    2017-07-01

    Density functional theory (DFT) calculations were performed to investigate oxygen adsorption on Mo2C(001) and (201)surfaces at different coverage. The energies and structures of oxygen from lowest to saturated coverages were clearly identified on each surface. Thermodynamics method was introduced to reveal the roles of temperature, pressure as well as oxygen sources (O2, H2O and CO2) on the surface oxygen coverage, which is related to the surface oxidation. On the basis of phase diagram, we can easily identify the stable oxygen coverage at different defined conditions. In addition, it reveals that O2 is the strongest oxidant, which results in the full coverage of oxygen on both surfaces in a wide range of temperature and pressure. Then, H2O and CO2 are weaker oxidants, which could only cause partial oxidation of Mo2C surfaces. These results indicate the facile oxidation of Mo2C catalyst. The possible ways to avoid surface oxidation are keeping higher temperature and H2 pressure in the gas phase.

  17. Evidence that the anorexia induced by lipopolysaccharide is mediated by the 5-HT2C receptor.

    Science.gov (United States)

    von Meyenburg, Claudia; Langhans, Wolfgang; Hrupka, Brian J

    2003-01-01

    Rats consistently reduce their food intake following injections of bacterial lipopolysaccharides (LPS). Because inhibition of serotonergic (5-HT) activity by 8-OH-DPAT (5-HT(1A) activation) attenuates LPS-induced anorexia, we conducted a series of studies to examine whether other 5-HT-receptors are involved in the mediation of peripheral LPS-induced anorexia. In all experiments, rats were injected with LPS (100 microg/kg body weight [BW] ip) at lights out (hour 0). Antagonists were administered peripherally at hour 4, shortly after the onset of anorexia, which presumably follows the enhanced cytokine production after LPS. Food intake was then recorded during the subsequent 2 h or longer. 5-HT receptor antagonists cyanopindolol and SB 224289 (5-HT(1B)), ketanserin (5-HT(2A)), RS-102221 (5-HT(2C)), and metoclopramide (5-HT(3)) failed to attenuate LPS-induced anorexia. In contrast, both ritanserin (5-HT(2A/C)-receptor antagonist) (0.5 mg/kg BW) and SB 242084 (5-HT(2C)) (0.3 mg/kg BW) attenuated LPS-induced anorexia at doses that did not alter food intake in non-LPS-treated rats (all Panorexia following peripheral LPS administration is mediated through an enhanced 5-HT-ergic activity and the 5-HT(2C) receptor.

  18. Medial parabrachial nucleus neurons modulate d-fenfluramine-induced anorexia through 5HT2C receptors.

    Science.gov (United States)

    Trifunovic, Radmila; Reilly, Steve

    2006-01-05

    We previously reported that lesions of the medial parabrachial nucleus (PBN) enhanced d-fenfluramine (DFEN)-induced anorexia; a finding that suggests these lesions may potentiate the release of serotonin (5HT) or increase the postsynaptic action of 5HT. In the present study, we used SB 206553 (a 5HT2B/2C receptor antagonist) or m-CPP (a 5HT2C/1B receptor agonist) in a standard behavioral procedure (deprivation-induced feeding) to further explore the role of the medial PBN in drug-induced anorexia. In Experiment 1, DFEN (0 or 1.0 mg/kg) was given alone or in combination with SB 206553 (2.0 or 5.0 mg/kg). In Experiment 2, we investigated the food-suppressive effects of m-CPP (0.5, 1.0 or 2.0 mg/kg). The results of Experiment 1 show that SB 206553, while having no influence on the performance of control subjects, attenuated (2.0 mg/kg) or abolished (5 mg/kg) the potentiating effect of the lesions on DFEN-induced anorexia. In Experiment 2, m-CPP induced a suppression of food intake in nonlesioned animals that was significantly potentiated in rats with medial PBN lesions. These results are consistent with the hypothesis that medial PBN neurons mediate anorexia through 5HT2C receptors.

  19. Characterization of triclosan metabolism in Sphingomonas sp. strain YL-JM2C

    Science.gov (United States)

    Mulla, Sikandar I.; Wang, Han; Sun, Qian; Hu, Anyi; Yu, Chang-Ping

    2016-02-01

    Triclosan (TCS) is one of the most widespread emerging contaminants and has adverse impact on aquatic ecosystem, yet little is known about its complete biodegradation mechanism in bacteria. Sphingomonas sp, strain YL-JM2C, isolated from activated sludge of a wastewater treatment plant, was very effective on degrading TCS. Response surface methodology (RSM) was applied to optimize the conditions like temperature and pH. From RSM, the optimal TCS degradation conditions were found to be 30 °C and pH 7.0. Under optimal conditions, strain YL-JM2C completely mineralized TCS (5 mg L-1) within 72 h. Gas chromatography-mass spectrometry analysis revealed that 2,4-dichlorophenol, 2-chlorohydroquinone and hydroquinone are three main by-products of TCS. Furthermore, stable isotope experimental results revealed that the 13C12-TCS was completely mineralized into CO2 and part of heavier carbon (13C) of labeled TCS was utilized by strain YL-JM2C to synthesize fatty acids (PLFAs). Cell surface hydrophobicity (CSH) and degradation test results suggested that the strain could enhance degradation capacity of TCS through increasing CSH. In addition, the bacterium also completely degraded spiked TCS (5 mg L-1) in wastewater collected from the wastewater treatment plant. Hence, these results suggest that the strain has potential to remediate TCS in the environment.

  20. Cited3 activates Mef2c to control muscle cell differentiation and survival.

    Science.gov (United States)

    Devakanmalai, Gnanapackiam Sheela; Zumrut, Hasan E; Ozbudak, Ertuğrul M

    2013-05-15

    Vertebrate muscle development occurs through sequential differentiation of cells residing in somitic mesoderm - a process that is largely governed by transcriptional regulators. Our recent spatiotemporal microarray study in zebrafish has identified functionally uncharacterized transcriptional regulators that are expressed at the initial stages of myogenesis. cited3 is one such novel gene encoding a transcriptional coactivator, which is expressed in the precursors of oxidative slow-twitch myofibers. Our experiments placed cited3 into a gene regulatory network, where it acts downstream of Hedgehog signaling and myoD/myf5 but upstream of mef2c. Knockdown of expression of cited3 by antisense morpholino oligonucleotides impaired muscle cell differentiation and growth, caused muscle cell death and eventually led to total immotility. Transplantation experiments demonstrated that Cited3 cell-autonomously activates the expression of mef2c in slow myofibers, while it non-cell-autonomously regulates expression of structural genes in fast myofibers. Restoring expression of cited3 or mef2c rescued all the cited3 loss-of-function phenotypes. Protein truncation experiments revealed the functional necessity of C-terminally conserved domain of Cited3, which is known to mediate interactions of Cited-family proteins with histone acetylases. Our findings demonstrate that Cited3 is a critical transcriptional coactivator functioning during muscle differentiation and its absence leads to defects in terminal differentiation and survival of muscle cells.

  1. Proteasome inhibition compromises direct retention of cytochrome P450 2C2 in the endoplasmic reticulum.

    Science.gov (United States)

    Szczesna-Skorupa, Elzbieta; Kemper, Byron

    2008-10-15

    To determine whether protein degradation plays a role in the endoplasmic reticulum (ER) retention of cytochromes P450, the effects of proteasomal inhibitors on the expression and distribution of green fluorescent protein chimeras of CYP2C2 and related proteins was examined. In transfected cells, expression levels of chimeras of full-length CYP2C2 and its cytosolic domain, but not its N-terminal transmembrane sequence, were increased by proteasomal inhibition. Redistribution of all three chimeras from the reticular ER into a perinuclear compartment and, in a subset of cells, also to the cell surface was observed after proteasomal inhibition. Redistribution was blocked by the microtubular inhibitor, nocodazole, suggesting that redistribution to the cell surface followed the conventional vesicular transport pathway. Similar redistributions were detected for BAP31, a CYP2C2 binding chaperone; CYP2E1 and CYP3A4, which are also degraded by the proteasomal pathway; and for cytochrome P450 reductase, which does not undergo proteasomal degradation; but not for the ER membrane proteins, sec61 and calnexin. Redistribution does not result from saturation of an ER retention "receptor" since in some cases protein levels were unaffected. Proteasomal inhibition may, therefore, alter ER retention by affecting a protein critical for ER retention, either directly, or indirectly by affecting the composition of the ER membranes.

  2. TiO2@C Core-Shell Nanoparticles Formed by Polymeric Nano-Encapsulation

    Directory of Open Access Journals (Sweden)

    Mitra eVasei

    2014-07-01

    Full Text Available TiO2 semiconducting nanoparticles are known to be photocatalysts of moderate activity due to their high band-gap and high rate of electron-hole recombination. The formation of a shell of carbon around the core of TiO2, i.e. the formation of TiO2@C nanoparticles, is believed to partly alleviate these problems. It is usually achieved by a hydrothermal treatment in a presence of a sugar derivative. We present here a novel method for the formation of highly uniform C shell around TiO2 nanoparticles. For this purpose, TiO2 nanoparticles were dispersed in water using an oligomeric dispersant prepared by Reversible Addition-Fragmentation chain Transfer (RAFT polymerization. Then the nanoparticles were engaged into an emulsion polymerization of acrylonitrile, resulting in the formation of a shell of polyacrylonitrile (PAN around each TiO2 nanoparticles. Upon pyrolisis, the PAN was transformed into carbon, resulting in the formation of TiO2@C nanoparticles. The structure of the resulting particles was elucidated by X-Ray diffraction, FTIR, UV-VIS and Raman spectroscopy as well as TEM microscopy. Preliminary results about the use of the TiO2@C particles as photocatalysts for the splitting of water are presented. They indicate that the presence of the C shell is responsible for a significant enhancement of the photocurrent.

  3. TiO2@C core-shell nanoparticles formed by polymeric nano-encapsulation.

    Science.gov (United States)

    Vasei, Mitra; Das, Paramita; Cherfouth, Hayet; Marsan, Benoît; Claverie, Jerome P

    2014-01-01

    TiO2 semiconducting nanoparticles are known to be photocatalysts of moderate activity due to their high band-gap and high rate of electron-hole recombination. The formation of a shell of carbon around the core of TiO2, i.e., the formation of TiO2@C nanoparticles, is believed to partly alleviate these problems. It is usually achieved by a hydrothermal treatment in a presence of a sugar derivative. We present here a novel method for the formation of highly uniform C shell around TiO2 nanoparticles. For this purpose, TiO2 nanoparticles were dispersed in water using an oligomeric dispersant prepared by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. Then the nanoparticles were engaged into an emulsion polymerization of acrylonitrile, resulting in the formation of a shell of polyacrylonitrile (PAN) around each TiO2 nanoparticles. Upon pyrolysis, the PAN was transformed into carbon, resulting in the formation of TiO2@C nanoparticles. The structure of the resulting particles was elucidated by X-Ray diffraction, FTIR, UV-VIS and Raman spectroscopy as well as TEM microscopy. Preliminary results about the use of the TiO2@C particles as photocatalysts for the splitting of water are presented. They indicate that the presence of the C shell is responsible for a significant enhancement of the photocurrent.

  4. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

  5. Oxygen adsorption and dissociation during the oxidation of monolayer Ti2C

    KAUST Repository

    Gan, Liyong

    2013-08-20

    Exfoliated two-dimensional early transition metal carbides and carbonitrides are usually not terminated by metal atoms but saturated by O, OH, and/or F, thus making it difficult to understand the surface structure evolution and the induced electronic modifications. To fill this gap, density functional theory and molecular dynamics simulations are performed to capture the initial stage of the oxidation process of Ti2C, a prototypical example from the recently fabricated class of two-dimensional carbides and carbonitrides. It is shown that the unsaturated Ti 3d orbitals of the pristine Ti2C surface interact strongly with the approaching O2 molecules, resulting in barrierless O2 dissociation. The diffusion of the dissociated O atoms is also found to be very facile. Molecular dynamics simulations suggest that both dissociation and diffusion are enhanced as the O2 coverage increases to 0.25 monolayer. For a coverage of less than 0.11 monolayer, the adsorbates lead to a minor modification of the electronic properties of Ti2C, while the modification is remarkable at 0.25 monolayer. The formed Ti2CO2 after O saturation is an indirect narrow gap semiconductor (0.33 eV) with high intrinsic carrier concentration at room temperature and high thermodynamic stability at intermediate temperature (e.g., 550 °C).

  6. Magnetic structure and spin reorientation of quaternary Dy2Fe2Si2C

    Science.gov (United States)

    Susilo, R. A.; Cadogan, J. M.; Hutchison, W. D.; Stewart, G. A.; Avdeev, M.; Campbell, S. J.

    2017-03-01

    We have investigated the low temperature magnetic properties of Dy2Fe2Si2C by using magnetisation, specific heat, x-ray diffraction, neutron powder diffraction and 57Fe Mössbauer spectroscopy measurements over the temperature range 1.5 K–300 K. Dy2Fe2Si2C exhibits two magnetic transitions at low temperatures: an antiferromagnetic transition at {{T}\\text{N}}∼ 26 K and a spin-reorientation transition at {{T}t}∼ 6 K. The magnetic structure above T t can be described with a propagation vector \\mathbf{k}~=~≤ft(0~0~\\frac{1}{2}\\right) with the ordering of the Dy magnetic moments along the monoclinic b-axis whereas on cooling below T t the Dy moment tips away from the b-axis towards the ac-plane. We find that the spin-reorientation in Dy2Fe2Si2C is mainly driven by the competition between the second-order crystal field term B 20 and the higher-order terms, in particular B 40 and B 64.

  7. High efficiency photocatalysis for pollutant degradation with MoS2/C3N4 heterostructures.

    Science.gov (United States)

    Li, Qian; Zhang, Ning; Yang, Yong; Wang, Guozhong; Ng, Dickon H L

    2014-07-29

    Porous graphitic carbon nitride was synthesized by controllable thermal polymerization of urea in air. Their textural, electrical, and optical properties were tuned by varying the heating rate. The presence of proper residual oxygen in carbon nitride matrix had enhanced light absorption and inhibited the recombination of charge carriers. Furthermore, the MoS2 nanosheets were coupled into the carbon nitride to form MoS2/C3N4 heterostructures via a facile ultrasonic chemical method. The optimized MoS2/C3N4 heterostructure with 0.05 wt % MoS2 showed a reaction rate constant as high as 0.301 min(-1), which was 3.6 times that of bare carbon nitride. As analyzed by SEM, TEM, UV-vis absorption, PL and photoelectrochemical measurements, intimate contact interface, extended light response range, enhanced separation speed of charge carriers, and high photocurrent density upon MoS2 coupling led to the photocatalytic promotion of the MoS2/C3N4 heterostructures. In this architecture, MoS2 served as electron trapper to extend the lifetime of separated electron-hole pairs. Meanwhile, the accumulated holes on the surface of carbon nitride oxidized the organic dye directly, which was a predominant process in the photodegradation of organic pollutants in water treatment. The promotional mechanisms and principles reported here would have great significance in heterogeneous photocatalysis.

  8. Li2C2, a High-Capacity Cathode Material for Lithium Ion Batteries.

    Science.gov (United States)

    Tian, Na; Gao, Yurui; Li, Yurong; Wang, Zhaoxiang; Song, Xiaoyan; Chen, Liquan

    2016-01-11

    As a typical alkaline earth metal carbide, lithium carbide (Li2C2) has the highest theoretical specific capacity (1400 mA h g(-1)) among all the reported lithium-containing cathode materials for lithium ion batteries. Herein, the feasibility of using Li2C2 as a cathode material was studied. The results show that at least half of the lithium can be extracted from Li2C2 and the reversible specific capacity reaches 700 mA h g(-1). The C≡C bond tends to rotate to form C4 (C≡C⋅⋅⋅C≡C) chains during lithium extraction, as indicated with the first-principles molecular dynamics (FPMD) simulation. The low electronic and ionic conductivity are believed to be responsible for the potential gap between charge and discharge, as is supported with density functional theory (DFT) calculations and Arrhenius fitting results. These findings illustrate the feasibility to use the alkali and alkaline earth metal carbides as high-capacity electrode materials for secondary batteries.

  9. Arecoline inhibits myogenic differentiation of C2C12 myoblasts by reducing STAT3 phosphorylation.

    Science.gov (United States)

    Chang, Yung-Fu; Liu, Ting-Yuan; Liu, Shao-Tung; Tseng, Chao-Neng

    2012-10-01

    Areca nut (Areca catechu) is chewed regularly as a medical and psychoactive food by about 10% of the world population, in countries including India, Taiwan and parts of Southern Asia. Areca nut chewing during pregnancy has been associated with both lower birth weight and premature birth. Animals of low birth weights showed retardation of muscle development. Our previous study showed that arecoline, the major areca alkaloid, decreased the number of implanted embryos. Here we sought to determine the effects of arecoline in myogenic differentiation by in vitro assays using C2C12 myoblast cells. The results showed that arecoline higher than 0.4mM significantly increased apoptosis and decreased viability of C2C12 cells. Morphometric measurements of myotube formation and analyses of myogenic markers, myosin heavy chain and myogenin, revealed that myogenic differentiation was inhibited by 0.04-0.08 mM arecoline. Moreover, phosphorylated but not total STAT3 was significantly inhibited by arecoline during myotube formation. These results indicate that arecoline inhibits the myogenic differentiation of C2C12 cells by reducing the activation of STAT3, an upstream regulator of myogenesis. Improved understanding of the effects of arecoline during myogenic differentiation may help to establish public health policies and to develop potential treatments for such patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Cyclotron Production of (99m)Tc using (100)Mo2C targets.

    Science.gov (United States)

    Richards, Vernal N; Mebrahtu, Efrem; Lapi, Suzanne E

    2013-10-01

    An investigative study of the (100)Mo (p,2n)(99m)Tc reaction on a medical cyclotron using (100)Mo2C is reported. This is the first report of this compound being used as a target for this reaction. (100)Mo2C, a refractory carbide with high thermal conductivity, properties which underscore its use on a cyclotron, was synthesized using (100)MoO3. Its ease of oxidation back to (100)MoO3 under air at elevated temperatures facilitates the use of thermo-chromatography, a high temperature gas phase separation technique for the separation and isolation of (99m)Tc. Activity yields for (99m)Tc averaged 84% of the calculated theoretical yields. Additionally, the percent recovery of MoO3, the precursor for Mo2C, was consistently high at 85% ensuring a good life cycle for this target material. The produced (99m)Tc was radio-chemically pure and easily labeled MDP for imaging purposes.

  11. Interface observation of heat-treated Co/Mo2C multilayers

    Science.gov (United States)

    Yuan, Yanyan; Le Guen, Karine; André, Jean-Michel; Mény, Christian; Ulhaq, Corinne; Galtayries, Anouk; Zhu, Jingtao; Wang, Zhanshan; Jonnard, Philippe

    2015-03-01

    We study the interface evolution of a series of periodic Co/Mo2C multilayers as a function of the annealing temperature up to 600 °C. Different complementary techniques are implemented to get information on the phenomenon taking place at the interfaces of the stack. The periodical structure of Co/Mo2C multilayer is proven by time-of-flight secondary ion mass spectrometry (ToF-SIMS) depth profiles which demonstrate the formation of an oxide layer at both air/stack and stack/substrate interfaces. From Nuclear magnetic resonance (NMR) spectra, we observed the intermixing phenomenon of Co and C atoms for the as-deposited sample, and then at annealing temperature above 300 °C Co and C atoms separate from their mixed regions. Comparison of NMR results between Co/Mo2C and Co/C references confirms this phenomenon. This is in agreement with X-ray emission spectroscopy (XES) measurements. Furthermore the calculation of the Co-C, Co-Mo and Mo-C mixing enthalpy using Miedema's model gives a proof of the demixing of Co and C atoms present within the stacks above 300 °C. From the transmission electron microscopy (TEM) analysis, we found the presence of some crystallites within the as-deposited sample as well as the mainly amorphous nature of all layers. This is confirmed using X-ray diffraction (XRD) patterns which also demonstrate the growth of crystallites induced upon annealing.

  12. Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake.

    Science.gov (United States)

    Zhang, Zhaiyi; Shen, Manli; Gresch, Paul J; Ghamari-Langroudi, Masoud; Rabchevsky, Alexander G; Emeson, Ronald B; Stamm, Stefan

    2016-08-01

    The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in intracellular membranes. We developed an oligonucleotide that promotes exon inclusion, which increases the ratio of the full-length to truncated receptor protein. Decreasing the amount of truncated receptor results in the accumulation of full-length, constitutively active receptor at the cell surface. After injection into the third ventricle of mice, the oligonucleotide accumulates in the arcuate nucleus, where it changes alternative splicing of the serotonin 2C receptor and increases pro-opiomelanocortin expression. Oligonucleotide injection reduced food intake in both wild-type and ob/ob mice. Unexpectedly, the oligonucleotide crossed the blood-brain barrier and its systemic delivery reduced food intake in wild-type mice. The physiological effect of the oligonucleotide suggests that a truncated splice variant regulates the activity of the serotonin 2C receptor, indicating that therapies aimed to change pre-mRNA processing could be useful to treat hyperphagia, characteristic for disorders like Prader-Willi syndrome.

  13. First intron of nestin gene regulates its expression during C2C12 myoblast ifferentiation

    Institute of Scientific and Technical Information of China (English)

    Hua Zhong; Zhigang Jin; Yongfeng Chen; Ting Zhang; Wei Bian; Xing Cui; Naihe Jing

    2008-01-01

    Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Nestin is an intermediate filament protein expressed in neural progenitor cells and in developing skeletal muscle. Nestin has been widely used as a neural progenitor cell marker. It is well established that the specific expression of the nestin gene in neural progenitor cells is conferred by the neural-specific enhancer located in the second intron of the nestin gene. However, the transcriptional mechanism of nestin expression in developing muscle is still unclear. In this study, we identified a muscle cell-specific enhancer in the first intron of mouse nestin gene in mouse myoblast C2C12 cells.We localized the core enhancer activity to the 291-661 region of the first intron, and showed that the two E-boxes in the core enhancer region were important for enhancer activity in differentiating C2C12 cells. We also showed that MyoD protein was involved in the regulation of nestin expression in the myogenic differentiation of C2C12 cells.

  14. Composite Interlaminar Shear Fracture Toughness, G(sub 2c): Shear Measurement of Sheer Myth?

    Science.gov (United States)

    OBrien, T. Kevin

    1997-01-01

    The concept of G2c as a measure of the interlaminar shear fracture toughness of a composite material is critically examined. In particular, it is argued that the apparent G2c as typically measured is inconsistent with the original definition of shear fracture. It is shown that interlaminar shear failure actually consists of tension failures in the resin rich layers between plies followed by the coalescence of ligaments created by these failures and not the sliding of two planes relative to one another that is assumed in fracture mechanics theory. Several strain energy release rate solutions are reviewed for delamination in composite laminates and structural components where failures have been experimentally documented. Failures typically occur at a location where the mode 1 component accounts for at least one half of the total G at failure. Hence, it is the mode I and mixed-mode interlaminar fracture toughness data that will be most useful in predicting delamination failure in composite components in service. Although apparent G2c measurements may prove useful for completeness of generating mixed-mode criteria, the accuracy of these measurements may have very little influence on the prediction of mixed-mode failures in most structural components.

  15. Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    Chunzi Liang

    2014-01-01

    Full Text Available Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, β-hydroxy-β-methyl butyrate (HMB, a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM, alanine (0.5 mM, valine (0.5 mM, EX527 (SIRT1 inhibitor, 25 μM, and Compound C (AMPK inhibitor, 25 μM alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

  16. Elementary Steps of Syngas Reactions on Mo2C(001): Adsorption Thermochemistry and Bond Dissociation

    Energy Technology Data Exchange (ETDEWEB)

    Medford, Andrew

    2012-02-16

    Density functional theory (DFT) and ab initio thermodynamics are applied in order to investigate the most stable surface and subsurface terminations of Mo{sub 2}C(001) as a function of chemical potential and in the presence of syngas. The Mo-terminated (001) surface is then used as a model surface to evaluate the thermochemistry and energetic barriers for key elementary steps in syngas reactions. Adsorption energy scaling relations and Broensted-Evans-Polanyi relationships are established and used to place Mo{sub 2}C into the context of transition metal surfaces. The results indicate that the surface termination is a complex function of reaction conditions and kinetics. It is predicted that the surface will be covered by either C{sub 2}H{sub 2} or O depending on conditions. Comparisons to transition metals indicate that the Mo-terminated Mo{sub 2}C(001) surface exhibits carbon reactivity similar to transition metals such as Ru and Ir, but is significantly more reactive towards oxygen.

  17. Activation of Methane Promoted by Adsorption of CO on Mo2 C2 (-) Cluster Anions.

    Science.gov (United States)

    Liu, Qing-Yu; Ma, Jia-Bi; Li, Zi-Yu; Zhao, Chongyang; Ning, Chuan-Gang; Chen, Hui; He, Sheng-Gui

    2016-05-04

    Atomic clusters are being actively studied for activation of methane, the most stable alkane molecule. While many cluster cations are very reactive with methane, the cluster anions are usually not very reactive, particularly for noble metal free anions. This study reports that the reactivity of molybdenum carbide cluster anions with methane can be much enhanced by adsorption of CO. The Mo2 C2 (-) is inert with CH4 while the CO addition product Mo2 C3 O(-) brings about dehydrogenation of CH4 under thermal collision conditions. The cluster structures and reactions are characterized by mass spectrometry, photoelectron spectroscopy, and quantum chemistry calculations, which demonstrate that the Mo2 C3 O(-) isomer with dissociated CO is reactive but the one with non-dissociated CO is unreactive. The enhancement of cluster reactivity promoted by CO adsorption in this study is compared with those of reported systems of a few carbonyl complexes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Identification of the Most Stable Sc2C80 Isomers: Structure, Electronic Property, and Molecular Spectra Investigations

    Institute of Scientific and Technical Information of China (English)

    吴静怡; 王太山; 舒春英; 吕鑫; 王春儒

    2012-01-01

    A systematic density functional theory investigation has been carried out to explore the possible structures of Sc2C80 at the BMK/6-31 G(d) level. The results clearly show that Sc2@C80-Ih, Sc2@Cso-Dsh, and Sc2C2@C78-C2v can be identified as three isomers of Sc2C80 metallofullerene with the lowest energy. Frontier molecular orbital analysis indicates that the two Sc2@C80 isomers have a charge state as (Sc〉)2@ C60 and the Sc2C2@C78 has a charge state of (Sc3+)2 C22- @ C784-. Moreover, the metal-cage covalent interactions have been studied to reveal the dynamics of endohedral moiety. The vertical electron affinity, vertical ionization potential, infrared spectra and 13C nuclear mag- netic resonance spectra have been also computed to further disclose the molecular structures and properties.

  19. g4c2c: A Model for Citizen Engagement at Arms’ Length from Government

    Directory of Open Access Journals (Sweden)

    Axel Bruns

    2011-03-01

    Full Text Available Normal 0 false false false EN-AU X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The recognition that Web 2.0 applications and social media sites will strengthen and improve interaction between governments and citizens has resulted in a global push into new e-democracy or Government 2.0 spaces. These typically follow government-to-citizen (g2c or citizen-to-citizen (c2c models, but both these approaches are problematic: g2c is often concerned more with service delivery to citizens as clients, or exists to make a show of ‘listening to the public’ rather than to genuinely source citizen ideas for government policy, while c2c often takes place without direct government participation and therefore cannot ensure that the outcomes of citizen deliberations are accepted into the government policy-making process. Building on recent examples of Australian Government 2.0 initiatives, we suggest a new approach based on government support for citizen-to-citizen engagement, or g4c2c, as a workable compromise, and suggest that public service broadcasters should play a key role in facilitating this model of citizen engagement.

  20. IMPACT2C: Quantifying projected impacts under 2°C warming

    Science.gov (United States)

    Jacob, D.; Kotova, L.; Impact2C Team

    2012-04-01

    Political discussions on the European goal to limit global warming to 2°C demand, that information is provided to society by the best available science on projected impacts and possible benefits. The new project IMPACT2C is supported by the European Commission's 7th Framework Programme as a 4 year large-scale integrating project. IMPACT2C is coordinated by the Climate Service Center, Helmholtz-Zentrum Geesthacht. IMPACT2C enhances knowledge, quantifies climate change impacts, and adopts a clear and logical structure, with climate and impacts modelling, vulnerabilities, risks and economic costs, as well as potential responses, within a pan-European sector based analysis. The project utilises a range of models within a multi-disciplinary international expert team and assesses effects on water, energy, infrastructure, coasts, tourism, forestry, agriculture, ecosystems services, and health and air quality-climate interactions. IMPACT2C introduces key innovations. First, harmonised socio-economic assumptions/scenarios will be used, to ensure that both individual and cross-sector assessments are aligned to the 2°C (1.5°C) scenario for both impacts and adaptation, e.g. in relation to land-use pressures between agriculture and forestry. Second, it has a core theme of uncertainty, and will develop a methodological framework integrating the uncertainties within and across the different sectors, in a consistent way. In so doing, analysis of adaptation responses under uncertainty will be enhanced. Finally, a cross-sectoral perspective is adopted to complement the sector analysis. A number of case studies will be developed for particularly vulnerable areas, subject to multiple impacts (e.g. the Mediterranean), with the focus being on cross-sectoral interactions (e.g. land use competition) and cross-cutting themes (e.g. cities). The project also assesses climate change impacts in some of the world's most vulnerable regions: Bangladesh, Africa (Nile and Niger basins), and the

  1. Breach of information duties in the B2C e-commerce: adequacy of available remedies

    Directory of Open Access Journals (Sweden)

    Zofia Bednarz

    2016-07-01

    Full Text Available

    B2C e-commerce is characterised by the information asymmetry between the contracting parties. Various information duties are imposed on traders, both at the European and national level to correct this asymmetry and to ensure proper market functioning. The mandated disclosure is based on the assumption of consumers' rationality. However, developments of behavioural economics challenge this assumption. The utility of mandated disclosure in consumer contracts depends also on the remedies available to consumers in a case of breach of information duties. Those remedies are often heavily influenced by the national general private law applicable to the contractual relationship between the parties. Nevertheless, since the economics of general contract law differ importantly from principles of consumer e-commerce, various problems can be associated with the application of general law remedies to the breach of information duties in B2C contracts. The limited value of the majority of the online B2C transactions is incompatible with costly and lengthy court proceedings. Moreover, breach of information duties will often not produce enough material damage on the side of the consumer to make the remedies available. Different solutions are explored, from ADR, to the duty to advise, to non-legal mechanisms making the information easier to use for consumers throughlimiting disclosure. Finally, the right of withdrawal is analysed as an example of a specific remedy, adapted to the economics of the B2C electronic transactions, where the aims parties pursue through contracts are different than in commercial contracts, and their relationship is marked with the inequality of economic power and information asymmetry. However, the legally established cooling-off period is not free from limitations, and only a combination of various measures, including effective

  2. CYP2C19基因型和CYP2C9对人肝微粒体中氟西汀N-去甲基代谢的影响%Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes

    Institute of Scientific and Technical Information of China (English)

    刘昭前; 舒焱; 黄松林; 王连生; 何楠; 周宏灏

    2001-01-01

    目的:本实验旨在研究CYP2C19基因型人肝微粒体中氟西汀N-去甲基代谢的酶促动力学特点并鉴定参与此代谢途径的细胞色素P-450酶.方法:测定基因型CYP2C19肝微粒体中去甲氟西汀形成的酶促动力学.鉴定氟西汀N-去甲基酶活性与细胞色素P-450 2C9,2C19,1A2和2D6酶活性的相关性,同时应用各种细胞色素P-450酶的选择性抑制剂和化学探针进行抑制实验,从而确定参与氟西汀N-去甲基代谢的细胞色素P-450酶.结果:去甲氟西汀生成的酶促动力学数据符合单酶模型,并具有Michaelis-Menten动力学特征.当底物浓度为氟西汀25μmol/L和100 μmol/L时,去甲氟西汀(N-FLU)的生成率分别与甲磺丁脲3-羟化酶活性显著相关(r1=0.821,P1=0.001;r2=0.668,P2=0.013),当底物浓度为氟西汀100 μmol/L时,N-FLU的生成率与S-美芬妥因4'-羟化酶活性显著相关(r=0.717,P=0.006).PM肝微粒中磺胺苯吡唑和醋竹桃霉素对氟西汀N-去甲基代谢的抑制作用显著大于EM(73%vs 45%,P<0.01).结论:在生理底物浓度下,CYP2C9是催化人肝微粒体中氟西汀N-去甲基代谢的主要CYP-450酶;而高底物浓度时,以CYP2C19的作用为主.%AIM: The present study was designed to define the kinetic behavior of fluoxetine N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P-450 (CYP) involved in this metabolic pathway. METHODS: The kinetics of the formation of norfluoxetine was determined in human liver microsomes from six genotyped CYP2C19 extensive metabolizers (EM). The correlation studies between the fluoxetine N-demethylase activity and various CYP enzyme activities were performed. Selective inhibitors or chemical probes of various cytochrome P-450 isoforms were also employed. RESULTS: The kinetics of norfluoxetine formation in all liver microsomes were fitted by a singleenzyme Michaelis-Menten equation (mean Km=32 μmol/L±7

  3. Genetic variability of CYP2C19 in a Mexican population: contribution to the knowledge of the inheritance pattern of CYP2C19*17 to develop the ultrarapid metabolizer phenotype

    Indian Academy of Sciences (India)

    Alma Faviola Favela-Mendoza; Gabriela Martinez-Cortes; Marcelo Hernandez-Zaragoza; Joel Salazar-Flores; Jose Francisco Muñoz-Valle; Victor Manuel Martinez-Sevilla; Noemi Yolanda Velazquez-Suarez; Hector Rangel-Villalobos

    2015-03-01

    CYP2C19 is a polymorphic enzyme that metabolizes a wide variety of therapeutic drugs that has been associated with altered enzymatic activity and adverse drug reactions. Differences in allele frequencies of the CYP2C19 gene have been detected in populations worldwide. Thus, we analysed the alleles CYP2C19*2, CYP2C19*3, CYP2C19*4 and CYP2C19*5 related to the poor metabolizer (PM) phenotype in a Mexican population sample ( = 238), as well as CYP2C19*17, unique allele related to ultrarapid metabolizer phenotype (UMs). Genotypes were determined using SNaPshot and TaqManqPCR assays. In addition to the wild-type CYP2C19*1 allele (77.1%), we only found CYP2C19*17 (14.3%) and CYP2C19*2 (8.6%). Comparison with previous population reports demonstrated that these two SNPs are homogeneously distributed in Latin America ( > 0.05). Based on comparison with a previous pharmacokinetic study that determined the frequency of CYP2C19 phenotypes in the same population (western Mexican), we obtained the following findings: (i) based on the difference between the frequency of genotypes CYP2C19*2/*2 (presumably PM) versus the observed prevalence of PM phenotypes (0.4 versus 6.3%; 2 = 9.58, = 0.00196), we inferred the plausible presence of novel CYP2C19 alleles related to the PM phenotype; (ii) the prevalence of UMs was in disagreement with the dominant inheritance pattern suggested for CYP2C19*17 (23.1 versus 4%; < 0.00001); (iii) the apparent recessive inheritance pattern of CYP2C19*17, based on the agreement between homozygous CYP2C19*17/*17 (presumably UMs) and the observed prevalence of UMs (2.1 versus 4%; (2 = 1.048; = 0.306).

  4. Support for 5-HT2C receptor functional selectivity in vivo utilizing structurally diverse, selective 5-HT2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine elicited head-twitch response model.

    Science.gov (United States)

    Canal, Clinton E; Booth, Raymond G; Morgan, Drake

    2013-07-01

    There are seemingly conflicting data in the literature regarding the role of serotonin (5-HT) 5-HT2C receptors in the mouse head-twitch response (HTR) elicited by the hallucinogenic 5-HT2A/2B/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Namely, both 5-HT2C receptor agonists and antagonists, regarding 5-HT2C receptor-mediated Gq-phospholipase C (PLC) signaling, reportedly attenuate the HTR response. The present experiments tested the hypothesis that both classes of 5-HT2C receptor compounds could attenuate the DOI-elicited-HTR in a single strain of mice, C57Bl/6J. The expected results were considered in accordance with ligand functional selectivity. Commercially-available 5-HT2C agonists (CP 809101, Ro 60-0175, WAY 161503, mCPP, and 1-methylpsilocin), novel 4-phenyl-2-N,N-dimethyl-aminotetralin (PAT)-type 5-HT2C agonists (with 5-HT2A/2B antagonist activity), and antagonists selective for 5-HT2A (M100907), 5-HT2C (SB-242084), and 5-HT2B/2C (SB-206553) receptors attenuated the DOI-elicited-HTR. In contrast, there were differential effects on locomotion across classes of compounds. The 5-HT2C agonists and M100907 decreased locomotion, SB-242084 increased locomotion, SB-206553 resulted in dose-dependent biphasic effects on locomotion, and the PATs did not alter locomotion. In vitro molecular pharmacology studies showed that 5-HT2C agonists potent for attenuating the DOI-elicited-HTR also reduced the efficacy of DOI to activate mouse 5-HT2C receptor-mediated PLC signaling in HEK cells. Although there were differences in affinities of a few compounds at mouse compared to human 5-HT2A or 5-HT2C receptors, all compounds tested retained their selectivity for either receptor, regardless of receptor species. Results indicate that 5-HT2C receptor agonists and antagonists attenuate the DOI-elicited-HTR in C57Bl/6J mice, and suggest that structurally diverse 5-HT2C ligands result in different 5-HT2C receptor signaling outcomes compared to DOI.

  5. The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers

    Directory of Open Access Journals (Sweden)

    Yanti Nasyuhana Sani

    2013-01-01

    Full Text Available Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n=17, CYP2C19*1/*2 (n=21, and CYP2C19*2/*2 (n=7. All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs, and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P<0.001 carriers. Almost half of the participants (46.7% were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2. Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.

  6. Product formulas for volumes of flow polytopes

    CERN Document Server

    Meszaros, Karola

    2011-01-01

    Intrigued by the product formula prod_{i=1}^{n-2} C_i for the volume of the Chan-Robbins-Yuen polytope CRY_n, where C_i is the ith Catalan number, we construct a family of polytopes P_{m,n}, whose volumes are given by the product \\prod_{i=m+1}^{m+n-2}\\frac{1}{2i+1}{{m+n+i} \\choose {2i}}. The Chan-Robbins-Yuen polytope CRY_n coincides with P_{0,n-1}. Our construction of the polytopes P_{m,n} is an application of a systematic method we develop for expressing volumes of a class of flow polytopes as the number of certain triangular arrays. This method can also be used as a heuristic technique for constructing polytopes with combinatorial volumes. As an illustration of this we construct polytopes whose volumes equal the number of r-ary trees on n internal nodes, \\frac{1}{(r-1)n+1} {{rn} \\choose n}. Using triangular arrays we also express the volumes of flow polytopes as constant terms of formal Laurent series.

  7. Direct conversion of cellulose using carbon monoxide and water on a Pt-Mo2C/C catalyst

    KAUST Repository

    Li, Jing

    2014-01-01

    CO and H2O were employed as the hydrogen source for cellulose conversion to polyols. Pt-Mo2C/C tandem catalyst with the Pt-Mo 2C domain responsible for H2 and/or H production and the Pt-C domain for cellulose conversion was fabricated. Considerable polyols were obtained over this tandem Pt-Mo2C/C catalyst. This journal is © 2014 The Royal Society of Chemistry.

  8. File list: ALL.Myo.10.AllAg.C2C12 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.10.AllAg.C2C12 mm9 All antigens Muscle C2C12 SRX1482291,SRX1482269,SRX14822...,SRX143610,SRX373248,SRX039345,DRX020502,SRX026101,SRX062104,SRX062105 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Myo.10.AllAg.C2C12.bed ...

  9. File list: ALL.Myo.20.AllAg.C2C12 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.20.AllAg.C2C12 mm9 All antigens Muscle C2C12 SRX1482269,SRX262223,SRX262224...,SRX683673,DRX000355,SRX103216,SRX373248,SRX039345,SRX695944,DRX000353 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Myo.20.AllAg.C2C12.bed ...

  10. File list: ALL.Myo.50.AllAg.C2C12 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.50.AllAg.C2C12 mm9 All antigens Muscle C2C12 SRX1482269,SRX262223,SRX262224...,SRX115557,SRX115559,SRX062124,DRX020490,DRX020492,SRX022849,SRX022851 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Myo.50.AllAg.C2C12.bed ...

  11. Transgenic Overexpression of Tcfap2c/AP-2gamma Results in Liver Failure and Intestinal Dysplasia

    Science.gov (United States)

    Woynecki, Tatiana; Egert, Angela; Becker, Astrid; Huss, Sebastian; Stabenow, Dirk; Zimmer, Andreas; Knolle, Percy; Tolba, René; Fischer, Hans-Peter; Schorle, Hubert

    2011-01-01

    Background The transcription factor Tcfap2c has been demonstrated to be essential for various processes during mammalian development. It has been found to be upregulated in various undifferentiated tumors and is implicated with poor prognosis. Tcfap2c is reported to impinge on cellular proliferation, differentiation and apoptosis. However, the physiological consequences of Tcfap2c-expression remain largely unknown. Methodology/Principal Findings Therefore we established a gain of function model to analyze the role of Tcfap2c in development and disease. Induction of the transgene led to robust expression in all tissues (except brain and testis) and lead to rapid mortality within 3–7 days. In the liver cellular proliferation and apoptosis was detected. Accumulation of microvesicular lipid droplets and breakdown of major hepatic metabolism pathways resulted in steatosis. Serum analysis showed a dramatic increase of enzymes indicative for hepatic failure. After induction of Tcfap2c we identified a set of 447 common genes, which are deregulated in both liver and primary hepatocyte culture. Further analysis showed a prominent repression of the cytochrome p450 system, PPARA, Lipin1 and Lipin2. These data indicate that in the liver Tcfap2c represses pathways, which are responsible for fatty acid metabolism. In the intestine, Tcfap2c expression resulted in expansion of Sox9 positive and proliferative active epithelial progenitor cells resulting in dysplastic growth of mucosal crypt cells and loss of differentiated mucosa. Conclusions The transgenic mice show that ectopic expression of Tcfap2c is not tolerated. Due to the phenotype observed, iTcfap2c-mice represent a model system to study liver failure. In intestine, Tcfap2c induced cellular hyperplasia and suppressed terminal differentiation indicating that Tcfap2c serves as a repressor of differentiation and inducer of proliferation. This might be achieved by the Tcfap2c mediated activation of Sox9 known to be expressed

  12. Transgenic overexpression of Tcfap2c/AP-2gamma results in liver failure and intestinal dysplasia.

    Directory of Open Access Journals (Sweden)

    Daniel Holl

    Full Text Available BACKGROUND: The transcription factor Tcfap2c has been demonstrated to be essential for various processes during mammalian development. It has been found to be upregulated in various undifferentiated tumors and is implicated with poor prognosis. Tcfap2c is reported to impinge on cellular proliferation, differentiation and apoptosis. However, the physiological consequences of Tcfap2c-expression remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Therefore we established a gain of function model to analyze the role of Tcfap2c in development and disease. Induction of the transgene led to robust expression in all tissues (except brain and testis and lead to rapid mortality within 3-7 days. In the liver cellular proliferation and apoptosis was detected. Accumulation of microvesicular lipid droplets and breakdown of major hepatic metabolism pathways resulted in steatosis. Serum analysis showed a dramatic increase of enzymes indicative for hepatic failure. After induction of Tcfap2c we identified a set of 447 common genes, which are deregulated in both liver and primary hepatocyte culture. Further analysis showed a prominent repression of the cytochrome p450 system, PPARA, Lipin1 and Lipin2. These data indicate that in the liver Tcfap2c represses pathways, which are responsible for fatty acid metabolism. In the intestine, Tcfap2c expression resulted in expansion of Sox9 positive and proliferative active epithelial progenitor cells resulting in dysplastic growth of mucosal crypt cells and loss of differentiated mucosa. CONCLUSIONS: The transgenic mice show that ectopic expression of Tcfap2c is not tolerated. Due to the phenotype observed, iTcfap2c-mice represent a model system to study liver failure. In intestine, Tcfap2c induced cellular hyperplasia and suppressed terminal differentiation indicating that Tcfap2c serves as a repressor of differentiation and inducer of proliferation. This might be achieved by the Tcfap2c mediated activation of Sox9

  13. Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population.

    Science.gov (United States)

    Yousef, Al-Motassem; Bulatova, Nailya R; Newman, William; Hakooz, Nancy; Ismail, Said; Qusa, Hisham; Zahran, Farah; Anwar Ababneh, Nidaa; Hasan, Farah; Zaloom, Imad; Khayat, Ghada; Al-Zmili, Rawan; Naffa, Randa; Al-Diab, Ola

    2012-10-01

    Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (2 and 3), CYP2C19 (2 and 3), CYP3A4 5, CYP3A5 (3 and 6), was carried out on Jordanian subjects. Different variants allele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1 1, 0.165 for CYP1A1 2A and 0.071 for CYP1A1 2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9 1, 0.135 for CYP2C9 2 and 0.068 for CYP2C9 3. For CYP2C19, the frequencies of the wild type (CYP2C19 1) and the nonfunctional (2 and 3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for 2/2. Regarding CYP3A4 1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5 1, 3 and 6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.

  14. Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52 000 individuals

    DEFF Research Database (Denmark)

    Kaur-Knudsen, D.; Bojesen, S.E.; Nordestgaard, Børge

    2009-01-01

    Cytochrome P450 2C9 (CYP2C9) enzymes metabolize warfarin and arachidonic acid. We hypothesized that the CYP2C9*2 (rs. 1799853) and CYP2C9*3 (rs. 1057910) polymorphisms with decreased enzyme activity affect risk of subclinical atherosclerosis (reduced ankle brachial index and increased C-reactive...... protein), ischemic vascular diseases (ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease and ischemic stroke) and death after an ischemic heart disease diagnosis. We genotyped the Copenhagen City Heart Study, a prospective study including 10 398 participants with 30-32 years...

  15. Investigation of the CYP2C9 induction profile in human hepatocytes by combining experimental and modelling approaches.

    Science.gov (United States)

    Belic, Ales; Temesvári, Manna; Kohalmy, Krisztina; Vrzal, Radim; Dvorak, Zdenek; Rozman, Damjana; Monostory, Katalin

    2009-12-01

    The goal of the present review is to characterise the induction profile of CYP2C9, a member of the cytochrome P450 superfamily. Since the mechanism of CYP2C9 induction is fairly complex, with parallel processes triggered by various inducers, an evaluation of the experimental results is often a great challenge. At least three nuclear receptors, the glucocrticoid receptor (GR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), are known to mediate the CYP2C9 gene induction in man. However, mathematical modelling and simulation can provide an appropriate tool for the interpretation of CYP2C9 regulatory mechanisms. As an example, we present modelling and simulation approaches of the CYP2C9 gene expression in human hepatocytes treated with well-known CYP2C9 inducers: the steroid hormone precursor dehydroepiandrosterone (DHEA) and the synthetic glucocorticoid dexamethasone (DXM). The results of the analysis suggest that in addition to the potent function of GR and the further involvement of PXR and CAR activated by DXM or DHEA, an additional factor might play a role in CYP2C9 regulation by DHEA. The novel potential candidate for DHEA action in CYP2C9 induction is likely to be the estrogen receptor. Additionally, the balance of DHEA sulphation-desulphation processes should also be considered in any description of DHEA-induced CYP2C9 profiles.

  16. Molecular dynamic simulation of the self-assembly of DAP12-NKG2C activating immunoreceptor complex.

    Directory of Open Access Journals (Sweden)

    Peng Wei

    Full Text Available The DAP12-NKG2C activating immunoreceptor complex is one of the multisubunit transmembrane protein complexes in which ligand-binding receptor chains assemble with dimeric signal-transducing modules through non-covalent associations in their transmembrane (TM domains. In this work, both coarse grained and atomistic molecular dynamic simulation methods were applied to investigate the self-assembly dynamics of the transmembrane domains of the DAP12-NKG2C activating immunoreceptor complex. Through simulating the dynamics of DAP12-NKG2C TM heterotrimer and point mutations, we demonstrated that a five-polar-residue motif including: 2 Asps and 2 Thrs in DAP12 dimer, as well as 1 Lys in NKG2C TM plays an important role in the assembly structure of the DAP12-NKG2C TM heterotrimer. Furthermore, we provided clear evidences to exclude the possibility that another NKG2C could stably associate with the DAP12-NKG2C heterotrimer. Based on the simulation results, we proposed a revised model for the self-assembly of DAP12-NKG2C activating immunoreceptor complex, along with a plausible explanation for the association of only one NKG2C with a DAP12 dimer.

  17. Hydroxylation index of omeprazole in relation to CYP2C19 polymorphism and sex in a healthy Iranian population.

    Science.gov (United States)

    Payan, Maryam; Rouini, Mohammad Reza; Tajik, Nader; Ghahremani, Mohammad Hossein; Tahvilian, Reza

    2014-12-11

    Polymorphism of CYP2C19 gene is one of the important factors in pharmacokinetics of CYP2C19 substrates. Omeprazole is a proton pump inhibitor which is mainly metabolized by cytochrome P450 2C19 (CYP2C19). The aim of present study was to assess omeprazole hydroxylation index as a measure of CYP2C19 activity considering new variant allele (CYP2C19*17) in Iranian population and also to see if this activity is sex dependent. One hundred and eighty healthy unrelated Iranian individuals attended in this study. Blood samples for genotyping and phenotyping were collected 3 hours after administration of 20 mg omeprazole orally. Genotyping of 2C19 variant alleles *2, *3 and *17 was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and semi-nested PCR methods. Plasma concentrations of omeprazole and hydroxyomeprazole were determined by high performance liquid chromatography (HPLC) technique and hydxroxylation index (HI) (omeprazole/ hydroxyomeprazole) was calculated. The CYP2C19*17 was the most common variant allele in the studied population (21.6%). Genotype frequencies of CYP2C19*17*17, *1*17, and *2*17 were 5.5%, 28.8% and 3.3% respectively. The lowest and the highest median omeprazole HI was observed in *17*17 and *2*2 genotypes respectively (0.36 vs. 13.09). The median HI of omeprazole in subjects homozygous for CYP2C19*1 was 2.16-fold higher than individuals homozygous for CYP2C19*17 (P < 0.001) and the median HI of CYP2C19*1*17 genotype was 1.98-fold higher than CYP2C19 *17*17 subjects (P < 0.001). However, subjects with CYP2C19*2*17 (median HI: 1.74) and CYP2C19*1*2 (median HI: 1.98) genotypes and also CYP2C19*1*17 (median HI: 0.71) and CYP2C19*1*1 (mean HI: 0.78) did not show any significantly different enzyme activity. In addition, no statistically significant difference was found between women and men in distribution of CYP2C19 genotypes. Furthermore, the hydroxylation index of Omeprazole was not different

  18. Recombinant myostatin reduces highly expressed microRNAs in differentiating C2C12 cells

    Directory of Open Access Journals (Sweden)

    Zachary A. Graham

    2017-03-01

    Full Text Available Myostatin is small glycopeptide that is produced and secreted by skeletal muscle. It is a potent negative regulator of muscle growth that has been associated with conditions of frailty. In C2C12 cells, myostatin limits cell differentiation. Myostatin acts through activin receptor IIB, activin receptor-like kinase (ALK and Smad transcription factors. microRNAs (miRNA are short, 22 base pair nucleotides that bind to the 3′ UTR of target mRNA to repress translation or reduce mRNA stability. In the present study, expression in differentiating C2C12 cells of the myomiRs miR-1 and 133a were down-regulated following treatment with 1 µg of recombinant myostatin at 1 d post-induction of differentiation while all myomiRs (miR-1, 133a/b and 206 were upregulated by SB431542, a potent ALK4/5/7 inhibitor which reduces Smad2 signaling, at 1 d and all, with the exception of miR-206, were upregulated by SB431542 at 3 d. The expression of the muscle-enriched miR-486 was greater following treatment with SB431542 but not altered by myostatin. Other highly expressed miRNAs in skeletal muscle, miR-23a/b and 145, were altered only at 1 d post-induction of differentiation. miR-27b responded differently to treatments at 1 d, where it was upregulated, as compared to 3 d, where it was downregulated. Neither myostatin nor SB431542 altered cell size or cell morphology. The data indicate that myostatin represses myomiR expression in differentiating C2C12 cells and that inhibition of Smad signaling with SB431542 can result in large changes in highly expressed miRNAs in differentiating myoblasts.

  19. Gold complexes with the selenolate ligand [2-(Me2NCH2)C6H4Se]-.

    Science.gov (United States)

    Crespo, Olga; Gimeno, M Concepción; Laguna, Antonio; Kulcsar, Monika; Silvestru, Cristian

    2009-05-04

    The reaction of [2-(Me(2)NCH(2))C(6)H(4)Se]M (M = Li, K) with the gold(phosphine) complexes [AuCl(PR(3))] gives the mononuclear gold-selenolate species [Au{SeC(6)H(4)(CH(2)NMe(2))-2}(PPh(3))] (1) or [Au{SeC(6)H(4)(CH(2)NMe(2))-2}(PPh(2)py)] (2), respectively. The treatment of the [2-(Me(2)NCH(2))C(6)H(4)Se]M with [Au(2)Cl(2)(mu-P-P)] [P-P = bis(diphenylphosphino)methane (dppm), bis(diphenylphosphino)ethane (dppe), 1,1'-bis(diphenylphosphino)ferrocene (dppf)] derivatives gives complexes with stoichiometry [Au(2){SeC(6)H(4)(CH(2)NMe(2))-2}(2)(mu-P-P)] [P-P = dppm (3), dppe (4), or dppf (5)]. These complexes exhibit a different structural framework, that is, 4 crystallizes as a chain polymer with intermolecular aurophilic bonding, while 5 shows an intramolecular Au(I)...Au(I) interaction. The gold(III) derivative Bu(4)N[Au(C(6)F(5))(3){SeC(6)H(4)(CH(2)NMe(2))-2}] (6) is obtained by reaction of [2-(Me(2)NCH(2))C(6)H(4)Se]K and Bu(4)N[AuBr(C(6)F(5))(3)], in a 1:1 molar ratio. These species exhibit luminescence which probably arises from a mixed (3)LMMCT and (3)MC excited state. The emission properties in these complexes seem to be useful for structural predictions and lead to the proposal of intermolecular aggregation in the solid state and frozen solution for complexes 1, 2, 3, whose crystal structures have not been elucidated.

  20. Observed and simulated global distribution and budget of atmospheric C2-C5 alkanes

    Directory of Open Access Journals (Sweden)

    J. Lelieveld

    2010-05-01

    Full Text Available The primary sources and atmospheric chemistry of C2-C5 alkanes were incorporated into the atmospheric chemistry general circulation model EMAC. Model output is compared with new observations from the NOAA/ESRL GMD Cooperative Air Sampling Network. Based on the global coverage of the data, two different anthropogenic emission datasets for C4-C5 alkanes, widely used in the modelling community, are evaluated. We show that the model reproduces the main atmospheric features of the C2-C5 alkanes (e.g., seasonality. While the simulated values for ethane and propane are within a 20% range of the measurements, larger deviations are found for the other tracers. According to the analysis, an oceanic source of butanes and pentanes larger than the current estimates would be necessary to match the observations at some coastal stations. Finally the effect of C2-C5 alkanes on the concentration of acetone and acetaldehyde are assessed. Their chemical sources are largely controlled by the reaction with OH, while the reactions with NO3 and Cl contribute only to a little extent. The total amount of acetone produced by propane, i-butane and i-pentane oxidation is 11.2 Tg/yr, 4.3 Tg/yr, and 5.8 Tg/yr, respectively. Moreover, 18.1, 3.1, 3.4, 1.4 and 4.8 Tg/yr of acetaldehyde are formed by the oxidation of ethane, propane, n-butane, n-pentane and i-pentane, respectively.

  1. Design guidelines for B2C e-commerce in virtual worlds

    OpenAIRE

    Tran, Minh; Minocha, Shailey; Roberts, David; Laing, Angus; Langdridge, Darren

    2011-01-01

    Virtual worlds are three-dimensional (3D) persistent multi-user online environments in which users interact through avatars. Virtual worlds support many kinds of activities, including education, socialising, gaming and e-commerce. Our research focuses on how virtual worlds can be used to facilitate business-to-consumer (B2C) e-commerce involving real items. Examples of affordances of virtual worlds for e-commerce include 3D simulations, multi-user environments and avatar-based interactions. W...

  2. Search for an interstellar Si2C molecule: A theoretical prediction

    Indian Academy of Sciences (India)

    Suresh Chandra

    2004-09-01

    We suggest that Si2C molecule may be identified in astronomical objects through its transitions 414 → 505, 515 → 606, 212 → 303, 313 → 404, and 111 → 202 at 15.9, 5.1, 33.6, 24.9, and 42.3 GHz in absorption even against the cosmic 2.7 K background, in a region having low temperature. The absorption phenomenon is found rather large in the first two transitions. Dependence of results on the set of molecular parameters is discussed.

  3. LT^2C^2: A language of thought with Turing-computable Kolmogorov complexity

    Directory of Open Access Journals (Sweden)

    Santiago Figueira

    2013-03-01

    Full Text Available In this paper, we present a theoretical effort to connect the theory of program size to psychology by implementing a concrete language of thought with Turing-computable Kolmogorov complexity (LT^2C^2 satisfying the following requirements: 1 to be simple enough so that the complexity of any given finite binary sequence can be computed, 2 to be based on tangible operations of human reasoning (printing, repeating,. . . , 3 to be sufficiently powerful to generate all possible sequences but not too powerful as to identify regularities which would be invisible to humans. We first formalize LT^2C^2, giving its syntax and semantics, and defining an adequate notion of program size. Our setting leads to a Kolmogorov complexity function relative to LT^2C^2 which is computable in polynomial time, and it also induces a prediction algorithm in the spirit of Solomonoff’s inductive inference theory. We then prove the efficacy of this language by investigating regularities in strings produced by participants attempting to generate random strings. Participants had a profound understanding of randomness and hence avoided typical misconceptions such as exaggerating the number of alternations. We reasoned that remaining regularities would express the algorithmic nature of human thoughts, revealed in the form of specific patterns. Kolmogorov complexity relative to LT^2C^2 passed three expected tests examined here: 1 human sequences were less complex than control PRNG sequences, 2 human sequences were not stationary showing decreasing values of complexity resulting from fatigue 3 each individual showed traces of algorithmic stability since fitting of partial data was more effective to predict subsequent data than average fits. This work extends on previous efforts to combine notions of Kolmogorov complexity theory and algorithmic information theory to psychology, by explicitly proposing a language which may describe the patterns of human thoughts.Received: 12

  4. SL(2,C) Gauge Theory of Gravitation and the Quantization of the Gravitational Field

    CERN Document Server

    Carmeli, M; Carmeli, Moshe; Malin, Shimon

    1998-01-01

    A new approach to quantize the gravitational field is presented. It is based on the observation that the quantum character of matter becomes more significant as one gets closer to the big bang. As the metric loses its meaning, it makes sense to consider Schrodinger's three generic types of manifolds - unconnected differentiable, affinely connected, and metrically connected - as a temporal sequence following the big bang. Hence one should quantize the gravitational field on general differentiable manifolds or on affinely connected manifolds. The SL(2,C) gauge theory of gravitation is employed to explore this possibility. Within this framework, the quantization itself may well be canonical.

  5. Using the I2C Interface and Localization Inforamtion to Achieve Personalization of a Device Operation

    Directory of Open Access Journals (Sweden)

    Jacek Dlugopolski

    2000-01-01

    Full Text Available The article refers to the part of the hardware and software research which concerns the problem of personalization of a common used device operation. The proposed solution is bascd on the ABS system (Active Badge System developed by ORL (Olivetti research Laboratories in the United Kingdom, which delivers localization and identification information, and the universal communication interface I2C (Inter Integrated Circuit developed by PHILIPS. The two above mentioned elements were used to create both the system of the automatic video signal flow control and the system to identify a TV program being currently viewed.

  6. Impact of CYP2C8*3 on paclitaxel clearance in ovarian cancer patients

    DEFF Research Database (Denmark)

    Bergmann, Troels Korshøj; Vach, Werner; Gréen, Henrik

    .05). CYP2C8 variant N Paclitaxel CL  geometric mean (l/h) 95% c.i P-value (T-test of log transformed CL) Wt/Wt 49 395.0 [370.3;421.4]   Wt/*1b + *1b/*1b(n=1) 44 374.5 [348.8;402.2] 0.267 Wt/Wt 69 382.4 [362.1;404.0]   Wt/*1c 24 393.1 [355.4;434.8] 0.617 Wt/Wt 74 394.7 [375.2;415.3]   Wt/*3 19 350.0 [310...

  7. A B2C Digital Marketing Plan for the Sushi Restaurant Makuja

    OpenAIRE

    Maisuradze, Veronika

    2016-01-01

    This thesis was made for the sushi restaurant Makuja, which operates in Helsinki. The objective of the project was to create and partly implement a B2C digital marketing plan for the company: to make the first steps in building online presence, which would allow people to find Makuja on the Internet, get to know the restaurant better and interact with it. One of the main goals of online presence was to spread awareness and to gain followers, fans and customers. Five project tasks were set...

  8. Longitudinal Structure Function FL from Charm Structure Function F2c

    Institute of Scientific and Technical Information of China (English)

    B.Rezaei; G.R.Boroun

    2013-01-01

    We predict the effect of the charm structure function on the longitudinal structure function at small x.In NLO analysis we find that the hard Pomeron behavior gives a good description of FL and Fkc (k =2,L) at small x values.We conclude that a direct relation between FL∝ F2c would provide useful information on how to measure longitudinal structure function at high Q2 values.Having checked that this model gives a good description of the data,when compared with other models.

  9. Electronic spectra of linear HC$_5$H and cumulene carbene H$_2$C$_5$

    CERN Document Server

    Steglich, M; Maity, S; Nagy, A; Maier, J P

    2015-01-01

    The $1 ^3\\Sigma_u^- \\leftarrow X^3\\Sigma_g^-$ transition of linear HC$_5$H (A) has been observed in a neon matrix and gas phase. The assignment is based on mass-selective experiments, extrapolation of previous results of the longer HC$_{2n+1}$H homologues, and density functional and multi-state CASPT2 theoretical methods. Another band system starting at 303 nm in neon is assigned as the $1 ^1 A_1 \\leftarrow X ^1 A_1$ transition of the cumulene carbene pentatetraenylidene H$_2$C$_5$ (B).

  10. Supply-side hurdles in internet B2C e-commerce: An empirical investigation

    OpenAIRE

    Cheung, MT; Liao, Z

    2003-01-01

    Given Hong Kong's special circumstances of small physical size, advanced infrastructure, and low shopping cost, a survey is designed under which supply-side problems in Internet business-to-consumer (B2C) e-commerce are indirectly revealed by responses on the demand side. Difficulties arising from the reluctance to answer questionnaires on the part of e-firms wary about trade and innovation secrets and their small number at the outset are thereby overcome. Survey data on demand-side obstacle ...

  11. The diversion of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate from the 2-C-methyl-D-erythritol 4-phosphate pathway to hemiterpene glycosides mediates stress responses in Arabidopsis thaliana

    NARCIS (Netherlands)

    Gonzalez-Cabanelas, D.; Wright, L.P.; Paetz, C.; Onkokesung, N.; Gershenzon, J.; Rodriguez-Concepcion, M.; Phillips, M.A.

    2015-01-01

    2-C-Methyl-D-erythritol-2,4-cyclodiphosphate (MEcDP) is an intermediate of the plastid-localized 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway which supplies isoprenoid precursors for photosynthetic pigments, redox co-factor side chains, plant volatiles, and phytohormones. The Arabidopsis hds-3

  12. BAP31 is involved in the retention of cytochrome P450 2C2 in the endoplasmic reticulum.

    Science.gov (United States)

    Szczesna-Skorupa, Elzbieta; Kemper, Byron

    2006-02-17

    Microsomal cytochrome P450 2C2 is an integral endoplasmic reticulum (ER) membrane protein that is directly retained in the ER and excluded from transport vesicles. We have used bimolecular fluorescence complementation and co-immunoprecipitation to show that a ubiquitous ER membrane protein (BAP31) interacts with P450 2C2 in transfected COS-1 cells. A chimera containing only the N-terminal signal anchor of P450 2C1 (P450 2C1-(1-29)) also interacted with BAP31, which is consistent with interaction of the two proteins via their transmembrane domains. Down-regulation of BAP31 expression with small interfering RNA resulted in redistribution of green fluorescent protein-tagged P450 2C2 or P450 2C1-(1-29) from the ER into the nuclear membrane and compact perinuclear compartment structures as well as the cell surface in a small fraction of the cells. In Bap31-null embryonic stem cells, a significant fraction of P450 2C2 or P450 2C1-(1-29) was detected at the cell surface and nuclear envelope, but was redistributed to the ER by expression of BAP31. The expression level of P450 2C2 was significantly increased in COS-1 cells with repressed levels of BAP31. Formation of the pro-apoptotic p20 fragment of BAP31 was detected in transfected COS-1 cells expressing P450 2C2, and annexin V staining was consistent with the activation of an apoptotic pathway in these cells. Down-regulation of BAP31 with small interfering RNA partially reversed the apoptosis. These results suggest that interaction of P450 2C2 with BAP31 is important for its ER retention and expression level and that BAP31 may be involved in the regulation of apoptosis induced by the ER overload response to increased expression of P450.

  13. Association and treatment response to capecitabine-based chemoradiotherapy with CYP2C9 polymorphism in head and neck cancer

    Directory of Open Access Journals (Sweden)

    S Paul

    2011-01-01

    Full Text Available Aims : The aim of the present study is to investigate the association of polymorphism in cytochrome P450 2C9 (CYP2C9 with head and neck squamous cell carcinoma (HNSCC and response in patients receiving chemoradiotherapy. Materials and Methods : One hundred ten males suffering from locally advanced head and neck squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9FNx012 and CYP2C9FNx013, leading to poor metabolizers (PMs by PCR-based RFLP. Each case was assessed thoroughly for treatment response following WHO criteria. Results : The frequency of heterozygous genotypes of both CYP2C9FNx012 (27.3% and CYP2C9FNx013 (20.1% were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several fold increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9FNx012 or CYP2C9FNx013. Further, majority of the cases assessed for response (134 carrying variant alleles of both CYP2C9FNx012 (65.3% or CYP2C9FNx013 (70.58% were found to respond poorly to the radio-chemotherapy. Conclusions : The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment schedule.

  14. Climate change impacts in the Mediterranean resulting from a 2C global temperature rise

    Energy Technology Data Exchange (ETDEWEB)

    Giannakopoulos, C.; Tin, T. [National Observatory of Athens, Athens (Greece); Bindi, M.; Moriondo, M. [Department of Agronomy and Land Management, Florence (Italy)

    2005-07-01

    The goal of the present study is to provide the first piece of the puzzle in understanding the impacts of a 2C global temperature rise on the Mediterranean region, using high temporal resolution climate model output that has been made newly available. The analysis has been based on the temperature, precipitation and wind daily outputs of the HadCM3 model using the IPCC SRES A2 and B2 emission scenarios. The study is focussed on the thirty-year period (2031-2060) centred on the time that global temperature is expected to reach 2C above pre-industrial levels, as defined by an earlier companion study. Changes in both the mean (temperature, precipitation) and the extremes (heatwaves, drought) under the different scenarios were assessed. The impacts of these climatic changes on energy demand, forest fire, tourism and agriculture were subsequently investigated either using existing numerical models or an expertbased approach. Based on recent studies, the impacts on biodiversity, water resources and sea level rise in the region were also discussed.

  15. The Effect of Non-technical Factors in B2C E-Commerce

    Science.gov (United States)

    Sanayei, Ali; Shafe'Ei, Reza

    As e-commerce grows across industries worldwide , business are building web sites for presence as well as for online business. It is more than transferring current business operations to a new medium. This situation requires explaining main models, changing infrastructures, and notice to customer needs as their vital rights. Whilst increasing numbers of firms have launched themselves on the Internet, they are trying to consideration of the strategic implications of developing, implementing or running a Web site. Global competition, laws, and customer preferences are among the issues being affected by e-commerce. In this study many factors that effect on e-commerce are considered these factors have no technical issue in nature. Companies related factors, customers' knowledge, customers' trust and customers' behavior are the main effective factors in development of B2C e-commerce. In this research we surveyed the mentioned aspects by offering questionnaire to experts of e-commerce for companies. The results show there is a meaningful relationship between perception, knowledge, trust and attitude of customers and the company's capabilities in the other side with B2C e-commerce development.

  16. Canine parvovirus--a review of epidemiological and diagnostic aspects, with emphasis on type 2c.

    Science.gov (United States)

    Decaro, Nicola; Buonavoglia, Canio

    2012-02-24

    Canine parvovirus type 2 (CPV-2) emerged in late 1970s causing severe epizootics in kennels and dog shelters worldwide. Soon after its emergence, CPV-2 underwent genetic evolution giving rise consecutively to two antigenic variants, CPV-2a and CPV-2b that replaced progressively the original type. In 2000, a new antigenic variant, CPV-2c, was detected in Italy and rapidly spread to several countries. In comparison to the original type CPV-2, the antigenic variants display increased pathogenicity in dogs and extended host range, being able to infect and cause disease in cats. Epidemiological survey indicate that the newest type CPV-2c is becoming prevalent in different geographic regions and is often associated to severe disease in adult dogs and also in dogs that have completed the vaccination protocols. However, the primary cause of failure of CPV vaccination is interference by maternally derived immunity. Diagnosis of CPV infection by traditional methods has been shown to be poorly sensitive, especially in the late stages of infections. New diagnostic approaches based on molecular methods have been developed for sensitive detection of CPV in clinical samples and rapid characterisation of the viral type. Continuous surveillance will help assess whether there is a real need to update currently available vaccines and diagnostic tests.

  17. Notch Inhibition Enhances Cardiac Reprogramming by Increasing MEF2C Transcriptional Activity

    Directory of Open Access Journals (Sweden)

    Maria Abad

    2017-03-01

    Full Text Available Conversion of fibroblasts into functional cardiomyocytes represents a potential means of restoring cardiac function after myocardial infarction, but so far this process remains inefficient and little is known about its molecular mechanisms. Here we show that DAPT, a classical Notch inhibitor, enhances the conversion of mouse fibroblasts into induced cardiac-like myocytes by the transcription factors GATA4, HAND2, MEF2C, and TBX5. DAPT cooperates with AKT kinase to further augment this process, resulting in up to 70% conversion efficiency. Moreover, DAPT promotes the acquisition of specific cardiomyocyte features, substantially increasing calcium flux, sarcomere structure, and the number of spontaneously beating cells. Transcriptome analysis shows that DAPT induces genetic programs related to muscle development, differentiation, and excitation-contraction coupling. Mechanistically, DAPT increases binding of the transcription factor MEF2C to the promoter regions of cardiac structural genes. These findings provide mechanistic insights into the reprogramming process and may have important implications for cardiac regeneration therapies.

  18. Automatic Tracking and Characterization of Cumulonimbus Clouds from FY-2C Geostationary Meteorological Satellite Images

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-01-01

    Full Text Available This paper presents an automated method to track cumulonimbus (Cb clouds based on cloud classification and characterizes Cb behavior from FengYun-2C (FY-2C. First, a seeded region growing (SRG algorithm is used with artificial neural network (ANN cloud classification as preprocessing to identify consistent homogeneous Cb patches from infrared images. Second, a cross-correlation-based approach is used to track Cb patches within an image sequence. Third, 7 pixel parameters and 19 cloud patch parameters of Cb are derived. To assess the performance of the proposed method, 8 cases exhibiting different life stages and the temporal evolution of a single case are analyzed. The results show that (1 the proposed method is capable of locating and tracking Cb until dissipation and can account for the eventual splitting or merging of clouds; (2 compared to traditional brightness temperature (TB thresholds-based cloud tracking methods, the proposed method reduces the uncertainty stemming from TB thresholds by classifying clouds with multichannel data in an advanced manner; and (3 the configuration and developmental stages of Cb that the method identifies are close to reality, suggesting that the characterization of Cb can provide detailed insight into the study of the motion and development of thunderstorms.

  19. Research on CPFR pattern of the Internet of things based on B2C

    Science.gov (United States)

    Zhou, Ling; Yang, Jie

    2013-03-01

    The CPFR pattern proposed by this article is based on the internet of things platform, using frontier technology of internet of things to realize real-time monitoring and the feedback in logistics, information stream in B2C mode, and simultaneously construct an e-business mode which takes the customer guidance as the center to be possible to meet the customers' need and realize the service made by customer. This new pattern uses the coordination, plan, prediction and replenishment of CPFR to realize custom-made stock based on B2C for terminal customer and specialized service for commodity stock. Moreover, it can bring suppliers real-time monitoring of terminal logistics, storage and users' notes for use, and feed back users' bugs, adjustment of orders and plan of replenishment. Furthermore, based on new pattern, we can data min users' interests and undertake a study in increment modeling, process reengineering in enterprise, optimizing enterprise's interior resources and conformity industry of supply chain. Above all it provides a new mentality and the operation pattern for the electronic commerce marketing.

  20. Magnetic ordering in Ho{sub 2}Fe{sub 2}Si{sub 2}C

    Energy Technology Data Exchange (ETDEWEB)

    Susilo, R. A., E-mail: resta.susilo@student.adfa.edu.au; Cadogan, J. M.; Cobas, R.; Hutchison, W. D.; Campbell, S. J. [School of Physical, Environmental and Mathematical Sciences, UNSW Canberra at the Australian Defence Force Academy, Canberra BC 2610 (Australia); Avdeev, M. [Bragg Institute, ANSTO, PMB 1, Menai, New South Wales 2234 (Australia)

    2015-05-07

    We have used neutron diffraction and {sup 57}Fe Mössbauer spectroscopy, complemented by magnetisation and specific heat measurements, to examine the magnetic ordering of Ho{sub 2}Fe{sub 2}Si{sub 2}C. We have established that Ho{sub 2}Fe{sub 2}Si{sub 2}C orders antiferromagnetically below T{sub N} = 16(1) K with a magnetic structure involving ordering of the Ho sublattice along the b-axis with a propagation vector k=[0 0 1/2 ]. {sup 57}Fe Mössbauer spectra collected below T{sub N} show no evidence of a magnetic splitting, demonstrating the absence of long range magnetic ordering of the Fe sublattice. A small line broadening is observed in the {sup 57}Fe spectra below T{sub N}, which is due to a transferred hyperfine field—estimated to be around 0.3 T at 10 K—from the Ho sublattice.

  1. Evolutionary genetic analyses of MEF2C gene: implications for learning and memory in Homo sapiens.

    Science.gov (United States)

    Kalmady, Sunil V; Venkatasubramanian, Ganesan; Arasappa, Rashmi; Rao, Naren P

    2013-02-01

    MEF2C facilitates context-dependent fear conditioning (CFC) which is a salient aspect of hippocampus-dependent learning and memory. CFC might have played a crucial role in human evolution because of its advantageous influence on survival of species. In this study, we analyzed 23 orthologous mammalian gene sequences of MEF2C gene to examine the evidence for positive selection on this gene in Homo sapiens using Phylogenetic Analysis by Maximum Likelihood (PAML) and HyPhy software. Both PAML Bayes Empirical Bayes (BEB) and HyPhy Fixed Effects Likelihood (FEL) analyses supported significant positive selection on 4 codon sites in H. sapiens. Also, haplotter analysis revealed significant ongoing positive selection on this gene in Central European population. The study findings suggest that adaptive selective pressure on this gene might have influenced human evolution. Further research on this gene might unravel the potential role of this gene in learning and memory as well as its pathogenetic effect in certain hippocampal disorders with evolutionary basis like schizophrenia.

  2. Dynamic Entangled Porous Framework for Hydrocarbon (C2-C3) Storage, CO2 Capture, and Separation.

    Science.gov (United States)

    Sikdar, Nivedita; Bonakala, Satyanarayana; Haldar, Ritesh; Balasubramanian, Sundaram; Maji, Tapas Kumar

    2016-04-18

    Storage and separation of small (C1-C3) hydrocarbons are of great significance as these are alternative energy resources and also can be used as raw materials for many industrially important materials. Selective capture of greenhouse gas, CO2 from CH4 is important to improve the quality of natural gas. Among the available porous materials, MOFs with permanent porosity are the most suitable to serve these purposes. Herein, a two-fold entangled dynamic framework {[Zn2 (bdc)2 (bpNDI)]⋅4DMF}n with pore surface carved with polar functional groups and aromatic π clouds is exploited for selective capture of CO2 , C2, and C3 hydrocarbons at ambient condition. The framework shows stepwise CO2 and C2 H2 uptake at 195 K but type I profiles are observed at 298 K. The IAST selectivity of CO2 over CH4 is the highest (598 at 298 K) among the MOFs without open metal sites reported till date. It also shows high selectivity for C2 H2 , C2 H4 , C2 H6 , and C3 H8 over CH4 at 298 K. DFT calculations reveal that aromatic π surface and the polar imide (RNC=O) functional groups are the primary adsorption sites for adsorption. Furthermore, breakthrough column experiments showed CO2 /CH4 C2 H6 /CH4 and CO2 /N2 separation capability at ambient condition.

  3. Thermodynamic analysis of Mo{sub 2}C powder synthesis by chemical vapor reaction method

    Energy Technology Data Exchange (ETDEWEB)

    Eroglu, S.; Bakan, H. [TUBITAK-Marmara Research Center, MCTRI, Gebze-Kocaeli (Turkey)

    2004-07-01

    Thermodynamic analysis was carried out to determine the processing conditions for the synthesis of Mo{sub 2}C powders by chemical vapor reaction (CVR) method using MoO{sub 3}-CH{sub 4}-H{sub 2}-N{sub 2} and MoCl{sub 5}-CH{sub 4}-H{sub 2}-N{sub 2} gaseous mixtures. Equilibrium solid stability diagrams were produced as a function of temperature and MoO{sub 3}/(MoO{sub 3}+CH{sub 4}) or MoCl{sub 5}/(MoCl{sub 5}+CH{sub 4}) reactant gas ratio. The diagrams show that Mo{sub 2}C powders are synthesized at narrow range of experimental variables. Mo powder is produced at high yields when the MoO{sub 3}-CH{sub 4}-H{sub 2} gases are used. Equilibrium gas phase composition and solid yields were also determined. The results of the calculations were compared with those reported in the literature. (orig.)

  4. Implementation of I2C-DMA & SPI-DMA Interface: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Gurkesar

    2014-06-01

    Full Text Available This paper describes the designing and implementation of I2C (master-DMA and SPI (master-DMA interface. Direct Memory Access (DMA, being the feature of modern computers and microprocessors permits certain hardware subsystem in a computer machine to access system memory for reading/writing independently of CPU. Sometimes CPU is fully occupied for entire duration of read/write operation and unavailable to perform other work. With DMA, CPU would initiate data transfers and performs other operations while transfer is in progress. For intra-chip serial data transfers, SPI and I2C are used. Both serial protocols are widely used but both have some merits and demerits. In this research work both protocols are interfaced with DMA for SoC (System on Chip applications and their performance analysis is carried out by implementing on FPGA. VERILOG-HDL is used for designing RTL Code and test-bench verification. Simulations are observed in Modelsim-Altera 6.3 (Quartus II 8.1 simulator.

  5. Electronic Commerce in Tourism in China: B2B or B2C?

    Science.gov (United States)

    Li, Hongxiu; Suomi, Reima

    E-commerce has significantly changed the distribution channels of travel products in the world including China. Online channels are growing important in travel service distribution. In China tourism industry has been developed rapidly with the economic development, more and more international travel service providers are trying to expand their Chinese market through the Internet. This paper sheds lights on the e-commerce development models in China for international travel service providers. It explores the current e-tourism in China from the three different participants in the value chain in tourism industry - consumer, travel agent and travel service provider. The paper also identifies the barriers in B2C arena in international outbound travel market, and discusses the possible approaches for international travel service providers to develop their e-commerce in the huge Chinese market. The results in this study reveal that international travel service providers should focus on B2B model to expand their electronic market in China. B2C development in tourism largely depends on the change of Chinese customers' behavior and the change of international tourism regulations. The findings of the study are expected to assist international travel service providers to understand current e-tourism in China and to support their planning for future e-commerce development in China.

  6. Ovarian volume throughout life

    DEFF Research Database (Denmark)

    Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham

    2013-01-01

    cancer. To date there is no normative model of ovarian volume throughout life. By searching the published literature for ovarian volume in healthy females, and using our own data from multiple sources (combined n=59,994) we have generated and robustly validated the first model of ovarian volume from...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis...

  7. An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19

    NARCIS (Netherlands)

    Tamminga, C.A; Wemer, J; Oosterhuis, B; Brakenhoff, J.P G; Gerrits, M.G F; de Zeeuw, R.A; de Leij, Lou; Jonkman, J.H.G.

    2001-01-01

    A method for simultaneous phenotyping and genotyping for CYP2D6 and CYP2C19 was tested. Six healthy volunteers were selected (three extensive and three poor metabolisers for CYP2D6). CYP2D6 was probed with dextromethorphan and metoprolol and CYP2C19 was probed with omeprazole. Blood samples were col

  8. The prevalence of CYP2D6 and CYP2C19 genotypes in a population of healthy Dutch volunteers

    NARCIS (Netherlands)

    Tamminga, W.J; Wemer, J; Oosterhuis, B; de Zeeuw, R.A; de Leij, Lou; Jonkman, J.H.G.

    2001-01-01

    Aim: This study was performed in a sample of the Dutch population to estimate the prevalence of noncoding mutations of CYP2D6 and CYP2C19 as obtained by genotyping. In addition, the predictability of the genotyping strategy was assessed. Methods: The CYP2D6 and CYP2C19 status of 765 unrelated health

  9. Vergelijking van de zuurremmende effecten van esomeprazol en pantoprazol in relatie tot farmacokinetiek en CYP2C19-polymorfisme

    NARCIS (Netherlands)

    Hunfeld, Nicole G. M.; Touw, Daan J.; Mathôt, Ron A. A.; Mulder, Paul G. H.; Van Schaik, Ron H. N.; Kuipers, Ernst J.; Kooiman, Johan C.; Geus, Willem P.

    2012-01-01

    OBJECTIVE: To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics. Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved

  10. Influence of the genetic polymorphisms in the 5' flanking and exonic regions of CYP2C19 on proguanil oxidation.

    Science.gov (United States)

    Satyanarayana, Chakradhara Rao Uppugunduri; Devendran, Anichavezhi; Jayaraman, Muthukumaran; Mannu, Jayakanthan; Mathur, Premendu P; Gopal, Shewade Deepak; Rajagopal, Krishnamoorthy; Chandrasekaran, Adithan

    2009-01-01

    CYP2C19 is a polymorphic enzyme which metabolizes several clinically important drugs including proguanil. Variation in the 5' regulatory region may influence CYP2C19 activity. This study evaluates the relationship between proguanil metabolic ratio and genetic variations of CYP2C19 in a South Indian population. Fifty unrelated healthy subjects were genotyped for CYP2C19 (*)2 and (*)3 alleles and the 5' flanking region of CYP2C19 was sequenced. Plasma concentrations of proguanil and cycloguanil were estimated by reverse phase HPLC after single oral doses (200 mg) of proguanil. In silico docking analysis of transcription factors binding to its sites in CYP2C19 5' regulatory region was performed. The mean metabolic ratios (proguanil/cycloguanil) were highest in (*)1/(*)2 or (*)1/(*)3 subjects and in (*)2/(*)2 or (*)2/(*)3 as compared to (*)1/(*)1 subjects. Subjects with promoter region variation -98T>C showed decrease in the metabolic ratios irrespective of other variation, which may explain the deviation from the genotype-phenotype association of CYP2C19. In silico analysis predicted alteration in the interaction of transcription factors to their binding sites in the presence of variant alleles. The results of this study would be useful in predicting interindividual differences in the metabolism of substrates of CYP2C19.

  11. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients Using Antipsychotics: A Replication Study

    NARCIS (Netherlands)

    Risselada, Arne; Vehof, Jelle; Bruggeman, Richard; Wilffert, Bob; Cohen, Dan; Al Hadithy, Asmar; Arends, Johan; Mulder, Hans

    2010-01-01

    Background: In two previous studies we investigated the association between the rs1414334 C/G and 759 C/T polymorphisms in the HTR2C gene, coding for the 5HT2c-receptor, and prevalence of the metabolic syndrome in a schizophrenic population. In both studies we found an association between the varian

  12. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics : a replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A. F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  13. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics: A replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A.F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  14. Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes

    NARCIS (Netherlands)

    Filip, Malgorzata; Spampinato, Umberto; McCreary, Andrew C.; Przegalinski, Edmund

    2012-01-01

    The present review provides an overview on serotonin (5-hydroxytryptamine; 5-HT)(2C) receptors and their relationship to drug dependence. We have focused our discussion on the impact of 5-HT2C receptors on the effects of different classes of addictive drugs, illustrated by reference to data using ph

  15. Vergelijking van de zuurremmende effecten van esomeprazol en pantoprazol in relatie tot farmacokinetiek en CYP2C19-polymorfisme

    NARCIS (Netherlands)

    Hunfeld, Nicole G. M.; Touw, Daan J.; Mathôt, Ron A. A.; Mulder, Paul G. H.; Van Schaik, Ron H. N.; Kuipers, Ernst J.; Kooiman, Johan C.; Geus, Willem P.

    2012-01-01

    OBJECTIVE: To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics. Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved

  16. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics : a replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A. F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  17. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics: A replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A.F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  18. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients Using Antipsychotics: A Replication Study

    NARCIS (Netherlands)

    Risselada, Arne; Vehof, Jelle; Bruggeman, Richard; Wilffert, Bob; Cohen, Dan; Al Hadithy, Asmar; Arends, Johan; Mulder, Hans

    2010-01-01

    Background: In two previous studies we investigated the association between the rs1414334 C/G and 759 C/T polymorphisms in the HTR2C gene, coding for the 5HT2c-receptor, and prevalence of the metabolic syndrome in a schizophrenic population. In both studies we found an association between the varian

  19. Foot-and-Mouth Disease Virus 2C Is a Hexameric AAA+ Protein with a Coordinated ATP Hydrolysis Mechanism

    DEFF Research Database (Denmark)

    Sweeney, Trevor; Cisnetto, Valentina; Bose, Daniel

    2010-01-01

    . Unliganded 2C(34–318) exhibits concentration-dependent self-association to yield oligomeric forms, the largest of which is tetrameric. Strikingly, in the presence of ATP and RNA, FMDV 2C(34–318) containing the N207A mutation, which binds but does not hydrolyze ATP, was found to oligomerize specifically...... into hexamers. Visualization of FMDV 2C-ATP-RNA complexes by negative stain electron microscopy revealed hexameric ring structures with 6-fold symmetry that are characteristic of AAA+ ATPases. ATPase assays performed by mixing purified active and inactive 2C(34–318) subunits revealed a coordinated mechanism...... of ATP hydrolysis. Our results provide new insights into the structure and mechanism of picornavirus 2C proteins that will facilitate new investigations of their roles in infection....

  20. Photobiomodulation Protects and Promotes Differentiation of C2C12 Myoblast Cells Exposed to Snake Venom

    Science.gov (United States)

    da Silva, Aline; Vieira, Rodolfo Paula; Mesquita-Ferrari, Raquel Agnelli; Cogo, José Carlos; Zamuner, Stella Regina

    2016-01-01

    Background Snakebites is a neglected disease and in Brazil is considered a serious health problem, with the majority of the snakebites caused by the genus Bothrops. Antivenom therapy and other first-aid treatments do not reverse local myonecrose which is the main sequel caused by the envenomation. Several studies have shown the effectiveness of low level laser (LLL) therapy in reducing local myonecrosis induced by Bothropic venoms, however the mechanism involved in this effect is unknown. In this in vitro study, we aimed to analyze the effect of LLL irradiation against cytotoxicity induced by Bothrops jararacussu venom on myoblast C2C12 cells. Methodology C2C12 were utilized as a model target and were incubated with B. jararacussu venom (12.5 μg/mL) and immediately irradiated with LLL at wavelength of red 685 nm or infrared 830 nm with energy density of 2.0, 4.6 and 7.0 J/cm2. Effects of LLL on cellular responses of venom-induced cytotoxicity were examined, including cell viability, measurement of cell damage and intra and extracellular ATP levels, expression of myogenic regulatory factors, as well as cellular differentiation. Results In non-irradiated cells, the venom caused a decrease in cell viability and a massive release of LDH and CK levels indicating myonecrosis. Infrared and red laser at all energy densities were able to considerably decrease venom-induced cytotoxicity. Laser irradiation induced myoblasts to differentiate into myotubes and this effect was accompanied by up regulation of MyoD and specially myogenin. Moreover, LLL was able to reduce the extracellular while increased the intracellular ATP content after venom exposure. In addition, no difference in the intensity of cytotoxicity was shown by non-irradiated and irradiated venom. Conclusion LLL irradiation caused a protective effect on C2C12 cells against the cytotoxicity caused by B. jararacussu venom and promotes differentiation of these cells by up regulation of myogenic factors. A modulatory

  1. Mean nuclear volume

    DEFF Research Database (Denmark)

    Mogensen, O.; Sørensen, Flemming Brandt; Bichel, P.

    1999-01-01

    We evaluated the following nine parameters with respect to their prognostic value in females with endometrial cancer: four stereologic parameters [mean nuclear volume (MNV), nuclear volume fraction, nuclear index and mitotic index], the immunohistochemical expression of cancer antigen (CA125...

  2. SL (2, C) Chern-Simons theory, a non-planar graph operator, and 4D quantum gravity with a cosmological constant: Semiclassical geometry

    Science.gov (United States)

    Haggard, Hal M.; Han, Muxin; Kamiński, Wojciech; Riello, Aldo

    2015-11-01

    We study the expectation value of a nonplanar Wilson graph operator in SL (2, C) Chern-Simons theory on S3. In particular we analyze its asymptotic behavior in the double-scaling limit in which both the representation labels and the Chern-Simons coupling are taken to be large, but with fixed ratio. When the Wilson graph operator has a specific form, motivated by loop quantum gravity, the critical point equations obtained in this double-scaling limit describe a very specific class of flat connection on the graph complement manifold. We find that flat connections in this class are in correspondence with the geometries of constant curvature 4-simplices. The result is fully non-perturbative from the perspective of the reconstructed geometry. We also show that the asymptotic behavior of the amplitude contains, at the leading order, an oscillatory part proportional to the Regge action for the single 4-simplex in the presence of a cosmological constant. In particular, the cosmological term contains the full-fledged curved volume of the 4-simplex. Interestingly, the volume term stems from the asymptotics of the Chern-Simons action. This can be understood as arising from the relation between Chern-Simons theory on the boundary of a region, and a theory defined by an F2 action in the bulk. Another peculiarity of our approach is that the sign of the curvature of the reconstructed geometry, and hence of the cosmological constant in the Regge action, is not fixed a priori, but rather emerges semiclassically and dynamically from the solution of the equations of motion. In other words, this work suggests a relation between 4-dimensional loop quantum gravity with a cosmological constant and SL (2, C) Chern-Simons theory in 3 dimensions with knotted graph defects.

  3. SL(2,C Chern–Simons theory, a non-planar graph operator, and 4D quantum gravity with a cosmological constant: Semiclassical geometry

    Directory of Open Access Journals (Sweden)

    Hal M. Haggard

    2015-11-01

    Full Text Available We study the expectation value of a nonplanar Wilson graph operator in SL(2,C Chern–Simons theory on S3. In particular we analyze its asymptotic behavior in the double-scaling limit in which both the representation labels and the Chern–Simons coupling are taken to be large, but with fixed ratio. When the Wilson graph operator has a specific form, motivated by loop quantum gravity, the critical point equations obtained in this double-scaling limit describe a very specific class of flat connection on the graph complement manifold. We find that flat connections in this class are in correspondence with the geometries of constant curvature 4-simplices. The result is fully non-perturbative from the perspective of the reconstructed geometry. We also show that the asymptotic behavior of the amplitude contains, at the leading order, an oscillatory part proportional to the Regge action for the single 4-simplex in the presence of a cosmological constant. In particular, the cosmological term contains the full-fledged curved volume of the 4-simplex. Interestingly, the volume term stems from the asymptotics of the Chern–Simons action. This can be understood as arising from the relation between Chern–Simons theory on the boundary of a region, and a theory defined by an F2 action in the bulk. Another peculiarity of our approach is that the sign of the curvature of the reconstructed geometry, and hence of the cosmological constant in the Regge action, is not fixed a priori, but rather emerges semiclassically and dynamically from the solution of the equations of motion. In other words, this work suggests a relation between 4-dimensional loop quantum gravity with a cosmological constant and SL(2,C Chern–Simons theory in 3 dimensions with knotted graph defects.

  4. Ni-CeO2/C Catalysts with Enhanced OSC for the WGS Reaction

    Directory of Open Access Journals (Sweden)

    Laura Pastor-Pérez

    2015-03-01

    Full Text Available In this work, the WGS performance of a conventional Ni/CeO2 bulk catalyst is compared to that of a carbon-supported Ni-CeO2 catalyst. The carbon-supported sample resulted to be much more active than the bulk one. The higher activity of the Ni-CeO2/C catalyst is associated to its oxygen storage capacity, a parameter that strongly influences the WGS behavior. The stability of the carbon-supported catalyst under realistic operation conditions is also a subject of this paper. In summary, our study represents an approach towards a new generation of Ni-ceria based catalyst for the pure hydrogen production via WGS. The dispersion of ceria nanoparticles on an activated carbon support drives to improved catalytic skills with a considerable reduction of the amount of ceria in the catalyst formulation.

  5. Magnetic phase diagram of ErNi2B2C

    DEFF Research Database (Denmark)

    Jensen, A.; Toft, K.N.; Abrahamsen, A.B.;

    2004-01-01

    an analysis of bulk magnetization and zero-field neutron diffraction data. The model accounts for most of the observed features but fails to explain the occurrence of a small component Qdelta approximate to -0.005b* observed close to H-c2 when the field is applied along [110]. (C) 2004 Elsevier B.V. All......The magnetic phase diagram of the superconductor ErNi2B2C (T-c = 11 K and T-N = 6 K) has been studied by neutron diffraction as a function of temperature and magnetic field applied along the symmetry directions [010], [110] and [001] of the tetragonal crystal structure. A series of commensurate...... magnetic structures, consistent with a transversely polarized spin-density wave with modulation vectors Q = n/ma* (0.55 less than or equal to n/m

  6. A Study of Online Review Promptness in a B2C System

    Directory of Open Access Journals (Sweden)

    Junqiang Zhang

    2016-01-01

    Full Text Available Web 2.0 technologies have attracted an increasing number of active online writers and viewers. A deeper understanding of when customers will review and what motivates them to write online reviews is of both theoretical and practical significance. In this paper, we present a novel methodological framework, which consists of theoretical modeling and text-mining technologies, to study the relationships among customers’ review promptness, their review opinions, and their review motivations. We first study customers’ online “purchase-review” behavior dynamics; then, we introduce the LDA method to mine customers’ opinion from their review text; finally, we propose a theoretical model to explore some motivations for those people publishing review online. The analytical and experimental results with real data from a Chinese B2C website demonstrate that the behavior dynamics of customers’ online review are influenced by the multidimensional motivations, and some of them can be observed from their review behaviors, such as review promptness.

  7. Perceived Compatibility and the Adoption of B2C E-Commerce by Non-buyers

    Science.gov (United States)

    Hernández-García, Ángel; Iglesias-Pradas, Santiago; Chaparro-Peláez, Julián; Pascual-Miguel, Félix

    The purpose of this article is to study the factors which affect the intention to buy online for users who have never made any prior purchase using the electronic channel, with special focus to the role of perceived compatibility. To do so, an adoption model for e-commerce was proposed on the basis of the Technology Adoption Model (TAM) and the Innovations Diffusion Theory (IDT). In order to validate the model, data gathered amongst Spanish consumers who had no experience using e-commerce, were analyzed using the partial least squares (PLS) method. The results have demonstrated the importance of perceived compatibility as a significant factor to foster non-buyers' adoption of electronic business-to-consumer e-commerce (eB2C).

  8. On-line Shopping on B2C Markets in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Pilík Michal

    2012-12-01

    Full Text Available The paper deals with the e-commerce theory and is aimed primarily at its usage in business-toconsumer markets. On-line purchasing management is increasing not only in the Czech Republic but also in Europe and all over the world. The customers who think rationally use on-line shopping because of money saving, speed delivery and the possibility of product comparison. This paper presents the results of a project financed by the Czech Science Foundation P403/11/ P175: The factors influencing customers’ on-line behaviour in e-commerce environment on B2C and B2B markets in the Czech Republic. 89 % of respondents use e-shops for buying products in the Czech Republic. 32 % of them use the Internet for regular purchases and 57 % of them irregularly. 11 % of respondents have not used e-shops yet.

  9. On Desideratum for B2C E-Commerce Reputation Systems

    Institute of Scientific and Technical Information of China (English)

    Anna Gutowska; Andrew Sloane; Kevan A.Buckley

    2009-01-01

    This paper reviews existing approaches to reputation systems,their constraints as well as available solutions.Furthermore.it presents and evaluates a novel and comprehensive reputation model devoted to the distributed reputation system for Business-to-Consumer(B2C)E-commerce applications that overcomes the discussed drawbacks.The algorithm offers a comprehensive approach as it considers a number of issues that have a bearing on trust and reputation such as age of ratings,transaction value,credibility of referees,number of malicious incidents,collusion and unfair ratings.Moreover,it also extends the existing frameworks based on information about past behaviour,with other aspects affecting online trading decisions which relate to the characteristic of the providers,such as existence of trustmark seals,payment intermediaries,privacy statements,security/privacy strategies,purchase protection/insurance,alternative dispute resolutions as well as the existence of first party information.

  10. Algebraic theory of endohedrally confined diatomic molecules: application to H$_2$@C$_{60}$

    CERN Document Server

    Fortunato, Lorenzo

    2016-01-01

    A simple and yet powerful approach for modeling the structure of endohedrally confined diatomic molecules is introduced. The theory, based on a $u(4)\\oplus u(3)$ dynamical algebra, combines the vibron model with an isotropic three dimensional oscillator. The first describes the internal roto-vibrations degrees of freedom of the molecule, while the second takes into account the confined molecule center-of-mass degrees of freedom. A resulting subalgebra chain is connected to the underlying physics and the model is applied to the prototypical case of H$_2$ caged in a fullerene molecule. The spectrum of the supramolecular complex H$_2$@C$_{60}$ is described with a few parameters and predictions for not yet detected levels are made. Our fits suggest that the quantum numbers of a few lines should be reassigned to obtain better agreement with data.

  11. Magnetism and superconductivity in ErNi2B2C

    Indian Academy of Sciences (India)

    N J Bancroft; D McK Paul; G McIntyre; C D Dewhurst; R Cubitt

    2002-05-01

    We have performed a series of neutron diffraction experiments from the magnetic order and the vortex lattice in single crystal ErNi2B2C. The incommensurate magnetic structure develops additional even harmonics below the `ferromagnetic' ordering temperature, F of 2.3 K. This feature and the existence of rods of diffuse scattering suggest the development of ferromagnetic microdomain walls. The magnetic structure is very sensitive to the application of a magnetic field with changes in modulation vector and harmonic content. Studies of the vortex lattice show the presence of a 45° reorientation transition and a distorted hexagonal to square transition as a function of applied field. Further distortions of the vortex lattice occur at N, but no changes are seen at F.

  12. Fungal volatile compounds induce production of the secondary metabolite Sodorifen in Serratia plymuthica PRI-2C.

    Science.gov (United States)

    Schmidt, Ruth; Jager, Victor de; Zühlke, Daniela; Wolff, Christian; Bernhardt, Jörg; Cankar, Katarina; Beekwilder, Jules; Ijcken, Wilfred van; Sleutels, Frank; Boer, Wietse de; Riedel, Katharina; Garbeva, Paolina

    2017-04-13

    The ability of bacteria and fungi to communicate with each other is a remarkable aspect of the microbial world. It is recognized that volatile organic compounds (VOCs) act as communication signals, however the molecular responses by bacteria to fungal VOCs remain unknown. Here we perform transcriptomics and proteomics analyses of Serratia plymuthica PRI-2C exposed to VOCs emitted by the fungal pathogen Fusarium culmorum. We find that the bacterium responds to fungal VOCs with changes in gene and protein expression related to motility, signal transduction, energy metabolism, cell envelope biogenesis, and secondary metabolite production. Metabolomic analysis of the bacterium exposed to the fungal VOCs, gene cluster comparison, and heterologous co-expression of a terpene synthase and a methyltransferase revealed the production of the unusual terpene sodorifen in response to fungal VOCs. These results strongly suggest that VOCs are not only a metabolic waste but important compounds in the long-distance communication between fungi and bacteria.

  13. Measurement of D^(*+-) Meson Production and F_2^c in Deep-Inelastic Scattering at HERA

    CERN Document Server

    Adloff, C.; Andrieu, B.; Anthonis, T.; Arkadov, V.; Astvatsatourov, A.; Babaev, A.; Bahr, J.; Baranov, P.; Barrelet, E.; Bartel, W.; Bate, P.; Beglarian, A.; Behnke, O.; Beier, C.; Belousov, A.; Benisch, T.; Berger, C.; Berndt, T.; Bizot, J.C.; Boudry, V.; Braunschweig, W.; Brisson, V.; Broker, H.B.; Brown, D.P.; Bruckner, W.; Bruncko, D.; Burger, J.; Busser, F.W.; Bunyatyan, A.; Burrage, A.; Buschhorn, G.; Campbell, A.J.; Cao, Jun; Carli, T.; Caron, S.; Clarke, D.; Clerbaux, B.; Collard, C.; Contreras, J.G.; Coppens, Y.R.; Coughlan, J.A.; Cousinou, M.C.; Cox, B.E.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Dau, W.D.; Daum, K.; Davidsson, M.; Delcourt, B.; Delerue, N.; Demirchyan, R.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dingfelder, J.; Dixon, P.; Dodonov, V.; Dowell, J.D.; Droutskoi, A.; Dubak, A.; Duprel, C.; Eckerlin, Guenter; Eckstein, D.; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eisenhandler, E.; Ellerbrock, M.; Elsen, E.; Erdmann, M.; Erdmann, W.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Ferencei, J.; Ferron, S.; Fleischer, M.; Fleming, Y.H.; Flugge, G.; Fomenko, A.; Foresti, I.; Formanek, J.; Foster, J.M.; Franke, G.; Gabathuler, E.; Gabathuler, K.; Garvey, J.; Gassner, J.; Gayler, Joerg; Gerhards, R.; Gerlich, C.; Ghazaryan, Samvel; Goerlich, L.; Gogitidze, N.; Goldberg, M.; Goodwin, C.; Grab, C.; Grassler, H.; Greenshaw, T.; Grindhammer, Guenter; Hadig, T.; Haidt, D.; Hajduk, L.; Haynes, W.J.; Heinemann, B.; Heinzelmann, G.; Henderson, R.C.W.; Hengstmann, S.; Henschel, H.; Heremans, R.; Herrera, G.; Herynek, I.; Hildebrandt, M.; Hilgers, M.; Hiller, K.H.; Hladky, J.; Hoting, P.; Hoffmann, D.; Horisberger, R.; Hurling, S.; Ibbotson, M.; Issever, C .; Jacquet, M.; Jaffre, M.; Janauschek, L.; Jansen, D.M.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jones, M.A.S.; Jung, H.; Kastli, H.K.; Kant, D.; Kapichine, M.; Karlsson, M.; Karschnick, O.; Keil, F.; Keller, N.; Kennedy, J.; Kenyon, I.R.; Kermiche, S.; Kiesling, Christian M.; Kjellberg, P.; Klein, M.; Kleinwort, C.; Kluge, T.; Knies, G.; Koblitz, B.; Kolya, S.D.; Korbel, V.; Kostka, P.; Kotelnikov, S.K.; Koutouev, R.; Koutov, A.; Krehbiel, H.; Kroseberg, J.; Kruger, K.; Kupper, A.; Kuhr, T.; Kurca, T.; Lahmann, R.; Lamb, D.; Landon, M.P.J.; Lange, W.; Lastovicka, T.; Laycock, P.; Lebailly, E.; Lebedev, A.; Leissner, B.; Lemrani, R.; Lendermann, V.; Levonian, S.; Lindstroem, M.; List, B.; Lobodzinska, E.; Lobodzinski, B.; Loginov, A.; Loktionova, N.; Lubimov, V.; Luders, S.; Luke, D.; Lytkin, L.; Mahlke-Kruger, H.; Malden, N.; Malinovski, E.; Malinovski, I.; Maracek, R.; Marage, P.; Marks, J.; Marshall, R.; Martyn, H.U.; Martyniak, J.; Maxfield, S.J.; Meer, D.; Mehta, A.; Meier, K.; Merkel, P.; Meyer, A.B.; Meyer, H.; Meyer, J.; Meyer, P.O.; Mikocki, S.; Milstead, D.; Mkrtchyan, T.; Mohr, R.; Mohrdieck, S.; Mondragon, M.N.; Moreau, F.; Morozov, A.; Morris, J.V.; Muller, K.; Murin, P.; Nagovizin, V.; Naroska, B.; Naumann, J.; Naumann, T.; Nellen, G.; Newman, Paul R.; Nicholls, T.C.; Niebergall, F.; Niebuhr, C.; Nix, O.; Nowak, G.; Olsson, J.E.; Ozerov, D.; Panassik, V.; Pascaud, C.; Patel, G.D.; Peez, M.; Perez, E.; Phillips, J.P.; Pitzl, D.; Poschl, R.; Potachnikova, I.; Povh, B.; Rabbertz, K.; Radel, G.; Rauschenberger, J.; Reimer, P.; Reisert, B.; Reyna, D.; Risler, C.; Rizvi, E.; Robmann, P.; Roosen, R.; Rostovtsev, A.; Rusakov, S.; Rybicki, K.; Sankey, D.P.C.; Scheins, J.; Schilling, F.P.; Schleper, P.; Schmidt, D.; Schmitt, S.; Schneider, M.; Schoeffel, L.; Schoning, A.; Schorner, T.; Schroder, V.; Schultz-Coulon, H.C.; Schwanenberger, C.; Sedlak, K.; Sefkow, F.; Chekelian, V.; Sheviakov, I.; Shtarkov, L.N.; Sirois, Y.; Sloan, T.; Smirnov, P.; Solochenko, V.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, Arnd E.; Spitzer, H.; Stamen, R.; Stella, B.; Stiewe, J.; Straumann, U.; Swart, M.; Tasevsky, M.; Tchernyshov, V.; Chetchelnitski, S.; Thompson, Graham; Thompson, P.D.; Tobien, N.; Traynor, D.; Truoel, Peter; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Turney, J.E.; Tzamariudaki, E.; Udluft, S.; Usik, A.; Valkar, S.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vassiliev, S.; Vazdik, Y.; Vichnevski, A.; Wacker, K.; Wallny, R.; Waugh, B.; Weber, G.; Weber, M.; Wegener, D.; Werner, C.; Werner, M.; Werner, N.; White, G.; Wiesand, S.; Wilksen, T.; Winde, M.; Winter, G.G.; Wissing, C.; Wobisch, M.; Wunsch, E.; Wyatt, A.C.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zomer, F.; Zsembery, J.; zur Nedden, M.

    2002-01-01

    The inclusive production of D^{*+-}(2010) mesons in deep-inelastic scattering is studied with the H1 detector at HERA. In the kinematic region 11.5 GeV and |\\eta_(D^*)|<1.5. Single and double differential inclusive D^(*+-) meson cross sections are compared to perturbative QCD calculations in two different evolution schemes. The charm contribution to the proton structure, F_2^c(x,Q^2), is determined by extrapolating the visible charm cross section to the full phase space. This contribution is found to rise from about 10% at Q^2 = 1.5 GeV^2 to more than 25% at Q^2 = 60 GeV^2 corresponding to x values ranging from 5*10^(-5) to 3*10^(-3)$.

  14. Flux line lattice symmetries in the borocarbide superconductor LuNi2B2C

    Indian Academy of Sciences (India)

    M R Eskildsen; A B Abrahamsen; P L Gammel; D J Bishop; N H Andersen; K Mortensen; P C Canfield

    2002-05-01

    We compare the results of small angle neutron scattering on the flux line lattice (FLL) obtained in the borocarbide superconductor LuNi2B2C with the applied field along the - and -axes. For $\\mathbf{H}||\\mathbf{c}$ the temperature dependence of the FLL structural phase transition from square to hexagonal symmetry was investigated. Above 10 K the transition onset field, 2(), rises sharply, bending away from c2() in contradiction to theoretical predictions of the two merging. For $\\mathbf{H}||\\mathbf{a}$ a first order FLL reorientation transition is observed at tr =3-3.5 kOe. Below tr the FLL nearest neighbor direction is parallel to the -axis, and above tr to the -axis. This transition cannot be explained using nonlocal corrections to the London model.

  15. Biped 4R2C six-bar mechanism with inner and outer feet

    Science.gov (United States)

    Liu, Chao; Wang, Hao; Yao, Yan-an

    2016-01-01

    Most current biped robots are equipped with two feet arranged in the right and left which inspired by the human body system. Different from the existing configurations, a novel biped robot with inner and outer feet based on a spatial six-bar 4R2C(R and C denote revolute and cylindric joints, respectively) mechanism is proposed. It can move along a line or a curve by three walking modes that are dwell adjustment mode, limit position adjustment mode and any position adjustment mode. Kinematic, gait planning and stability analyses are performed respectively, and a prototype is developed. Lastly, a potential application is considered and two manipulating modes(sphere and cylinder manipulating modes) are carried out. This interesting mechanism feathering its single closed-chain structure and unique work performance is expected to motivate the configuration creation of biped robots.

  16. Bio-based production of C2-C6 platform chemicals.

    Science.gov (United States)

    Jang, Yu-Sin; Kim, Byoungjin; Shin, Jae Ho; Choi, Yong Jun; Choi, Sol; Song, Chan Woo; Lee, Joungmin; Park, Hye Gwon; Lee, Sang Yup

    2012-10-01

    Platform chemicals composed of 2-6 carbons derived from fossil resources are used as important precursors for making a variety of chemicals and materials, including solvents, fuels, polymers, pharmaceuticals, perfumes, and foods. Due to concerns regarding our environment and the limited nature of fossil resources, however, increasing interest has focused on the development of sustainable technologies for producing these platform chemicals from renewable resources. The techniques and strategies for developing microbial strains for chemicals production have advanced rapidly, and it is becoming feasible to develop microbes for producing additional types of chemicals, including non-natural molecules. In this study, we review the current status of the bio-based production of major C2-C6 platform chemicals, focusing on the microbial production of platform chemicals that have been used for the production of chemical intermediates, building block compounds, and polymers. Copyright © 2012 Wiley Periodicals, Inc.

  17. New Synthetic Method of Azuleno[1,2-c]thiophenes

    Institute of Scientific and Technical Information of China (English)

    WANG,Bing; WANG,Dao-Lin; IMAFUKU,Kimiakic

    2004-01-01

    @@ On the viewpoints of physical and chemical properties and biological activities, syntheses of a variety of heterocycle-fused azulenes have been repoted.[1] Of them, thiophene-fused azulenes were prepared by using different types of stating materials as follows. Azuleno[2,1-b] thiophenes are readily obtained from the reactions of 2-chloroazulene derivatives with ethyl mercaptoacetate in a few steps in good yield by Matsui[2] and Yamane.[3] On the other hand, the first synthesis of azuleno[1,2-c]thiophenes was accomplished by the reaction of 3-methoxycarbonyl-2H-cyclohepta[b]furan2-one with morpholino enamine of 3-oxotetrahydro-thiophene followed by dehydrogenation in poor yield by Fujimori.

  18. Many-body effects in LuNi{sub 2}B{sub 2}C

    Energy Technology Data Exchange (ETDEWEB)

    Bergk, B; Bartkowiak, M; Ignatchik, O; Wosnitza, J [Hochfeld-Magnetlabor Dresden (HLD), Forschungszentrum Dresden-Rossendorf, D-01314 Dresden (Germany); Petzold, V; Rosner, H [Max-Planck-Institut fuer Chemische Physik fester Stoffe, D-01187 Dresden (Germany); Drechsler, S-L; Sheikin, I [Leibniz-Institute for Solid State and Materials Research (IFW-Dresden), D-01171 Dresden (Germany); Canfield, P C, E-mail: b.bergk@fzd.d [Grenoble High Magnetic Field Laboratory, CNRS, BP 166, F-38042 Grenoble Cedex 09 (France)

    2009-03-01

    We present de Haas-van Alphen measurements of the nonmagnetic borocarbide superconductor LuNi{sub 2}B{sub 2}C. The electronic band structure is extracted from the magnetic quantum oscillations in the normal state. In accordance with previous investigations we find a complex band structure with different open and closed Fermi-surface sheets. From the temperature dependence of the oscillations amplitude the effective mass of the single bands can be determined. Due to many-body interactions we observe enhancements of the effective masses compared to the results by full-potential-density-functional calculations. Therefore, we are able to determine the angular dependence of the interaction strength for the different bands separately.

  19. Mo2C nanowires and nanoribbons on Si by two-step vapor-phase growth

    Science.gov (United States)

    Tsakalakos, L.; Rahmane, M.; Larsen, M.; Gao, Y.; Denault, L.; Wilson, P.; Balch, J.

    2005-08-01

    Transition-metal carbides in bulk form have historically been of technological interest primarily due to their excellent mechanical and refractory properties. As electronic materials these ceramic compounds are also particularly intriguing in that their electrical resistivity is relatively low compared to other ceramics and shows metallic temperature-dependent behavior. Some compositions also have superconducting transitions temperatures above 10°K. However, the synthesis of such materials in the form of one-dimensional nanostructures, which may be of interest for various nanoelectronic applications, is relatively difficult due to their refractory nature (Tmelt⩾2000°C). Here we report the synthesis of well-defined Mo2C nanowires and ribbons using a two-step approach in which we catalytically grow metal oxide nanostructures followed by in situ carburization. The growth mechanisms, microstructure, and initial electrical property measurements are discussed.

  20. Lorcaserin: a selective serotonin receptor (5-HT2C agonist for the treatment of obesity

    Directory of Open Access Journals (Sweden)

    Bhaven C. Kataria

    2012-02-01

    Full Text Available Lorcaserin is a selective serotonin receptor (5-HT2C agonist that recently received the U.S. Food and Drug Administration (FDA approval for chronic weight management. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in three phase-3 clinical trials. The available evidence indicates that this drug does not show heart valve abnormalities, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. However, the drug's manufacturer will be required to conduct postmarketing studies, including a long-term cardiovascular outcomes trial to assess the effect of Lorcaserin on the risk for major adverse cardiac events such as heart attack and stroke. [Int J Basic Clin Pharmacol 2012; 1(1.000: 45-47

  1. Scanning Hall Probe Imaging of ErNi2B2C

    Energy Technology Data Exchange (ETDEWEB)

    Bluhm, Hendrik; Sebastian, Suchitra; Guikema, Janice W.; Fisher, I.R.; Moler, Kathryn A.; /Stanford U., Appl. Phys. Dept.

    2005-12-02

    We report scanning Hall probe imaging of ErNi{sub 2}B{sub 2}C in the superconducting, antiferromagnetic, and weakly ferromagnetic regimes in magnetic fields up to 20 Oe, well below H{sub c1}, with two results. First, imaging isolated vortices shows that they spontaneously rearrange on cooling through the antiferromagnetic transition temperature T{sub N} = 6 K to pin on twin boundaries, forming a striped pattern. Second, a weak, random magnetic signal appears in the ferromagnetic phase below T{sub WFM} = 2.3 K, and no spontaneous vortex lattice is present down to 1.9 K. We conclude that ferromagnetism coexists with superconductivity either by forming small ferromagnetic domains or with oscillatory variation of the magnetization on sub-penetration depth length scales.

  2. Existence of aromatic sp~2 C-H…O = C intramolecular interaction similar to hydrogen bond

    Institute of Scientific and Technical Information of China (English)

    Zeper Abliz; Hiroshi Moriyama; Junji Aoki; Toyotoshi Ueda

    1996-01-01

    A ’H NMR signal shifted drastically to down field (δ - 10.0) at the bay area and in dose proximity to C = O group for H-1 was observed through complete assignments of 1H NMR spectra for pyridino- and benzobenzanthrones. It is concluded that this phenomenon is due not only to the anisotropy effect of C=O plus aromatic ring current effect, but also to the electrostatic attraction of C-H (δ+)…O(δ-)=C interaction. The evidence for the sp2C-H…O = C intramolecular interaction similar to hydrogen bond has also been given by EI-MS and MS/MS (CID) spectroscopy and IR spectroscopy, as well as MNDO-PM3 calculations. This new kind of interaction might be called ’quasi-hydrogen bond’.

  3. Possibility of spontaneous vortex phase in ErNi_2^11B_2C

    Science.gov (United States)

    Kawano-Furukawa, Hazuki; Habuta, Emi; Nagata, Takashi; Yoshizawa, Hideki; Takeya, Hiroyuki; Kadowaki, Kazuo

    2001-03-01

    Recently, a possible coexistence of ferromagnetism and superconductivity was proposed in ErNi_2^11B_2C [P. C. Canfield et. al., Physica C 262, 249 (1996)]. Following this finding, we have performed unpolarized and polarized neutron diffraction experiments on a ^11B substituted large single crystal, and confirmed microscopically that such an exotic phase is realized below T_WFM=2.75K [H. Kawano et al., The Journal of Physics and Chemistry of Solids 60 (1999) 1053]. In the present study, we aim to search a possibility of the spontaneous vortex phase in this material by means of magnetization and neutron diffraction measurements. After the zero field cooled procedure the magnetization curve shows diamagnetic behavior even below T_WFM, indicating that there is no spontaneous vortex phase in this condition. The data in the field cooled condition, on the other hand, indicates H_c1 becomes zero below T_WFM.

  4. A new tetragonal structure type for Li2B2C.

    Science.gov (United States)

    Pavlyuk, Volodymyr; Milashys, Viktoriya; Dmytriv, Grygoriy; Ehrenberg, Helmut

    2015-01-01

    The ternary dilithium diboron carbide, Li2B2C (tetragonal, space group P-4m2, tP10), crystallizes as a new structure type and consists of structural fragments which are typical for structures of elemental lithium and boron or binary borocarbide B13C2. The symmetries of the occupied sites are .m. and 2mm. for the B and C atoms, and -4m2 and 2mm. for the Li atoms. The coordination polyhedra around the Li atoms are cuboctahedra and 15-vertex distorted pseudo-Frank-Kasper polyhedra. The environment of the B atom is a ten-vertex polyhedron. The nearest neighbours of the C atom are two B atoms, and this group is surrounded by a deformed cuboctahedron with one centred lateral facet. Electronic structure calculations using the TB-LMTO-ASA method reveal strong B...C and B...B interactions.

  5. Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

    Directory of Open Access Journals (Sweden)

    Manna Jose

    2014-01-01

    Full Text Available Aim: Pregnancy in women with epilepsy (WWE who are on anti-epileptic drugs (AEDs has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M and 123 WWE who had normal offsprings (WWE-N. Results: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032 whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively. All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations. Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

  6. Climate and Health Impacts of US Emissions Reductions Consistent with 2 C

    Science.gov (United States)

    Shindell, Drew T.; Lee, Yunha; Faluvegi, Greg

    2016-01-01

    An emissions trajectory for the US consistent with 2 C warming would require marked societal changes, making it crucial to understand the associated benefits. Previous studies have examined technological potentials and implementation costs and public health benefits have been quantified for less-aggressive potential emissions-reduction policies, but researchers have not yet fully explored the multiple benefits of reductions consistent with 2 C. We examine the impacts of such highly ambitious scenarios for clean energy and vehicles. US transportation emissions reductions avoid approx.0.03 C global warming in 2030 (0.15 C in 2100), whereas energy emissions reductions avoid approx.0.05-0.07 C 2030 warming (approx.0.25 C in 2100). Nationally, however, clean energy policies produce climate disbenefits including warmer summers (although these would be eliminated by the remote effects of similar policies if they were undertaken elsewhere). The policies also greatly reduce damaging ambient particulate matter and ozone. By 2030, clean energy policies could prevent approx.175,000 premature deaths, with approx.22,000 (11,000-96,000; 95% confidence) fewer annually thereafter, whereas clean transportation could prevent approx.120,000 premature deaths and approx.14,000 (9,000-52,000) annually thereafter. Near-term national benefits are valued at approx.US$250 billion (140 billion to 1,050billion) per year, which is likely to exceed implementation costs. Including longer-term, worldwide climate impacts, benefits roughly quintuple, becoming approx.5-10 times larger than estimated implementation costs. Achieving the benefits, however, would require both larger and broader emissions reductions than those in current legislation or regulations.

  7. Cytoprotective Role of Nrf2 in Electrical Pulse Stimulated C2C12 Myotube.

    Directory of Open Access Journals (Sweden)

    Masaki Horie

    Full Text Available Regular physical exercise is central to a healthy lifestyle. However, exercise-related muscle contraction can induce reactive oxygen species and reactive nitrogen species (ROS/RNS production in skeletal muscle. The nuclear factor-E2-related factor-2 (Nrf2 transcription factor is a cellular sensor for oxidative stress. Regulation of nuclear Nrf2 signaling regulates antioxidant responses and protects organ structure and function. However, the role of Nrf2 in exercise- or contraction-induced ROS/RNS production in skeletal muscle is not clear. In this study, using differentiated C2C12 cells and electrical pulse stimulation (EPS of muscle contraction, we explored whether Nrf2 plays a role in the skeletal muscle response to muscle contraction-induced ROS/RNS. We found that EPS (40 V, 1 Hz, 2 ms stimulated ROS/RNS accumulation and Nrf2 activation. We also showed that expression of NQO1, HO-1 and GCLM increased after EPS-induced muscle contraction and was remarkably suppressed in cells with Nrf2 knockdown. We also found that the antioxidant N-acetylcysteine (NAC significantly attenuated Nrf2 activation after EPS, whereas the nitric oxide synthetase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME did not. Furthermore, Nrf2 knockdown after EPS markedly decreased ROS/RNS redox potential and cell viability and increased expression of the apoptosis marker Annexin V in C2C12 myotubes. These results indicate that Nrf2 activation and expression of Nrf2 regulated-genes protected muscle against the increased ROS caused by EPS-induced muscle contraction. Thus, our findings suggest that Nrf2 may be a key factor for preservation of muscle function during muscle contraction.

  8. Impact Studies of a 2 C Global Warming on the Arctic Sea Ice Cover

    Science.gov (United States)

    Comiso, Josefino C.

    2004-01-01

    The possible impact of an increase in global temperatures of about 2 C, as may be caused by a doubling of atmospheric CO2, is studied using historical satellite records of surface temperatures and sea ice from late 1970s to 2003. Updated satellite data indicate that the perennial ice continued to decline at an even faster rate of 9.2 % per decade than previously reported while concurrently, the surface temperatures have steadily been going up in most places except for some parts of northern Russia. Surface temperature is shown to be highly correlated with sea ice concentration in the seasonal sea ice regions. Results of regression analysis indicates that for every 1 C increase in temperature, the perennial ice area decreases by about 1.48 x 10(exp 6) square kilometers with the correlation coefficient being significant but only -0.57. Arctic warming is estimated to be about 0.46 C per decade on average in the Arctic but is shown to be off center with respect to the North Pole, and is prominent mainly in the Western Arctic and North America. The length of melt has been increasing by 13 days per decade over sea ice covered areas suggesting a thinning in the ice cover. The length of melt also increased by 5 days per decade over Greenland, 7 days per decade over the permafrost areas of North America but practically no change in Eurasia. Statistically derived projections indicate that the perennial sea ice cover would decline considerably in 2025, 2035, and 2060 when temperatures are predicted by models to reach the 2 C global increase.

  9. FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial

    Science.gov (United States)

    Li, Shuying S.; Gilbert, Peter B.; Tomaras, Georgia D.; Kijak, Gustavo; Ferrari, Guido; Thomas, Rasmi; Pyo, Chul-Woo; Zolla-Pazner, Susan; Montefiori, David; Liao, Hua-Xin; Nabel, Gary; Pinter, Abraham; Evans, David T.; Gottardo, Raphael; Dai, James Y.; Janes, Holly; Morris, Daryl; Fong, Youyi; Edlefsen, Paul T.; Li, Fusheng; Frahm, Nicole; Alpert, Michael D.; Prentice, Heather; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Robb, Merlin L.; O’Connell, Robert J.; Haynes, Barton F.; Michael, Nelson L.; Kim, Jerome H.; McElrath, M. Juliana; Geraghty, Daniel E.

    2014-01-01

    The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1–specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection. Moreover, Ab-dependent cellular cytotoxicity responses inversely correlated with risk of infection in vaccine recipients with low IgA; therefore, we hypothesized that vaccine-induced Fc receptor–mediated (FcR-mediated) Ab function is indicative of vaccine protection. We sequenced exons and surrounding areas of FcR-encoding genes and found one FCGR2C tag SNP (rs114945036) that associated with VE against HIV-1 subtype CRF01_AE, with lysine at position 169 (169K) in the V2 loop (CRF01_AE 169K). Individuals carrying CC in this SNP had an estimated VE of 15%, while individuals carrying CT or TT exhibited a VE of 91%. Furthermore, the rs114945036 SNP was highly associated with 3 other FCGR2C SNPs (rs138747765, rs78603008, and rs373013207). Env-specific IgG and IgG3 Abs, IgG avidity, and neutralizing Abs inversely correlated with CRF01_AE 169K HIV-1 infection risk in the CT- or TT-carrying vaccine recipients only. These data suggest a potent role of Fc-γ receptors and Fc-mediated Ab function in conferring protection from transmission risk in the RV144 VE trial. PMID:25105367

  10. The Effect of Mo2C Synthesis and Pretreatment on Catalytic Stability in Oxidative Reforming Environments

    Energy Technology Data Exchange (ETDEWEB)

    Lamont, David C.(8392); Gilligan, Andrew J.(Washington University); Darujati, Anna R S.(Washington State University); Chellappa, Anand S.(WASHINGTON STATE UNIV); Thomson, Wiliam J.(8392)

    2003-07-10

    The role of catalyst pretreatment on the stability of Mo2C catalysts in oxidative reforming environments has been studied. Catalysts were produced by both the temperature programmed reaction (TPR) and a solution-derived (SD) synthesis method, and compared to a low surface area commercial catalyst. Using a variety of techniques, including in situ dynamic X-ray diffraction (DXRD), the effects of various hydrogen pretreatment protocols were evaluated, including catalyst thermal stability, oxidation resistance and susceptibility to coking. The high surface areas produced by the SD synthesis is attributed to the presence of excess synthesis carbon and, whereas the presence of excess synthesis carbon enhances thermal stability, it also appears to accelerate coking. It is pointed out that the lowered oxidation resistance of the high surface area catalysts is due to a combination of smaller crystallite sizes and competitive oxidation of the excess synthesis carbon, which alters the oxidation mechanism. In addition, it was also found that incomplete carburization during TPR synthesis, forms an oxycarbide and its acidity also promotes coking. Hydrogen pretreatment at 700 .C not only removes all excess synthesis carbon, but it also reduces the oxycarbide to Mo, which is easily carburized under reforming conditions. Pretreatment at 600 .C, was largely ineffective and it is concluded that high temperature pretreatment is necessary to form the stoichiometric carbide, which is required for stability during reforming. Both the TPR and SD catalysts pretreated at 700 .C, were found to be stable over a 72 h period, whereas the commercial carbide had almost identical activity but slowly deactivated over the same period, probably because of its low surface area. Finally, labeled isotope experiments revealed that carbon exchange occurs readily with bulk Mo2C at temperatures above 550 .C, lending credence to a reforming redox mechanism.

  11. Phenotypes of Myopathy-related Actin Mutants in differentiated C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    Machesky Laura M

    2007-01-01

    Full Text Available Abstract Background About 20 % of nemaline myopathies are thus far related to skeletal muscle alpha-actin. Seven actin mutants located in different parts of the actin molecule and linked to different forms of the disease were selected and expressed as EGFP-tagged constructs in differentiated C2C12 mytoubes. Results were compared with phenotypes in patient skeletal muscle fibres and with previous expression studies in fibroblasts and C2C12 myoblasts/myotubes. Results Whereas EGFP wt-actin nicely incorporated into endogenous stress fibres and sarcomeric structures, the mutants showed a range of phenotypes, which generally changed upon differentiation. Many mutants appeared delocalized in myoblasts but integrated into endogenous actin structures after 4–6 days of differentiation, demonstrating a poor correlation between the appearance in myotubes and the severity of the disease. However, for some mutants, integration into stress fibres induced aberrant structures in differentiated cells, like thickening or fragmentation of stress fibres. Other mutants almost failed to integrate but formed huge aggregates in the cytoplasm of myotubes. Those did not co-stain with alpha-actinin, a main component of nemaline bodies found in patient muscle. Interestingly, nuclear aggregates as formed by two of the mutants in myoblasts were found less frequently or not at all in differentiated cells. Conclusion Myotubes are a suitable system to study the capacity of a mutant to incorporate into actin structures or to form or induce pathological changes. Some of the phenotypes observed in undifferentiated myoblasts may only be in vitro effects. Other phenotypes, like aberrant stress fibres or rod formation may be more directly correlated with disease phenotypes. Some mutants did not induce any changes in the cellular actin system, indicating the importance of additional studies like functional assays to fully characterize the pathological impact of a mutant.

  12. CYP2C9基因多态性对美洛昔康代谢动力学的影响%Effect of CYP2C9 Genetic Polymorphism on the Pharmacokinetics of Meloxicam Metabolism in Chiness Subjects

    Institute of Scientific and Technical Information of China (English)

    张梅; 许景峰; 杨永革; 徐林; 邸晓辉; 姜楠; 徐娟; 许雪廷

    2012-01-01

    目的 研究CYP2C9基因多态性对美洛昔康代谢动力学的影响.方法 用焦磷酸测序法对24名健康受试者进行CYP2C9基因多态性检测;用LC-MS-MS法测定美洛昔康的血药浓度;用DAS2.0软件进行房室拟合及药代动力学参数计算,分析美洛昔康人体药代动力学特征,并比较CYP2C9*3突变型和野生型个体对美洛昔康代谢动力学特性的差异.结果 24名受试者中CYP2C9*3等位基因有2种表型(A/A,A/C),其中2名受试者为CYP2C9 * 3杂合突变型(A/C),其余为野生型(A/A);CYP2C9*3代谢美洛昔康的酶活性A/A>A/C.结论 CYP2C9基因多态性对美洛昔康的代谢具有显著影响,CYP2C9*3代谢美洛昔康的酶活性是A/A>A/C.检测突变型个体对指导美洛昔康临床个体化用药具有重要意义.%Objective To investigate the effect of CYP2C9 polymorphism on the pharmacokinetics of meloxi-cam in Chinese healthy subjects. Methods The CYP2C9 genotypes of twenty-four Chinese healthy male subjects were selected by the pyrosequencing method. The subjects were genotyped with CYP2C9 * 3 wild-type and mutation. HPLC-MS-MS method was used for the determination of meloxicam in plasma. The important pharmacokinetic parameters were caculated by DAS 2.0 software. The pharmacokinetics of meloxicam based on identification of genotypes (CYP2C9 * 3 wild-type and mutation) was compared. Results Two kinds of CYP2C9 * 3 phenotype existed in the subjects . CYP2C9 * 3 (A/A) was found in twenty-two subjects while CYP2C9 *3(A/C) in two subjects. For meloxicam,the A/A of CYP2C9 * 3 alleles was more active than the A/C. Conclusion CYP2C9 genetic polymorphism has significant influence on the pharmacokinetics of meloxicam. A/A is more active than A/C. Pharma-cogenomic studies will help rational and individualized medication.

  13. UBE2C is overexpressed in ESCC tissues and its abrogation attenuates the malignant phenotype of ESCC cell lines

    Science.gov (United States)

    Palumbo, Antonio; Costa, Nathalia Meireles Da; De Martino, Marco; Sepe, Romina; Pellecchia, Simona; Leite de Sousa, Vanessa Paiva; Neto, Pedro Nicolau; Kruel, Cleber Dario; Bergman, Anke; Nasciutti, Luiz Eurico; Fusco, Alfredo; Pinto, Luis Felipe Ribeiro

    2016-01-01

    The esophageal squamous cell carcinoma (ESCC) is widely known as a highly lethal and poor understood cancer, then requiring the search for novel molecular markers to improve its management and patients survival. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been figuring as a prominent tumor biomarker candidate, once it has been recognized as a key player in cell cycle progression. In this way, the aim of this study was to evaluate the expression profile of UBE2C gene and protein in ESCC samples, as well as its diagnostic and prognostic marker potential, and its contribution to ESSC genesis and/or progression by performing in vitro functional assays. The analysis of UBE2C gene expression in 52 paired ESCC samples (tumor and respective histologically normal surrounding tissue), by qRT-PCR, revealed that this gene is overexpressed in 73% of ESCC samples. Subsequently, immunohistochemical analysis confirmed that UBE2C protein expression was upregulated in all ESCC cases, but absent in the histologically normal tumor surrounding tissues. Moreover, we showed that UBE2C mRNA expression was able to accurately discriminate ESCC tissue from both healthy esophageal and histologically normal tumor surrounding tissues, pointing out its role as a diagnostic marker for this cancer. Finally, we report that UBE2C affects proliferation rates and cell cycle profile of ESCC cell lines, by directly interfering with cyclin B1 protein levels, suggesting its involvement in crucial steps of ESCC carcinogenesis. PMID:27588470

  14. Actin-associated protein palladin is required for migration behavior and differentiation potential of C2C12 myoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Ngoc Uyen Nhi; Liang, Vincent Roderick; Wang, Hao-Ven, E-mail: hvwang@mail.ncku.edu.tw

    2014-09-26

    Highlights: • Palladin is involved in myogenesis in vitro. • Palladin knockdown by siRNA increases myoblast proliferation, viability and differentiation. • Palladin knockdown decreases C2C12 myoblast migration ability. - Abstract: The actin-associated protein palladin has been shown to be involved in differentiation processes in non-muscle tissues. However, but its function in skeletal muscle has rarely been studied. Palladin plays important roles in the regulation of diverse actin-related signaling in a number of cell types. Since intact actin-cytoskeletal remodeling is necessary for myogenesis, in the present study, we pursue to investigate the role of actin-associated palladin in skeletal muscle differentiation. Palladin in C2C12 myoblasts is knocked-down using specific small interfering RNA (siRNA). The results show that down-regulation of palladin decreased migratory activity of mouse skeletal muscle C2C12 myoblasts. Furthermore, the depletion of palladin enhances C2C12 vitality and proliferation. Of note, the loss of palladin promotes C2C12 to express the myosin heavy chain, suggesting that palladin has a role in the modulation of C2C12 differentiation. It is thus proposed that palladin is required for normal C2C12 myogenesis in vitro.

  15. Cu-Mo2C/MCM-41: An Efficient Catalyst for the Selective Synthesis of Methanol from CO2

    Directory of Open Access Journals (Sweden)

    Xiaoran Liu

    2016-05-01

    Full Text Available Supported molybdenum carbide (yMo2C/M41 and Cu-promoted molybdenum carbide, using a mechanical mixing and co-impregnation method (xCuyMo2C/M41-M and xCuyMo2C/M41-I on a mesoporous molecular sieve MCM-41, were prepared by temperature-programmed carburization method in a CO/H2 atmosphere at 1073 K, and their catalytic performances were tested for CO2 hydrogenation to form methanol. Both catalysts, which were promoted by Cu, exhibited higher catalytic activity. In comparison to 20Cu20Mo2C/M41-M, the 20Cu20Mo2C/M41-I catalyst exhibited a stronger synergistic effect between Cu and Mo2C on the catalyst surface, which resulted in a higher selectivity for methanol in the CO2 hydrogenation reaction. Under the optimal reaction conditions, the highest selectivity (63% for methanol was obtained at a CO2 conversion of 8.8% over the 20Cu20Mo2C/M41-I catalyst.

  16. LAMP-2C Inhibits MHC Class II Presentation of Cytoplasmic Antigens by Disrupting Chaperone-Mediated Autophagy.

    Science.gov (United States)

    Pérez, Liliana; McLetchie, Shawna; Gardiner, Gail J; Deffit, Sarah N; Zhou, Delu; Blum, Janice S

    2016-03-15

    Cells use multiple autophagy pathways to sequester macromolecules, senescent organelles, and pathogens. Several conserved isoforms of the lysosome-associated membrane protein-2 (LAMP-2) regulate these pathways influencing immune recognition and responses. LAMP-2A is required for chaperone-mediated autophagy (CMA), which promotes Ag capture and MHC class II (MHCII) presentation in B cells and signaling in T cells. LAMP-2B regulates lysosome maturation to impact macroautophagy and phagocytosis. Yet, far less is known about LAMP-2C function. Whereas LAMP2A and LAMP2B mRNA were broadly detected in human tissues, LAMP2C expression was more limited. Transcripts for the three LAMP2 isoforms increased with B cell activation, although specific gene induction varied depending on TLR versus BCR engagement. To examine LAMP-2C function in human B cells and specifically its role in Ag presentation, we used ectopic gene expression. Increased LAMP-2C expression in B cells did not alter MHCII expression or invariant chain processing, but did perturb cytoplasmic Ag presentation via CMA. MHCII presentation of epitopes from exogenous and membrane Ags was not affected by LAMP-2C expression in B cells. Similarly, changes in B cell LAMP-2C expression did not impact macroautophagy. The gene expression of other LAMP2 isoforms and proteasome and lysosomal proteases activities were unperturbed by LAMP-2C ectopic expression. LAMP-2C levels modulated the steady-state expression of several cytoplasmic proteins that are targeted for degradation by CMA and diminished peptide translocation via this pathway. Thus, LAMP-2C serves as a natural inhibitor of CMA that can selectively skew MHCII presentation of cytoplasmic Ags.

  17. Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice.

    Science.gov (United States)

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-10-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice.

  18. The GSTM2 C-Terminal Domain Depresses Contractility and Ca2+ Transients in Neonatal Rat Ventricular Cardiomyocytes

    Science.gov (United States)

    Hewawasam, Ruwani P.; Liu, Dan; Casarotto, Marco G.; Board, Philip G.; Dulhunty, Angela F.

    2016-01-01

    The cardiac ryanodine receptor (RyR2) is an intracellular ion channel that regulates Ca2+ release from the sarcoplasmic reticulum (SR) during excitation–contraction coupling in the heart. The glutathione transferases (GSTs) are a family of phase II detoxification enzymes with additional functions including the selective inhibition of RyR2, with therapeutic implications. The C-terminal half of GSTM2 (GSTM2C) is essential for RyR2 inhibition, and mutations F157A and Y160A within GSTM2C prevent the inhibitory action. Our objective in this investigation was to determine whether GSTM2C can enter cultured rat neonatal ventricular cardiomyocytes and influence contractility. We show that oregon green-tagged GSTM2C (at 1 μM) is internalized into the myocytes and it reduces spontaneous contraction frequency and myocyte shortening. Field stimulation of myocytes evoked contraction in the same percentage of myocytes treated either with media alone or media plus 15 μM GSTM2C. Myocyte shortening during contraction was significantly reduced by exposure to 15 μM GSTM2C, but not 5 and 10 μM GSTM2C and was unaffected by exposure to 15 μM of the mutants Y160A or F157A. The amplitude of the Ca2+ transient in the 15 μM GSTM2C - treated myocytes was significantly decreased, the rise time was significantly longer and the decay time was significantly shorter than in control myocytes. The Ca2+ transient was not altered by exposure to Y160A or F157A. The results are consistent with GSTM2C entering the myocytes and inhibiting RyR2, in a manner that indicates a possible therapeutic potential for treatment of arrhythmia in the neonatal heart. PMID:27612301

  19. Electronic spectrum and photodissociation chemistry of the linear methyl propargyl cation H2C4H3+

    Science.gov (United States)

    Catani, Katherine J.; Muller, Giel; da Silva, Gabriel; Bieske, Evan J.

    2017-01-01

    The electronic spectrum of the methyl propargyl cation (2-butyn-1-yl cation, H2C4H3+) is measured over the 230-270 nm range by photodissociating the bare cation and its Ar and N2 tagged complexes in a tandem mass spectrometer. The observed '1A←'1A band system has an origin at 37 753 cm-1 for H2C4H3+ , 37738 cm-1 for H2C4H3+ - Ar, and 37 658 cm-1 for H2C4H3+ - N2. The methyl propargyl cation photodissociates to produce either C2H3++C2H2 (protonated acetylene + acetylene) or H2C4H+ +H2 (protonated diacetylene + dihydrogen). Photodissociation spectra of H2C4H3+ , H2C4H3+ - Ar, and H2C4H3+ - N2 exhibit similar vibronic structure, with a strong progression of spacing 630 cm-1 corresponding to excitation of the C—C stretch mode. Interpretation of the spectra is aided by ground and excited state calculations using time dependent density functional theory at the ωB97X-D/aug-cc-pVDZ level of theory. Ab initio calculations and master equation simulations were used to interpret the dissociation of H2C4H3+ on the ground state manifold. These calculations support the experimentally observed product branching ratios in which acetylene elimination dominates and also suggests that channel switching occurs at higher energies to favor H2 elimination.

  20. Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8.

    Science.gov (United States)

    Thomas, Maria; Winter, Stefan; Klumpp, Britta; Turpeinen, Miia; Klein, Kathrin; Schwab, Matthias; Zanger, Ulrich M

    2015-01-01

    The cytochrome P450, CYP2C8, metabolizes more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However, predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated that peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor primarily involved in control of lipid and energy homeostasis directly regulates the transcription of CYP3A4. Here we investigated the potential regulation of CYP2C8 by PPARα. Two linked intronic SNPs in PPARα (rs4253728, rs4823613) previously associated with hepatic CYP3A4 status showed significant association with CYP2C8 protein level in human liver samples (N = 150). Furthermore, siRNA-mediated knock-down of PPARα in HepaRG human hepatocyte cells resulted in up to ∼60 and ∼50% downregulation of CYP2C8 mRNA and activity, while treatment with the PPARα agonist WY14,643 lead to an induction by >150 and >100%, respectively. Using chromatin immunoprecipitation scanning assay we identified a specific upstream gene region that is occupied in vivo by PPARα. Electromobility shift assay demonstrated direct binding of PPARα to a DR-1 motif located at positions -2762/-2775 bp upstream of the CYP2C8 transcription start site. We further validated the functional activity of this element using luciferase reporter gene assays in HuH7 cells. Moreover, based on our previous studies we demonstrated that WNT/β-catenin acts as a functional inhibitor of PPARα-mediated inducibility of CYP2C8 expression. In conclusion, our data suggest direct involvement of PPARα in both constitutive and inducible regulation of CYP2C8 expression in human liver, which is further modulated by WNT/β-catenin pathway. PPARA gene polymorphism could have a modest influence on CYP2C8 phenotype.

  1. Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8

    Directory of Open Access Journals (Sweden)

    Maria eThomas

    2015-11-01

    Full Text Available The cytochrome P450, CYP2C8, metabolises more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated that peroxisome proliferator-activated receptor alpha (PPARα, a nuclear receptor primarily involved in control of lipid and energy homeostasis directly regulates the transcription of CYP3A4. Here we investigated the potential regulation of CYP2C8 by PPARα. Two linked intronic SNPs in PPARα (rs4253728, rs4823613 previously associated with hepatic CYP3A4 status showed significant association with CYP2C8 protein level in human liver samples (N=150. Furthermore, siRNA-mediated knock-down of PPARα in HepaRG human hepatocyte cells resulted in up to ~60% and ~50% downregulation of CYP2C8 mRNA and activity, while treatment with the PPARα agonist WY14,643 lead to an induction by >150% and >100%, respectively. Using chromatin immunoprecipitation scanning assay we identified a specific upstream gene region that is occupied in vivo by PPARα. Electromobility shift assay demonstrated direct binding of PPARα to a DR-1 motif located at positions -2762/-2775bp upstream of the CYP2C8 transcription start site. We further validated the functional activity of this element using luciferase reporter gene assays in HuH7 cells. Moreover, based on our previous studies we demonstrated that WNT/β-catenin acts as a functional inhibitor of PPARα-mediated inducibility of CYP2C8 expression. In conclusion, our data suggest direct involvement of PPARα in both constitutive and inducible regulation of CYP2C8 expression in human liver, which is further modulated by WNT/ β-catenin pathway. PPARA gene polymorphism could have a modest influence on CYP2C8 phenotype.

  2. 加味逍遥丸对CYP2C19酶活性的影响%Effect of Modified Xiaoyao pill on the activity of CYP2C19

    Institute of Scientific and Technical Information of China (English)

    赵钢涛; 杨凡; 许茜; 丁媛媛; 郑绯; 许景峰

    2011-01-01

    AIM: To investigate the effect of Modified Xiaoyao pill on CYP2C19, and provide foundation for clinical drug using. METHODS: Twenty volunteers were divided into two groups according to CYP2C19* 2 gene type, ten for WW gene type and ten for MM gene type. Omeprazole used as probe drug of CYP2C19, the effect of Modified Xiaoyao pill on the activity of CYP2C19 were investigated. Genetic classification was fulfilled by pyrosequencing method, and the blood concentration of probe drug and its metabolic product were determined by HPLCMS/MS. RESULTS: The volunteers took Modified Xiaoyao pill for two weeks, AUC0-12 was used as the standard of the activity of CYP2C19. The activity value was 5.7±1.6 before drug and 6.0±1.7 after drug using. So the activity of CYP2C19 was increased after drug using, t-test was used for comparison, there was no remarkable difference between the data. CONCLUSION: Modified Xiaoyao pill has no obvious affection on the activity of CYP2C19.%目的:探讨加味逍遥丸对CYP2C19活性的影响,为临床指导联合用药提供依据.方法:将20名受试者按照CYP2C19 2基因型进行分类,野生型纯合子(WW)及突变型纯合子(MM)各10名.以奥美拉唑作为CYP2C19的探针药,研究服用加味道遥丸对人体内代谢酶CYP2C19活性的影响.采用pyrosequencing测序法对CYP2C19进行基因分型,采用HPLC-MS/MS法测定探针药及其代谢产物的血药浓度.结果:连续服用14 d加味逍遥丸.以AUCo-12为指标,评价CYP2C19代谢酶的活性.受试者用药前CYP2C19代谢酶活性为5.7±1.6,服用加味逍遥丸后CYP2C19代谢酶活性为6.0±1.7.用药后代谢酶的活性升高,用药前后比较采用配对t检验,差异没有统计学意义.结论:服用加味逍遥丸对CYP2C19代谢酶活性没有明显影响.

  3. Foot-and-Mouth Disease Virus 2C Is a Hexameric AAA+ Protein with a Coordinated ATP Hydrolysis Mechanism

    DEFF Research Database (Denmark)

    Sweeney, Trevor; Cisnetto, Valentina; Bose, Daniel

    2010-01-01

    Foot-and-mouth disease virus (FMDV), a positive sense, single-stranded RNA virus, causes a highly contagious disease in cloven-hoofed livestock. Like other picornaviruses, FMDV has a conserved 2C protein assigned to the superfamily 3 helicases a group of AAA+ ATPases that has a predicted N...... into hexamers. Visualization of FMDV 2C-ATP-RNA complexes by negative stain electron microscopy revealed hexameric ring structures with 6-fold symmetry that are characteristic of AAA+ ATPases. ATPase assays performed by mixing purified active and inactive 2C(34–318) subunits revealed a coordinated mechanism...

  4. Synthesis and Photooxygenation of Furo[3,2-c]coumarin Derivatives as Antibacterial and DNA Intercalating Agent

    Institute of Scientific and Technical Information of China (English)

    Al-Sehemi, Abdullah G.; EI-Gogary, Sameh R.

    2012-01-01

    Syntheses of 2,3-dimethyl-4H-furo[3,2-c]coumarin and 3-phenyl-4H-furo[3,2-c]coumarin as angular furocou- marins were carried out through Williamson reaction of 4-hydroxycoumarin with a-haloketones followed by cycli- zation. Photooxygenation of the synthesized furocoumarin derivatives was performed and the photoproducts were isolated and characterized. The affinity of 2,3-dimethyl-4H-furo[3,2-c]coumarin towards DNA and the antibacterial activity were evaluated and compared with 8-methoxypsoralen (8-MOP).

  5. Trivalent graphs, volume conjectures and character varieties

    CERN Document Server

    Nawata, Satoshi; Zodinmawia,

    2014-01-01

    The generalized volume conjecture and the AJ conjecture (a.k.a. the quantum volume conjecture) are extended to $U_q(sl_2)$ colored quantum invariants of trivalent graphs. The SL(2,C) character variety of the fundamental group of the complement of a trivalent graph with $E$ edges in $S^3$ is a Lagrangian subvariety of the Hitchin moduli space over the Riemann surface of genus $g=E/3+1$. The configuration of the character variety is locally determined by large color asymptotics of the quantum invariants of the trivalent graph in terms of complex Fenchel-Nielsen coordinates. Moreover, the q-holonomic difference equation of the quantum invariants provides the quantization of the character variety. In particular, we investigate both the conjectures for the theta and tetrahedron graphs.

  6. Role of the intracellular domain of the human type I interferon receptor 2 chain (IFNAR2c) in interferon signaling. Expression of IFNAR2c truncation mutants in U5A cells.

    Science.gov (United States)

    Russell-Harde, D; Wagner, T C; Rani, M R; Vogel, D; Colamonici, O; Ransohoff, R M; Majchrzak, B; Fish, E; Perez, H D; Croze, E

    2000-08-01

    A human cell line (U5A) lacking the type I interferon (IFN) receptor chain 2 (IFNAR2c) was used to determine the role of the IFNAR2c cytoplasmic domain in regulating IFN-dependent STAT activation, interferon-stimulated gene factor 3 (ISGF3) and c-sis-inducible factor (SIF) complex formation, gene expression, and antiproliferative effects. A panel of U5A cells expressing truncation mutants of IFNAR2c on their cell surface were generated for study. Janus kinase (JAK) activation was detected in all mutant cell lines; however, STAT1 and STAT2 activation was observed only in U5A cells expressing full-length IFNAR2c and IFNAR2c truncated at residue 462 (R2.462). IFNAR2c mutants truncated at residues 417 (R2. 417) and 346 (R2.346) or IFNAR2c mutant lacking tyrosine residues in its cytoplasmic domain (R2.Y-F) render the receptor inactive. A similar pattern was observed for IFN-inducible STAT activation, STAT complex formation, and STAT-DNA binding. Consistent with these data, IFN-inducible gene expression was ablated in U5A, R2.Y-F, R2.417, and R2.346 cell lines. The implications are that tyrosine phosphorylation and the 462-417 region of IFNAR2c are independently obligatory for receptor activation. In addition, the distal 53 amino acids of the intracellular domain of IFNAR2c are not required for IFN-receptor mediated STAT activation, ISFG3 or SIF complex formation, induction of gene expression, and inhibition of thymidine incorporation. These data demonstrate for the first time that both tyrosine phosphorylation and a specific domain of IFNAR2c are required in human cells for IFN-dependent coupling of JAK activation to STAT phosphorylation, gene induction, and antiproliferative effects. In addition, human and murine cells appear to require different regions of the cytoplasmic domain of IFNAR2c for regulation of IFN responses.

  7. Effects of green tea catechins on cytochrome P450 2B6, 2C8, 2C19, 2D6 and 3A activities in human liver and intestinal microsomes.

    Science.gov (United States)

    Misaka, Shingen; Kawabe, Keisuke; Onoue, Satomi; Werba, José Pablo; Giroli, Monica; Tamaki, Sekihiro; Kan, Toshiyuki; Kimura, Junko; Watanabe, Hiroshi; Yamada, Shizuo

    2013-01-01

    The effects of green tea catechins on the main drug-metabolizing enzymatic system, cytochrome P450 (CYP), have not been fully elucidated. The objective of the present study was to evaluate the effects of green tea extract (GTE, total catechins 86.5%, w/w) and (-)-epigallocatechin-3-gallate (EGCG) on the activities of CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A in vitro, using pooled human liver and intestinal microsomes. Bupropion hydroxylation, amodiaquine N-deethylation, (S)-mephenytoin 4'-hydroxylation, dextromethorphan O-demethylation and midazolam 1'-hydroxylation were assessed in the presence or absence of various concentrations of GTE and EGCG to test their effects on CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A activities, respectively. Each metabolite was quantified using UPLC/ESI-MS, and the inhibition kinetics of GTE and EGCG on CYP enzymes was analyzed. In human liver microsomes, IC50 values of GTE were 5.9, 4.5, 48.7, 25.1 and 13.8 µg/mL, for CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP3A, respectively. ECGC also inhibited these CYP isoforms with properties similar to those of GTE, and produced competitive inhibitions against CYP2B6 and CYP2C8, and noncompetitive inhibition against CYP3A. In human intestinal microsomes, IC50 values of GTE and EGCG for CYP3A were 18.4 µg/mL and 31.1 µM, respectively. EGCG moderately inhibited CYP3A activity in a noncompetitive manner. These results suggest that green tea catechins cause clinically relevant interactions with substrates for CYP2B6 and CYP2C8 in addition to CYP3A.

  8. A mouse model for Betacoronavirus subgroup 2c using a bat coronavirus strain HKU5 variant.

    Science.gov (United States)

    Agnihothram, Sudhakar; Yount, Boyd L; Donaldson, Eric F; Huynh, Jeremy; Menachery, Vineet D; Gralinski, Lisa E; Graham, Rachel L; Becker, Michelle M; Tomar, Sakshi; Scobey, Trevor D; Osswald, Heather L; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R; Baric, Ralph S

    2014-03-25

    Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis. IMPORTANCE The 2012 outbreak of MERS-CoV raises the specter

  9. Mo2 C as Non-Noble Metal Co-Catalyst in Mo2 C/CdS Composite for Enhanced Photocatalytic H2 Evolution under Visible Light Irradiation.

    Science.gov (United States)

    Ma, Baojun; Xu, Haojie; Lin, Keying; Li, Jie; Zhan, Haijuan; Liu, Wanyi; Li, Can

    2016-04-21

    Co-catalysts are a major factor to enhance photocatalytic H2 activity; they are mainly composed of expensive noble metals. Here, we reported a new non-noble-metal co-catalyst Mo2 C that efficiently improves the photocatalytic H2 evolution of CdS under visible light irradiation. Mo2 C is prepared by temperature-programmed reaction with molybdenum oxide as precursor, and the Mo2 C/CdS composite is prepared by deposition of CdS on Mo2 C. The optimum composite 2.0 % Mo2 C/CdS shows a high H2 evolution rate of 161 μmol h(-1) , which is ten times higher than that of CdS alone and 2.3 times higher than the optimum for 1.0 % Pt/CdS. Moreover, the Mo2 C/CdS is stable for 50 h. This study presents a new low-cost non-noble-metal co-catalyst as a photocatalyst to achieve highly efficient H2 evolution.

  10. Effects of New Fossil Fuel Developments on the Possibilities of Meeting 2C Scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Meindertsma, W.; Blok, K.

    2012-12-15

    Recent years have seen an increasing activity in developing new fossil fuel production capacity. This includes unconventional fossil fuels, such as tar sands and shale gas, fossil fuels from remote locations, and fossil fuels with a very large increase in production in the near future. In this report, the impact of such developments on our ability to mitigate climate change is investigated. Our inventory shows that the new fossil fuel developments currently underway consist of 29,400 billion cubic meters of natural gas, 260,000 million barrels of oil and 49,600 million tonnes of coal. The development of these new fossil fuels would result in emissions of 300 billion tonnes of CO2 -equivalent (CO2e) from 2012 until 2050. Until 2050, a 'carbon budget' of 1550 billion tonnes CO2e is still available if we want to of keep global warming below 2C with a 50% probability. For a 75% probability to stay below 2C this budget is only 1050 billion tonnes CO2e. So, the new fossil fuel developments identified in this report consume 20-33% of the remaining carbon budget until 2050. In a scenario where the new fossil fuels are developed, we need to embark on a rapid emission reductions pathway at the latest in 2019 in order to meet the 50% probability carbon budget. Avoiding the development of new fossil fuels will give us until 2025 to start further rapid emission reductions. These calculations are based on the assumption that the maximum emission reduction rate is 4% per year and that the maximum change in emission trend is 0.5 percentage point per year. The starting year for rapid emission reductions depends on the choice of these parameters. A sensitivity analysis shows that, in all cases, refraining from new fossil fuel development allows for a delay of 5 to 8 years before we should embark on a rapid emission reduction pathway. The high investments required for developing new fossil fuels lead to a lock in effect; once developed, these fossil fuels need to be

  11. Electronic structure and electrical transport characteristics of C60, 2C60 and 4C60 fullerene molecules

    Institute of Scientific and Technical Information of China (English)

    SHEN Haijun; MU Xiancai

    2007-01-01

    The extended Hückel method and the Green's function method were used to calculate the electronic struc-ture and electrical transport of Au electrode-C60,2C60 or 4C60 fullerene-Au electrode systems.Furthermore,their electronic structure and electrical transport characteristics were com-pared and analyzed.The results show that (I) owing to the contact with the Au electrodes,the C60,2C60 and 4C60 mole-cules change in their electronic structures ignificantly,and their energy gaps between LUMO and HOMO are narrow;(ii) the bonding between C60,2C60 or 4C60 fullerene and Au electrodes is partially covalent and partially electrovalent;and (iii) the conductance of the three fullerenes conforms to the order of C60>2C60>4C60.

  12. Impact of CYP2C19 phenotypes on escitalopram metabolism and an evaluation of pupillometry as a serotonergic biomarker

    DEFF Research Database (Denmark)

    Noehr-Jensen, L; Zwisler, S; Larsen, F

    2009-01-01

    PURPOSE: To investigate the impact of cytochrome P450 2C19 (CYP2C19) phenotypes on escitalopram metabolism and to evaluate pupillometry as a serotonergic biomarker. METHODS: This was a double-blind, crossover design study with single and multiple doses of 10 mg escitalopram and placebo in panels...... of CYP2C19 extensive (EM) and poor metabolisers (PM). Pupillometry was measured by a NeurOptics Pupillometer-PLR. RESULTS: Five PM and eight EM completed the study. The CYP2C19 phenotype significantly affected the metabolism of escitalopram. The area under the time-plasma concentration curve (AUC(0......-24)) was 1.8-fold higher in PM than in EM after both single and multiple doses. Escitalopram treatment did not affect the maximum pupil size, but it did statistically significantly decrease the relative amplitude of the pupil light reflex compared to the placebo; this effect was equal in both phenotype...

  13. Identification of cytochrome P450 2D6 and 2C9 substrates and inhibitors by QSAR analysis

    DEFF Research Database (Denmark)

    Jónsdóttir, Svava Ósk; Ringsted, Tine; Nikolov, Nikolai G.;

    2012-01-01

    these compounds. A large fraction of these chemicals were found to be CYP active, and thus potentially capable of affecting human physiology. 20% of the compounds within applicability domain of the models were predicted to be CYP2C9 substrates, and 17% to be inhibitors. The corresponding numbers for CYP2D6 were 9...... of specific CYP activity. An overrepresentation was seen for poly-aromatic hydrocarbons (group of procarcinogens) among CYP2C9 active and mutagenic compounds compared to CYP2C9 inactive and mutagenic compounds. The mutagenicity was predicted with a QSAR model based on Ames in vitro test data.......% and 21%. Where the majority of CYP2C9 active compounds were predicted to be both a substrate and an inhibitor at the same time, the CYP2D6 active compounds were primarily predicted to be only inhibitors. It was demonstrated that the models could identify compound classes with a high occurrence...

  14. Surface Turbulent Fluxes, 1x1 deg Monthly Grid, Set1 and Interpolated Data V2c

    Data.gov (United States)

    National Aeronautics and Space Administration — These data are the Goddard Satellite-based Surface Turbulent Fluxes Version-2c Dataset recently produced through a MEaSUREs funded project led by Dr. Chung-Lin Shie...

  15. Pseudosubluxación C2-C3: un hallazgo radiológico frecuente en la infancia

    OpenAIRE

    Pellicer García, V.; Baeza Oliete, J.; Miranda, L.; Bas Hermida, T.; Bas Hermida, P.

    2009-01-01

    Objetivo: Mostrar un hallazgo radiológico fisiológico de la columna cervical infantil que tiende a ser malinterpretado como patológico: la pseudosubluxación C2-C3. Se presenta un caso de una niña de 14 meses de edad remitida a nuestro centro bajo sospecha de subluxación C2-C3. Se aporta una metodología para el diagnóstico diferencial entre pseudosubluxación C2-C3 y subluxación C2-C3 verdadera. Una anamnesis detallada así como una exploración clínica y radiográfica minuciosas, perm...

  16. Analysis of Interactions of Key Stakeholders on B2C e-Markets - Agent Based Modelling and Simulation Approach

    National Research Council Canada - National Science Library

    Aleksandar Marković; Sava Čavoški; Andrej Novović

    2016-01-01

    Background/purpose: This paper discusses the application of ABMS - agent-based modelling and simulation in the analysis of customer behaviour on B2C e-commerce websites as well as in the analysis of various business...

  17. Cloning of cytochrome P-450 2C9 cDNA from human liver and its expression in CHL cells

    Institute of Scientific and Technical Information of China (English)

    Ge-Jian Zhu; Ying-Nian Yu; Xin Li; Yu-Li Qian

    2002-01-01

    AIM: Using bacterial, yeast, or mammalian cell expressing a human drug metabolism enzyme would seem good way to study drug metabolism-related problems. Human cytochrome P-450 2C9 ( CYP2 C9) is a polymorphic enzyme responsible for the metabolism of a large number of clinically important drugs. It ranks among the most important drug metabolizing enzymes in humans. In order to provide a sufficient amount of the enzyme for drug metabolic research, the CYP2 C9 eDNA was cloned and expressed stably in CHL cellsMETHODS: After extraction of total RNA from human livertissue, the human CYP2C9 eDNA was amplified withreverse transcription-polymerase chain reaction (RT-PCR),and cloned into cloning vector pGEM-T. The cDNA fragmentwas identified by DNA sequencing and subcloned into amammalian expression vector pREP9. A transgenic cell linewas established by transfecting the recombinant vector ofpREP9-CYP2C9 into CHL cells. The enzyme activity ofCYP2C9 catalyzing oxidation of tolbutamide to hydroxytolbutamide in S9 fraction of the cell was determined by highperformance liquid chromatography(HPLC).RESULTS: The amino acid sequence predicted from theeDNA segment was identical to that of CYP2 C9 * 1, the wildtype CYP2 C9. However, there were two base differences, i.e. 21T > C, 1146C > T, but the encoding amino acidsequence was the same, L7, P382. The S9 fraction of theestablished cell line metabolizes tolbutamide to hydroxytolbutamide; tolbutamide hydroxylass activity was found to be0.465 ± 0.109 μmol@ min-1 . g1 S9 protein or 8.62 ± 2.02 mol@ min 1 ~mol-1 CYP, but was undetectable in parental CHL cell.CONCLUSION: The cDNA of human CYP2C9 was successfullycloned and a cell line of CHL- CYP2C9, efficiently expressingthe protein of CYP2C9, was established.

  18. The effect of human image in B2C website design: an eye-tracking study

    Science.gov (United States)

    Wang, Qiuzhen; Yang, Yi; Wang, Qi; Ma, Qingguo

    2014-09-01

    On B2C shopping websites, effective visual designs can bring about consumers' positive emotional experience. From this perspective, this article developed a research model to explore the impact of human image as a visual element on consumers' online shopping emotions and subsequent attitudes towards websites. This study conducted an eye-tracking experiment to collect both eye movement data and questionnaire data to test the research model. Questionnaire data analysis showed that product pictures combined with human image induced positive emotions among participants, thus promoting their attitudes towards online shopping websites. Specifically, product pictures with human image first produced higher levels of image appeal and perceived social presence, thus stimulating higher levels of enjoyment and subsequent positive attitudes towards the websites. Moreover, a moderating effect of product type was demonstrated on the relationship between the presence of human image and the level of image appeal. Specifically, human image significantly increased the level of image appeal when integrated in entertainment product pictures while this relationship was not significant in terms of utilitarian products. Eye-tracking data analysis further supported these results and provided plausible explanations. The presence of human image significantly increased the pupil size of participants regardless of product types. For entertainment products, participants paid more attention to product pictures integrated with human image whereas for utilitarian products more attention was paid to functional information of products than to product pictures no matter whether or not integrated with human image.

  19. Mitochondria dysfunction in lung cancer-induced muscle wasting in C2C12 myotubes

    Directory of Open Access Journals (Sweden)

    Julie eMcLean

    2014-12-01

    Full Text Available Aims: Cancer cachexia is a syndrome which results in severe loss of muscle mass and marked fatigue. Conditioned media from cachexia-inducing cancer cells triggers metabolic dysfunction in skeletal muscle, including decreased mitochondrial respiration, which may contribute to fatigue. We hypothesized that Lewis lung carcinoma conditioned medium (LCM would impair the mitochondrial electron transport chain (ETC and increase production of reactive oxygen species, ultimately leading to decreased mitochondrial respiration. We incubated C2C12 myotubes with LCM for 30 minutes, 2hrs, 4hrs, 24hrs or 48hrs. We measured protein content by western blot; oxidant production by 2′,7′-dichlorofluorescin diacetate (DCF, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF, and MitoSox; cytochrome c oxidase activity by oxidation of cytochrome c substrate; and oxygen consumption rate (OCR of intact myotubes by Seahorse XF Analyzer. Results: LCM treatment for 2hrs or 24hrs decreased basal OCR and ATP-related OCR, but did not alter the content of mitochondrial complexes I, III, IV and V. LCM treatment caused a transient rise in reactive oxygen species (ROS. In particular, mitochondrial superoxide (MitoSOX was elevated at 2hrs. 4-Hydroxynonenal, a marker of oxidative stress, was elevated in both cytosolic and mitochondrial fractions of cell lysates after LCM treatment. Conclusion: These data show that lung cancer-conditioned media alters electron flow in the ETC and increases mitochondrial ROS production, both of which may ultimately impair aerobic metabolism and decrease muscle endurance.

  20. Graphene oxide increases the viability of C2C12 myoblasts microencapsulated in alginate.

    Science.gov (United States)

    Ciriza, J; Saenz del Burgo, L; Virumbrales-Muñoz, M; Ochoa, I; Fernandez, L J; Orive, G; Hernandez, R M; Pedraz, J L

    2015-09-30

    Cell microencapsulation represents a great promise for long-term drug delivery, but still several challenges need to be overcome before its translation into the clinic, such as the long term cell survival inside the capsules. On this regard, graphene oxide has shown to promote proliferation of different cell types either in two or three dimensions. Therefore, we planned to combine graphene oxide with the cell microencapsulation technology. We first studied the effect of this material on the stability of the capsules and next we analyzed the biocompatibility of this chemical compound with erythropoietin secreting C2C12 myoblasts within the microcapsule matrix. We produced 160 μm-diameter alginate microcapsules with increasing concentrations of graphene oxide and did not find modifications on the physicochemical parameters of traditional alginate microcapsules. Moreover, we observed that the viability of encapsulated cells within alginate microcapsules containing specific graphene oxide concentrations was enhanced. These results provide a relevant step for the future clinical application of graphene oxide on cell microencapsulation.

  1. TC2 C776G polymorphism studies in patients with oral cancer in the Polish population

    Directory of Open Access Journals (Sweden)

    Katarzyna Malinowska

    2016-11-01

    Full Text Available The first signs of oral cancer may resemble developing infections in the mucous membranes, with throat cancer symptoms being similar to those of upper respiratory tract infections. This greatly hinders rapid diagnosis and treatment. Better knowledge of the changes occurring in the metabolism of folic acid can help in understanding the carcinogenesis affecting DNA methylation and genome stability. Polymorphisms in genes encoding enzymes involved in this pathway may influence enzyme activity and thereby interfere with the concentrations of homocysteine and S-adenosylmethionine, which are important for DNA synthesis and cellular methylation reactions. The aim of the study was to determine the risk of oral cancer associated with the TC2 C776G polymorphism, as determined in 119 patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. The test genotype was found to correspond to the Hardy-Weinberg (HW equilibrium (p > 0.05. In our population G/G homozygosity of C776G TC2 gene polymorphism increases the risk of oral cancer; OR (odds ratio: 4.3875; 95% CI (confidence interval: 2.0518-9.319; p = 0.001. Regarding C/G genotype of the C776G TC2 gene, polymorphism also increases the risk of developing this cancer; OR 2.4146 95% CI: 1.2803-4.5541; p = 0.01.

  2. Antioxidant effects of whey protein on muscle C2C12 cells.

    Science.gov (United States)

    Kerasioti, Efthalia; Stagos, Dimitrios; Priftis, Alexandros; Aivazidis, Stefanos; Tsatsakis, Aristidis M; Hayes, A Wallace; Kouretas, Demetrios

    2014-07-15

    In the present study, the in vitro scavenging activity of sheep whey protein against free radicals, as well as its reducing power were determined and compared with that of beef protein, soy protein and cow whey protein. Moreover, the possible protective effects of sheep whey protein from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in muscle C2C12 cells were determined by assessing oxidative stress markers by flow cytometry and spectrophotometry. The results showed that sheep whey protein scavenged DPPH, ABTS(+) and OH radicals with IC50 values of 3.1, 4.1 and 1.8 mg of protein/ml. Moreover, the reducing power activity assessed with potassium ferricyanide of sheep whey protein was 1.3mg/ml. As regards to the antioxidant effects in muscle cell line, sheep whey protein at 0.78, 1.56, 3.12 and 6.24 mg of protein/ml increased GSH levels up to 138%, lowered TBARS levels up to 25% and decreased ROS levels up to 41.4%.

  3. CRank: A Credit Assessment Model in C2C e-Commerce

    Science.gov (United States)

    Zhang, Zhiqiang; Xie, Xiaoqin; Pan, Haiwei; Han, Qilong

    An increasing number of consumers not only purchase but also resell merchandise through C2C web sites. One of the greatest concerns for the netizens is the lacking of a fair credit assessment system. Trust and trustworthiness are crucial to the survival of online markets. Reputation systems that rely on feedback from traders help to sustain the trust. And reputation systems provide one of the ways of building trusts online. In this chapter, we investigate a credit assessment model, CRank, for the members in the context of e-market systems, such as Alibaba, eBay, to solve such problem as how to choose a credible business partner when the customer wants to purchase some products from the Internet. CRank makes use of feedback profile made up of ranks from other users as well as an overall feedback rating for the user based on the idea of PageRank. This model can be used to build a trustable relation network among business participants.

  4. The Third Party Logistics Partner Selection of B2C E-Commerce Enterprise

    Directory of Open Access Journals (Sweden)

    Xu Wei

    2017-01-01

    Full Text Available In recent years, with the rapid development of Internet, e-commerce enterprises in China is at an alarming rate of sustainable development, the B2C e-commerce in the online shopping market accounted for a large proportion, with the rapid change of the market and customer needs to establish a flexible distribution service is one of the many e-commerce companies need to solve. Using self logistics capital occupancy bigger; the logistics alliance, with the risk of internal information disclosure; and on the third party logistics, not only capital and manpower can be effectively used, helps enterprises to strengthen the core business. Therefore, it is very important to choose the appropriate third party logistics providers to reduce operating costs and improve the market influence. This paper analyses the existing problems in the third party logistics, the establishment of a more complete index system, according to the actual situation of the suppliers, using the improved AHP method and the entropy coefficient method to get the comprehensive weight, finally get the approximation method to meet the business requirements of the logistics service providers use the ideal, for commercial enterprises to third party logistics service provider selection and puts forward some available models.

  5. C2-C10 hydrocarbon emissions from a boreal wetland and forest floor

    Directory of Open Access Journals (Sweden)

    H. Hellén

    2006-01-01

    Full Text Available Emissions of various C2-C10 hydrocarbons (VOCs and halogenated hydrocarbons (VHOCs from a boreal wetland and a Scots pine forest floor in south-western Finland were measured by the static chamber technique. Isoprene was the main non-methane hydrocarbon emitted by the wetland, but small emissions of ethene, propane, propene, 1-butene, 2-methylpropene, butane, pentane and hexane were also detected. The isoprene emission from the wetland was observed to follow the commonly-used isoprene emission algorithm. The mean emission potential of isoprene was 224 µg m-2 h-1 for the whole season. This is lower than the emission potentials published earlier; that is probably at least partly due to the cold and cloudy weather during the measurements. No emissions were detected of monoterpenes or halogenated hydrocarbons from the wetland. The highest hydrocarbon emissions from the Scots pine forest floor were measured in spring and autumn. However, only a few measurements were conducted during summer. The main compounds emitted were monoterpenes. Isoprene emissions were negligible. The total monoterpene emission rates varied from zero to 373 µg m-2 h-1. The results indicated that decaying plant litter may be the source for these emissions. Small emissions of chloroform (100-800 ng m-2 h-1, ethene, propane, propene, 2-methylpropene, cis-2-butene, pentane, hexane and heptane were detected. Comparison with Scots pine emissions showed that the forest floor may be an important monoterpene source, especially in spring.

  6. Převodník mezi sběrnicemi I2C a RS232

    OpenAIRE

    Bednařík, Martin

    2009-01-01

    Cílem tohoto projektu je obeznámit se s funkcí sběrnice I2C a mikrokontroléry AVR a s principem propojení mikrokontroléru s ostatními obvody pomocí této sběrnice. Dále navrhnout takové zařízení, které bude schopno zprostředkovat komunikaci mezi osobním počítačem a ovládanými obvody. Součástí projektu je tvorba potřebného programového vybavení pro mikrokontrolér a návrh vlastního komunikačního protokolu. Dalším cílem projektu je získat přehled o použitích technologiích, možnostech jejich využi...

  7. Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Dunham, Ian [EMBL-European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD (United Kingdom); Murai, Kasumi [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Jones, Philip H., E-mail: phj20@cam.ac.uk [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom)

    2011-07-01

    Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

  8. An adaptable stage perfusion incubator for the controlled cultivation of C2C12 myoblasts.

    Science.gov (United States)

    Kurth, Felix; Franco-Obregón, Alfredo; Bärtschi, Christoph A; Dittrich, Petra S

    2015-01-01

    Here we present a stage perfusion incubation system that allows for the cultivation of mammalian cells within PDMS microfluidic devices for long-term microscopic examination and analysis. The custom-built stage perfusion incubator is adaptable to any x-y microscope stage and is enabled for temperature, gas and humidity control as well as equipped with chip and tubing holder. The applied double-layered microfluidic chip allows the predetermined positioning and concentration of cells while the gas permeable PDMS material facilitates pH control via CO2 levels throughout the chip. We demonstrate the functionality of this system by culturing C2C12 murine myoblasts in buffer free medium within its confines for up to 26 hours. We moreover demonstrated the system's compatibility with various chip configurations, other cells lines (HEK-293 cells) and for longer-term culturing. The cost-efficient system are applicable for any type of PDMS-based cell culture system. Detailed technical drawings and specification to reproduce this perfusion incubation system is provided in the ESI.

  9. Determination of the band structure of LuNi{sub 2}B{sub 2}C

    Energy Technology Data Exchange (ETDEWEB)

    Bergk, B. [Hochfeld-Magnetlabor, Forschungszentrum Rossendorf, Dresden (Germany); Inst. fuer Festkoerperphysik, Technische Univ. Dresden (Germany); Bartkowiak, M.; Ignatchik, O. [Hochfeld-Magnetlabor, Forschungszentrum Rossendorf, Dresden (Germany); Jaeckel, M. [Inst. fuer Festkoerperphysik, Technische Univ. Dresden (Germany); Wosnitza, J.; Rosner, H.; Petzold, V. [MPI fuer chemische Physik fester Stoffe, Dresden (Germany); Canfield, P. [Iowa State Univ. of Science and Technology, Ames (United States). Ames Lab., Condensed Matter Physics

    2007-07-01

    We present de Haas-van Alphen (dHvA) investigations on the nonmagnetic borocarbide superconductor LuNi{sub 2}B{sub 2}C which have been performed by use of the torque method in high magnetic fields up to 32 T and at low temperatures down to 50 mK. The complex band structure is extracted from the quantum oscillations in the normal state. In comparison with full-potential-local-orbital calculations of the band structure we are able to assign the observed dHvA frequencies to the different bands. Temperature dependent dHvA investigations allowed the extraction of the effective band masses for the several Fermi-surface sheets. We observe an enhancement of the effective masses compared to the theoretical calculations which is due to electron-phonon interaction. Finally, we are able to examine the angular dependence of the electron-phonon coupling for the different Fermi-surface sheets. (orig.)

  10. Large-area high-quality 2D ultrathin Mo2C superconducting crystals

    Science.gov (United States)

    Xu, Chuan; Wang, Libin; Liu, Zhibo; Chen, Long; Guo, Jingkun; Kang, Ning; Ma, Xiu-Liang; Cheng, Hui-Ming; Ren, Wencai

    2015-11-01

    Transition metal carbides (TMCs) are a large family of materials with many intriguing properties and applications, and high-quality 2D TMCs are essential for investigating new physics and properties in the 2D limit. However, the 2D TMCs obtained so far are chemically functionalized, defective nanosheets having maximum lateral dimensions of ~10 μm. Here we report the fabrication of large-area high-quality 2D ultrathin α-Mo2C crystals by chemical vapour deposition (CVD). The crystals are a few nanometres thick, over 100 μm in size, and very stable under ambient conditions. They show 2D characteristics of superconducting transitions that are consistent with Berezinskii-Kosterlitz-Thouless behaviour and show strong anisotropy with magnetic field orientation; moreover, the superconductivity is also strongly dependent on the crystal thickness. Our versatile CVD process allows the fabrication of other high-quality 2D TMC crystals, such as ultrathin WC and TaC crystals, which further expand the large family of 2D materials.

  11. Possibilities of B2C buying and selling using mobile devices in comparison with Internet

    Directory of Open Access Journals (Sweden)

    Sonia San Martín Gutiérrez

    2010-05-01

    Full Text Available New technologies have involved a great opportunity to improve business management. On the one hand, Internet is beginning to be a selling channel that is valid and complementary of the traditional channel, apart from being a channel to search information and socialize. On the other hand and recently, mobile marketing is useful in a commercial sense: the mobile phone incorporates television, camera, radio, chat and now firms are introducing in the issue of advertising and in other regions in selling through the mobile phone. In spite of the increasing number of studies on traditional distribution and on electronic commerce, the studies that explore the possibilities and challenges of the mobile telephone and that compare it with Internet as buying and selling channels are scarce. The goal of this study is to compare the situation of B2C buying and selling through Internet and through the mobile phone and the theoretical approaches applied in each case. This paper presents common advantages for consumers and firms in both buying and selling channels and also clear differences between them. Besides, this study revises the main approaches and determinants of the buying in each case.

  12. Diazinon is activated by CYP2C19 in human liver.

    Science.gov (United States)

    Kappers, W A; Edwards, R J; Murray, S; Boobis, A R

    2001-11-15

    Phosphorothioate compounds are used throughout the world as agricultural and domestic pesticides. Here, the activation of the phosphorothioate diazinon to diazoxon in human liver is described. In an initial study using three human liver microsomal samples, K(m) for diazoxon formation varied markedly (31, 208, and 660 microM; V(max) 1125, 685, and 1028 pmol/min/mg protein, respectively), suggesting the involvement of more than one P450 enzyme. A wide variation in activity was found using 50 microM diazinon as substrate, (11-648 pmol/min/mg protein, n = 15), whereas, with 500 microM, variation was less (164-978 pmol/min/mg protein). Among eight P450-catalyzed reactions, the putative high-affinity component (50 microM diazinon) correlated with S-mephenytoin 4'-hydroxylase activity (r = 0.686, p diazinon) correlated with both S-mephenytoin 4'-hydroxylase (r = 0.714; p diazinon (500 microM) at the fastest rate, followed by CYP3A4, CYP1A2, and CYP2C9. Both hepatic microsomal S-mephenytoin 4'-hydroxylase and high-affinity phenacetin O-deethylase activities were strongly inhibited by diazinon (IC50 diazinon activation in human liver, while other enzymes including CYP1A2 may play a more minor role.

  13. Complex Structures in the Reentrant Phase Diagram of HoNi_2B_2C

    Science.gov (United States)

    Childers, J.; Zhang, J.; Olinger, A., Jr.; Metlushko, V.; Delong, L.; Canfield, P.

    1996-03-01

    HoNi_2B_2C exhibits a resistive onset to superconductivity near 9.0 K, followed by transitions to incommensurate magnetic order (IMO) at 6.0 K and 5.5 K, and commensurate antiferromagnetic order (AFM) at TN = 5.2 K. Vibrating reed (VR) and resistance data reveal two previously unobserved lines of magnetic anomalies in both the upper superconducting (SC) and lower reentrant SC regions for H || a*b*. The wide region between the upper onset of SC and the first magnetic anomaly reflects weak vortex pinning, possibly due to a subtle buildup of IMO from well above 8K. The interplay between SC and magnetic order is evident in abrupt displacements of transition lines to IMO near their crossing with the reentrant normal transition line for 5.2

  14. The time course of serotonin 2C receptor expression after spinal transection of rats

    DEFF Research Database (Denmark)

    Ren, Li-Qun; Wienecke, Jacob; Chen, Meng

    2013-01-01

    -IR analysis was confined to the ventral horn motoneuron somata (including a proportion of proximal dendrites) a significant increase was not detected until 45 day post-operation. 5-HT2CR upregulation in the spinal gray matter is confirmed with Western blot in the rats 60 days post-operation. The time course......In the spinal cord 5-HT systems modulate the spinal network via various 5-HT receptors. 5-HT2A and 2C receptors are likely the most important 5-HT receptors for enhancing the motoneuron excitability by facilitating the persistent inward current, and thus play an important role for the pathogenesis...... after transection (with an average ~1.3-fold higher than in sham-operated group) but did not reach a significant level until at 21 days (~1.4-fold). The increase sustained thereafter and a plateau level was reached at 45 days (~1.7-fold higher), a value similar as that at 60 days. When 5-HT2CR...

  15. Computer navigation assisted fixation in neglected C2-C3 dislocation in an adult

    Directory of Open Access Journals (Sweden)

    S Rajasekaran

    2011-01-01

    Full Text Available A 49-year-old male presented with neck pain and deformity following an industrial accident sustained two months back. His neurology was normal except for a minimal weakness in left biceps (grade 4/5. Radiographs, magnetic resonance imaging and computed tomographic scan revealed fracture dislocation of C2-C3 with significant lateral translation of C2 over C3 without disc herniation. In view of unsuccessful closed reduction and absent disc herniation at the level of dislocation, a posterior only reduction, stabilisation and fusion with Iso-C 3D computer navigation-assisted cervical pedicle screw fixation with transverse rod-screw construct was performed. At 6 months followup the patient was completely relieved of his symptoms and was able to return to his previous occupation. The rare case is reported for the management by Iso-C 3D computer navigation assisted cervical pedicle screw fixation and reduction with transverse rod-screw construct at each involved level.

  16. Effect of Cytochrome P450 2C19 681G>A Polymorphism on Premature Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Zhong-hai Chi

    2016-03-01

    Full Text Available Objective: The aim of our study was to evaluate the association between cytochrome P450 2C19 (CYP2C19 681G>A polymorphisms and the age of development of coronary heart disease. Additionally, the study might find some biological indicators at the gene level that could help to predict and evaluate the risk of coronary heart disease in time. Methods: This study included 352 individuals with coronary heart disease. Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP was used to identify CYP2C19 681G>A. The objects were divided into wild type (GG or homozygous CYP2C19*1 wild-type and mutant type (GA/AA or the mutant CYP2C19*2 allele on the basis of genotype. The association between CYP2C19 gene polymorphism and the age of onset of coronary heart disease was assessed by multivariate linear regression analysis. Results: There was a significant association in the age of onset between the two groups (t=3.398, P=0.001, which was 58.51+12.72 years in the wild type and 53.95+11.63 years in the mutant group. The frequency of CYP2C19 681A (CYP2C19*2 allele was 3.32, 0.268, 0.227 in different age groups, which was significantly different (χ2=10.745, P=0.005 in different groups, as well as in the genotype. The result, assessed by multiple linear regression, showed that genotype, smoking, obesity, and hyperlipidemia affect the age of onset of coronary heart disease (β was -0.167, 0.156, 0.155, and 0.112, PA gene polymorphism may be one of the risk factors in susceptibility to early onset of coronary heart disease, but not an independent factor because other factors may play a synergistic role.

  17. Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

    Science.gov (United States)

    Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

    2012-12-15

    Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation.

  18. Canine parvovirus types 2c and 2b circulating in North American dogs in 2006 and 2007.

    Science.gov (United States)

    Kapil, Sanjay; Cooper, Emily; Lamm, Cathy; Murray, Brandy; Rezabek, Grant; Johnston, Larry; Campbell, Gregory; Johnson, Bill

    2007-12-01

    Parvovirus is the most common viral cause of diarrhea in young puppies. Based on the analysis of a partial VP2 sequence of 54 samples, canine parvovirus type 2c (CPV-2c) (n = 26), CPV-2b (n = 25), and CPV-2 (n = 3) were detected in the United States. The American CPV-2b isolates have unique codons (494 and 572) in VP2.

  19. Drug-drug Interaction between Losartan and Paclitaxel in Human Liver Microsomes with Different CYP2C8 Genotypes.

    Science.gov (United States)

    Mukai, Yuji; Senda, Asuna; Toda, Takaki; Hayakawa, Toru; Eliasson, Erik; Rane, Anders; Inotsume, Nobuo

    2015-06-01

    The cytochrome P450 (CYP) 2C8*3 allele is associated with reduced metabolic activity of paclitaxel. This study was aimed to investigate the inhibitory effect of losartan on paclitaxel metabolism in human liver microsomes (HLMs) and to determine the impact of the CYP2C8*3 polymorphism. HLMs that contained the CYP2C8*1 homozygote (HL60) or CYP2C8*3 heterozygote (HL54) genotype were used for the inhibition study. Losartan, at a concentration of 50 μmol/L, significantly inhibited paclitaxel metabolism by 29% and 57% in the HL60 (p losartan and the CYP3A4-selective inhibitors, erythromycin and ketoconazole, caused a greater inhibition of the paclitaxel metabolism than quercetin, a CYP2C8-selective inhibitor. This demonstrated that the paclitaxel metabolism was mainly catalysed by CYP3A4 in HL60. There were no significant differences found for the inhibitory effects caused by the four inhibitors of the paclitaxel metabolism in HL54, indicating that both CYP2C8 and CYP3A4 play important roles in paclitaxel metabolism in HL54. These findings suggest that 50 μmol/L of losartan inhibits both CYP2C8 and CYP3A4 in HLMs. In summary, losartan inhibited paclitaxel metabolism, with concentrations over 50 μmol/L in HLMs. The CYP2C8*3 allele carriers are likely susceptible to the interactions of losartan and CYP3A4 inhibitors to paclitaxel metabolism.

  20. Determination of the inhibitory potential of 6 fluoroquinolones on CYPIA2 and CYP2C9 in human liver microsomes

    Institute of Scientific and Technical Information of China (English)

    Li ZHANG; Min-ji WEI; Cai-yun ZHAO; Hui-min QI

    2008-01-01

    Aim: To determine the inhibitory potential of 2 new fluoroquinolones, caderofloxacin and antofloxacin, together with 4 marketed fluoroquinolones, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin, on the activity of cytochrome P450 isoforms 1A2 (CYP1A2) and 2C9 (CYP2C9). Methods: Probe substrates, phenacetin (CYP1A2), and tolbutamide (CYP2C9) were incubated with human liver microsomes and the metabolites were analyzed by liquid chromatography/mass spectrometry using electrospray ionization in positive or negative mode. Glipizide was used as the internal standard in both modes. The inhibitory potential of fluoroquinolones on CYP1A2 and CYP2C9 was investigated. Results: The IC50 values (μmol/L) determined with the cocktail were in agreement with individual probe substrates (α-naphthoflavone: 0.27 vs 0.26; sulfaphenazole: 0.49 vs 0.37). Ciprofloxacin showed weak inhibition on both the activity of CYPIA2 (IC50 135 μmol/L) and CYP2C9 (IC50 180 μmol/L), whereas levofloxacin inhibited only CYP2C9 (IC50 210 μmol/L). Caderofloxacin, antofloxacin, moxifloxacin, and gatifloxacin showed little or no inhibition on the activity of CYPIA2 or CYP2C9 when tested at comparable concentrations (0-200 mg/L). Conclusion: Caderofloxacin, antofloxacin, moxifloxacin, and gatifloxacin are negligible inhibitors to CYP1A2 and CYP2C9. The in vitro system can be used as a high-throughput model to screen similar compounds for the early identification of drug-drug interaction potential.

  1. Pharmacogenetic relevance of the CYP2C9*3 allele in a tenoxicam bioequivalence study performed on Spaniards.

    Science.gov (United States)

    Peiró, A M; Novalbos, J; Zapater, P; Moreu, R; López-Rodríguez, R; Rodríguez, V; Abad-Santos, F; Horga, J F

    2009-01-01

    We performed a study to quantify CYP2C9 and CYP2C8 alleles influence on the variability observed in tenoxicam pharmacokinetic (PK) and implication in a bioequivalence study design performed on Spaniards. Eighteen healthy volunteers were included in an open, randomized, crossover, phase I bioequivalence study. Significant increases were found in CYP2C9*3 alleles vs. *1 and *2 in AUC(0-infinity) (median (min-max)): 256 (230-516) vs. 150 (100-268) and 169 (124-197) microg h/mL (p<0.01) and half-life time (t1/2) 102 (79-36) vs. 56 (45-94) and 64 (60-80)h (p<0.01). Non-significant differences were observed in C(max) 1.9 (1.8-2.9) vs. 2.4 (1.7-3.4), 2.5 (1.6-2.9) microg/mL or in according to CYP2C8 alleles presence. CYP2C9*3 allele is associated to a longer elimination time of tenoxicam. PK parameters calculated in bioequivalence studies (AUC(0-infinity), t1/2) may be influenced by the presence of CYP2C9*3 allele resulting in a high variability. Thus, bioequivalence studies of tenoxicam formulations should be designed considering genotype profile.

  2. The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

    Directory of Open Access Journals (Sweden)

    Agustinus Wijaya

    2012-05-01

    Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

  3. Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

    Science.gov (United States)

    Lin, Jieru E; Colon-Gonzalez, Francheska; Blomain, Erik; Kim, Gilbert W; Aing, Amanda; Stoecker, Brian; Rock, Justin; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Tomczak, Michal; Blumberg, Richard S; Waldman, Scott A

    2016-01-15

    Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide. ©2016 American Association for Cancer Research.

  4. PAM-Dependent Target DNA Recognition and Cleavage by C2c1 CRISPR-Cas Endonuclease

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hui; Gao, Pu; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J. (MSKCC); (Cornell); (Chinese Aca. Sci.)

    2016-12-01

    C2c1 is a newly identified guide RNA-mediated type V-B CRISPR-Cas endonuclease that site-specifically targets and cleaves both strands of target DNA. We have determined crystal structures of Alicyclobacillus acidoterrestris C2c1 (AacC2c1) bound to sgRNA as a binary complex and to target DNAs as ternary complexes, thereby capturing catalytically competent conformations of AacC2c1 with both target and non-target DNA strands independently positioned within a single RuvC catalytic pocket. Moreover, C2c1-mediated cleavage results in a staggered seven-nucleotide break of target DNA. crRNA adopts a pre-ordered five-nucleotide A-form seed sequence in the binary complex, with release of an inserted tryptophan, facilitating zippering up of 20-bp guide RNA:target DNA heteroduplex on ternary complex formation. Notably, the PAM-interacting cleft adopts a “locked” conformation on ternary complex formation. Structural comparison of C2c1 ternary complexes with their Cas9 and Cpf1 counterparts highlights the diverse mechanisms adopted by these distinct CRISPR-Cas systems, thereby broadening and enhancing their applicability as genome editing tools.

  5. [Association between serotonin receptor 2C gene Cys23Ser polymorphism and social behavior in schizophrenia patients and healthy individuals].

    Science.gov (United States)

    Alfimova, M V; Golimbet, V E; Korovaitseva, G I; Abramova, L I; Kaleda, V G

    2015-02-01

    The purpose of this work was to search for associations between the serotonin receptor 2C gene (HTR2C) and the peculiarities of social behavior and social cognition in schizophrenia. To do this, patients with schizophrenia spectrum disorders and healthy control subjects were genotyped for the Cys23Ser HTR2C marker and underwent psychological examination, including assessment of Machiavellianism, recognition of emotions in facial expression, and theory of mind. In addition, we estimated the trait anxiety level as a potential factor affecting the relationship between the gene HTR2C and social behavior. We found a significant association between the Ser allele and a reduction of estimates on the Mach-LV Machiavellianism scale in the total sample of patients (n = 182) and control subjects (n = 189), which did not reach the confidence level in either of the groups. A tendency towards a HTR2C gene influence on the trait anxiety level was also revealed. The association between HTR2C and Machiavellianism was retained if the anxiety level was taken into account. The results suggest a pleiotropic effect of HTR2Con anxiety and Machiavellianism.

  6. A Proximal Promoter Region of Arabidopsis DREB2C Confers Tissue-specific Expression under Heat Stress

    Institute of Scientific and Technical Information of China (English)

    Huan Chen; Jihyun Je; Chieun Song; Jung Eun Hwang; Chae Oh Lim

    2012-01-01

    The dehydration-responsive element-binding factor 2C (DREB2C) is a member of the CBF/DREB subfamily of proteins,which contains a single APETALA2/Ethylene responsive element-binding factor (AP2/ERF)domain.To identify the expression pattern of the DREB2C gene,which contains multiple transcription cis-regulatory elements in its promoter,an approximately 1.4 kb upstream DREB2C sequence was fused to the β-glucuronidase reporter gene (GUS) and the recombinant p1244 construct was transformed into Arabidopsis thaliana (L.) Heynh.The promoter of the gene directed prominent GUS activity in the vasculature in diverse young dividing tissues.Upon applying heat stress (HS),GUS staining was also enhanced in the vasculature of the growing tissues.Analysis of a series of 5'-deletions of the DREB2C promoter revealed that a proximal upstream sequence sufficient for the tissue-specific spatial and temporal induction of GUS expression by HS is localized in the promoter region between -204 and -34 bps relative to the transcriptional start site.Furthermore,electrophoretic mobility shift assay (EMSA) demonstrated that nuclear protein binding activities specific to a -120 to -32 bp promoter fragment increased after HS.These results indicate that the TATA-proximal region and some latent trans-acting factors may cooperate in HS-induced activation of the Arabidopsis DREB2C promoter.

  7. Graphite Carbon-Supported Mo2C Nanocomposites by a Single-Step Solid State Reaction for Electrochemical Oxygen Reduction.

    Science.gov (United States)

    Huang, K; Bi, K; Liang, C; Lin, S; Wang, W J; Yang, T Z; Liu, J; Zhang, R; Fan, D Y; Wang, Y G; Lei, M

    2015-01-01

    Novel graphite-molybdenum carbide nanocomposites (G-Mo2C) are synthesized by a typical solid state reaction with melamine and MoO3 as precursors under inert atmosphere. The characterization results indicate that G-Mo2C composites are composed of high crystallization and purity of Mo2C and few layers of graphite carbon. Mo2C nanoparticles with sizes ranging from 5 to 50 nm are uniformly supported by surrounding graphite layers. It is believed that Mo atom resulting from the reduction of MoO3 is beneficial to the immobilization of graphite carbon. Moreover, the electrocatalytic performances of G-Mo2C for ORR in alkaline medium are investigated by cyclic voltammetry (CV), rotating disk electrode (RDE) and chronoamperometry test with 3M methanol. The results show that G-Mo2C has a considerable catalytic activity and superior methanol tolerance performance for the oxygen reduction reaction (ORR) benefiting from the chemical interaction between the carbide nanoparticles and graphite carbon.

  8. Soil and crop residue CO2-C emission under tillage systems in sugarcane-producing areas of southern Brazil

    Directory of Open Access Journals (Sweden)

    Luís Gustavo Teixeira

    2013-10-01

    Full Text Available Appropriate management of agricultural crop residues could result in increases on soil organic carbon (SOC and help to mitigate gas effect. To distinguish the contributions of SOC and sugarcane (Saccharum spp. residues to the short-term CO2-C loss, we studied the influence of several tillage systems: heavy offset disk harrow (HO, chisel plow (CP, rotary tiller (RT, and sugarcane mill tiller (SM in 2008, and CP, RT, SM, moldboard (MP, and subsoiler (SUB in 2009, with and without sugarcane residues relative to no-till (NT in the sugarcane producing region of Brazil. Soil CO2-C emissions were measured daily for two weeks after tillage using portable soil respiration systems. Daily CO2-C emissions declined after tillage regardless of tillage system. In 2008, total CO2-C from SOC and/or residue decomposition was greater for RT and lowest for CP. In 2009, emission was greatest for MP and CP with residues, and smallest for NT. SOC and residue contributed 47 % and 41 %, respectively, to total CO2-C emissions. Regarding the estimated emissions from sugarcane residue and SOC decomposition within the measurement period, CO2-C factor was similar to sugarcane residue and soil organic carbon decomposition, depending on the tillage system applied. Our approach may define new emission factors that are associated to tillage operations on bare or sugarcane-residue-covered soils to estimate the total carbon loss.

  9. CYP2C9 genotype does not affect risk of tobacco-related cancer in the general population

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Nordestgaard, B.G.; Bojesen, S.E.

    2010-01-01

    tolbutamide and warfarin, while this has not been investigated for PAHs. We hypothesised that these two variants in the CYP2C9 gene influence risk of tobacco-related cancer. Methods: In a prospective study of the general population (n = 10 392) with 60 years of follow-up, the Copenhagen City Heart Study, we.......9/1.1 in the Copenhagen City Heart Study and below/above 0.8/1.3 and 0.9/1.1 in the Copenhagen General Population Study for tobacco-related cancer and all cancer, respectively. Conclusion: Genetic variations in CYP2C9 do not affect risk of tobacco-related cancers. (C) 2010 Elsevier Ltd. All rights reserved...... associated two variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) with risk of tobacco-related cancer and all cancer. All results were re-tested in a cross-sectional study of the general population (n = 36 856), the Copenhagen General Population Study. Results: We found no association between any of the CYP2C9...

  10. Graphite Carbon-Supported Mo2C Nanocomposites by a Single-Step Solid State Reaction for Electrochemical Oxygen Reduction.

    Directory of Open Access Journals (Sweden)

    K Huang

    Full Text Available Novel graphite-molybdenum carbide nanocomposites (G-Mo2C are synthesized by a typical solid state reaction with melamine and MoO3 as precursors under inert atmosphere. The characterization results indicate that G-Mo2C composites are composed of high crystallization and purity of Mo2C and few layers of graphite carbon. Mo2C nanoparticles with sizes ranging from 5 to 50 nm are uniformly supported by surrounding graphite layers. It is believed that Mo atom resulting from the reduction of MoO3 is beneficial to the immobilization of graphite carbon. Moreover, the electrocatalytic performances of G-Mo2C for ORR in alkaline medium are investigated by cyclic voltammetry (CV, rotating disk electrode (RDE and chronoamperometry test with 3M methanol. The results show that G-Mo2C has a considerable catalytic activity and superior methanol tolerance performance for the oxygen reduction reaction (ORR benefiting from the chemical interaction between the carbide nanoparticles and graphite carbon.

  11. In Silico Investigation of Cytochrome P450 2C9 in relation to Aging Using Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Tzu-Chieh Hung

    2014-01-01

    Full Text Available Cytochrome P450 2C9 (CYP2C9 metabolizes dehydroepiandrosterone-sulfate (DHEA-S, but in elderly people the amount of DHEA-S remaining after CYP2C9 metabolization may be insufficient for optimal health. A prediction model, molecular docking, and molecular dynamics were used to screen the Traditional Chinese Medicine (TCM database to determine molecular compounds that may inhibit CYP2C9. The candidate compounds apocynoside(I, 4-methoxymagndialdehyde, and prunasin have higher Dock Scores, and prediction bioactivity than warfarin (the control drug. The interaction between 4-methoxymagndialdehyde and CYP2C9 is more intense than with other TCM compounds, but the simulation is longer. In these compounds, apocynoside(I and prunasin have a greater number of pathways for their flexible structure, but these structures create weak interactions. These candidate compounds, which are known to have antioxidation and hypolipidemic functions that have an indirect effect on the aging process, can be extracted from traditional Chinese medicines. Thus, these candidate compounds may become CYP2C9 inhibitors and play an important role in providing optimal health in the elderly.

  12. Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration.

    Science.gov (United States)

    Afrin, Lawrence B; Afrin, Jessica B

    2011-01-01

    Pneumocystis jirovecii prophylaxis is standard in allogeneic stem cell transplantation (alloSCT), sometimes with pentamidine at a low dose inhaled monthly. Human metabolism of pentamidine depends on cytochrome P450 2C19 (CYP2C19). The frequency of mutant CYP2C19 forms with decreased function (from 2% of Caucasians to 30% of Asians and 79% of certain Polynesians), together with common use of CYP2C19 inhibitors in the alloSCT process, creates risk for impaired pentamidine clearance resulting in toxicity ordinarily expected only with high doses given for active infection. We examined the charts of 32 consecutive pentamidine-prophylaxed alloSCT patients at our center. We assessed hospital charges for the management of toxicities unexplained at the time but likely attributable, in retrospect, to pentamidine. Twenty-eight percent experienced significant toxicities (incurring added charges of at least US$5000). Thirteen percent suffered major toxicity (incurring added charges of at least US$25, 000; median added charge $351, 701) and shorter survival (326 vs. 622 d for all pentamidine recipients), including 6% who died of pentamidine toxicities [one proven postmortem to have a (non-functional) homozygous CYP2C19*2 mutation]. Charges for care attributable to pentamidine toxicity exceeded what preemptive genotyping would have cost by 73-fold. These findings encourage routine use of preemptive CYP2C19 genotyping in alloSCT patients considered for pentamidine.

  13. Study of Multi-source Fusion B2C Business Process Reengineering of the Petri net Model

    Directory of Open Access Journals (Sweden)

    Feng Tian

    2013-11-01

    Full Text Available In order to fuse a multi-source B2C E-commerce system, this paper implements a new multi-source fusion B2C mode business system application development, which can provide customers with efficient and reliable comparison and cross-platform business system of choose and buy goods. By analyzing the Multi-source fusion B2C E-commerce system demand of business process reengineering and Petri net theory, the B2C electronic commerce system of multi-source fusion structure is proposed, graphical workflow modeling methods is adopted, the multi-source fusion of B2C business process reengineering Petri model is established, with the help of CPNtool simulation system and the establishment of correlation matrix analysis of the model. The experimental simulation analysis and output of experimental reports indicate that the business processes are properly designed, no deadlocks node exist at runtime, accessibility meets which provides the reference model for the development of multi-source fusion of B2C electronic commerce system.    

  14. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    - serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...... of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume......, controlled cell death and cellular migration. Volume regulatory mechanisms has long been in focus for regulating cellular proliferation and my thesis work have been focusing on the role of Cl- channels in proliferation with specific emphasis on ICl, swell. Pharmacological blockage of the ubiquitously...

  15. Precision volume measurement system.

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Erin E.; Shugard, Andrew D.

    2004-11-01

    A new precision volume measurement system based on a Kansas City Plant (KCP) design was built to support the volume measurement needs of the Gas Transfer Systems (GTS) department at Sandia National Labs (SNL) in California. An engineering study was undertaken to verify or refute KCP's claims of 0.5% accuracy. The study assesses the accuracy and precision of the system. The system uses the ideal gas law and precise pressure measurements (of low-pressure helium) in a temperature and computer controlled environment to ratio a known volume to an unknown volume.

  16. Trifluoromethylation of perfluorinated diacylfluorides: synthesis of the diketone CF3C(O)CF2C(O)CF3 and of new perfluorinated diol (CF3)2C(OH)CF2C(OH)(CF3)2.

    Science.gov (United States)

    Corti, Sandra; Pennington, William T; DesMarteau, Darryl D

    2013-01-01

    Perfluoromalonyl difluoride reacts with TMS-CF3 (1:1) in the presence of KF to give the new diketone CF2(C(O)CF3)2. A large excess (5:1) of TMS-CF3 results in the presumed potassium dialkoxide [(CF3)2COK]2CF2 which yields the 1,3-ditertiarydiol [(CF3)2C(OH)]2CF2 on reaction with H2SO4.

  17. Receptor reserve analysis of the human alpha(2C)-adrenoceptor using.

    Science.gov (United States)

    Umland, S P; Wan, Y; Shah, H; Billah, M; Egan, R W; Hey, J A

    2001-01-12

    Here we determine for norepinephrine, (5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline) (UK14,304), 5,6,7,8-tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (BHT-920), (2-[3-hydroxy-2,6-dimethyl-4-t-butylbenzyl]-2-imidazoline) (oxymetazoline), and ((R)-3-Hydroxy-alpha-[(methylamino)methyl]-benzenemethanol hydrochloride) (phenylephrine), affinities using a radiolabeled agonist and antagonist, and potency and efficacy values in membrane [(35)S]guanosine-5'-O-(3-thiotriphosphate) ([(35)S]GTP gamma S) binding and cAMP cellular inhibition assays, in Chinese hamster ovary cells (CHO-K1) expressing the human alpha(2c)-adrenoceptor. These cells express a high ratio of receptor to G-protein because each agonist, but not several antagonists, displaced [(3)H]UK14,304 with higher affinity than [(3)H]rauwolscine. The rank order of potency of high affinity K(i) and EC(50) in both functional assays was norepinephrine > or =UK14,304>BHT-920>oxymetazoline>phenylephrine. The receptor reserve of G-protein activation and cAMP responses was measured with the irreversible antagonist, benextramine; K(A) values of norepinephrine or UK14,304 were similar (289, 271 or 150, 163 nM, respectively). A 20-fold greater receptor occupancy was required for agonist-induced half-maximal [(35)S]GTP gamma S binding compared to cAMP inhibition, indicating significant signal amplification in cells. Therefore, the G-protein activation assay is better at distinguishing full and partial agonists.

  18. Regulation of nonmuscle myosin II during 3-methylcholanthrene induced dedifferentiation of C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Sumit K.; Saha, Shekhar; Das, Provas; Das, Mahua R.; Jana, Siddhartha S., E-mail: bcssj@iacs.res.in

    2014-08-01

    3-Methylcholanthrene (3MC) induces tumor formation at the site of injection in the hind leg of mice within 110 days. Recent reports reveal that the transformation of normal muscle cells to atypical cells is one of the causes for tumor formation, however the molecular mechanism behind this process is not well understood. Here, we show in an in vitro study that 3MC induces fragmentation of multinucleate myotubes into viable mononucleates. These mononucleates form colonies when they are seeded into soft agar, indicative of cellular transformation. Immunoblot analysis reveals that phosphorylation of myosin regulatory light chain (RLC{sub 20}) is 5.6±0.5 fold reduced in 3MC treated myotubes in comparison to vehicle treated myotubes during the fragmentation of myotubes. In contrast, levels of myogenic factors such as MyoD, Myogenin and cell cycle regulators such as Cyclin D, Cyclin E1 remain unchanged as assessed by real-time PCR array and reverse transcriptase PCR analysis, respectively. Interestingly, addition of the myosin light chain kinase inhibitor, ML-7, enhances the fragmentation, whereas phosphatase inhibitor perturbs the 3MC induced fragmentation of myotubes. These results suggest that decrease in RLC{sub 20} phosphorylation may be associated with the fragmentation step of dedifferentiation. - Highlights: • 3-Methylcholanthrene induces fragmentation of C2C12-myotubes. • Dedifferentiation can be divided into two steps – fragmentation and proliferation. • Fragmentation is associated with rearrangement of nonmuscle myosin II. • Genes associated with differentiation and proliferation are not altered during fragmentation. • Phosphorylation of myosin regulatory light chain is reduced during fragmentation.

  19. C 2-C 10 nonmethane hydrocarbons measured in Dallas, USA—Seasonal trends and diurnal characteristics

    Science.gov (United States)

    Qin, Y.; Walk, T.; Gary, R.; Yao, X.; Elles, S.

    Nonmethane hydrocarbons (NMHCs) are important precursors of ozone and other photo oxidants. We presented continuous hourly average concentrations of 45 C 2-C 10 NMHCs measured in urban area of Dallas, USA from 1996 to 2004. Most of the selected compounds are good variables with less noise. The top 10 species with high ozone-generating potential were identified according to their concentrations and reactivities. The ambient concentrations of abundant anthropogenic emission hydrocarbons measured in Dallas were about 2-4 times of the background values measured in the remote areas with adjacent latitude. The time series for anthropogenic emission hydrocarbons showed an obvious seasonal cycle with relatively high concentration in winter and low concentration in summer. The sinusoidal function with a linearly decreasing factor could well fit the time series of NMHCs. The phase of seasonal cycle for the aromatic hydrocarbons of toluene, m/ p xylene and o-xylene that might come from both vehicle emission and solvent utilities evaporation was about 1 month earlier than that for alkanes and alkenes that mainly came from vehicle emission. Ambient NMHCs in Dallas decreased with a stable rate during 1996-2004. For most of compounds with high ozone-generating potential, the rate of ambient concentration decrease was higher or much higher than the rate of volatile organic compounds (VOCs) source emission reduction estimated by EPA's National Emission Inventory. On weekdays, the morning hydrocarbon concentration peak was coincident with morning traffic rush time in Dallas. Another concentration peak was delayed to afternoon traffic rush time. The characteristics of VOCs sources, photochemical removal processes and atmospheric dilution could be interpreted by the diurnal variations of benzene/ethylbenzene (B/E), toluene/ethylbenzene (T/E) and xylene/ethylbenzene (X/E). The ratio of VOC/NO x measured in Dallas was substantially smaller than that calculated for USA cities. Ozone

  20. Improvement in the incident reporting and investigation procedures using process excellence (DMAI2C) methodology.

    Science.gov (United States)

    Miles, Elizabeth N

    2006-03-17

    In 1996, Health & Safety introduced an incident investigation process called Learning to Look to Johnson & Johnson. This process provides a systematic way of analyzing work-related injuries and illness, uncovers root cause that leads to system defects, and points to viable solutions. The process analyzed involves three steps: investigation and reporting of the incident, determination of root cause, and development and implementation of a corrective action plan. The process requires the investigators to provide an initial communication for work-related serious injuries and illness as well as lost workday cases to Corporate Headquarters within 72 h