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Sample records for 1r camphorylsulphonyl oxaziridine impregnated

  1. Hypolipidemic effect of dihydroisoquinoline oxaziridine in high-fat diet-fed rats.

    PubMed

    Aydi, Rihab; Gara, Amel Ben; Chaaben, Rim; Saad, Hajer Ben; Fki, Lotfi; ElFeki, Abdelfattah; Belghith, Hafedh; Belghith, Karima; Kammoun, Majed

    2016-08-01

    Obesity is a serious health problem that increases the risk of many complications, including diabetes and cardiovascular disease. This study aims to evaluate, for the first time, the effects of oxaziridine 3 on lipoprotein lipase activity in the serum of rats fed with a high-fat diet (HFD) on body weight, lipid profile and liver-kidney functions. The administration of oxaziridine 3 to HFD-rats lowered body weight and inhibited the lipase activity of obese rats leading to notable decrease of T-Ch, TGs and LDL-Ch levels accompanied with an increase in HDL-Ch concentration in serum. Moreover, the findings of this study revealed that oxaziridine 3 helped to protect liver tissue from the appearance of fatty cysts. Additionally, oxaziridine 3 administration to HFD-rats induces antioxidant activity proven by the increase of superoxide dismutase (SOD) and catalase (CAT) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels. It also induces the protection of liver-kidney functions confirmed by a decrease in the levels of toxicity parameters in blood. PMID:27470409

  2. Copper-catalyzed oxaziridine-mediated oxidation of C-H bonds.

    PubMed

    Motiwala, Hashim F; Gülgeze, Belgin; Aubé, Jeffrey

    2012-08-17

    The highly regio- and chemoselective oxidation of activated C-H bonds has been observed via copper-catalyzed reactions of oxaziridines. The oxidation proceeded with a variety of substrates, primarily comprising allylic and benzylic examples, as well as one example of an otherwise unactivated tertiary C-H bond. The mechanism of the reaction is proposed to involve single-electron transfer to the oxaziridines to generate a copper-bound radical anion, followed by hydrogen atom abstraction and collapse to products, with regeneration of the catalyst by a final single-electron transfer event. The involvement of allylic radical intermediates was supported by a radical-trapping experiment with TEMPO. PMID:22830300

  3. Impregnated silica nanoparticles for the reactive removal of sulphur mustard from solutions.

    PubMed

    Singh, Beer; Saxena, Amit; Nigam, Anil Kumar; Ganesan, Kumaran; Pandey, Pratibha

    2009-01-30

    High surface area (887.3m(2)/g) silica nanoparticles were synthesized using aerogel route and thereafter, characterized by N(2)-Brunauer-Emmet-Teller (BET), SEM and TEM techniques. The data indicated the formation of nanoparticles of silica in the size range of 24-75 nm with mesoporous characteristics. Later, these were impregnated with reactive chemicals such as N-chloro compounds, oxaziridines, polyoxometalates, etc., which have already been proven to be effective against sulphur mustard (HD). Thus, developed novel mesoporous reactive sorbents were tested for their self-decontaminating feature by conducting studies on kinetics of adsorptive removal of HD from solution. Trichloroisocyanuric acid impregnated silica nanoparticles (10%, w/w)-based system was found to be the best with least half-life value (t(1/2)=2.8 min) among prepared systems to remove and detoxify HD into nontoxic degradation products. Hydrolysis, dehydrohalogenation and oxidation reactions were found to be the route of degradation of HD over prepared sorbents. The study also inferred that 10% loading of impregnants over high surface area and low density silica nanoparticles enhances the rate of reaction kinetics and seems to be useful in the field of heterogeneous reaction kinetics.

  4. Composite material impregnation unit

    NASA Technical Reports Server (NTRS)

    Wilkinson, S. P.; Marchello, J. M.; Johnston, N. J.

    1993-01-01

    This memorandum presents an introduction to the NASA multi-purpose prepregging unit which is now installed and fully operational at the Langley Research Center in the Polymeric Materials Branch. A description of the various impregnation methods that are available to the prepregger are presented. Machine operating details and protocol are provided for its various modes of operation. These include, where appropriate, the related equations for predicting the desired prepreg specifications. Also, as the prepregger is modular in its construction, each individual section is described and discussed. Safety concerns are an important factor and a chapter has been included that highlights the major safety features. Initial experiences and observations for fiber impregnation are described. These first observations have given great insight into the areas of future work that need to be addressed. Future memorandums will focus on these individual processes and their related problems.

  5. GRAPHITE IMPREGNATION METHOD

    DOEpatents

    Kertesz, F.; Buttram, H.J.

    1962-04-24

    ABS>A method for impregnating a refractory material by filling its pores with a first salt having a high melting temperature is described. The salt is mixed with another, more volatile salt, giving the mixture a much lower melting temperature than that of the first salt. The material is coated with the mixture, then heated to drive off the volatile salt, leaving the first salt in place. (AEC)

  6. Adhesive, elastomeric gel impregnating composition

    DOEpatents

    Shaw, David Glenn; Pollard, John Randolph; Brooks, Robert Aubrey

    2002-01-01

    An improved capacitor roll with alternating film and foil layers is impregnated with an adhesive, elastomeric gel composition. The gel composition is a blend of a plasticizer, a polyol, a maleic anhydride that reacts with the polyol to form a polyester, and a catalyst for the reaction. The impregnant composition is introduced to the film and foil layers while still in a liquid form and then pressure is applied to aid with impregnation. The impregnant composition is cured to form the adhesive, elastomeric gel. Pressure is maintained during curing.

  7. Secondary polymer layered impregnated tile

    NASA Technical Reports Server (NTRS)

    Tran, Huy K. (Inventor); Rasky, Daniel J. (Inventor); Szalai, Christine E. (Inventor); Carroll, Joseph A. (Inventor); Hsu, Ming-ta S. (Inventor)

    2005-01-01

    A low density organic polymer impregnated preformed fibrous ceramic article includes a plurality of layers. A front layer includes ceramic fibers or carbon fibers or combinations of ceramic fibers and carbon fibers, and is impregnated with an effective amount of at least one organic polymer. A middle layer includes polymer impregnated ceramic fibers. A back layer includes ceramic fibers or carbon fibers or combinations of ceramic fibers and carbon fibers, and is impregnated with an effective amount of at least one low temperature pyrolyzing organic polymer capable of decomposing without depositing residues.

  8. Impregnating Coal With Calcium Carbonate

    NASA Technical Reports Server (NTRS)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

    1991-01-01

    Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

  9. Dynamic Impregnator Reactor System (Poster)

    SciTech Connect

    Not Available

    2012-09-01

    IBRF poster developed for the IBRF showcase. Describes the multifarious system designed for complex feedstock impregnation and processing. IBRF feedstock system has several unit operations combined into one robust system that provides for flexible and staged process configurations, such as spraying, soaking, low-severity pretreatment, enzymatic hydrolysis, fermentation, concentration/evaporation, and distillation.

  10. Impregnation transition in a powder

    NASA Astrophysics Data System (ADS)

    Raux, Pascal; Cockenpot, Heloise; Quere, David; Clanet, Christophe

    2011-11-01

    When an initially dry pile of micrometrical grains comes into contact with a liquid, one can observe different behaviors, function of the wetting properties. If the contact angle with the solid is low, the liquid will invade the pile (impregnation), while for higher contact angles, the grains will stay dry. We present an experimental study of this phenomenon: a dry pile of glass beads is deposed on the liquid surface, and we vary the contact angle of the liquid on the grains. We report a critical contact angle below which impregnation always occurs, and develop a model to explain its value. Different parameters modifying this critical contact angle are also investigated. Collaboration with Marco Ramaioli, Nestle Research Center, Lausanne, Switzerland.

  11. Draft genome sequences of the Pseudomonas fluorescens biocontrol strains Wayne1R and Wood1R.

    PubMed

    Rong, Xiaoqing; Gurel, Fulya Baysal; Meulia, Tea; McSpadden Gardener, Brian B

    2012-02-01

    Pseudomonas fluorescens strains Wayne1R and Wood1R have proven capacities to improve plant health. Here we report the draft genome sequences and automatic annotations of both strains. Genome comparisons reveal similarities with P. fluorescens strain Pf-5, reveal the novelty of Wood1R, and indicate some genes that may be related to biocontrol.

  12. Distinct Human and Mouse Membrane Trafficking Systems for Sweet Taste Receptors T1r2 and T1r3

    PubMed Central

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system. PMID:25029362

  13. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    PubMed

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  14. Press Kit: Project RCA (Satcom 1R)

    NASA Technical Reports Server (NTRS)

    1983-01-01

    To replace the RCA SATCOM 1 satellite which provided Earth communications for seven years, NASA is to launch RCA SATCOM 1R using a Delta 3924 launch vehicle. The satellite is to be placed at 139 degrees W longitude, 35,900 kilometers (23,000) miles above the equator. On the seventh apogee, the kick motor will be fired to produce a near synchronous orbit. Satellite life, with continuous full power, is designed to be 10 years. Features of the satellite and launch operations are described.

  15. Curing of Furfuryl Alcohol-Impregnated Parts

    NASA Technical Reports Server (NTRS)

    Lawton, J. W.; Brayden, T. H.

    1983-01-01

    Delamination problem in reinforced carbon/carbon parts impregnated with oxalic acid-catalyzed furfuryl alcohol overcome by instituting two additional quality-control tests on alcohol and by changing curing conditions.

  16. OARE STS-94 (MSL-1R)

    NASA Technical Reports Server (NTRS)

    Rice, James E.

    1998-01-01

    The report is organized into sections representing the phases of work performed in analyzing the STS-94 (MSL-IR) results. STS-94 (MSL1R) is a reflight of the STS-83 (MSL-1) mission which was terminated early because of a fuel cell problem. Section I briefly outlines the OARE system features, coordinates, and measurement parameters. Section 2 describes the results from STS-94. The mission description, data calibration, and representative data obtained on STS-94 are presented. Also, the anomalous performance of OARE on STS-94 is discussed. Finally, Section 3 presents a discussion of accuracy achieved and achievable with OARE. Appendix A discuss the calibration and data processing methodology in detail.

  17. Drug smuggling using clothing impregnated with cocaine.

    PubMed

    McDermott, Seán D; Power, John D

    2005-11-01

    A case study is presented where a woman travelling from South America to the Republic of Ireland was detained at Dublin Airport and articles of clothing she had in her luggage were found to be impregnated with cocaine. The study shows that the amount of powder recovered from the garments was approximately 14% of the total weight of the garments. The cocaine was in the form of cocaine hydrochloride and the purity was approximately 80%. An examination of the garments under filtered light highlighted the areas exposed to cocaine and indicated that the method of impregnation was by pouring liquid containing cocaine onto the clothing.

  18. Apparatus for coating and impregnating filament with resin

    DOEpatents

    Robinson, S.C.; Pollard, R.E.

    1986-12-17

    The present invention is directed to an apparatus for evenly coating and impregnating a filament with binder material. Dimension control and repeatability of the coating and impregnating characteristics are obtained with the apparatus.

  19. Impregnating magnetic components with MDA free epoxy

    NASA Astrophysics Data System (ADS)

    Sanchez, R. O.; Domeier, L.; Gunewardena, S.

    1995-08-01

    This paper describes the use of 'Formula 456' an aliphatic amine cured epoxy for impregnating coils. Methylene dianiline (MDA) has been used for more than 20 years as the curing agent for various epoxy formulations throughout the Department of Energy. Sandia National Laboratories began the process of replacing MDA with other formulations because of regulations imposed by OSHA on the use of MDA.

  20. Meeting on insecticide-impregnated materials.

    PubMed

    1996-06-01

    Malaria causes considerable morbidity and mortality in Africa, killing 1.5-2.7 million people on the continent annually. A meeting on insecticide-impregnated materials was held at the World Health Organization (WHO) Regional Office for Africa (AFRO) during March 18-20, 1996, to promote the use of insecticide-impregnated materials by communities in Africa, review and discuss the results of recently conducted studies in the Africa Region on the use of insecticide-treated nets (ITNs) in malaria control, examine the best ways of implementing the wide-scale use of insecticide-impregnated materials under differing epidemiological and socioeconomic conditions, discuss major operational research priorities, and make recommendations for the promotion and wide use of insecticide-impregnated materials by malaria control programs and communities. The meeting was jointly organized by the WHO Division of Control of Tropical Diseases (CTD), the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR), and AFRO, and attended by experts, malaria control program managers, private sector representatives, nongovernmental organizations, and technical and scientific institutions. Conclusions and recommendations include the need to assess whether pregnant women could benefit from the use of ITNs. Elements of the successful implementation of sustained malaria control activities involving the use of ITNs are listed. Problems encountered in the large-scale implementation of ITNs in Africa should be addressed collaboratively at the regional and global levels, and coordinated by WHO.

  1. Mathematical models for electrochemical impregnation of nickel electrodes

    NASA Technical Reports Server (NTRS)

    Ho, Chien-Hsien; Nagarajan, Gowri S.; Murthy, Mahesh; VanZee, J. W.

    1996-01-01

    Single step and two-step tetramer precipitation models for electrochemical impregnation of nickel electrodes are presented. The objectives for developing the impregnation model are: to predict the impregnation conditions for uniform loading, to develop quality control tools for electrode manufacturing, and to use it as basis for predicting the performance of batteries with non-uniform loadings. This paper, with the help of graphs and charts, discusses the development and application of the impregnation model.

  2. Methods for Tumor Targeting with Salmonella typhimurium A1-R.

    PubMed

    Hoffman, Robert M; Zhao, Ming

    2016-01-01

    Salmonella typhimurium A1-R (S. typhimurium A1-R) has shown great preclinical promise as a broad-based anti-cancer therapeutic (please see Chapter 1 ). The present chapter describes materials and methods for the preclinical study of S. typhimurium A1-R in clinically-relevant mouse models. Establishment of orthotopic metastatic mouse models of the major cancer types is described, as well as other useful models, for efficacy studies of S. typhimurium A1-R or other tumor-targeting bacteria, as well. Imaging methods are described to visualize GFP-labeled S. typhimurium A1-R, as well as GFP- and/or RFP-labeled cancer cells in vitro and in vivo, which S. typhimurium A1-R targets. The mouse models include metastasis to major organs that are life-threatening to cancer patients including the liver, lung, bone, and brain and how to target these metastases with S. typhimurium A1-R. Various routes of administration of S. typhimurium A1-R are described with the advantages and disadvantages of each. Basic experiments to determine toxic effects of S. typhimurium A1-R are also described. Also described are methodologies for combining S. typhimurium A1-R and chemotherapy. The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies. PMID:26846809

  3. Dynamics of condensation on lubricant impregnated surfaces

    NASA Astrophysics Data System (ADS)

    Anand, Sushant; Paxson, Adam; Rykaczewski, Konrad; Beysens, Daniel; Varanasi, Kripa

    2013-03-01

    Replacing the filmwise condensation mode with dropwise condensation promises large improvements in heat transfer that will lead to large cost savings in material, water consumption and decreased size of the systems. In this regards, use of superhydrophobic surfaces fabricated by texturing surfaces with nano/microstructures has been shown to lead decrease in contact line pinning of millimetric drops resulting in fast shedding. However, these useful properties are lost during condensation where droplets that nucleate within texture grow by virtue of condensation to large sized droplets while still adhering to the surface. Recently we have shown that liquid impregnated surfaces can overcome many limitations of conventional superhydrophobic surfaces during condensation. Here we discuss aspects related to condensation on lubricant surfaces, such as behavior of growing droplets. We compare the characteristics of droplets condensing on these surfaces with their behavior on conventional un-impregnated superhydrophobic surfaces and show how use of lubricant impregnated surfaces may lead to large enhancement in heat transfer and energy efficiencies.

  4. Cation adsorption on manganese dioxide impregnated fibers

    SciTech Connect

    Fisher, S. ); Stahel, E.P. )

    1992-12-01

    Complete removal of radioactive cations by standard mixed bed ion exchange resins is sometimes not achieved in liquid radwaste systems. Based on a literature survey, acrylic fibers impregnated with manganese dioxide were chosen as a media warranting study of their ability to adsorb the cations present in radwaste systems in the hope of improving performance of such treatment processes. A system to produce impregnated fiber with a heavy MnO[sub 2] loading was designed, constructed, and operated. The system produced fiber at an average fiber loading of 22.5 percent MnO[sub 2] by weight. Leaching tests made on the MnO[sub 2] fiber exhibited no signs of soluble manganese, insoluble MnO[sub 2], acrylonitrile leaching or fiber loss. Laboratory testing has been performed on the adsorption of calcium, cadmium, cesium, cobalt, iron, and manganese on MnO[sub 2] impregnated fiber. Removal of metals from solution was measured at levels specific for each metal tested. The removal efficiency when they were present in combination was also evaluated.

  5. Impregnated Netting Slows Infestation by Triatoma infestans

    PubMed Central

    Levy, Michael Z.; Quíspe-Machaca, Victor R.; Ylla-Velasquez, Jose L.; Waller, Lance A.; Richards, Jean M.; Rath, Bruno; Borrini-Mayori, Katty; del Carpio, Juan G. Cornejo; Cordova-Benzaquen, Eleazar; McKenzie, F. Ellis; Wirtz, Robert A.; Maguire, James H.; Gilman, Robert H.; Bern, Caryn

    2008-01-01

    We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13–0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease. PMID:18840739

  6. Impregnated netting slows infestation by Triatoma infestans.

    PubMed

    Levy, Michael Z; Quíspe-Machaca, Victor R; Ylla-Velasquez, Jose L; Waller, Lance A; Richards, Jean M; Rath, Bruno; Borrini-Mayori, Katty; del Carpio, Juan G Cornejo; Cordova-Benzaquen, Eleazar; McKenzie, F Ellis; Wirtz, Robert A; Maguire, James H; Gilman, Robert H; Bern, Caryn

    2008-10-01

    We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

  7. Two Distinct Determinants of Ligand Specificity in T1R1/T1R3 (the Umami Taste Receptor)*

    PubMed Central

    Toda, Yasuka; Nakagita, Tomoya; Hayakawa, Takashi; Okada, Shinji; Narukawa, Masataka; Imai, Hiroo; Ishimaru, Yoshiro; Misaka, Takumi

    2013-01-01

    Umami taste perception in mammals is mediated by a heteromeric complex of two G-protein-coupled receptors, T1R1 and T1R3. T1R1/T1R3 exhibits species-dependent differences in ligand specificity; human T1R1/T1R3 specifically responds to l-Glu, whereas mouse T1R1/T1R3 responds more strongly to other l-amino acids than to l-Glu. The mechanism underlying this species difference remains unknown. In this study we analyzed chimeric human-mouse receptors and point mutants of T1R1/T1R3 and identified 12 key residues that modulate amino acid recognition in the human- and mouse-type responses in the extracellular Venus flytrap domain of T1R1. Molecular modeling revealed that the residues critical for human-type acidic amino acid recognition were located at the orthosteric ligand binding site. In contrast, all of the key residues for the mouse-type broad response were located at regions outside of both the orthosteric ligand binding site and the allosteric binding site for inosine-5′-monophosphate (IMP), a known natural umami taste enhancer. Site-directed mutagenesis demonstrated that the newly identified key residues for the mouse-type responses modulated receptor activity in a manner distinct from that of the allosteric modulation via IMP. Analyses of multiple point mutants suggested that the combination of two distinct determinants, amino acid selectivity at the orthosteric site and receptor activity modulation at the non-orthosteric sites, may mediate the ligand specificity of T1R1/T1R3. This hypothesis was supported by the results of studies using nonhuman primate T1R1 receptors. A complex molecular mechanism involving changes in the properties of both the orthosteric and non-orthosteric sites of T1R1 underlies the determination of ligand specificity in mammalian T1R1/T1R3. PMID:24214976

  8. Evasion mechanisms to Igf1r inhibition in rhabdomyosarcoma.

    PubMed

    Abraham, Jinu; Prajapati, Suresh I; Nishijo, Koichi; Schaffer, Beverly S; Taniguchi, Eri; Kilcoyne, Aoife; McCleish, Amanda T; Nelon, Laura D; Giles, Francis G; Efstratiadis, Argiris; LeGallo, Robin D; Nowak, Brent M; Rubin, Brian P; Malempati, Suman; Keller, Charles

    2011-04-01

    Inhibition of the insulin-like growth factor 1 receptor (Igf1r) is an approach being taken in clinical trials to overcome the dismal outcome for metastatic alveolar rhabdomyosarcoma (ARMS), an aggressive muscle cancer of children and young adults. In our study, we address the potential mechanism(s) of Igf1r inhibitor resistance that might be anticipated for patients. Using a genetically engineered mouse model of ARMS, validated for active Igf1r signaling, we show that the prototypic Igf1r inhibitor NVP-AEW541 can inhibit cell growth and induce apoptosis in vitro in association with decreased Akt and Mapk phosphorylation. However, drug resistance in vivo is more common and is accompanied by Igf1r overexpression, Mapk reactivation, and Her2 overexpression. Her2 is found to form heterodimers with Igf1r in resistant primary tumor cell cultures, and stimulation with Igf2 leads to Her2 phosphorylation. The Her2 inhibitor lapatinib cooperates with NVP-AEW541 to reduce Igf1r phosphorylation and to inhibit cell growth even though lapatinib alone has little effect on growth. These results point to the potential therapeutic importance of simultaneous targeting of Igf1r and Her2 to abrogate resistance.

  9. METHOD OF IMPREGNATING A POROUS MATERIAL

    DOEpatents

    Steele, G.N.

    1960-06-01

    A method of impregnating a porous body with an inorganic uranium- containing salt is outlined and comprises dissolving a water-soluble uranium- containing salt in water; saturating the intercommunicating pores of the porous body with the salt solution; infusing ammonia gas into the intercommunicating pores of the body, the ammonia gas in water chemically reacting with the water- soluble uranium-containing salt in the water solvent to form a nonwater-soluble uranium-containing precipitant; and evaporating the volatile unprecipitated products from the intercommunicating pores whereby the uranium-containing precipitate is uniformly distributed in the intercommunicating peres of the porous body.

  10. Multilayer Impregnated Fibrous Thermal Insulation Tiles

    NASA Technical Reports Server (NTRS)

    Tran, Huy K.; Rasky, Daniel J.; Szalai, Christine e.; Hsu, Ming-ta; Carroll, Joseph A.

    2007-01-01

    The term "secondary polymer layered impregnated tile" ("SPLIT") denotes a type of ablative composite-material thermal- insulation tiles having engineered, spatially non-uniform compositions. The term "secondary" refers to the fact that each tile contains at least two polymer layers wherein endothermic reactions absorb considerable amounts of heat, thereby helping to prevent overheating of an underlying structure. These tiles were invented to afford lighter-weight alternatives to the reusable thermal-insulation materials heretofore variously used or considered for use in protecting the space shuttles and other spacecraft from intense atmospheric-entry heating.

  11. Tumor-Targeting Salmonella typhimurium A1-R: An Overview.

    PubMed

    Hoffman, Robert M

    2016-01-01

    The present chapter reviews the development of the tumor-targeting amino-acid auxotrophic strain S. typhimurium A1 and the in vivo selection and characterization of the high-tumor-targeting strain S. typhimurium A1-R. Efficacy of S. typhimurium A1-R in nude-mouse models of prostate, breast, pancreatic, and ovarian cancer, as well as sarcoma and glioma in orthotopic mouse models is described. Also reviewed is efficacy of S. typhimurium A1-R targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma, breast-cancer brain metastasis, and experimental breast-cancer bone metastasis in orthotopic mouse models. The efficacy of S. typhimurium A1-R on pancreatic cancer stem cells, on pancreatic cancer in combination with anti-angiogenic agents, as well as on cervical cancer, soft-tissue sarcoma, and pancreatic cancer patient-derived orthotopic xenograft (PDOX) mouse models, is also described.

  12. 6. (1r) Arches EF, DE. View southeast Ashton Viaduct, ...

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

    6. (1-r) Arches E-F, D-E. View southeast - Ashton Viaduct, State Route 116 (Washington Highway) spanning Blackstone River, Blackstone Canal, & Providence & Worcester Railroad, Ashton, Providence County, RI

  13. Extreme variability among mammalian V1R gene families

    PubMed Central

    Young, Janet M.; Massa, Hillary F.; Hsu, Li; Trask, Barbara J.

    2010-01-01

    We report an evolutionary analysis of the V1R gene family across 37 mammalian genomes. V1Rs comprise one of three chemosensory receptor families expressed in the vomeronasal organ, and contribute to pheromone detection. We first demonstrate that Trace Archive data can be used effectively to determine V1R family sizes and to obtain sequences of most V1R family members. Analyses of V1R sequences from trace data and genome assemblies show that species-specific expansions previously observed in only eight species were prevalent throughout mammalian evolution, resulting in “semi-private” V1R repertoires for most mammals. The largest families are found in mouse and platypus, whose V1R repertoires have been published previously, followed by mouse lemur and rabbit (∼215 and ∼160 intact V1Rs, respectively). In contrast, two bat species and dolphin possess no functional V1Rs, only pseudogenes, and suffered inactivating mutations in the vomeronasal signal transduction gene Trpc2. We show that primate V1R decline happened prior to acquisition of trichromatic vision, earlier during evolution than was previously thought. We also show that it is extremely unlikely that decline of the dog V1R repertoire occurred in response to selective pressures imposed by humans during domestication. Functional repertoire sizes in each species correlate roughly with anatomical observations of vomeronasal organ size and quality; however, no single ecological correlate explains the very diverse fates of this gene family in different mammalian genomes. V1Rs provide one of the most extreme examples observed to date of massive gene duplication in some genomes, with loss of all functional genes in other species. PMID:19952141

  14. Extreme variability among mammalian V1R gene families.

    PubMed

    Young, Janet M; Massa, Hillary F; Hsu, Li; Trask, Barbara J

    2010-01-01

    We report an evolutionary analysis of the V1R gene family across 37 mammalian genomes. V1Rs comprise one of three chemosensory receptor families expressed in the vomeronasal organ, and contribute to pheromone detection. We first demonstrate that Trace Archive data can be used effectively to determine V1R family sizes and to obtain sequences of most V1R family members. Analyses of V1R sequences from trace data and genome assemblies show that species-specific expansions previously observed in only eight species were prevalent throughout mammalian evolution, resulting in "semi-private" V1R repertoires for most mammals. The largest families are found in mouse and platypus, whose V1R repertoires have been published previously, followed by mouse lemur and rabbit (approximately 215 and approximately 160 intact V1Rs, respectively). In contrast, two bat species and dolphin possess no functional V1Rs, only pseudogenes, and suffered inactivating mutations in the vomeronasal signal transduction gene Trpc2. We show that primate V1R decline happened prior to acquisition of trichromatic vision, earlier during evolution than was previously thought. We also show that it is extremely unlikely that decline of the dog V1R repertoire occurred in response to selective pressures imposed by humans during domestication. Functional repertoire sizes in each species correlate roughly with anatomical observations of vomeronasal organ size and quality; however, no single ecological correlate explains the very diverse fates of this gene family in different mammalian genomes. V1Rs provide one of the most extreme examples observed to date of massive gene duplication in some genomes, with loss of all functional genes in other species. PMID:19952141

  15. Interlaboratory comparison of thin section epoxy impregnation procedures

    SciTech Connect

    Wilson, M.D.; Byrnes, A.P.

    1987-05-01

    Evidence of the ineffective blue-dye epoxy impregnation is encountered all too commonly in thin sections. A study involving ceramic disks was conducted to compare the efficiencies of a variety of epoxy impregnation procedures used by major laboratories. Disks were sent to five commercial and four major oil company thin section laboratories which then impregnated the disks and returned them for analysis. Porcelain disks were used because of their high degree of uniformity, white color, rocklike composition and pore geometry, uniform pore size, and high pore connectivity. Impregnation efficiency was determined by calculating the pore volume invaded using helium porosimetry and by determining the areas and distances of invasion based on extent of blue-dye invasion in cross-sectional cuts through the disks. Techniques which proved very highly effective are vacuum or vacuum/pressure impregnation in which the epoxy was added to the sample container subsequent to evacuation. Relatively ineffective are vacuum techniques, at room or elevated temperatures, where the sample is submerged in epoxy prior to evacuation. The key to effective impregnation is to remove air from the sample before it is covered by epoxy. Factors which have little or no influence on the effectiveness of impregnation include type of blue dye, epoxy type, and presence of fluorescent dye. High-quality thin sections can be prepared using less-effective techniques if care is taken to prepare them from the outer edge of the impregnated sample.

  16. Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide.

    PubMed

    Bouledjouidja, Abir; Masmoudi, Yasmine; Van Speybroeck, Michiel; Schueller, Laurent; Badens, Elisabeth

    2016-02-29

    Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation.

  17. Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide.

    PubMed

    Bouledjouidja, Abir; Masmoudi, Yasmine; Van Speybroeck, Michiel; Schueller, Laurent; Badens, Elisabeth

    2016-02-29

    Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug. While incipient wetness method led to a Fenofibrate loading up to 300 mgdrug/gsilica in 48 h of impregnation, the supercritical impregnation method yielded loading up to 485 mgdrug/gsilica in 120 min of impregnation duration, at 16 MPa and 308 K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation. PMID:26732521

  18. Performance of suspension-impregnated sintered nickel composite electrodes

    SciTech Connect

    Ferrando, W.A.

    1985-10-01

    Direct impregnation for the development of a porous, sintered, nickel-plated graphite fiber plaque by fine particulate Ni(OH)2 is examined. The suspension impregnation method is described, noting that the entire process can be carried out in a very short time. The use of a cobalt additive to improve utilization and the life cycle of nickel electrodes is mentioned. It is found that the suspension method of active material impregnation has potential to produce high energy density, electrically durable, light weight nickel composite electrodes. It is also found that excellent life cycle durability results are obtained with the suspension-impregnated composite electrode. Finally, the electrochemical process, an alternative method of active material Ni(OH)2 impregnation, is mentioned.

  19. Plasma impregnation of wood with fire retardants

    NASA Astrophysics Data System (ADS)

    Pabeliña, Karel G.; Lumban, Carmencita O.; Ramos, Henry J.

    2012-02-01

    The efficacy of chemical and plasma treatments with phosphate and boric compounds, and nitrogen as flame retardants on wood are compared in this study. The chemical treatment involved the conventional method of spraying the solution over the wood surface at atmospheric condition and chemical vapor deposition in a vacuum chamber. The plasma treatment utilized a dielectric barrier discharge ionizing and decomposing the flame retardants into innocuous simple compounds. Wood samples are immersed in either phosphoric acid, boric acid, hydrogen or nitrogen plasmas or a plasma admixture of two or three compounds at various concentrations and impregnated by the ionized chemical reactants. Chemical changes on the wood samples were analyzed by Fourier transform infrared spectroscopy (FTIR) while the thermal changes through thermo gravimetric analysis (TGA). Plasma-treated samples exhibit superior thermal stability and fire retardant properties in terms of highest onset temperature, temperature of maximum pyrolysis, highest residual char percentage and comparably low total percentage weight loss.

  20. Nonequilibrium Ablation of Phenolic Impregnated Carbon Ablator

    NASA Technical Reports Server (NTRS)

    Milos, Frank S.; Chen, Yih K.; Gokcen, Tahir

    2012-01-01

    In previous work, an equilibrium ablation and thermal response model for Phenolic Impregnated Carbon Ablator was developed. In general, over a wide range of test conditions, model predictions compared well with arcjet data for surface recession, surface temperature, in-depth temperature at multiple thermocouples, and char depth. In this work, additional arcjet tests were conducted at stagnation conditions down to 40 W/sq cm and 1.6 kPa. The new data suggest that nonequilibrium effects become important for ablation predictions at heat flux or pressure below about 80 W/sq cm or 10 kPa, respectively. Modifications to the ablation model to account for nonequilibrium effects are investigated. Predictions of the equilibrium and nonequilibrium models are compared with the arcjet data.

  1. Desorption of TEDA from impregnated charcoals

    SciTech Connect

    Wood, G.

    1980-01-01

    Triethylenediamine (TEDA) is one of the most effective charcoal impregnants for trapping organic forms of radioiodine from air. It is used in air cleaning adsorbers, air samplers, and air purifying respirator canisters and cartridges for airborne radioiodine. Volatility of the pure crystals suggested the possibility of significant TEDA desorption in these applications, resulting in toxic levels of amine and/or degradation of sorbent efficiency. Measurements of TEDA desorption rates were made for four commercial charcoals. Temperatures of 70 to 120/sup 0/C were used to give levels detectable with a photoionization detector. Extrapolations to temperatures nearer normal ambient were made by using Clapeyron equation plots. Among three charcoals with the same 5% level of TEDA impregnation, desorption rates varied over factors as great as 10. Slopes of Clapeyron plots were similar, giving an average 25 kcal/mol heat of desorption. This corresponds to a doubling of the TEDA desorption rate with each 5/sup 0/C (9/sup 0/F) rise in temperature. Desorption rates were directly proportional to airflow rates or velocities through the test beds and independent of humidity. Desorption rates per unit weight of charcoal decreased exponentially with bed depth, presumably due to TEDA readsorption. Calculations based on this data and the geometry of a standard adsorber cell showed that at normal ambient temperatures: (1) concentrations of TEDA in effluent air are well below expected toxic levels; and (2) losses of TEDA may be significant. At elevated temperatures TEDA desorption rates are high enough to affect methyl iodide trapping efficiencies and, possibly, charcoal ignition temperatures.

  2. 1/R correction to gravity in the early universe

    SciTech Connect

    Pi Shi; Wang Tower

    2009-08-15

    To explain the accelerated expansion of the late universe, the 1/R correction to Einstein gravity is usually considered, where R is the Ricci scalar. This correction term, if stable, is generally believed to be negligible during inflation. However, if the 1/R term is inflaton dependent, it will dramatically change the story of inflation. The entropy perturbation will naturally appear and drive the evolution of curvature perturbation outside the Hubble horizon. In a large class of models, the entropy perturbation can be made nearly scale invariant. In Einstein gravity the single-field inflation with a quartic potential has been ruled out by recent observations, but it revives when the 1/R term is turned on. The evolution of non-Gaussianities on a large scale are also studied and applied to inflation with 1/R correction. In some specific models, a large non-Gaussianity can be naturally generated outside the horizon. A recent study ruled out almost all f(R) models during the matter-dominated phase. Taking this into consideration, we are left with a limited class of model which recovers the Einstein gravity soon after reheating.

  3. Generalized Second-Order Partial Derivatives of 1/r

    ERIC Educational Resources Information Center

    Hnizdo, V.

    2011-01-01

    The generalized second-order partial derivatives of 1/r, where r is the radial distance in three dimensions (3D), are obtained using a result of the potential theory of classical analysis. Some non-spherical-regularization alternatives to the standard spherical-regularization expression for the derivatives are derived. The utility of a…

  4. The Role of MC1R in Speciation & Phylogeny

    ERIC Educational Resources Information Center

    Offner, Susan

    2013-01-01

    A point mutation in the MC1R gene, a G-protein-coupled receptor, has been found that could have led to the formation of two subspecies of Solomon Island flycatcher from a single ancestral population. I discuss the many roles that G-protein-coupled receptors play in vertebrate physiology and how one particular point mutation can have enormous…

  5. Epoxy impregnation procedure for hardened-cement samples. Progress report

    SciTech Connect

    Struble, L.; Stutzman, P.

    1988-05-01

    A method was previously developed for epoxy impregnation of hydrated cementitious materials for microscopical examination without drying the samples, by sequentially replacing pore solution with ethanol, then the ethanol with epoxy. During subsequent application of the procedure, many specimens were cured. Studies were carried out to identify the cause of these problems and to modify the procedure for more reliable impregnation. Contamination with low levels (4%) of water or ethanol was found to prevent proper curing. Modifications in the procedure to prevent contamination, including monitoring the replacement of pore solution by ethanol, were shown to provide consistent and reliable impregnation.

  6. Antibiotic release from impregnated pellets and beads.

    PubMed

    Bowyer, G W; Cumberland, N

    1994-03-01

    Antibiotic impregnated beads are being used increasingly in the initial treatment of open fracture wounds, producing high antibiotic levels locally, over the first few days. Pellets were prepared to assess the release of the following antibiotics: benzylpenicillin, flucloxacillin, amoxycillin, amoxycillin-clavulanate (Co-Amoxiclav), ciprofloxacin, imipenem, or gentamicin; the carrier material was either polymethylmethacrylate (PMMA) or plaster of Paris (PoP). Elution of antibiotic over 72 hours from the pellets in vitro was determined using an agar-diffusion microbiologic assay. The initial rapid release of antibiotic lasted 12-24 hours, with release from PoP pellets at least four-fold greater than that from corresponding PMMA pellets. A second phase consisted of a sustained but gradually diminishing elution. The release of antibiotics from PoP pellets compared favorably with that from the PMMA beads currently used. We conclude that PoP pellets may be particularly suitable for short-term applications such as infection prophylaxis in open fractures.

  7. Fracture in Phenolic Impregnated Carbon Ablator

    NASA Technical Reports Server (NTRS)

    Agrawal, Parul; Chavez-Garcia, Jose F.

    2011-01-01

    The thermal protection materials used for spacecraft heat shields are subjected to various thermal-mechanical loads during an atmospheric reentry which can threaten the structural integrity of the system. This paper discusses the development of a novel technique to understand the failure mechanisms inside the thermal protection material, Phenolic Impregnated Carbon Ablator (PICA). PICA has successfully flown on the Stardust spacecraft and was the TPS material chosen for the Mars Science Laboratory (MSL), that will fly in 2011. Although PICA has good thermal properties, structurally, it is a weak material. To thoroughly understand failure in PICA, experiments were performed using FiberForm(Registered TradeMark) (precursor of PICA), virgin and furnace-charred PICA. Several small samples were tested inside an electron microscope to investigate the failure mechanisms. Micrographs were obtained before and after the failure in order to study crack initiation and growth. Videos were obtained to capture failure mechanisms in real time. Stress-strain data was obtained simultaneously for all the samples with the help of a data acquisition system, integrated to the mechanical stages. It was found that cracks initiated and grew in the FiberForm when a critical stress limit was reached such that the carbon fibers separated from the binder. However, both for virgin and charred PICA, crack initiation and growth occurred in the matrix (phenolic) phase. Both virgin and charred PICA showed greater strength values compared to FiberForm coupons, confirming that the presence of the porous matrix helps in absorbing the fracture energy.

  8. Fracture in Phenolic Impregnated Carbon Ablator

    NASA Technical Reports Server (NTRS)

    Agrawal, Parul; Chavez-Garcia, Jose; Pham, John

    2013-01-01

    This paper describes the development of a novel technique to understand the failure mechanisms inside thermal protection materials. The focus of this research is on the class of materials known as phenolic impregnated carbon ablators. It has successfully flown on the Stardust spacecraft and is the thermal protection system material chosen for the Mars Science Laboratory and SpaceX Dragon spacecraft. Although it has good thermal properties, structurally, it is a weak material. To understand failure mechanisms in carbon ablators, fracture tests were performed on FiberForm(Registered TradeMark) (precursor), virgin, and charred ablator materials. Several samples of these materials were tested to investigate failure mechanisms at a microstructural scale. Stress-strain data were obtained simultaneously to estimate the tensile strength and toughness. It was observed that cracks initiated and grew in the FiberForm when a critical stress limit was reached such that the carbon fibers separated from the binder. However, both for virgin and charred carbon ablators, crack initiation and growth occurred in the matrix (phenolic) phase. Both virgin and charred carbon ablators showed greater strength values compared with FiberForm samples, confirming that the presence of the porous matrix helps in absorbing the fracture energy.

  9. Wood impregnation of yeast lees for winemaking.

    PubMed

    Palomero, Felipe; Bertani, Paolo; Fernández de Simón, Brígida; Cadahía, Estrella; Benito, Santiago; Morata, Antonio; Suárez-Lepe, José A

    2015-03-15

    This study develops a new method to produce more complex wines by means of an indirect diffusion of wood aromas from yeast cell-walls. An exogenous lyophilized biomass was macerated with an ethanol wood extract solution and subsequently dried. Different times were used for the adsorption of polyphenols and volatile compounds to the yeast cell-walls. The analysis of polyphenols and volatile compounds (by HPLC/DAD and GC-MS, respectively) demonstrate that the adsorption/diffusion of these compounds from the wood to the yeast takes place. Red wines were also aged with Saccharomyces cerevisiae lees that had been impregnated with wood aromas and subsequently dried. Four different types of wood were used: chestnut, cherry, acacia and oak. Large differences were observed between the woods studied with regards to their volatile and polyphenolic profiles. Sensory evaluations confirmed large differences even with short-term contact between the wines and the lees, showing that the method could be of interest for red wine making. In addition, the results demonstrate the potential of using woods other than oak in cooperage.

  10. Fracture in Phenolic Impregnated Carbon Ablator

    NASA Technical Reports Server (NTRS)

    Agrawal, Parul; Chavez-Garcia, Jose F.

    2011-01-01

    The thermal protection materials used for spacecraft heat shields are subjected to various thermal-mechanical loads during an atmospheric entry which can threaten the structural integrity of the system. This paper discusses the development of a novel technique to understand the failure mechanisms inside thermal protection materials. The focus of research is Phenolic Impregnated Carbon Ablator (PICA). It has successfully flown on the Stardust spacecraft and is the TPS material chosen for the Mars Science Laboratory (MSL) and Dragon spacecraft. Although PICA has good thermal properties, structurally, it is a weak material. In order to thoroughly understand failure in PICA, fracture tests were performed on FiberForm* (precursor of PICA), virgin and charred PICA materials. Several samples of these materials were tested to investigate failure mechanisms at a microstructural scale. Stress-strain data were obtained simultaneously to estimate the fracture toughness. It was found that cracks initiated and grew in the FiberForm when a critical stress limit was reached such that the carbon fibers separated from the binder. However, both for virgin and charred PICA, crack initiation and growth occurred in the matrix (phenolic) phase. Both virgin and charred PICA showed greater strength values compared to FiberForm coupons, confirming that the presence of the porous matrix helps in absorbing the fracture energy.

  11. Monoethanolamine Impregnation of Titanosilicate Zeolite ETS-10.

    PubMed

    Tanchuk, Brenden; Sawada, James A; Kuznicki, Steven M

    2015-03-01

    ETS-10, a mixed octahedral/tetrahedral titanosilicate molecular sieve, has a unique architecture where its 0.8 nm pores are lined exclusively with silicon which imparts a high degree of chemical stability, yet the anionic framework can be modified by cation exchange. In this work, the hydrogen-exchanged form of ETS-10 was impregnated with monoethanolamine and the thermal stability and CO2 adsorption characteristics were analyzed. The surface area of the material was characterized by N2 physisorption, the thermal stability of the material assessed through TG-MS experiments, the CO2 capacity was measured via static volumetric adsorption experiments, and the influence of moisture as a carbamate promoter was investigated through a series of gravimetric CO2 adsorption/desorption cycling experiments. Several measurements converge on ~7 wt% monoethanolamine loading which occupies about half of the available pore volume of the sieve. The results suggest that the monoethanolamine is so effectively retained by the molecular sieve that, while the amine is effectively immobilized, under both humid and dry process streams the monoethanolamine is either chemically or sterically hindered and is unable to react measurable quantities of CO2. PMID:26413705

  12. A regulatory gene network related to the porcine umami taste receptor (TAS1R1/TAS1R3).

    PubMed

    Kim, J M; Ren, D; Reverter, A; Roura, E

    2016-02-01

    Taste perception plays an important role in the mediation of food choices in mammals. The first porcine taste receptor genes identified, sequenced and characterized, TAS1R1 and TAS1R3, were related to the dimeric receptor for umami taste. However, little is known about their regulatory network. The objective of this study was to unfold the genetic network involved in porcine umami taste perception. We performed a meta-analysis of 20 gene expression studies spanning 480 porcine microarray chips and screened 328 taste-related genes by selective mining steps among the available 12,320 genes. A porcine umami taste-specific regulatory network was constructed based on the normalized coexpression data of the 328 genes across 27 tissues. From the network, we revealed the 'taste module' and identified a coexpression cluster for the umami taste according to the first connector with the TAS1R1/TAS1R3 genes. Our findings identify several taste-related regulatory genes and extend previous genetic background of porcine umami taste.

  13. A Modeling Approach to Fiber Fracture in Melt Impregnation

    NASA Astrophysics Data System (ADS)

    Ren, Feng; Zhang, Cong; Yu, Yang; Xin, Chunling; Tang, Ke; He, Yadong

    2016-08-01

    The effect of process variables such as roving pulling speed, melt temperature and number of pins on the fiber fracture during the processing of thermoplastic based composites was investigated in this study. The melt impregnation was used in this process of continuous glass fiber reinforced thermoplastic composites. Previous investigators have suggested a variety of models for melt impregnation, while comparatively little effort has been spent on modeling the fiber fracture caused by the viscous resin. Herein, a mathematical model was developed for impregnation process to predict the fiber fracture rate and describe the experimental results with the Weibull intensity distribution function. The optimal parameters of this process were obtained by orthogonal experiment. The results suggest that the fiber fracture is caused by viscous shear stress on fiber bundle in melt impregnation mold when pulling the fiber bundle.

  14. REDFORD CORE MAKING MACHINE. RESIN IMPREGNATED SAND IS BLOWN INTO ...

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

    REDFORD CORE MAKING MACHINE. RESIN IMPREGNATED SAND IS BLOWN INTO THE HEATED CORE BOX THAT SETS THE RESIN CREATING THE HARDENED CORE SHOWN HERE. - Southern Ductile Casting Company, Core Making, 2217 Carolina Avenue, Bessemer, Jefferson County, AL

  15. Vacuum powder injector and method of impregnating fiber with powder

    NASA Technical Reports Server (NTRS)

    Working, Dennis C. (Inventor)

    1993-01-01

    A method and apparatus uniformly impregnate stranded material with dry powder such as low solubility, high melt flow polymer powder to produce, for example, composite prepregs. The stranded material is expanded in an impregnation chamber by an influx of air so that the powder, which may enter through the same inlet as the air, penetrates to the center of the stranded material. The stranded material then is contracted for holding the powder therein. The stranded material and powder may be pulled through the impregnation chamber in the same direction by vacuum. Larger particles of powder which do not fully penetrate the stranded material may be combed into the stranded material and powder which does not impregnate the stranded material may be collected and reused.

  16. Ice adhesion on lubricant-impregnated textured surfaces.

    PubMed

    Subramanyam, Srinivas Bengaluru; Rykaczewski, Konrad; Varanasi, Kripa K

    2013-11-01

    Ice accretion is an important problem and passive approaches for reducing ice-adhesion are of great interest in various systems such as aircrafts, power lines, wind turbines, and oil platforms. Here, we study the ice-adhesion properties of lubricant-impregnated textured surfaces. Force measurements show ice adhesion strength on textured surfaces impregnated with thermodynamically stable lubricant films to be higher than that on surfaces with excess lubricant. Systematic ice-adhesion measurements indicate that the ice-adhesion strength is dependent on texture and decreases with increasing texture density. Direct cryogenic SEM imaging of the fractured ice surface and the interface between ice and lubricant-impregnated textured surface reveal stress concentrators and crack initiation sites that can increase with texture density and result in lowering adhesion strength. Thus, lubricant-impregnated surfaces have to be optimized to outperform state-of-the-art icephobic treatments.

  17. Reducing Sliding Friction with Liquid-Impregnated Surfaces

    NASA Astrophysics Data System (ADS)

    Habibi, Mohammad; Collier, C. Patrick; Boreyko, Jonathan; Nature Inspired Fluids; Interfaces Team; CenterNanophase Materials Sciences Team

    2015-11-01

    Liquid-impregnated surfaces are fabricated by infusing a lubricating liquid into the micro/nano roughness of a textured substrate, such that the surface is slippery for any deposited liquid immiscible with the lubricant. To date, liquid-impregnated surfaces have almost exclusively focused on repelling liquids by minimizing the contact angle hysteresis. Here, we demonstrate that liquid-impregnated surfaces are also capable of reducing sliding friction for solid objects. Ordered arrays of silicon micropillars were infused with lubricating liquids varying in viscosity by two orders of magnitude. Five test surfaces were used: two different micropillared surfaces with and without liquid infusion and a smooth, dry control surface. The static and kinetic coefficients of friction were measured using a polished aluminum cube as the sliding object. Compared to the smooth control surface, the sliding friction was reduced by at least a factor of two on the liquid-impregnated surfaces.

  18. Wide-spectrum activity of a silver-impregnated fabric.

    PubMed

    Gerba, Charles P; Sifuentes, Laura Y; Lopez, Gerardo U; Abd-Elmaksoud, Sherif; Calabrese, Jesse; Tanner, Benjamin

    2016-06-01

    Fabrics, such as clothing, drapes, pillowcases, and bedsheets are potential sources of pathogenic bacteria and viruses. We found fabrics (ie, professional clothing, pillowcases, and lab coats) treated with a silver-impregnated material to be effective in significantly reducing a wide spectrum of ordinary and drug-resistant microorganisms, including Salmonella, methicillin-resistant Staphylococcus aureus, Propionibacterium acnes, Trichphyton mentagrophytes, and norovirus. Fabrics impregnated with antimicrobial agents help provide an additional barrier to the transport or reservoir of pathogens in health care environments.

  19. The MC1R Gene and Youthful Looks.

    PubMed

    Liu, Fan; Hamer, Merel A; Deelen, Joris; Lall, Japal S; Jacobs, Leonie; van Heemst, Diana; Murray, Peter G; Wollstein, Andreas; de Craen, Anton J M; Uh, Hae-Won; Zeng, Changqing; Hofman, Albert; Uitterlinden, André G; Houwing-Duistermaat, Jeanine J; Pardo, Luba M; Beekman, Marian; Slagboom, P Eline; Nijsten, Tamar; Kayser, Manfred; Gunn, David A

    2016-05-01

    Looking young for one's age has been a desire since time immemorial. This desire is attributable to the belief that appearance reflects health and fecundity. Indeed, perceived age predicts survival [1] and associates with molecular markers of aging such as telomere length [2]. Understanding the underlying molecular biology of perceived age is vital for identifying new aging therapies among other purposes, but studies are lacking thus far. As a first attempt, we performed genome-wide association studies (GWASs) of perceived facial age and wrinkling estimated from digital facial images by analyzing over eight million SNPs in 2,693 elderly Dutch Europeans from the Rotterdam Study. The strongest genetic associations with perceived facial age were found for multiple SNPs in the MC1R gene (p < 1 × 10(-7)). This effect was enhanced for a compound heterozygosity marker constructed from four pre-selected functional MC1R SNPs (p = 2.69 × 10(-12)), which was replicated in 599 Dutch Europeans from the Leiden Longevity Study (p = 0.042) and in 1,173 Europeans of the TwinsUK Study (p = 3 × 10(-3)). Individuals carrying the homozygote MC1R risk haplotype looked on average up to 2 years older than non-carriers. This association was independent of age, sex, skin color, and sun damage (wrinkling, pigmented spots) and persisted through different sun-exposure levels. Hence, a role for MC1R in youthful looks independent of its known melanin synthesis function is suggested. Our study uncovers the first genetic evidence explaining why some people look older for their age and provides new leads for further investigating the biological basis of how old or young people look. PMID:27133870

  20. The MC1R Gene and Youthful Looks.

    PubMed

    Liu, Fan; Hamer, Merel A; Deelen, Joris; Lall, Japal S; Jacobs, Leonie; van Heemst, Diana; Murray, Peter G; Wollstein, Andreas; de Craen, Anton J M; Uh, Hae-Won; Zeng, Changqing; Hofman, Albert; Uitterlinden, André G; Houwing-Duistermaat, Jeanine J; Pardo, Luba M; Beekman, Marian; Slagboom, P Eline; Nijsten, Tamar; Kayser, Manfred; Gunn, David A

    2016-05-01

    Looking young for one's age has been a desire since time immemorial. This desire is attributable to the belief that appearance reflects health and fecundity. Indeed, perceived age predicts survival [1] and associates with molecular markers of aging such as telomere length [2]. Understanding the underlying molecular biology of perceived age is vital for identifying new aging therapies among other purposes, but studies are lacking thus far. As a first attempt, we performed genome-wide association studies (GWASs) of perceived facial age and wrinkling estimated from digital facial images by analyzing over eight million SNPs in 2,693 elderly Dutch Europeans from the Rotterdam Study. The strongest genetic associations with perceived facial age were found for multiple SNPs in the MC1R gene (p < 1 × 10(-7)). This effect was enhanced for a compound heterozygosity marker constructed from four pre-selected functional MC1R SNPs (p = 2.69 × 10(-12)), which was replicated in 599 Dutch Europeans from the Leiden Longevity Study (p = 0.042) and in 1,173 Europeans of the TwinsUK Study (p = 3 × 10(-3)). Individuals carrying the homozygote MC1R risk haplotype looked on average up to 2 years older than non-carriers. This association was independent of age, sex, skin color, and sun damage (wrinkling, pigmented spots) and persisted through different sun-exposure levels. Hence, a role for MC1R in youthful looks independent of its known melanin synthesis function is suggested. Our study uncovers the first genetic evidence explaining why some people look older for their age and provides new leads for further investigating the biological basis of how old or young people look.

  1. A Model for Tow Impregnation and Consolidation for Partially Impregnated Thermoset Prepregs

    SciTech Connect

    John J. Gangloff Jr; Shatil Sinha; Suresh G. Advani

    2011-05-23

    The formation and transport of voids in composite materials remains a key research area in composite manufacturing science. Knowledge of how voids, resin, and fiber reinforcement propagate throughout a composite material continuum from green state to cured state during an automated tape layup process is key to minimizing defects induced by void-initiated stress concentrations under applied loads for a wide variety of composite applications. This paper focuses on modeling resin flow in a deforming fiber tow during an automated process of partially impregnated thermoset prepreg composite material tapes. In this work, a tow unit cell based model has been presented that determines the consolidation and impregnation of a thermoset prepreg tape under an input pressure profile. A parametric study has been performed to characterize the behavior of varying tow speed and compaction forces on the degree of consolidation. Results indicate that increased tow consolidation is achieved with slower tow speeds and higher compaction forces although the relationship is not linear. The overall modeling of this project is motivated to address optimization of the 'green state' composite properties and processing parameters to reduce or eliminate 'cured state' defects, such as porosity and de-lamination. This work is partially funded by the Department of Energy under Award number DE-EE0001367.

  2. TSS-1R satellite integration in O&C Building

    NASA Technical Reports Server (NTRS)

    1995-01-01

    John Powell (left) and Jim Nail (second from right) of McDonnell Douglas Space and Defense Systems prepare the satellite element of the Tethered Satellite System-1R (TSS-1R) for integration with its support unit in the Operations and Checkout (O&C) Building. The TSS-1R is one of two primary payloads scheduled to fly aboard the Orbiter Columbia during the STS-75 mission in early 1996. The TSS program is a joint venture between NASA and the Agenzia Spaziale Italiana, or Italian Space Agency. The 'R' designation indicates a reflight. The TSS-1 flew aboard Atlantis during the STS-46 mission in July 1992 and achieved only a partial success when its tether reel mechanism became jammed after only approximately 840 feet of the 12-mile-long tether had been unwound as the satellite rose from its cradle in the orbiter's payload bay. Once deployed to the 12-mile height on the STS-75 mission, the satellite will be used to validate theories that such a system could possibly be used in the future to generate electrical power to power orbital systems, raise and lower spacecraft, study atmospheric conditions at several different heights and for many other applications.

  3. Pyrolysis of phenolic impregnated carbon ablator (PICA).

    PubMed

    Bessire, Brody K; Lahankar, Sridhar A; Minton, Timothy K

    2015-01-28

    Molar yields of the pyrolysis products of thermal protection systems (TPSs) are needed in order to improve high fidelity material response models. The volatile chemical species evolved during the pyrolysis of a TPS composite, phenolic impregnated carbon ablator (PICA), have been probed in situ by mass spectrometry in the temperature range 100 to 935 °C. The relative molar yields of the desorbing species as a function of temperature were derived by fitting the mass spectra, and the observed trends are interpreted in light of the results of earlier mechanistic studies on the pyrolysis of phenolic resins. The temperature-dependent product evolution was consistent with earlier descriptions of three stages of pyrolysis, with each stage corresponding to a temperature range. The two main products observed were H2O and CO, with their maximum yields occurring at ∼350 °C and ∼450 °C, respectively. Other significant products were CH4, CO2, and phenol and its methylated derivatives; these products tended to desorb concurrently with H2O and CO, over the range from about 200 to 600 °C. H2 is presumed to be the main product, especially at the highest pyrolysis temperatures used, but the relative molar yield of H2 was not quantified. The observation of a much higher yield of CO than CH4 suggests the presence of significant hydroxyl group substitution on phenol prior to the synthesis of the phenolic resin used in PICA. The detection of CH4 in combination with the methylated derivatives of phenol suggests that the phenol also has some degree of methyl substitution. The methodology developed is suitable for real-time measurements of PICA pyrolysis and should lend itself well to the validation of nonequilibrium models whose aim is to simulate the response of TPS materials during atmospheric entry of spacecraft.

  4. Fracture Resistance of Composite Fixed Partial Dentures Reinforced with Pre-impregnated and Non-impregnated Fibers

    PubMed Central

    Mosharraf, Ramin; Torkan, Sepideh

    2012-01-01

    Background and aims The mechanical properties of fiber-reinforced composite fixed partial dentures (FPDs) are af-fected by fiber impregnation. The aim of this in vitro study was to compare the fracture resistance of composite fixed partialdentures reinforced with pre-impregnated and non-impregnated fibers. Materials and methods Groups (n=5) of three-unit fiber-reinforced composite FPDs (23 mm in length) from maxillary second premolar to maxillary second molar were fabricated on two abutments with pontic width of 12 mm. One group was fabricated as the control group with composite (Gradia) and the other two groups were fabricated with composite (Gradia) reinforced with pre-impregnated fiber (Fibrex ribbon) and non-impregnated fiber (Fiber braid), respectively. The specimens were stored in distilled water for one week at 37°C and then tested in a universal testing machine by means of a three-point bending test. Statistical analysis consisted of one-way ANOVA and a post hoc Scheffé’s test for the test groups (α=0.05). Results Fracture resistance (N) differed significantly between the control group and the other two groups (P<0.001), but there were no statistically significant differences between the pre-impregnated and non-impregnated groups (P=0.565). The degree of deflection measured (mm) did not differ significantly between the three groups (P=0.397), yet the mean deflection measured in pre-impregnated group was twice as that in the other two groups. Conclusion Reinforcement of composite with fiber might considerably increase the fracture resistance of FPDs; how-ever, the type of the fiber used resulted in no significant difference in fracture resistance of FPD specimens. PMID:22991628

  5. Degradation free epoxy impregnation of REBCO coils and cables

    NASA Astrophysics Data System (ADS)

    Barth, C.; Bagrets, N.; Weiss, K.-P.; Bayer, C. M.; Bast, T.

    2013-05-01

    In applications utilizing high-temperature superconductors (HTS) under high mechanical loads as high-field magnets or rotors of generators and motors, the rare-earth-barium-copper-oxide (REBCO) tapes have to be stabilized mechanically. This is achieved using support structures of structural materials and filling the voids in the support through the impregnation of the tapes. The impregnation prevents movement of the tapes and distributes mechanical loads evenly. With high mechanical strengths and low sensitivities to rapid temperature changes, epoxy resins are desired materials for the impregnation of superconductor tapes. However, a strong decrease of the current-carrying capabilities was observed in previous epoxy-impregnated REBCO coils. In this work the thermal expansion mismatches between epoxy resins and REBCO tapes are identified as the cause of these degradations. Fillers are used to reduce the thermal expansions of glues and resins. Mixtures with varying filler contents are analyzed systematically. Their thermal expansions and the corresponding degradations of short REBCO tape samples are measured. A mixture of epoxy resin and filler is found which allows degradation-free impregnation of REBCO tapes. This mixture is validated on a 1.2 m long 15 × 5 Roebel-assembled-coated-conductor (RACC) cable from Industrial Research Limited (IRL).

  6. Evaluation of IGF1R and phosphorylated IGF1R as targets in HER2-positive breast cancer cell lines and tumours.

    PubMed

    Browne, Brigid C; Eustace, Alex J; Kennedy, Susan; O'Brien, Neil A; Pedersen, Kasper; McDermott, Martina S J; Larkin, Annemarie; Ballot, Jo; Mahgoub, Thamir; Sclafani, Francesco; Madden, Stephen; Kennedy, John; Duffy, Michael J; Crown, John; O'Donovan, Norma

    2012-12-01

    Insulin-like growth factor-1 receptor (IGF1R) signalling is implicated in resistance to trastuzumab. However, the benefit of co-targeting HER2 and IGF1R has not been extensively studied, and the relationship between activated IGF1R and clinical response to trastuzumab has not been reported. This study aimed to evaluate the combination of trastuzumab with IGF1R tyrosine kinase inhibitors (TKIs) in a panel of HER2-positive breast cancer cell lines, and to examine the relationship between IGF1R expression and activation and response to trastuzumab in HER2-positive breast cancer patients. The anti-proliferative effects of trastuzumab combined with IGF1R TKIs BMS-536924 or NVP-AEW541 were measured in nine HER2-positive cell lines. IGF1R and phosphorylated IGF1R/insulin receptor (pIGF1R/IR) were measured by immunohistochemistry in 160 tumour samples from trastuzumab-treated patients (ICORG 06-22). The HER2-positive cell lines displayed varying sensitivity to IGF1R TKIs alone (IC(50)s: 0.7 to >10 μM). However, when combined with trastuzumab, a significantly enhanced effect was observed in five cell lines treated with BMS-536924, and three with NVP-AEW541. While IGF1R levels correlated with reduced response to NVP-AEW541 alone, neither IGF1R nor pIGF1R were predictive of response to BMS-536924 or NVP-AEW541 in combination with trastuzumab. Low HER2 levels correlated with response to BMS-536924 in combination with trastuzumab. Akt levels correlated with improved response to trastuzumab and NVP-AEW541 (P = 0.039). Cytoplasmic IGF1R staining was observed in all tumours, membrane IGF1R was detected in 13.8 %, and pIGF1R/IR was detected in 48.8 %. Although membrane IGF1R staining was associated with larger tumour size (P = 0.041), and lower tumour grade (P = 0.024), no association between IGF1R or pIGF1R/IR and patient survival was observed. In conclusion, while neither IGF1R expression nor activation was predictive of response to trastuzumab, these pre-clinical data provide

  7. Nitric acid vapor removal by activated, impregnated carbons

    SciTech Connect

    Wood, G.O.

    1996-12-31

    Laboratory and industrial workers can be exposed to vapors of nitric acid, especially in accidents, such as spills. Nitric acid can also be a product of incineration for energy production or waste (e.g., CW agent) disposal. Activated carbons containing impregnants for enhancing vapor and gas removal have been tested for effectiveness in removing vapors of nitric acid from air. The nitric acid vapor was generated from concentrated acid solutions and detected by trapping in a water bubbler for pH measurements. Both low and moderate relative humidity conditions were used. All carbons were effective at vapor contact times representative of air-purifying respirator use. One surprising observation was the desorption of low levels of ammonia from impregnated carbons. This was apparently due to residual ammonia from the impregnation processes.

  8. Impregnation of softwood cell walls with melamine-formaldehyde resin.

    PubMed

    Gindl, W; Zargar-Yaghubi, F; Wimmer, R

    2003-05-01

    Melamine-formaldehyde (MF) resin impregnation has shown considerable potential to improve a number of wood properties, such as surface hardness and weathering resistance. In this study, selected factors influencing the uptake of MF resin into the cell wall of softwood were studied. Using UV-microspectroscopy, it could be shown that water soluble MF diffused well into the secondary cell wall and the middle lamella. Concentrations as high as 24% (v/v) were achieved after an impregnation of 20 h. High cell wall moisture content, high water content of the resin used for impregnation, and low extractive content are factors which are favourable for MF resin uptake into the cell wall. For dry cell walls, solvent exchange drying improved resin uptake to a similar extent, as was the case when cell walls were soaked in water.

  9. Resin impregnation process for producing a resin-fiber composite

    NASA Technical Reports Server (NTRS)

    Palmer, Raymond J. (Inventor); Moore, William E. (Inventor)

    1994-01-01

    Process for vacuum impregnation of a dry fiber reinforcement with a curable resin to produce a resin-fiber composite, by drawing a vacuum to permit flow of curable liquid resin into and through a fiber reinforcement to impregnate same and curing the resin-impregnated fiber reinforcement at a sufficient temperature and pressure to effect final curing. Both vacuum and positive pressure, e.g. autoclave pressure, are applied to the dry fiber reinforcement prior to application of heat and prior to any resin flow to compact the dry fiber reinforcement, and produce a resin-fiber composite of reduced weight, thickness and resin content, and improved mechanical properties. Preferably both a vacuum and positive pressure, e.g. autoclave pressure, are also applied during final curing.

  10. Impregnation of softwood cell walls with melamine-formaldehyde resin.

    PubMed

    Gindl, W; Zargar-Yaghubi, F; Wimmer, R

    2003-05-01

    Melamine-formaldehyde (MF) resin impregnation has shown considerable potential to improve a number of wood properties, such as surface hardness and weathering resistance. In this study, selected factors influencing the uptake of MF resin into the cell wall of softwood were studied. Using UV-microspectroscopy, it could be shown that water soluble MF diffused well into the secondary cell wall and the middle lamella. Concentrations as high as 24% (v/v) were achieved after an impregnation of 20 h. High cell wall moisture content, high water content of the resin used for impregnation, and low extractive content are factors which are favourable for MF resin uptake into the cell wall. For dry cell walls, solvent exchange drying improved resin uptake to a similar extent, as was the case when cell walls were soaked in water. PMID:12507874

  11. Epoxy resin developments for large superconducting magnets impregnation

    NASA Astrophysics Data System (ADS)

    Rey, J. M.; Gallet, B.; Kircher, F.; Lottin, J. C.

    The future detectors ATLAS and CMS of the Large Hadron Collider at CERN will use two huge superconducting magnets. Both are now under design, and their electrical insulation could be realized using epoxy resin and a wet impregnation technique. Because of their large dimensions, and the indirect cooling of the superconductor, the strengths of the resin and of the resin/conductor interface are of major importance. A new generation of epoxy resins for vacuum/pressure impregnation methods has been tested, and compared with some classical and well-known epoxy resins used in impregnation techniques. In order to understand the mechanical behaviour at 4 K, the complete evolution from liquid state to low temperature service condition is considered. The paper will present some results on the mechanical properties, the density and the chemical shrinkage occurring during the polymerization and the thermal contraction between room temperature and 4 K for these different types of epoxy resins.

  12. Distribution of the orexin-1 receptor (OX1R) in the mouse forebrain and rostral brainstem: A characterisation of OX1R-eGFP mice.

    PubMed

    Ch'ng, Sarah Sulaiman; Lawrence, Andrew J

    2015-01-01

    We have utilised a transgenic reporter mouse in which green fluorescent protein (GFP) expression is driven by the orexin-1 receptor (OX1R) promoter to systematically map the distribution of OX1R-expressing neurons throughout the mouse forebrain and rostral brainstem. GFP labelling was observed in perikarya and fibres in an extensive range of brain loci encompassing the olfactory and cerebral cortices, dorsal and ventral pallidum, hippocampus, amygdaloid regions, septal areas, thalamic nuclei, hypothalamic nuclei and several brainstem regions, consistent with previous studies of OX1R mRNA expression. This is the first study to systematically characterise the neuroanatomical distribution of OX1R in the OX1R-eGFP mouse, confirming its veracity as a faithful reporter of OX1R expression and utility for future studies assessing the role of OX1R in more complex behaviours.

  13. Gallocyanin-chrome alum counterstaining of Golgi-Kopsch impregnations.

    PubMed

    Tieman, S B

    1983-05-01

    A simple technique is described for counterstaining Golgi-Kopsch impregnations. The sections are first stabilized by the method of Geisert and Updyke and then stained in 0.15% gallocyanin and 5% chromium potassium sulfate for 45 minutes at 55-60 C. The sections are then rinsed, dehydrated to 70% ethanol, cleared in terpineol, mounted and coverslipped. This procedure results in a light to medium blue stain of those cells not impregnated by the silver chromate. The major advantages of this procedure over earlier methods are: (1) the counterstain does not fade and (2) since no differentiation is required, many sections may be stained simultaneously.

  14. PROCESS OF PREPARING URANIUM-IMPREGNATED GRAPHITE BODY

    DOEpatents

    Kanter, M.A.

    1958-05-20

    A method for the fabrication of graphite bodies containing uniformly distributed uranium is described. It consists of impregnating a body of graphite having uniform porosity and low density with an aqueous solution of uranyl nitrate hexahydrate preferably by a vacuum technique, thereafter removing excess aqueous solution from the surface of the graphite, then removing the solvent water from the body under substantially normal atmospheric conditions of temperature and pressure in the presence of a stream of dry inert gas, and finally heating the dry impregnated graphite body in the presence of inert gas at a temperature between 800 and 1400 d C to convert the uranyl nitrate hexahydrate to an oxide of uranium.

  15. Preparation and properties of polytetrafluoroethylene impregnated with rhenium oxides

    NASA Technical Reports Server (NTRS)

    Leibecki, H. F.; Easter, R. W.

    1973-01-01

    The results of tests carried out to determine the properties of polytetrafluorethylene (PTFE) impregnated with rhenium oxides are presented. The tests included measurement of physical properties of the impregnated material and investigation of the effects of preparation process variables. Based on the latter tests a mechanism to describe the permeation process is postulated which identifies the rate controlling step to be diffusion of ReF6 molecules into the solid during the initial ReF6 soak. Physical property tests indicated that the electronic conductance is increased by many orders of magnitude while the desirable properties of the PTFE remain virtually unchanged.

  16. Environmental Testing of the NEXT PM1R Ion Engine

    NASA Technical Reports Server (NTRS)

    Snyder, John S.; Anderson, John R.; VanNoord, Jonathan L.; Soulas, George C.

    2007-01-01

    The NEXT propulsion system is an advanced ion propulsion system presently under development that is oriented towards robotic exploration of the solar system using solar electric power. The subsystem includes an ion engine, power processing unit, feed system components, and thruster gimbal. The Prototype Model engine PM1 was subjected to qualification-level environmental testing in 2006 to demonstrate compatibility with environments representative of anticipated mission requirements. Although the testing was largely successful, several issues were identified including the fragmentation of potting cement on the discharge and neutralizer cathode heater terminations during vibration which led to abbreviated thermal testing, and generation of particulate contamination from manufacturing processes and engine materials. The engine was reworked to address most of these findings, renamed PM1R, and the environmental test sequence was repeated. Thruster functional testing was performed before and after the vibration and thermal-vacuum tests. Random vibration testing, conducted with the thruster mated to the breadboard gimbal, was executed at 10.0 Grms for 2 min in each of three axes. Thermal-vacuum testing included three thermal cycles from 120 to 215 C with hot engine re-starts. Thruster performance was nominal throughout the test program, with minor variations in a few engine operating parameters likely caused by facility effects. There were no significant changes in engine performance as characterized by engine operating parameters, ion optics performance measurements, and beam current density measurements, indicating no significant changes to the hardware as a result of the environmental testing. The NEXT PM1R engine and the breadboard gimbal were found to be well-designed against environmental requirements based on the results reported herein. The redesigned cathode heater terminations successfully survived the vibration environments. Based on the results of this test

  17. Prognostic significance of MST1R dysregulation in renal cell tumors

    PubMed Central

    Pires-Luís, Ana S; Vieira-Coimbra, Márcia; Ferreira, Maria João; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Antunes, Luís; Dias, Paula C; Lobo, Francisco; Oliveira, Jorge; Graça, Inês; Henrique, Rui; Jerónimo, Carmen

    2016-01-01

    Macrophage stimulating 1 receptor (MST1R) is a C-MET proto-oncogene family receptor tyrosine kinase. Promoter methylation patterns determine transcription of MST1R variants as hypermethylation of a region upstream of transcription start site (TSS) is associated with lack of MST1R long transcript (MST1R long) and expression of a short transcript with oncogenic potential. Thus, we aimed to investigate MST1R variant transcript regulation in renal cell tumors (RCT) and assess their prognostic potential. We found, in a series of 120 RCT comprising the four main subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma), that higher methylation levels close to TSS were associated with total MST1R expression levels (MST1R total) in primary tumors (p=0.049) and renal cancer cell lines. After demethylating treatment, MST1R long/MST1R total ratio increased, as expected, in two renal cell carcinoma cell lines tested. However, in primary tumors with hypermethylation upstream of TSS, a decrease in MST1R long/MST1R total ratio was not detected, although higher expression ratio of nuclear factor-κB was apparent. Furthermore, survival analysis demonstrated that MST1R long/MST1R total ratio was independently associated with shorter disease-specific and disease-free survival, whereas MST1R total expression associated with shorter disease-specific survival. In conclusion, although promoter methylation patterns seem to determine MST1R global transcription regulation in renal cell carcinoma, other mechanisms might contribute to deregulate MST1R variant expression in RCT. Nevertheless, MST1R total expression and MST1R long/MST1R total ratio modulate the biological and clinical aggressiveness of renal cell carcinoma, as depicted by its prognostic significance, a finding that requires validation in a larger independent series. PMID:27648366

  18. Prognostic significance of MST1R dysregulation in renal cell tumors

    PubMed Central

    Pires-Luís, Ana S; Vieira-Coimbra, Márcia; Ferreira, Maria João; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Antunes, Luís; Dias, Paula C; Lobo, Francisco; Oliveira, Jorge; Graça, Inês; Henrique, Rui; Jerónimo, Carmen

    2016-01-01

    Macrophage stimulating 1 receptor (MST1R) is a C-MET proto-oncogene family receptor tyrosine kinase. Promoter methylation patterns determine transcription of MST1R variants as hypermethylation of a region upstream of transcription start site (TSS) is associated with lack of MST1R long transcript (MST1R long) and expression of a short transcript with oncogenic potential. Thus, we aimed to investigate MST1R variant transcript regulation in renal cell tumors (RCT) and assess their prognostic potential. We found, in a series of 120 RCT comprising the four main subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma), that higher methylation levels close to TSS were associated with total MST1R expression levels (MST1R total) in primary tumors (p=0.049) and renal cancer cell lines. After demethylating treatment, MST1R long/MST1R total ratio increased, as expected, in two renal cell carcinoma cell lines tested. However, in primary tumors with hypermethylation upstream of TSS, a decrease in MST1R long/MST1R total ratio was not detected, although higher expression ratio of nuclear factor-κB was apparent. Furthermore, survival analysis demonstrated that MST1R long/MST1R total ratio was independently associated with shorter disease-specific and disease-free survival, whereas MST1R total expression associated with shorter disease-specific survival. In conclusion, although promoter methylation patterns seem to determine MST1R global transcription regulation in renal cell carcinoma, other mechanisms might contribute to deregulate MST1R variant expression in RCT. Nevertheless, MST1R total expression and MST1R long/MST1R total ratio modulate the biological and clinical aggressiveness of renal cell carcinoma, as depicted by its prognostic significance, a finding that requires validation in a larger independent series.

  19. Prognostic significance of MST1R dysregulation in renal cell tumors.

    PubMed

    Pires-Luís, Ana S; Vieira-Coimbra, Márcia; Ferreira, Maria João; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Antunes, Luís; Dias, Paula C; Lobo, Francisco; Oliveira, Jorge; Graça, Inês; Henrique, Rui; Jerónimo, Carmen

    2016-01-01

    Macrophage stimulating 1 receptor (MST1R) is a C-MET proto-oncogene family receptor tyrosine kinase. Promoter methylation patterns determine transcription of MST1R variants as hypermethylation of a region upstream of transcription start site (TSS) is associated with lack of MST1R long transcript (MST1R long) and expression of a short transcript with oncogenic potential. Thus, we aimed to investigate MST1R variant transcript regulation in renal cell tumors (RCT) and assess their prognostic potential. We found, in a series of 120 RCT comprising the four main subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma), that higher methylation levels close to TSS were associated with total MST1R expression levels (MST1R total) in primary tumors (p=0.049) and renal cancer cell lines. After demethylating treatment, MST1R long/MST1R total ratio increased, as expected, in two renal cell carcinoma cell lines tested. However, in primary tumors with hypermethylation upstream of TSS, a decrease in MST1R long/MST1R total ratio was not detected, although higher expression ratio of nuclear factor-κB was apparent. Furthermore, survival analysis demonstrated that MST1R long/MST1R total ratio was independently associated with shorter disease-specific and disease-free survival, whereas MST1R total expression associated with shorter disease-specific survival. In conclusion, although promoter methylation patterns seem to determine MST1R global transcription regulation in renal cell carcinoma, other mechanisms might contribute to deregulate MST1R variant expression in RCT. Nevertheless, MST1R total expression and MST1R long/MST1R total ratio modulate the biological and clinical aggressiveness of renal cell carcinoma, as depicted by its prognostic significance, a finding that requires validation in a larger independent series. PMID:27648366

  20. IGF-1R Inhibition Activates a YES/SFK Bypass Resistance Pathway: Rational Basis for Co-Targeting IGF-1R and Yes/SFK Kinase in Rhabdomyosarcoma.

    PubMed

    Wan, Xiaolin; Yeung, Choh; Heske, Christine; Mendoza, Arnulfo; Helman, Lee J

    2015-04-01

    The insulin-like growth factor 1 receptor (IGF-1R) has surfaced as a significant target in multiple solid cancers due to its fundamental roles in pro-survival and anti-apoptotic signaling. However, development of resistance to IGF-1R blockade represents a significant hindrance and limits treatment efficacy in the clinic. In this study, we identified acquired resistance to IGF-1R blockade with R1507, an antibody against IGF-1R, and with BMS-754807, a small molecular inhibitor of IGF-1R/insulin receptor (IR). We showed that treatment with an IGF-IR antibody, R1507, or an IR/IGF-IR kinase inhibitor, BMS-754807, was associated with increased activation of YES/SRC family tyrosine kinase (SFK) in rhabdomyosarcoma (RMS). Combining anti-IGF-1R agents with SFK inhibitors resulted in blockade of IGF-1R inhibition-induced activation of YES/SFK and displayed advantageous antitumor activity in vitro and in vivo. Our data provide evidence that IGF-1R blockade results in activation of the YES/SRC family kinase bypass resistance pathway in vitro and in vivo. This may be of particular clinical relevance since both Yes and IGF components are overexpressed in RMS. Increased YES/SFK activation might serve as a clinical biomarker for predicting tumor resistance to IGF-1R inhibition. Dual inhibition of IGF-1R and SFK may have a broader and enhanced clinical benefit for patients with RMS.

  1. ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents.

    PubMed

    Mancarella, Caterina; Casanova-Salas, Irene; Calatrava, Ana; Ventura, Selena; Garofalo, Cecilia; Rubio-Briones, José; Magistroni, Vera; Manara, Maria Cristina; López-Guerrero, José Antonio; Scotlandi, Katia

    2015-06-30

    Identifying patients who may benefit from targeted therapy is an urgent clinical issue in prostate cancer (PCa). We investigated the molecular relationship between TMPRSS2-ERG (T2E) fusion gene and insulin-like growth factor receptor (IGF-1R) to optimize the use of IGF-1R inhibitors.IGF-1R was analyzed in cell lines and in radical prostatectomy specimens in relation to T2E status. ERG binding to IGF-1R promoter was evaluated by chromatin immunoprecipitation (ChIP). Sensitivity to anti-IGF-1R agents was evaluated alone or in combination with anti-androgen abiraterone acetate in vitro at basal levels or upon ERG modulation.IGF-1R analysis performed in PCa cells or clinical samples showed that T2E expression correlated with higher IGF-1R expression at mRNA and protein levels. Genetic modulation of ERG directly affected IGF-1R protein levels in vitro. ChIP analysis showed that ERG binds IGF-1R promoter and that promoter occupancy is higher in T2E-positive cells. IGF-1R inhibition was more effective in cell lines expressing the fusion gene and combination of IGF-1R inhibitors with abiraterone acetate produced synergistic effects in T2E-expressing cells.Here, we provide the rationale for use of T2E fusion gene to select PCa patients for anti-IGF-1R treatments. The combination of anti-IGF-1R-HAbs with an anti-androgen therapy is strongly advocated for patients expressing T2E.

  2. ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents

    PubMed Central

    Mancarella, Caterina; Casanova-Salas, Irene; Calatrava, Ana; Ventura, Selena; Garofalo, Cecilia; Rubio-Briones, José; Magistroni, Vera; Manara, Maria Cristina; López-Guerrero, José Antonio; Scotlandi, Katia

    2015-01-01

    Identifying patients who may benefit from targeted therapy is an urgent clinical issue in prostate cancer (PCa). We investigated the molecular relationship between TMPRSS2-ERG (T2E) fusion gene and insulin-like growth factor receptor (IGF-1R) to optimize the use of IGF-1R inhibitors. IGF-1R was analyzed in cell lines and in radical prostatectomy specimens in relation to T2E status. ERG binding to IGF-1R promoter was evaluated by chromatin immunoprecipitation (ChIP). Sensitivity to anti-IGF-1R agents was evaluated alone or in combination with anti-androgen abiraterone acetate in vitro at basal levels or upon ERG modulation. IGF-1R analysis performed in PCa cells or clinical samples showed that T2E expression correlated with higher IGF-1R expression at mRNA and protein levels. Genetic modulation of ERG directly affected IGF-1R protein levels in vitro. ChIP analysis showed that ERG binds IGF-1R promoter and that promoter occupancy is higher in T2E-positive cells. IGF-1R inhibition was more effective in cell lines expressing the fusion gene and combination of IGF-1R inhibitors with abiraterone acetate produced synergistic effects in T2E-expressing cells. Here, we provide the rationale for use of T2E fusion gene to select PCa patients for anti-IGF-1R treatments. The combination of anti-IGF-1R-HAbs with an anti-androgen therapy is strongly advocated for patients expressing T2E. PMID:25906745

  3. Leaching of Silver from Silver-Impregnated Food Storage Containers

    ERIC Educational Resources Information Center

    Hauri, James F.; Niece, Brian K.

    2011-01-01

    The use of silver in commercial products has proliferated in recent years owing to its antibacterial properties. Food containers impregnated with micro-sized silver promise long food life, but there is some concern because silver can leach out of the plastic and into the stored food. This laboratory experiment gives students the opportunity to…

  4. X-ray initiated polymerization of wood impregnants

    NASA Astrophysics Data System (ADS)

    Cleland, Marshall R.; Galloway, Richard A.; Berejka, Anthony J.; Montoney, Daniel; Driscoll, Mark; Smith, Leonard; Scott Larsen, L.

    2009-07-01

    X-rays, derived from a high energy, high-current electron beam (EB), initiated in-situ polymerization of a unique class of monomers that were found to penetrate the cell walls of wood. X-rays initiated an auto-catalytic acrylic polymerization and penetrated through thick pieces of wood. The final cured product having the polymerizate, a polymer, both in the wood cell lumens and in the cell walls is called wood impregnated with a wood-polymer penetrant (WPP). The controlled lower dose rate of X-rays overcame disproportionation encountered when using higher dose-rate electron beam initiation. With X-rays, the in-situ polymerization took place in one exposure of modest dose. With EB, multiple passes were needed to avoid excessive heat build-up and monomer volatilization. Having entered the cell walls of the wood and then being polymerized within the cell walls, these radiation-cured unique monomers imparted outstanding dimensional stability upon exposure of the impregnated wood to humidity cycling. The preferred monomer system was also chemically modified prior to impregnation with agents that would remain in the wood and prevent the growth of fungi and other microbials. This technique differs from historic uses of monomers that merely filled the lumens of the wood (historic wood-polymer composites), which are only suitable for indoor use. The WPP impregnated wood that was either X-ray cured or EB cured demonstrated enhanced structural properties, dimensional stability, and decay resistance.

  5. Optical Imaging of Water Condensation on Lubricant Impregnated Micropillar Arrays

    NASA Astrophysics Data System (ADS)

    Kajiya, Tadashi; Schellenberger, Frank; Papadopoulos, Periklis; Vollmer, Doris; Butt, Hans-Jürgen

    2015-11-01

    We explored the condensation of water drops on a lubricant-impregnated surface, i.e., a micropillar patterned surface impregnated with a ionic liquid. Growing drops were imaged in 3D using a laser scanning confocal microscope equipped with a temperature and humidity control. On a lubricant-impregnated hydrophobic micropillar array, different stages of condensation can be discriminated: - Nucleation on a lubricant surface. - Regular alignement between micropillars and formation of a three-phase contact line on a bottom of the substrate. - Deformation and bridging by coalescence, leading to a detachment of the drops from the bottom substrate to pillars'top faces. However, on a lubricant-impregnated hydrophilic micropillar array, the condensed water covers the micropillars by dewetting the lubricant. As a result, the surface loses its slippery property. Our results provide fundamental concepts how these solid/liquid hybrid surfaces can be applied for facile removal of condensed water, as well as necessity of the appropriate surface treatment. Financial support from ERC for the advanced grant 340391-SUPRO is gratefully acknowledged.

  6. Improved method facilitates debulking and curing of phenolic impregnated asbestos

    NASA Technical Reports Server (NTRS)

    Gaines, P.

    1966-01-01

    Workpieces covered with phenolic impregnated asbestos tape and then wrapped with a specified thickness of nylon yarn under pressure, are debulked and cured in a standard oven. This method of debulking and curing is used in the fabrication of ablative chambers for the Gemini and Apollo attitude control engines.

  7. Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing.

    PubMed

    Shirazi-Beechey, Soraya P; Daly, Kristian; Al-Rammahi, Miran; Moran, Andrew W; Bravo, David

    2014-06-01

    Luminal nutrient sensing by G-protein-coupled receptors (GPCR) expressed on the apical domain of enteroendocrine cells activates intracellular pathways leading to secretion of gut hormones that control vital physiological processes such as digestion, absorption, food intake and glucose homeostasis. The taste 1 receptor (T1R) family of GPCR consists of three members: T1R1; T1R2; T1R3. Expression of T1R1, T1R2 and T1R3 at mRNA and protein levels has been demonstrated in the intestinal tissue of various species. It has been shown that T1R2-T1R3, in association with G-protein gustducin, is expressed in intestinal K and L endocrine cells, where it acts as the intestinal glucose (sweet) sensor. A number of studies have demonstrated that activation of T1R2-T1R3 by natural sugars and artificial sweeteners leads to secretion of glucagon-like peptides 1&2 (GLP-1 and GLP-2) and glucose dependent insulinotropic peptide (GIP). GLP-1 and GIP enhance insulin secretion; GLP-2 increases intestinal growth and glucose absorption. T1R1-T1R3 combination co-expressed on the apical domain of cholecystokinin (CCK) expressing cells is a luminal sensor for a number of L-amino acids; with amino acid-activation of the receptor eliciting CCK secretion. This article focuses on the role of the gut-expressed T1R1, T1R2 and T1R3 in intestinal sweet and L-amino acid sensing. The impact of exploiting T1R2-T1R3 as a nutritional target for enhancing intestinal glucose absorption and gut structural maturity in young animals is also highlighted.

  8. Hollow cathodes with BaO impregnated, porous tungsten inserts and tips

    NASA Technical Reports Server (NTRS)

    Hudson, W. R.; Weigand, A. J.

    1973-01-01

    The technology of impregnated materials is described and some inherently advantageous characteristics of impregnated cathodes are discussed. Thermionic emission measurements are presented for oxide coated and impregnated cathodes. Five cathode configurations with barium oxide impregnated porous tungsten inserts and/or tips have been fabricated and tested. Reliability, durability, and stability of operation are characterized. One of the cathodes has accumulated over 9000 operational hours, another has been cycled on and off more than 800 times.

  9. Hygienic relevance and risk assessment of antimicrobial-impregnated textiles.

    PubMed

    Kramer, A; Guggenbichler, P; Heldt, P; Jünger, M; Ladwig, A; Thierbach, H; Weber, U; Daeschlein, G

    2006-01-01

    The antimicrobial impregnation of textiles is intended to provide protection of textiles against microbial corrosion, prevention of malodor or prophylaxis and therapy of infections, respectively. For every biocidal product a careful risk assessment for humans and the environment has to be performed. The advantage of antimicrobially active textiles has to be documented for every agent as well as for every application, and a balance has to be found between a textile's quality rating and the potential risks, e.g. sensitization, disturbance of the ecology of the skin, toxic side effects by means of systemic absorption, cytotoxicity, genotoxicity, carcinogenicity, teratogenicity and ecotoxicity. This article evaluates the applicability of silver compounds as well as the classic antimicrobials triclosan, quaternary ammonium compounds, copper and further new options like chitosan and zeolite. It has to be emphasized that there are no objections against the use of antimicrobially active textiles if their use is equal or superior to other preventive or therapeutic measures. This applies to the amelioration of the course of dermatological diseases with disturbed skin flora, in particular atopic dermatitis, the prevention and therapy of acute and chronic wound infections by wound dressings, the use of impregnated surgical suture material as well as special indications in the prevention of infection in medical facilities. The use of antimicrobial textiles for the prevention of dermatomycosis by antifungal impregnation is of questionable use; the antimicrobial impregnation of textiles for deodorization purposes has to be avoided. Presently, from a hygienic point of view, the following questions have to be clearly determined: declaration of any antimicrobial impregnation; development of international standards for in vitro testing and preclinical evaluation of efficacy and tolerance; evaluation of the advantage of the antimicrobial properties for the intended use including the

  10. A general enantioselective approach to jasmonoid fragrances: synthesis of (+)-(1R,2S)-methyl dihydrojasmonate and (+)-(1R,2S)-magnolione.

    PubMed

    Porta, Alessio; Vidari, Giovanni; Zanoni, Giuseppe

    2005-06-10

    Methyl dihydrojasmonate 1 and magnolione 3 are of both academic and industrial interest. In this paper, we describe a flexible, high-yielding route to diastereomerically pure (+)-cis-(1R,2S)-methyl dihydrojasmonate 1 and the first synthesis of (+)-cis-(1R,2S)-magnolione 3, both with enantiomeric excesses up to 93%. The two syntheses diverged from the same advanced intermediate 5, readily available from the enantioenriched hydroxymethyl delta-lactone (-)-(3aS,4S,6aR)-6. The olfactory properties of (1R,2S)-1 and (1R,2S)-3 are reported.

  11. Different functional roles of T1R subunits in the heteromeric taste receptors.

    PubMed

    Xu, Hong; Staszewski, Lena; Tang, Huixian; Adler, Elliot; Zoller, Mark; Li, Xiaodong

    2004-09-28

    The T1R receptors, a family of taste-specific class C G protein-coupled receptors, mediate mammalian sweet and umami tastes. The structure-function relationships of T1R receptors remain largely unknown. In this study, we demonstrate the different functional roles of T1R extracellular and transmembrane domains in ligand recognition and G protein coupling. Similar to other family C G protein-coupled receptors, the N-terminal Venus flytrap domain of T1R2 is required for recognizing sweeteners, such as aspartame and neotame. The G protein coupling requires the transmembrane domain of T1R2. Surprisingly, the C-terminal transmembrane domain of T1R3 is required for recognizing sweetener cyclamate and sweet taste inhibitor lactisole. Because T1R3 is the common subunit in the sweet taste receptor and the umami taste receptor, we tested the interaction of lactisole and cyclamate with the umami taste receptor. Lactisole inhibits the activity of the human T1R1/T1R3 receptor, and, as predicted, blocked the umami taste of l-glutamate in human taste tests. Cyclamate does not activate the T1R1/T1R3 receptor by itself, but potentiates the receptor's response to l-glutamate. Taken together, these findings demonstrate the different functional roles of T1R3 and T1R2 and the presence of multiple ligand binding sites on the sweet taste receptor. PMID:15353592

  12. Different functional roles of T1R subunits in the heteromeric taste receptors.

    PubMed

    Xu, Hong; Staszewski, Lena; Tang, Huixian; Adler, Elliot; Zoller, Mark; Li, Xiaodong

    2004-09-28

    The T1R receptors, a family of taste-specific class C G protein-coupled receptors, mediate mammalian sweet and umami tastes. The structure-function relationships of T1R receptors remain largely unknown. In this study, we demonstrate the different functional roles of T1R extracellular and transmembrane domains in ligand recognition and G protein coupling. Similar to other family C G protein-coupled receptors, the N-terminal Venus flytrap domain of T1R2 is required for recognizing sweeteners, such as aspartame and neotame. The G protein coupling requires the transmembrane domain of T1R2. Surprisingly, the C-terminal transmembrane domain of T1R3 is required for recognizing sweetener cyclamate and sweet taste inhibitor lactisole. Because T1R3 is the common subunit in the sweet taste receptor and the umami taste receptor, we tested the interaction of lactisole and cyclamate with the umami taste receptor. Lactisole inhibits the activity of the human T1R1/T1R3 receptor, and, as predicted, blocked the umami taste of l-glutamate in human taste tests. Cyclamate does not activate the T1R1/T1R3 receptor by itself, but potentiates the receptor's response to l-glutamate. Taken together, these findings demonstrate the different functional roles of T1R3 and T1R2 and the presence of multiple ligand binding sites on the sweet taste receptor.

  13. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon.

    PubMed

    Kendig, Derek M; Hurst, Norman R; Bradley, Zachary L; Mahavadi, Sunila; Kuemmerle, John F; Lyall, Vijay; DeSimone, John; Murthy, Karnam S; Grider, John R

    2014-12-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5'-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1(-/-) mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. PMID:25324508

  14. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon

    PubMed Central

    Kendig, Derek M.; Hurst, Norman R.; Bradley, Zachary L.; Mahavadi, Sunila; Kuemmerle, John F.; Lyall, Vijay; DeSimone, John; Murthy, Karnam S.

    2014-01-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5′-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1−/− mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion. PMID:25324508

  15. Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon.

    PubMed

    Kendig, Derek M; Hurst, Norman R; Bradley, Zachary L; Mahavadi, Sunila; Kuemmerle, John F; Lyall, Vijay; DeSimone, John; Murthy, Karnam S; Grider, John R

    2014-12-01

    Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5'-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1(-/-) mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion.

  16. Taste information derived from T1R-expressing taste cells in mice.

    PubMed

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-03-01

    The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination.

  17. Taste information derived from T1R-expressing taste cells in mice.

    PubMed

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-03-01

    The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination. PMID:26912569

  18. Research on the melt impregnation of continuous carbon fiber reinforced nylon 66 composites

    NASA Astrophysics Data System (ADS)

    Jia, M. Y.; Li, C. X.; Xue, P.; Chen, K.; Chen, T. H.

    2016-07-01

    Impregnation mold of continuous carbon fiber reinforced thermoplastic composites was designed and built in the article. Based on the theory of fluid mechanics and Darcy's law, a model of the melt impregnation was also established. The influences of fiber bundle width and impregnation pins’ diameter on the impregnation degree were studied by numerical simulation. Continuous carbon fiber reinforced nylon 66 composites were prepared. The effects of coated angle and impregnation mold temperature on the mechanical properties of the composites were also described.The agreement between the experimental data and prediction by the model was found to be satisfactory.

  19. Abnormal mitosis induced by wheat-rye 1R monosomic addition lines.

    PubMed

    Fu, Shu-Lan; Yang, Man-Yu; Ren, Zheng-Long; Yan, Ben-Ju; Tang, Zong-Xiang

    2014-01-01

    Octoploid triticale were derived from common wheat (Triticum aestivum L. 'Mianyang11') × rye (Secale cereale L. 'Kustro'), and some progeny were obtained by the backcrossing of triticale with 'Mianyang11' followed by self-fertilization. In situ hybridization using rye genomic DNA and repetitive sequences pAs1 and pSc119.2 as probes was used to analyze the mitotic chromosomes of these progeny. Three wheat-rye 1R monosomic addition lines and a wheat line (12FT-1685) containing a 1R and a 1BL.1RS translocation chromosome were identified. Abnormal mitosis was observed in the two lines. During mitosis of a 1R monosomic addition line (3-8-20-1R-2), lagging chromosomes, micronuclei, chromosomal bridges, and the one pole segregation of 1R chromosome were observed. Abnormal mitotic behaviour of chromosomes was also observed in some of the self-progeny plants of lines 12FT-1685 and 3-8-20-1R-2. These progeny contained 1R chromosome or 1R chromosome arm. In addition, 4B chromosomes were absent from one of the progeny of 3-8-20-1R-2. This abnormal mitotic behaviour of chromosomes was not observed in two other 1R monosomic addition lines. These results indicate that a single 1R chromosome added to wheat might cause abnormal mitotic behaviour of both wheat and rye chromosomes and different genetic variations might occurr among the sibling 1R monosomic addition lines. PMID:24564212

  20. Abnormal mitosis induced by wheat-rye 1R monosomic addition lines.

    PubMed

    Fu, Shu-Lan; Yang, Man-Yu; Ren, Zheng-Long; Yan, Ben-Ju; Tang, Zong-Xiang

    2014-01-01

    Octoploid triticale were derived from common wheat (Triticum aestivum L. 'Mianyang11') × rye (Secale cereale L. 'Kustro'), and some progeny were obtained by the backcrossing of triticale with 'Mianyang11' followed by self-fertilization. In situ hybridization using rye genomic DNA and repetitive sequences pAs1 and pSc119.2 as probes was used to analyze the mitotic chromosomes of these progeny. Three wheat-rye 1R monosomic addition lines and a wheat line (12FT-1685) containing a 1R and a 1BL.1RS translocation chromosome were identified. Abnormal mitosis was observed in the two lines. During mitosis of a 1R monosomic addition line (3-8-20-1R-2), lagging chromosomes, micronuclei, chromosomal bridges, and the one pole segregation of 1R chromosome were observed. Abnormal mitotic behaviour of chromosomes was also observed in some of the self-progeny plants of lines 12FT-1685 and 3-8-20-1R-2. These progeny contained 1R chromosome or 1R chromosome arm. In addition, 4B chromosomes were absent from one of the progeny of 3-8-20-1R-2. This abnormal mitotic behaviour of chromosomes was not observed in two other 1R monosomic addition lines. These results indicate that a single 1R chromosome added to wheat might cause abnormal mitotic behaviour of both wheat and rye chromosomes and different genetic variations might occurr among the sibling 1R monosomic addition lines.

  1. Performance of Conformable Phenolic Impregnated Carbon Ablator in Aerothermal Environments

    NASA Technical Reports Server (NTRS)

    Thornton, Jeremy; Fan, Wendy; Stackpoole, Mairead; Kao, David; Skokova, Kristina; Chavez-Garcia, Jose

    2012-01-01

    Conformable Phenolic Impregnated Carbon Ablator, a cousin of Phenolic Impregnated Carbon Ablator (PICA), was developed at NASA Ames Research Center as a lightweight thermal protection system under the Fundamental Aeronautics Program. PICA is made using a brittle carbon substrate, which has a very low strain to failure. Conformable PICA is made using a flexible carbon substrate, a felt in this case. The flexible felt significantly increases the strain to failure of the ablator. PICA is limited by its thermal mechanical properties. Future NASA missions will require heatshields that are more fracture resistant than PICA and, as a result, NASA Ames is working to improve PICA's performance by developing conformable PICA to meet these needs. Research efforts include tailoring the chemistry of conformable PICA with varying amounts of additives to enhance mechanical properties and testing them in aerothermal environments. This poster shows the performance of conformable PICA variants in arc jets tests. Some mechanical and thermal properties will also be presented.

  2. Electrochemical impregnation of nickel hydroxide in porous electrodes

    NASA Technical Reports Server (NTRS)

    Ho, Kuo-Chuan; Jorne, Jacob

    1987-01-01

    The electrochemical impregnation of nickel hydroxide in porous electrode was investigated both experimentally and theoretically. The loading level and plaque expansion were the most important parameters to be considered. The effects of applied current density, stirring, ratio of solution to electrode volume and pH were identified. A novel flow through electrochemical impregnation is proposed in which the electrolyte is forced through the porous nickel plaque. The thickening of the plaque can be reduced while maintaining high loading capacity. A mathematical model is presented which describes the transport of the nitrate, nickel and hydroxyl ions and the consecutive heterogeneous electrochemical reduction of nitrate and the homogeneous precipitation reaction of nickel hydroxide. The distributions of precipitation rate and active material within the porous electrode are obtained. A semiempirical model is also proposed which takes into account the plugging of the pores.

  3. Enhanced arsenic removal using mixed metal oxide impregnated chitosan beads.

    PubMed

    Yamani, Jamila S; Miller, Sarah M; Spaulding, Matthew L; Zimmerman, Julie B

    2012-09-15

    Mixed metal oxide impregnated chitosan beads (MICB) containing nanocrystalline Al₂O₃ and nanocrystalline TiO₂ were successfully developed. This adsorbent exploits the high capacity of Al₂O₃ for arsenate and the photocatalytic activity of TiO₂ to oxidize arsenite to arsenate, resulting in a removal capacity higher than that of either metal oxide alone. The composition of the beads was optimized for maximum arsenite removal in the presence of UV light. The mechanism of removal was investigated and a mode of action was proposed wherein TiO₂ oxidizes arsenite to arsenate which is then removed from solution by Al₂O₃. Pseudo-second order kinetics were used to validate the proposed mechanism. MICB is a more efficient and effective adsorbent for arsenic than TiO₂-impregnated chitosan beads (TICB), previously reported on, yet maintains a desirable life cycle, free of complex synthesis processes, toxic materials, and energy inputs. PMID:22743162

  4. T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to Polycose: implications for saccharide taste receptors in mice.

    PubMed

    Treesukosol, Yada; Blonde, Ginger D; Spector, Alan C

    2009-04-01

    The T1R2 and T1R3 proteins are expressed in taste receptor cells and form a heterodimer binding with compounds described as sweet by humans. We examined whether Polycose taste might be mediated through this heterodimer by testing T1R2 knockout (KO) and T1R3 KO mice and their wild-type (WT) littermate controls in a series of brief-access taste tests (25-min sessions with 5-s trials). Sucrose, Na-saccharin, and Polycose were each tested for three consecutive sessions with order of presentation varied among subgroups in a Latin-Square manner. Both KO groups displayed blunted licking responses and initiated significantly fewer trials of sucrose and Na-saccharin across a range of concentrations. KO mice tested after Polycose exposure demonstrated some degree of concentration-dependent licking of sucrose, likely attributable to learning related to prior postingestive experience. These results are consistent with prior findings in the literature, implicating the T1R2+3 heterodimer as the principal taste receptor for sweet-tasting ligands, and also provide support for the potential of postingestive experience to influence responding in the KO mice. In contrast, T1R2 KO and T1R3 KO mice displayed concentration-dependent licking responses to Polycose that tracked those of their WT controls and in some cases licked midrange concentrations more; the number of Polycose trials initiated overall did not differ between KO and WT mice. Thus, the T1R2 and T1R3 proteins are individually unnecessary for normal concentration-dependent licking of Polycose to be expressed in a brief-access test. Whether at least one of these T1R protein subunits is necessary for normal Polycose responsiveness remains untested. Alternatively, there may be a novel taste receptor(s) that mediates polysaccharide taste. PMID:19158407

  5. The Functional Role of the T1R Family of Receptors in Sweet Taste and Feeding

    PubMed Central

    Treesukosol, Yada; Smith, Kimberly R.; Spector, Alan C.

    2011-01-01

    The discovery of the T1R family of Class C G protein-coupled receptors in the peripheral gustatory system a decade ago has been a tremendous advance for taste research, and its conceptual reach has extended to other organ systems. There are three proteins in the family, T1R1, T1R2, and T1R3, encoded by their respective genes, Tas1r1, Tas1r2, and Tas1r3. T1R2 combines with T1R3 to form a heterodimer that binds with sugars and other sweeteners. T1R3 also combines with T1R1 to form a heterodimer that binds with L-amino acids. These proteins are expressed not only in taste bud cells, but one or more of these T1Rs have also been identified in the nasal epithelium, gut, pancreas, liver, kidney, testes and brain in various mammalian species. Here we review current perspectives regarding the functional role of these receptors, concentrating on sweet taste and feeding. We also discuss behavioral findings suggesting that a glucose polymer mixture, Polycose, which rodents avidly prefer, appears to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In addition, although the T1Rs have been implicated as playing a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow and fluid intake as well as normal body weight compared with same-sex littermate wild type (WT) controls. Moreover, regardless of whether they are fasted or not, these KO mice do not differ from their WT counterparts in their Polycose intake across a broad range of concentrations in 30-min intake tests. The functional implications of these results and those in the literature are considered. PMID:21376068

  6. Muscle regulatory factors regulate T1R3 taste receptor expression.

    PubMed

    Kokabu, Shoichiro; Lowery, Jonathan W; Toyono, Takashi; Seta, Yuji; Hitomi, Suzuro; Sato, Tsuyoshi; Enoki, Yuichiro; Okubo, Masahiko; Fukushima, Yosuke; Yoda, Tetsuya

    2015-12-25

    T1R3 is a T1R class of G protein-coupled receptors, composing subunit of the umami taste receptor when complexed with T1R1. T1R3 was originally discovered in gustatory tissue but is now known to be expressed in a wide variety of tissues and cell types such the intestine, pancreatic β-cells, skeletal muscle, and heart. In addition to taste recognition, the T1R1/T1R3 complex functions as an amino acid sensor and has been proposed to be a control mechanism for the secretion of hormones, such as cholecystokinin, insulin, and duodenal HCO3(-) and activates the mammalian rapamycin complex 1 (MTORC1) to inhibit autophagy. T1R3 knockout mice have increased rate of autophagy in the heart, skeletal muscle and liver. Thus, T1R3 has multiple physiological functions and is widely expressed in vivo. However, the exact mechanisms regulating T1R3 expression are largely unknown. Here, we used comparative genomics and functional analyses to characterize the genomic region upstream of the annotated transcriptional start of human T1R3. This revealed that the T1R3 promoter in human and mouse resides in an evolutionary conserved region (ECR). We also identified a repressive element located upstream of the human T1R3 promoter that has relatively high degree of conservation with rhesus macaque. Additionally, the muscle regulatory factors MyoD and Myogenin regulate T1R3 expression and T1R3 expression increases with skeletal muscle differentiation of murine myoblast C2C12 cells. Taken together, our study raises the possibility that MyoD and Myogenin might control skeletal muscle metabolism and homeostasis through the regulation of T1R3 promoter activity. PMID:26545778

  7. The Application of Perfluorocarbons as Impregnants for Plastic Film Capacitors

    NASA Technical Reports Server (NTRS)

    Mauldin, G. H.

    1981-01-01

    A liquid impregnated, plastic film (wet) capacitor was developed that is thought to be the most reliable and space efficient capacitor of any type ever produced for high voltage, pulse discharge service. The initial design stores five times the energy of a premium quality dry capacitor of equivalent energy and reliability. The technology, as well as a production capacitor design using this technology are described.

  8. Review of electrochemical impregnation for nickel cadmium cells. [aerospace applications

    NASA Technical Reports Server (NTRS)

    Gross, S.

    1977-01-01

    A method of loading active material within the electrodes of nickel cadmium cells is examined. The basic process of electrochemical impregnation of these electrodes is detailed, citing the principle that when current is applied reactions occur which remove hydrogen ions from solution, making the interior of the plaque less acidic. Electrodes result which are superior in energy density, stability, and life. The technology is reviewed and illustrated with typical performance data. Recommendations are made for additional research and development.

  9. Insoluble polyelectrolyte and ion-exchange hollow fiber impregnated therewith

    NASA Technical Reports Server (NTRS)

    Rembaum, A. (Inventor)

    1977-01-01

    The number of quaternary sites and ion exchange capacity of a polyquaternary, cross linked, insoluble copolymer of a vinyl pyridine and a dihalo organic compound is increased by about 15-35% by reaction of the polymer with an amine followed by quaternization, if required. The polymer forms spontaneously in the presence of a substrate such as within the pores of a hollow fiber. The improved resin impregnated fiber may be utilized to remove ions from waste or process steams.

  10. Mercury adsorption properties of sulfur-impregnated adsorbents

    USGS Publications Warehouse

    Hsi, N.-C.; Rood, M.J.; Rostam-Abadi, M.; Chen, S.; Chang, R.

    2002-01-01

    Carbonaceous and noncarbonaceous adsorbents were impregnated with elemental sulfur to evaluate the chemical and physical properties of the adsorbents and their equilibrium mercury adsorption capacities. Simulated coal combustion flue gas conditions were used to determine the equilibrium adsorption capacities for Hg0 and HgCl2 gases to better understand how to remove mercury from gas streams generated by coal-fired utility power plants. Sulfur was deposited onto the adsorbents by monolayer surface deposition or volume pore filling. Sulfur impregnation increased the total sulfur content and decreased the total and micropore surface areas and pore volumes for all of the adsorbents tested. Adsorbents with sufficient amounts of active adsorption sites and sufficient microporous structure had mercury adsorption capacities up to 4,509 ??g Hg/g adsorbent. Elemental sulfur, organic sulfur, and sulfate were formed on the adsorbents during sulfur impregnation. Correlations were established with R2>0.92 between the equilibrium Hg0/HgCl2 adsorption capacities and the mass concentrations of elemental and organic sulfur. This result indicates that elemental and organic sulfur are important active adsorption sites for Hg0 and HgCl2.

  11. Dispersion type zirconium matrix fuels fabricated by capillary impregnation method

    NASA Astrophysics Data System (ADS)

    Savchenko, A.; Konovalov, I.; Vatulin, A.; Morozov, A.; Orlov, V.; Uferov, O.; Ershov, S.; Laushkin, A.; Kulakov, G.; Maranchak, S.; Petrova, Z.

    2007-05-01

    Several novel dispersion fuel compositions with a high uranium content fuel (U9Mo, U5Zr5Nb, U3Si) and a zirconium alloy matrix with low melting point (1063-1133 K) have been developed at A.A. Bochvar Institute using a capillary impregnation fabrication method. The capillary impregnation method introduces fuel granules and granules of a zirconium alloy into a fuel element followed by a short-term anneal at a temperature above the melting temperature of alloy. The alloy melts down and under capillary forces moves into the joints between the fuel element components to form metallurgical bonds. The volume ratios between the components are: 55-65% fuel, 10-20% matrix, and 15-30% pores. Fuel elements produced by capillary impregnation method have a high uranium content (9-10 g cm-3) and a high thermal conductivity (18-22 W m-1 K-1), which, when used as PWR or BWR fuels allow the fuel temperature to be lowered to 723-773 K. They also feature porosity to accommodate swelling. The metallurgical fuel-cladding bond makes the fuel elements serviceable in power transients. The primary advantages for PWR, BWR and CANDU use of these fuels elements, would be the high uranium content, low fuel temperature and serviceability under transient conditions. Consideration is given to their applicability in Floating Nuclear Power Plants (FNPP) as well as for the feasibility of burning civil and weapon grade plutonium.

  12. Cyanate Ester and Phthalonitrile Impregnated Carbon Ablative TPS

    NASA Technical Reports Server (NTRS)

    Boghozian, Tane; Stackpoole, Margaret M.; Gasch, Matt

    2016-01-01

    Phenolic resin has extensive heritage as a TPS (Thermal Protection Systems) material, however, alternative resin systems such as Cyanate Ester and Phthalonitrile may offer improved performance compared to state-of-the-art phenolic resin. These alternative resin systems may have higher char yield, higher char strength, lower thermal conductivity and improved mechanical properties. In current work at NASA Ames alternative resin systems were uniformly infused into fibrous substrates and preliminary properties characterized. The density of the cyanate ester infused in fibrous substrate ranged from 0.25-0.3 grams per cubic centimeter compared to PICA (Phenolic resin impregnated carbon ablative) having a density of approximately 0.25 grams per cubic centimeter. The density of Phthalonitrile varies from 0.22-0.25 grams per cubic centimeter. Initial formulations of these new resin systems were recently tested at the LARC HyMETs (Hypersonic Materials Environmental Test System) facility to evaluate their performance and data such as back face temperature, char yield, and recession are compared to PICA. Cyanate Ester and Phthalonitrile impregnated carbon ablative samples showed comparable performance to phenolic resin impregnated carbon ablative samples.

  13. Cation adsorption on manganese dioxide impregnated fibers. Final report

    SciTech Connect

    Fisher, S.; Stahel, E.P.

    1992-12-01

    Complete removal of radioactive cations by standard mixed bed ion exchange resins is sometimes not achieved in liquid radwaste systems. Based on a literature survey, acrylic fibers impregnated with manganese dioxide were chosen as a media warranting study of their ability to adsorb the cations present in radwaste systems in the hope of improving performance of such treatment processes. A system to produce impregnated fiber with a heavy MnO{sub 2} loading was designed, constructed, and operated. The system produced fiber at an average fiber loading of 22.5 percent MnO{sub 2} by weight. Leaching tests made on the MnO{sub 2} fiber exhibited no signs of soluble manganese, insoluble MnO{sub 2}, acrylonitrile leaching or fiber loss. Laboratory testing has been performed on the adsorption of calcium, cadmium, cesium, cobalt, iron, and manganese on MnO{sub 2} impregnated fiber. Removal of metals from solution was measured at levels specific for each metal tested. The removal efficiency when they were present in combination was also evaluated.

  14. Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism

    PubMed Central

    Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K.; Lehtonen, Jukka Y.A.

    2016-01-01

    As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3′-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. PMID:26681690

  15. The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas.

    PubMed

    Quail, Daniela F; Bowman, Robert L; Akkari, Leila; Quick, Marsha L; Schuhmacher, Alberto J; Huse, Jason T; Holland, Eric C; Sutton, James C; Joyce, Johanna A

    2016-05-20

    Macrophages accumulate with glioblastoma multiforme (GBM) progression and can be targeted via inhibition of colony-stimulating factor-1 receptor (CSF-1R) to regress high-grade tumors in animal models of this cancer. However, whether and how resistance emerges in response to sustained CSF-1R blockade is unknown. We show that although overall survival is significantly prolonged, tumors recur in >50% of mice. Gliomas reestablish sensitivity to CSF-1R inhibition upon transplantation, indicating that resistance is tumor microenvironment-driven. Phosphatidylinositol 3-kinase (PI3K) pathway activity was elevated in recurrent GBM, driven by macrophage-derived insulin-like growth factor-1 (IGF-1) and tumor cell IGF-1 receptor (IGF-1R). Combining IGF-1R or PI3K blockade with CSF-1R inhibition in recurrent tumors significantly prolonged overall survival. Our findings thus reveal a potential therapeutic approach for treating resistance to CSF-1R inhibitors. PMID:27199435

  16. The human Kell blood group binds the erythroid 4.1R protein: new insights into the 4.1R-dependent red cell membrane complex.

    PubMed

    Azouzi, Slim; Collec, Emmanuel; Mohandas, Narla; An, Xiuli; Colin, Yves; Le Van Kim, Caroline

    2015-12-01

    Protein 4.1R plays an important role in maintaining the mechanical properties of the erythrocyte membrane. We analysed the expression of Kell blood group protein in erythrocytes from a patient with hereditary elliptocytosis associated with complete 4.1R deficiency (4.1(-) HE). Flow cytometry and Western blot analyses revealed a severe reduction of Kell. In vitro pull down and co-immunoprecipitation experiments from erythrocyte membranes showed a direct interaction between Kell and 4.1R. Using different recombinant domains of 4.1R and the cytoplasmic domain of Kell, we demonstrated that the R(46) R motif in the juxta-membrane region of Kell binds to lobe B of the 4.1R FERM domain. We also observed that 4.1R deficiency is associated with a reduction of XK and DARC (also termed ACKR1) proteins, the absence of the glycosylated form of the urea transporter B and a slight decrease of band 3. The functional alteration of the 4.1(-) HE erythrocyte membranes was also determined by measuring various transport activities. We documented a slower rate of HCO3 (-) /Cl(-) exchange, but normal water and ammonia transport across erythrocyte membrane in the absence of 4.1. These findings provide novel insights into the structural organization of blood group antigen proteins into the 4.1R complex of the human red cell membrane.

  17. The human Kell blood group binds the erythroid 4.1R protein: new insights into the 4.1R-dependent red cell membrane complex.

    PubMed

    Azouzi, Slim; Collec, Emmanuel; Mohandas, Narla; An, Xiuli; Colin, Yves; Le Van Kim, Caroline

    2015-12-01

    Protein 4.1R plays an important role in maintaining the mechanical properties of the erythrocyte membrane. We analysed the expression of Kell blood group protein in erythrocytes from a patient with hereditary elliptocytosis associated with complete 4.1R deficiency (4.1(-) HE). Flow cytometry and Western blot analyses revealed a severe reduction of Kell. In vitro pull down and co-immunoprecipitation experiments from erythrocyte membranes showed a direct interaction between Kell and 4.1R. Using different recombinant domains of 4.1R and the cytoplasmic domain of Kell, we demonstrated that the R(46) R motif in the juxta-membrane region of Kell binds to lobe B of the 4.1R FERM domain. We also observed that 4.1R deficiency is associated with a reduction of XK and DARC (also termed ACKR1) proteins, the absence of the glycosylated form of the urea transporter B and a slight decrease of band 3. The functional alteration of the 4.1(-) HE erythrocyte membranes was also determined by measuring various transport activities. We documented a slower rate of HCO3 (-) /Cl(-) exchange, but normal water and ammonia transport across erythrocyte membrane in the absence of 4.1. These findings provide novel insights into the structural organization of blood group antigen proteins into the 4.1R complex of the human red cell membrane. PMID:26455906

  18. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene

    PubMed Central

    2015-01-01

    The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain. PMID:26107521

  19. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    PubMed

    Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A

    2015-01-01

    The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  20. Orosensory detection of sucrose, maltose, and glucose is severely impaired in mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal

    PubMed Central

    Treesukosol, Yada

    2012-01-01

    Evidence in the literature supports the hypothesis that the T1R2+3 heterodimer binds to compounds that humans describe as sweet. Here, we assessed the necessity of the T1R2 and T1R3 subunits in the maintenance of normal taste sensitivity to carbohydrate stimuli. We trained and tested water-restricted T1R2 knockout (KO), T1R3 KO and their wild-type (WT) same-sex littermate controls in a two-response operant procedure to sample a fluid and differentially respond on the basis of whether the stimulus was water or a tastant. Correct responses were reinforced with water and incorrect responses were punished with a time-out. Testing was conducted with a modified descending method of limits procedure across daily 25-min sessions. Both KO groups displayed severely impaired performance and markedly decreased sensitivity when required to discriminate water from sucrose, glucose, or maltose. In contrast, when Polycose was tested, KO mice had normal EC50 values for their psychometric functions, with some slight, but significant, impairment in performance. Sensitivity to NaCl did not differ between these mice and their WT controls. Our findings support the view that the T1R2+3 heterodimer is the principal receptor that mediates taste detection of natural sweeteners, but not of all carbohydrate stimuli. The combined presence of T1R2 and T1R3 appears unnecessary for the maintenance of relatively normal sensitivity to Polycose, at least in this task. Some detectability of sugars at high concentrations might be mediated by the putative polysaccharide taste receptor, the remaining T1R subunit forming either a homodimer or heteromer with another protein(s), or nontaste orosensory cues. PMID:22621968

  1. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

    PubMed Central

    Inoue, Masashi; Glendinning, John I.; Theodorides, Maria L.; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K.; Bachmanov, Alexander A.

    2008-01-01

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (d-tryptophan, d-phenylalanine, l-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (l-glutamine, l-threonine, l-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5′-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system. PMID:17911381

  2. Taste responses in mice lacking taste receptor subunit T1R1

    PubMed Central

    Kusuhara, Yoko; Yoshida, Ryusuke; Ohkuri, Tadahiro; Yasumatsu, Keiko; Voigt, Anja; Hübner, Sandra; Maeda, Katsumasa; Boehm, Ulrich; Meyerhof, Wolfgang; Ninomiya, Yuzo

    2013-01-01

    The T1R1 receptor subunit acts as an umami taste receptor in combination with its partner, T1R3. In addition, metabotropic glutamate receptors (brain and taste variants of mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate the function of T1R1 and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock-out (T1R1−/−) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1-expressing cells. Gustatory nerve recordings demonstrated that T1R1−/− mice exhibited a serious deficit in inosine monophosphate-elicited synergy but substantial residual responses to glutamate alone in both chorda tympani and glossopharyngeal nerves. Interestingly, chorda tympani nerve responses to sweeteners were smaller in T1R1−/− mice. Taste cell recordings demonstrated that many mCherry-expressing taste cells in T1R1+/− mice responded to sweet and umami compounds, whereas those in T1R1−/− mice responded to sweet stimuli. The proportion of sweet-responsive cells was smaller in T1R1−/− than in T1R1+/− mice. Single-cell RT-PCR demonstrated that some single mCherry-expressing cells expressed all three T1R subunits. Chorda tympani and glossopharyngeal nerve responses to glutamate were significantly inhibited by addition of mGluR antagonists in both T1R1−/− and T1R1+/− mice. Conditioned taste aversion tests demonstrated that both T1R1−/− and T1R1+/− mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1-expressing cells mainly contribute to umami taste synergism and partly to sweet sensitivity and that mGluRs are involved in the detection of umami compounds. PMID:23339178

  3. Delivery of CSF-1R to the lumen of macropinosomes promotes its destruction in macrophages

    PubMed Central

    Lou, Jieqiong; Low-Nam, Shalini T.; Kerkvliet, Jason G.; Hoppe, Adam D.

    2014-01-01

    ABSTRACT Activation of the macrophage colony stimulating factor-1 receptor (CSF-1R) by CSF-1 stimulates pronounced macropinocytosis and drives proliferation of macrophages. Although the role of macropinocytosis in CSF-1R signaling remains unknown, we show here that, despite internalizing large quantities of plasma membrane, macropinosomes contribute little to the internalization of the CSF-1–CSF-1R complex. Rather, internalization of the CSF-1R in small endocytic vesicles that are sensitive to clathrin disruption, outcompetes macropinosomes for CSF-1R endocytosis. Following internalization, small vesicles carrying the CSF-1R underwent homotypic fusion and then trafficked to newly formed macropinosomes bearing Rab5. As these macropinosomes matured, acquiring Rab7, the CSF-1R was transported into their lumen and degraded. Inhibition of macropinocytosis delayed receptor degradation despite no disruption to CSF-1R endocytosis. These data indicate that CSF-1-stimulated macropinosomes are sites of multivesicular body formation and accelerate CSF-1R degradation. Furthermore, we demonstrate that macropinocytosis and cell growth have a matching dose dependence on CSF-1, suggesting that macropinosomes might be a central mechanism coupling CSF-1R signaling and macrophage growth. PMID:25335894

  4. Establishment of a novel monoclonal antibody SMab-1 specific for IDH1-R132S mutation

    SciTech Connect

    Kaneko, Mika Kato; Tian, Wei; Takano, Shingo; Suzuki, Hiroyuki; Sawa, Yoshihiko; Hozumi, Yasukazu; Goto, Kaoru; Yamazaki, Kentaro; Kitanaka, Chifumi; Kato, Yukinari

    2011-03-25

    Research highlights: {yields} IDH1 mutations are early and frequent genetic alterations in gliomas. {yields} We newly established an anti-IDH1-R132S-specific mAb SMab-1. {yields} SMab-1 reacted with the IDH1-R132S peptide, but not with other IDH1 mutants. {yields} SMab-1 specifically stained the IDH1-R132S-expressing glioblastoma cells in immunocytochemistry and immunohistochemistry. {yields} SMab-1 should be useful in diagnosis of mutation-bearing gliomas. -- Abstract: Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic alterations in gliomas, are specific to a single codon in the conserved and functionally important Arginine 132 (R132) in IDH1. We earlier established a monoclonal antibody (mAb), IMab-1, which is specific for R132H-containing IDH1 (IDH1-R132H), the most frequent IDH1 mutation in gliomas. To establish IDH1-R132S-specific mAb, we immunized mice with R132S-containing IDH1 (IDH1-R132S) peptide. After cell fusion using Sendai virus envelope, IDH1-R132S-specific mAbs were screened in ELISA. One mAb, SMab-1, reacted with the IDH1-R132S peptide, but not with other IDH1 mutants. Western-blot analysis showed that SMab-1 reacted only with the IDH1-R132S protein, not with IDH1-WT protein or IDH1 mutants, indicating that SMab-1 is IDH1-R132S-specific. Furthermore, SMab-1 specifically stained the IDH1-R132S-expressing glioblastoma cells in immunocytochemistry and immunohistochemistry, but did not react with IDH1-WT or IDH1-R132H-containing glioblastoma cells. We newly established an anti-IDH1-R132S-specific mAb SMab-1 for use in diagnosis of mutation-bearing gliomas.

  5. Distinct Contributions of T1R2 and T1R3 Taste Receptor Subunits to the Detection of Sweet Stimuli

    SciTech Connect

    Nie,Y.; Vigues, S.; Hobbs, J.; Conn, G.; Munger, S.

    2005-01-01

    The molecular mechanisms by which G protein-coupled receptor (GPCR)-type chemosensory receptors of animals selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes, though little is known about the relative contributions of individual subunits to receptor functions. This study showed that each of the two subunits in the mammalian heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli, though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in mice. Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.

  6. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice

    PubMed Central

    Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F.; Vasselli, Joseph R.; Sclafani, Anthony

    2015-01-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. PMID:26157055

  7. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

    PubMed

    Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

    2015-09-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.

  8. The enzymatic nature of C'1r. Conversion of C'1s to C'1 esterase and digestion of amino acid esters by C'1r.

    PubMed

    Naff, G B; Ratnoff, O S

    1968-10-01

    Human C'1, a macromolecular complex composed of three subunits, is the zymogen for at least two distinct enzymes. Preparations of one subunit, C'1r, functioned as a protease which converted another subunit, C'1s, to C'1 esterase. The conversion of C'1s to C'1 esterase by C'1r was blocked by Liquoid, phenyl methylsulfonyl fluoride, and calcium ions, but not by soybean trypsin inhibitor, hirudin, or heparin. Preparations of C'1r also possessed two additional functions, i.e., the ability to hydrolyze certain synthetic amino acid esters and to participate in immune hemolysis. Evidence was presented which indicates that these three functions are properties of a single entity, C'1r, but not of the same portion of its molecular structure. These observations suggest that C'1r has at least two active sites, one for its reaction with C'1q, an additional subunit of C'1, and one for its reaction with C'1s; together, the three subcomponents, C'1q, C'1r, and C'1s, form a single functional unit, the first component of complement.

  9. A Csf1r-EGFP Transgene Provides a Novel Marker for Monocyte Subsets in Sheep

    PubMed Central

    Pridans, Clare; Davis, Gemma M.; Sauter, Kristin A.; Lisowski, Zofia M.; Corripio-Miyar, Yolanda; Raper, Anna; Lefevre, Lucas; Young, Rachel; McCulloch, Mary E.; Lillico, Simon; Milne, Elspeth; Whitelaw, Bruce

    2016-01-01

    Expression of Csf1r in adults is restricted to cells of the macrophage lineage. Transgenic reporters based upon the Csf1r locus require inclusion of the highly conserved Fms-intronic regulatory element for expression. We have created Csf1r-EGFP transgenic sheep via lentiviral transgenesis of a construct containing elements of the mouse Fms-intronic regulatory element and Csf1r promoter. Committed bone marrow macrophage precursors and blood monocytes express EGFP in these animals. Sheep monocytes were divided into three populations, similar to classical, intermediate, and nonclassical monocytes in humans, based upon CD14 and CD16 expression. All expressed EGFP, with increased levels in the nonclassical subset. Because Csf1r expression coincides with the earliest commitment to the macrophage lineage, Csf1r-EGFP bone marrow provides a tool for studying the earliest events in myelopoiesis using the sheep as a model. PMID:27521343

  10. A Csf1r-EGFP Transgene Provides a Novel Marker for Monocyte Subsets in Sheep.

    PubMed

    Pridans, Clare; Davis, Gemma M; Sauter, Kristin A; Lisowski, Zofia M; Corripio-Miyar, Yolanda; Raper, Anna; Lefevre, Lucas; Young, Rachel; McCulloch, Mary E; Lillico, Simon; Milne, Elspeth; Whitelaw, Bruce; Hume, David A

    2016-09-15

    Expression of Csf1r in adults is restricted to cells of the macrophage lineage. Transgenic reporters based upon the Csf1r locus require inclusion of the highly conserved Fms-intronic regulatory element for expression. We have created Csf1r-EGFP transgenic sheep via lentiviral transgenesis of a construct containing elements of the mouse Fms-intronic regulatory element and Csf1r promoter. Committed bone marrow macrophage precursors and blood monocytes express EGFP in these animals. Sheep monocytes were divided into three populations, similar to classical, intermediate, and nonclassical monocytes in humans, based upon CD14 and CD16 expression. All expressed EGFP, with increased levels in the nonclassical subset. Because Csf1r expression coincides with the earliest commitment to the macrophage lineage, Csf1r-EGFP bone marrow provides a tool for studying the earliest events in myelopoiesis using the sheep as a model.

  11. A Csf1r-EGFP Transgene Provides a Novel Marker for Monocyte Subsets in Sheep.

    PubMed

    Pridans, Clare; Davis, Gemma M; Sauter, Kristin A; Lisowski, Zofia M; Corripio-Miyar, Yolanda; Raper, Anna; Lefevre, Lucas; Young, Rachel; McCulloch, Mary E; Lillico, Simon; Milne, Elspeth; Whitelaw, Bruce; Hume, David A

    2016-09-15

    Expression of Csf1r in adults is restricted to cells of the macrophage lineage. Transgenic reporters based upon the Csf1r locus require inclusion of the highly conserved Fms-intronic regulatory element for expression. We have created Csf1r-EGFP transgenic sheep via lentiviral transgenesis of a construct containing elements of the mouse Fms-intronic regulatory element and Csf1r promoter. Committed bone marrow macrophage precursors and blood monocytes express EGFP in these animals. Sheep monocytes were divided into three populations, similar to classical, intermediate, and nonclassical monocytes in humans, based upon CD14 and CD16 expression. All expressed EGFP, with increased levels in the nonclassical subset. Because Csf1r expression coincides with the earliest commitment to the macrophage lineage, Csf1r-EGFP bone marrow provides a tool for studying the earliest events in myelopoiesis using the sheep as a model. PMID:27521343

  12. Effect of autohydrolysis on the wettability, absorbility and further alkali impregnation of poplar wood chips.

    PubMed

    Xu, Ningpan; Liu, Wei; Hou, Qingxi; Wang, Peiyun; Yao, Zhirong

    2016-09-01

    Autohydrolysis with different severity factors was performed on poplar wood chips prior to pulping, and the wettability, absorbility and the following impregnation of NaOH solution for the poplar wood chips were then investigated. The results showed that after autohydrolysis pretreatment the porosity, shrinkage and fiber saturation point (FSP) of the poplar wood chips were increased, while the surface contact angle decreased as the severity factor was increased. The autohydrolyzed chips absorbed more NaOH in impregnation that resulted in a low NaOH concentration in the bulk impregnation liquor (i.e., the impregnation liquor outside wood chips), while the concentration in the entrapped liquor (i.e., the impregnation liquor inside wood chips) was increased. Autohydrolysis substantially improved the effectiveness of alkali impregnation. PMID:27259186

  13. Effect of calcination on Co-impregnated active carbon

    SciTech Connect

    Bekyarova, E.; Mehandjiev, D. . Inst. of General and Inorganic Chemistry)

    1993-11-01

    Active carbon (AC) from apricot shells with known characteristics has been impregnated with a 9.88% Co(NO[sub 3])[sub 2] [center dot] 6H[sub 2]O solution. The samples are destroyed in air at 200, 300, 400, and 550 C. The processes accompanying the thermal treatment are studied by DTA. Two processes are established during calcination of Co-impregnated active carbon: (i) destruction of the support as a result of oxidation catalyzed by the impregnated cobalt and (ii) interaction of the active phase (Co[sub 3]O[sub 4]) with the support (AC), during which Co[sub 3]O[sub 4] is reduced to CoO and Co. The presence of Co[sub 3]O[sub 4], and CoO phases is proved by X-ray measurements, while that of metal Co is established by magnetic measurements. The porous structure changes are investigated by adsorption studies. The characterization of the samples is performed by physical adsorption of N[sub 2] (77.4 K) and CO[sub 2] (273 K). The poresize distribution curves are plotted over the range 0.4--10 nm by the methods of Pierce (for the mesopores) and Medek (for the micropores). The micropore volume is determined by two independent methods: t/F method and D-R plot. The results from adsorption studies indicate a decrease of S[sub BET], V[sub mi], and, especially, the supermicropores of the samples.

  14. Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa

    PubMed Central

    2013-01-01

    Background Protein Ser/Thr Phosphatase PPP1CC2 is an alternatively spliced isoform of PPP1C that is highly enriched in testis and selectively expressed in sperm. Addition of the phosphatase inhibitor toxins okadaic acid or calyculin A to caput and caudal sperm triggers and stimulates motility, respectively. Thus, the endogenous mechanisms of phosphatase inhibition are fundamental for controlling sperm function and should be characterized. Preliminary results have shown a protein phosphatase inhibitor activity resembling PPP1R2 in bovine and primate spermatozoa. Results Here we show conclusively, for the first time, that PPP1R2 is present in sperm. In addition, we have also identified a novel protein, PPP1R2P3. The latter was previously thought to be an intron-less pseudogene. We show that the protein corresponding to the pseudogene is expressed. It has PPP1 inhibitory potency similar to PPP1R2. The potential phosphosites in PPP1R2 are substituted by non-phosphorylable residues, T73P and S87R, in PPP1R2P3. We also confirm that PPP1R2/PPP1R2P3 are phosphorylated at Ser121 and Ser122, and report a novel phosphorylation site, Ser127. Subfractionation of sperm structures show that PPP1CC2, PPP1R2/PPP1R2P3 are located in the head and tail structures. Conclusions The conclusive identification and localization of sperm PPP1R2 and PPP1R2P3 lays the basis for future studies on their roles in acrosome reaction, sperm motility and hyperactivation. An intriguing possibility is that a switch in PPP1CC2 inhibitory subunits could be the trigger for sperm motility in the epididymis and/or sperm hyperactivation in the female reproductive tract. PMID:23506001

  15. Pressure Venting Tests of Phenolic Impregnated Carbon Ablator (PICA)

    NASA Technical Reports Server (NTRS)

    Blosser, Max L.; Knutson, Jeffrey R.

    2015-01-01

    A series of tests was devised to investigate the pressure venting behavior of one of the candidate ablators for the Orion capsule heat shield. Three different specimens of phenolic impregnated carbon ablator (PICA) were instrumented with internal pressure taps and subjected to rapid pressure changes from near vacuum to one atmosphere and simulated Orion ascent pressure histories. The specimens vented rapidly to ambient pressure and sustained no detectable damage during testing. Peak pressure differences through the thickness of a 3-inch-thick specimen were less than 1 psi during a simulated ascent pressure history.

  16. Implant infections and antibiotic-impregnated silicone rubber coating.

    PubMed Central

    Rushton, D N; Brindley, G S; Polkey, C E; Browning, G V

    1989-01-01

    A method is described for coating silicone rubber-encapsulated implant devices with an outer layer of silicone rubber impregnated with a mixture of gentamicin sulphate and diethanolamine fusidate. A coating of this sort provides bactericidal activity lasting for a few days in the film of fluid surrounding such an implant. When used for coating our implants, the retrospective rate of implant infections believed to have been introduced at the time of surgery was reduced to 0.7% (coated), compared with 10.0% (uncoated), a highly significant difference (p less than 0.001). Systemic perioperative antibiotic prophylaxis was not shown to confer any such benefit. PMID:2649641

  17. IGF-1R as an anti-cancer target—trials and tribulations

    PubMed Central

    Chen, Helen X.; Sharon, Elad

    2013-01-01

    Type I insulin-like growth factor receptor (IGF-1R) has long been recognized for its role in tumorigenesis and growth, but only recently have the tools for targeting the IGF pathway become available. More than 10 IGF/IGF-1R inhibitors have entered clinical trials, and these belong to three main classes: (1) monoclonal antibodies against IGF-1R, (2) monoclonal antibodies against IGF-1R ligands (IGF-1 and IGF-2), and (3) IGF-1R tyrosine kinase inhibitors. These IGF-1R–targeting agents share common effects on IGF-1R signaling but differ in mechanisms of action, spectrum of target inhibition, and pharmacological features. Clinical activity of IGF-1R inhibitors has been demonstrated with sustained responses in a small number of patients with select tumor types, such as Ewing sarcoma and thymoma. However, many large clinical trials involving patients with adult tumors, including non–small cell lung cancer, breast cancer, and pancreatic cancer, failed to show clinical benefit in the overall patient population. Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development. PMID:23601239

  18. Up-regulation of IGF-1R by mutant RAS in leukemia and potentiation of RAS signaling inhibitors by small molecule inhibition of IGF-1R

    PubMed Central

    Weisberg, Ellen; Nonami, Atsushi; Chen, Zhao; Nelson, Erik; Chen, Yongfei; Liu, Feiyang; Cho, Haeyeon; Zhang, Jianming; Sattler, Martin; Mitsiades, Constantine; Wong, Kwok-Kin; Liu, Qingsong; Gray, Nathanael; Griffin, James D.

    2014-01-01

    Purpose Activating mutations in the RAS oncogene occur frequently in human leukemias. Direct targeting of RAS has proven to be challenging, although targeting of downstream RAS mediators, such as MEK, is currently being tested clinically. Given the complexity of RAS signaling, it is likely that combinations of targeted agents will be more effective than single agents. Experimental Design A chemical screen using RAS-dependent leukemia cells was developed to identify compounds with unanticipated activity in the presence of a MEK inhibitor, and led to identification of inhibitors of IGF-1R. Results were validated using cell-based proliferation assays and apoptosis, cell cycle, and gene knockdown assays, immunoprecipitation and immunoblotting, and a non-invasive in vivo bioluminescence model of acute myeloid leukemia (AML). Results Mechanistically, IGF-1R protein expression/activity was substantially increased in mutant RAS-expressing cells, and suppression of RAS led to decreases in IGF-1R. Synergy between MEK and IGF-1R inhibitors correlated with induction of apoptosis, inhibition of cell cycle progression, and decreased phospho-S6 and phospho-4E-BP1. In vivo, NSG mice tail vein-injected with OCI-AML3-luc+ cells showed significantly lower tumor burden following one week of daily oral administration of 50 mg/kg NVP-AEW541 (IGF-1R inhibitor) combined with 25 mg/kg AZD6244 (MEK inhibitor), as compared to mice treated with either agent alone. Drug combination effects observed in cell-based assays were generalized to additional mutant RAS-positive neoplasms. Conclusions The finding that downstream inhibitors of RAS signaling and IGF-1R inhibitors have synergistic activity warrants further clinical investigation of IGF-1R and RAS signaling inhibition as a potential treatment strategy for RAS-driven malignancies. PMID:25186968

  19. Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation.

    PubMed

    Wu, Chang-Chin; Kuo, Chih-Lin; Fan, Fang-Yu; Yang, Kai-Chiang

    2015-10-01

    Osteoporosis impairs the bone-healing process as well as bone fracture fixation. The intervention of osteoporosis is considered to be one part of bone fracture treatment. Thus, orthopedic fixators impregnated with antiosteoporosis regimens will improve fracture fixation in osteoporotic bone. In this study, the strontium (Sr) and calcium phosphate ceramic (CPC) were mixed first and then mixed with poly(ε-caprolactone) (PCL) to fabricate a bioactive and bioabsorbable bone fixators. The prepared Sr-CPC/PCL screws were implanted into the distal femur of ovariectomized rabbits. The results showed that Sr-CPC/PCL composite had the appropriate mechanical properties, good biocompatibility, and radio-opacity. The Sr addition created a porous structure and accelerated the degradation of bone screws, but the degradation products did not acidify the surrounding environment. For osteoporotic animals, favorable osteointegration around the Sr-CPC/PCL screws was found, and the total porosity of trabecular bone was decreased under the inspections of micro-computerized tomography. Compared with PCL or CPC/PCL screw, animals which received Sr-CPC/PCL were found to have better results in terms of trabecular number, thickness, and separation. This study reveals that the Sr-impregnated bone fixator improves osseointegration in osteoporotic animals. Sr-CPC/PCL composite is a good candidate material for osteofixation in osteoporotic patients.

  20. Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation.

    PubMed

    Wu, Chang-Chin; Kuo, Chih-Lin; Fan, Fang-Yu; Yang, Kai-Chiang

    2015-10-01

    Osteoporosis impairs the bone-healing process as well as bone fracture fixation. The intervention of osteoporosis is considered to be one part of bone fracture treatment. Thus, orthopedic fixators impregnated with antiosteoporosis regimens will improve fracture fixation in osteoporotic bone. In this study, the strontium (Sr) and calcium phosphate ceramic (CPC) were mixed first and then mixed with poly(ε-caprolactone) (PCL) to fabricate a bioactive and bioabsorbable bone fixators. The prepared Sr-CPC/PCL screws were implanted into the distal femur of ovariectomized rabbits. The results showed that Sr-CPC/PCL composite had the appropriate mechanical properties, good biocompatibility, and radio-opacity. The Sr addition created a porous structure and accelerated the degradation of bone screws, but the degradation products did not acidify the surrounding environment. For osteoporotic animals, favorable osteointegration around the Sr-CPC/PCL screws was found, and the total porosity of trabecular bone was decreased under the inspections of micro-computerized tomography. Compared with PCL or CPC/PCL screw, animals which received Sr-CPC/PCL were found to have better results in terms of trabecular number, thickness, and separation. This study reveals that the Sr-impregnated bone fixator improves osseointegration in osteoporotic animals. Sr-CPC/PCL composite is a good candidate material for osteofixation in osteoporotic patients. PMID:25847487

  1. Bone impregnated hip screw in femoral neck fracture: Clinicoradiological results

    PubMed Central

    Sundar Raj, PK; Nuuman, Jiju A; Pattathil, Amish Sunder

    2015-01-01

    Background: Femoral neck fractures are treated either by internal fixation or arthroplasty. Usually, cannulated cancellous screws are used for osteosynthesis of fracture neck of femur. The bone impregnated hip screw (BIHS) is an alternative implant, where osteosyntehsis is required in femoral neck fracture. Materials and Methods: The BIHS is a hollow screw with thread diameter 8.3 mm, shank diameter 6.5 mm and wall thickness 2.2 mm and holes in the shaft of the screw with diameter 2 mm, placed in a staggered fashion. Biomechanical and animal experimental studies were done. Clinical study was done in two phases: Phase 1 in a group of volunteers, only with BIHS was used in a pilot study and phase 2 comparative study was done in a group with AO cannulated screws and the other group treated with BIHS. Results: In the phase 1 study, out of 15 patients, only one patient had delayed union. In phase 2, there were 78 patients, 44 patients in BIHS showed early union, compared to the rest 34 cases of AO cannulated screws Out of 44 patients with BIHS, 41 patients had an excellent outcome, 2 had nonunions and one implant breakage was noted. Conclusions: Bone impregnated hip screw has shown to provide early solid union since it incorporates the biomechanical principles and also increases the osteogenic potential and hence, found superior to conventional cannulated cancellous screw. PMID:26015608

  2. Zinc impregnated cellulose nanocomposites: Synthesis, characterization and applications

    NASA Astrophysics Data System (ADS)

    Ali, Attarad; Ambreen, Sidra; Maqbool, Qaisar; Naz, Sania; Shams, Muhammad Fahad; Ahmad, Madiha; Phull, Abdul Rehman; Zia, Muhammad

    2016-11-01

    Nanocomposite materials have broad applicability due to synergistic effect of combined components. In present investigation, cellulose isolated from citrus peel waste is used as a supporting material; impregnation of zinc oxide nanoparticles via co-precipitation method. The characterization of nano composite is carried out through Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) and Thermo-gravimetric analysis (TGA) resulting less than 10 μm cellulose fiber and approx. 50 nm ZnO NPs. Zinc oxide impregnated cellulose (ZnO-Cel) exhibited significant bacterial devastation property when compared to ZnO NPs or Cellulose via disc diffusion and colony forming unit methods. In addition, the ZnO-Cel exhibited significant total antioxidant, and minor DPPH free radical scavenging and total reducing power activities. The nano composite also showed time dependent increase in photocatalytic by effectively degrading methylene blue dye up to 69.5% under sunlight irradiation within 90 min. The results suggest effective utilization of cellulose obtained from citrus waste and synthesis of pharmacologically important nano-composites that can be exploited in wound dressing; defence against microbial attack and healing due to antioxidative property, furthermore can also be used for waste water treatment.

  3. The expression of IGF-1R in Helicobacter pylori-infected intestinal metaplasia and gastric cancer

    PubMed Central

    Nakajima, Noriko; Kozu, Karina; Kobayashi, Shun; Nishiyama, Ryu; Okubo, Rie; Akai, Yuichi; Moriyama, Mitsuhiko; Kinukawa, Noriko

    2016-01-01

    Overexpression of IGF-1R has been demonstrated in gastrointestinal cancers, and its expression is reported as the result of the loss of tumor suppressors. IL-16 is involved in the pathophysiological process of chronic inflammatory diseases. The aim of this study is to determine the changes in the expression of IGF-1R in intestinal metaplasia (IM) and gastric cancer (GC) as well as the effect of Helicobacter pylori (H. pylori) and IL-16 on cell proliferation and IGF-1R expression in gastric cells. AGS cells were incubated with combinations of IL-16 and H. pylori. Gastric cell proliferation was studied by BrdU uptake. In H. pylori infected mucosa, IGF-1R was significantly higher in IM than chronic gastritis (CG), and also higher in GC than CG and IM. H. pylori significantly decreased BrdU uptake. IL-16 increased BrdU uptake and IGF-1R on AGS cells which had been decreased by H. pylori. Co-incubation with IL-16 increased the expression of IGF-1R mRNA in H. pylori infected cells. We conclude that the expression of IGF-1R in H. pylori infected gastric mucosa may indicate an early stage of carcinogenesis. The IL-16 secretion by H. pylori can be a trigger for the expression of IGF-1R, and it may also be a factor for gastric carcinogenesis. PMID:27499580

  4. The expression of IGF-1R in Helicobacter pylori-infected intestinal metaplasia and gastric cancer.

    PubMed

    Nakajima, Noriko; Kozu, Karina; Kobayashi, Shun; Nishiyama, Ryu; Okubo, Rie; Akai, Yuichi; Moriyama, Mitsuhiko; Kinukawa, Noriko

    2016-07-01

    Overexpression of IGF-1R has been demonstrated in gastrointestinal cancers, and its expression is reported as the result of the loss of tumor suppressors. IL-16 is involved in the pathophysiological process of chronic inflammatory diseases. The aim of this study is to determine the changes in the expression of IGF-1R in intestinal metaplasia (IM) and gastric cancer (GC) as well as the effect of Helicobacter pylori (H. pylori) and IL-16 on cell proliferation and IGF-1R expression in gastric cells. AGS cells were incubated with combinations of IL-16 and H. pylori. Gastric cell proliferation was studied by BrdU uptake. In H. pylori infected mucosa, IGF-1R was significantly higher in IM than chronic gastritis (CG), and also higher in GC than CG and IM. H. pylori significantly decreased BrdU uptake. IL-16 increased BrdU uptake and IGF-1R on AGS cells which had been decreased by H. pylori. Co-incubation with IL-16 increased the expression of IGF-1R mRNA in H. pylori infected cells. We conclude that the expression of IGF-1R in H. pylori infected gastric mucosa may indicate an early stage of carcinogenesis. The IL-16 secretion by H. pylori can be a trigger for the expression of IGF-1R, and it may also be a factor for gastric carcinogenesis. PMID:27499580

  5. Taste substance binding elicits conformational change of taste receptor T1r heterodimer extracellular domains

    PubMed Central

    Nango, Eriko; Akiyama, Shuji; Maki-Yonekura, Saori; Ashikawa, Yuji; Kusakabe, Yuko; Krayukhina, Elena; Maruno, Takahiro; Uchiyama, Susumu; Nuemket, Nipawan; Yonekura, Koji; Shimizu, Madoka; Atsumi, Nanako; Yasui, Norihisa; Hikima, Takaaki; Yamamoto, Masaki; Kobayashi, Yuji; Yamashita, Atsuko

    2016-01-01

    Sweet and umami tastes are perceived by T1r taste receptors in oral cavity. T1rs are class C G-protein coupled receptors (GPCRs), and the extracellular ligand binding domains (LBDs) of T1r1/T1r3 and T1r2/T1r3 heterodimers are responsible for binding of chemical substances eliciting umami or sweet taste. However, molecular analyses of T1r have been hampered due to the difficulties in recombinant expression and protein purification, and thus little is known about mechanisms for taste perception. Here we show the first molecular view of reception of a taste substance by a taste receptor, where the binding of the taste substance elicits a different conformational state of T1r2/T1r3 LBD heterodimer. Electron microscopy has showed a characteristic dimeric structure. Förster resonance energy transfer and X-ray solution scattering have revealed the transition of the dimerization manner of the ligand binding domains, from a widely spread to compactly organized state upon taste substance binding, which may correspond to distinct receptor functional states. PMID:27160511

  6. Taste substance binding elicits conformational change of taste receptor T1r heterodimer extracellular domains.

    PubMed

    Nango, Eriko; Akiyama, Shuji; Maki-Yonekura, Saori; Ashikawa, Yuji; Kusakabe, Yuko; Krayukhina, Elena; Maruno, Takahiro; Uchiyama, Susumu; Nuemket, Nipawan; Yonekura, Koji; Shimizu, Madoka; Atsumi, Nanako; Yasui, Norihisa; Hikima, Takaaki; Yamamoto, Masaki; Kobayashi, Yuji; Yamashita, Atsuko

    2016-01-01

    Sweet and umami tastes are perceived by T1r taste receptors in oral cavity. T1rs are class C G-protein coupled receptors (GPCRs), and the extracellular ligand binding domains (LBDs) of T1r1/T1r3 and T1r2/T1r3 heterodimers are responsible for binding of chemical substances eliciting umami or sweet taste. However, molecular analyses of T1r have been hampered due to the difficulties in recombinant expression and protein purification, and thus little is known about mechanisms for taste perception. Here we show the first molecular view of reception of a taste substance by a taste receptor, where the binding of the taste substance elicits a different conformational state of T1r2/T1r3 LBD heterodimer. Electron microscopy has showed a characteristic dimeric structure. Förster resonance energy transfer and X-ray solution scattering have revealed the transition of the dimerization manner of the ligand binding domains, from a widely spread to compactly organized state upon taste substance binding, which may correspond to distinct receptor functional states. PMID:27160511

  7. Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer.

    PubMed

    Borcherding, D C; Tong, W; Hugo, E R; Barnard, D F; Fox, S; LaSance, K; Shaughnessy, E; Ben-Jonathan, N

    2016-06-16

    Patients with advanced breast cancer often fail to respond to treatment, creating a need to develop novel biomarkers and effective therapeutics. Dopamine (DA) is a catecholamine that binds to five G protein-coupled receptors. We discovered expression of DA type-1 receptors (D1Rs) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas, and was associated with larger tumors, higher tumor grades, node metastasis and shorter patient survival. DA and D1R agonists, signaling through the cGMP/protein kinase G (PKG) pathway, suppressed cell viability, inhibited invasion and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist that does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenografts by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA (Food and Drug Administration) approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors.

  8. IGF1R mutation analysis in short children with Silver-Russell syndrome features

    PubMed Central

    Soellner, Lukas; Spengler, Sabrina; Begemann, Matthias; Wollmann, Hartmut A.; Binder, Gerhard; Eggermann, Thomas

    2013-01-01

    The insulin-like growth factor 1 receptor (IGF1R) is a key factor in intrauterine and postnatal growth by mediating the biological function of IGF-I. Mutations of IGF1R gene are usually associated with growth retardation, but the clinical picture of IGF1R mutation carriers is heterogeneous. Indeed, these patients show clinical signs compatible with Silver-Russell syndrome (SRS), and some IGF1R mutation carriers have been identified in SRS cohorts. We therefore investigated deoxyribonucleic acid samples of 19 growth-retarded patients with SRS features. Apart from 8 non-pathogenic variants, we detected heterozygosity for the unknown duplication, c.1056_1057dup, leading to a premature termination in one patient and his growth retarded sister. Due to its nature, we assumed that this variant is probably pathogenic. However, the patient and his sister exhibited spontaneous catch-up growth in later life. We therefore hypothesize that the c.1056_1057dup does not result in a significant disruption to the GH-IGFI axis. Thus, this IGF1R mutation without obvious clinical consequence might challenge the actual concept of IGF1R haploinsufficiency as a general cause for disturbed growth in IGF1R mutation carriers. In the future, mutation analysis of IGF1R should be considered in growth-retarded patients with microcephaly and minor SRS features, but not in probands with the characteristic SRS phenotype including macrocephaly. PMID:27625849

  9. IGF1R mutation analysis in short children with Silver-Russell syndrome features.

    PubMed

    Soellner, Lukas; Spengler, Sabrina; Begemann, Matthias; Wollmann, Hartmut A; Binder, Gerhard; Eggermann, Thomas

    2013-09-01

    The insulin-like growth factor 1 receptor (IGF1R) is a key factor in intrauterine and postnatal growth by mediating the biological function of IGF-I. Mutations of IGF1R gene are usually associated with growth retardation, but the clinical picture of IGF1R mutation carriers is heterogeneous. Indeed, these patients show clinical signs compatible with Silver-Russell syndrome (SRS), and some IGF1R mutation carriers have been identified in SRS cohorts. We therefore investigated deoxyribonucleic acid samples of 19 growth-retarded patients with SRS features. Apart from 8 non-pathogenic variants, we detected heterozygosity for the unknown duplication, c.1056_1057dup, leading to a premature termination in one patient and his growth retarded sister. Due to its nature, we assumed that this variant is probably pathogenic. However, the patient and his sister exhibited spontaneous catch-up growth in later life. We therefore hypothesize that the c.1056_1057dup does not result in a significant disruption to the GH-IGFI axis. Thus, this IGF1R mutation without obvious clinical consequence might challenge the actual concept of IGF1R haploinsufficiency as a general cause for disturbed growth in IGF1R mutation carriers. In the future, mutation analysis of IGF1R should be considered in growth-retarded patients with microcephaly and minor SRS features, but not in probands with the characteristic SRS phenotype including macrocephaly. PMID:27625849

  10. Rationale for co-targeting IGF-1R and ALK in ALK fusion positive lung cancer

    PubMed Central

    Lovly, Christine M.; McDonald, Nerina T.; Chen, Heidi; Ortiz-Cuaran, Sandra; Heukamp, Lukas C.; Yan, Yingjun; Florin, Alexandra; Ozretić, Luka; Lim, Diana; Wang, Lu; Chen, Zhao; Chen, Xi; Lu, Pengcheng; Paik, Paul K.; Shen, Ronglai; Jin, Hailing; Buettner, Reinhard; Ansén, Sascha; Perner, Sven; Brockmann, Michael; Bos, Marc; Wolf, Jürgen; Gardizi, Masyar; Wright, Gavin M.; Solomon, Benjamin; Russell, Prudence A.; Rogers, Toni-Maree; Suehara, Yoshiyuki; Red-Brewer, Monica; Tieu, Rudy; de Stanchina, Elisa; Wang, Qingguo; Zhao, Zhongming; Johnson, David H.; Horn, Leora; Wong, Kwok-Kin; Thomas, Roman K.; Ladanyi, Marc; Pao, William

    2014-01-01

    The ALK tyrosine kinase inhibitor (TKI), crizotinib, shows significant activity in patients whose lung cancers harbor ALK fusions but its efficacy is limited by variable primary responses and acquired resistance. In work arising from the intriguing clinical observation of a patient with ALK fusion+ lung cancer who had an ‘exceptional response’ to an IGF-1R antibody, we define a therapeutic synergism between ALK and IGF-1R inhibitors. Similar to IGF-1R, ALK fusion proteins bind to the adaptor, IRS-1, and IRS-1 knockdown enhances the anti-tumor effects of ALK inhibitors. In models of ALK TKI resistance, the IGF-1R pathway is activated, and combined ALK/IGF-1R inhibition improves therapeutic efficacy. Consistent with this finding, IGF-1R/IRS-1 levels are increased in biopsy samples from patients progressing on crizotinib therapy. Collectively, these data support a role for the IGF-1R/IRS-1 pathway in both ALK TKI-sensitive and TKI-resistant states and provide biological rationale for further clinical development of dual ALK/IGF-1R inhibitors. PMID:25173427

  11. Anxiolytic Effects of the MCH1R Antagonist TPI 1361-17

    PubMed Central

    Lee, Cheol; Parks, Gregory S.

    2010-01-01

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts on the MCH1 receptor. MCH1R is expressed widely throughout the brain, particularly in regions thought to be involved in the regulation of stress and emotional response. The role of MCH in anxiety has been controversial, however. Central administration of MCH has been reported to promote or reduce anxiety-like behaviors. The anxiolytic activity of several MCH1R antagonists has also been debated. To address this issue, we have tested whether TPI 1361-17, a highly specific and high affinity MCH1R antagonist, exerts anxiolytic effects in two commonly used models of anxiety, the elevated plus maze and the light–dark transition test. We show that this MCH1R antagonist exerts potent anxiolytic effects in both assays. Our study therefore supports previous studies indicating that MCH1R antagonists may be useful in the treatment of anxiety. PMID:20635163

  12. Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma

    PubMed Central

    Dai, Wei; Zheng, Hong; Cheung, Arthur Kwok Leung; Tang, Clara Sze-man; Ko, Josephine Mun Yee; Wong, Bonnie Wing Yan; Leong, Merrin Man Long; Sham, Pak Chung; Cheung, Florence; Kwong, Dora Lai-Wan; Ngan, Roger Kai Cheong; Ng, Wai Tong; Yau, Chun Chung; Pan, Jianji; Peng, Xun; Tung, Stewart; Zhang, Zengfeng; Ji, Mingfang; Chiang, Alan Kwok-Shing; Lee, Anne Wing-Mui; Lee, Victor Ho-fun; Lam, Ka-On; Au, Kwok Hung; Cheng, Hoi Ching; Yiu, Harry Ho-Yin; Lung, Maria Li

    2016-01-01

    Multiple factors, including host genetics, environmental factors, and Epstein–Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germ-line variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%, P = 7.94 × 10−12). The validation study, including 2,160 cases and 2,433 controls, showed that the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways. PMID:26951679

  13. Impregnating unconsolidated pyroclastic sequences: A tool for detailed facies analysis

    NASA Astrophysics Data System (ADS)

    Klapper, D.; Kueppers, U.; Castro, J. M.

    2009-12-01

    The interpretation of volcanic eruptions is usually derived from direct observation and the thorough analysis of the deposits. Processes in vent-proximal areas are usually not directly accessible or likely to be obscured. Hence, our understanding of proximal deposits is often limited as they were produced by the simultaneous events stemming from primary eruptive, transportative, and meteorological conditions. Here we present a method that permits for a direct and detailed quasi in-situ investigation of loose pyroclastic units that are usually analysed in the laboratory for their 1) grain-size distribution, 2) componentry, and 3) grain morphology. As the clast assembly is altered during sampling, the genesis of a stratigraphic unit and the relative importance of the above mentioned deposit characteristics is hard to achieve. In an attempt to overcome the possible loss of information during conventional sampling techniques, we impregnated the cleaned surfaces of proximal, unconsolidated units of the 1957-58 Capelinhos eruption on Faial, Azores. During this basaltic, emergent eruption, fluxes in magma rise rate led to a repeated build-up and collapse of tuff cones and consequently to a shift between phreatomagmatic and magmatic eruptive style. The deposits are a succession of generally parallel bedded, cm- to dm-thick layers with a predominantly ashy matrix. The lapilli content is varying gradually; the content of bombs is enriched in discrete layers without clear bomb sags. The sample areas have been cleaned and impregnated with a two-component glue (EPOTEK 301). For approx. 10 * 10 cm, a volume of mixed glue of 20 ml was required. This low-viscosity, transparent glue allowed for an easy application on the target area by means of a syringe and permeated the deposit as deep as 5 mm. After > 24 h, the glue was sufficiently dry to enable the sample to be laid open. This impregnation method renders it possible to cut and polish the sample and investigate grain

  14. Impregnating unconsolidated pyroclastic sequences: A tool for detailed facies analysis

    NASA Astrophysics Data System (ADS)

    Klapper, Daniel; Kueppers, Ulrich; Castro, Jon M.; Pacheco, Jose M. R.; Dingwell, Donald B.

    2010-05-01

    The interpretation of volcanic eruptions is usually derived from direct observation and the thorough analysis of the deposits. Processes in vent-proximal areas are usually not directly accessible or likely to be obscured. Hence, our understanding of proximal deposits is often limited as they were produced by the simultaneous events stemming from primary eruptive, transportative, and meteorological conditions. Here we present a method that permits for a direct and detailed quasi in-situ investigation of loose pyroclastic units that are usually analysed in the laboratory for their 1) grain-size distribution, 2) componentry, and 3) grain morphology. As the clast assembly is altered during sampling, the genesis of a stratigraphic unit and the relative importance of the above mentioned deposit characteristics is hard to achieve. In an attempt to overcome the possible loss of information during conventional sampling techniques, we impregnated the cleaned surfaces of proximal, unconsolidated units of the 1957-58 Capelinhos eruption on Faial, Azores. During this basaltic, emergent eruption, fluxes in magma rise rate led to a repeated build-up and collapse of tuff cones and consequently to a shift between phreatomagmatic and magmatic eruptive style. The deposits are a succession of generally parallel bedded, cm- to dm-thick layers with a predominantly ashy matrix. The lapilli content is varying gradually; the content of bombs is enriched in discrete layers without clear bomb sags. The sample areas have been cleaned and impregnated with two-component glue (EPOTEK 301). For approx. 10 * 10 cm, a volume of mixed glue of 20 ml was required. Using a syringe, this low-viscosity, transparent glue could be easily applied on the target area. We found that the glue permeated the deposit as deep as 5 mm. After > 24 h, the glue was sufficiently dry to enable the sample to be laid open. This impregnation method renders it possible to cut and polish the sample and investigate grain

  15. 21 CFR 529.1003 - Flurogestone acetate-impregnated vaginal sponge.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Flurogestone acetate-impregnated vaginal sponge... § 529.1003 Flurogestone acetate-impregnated vaginal sponge. (a) Specifications. Each vaginal sponge... ewes during their normal breeding season. (2) Limitations. Using applicator provided, insert...

  16. 21 CFR 529.1003 - Flurogestone acetate-impregnated vaginal sponge.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Flurogestone acetate-impregnated vaginal sponge... § 529.1003 Flurogestone acetate-impregnated vaginal sponge. (a) Specifications. Each vaginal sponge... ewes during their normal breeding season. (2) Limitations. Using applicator provided, insert...

  17. 21 CFR 529.1003 - Flurogestone acetate-impregnated vaginal sponge.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Flurogestone acetate-impregnated vaginal sponge... § 529.1003 Flurogestone acetate-impregnated vaginal sponge. (a) Specifications. Each vaginal sponge... ewes during their normal breeding season. (2) Limitations. Using applicator provided, insert...

  18. Modification of fast-growing Chinese Fir wood with unsaturated polyester resin: Impregnation technology and efficiency

    NASA Astrophysics Data System (ADS)

    Ma, Qing; Zhao, Zijian; Yi, Songlin; Wang, Tianlong

    In this study, Chinese Fir was impregnated with unsaturated polyester resin to enhance its properties. Samples 20 mm × 20 mm × 20 mm in size were split into different sections with epoxy resin and tinfoil and subjected to an impregnation experiment under various parameters. Vacuum degree was -0.04 MPa, -0.06 MPa or -0.08 MPa and vacuum duration was 15 min, 30 min, or 45 min. The results indicated that impregnation weight percent gain is linearly dependent on curing weight percent gain. Vacuum duration appears to have less influence on the curing weight percent gain than vacuum degree, and impregnation was most successful at the transverse section compared to other sections. The optimal impregnation parameters were 30 min modification under -0.08 MPa vacuum followed by 120 min at atmospheric pressure for samples 200 mm × 100 mm × 20 mm in size. Uneven distribution of weight percent gain and cracking during the curing process suggested that 30 min post-processing at -0.09 MPa vacuum was the most effective way to complete the impregnation process. The sample's bending strength and modulus of elasticity increased after impregnation treatment. Bending strength after impregnation without post-processing reached 112.85%, but reached 71.65% with vacuum-processing; modulus of elasticity improved 67.13% and 58.28% without and with post-processing, respectively.

  19. IN-FLIGHT CAPTURE OF ELEMENTAL MERCURY BY A CHLORINE-IMPREGNATED ACTIVATED CARBON

    EPA Science Inventory

    The paper discusses the in-flight capture of elemental mercury (Hgo) by a chlorine (C1)-impregnated activated carbon. Efforts to develop sorbents for the control of Hg emissions have demonstrated that C1-impregnation of virgin activated carbons using dilute solutions of hydrogen ...

  20. Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes1234

    PubMed Central

    Chen, Qing-Ying; Alarcon, Suzanne; Tharp, Anilet; Ahmed, Osama M; Estrella, Nelsa L; Greene, Tiffani A; Rucker, Joseph; Breslin, Paul AS

    2009-01-01

    Background: The TAS1R1 and TAS1R3 G protein–coupled receptors are believed to function in combination as a heteromeric glutamate taste receptor in humans. Objective: We hypothesized that variations in the umami perception of glutamate would correlate with variations in the sequence of these 2 genes, if they contribute directly to umami taste. Design: In this study, we first characterized the general sensitivity to glutamate in a sample population of 242 subjects. We performed these experiments by sequencing the coding regions of the genomic TAS1R1 and TAS1R3 genes in a separate set of 87 individuals who were tested repeatedly with monopotassium glutamate (MPG) solutions. Last, we tested the role of the candidate umami taste receptor hTAS1R1-hTAS1R3 in a functional expression assay. Results: A subset of subjects displays extremes of sensitivity, and a battery of different psychophysical tests validated this observation. Statistical analysis showed that the rare T allele of single nucleotide polymorphism (SNP) R757C in TAS1R3 led to a doubling of umami ratings of 25 mmol MPG/L. Other suggestive SNPs of TAS1R3 include the A allele of A5T and the A allele of R247H, which both resulted in an approximate doubling of umami ratings of 200 mmol MPG/L. We confirmed the potential role of the human TAS1R1-TAS1R3 heteromer receptor in umami taste by recording responses, specifically to l-glutamate and inosine 5′-monophosphate (IMP) mixtures in a heterologous expression assay in HEK (human embryonic kidney) T cells. Conclusions: There is a reliable and valid variation in human umami taste of l-glutamate. Variations in perception of umami taste correlated with variations in the human TAS1R3 gene. The putative human taste receptor TAS1R1-TAS1R3 responds specifically to l-glutamate mixed with the ribonucleotide IMP. Thus, this receptor likely contributes to human umami taste perception. PMID:19587085

  1. V1R promoters are well conserved and exhibit common putative regulatory motifs

    PubMed Central

    Stewart, Robert; Lane, Robert P

    2007-01-01

    Background The mouse vomeronasal organ (VNO) processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites. Results We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, LogoAlign, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence). We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation. Conclusion Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new motif-finding algorithm, Logo

  2. A Mathematical Model for Continuous Fiber Reinforced Thermoplastic Composite in Melt Impregnation

    NASA Astrophysics Data System (ADS)

    Ren, Feng; Yu, Yang; Yang, Jianjun; Xin, Chunling; He, Yadong

    2016-10-01

    Through the combination of Reynolds equation and Darcy's law, a mathematical model was established to calculate the pressure distribution in wedge area, which contributed to the forecast effect of processing parameters on impregnation degree of the fiber bundle. The experiments were conducted to verify the capacity of the proposed model with satisfactory results, which means that the model is effective in predicting the influence of processing parameters on impregnation. From the mathematical model, it was known that the impregnation degree of the fiber bundle would be improved by increasing the processing temperature, number and radius of pins, or decreasing the pulling speed and the center distance of pins, which provided a possible solution to the difficulty of melt with high viscosity in melt impregnation and optimization of impregnation processing.

  3. Melanocortin receptor 1 (MC1R) mutations and coat color in pigs.

    PubMed Central

    Kijas, J M; Wales, R; Törnsten, A; Chardon, P; Moller, M; Andersson, L

    1998-01-01

    The melanocortin receptor 1 (MC1R) plays a central role in regulation of eumelanin (black/brown) and phaeomelanin (red/yellow) synthesis within the mammalian melanocyte and is encoded by the classical Extension (E) coat color locus. Sequence analysis of MC1R from seven porcine breeds revealed a total of four allelic variants corresponding to five different E alleles. The European wild boar possessed a unique MC1R allele that we believe is required for the expression of a wild-type coat color. Two different MC1R alleles were associated with the dominant black color in pigs. MC1R*2 was found in European Large Black and Chinese Meishan pigs and exhibited two missense mutations compared with the wild-type sequence. Comparative data strongly suggest that one of these, L99P, may form a constitutively active receptor. MC1R*3 was associated with the black color in the Hampshire breed and involved a single missense mutation D121N. This same MC1R variant was also associated with EP, which results in black spots on a white or red background. Two different missense mutations were identified in recessive red (e/e) animals. One of these, A240T, occurs at a highly conserved position, making it a strong candidate for disruption of receptor function. PMID:9799269

  4. Downregulation of Protein 4.1R impairs centrosome function,bipolar spindle organization and anaphase

    SciTech Connect

    Spence, Jeffrey R.; Go, Minjoung M.; Bahmanyar, S.; Barth,A.I.M.; Krauss, Sharon Wald

    2006-03-17

    Centrosomes nucleate and organize interphase MTs and areinstrumental in the assembly of the mitotic bipolar spindle. Here wereport that two members of the multifunctional protein 4.1 family havedistinct distributions at centrosomes. Protein 4.1R localizes to maturecentrioles whereas 4.1G is a component of the pericentriolar matrixsurrounding centrioles. To selectively probe 4.1R function, we used RNAinterference-mediated depletion of 4.1R without decreasing 4.1Gexpression. 4.1R downregulation reduces MT anchoring and organization atinterphase and impairs centrosome separation during prometaphase.Metaphase chromosomes fail to properly condense/align and spindleorganization is aberrant. Notably 4.1R depletion causes mislocalizationof its binding partner NuMA (Nuclear Mitotic Apparatus Protein),essential for spindle pole focusing, and disrupts ninein. Duringanaphase/telophase, 4.1R-depleted cells have lagging chromosomes andaberrant MT bridges. Our data provide functional evidence that 4.1R makescrucial contributions to centrosome integrity and to mitotic spindlestructure enabling mitosis and anaphase to proceed with the coordinatedprecision required to avoid pathological events.

  5. Pleiotropic effects of extended blockade of CSF1R signaling in adult mice.

    PubMed

    Sauter, Kristin A; Pridans, Clare; Sehgal, Anuj; Tsai, Yi Ting; Bradford, Barry M; Raza, Sobia; Moffat, Lindsey; Gow, Deborah J; Beard, Philippa M; Mabbott, Neil A; Smith, Lee B; Hume, David A

    2014-08-01

    We investigated the role of CSF1R signaling in adult mice using prolonged treatment with anti-CSF1R antibody. Mutation of the CSF1 gene in the op/op mouse produces numerous developmental abnormalities. Mutation of the CSF1R has an even more penetrant phenotype, including perinatal lethality, because of the existence of a second ligand, IL-34. These effects on development provide limited insight into functions of CSF1R signaling in adult homeostasis. The carcass weight and weight of several organs (spleen, kidney, and liver) were reduced in the treated mice, but overall body weight gain was increased. Despite the complete loss of Kupffer cells, there was no effect on liver gene expression. The treatment ablated OCL, increased bone density and trabecular volume, and prevented the decline in bone mass seen in female mice with age. The op/op mouse has a deficiency in pancreatic β cells and in Paneth cells in the gut wall. Only the latter was reproduced by the antibody treatment and was associated with increased goblet cell number but no change in villus architecture. Male op/op mice are infertile as a result of testosterone insufficiency. Anti-CSF1R treatment ablated interstitial macrophages in the testis, but there was no sustained effect on testosterone or LH. The results indicate an ongoing requirement for CSF1R signaling in macrophage and OCL homeostasis but indicate that most effects of CSF1 and CSF1R mutations are due to effects on development.

  6. IDH-1R132H mutation status in diffuse glioma patients: implications for classification

    PubMed Central

    Wang, Peng-fei; Liu, Ning; Song, Hong-wang; Yao, Kun; Jiang, Tao; Li, Shou-wei; Yan, Chang-Xiang

    2016-01-01

    WHO2007 grading of diffuse gliomas in adults is well-established. However, IDH mutations make classification of gliomas according to the WHO2007 edition controversial. Here, we characterized IDH-1R132H mut status in a cohort of 670 adult patients with different WHO2007 grades of diffuse glioma. Patient characteristics, clinical data and prognoses were obtained from medical records. Patients with IDH-1R132H mut were younger and had better clinical outcomes than those without mutations. Differences in age among patients with astrocytomas of different WHO2007 grades were eliminated after patients were grouped based on IDH-1R132H status. IDH-1R132H mut was present more often in patients with lower Ki-67 and MGMT protein levels and higher mutant p53 levels. Ki-67 was also strongly associated with WHO2007 grade independently of IDH-1R132H mut status. Moreover, patients with Ki-67<30 survived longer than those with Ki-67≥30, regardless of IDH-1R132H mut status. Patients in the IDH-1R132H mut group with lower MGMT protein levels also had better clinical outcomes than those in other groups. Our results indicate that to better treat gliomas, IDH mutation status should be included when determining WHO2007 grade in glioma patients. PMID:27120786

  7. Investigation of Performance Envelope for Phenolic Impregnated Carbon Ablator (PICA)

    NASA Technical Reports Server (NTRS)

    Agrawal, Parul; Prabhu, Dinesh; Milos, Frank S.; Stackpoole, Mairead

    2016-01-01

    The present work provides the results of a short exploratory study on the performance of Phenolic Impregnated Carbon Ablator, or PICA, at high heat flux and pressure in an arcjet facility at NASA Ames Research Center. The primary objective of the study was to explore the thermal response of PICA at cold-wall heat fluxes well in excess of 1500 W/cm (exp 2). Based on the results of a series of flow simulations, multiple PICA samples were tested at an estimated cold wall heat flux and stagnation pressure of 1800 W/cm (exp 2) and 130 kPa, respectively. All samples survived the test, and no failure was observed either during or after the exposure. The results indicate that PICA has a potential to perform well at environments with significantly higher heat flux and pressure than it has currently been flown.

  8. Microwave impregnation of porous materials with thermal energy storage materials

    DOEpatents

    Benson, David K.; Burrows, Richard W.

    1993-01-01

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent to the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  9. Microwave impregnation of porous materials with thermal energy storage materials

    DOEpatents

    Benson, D.K.; Burrows, R.W.

    1993-04-13

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent to the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  10. Development of metal oxide impregnated stilbite thick film ethanol sensor

    NASA Astrophysics Data System (ADS)

    Mahabole, M. P.; Lakhane, M. A.; Choudhari, A. L.; Khairnar, R. S.

    2016-05-01

    This paper presents the study of the sensing efficiency of Titanium oxide/ Stilbite and Copper oxide /Stilbite composites towards detection of hazardous pollutants like ethanol. Stilbite based composites are prepared by physically mixing zeolite with metal oxides namely TiO2 and CuO with weight ratios of 25:75, 50:50 and 75:25. The resulting sensor materials are characterized by X-ray diffraction and Fourier Transform Infrared Spectroscopy techniques. Composite sensors are fabricated in the form of thick film by using screen printing technique. The effect of metal oxide concentration on various ethanol sensing parameters such as operating temperature, maximum uptake capacity and response/recovery time are investigated. The results indicate that metal oxide impregnated stilbite composites have great potential as low temperature ethanol sensor.

  11. Microwave impregnation of porous materials with thermal energy storage materials

    SciTech Connect

    Benson, D.K.; Burrows, R.W.

    1991-03-13

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent tc the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  12. Turbulent drag reduction over air- and liquid- impregnated surfaces

    NASA Astrophysics Data System (ADS)

    Rosenberg, Brian J.; Van Buren, Tyler; Fu, Matthew K.; Smits, Alexander J.

    2016-01-01

    Results on turbulent skin friction reduction over air- and liquid-impregnated surfaces are presented for aqueous Taylor-Couette flow. The surfaces are fabricated by mechanically texturing the inner cylinder and chemically modifying the features to make them either non-wetting with respect to water (air-infused, or superhydrophobic case), or wetting with respect to an oil that is immiscible with water (liquid-infused case). The drag reduction, which remains fairly constant over the Reynolds number range tested (100 ≤ Reτ ≤ 140), is approximately 10% for the superhydrophobic surface and 14% for the best liquid-infused surface. Our results suggest that liquid-infused surfaces may enable robust drag reduction in high Reynolds number turbulent flows without the shortcomings associated with conventional superhydrophobic surfaces, namely, failure under conditions of high hydrodynamic pressure and turbulent flow fluctuations.

  13. Microwave impregnation of porous materials with thermal energy storage materials

    SciTech Connect

    Benson, D.K.; Burrows, R.W.

    1992-12-31

    A method for impregnating a porous, non-metallic construction material with a solid phase-change material is described. The phase-change material in finely divided form is spread onto the surface of the porous material, after which the porous material is exposed to microwave energy for a time sufficient to melt the phase-change material. The melted material is spontaneously absorbed into the pores of the porous material. A sealing chemical may also be included with the phase-change material (or applied subsequent to the phase-change material) to seal the surface of the porous material. Fire retardant chemicals may also be included with the phase-change materials. The treated construction materials are better able to absorb thermal energy and exhibit increased heat storage capacity.

  14. Impregnating a heated filler with a non-Newtonian fluid

    SciTech Connect

    Kosachevskii, L.A.; Kosachevskaya, E.A.; Syui, L.S.

    1992-04-01

    Here we examine an analogous problem of a power filtration law for arbitrary temperature-dependence of the non-Newtonian viscosity and for more general heat-transfer boundary conditions at the surface of the filler. We also use a parametric method, but with a different representation of the temperature profile, which allows us to obtain the solution in a compact form suitable for numerical computations. The problem is solved analytically in the particular cases of small and large pressure gradients, and also for weak temperature dependence of the non-Newtonian viscosity. An approximate parametric method is used to solve the planar temperature-dependent problem of continuously impregnating a heated filler with a fluid that has a power-law non-Newtonian viscosity. 5 refs., 1 fig., 2 tabs.

  15. Deciphering the nuclear import pathway for the cytoskeletal red cell protein 4.1R.

    PubMed

    Gascard, P; Nunomura, W; Lee, G; Walensky, L D; Krauss, S W; Takakuwa, Y; Chasis, J A; Mohandas, N; Conboy, J G

    1999-06-01

    The erythroid membrane cytoskeletal protein 4.1 is the prototypical member of a genetically and topologically complex family that is generated by combinatorial alternative splicing pathways and is localized at diverse intracellular sites including the nucleus. To explore the molecular determinants for nuclear localization, we transfected COS-7 cells with epitope-tagged versions of natural red cell protein 4.1 (4.1R) isoforms as well as mutagenized and truncated derivatives. Two distant topological sorting signals were required for efficient nuclear import of the 4.1R80 isoform: a basic peptide, KKKRER, encoded by alternative exon 16 and acting as a weak core nuclear localization signal (4.1R NLS), and an acidic peptide, EED, encoded by alternative exon 5. 4.1R80 isoforms lacking either of these two exons showed decreased nuclear import. Fusion of various 4.1R80 constructs to the cytoplasmic reporter protein pyruvate kinase confirmed a requirement for both motifs for full NLS function. 4.1R80 was efficiently imported in the nuclei of digitonin-permeabilized COS-7 cells in the presence of recombinant Rch1 (human importin alpha2), importin beta, and GTPase Ran. Quantitative analysis of protein-protein interactions using a resonant mirror detection technique showed that 4.1R80 bound to Rch1 in vitro with high affinity (KD = 30 nM). The affinity decreased at least 7- and 20-fold, respectively, if the EED motif in exon 5 or if 4.1R NLS in exon 16 was lacking or mutated, confirming that both motifs were required for efficient importin-mediated nuclear import of 4.1R80.

  16. IGF1R Signaling in Ewing Sarcoma Is Shaped by Clathrin-/Caveolin-Dependent Endocytosis

    PubMed Central

    Martins, Ana Sofia; Ordóñez, José Luis; Amaral, Ana Teresa; Prins, Frans; Floris, Giuseppe; Debiec-Rychter, Maria; Hogendoorn, Pancras C. W.; de Alava, Enrique

    2011-01-01

    Receptor endocytosis is critical for cell signaling. IGF1R mediates an autocrine loop that is de-regulated in Ewing Sarcoma (ES) cells. Here we study the impact of IGF1R internalization, mediated by clathrin and caveolin-1 (CAV1), in ES signaling. We used clathrin and CAV1-siRNA to interfere in clathrin- and caveolin-dependent endocytosis. Chlorpromazine (CPMZ) and methyl-beta-cyclo-dextrin (MCD) were also used in order to inhibit clathrin- and caveolin-dependent endocytosis, respectively. We analyzed IGF1R internalization and co-localization with clathrin and CAV1 upon ligand binding, as well as the status of the IGF1R pathway, cellular proliferation, and the apoptosis of interfered and inhibited ES cells. We performed a high-throughput tyrosine kinase phosphorylation assay to analyze the effects of combining the IGF1R tyrosine kinase inhibitor AEW541 (AEW) with CPMZ or MCD on the intracellular phospho-proteome. We observed that IGF1R is internalized upon ligand binding in ES cells and that this process is dependent on clathrin or CAV1. The blockage of receptor internalization inhibited AKT and MAPK phosphorylation, reducing the proliferative rate of ES cells and increasing the levels of apoptosis. Combination of AEW with CPMZ or MCD largely enhanced these effects. CAV1 and clathrin endocytosis controls IGF1R internalization and signaling and has a profound impact on ES IGF1R-promoted survival signaling. We propose the combination of tyrosine-kinase inhibitors with endocytosis inhibitors as a new therapeutic approach to achieve a stronger degree of receptor inhibition in this, or other neoplasms dependent on IGF1R signaling. PMID:21611203

  17. Can we unlock the potential of IGF-1R inhibition in cancer therapy?

    PubMed Central

    King, Helen; Aleksic, Tamara; Haluska, Paul; Macaulay, Valentine M.

    2014-01-01

    IGF-1R inhibitors arrived in the clinic accompanied by optimism based on preclinical activity of IGF-1R targeting, and recognition that low IGF bioactivity protects from cancer. This was tempered by concerns about toxicity to normal tissue IGF-1R and cross-reactivity with insulin receptor (InsR). In fact, toxicity is not a show-stopper; the key issue is efficacy. While IGF-1R inhibition induces responses as monotherapy in sarcomas and with chemotherapy or targeted agents in common cancers, negative Phase 2/3 trials in unselected patients prompted the cessation of several Pharma programs. Here, we review completed and on-going trials of IGF-1R antibodies, kinase inhibitors and ligand antibodies. We assess candidate bio-markers for patient selection, highlighting the potential predictive value of circulating IGFs/IGFBPs, the need for standardized assays for IGF-1R, and preclinical evidence that variant InsRs mediate resistance to IGF-1R antibodies. We review hypothesis-led and unbiased approaches to evaluate IGF-1R inhibitors with other agents, and stress the need to consider sequencing with chemotherapy. The last few years were a tough time for IGF-1R therapeutics, but also brought progress in understanding IGF biology. Even failed studies include patients who derived benefit; they should be investigated to identify features distinguishing the tumors and host environment of responders from non-responders. We emphasize the importance of incorporating biospecimen collection into trial design, and wording patient consents to allow post hoc analysis of trial material as new data become available. Such information represents the key to unlocking the potential of this approach, to inform the next generation of trials of IGF signalling inhibitors. PMID:25123819

  18. IGF1R signaling in Ewing sarcoma is shaped by clathrin-/caveolin-dependent endocytosis.

    PubMed

    Martins, Ana Sofia; Ordóñez, José Luis; Amaral, Ana Teresa; Prins, Frans; Floris, Giuseppe; Debiec-Rychter, Maria; Hogendoorn, Pancras C W; de Alava, Enrique

    2011-01-01

    Receptor endocytosis is critical for cell signaling. IGF1R mediates an autocrine loop that is de-regulated in Ewing Sarcoma (ES) cells. Here we study the impact of IGF1R internalization, mediated by clathrin and caveolin-1 (CAV1), in ES signaling. We used clathrin and CAV1-siRNA to interfere in clathrin- and caveolin-dependent endocytosis. Chlorpromazine (CPMZ) and methyl-beta-cyclo-dextrin (MCD) were also used in order to inhibit clathrin- and caveolin-dependent endocytosis, respectively. We analyzed IGF1R internalization and co-localization with clathrin and CAV1 upon ligand binding, as well as the status of the IGF1R pathway, cellular proliferation, and the apoptosis of interfered and inhibited ES cells. We performed a high-throughput tyrosine kinase phosphorylation assay to analyze the effects of combining the IGF1R tyrosine kinase inhibitor AEW541 (AEW) with CPMZ or MCD on the intracellular phospho-proteome. We observed that IGF1R is internalized upon ligand binding in ES cells and that this process is dependent on clathrin or CAV1. The blockage of receptor internalization inhibited AKT and MAPK phosphorylation, reducing the proliferative rate of ES cells and increasing the levels of apoptosis. Combination of AEW with CPMZ or MCD largely enhanced these effects. CAV1 and clathrin endocytosis controls IGF1R internalization and signaling and has a profound impact on ES IGF1R-promoted survival signaling. We propose the combination of tyrosine-kinase inhibitors with endocytosis inhibitors as a new therapeutic approach to achieve a stronger degree of receptor inhibition in this, or other neoplasms dependent on IGF1R signaling.

  19. CSF1R mutations in hereditary diffuse leukoencephalopathy with spheroids are loss of function.

    PubMed

    Pridans, Clare; Sauter, Kristin A; Baer, Kristin; Kissel, Holger; Hume, David A

    2013-10-22

    Hereditary diffuse leukoencephalopathy with spheroids (HDLS) in humans is a rare autosomal dominant disease characterized by giant neuroaxonal swellings (spheroids) within the CNS white matter. Symptoms are variable and can include personality and behavioural changes. Patients with this disease have mutations in the protein kinase domain of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for microglia development. We investigated the effects of these mutations on Csf1r signalling using a factor dependent cell line. Corresponding mutant forms of murine Csf1r were expressed on the cell surface at normal levels, and bound CSF1, but were not able to sustain cell proliferation. Since Csf1r signaling requires receptor dimerization initiated by CSF1 binding, the data suggest a mechanism for phenotypic dominance of the mutant allele in HDLS.

  20. MC1R variants in Chinese Han patients with sporadic Parkinson's disease.

    PubMed

    Shi, Chang-He; Wang, Hui; Mao, Cheng-Yuan; Yang, Jing; Song, Bo; Liu, Yu-Tao; Yang, Zhi-Hua; Luo, Hai-Yang; Zhang, Shu-Yu; Wu, Jun; Xu, Yu-Ming

    2016-06-01

    Recently, a variant p.R160W in the MC1R gene was identified that increased the risk of Parkinson's disease (PD) in Spanish population. To explore whether the MC1R gene variants are associated with sporadic PD in Chinese population, we performed a case-control comparison study for comprehensive MC1R variant screening in 510 Chinese Han patients and 495 healthy controls as ethnically matched controls. We identify 5 nonsynonymous variants, including rs34090186 (p.R67Q), rs2228479 (p.V92M), rs33932559 (p.I120T), rs885479 (p.R163Q), and rs372152373 (p.R223W). However, variants mentioned previously did not show association with PD. Our results suggest that variants in MC1R do not play a major role in PD in the Chinese population.

  1. 2. South elevation, (1r) arches CD and DE. View north ...

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

    2. South elevation, (1-r) arches C-D and D-E. View north - Ashton Viaduct, State Route 116 (Washington Highway) spanning Blackstone River, Blackstone Canal, & Providence & Worcester Railroad, Ashton, Providence County, RI

  2. 3. South elevation, (1r) arches DE and EF. View north ...

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

    3. South elevation, (1-r) arches D-E and E-F. View north - Ashton Viaduct, State Route 116 (Washington Highway) spanning Blackstone River, Blackstone Canal, & Providence & Worcester Railroad, Ashton, Providence County, RI

  3. IGF1R tyrosine kinase inhibitor enhances the cytotoxic effect of methyl jasmonate in endometrial cancer.

    PubMed

    Bruchim, Ilan; Sarfstein, Rive; Reiss, Ari; Flescher, Eliezer; Werner, Haim

    2014-10-01

    The present study evaluated the cytotoxic activity of methyl jasmonate (MJ) in endometrial cancer cells and examined the hypothesis that the apoptotic and anti-proliferative actions of MJ in these cell lines can be enhanced by co-targeting the insulin-like growth factor-1 receptor (IGF1R) signaling pathway. MJ had a potent pro-apoptotic effect and exhibited significant toxicity in all cell lines tested. MJ in combination with NVP-AEW541, a selective IGF1R tyrosine kinase inhibitor, had significantly increased cytotoxicity. MJ decreased IGF1R phosphorylation, however, it enhanced AKT phosphorylation and abolished the anti-apoptotic effect of IGF1. These findings suggest that combined IGF1R inhibitor and MJ administration may constitute an attractive modality for treating endometrial cancer.

  4. CSF1R mutations in hereditary diffuse leukoencephalopathy with spheroids are loss of function

    NASA Astrophysics Data System (ADS)

    Pridans, Clare; Sauter, Kristin A.; Baer, Kristin; Kissel, Holger; Hume, David A.

    2013-10-01

    Hereditary diffuse leukoencephalopathy with spheroids (HDLS) in humans is a rare autosomal dominant disease characterized by giant neuroaxonal swellings (spheroids) within the CNS white matter. Symptoms are variable and can include personality and behavioural changes. Patients with this disease have mutations in the protein kinase domain of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for microglia development. We investigated the effects of these mutations on Csf1r signalling using a factor dependent cell line. Corresponding mutant forms of murine Csf1r were expressed on the cell surface at normal levels, and bound CSF1, but were not able to sustain cell proliferation. Since Csf1r signaling requires receptor dimerization initiated by CSF1 binding, the data suggest a mechanism for phenotypic dominance of the mutant allele in HDLS.

  5. Inherited variation at MC1R and ASIP and association with melanoma-specific survival

    PubMed Central

    Taylor, Nicholas J.; Reiner, Anne S.; Begg, Colin B.; Cust, Anne E.; Busam, Klaus J; Anton-Culver, Hoda; Dwyer, Terence; From, Lynn; Gallagher, Richard P; Gruber, Stephen B.; Rosso, Stefano; White, Kirsten A.; Zanetti, Roberto; Orlow, Irene; Thomas, Nancy E.; Rebbeck, Timothy R.; Berwick, Marianne; Kanetsky, Peter A.

    2014-01-01

    MC1R is a marker of melanoma risk in populations of European ancestry. However, MC1R effects on survival are much less studied. We investigated associations between variation at MC1R and survival in an international, population-based series of single primary melanoma patients enrolled into the GEM study. MC1R genotype data was available for 2,200 participants with a first incident primary melanoma diagnosis. We estimated the association of MC1R genotypes with melanoma-specific survival (i.e. death due to melanoma) and overall survival using Cox proportional hazards modeling, adjusting for established prognostic factors for melanoma. We also conducted stratified analyses by Breslow thickness, tumor site, phenotypic index and age. Additionally, we evaluated haplotypes involving polymorphisms near the ASIP locus for their impacts on survival. Melanoma-specific survival was inversely associated with carriage of MC1R variants in the absence of consensus alleles compared to carriage of at least one consensus allele (HR=0.60; 95%CI: 0.40, 0.90). MC1R results for overall survival were consistent with no association. We did not observe any statistical evidence of heterogeneity of effect estimates in stratified analyses. We observed increased hazard of melanoma-specific death among carriers of the risk haplotype TG near the ASIP locus (HR=1.37; 95%CI: 0.91, 2.04) when compared to carriers of the most common GG haplotype. Similar results were noted for overall survival. Upon examining the ASIP TG/TG diplotype, we observed considerably increased hazard of melanoma-specific death (HR=5.11; 95%CI: 1.88, 13.88) compared to carriers of the most common GG/GG diplotype. Our data suggest improved melanoma-specific survival among carriers of two inherited MC1R variants. PMID:25382380

  6. Inherited Variation at MC1R and Histological Characteristics of Primary Melanoma

    PubMed Central

    Taylor, Nicholas J.; Busam, Klaus J.; From, Lynn; Groben, Pamela A.; Anton-Culver, Hoda; Cust, Anne E.; Begg, Colin B.; Dwyer, Terence; Gallagher, Richard P.; Gruber, Stephen B.; Orlow, Irene; Rosso, Stefano; Thomas, Nancy E.; Zanetti, Roberto; Rebbeck, Timothy R.; Berwick, Marianne; Kanetsky, Peter A.

    2015-01-01

    Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nine geographic regions in Australia, Canada, Italy and the United States and were genotyped for MC1R variants classified as high-risk [R] (D84E, R142H, R151C, R160W, and D294H, all nonsense and insertion/deletion) or low-risk [r] (all other nonsynonymous) variants. Tissue was available for 2,160 white participants of the Genes, Environment and Melanoma (GEM) Study with a first incident primary melanoma diagnosis, and underwent centralized pathologic review. No statistically significant associations were observed between MC1R variants and AJCC established prognostic tumor characteristics: Breslow thickness, presence of mitoses or presence of ulceration. However, MC1R was significantly associated with anatomic site of melanoma (p = 0.002) and a positive association was observed between carriage of more than one [R] variant and melanomas arising on the arms (OR = 2.39; 95% CI: 1.40, 4.09). We also observed statistically significant differences between sun-sensitive and sun-resistant individuals with respect to associations between MC1R genotype and AJCC prognostic tumor characteristics. Our results suggest inherited variation in MC1R may play an influential role in anatomic site presentation of melanomas and may differ with respect to skin pigmentation phenotype. PMID:25790105

  7. Effect of the MC1R gene on sexual dimorphism in melanin-based colorations.

    PubMed

    San-Jose, Luis M; Ducrest, Anne-Lyse; Ducret, Valérie; Béziers, Paul; Simon, Céline; Wakamatsu, Kazumasa; Roulin, Alexandre

    2015-06-01

    Variants of the melanocortin-1 receptor (MC1R) gene result in abrupt, naturally selected colour morphs. These genetic variants may differentially affect sexual dimorphism if one morph is naturally selected in the two sexes but another morph is naturally or sexually selected only in one of the two sexes (e.g. to confer camouflage in reproductive females or confer mating advantage in males). Therefore, the balance between natural and sexual selections can differ between MC1R variants, as suggest studies showing interspecific correlations between sexual dimorphism and the rate of nonsynonymous vs. synonymous amino acid substitutions at the MC1R. Surprisingly, how MC1R is related to within-species sexual dimorphism, and thereby to sex-specific selection, has not yet been investigated. We tackled this issue in the barn owl (Tyto alba), a species showing pronounced variation in the degree of reddish pheomelanin-based coloration and in the number and size of black feather spots. We found that a valine (V)-to-isoleucine (I) substitution at position 126 explains up to 30% of the variation in the three melanin-based colour traits and in feather melanin content. Interestingly, MC1R genotypes also differed in the degree of sexual colour dimorphism, with individuals homozygous for the II MC1R variant being 2 times redder and 2.5 times less sexually dimorphic than homozygous individuals for the VV MC1R variant. These findings support that MC1R interacts with the expression of sexual dimorphism and suggest that a gene with major phenotypic effects and weakly influenced by variation in body condition can participate in sex-specific selection processes. PMID:25857339

  8. Role of IGF1R+ MSCs in modulating neuroplasticity via CXCR4 cross-interaction

    PubMed Central

    Lee, Hsu-Tung; Chang, Hao-Teng; Lee, Sophie; Lin, Chen-Huan; Fan, Jia-Rong; Lin, Shinn-Zong; Hsu, Chung Y.; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2016-01-01

    To guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like-markers for selecting MSCs that retain potent self-renewal-ability should be addressed. Here, an insulin-like growth factor 1 receptor (IGF1R)–expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB). These cytokines modulates the signaling events in the hDSCs and potentially enhances engraftment upon transplantation. Specifically, a bidirectional cross-talk between IGF1R/IGF1 and CXCR4/SDF-1α signaling pathways in hDSCs, as revealed by interaction of the two receptors and synergistic activation of both signaling pathways. In rat stroke model, animals receiving IGF1R+ hDSCs transplantation, interaction between IGF1R and CXCR4 was demonstrated to promote neuroplasticity, therefore improving neurological function through increasing glucose metabolic activity, enhancing angiogenesis and anti-inflammatiory effects. Therefore, PDGF in hUCS-culture system contributed to the maintenance of the expression of IGF1R in hDSCs. Furthermore, implantation of IGF1R+ hDSCs exerted enhanced neuroplasticity via integrating inputs from both CXCR4 and IGF1R signaling pathways. PMID:27586516

  9. ADCYAP1R1 GENOTYPE, POSTTRAUMATIC STRESS DISORDER, AND DEPRESSION AMONG WOMEN EXPOSED TO CHILDHOOD MALTREATMENT

    PubMed Central

    Uddin, Monica; Chang, Shun-Chiao; Zhang, Chao; Ressler, Kerry; Mercer, Kristina B.; Galea, Sandro; Keyes, Katherine M.; McLaughlin, Katie A.; Wildman, Derek E.; Aiello, Allison E.; Koenen, Karestan C.

    2014-01-01

    Background A growing literature indicates that genetic variation, in combination with adverse early life experiences, shapes risk for later mental illness. Recent work also suggests that molecular variation at the ADCYAP1R1 locus is associated with posttraumatic stress disorder (PTSD) in women. We sought to test whether childhood maltreatment (CM) interacts with ADCYAP1R1 geno-type to predict PTSD in women. Methods Data were obtained from 495 adult female participants from the Detroit Neighborhood Health Study. Genotyping of rs2267735, an ADCYAP1R1 variant, was conducted via TaqMan assay. PTSD, depression, and CM exposure were assessed via structured interviews. Main and interacting effects of ADCYAP1R1 and CM levels on past month PTSD and post-traumatic stress (PTS) severity were examined using logistic regression and a general linear model, respectively. As a secondary analysis, we also assessed main and interacting effects of ADCYAP1R1 and CM variation on risk of past-month depression diagnosis and symptom severity. Results No significant main effects were observed for ADCYAP1R1 genotype on either PTSD/PTS severity. In contrast, a significant ADCYAP1R1 × CM interaction was observed for both past month PTSD and PTS severity, with carriers of the “C” allele showing enhanced risk for these outcomes among women exposed to CM. No significant main or interaction effects were observed for past month depression/depression severity. Conclusions Genetic variation at the ADCYAP1R1 locus interacts with CM to shape risk of later PTSD, but not depression, among women. The molecular mechanisms contributing to this interaction require further investigation. PMID:23280952

  10. Role of IGF1R(+) MSCs in modulating neuroplasticity via CXCR4 cross-interaction.

    PubMed

    Lee, Hsu-Tung; Chang, Hao-Teng; Lee, Sophie; Lin, Chen-Huan; Fan, Jia-Rong; Lin, Shinn-Zong; Hsu, Chung Y; Hsieh, Chia-Hung; Shyu, Woei-Cherng

    2016-01-01

    To guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like-markers for selecting MSCs that retain potent self-renewal-ability should be addressed. Here, an insulin-like growth factor 1 receptor (IGF1R)-expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB). These cytokines modulates the signaling events in the hDSCs and potentially enhances engraftment upon transplantation. Specifically, a bidirectional cross-talk between IGF1R/IGF1 and CXCR4/SDF-1α signaling pathways in hDSCs, as revealed by interaction of the two receptors and synergistic activation of both signaling pathways. In rat stroke model, animals receiving IGF1R(+) hDSCs transplantation, interaction between IGF1R and CXCR4 was demonstrated to promote neuroplasticity, therefore improving neurological function through increasing glucose metabolic activity, enhancing angiogenesis and anti-inflammatiory effects. Therefore, PDGF in hUCS-culture system contributed to the maintenance of the expression of IGF1R in hDSCs. Furthermore, implantation of IGF1R(+) hDSCs exerted enhanced neuroplasticity via integrating inputs from both CXCR4 and IGF1R signaling pathways. PMID:27586516

  11. CSF1R mutations identified in three families with autosomal dominantly inherited leukoencephalopathy.

    PubMed

    Mitsui, Jun; Matsukawa, Takashi; Ishiura, Hiroyuki; Higasa, Koichiro; Yoshimura, Jun; Saito, Taro L; Ahsan, Budrul; Takahashi, Yuji; Goto, Jun; Iwata, Atsushi; Niimi, Yuki; Riku, Yuuichi; Goto, Yoji; Mano, Kazuo; Yoshida, Mari; Morishita, Shinichi; Tsuji, Shoji

    2012-12-01

    Genetic and phenotypic heterogeneities are considerably high in adult-onset leukoencephalopathy, in which comprehensive mutational analyses of the candidate genes by conventional methods are too laborious. We applied exome sequencing to conduct a comprehensive mutational analysis of genes for autosomal dominant leukoencephalopathies. Genomic DNA samples from four patients of three families with autosomal dominantly inherited adult-onset leukodystrophy were subjected to exome sequencing. On the basis of the results, 21 patients with adult-onset sporadic leukodystrophy and one patient with pathologically proven HDLS were additionally screened for CSF1R mutations. Exome sequencing identified heterozygous CSF1R mutations (p.I794T and p.R777W) in two families. I794T has recently been reported as a causative mutation for hereditary diffuse leukoencephalopathy with spheroids (HDLS), and R777W is a novel mutation. Although mutational analysis of CSF1R in 21 sporadic cases revealed no mutations, another novel CSF1R mutation, p.C653Y, was identified in one patient with autopsy-proven HDSL. These variants were located in the PTK domain where the causative mutations cluster. Functional prediction of the mutant CSF1R as well as cross-species conservation of the affected amino acids supports the notion that these variants are pathogenic for HDLS. Exome sequencing is useful for a comprehensive mutational analysis of causative genes for hereditary leukoencephalopathies, and CSF1R should be considered a candidate gene for patients with autosomal dominant leukoencephalopathies.

  12. MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

    PubMed Central

    Qiao, Yingjin; Berg, Anna-Lena; Wang, Pei; Ge, Yan; Quan, Songxia; Zhou, Sijie; Wang, Hai; Liu, Zhangsuo; Gong, Rujun

    2016-01-01

    Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle4, D-Phe7]-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms. PMID:27270328

  13. A rapid preparation of acicular Ni impregnated anode with enhanced conductivity and operational stability

    NASA Astrophysics Data System (ADS)

    Zhu, Xingbao; Guan, Chengzhi; Lü, Zhe; Wei, Bo; Li, Yiqian; Su, Wenhui

    2014-06-01

    A novel method for fabricating Ni(NO3)2 solution impregnated YSZ (YSZ: Yttria Stabilized Zirconia) anodes for solid oxide fuel cells (SOFCs) is presented. In order to reduce the impregnation cycles and increase the reliability of the YSZ membrane, a YSZ support with a porosity of ∼60% is soaked in a saturated Ni(NO3)2 solution with an increased temperature of 80 °C. The impregnated anode is dried in a vacuum drying device without heating, resulting in a flower-like Ni(NO3)2·6H2O crystal. The formed porous structure is likely to facilitate the impregnating process and considered to be the key to success of the impregnation process with saturated solution. After heating at 700 °C, a novel needle-shaped NiO is presented, which exhibits some advantages including fast preparation, high connectivity, large specific surface area and high operational stability (i.e. high aggregation resistance). For the purpose of comparison, Ni(NO3)2 solution impregnated YSZ anodes prepared through the conventional impregnation process are also characterized under the same conditions.

  14. Electrical performance of nanostructured strontium-doped lanthanum manganite impregnated onto yttria-stabilized zirconia backbone

    NASA Astrophysics Data System (ADS)

    Ju, Jiangwei; Lin, Jie; Wang, Yusu; Zhang, Yanxiang; Xia, Changrong

    2016-01-01

    Strontium-doped lanthanum manganite (LSM) nanoparticles are deposited onto porous yttria-stabilized zirconia frameworks via an ion impregnation/infiltration process. The apparent conductivity of the impregnated LSM nanostructure is investigated regarding the fabricating parameters including LSM loading, heat treatment temperature, heating rate, and annealing at 750 °C for 400 h. Besides, the conductivity, the intrinsic conductivity as well as Bruggeman factor of the impregnated LSM is estimated from the apparent conductivity using the analytical model for the three-dimensional impregnate network. The conductivity increases with LSM loading while the interfacial polarization resistance exhibits the lowest value at an optimal loading of about 5 vol.%, which corresponds to the largest three-phase boundary as predicted using the numerical infiltration methodology. At the optimal loading, the area specific ohmic resistance of the impregnated LSM is about 0.032 Ω cm2 at 700 °C for a typical impregnated cathode of 30 μm thick. It is only 5.5% of the cathode interfacial polarization resistance and 3.3% of the total resistance for a single cell consisting of a Ni-YSZ support, a 10 μm thick electrolyte and a 30 μm thick cathode, demonstrating that the ohmic resistance is negligible in the LSM impregnated cathode for SOFCs.

  15. Iron-impregnated granular activated carbon for arsenic removal from drinking water

    NASA Astrophysics Data System (ADS)

    Chang, Qigang

    A new multi-step iron impregnation method was developed in this study to impregnate GAC with a high amount of iron that possesses desired characteristics: stable, even distribution, and high arsenic adsorption capacity. Research was carried out to investigate the impact of the amount of impregnated iron on arsenic adsorption properties: capacity, affinity, and kinetics. Fe-GACs were characterized in terms of the amount, stability, distribution, morphology, and species of impregnated iron. It was found that a high amount of iron was stably impregnated in GAC. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis demonstrated that the impregnated iron was evenly distributed on the internal surface of GAC. Impregnated iron formed nano-size particles and existed in both crystalline (akaganeite) and amorphous iron. Arsenic adsorption tests were conducted using Fe-GACs with iron content of 1.64--28.90% in a low arsenic concentration that is typical for drinking water treatment. The amount of impregnated iron affects arsenic maximum adsorption capacity (qm) but has little impact on the Langmuir constant h (the affinity of adsorbent for adsorbate). The qm for both As(V) and As(III) adsorptions increased significantly with increase of the amount of impregnated iron up to 13.59%. Further increase of iron amounts caused a gradual decrease of qm for As(V). BET analysis indicated impregnated iron possesses the highest surface area at iron content of 13.59%. A new second-order kinetic model was developed to investigate the impact of the amounts of impregnated iron on arsenic adsorption kinetics. With iron content increased from 1.64% to 28.90%, the intrinsic adsorption rate constants reduced from 4.6x10-2 1/hr to 1.18x10 -3 1/hr, which indicates that impregnated iron slows arsenic intraparticle diffusion rate in Fe-GAC. The decreased arsenic intraparticle diffusion rate was most likely caused by reduced pore size of Fe-GACs. Column tests were

  16. Electrochemical properties of a lithium-impregnated metal foam anode for thermal batteries

    NASA Astrophysics Data System (ADS)

    Choi, Yu-Song; Yu, Hye-Ryeon; Cheong, Hae-Won

    2015-02-01

    Lithium-impregnated metal foam anodes (LIMFAs) are fabricated and investigated. The LIMFAs are prepared by the impregnation of lithium into molten-salt-coated nickel metal foam. A single cell with the LIMFA exhibits a specific capacity of 3009 As g-1. For comparison, a single cell with a LiSi alloy anode is also discharged, demonstrating a specific capacity of 1050 As g-1. These significant improvements can be attributed to the large amount of lithium impregnated into the metal foam as well as the molten lithium holding capability of the foam. Due to their excellent electrochemical properties, LIMFAs are suitable for use in thermal batteries.

  17. Investigation of silver-impregnated alumina for removal of radioactive methyl iodide

    SciTech Connect

    Funabashi, Kiyomi; Fukasawa, Tetsuo; Kikuchi, Makoto

    1995-03-01

    The removal efficiency of methyl iodide for silver-impregnated alumina from gaseous waste has been experimentally evaluated as a function of atmospheric relative humidity. A new adsorbent has been developed for the iodine filter installed in the off-gas treatment system of a radioactive waste tank vent. To improve its removal efficiency under a highly humid atmosphere, the optimum average pore size of alumina was determined to be {approximately}60 nm, and the most effective chemical form of the impregnated silver was identified as silver nitrate. Holding capability of the impregnated silver was also improved by developing a double-pore-structure alumina.

  18. Development of 2D deconvolution method to repair blurred MTSAT-1R visible imagery

    NASA Astrophysics Data System (ADS)

    Khlopenkov, Konstantin V.; Doelling, David R.; Okuyama, Arata

    2014-09-01

    Spatial cross-talk has been discovered in the visible channel data of the Multi-functional Transport Satellite (MTSAT)-1R. The slight image blurring is attributed to an imperfection in the mirror surface caused either by flawed polishing or a dust contaminant. An image processing methodology is described that employs a two-dimensional deconvolution routine to recover the original undistorted MTSAT-1R data counts. The methodology assumes that the dispersed portion of the signal is small and distributed randomly around the optical axis, which allows the image blurring to be described by a point spread function (PSF) based on the Gaussian profile. The PSF is described by 4 parameters, which are solved using a maximum likelihood estimator using coincident collocated MTSAT-2 images as truth. A subpixel image matching technique is used to align the MTSAT-2 pixels into the MTSAT-1R projection and to correct for navigation errors and cloud displacement due to the time and viewing geometry differences between the two satellite observations. An optimal set of the PSF parameters is derived by an iterative routine based on the 4-dimensional Powell's conjugate direction method that minimizes the difference between PSF-corrected MTSAT-1R and collocated MTSAT-2 images. This iterative approach is computationally intensive and was optimized analytically as well as by coding in assembly language incorporating parallel processing. The PSF parameters were found to be consistent over the 5-days of available daytime coincident MTSAT-1R and MTSAT-2 images, and can easily be applied to the MTSAT-1R imager pixel level counts to restore the original quality of the entire MTSAT-1R record.

  19. KISS1R: Hallmarks of an Effective Regulator of the Neuroendocrine Axis.

    PubMed

    Millar, Robert P; Babwah, Andy V

    2015-01-01

    Kisspeptin (KP) is now well recognized as a potent stimulator of gonadotropin-releasing hormone (GnRH) secretion and thereby a major regulator of the neuroendocrine-reproductive axis. KP signals via KISS1R, a G protein-coupled receptor (GPCR) that activates the G proteins Gαq/11. Modulation of the interaction of KP with KISS1R is therefore a potential new therapeutic target for stimulating (in infertility) or inhibiting (in hormone-dependent diseases) the reproductive hormone cascade. Major efforts are underway to target KISS1R in the treatment of sex steroid hormone-dependent disorders and to stimulate endogenous hormonal responses along the neuroendocrine axis as part of in vitro fertilization protocols. The development of analogs modulating KISS1R signaling will be aided by an understanding of the intracellular pathways and dynamics of KISS1R signaling under normal and pathological conditions. This review focuses on KISS1R recruitment of intracellular signaling (Gαq/11- and β-arrestin-dependent) pathways that mediate GnRH secretion and the respective roles of rapid desensitization, internalization, and recycling of resensitized receptors in maintaining an active population of KISS1R at the cell surface to facilitate prolonged KP signaling. Additionally, this review summarizes and discusses the major findings of an array of studies examining the desensitization of KP signaling in man, domestic and laboratory animals. This discussion highlights the major effects of ligand efficacy and concentration and the physiological, developmental, and metabolic status of the organism on KP signaling. Finally, the potential for the utilization of KP and analogs in stimulating and inhibiting the reproductive hormone cascade as an alternative to targeting the downstream GnRH receptor is discussed.

  20. Evolution of the sweet taste receptor gene Tas1r2 in bats.

    PubMed

    Zhao, Huabin; Zhou, Yingying; Pinto, C Miguel; Charles-Dominique, Pierre; Galindo-González, Jorge; Zhang, Shuyi; Zhang, Jianzhi

    2010-11-01

    Taste perception is an important component of an animal's fitness. The identification of vertebrate taste receptor genes in the last decade has enabled molecular genetic studies of the evolution of taste perception in the context of the ecology and dietary preferences of organisms. Although such analyses have been conducted in a number of species for bitter taste receptors, a similar analysis of sweet taste receptors is lacking. Here, we survey the sole sweet taste-specific receptor gene Tas1r2 in 42 bat species that represent all major lineages of the order Chiroptera, one of the most diverse groups of mammals in terms of diet. We found that Tas1r2 is under strong purifying selection in the majority of the bats studied, with no significant difference in the strength of the selection between insect eaters and fruit eaters. However, Tas1r2 is a pseudogene in all three vampire bat species and the functional relaxation likely started in their common ancestor, probably due to the exclusive feeding of vampire bats on blood and their reliance on infrared sensors rather than taste perception to locate blood sources. Our survey of available genome sequences, together with previous reports, revealed additional losses of Tas1r2 in horse, cat, chicken, zebra finch, and western clawed frog, indicating that sweet perception is not as conserved as previously thought. Nonetheless, we found no common dietary pattern among the Tas1r2-lacking vertebrates, suggesting different causes for the losses of Tas1r2 in different species. The complexity of the ecological factors that impact the evolution of Tas1r2 calls for a better understanding of the physiological roles of sweet perception in different species.

  1. ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer.

    PubMed

    Zinn, Rebekah L; Gardner, Eric E; Marchionni, Luigi; Murphy, Sara C; Dobromilskaya, Irina; Hann, Christine L; Rudin, Charles M

    2013-06-01

    New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways, including phosphatidylinositol-3-kinase-Akt and mitogen-activated protein kinase. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R, and the closely related insulin receptor. Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 < 1 μmol/L. Cell line expression of IGF-1R, IR, IGF-1, IGF-2, IGFBP3, and IGFBP6 did not correlate with sensitivity to OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (P = 0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell-cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared with mock-treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. PMID:23515613

  2. Pleiotropic effects of extended blockade of CSF1R signaling in adult mice

    PubMed Central

    Sauter, Kristin A.; Pridans, Clare; Sehgal, Anuj; Tsai, Yi Ting; Bradford, Barry M.; Raza, Sobia; Moffat, Lindsey; Gow, Deborah J.; Beard, Philippa M.; Mabbott, Neil A.; Smith, Lee B.; Hume, David A.

    2014-01-01

    We investigated the role of CSF1R signaling in adult mice using prolonged treatment with anti-CSF1R antibody. Mutation of the CSF1 gene in the op/op mouse produces numerous developmental abnormalities. Mutation of the CSF1R has an even more penetrant phenotype, including perinatal lethality, because of the existence of a second ligand, IL-34. These effects on development provide limited insight into functions of CSF1R signaling in adult homeostasis. The carcass weight and weight of several organs (spleen, kidney, and liver) were reduced in the treated mice, but overall body weight gain was increased. Despite the complete loss of Kupffer cells, there was no effect on liver gene expression. The treatment ablated OCL, increased bone density and trabecular volume, and prevented the decline in bone mass seen in female mice with age. The op/op mouse has a deficiency in pancreatic β cells and in Paneth cells in the gut wall. Only the latter was reproduced by the antibody treatment and was associated with increased goblet cell number but no change in villus architecture. Male op/op mice are infertile as a result of testosterone insufficiency. Anti-CSF1R treatment ablated interstitial macrophages in the testis, but there was no sustained effect on testosterone or LH. The results indicate an ongoing requirement for CSF1R signaling in macrophage and OCL homeostasis but indicate that most effects of CSF1 and CSF1R mutations are due to effects on development. PMID:24652541

  3. Evolution of the sweet taste receptor gene Tas1r2 in bats.

    PubMed

    Zhao, Huabin; Zhou, Yingying; Pinto, C Miguel; Charles-Dominique, Pierre; Galindo-González, Jorge; Zhang, Shuyi; Zhang, Jianzhi

    2010-11-01

    Taste perception is an important component of an animal's fitness. The identification of vertebrate taste receptor genes in the last decade has enabled molecular genetic studies of the evolution of taste perception in the context of the ecology and dietary preferences of organisms. Although such analyses have been conducted in a number of species for bitter taste receptors, a similar analysis of sweet taste receptors is lacking. Here, we survey the sole sweet taste-specific receptor gene Tas1r2 in 42 bat species that represent all major lineages of the order Chiroptera, one of the most diverse groups of mammals in terms of diet. We found that Tas1r2 is under strong purifying selection in the majority of the bats studied, with no significant difference in the strength of the selection between insect eaters and fruit eaters. However, Tas1r2 is a pseudogene in all three vampire bat species and the functional relaxation likely started in their common ancestor, probably due to the exclusive feeding of vampire bats on blood and their reliance on infrared sensors rather than taste perception to locate blood sources. Our survey of available genome sequences, together with previous reports, revealed additional losses of Tas1r2 in horse, cat, chicken, zebra finch, and western clawed frog, indicating that sweet perception is not as conserved as previously thought. Nonetheless, we found no common dietary pattern among the Tas1r2-lacking vertebrates, suggesting different causes for the losses of Tas1r2 in different species. The complexity of the ecological factors that impact the evolution of Tas1r2 calls for a better understanding of the physiological roles of sweet perception in different species. PMID:20558596

  4. DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

    PubMed Central

    Aziz, Azhari; Harrop, Sean P.; Bishop, Naomi E.

    2011-01-01

    Background Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation. PMID:21264219

  5. Evolution of the Sweet Taste Receptor Gene Tas1r2 in Bats

    PubMed Central

    Zhao, Huabin; Zhou, Yingying; Pinto, C. Miguel; Charles-Dominique, Pierre; Galindo-González, Jorge; Zhang, Shuyi; Zhang, Jianzhi

    2010-01-01

    Taste perception is an important component of an animal's fitness. The identification of vertebrate taste receptor genes in the last decade has enabled molecular genetic studies of the evolution of taste perception in the context of the ecology and dietary preferences of organisms. Although such analyses have been conducted in a number of species for bitter taste receptors, a similar analysis of sweet taste receptors is lacking. Here, we survey the sole sweet taste–specific receptor gene Tas1r2 in 42 bat species that represent all major lineages of the order Chiroptera, one of the most diverse groups of mammals in terms of diet. We found that Tas1r2 is under strong purifying selection in the majority of the bats studied, with no significant difference in the strength of the selection between insect eaters and fruit eaters. However, Tas1r2 is a pseudogene in all three vampire bat species and the functional relaxation likely started in their common ancestor, probably due to the exclusive feeding of vampire bats on blood and their reliance on infrared sensors rather than taste perception to locate blood sources. Our survey of available genome sequences, together with previous reports, revealed additional losses of Tas1r2 in horse, cat, chicken, zebra finch, and western clawed frog, indicating that sweet perception is not as conserved as previously thought. Nonetheless, we found no common dietary pattern among the Tas1r2-lacking vertebrates, suggesting different causes for the losses of Tas1r2 in different species. The complexity of the ecological factors that impact the evolution of Tas1r2 calls for a better understanding of the physiological roles of sweet perception in different species. PMID:20558596

  6. The effect of co-impregnated acids on the performance of Zn-based broad spectrum respirator carbons.

    PubMed

    Smith, J W H; Romero, J V; Dahn, T R; Dunphy, K; Croll, L M; Dahn, J R

    2012-10-15

    Impregnated activated carbons (IACs) that are used in multi-gas respirator applications usually contain copper and/or zinc impregnants. Co-impregnating with properly selected acids can improve the distribution of the metallic impregnant on the carbon and improve the gas adsorption capacity of the IAC. In this work a comparative study of some common acids co-impregnated with a zinc nitrate (Zn(NO(3))(2)) precursor is performed. The IACs were heated in an inert atmosphere at temperatures which promoted the thermal decomposition of Zn(NO(3))(2) to zinc oxide (ZnO). The gas adsorption properties of the IACs were tested using ammonia (NH(3)), sulphur dioxide (SO(2)) and hydrogen cyanide (HCN) challenge gases. Powder X-ray diffraction (XRD) was used to identify the impregnant species present after heating and to study impregnant distribution. Gravimetric analysis was used to determine the impregnant loading, and help to identify the impregnant species after heating. The interactions between the co-impregnated acid and Zn(NO(3))(2) precursor during heating are discussed. The relationship between impregnant species and gas adsorption capacity is discussed.

  7. Understanding the role of each ingredient in a basic copper carbonate based impregnation recipe for respirator carbons.

    PubMed

    Smith, J W H; Westreich, P; Croll, L M; Reynolds, J H; Dahn, J R

    2009-09-15

    Basic copper carbonate (Cu(2)CO(3)(OH)(2)) is often used as an impregnant in activated carbons for respiratory filters. The mechanisms that allow adsorption of toxic gases by an activated carbon loaded with a Cu(2)CO(3)(OH)(2)-based impregnation recipe are studied here. Several samples were studied to determine the effect of ingredients added during impregnation, impregnant loading and drying temperature on performance. The filtering capacity of the samples is quantified by the stoichiometric ratio of reaction (SRR) between the impregnant and the challenge gas. X-ray diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) were used to characterize the impregnant both on and off the carbon as a function of loading and heat-treatment temperature. The influence of the phase and dispersion of the impregnant on the SRR is the focus of this report. PMID:19539946

  8. Dry dilute acid pretreatment by co-currently feeding of corn stover feedstock and dilute acid solution without impregnation.

    PubMed

    He, Yanqing; Zhang, Jian; Bao, Jie

    2014-04-01

    Impregnation of lignocellulose materials with dilute acid solution is a routine operation in conventional dilute acid pretreatment. The dry dilute acid pretreatment (DDAP) at high solids content up to 70% is naturally considered to require longer impregnation time. In this study, a co-currently feeding operation of corn stover and dilute sulfuric acid solution without any impregnation was tested for DDAP. The DDAP pretreated corn stover without impregnation is found to be essentially no difference in pretreatment efficiency compared to those with impregnation in the helically agitated reactor. The yield from cellulose to ethanol in SSF again shows no obvious difference between the DDAP pretreated corn stover with and without impregnation. This study suggests that impregnation in DDAP was not necessary under the helical agitation mixing. The results provided a useful way of cost reduction and process simplification in pretreatment. PMID:24630497

  9. Dry dilute acid pretreatment by co-currently feeding of corn stover feedstock and dilute acid solution without impregnation.

    PubMed

    He, Yanqing; Zhang, Jian; Bao, Jie

    2014-04-01

    Impregnation of lignocellulose materials with dilute acid solution is a routine operation in conventional dilute acid pretreatment. The dry dilute acid pretreatment (DDAP) at high solids content up to 70% is naturally considered to require longer impregnation time. In this study, a co-currently feeding operation of corn stover and dilute sulfuric acid solution without any impregnation was tested for DDAP. The DDAP pretreated corn stover without impregnation is found to be essentially no difference in pretreatment efficiency compared to those with impregnation in the helically agitated reactor. The yield from cellulose to ethanol in SSF again shows no obvious difference between the DDAP pretreated corn stover with and without impregnation. This study suggests that impregnation in DDAP was not necessary under the helical agitation mixing. The results provided a useful way of cost reduction and process simplification in pretreatment.

  10. Effects of Vacuum Impregnation with Sucrose Solution on Mango Tissue.

    PubMed

    Lin, Xian; Luo, Cailian; Chen, Yulong

    2016-06-01

    The influences of vacuum impregnation (VI) on the tissue of mango cubes during atmospheric immersion in sucrose solution were investigated. Results showed that VI effectively facilitated water loss (WL) and sugar gain (SG) during the 300min immersion process, with increases of 20.59% and 31.26%, respectively. A pectin solubilization/degradation phenomenon was observed in the immersion process. The intercellular space and cross section area in the VI-treated mango tissue increased immediately after being released to atmospheric pressure. And it was noted that after experiencing shrinkage-relaxation period twice in the 300 min immersion process, the size of VI-treated mango cells recovered to the original level of fresh ones. Major variations in WL, protopectin content, water soluble pectin content, firmness and microstructure of mango cubes appeared within the first 60 min. In addition, the firmness of mango cubes was positively correlated with the protopectin content (P < 0.01), but negatively correlated with WL and the water soluble pectin content (P < 0.01), indicating that WL and degradation of protopectin contributed greatly to the loss of firmness. PMID:27100561

  11. Alcohol-impregnated wipes as an alternative in hand hygiene.

    PubMed

    Butz, A M; Laughon, B E; Gullette, D L; Larson, E L

    1990-04-01

    The antimicrobial effectiveness of four hand-wash products for health care personnel included three liquid soaps that contained 4% chlorhexidine gluconate, 1% triclosan, or no antiseptic ingredient, respectively, and a 30% w/w ethyl alcohol-impregnated hand wipe. These products were evaluated for reduction in bacterial counts on hands after extended use of 15 handwashes per day for 5 consecutive days. The order of greatest to least log reduction among products at the end of the 5-day test period was chlorhexidine gluconate (2.01), triclosan (1.52), alcohol wipe (0.04), and control soap (0.03). Skin condition before and after handwash was assessed for each treatment group. Subjects reported less skin irritation with alcohol wipes than with the two antiseptic products. Repeated washing with alcohol wipes results in reductions in bacterial colony counts comparable with nonmedicated soap, sufficient to prevent transmission of pathogens by the hands in most situations that arise in nonacute health care settings. This evidence, in addition to increased user acceptability reported by the subjects who used alcohol wipes, suggests that alcohol wipes are an acceptable alternative to soap-and-water handwashing in nonacute health care settings.

  12. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    PubMed

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (P<0.01), cleaved caspase 3, and the caspase-cleaved product of cytokeratin 18. Decreased levels of VEGF (P<0.01) and reduced vessel size (P<0.05) were also observed, the latter only in the ZM198,615-pretreatment group. Furthermore, we performed a series of in vitro studies using the colon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  13. MC1R and the response of melanocytes to ultraviolet radiation.

    PubMed

    Rouzaud, Francois; Kadekaro, Ana Luisa; Abdel-Malek, Zalfa A; Hearing, Vincent J

    2005-04-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists alpha-melanocyte-stimulating hormone (alphaMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of alphaMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

  14. ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors.

    PubMed

    Becker, Amy M; Walcheck, Bruce; Bhattacharya, Deepta

    2015-01-01

    All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17(-/-) ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17(-/-) ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential.

  15. Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain.

    PubMed

    Seltzman, Herbert H; Shiner, Craig; Hirt, Erin E; Gilliam, Anne F; Thomas, Brian F; Maitra, Rangan; Snyder, Rod; Black, Sherry L; Patel, Purvi R; Mulpuri, Yatendra; Spigelman, Igor

    2016-08-25

    Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with <1% blood-brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of ∼0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain. PMID:27482723

  16. β-Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury.

    PubMed

    Kim, Ki-Seok; Abraham, Dennis; Williams, Barbara; Violin, Jonathan D; Mao, Lan; Rockman, Howard A

    2012-10-15

    Pharmacological blockade of the ANG II type 1 receptor (AT1R) is a common therapy for treatment of congestive heart failure and hypertension. Increasing evidence suggests that selective engagement of β-arrestin-mediated AT1R signaling, referred to as biased signaling, promotes cardioprotective signaling. Here, we tested the hypothesis that a β-arrestin-biased AT1R ligand TRV120023 would confer cardioprotection in response to acute cardiac injury compared with the traditional AT1R blocker (ARB), losartan. TRV120023 promotes cardiac contractility, assessed by pressure-volume loop analyses, while blocking the effects of endogenous ANG II. Compared with losartan, TRV120023 significantly activates MAPK and Akt signaling pathways. These hemodynamic and biochemical effects were lost in β-arrestin-2 knockout (KO) mice. In response to cardiac injury induced by ischemia reperfusion injury or mechanical stretch, pretreatment with TRV120023 significantly diminishes cell death compared with losartan, which did not appear to be cardioprotective. This cytoprotective effect was lost in β-arrestin-2 KO mice. The β-arrestin-biased AT1R ligand, TRV120023, has cardioprotective and functional properties in vivo, which are distinct from losartan. Our data suggest that this novel class of drugs may provide an advantage over conventional ARBs by supporting cardiac function and reducing cellular injury during acute cardiac injury.

  17. Heightened Avidity for Trisodium Pyrophosphate in Mice Lacking Tas1r3

    PubMed Central

    Aleman, Tiffany R.; McCaughey, Stuart A.

    2015-01-01

    Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6–56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8–56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate. PMID:25452580

  18. Heightened avidity for trisodium pyrophosphate in mice lacking Tas1r3.

    PubMed

    Tordoff, Michael G; Aleman, Tiffany R; McCaughey, Stuart A

    2015-01-01

    Laboratory rats and mice prefer some concentrations of tri- and tetrasodium pyrophosphate (Na3HP2O7 and Na4P2O7) to water, but how they detect pyrophosphates is unknown. Here, we assessed whether T1R3 is involved. We found that relative to wild-type littermate controls, Tas1r3 knockout mice had stronger preferences for 5.6-56mM Na3HP2O7 in 2-bottle choice tests, and they licked more 17.8-56mM Na3HP2O7 in brief-access tests. We hypothesize that pyrophosphate taste in the intact mouse involves 2 receptors: T1R3 to produce a hedonically negative signal and an unknown G protein-coupled receptor to produce a hedonically positive signal; in Tas1r3 knockout mice, the hedonically negative signal produced by T1R3 is absent, leading to a heightened avidity for pyrophosphate.

  19. Development and characterisation of monoclonal antibodies reactive with porcine CSF1R (CD115).

    PubMed

    Moffat, L; Rothwell, L; Garcia-Morales, C; Sauter, K A; Kapetanovic, R; Gow, D J; Hume, D A

    2014-11-01

    Macrophage colony-stimulating factor (CSF1) controls the proliferation and differentiation of cells of the mononuclear phagocyte system. CSF1, alongside a second ligand, interleukin-34 (IL-34), acts by binding to a cell surface receptor (CSF1R). We previously cloned and expressed pig CSF1 and IL-34. Here we produced a pig CSF1R-Ig+pFUSE Fc fusion protein and used it as an immunogen to produce three monoclonal antibodies (ROS8G11, ROS3A5 and ROS3B10) targeted against porcine CSF1R. Specific binding of each monoclonal antibody was confirmed by ELISA, Western blot, flow cytometry and immunocytochemistry. The antibodies did not block CSF1 signalling. The surface expression of CSF1R in pig peripheral blood was restricted to CD14-positive monocytes and was also detected on lung macrophages. These antibodies provided an opportunity to investigate the increase of available CSF1R during pig BMDM differentiation. The new monoclonal antibodies provide useful reagents to support the study of monocyte and macrophage biology in the pig.

  20. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels.

    PubMed

    Alsina-Sanchis, Elisenda; Figueras, Agnès; Lahiguera, Álvaro; Vidal, August; Casanovas, Oriol; Graupera, Mariona; Villanueva, Alberto; Viñals, Francesc

    2016-10-15

    In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition.

  1. The role of MC1R gene in buffalo coat color.

    PubMed

    Miao, YongWang; Wu, GuiSheng; Wang, Lei; Li, DaLin; Tang, ShouKun; Liang, JianPing; Mao, HuaMing; Luo, HuaiRong; Zhang, YaPing

    2010-02-01

    Melanocortin-1 receptor (MC1R) plays a major role in pigmentation in many species. To investigate if the MC1R gene is associated with coat color in water buffalo, the coding region of MC1R gene of 216 buffalo samples was sequenced, which included 49 black river buffalo (Murrah and Nili-Ravi), 136 swamp buffalo (Dehong, Diandongnan, Dechang, Guizhou, and Xilin) with white and gray body, and 31 hybrid offspring of river buffalo Nili-Ravi (or Murrah) and swamp buffalo. Among the three variation sites found, SNP684 was synonymous, while SNP310 and SNP384 were nonsynonymous, leading to p.S104G and p.I128M changes, respectively. Only Individuals carrying homozygote E(BR)/E(BR) were black. The genotype and phenotype analysis of the hybrid offspring of black river buffalo and gray swamp buffalo further revealed that the river buffalo type allele E(BR) or the allele carrying the amino acid p.104S was important for the full function of MC1R. The in silico functional analysis showed that the amino acid substitutions p.G104S and p.M128I had significant impact on the function of MC1R. Above results indicate that the allele E(BR) or the allele carrying the amino acid p.104S was associated with the black coat color in buffalo.

  2. CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids.

    PubMed

    Eichler, Florian S; Li, Jiankang; Guo, Yiran; Caruso, Paul A; Bjonnes, Andrew C; Pan, Jessica; Booker, Jessica K; Lane, Jacqueline M; Tare, Archana; Vlasac, Irma; Hakonarson, Hakon; Gusella, James F; Zhang, Jianguo; Keating, Brendan J; Saxena, Richa

    2016-06-01

    Mutations in the colony stimulating factor 1 receptor (CSF1R) have recently been discovered as causal for hereditary diffuse leukoencephalopathy with axonal spheroids. We identified a novel, heterozygous missense mutation in CSF1R [c.1990G > A p.(E664K)] by exome sequencing in five members of a family with hereditary diffuse leukoencephalopathy with axonal spheroids. Three affected siblings had characteristic white matter abnormalities and presented with progressive neurological decline. In the fourth affected sibling, early progression halted after allogeneic haematopoietic stem cell transplantation from a related donor. Blood spot DNA from this subject displayed chimerism in CSF1R acquired after haematopoietic stem cell transplantation. Interestingly, both parents were unaffected but the mother's blood and saliva were mosaic for the CSF1R mutation. Our findings suggest that expression of wild-type CSF1R in some cells, whether achieved by mosaicism or chimerism, may confer benefit in hereditary diffuse leukoencephalopathy with axonal spheroids and suggest that haematopoietic stem cell transplantation might have a therapeutic role for this disorder. PMID:27190017

  3. Droplet condensation and growth on nanotextured surfaces impregnated with an immiscible liquid

    NASA Astrophysics Data System (ADS)

    Anand, Sushant; Paxson, Adam; Smith, Jonathan; Dhiman, Rajeev; Varanasi, Kripa

    2012-02-01

    For effective dropwise condensation, a surface that sheds droplets easily is desirable due to the enhancement in accompanying heat transfer. Incorporating nano-textures on the surface can enhance the droplet shedding or spreading. We demonstrate that droplet shedding can be further influenced by impregnating the nano-textured surface with a liquid which is immiscible with respect to the droplet. In this study, the dynamics of dropwise condensation on such immiscible liquid impregnated nano-textured surfaces have been investigated in pure quiescent water vapor conditions. Condensation experiments were conducted using an Environmental Scanning Electron Microscope by controlling the chamber water vapor pressure and substrate temperature. We show preferential sites for condensation and different modes under which droplets grow, depending upon the surface chemistry, surface texture, and the impregnating liquid properties. Concurrently, we show an evolution of apparent contact angles during the condensation process on the impregnated surfaces.

  4. Effect of high energy electron radiation on MIPB-impregnated polypropylene film

    SciTech Connect

    Hammoud, A.N.; Laghari, J.R.; Krishnakumar, B.

    1988-08-01

    This work examines the effect of impregnating capacitor-grade polypropylene film with an aromatic hydrocarbon fluid with a view towards assessing the response under radiation of the relevant properties of the film. Monoisopropyl biphenyl (MIPB)-impregnated polypropylene film was exposed in air to 1 MeV electrons to different doses and the post-radiation effects on the electrical, mechanical, morphological and chemical properties were evaluated. The results obtained indicate that the oil-impregnated films remain relatively stable even at the highest dose of 10/sup 8/ rads. This is in contrast to the results reported earlier for dry polypropylene films which underwent degradation primarily due to chain scission and oxidation. In the present instance, it is believed that impregnation of the film has inhibited the diffusion of oxygen and consequently favored crosslinking. The chemical characterizations as well as the changes in some of the measured properties of the film seem to corroborate this belief.

  5. Fundamental studies of methyl iodide adsorption in DABCO impregnated activated carbons.

    PubMed

    Herdes, Carmelo; Prosenjak, Claudia; Román, Silvia; Müller, Erich A

    2013-06-11

    Methyl iodide capture from a water vapor stream using 1,4-diazabicyclo[2.2.2]octane (DABCO)-impregnated activated carbons is, for the first time, fundamentally described here on the atomic level by means of both molecular dynamics and grand canonical Monte Carlo simulations. A molecular dynamics annealing strategy was adopted to mimic the DABCO experimental impregnation procedure in a selected slitlike carbon pore. Predictions, restricted to the micropore region, are made about the adsorption isotherms of methyl iodide, water, and nitrogen on both impregnated and bare activated carbon models. Experimental and simulated nitrogen adsorption isotherms are compared for the validation of the impregnation strategy. Selectivity analyses of the preferential adsorption toward methyl iodide over water are also reported. These simulated adsorption isotherms sum up to previous experimental studies to provide an enhanced picture for this adsorption system of widespread use at nuclear plant HVAC facilities for the capture of radioactive iodine compounds. PMID:23679202

  6. Multistep impregnation method for incorporation of high amount of titania into SBA-15

    SciTech Connect

    Wang Wei; Song Mo . E-mail: m.song@lboro.ac.uk

    2006-02-02

    A multistep impregnation method was employed to incorporate high amount of titania into the mesoporous SBA-15 silica. No damage to the SBA-15 silica mesostructures was caused by the loading of titania in every cycle. The existence of titania small nanodomains were confirmed to be present by Raman spectra and UV-vis DRS measurements. High dispersion of them was realized via this method according to the results of low-angle X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and N{sub 2} sorption measurements. Importantly, no blockage of mesostructures was acknowledged with titania content up to 24.4 wt.%. In comparison, normally used one-step impregnation method led to serious blockage of mesopores as the results of formation of bulk titania particles in the mesochannels. Photo-activity test for the removal of oestrogen showed the superiority of the materials synthesized by multistep impregnation method to one-step impregnation method.

  7. A new rapid silver impregnation for neuronal bodies on methacrylate sections.

    PubMed

    Tolivia, D; Tolivia, J

    1991-02-01

    A simple and rapid method for the impregnation of neuronal bodies applicable to methacrylate embedded sections is described in the present paper. Sections of 10-12 microns in thickness were attached to slides, placed in mordant for 1 min, rinsed in distilled water and impregnated in ammoniacal silver solution for 1 min. They were then rinsed in absolute ethanol for 30 s and developed in 50% formalin. Sections were toned in 0.25% gold chloride, reduced in 10% oxalic acid and fixed in 5% sodium thiosulfate. After washing, the sections were dehydrated through 90% and absolute ethanol, cleared in eucalyptol, and mounted in the usual way. When this method is used most of the neuronal somata and proximal dendritic trees are impregnated. Frequently some glial cell are also weakly impregnated but their density does not obscure the neurons.

  8. Investigation of alternative materials for impregnation of Nb3Sn accelerator magnets

    SciTech Connect

    Deepak Reddy Chichili, Jay Hoffman and Alexander Zlobin

    2003-11-17

    Insulation is one of the most important elements of magnet design, which determines the electrical, mechanical, and thermal performance as well as lifetime of the magnet. The exposure to high radiation loads especially for the proposed LHC second-generation interaction region Nb{sub 3}Sn quadrupoles further limits the choices of the insulation materials. Traditionally Nb{sub 3}Sn magnets were impregnated with epoxy to improve both the mechanical and electrical properties. However, the acceptable radiation limit for epoxy is low which reduces the lifetime of the magnet. The paper presents the results of the feasibility study to replace epoxy with high radiation-resistant material during vacuum impregnation. The mechanical, thermal and electrical properties of samples impregnated with Matrimid were measured and compared with epoxy-impregnated samples.

  9. Fabrication of Impregnated-Electrode-Type Polyatomic Ion Source with Ionic Liquid

    SciTech Connect

    Takeuchi, Mitsuaki; Ryuto, Hiromichi; Takaoka, Gikan H.

    2011-01-07

    Three types of ionic liquid ion source characterized by needle-type, capillary-needle-type and impregnated-electrode-type emitters were fabricated and demonstrated. The ion emission of a pure ionic liquid was demonstrated for the capillary-needle- and impregnated-electrode-type emitters. The emission stability of the impregnated-electrode-type emitter is currently insufficient for the shallow implantation of carbon due to occasional discharge. However, the impregnated-electrode-type emitter showed the largest emission current of 14 {mu}A at 6 kV among these emitters. This was considered to be caused by the relatively high feedability of the ionic liquid obtained from the emitter tip made of porous copper.

  10. Evaluation of reagent-impregnated coagulase-mannitol test strip for speciation of staphylococci.

    PubMed

    Washington, J A; Yu, P K

    1970-04-01

    A new coagulase-mannitol reagent-impregnated strip test has been evaluated with 322 Micrococcaceae. Mannitol fermentation was determined accurately by this test; however, the coagulase reaction was difficult to interpret and was subject to significant error.

  11. [The prevention of malaria with impregnated mosquito netting: impact of a social mobilization day in Brazzaville].

    PubMed

    Talani, P; Biahouila-Satounkazi, F; Moyen, G

    2002-06-01

    A study of malaria prevention was conducted in two areas of Brazzaville: Makelekele and Bacongo, 10-12 November 1997, following a day of mobilisation. The study included 111 households in each area. In Makelekele, people were informed about the use of impregnated mosquito nets. Bacongo was used as a control area. The answers to the questionnaire indicated that 56.7% of households in the informed area knew about impregnated mosquito nets versus 30.6% in the control area. Likewise, 47.7% of the households in the informed area versus 10.8% in the control area knew where to locate centers for impregnating the nets. From these findings we conclude that information concerning the use of impregnated bed nets as prevention for malaria needs to be spread to all areas of Brazzaville.

  12. Application of Silver and Silver Oxide Nanoparticles Impregnated on Activated Carbon to the Degradation of Bromate.

    PubMed

    Choi, J S; Lee, H; Park, Y K; Kim, S J; Kim, B J; An, K H; Kim, B H; Jung, S C

    2016-05-01

    Silver and silver oxide nanoparticles were impregnated on the surface of powdered activated carbon (PAC) using a single-step liquid phase plasma (LPP) method. Spherical silver and silver oxide nanoparticles of 20 to 100 nm size were dipersed evenly on the surface of PAC. The impregnated PAC exhibited a higher activity for the decomposition of bromate than bare PAC. The XPS, Raman and EDX analyses showed that the Ag/PAC composites synthesized by the LPP process. PMID:27483780

  13. Ketoprofen-eluting biodegradable ureteral stents by CO2 impregnation: In vitro study.

    PubMed

    Barros, Alexandre A; Oliveira, Carlos; Reis, Rui L; Lima, Estevão; Duarte, Ana Rita C

    2015-11-30

    Ureteral stents are indispensable tools in urologic practice. The main complications associated with ureteral stents are dislocation, infection, pain and encrustation. Biodegradable ureteral stents are one of the most attractive designs with the potential to eliminate several complications associated with the stenting procedure. In this work we hypothesize the impregnation of ketoprofen, by CO2-impregnation in a patented biodegradable ureteral stent previously developed in our group. The biodegradable ureteral stents with each formulation: alginate-based, gellan gum-based were impregnated with ketoprofen and the impregnation conditions tested were 100 bar, 2 h and three different temperatures (35 °C, 40 °C and 50 °C). The impregnation was confirmed by FTIR and DSC demonstrated the amorphization of the drug upon impregnation. The in vitro elution profile in artificial urine solution (AUS) during degradation of a biodegradable ureteral stent loaded with ketoprofen was evaluated. According to the kinetics results these systems have shown to be very promising for the release ketoprofen in the first 72 h, which is the necessary time for anti-inflammatory delivery after the surgical procedure. The in vitro release studied revealed an influence of the temperature on the impregnation yield, with a higher impregnation yield at 40 °C. Higher yields were also obtained for gellan gum-based stents. The non-cytotoxicity characteristic of the developed ketoprofen-eluting biodegradable ureteral stents was evaluated in L929 cell line by MTS assay which demonstrated the feasibility of this product as a medical device.

  14. IGF1R and c-met as therapeutic targets for colorectal cancer.

    PubMed

    Shali, Hajar; Ahmadi, Majid; Kafil, Hossein Samadi; Dorosti, Abbasali; Yousefi, Mehdi

    2016-08-01

    The type 1 IGF receptor (IGF1R) and mesenchymal-epithelial transition (MET) are hetrodimeric and transmembrane receptor tyrosine kinases, which are frequently overexpressed by several tumor types, including colorectal cancer (CRC). These receptors bind to their specific ligands, insulin growth factors (IGFs) and hepatocyte growth factor (HGF), respectively, and promote signaling cascades which mediates many functions such as proliferation and protection against apoptosis, cell scattering, tumor cell motility, invasion and metastasis. In patients with metastatic colorectal cancer (mCRC), IGF1R and c-met expression confer resistance to cetuximab (monoclonal antibodies against EGFR). Therefore, the c-met and IGF1R are now an attractive novel target for anticancer therapy. In this review, we will describe correlation between two receptors and their activation effects in tumor cells, and finally introduce useful and available strategies for their targeting. PMID:27470393

  15. Approximative "one particle" bridge function B(1)(r) for the theory of simple fluids.

    PubMed

    Bomont, Jean-Marc; Bretonnet, Jean-Louis

    2007-06-01

    New properties for the one particle bridge function B(1)(r), which are necessary to the calculation of the excess chemical potential betamue), are derived for the hard sphere fluid. The method, which only requires the knowledge of the bridge function B(2)(r), is based on an investigation of the correlation function dependence on the Kirkwood charging parameter. In this framework, the unavoidable question of topological homotopy is addressed. As far as B(2)(r) is considered as exact, this work provides useful information on B(1)(r) in the well identified dynamical regimes of the hard sphere fluid. Signatures of the transitions between these regimes are identified on the trends of B(1)(r). This approach provides self-consistent results for betamue) that agree very well with simulation data.

  16. Thermal and mechanical properties of advanced impregnation materials for HTS cables and coils

    NASA Astrophysics Data System (ADS)

    Bagrets, N.; Otten, S.; Weiss, K.-P.; Kario, A.; Goldacker, W.

    2015-12-01

    In the growing field of high-temperature superconducting (HTS) applications, finding an appropriate impregnation material for cables and coils remains a challenging task. In HTS cables and coils, tapes have to be able to withstand mechanical loads during operation. Impregnation is playing a role as mechanical stabilization. However, material properties usually change significantly when going to low temperatures which can decrease performance of superconducting devices. For example, a large mismatch in thermal expansion between a conductor and impregnation material at low temperatures can lead to delamination and to degradation of the critical current. Impregnation materials can insulate tapes thermally which can lead to damage of the superconducting device in case of quench. Thus, thermal conductivity is an important property which is responsible for the temperature distribution in a superconducting cable or in a coil. Due to Lorentz forces acting on structural materials in a superconducting device, the mechanical properties of these materials should be investigated at operating temperatures of this device. Therefore, it is important to identify an advanced impregnation material meeting all specific requirements. In this paper, thermal and mechanical properties of impregnation material candidates with added fillers are presented in a temperature range from 300 K to 4 K.

  17. Preparation of functionalized and metal-impregnated activated carbon by a single-step activation method

    NASA Astrophysics Data System (ADS)

    Dastgheib, Seyed A.; Ren, Jianli; Rostam-Abadi, Massoud; Chang, Ramsay

    2014-01-01

    A rapid method to prepare functionalized and metal-impregnated activated carbon from coal is described in this paper. A mixture of ferric chloride and a sub-bituminous coal was used to demonstrate simultaneous coal activation, chlorine functionalization, and iron/iron oxides impregnation in the resulting porous carbon products. The FeCl3 concentration in the mixture, the method to prepare the FeCl3-coal mixture (solid mixing or liquid impregnation), and activation atmosphere and temperature impacted the surface area and porosity development, Cl functionalization, and iron species impregnation and dispersion in the carbon products. Samples activated in nitrogen or a simulated flue gas at 600 or 1000 °C for 1-2 min had surface areas up to ∼800 m2/g, bulk iron contents up to 18 wt%, and surface chlorine contents up to 27 wt%. Potential catalytic and adsorption application of the carbon materials was explored in catalytic wet air oxidation (CWAO) of phenol and adsorption of ionic mercury from aqueous solutions. Results indicated that impregnated activated carbons outperformed their non-impregnated counterparts in both the CWAO and adsorption tests.

  18. IGF-1R inhibition in mammary epithelia promotes canonical Wnt signaling and Wnt1-driven tumors

    PubMed Central

    Rota, Lauren M.; Albanito, Lidia; Shin, Marcus E.; Goyeneche, Corey L.; Shushanov, Sain; Gallagher, Emily J.; LeRoith, Derek; Lazzarino, Deborah A.; Wood, Teresa L.

    2014-01-01

    Triple-negative breast cancers (TNBC) are an aggressive disease subtype which unlike other subtypes lack an effective targeted therapy. Inhibitors of the insullin-like growth factor receptor (IGF-1R) have been considered for use in treating TNBC. Here we provide genetic evidence that IGF-1R inhibition promotes development of Wnt1-mediated murine mammary tumors that offer a model of TNBC. We found that in a double transgenic mouse model carrying activated Wnt-1 and mutant IGF-1R, a reduction in IGF-1R signaling reduced tumor latency and promoted more aggressive phenotypes. These tumors displayed a squamal cell phenotype with increased expression of keratins 5/6 and β-catenin. Notably, cell lineage analyses revealed an increase in basal (CD29hi/CD24+) and luminal (CD24+/CD61+/CD29lo) progenitor cell populations, along with increased Nanog expression and decreased Elf5 expression. In these doubly transgenic mice, lung metastases developed with characteristics of the primary tumors, unlike MMTV-Wnt1 mice. Mechanistic investigations showed that pharmacological inhibition of the IGF-1R in vitro was sufficient to increase the tumorsphere-forming efficiency of MMTV-Wnt1 tumor cells. Tumors from doubly transgenic mice also exhibited an increase in the expression ratio of the IGF-II-sensitive, A isoform of the insulin receptor vs the IR-B isoform, which in vitro resulted in enhanced expression of β-catenin. Overall, our results revealed that in Wnt-driven tumors an attenuation of IGF-1R signaling accelerates tumorigenesis and promotes more aggressive phenotypes, with potential implications for understanding TNBC pathobiology and treatment. PMID:25092896

  19. IDH1R132H in Neural Stem Cells: Differentiation Impaired by Increased Apoptosis

    PubMed Central

    Rosiak, Kamila; Smolarz, Maciej; Stec, Wojciech J.; Peciak, Joanna; Grzela, Dawid; Winiecka-Klimek, Marta; Stoczynska-Fidelus, Ewelina; Krynska, Barbara; Piaskowski, Sylwester; Rieske, Piotr

    2016-01-01

    Background The high frequency of mutations in the isocitrate dehydrogenase 1 (IDH1) gene in diffuse gliomas indicates its importance in the process of gliomagenesis. These mutations result in loss of the normal function and acquisition of the neomorphic activity converting α-ketoglutarate to 2-hydroxyglutarate. This potential oncometabolite may induce the epigenetic changes, resulting in the deregulated expression of numerous genes, including those related to the differentiation process or cell survivability. Methods Neural stem cells were derived from human induced pluripotent stem cells following embryoid body formation. Neural stem cells transduced with mutant IDH1R132H, empty vector, non-transduced and overexpressing IDH1WT controls were differentiated into astrocytes and neurons in culture. The neuronal and astrocytic differentiation was determined by morphology and expression of lineage specific markers (MAP2, Synapsin I and GFAP) as determined by real-time PCR and immunocytochemical staining. Apoptosis was evaluated by real-time observation of Caspase-3 activation and measurement of PARP cleavage by Western Blot. Results Compared with control groups, cells expressing IDH1R132H retained an undifferentiated state and lacked morphological changes following stimulated differentiation. The significant inhibitory effect of IDH1R132H on neuronal and astrocytic differentiation was confirmed by immunocytochemical staining for markers of neural stem cells. Additionally, real-time PCR indicated suppressed expression of lineage markers. High percentage of apoptotic cells was detected within IDH1R132H-positive neural stem cells population and their derivatives, if compared to normal neural stem cells and their derivatives. The analysis of PARP and Caspase-3 activity confirmed apoptosis sensitivity in mutant protein-expressing neural cells. Conclusions Our study demonstrates that expression of IDH1R132H increases apoptosis susceptibility of neural stem cells and their

  20. Loss of inhibition by formate in newly constructed photosystem II D1 mutants, D1-R257E and D1-R257M, of Chlamydomonas reinhardtii.

    PubMed

    Xiong, J; Minagawa, J; Crofts, A; Govindjee

    1998-07-20

    Formate is known to cause significant inhibition in the electron and proton transfers in photosystem II (PSII); this inhibition is uniquely reversed by bicarbonate. It has been suggested that bicarbonate functions by providing ligands to the non-heme iron and by facilitating protonation of the secondary plastoquinone QB. Numerous lines of evidence indicate an intimate relationship of bicarbonate and formate binding of PSII. To investigate the potential amino acid binding environment of bicarbonate/formate in the QB niche, arginine 257 of the PSII D1 polypeptide in the unicellular green alga Chlamydomonas reinhardtii was mutated into a glutamate (D1-R257E) and a methionine (DQ-R257M). The two mutants share the following characteristics. (1) Both have a drastically reduced sensitivity to formate. (2) A larger fraction of QA- persists after flash illumination, which indicates an altered equilibrium constant of the reaction QA-QB<-->QA QB-, in the direction of [QA-], or a larger fraction of non-QB centers. However, there appears to be no significant difference in the rate of electron transfer from QA- to QB. (3) The overall rate of oxygen evolution is significantly reduced, most likely due to changes in the equilibrium constant on the electron acceptor side of PSII or due to a larger fraction in non-QB centers. Additional effects on the donor side cannot yet be excluded. (4) The binding affinity for the herbicide DCMU is unaltered. (5) The mutants grow photosynthetically, but at a decreased (approximately 70% of the wild type) level. (6) The Fo level was elevated (approximately 40-50%) which could be due to a decrease in the excitation energy transfer from the antenna to the PSII reaction center, and/or to an increased level of [QA-] in the dark. (7) A decreased (approximately 10%) ratio of F685 (mainly from CP43) and F695 (mainly from CP47) to F715 (mainly from PSI) emission bands at 77 K suggests a change in the antenna complex. Taken together these results lead to

  1. Fear of Pain Mediates the Association between MC1R Genotype and Dental Fear.

    PubMed

    Randall, C L; McNeil, D W; Shaffer, J R; Crout, R J; Weyant, R J; Marazita, M L

    2016-09-01

    Fear of pain is experienced in acute and chronic pain populations, as well as in the general population, and it affects numerous aspects of the orofacial pain experience, including pain intensity, pain-related disability, and pain behavior (e.g., avoidance). A related but separate construct-dental fear-is also experienced in the general population, and it influences dental treatment-seeking behavior and oral and systemic health. Minimal work has addressed the role of genetics in the etiologies of fear of pain and dental fear. Limited available data suggest that variants of the melanocortin 1 receptor (MC1R) gene may predict greater levels of dental fear. The MC1R gene also may be etiologically important for fear of pain. This study aimed to replicate the finding that MC1R variant status predicts dental fear and to determine, for the first time, whether MC1R variant status predicts fear of pain. Participants were 817 Caucasian participants (62.5% female; mean ± SD age: 34.7 ± 8.7 y) taking part in a cross-sectional project that identified determinants of oral diseases at the community, family, and individual levels. Participants were genotyped for single-nucleotide polymorphisms on MC1R and completed self-report measures of fear of pain and dental fear. Presence of MC1R variant alleles predicted higher levels of dental fear and fear of pain. Importantly, fear of pain mediated the relation between MC1R variant status and dental fear (B = 1.60, 95% confidence interval: 0.281 to 3.056). MC1R variants may influence orofacial pain perception and, in turn, predispose individuals to develop fears about pain. Such fears influence the pain experience and associated pain behaviors, as well as fears about dental treatment. This study provides support for genetic contributions to the development/maintenance of fear of pain and dental fear, and it offers directions for future research to identify potential targets for intervention in the treatment of fear of pain and dental

  2. Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor.

    PubMed

    Aware, Valmik; Gaikwad, Nitin; Chavan, Sambhaji; Manohar, Sonal; Bose, Julie; Khanna, Smriti; B-Rao, Chandrika; Dixit, Neeta; Singh, Kishori Sharan; Damre, Anagha; Sharma, Rajiv; Patil, Sambhaji; Roychowdhury, Abhijit

    2015-03-01

    A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2- amino ring, 4-pyrazolo moieties and size of fused saturated ring with the central pyrimidine core. A stepwise optimization by combination of active fragments led to discovery of compound 6f and 6k, two structures with IGF-1R IC50 of 20 nM and 10 nM, respectively. 6f was further profiled for its anti cancer activity across various cell lines and pharmacokinetic studies in Sprague Dawley rats. PMID:25559205

  3. Identification of Novel IGF1R Kinase Inhibitors by Molecular Modeling and High-Throughput Screening

    PubMed Central

    Moriev, R.; Vasylchenko, O.; Platonov, M.; Grygorenko, O.; Volkova, K.; Zozulya, S.

    2013-01-01

    The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to develop drug candidates that are superior to the existing experimental anti-IGF1R therapeuticals. To this end, targeted compound libraries were produced by virtual screening using molecular modeling and docking strategies, as well as the ligand-based pharmacophore model. High-throughput screening of the resulting compound sets in a biochemical kinase inhibition assay allowed us to identify several novel chemotypes that represent attractive starting points for the development of advanced IGF1R inhibitory compounds. PMID:23819040

  4. Evolutionary and phylogeographic views on Mc1r and Asip variation in mammals.

    PubMed

    Suzuki, Hitoshi

    2013-01-01

    The purpose of this article is to provide basic knowledge about the Mc1r-Asip system that promotes the evolution of coat color in mammals, and to stimulate genetic, ecological, and phylogeographic studies focusing on color variation in natural populations. The topics reviewed herein include: the genetic system of the Mc1r and Asip genes related to phenotypic variation; the evolutionary implications of the genetic features recorded in their nucleotide sequences; and the validity of surveys in the wild of genetic variations in coat color, which would facilitate a better understanding of the genetic system, ecological meaning, natural history, and taxonomic reevaluation of species and local populations. PMID:24025244

  5. Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor.

    PubMed

    Aware, Valmik; Gaikwad, Nitin; Chavan, Sambhaji; Manohar, Sonal; Bose, Julie; Khanna, Smriti; B-Rao, Chandrika; Dixit, Neeta; Singh, Kishori Sharan; Damre, Anagha; Sharma, Rajiv; Patil, Sambhaji; Roychowdhury, Abhijit

    2015-03-01

    A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2- amino ring, 4-pyrazolo moieties and size of fused saturated ring with the central pyrimidine core. A stepwise optimization by combination of active fragments led to discovery of compound 6f and 6k, two structures with IGF-1R IC50 of 20 nM and 10 nM, respectively. 6f was further profiled for its anti cancer activity across various cell lines and pharmacokinetic studies in Sprague Dawley rats.

  6. Protein engineering studies on C1r and C1s.

    PubMed

    Závodszky, P; Gál, P; Cseh, S; Schumaker, V N

    1993-12-01

    1. C1r and C1s cDNAs were placed downstream the strong polyhedrin promoter in the Autographa californica nuclear polyhedrosis virus and the recombinant proteins were expressed in insect cells, in biologically active form. The yield of expression is high enough to get recombinant components for chemical and functional studies (5 micrograms/ml cell culture supernatant). 2. The biological activity and the post-translational modifications of the recombinant subcomponents were checked. The rC1r and rC1s proved to be biologically active in the hemolytic assay, although their glycosylations were different compared to that of the serum proteins. The insect cells are able to beta-hydroxylate the Asn residue of the EGF domain in the C1r but with a low efficiency. It is clear now, that this post-translational modification does not play a role in the Ca2+ dependent C1r-C1s interaction. 3. Two deletion mutants of C1r cDNA were constructed in order to clarify the role of domain I and II. The results show that both, domain I, and II are absolutely necessary for the tetramer formation and both have a regulatory role in the autoactivation. The autoactivation of the mutants is accelerated significantly. 4. Hybrid cDNA constructions were also made, and one of them was expressed. In the C1s alpha R hybrid the C1s alpha part cannot dimerize in presence of Ca2+, but it can form a tetramer with C1r2, that can bind to C1q. This observation indicates that the function of the C1s alpha part in the hybrid is modulated by the C1r part (gamma B) of the molecule. 5. In order to control the autoactivation process point mutant cDNAs were constructed through altering the Arg-Ile bond in the catalytic domain of the C1r. The Gln-Ile construction is a stable zymogen while the Arg-Phe mutant has a lower rate of autoactivation. These results do justify our approach of using domain-domain interchange, domain deletion and point mutations in combination, to reveal the structural background of C1 function

  7. Synthesis and characterization of aluminosilicate catalyst impregnated by nickel oxide

    NASA Astrophysics Data System (ADS)

    Maulida, Iffana Dani; Sriatun, Taslimah

    2015-09-01

    Aluminosilicate as a catalyst has been synthesized by pore-engineering using CetylTrimethylAmmonium-Bromide (CTAB) as templating agent. It can produce bigger aluminosilicate pore therefore it will be more suitable for bulky molecule. The aims of this research are to synthesize aluminosilicate supported by Nickel, using CTAB surfactant as templating agent for larger pore radius than natural zeolite and characterize the synthesis product, consist of total acid sites and surface area characteristic. This research has been done with following steps. First, making sodium silicate and sodium aluminate. Second, aluminosilicate was synthesized by direct methods, calcined at 550, 650 and 750°C variation temperature, characterized product by X-RD and FTIR spectrometer. Third, NiCl2 was impregnated to the aluminosilicate that has the best cristallinity and main TO4 functional groups product (550 sample). Variation of NiCl2:aluminosilicate (w/w) ratio were 25%:75%, 50%:50% and 75%:25%. Last but not least characterization of catalytic properties was performed. It comprised total acidity test (gravimetric method) and Surface Area Analyzer. The result shows that the product synthesized by direct method at 550oC calcination temperature has the best cristallinity and main functional groups of TO4. The highest total acid sites was 31.6 mmole/g (Imp-A sample). Surface Area Analyzer shows that Imp-B sample has the best pore distribution and highest total pore volume and specific surface area with value 32.424 cc/g and 46.8287 m2/g respectively. We can draw the conclusion that the most potential catalyst is Imp-A sample compared to Imp-B and Imp-C because it has the highest total acid sites. However the most effective catalyst used for product selectivity was Imp-B sample among all samples.

  8. Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells

    PubMed Central

    Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

    2016-01-01

    The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca2+ stimulation and extracellular signal–regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca2+-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism. PMID:27727170

  9. Application of sulfur impregnated activated carbons for the control of mercury emissions

    SciTech Connect

    Vidic, R.D.; Liu, W.; Brown, T.D.

    1998-12-31

    The dynamics of granular activated carbon (GAC) adsorbers for the uptake of vapor-phase mercury was evaluated as a function of temperature, influent mercury concentration, and empty bed contact time. Sulfur-impregnated carbons exhibited enhanced mercury removal efficiency over virgin carbon due to formation of mercuric sulfide on the carbon surface. The effect of the sulfur impregnation method on mercury removal efficiency was examined through experiments conducted on commercially available sulfur-impregnated carbon (HGR) and carbon impregnated with sulfur in the laboratory (BPL-S). Although HGR and BPL-S possess similar sulfur contents, BPL-S is impregnated at a higher temperature which promotes a more uniform distribution of sulfur in the GAC pore structure. At low influent mercury concentrations and low temperatures, HGR and BPL-S performed similarly in the removal of mercury vapor. However, as the temperature was increased above the melting point of sulfur, the performance of HGR deteriorated significantly, while the performance of BPL-S slightly improved. For both HGR and BPL-S, the observed dynamic mercury adsorptive capacities were far below the capacities predicted by the stoichiometry of mercuric sulfide formation. In HGR carbon the sulfur is very accessible, but agglomeration which occurs at high temperatures causes the sulfur to become relatively unreactive. In BPL-S carbon, on the other hand, the sulfur remains in a highly reactive form, but its location deep in the internal pores makes it relatively inaccessible and susceptible to blockage by HgS formation. Impregnation temperature and the initial sulfur to carbon ratio (SCR) during the impregnation are the two key control parameters for the preparation of these new (BPL-S) sorbents. Higher impregnation temperatures can significantly enhance mercury removal capacity for adsorbents derived either from virgin or re-generated activated carbons. Large fraction of active sulfur atoms that are created at

  10. A novel mutation in the CSF1R gene causes a variable leukoencephalopathy with spheroids.

    PubMed

    La Piana, Roberta; Webber, Alina; Guiot, Marie-Christine; Del Pilar Cortes, Maria; Brais, Bernard

    2014-10-01

    Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids is a neurodegenerative disease associated with mutations in the colony-stimulating factor 1 receptor gene (CSF1R). A 44-year-old woman with a 7-year history of depression presented with neurological signs and a recent cognitive decline. The diagnosis of hereditary diffuse leukoencephalopathy with neuroaxonal spheroids was suspected based on the findings of a predominant frontal leukoencephalopathy and neuroaxonal spheroids on brain biopsy. She shares with her mother a novel CSF1R exon 18 missense mutation (c.2350G > A; p.V784M). The mother has a long-standing bipolar disorder and mild multifocal white matter abnormalities in her 70s. This is the first report of hereditary diffuse leukoencephalopathy with neuroaxonal spheroids due to this novel CSF1R missense mutation. Our report suggests that either marked intrafamilial variability or incomplete penetrance can be associated with CSF1R mutations. The observation of a small bone cyst in our patient supports the hypothesis that hereditary diffuse leukoencephalopathy with neuroaxonal spheroids and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy may belong to a spectrum of overlapping phenotypes.

  11. Melanocortin 1-receptor (MC1R) mutations are associated with plumage colour in chicken.

    PubMed

    Kerje, S; Lind, J; Schütz, K; Jensen, P; Andersson, L

    2003-08-01

    The co-segregation of plumage colour and sequence polymorphism in the melanocortin 1-receptor gene (MC1R) was investigated using an intercross between the red junglefowl and White Leghorn chickens. The results provided compelling evidence that the Extended black (E) locus controlling plumage colour is equivalent to MC1R. E/MC1R was assigned to chromosome 11 with overwhelming statistical support. Sequence analysis indicated that the E92K substitution, causing a constitutively active receptor in the sombre mouse, is the most likely causative mutation for the Extended black allele carried by the White Leghorn founders in this intercross. The MC1R sequence associated with the recessive buttercup (ebc) allele indicated that this allele evolved from a dominant Extended black allele as it shared the E92K and M71T substitutions with some E alleles. It also carried a third missense mutation H215P which thus may interfere with the constitutive activation of the receptor caused by E92K (and possibly M71T). PMID:12873211

  12. RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity

    PubMed Central

    McKelvey, Alison C; Lear, Travis B; Dunn, Sarah R; Evankovich, John; Londino, James D; Bednash, Joseph S; Zhang, Yingze; McVerry, Bryan J; Liu, Yuan; Chen, Bill B

    2016-01-01

    Toll-like receptor 2 (TLR2) is a pattern recognition receptor that recognizes many types of PAMPs that originate from gram-positive bacteria. Here we describe a novel mechanism regulating TLR2 protein expression and subsequent cytokine release through the ubiquitination and degradation of the receptor in response to ligand stimulation. We show a new mechanism in which an uncharacterized RING finger E3 ligase, PPP1R11, directly ubiquitinates TLR2 both in vitro and in vivo, which leads to TLR2 degradation and disruption of the signaling cascade. Lentiviral gene transfer or knockdown of PPP1R11 in mouse lungs significantly affects lung inflammation and the clearance of Staphylococcus aureus. There is a negative correlation between PPP1R11 and TLR2 levels in white blood cell samples isolated from patients with Staphylococcus aureus infections. These results suggest that PPP1R11 plays an important role in regulating innate immunity and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2. DOI: http://dx.doi.org/10.7554/eLife.18496.001 PMID:27805901

  13. Signature of balancing selection at the MC1R gene in Kunming dog populations.

    PubMed

    Wang, Guo-dong; Cheng, Lu-guang; Fan, Ruo-xi; Irwin, David M; Tang, Shu-sheng; Peng, Jian-guo; Zhang, Ya-ping

    2013-01-01

    Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment) or eumelanin (a black or brown pigment) through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1), CBD103 (β-defensin 103), and ASIP (agouti-signaling protein precursor). The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.

  14. Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects

    PubMed Central

    Zhang, Hongkai; Sturchler, Emmanuel; Zhu, Jiang; Nieto, Ainhoa; Cistrone, Philip A.; Xie, Jia; He, LinLing; Yea, Kyungmoo; Jones, Teresa; Turn, Rachel; Di Stefano, Peter S.; Griffin, Patrick R.; Dawson, Philip E.; McDonald, Patricia H.; Lerner, Richard A.

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists have emerged as treatment options for type 2 diabetes mellitus (T2DM). GLP-1R signals through G-protein-dependent, and G-protein-independent pathways by engaging the scaffold protein β-arrestin; preferential signalling of ligands through one or the other of these branches is known as ‘ligand bias'. Here we report the discovery of the potent and selective GLP-1R G-protein-biased agonist, P5. We identified P5 in a high-throughput autocrine-based screening of large combinatorial peptide libraries, and show that P5 promotes G-protein signalling comparable to GLP-1 and Exendin-4, but exhibited a significantly reduced β-arrestin response. Preclinical studies using different mouse models of T2DM demonstrate that P5 is a weak insulin secretagogue. Nevertheless, chronic treatment of diabetic mice with P5 increased adipogenesis, reduced adipose tissue inflammation as well as hepatic steatosis and was more effective at correcting hyperglycaemia and lowering haemoglobin A1c levels than Exendin-4, suggesting that GLP-1R G-protein-biased agonists may provide a novel therapeutic approach to T2DM. PMID:26621478

  15. Signature of balancing selection at the MC1R gene in Kunming dog populations.

    PubMed

    Wang, Guo-dong; Cheng, Lu-guang; Fan, Ruo-xi; Irwin, David M; Tang, Shu-sheng; Peng, Jian-guo; Zhang, Ya-ping

    2013-01-01

    Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment) or eumelanin (a black or brown pigment) through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1), CBD103 (β-defensin 103), and ASIP (agouti-signaling protein precursor). The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations. PMID:23424634

  16. Salmonella typhimurium A1-R tumor targeting in immunocompetent mice is enhanced by a traditional Chinese medicine herbal mixture.

    PubMed

    Zhang, Yong; Zhang, Nan; Su, Shibing; Hoffman, Robert M; Zhao, Ming

    2013-05-01

    We have developed a bacterial cancer therapy strategy using the genetically-engineered strain Salmonella typhimurium A1-R (A1-R). A1-R is auxotrophic for leu and arg which attenuates bacterial growth in normal tissue but allows high tumor virulence. A1-R is effective against metastatic human and murine cancer cell lines in clinically-relevant nude-mouse models. However, A1-R treatment of tumors in immunocompetent mouse models with high doses is limited by toxicity. The current study evaluated a traditional Chinese medicine (TCM) herbal mixture in combination with A1-R therapy in a syngeneic metastatic immunocompetent mouse model of highly aggressive lung cancer. In a model of Lewis lung carcinoma, the combination of a TCM herbal mixture and S. typhimurium A1-R enabled bacteria to be safely administered at the large dose of 2 × 10(7) colony forming units once a week i.v. with increased treatment efficacy and reduced toxicity compared to monotherapy with A1-R. The herbal mixture prevented body weight loss, spleen weight gain and liver infection by A1-R, as well as hemorrhagic lesions on the skin, liver, and spleen, all observed with A1-R monotherapy. The results of the present study suggest that the combination of A1-R and TCM has important potential for therapy of highly aggressive types of cancer, including those which are resistant to standard therapy.

  17. Durable Response of Spinal Chordoma to Combined Inhibition of IGF-1R and EGFR.

    PubMed

    Aleksic, Tamara; Browning, Lisa; Woodward, Martha; Phillips, Rachel; Page, Suzanne; Henderson, Shirley; Athanasou, Nicholas; Ansorge, Olaf; Whitwell, Duncan; Pratap, Sarah; Hassan, A Bassim; Middleton, Mark R; Macaulay, Valentine M

    2016-01-01

    Chordomas are rare primary malignant bone tumors arising from embryonal notochord remnants of the axial skeleton. Chordomas commonly recur following surgery and radiotherapy, and there is no effective systemic therapy. Previous studies implicated receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF-1R), in chordoma biology. We report an adult female patient who presented in 2003 with spinal chordoma, treated with surgery and radiotherapy. She underwent further surgery for recurrent chordoma in 2008, with subsequent progression in pelvic deposits. In June 2009, she was recruited onto the Phase I OSI-906-103 trial of EGFR inhibitor erlotinib with linsitinib, a novel inhibitor of IGF-1R/insulin receptor (INSR). Treatment with 100 mg QD erlotinib and 50 mg QD linsitinib was well-tolerated, and after 18 months a partial response was achieved by RECIST criteria. From 43 months, a protocol modification allowed intra-patient linsitinib dose escalation to 50 mg BID. The patient remained stable on trial treatment for a total of 5 years, discontinuing treatment in August 2014. She subsequently experienced further disease progression for which she underwent pelvic surgery in April 2015. Analysis of DNA extracted from 2008 (pre-trial) tissue showed that the tumor harbored wild-type EGFR, and a PIK3CA mutation was detected in plasma, but not tumor DNA. The 2015 (post-trial) tumor harbored a mutation of uncertain significance in ATM, with no detectable mutations in other components of a 50 gene panel, including EGFR, PIK3CA, and TP53. By immunohistochemistry, the tumor was positive for brachyury, the molecular hallmark of chordoma, and showed weak-moderate membrane and cytoplasmic EGFR. IGF-1R was detected in the plasma membrane and cytoplasm and was expressed more strongly in recurrent tumor than the primary. We also noted heterogeneous nuclear IGF-1R, which has been linked with sensitivity

  18. Durable Response of Spinal Chordoma to Combined Inhibition of IGF-1R and EGFR

    PubMed Central

    Aleksic, Tamara; Browning, Lisa; Woodward, Martha; Phillips, Rachel; Page, Suzanne; Henderson, Shirley; Athanasou, Nicholas; Ansorge, Olaf; Whitwell, Duncan; Pratap, Sarah; Hassan, A. Bassim; Middleton, Mark R.; Macaulay, Valentine M.

    2016-01-01

    Chordomas are rare primary malignant bone tumors arising from embryonal notochord remnants of the axial skeleton. Chordomas commonly recur following surgery and radiotherapy, and there is no effective systemic therapy. Previous studies implicated receptor tyrosine kinases, including epidermal growth factor receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF-1R), in chordoma biology. We report an adult female patient who presented in 2003 with spinal chordoma, treated with surgery and radiotherapy. She underwent further surgery for recurrent chordoma in 2008, with subsequent progression in pelvic deposits. In June 2009, she was recruited onto the Phase I OSI-906-103 trial of EGFR inhibitor erlotinib with linsitinib, a novel inhibitor of IGF-1R/insulin receptor (INSR). Treatment with 100 mg QD erlotinib and 50 mg QD linsitinib was well-tolerated, and after 18 months a partial response was achieved by RECIST criteria. From 43 months, a protocol modification allowed intra-patient linsitinib dose escalation to 50 mg BID. The patient remained stable on trial treatment for a total of 5 years, discontinuing treatment in August 2014. She subsequently experienced further disease progression for which she underwent pelvic surgery in April 2015. Analysis of DNA extracted from 2008 (pre-trial) tissue showed that the tumor harbored wild-type EGFR, and a PIK3CA mutation was detected in plasma, but not tumor DNA. The 2015 (post-trial) tumor harbored a mutation of uncertain significance in ATM, with no detectable mutations in other components of a 50 gene panel, including EGFR, PIK3CA, and TP53. By immunohistochemistry, the tumor was positive for brachyury, the molecular hallmark of chordoma, and showed weak–moderate membrane and cytoplasmic EGFR. IGF-1R was detected in the plasma membrane and cytoplasm and was expressed more strongly in recurrent tumor than the primary. We also noted heterogeneous nuclear IGF-1R, which has been linked with sensitivity

  19. Evolution and phylogenetic application of the MC1R gene in the Cobitoidea (Teleostei: Cypriniformes)

    PubMed Central

    TANG, Qiong-Ying; LIANG, Li-Xia; LIU, Fei; YU, Dan; LIU, Huan-Zhang

    2016-01-01

    Fish of the superfamily Cobitoidea sensu stricto (namely loaches) exhibit extremely high diversity of color patterns, but so far little is known about their evolutionary mechanism. Melanocortin 1 receptor gene (MC1R) plays an important role during the synthesis of melanin and formation of animal body color patterns. In this study, we amplified and sequenced the partial MC1R gene for 44 loach individuals representing 31 species of four families. Phylogenetic analyses yielded a topology congruent with previous studies using multiple nuclear loci, showing that each of the four families was monophyletic with sister relationships of Botiidae+ (Cobitidae+(Balitoridae+Nemacheilidae)). Gene evolutionary analyses indicated that MC1R in loaches was under purifying selection pressure, with various sites having different dN/dS values. Both Botiidae and Cobitidae had lower dN/dS values than those of background lineages, suggesting their evolution might be strongly affected by purifying selection pressure. For Balitoridae and Nemacheilidae, both had larger dN/dS values than those of background lineages, suggesting they had a faster evolutionary rate under more relaxed selection pressure. Consequently, we inferred that the relatively stable color patterns in Botiidae and Cobitidae might result from the strong purifying selection pressure on the MC1R gene, whereas the complicated and diverse color patterns in Balitoridae and Nemacheilidae might be associated with the relaxed selection pressure. Given the easy experimental procedure for the partial MC1R gene and its excellent performance in reconstructing phylogeny, we suggest this gene could be used as a good molecular marker for the phylogenetic study of fish species. PMID:27686787

  20. Evolution of the melanocortin-1 receptor (MC1R) in Boobies and Gannets (Aves, Suliformes).

    PubMed

    Baião, Patricia C; Parker, Patricia G

    2012-01-01

    The melanocortin-1 receptor (MC1R) has been linked to intraspecific variation of melanin-based plumage color in several unrelated bird species. However, its involvement in interspecific variation has far less evidence. The Sulidae is a family in the Suliformes composed of 10 species of pelagic seabirds, distributed in 3 genera. There is significant variation in the amount and distribution of melanin pigments among species in the family Sulidae, and 2 species, the brown booby (Sula leucogaster) and the red-footed booby (S. sula), present plumage polymorphisms, with the latter being considered one of the most plumage polymorphic birds. We performed a survey of the MC1R evolution in 68 individuals representing all 9 species in the Sulidae, except the Abbott's booby, to determine the role played by this locus in explaining the melanic variation observed in the Sulidae. We found the amino acid substitution R112H to be in full concordance with the plumage color observed in the brown booby, which shows a unique phaeomelanin-dominant coloration. Furthermore, all amino acid residues known to be important for function at the MC1R were completely conserved in the Sulidae, except for the previously described V85M and H207R substitutions among the 2 red-footed booby's color morphs. A total of 14 substitutions were inferred from estimated ancestral nodes throughout the Sulidae phylogeny. Finally, we found evidence that the MC1R is under strong purifying selection in all Sulid species. This study provides additional evidence of the potential involvement of the MC1R in melanin-based plumage variation at the interspecific level.

  1. Polymorphisms of interleukin-1R receptor antagonist genes in patients with chronic hepatitis B in Iran

    PubMed Central

    Ranjbar, Mitra; Alizadeh, Amir Houshang Mohammad; Hajilooi, Mehrdad; Mousavi, Seyed Mohsen

    2006-01-01

    AIM: To investigate the relationships between polymorphisms of interleukin-1R receptor antagonist genes and susceptibility to chronic hepatitis B in Iran population. METHODS: Genomic DNA was extracted from the peripheral blood of 80 patients with chronic hepatitis B (57 males, 23 females) aged 12-77 years (mean 36.1 ± 13.8 years) and 147 normal controls (96 males, 51 females) aged 6-75 years (mean 41 ± 18.7 years) who referred to a liver clinic of Tehran and then subjected to polymerase chain reaction (PCR) amplification. PCR products were resolved on a 3% agarose gel and stained with ethidium bromide. RESULTS: Only three of the five kinds of polymorphism (2/2, 2/4, and 4/4) were found in this study. The frequencies of 2/2, 2/4, and 4/4 were 12.5%, 17.5%, 70% respectively in chronic hepatitis B patients and 6.8%, 24.5%, and 68.7% respectively in controls. IL-1 R allele 2 was detected in 30% of chronic hepatitis B patients and in 31.3% of controls, while IL-1 R allele 4 was detected in 87.5% of chronic hepatitis B patients and in 93.2% of controls. The frequency of IL-1R alleles 2 and 4 was detected in 21.25% and 78.75% of the patients and 19.04% and 80.96% of the controls, respectively. CONCLUSION: Our results suggest that the carriage of IL-1R receptor antagonist alleles 2, 4, 6 may not play any role in the development of HBV infection. Large population-based studies are needed to investigate the role of IL-1 polymorphisms in the pathogenesis of developing chronic hepatitis B. PMID:16937503

  2. Evolution of the melanocortin-1 receptor (MC1R) in Boobies and Gannets (Aves, Suliformes).

    PubMed

    Baião, Patricia C; Parker, Patricia G

    2012-01-01

    The melanocortin-1 receptor (MC1R) has been linked to intraspecific variation of melanin-based plumage color in several unrelated bird species. However, its involvement in interspecific variation has far less evidence. The Sulidae is a family in the Suliformes composed of 10 species of pelagic seabirds, distributed in 3 genera. There is significant variation in the amount and distribution of melanin pigments among species in the family Sulidae, and 2 species, the brown booby (Sula leucogaster) and the red-footed booby (S. sula), present plumage polymorphisms, with the latter being considered one of the most plumage polymorphic birds. We performed a survey of the MC1R evolution in 68 individuals representing all 9 species in the Sulidae, except the Abbott's booby, to determine the role played by this locus in explaining the melanic variation observed in the Sulidae. We found the amino acid substitution R112H to be in full concordance with the plumage color observed in the brown booby, which shows a unique phaeomelanin-dominant coloration. Furthermore, all amino acid residues known to be important for function at the MC1R were completely conserved in the Sulidae, except for the previously described V85M and H207R substitutions among the 2 red-footed booby's color morphs. A total of 14 substitutions were inferred from estimated ancestral nodes throughout the Sulidae phylogeny. Finally, we found evidence that the MC1R is under strong purifying selection in all Sulid species. This study provides additional evidence of the potential involvement of the MC1R in melanin-based plumage variation at the interspecific level. PMID:22351934

  3. Evolution and phylogenetic application of the MC1R gene in the Cobitoidea (Teleostei: Cypriniformes).

    PubMed

    Tang, Qiong-Ying; Shi, Li-Xia; Liu, Fei; Yu, Dan; Liu, Huan-Zhang

    2016-09-18

    Fish of the superfamily Cobitoidea sensu stricto (namely loaches) exhibit extremely high diversity of color patterns, but so far little is known about their evolutionary mechanism. Melanocortin 1 receptor gene (MC1R) plays an important role during the synthesis of melanin and formation of animal body color patterns. In this study, we amplified and sequenced the partial MC1R gene for 44 loach individuals representing 31 species of four families. Phylogenetic analyses yielded a topology congruent with previous studies using multiple nuclear loci, showing that each of the four families was monophyletic with sister relationships of Botiidae+ (Cobitidae+(Balitoridae+Nemacheilidae)). Gene evolutionary analyses indicated that MC1R in loaches was under purifying selection pressure, with various sites having different dN/dS values. Both Botiidae and Cobitidae had lower dN/dS values than those of background lineages, suggesting their evolution might be strongly affected by purifying selection pressure. For Balitoridae and Nemacheilidae, both had larger dN/dS values than those of background lineages, suggesting they had a faster evolutionary rate under more relaxed selection pressure. Consequently, we inferred that the relatively stable color patterns in Botiidae and Cobitidae might result from the strong purifying selection pressure on the MC1R gene, whereas the complicated and diverse color patterns in Balitoridae and Nemacheilidae might be associated with the relaxed selection pressure. Given the easy experimental procedure for the partial MC1R gene and its excellent performance in reconstructing phylogeny, we suggest this gene could be used as a good molecular marker for the phylogenetic study of fish species. PMID:27686787

  4. Alterations in Mc1r gene expression are associated with regressive pigmentation in Astyanax cavefish.

    PubMed

    Stahl, Bethany A; Gross, Joshua B

    2015-11-01

    Diverse changes in coloration across distant taxa are mediated through alterations in certain highly conserved pigmentation genes. Among these genes, Mc1r is a frequent target for mutation, and many documented alterations involve coding sequence changes. We investigated whether regulatory mutations in Mc1r may also contribute to pigmentation loss in the blind Mexican cavefish, Astyanax mexicanus. This species comprises multiple independent cave populations that have evolved reduced (or absent) melanic pigmentation as a consequence of living in darkness for millions of generations. Among the most salient cave-associated traits, complete absence (albinism) or reduced levels of pigmentation (brown) have long been the focus of degenerative pigmentation research in Astyanax. These two Mendelian traits have been linked to specific coding mutations in Oca2 (albinism) and Mc1r (brown). However, four of the seven caves harboring the brown phenotype exhibit unaffected coding sequences compared to surface fish. Thus, diverse genetic changes involving the same genes likely impact reduced pigmentation among cavefish populations. Using both sequence and expression analyses, we show that certain cave-dwelling populations harboring the brown mutation have substantial alterations to the putative Mc1r cis-regulatory region. Several of these sequence mutations in the Mc1r 5' region were present across multiple, independent cave populations. This study suggests that pigmentation reduction in Astyanax cavefish evolves through a combination of both coding and cis-regulatory mutations. Moreover, this study represents one of the first attempts to identify regulatory alterations linked to regressive changes in cave-dwelling populations of A. mexicanus. PMID:26462499

  5. Alterations in Mc1r gene expression are associated with regressive pigmentation in Astyanax cavefish.

    PubMed

    Stahl, Bethany A; Gross, Joshua B

    2015-11-01

    Diverse changes in coloration across distant taxa are mediated through alterations in certain highly conserved pigmentation genes. Among these genes, Mc1r is a frequent target for mutation, and many documented alterations involve coding sequence changes. We investigated whether regulatory mutations in Mc1r may also contribute to pigmentation loss in the blind Mexican cavefish, Astyanax mexicanus. This species comprises multiple independent cave populations that have evolved reduced (or absent) melanic pigmentation as a consequence of living in darkness for millions of generations. Among the most salient cave-associated traits, complete absence (albinism) or reduced levels of pigmentation (brown) have long been the focus of degenerative pigmentation research in Astyanax. These two Mendelian traits have been linked to specific coding mutations in Oca2 (albinism) and Mc1r (brown). However, four of the seven caves harboring the brown phenotype exhibit unaffected coding sequences compared to surface fish. Thus, diverse genetic changes involving the same genes likely impact reduced pigmentation among cavefish populations. Using both sequence and expression analyses, we show that certain cave-dwelling populations harboring the brown mutation have substantial alterations to the putative Mc1r cis-regulatory region. Several of these sequence mutations in the Mc1r 5' region were present across multiple, independent cave populations. This study suggests that pigmentation reduction in Astyanax cavefish evolves through a combination of both coding and cis-regulatory mutations. Moreover, this study represents one of the first attempts to identify regulatory alterations linked to regressive changes in cave-dwelling populations of A. mexicanus.

  6. CO2 adsorption properties of char produced from brown coal impregnated with alcohol amine solutions.

    PubMed

    Baran, Paweł; Zarębska, Katarzyna; Czuma, Natalia

    2016-07-01

    Carbon dioxide (CO2) emission reduction is critical to mitigating climate change. Power plants for heating and industry are significant sources of CO2 emissions. There is a need for identifying and developing new, efficient methods to reduce CO2 emissions. One of the methods used is flue gas purification by CO2 capture through adsorption. This study aimed to develop CO2 adsorbent out of modified brown coal impregnated with solutions of first-, second-, and third-order amines. Low-temperature nitrogen adsorption isotherms and CO2 isotherms were measured for the prepared samples. The results of experiments unexpectedly revealed that CO2 sorption capacity decreased after impregnation. Due to lack of strait trends in CO2 sorption capacity decrease, the results were closely analyzed to find the reason for the inconsistencies. It was revealed that different amines represent different affinities for CO2 and that the size and structure of impregnating factor has influence on the CO2 sorption capacity of impregnated material. The character of a support was also noticeable as well for impregnation results as for the affinity to CO2. The influence of amine concentration used was investigated along with the comparison on how the theoretical percentage of the impregnation on the support influenced the results. The reaction mechanism of tertiary amine was taken into consideration in connection to no presence of water vapor during the experiments. Key findings were described in the work and provide a strong basis for further studies on CO2 adsorption on amine-impregnated support. PMID:27317051

  7. Differential organ phenotypes after postnatal Igf1r gene conditional deletion induced by tamoxifen in UBC-CreERT2; Igf1r fl/fl double transgenic mice.

    PubMed

    López, Icíar Paula; Rodriguez-de la Rosa, Lourdes; Pais, Rosete Sofia; Piñeiro-Hermida, Sergio; Torrens, Raquel; Contreras, Julio; Varela-Nieto, Isabel; Pichel, José García

    2015-04-01

    Insulin-like growth factor type 1 receptor (IGF1R) is a ubiquitously expressed tyrosine kinase that regulates cell proliferation, differentiation and survival. It controls body growth and organ homeostasis, but with specific functions depending on developmental time and cell type. Human deficiency in IGF1R is involved in growth failure, microcephaly, mental retardation and deafness, and its overactivation is implicated in oncogenesis. Igf1r-deficient mice die at birth due to growth retardation and respiratory failure. Although multiple Igf1r tissue-specific mutant lines have been analyzed postnatally, using Igf1r-floxed (Igf1r (fl/fl) ) mice mated with diverse cell-type recombinase Cre-expressing transgenics, no mouse models for the study of generalized Igf1r deficiency in adults have been reported. To this end we generated UBC-CreERT2; Igf1r (fl/fl) transgenic mice with an inducible deletion of Igf1r activated by tamoxifen. Tamoxifen administration to 4 week-old prepuberal male mice delayed their growth, producing a distinct impact on organ size 4 weeks later. Whereas testes were smaller, spleen and heart showed an increased organ to body weight ratio. Mosaic Igf1r genomic deletions caused a significant reduction in Igf1r mRNA in all organs analyzed, resulting in diverse phenotypes. While kidneys, spleen and cochlea had unaltered gross morphology, testes revealed halted spermatogenesis, and liver and alveolar lung parenchyma showed increased cell proliferation rates without affecting apoptosis. We demonstrate that UBC-CreERT2 transgenic mice efficiently delete Igf1r upon postnatal tamoxifen treatment in multiple mouse organs, and corroborate that IGF1R function is highly dependent on cell, tissue and organ type.

  8. Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor

    PubMed Central

    Davaadelger, Batzaya; Duan, Lei; Perez, Ricardo E.; Gitelis, Steven; Maki, Carl G.

    2016-01-01

    The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is aberrantly activated in multiple cancers and can promote proliferation and chemotherapy resistance. Multiple IGF-1R inhibitors have been developed as potential therapeutics. However, these inhibitors have failed to increase patient survival when given alone or in combination with chemotherapy agents. The reason(s) for the disappointing clinical effect of these inhibitors is not fully understood. Cisplatin (CP) activated the IGF-1R/AKT/mTORC1 pathway and stabilized p53 in osteosarcoma (OS) cells. p53 knockdown reduced IGF-1R/AKT/mTORC1 activation by CP, and IGF-1R inhibition reduced the accumulation of p53. These data demonstrate positive crosstalk between p53 and the IGF-1R/AKT/mTORC1 pathway in response to CP. Further studies showed the effect of IGF-1R inhibition on CP response is dependent on p53 status. In p53 wild-type cells treated with CP, IGF-1R inhibition increased p53s apoptotic function but reduced p53-dependent senescence, and had no effect on long term survival. In contrast, in p53-null/knockdown cells, IGF-1R inhibition reduced apoptosis in response to CP and increased long term survival. These effects were due to p27 since IGF-1R inhibition stabilized p27 in CP-treated cells, and p27 depletion restored apoptosis and reduced long term survival. Together, the results demonstrate 1) p53 expression determines the effect of IGF-1R inhibition on cancer cell CP response, and 2) crosstalk between the IGF-1R/AKT/mTORC1 pathway and p53 and p27 can reduce cancer cell responsiveness to chemotherapy and may ultimately limit the effectiveness of IGF-1R pathway inhibitors in the clinic. PMID:27050276

  9. NASA's Evolutionary Xenon Thruster (NEXT) Prototype Model 1R (PM1R) Ion Thruster and Propellant Management System Wear Test Results

    NASA Technical Reports Server (NTRS)

    VanNoord, Jonathan L.; Soulas, George C.; Sovey, James S.

    2010-01-01

    The results of the NEXT wear test are presented. This test was conducted with a 36-cm ion engine (designated PM1R) and an engineering model propellant management system. The thruster operated with beam extraction for a total of 1680 hr and processed 30.5 kg of xenon during the wear test, which included performance testing and some operation with an engineering model power processing unit. A total of 1312 hr was accumulated at full power, 277 hr at low power, and the remainder was at intermediate throttle levels. Overall ion engine performance, which includes thrust, thruster input power, specific impulse, and thrust efficiency, was steady with no indications of performance degradation. The propellant management system performed without incident during the wear test. The ion engine and propellant management system were also inspected following the test with no indication of anomalous hardware degradation from operation.

  10. Enhanced antimicrobial effect of organic acid washing against foodborne pathogens on broccoli by vacuum impregnation.

    PubMed

    Kang, Jun-Won; Kang, Dong-Hyun

    2016-01-18

    This study was undertaken to evaluate the effect of vacuum impregnation applied to the washing process for removal of Salmonella Typhimurium and Listeria monocytogenes from broccoli surfaces. Broccoli was inoculated with the two foodborne pathogens and treated with simple dipping washing or with vacuum impregnation in 2% malic acid for 5, 10, 20, or 30 min. There were two methods of vacuum impregnation: continuous and intermittent. After 30 min of 101.3 kPa (=14.7 psi, simple dipping), 61.3 kPa (=8.9 psi), and 21.3 kPa (=3.1 psi) of continuous vacuum impregnation treatment, there were 1.6, 2.0, and 2.4 log 10 CFU/g reductions of S. Typhimurium and 1.5, 1.7, and 2.3 log 10 CFU/g reductions of L. monocytogenes, respectively. After 30 min of 101.3, 61.3, and 21.3 kPa of intermittent vacuum impregnation treatment, there were 1.5, 2.3, and 3.7 log 10 CFU/g reductions of S. Typhimurium and 1.6, 2.1, and 3.2 log 10 CFU/g reductions of L. monocytogenes, respectively. Scanning electron photomicrographs showed that bacteria tend to attach to or become entrapped in protective sites after simple wash processing (dipping). However, most bacteria were washed out of protective sites after intermittent treatment. Direct treatment of cell suspensions with vacuum impregnation showed that it had no inactivation capacity in itself since there were no significant differences (P ≥ 0.05) between the reduction rates of non- and vacuum impregnation treatment. These results demonstrate that the increased antimicrobial effect of vacuum impregnation can be attributed to increased accessibility of sanitizer and an enhanced washing effect in protected sites on produce. Color, texture and titratable acidity values of broccoli treated with intermittent vacuum impregnation in 2% malic acid for 30 min were not significantly (P ≥ 0.05) different from those of untreated samples even though a storage interval was needed for titratable acidity values to be reduced to levels comparable to those of

  11. Enhanced antimicrobial effect of organic acid washing against foodborne pathogens on broccoli by vacuum impregnation.

    PubMed

    Kang, Jun-Won; Kang, Dong-Hyun

    2016-01-18

    This study was undertaken to evaluate the effect of vacuum impregnation applied to the washing process for removal of Salmonella Typhimurium and Listeria monocytogenes from broccoli surfaces. Broccoli was inoculated with the two foodborne pathogens and treated with simple dipping washing or with vacuum impregnation in 2% malic acid for 5, 10, 20, or 30 min. There were two methods of vacuum impregnation: continuous and intermittent. After 30 min of 101.3 kPa (=14.7 psi, simple dipping), 61.3 kPa (=8.9 psi), and 21.3 kPa (=3.1 psi) of continuous vacuum impregnation treatment, there were 1.6, 2.0, and 2.4 log 10 CFU/g reductions of S. Typhimurium and 1.5, 1.7, and 2.3 log 10 CFU/g reductions of L. monocytogenes, respectively. After 30 min of 101.3, 61.3, and 21.3 kPa of intermittent vacuum impregnation treatment, there were 1.5, 2.3, and 3.7 log 10 CFU/g reductions of S. Typhimurium and 1.6, 2.1, and 3.2 log 10 CFU/g reductions of L. monocytogenes, respectively. Scanning electron photomicrographs showed that bacteria tend to attach to or become entrapped in protective sites after simple wash processing (dipping). However, most bacteria were washed out of protective sites after intermittent treatment. Direct treatment of cell suspensions with vacuum impregnation showed that it had no inactivation capacity in itself since there were no significant differences (P ≥ 0.05) between the reduction rates of non- and vacuum impregnation treatment. These results demonstrate that the increased antimicrobial effect of vacuum impregnation can be attributed to increased accessibility of sanitizer and an enhanced washing effect in protected sites on produce. Color, texture and titratable acidity values of broccoli treated with intermittent vacuum impregnation in 2% malic acid for 30 min were not significantly (P ≥ 0.05) different from those of untreated samples even though a storage interval was needed for titratable acidity values to be reduced to levels comparable to those of

  12. Metformin ameliorates lipotoxicity-induced mesangial cell apoptosis partly via upregulation of glucagon like peptide-1 receptor (GLP-1R).

    PubMed

    Kim, Dong-il; Park, Min-jung; Heo, Young-ran; Park, Soo-hyun

    2015-10-15

    Glucagon like peptide-1 receptor (GLP-1R), known to be expressed in pancreatic beta cells, is also expressed in glomerular mesangial cells and its agonist has protective effects in diabetic nephropathy. However, its regulatory mechanisms by lipotoxicity in glomerular mesangial cells are not understood. We found that palmitate-mediated lipotoxicity increased apoptosis and decreased GLP-1R expression in a rat mesangial cell line. Silencing GLP-1R expression also increased mesangial cell apoptosis. Interestingly, metformin, one of the biguanide drugs that has anti-diabetic effects, attenuated lipotoxicity-induced mesangial cell apoptosis and restored GLP-1R expression. Moreover, this treatment alleviated GLP-1R knockdown-induced mesangial cell apoptosis. To further evaluate in vivo, diabetic obese db/db mice were administered metformin. Glomerular GLP-1R expression was diminished in db/db mice, as compared with db/m control mice. However, this decrease significantly recovered on metformin administration. Together, these data provide novel evidence that lipotoxicity decreases the mesangial GLP-1R expression in intact cells and in vivo. The decrease induced mesangial cell apoptosis. Furthermore, we provided the evidence that metformin treatment has a renal protective effect partly via increased mesangial GLP-1R expression. Our data suggested that regulation of GLP-1R expression could be a promising approach to treat diabetic nephropathy and the novel mechanism of metformin mediated GLP-1R regulation.

  13. Shrinkage of renal tissue after impregnation via the cold Biodur plastination technique.

    PubMed

    Pereira-Sampaio, Marco A; Marques-Sampaio, Beatriz P S; Sampaio, Francisco J B; Henry, Robert W

    2011-08-01

    Thorough dehydration is a key for good plastination and invariably it leads to shrinkage. Shrinkage during plastination has been studied to lesser extent. Shrinkage was studied in 10 pig kidneys including regional shrinkage (cortex, medulla, sinus) and at which stages of the process (dehydration, impregnation, curing) shrinkage occurred. Kidneys were fixation by perfusion of 10% neutral buffered formalin solution via the renal artery. The vessels and ureter were filled with colored silicone (Dow Corning, Silastic E RTV Silicone Rubber) and the kidneys were cut into one centimeter transverse slices. Two slices of each kidney were plastinated via the classic von Hagens' method. Slices were photographed at the same focal length after preparation and at the end of each stage of plastination. Slice surface area was determined by a point-counting planimetry method. Post dehydration shrinkage of the kidney was 10.21% while post impregnation 10.11%. After completion of plastination, total area of kidney slice shrinkage was 19.72%. Cortical area shrunk 12.81% after dehydration and 13.16% after impregnation. After plastination, cortical area had shrunk 24.28%. No significant shrinkage occurred in the medulla and sinus. Results demonstrate that kidney shrinkage during impregnation is as intense as during dehydration. Significant shrinkage occurred in the renal cortex but not in the medulla and sinus. This demonstrates that different tissue types, even in the same specimen, have different rates of shrinkage during dehydration and impregnation. Therefore, plastinated specimens should be used carefully in research where obtaining measures is important.

  14. Enhancement of the transverse stress tolerance of REBCO Roebel cables by epoxy impregnation

    NASA Astrophysics Data System (ADS)

    Otten, S.; Dhallé, M.; Gao, P.; Wessel, W.; Kario, A.; Kling, A.; Goldacker, W.

    2015-06-01

    REBCO Roebel cables are considered for application in high-temperature superconducting inserts for accelerator magnets because of their fully transposed geometry, high-engineering current density, and adequate bending tolerance. In these magnets the cables experience Lorentz forces leading to transverse stresses up to 100-150 MPa. Previous reports have shown bare Roebel cables to degrade under such high stresses so that additional reinforcement is required. In this work, two identical Roebel cables are vacuum impregnated with a mixture of epoxy and fused silica in order to improve their tolerance to transverse stress. After impregnation, the critical current of the cables is measured under transverse mechanical loading at T = 4.2 K, {{B}\\bot }=10.5 T. A reference cable without impregnation is tested as well. Pressures up to 350 MPa are applied to a short (30 mm) section of each cable. No degradation was observed for pressures up to 250 MPa and 170 MPa in the two impregnated cables. The critical current of the non-impregnated cable, in contrast, started to decrease at stresses as low as 40 MPa.

  15. Phosphate adsorption on aluminum-impregnated mesoporous silicates: surface structure and behavior of adsorbents.

    PubMed

    Shin, Eun Woo; Han, James S; Jang, Min; Min, Soo-Hong; Park, Jae Kwang; Rowell, Roger M

    2004-02-01

    Phosphorus from excess fertilizers and detergents ends up washing into lakes, creeks, and rivers. This overabundance of phosphorus causes excessive aquatic plant and algae growth and depletes the dissolved oxygen supply in the water. In this study, aluminum-impregnated mesoporous adsorbents were tested for their ability to remove phosphate from water. The surface structure of the materials was investigated with X-ray diffraction (XRD), a N2 adsorption-desorption technique, Fourier transform-infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS) to understand the effect of surface properties on the adsorption behavior of phosphate. The mesoporous materials were loaded with Al components by reaction with surface silanol groups. In the adsorption test, the Al-impregnated mesoporous materials showed fast adsorption kinetics as well as high adsorption capacities, compared with activated alumina. The uniform mesopores of the Al-impregnated mesoporous materials caused the diffusion rate in the adsorption process to increase, which in turn caused the fast adsorption kinetics. High phosphate adsorption capacities of the Al-impregnated mesoporous materials were attributed to not only the increase of surface hydroxyl density on Al oxide due to well-dispersed impregnation of Al components but also the decrease in stoichiometry of surface hydroxyl ions to phosphate by the formation of monodentate surface complexes. PMID:14968882

  16. Fractionation of oil palm frond hemicelluloses by water or alkaline impregnation and steam explosion.

    PubMed

    Sabiha-Hanim, Saleh; Mohd Noor, Mohd Azemi; Rosma, Ahmad

    2015-01-22

    Steam explosion of oil palm frond has been carried out under different temperatures between 180 and 210°C for 4 min (severity of 2.96-3.84) after impregnation of the frond chips with water or KOH solution. The effects of impregnation and steam explosion conditions of oil palm fronds on the water soluble fraction and insoluble fraction were investigated. The maximum yield of hemicelluloses in water soluble fractions recovered was 23.49% and 25.33% for water and KOH impregnation, treated with steam explosion at temperature of 210°C (severity of 3.84) with a fractionation efficiency of 77.30% and 83.32%, respectively. Under this condition, the water insoluble fractions contained celluloses at 60.83% and 64.80% for water and KOH impregnation, respectively. The steam explosion temperature of 210°C for 4 min (logR(o) 3.84) was found to be the best condition in the extraction of hemicelluloses from OPF for both types of impregnation.

  17. The effect of fluoride impregnated dental floss on enamel fluoride uptake in vitro and streptococcus mutans colonization in vivo.

    PubMed

    Chaet, R; Wei, S H

    1977-01-01

    The conclusions reached from this investigation can be summarized as follows: Fluoride can be incorporated into unwaxed dental floss. Placement of the fluoride impregnated dental floss in acid-buffer solution results in the release of most of the fluoride in the floss. Interproximal surfaces of teeth treated in vitro with fluoride impregnated dental floss acquired significantly (approximately three fold) more enamel fluoride than those treated with plain dental floss. The number of in vivo interproximal areas harboring Streptococcus mutans was reduced significantly after treatment with fluoride impregnated dental floss. Further studies should be done to establish the biological, physiochemical, manufacturing, and practical aspects of fluoride impregnated dental floss.

  18. Modulation of the hypothalamic-pituitary-gonadal axis by selective ligands of the KISS1R.

    PubMed

    Thompson, Emily L; Murphy, Kevin G

    2010-04-01

    The kisspeptin/kisspeptin receptor (KISS1R) system is a critical regulator of reproductive function. The kisspeptins are potent stimulators of the hypothalamic-pituitary-gonadal (HPG) axis via their actions ongonadotropin-releasing hormone. Therefore, kisspeptins represent putative drug targets for the treatment of reproductive diseases. Kisspeptins of 10, 13, 14 and 54 amino acids in length have been identified, all of which contain a C-terminal decapeptide that is essential for biological activity. The longest form, kisspeptin-54, may be the most bioactive in vivo. Moreover, the pattern of kisspeptin administration is important; whereas single or intermittent injections of kisspeptin generally stimulate the HPG axis, continuous administration leads to the desensitization of the HPG axis to the effects of the peptide. Several kisspeptin analogs have been developed, and are discussed in relation to their activity at the KISS1R and to their in vivo HPG axis effects.

  19. Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations.

    PubMed

    Sundal, Christina; Fujioka, Shinsuke; Van Gerpen, Jay A; Wider, Christian; Nicholson, Alexandra M; Baker, Matt; Shuster, Elizabeth A; Aasly, Jan; Spina, Salvatore; Ghetti, Bernardino; Roeber, Sigrun; Garbern, James; Tselis, Alex; Swerdlow, Russell H; Miller, Bradley B; Borjesson-Hanson, Anne; Uitti, Ryan J; Ross, Owen A; Stoessl, A Jon; Rademakers, Rosa; Josephs, Keith A; Dickson, Dennis W; Broderick, Daniel; Wszolek, Zbigniew K

    2013-10-01

    Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by non-inflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We studied neuropathologically verified HDLS patients with CSF1R mutations to assess parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18-71) and the mean disease duration was approximately six years (range, 3-11). We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations.

  20. Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations

    PubMed Central

    Sundal, Christina; Fujioka, Shinsuke; Van Gerpen, Jay A.; Wider, Christian; Nicholson, Alexandra M.; Baker, Matt; Shuster, Elizabeth A.; Aasly, Jan; Spina, Salvatore; Ghetti, Bernardino; Roeber, Sigrun; Garbern, James; Tselis, Alex; Swerdlow, Russell H.; Miller, Bradley B.; Borjesson-Hanson, Anne; Uitti, Ryan J.; Ross, Owen; Stoessl, John A.; Rademakers, Rosa; Josephs, Keith A.; Dickson, Dennis W.; Broderick, Daniel; Wszolek, Zbigniew K.

    2014-01-01

    Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies including leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by non-inflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We studied neuropathologically verified HDLS patients with CSF1R mutations to assess Parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with Parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18-71) and the mean disease duration was approximately six years (range, 3-11). We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of Parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations. PMID:23787135

  1. Sex-specific allelic transmission bias suggests sexual conflict at MC1R.

    PubMed

    Ducret, Valérie; Gaigher, Arnaud; Simon, Céline; Goudet, Jérôme; Roulin, Alexandre

    2016-09-01

    Sexual conflict arises when selection in one sex causes the displacement of the other sex from its phenotypic optimum, leading to an inevitable tension within the genome - called intralocus sexual conflict. Although the autosomal melanocortin-1-receptor gene (MC1R) can generate colour variation in sexually dichromatic species, most previous studies have not considered the possibility that MC1R may be subject to sexual conflict. In the barn owl (Tyto alba), the allele MC1RWHITE is associated with whitish plumage coloration, typical of males, and the allele MC1RRUFOUS is associated with dark rufous coloration, typical of females, although each sex can express any phenotype. Because each colour variant is adapted to specific environmental conditions, the allele MC1RWHITE may be more strongly selected in males and the allele MC1RRUFOUS in females. We therefore investigated whether MC1R genotypes are in excess or deficit in male and female fledglings compared with the expected Hardy-Weinberg proportions. Our results show an overall deficit of 7.5% in the proportion of heterozygotes in males and of 12.9% in females. In males, interannual variation in assortative pairing with respect to MC1R explained the year-specific deviations from Hardy-Weinberg proportions, whereas in females, the deficit was better explained by the interannual variation in the probability of inheriting the MC1RWHITE or MC1RRUFOUS allele. Additionally, we observed that sons inherit the MC1RRUFOUS allele from their fathers on average slightly less often than expected under the first Mendelian law. Transmission ratio distortion may be adaptive in this sexually dichromatic species if males and females are, respectively, selected to display white and rufous plumages. PMID:27480981

  2. Cyclic alpha-conotoxin peptidomimetic chimeras as potent GLP-1R agonists.

    PubMed

    Swedberg, Joakim E; Schroeder, Christina I; Mitchell, Justin M; Durek, Thomas; Fairlie, David P; Edmonds, David J; Griffith, David A; Ruggeri, Roger B; Derksen, David R; Loria, Paula M; Liras, Spiros; Price, David A; Craik, David J

    2015-10-20

    Type 2 diabetes mellitus (T2DM) results from compromised pancreatic β-cell function, reduced insulin production, and lowered insulin sensitivity in target organs resulting in hyperglycemia. The GLP-1 hormone has two biologically active forms, GLP-1-(7-37) and GLP-1-(7-36)amide, which are equipotent at the glucagon-like peptide-1 receptor (GLP-1R). These peptides are central both to normal glucose metabolism and dysregulation in T2DM. Several structurally modified GLP-1 analogues are now approved drugs, and a number of other analogues are in clinical trials. None of these compounds is orally bioavailable and all require parenteral delivery. Recently, a number of smaller peptidomimetics containing 11-12 natural and unnatural amino acids have been identified that have similar insulin regulating profiles as GLP-1. The α-conotoxins are a class of disulfide rich peptide venoms isolated from cone snails, and are known for their highly constrained structures and resistance to enzymatic degradation. In this study, we examined whether 11-residue peptidomimetics incorporated into α-conotoxin scaffolds, forming monocyclic or bicyclic compounds constrained by disulfide bonds and/or backbone cyclization, could activate the GLP-1 receptor (GLP-1R). Several compounds showed potent (nanomolar) agonist activity at GLP-1R, as evaluated via cAMP signaling. In addition, HPLC retention times and in silico calculations suggested that mono- and bicyclic compounds had more favorable n-octanol/water partition coefficients according to the virtual partition coefficient model (vLogP), while maintaining a smaller radius of gyration compared to corresponding uncyclized peptidomimetics. Our findings suggest that cyclic peptidomimetics provide a potential avenue for future design of potent, compact ligands targeting GLP-1R and possessing improved physicochemical properties. PMID:26352676

  3. Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R.

    PubMed

    Patel, Bhaumik B; Gupta, Deepshika; Elliott, Althea A; Sengupta, Vivek; Yu, Yingjie; Majumdar, Adhip P N

    2010-02-01

    Curcumin (diferuloylmethane), which has no discernible toxicity, inhibits initiation, promotion and progression of carcinogenesis. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces an incomplete response resulting in survival of cells (chemo-surviving cells) that may lead to cancer recurrence. The present investigation was, therefore, undertaken to examine whether addition of curcumin to FOLFOX is a superior therapeutic strategy for chemo-surviving cells. Forty-eight-hour treatment of colon cancer HCT-116 and HT-29 cells with FOLFOX resulted in 60-70% survival, accompanied by a marked activation of insulin like growth factor-1 receptor (IGF-1R) and minor to moderate increase in epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2) as well as v-akt murine thymoma viral oncogene homolog 1 (AKT), cyclooxygenase-2 (COX-2) and cyclin-D1. However, inclusion of curcumin to continued FOLFOX treatment for another 48 h greatly reduced the survival of these cells, accompanied by a concomitant reduction in activation of EGFR, HER-2, IGF-1R and AKT, as well as expression of COX-2 and cyclin-D1. More importantly, EGFR tyrosine kinase inhibitor gefitinib or attenuation of IGF-1R expression by the corresponding si-RNA caused a 30-60% growth inhibition of chemo-surviving HCT-116 cells. However, curcumin alone was found to be more effective than both gefitinib and IGF-1R si-RNA mediated growth inhibition of chemo-surviving HCT-116 cells and addition of FOLFOX to curcumin did not increase the growth inhibitory effect of curcumin. Our data suggest that inclusion of curcumin in conventional chemotherapeutic regimens could be an effective strategy to prevent the emergence of chemoresistant colon cancer cells.

  4. IGF-1R contributes to stress-induced hepatocellular damage in experimental cholestasis.

    PubMed

    Cadoret, Axelle; Rey, Colette; Wendum, Dominique; Elriz, Khaldoun; Tronche, François; Holzenberger, Martin; Housset, Chantal

    2009-08-01

    The insulin-like growth factor type 1 receptor (IGF-1R) controls aging and cellular stress, both of which play major roles in liver disease. Stimulation of insulin-like growth factor signaling can generate cell death in vitro. Here, we tested whether IGF-1R contributes to stress insult in the liver. Cholestatic liver injury was induced by bile duct ligation in control and liver-specific IGF-1R knockout (LIGFREKO) mice. LIGFREKO mice displayed less bile duct ligation-induced hepatocyte damage than controls, while no differences in bile acid serum levels or better adaptation to cholestasis by efflux transporters were found. We therefore tested whether stress pathways contributed to this phenomenon; oxidative stress, ascertained by both malondialdehyde content and heme oxygenase-1 expression, was similar in knockout and control animals. However, together with a lower level of eukaryotic initiation factor-2 alpha phosphorylation, the endoplasmic reticulum stress protein CHOP and its downstream pro-apoptotic target Bax were induced to lesser extents in LIGFREKO mice than in controls. Expression levels of cytokeratin 19, transforming growth factor-beta1, alpha-smooth muscle actin, and collagen alpha1(I) in LIGFREKO mice were all lower than in controls, indicating reduced ductular and fibrogenic responses and increased cholestasis tolerance in these mutants. This stress resistance phenotype was also evidenced by longer post-bile duct ligation survival in mutants than controls. These results indicate that IGF-1R contributes to cholestatic liver injury, and suggests the involvement of both CHOP and Bax in this process. PMID:19628767

  5. Serum stability of selected decapeptide agonists of KISS1R using pseudopeptides.

    PubMed

    Asami, Taiji; Nishizawa, Naoki; Ishibashi, Yoshihiro; Nishibori, Kimiko; Nakayama, Masaharu; Horikoshi, Yasuko; Matsumoto, Shin-ichi; Yamaguchi, Masashi; Matsumoto, Hirokazu; Tarui, Naoki; Ohtaki, Tetsuya; Kitada, Chieko

    2012-10-15

    Metastin/kisspeptin, a 54-amino acid peptide, is the ligand of the G-protein-coupled receptor KISS1R which plays a key role in pathways that regulate reproduction and cell migration in many endocrine and gonadal tissues. The N-terminally truncated decapeptide, metastin(45-54), has 3-10 times higher receptor affinity and intracellular calcium ion-mobilizing activity but is rapidly inactivated in serum. In this study we designed and synthesized stable KISS1R agonistic decapeptide analogs with selected substitutions at positions 47, 50, and 51. Replacement of glycine with azaglycine (azaGly) in which the α-carbon is replaced with a nitrogen atom at position 51 improved the stability of amide bonds between Phe(50)-Gly(51) and Gly(51)-Leu(52) as determined by in vitro mouse serum stability studies. Substitution for tryptophan at position 47 with other amino acids such as serine, threonine, β-(3-pyridyl)alanine, and D-tryptophan (D-Trp), produced analogs that were highly stable in mouse serum. D-Trp(47) analog 13 showed not only high metabolic stability but also excellent KISS1R agonistic activity. Other labile peptides may have increased serum stability using amino acid substitution. PMID:22975302

  6. Molecular Evolutionary Characterization of a V1R Subfamily Unique to Strepsirrhine Primates

    PubMed Central

    Yoder, Anne D.; Chan, Lauren M.; dos Reis, Mario; Larsen, Peter A.; Campbell, C. Ryan; Rasoloarison, Rodin; Barrett, Meredith; Roos, Christian; Kappeler, Peter; Bielawski, Joseph; Yang, Ziheng

    2014-01-01

    Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1Rstrep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1Rstrep-α and V1Rstrep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1Rstrep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available. PMID:24398377

  7. DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins.

    PubMed

    Tsai, Pei-Chien; Van Dongen, Jenny; Tan, Qihua; Willemsen, Gonneke; Christiansen, Lene; Boomsma, Dorret I; Spector, Tim D; Valdes, Ana M; Bell, Jordana T

    2015-12-01

    Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10(-8)), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

  8. Expression and Purification of Functional Ligand-binding Domains of T1R3 Taste Receptors

    SciTech Connect

    Nie,Y.; Hobbs, J.; Vigues, S.; Olson, W.; Conn, G.; Munger, S.

    2006-01-01

    Chemosensory receptors, including odor, taste, and vomeronasal receptors, comprise the largest group of G protein-coupled receptors (GPCRs) in the mammalian genome. However, little is known about the molecular determinants that are critical for the detection and discrimination of ligands by most of these receptors. This dearth of understanding is due in part to difficulties in preparing functional receptors suitable for biochemical and biophysical analyses. Here we describe in detail two strategies for the expression and purification of the ligand-binding domain of T1R taste receptors, which are constituents of the sweet and umami taste receptors. These class C GPCRs contain a large extracellular N-terminal domain (NTD) that is the site of interaction with most ligands and that is amenable to expression as a separate polypeptide in heterologous cells. The NTD of mouse T1R3 was expressed as two distinct fusion proteins in Escherichia coli and purified by column chromatography. Spectroscopic analysis of the purified NTD proteins shows them to be properly folded and capable of binding ligands. This methodology should not only facilitate the characterization of T1R ligand interactions but may also be useful for dissecting the function of other class C GPCRs such as the large family of orphan V2R vomeronasal receptors.

  9. Molecular evolutionary characterization of a V1R subfamily unique to strepsirrhine primates.

    PubMed

    Yoder, Anne D; Chan, Lauren M; dos Reis, Mario; Larsen, Peter A; Campbell, C Ryan; Rasoloarison, Rodin; Barrett, Meredith; Roos, Christian; Kappeler, Peter; Bielawski, Joseph; Yang, Ziheng

    2014-01-01

    Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1Rstrep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1Rstrep-α and V1Rstrep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1Rstrep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available. PMID:24398377

  10. Synthesis of neoalkanes. [R/sub 1/R/sub 2/R/sub 3/CCOOH

    SciTech Connect

    Butter, S.A.; Stoll, I.

    1986-06-03

    A process is described for the synthesis of an alkyl-substituted 1,1,1-trialkylalkane of the formula R/sub 1/R/sub 2/R/sub 3/CCH/sub 3/ by hydrogenation, wherein R/sub 1/, R/sub 2/ and R/sub 3/ are the same or different alkyl of 1-10 carbon atoms in the presence of a hydrogenation catalyst and hydrogen, the improvement which comprises hydrogenating a feed of a neoacid of the formula R/sub 1/R/sub 2/R/sub 3/CCOOH, at a temperature from about 325/sup 0/C to about 375/sup 0/C; a hydrogen feed rate of 1500 to 8000 m1/g catalyst/h; a neoacid feed rate of 0.2 to 4.9 mM/g catlyst/h and a hydrogen pressure of 35-140 Kg/cm/sup 2/ over a copper oxide/zinc oxide catalyst comprising 80-95% by weight of copper oxide/zinc oxide in an 8:1 to 1:1 weight ratio and 20-5% by weight alumina to obtain substantially complete conversion of the neoacid and recovering a product containing at least about 15 mol % yield of neoalkane based on the neoacid feed.

  11. Dielectric properties of transformer paper impregnated by mineral oil based magnetic fluid

    NASA Astrophysics Data System (ADS)

    Timko, M.; Kopčanský, P.; Marton, K.; Tomčo, L.; Koneracká, M.

    2010-01-01

    The influence of combined magnetic and electric field on permittivity of transformer paper used in power transformers was observed. Transformer paper was impregnated by pure transformer oil ITO 100 and magnetic fluids based on transformer oil ITO 100 with different concentrations of magnetite nanoparticles. The measurements were carried out with help of high precision capacitance bridge. The electric intensity between circular planar electrodes was in the region of weak electric field (E > 106 V/m). The increase of electric permittivity of transformer paper impregnated by magnetic fluid opposite pure transformer paper was observed. The experiments showed that permittivity of insulator system consisting of pure transformer paper and impregnated transformer paper naturally depends on number of paper layers. The magnetodielectric effect was found to be dependent on magnetite nanoparticles concentration in magnetic fluids.

  12. The Formation of Carbon Nanofibers on Powdered Activated Carbon Impregnated with Nickel

    NASA Astrophysics Data System (ADS)

    Ahmed, Y. M.; Al-Mamun, A. A.; Muyibi, S. A.; Al-Khatib, M. F. R.; Jameel, A. T.; AlSaadi, M. A.

    2009-06-01

    In the present work, the production and characterization of carbon nanofibers (CNFs) composite is reported. Carbon nanofibers (CNF) were produced on powdered activated carbon PAC—impregnated with nickel—by Chemical Vapor Deposition (CVD) of a hydrocarbon in the presence of hydrogen at ˜780° C. The flow rates of carbon source and hydrogen were fixed. The CNFs were formed directly over the impregnated AC. Variable weight percentage ratios of the catalyst salt (Ni+2) were used for the impregnation (1, 3, 5, 7 and 9%, respectively). The product displays a relatively high surface area, essentially constituted by the external surface, and the absence of the bottled pores encountered with activated carbon. FSEM, TEM and TGA were used for the characterization of the product.

  13. Solvent impregnated resin for isolation of U(VI) from industrial wastes

    SciTech Connect

    Karve, M.; Rajgor, R.V.

    2008-07-01

    A solid-phase extraction method based upon impregnation of Cyanex 302 (bis(2,4,4- trimethylpentyl)mono-thio-phosphinic acid) on Amberlite XAD-2 resin is proposed for isolation of U(VI) from uranmicrolite ore tailing samples and industrial effluent samples. U(VI) was sorbed from nitric acid media on the solvent-impregnated resin (SIR) and was recovered completely with 1.0 M HCl. Based upon sorption behavior of U(VI) with Cyanex 302, it was quantitatively sorbed on the SIR in a dynamic method, while the other metal ions were not sorbed by the modified resin. The preparation of impregnated resin is simple, based upon physical interaction of the extractant and solid support, has good sorption capacity for U(VI), and is also reliable for detection of traces of U(VI). (authors)

  14. Modeling and Experiment of Melt Impregnation of Continuous Fiber-reinforced Thermoplastic with Pins

    NASA Astrophysics Data System (ADS)

    Yang, Jian-Jun; Xin, Chun-Ling; Tang, Ke; Zhang, Zhi-Cheng; Yan, Bao-Rui; Ren, Feng; He, Ya-Dong

    2016-05-01

    Melt impregnation is a crucial method for continuous fiber-reinforced thermoplastic. It was developed several years ago for thermosetting plastic, but it is very popular now in the thermoplastic matrices, with a much higher viscosity. In this paper, we propose a mathematic model based on Darcy's law, which combined with processing parameters and material physical parameters. Then we use this model to predict the influence of processing parameters on the degree of impregnation of the prepreg, and the trend of prediction is consistent with the experimental results. Therefore, the exhaustive numerical study enables to define the optimal processing conditions for a perfect impregnation. The results are shown to be effective tools for finding optimal pulling speed, pin number and pressure for a given fluid/fibers pair.

  15. Study on pyrolysis characteristics of lignocellulosic biomass impregnated with ammonia source.

    PubMed

    Li, Kai; Zhu, Changpeng; Zhang, Liqiang; Zhu, Xifeng

    2016-06-01

    The current study presents the pyrolysis characteristics of rice husk impregnated with different kinds of ammonia source (ammonium acetate, urea, ammonium sulfate and ammonium dihydrogen phosphate) in a fixed bed reactor. The introduction of ammonia source in pyrolysis process achieved the conversation from carbonyl compounds to nitrogenous heterocyclic compounds. The liquid product of urea-impregnated biomass has higher content of nitrogenous heterocyclic compounds (8.35%) and phenols (30.4%). For ammonium sulfate and ammonium dihydrogen phosphate-impregnated biomass, the quantity of compounds in liquid products reduces remarkably, and the gas products are rich in CO and H2. All the solid products of pyrolysis have great potential application in biochar-based fertilizer and activated carbon for their high N content.

  16. Recent progress and tests of radiation resistant impregnation materials for Nb{sub 3}Sn coils

    SciTech Connect

    Bossert, R.; Krave, S.; Ambrosio, G.; Andreev, N.; Chlachidze, G.; Nobrega, A.; Novitski, I.; Yu, M.; Zlobin, A. V.

    2014-01-27

    Fermilab is collaborating with Lawrence Berkeley National Laboratory (LBNL) and Brookhaven National Laboratory (BNL) (US-LARP collaboration) to develop a large-aperture Nb{sub 3}Sn superconducting quadrupole for the Large Hadron Collider (LHC) luminosity upgrade. An important component of this work is the development of materials that are sufficiently radiation resistant for use in critical areas of the upgrade. This paper describes recent progress in characterization of materials, including the baseline CTD101K epoxy, cyanate ester blends, and Matrimid 5292, a bismaleimide-based system. Structural properties of “ten stacks” of cable impregnated with these materials are tested at room and cryogenic temperatures and compared to the baseline CT-101K. Experience with potting 1 and 2 meter long coils with Matrimid 5292 are described. Test results of a single 1-m coil impregnated with Matrimid 5292 are reported and compared to similar coils impregnated with the traditional epoxy.

  17. Recent progress and tests of radiation resistant impregnation materials for Nb3Sn coils

    NASA Astrophysics Data System (ADS)

    Bossert, R.; Krave, S.; Ambrosio, G.; Andreev, N.; Chlachidze, G.; Nobrega, A.; Novitski, I.; Yu, M.; Zlobin, A. V.

    2014-01-01

    Fermilab is collaborating with Lawrence Berkeley National Laboratory (LBNL) and Brookhaven National Laboratory (BNL) (US-LARP collaboration) to develop a large-aperture Nb3Sn superconducting quadrupole for the Large Hadron Collider (LHC) luminosity upgrade. An important component of this work is the development of materials that are sufficiently radiation resistant for use in critical areas of the upgrade. This paper describes recent progress in characterization of materials, including the baseline CTD101K epoxy, cyanate ester blends, and Matrimid 5292, a bismaleimide-based system. Structural properties of "ten stacks" of cable impregnated with these materials are tested at room and cryogenic temperatures and compared to the baseline CT-101K. Experience with potting 1 and 2 meter long coils with Matrimid 5292 are described. Test results of a single 1-m coil impregnated with Matrimid 5292 are reported and compared to similar coils impregnated with the traditional epoxy.

  18. Development of nitrocellulose membrane filters impregnated with different biosynthesized silver nanoparticles applied to water purification.

    PubMed

    Fernández, Jorge G; Almeida, César A; Fernández-Baldo, Martín A; Felici, Emiliano; Raba, Julio; Sanz, María I

    2016-01-01

    Bactericidal water filters were developed. For this purpose, nitrocellulose membrane filters were impregnated with different biosynthesized silver nanoparticles. Silver nanoparticles (AgNPs) from Aspergillus niger (AgNPs-Asp), Cryptococcus laurentii (AgNPs-Cry) and Rhodotorula glutinis (AgNPs-Rho) were used for impregnating nitrocellulose filters. The bactericidal properties of these nanoparticles against Escherichia coli, Enterococcus faecalis and Pseudomona aeruginosa were successfully demonstrated. The higher antimicrobial effect was observed for AgNPs-Rho. This fact would be related not only to the smallest particles, but also to polysaccharides groups that surrounding these particles. Moreover, in this study, complete inhibition of bacterial growth was observed on nitrocellulose membrane filters impregnated with 1 mg L(-1) of biosynthesized AgNPs. This concentration was able to reduce the bacteria colony count by over 5 orders of magnitude, doing suitable for a water purification device. PMID:26695258

  19. Development of nitrocellulose membrane filters impregnated with different biosynthesized silver nanoparticles applied to water purification.

    PubMed

    Fernández, Jorge G; Almeida, César A; Fernández-Baldo, Martín A; Felici, Emiliano; Raba, Julio; Sanz, María I

    2016-01-01

    Bactericidal water filters were developed. For this purpose, nitrocellulose membrane filters were impregnated with different biosynthesized silver nanoparticles. Silver nanoparticles (AgNPs) from Aspergillus niger (AgNPs-Asp), Cryptococcus laurentii (AgNPs-Cry) and Rhodotorula glutinis (AgNPs-Rho) were used for impregnating nitrocellulose filters. The bactericidal properties of these nanoparticles against Escherichia coli, Enterococcus faecalis and Pseudomona aeruginosa were successfully demonstrated. The higher antimicrobial effect was observed for AgNPs-Rho. This fact would be related not only to the smallest particles, but also to polysaccharides groups that surrounding these particles. Moreover, in this study, complete inhibition of bacterial growth was observed on nitrocellulose membrane filters impregnated with 1 mg L(-1) of biosynthesized AgNPs. This concentration was able to reduce the bacteria colony count by over 5 orders of magnitude, doing suitable for a water purification device.

  20. Thick-target PIXE analysis of chromium, copper and arsenic impregnated lumber

    NASA Astrophysics Data System (ADS)

    Saarela, K.-E.; Harju, L.; Lill, J.-O.; Rajander, J.; Lindroos, A.; Heselius, S.-J.

    1999-04-01

    Chromium, copper and arsenic (CCA) have for decades been used for wood preservation. Of these elements especially arsenic is very toxic. As CCA impregnated wood is still today used for many construction purposes, a monitoring of these metal ions is of great environmental importance. Thick-target PIXE is a powerful method for the determination of trace metals in wood. The TTPIXE method enabled study of variations of the elemental concentrations in lumber treated with CCA impregnation solution. Distribution patterns were obtained for both naturally occurring elements and elements introduced in the treatment process. During the impregnation process a desorption of e.g. alkali metal ions takes place from the wood. The sensitivity of the method is improved by dry ashing of the samples prior to PIXE analysis. The TTPIXE method was calibrated and validated using international certified reference materials (CRM) based on wood material.

  1. Surface studies of thermionic cathodes and the mechanism of operation of an impregnated tungsten cathode

    NASA Technical Reports Server (NTRS)

    Forman, R.

    1976-01-01

    The surface properties of conventional impregnated cathodes were investigated by the use of Auger spectroscopy and work function measurements, and these were compared with a synthesized barium or barium oxide coated tungsten surface. The barium and barium oxide coated surfaces were prepared by evaporating barium onto a tungsten surface that can be heated to elevated temperatures. Multilayer or monolayer coverages can be investigated using this technique. The results of this study show that the surface of an impregnated tungsten cathode is identical to that observed for a synthesized monolayer or partial monolayer of barium on partially oxidized tungsten, using the criteria of identical Auger patterns and work functions. Desorption measurements of barium from a tungsten surface were also made. These results in conjunction with Auger and work function data were interpreted to show that throughout most of its life an impregnated cathode operating in the range of 1100 C has a partial monolayer rather than a monolayer of barium on its surface.

  2. Selective Catalytic Oxidation of Hydrogen Sulfide on Activated Carbons Impregnated with Sodium Hydroxide

    SciTech Connect

    Schwartz, Viviane; Baskova, Svetlana; Armstrong, Timothy R.

    2009-01-01

    Two activated carbons of different origin were impregnated with the solution of sodium hydroxide (NaOH) of various concentrations up to 10 wt %, and the effect of impregnation on the catalytic performance of the carbons was evaluated. The catalytic activity was analyzed in terms of the capacity of carbons for hydrogen sulfide (H2S) conversion and removal from hydrogen-rich fuel streams and the emission times of H2S and the products of its oxidation [e.g., sulfur dioxide (SO2) and carbonyl sulfide (COS)]. The results of impregnation showed a significant improvement in the catalytic activity of both carbons proportional to the amount of NaOH introduced. NaOH introduces hydroxyl groups (OH-) on the surface of the activated carbon that increase its surface reactivity and its interaction with sulfur-containing compounds.

  3. Life Model of Hollow Cathodes Using a Barium Calcium Aluminate Impregnated Tungsten Emitter

    NASA Technical Reports Server (NTRS)

    Kovaleski, S. D.; Burke, Tom (Technical Monitor)

    2001-01-01

    Hollow cathodes with barium calcium aluminate impregnated tungsten emitters for thermionic emission are widely used in electric propulsion. These high current, low power cathodes are employed in ion thrusters, Hall thrusters, and on the International Space Station in plasma contactors. The requirements on hollow cathode life are growing more stringent with the increasing use of electric propulsion technology. The life limiting mechanism that determines the entitlement lifetime of a barium impregnated thermionic emission cathode is the evolution and transport of barium away from the emitter surface. A model is being developed to study the process of barium transport and loss from the emitter insert in hollow cathodes. The model accounts for the production of barium through analysis of the relevant impregnate chemistry. Transport of barium through the approximately static gas is also being treated. Finally, the effect of temperature gradients within the cathode are considered.

  4. Enhanced molar sorption ratio for naphthalene through the impregnation of surfactant into chitosan hydrogel beads.

    PubMed

    Chatterjee, Sudipta; Lee, Dae S; Lee, Min W; Woo, Seung H

    2010-06-01

    Surfactants in their impregnated forms in chitosan beads (CBs) were used for sorption of naphthalene (NAP) from aqueous solutions. Three different surfactants, Triton X-100 (TX100), cetyltrimethyl ammonium bromide (CTAB) and sodium dodecyl sulfate (SDS), were selected for this study. The results showed that surfactant-impregnated CS beads (SICBs) in the form of a separate phase surfactant were very effective for NAP sorption. The calculated molar sorption ratio (MSR(B) mol NAP/mol surfactant) of the surfactant impregnated into SICBs was much greater than the intrinsic molar solubilization ratio (MSR) in liquid phase. The high MSR(B) value could be explained by favorable configurations of surfactants in beads, such as micelles in sorbed form. The equilibrium isotherm did not follow Langmuir or Freundlich models, but followed Chapman sigmoidal equation, indicating co-operative sorption of solutes. Using SICBs as a separate phase surfactant may be a valuable tool for remediation of groundwater contaminated with hydrophobic organic compounds.

  5. Dielectric insulation characteristics of liquid-nitrogen-impregnated laminated paper-insulated cable

    SciTech Connect

    Suzuki, H.; Ishihara, K.; Akita, S. )

    1992-10-01

    This paper reports that the electric characteristics and insulation design strength of a liquid-nitrogen-impregnated synthetic insulation was considered. It found to detect the impregnation of liquid nitrogen by measuring the electrostatic capacitance of the cable [epsilon] [center dot] tan [delta] an index of the dielectric loss, was 0.31% for cellulose paper and 0.18% for semisynthetic paper, PPLP and OPPL. It is found that the decline of the thickness dependence of the breakdown strength of the liquid-nitrogen-impregnated insulating cable is steeper than that of the OF cables. It is possible to design the insulation strength of the 66 kV cable to 10 kV/mm.

  6. A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1

    PubMed Central

    Porter, A J; Pillidge, K; Tsai, Y C; Dudley, J A; Hunt, S P; Peirson, S N; Brown, L A; Stanford, S C

    2015-01-01

    Mice lacking functional neurokinin-1 receptors (NK1R-/-) display abnormal behaviours seen in Attention Deficit Hyperactivity Disorder (hyperactivity, impulsivity and inattentiveness). These abnormalities were evident when comparing the behaviour of separate (inbred: ‘Hom’) wildtype and NK1R-/- mouse strains. Here, we investigated whether the inbreeding protocol could influence their phenotype by comparing the behaviour of these mice with that of wildtype (NK1R+/+) and NK1R-/- progeny of heterozygous parents (‘Het’, derived from the same inbred strains). First, we recorded the spontaneous motor activity of the two colonies/genotypes, over 7 days. This continuous monitoring also enabled us to investigate whether the diurnal rhythm in motor activity differs in the two colonies/genotypes. NK1R-/- mice from both colonies were hyperactive compared with their wildtypes and their diurnal rhythm was also disrupted. Next, we evaluated the performance of the four groups of mice in the 5-Choice Serial Reaction-Time Task (5-CSRTT). During training, NK1R-/- mice from both colonies expressed more impulsive and perseverative behaviour than their wildtypes. During testing, only NK1R-/- mice from the Hom colony were more impulsive than their wildtypes, but NK1R-/- mice from both colonies were more perseverative. There were no colony differences in inattentiveness. Moreover, a genotype difference in this measure depended on time of day. We conclude that the hyperactivity, perseveration and, possibly, inattentiveness of NK1R-/- mice is a direct consequence of a lack of functional NK1R. However, the greater impulsivity of NK1R-/- mice depended on an interaction between a functional deficit of NK1R and other (possibly environmental and/or epigenetic) factors. PMID:25558794

  7. IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide.

    PubMed

    Ramcharan, Roger; Aleksic, Tamara; Kamdoum, Wilfride Petnga; Gao, Shan; Pfister, Sophia X; Tanner, Jordan; Bridges, Esther; Asher, Ruth; Watson, Amanda J; Margison, Geoffrey P; Woodcock, Mick; Repapi, Emmanouela; Li, Ji-Liang; Middleton, Mark R; Macaulay, Valentine M

    2015-11-24

    Prior studies implicate type 1 IGF receptor (IGF-1R) in mediating chemo-resistance. Here, we investigated whether IGF-1R influences response to temozolomide (TMZ), which generates DNA adducts that are removed by O6-methylguanine-DNA methyltransferase (MGMT), or persist causing replication-associated double-strand breaks (DSBs). Initial assessment in 10 melanoma cell lines revealed that TMZ resistance correlated with MGMT expression (r = 0.79, p = 0.009), and in MGMT-proficient cell lines, with phospho-IGF-1R (r = 0.81, p = 0.038), suggesting that TMZ resistance associates with IGF-1R activation. Next, effects of IGF-1R inhibitors (IGF-1Ri) AZ3801 and linsitinib (OSI-906) were tested on TMZ-sensitivity, cell cycle progression and DSB induction. IGF-1Ri sensitized BRAF wild-type and mutant melanoma cells to TMZ in vitro, an effect that was independent of MGMT. Cells harboring wild-type p53 were more sensitive to IGF-1Ri, and showed schedule-dependent chemo-sensitization that was most effective when IGF-1Ri followed TMZ. This sequence sensitized to clinically-achievable TMZ concentrations and enhanced TMZ-induced apoptosis. Simultaneous or prior IGF-1Ri caused less effective chemo-sensitization, associated with increased G1 population and reduced accumulation of TMZ-induced DSBs. Clinically relevant sequential (TMZ → IGF-1Ri) treatment was tested in mice bearing A375M (V600E BRAF, wild-type p53) melanoma xenografts, achieving peak plasma/tumor IGF-1Ri levels comparable to clinical Cmax, and inducing extensive intratumoral apoptosis. TMZ or IGF-1Ri caused minor inhibition of tumor growth (gradient reduction 13%, 25% respectively), while combination treatment caused supra-additive growth delay (72%) that was significantly different from control (p < 0.01), TMZ (p < 0.01) and IGF-1Ri (p < 0.05) groups. These data highlight the importance of scheduling when combining IGF-1Ri and other targeted agents with drugs that induce replication-associated DNA damage. PMID

  8. IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide

    PubMed Central

    Ramcharan, Roger; Aleksic, Tamara; Kamdoum, Wilfride Petnga; Gao, Shan; Pfister, Sophia X.; Tanner, Jordan; Bridges, Esther; Asher, Ruth; Watson, Amanda J.; Margison, Geoffrey P.; Woodcock, Mick; Repapi, Emmanouela; Li, Ji-Liang; Middleton, Mark R.; Macaulay, Valentine M.

    2015-01-01

    Prior studies implicate type 1 IGF receptor (IGF-1R) in mediating chemo-resistance. Here, we investigated whether IGF-1R influences response to temozolomide (TMZ), which generates DNA adducts that are removed by O6-methylguanine-DNA methyltransferase (MGMT), or persist causing replication-associated double-strand breaks (DSBs). Initial assessment in 10 melanoma cell lines revealed that TMZ resistance correlated with MGMT expression (r = 0.79, p = 0.009), and in MGMT-proficient cell lines, with phospho-IGF-1R (r = 0.81, p = 0.038), suggesting that TMZ resistance associates with IGF-1R activation. Next, effects of IGF-1R inhibitors (IGF-1Ri) AZ3801 and linsitinib (OSI-906) were tested on TMZ-sensitivity, cell cycle progression and DSB induction. IGF-1Ri sensitized BRAF wild-type and mutant melanoma cells to TMZ in vitro, an effect that was independent of MGMT. Cells harboring wild-type p53 were more sensitive to IGF-1Ri, and showed schedule-dependent chemo-sensitization that was most effective when IGF-1Ri followed TMZ. This sequence sensitized to clinically-achievable TMZ concentrations and enhanced TMZ-induced apoptosis. Simultaneous or prior IGF-1Ri caused less effective chemo-sensitization, associated with increased G1 population and reduced accumulation of TMZ-induced DSBs. Clinically relevant sequential (TMZ → IGF-1Ri) treatment was tested in mice bearing A375M (V600E BRAF, wild-type p53) melanoma xenografts, achieving peak plasma/tumor IGF-1Ri levels comparable to clinical Cmax, and inducing extensive intratumoral apoptosis. TMZ or IGF-1Ri caused minor inhibition of tumor growth (gradient reduction 13%, 25% respectively), while combination treatment caused supra-additive growth delay (72%) that was significantly different from control (p < 0.01), TMZ (p < 0.01) and IGF-1Ri (p < 0.05) groups. These data highlight the importance of scheduling when combining IGF-1Ri and other targeted agents with drugs that induce replication-associated DNA damage. PMID

  9. CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma.

    PubMed

    Martín-Moreno, Ana M; Roncador, Giovanna; Maestre, Lorena; Mata, Elena; Jiménez, Scherezade; Martínez-Torrecuadrada, Jorge L; Reyes-García, Ana I; Rubio, Carmen; Tomás, José F; Estévez, Mónica; Pulford, Karen; Piris, Miguel A; García, Juan F

    2015-01-01

    Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.

  10. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models

    PubMed Central

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M.; Zhao, Ming

    2015-01-01

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting. PMID:26431498

  11. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods

    PubMed Central

    Lu, Fang; Jiang, Lu-di; Qiao, Lian-sheng; Xiang, Yu-hong

    2016-01-01

    P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation. The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes. And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile. In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists. 2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R. Based on the result, pharmacophore models were constructed and validated by the test set. Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM). And the hits were filtered by Lipinski's rule. Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R. Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design. This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM.

  12. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

    PubMed

    Toneri, Makoto; Miwa, Shinji; Zhang, Yong; Hu, Cameron; Yano, Shuya; Matsumoto, Yasunori; Bouvet, Michael; Nakanishi, Hayao; Hoffman, Robert M; Zhao, Ming

    2015-10-13

    Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

  13. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods

    PubMed Central

    Lu, Fang; Jiang, Lu-di; Qiao, Lian-sheng; Xiang, Yu-hong

    2016-01-01

    P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation. The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes. And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile. In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists. 2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R. Based on the result, pharmacophore models were constructed and validated by the test set. Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM). And the hits were filtered by Lipinski's rule. Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R. Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design. This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM. PMID:27635149

  14. CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

    PubMed Central

    Maestre, Lorena; Mata, Elena; Jiménez, Scherezade; Martínez-Torrecuadrada, Jorge L.; Reyes-García, Ana I.; Rubio, Carmen; Tomás, José F.; Estévez, Mónica; Pulford, Karen; Piris, Miguel A.; García, Juan F.

    2015-01-01

    Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases. PMID:26066800

  15. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods.

    PubMed

    Zhang, Xu; Lu, Fang; Chen, Yan-Kun; Luo, Gang-Gang; Jiang, Lu-di; Qiao, Lian-Sheng; Zhang, Yan-Ling; Xiang, Yu-Hong

    2016-01-01

    P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation. The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes. And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile. In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists. 2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R. Based on the result, pharmacophore models were constructed and validated by the test set. Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM). And the hits were filtered by Lipinski's rule. Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R. Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design. This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM. PMID:27635149

  16. The definition of the process of electrochemical impregnation of nickel electrodes

    NASA Technical Reports Server (NTRS)

    Antoine, P.

    1983-01-01

    Electrochemical impregnation was studied during a series of experiments designed to define the optimal conditions for the fabrication of dimensionally stable cell anodes of Ni-H2 and Ni-Cd systems. The influence of various parameters, such as current and duration of electrolysis, temperature and acidity of the chemical bath, the concentrations of Ni and Co as well as the use of ethanol was determined. Results show that the electrochemical impregnation process as defined is industrially feasible and it is suggested that Ni-H2 and Ni-Cd type electrodes be produced in sufficient quantity to further evaluate their performance characteristics.

  17. An in vitro study of the antiviral properties of an alginate impression material impregnated with disinfectant.

    PubMed

    Tyler, R; Tobias, R S; Ayliffe, G A; Browne, R M

    1989-06-01

    The antiviral properties of a new alginate impression material impregnated with a disinfectant (didecyldimethyl ammonium chloride) were evaluated in vitro against herpes simplex virus type I and poliovirus type I. The material was exposed to the virus suspension for periods of up to 60 min. The impregnated alginate material showed no clinically acceptable effect against either virus, although log reductions of 1.0 and 1.7 plaque-forming units of herpes virus were obtained after exposure to the material containing the disinfectant for 5 and 60 min, respectively. PMID:2549107

  18. An in vitro study of the antiviral properties of an alginate impression material impregnated with disinfectant.

    PubMed

    Tyler, R; Tobias, R S; Ayliffe, G A; Browne, R M

    1989-06-01

    The antiviral properties of a new alginate impression material impregnated with a disinfectant (didecyldimethyl ammonium chloride) were evaluated in vitro against herpes simplex virus type I and poliovirus type I. The material was exposed to the virus suspension for periods of up to 60 min. The impregnated alginate material showed no clinically acceptable effect against either virus, although log reductions of 1.0 and 1.7 plaque-forming units of herpes virus were obtained after exposure to the material containing the disinfectant for 5 and 60 min, respectively.

  19. A novel ultrasonication method in the preparation of zirconium impregnated cellulose for effective fluoride adsorption.

    PubMed

    Barathi, M; Kumar, A Santhana Krishna; Rajesh, N

    2014-05-01

    In the present work, we propose for the first time a novel ultrasound assisted methodology involving the impregnation of zirconium in a cellulose matrix. Fluoride from aqueous solution interacts with the cellulose hydroxyl groups and the cationic zirconium hydroxide. Ultrasonication ensures a green and quick alternative to the conventional time intensive method of preparation. The effectiveness of this process was confirmed by comprehensive characterization of zirconium impregnated cellulose (ZrIC) adsorbent using Fourier transform infrared spectroscopy (FT-IR), energy dispersive X-ray spectrometry (EDX) and X-ray diffraction (XRD) studies. The study of various adsorption isotherm models, kinetics and thermodynamics of the interaction validated the method.

  20. Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor

    PubMed Central

    Herraiz, Cecilia; Olivares, Conchi; Castejón-Griñán, Maria; Abrisqueta, Marta; Jiménez-Cervantes, Celia; García-Borrón, José Carlos

    2015-01-01

    The melanocortin 1 receptor gene (MC1R) expressed in melanocytes is a major determinant of skin pigmentation. It encodes a Gs protein-coupled receptor activated by α-melanocyte stimulating hormone (αMSH). Human MC1R has an inefficient poly(A) site allowing intergenic splicing with its downstream neighbour Tubulin-β-III (TUBB3). Intergenic splicing produces two MC1R isoforms, designated Iso1 and Iso2, bearing the complete seven transmembrane helices from MC1R fused to TUBB3-derived C-terminal extensions, in-frame for Iso1 and out-of-frame for Iso2. It has been reported that exposure to ultraviolet radiation (UVR) might promote an isoform switch from canonical MC1R (MC1R-001) to the MC1R-TUBB3 chimeras, which might lead to novel phenotypes required for tanning. We expressed the Flag epitope-tagged intergenic isoforms in heterologous HEK293T cells and human melanoma cells, for functional characterization. Iso1 was expressed with the expected size. Iso2 yielded a doublet of Mr significantly lower than predicted, and impaired intracellular stability. Although Iso1- and Iso2 bound radiolabelled agonist with the same affinity as MC1R-001, their plasma membrane expression was strongly reduced. Decreased surface expression mostly resulted from aberrant forward trafficking, rather than high rates of endocytosis. Functional coupling of both isoforms to cAMP was lower than wild-type, but ERK activation upon binding of αMSH was unimpaired, suggesting imbalanced signaling from the splice variants. Heterodimerization of differentially labelled MC1R-001 with the splicing isoforms analyzed by co-immunoprecipitation was efficient and caused decreased surface expression of binding sites. Thus, UVR-induced MC1R isoforms might contribute to fine-tune the tanning response by modulating MC1R-001 availability and functional parameters. PMID:26657157

  1. Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor.

    PubMed

    Herraiz, Cecilia; Olivares, Conchi; Castejón-Griñán, Maria; Abrisqueta, Marta; Jiménez-Cervantes, Celia; García-Borrón, José Carlos

    2015-01-01

    The melanocortin 1 receptor gene (MC1R) expressed in melanocytes is a major determinant of skin pigmentation. It encodes a Gs protein-coupled receptor activated by α-melanocyte stimulating hormone (αMSH). Human MC1R has an inefficient poly(A) site allowing intergenic splicing with its downstream neighbour Tubulin-β-III (TUBB3). Intergenic splicing produces two MC1R isoforms, designated Iso1 and Iso2, bearing the complete seven transmembrane helices from MC1R fused to TUBB3-derived C-terminal extensions, in-frame for Iso1 and out-of-frame for Iso2. It has been reported that exposure to ultraviolet radiation (UVR) might promote an isoform switch from canonical MC1R (MC1R-001) to the MC1R-TUBB3 chimeras, which might lead to novel phenotypes required for tanning. We expressed the Flag epitope-tagged intergenic isoforms in heterologous HEK293T cells and human melanoma cells, for functional characterization. Iso1 was expressed with the expected size. Iso2 yielded a doublet of Mr significantly lower than predicted, and impaired intracellular stability. Although Iso1- and Iso2 bound radiolabelled agonist with the same affinity as MC1R-001, their plasma membrane expression was strongly reduced. Decreased surface expression mostly resulted from aberrant forward trafficking, rather than high rates of endocytosis. Functional coupling of both isoforms to cAMP was lower than wild-type, but ERK activation upon binding of αMSH was unimpaired, suggesting imbalanced signaling from the splice variants. Heterodimerization of differentially labelled MC1R-001 with the splicing isoforms analyzed by co-immunoprecipitation was efficient and caused decreased surface expression of binding sites. Thus, UVR-induced MC1R isoforms might contribute to fine-tune the tanning response by modulating MC1R-001 availability and functional parameters. PMID:26657157

  2. Impregnation of cinnamaldehyde into cassava starch biocomposite films using supercritical fluid technology for the development of food active packaging.

    PubMed

    de Souza, Ana Cristina; Dias, Ana M A; Sousa, Hermínio C; Tadini, Carmen C

    2014-02-15

    In this work, supercritical solvent impregnation (SSI) has been tested for the incorporation of natural compounds into biocomposite materials for food packaging. Cinnamaldehyde, with proved antimicrobial activity against fungi commonly found in bread products, was successfully impregnated on biocomposite cassava starch based materials using supercritical carbon dioxide as solvent. Different process experimental conditions were tested (pressure, impregnation time and depressurization rate) at a fixed temperature (35 °C) in order to study their influence on the amount of impregnated cinnamaldehyde as well as on the morphology of the films. Results showed that all conditions permitted to impregnate antimicrobial active amounts superior to those previously obtained using conventional incorporation methods. Moreover, a significant decrease of the equilibrium water vapor sorption capacity and water vapor permeability of the films was observed after SSI processing which is a clear advantage of the process, considering the envisaged applications. PMID:24507353

  3. The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse.

    PubMed

    Jacobs, Lauren N; Staiger, Elizabeth A; Albright, Julia D; Brooks, Samantha A

    2016-05-01

    Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes. PMID:26884605

  4. The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse.

    PubMed

    Jacobs, Lauren N; Staiger, Elizabeth A; Albright, Julia D; Brooks, Samantha A

    2016-05-01

    Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes.

  5. CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas.

    PubMed

    Soares, Maria J; Pinto, Mafalda; Henrique, Rui; Vieira, Joana; Cerveira, Nuno; Peixoto, Ana; Martins, Ana T; Oliveira, Jorge; Jerónimo, Carmen; Teixeira, Manuel R

    2009-06-01

    Renal cell carcinomas comprise a heterogeneous group of tumors. Of these, 80% are clear cell renal cell carcinomas, which are characterized by loss of 3p, often with concomitant gain of 5q22qter. Although VHL is considered the main target gene of the 3p deletions, none has been identified as the relevant target gene for the 5q gain. We have studied 75 consecutive kidney tumors and paired normal kidney samples to evaluate at the genomic and expression levels the tyrosine kinase genes CSF1R and PDGFRB as potential targets in this region. Our findings show that RNA expression of CSF1R, but not of PDGFRB, was significantly higher in clear cell renal cell carcinomas than in normal tissue samples, something that was corroborated at the protein level by immunohistochemistry. The CSF1R staining pattern in clear cell renal cell carcinomas was clearly different from that observed in other renal cell carcinomas, suggesting its potential usefulness in differential diagnosis. FISH analysis demonstrated whole chromosomal gain and relative CSF1R/PDGFRB copy number gain in clear cell renal cell carcinomas, which might contribute to CSF1R overexpression. Finally, one polymorphism and two novel mutations were identified in CSF1R in clear cell renal cell carcinoma patients. Our data allow us to conclude that CSF1R plays a relevant role in clear cell renal cell carcinoma carcinogenesis and raise the possibility that CSF1R may represent a future valuable therapeutic target in these patients.

  6. Draft Genome Sequence of a Biocontrol Rhizobacterium, Chryseobacterium kwangjuense Strain KJ1R5, Isolated from Pepper (Capsicum annuum)

    PubMed Central

    Jeong, Jin-Ju; Park, Hongjae; Park, Byeong Hyeok; Mannaa, Mohamed; Sang, Mee Kyung

    2016-01-01

    Strain KJ1R5 of the rhizobacterium Chryseobacterium kwangjuense is an effective biocontrol agent against Phytophthora blight of pepper caused by a destructive soilborne oomycete, Phytophthora capsici. Here, we present the draft genome sequence of strain KJ1R5, which contains genes related to biocontrol, plant growth promotion, and environmental stress adaptation. PMID:27103726

  7. Do Polymorphisms in the TAS1R1 Gene Contribute to Broader Differences in Human Taste Intensity?

    PubMed Central

    2013-01-01

    The TAS1R genes encode heterodimeric receptors that mediate umami (hTAS1R1 + hTAS1R3) and sweet (hTAS1R2 + hTAS1R3) sensations. The question of interest for this study is if TAS1R1 variation associates with differences in overall taste intensity. We leveraged an existing database of adults (n = 92, primarily European American) to test associations between 2 TAS1R1 single nucleotide polymorphisms (SNPs) (intronic rs17492553, C/T and exonic rs34160967, G/A) and intensity of 4 prototypical tastants (NaCl, sucrose, citric acid, and quinine), applied regionally to fungiform and circumvallate loci, and sampled with the whole mouth. Both SNPs were associated with modest shifts in perceived intensities across all taste qualities. Three genotype groups were represented for the intronic SNP—minor allele homozygotes (TT) averaged 40% lower intensities than did CC homozygotes for all regionally applied tastants, as well as whole-mouth NaCl and citric acid. Similar, but less pronounced, intensity differences were seen for the exonic SNP (GG homozygotes reported greater intensities than did the AA/AG group). Our predominantly European American cohort had a low frequency of AA homozygotes, which may have attenuated the SNP-related differences in perceived intensity. These preliminary findings, if replicated, could add TAS1R1 polymorphisms to the repertoire of genotypic and phenotypic markers of heightened taste sensation. PMID:24000232

  8. Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC

    PubMed Central

    Cao, Hongxin; Dong, Wei; Qu, Xiao; Shen, Hongchang; Xu, Jun; Zhu, Linhai; Liu, Qi; Du, Jiajun

    2016-01-01

    The insulin-like growth factor (IGF) signaling system plays a critical role in tumorigenesis, highlighting the potential of targeting IGF-1R as an anti-cancer therapy. Although multiple anti-IGF-1R monoclonal antibody (mAb) drugs have been developed, challenges remain in the validation of the therapeutic effects and understanding the molecular mechanism of these mAbs. Herein, we conducted a study to validate the effect of Figitumumab (CP), an anti-IGF-1R mAb, in a panel of non-small cell lung cancer (NSCLC) cell lines. We found all tested cell lines were sensitive to CP, and CP could block IGF-1R and the downstream PI3K/AKT pathway activation. Unexpectedly, we found CP could activate ERK signaling pathway in IGF-1R kinase independent manner, which we further verified was mainly mediated by β-arrestin2. We also investigated the anti-tumor effect of metformin alone as well as its combination with CP to target NSCLC. Metformin could target IGF-1R signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down-regulating IGF-1R. Finally, we found that combining metformin with CP could further induce IGF-1R down-regulation and was more effective to target NSCLC cells. Our data suggests the combining of metformin with CP has additive therapeutic value against NSCLC. PMID:27488947

  9. RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

    PubMed Central

    Catenacci, Daniel VT; Cervantes, Gustavo; Yala, Soheil; Nelson, Erik A; El-Hashani, Essam; Kanteti, Rajani; El Dinali, Mohamed; Hasina, Rifat; Brägelmann, Johannes; Seiwert, Tanguy; Sanicola, Michele; Henderson, Les; Grushko, Tatyana A; Olopade, Olufunmilayo; Karrison, Theodore; Bang, Yung-Jue; Ho Kim, Woo; Tretiakova, Maria; Vokes, Everett; Frank, David A; Kindler, Hedy L; Huet, Heather

    2011-01-01

    RON (MST1R) is one of two members of the MET receptor tyrosine kinase family, along with parent receptor MET. RON has a putative role in several cancers, but its expression and function is poorly characterized in gastroesophageal adenocarcinoma. A recognized functional role of MET tyrosine kinase in gastroesophageal cancer has led to early phase clinical trials using MET inhibitors, with unimpressive results. Therefore, the role of RON in gastroesophageal cancer, as well as its role in cooperative signaling with MET and as a mechanism of resistance to MET inhibition, was studied in gastroesophageal tissues and cell lines. By IHC, RON was highly overexpressed in 74% of gastroesophageal samples (n = 94) and overexpression was prognostic of poor survival (p = 0.008); RON and MET co-expression occurred in 43% of samples and was prognostic of worst survival (p = 0.03). High MST1R gene copy number by quantitative polymerase chain reaction and confirmed by fluorescence in situ hybridization and/or array comparative genomic hybridization, was seen in 35.5% (16/45) of cases. High MST1R gene copy number correlated with poor survival (p = 0.01), and was associated with high MET and ERBB2 gene copy number. a novel somatic MST1R juxtamembrane mutation R1018G was found in 11% of samples. RON signaling was functional in cell lines, activating downstream effector STAT3, and resulted in increased viability over controls. RON and MET co-stimulation assays led to enhanced malignant phenotypes over stimulation of either receptor alone. Growth inhibition as evidenced by viability and apoptosis assays was optimal using novel blocking monoclonal antibodies to both ROn and MET, versus either alone. SU11274, a classic MET small molecule tyrosine kinase inhibitor, blocked signaling of both receptors and proved synergistic when combined with STAT3 inhibition (combination index <1). These preclinical studies define RON as an important novel prognostic marker and therapeutic target for

  10. Radiocarbon dating of petroleum-impregnated bone from tar pits at Rancho La Brea, California.

    PubMed

    Ho, T Y; Marcus, L F; Berger, R

    1969-05-30

    A liquid-chromatography method has been developed for the separation of amino acids with the same specific activity in radiocarbon from bones impregnated with isotopically dead petroleum compounds found in the La Brea tar pits. This technique permits the application of radiocarbon dating to such bone assemblages.

  11. Electrochemically triggered release of human insulin from an insulin-impregnated reduced graphene oxide modified electrode.

    PubMed

    Teodorescu, Florina; Rolland, Laure; Ramarao, Viswanatha; Abderrahmani, Amar; Mandler, Daniel; Boukherroub, Rabah; Szunerits, Sabine

    2015-09-28

    An electrochemical insulin-delivery system based on reduced graphene oxide impregnated with insulin is described. Upon application of a potential pulse of -0.8 V for 30 min, up to 70 ± 4% of human insulin was released into a physiological medium while preserving its biological activity.

  12. Effect of nickel impregnated hollow fiber anode for micro tubular solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    He, Beibei; Ling, Yihan; Xu, Jianmei; Zhao, Ling; Cheng, Jigui

    2014-07-01

    A micro tubular solid oxide fuel cells (MT-SOFCs) with a cell configuration of Ni impregnated Ni-Gd0.1Ce0.9O1.95 (GDC)/GDC/La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF)-GDC has been prepared by the phase inversion and impregnation technique. A special asymmetrical structure consisting of a sponge-like layer and a finger-like porous layer for hollow fiber anode is obtained by the phase inversion. Fine Ni specie particles are then coated on the surface of anode using impregnation method. The enhancement in electronic conductivity of anode by Ni modification is beneficial to current collection of MT-SOFCs. Meanwhile, the catalytic activity of anode is also improved due to the introduction of Ni nano-particles. Thus, the Ni modified MT-SOFCs exhibit high power densities, such as 0.69 W cm-2 at 600 °C. The encouraging results demonstrate that the Ni impregnation is an effective way to improve anode microstructure of MT-SOFCs.

  13. 3D Imaging of Water-Drop Condensation on Hydrophobic and Hydrophilic Lubricant-Impregnated Surfaces.

    PubMed

    Kajiya, Tadashi; Schellenberger, Frank; Papadopoulos, Periklis; Vollmer, Doris; Butt, Hans-Jürgen

    2016-01-01

    Condensation of water from the atmosphere on a solid surface is an ubiquitous phenomenon in nature and has diverse technological applications, e.g. in heat and mass transfer. We investigated the condensation kinetics of water drops on a lubricant-impregnated surface, i.e., a micropillar array impregnated with a non-volatile ionic liquid. Growing and coalescing drops were imaged in 3D using a laser scanning confocal microscope equipped with a temperature and humidity control. Different stages of condensation can be discriminated. On a lubricant-impregnated hydrophobic micropillar array these are: (1) Nucleation on the lubricant surface. (2) Regular alignment of water drops between micropillars and formation of a three-phase contact line on a bottom of the substrate. (3) Deformation and bridging by coalescence which eventually leads to a detachment of the drops from the bottom substrate. The drop-substrate contact does not result in breakdown of the slippery behaviour. Contrary, on a lubricant-impregnated hydrophilic micropillar array, the condensed water drops replace the lubricant. Consequently, the surface loses its slippery property. Our results demonstrate that a Wenzel-like to Cassie transition, required to maintain the facile removal of condensed water drops, can be induced by well-chosen surface hydrophobicity. PMID:27040483

  14. Method for initiating in-situ vitrification using an impregnated cord

    DOEpatents

    Carter, John G.

    1991-01-01

    In-situ vitrification of soil is initiated by placing a cord of dielectric material impregnated with conductive material in thermally-conductive contact with the soil, and energizing the cord with an electric current for heating the cord and starting the vitrification process.

  15. 3D Imaging of Water-Drop Condensation on Hydrophobic and Hydrophilic Lubricant-Impregnated Surfaces

    PubMed Central

    Kajiya, Tadashi; Schellenberger, Frank; Papadopoulos, Periklis; Vollmer, Doris; Butt, Hans-Jürgen

    2016-01-01

    Condensation of water from the atmosphere on a solid surface is an ubiquitous phenomenon in nature and has diverse technological applications, e.g. in heat and mass transfer. We investigated the condensation kinetics of water drops on a lubricant-impregnated surface, i.e., a micropillar array impregnated with a non-volatile ionic liquid. Growing and coalescing drops were imaged in 3D using a laser scanning confocal microscope equipped with a temperature and humidity control. Different stages of condensation can be discriminated. On a lubricant-impregnated hydrophobic micropillar array these are: (1) Nucleation on the lubricant surface. (2) Regular alignment of water drops between micropillars and formation of a three-phase contact line on a bottom of the substrate. (3) Deformation and bridging by coalescence which eventually leads to a detachment of the drops from the bottom substrate. The drop-substrate contact does not result in breakdown of the slippery behaviour. Contrary, on a lubricant-impregnated hydrophilic micropillar array, the condensed water drops replace the lubricant. Consequently, the surface loses its slippery property. Our results demonstrate that a Wenzel-like to Cassie transition, required to maintain the facile removal of condensed water drops, can be induced by well-chosen surface hydrophobicity. PMID:27040483

  16. 3D Imaging of Water-Drop Condensation on Hydrophobic and Hydrophilic Lubricant-Impregnated Surfaces

    NASA Astrophysics Data System (ADS)

    Kajiya, Tadashi; Schellenberger, Frank; Papadopoulos, Periklis; Vollmer, Doris; Butt, Hans-Jürgen

    2016-04-01

    Condensation of water from the atmosphere on a solid surface is an ubiquitous phenomenon in nature and has diverse technological applications, e.g. in heat and mass transfer. We investigated the condensation kinetics of water drops on a lubricant-impregnated surface, i.e., a micropillar array impregnated with a non-volatile ionic liquid. Growing and coalescing drops were imaged in 3D using a laser scanning confocal microscope equipped with a temperature and humidity control. Different stages of condensation can be discriminated. On a lubricant-impregnated hydrophobic micropillar array these are: (1) Nucleation on the lubricant surface. (2) Regular alignment of water drops between micropillars and formation of a three-phase contact line on a bottom of the substrate. (3) Deformation and bridging by coalescence which eventually leads to a detachment of the drops from the bottom substrate. The drop-substrate contact does not result in breakdown of the slippery behaviour. Contrary, on a lubricant-impregnated hydrophilic micropillar array, the condensed water drops replace the lubricant. Consequently, the surface loses its slippery property. Our results demonstrate that a Wenzel-like to Cassie transition, required to maintain the facile removal of condensed water drops, can be induced by well-chosen surface hydrophobicity.

  17. Method for initiating in-situ vitrification using an impregnated cord

    DOEpatents

    Carter, J.G.

    1991-04-02

    In-situ vitrification of soil is initiated by placing a cord of dielectric material impregnated with conductive material in thermally-conductive contact with the soil, and energizing the cord with an electric current for heating the cord and starting the vitrification process. 1 figure.

  18. Microemulsion impregnated catalyst composite and use thereof in a synthesis gas conversion process

    DOEpatents

    Abrevaya, H.; Targos, W.M.

    1987-12-22

    A catalyst composition is described for synthesis gas conversion comprising a ruthenium metal component deposited on a support carrier wherein the average metal particle size is less than about 100 A. The method of manufacture of the composition via a reverse micelle impregnation technique and the use of the composition in a Fischer-Tropsch conversion process is also disclosed.

  19. Microemulsion impregnated catalyst composite and use thereof in a synthesis gas conversion process

    DOEpatents

    Abrevaya, Hayim; Targos, William M.

    1987-01-01

    A catalyst composition for synthesis gas conversion comprising a ruthenium metal component deposited on a support carrier wherein the average metal particle size is less than about 100 A. The method of manufacture of the composition via a reverse micelle impregnation technique and the use of the composition in a Fischer-Tropsch conversion process is also disclosed.

  20. DEVELOPMENT OF A CL-IMPREGNATED ACTIVATED CARBON FOR ENTRAINED-FLOW CAPTURE OF ELEMENTAL MERCURY

    EPA Science Inventory

    Efforts to discern the role of an activated carbon's surface functional groups on the adsorption of elemental mercury [Hg(0)] and mercuric chloride demonstrated that chlorine (Cl) impregnation of a virgin activated carbon using dilute solutions of hydrogen chloride leads to incre...

  1. Removal of vapor-phase elemental mercury from stack emissions with sulfur-impregnated activated carbon.

    PubMed

    Sowlat, Mohammad Hossein; Abdollahi, Mohammad; Gharibi, Hamed; Yunesian, Masud; Rastkari, Noushin

    2014-01-01

    This systematic review of high-quality, relevant original research articles existing in the literature was conducted to comprehensively explore the efficiency of Hg11 capture from stack emissions by sulfur-impregnated vs. virgin ACs. Our systematic overview suggested that significantly higher amounts of Hg0 are absorbed by sulfurimpregnated ACs than by virgin ones ( 1.5-32 times higher, based on the applied operational conditions). The main reason for this is because Hg11 capture by virgin ACs follows a physisorption mechanism, whereas that by sulfur-impregnated ACs occurs from a combination of physisorption of Hg11 on carbon texture and chemical reaction between Hg0 and impregnated sulfur, with subsequent formation of HgS. Temperature increased the Hg0 adsorption capacity of virgin ACs, especially when temperatures exceeded 100 oc. For sulfur-impregnated ACs, increasing the temperature up to I 00 oc increased the Hg0 adsorption capacity by enhancing the chemisorption of Hg0 capture. A further increase in temperature enhanced the efficiency of ACs that were impregnated with Sat higher temperatures (600 °C, for instance). This mainly resulted from production of stronger bonding of sulfur to carbon at higher impregnation temperatures and also from a more even distribution of sulfur in the carbon matrix. The authors of different papers reported different results with respect to whether there is an effect of initial Hg11 concentration on AC adsorption capacity. The authors of two studies could find no such etl'ect. The predominant evidence, however, favors the view that increased Hg0 adsorption capacities exist at higher inlet Hg0 concentrations. Such behavior is attributed to faster kinetics of Hg0 capture and an enhanced higher driving force at higher initial Hg0 inlet concentrations. Results from reviewed studies also indicated that the optimum SIC ratio and sulfur content are 2/1 and I 0-20%, respectively. Surface area has a less significant impact on Hg11

  2. Removal of vapor-phase elemental mercury from stack emissions with sulfur-impregnated activated carbon.

    PubMed

    Sowlat, Mohammad Hossein; Abdollahi, Mohammad; Gharibi, Hamed; Yunesian, Masud; Rastkari, Noushin

    2014-01-01

    This systematic review of high-quality, relevant original research articles existing in the literature was conducted to comprehensively explore the efficiency of Hg11 capture from stack emissions by sulfur-impregnated vs. virgin ACs. Our systematic overview suggested that significantly higher amounts of Hg0 are absorbed by sulfurimpregnated ACs than by virgin ones ( 1.5-32 times higher, based on the applied operational conditions). The main reason for this is because Hg11 capture by virgin ACs follows a physisorption mechanism, whereas that by sulfur-impregnated ACs occurs from a combination of physisorption of Hg11 on carbon texture and chemical reaction between Hg0 and impregnated sulfur, with subsequent formation of HgS. Temperature increased the Hg0 adsorption capacity of virgin ACs, especially when temperatures exceeded 100 oc. For sulfur-impregnated ACs, increasing the temperature up to I 00 oc increased the Hg0 adsorption capacity by enhancing the chemisorption of Hg0 capture. A further increase in temperature enhanced the efficiency of ACs that were impregnated with Sat higher temperatures (600 °C, for instance). This mainly resulted from production of stronger bonding of sulfur to carbon at higher impregnation temperatures and also from a more even distribution of sulfur in the carbon matrix. The authors of different papers reported different results with respect to whether there is an effect of initial Hg11 concentration on AC adsorption capacity. The authors of two studies could find no such etl'ect. The predominant evidence, however, favors the view that increased Hg0 adsorption capacities exist at higher inlet Hg0 concentrations. Such behavior is attributed to faster kinetics of Hg0 capture and an enhanced higher driving force at higher initial Hg0 inlet concentrations. Results from reviewed studies also indicated that the optimum SIC ratio and sulfur content are 2/1 and I 0-20%, respectively. Surface area has a less significant impact on Hg11

  3. Oxidative stress regulates IGF1R expression in vascular smooth-muscle cells via p53 and HDAC recruitment

    PubMed Central

    Kavurma, Mary M.; Figg, Nichola; Bennett, Martin R.; Mercer, John; Khachigian, Levon M.; Littlewood, Trevor D.

    2007-01-01

    Apoptosis of VSMCs (vascular smooth-muscle cells) leads to features of atherosclerotic plaque instability. We have demonstrated previously that plaque-derived VSMCs have reduced IGF1 (insulin-like growth factor 1) signalling, resulting from a decrease in the expression of IGF1R (IGF1 receptor) compared with normal aortic VSMCs [Patel, Zhang, Siddle, Soos, Goddard, Weissberg and Bennett (2001) Circ. Res. 88, 895–902]. In the present study, we show that apoptosis induced by oxidative stress is inhibited by ectopic expression of IGF1R. Oxidative stress repressed IGF1R expression at multiple levels, and this was also blocked by mutant p53. Oxidative stress also induced p53 phosphorylation and apoptosis in VSMCs. p53 negatively regulated IGF1R promoter activity and expression and, consistent with this, p53−/− VSMCs demonstrated increased IGF1R expression, both in vitro and in advanced atherosclerotic plaques in vivo. Oxidative-stress-induced interaction of endogenous p53 with TBP (TATA-box-binding protein) was dependent on p53 phosphorylation. Oxidative stress also increased the association of p53 with HDAC1 (histone deacetylase 1). Trichostatin A, a specific HDAC inhibitor, or p300 overexpression relieved the repression of IGF1R following oxidative stress. Furthermore, acetylated histone-4 association with the IGF1R promoter was reduced in cells subjected to oxidative stress. These results suggest that oxidative-stress-induced repression of IGF1R is mediated by the association of phosphorylated p53 with the IGF1R promoter via TBP, and by the subsequent recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF1R promoter–TBP–p53 complex. PMID:17600529

  4. Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia

    PubMed Central

    Hirakawa, Toshiki; Yashiro, Masakazu; Doi, Yosuke; Kinoshita, Haruhito; Morisaki, Tamami; Fukuoka, Tatsunari; Hasegawa, Tsuyoshi; Kimura, Kenjiro; Amano, Ryosuke; Hirakawa, Kosei

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9) was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2) and hypoxia (1% O2). IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC. PMID:27487118

  5. Modulation of sweet taste by umami compounds via sweet taste receptor subunit hT1R2.

    PubMed

    Shim, Jaewon; Son, Hee Jin; Kim, Yiseul; Kim, Ki Hwa; Kim, Jung Tae; Moon, Hana; Kim, Min Jung; Misaka, Takumi; Rhyu, Mee-Ra

    2015-01-01

    Although the five basic taste qualities-sweet, sour, bitter, salty and umami-can be recognized by the respective gustatory system, interactions between these taste qualities are often experienced when food is consumed. Specifically, the umami taste has been investigated in terms of whether it enhances or reduces the other taste modalities. These studies, however, are based on individual perception and not on a molecular level. In this study we investigated umami-sweet taste interactions using umami compounds including monosodium glutamate (MSG), 5'-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu) and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3-expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly attenuated by MSG and umami active peptides but not by umami active nucleotides. Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious when sweet receptors are activated by sweeteners that target the extracellular domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate, which interact with the T1R3 transmembrane domain (TMD). Application of umami compounds with lactisole, inhibitory drugs that target T1R3, exerted a more severe inhibitory effect. The inhibition was also observed with F778A sweet receptor mutant, which have the defect in function of T1R3 TMD. These results suggest that umami peptides affect sweet taste receptors and this interaction prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric manner, not to the T1R3. This is the first report to define the interaction between umami and sweet taste receptors. PMID:25853419

  6. Modulation of Sweet Taste by Umami Compounds via Sweet Taste Receptor Subunit hT1R2

    PubMed Central

    Kim, Yiseul; Kim, Ki Hwa; Kim, Jung Tae; Moon, Hana; Kim, Min Jung; Misaka, Takumi; Rhyu, Mee-Ra

    2015-01-01

    Although the five basic taste qualities—sweet, sour, bitter, salty and umami—can be recognized by the respective gustatory system, interactions between these taste qualities are often experienced when food is consumed. Specifically, the umami taste has been investigated in terms of whether it enhances or reduces the other taste modalities. These studies, however, are based on individual perception and not on a molecular level. In this study we investigated umami-sweet taste interactions using umami compounds including monosodium glutamate (MSG), 5’-mononucleotides and glutamyl-dipeptides, glutamate-glutamate (Glu-Glu) and glutamate-aspartic acid (Glu-Asp), in human sweet taste receptor hT1R2/hT1R3-expressing cells. The sensitivity of sucrose to hT1R2/hT1R3 was significantly attenuated by MSG and umami active peptides but not by umami active nucleotides. Inhibition of sweet receptor activation by MSG and glutamyl peptides is obvious when sweet receptors are activated by sweeteners that target the extracellular domain (ECD) of T1R2, such as sucrose and acesulfame K, but not by cyclamate, which interact with the T1R3 transmembrane domain (TMD). Application of umami compounds with lactisole, inhibitory drugs that target T1R3, exerted a more severe inhibitory effect. The inhibition was also observed with F778A sweet receptor mutant, which have the defect in function of T1R3 TMD. These results suggest that umami peptides affect sweet taste receptors and this interaction prevents sweet receptor agonists from binding to the T1R2 ECD in an allosteric manner, not to the T1R3. This is the first report to define the interaction between umami and sweet taste receptors. PMID:25853419

  7. An in vitro method for predicting inhalation toxicity of impregnation spray products.

    PubMed

    Sørli, Jorid B; Hansen, Jitka S; Nørgaard, Asger W; Levin, Marcus; Larsen, Søren T

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases are reported frequently. The toxicity appears to be driven by a disruption of the pulmonary surfactant film, which coats the inside of the lungs. Due to the complex chemistry of impregnation spray products, it is impossible to predict if inhalation of an aerosolized product is toxic in vivo. The aim of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film-forming compounds, were identified by mass spectrometry. We used a capillary surfactometry method to assess disruption of pulmonary surfactant function in vitro and a mouse model to evaluate acute respiratory toxicity during inhalation. Concentration-response relationships were successfully determined both in vitro and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing.

  8. An in vitro method for predicting inhalation toxicity of impregnation spray products.

    PubMed

    Sørli, Jorid B; Hansen, Jitka S; Nørgaard, Asger W; Levin, Marcus; Larsen, Søren T

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases are reported frequently. The toxicity appears to be driven by a disruption of the pulmonary surfactant film, which coats the inside of the lungs. Due to the complex chemistry of impregnation spray products, it is impossible to predict if inhalation of an aerosolized product is toxic in vivo. The aim of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film-forming compounds, were identified by mass spectrometry. We used a capillary surfactometry method to assess disruption of pulmonary surfactant function in vitro and a mouse model to evaluate acute respiratory toxicity during inhalation. Concentration-response relationships were successfully determined both in vitro and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing. PMID:25651757

  9. Heterogeneous catalytic degradation of cyanide using copper-impregnated pumice and hydrogen peroxide.

    PubMed

    Kitis, Mehmet; Karakaya, Emine; Yigit, Nevzat O; Civelekoglu, Gokhan; Akcil, Ata

    2005-04-01

    The main objective of this research was to investigate the oxidative destruction of free cyanide with hydrogen peroxide and copper-impregnated pumice as a heterogeneous catalyst. Original or copper-impregnated pumices added alone were not effective adsorbents of negatively charged cyanide ions due to incompatible surface interactions. Peroxide and original pumices added together were also ineffective in removing cyanide. However, for all of the three natural pumices tested with various particle size fractions, the use of copper-impregnated pumices and peroxide together significantly enhanced both the initial rate and extent of cyanide removal. Although copper-impregnated specific surface area was the major factor affecting the rate and extent of cyanide destruction for a particular pumice source with similar surface chemistries, the type of surface chemistry (i.e., specific functional groups) within different pumice sources also appears to be a very important factor. Lower rates and extents of cyanide removals were observed at pH 11 compared to pH 8 probably because of the negative impacts of alkaline conditions in terms of scavenging peroxide and forming more negatively charged pumice surfaces. Both the initial rate and ultimate extent of cyanide removals were generally higher at a temperature of 20 degrees C compared with those found at 10 degrees C. The use of copper-impregnated pumice as a light, cheap, readily available, natural, and porous heterogeneous catalyst either in completely mixed/suspended or fixed-bed reactor configurations may be an effective treatment technology for cyanide removal from solution. This new approach may minimize downstream metal removal problems experienced in conventional cyanide oxidation technologies.

  10. Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene

    SciTech Connect

    Conboy, John G.; Parra, Marilyn K.; Tan, Jeff S.; Mohandas, Narla; Conboy, John G.

    2008-11-07

    In the protein 4.1R gene, alternative first exons splice differentially to alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branch points for both intrasplicing reactions and demonstrated that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism whereby alternative promoters can be coordinated with downstream alternative splicing.

  11. Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(-)-myrtenol nitrate.

    PubMed

    Bew, Sean P; Hiatt-Gipson, Glyn D; Mills, Graham P; Reeves, Claire E

    2016-01-01

    Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a 'halide for nitrate' substitution. Employing readily available starting materials, reagents and Horner-Wadsworth-Emmons chemistry the synthesis of easily separable, synthetically versatile 'key building blocks' (E)- and (Z)-3-methyl-4-chlorobut-2-en-1-ol as well as (E)- and (Z)-1-((2-methyl-4-bromobut-2-enyloxy)methyl)-4-methoxybenzene has been achieved using cheap, 'off the shelf' materials. Exploiting their reactivity we have studied their ability to undergo an 'allylic halide for allylic nitrate' substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates ('isoprene nitrates') in 66-80% overall yields. Using NOESY experiments the elucidation of the carbon-carbon double bond configuration within the purified isoprene nitrates has been established. Further exemplifying our 'halide for nitrate' substitution chemistry we outline the straightforward transformation of (1R,2S)-(-)-myrtenol bromide into the previously unknown monoterpene nitrate (1R,2S)-(-)-myrtenol nitrate. PMID:27340495

  12. TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung adenocarcinoma.

    PubMed

    Lin, Jau-Chen; Wu, Yi-Ying; Wu, Jing-Yi; Lin, Tzu-Chieh; Wu, Chen-Tu; Chang, Yih-Leong; Jou, Yuh-Shan; Hong, Tse-Ming; Yang, Pan-Chyr

    2012-06-01

    Trop-2, a cell surface glycoprotein, contains both extracellular epidermal growth factor-like and thyroglobulin type-1 repeat domains. Low TROP2 expression was observed in lung adenocarcinoma tissues as compared with their normal counterparts. The lack of expression could be due to either the loss of heterozygosity (LOH) or hypermethylation of the CpG island DNA of TROP2 upstream promoter region as confirmed by bisulphite sequencing and methylation-specific (MS) polymerase chain reaction (PCR). 5-Aza-2'-deoxycytidine treatment on lung cancer cell (CL) lines, CL1-5 and A549, reversed the hypermethylation status and elevated both TROP2 mRNA and protein expression levels. Enforced expression of TROP2 in the lung CL line H1299 reduced AKT as well as ERK activation and suppressed cell proliferation and colony formation. Conversely, silencing TROP2 with shRNA transfection in the less efficiently tumour-forming cell line H322M enhanced AKT activation and increased tumour growth. Trop-2 could attenuate IGF-1R signalling-mediated AKT/β-catenin and ERK activation through a direct binding of IGF1. In conclusion, inactivation of TROP2 due to LOH or by DNA methylation may play an important role in lung cancer tumourigenicity through losing its suppressive effect on IGF-1R signalling and tumour growth. PMID:22419550

  13. Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis.

    PubMed

    Zhang, Yong; Miwa, Shinji; Zhang, Nan; Hoffman, Robert M; Zhao, Ming

    2015-02-20

    Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). ND-GFP mice express GFP in nascent blood vessels. In the orthotopically-injected mice, the primary tumor was surgically-resected in order to allow brain metastasis to develop. At various time points, the tumors and vasculature in the brain were imaged by confocal and stereo fluorescence microscopy. Some of the breast cancer cells that reached the brain extravasated and grew perivascularly and some of the cells proliferated within the vasculature. S. typhimurium A1-R significantly inhibited brain metastasis in both metastatic models and increased survival of the orthotopically-transplanted, primary-tumor-resected mice (p<0.05). The results of the present study suggest the clinical potential of bacterial therapy of breast cancer brain metastasis.

  14. ENP11, a potential CB1R antagonist, induces anorexia in rats.

    PubMed

    Méndez-Díaz, Mónica; Amancio-Belmont, Octavio; Hernández-Vázquez, Eduardo; Ruiz-Contreras, Alejandra E; Hernández-Luis, Francisco; Prospéro-García, Oscar

    2015-08-01

    Over the past decade, pharmacological manipulation of cannabinoid 1 receptor (CB1R) has become an interesting approach for the management of food ingestion disorders, among other physiological functions. Searching for new substances with similar desirable effects, but fewer side-effects we have synthesized a SR141716A (a cannabinoid receptor inverse agonist also called Rimonabant) analog, 1-(2,4-Difluorophenyl)-4-methyl-N-(1-piperidinyl)-5-[4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, ENP11, that so far, as we have previously shown, has induced changes in glucose availability, i.e. hypoglycemia, in rats. In this study we tested the effects, if any, of ENP11 (0.5, 1.0, and 3.0mg/kg) in food ingestion, core temperature, pain perception and motor control in adult Wistar rats. Results showed that ENP11 reduced food ingestion during the first hour immediately after administration. Likewise, ENP11 (1.0mg/kg) blocked anandamide (AEA)-induced hyperphagia during the first 4h of the dark phase of the light-dark cycle, and it also blocked AEA-induced hypothermia. However, none of the ENP11 doses used affected pain perception or motor control. We believe that ENP11 is a potential useful CB1R antagonist that reduces food ingestion and regulates core temperature.

  15. Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(-)-myrtenol nitrate.

    PubMed

    Bew, Sean P; Hiatt-Gipson, Glyn D; Mills, Graham P; Reeves, Claire E

    2016-01-01

    Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a 'halide for nitrate' substitution. Employing readily available starting materials, reagents and Horner-Wadsworth-Emmons chemistry the synthesis of easily separable, synthetically versatile 'key building blocks' (E)- and (Z)-3-methyl-4-chlorobut-2-en-1-ol as well as (E)- and (Z)-1-((2-methyl-4-bromobut-2-enyloxy)methyl)-4-methoxybenzene has been achieved using cheap, 'off the shelf' materials. Exploiting their reactivity we have studied their ability to undergo an 'allylic halide for allylic nitrate' substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates ('isoprene nitrates') in 66-80% overall yields. Using NOESY experiments the elucidation of the carbon-carbon double bond configuration within the purified isoprene nitrates has been established. Further exemplifying our 'halide for nitrate' substitution chemistry we outline the straightforward transformation of (1R,2S)-(-)-myrtenol bromide into the previously unknown monoterpene nitrate (1R,2S)-(-)-myrtenol nitrate.

  16. Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

    PubMed Central

    Hiatt-Gipson, Glyn D; Mills, Graham P; Reeves, Claire E

    2016-01-01

    Summary Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a ’halide for nitrate’ substitution. Employing readily available starting materials, reagents and Horner–Wadsworth–Emmons chemistry the synthesis of easily separable, synthetically versatile ‘key building blocks’ (E)- and (Z)-3-methyl-4-chlorobut-2-en-1-ol as well as (E)- and (Z)-1-((2-methyl-4-bromobut-2-enyloxy)methyl)-4-methoxybenzene has been achieved using cheap, ’off the shelf’ materials. Exploiting their reactivity we have studied their ability to undergo an ‘allylic halide for allylic nitrate’ substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates (‘isoprene nitrates’) in 66–80% overall yields. Using NOESY experiments the elucidation of the carbon–carbon double bond configuration within the purified isoprene nitrates has been established. Further exemplifying our ‘halide for nitrate’ substitution chemistry we outline the straightforward transformation of (1R,2S)-(−)-myrtenol bromide into the previously unknown monoterpene nitrate (1R,2S)-(−)-myrtenol nitrate. PMID:27340495

  17. IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma

    PubMed Central

    Svalina, Matthew N.; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Peckham, Jennifer L.; Cho, Yoon-Jae; Michalek, Joel E.; Hernandez, Brian S.; Berlow, Noah E.; Jackson, Melanie; Guillaume, Daniel J.; Selden, Nathan R.; Bigner, Darell D.; Nazemi, Kellie J.; Green, Sarah C.; Corless, Christopher L.; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P.; Woltjer, Randall; Keller, Charles

    2016-01-01

    Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663

  18. ENP11, a potential CB1R antagonist, induces anorexia in rats.

    PubMed

    Méndez-Díaz, Mónica; Amancio-Belmont, Octavio; Hernández-Vázquez, Eduardo; Ruiz-Contreras, Alejandra E; Hernández-Luis, Francisco; Prospéro-García, Oscar

    2015-08-01

    Over the past decade, pharmacological manipulation of cannabinoid 1 receptor (CB1R) has become an interesting approach for the management of food ingestion disorders, among other physiological functions. Searching for new substances with similar desirable effects, but fewer side-effects we have synthesized a SR141716A (a cannabinoid receptor inverse agonist also called Rimonabant) analog, 1-(2,4-Difluorophenyl)-4-methyl-N-(1-piperidinyl)-5-[4-(trifluoromethyl)phenyl]-1H-pyrazole-3-carboxamide, ENP11, that so far, as we have previously shown, has induced changes in glucose availability, i.e. hypoglycemia, in rats. In this study we tested the effects, if any, of ENP11 (0.5, 1.0, and 3.0mg/kg) in food ingestion, core temperature, pain perception and motor control in adult Wistar rats. Results showed that ENP11 reduced food ingestion during the first hour immediately after administration. Likewise, ENP11 (1.0mg/kg) blocked anandamide (AEA)-induced hyperphagia during the first 4h of the dark phase of the light-dark cycle, and it also blocked AEA-induced hypothermia. However, none of the ENP11 doses used affected pain perception or motor control. We believe that ENP11 is a potential useful CB1R antagonist that reduces food ingestion and regulates core temperature. PMID:26072692

  19. Italian aerospace company Alenia prepare TSS-1R in O&C

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Employees of the Italian aerospace company Alenia Spazio S.p.A. prepare the Tethered Satellite System-1R (TSS-1R) that is one of two primary payloads scheduled to fly aboard the Orbiter Columbia during the STS-75 mission in early 1996 for a series of tests in the Operations and Checkout (O&C) Building. The TSS program is a joint venture between NASA and the Agenzia Spaziale Italiana, or Italian Space Agency. The 'R' designation indicates a reflight. The TSS-1 flew aboard Atlantis during the STS-46 mission in July 1992 and achieved only a partial success when its tether reel mechanism became jammed after only approximately 840 feet of the 12-mile-long tether had been unwound as the satellite rose from its cradle in the orbiter's payload bay. Once deployed to the 12- mile height on the STS-75 mission, the satellite will be used to validate theories that such a system could possibly be used in the future to generate electrical power to power orbital systems, raise and lower spacecraft, study atmospheric conditions at several different heights and for many other applications.

  20. An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva.

    PubMed

    Chakkalakal, Salin A; Zhang, Deyu; Culbert, Andria L; Convente, Michael R; Caron, Robert J; Wright, Alexander C; Maidment, Andrew D A; Kaplan, Frederick S; Shore, Eileen M

    2012-08-01

    Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of dysregulated cellular differentiation characterized by malformation of the great toes during embryonic skeletal development and by progressive heterotopic endochondral ossification postnatally. Patients with these classic clinical features of FOP have the identical heterozygous single nucleotide substitution (c.617G > A; R206H) in the gene encoding ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. Gene targeting was used to develop an Acvr1 knock-in model for FOP (Acvr1(R206H/+)). Radiographic analysis of Acvr1(R206H/+) chimeric mice revealed that this mutation induced malformed first digits in the hind limbs and postnatal extraskeletal bone formation, recapitulating the human disease. Histological analysis of murine lesions showed inflammatory infiltration and apoptosis of skeletal muscle followed by robust formation of heterotopic bone through an endochondral pathway, identical to that seen in patients. Progenitor cells of a Tie2(+) lineage participated in each stage of endochondral osteogenesis. We further determined that both wild-type (WT) and mutant cells are present within the ectopic bone tissue, an unexpected finding that indicates that although the mutation is necessary to induce the bone formation process, the mutation is not required for progenitor cell contribution to bone and cartilage. This unique knock-in mouse model provides novel insight into the genetic regulation of heterotopic ossification and establishes the first direct in vivo evidence that the R206H mutation in ACVR1 causes FOP.

  1. Identification of a third protein 4.1 tumor suppressor, protein 4.1R, in meningioma pathogenesis

    SciTech Connect

    Robb, Victoria A.; Li, Wen; Gascard, Philippe; Perry, Arie; Mohandas, Narla; Gutmann, David H.

    2003-06-11

    Meningiomas are common tumors of the central nervous system, however, the mechanisms under lying their pathogenesis are largely undefined. Two members of the Protein 4.1 super family, the neuro fibromatosis 2 (NF2) gene product (merlin/schwannomin) and Protein 4.1B have been implicated as meningioma tumor suppressors. In this report, we demonstrate that another Protein 4.1 family member, Protein 4.1R, also functions as a meningioma tumor suppressor. Based on the assignment of the Protein 4.1R gene to chromosome 1p32-36, a common region of deletion observed in meningiomas, we analyzed Protein 4.1R expression in meningioma cell lines and surgical tumor specimens. We observed loss of Protein 4.1R protein expression in two meningioma cell lines (IOMM-Lee, CH157-MN) by Western blotting as well as in 6 of 15 sporadic meningioma as by immuno histo chemistry (IHC). Analysis of a subset of these sporadic meningiomas by fluorescent in situ hybridization (FISH) with a Protein 4.1R specific probe demonstrated 100 percent concordance with the IHC results. In support of a meningioma tumor suppressor function, over expression of Protein 4.1R resulted in suppression of IOMM-Lee and CH157MN cell proliferation. Similar to the Protein 4.1B and merlin meningioma tumor suppressors, Protein 4.1R localization in the membrane fraction increased significantly under conditions of growth arrest in vitro. Lastly, Protein 4.1R interacted with some known merlin/Protein 4.1B interactors such as CD44 and bII-spectrin, but did not associate with the Protein 4.1B interactors 14-3-3 and PRMT3 or the merlin binding proteins SCHIP-1 and HRS. Collectively, these results suggest that Protein 4.1R functions as an important tumor suppressor important in the molecular pathogenesis of meningioma.

  2. Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In Vitro and In Vivo.

    PubMed

    Ofer, Philipp; Heidegger, Isabel; Eder, Iris E; Schöpf, Bernd; Neuwirt, Hannes; Geley, Stephan; Klocker, Helmut; Massoner, Petra

    2015-12-01

    The IGF network with its main receptors IGF receptor 1 (IGF1R) and insulin receptor (INSR) is of major importance for cancer initiation and progression. To date, clinical studies targeting this network were disappointing and call for thorough analysis of the IGF network in cancer models. We highlight the oncogenic effects controlled by IGF1R and INSR in prostate cancer cells and show similarities as well as differences after receptor knockdown (KD). In PC3 prostate cancer cells stably transduced with inducible short hairpin RNAs, targeting IGF1R or INSR attenuated cell growth and proliferation ultimately driving cells into apoptosis. IGF1R KD triggered rapid and strong antiproliferative and proapoptotic responses, whereas these effects were less pronounced and delayed after INSR KD. Down-regulation of the antiapoptotic proteins myeloid cell leukemia-1 and survivin was observed in both KDs, whereas IGF1R KD also attenuated expression of prosurvival proteins B cell lymphoma-2 and B cell lymphoma-xL. Receptor KD induced cell death involved autophagy in particular upon IGF1R KD; however, no difference in mitochondrial energy metabolism was observed. In a mouse xenograft model, induction of IGF1R or INSR KD after tumor establishment eradicated most of the tumors. After 20 days of receptor KD, tumor cells were found only in 1/14 IGF1R and 3/14 INSR KD tumor remnants. Collectively, our data underline the oncogenic functions of IGF1R and INSR in prostate cancer namely growth, proliferation, and survival in vitro as well as in vivo and identify myeloid cell leukemia-1 and survivin as important mediators of inhibitory and apoptotic effects.

  3. Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In Vitro and In Vivo

    PubMed Central

    Ofer, Philipp; Heidegger, Isabel; Eder, Iris E.; Schöpf, Bernd; Neuwirt, Hannes; Geley, Stephan; Massoner, Petra

    2015-01-01

    The IGF network with its main receptors IGF receptor 1 (IGF1R) and insulin receptor (INSR) is of major importance for cancer initiation and progression. To date, clinical studies targeting this network were disappointing and call for thorough analysis of the IGF network in cancer models. We highlight the oncogenic effects controlled by IGF1R and INSR in prostate cancer cells and show similarities as well as differences after receptor knockdown (KD). In PC3 prostate cancer cells stably transduced with inducible short hairpin RNAs, targeting IGF1R or INSR attenuated cell growth and proliferation ultimately driving cells into apoptosis. IGF1R KD triggered rapid and strong antiproliferative and proapoptotic responses, whereas these effects were less pronounced and delayed after INSR KD. Down-regulation of the antiapoptotic proteins myeloid cell leukemia-1 and survivin was observed in both KDs, whereas IGF1R KD also attenuated expression of prosurvival proteins B cell lymphoma-2 and B cell lymphoma-xL. Receptor KD induced cell death involved autophagy in particular upon IGF1R KD; however, no difference in mitochondrial energy metabolism was observed. In a mouse xenograft model, induction of IGF1R or INSR KD after tumor establishment eradicated most of the tumors. After 20 days of receptor KD, tumor cells were found only in 1/14 IGF1R and 3/14 INSR KD tumor remnants. Collectively, our data underline the oncogenic functions of IGF1R and INSR in prostate cancer namely growth, proliferation, and survival in vitro as well as in vivo and identify myeloid cell leukemia-1 and survivin as important mediators of inhibitory and apoptotic effects. PMID:26452103

  4. Repression of malignant tumor progression upon pharmacologic IGF1R blockade in a mouse model of insulinoma.

    PubMed

    Zumsteg, Adrian; Caviezel, Christoph; Pisarsky, Laura; Strittmatter, Karin; García-Echeverría, Carlos; Hofmann, Francesco; Christofori, Gerhard

    2012-06-01

    NVP-AEW541, a specific ATP-competitive inhibitor of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase, has been reported to interfere with tumor growth in various tumor transplantation models. We have assessed the efficacy of NVP-AEW541 in repressing tumor growth and tumor progression in the Rip1Tag2 transgenic mouse model of pancreatic β-cell carcinogenesis. In addition, we have tested NVP-AEW541 in Rip1Tag2;RipIGF1R double-transgenic mice which show accelerated tumor growth and increased tumor malignancy compared with Rip1Tag2 single-transgenic mice. Previously, we have shown that high levels of IGF-2, a high-affinity ligand for IGF1R, are required for Rip1Tag2 tumor cell survival and tumor growth. Unexpectedly, treatment of Rip1Tag2 mice with NVP-AEW541 in prevention and intervention trials neither did affect tumor growth nor tumor cell proliferation and apoptosis. Yet, it significantly repressed progression to tumor malignancy, that is, the rate of the transition from differentiated adenoma to invasive carcinoma. Treatment of Rip1Tag2;RipIGF1R double-transgenic mice resulted in moderately reduced tumor volumes and increased rates of tumor cell apoptosis. Sustained expression of IGF-2 and of the IGF-2-binding form of insulin receptor (IR-A) in tumor cells suggests a compensatory role of IR-A upon IGF1R blockade. The results indicate that inhibition of IGF1R alone is not sufficient to efficiently block insulinoma growth and imply an overlapping role of IGF1R and insulin receptor in executing mitogenic and survival stimuli elicited by IGF-2. The reduction of tumor invasion upon IGF1R blockade on the other hand indicates a critical function of IGF1R signaling for the acquisition of a malignant phenotype.

  5. Crystal structure of potassium (1R)-d-ribit-1-yl­sulfonate

    PubMed Central

    Haines, Alan H.; Hughes, David L.

    2014-01-01

    The title compound, K+·C5H11O8S− [systematic name: potassium (1R,2R,3R,4R)-1,2,3,4,5-penta­hydroxy­pentane-1-sulfonate], formed by reaction of d-ribose with potassium hydrogen sulfite in water, crystallizes as colourless plates. The anion has an open-chain structure in which the S atom and the C atoms of the sugar chain, excepting that of the hy­droxy­methyl group, form an essentially all-trans chain; the C atom of the hy­droxy­methyl group lies in a gauche relationship with the three contiguous C atoms. Through complex cation coordination (through seven oxygen atoms of six different anions) and inter­molecular O—H⋯O hydrogen bonding, a three-dimensional bonding network exists in the crystal structure. PMID:25484759

  6. Crystal structure of potassium (1R)-d-ribit-1-yl-sulfonate.

    PubMed

    Haines, Alan H; Hughes, David L

    2014-11-01

    The title compound, K(+)·C5H11O8S(-) [systematic name: potassium (1R,2R,3R,4R)-1,2,3,4,5-penta-hydroxy-pentane-1-sulfonate], formed by reaction of d-ribose with potassium hydrogen sulfite in water, crystallizes as colourless plates. The anion has an open-chain structure in which the S atom and the C atoms of the sugar chain, excepting that of the hy-droxy-methyl group, form an essentially all-trans chain; the C atom of the hy-droxy-methyl group lies in a gauche relationship with the three contiguous C atoms. Through complex cation coordination (through seven oxygen atoms of six different anions) and inter-molecular O-H⋯O hydrogen bonding, a three-dimensional bonding network exists in the crystal structure. PMID:25484759

  7. Germline MC1R status influences somatic mutation burden in melanoma

    PubMed Central

    Robles-Espinoza, Carla Daniela; Roberts, Nicola D.; Chen, Shuyang; Leacy, Finbarr P.; Alexandrov, Ludmil B.; Pornputtapong, Natapol; Halaban, Ruth; Krauthammer, Michael; Cui, Rutao; Timothy Bishop, D.; Adams, David J.

    2016-01-01

    The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of an R allele is estimated to be 42% (95% CI, 15–76%) higher than that among persons without an R allele. This figure is comparable to the expected mutational burden associated with an additional 21 years of age. We also find significant and similar enrichment of non-C>T mutation classes supporting a role for additional mutagenic processes in melanoma development in individuals carrying R alleles. PMID:27403562

  8. Rare SF3B1 R625 mutations in cutaneous melanoma.

    PubMed

    Kong, Yong; Krauthammer, Michael; Halaban, Ruth

    2014-08-01

    RNA splicing is the cellular process that has only recently been found to be an important target for various cancers. Among the spliceosome genes that are involved in cancers, SF3B1 is most frequently mutated. Recurrent mutation in codon 625 has been found in uveal melanoma, but this mutation has not been identified in cutaneous melanoma. We used whole-exome sequencing to explore the mutational landscape of 295 melanoma samples, 231 of which are cutaneous melanoma. Among these cutaneous melanoma samples, we found two samples with R625 mutation in SF3B1 gene. The results were validated by Sanger sequencing. We conclude that SF3B1 R625 mutation does occur in cutaneous melanoma, although with a low frequency (∼1%).

  9. Germline MC1R status influences somatic mutation burden in melanoma.

    PubMed

    Robles-Espinoza, Carla Daniela; Roberts, Nicola D; Chen, Shuyang; Leacy, Finbarr P; Alexandrov, Ludmil B; Pornputtapong, Natapol; Halaban, Ruth; Krauthammer, Michael; Cui, Rutao; Timothy Bishop, D; Adams, David J

    2016-07-12

    The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of an R allele is estimated to be 42% (95% CI, 15-76%) higher than that among persons without an R allele. This figure is comparable to the expected mutational burden associated with an additional 21 years of age. We also find significant and similar enrichment of non-C>T mutation classes supporting a role for additional mutagenic processes in melanoma development in individuals carrying R alleles.

  10. Supersymmetric extended string field theory in NSn sector and NSn - 1-R sector

    NASA Astrophysics Data System (ADS)

    Asano, Masako; Kato, Mitsuhiro

    2016-09-01

    We construct a class of quadratic gauge invariant actions for extended string fields defined on the tensor product of open superstring state space for multiple open string Neveu-Schwarz (NS) sectors with or without one Ramond (R) sector. The basic idea is the same as for the bosonic extended string field theory developed by the authors [1]. The theory for NSn sector and NS n - 1-R sector contains general n-th rank tensor fields and (n - 1)-th rank spinor-tensor fields in the massless spectrum respectively. In principle, consistent gauge invariant actions for any generic type of 10-dimensional massive or massless tensor or spinor-tensor fields can be extracted from the theory. We discuss some simple examples of bosonic and fermionic massless actions.

  11. Germline MC1R status influences somatic mutation burden in melanoma.

    PubMed

    Robles-Espinoza, Carla Daniela; Roberts, Nicola D; Chen, Shuyang; Leacy, Finbarr P; Alexandrov, Ludmil B; Pornputtapong, Natapol; Halaban, Ruth; Krauthammer, Michael; Cui, Rutao; Timothy Bishop, D; Adams, David J

    2016-01-01

    The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of an R allele is estimated to be 42% (95% CI, 15-76%) higher than that among persons without an R allele. This figure is comparable to the expected mutational burden associated with an additional 21 years of age. We also find significant and similar enrichment of non-C>T mutation classes supporting a role for additional mutagenic processes in melanoma development in individuals carrying R alleles. PMID:27403562

  12. Endocrine alterations around the time of abortion in mares impregnated with donkey or horse semen.

    PubMed

    Boeta, M; Zarco, L

    2010-08-01

    The objective of this study was to monitor and compare the concentrations of equine chorionic gonadotropin (eCG), progesterone and estrone sulphate during normal and failed pregnancies of mares impregnated with donkey or horse semen, relating their individual endocrine profiles to the time of pregnancy loss, and to the histopathologic findings in the aborted fetuses and placenta. Mares (n=54) were used, 32 of them impregnated with donkey semen and 22 impregnated with horse semen. Blood samples were taken twice a week from Day 35 to 120 of pregnancy. Ultrasonographic observations of the fetus were carried out twice a week. The incidence of abortion in mares impregnated with donkey semen (30%) was greater (P<0.05) than the 5% observed in mares impregnated with horse semen. From Week 8 to the end of the sampling period, the mean progesterone concentrations of mares with normal mule pregnancies were less (P<0.05) than those of mares with normal pregnancies with equine fetuses. The concentrations of eCG were less (P<0.05) in mule pregnancies from Week 6. Estrone sulphate concentrations were only different (P<0.05) between types of pregnancy on Weeks 13 and 14, being in this case greater with the mule pregnancies. Most of the abortions of mule fetuses were associated with lesser progesterone concentrations than the average for mares with successful mule pregnancies. Four of the abortions of mule fetuses and the only abortion of horse fetus occurred in mares with lesser progesterone and very low eCG concentrations, and were classified as caused by luteal impairment secondary to eCG deficiency; estrone sulphate concentrations were less than normal or absent before these abortions. Two mares aborted after several weeks of low progesterone concentrations in the presence of eCG concentrations that were normal for mule pregnancies, suggesting primary luteal deficiency. In three mares carrying a mule fetus, the concentrations of progesterone and estrone sulphate decreased

  13. Antimicrobial properties of erythromycin and colistin impregnated bone cement. An in vitro analysis.

    PubMed

    Ruzaimi, M Y; Shahril, Y; Masbah, O; Salasawati, H

    2006-02-01

    Deep surgical site infection is a devastating consequence of total joint arthroplasty. The use of antibiotic impregnated bone cement is a well-accepted adjunct for treatment of established infection and prevention of deep orthopaedic infection. It allows local delivery of the antibiotic at the cement-bone interface and sustained release of antibiotic provides adequate antibiotic coverage after the wound closure. Preclinical testing, randomised and clinical trials indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep surgical site infection following total joint arthroplasty. The purpose of this study was to assess antibacterial activity of erythromycin and colistin impregnated bone cement against strains of organisms' representative of orthopaedic infections including Gram-positive and Gram-negative aerobic organisms: Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp., Proteus sp., Klebsiella sp., Pseudomonas sp., and Escherichia coli. Pre-blended Simplex P bone cement with the addition of erythromycin and colistin (Howemedica Inc) was mixed thoroughly with 20ml liquid under sterile conditions to produce uniform cylindrical discs with a diameter of 14mm and thickness of 2mm. 24-48 hour agar cultures of Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp.,Proteus sp., Klebsiella sp.,Pseudomonas sp., and Escherichia coli were used for the agar diffusion tests. The agar plates were streaked for confluent growth followed by application of erythromycin and colistin impregnated bone cement disc to each agar plate. The plates were incubated at 30 degrees C and examined at 24, 48, 72 hours, and four and five days after the preparation of the impregnated cement. The susceptibility of Staphylococcus aureus to the control discs was most clearly demonstrated showing a distinct zone of inhibition. The zone observed around coagulase-negative Staphylococci

  14. Endocrine alterations around the time of abortion in mares impregnated with donkey or horse semen.

    PubMed

    Boeta, M; Zarco, L

    2010-08-01

    The objective of this study was to monitor and compare the concentrations of equine chorionic gonadotropin (eCG), progesterone and estrone sulphate during normal and failed pregnancies of mares impregnated with donkey or horse semen, relating their individual endocrine profiles to the time of pregnancy loss, and to the histopathologic findings in the aborted fetuses and placenta. Mares (n=54) were used, 32 of them impregnated with donkey semen and 22 impregnated with horse semen. Blood samples were taken twice a week from Day 35 to 120 of pregnancy. Ultrasonographic observations of the fetus were carried out twice a week. The incidence of abortion in mares impregnated with donkey semen (30%) was greater (P<0.05) than the 5% observed in mares impregnated with horse semen. From Week 8 to the end of the sampling period, the mean progesterone concentrations of mares with normal mule pregnancies were less (P<0.05) than those of mares with normal pregnancies with equine fetuses. The concentrations of eCG were less (P<0.05) in mule pregnancies from Week 6. Estrone sulphate concentrations were only different (P<0.05) between types of pregnancy on Weeks 13 and 14, being in this case greater with the mule pregnancies. Most of the abortions of mule fetuses were associated with lesser progesterone concentrations than the average for mares with successful mule pregnancies. Four of the abortions of mule fetuses and the only abortion of horse fetus occurred in mares with lesser progesterone and very low eCG concentrations, and were classified as caused by luteal impairment secondary to eCG deficiency; estrone sulphate concentrations were less than normal or absent before these abortions. Two mares aborted after several weeks of low progesterone concentrations in the presence of eCG concentrations that were normal for mule pregnancies, suggesting primary luteal deficiency. In three mares carrying a mule fetus, the concentrations of progesterone and estrone sulphate decreased

  15. An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva

    PubMed Central

    Chakkalakal, Salin A.; Zhang, Deyu; Culbert, Andria L.; Convente, Michael R.; Caron, Robert J.; Wright, Alexander C.; Maidment, Andrew D.A.; Kaplan, Frederick S.; Shore, Eileen M.

    2013-01-01

    Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of dysregulated cellular differentiation characterized by malformation of the great toes during embryonic skeletal development and by progressive heterotopic endochondral ossification post-natally. Patients with these classic clinical features of FOP have the identical heterozygous single nucleotide substitution (c.617G>A; R206H) in the gene encoding ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. Gene targeting was used to develop a knock-in mouse model for FOP (Acvr1R206H/+). Radiographic analysis of Acvr1R206H/+ chimeric mice revealed that this mutation induced malformed first digits in the hind limbs and post-natal extra-skeletal bone formation, recapitulating the human disease. Histological analysis of murine lesions showed inflammatory infiltration and apoptosis of skeletal muscle followed by robust formation of heterotopic bone through an endochondral pathway, identical to that seen in patients. Progenitor cells of a Tie2+ lineage participated in each stage of endochondral osteogenesis. We further determined that both wild-type and mutant cells are present within the ectopic bone tissue, an unexpected finding that indicates that although the mutation is necessary to induce the bone formation process, the mutation is not required for progenitor cell contribution to bone and cartilage. This unique knock-in mouse model provides novel insight into the genetic regulation of heterotopic ossification and establishes the first direct in vivo evidence that the R206H mutation in ACVR1 causes FOP. PMID:22508565

  16. MRI characteristics and scoring in HDLS due to CSF1R gene mutations

    PubMed Central

    Sundal, Christina; Van Gerpen, Jay A.; Nicholson, Alexandra M.; Wider, Christian; Shuster, Elizabeth A.; Aasly, Jan; Spina, Salvatore; Ghetti, Bernardino; Roeber, Sigrun; Garbern, James; Borjesson-Hanson, Anne; Tselis, Alex; Swerdlow, Russell H.; Miller, Bradley B.; Fujioka, Shinsuke; Heckman, Michael G.; Uitti, Ryan J.; Josephs, Keith A.; Baker, Matt; Andersen, Oluf; Rademakers, Rosa; Dickson, Dennis W.; Broderick, Daniel

    2012-01-01

    Objective: To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5. Methods: We reviewed 20 brain MRI scans of 15 patients with autopsy- or biopsy-verified HDLS and CSF1R mutations. We assessed sagittal T1-, axial T1-, T2-, proton density-weighted and axial fluid-attenuated inversion recovery images for distribution of white matter lesions (WMLs), gray matter involvement, and atrophy. We calculated a severity score based on a point system (0−57) for each MRI scan. Results: Of the patients, 93% (14 of 15) demonstrated localized WMLs with deep and subcortical involvement, whereas one patient revealed generalized WMLs. All WMLs were bilateral but asymmetric and predominantly frontal. Fourteen patients had a rapidly progressive clinical course with an initial MRI mean total severity score of 16.7 points (range 10−33.5). Gray matter pathology and brainstem atrophy were absent, and the corticospinal tracts were involved late in the disease course. There was no enhancement, and there was minimal cerebellar pathology. Conclusion: Recognition of the typical MRI patterns of HDLS and the use of an MRI severity score might help during the diagnostic evaluation to characterize the natural history and to monitor potential future treatments. Indicators of rapid disease progression were symptomatic disease onset before 45 years, female sex, WMLs extending beyond the frontal regions, a MRI severity score greater than 15 points, and mutation type of deletion. PMID:22843259

  17. Tethered Satellite System (TSS-1R)-Post Flight (STS-75) Engineering Performance Report

    NASA Technical Reports Server (NTRS)

    Lavoie, Anthony R.

    1996-01-01

    The first mission of the Tethered Satellite deployer was flown onboard Atlantis in 1992 during the Space Transportation System (STS) flight STS-46. Due to a mechanical interference with the level wind mechanism the satellite was only Deployed to 256 m rather than the planned 20,000 m. Other problems were also experienced during the STS-46 flight and several modifications were made to the Deployer and Satellite. STS-75 was a reflight of the Tethered Satellite System 1 (TSS-1) designated as Tethered Satellite System 1 Reflight (TSS-1 R) onboard Columbia. As on STS-46, the TSS payload consisted of the Deployer, the Satellite, 3 cargo bay mounted experiments: Shuttle Electrodynamic Tether System (SETS), Shuttle Potential and Return Electron Experiment (SPREE), Deployer Core Equipment (DCORE) 4 Satellite mounted experiments: Research on Electrodynamics Tether Effects (RETE), Research on Orbital Plasma Electrodynamics (ROPE), Satellite Core Instruments (SCORE), Tether Magnetic Field Experiment (TEMAG) and an aft flight deck camera: Tether Optical Phenomena Experiment (TOP). Following successful pre-launch, launch and pre-deployment orbital operations, the Deployer deployed the Tethered Satellite to 19,695 m at which point the tether broke within the Satellite Deployment Boom (SDB). The planned length for On-Station I (OST1) was 20,700 m The Satellite flew away from the Orbiter with the tether attached. The satellite was "safed" and placed in a limited power mode via the RF link. The Satellite was contacted periodically during overflights of ground stations. Cargo bay science activities continued for the period of time allocated to TSS-1 R operations.

  18. Containerless Processing in Reduced Gravity Using the TEMPUS Facility during MSL-1 and MSL-1R

    NASA Technical Reports Server (NTRS)

    Rogers, Jan R.

    1998-01-01

    Containerless processing provides a high purity environment for the study of high-temperature, very reactive materials. It is an important method which provides access to the metastable state of an undercooled melt. In the absence of container walls, the nucleation rate is greatly reduced and undercooling up to (Tm-Tn)/Tm approx. equal to 0.2 can be obtained, where Tm and Tn are the melting and nucleation temperatures, respectively. Electromagnetic levitation represents a method particularly well-suited for the study of metallic melts. The TEMPUS (Tiegelfreies ElektroMagnetisches Prozessieren Unter Schwerelosgkeit) facility is a research instrument designed to perform electromagnetic levitation studies in reduced gravity. TEMPUS is a joint undertaking between DARA, the German Space Agency, and the Microgravity Science and Applications Division of NASA. The George C. Marshall Space Flight Center provides the leadership for scientific and management efforts which support the four US PI teams which performed experiments in the TEMPUS facility. The facility is sensitive to accelerations in the 1-10 Hz range. This became evident during the MSL-1 mission. Analysis of accelerometer and video data indicated that loss of sample control occurred during crew exercise periods which created disturbances in this frequency range. Prior to the MSL-1R flight the TEMPUS team, the accelerometer support groups and the mission operations team developed a strategy to provide for the operation of the facility without such disturbances. The successful implementation of this plan led to the highly successful operation of this facility during MSL-1R.

  19. Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.

    PubMed

    Ohishi, Akihiro; Nishida, Kentaro; Yamanaka, Yuri; Miyata, Ai; Ikukawa, Akiko; Yabu, Miharu; Miyamoto, Karin; Bansho, Saho; Nagasawa, Kazuki

    2016-01-01

    As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible. PMID:27040630

  20. Clinical review: Efficacy of antimicrobial-impregnated catheters in external ventricular drainage - a systematic review and meta-analysis

    PubMed Central

    2013-01-01

    To assess the efficacy of antimicrobial-impregnated catheters in preventing catheter-related infections during external ventricular drainage (EVD), we performed a meta-analysis and systematic review. We systematically searched Medline, Embase, and the Cochrane Library. All randomized controlled trials (RCTs) and nonrandomized prospective studies (NPSs) related to antimicrobial-impregnated EVD catheters were included. The primary outcome was the rate of cerebrospinal fluid infection (CFI). The secondary outcomes included the rate of time-dependent CFI and catheter bacterial colonization. We further performed subgroup analysis, meta-regression analysis, and microbial spectrum analysis. Four RCTs and four NPSs were included. The overall rate of CFIs was 3.6% in the antimicrobial-impregnated catheter group and 13.7% in the standard catheter group. The pooled data demonstrated that antimicrobial-impregnated catheters were superior to standard catheters in lowering the rate of CFIs (odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.12 to 0.52, P <0.05). In survival analysis, the 20-day infection rate was significantly reduced with the use of antimicrobial-impregnated catheters (hazard ratio = 0.52, 95% CI = 0.29 to 0.95, P <0.05). Furthermore, a significantly decreased rate of catheter bacterial colonization was noticed for antimicrobial-impregnated catheters (OR = 0.37, 95% CI = 0.21 to 0.64, P <0.05). In subgroup analyses, although significant results remained for RCTs and NPSs, a subgroup difference was revealed (P <0.05). Compared with standard catheters, a significantly lower rate of CFIs was noticed for clindamycin/rifampin-impregnated catheters (OR = 0.27, 95% CI = 0.10 to 0.73, P <0.05) and for minocycline/rifampin-impregnated catheters (OR = 0.11, 95% CI = 0.06 to 0.21, P <0.05). However, no statistical significance was found when compared with silver-impregnated catheters (OR = 0.33, 95% CI = 0.07 to 1.69, P = 0.18). In microbial spectrum analysis

  1. A modified and highly sensitive Golgi-Cox method to enable complete and stable impregnation of embryonic neurons.

    PubMed

    Koyama, Yoshihisa; Tohyama, Masaya

    2012-07-30

    The FD Rapid GolgiStain Kit (FD NeuroTechnologies, Inc., Ellicott City, MD) was developed using an improved Golgi-Cox impregnation method to provide stable, sensitive, and convenient staining of mature neurons. However, embryonic neurons cannot be clearly visualized using this method. We have further improved the Golgi-Cox method by introducing an additional aldehyde fixation step before impregnation; thus, we can stably and sufficiently impregnate fetal brain neurons so that even the fine branches of the dendritic trees are visible.

  2. Imatinib sensitivity as a consequence of a CSF1R-Y571D mutation and CSF1/CSF1R signaling abnormalities in the cell line GDM1.

    PubMed

    Chase, A; Schultheis, B; Kreil, S; Baxter, J; Hidalgo-Curtis, C; Jones, A; Zhang, L; Grand, F H; Melo, J V; Cross, N C P

    2009-02-01

    Imatinib is usually a highly effective treatment for myeloproliferative neoplasms (MPNs) associated with ABL, PDGFRA or PDGFRB gene fusions; however, occasional imatinib-responsive patients have been reported without abnormalities of these genes. To identify novel imatinib-sensitive lesions, we screened 11 BCR-ABL-negative cell lines and identified GDM1, derived from a patient with an atypical MPN (aMPN), as being responsive to imatinib. Screening of genes encoding known imatinib targets revealed an exon 12 mutation in the colony-stimulating factor 1 receptor (CSF1R; c-FMS) with a predicted Y571D amino-acid substitution. CSF1R in GDM1 was constitutively phosphorylated, but rapidly dephosphorylated on exposure to imatinib. Y571D did not transform FDCP1 cells to growth factor independence, but resulted in a significantly increased colony growth compared with controls, constitutive CSF1R phosphorylation and elevated CSF1R signaling. We found that GDM1 expresses CSF1, and CSF1 neutralization partially inhibited proliferation, suggesting the importance of both autocrine and intrinsic mechanisms of CSF1R activation. An extensive screen of CSF1R in aMPNs and acute myeloid leukemia identified three additional novel missense variants. None of these variants were active in transformation assays and are therefore likely to be previously unreported rare polymorphisms or non-pathogenic passenger mutations.

  3. The transcriptional regulation of the Colony-Stimulating Factor 1 Receptor (csf1r) gene during hematopoiesis.

    PubMed

    Bonifer, Constanze; Hume, David A

    2008-01-01

    The colony-stimulating-factor 1 receptor (CSF-1 R) is a tyrosine kinase receptor that is absolutely required for macrophage differentiation and thus occupies a central role in hematopoiesis. Mice deficient for the csf1r gene show multiple defects in macrophage development, reproduction and tissue remodeling. Moreover, deregulation of this gene is a hallmark of many tumors. This includes repression of expression in acute myeloid leukemia and aberrant activation in certain solid tumors, such as breast cancer. Expression of this gene therefore needs to be tightly controlled. This review summarizes experiments providing a detailed picture of how transcription of csf1r gene expression is regulated. Aside from the direct relevance to hematopoiesis, studies of csf1r transcriptional regulation provide a model for understanding the molecular mechanisms that control mammalian cell fate.

  4. A melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma.

    PubMed

    Wolnicka-Glubisz, Agnieszka; Strickland, Faith M; Wielgus, Albert; Anver, Miriam; Merlino, Glenn; De Fabo, Edward C; Noonan, Frances P

    2015-02-15

    Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We crossed these mice with yellow C57BL/6-Mc1re/e animals which have a non-functional Mc1r and produce predominantly yellow phaeomelanin. Yellow C57BL/6-Mc1re/e-HGF mice produced no melanoma in response to UVR or spontaneously even though the HGF transgene and its receptor Met were expressed. Total melanin was less than in C57BL/6-Mc1r+/+-HGF mice, hyperpigmentation was not observed and there were few extra-follicular melanocytes. Thus, functional Mc1r was required for expression of the transgenic HGF phenotype. Heterozygous C57BL/6-Mc1re/+-HGF mice were black and hyperpigmented and, although extra-follicular melanocytes and skin melanin content were similar to C57BL/6-Mc1r+/+-HGF animals, they developed UV-induced and spontaneous melanomas with significantly less efficiency by all criteria. Thus, heterozygosity for Mc1r was sufficient to restore the transgenic HGF phenotype but insufficient to fully restore melanoma. We conclude that a previously unsuspected melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma and postulate that this pathway is involved in human melanoma.

  5. Insulin-like growth factor receptor-1 (IGF-1R) expression in normal breast, proliferative breast lesions, and breast carcinoma.

    PubMed

    Bhargava, Rohit; Beriwal, Sushil; McManus, Kim; Dabbs, David J

    2011-05-01

    Insulin-like growth factor receptor 1 (IGF-1R) is a receptor protein tyrosine kinase that is activated by ligand (IGF-1) binding and promotes mitogenic, metastatic, and antiapoptotic phenotypes of breast cancer. There is a dearth of studies analyzing IGF-1R expression by immunohistochemistry in breast carcinoma. This biomarker analysis will be important for pharmacologic interventions that target the IGF system. IGF-1R expression pattern was first analyzed in normal breast tissue and a variety of breast lesions (71 diagnoses from 35 patients), followed by analysis in 191 consecutive invasive breast carcinomas. Furthermore, 86 carcinomas treated with neoadjuvant chemotherapy were also analyzed. The carcinomas were classified using immunohistochemical surrogate (to molecular classes) markers-estrogen receptors (ER), progesterone receptors, and human epidermal growth factor receptor 2. IGF-1R is expressed at moderate level in normal breast tissue which was considered as normal expression. Overexpression and lower expression were defined as higher than normal or lower than normal expression, respectively. Among the benign and noninvasive breast lesions, IGF-1R expression was slightly increased in lesions that are hormonally driven (such as atypical ductal hyperplasia and columnar cells changes) whereas it was significantly reduced in ER-negative lesions (such as apocrine metaplasia). Similarly, in 191 consecutive breast carcinomas, IGF-1R overexpression was predominantly seen in ER-positive+ tumors. The tumor group that consistently showed reduced expression was the ERBB2 group (ER negative/progesterone receptors negative/human epidermal growth factor receptor 2 positive). The expression was somewhat heterogeneous in the triple-negative group. IGF-1R expression was not predictive of pathologic complete response or tumor volume reduction in ER-negative tumors, but reduced IGF-1R was associated with pathologic complete response and significant tumor volume reduction in

  6. CSF-1R as an inhibitor of apoptosis and promoter of proliferation, migration and invasion of canine mammary cancer cells

    PubMed Central

    2013-01-01

    Background Tumor-associated macrophages (TAMs) have high impact on the cancer development because they can facilitate matrix invasion, angiogenesis, and tumor cell motility. It gives cancer cells the capacity to invade normal tissues and metastasize. The signaling of colony-stimulating factor-1 receptor (CSF-1R) which is an important regulator of proliferation and differentiation of monocytes and macrophages regulates most of the tissue macrophages. However, CSF-1R is expressed also in breast epithelial tissue during some physiological stages i.g.: pregnancy and lactation. Its expression has been also detected in various cancers. Our previous study has showed the expression of CSF-1R in all examined canine mammary tumors. Moreover, it strongly correlated with grade of malignancy and ability to metastasis. This study was therefore designed to characterize the role of CSF-1R in canine mammary cancer cells proliferation, apoptosis, migration, and invasion. As far as we know, the study presented hereby is a pioneering experiment in this field of veterinary medicine. Results We showed that csf-1r silencing significantly increased apoptosis (Annexin V test), decreased proliferation (measured as Ki67 expression) and decreased migration (“wound healing” assay) of canine mammary cancer cells. Treatment of these cells with CSF-1 caused opposite effect. Moreover, csf-1r knock-down changed growth characteristics of highly invasive cell lines on Matrigel matrix, and significantly decreased the ability of these cells to invade matrix. CSF-1 treatment increased invasion of cancer cells. Conclusion The evidence of the expression and functional role of the CSF-1R in canine mammary cancer cells indicate that CSF-1R targeting may be a good therapeutic approach. PMID:23561040

  7. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology

    PubMed Central

    Olmos-Alonso, Adrian; Schetters, Sjoerd T. T.; Sri, Sarmi; Askew, Katharine; Mancuso, Renzo; Vargas-Caballero, Mariana; Holscher, Christian; Perry, V. Hugh

    2016-01-01

    The proliferation and activation of microglial cells is a hallmark of several neurodegenerative conditions. This mechanism is regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the progression of conditions such as Alzheimer’s disease. However, the study of microglial proliferation in Alzheimer’s disease and validation of the efficacy of CSF1R-inhibiting strategies have not yet been reported. In this study we found increased proliferation of microglial cells in human Alzheimer’s disease, in line with an increased upregulation of the CSF1R-dependent pro-mitogenic cascade, correlating with disease severity. Using a transgenic model of Alzheimer’s-like pathology (APPswe, PSEN1dE9; APP/PS1 mice) we define a CSF1R-dependent progressive increase in microglial proliferation, in the proximity of amyloid-β plaques. Prolonged inhibition of CSF1R in APP/PS1 mice by an orally available tyrosine kinase inhibitor (GW2580) resulted in the blockade of microglial proliferation and the shifting of the microglial inflammatory profile to an anti-inflammatory phenotype. Pharmacological targeting of CSF1R in APP/PS1 mice resulted in an improved performance in memory and behavioural tasks and a prevention of synaptic degeneration, although these changes were not correlated with a change in the number of amyloid-β plaques. Our results provide the first proof of the efficacy of CSF1R inhibition in models of Alzheimer’s disease, and validate the application of a therapeutic strategy aimed at modifying CSF1R activation as a promising approach to tackle microglial activation and the progression of Alzheimer’s disease. PMID:26747862

  8. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer's-like pathology.

    PubMed

    Olmos-Alonso, Adrian; Schetters, Sjoerd T T; Sri, Sarmi; Askew, Katharine; Mancuso, Renzo; Vargas-Caballero, Mariana; Holscher, Christian; Perry, V Hugh; Gomez-Nicola, Diego

    2016-03-01

    The proliferation and activation of microglial cells is a hallmark of several neurodegenerative conditions. This mechanism is regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the progression of conditions such as Alzheimer's disease. However, the study of microglial proliferation in Alzheimer's disease and validation of the efficacy of CSF1R-inhibiting strategies have not yet been reported. In this study we found increased proliferation of microglial cells in human Alzheimer's disease, in line with an increased upregulation of the CSF1R-dependent pro-mitogenic cascade, correlating with disease severity. Using a transgenic model of Alzheimer's-like pathology (APPswe, PSEN1dE9; APP/PS1 mice) we define a CSF1R-dependent progressive increase in microglial proliferation, in the proximity of amyloid-β plaques. Prolonged inhibition of CSF1R in APP/PS1 mice by an orally available tyrosine kinase inhibitor (GW2580) resulted in the blockade of microglial proliferation and the shifting of the microglial inflammatory profile to an anti-inflammatory phenotype. Pharmacological targeting of CSF1R in APP/PS1 mice resulted in an improved performance in memory and behavioural tasks and a prevention of synaptic degeneration, although these changes were not correlated with a change in the number of amyloid-β plaques. Our results provide the first proof of the efficacy of CSF1R inhibition in models of Alzheimer's disease, and validate the application of a therapeutic strategy aimed at modifying CSF1R activation as a promising approach to tackle microglial activation and the progression of Alzheimer's disease.

  9. Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor.

    PubMed

    Assadi-Porter, Fariba M; Maillet, Emeline L; Radek, James T; Quijada, Jeniffer; Markley, John L; Max, Marianna

    2010-05-14

    The sweet protein brazzein [recombinant protein with sequence identical with the native protein lacking the N-terminal pyroglutamate (the numbering system used has Asp2 as the N-terminal residue)] activates the human sweet receptor, a heterodimeric G-protein-coupled receptor composed of subunits Taste type 1 Receptor 2 (T1R2) and Taste type 1 Receptor 3 (T1R3). In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: site 1 (Loop43), site 2 (N- and C-termini and adjacent Glu36, Loop33), and site 3 (Loop9-19). Basic residues in site 1 and acidic residues in site 2 were essential for positive responses from each assay. Mutation of Y39A (site 1) greatly reduced positive responses. A bulky side chain at position 54 (site 2), rather than a side chain with hydrogen-bonding potential, was required for positive responses, as was the presence of the native disulfide bond in Loop9-19 (site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus flytrap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in brazzein response. The exception, hT1R2 (human T1R2 subunit of the sweet receptor):R217A/hT1R3 (human T1R3 subunit of the sweet receptor), which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase

  10. Active surfaces: Ferrofluid-impregnated surfaces for active manipulation of droplets

    NASA Astrophysics Data System (ADS)

    Khalil, Karim; Mahmoudi, Seyed Reza; Abu-Dheir, Numan; Varanasi, Kripa

    2014-11-01

    Droplet manipulation and mobility on non-wetting surfaces is of practical importance for diverse applications ranging from micro-fluidic devices, anti-icing, dropwise condensation, and biomedical devices. The use of active external fields has been explored via electric, acoustic, and vibrational, yet moving highly conductive and viscous fluids remains a challenge. Magnetic fields have been used for droplet manipulation; however, usually, the fluid is functionalized to be magnetic, and requires enormous fields of superconducting magnets when transitioning to diamagnetic materials such as water. Here we present a class of active surfaces by stably impregnating active fluids such as ferrofluids into a textured surface. Droplets on such ferrofluid-impregnated surfaces have extremely low hysteresis and high mobility such that they can be propelled by applying relatively low magnetic fields. Our surface is able to manipulate a variety of materials including diamagnetic, conductive and highly viscous fluids, and additionally solid particles.

  11. Active surfaces: Ferrofluid-impregnated surfaces for active manipulation of droplets

    NASA Astrophysics Data System (ADS)

    Khalil, Karim S.; Mahmoudi, Seyed Reza; Abu-dheir, Numan; Varanasi, Kripa K.

    2014-07-01

    Droplet manipulation and mobility on non-wetting surfaces is of practical importance for diverse applications ranging from micro-fluidic devices, anti-icing, dropwise condensation, and biomedical devices. The use of active external fields has been explored via electric, acoustic, and vibrational, yet moving highly conductive and viscous fluids remains a challenge. Magnetic fields have been used for droplet manipulation; however, usually, the fluid is functionalized to be magnetic, and requires enormous fields of superconducting magnets when transitioning to diamagnetic materials such as water. Here we present a class of active surfaces by stably impregnating active fluids such as ferrofluids into a textured surface. Droplets on such ferrofluid-impregnated surfaces have extremely low hysteresis and high mobility such that they can be propelled by applying relatively low magnetic fields. Our surface is able to manipulate a variety of materials including diamagnetic, conductive and highly viscous fluids, and additionally solid particles.

  12. Low density microcellular carbon or catalytically impregnated carbon forms and process for their preparation

    DOEpatents

    Hopper, Robert W.; Pekala, Richard W.

    1989-01-01

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  13. Low density microcellular carbon or catalytically impregnated carbon foams and process for their preparation

    DOEpatents

    Hooper, R.W.; Pekala, R.W.

    1987-04-30

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  14. Low density microcellular carbon or catalytically impregnated carbon foams and process for their prepartion

    DOEpatents

    Hopper, Robert W.; Pekala, Richard W.

    1988-01-01

    Machinable and structurally stable, low density microcellular carbon, and catalytically impregnated carbon, foams, and process for their preparation, are provided. Pulverized sodium chloride is classified to improve particle size uniformity, and the classified particles may be further mixed with a catalyst material. The particles are cold pressed into a compact having internal pores, and then sintered. The sintered compact is immersed and then submerged in a phenolic polymer solution to uniformly fill the pores of the compact with phenolic polymer. The compact is then heated to pyrolyze the phenolic polymer into carbon in the form of a foam. Then the sodium chloride of the compact is leached away with water, and the remaining product is freeze dried to provide the carbon, or catalytically impregnated carbon, foam.

  15. Radiation dose from a phosphorous-32 impregnated wire mesh vascular stent.

    PubMed

    Janicki, C; Duggan, D M; Coffey, C W; Fischell, D R; Fischell, T A

    1997-03-01

    The near field dose distribution of a realistic vascular stent impregnated with radioactive 32P is calculated employing the dose-point-kernel (DPK) method in a homogeneous and uniform medium. The cylindrical wire mesh geometry for the Palmaz-Schatz [Palmaz-Schatz is a tradename of Cordis (a Johnson & Johnson company)] stent is incorporated in the model calculation, and the dose distribution generated by the beta particles emitted from the decayed radioactive 32P is computed at distances ranging from 0.1 to 2 mm exterior to the stent surface. Dose measurements were obtained using radiochromic film dosimetry media on an actual Palmaz-Schatz half-stent impregnated with 32P using ion implantation, and compared to the DPK model predictions. The close agreement between the model calculation and the film dosimetry data confirms the validity of the model which can be adapted to a variety of different stent designs.

  16. Low-density resin impregnated ceramic article and method for making the same

    NASA Technical Reports Server (NTRS)

    Tran, Huy K. (Inventor); Henline, William D. (Inventor); Hsu, Ming-ta S. (Inventor); Rasky, Daniel J. (Inventor); Riccitiello, Salvatore R. (Inventor)

    1997-01-01

    A low-density resin impregnated ceramic article advantageously employed as a structural ceramic ablator comprising a matrix of ceramic fibers. The fibers of the ceramic matrix are coated with an organic resin film. The organic resin can be a thermoplastic resin or a cured thermosetting resin. In one embodiment, the resin is uniformly distributed within the ceramic article. In a second embodiment, the resin is distributed so as to provide a density gradient along at least one direction of the ceramic article. The resin impregnated ceramic article is prepared by providing a matrix of ceramic fibers; immersing the matrix of ceramic fibers in a solution of a solvent and an organic resin infiltrant; and removing the solvent to form a resin film on the ceramic fibers.

  17. Enhancement of eucalypt chips' enzymolysis efficiency by a combination method of alkali impregnation and refining pretreatment.

    PubMed

    Huo, Dan; Fang, Guigan; Yang, Qiulin; Han, Shanming; Deng, Yongjun; Shen, Kuizhong; Lin, Yan

    2013-12-01

    A combination process of alkali impregnation and refining was used as a pretreatment to improve the production of fermentable sugar. The surface structures and crystallinities of wood samples were characterized to explain the relationships between the pretreatment action and enzymatic efficiency. After refining, the reducing sugar contents in hydrolyzates were analyzed by UV-Vis and HPLC. The results showed that the enzymatic efficiency could be improved by the combined pretreatment, due to the increment of specific surface area and the release of more free hydroxyls. Comparing to the sodium hydroxide and deionized water, the impregnation with magnesium hydroxide had low refining energy consumption and high yield of reducing sugar (glucose and xylose) in enzymolysis process, where about 560 kWh/t of the energy was saved in refining, and the yield of the reducing sugar was as high as 91.53%. And the enzymolysis could be improved by a certain amount of magnesium ions.

  18. Increased anatomical detail by in vitro MR microscopy with a modified Golgi impregnation method.

    PubMed

    Zhang, Xiaowei; Bearer, Elaine L; Perles-Barbacaru, Adriana T; Jacobs, Russell E

    2010-05-01

    Golgi impregnation is unique in its ability to display the dendritic trees and axons of large numbers of individual neurons by histology. Here we apply magnetic resonance microscopy to visualize the neuroanatomy of animal models by combining histologic fixation chemistry with paramagnetic contrast agents. Although there is some differential uptake of the standard small-molecular-weight contrast agents by different tissue types, detailed discrimination of tissue architecture in MR images does not approach that of standard histology. Our modified Golgi impregnation method significantly increases anatomic detail in magnetic resonance microscopy images. Fixed mouse brains were treated with a solution containing a paramagnetic contrast agent (gadoteridol) and potassium dichromate. Results demonstrate a specific contrast enhancement likely due to diamagnetic hexavalent chromium undergoing tissue specific reduction to paramagnetic trivalent chromium. This new method dramatically improves neuroanatomical contrast compared to conventional fixation, displaying detail approximating that of histologic specimens at low (4x) magnification.

  19. Preparation of FeCeOx by ultrasonic impregnation method for heterogeneous Fenton degradation of diclofenac.

    PubMed

    Chong, Shan; Zhang, Guangming; Zhang, Nan; Liu, Yucan; Zhu, Jia; Huang, Ting; Fang, Shunyan

    2016-09-01

    FeCeOx has been successfully synthesized by ultrasonic impregnation method and applied in diclofenac removal in heterogeneous Fenton process. The effects of ultrasonic density, impregnation time, mole ratio of Fe and Ce and calcination temperature were investigated. Nitrogen adsorption/desorption, SEM, XRD, HRTEM, Raman and XPS analyses were characterized. Stability and reusability of FeCeOx were evaluated. The results indicated that 83% degradation efficiency of diclofenac was achieved by FeCeOx under the optimum preparation conditions. Fe ions were distributed uniformly in crystal structure and the solid solution structure of FeCeOx with a lattice constriction was formed. Exposed crystalline plane (200) with a relatively high surface energy may be the main reason to provide high catalytic activity of FeCeOx. Oxygen vacancies took part in catalytic process and a portion of them were oxidized after reaction. FeCeOx showed an excellent chemical stability and reusability in heterogeneous Fenton process.

  20. Reactivity of cellulose reducing end in pyrolysis as studied by methyl glucoside-impregnation.

    PubMed

    Matsuoka, Seiji; Kawamoto, Haruo; Saka, Shiro

    2016-02-01

    For better understanding of the roles of cellulose reducing ends during thermal degradation of cellulose and wood, cellulose samples impregnated with methyl-β-D-glucopyranoside (GlcβOMe), a simple non-reducing sugar model, were pyrolyzed under N2 at relatively low temperatures of 200-280 °C. By the impregnation, cellulose was rather stabilized against discoloration and weight-loss through converting the reducing ends into the glycosides with GlcβOMe. Alternatively, polymerization and discoloration of GlcβOMe were accelerated in the presence of cellulose. A mechanism via reducing sugars as reactive intermediates formed through hydrolysis is proposed to explain these phenomena. These information would be useful to understand the interactions between cellulose and hemicellulose in wood cell wall as well as the role of the reducing ends in cellulose thermal degradation. PMID:26717548

  1. Thermal-mechanical properties of epoxy-impregnated Bi-2212/Ag composite

    SciTech Connect

    Li, Pei; Wang, Yang; Godeke, Arno; Ye, Liyang; Flanagan, Gene; Shen, Tengming

    2014-11-26

    In this study, knowledge of the thermal-mechanical properties of epoxy/superconductor/insulation composite is important for designing, fabricating, and operating epoxy impregnated high field superconducting magnets near their ultimate potentials. We report measurements of the modulus of elasticity, Poisson's ratio, and the coefficient of thermal contraction of epoxy-impregnated composite made from the state-of-the-art powder-in-tube multifilamentary Ag/Bi2Sr2CaCu2Ox round wire at room temperature and cryogenic temperatures. Stress-strain curves of samples made from single-strand and Rutherford cables were tested under both monotonic and cyclic compressive loads, with single strands insulated using a thin TiO2 insulation coating and the Rutherford cable insulated with a braided ceramic sleeve.

  2. Thermal-mechanical Properties of Epoxy-impregnated Bi-2212/Ag Composite

    SciTech Connect

    Li, Pei; Wang, Yang; Godeke, Arno; Ye, Liyang; Flanagan, Gene; Shen, Tengming

    2014-11-26

    Knowledge of the thermal-mechanical properties of epoxy/superconductor/insulation composite is important for designing, fabricating, and operating epoxy impregnated high field superconducting magnets near their ultimate potentials. We report measurements of the modulus of elasticity, Poisson’s ratio, and the coefficient of thermal contraction of epoxy-impregnated composite made from the state-of-the-art powder-in-tube multifilamentary Ag/Bi2Sr2CaCu2Ox round wire at room temperature and cryogenic temperatures. Stress-strain curves of samples made from single-strand and Rutherford cables were tested under both monotonic and cyclic compressive loads, with single strands insulated using a thin TiO2 insulation coating and the Rutherford cable insulated with a braided ceramic sleeve.

  3. Suitability of LN2 impregnated Open-Cell Foam as Electric Insulant for Superconducting Power Equipment

    NASA Astrophysics Data System (ADS)

    Sumereder, C.; Mifka, M.; Muhr, M.

    2006-06-01

    The suitability of an open-cell foam is investigated for the application as electric insulant in superconducting power equipment. The tested foam is made from melamine resin, a thermoset plastic from the aminoplastics group; it is a mechanical very flexible material with excellence compatibility to high and low temperature. The aim of these investigations was to test the aptitude of the liquid nitrogen impregnated open-cell foam with respect to the dielectric properties and the electric strength under different conditions. In this paper the results of permittivity measurements and ramp voltage tests are discussed and an outlook for future applications is given. The tests showed excellence mechanical and thermal characteristics for the application in LN2 vessels. The ACBV of the LN2 impregnated foam was 50 % less than the ACBV of pure LN2.

  4. Photoluminescence of fluoroacrylate polymers impregnated with Eu(bta)3 using supercritical CO2

    NASA Astrophysics Data System (ADS)

    Gerasimova, V. I.; Antoshkov, A. A.; Zavorotny, Yu. S.; Lemenovskii, D. A.

    2012-05-01

    Optical properties (photoluminescence and absorption) of Eu(bta)3(B) n (B = H2O or 1,10-phenanthroline) polycrystalline powders and fluoroacrylate polymers (FAPs) impregnated with these compounds using supercritical CO2 (SC CO2) were investigated. It was established that impregnation of Eu(bta)3phen into the FAPs using an SC CO2 solution was difficult to achieve. The type of B (ancillary ligand) and the polymer matrix were shown to influence the temperature quenching of photoluminescence of Eu3+ ions in the range 25-100°C. A comparative analysis of quantum yields (λex = 300 and 380 nm) and photoluminescence decay times (λex = 337.1 nm) for Eu(bta)3B n and for Eu(bta)3B n -doped FAPs was performed.

  5. TiO2 impregnated graphene nanostructures: An effectual photocatalysts for water remediation application

    NASA Astrophysics Data System (ADS)

    Rakkesh, R. Ajay; Durgalakshmi, D.; Balakumar, S.

    2015-06-01

    In this work, we describe the fabrication of nanohybrid TiO2 impregnated Graphene nanostructures by modified Hummer's method. The chemically impregnated TiO2-Graphene hybrid nanostructures drastically enhanced their photodegradation activity of methylene blue (MB) dye in an aqueous medium compare to pure TiO2 nanoparticles. The enhancement in the photocatalytic activity was ascribed by a heterojunction between TiO2-Graphene interfaces. It remarkably decreased the recombination rate and likewise increased the number of holes participating in the photodegradation process, confirmed by XPS analysis. This study can provide a new insight for constructing the hybrid photocatalysts, which can be used in environmental pollution and water treatment applications.

  6. Surface composition and chemical state of Fe and Mo impregnated subbituminous coal

    SciTech Connect

    Ni, H.; Anderson, R.K.; Givens, E.N.; Stencel, J.M.

    1994-12-31

    The surface composition and chemical states of elements in samples of Wyodak subbituminous coal impregnated with Fe and Mo were investigated. The concentrations of Fe, Mo, S, Al, Si, Ca, C, O, and N were determined by x-ray photoelectron spectroscopy (XPS) in samples impregnated with 0.7-2.0 wt% Fe and 500-1000 ppm Mo. The metals were deposited on the samples by an incipient wetness technique using solutions of ferric nitrate, ferric sulfate, ferrous sulfate and ammonium molybdate. The effect of the metal precursor, the relative amounts of Fe and Mo loading, the effect of base-treatment with NH{sub 4}OH and the chemical states of the elements are discussed. Deconvolution of the overlapped S{sub 2}, and Mo{sub 3d} peaks is described along with a brief overview of the liquefaction performance of these coals.

  7. Increased Anatomical Detail by In Vitro MR Microscopy With a Modified Golgi Impregnation Method

    PubMed Central

    Zhang, Xiaowei; Bearer, Elaine L.; Perles-Barbacaru, Adriana T.; Jacobs, Russell E.

    2010-01-01

    Golgi impregnation is unique in its ability to display the dendritic trees and axons of large numbers of individual neurons by histology. Here we apply magnetic resonance microscopy to visualize the neuroanatomy of animal models by combining histologic fixation chemistry with paramagnetic contrast agents. Although there is some differential uptake of the standard small-molecular-weight contrast agents by different tissue types, detailed discrimination of tissue architecture in MR images does not approach that of standard histology. Our modified Golgi impregnation method significantly increases anatomic detail in magnetic resonance microscopy images. Fixed mouse brains were treated with a solution containing a paramagnetic contrast agent (gadoteridol) and potassium dichromate. Results demonstrate a specific contrast enhancement likely due to diamagnetic hexavalent chromium undergoing tissue specific reduction to paramagnetic trivalent chromium. This new method dramatically improves neuroanatomical contrast compared to conventional fixation, displaying detail approximating that of histologic specimens at low (4×) magnification. PMID:20432310

  8. Feasibility and Manufacturing Considerations of Hemp Textile Fabric Utilized in Pre-Impregnated Composites

    NASA Astrophysics Data System (ADS)

    Osusky, Gregory

    This study investigates the fabrication and mechanical properties of semicontinuous, hemp fiber reinforced thermoset composites. This research determines if off-the-shelf refined woven hemp fabric is suitable as composite reinforcement using resin pre-impregnated method. Industrial hemp was chosen for its low cost, low resource input as a crop, supply chain from raw product to refined textile and biodegradability potential. Detail is placed on specimen fabrication considerations. Lab testing of tension and compression is conducted and optimization considerations are examined. The resulting composite is limited in mechanical properties as tested. This research shows it is possible to use woven hemp reinforcement in pre-impregnated processed composites, but optimization in mechanical properties is required to make the process commercially practical outside niche markets.

  9. Thermal-mechanical properties of epoxy-impregnated Bi-2212/Ag composite

    DOE PAGESBeta

    Li, Pei; Wang, Yang; Fermi National Accelerator Lab.; Godeke, Arno; National High Magnetic Field Lab., Tallahassee, FL; Ye, Liyang; Fermi National Accelerator Lab.; Flanagan, Gene; Shen, Tengming

    2014-11-26

    In this study, knowledge of the thermal-mechanical properties of epoxy/superconductor/insulation composite is important for designing, fabricating, and operating epoxy impregnated high field superconducting magnets near their ultimate potentials. We report measurements of the modulus of elasticity, Poisson's ratio, and the coefficient of thermal contraction of epoxy-impregnated composite made from the state-of-the-art powder-in-tube multifilamentary Ag/Bi2Sr2CaCu2Ox round wire at room temperature and cryogenic temperatures. Stress-strain curves of samples made from single-strand and Rutherford cables were tested under both monotonic and cyclic compressive loads, with single strands insulated using a thin TiO2 insulation coating and the Rutherford cable insulated with a braided ceramicmore » sleeve.« less

  10. Long-Lasting Permethrin-Impregnated Clothing Protects Against Mosquito Bites in Outdoor Workers.

    PubMed

    Londono-Renteria, Berlin; Patel, Jaymin C; Vaughn, Meagan; Funkhauser, Sheana; Ponnusamy, Loganathan; Grippin, Crystal; Jameson, Sam B; Apperson, Charles; Mores, Christopher N; Wesson, Dawn M; Colpitts, Tonya M; Meshnick, Steven R

    2015-10-01

    Outdoor exposure to mosquitoes is a risk factor for many diseases, including malaria and dengue. We have previously shown that long-lasting permethrin-impregnated clothing protects against tick and chigger bites in a double-blind randomized controlled trial in North Carolina outdoor workers. Here, we evaluated whether this clothing is protective against mosquito bites by measuring changes in antibody titers to mosquito salivary gland extracts. On average, there was a 10-fold increase in titer during the spring and summer when mosquito exposure was likely to be the highest. During the first year of the study, the increase in titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of control subjects. This finding suggests that long-lasting permethrin-impregnated clothing provided protection against mosquito bites.

  11. Drug loading of polymer implants by supercritical CO2 assisted impregnation: A review.

    PubMed

    Champeau, M; Thomassin, J-M; Tassaing, T; Jérôme, C

    2015-07-10

    Drug loaded implants also called drug-eluting implants have proven their benefits over simple implants. Among the developed manufacturing processes, the supercritical CO2 (scCO2) assisted impregnation has attracted growing attention to load Active Pharmaceutical Ingredients into polymer implants since it enables to recover a final implant free of any solvent residue and to operate under mild temperature which is suitable for processing with thermosensitive drugs. This paper is a review of the state-of-the-art and the application of the scCO2 assisted impregnation process to prepare drug-eluting implants. It introduces the process and presents its advantages for biomedical applications. The influences of the characteristics of the implied binary systems and of the experimental conditions on the drug loading are described. Then, the various current applications of this process for manufacturing drug-eluting implants are reviewed. Finally, the new emerging variations of this process are described.

  12. Influence of loss of function MC1R variants in genetic susceptibility of familial melanoma in Spain.

    PubMed

    de Torre, Carlos; Garcia-Casado, Zaida; Martínez-Escribano, Jorge A; Botella-Estrada, Rafael; Bañuls, Jose; Oliver, Vicente; Mercader, Pedro; Azaña, Jose M; Frias, Javier; Nagore, Eduardo

    2010-08-01

    We explored the presence of germline alterations in CDK4 exon 2, CDKN2A and MC1R in a hospital-based study of 89 melanoma cases from 89 families with at least two members affected by cutaneous melanoma. A total of 30% of the melanoma kindreds studied were carriers of CDKN2A variants, and three of these variants were known predominant alleles that have been identified earlier in Mediterranean populations (p.G101W, p.V59G and c.358delG). We observed a higher frequency of nonsynonymous MC1R variants in these Spanish melanoma kindreds (72%) with respect to the general population (60%). We observed a higher frequency of nonsynonymous MC1R variants in this Spanish melanoma kindred (72%) respect to general population (60%). A new classification of MC1R variants based on their functional effects over melanocortin-1 receptor, including the dominant-negative effect of some of them in heterozygotes, suggested an association of loss of function MC1R variants and multiple primary melanoma cases from melanoma kindred (odds ratio: 6.07, 95% confidence interval: 1.35-27.20). This study proposes the relevance of loss of function MC1R variants in the risk of melanoma in multiple primary melanoma cases with family history from areas with low melanoma incidence rate. PMID:20539244

  13. Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis.

    PubMed

    Heidegger, Isabel; Kern, Johann; Ofer, Philipp; Klocker, Helmut; Massoner, Petra

    2014-05-15

    We scrutinized the effect of insulin receptor (INSR) in addition to IGF1R in PCa using in vitro and in vivo models. In-vitro overexpression of IGF1R and INSRA, but not INSRB increased cell proliferation, colony formation, migration, invasion and resistance to apoptosis in prostate cancer cells (DU145, LNCaP, PC3). Opposite effects were induced by downregulation of IGF1R and total INSR, but not INSRB. In contrast to tumor cells, non-cancerous epithelial cells of the prostate (EP156T, RWPE-1) were inhibited on overexpression and stimulated by knockdown of receptors. In-vivo analyses using the chicken allantoic membrane assay confirmed the tumorigenic effects of IGF1R and INSR. Apart of promoting tumor growth, IGF1R and INSR overexpression also enhanced angiogenesis indicated by higher vessel density and increased number of desmin-immunoreactive pericytes. Our study underscores the oncogenic impact of IGF1R including significant effects on tumor growth, cell migration, sensitivity to apoptotic/chemotherapeutic agents and angiogenesis, and characterizes the INSR, in particular the isoform INSRA, as additional cancer-promoting receptor in prostate cancer. Both, the insulin-like growth factor receptor 1 and the insulin receptor exert oncogenic functions, thus proposing that both receptors need to be considered in therapeutic settings.

  14. MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation.

    PubMed

    García-Borrón, Jose C; Abdel-Malek, Zalfa; Jiménez-Cervantes, Celia

    2014-09-01

    The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC1R gene are a major source of normal variation of human hair color and skin pigmentation, response to ultraviolet radiation (UVR), and skin cancer susceptibility. The identification of a surprisingly high number of MC1R natural variants strongly associated with pigmentary phenotypes and increased skin cancer risk has prompted research on the functional properties of the wild-type receptor and frequent mutant alleles. We summarize current knowledge on MC1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR.

  15. Biomimetic membranes with aqueous nano channels but without proteins: impedance of impregnated cellulose ester filters.

    PubMed

    Kocherginsky, Nikolai M; Lvovich, Vadim F

    2010-12-01

    Earlier we have shown that many important properties of ionic aqueous channels in biological membranes can be imitated using simple biomimetic membranes. These membranes are composed of mixed cellulose ester-based filters, impregnated with isopropyl myristate or other esters of fatty acids, and can be used for high-throughput drug screening. If the membrane separates two aqueous solutions, combination of relatively hydrophilic polymer support with immobilized carboxylic groups results in the formation of thin aqueous layers covering inner surface of the pores, while the pore volume is filled by lipid-like substances. Because of these aqueous layers biomimetic membranes even without proteins have a cation/anion ion selectivity and specific (per unit of thickness) electrical properties, which are similar to typical properties of biological membranes. Here we describe frequency-dependent impedance of the isopropyl myristate-impregnated biomimetic membranes in the 4-electrode arrangement and present the results as Bode and Nyquist diagrams. When the membranes are placed in deionized water, it is possible to observe three different dispersion processes in the frequency range 0.1 Hz to 30 kHz. Only one dispersion is observed in 5 mM KH(2)PO(4) solution. It is suggested that these three dispersion features are determined by (a) conductivity in aqueous structures/channels, formed near the internal walls of the filter pores at high frequencies, (b) dielectric properties of the whole membrane at medium frequencies, determined by polymer support, aqueous layers and impregnating oil, and, finally, (c) by the processes in hydrated liquid crystal structures formed in pores by impregnating oil in contact with water at low frequencies. PMID:21033753

  16. Preconcentration of trace metals from sea water with 7-dodecenyl-8-quinolinol impregnated macroporous resin

    SciTech Connect

    Isshiki, K.; Tsuji, F.; Kuwamoto, T.; Nakayama, E.

    1987-10-15

    7-Dodecenyl-8-quinolinol (DDQ) impregnated XAD-4 resin (DDQ resin) was prepared, and its extraction behavior was studied and compared with solvent extraction with DDQ for Aq, Al, Bi, Cd, Cu, Fe, Ga, Mn, Ni, Pb, and Ti. The results demonstrate that the DDQ resin is effective in the preconcentration of those metals from sea water. The column extraction method using the DDQ resin was applied to sea water analysis with satisfactory results being obtained.

  17. Improvement of the process for electrochemical impregnation of nickel hydroxide electrodes

    NASA Technical Reports Server (NTRS)

    Comtat, M.; Lafage, B.; Leonardi, J.

    1986-01-01

    Nickel hydroxide electrodes containing 11g/dsqm hydroxide, with capacities of 3.6 to 3.8 Ah/dsqm were prepared at 353 K by electrochemical impregnation. The reproducibility of the results is obtained by readjusting the pH before each preparation. The control of each electrode is done during two cycles of charge and discharge following the manufacture by a potential relaxation method.

  18. Ethylene sensing by silver(I) salt-impregnated luminescent films

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Luminescent oligomer /polymer films impregnated with Ag(I) salts are effective sensors for small gas molecules such as ethylene. Films composed of various Ag(I) salts (i.e. AgBF4, AgSbF6, AgB(C6F5)4, AgClO4 and AgOTf) and polymers (i.e. poly(vinylphenylketone) (PVPK), polystyrene (PS) or oligomers (...

  19. Salts of the iodine oxyacids in the impregnation of adsorbent charcoal for trapping radioactive methyliodide

    DOEpatents

    Deitz, Victor R.; Blachly, Charles H.

    1977-04-05

    Radioactive iodine and radioactive methyliodide can be more than 99.7 per cent removed from the air stream of a nuclear reactor by passing the air stream through a 2-inch thick filter which is made up of impregnated charcoal prepared by contacting the charcoal with a solution containing KOH, iodine or an iodide, and an oxyacid, followed by contacting with a solution containing a tertiary amine.

  20. Flexural Strength Comparison of Silorane- and Methacrylate-Based Composites with Pre-impregnated Glass Fiber

    PubMed Central

    Doozandeh, Maryam; Alavi, Ali Asghar; Karimizadeh, Zahra

    2016-01-01

    Statement of the Problem Sufficient adhesion between silorane/methacrylate-based composites and methacrylate impregnated glass fiber increases the benefits of fibers and enhances the mechanical and clinical performance of both composites. Purpose The aim of this study was to evaluate the compatibility of silorane and methacrylate-based composites with pre-impregnated glass fiber by using flexural strength (FS) test. Materials and Method A total of 60 bar specimens were prepared in a split mold (25×2×2 mm) in 6 groups (n=10). In groups 1 and 4 (control), silorane-based (Filtek P90) and nanohybrid (Filtek Z350) composites were placed into the mold and photopolymerized with a high-intensity curing unit. In groups 2 and 5, pre-impregnated glass fiber was first placed into the mold and after two minutes of curing, the mold was filled with respective composites. Prior to filling the mold in groups 3 and 6, an intermediate adhesive layer was applied to the glass fiber. The specimens were stored in distilled water for 24 hours and then their flexural strength was measured by 3 point bending test, using universal testing machine at the crosshead speed of 1 mm/min. Two-way ANOVA and post-hoc test were used for analyzing the data (p< 0.05). Results A significant difference was observed between the groups (p< 0.05). The highest FS was registered for combination of Z350 composite, impregnated glass fiber, and application of intermediate adhesive layer .The lowest FS was obtained in Filtek P90 alone. Cohesive failure in composite was the predominant failure in all groups, except group 5 in which adhesive failure between the composite and fiber was exclusively observed. Conclusion Significant improvement in FS was achieved for both composites with glass fiber. Additional application of intermediate adhesive layer before composite build up seems to increase FS. Nanohybrid composite showed higher FS than silorane-based composite. PMID:27284555

  1. Silver or Nitrofurazone Impregnation of Urinary Catheters Has a Minimal Effect on Uropathogen Adherence

    PubMed Central

    Desai, Devak G.; Liao, Kershena S.; Cevallos, Manuel E.; Trautner, Barbara W.

    2010-01-01

    Purpose Bacterial adherence to the urinary catheter is an early step in biofilm formation and the pathogenesis of catheter associated urinary tract infection. We studied in vitro the effect of silver or nitrofurazone impregnation of urinary catheters on uropathogen ability to adhere to urinary catheters. Materials and Methods We studied commercially available nitrofurazone-silicone, silicone only, silver-silicone-hydrogel, silicone-hydrogel, silver-latex-hydrogel and latex-hydrogel catheters. Catheters were incubated in sterile broth for 0, 3, 5, 7 and 10 days, respectively, before inoculation and overnight incubation with Escherichia coli or Enterococcus faecalis. Results Adherence of E. coli and E. faecalis to nitrofurazone catheters was significantly decreased compared to that of silicone-only catheters when catheters were fresh. The anti-adherence effect of nitrofurazone on E. coli decreased with time but was still significant at 5 days. For E. faecalis the effect of nitrofurazone was lost by 3 days of pre-incubation. E. coli adherence was not significantly decreased on silver impregnated catheters compared to that on control catheters of the same base material. Silver was associated with a significant decrease in E. faecalis adherence to latex-hydrogel catheters but not to silicone-hydrogel catheters. The adherence of each species to silicone catheters with hydrogel was significantly lower than that to silicone-only control catheters. Conclusions Silver impregnation had little effect on bacterial adherence in our model and nitrofurazone impregnation had a significant effect only for the first 5 days. Our results do not support a role for silver urinary catheters to prevent catheter associated urinary tract infection by decreasing bacterial adherence. PMID:21030042

  2. Biomimetic membranes with aqueous nano channels but without proteins: impedance of impregnated cellulose ester filters.

    PubMed

    Kocherginsky, Nikolai M; Lvovich, Vadim F

    2010-12-01

    Earlier we have shown that many important properties of ionic aqueous channels in biological membranes can be imitated using simple biomimetic membranes. These membranes are composed of mixed cellulose ester-based filters, impregnated with isopropyl myristate or other esters of fatty acids, and can be used for high-throughput drug screening. If the membrane separates two aqueous solutions, combination of relatively hydrophilic polymer support with immobilized carboxylic groups results in the formation of thin aqueous layers covering inner surface of the pores, while the pore volume is filled by lipid-like substances. Because of these aqueous layers biomimetic membranes even without proteins have a cation/anion ion selectivity and specific (per unit of thickness) electrical properties, which are similar to typical properties of biological membranes. Here we describe frequency-dependent impedance of the isopropyl myristate-impregnated biomimetic membranes in the 4-electrode arrangement and present the results as Bode and Nyquist diagrams. When the membranes are placed in deionized water, it is possible to observe three different dispersion processes in the frequency range 0.1 Hz to 30 kHz. Only one dispersion is observed in 5 mM KH(2)PO(4) solution. It is suggested that these three dispersion features are determined by (a) conductivity in aqueous structures/channels, formed near the internal walls of the filter pores at high frequencies, (b) dielectric properties of the whole membrane at medium frequencies, determined by polymer support, aqueous layers and impregnating oil, and, finally, (c) by the processes in hydrated liquid crystal structures formed in pores by impregnating oil in contact with water at low frequencies.

  3. Process for impregnating a concrete or cement body with a polymeric material

    DOEpatents

    Mattus, A.J.; Spence, R.D.

    1988-05-04

    A process for impregnating cementitious solids with polymeric materials by blending polymeric materials in a grout, allowing the grout to cure, and contacting the resulting solidified grout containing the polymeric materials with an organic mixture containing a monomer, a cross-linking agent and a catalyst. The mixture dissolves the polymerized particles and forms a channel for distributing the monomer throughout the network formed by the polymeric particles. The organic components are then cured to form a substantially water-impermeable mass.

  4. Process for impregnating a concrete or cement body with a polymeric material

    DOEpatents

    Mattus, Alfred J.; Spence, Roger D.

    1989-01-01

    A process for impregnating cementitious solids with polymeric materials by blending polymeric materials in a grout, allowing the grout to cure, and contacting the resulting solidified grout containing the polymeric materials with an organic mixture containing a monomer, a cross-linking agent and a catalyst. The mixture dissolves the polymerized particles and forms a channel for distributing the monomer throughout the network formed by the polymeric particles. The organic components are then cured to form a substantially water-impermeable mass.

  5. Bio-inspired surfactant assisted nano-catalyst impregnation of Solid-Oxide Fuel Cell (SOFC) electrodes

    DOE PAGESBeta

    Ozmen, Ozcan; Zondlo, John W.; Lee, Shiwoo; Gerdes, Kirk; Sabolsky, Edward M.

    2015-11-02

    A bio-inspired surfactant was utilized to assist in the efficient impregnation of a nano-CeO₂ catalyst throughout both porous Solid Oxide Fuel Cells (SOFC’s) electrodes simultaneously. The process included the initial modification of electrode pore walls with a polydopamine film. The cell was then submersed into a cerium salt solution. The amount of nano-CeO₂ deposited per impregnation step increased by 3.5 times by utilizing this two-step protocol in comparison to a conventional drip impregnation method. The impregnated cells exhibited a 20% higher power density than a baseline cell without the nano-catalyst at 750°C (using humid H₂ fuel).

  6. Effect Of Reaction Environments On The Reactivity Of PCB (2-Chlorobiphenyl) Over Activated Carbon Impregnated With Palladized Iron

    EPA Science Inventory

    Reactive activated carbon (RAC) impregnated with palladized iron nanoparticles has been developed to treat polychlorinated biphenyls (PCBs). In this study, we evaluated the effects of various reaction environments on the adsorption-mediated dechlorination of 2-chlorobiphenyl (2-...

  7. Preparation of alumina-supported ceria. II. Measurement of ceria surface area after impregnation with platinum or rhodium

    SciTech Connect

    Rogemond, E.; Frety, R.; Perrichon, V.; Primet, M. |

    1997-07-01

    The surface area of cerium oxide was evaluated in an aluminium oxide supported catalyst. The catalyst were impregnated with rhodium chlorides and platinum chlorides. The adsorption of carbon dioxide is discussed.

  8. Functional characterization of the heterodimeric sweet taste receptor T1R2 and T1R3 from a New World monkey species (squirrel monkey) and its response to sweet-tasting proteins.

    PubMed

    Liu, Bo; Ha, Matthew; Meng, Xuan-Yu; Khaleduzzaman, Mohammed; Zhang, Zhe; Li, Xia; Cui, Meng

    2012-10-19

    The family C G protein-coupled receptor (GPCR) T1R2 and T1R3 heterodimer functions as a broadly acting sweet taste receptor. Perception of sweet taste is a species-dependent physiological process. It has been widely reported that New World monkeys and rodents are not able to perceive some of the artificial sweeteners and sweet-tasting proteins that can be perceived by humans, apes, and Old World monkeys. Until now, only the sweet receptors of humans, mice and rats have been functionally characterized. Here we report characterization of the sweet taste receptor (T1R2/T1R3) from a species of New World primate, squirrel monkey. Our results show that the heterodimeric receptor of squirrel monkey does not respond to artificial sweeteners aspartame, neotame, cyclamate, saccharin and sweet-tasting protein monellin, but surprisingly, it does respond to thaumatin at high concentrations (>18 μM). This is the first report demonstrating that species of New World monkey can perceive some specific sweet-tasting proteins. Furthermore, the sweet receptor of squirrel monkey responses to the such sweeteners cannot be inhibited by the sweet inhibitor lactisole. We compared the response differences of the squirrel monkey and human receptors and found that the residues in T1R2 determine species-dependent sweet taste toward saccharin, while the residues in either T1R2 or T1R3 are responsible for the sweet taste difference between humans and squirrel monkeys toward monellin. Molecular models indicated that electrostatic properties of the receptors probably mediate the species-dependent response to sweet-tasting proteins.

  9. Are interpretations of other people's arguments value-impregnated? A pilot study among medical students.

    PubMed

    Juth, Niklas; Nilsonne, Åsa; Lynöe, Niels

    2013-08-01

    Analogously to Kuhn's and Hanson's understanding of observation as theory-impregnated, we try to test the hypothesis that observation and interpretation might also be value-impregnated. We use a written examination task for medical students who were asked to read and interpret a text where the authors provide arguments pro et contra euthanasia. Afterwards the students were asked to provide their own reflected opinion on the issue. We found that medical students who were against and indecisive provided interpretations of the text which accorded with their own reflected opinions (P = 0.02), indicating that their interpretations were influenced by their own values. When including those who were pro euthanasia, the association was no longer significant. Although the present investigation was a small pilot-study, we obtained partial support for our hypothesis and have adjusted it to read as follows: observations and interpretations might be value-impregnated for respondents who have rather strong value-based attitudes. We think the adjusted hypothesis deserves to be further examined.

  10. Efficacy of Antibiotic-Impregnated Polymethylmethacrylate Beads in a Rhesus Macaque (Macaca mulatta) with Osteomyelitis

    PubMed Central

    Kelly, Kristi R; Kapatkin, Amy R; Zwingenberger, Allison L; Christe, Kari L

    2012-01-01

    Here we describe the successful surgical implementation of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with marked osteomyelitis. The macaque presented to the veterinary clinic with grossly contaminated bite wounds in the left ankle secondary to conspecific trauma. Radiographic findings were highly suggestive of osteomyelitis. Additional differential diagnoses included bony infarct, fracture, and cellulitis. In light of the location of the lesion and extensive tissue trauma, the animal had a poor prognosis. Systemic, broad-spectrum antibiotics were instituted. After 2 wk of care, lesions did not respond to empirical therapies. On consultation, a veterinary orthopedic surgeon at another facility recommended placement of antibiotic-impregnated polymethylmethacrylate beads at the sites of osteomyelitis. The animal underwent minor surgery in which beads were introduced into the wound. The monkey had a positive response to therapy. The animal regained full function and was returned to outdoor social housing. Veterinarians are encouraged to consider using antibiotic-impregnated polymethylmethacrylate beads when treating osteomyelitis in other nonhuman primates and in other traditional laboratory animal species. PMID:23043785

  11. Impregnation of glass fibres with polymethylmethacrylate using a powder-coating method

    NASA Astrophysics Data System (ADS)

    Vallittu, Pekka K.

    1995-01-01

    The aim of this study was to evaluate the usefulness of a powder-coating method to impregnate glass fibres with polymethylmethacrylate (PMMA) for dental purposes. The continuous unidirectional E-glass fibres, the surface of which had been treated with precured silane, were powder-coated with spherical PMMA particles. Before the powder-coated prepregs were used, the incorporated PMMA powder was dissolved with methylmethacrylate monomer. The degree of impregnation of the polymerized composite was determined with a scanning electron microscope. The results revealed that the mean degree of impregnation varied from 0.87 to 0.92, being lower in the heat-cured PMMA group (which simulated fabrication of a new denture), and higher in the autopolymerizing group (which simulated the repair of a fractured denture). The means between the two groups did not, however, differ significantly ( p=0.249). The results suggest that, even though the method has some shortcomings in terms of dental laboratory technology, the powder-coating method can be used to fabricate or repair acrylic resin-based dentures.

  12. DGEBF epoxy blends for use in the resin impregnation of extremely large composite parts

    DOE PAGESBeta

    Madhukar, M. S.; Martovetsky, N. N.

    2015-01-16

    Large superconducting electromagnets used in fusion reactors utilize a large amount of glass/epoxy composite for electrical insulation and mechanical and thermal strengths. Moreover, the manufacture of these magnets involves wrapping each superconducting cable bundle with dry glass cloth followed by the vacuum-assisted resin transfer molding of the entire magnet. Due to their enormous size (more than 100 tons), it requires more than 40 h for resin impregnation and the subsequent pressure cycles to ensure complete impregnation and removal of any trapped air pockets. Diglycidyl ether of bisphenol F epoxy resin cross-linked with methyltetrahydrophthalic anhydride with an accelerator has been shownmore » to be a good candidate for use in composite parts requiring long impregnation cycles. Viscosity, gel time, and glass transition temperature of four resin-blends of diglycidyl ether of bisphenol F resin system were monitored as a function of time and temperature with an objective to find the blend that provides a working window longer than 40h at low viscosity without lowering its glass transition temperature. A resin-blend in the weight ratios of resin:hardener:accelerator=100:82:0.125 is shown to provide more than 60h at low resin viscosity while maintaining the same glass transition temperature as obtained with previously used resin-blends, based on the results.« less

  13. DGEBF epoxy blends for use in the resin impregnation of extremely large composite parts

    SciTech Connect

    Madhukar, M. S.; Martovetsky, N. N.

    2015-01-16

    Large superconducting electromagnets used in fusion reactors utilize a large amount of glass/epoxy composite for electrical insulation and mechanical and thermal strengths. Moreover, the manufacture of these magnets involves wrapping each superconducting cable bundle with dry glass cloth followed by the vacuum-assisted resin transfer molding of the entire magnet. Due to their enormous size (more than 100 tons), it requires more than 40 h for resin impregnation and the subsequent pressure cycles to ensure complete impregnation and removal of any trapped air pockets. Diglycidyl ether of bisphenol F epoxy resin cross-linked with methyltetrahydrophthalic anhydride with an accelerator has been shown to be a good candidate for use in composite parts requiring long impregnation cycles. Viscosity, gel time, and glass transition temperature of four resin-blends of diglycidyl ether of bisphenol F resin system were monitored as a function of time and temperature with an objective to find the blend that provides a working window longer than 40h at low viscosity without lowering its glass transition temperature. A resin-blend in the weight ratios of resin:hardener:accelerator=100:82:0.125 is shown to provide more than 60h at low resin viscosity while maintaining the same glass transition temperature as obtained with previously used resin-blends, based on the results.

  14. A new clothing impregnation method for personal protection against ticks and biting insects.

    PubMed

    Faulde, Michael; Uedelhoven, Waltraud

    2006-05-01

    The efficacy and residual activity of a factory-based, permethrin-impregnated military battle dress uniform (BDU) using a new polymer-coating technique has been evaluated by laboratory and field testing during deployment to Afghanistan and compared with two commercially available, widely used dipping methods. Residual permethrin concentrations and remaining contact toxicities on treated fabrics before laundering, after up to 100 launderings as well as after being worn-out during deployment were tested against Aedes aegypti (L.) and Ixodes ricinus (L.). The residual amount of permethrin was considerably higher with the polymer-coating technique with 280mg/m(2) remaining after 100 launderings. Polymer-coated BDUs collected for disposal after being worn-out during military deployment showed equivalent or better residual knockdown efficacy against test arthropods when compared with the results obtained with the US Army IDA (Illinois Department of Agriculture)-Kit after 50 launderings, which represent the recommended baseline for re-impregantion or disposal of the impregnated fabric. BDUs impregnated by the polymer-coating method were found to be effective throughout the lifetime of the uniform, ensuring protection of soldiers in the field from arthropod vectors, while simultaneously decreasing logistical constraints and occupational health threats. PMID:16524779

  15. Preparation of ibuprofen-loaded chitosan films for oral mucosal drug delivery using supercritical solution impregnation.

    PubMed

    Tang, Chuan; Guan, Yi-Xin; Yao, Shan-Jing; Zhu, Zi-Qiang

    2014-10-01

    Drug-loaded chitosan films suitable for oral mucosal drug delivery were prepared using supercritical solution impregnation (SSI) technology. Firstly, chitosan films were obtained via casting method, and the film properties including water-uptake, erosion and mucoadhesive were characterized. SSI process was then employed to load the drug of ibuprofen onto the prepared chitosan films, and the effects of impregnation pressure and temperature on morphologies of the ibuprofen-loaded chitosan films and drug loading capacity (DLC) were studied. The SEM and X-ray diffraction patterns suggested that distinct ibuprofen shapes such as microparticles, flake, rod-like and needle-like occurred after impregnation at different pressures, and DLC varied from 7.9% to 130.4% during the SSI process. The ex vivo release profiles showed that ibuprofen-loaded chitosan films could deliver the drug across the rabbit buccal mucosa, and up to 70% of the ibuprofen was released from the matrix in 460 min. SSI process is a promising method to prepare drug-loaded film formulations for oral mucosal drug delivery, which provides the advantages of low solvent residual and sustained- and controlled- release behavior.

  16. [Preparation and characterization of activated carbon-silver composite with antibacterial behavior via vacuum impregnation method].

    PubMed

    Wang, Zi-Qiang; Liu, Shou-Xin

    2011-01-01

    Activated carbon-silver composite (Ag/AC) for antibacterial performance by controlling silver release was prepared by silver acetate vacuum impregnation method. The antibacterial activity towards E. coil and resistance of water erosion was investigated through distilled water. Surface area and porosity analyzer, Scanning electron spectroscopy (SEM) and X-ray diffraction (XRD) were used to characterize the surface morphology and pore properties. The results show that Ag0 was deposited on AC symmetrically. The content of silver supported and particle size were increased by the increasing of the concentration of CH3 COOAg, while specific surface area, total pore volume and average pore size were decreased. Ag/AC prepared with silver content of 0.97% which killed 10(7) CFU/mL concentration of E. coil in 120 min exhibited the similar antibacterial activity for E. coil with that prepared by traditional impregnation method. However, the silver loss of the Ag/AC prepared with silver content of 0.97% was 37.6%, showing much higher resistance to water erosion. High antibacterial activity and control silver release can be simultaneously realized by the silver acetate vacuum impregnation method.

  17. A symmetrical solid oxide fuel cell prepared by dry-pressing and impregnating methods

    NASA Astrophysics Data System (ADS)

    Zhu, Xingbao; Lü, Zhe; Wei, Bo; Huang, Xiqiang; Zhang, Yaohui; Su, Wenhui

    In this study, a simple and cost-effective dry-pressing method has been used to fabricate a symmetrical solid oxide fuel cell (SOFC) where the dense yttria-stabilized zirconia (YSZ) electrolyte film is sandwiched between two symmetrical porous YSZ layers in which La 0.75Sr 0.25Cr 0.5Mn 0.5O 3- δ (LSCM) based anode and cathode are incorporated using wet impregnation techniques. The maximum power densities (P max) of a single cell with 32 wt.% LSCM impregnated YSZ anode and cathode reach 333 and 265 mW cm -2 at 900 °C in dry H 2 and CH 4, respectively. The cell performance is further improved with additional impregnation of a small amount of Sm-doped CeO 2 (SDC) or Ni. When 6 wt.% Ni as catalyst is added to both the anode and cathode, P max values of 559 and 547 mW cm -2 can be achieved, which are better than with SDC. The effect of Ni on the cathode performance is also investigated by impedance spectra analysis.

  18. Mechanical and electric characteristics of vacuum impregnated no-insulation HTS coil

    NASA Astrophysics Data System (ADS)

    Park, Heecheol; Kim, A.-rong; Kim, Seokho; Park, Minwon; Kim, Kwangmin; Park, Taejun

    2014-09-01

    For the conduction cooling application, epoxy impregnation is inevitable to enhance the thermal conduction. However, there have been several research results on the delamination problem with coated conductor and the main cause of the delamination is related with the different thermal contraction between epoxy, the insulation layer and the weak conductor. To avoid this problem, the amount of epoxy and insulation layer between conductors should be minimized or removed. Therefore, no insulation (NI) winding method and impregnation after dry winding can be considered to solve the problem. The NI coil winding method is very attractive due to high mechanical/thermal stability for the special purpose of DC magnets by removing the insulation layer. In this paper, the NI coil winding method and vacuum impregnation are applied to a HTS coil to avoid the delamination problem and enhance the mechanical/thermal stability for the conduction cooling application. Through the charging/discharging operation, electric/thermal characteristics are investigated at 77 K and 30 K.

  19. Development of regenerative dye impregnated mesoporous silica materials for assessing exposure to ammonia.

    PubMed

    Chang, Yu-Chang; Bai, Hsunling; Chiang, Hsueh-Shih; Karthik, Mani; Li, Shou-Nan; Hsu, Jung-Nan; Shih, Hui-Ya

    2012-07-01

    The mesostructured materials MCM-41 and SBA-15 were studied as possible supports of bromocresol green (BG) dye impregnation for the ammonia gas detection because of their large surface area, high regenerative property, and high thermal stability. X-ray diffraction, transmission electron microscopy, scanning electron microscope, and N2 adsorption analysis were used to characterize the prepared materials. These materials could sense ammonia via visible color change from yellowish-orange to blue color. The color change process of the nanostructured materials was fully reversible during 10 cyclic tests. The results indicated that the ammonia absorption responses of the two nanostructured materials were both very sensitive, and high linear correlation and high precision were achieved. As the gaseous ammonia concentrations were 50 and 5 ppmv, the response times for the SBA-15/BG were only 1 and 5 min, respectively. Moreover the BG dye-impregnated SBA-15 was less affected by the variation in the relative humidity. It also had faster response for the detection of NH3, as well as lower manufacturing price as compared to that of the dye-impregnated MCM-41. Such feature enables SBA-15/BG to be a very promising material for the detection of ammonia gas.

  20. Development of low-concentration mercury adsorbents from biohydrogen-generation agricultural residues using sulfur impregnation.

    PubMed

    Hsi, Hsing-Chengi; Tsai, Cheng-Yen; Kuo, Tien-Ho; Chiang, Cheng-Sheng

    2011-08-01

    Mercury adsorbents were derived from waste biohydrogen-generation barley husk and rice husk via carbonization, steam activation, and sulfur impregnation at 300-650°C. The samples derived from agricultural residues showed a greater Hg(0) adsorption than that of a coal-based activated carbon, confirming the feasibility of resource recovery of these agricultural residuals for low-concentration gaseous Hg adsorption. Sulfur impregnation reduced both the surface area and pore volume of the samples, with lower temperature causing a greater decrease. Elevating the impregnation temperature increased the organic sulfur contents, suggesting that in addition to elemental sulfur, organic sulfur may also act as active sites to improve Hg(0) adsorption. Oxygen and sulfur functional groups accompanying the microporous structures may account for the enhancing Hg(0) adsorption of the raw and sulfur-treated samples, respectively. The pseudo-second-order model can best describe the chemisorption characteristics, implying that Hg(0) adsorption on the samples was in a bimolecular reaction form.

  1. The photochromic properties of indoline spirooxazine-thermoplastic polymer systems obtained by supercritical fluid impregnation

    NASA Astrophysics Data System (ADS)

    Glagolev, N. N.; Solov'eva, A. B.; Kotova, A. V.; Shashkova, V. T.; Zapadinskii, B. I.; Zaichenko, N. L.; Kol'Tsova, L. S.; Shienok, A. I.; Timashev, P. S.; Bagratashvili, V. N.

    2009-05-01

    The impregnation of thermoplastic polymers (polyethylene, polypropylene, polymethyl methacrylate, and polycarbonate) with photochromic compounds from the class of indoline spirooxazines in supercritical carbon dioxide (SC-CO2) was studied. The concentration of the photochrome and the kinetics of decolorization of its colored form depended strongly on the type of the polymer matrix and the structure of spirooxazine. The introduction of 1,3',3'-trimethylspiro(indoline-2',3-3H-anthraceno[2,1-b][1,4]oxazine) (SAO) into polycarbonate caused anomalous stabilization (the prolonged conservation of the excited colored form of SAO in the polymer matrix). In contrast to other photochrome-polymer pairs, after supercritical impregnation into polycarbonate, at least 10% of all SAO molecules were in the colored form, which was highly stable and did not decolorize after 150 days; the rest of the impregnated SAO molecules were localized in the matrix as individual molecules, partially colorized after matrix relaxation, or nanocrystals of characteristic sizes ˜10-20 nm. The mechanisms of the anomalous stabilization of the colored SAO form in the polycarbonate matrix are discussed.

  2. Impregnation of β-tricalcium phosphate robocast scaffolds by in situ polymerization.

    PubMed

    Martínez-Vázquez, Francisco J; Perera, Fidel H; van der Meulen, Inge; Heise, Andreas; Pajares, Antonia; Miranda, Pedro

    2013-11-01

    Ring-opening polymerization of ε-caprolactone (ε-CL) and L-lactide (LLA) was performed to impregnate β-tricalcium phosphate (β-TCP) scaffolds fabricated by robocasting. Concentrated colloidal inks prepared from β-TCP commercial powders were used to fabricate porous structures consisting of a 3D mesh of interpenetrating rods. ε-CL and LLA were in situ polymerized within the ceramic structure by using a lipase and stannous octanoate, respectively, as catalysts. The results show that both the macropores inside the ceramic mesh and the micropores within the ceramic rods are full of polymer in either case. The mechanical properties of scaffolds impregnated by in situ polymerization (ISP) are significantly increased over those of the bare structures, exhibiting similar values than those obtained by other, more aggressive, impregnation methods such as melt-immersion (MI). ISP using enzymatic catalysts requires a reduced processing temperature which could facilitate the incorporation of growth factors and other drugs into the polymer composition, thus enhancing the bioactivity of the composite scaffold. The implications of these results for the optimization of the mechanical and biological performance of scaffolds for bone tissue engineering applications are discussed. PMID:23526780

  3. Anti-biofilm and cytotoxicity activity of impregnated dressings with silver nanoparticles.

    PubMed

    Velázquez-Velázquez, Jorge Luis; Santos-Flores, Andrés; Araujo-Meléndez, Javier; Sánchez-Sánchez, Roberto; Velasquillo, Cristina; González, Carmen; Martínez-Castañon, Gabriel; Martinez-Gutierrez, Fidel

    2015-04-01

    Infections arising from bacterial adhesion and colonization on chronic wounds are a significant healthcare problem. Silver nanoparticles (AgNPs) impregnated in dressing have attracted a great deal of attention as a potential solution. The goal of the present study was to evaluate the anti-biofilm activities of AgNPs impregnated in commercial dressings against Pseudomonas aeruginosa, bacteria isolated of chronic wounds from a hospital patient. The antimicrobial activity of AgNPs was tested within biofilms generated under slow fluid shear conditions using a standard bioreactor. A 2-log reduction in the number of colony-forming units of P. aeruginosa was recorded in the reactor on exposure to dressing impregnated with 250ppm of AgNPs, diameter 9.3±1.1nm, and also showed compatibility to mammalian cells (human fibroblasts). Our study suggests that the use of dressings with AgNPs may either prevent or reduce microbial growth in the wound environment, and reducing wound bioburden may improve wound-healing outcomes.

  4. Effect of impregnation method on cycle life of the nickel electrode

    NASA Technical Reports Server (NTRS)

    Smithrick, J. J.

    1986-01-01

    The nickel electrode has been identified as the life limiting component for individual pressure vessel (IPV) nickel-hydrogen cells when cycled under a low earth orbit (LEO) cycle regime at deep depths of discharge. As a part of an overall program to develop a long life nickel electrode for nickel-hydrogen cells, the effect of two different methods of electrochemical impregnation on the cycle life of the nickel electrode was investigated. One method was the Pickett (aqueous/ethanolic) process. The other was the modified Bell (aqueous) process. The plaques for both impregnation methods were made by sintering dry carbonyl nickel powder in a reducing atmosphere. The plaques contain a nickel screen substrate. Electrodes made from both processes were cycle tested in Air Force design IPV nickel-hydrogen cells. The only factor different for this test was the method of plaque impregnation; all other factors were the same. The cells were cycled to failure under a 90 min LEO cycle regime at a deep depth of discharge (80 percent DOD). Failure for this test was defined to occur when the cell voltage degraded to 1.0 V prior to the completion of the 35 min discharge.

  5. Development of silver impregnated alumina for iodine separation from off-gas streams

    SciTech Connect

    Funabashi, Kiyomi; Fukasawa, Tetsuo; Kikuchi, Makoto

    1995-02-01

    An inorganic iodine adsorbent, silver impregnated alumina (AgA), has been developed to separate iodine effectively from off-gas streams of nuclear facilities and to decrease the volume of waste (spent adsorbent). Iodine removal efficiency was improved at relatively high humidity by using alumina carrier with two different pore diameters. Waste volume reduction was achieved by impregnating relatively large amounts of silver into the alumina pores. The developed adsorbent was tested first with simulated off-gas streams under various experimental conditions and finally with actual off-gas streams of the Karlsruhe reprocessing plant. The decontamination factor (DF) was about 100 with the AgA bed depth of 2cm at 70% relative humidity, which was a DF one order higher than that when AgA with one pore size was used. Iodine adsorption capacity was checked by passing excess iodine into the AgA bed. Values were about 0.12 and 0.35 g-I/cm`-AgA bed for 10 and 24wt% silver impregnated AgA, respectively. The results obtained in this study demonstrated the applicability of the developed AgA to the off-gas treatment system of nuclear facilities.

  6. Bacterial flagella as biotemplate for the synthesis of silver nanoparticle impregnated bionanomaterial

    NASA Astrophysics Data System (ADS)

    Gopinathan, Priya; Ashok, Anuradha M.; Selvakumar, R.

    2013-07-01

    The present study was carried out to synthesize one dimensional silver nanoparticle impregnated flagellar bionanomaterial. Flagella was isolated from Salmonella typhimurium and depolymerised into flagellin monomers. The flagellin monomers were repolymerised again into flagella using suitable technique. The molecular weight of native (NF) and polymerized flagella (PF) was determined using polyacrylamide gel electrophoresis. The NF and PF were used as a template, over which silver nanoparticles were impregnated using in situ chemical reduction process. The synthesized flagellar-silver nanoparticle bionanomaterials were characterized using UV-vis, FT-IR Raman and XRD spectroscopy, and High resolution transmission electron microscopy (HR-TEM). The characterization studies confirmed the attachment of silver nanoparticles over flagella and repolymerised flagella. The size of the silver nanoparticles on the flagella and repolymerised flagella varied and was in the range of 3-11 nm. I-V characteristics of the bionanomaterials were analyzed using Kethley meter which indicated the increase of conductivity after impregnation of silver nanoparticles. The results indicated that flagellar-silver nanoparticle bionanomaterials can be used as a potential one dimensional bionanomaterials for various applications.

  7. Impregnation of the bacterial cellulose membrane with biologically produced silver nanoparticles.

    PubMed

    Pourali, Parastoo; Yahyaei, Behrooz; Ajoudanifar, Hatef; Taheri, Rahele; Alavi, Hassan; Hoseini, Ashraf

    2014-12-01

    Different wound dressings with antibacterial property have been surveyed and one among them is bacterial cellulose (BC). Since the BC does not have antibacterial property, the biologically produced silver nanoparticles (SNPs) were impregnated into the BC. For the BC production, Hestrin-Schramm broth was used. Formation of the BC was proven by enzymatic hydrolysis. For SNPs production, the bacterial supernatant was treated with AgNO3 and formation of SNPs was monitored through spectrophotometer, TEM and XRD. For impregnation of SNPs into the BC, the cleaned membrane was placed in the bacterial supernatant that contained 1 mmol of AgNO3. The antibacterial assay was done for the BC/SNPs. Enzymatic hydrolysis proved the presence of the BC. Spectrophotometer and XRD results showed the formation of SNPs. TEM analysis revealed the presence of SNPs with sizes around 5-100 nm. SEM micrographs showed the impregnation of SNPs into the BC. Antibacterial test exhibited the antibacterial activity of the BC/SNPs.

  8. Impregnation of β-tricalcium phosphate robocast scaffolds by in situ polymerization.

    PubMed

    Martínez-Vázquez, Francisco J; Perera, Fidel H; van der Meulen, Inge; Heise, Andreas; Pajares, Antonia; Miranda, Pedro

    2013-11-01

    Ring-opening polymerization of ε-caprolactone (ε-CL) and L-lactide (LLA) was performed to impregnate β-tricalcium phosphate (β-TCP) scaffolds fabricated by robocasting. Concentrated colloidal inks prepared from β-TCP commercial powders were used to fabricate porous structures consisting of a 3D mesh of interpenetrating rods. ε-CL and LLA were in situ polymerized within the ceramic structure by using a lipase and stannous octanoate, respectively, as catalysts. The results show that both the macropores inside the ceramic mesh and the micropores within the ceramic rods are full of polymer in either case. The mechanical properties of scaffolds impregnated by in situ polymerization (ISP) are significantly increased over those of the bare structures, exhibiting similar values than those obtained by other, more aggressive, impregnation methods such as melt-immersion (MI). ISP using enzymatic catalysts requires a reduced processing temperature which could facilitate the incorporation of growth factors and other drugs into the polymer composition, thus enhancing the bioactivity of the composite scaffold. The implications of these results for the optimization of the mechanical and biological performance of scaffolds for bone tissue engineering applications are discussed.

  9. Resveratrol inhibits collagen I synthesis by suppressing IGF-1R activation in intestinal fibroblasts

    PubMed Central

    Li, Ping; Liang, Mei-Lan; Zhu, Ying; Gong, Yao-Yao; Wang, Yun; Heng, Ding; Lin, Lin

    2014-01-01

    AIM: To investigate whether resveratrol (3,4,5-trihydroxy-trans-stilbene) inhibits collagen I synthesis induced by insulin growth factor-1 (IGF-1) in intestinal fibroblasts, and to explore the possible molecular mechanisms. METHODS: Male Sprague-Dawley rats were randomly divided into two groups: a control group and a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis group. After 21 d of TNBS administration, the degree of inflammation and fibrosis in colon was measured by HE staining and Masson’s trichrome staining. Western blotting was used to examine collagen I, IGF-1 and silent information regulator 1 (SIRT1) protein expression in colitis tissues. Western blotting and quantitative real-time polymerase chain reaction were used to characterize collagen I protein and col1a2 mRNA expression in mouse intestinal fibroblasts and CCD-18Co cells treated with IGF-1. A MEK inhibitor (U0126) was used to determine whether IGF-1-induced collagen I expression was mediated by extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent mechanism. Effects of resveratrol on collagen I protein level, insulin growth factor-1 receptor (IGF-1R) and ERK1/2 phosphorylation levels were also examined after IGF-1 treatment in fibroblasts. To evaluate whether SIRT1 was necessary for the anti-fibrosis effect of resveratrol, cells were transfected with SIRT1-specific small interfering RNAs, wild-type SIRT1, and deacetylase-inactive mutant SIRT1. RESULTS: Collagen I and IGF-1 expression was increased, and SIRT1 expression was decreased (0.67 ± 0.04 vs 1.05 ± 0.07, P < 0.001) in TNBS-induced colitis compared with the control group. In vitro, IGF-1 could induce collagen I expression, mainly through the ERK 1/2 signal pathway. Resveratrol reduced basal and IGF-1-induced collagen I gene and protein expression in intestinal fibroblasts. Overexpression of wild-type SIRT1, not deacetylase-inactive mutant SIRT1, decreased expression of collagen

  10. Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R

    PubMed Central

    LIU, SHUANGXIN; ZHU, WEIPING; LI, SIJIA; MA, JIANCHAO; ZHANG, HUITAO; LI, ZHONGHE; ZHANG, LI; ZHANG, BIN; LI, ZHUO; LIANG, XINLING; SHI, WEI

    2016-01-01

    The vacuolar-type H+ adenosine triphosphatase (V-ATPase) plays an important role in cellular acidification and bone resorption by osteoclasts. However, the direct effect of bovine parathyroid hormone (bPTH) on V-ATPase has not yet been elucidated. The aim of the present study was to assess the effects of bPTH on V-ATPase and osteoclasts. Osteoclasts from bone marrow (BM)-derived monocytes of C57BL/6 mice were cultured with or without bPTH. The mRNA and protein expression levels of the V-ATPase a3-subunit and d2-subunit (by RT-qPCR and western blot analysis), V-ATPase activity (using the V type ATPase Activity Assay kit) and the bone resorption function of osteoclasts (by bone resorption assay) were examined following treatment with various concentrations of bPTH (0.1, 1.0, 10 and 100 ng/ml) alone or with bPTH and its inhibitor, bafilomycin A1. Furthermore, the expression of parathyroid hormone (PTH) receptors in osteoclasts was also detected. The results revealed that the mRNA and protein expression levels of V-ATPase a3-subunit and d2-subunit increased in a dose-dependent manner, paralleling the level of bPTH present. In addition, an increase in the concentration of bPTH was accompanied by the increased resorption capability of osteoclasts, whereas bone resorption was inhibited in the presence of bafilomycin A1. In addition, we confirmed the existence of parathyroid hormone 1 receptor (PTH1R) in osteoclasts using three different methods (RT-qPCR, western blot analysis and immunofluorescence staining). We found that bPTH enhanced the bone resorption capability of osteoclasts by modulating the expression of V-ATPase subunits, intracellular acidification and V-ATPase activity. Thus, we propose that PTH has a direct effect on osteoblasts and osteoclasts, and that this effect is mediated through PTH1R, thus contributing to bone remodeling. PMID:26647715

  11. PD98059-Impregnated Functional PLGA Scaffold for Direct Tissue Engineering Promotes Chondrogenesis and Prevents Hypertrophy from Mesenchymal Stem Cells

    PubMed Central

    Lee, Jong Min; Kim, Jong Dae; Oh, Eun Jo; Oh, Se Heang; Lee, Jin Ho

    2014-01-01

    In cartilage tissue engineering from mesenchymal stem cells, it is important to suppress hypertrophy to produce a neocartilage with stable phenotypes of hyaline articular cartilage (AC). The aim of this study was to develop and test the usefulness of functional chondrogenic scaffolds that serve the purpose of hypertrophy suppression. PD98059-impregnated poly(lactic-co-glycolic acid) (PLGA) scaffold is fabricated and compared with transforming growth factor (TGF)-β2-immobilized scaffold. The PD98059 is continuously released from the scaffolds over 140 days in contrast to the rapid release in TGF-β2-immobilized scaffold. The in vitro culture results show that the PD98059-impregated scaffold is more effective in suppressing hypertrophy than the TGF-β2-immobilized scaffold while both scaffolds enhance chondrogenesis from human mesenchymal stem cells. After 10 weeks of in vivo implantation in rabbits, the osteochondral defects is successfully repaired in both PD98059-impregnated and TGF-β2-immobilized scaffold seeded with rabbit mesenchymal stem cells when evaluated grossly and microscopically. However, type X collagen is not observed from regenerated cartilage in PD98059-impregnated scaffold, whereas it is detected around chondrocytes in the TGF-β2-impregnated scaffolds. In addition, the PD98059-impregnated scaffold has better reconstitution of the subchondral plate. These results suggest that the use of the PD98059-impregnated scaffold leads to AC regeneration of better quality and prevents hypertrophy when implanted in the osteochondral defects. PMID:24188591

  12. Fe-Impregnated Mineral Colloids for Peroxide Activation: Effects of Mineral Substrate and Fe Precursor.

    PubMed

    Li, Yue; Machala, Libor; Yan, Weile

    2016-02-01

    Heterogeneous iron species at the mineral/water interface are important catalysts for the generation of reactive oxygen species at circumneutral pH. One significant pathway leading to the formation of such species arises from deposition of dissolved iron onto mineral colloids due to changes in redox conditions. This study investigates the catalytic properties of Fe impregnated on silica, alumina, and titania nanoparticles (as prototypical mineral colloids). Fe impregnation was carried out by immersing the mineral nanoparticles in dilute Fe(II) or Fe(III) solutions at pH 6 and 3, respectively, in an aerobic environment. The uptake of iron per unit surface area follows the order of nTiO2 > nAl2O3 > nSiO2 for both types of Fe precursors. Impregnation of mineral particles in Fe(II) solutions results in predominantly Fe(III) species due to efficient surface-mediated oxidation. The catalytic activity of the impregnated solids to produce hydroxyl radical (·OH) from H2O2 decomposition was evaluated using benzoic acid as a probe compound under dark conditions. Invariably, the rates of benzoic acid oxidation with different Fe-laden particles increase with the surface density of Fe until a critical density above which the catalytic activity approaches a plateau, suggesting active Fe species are formed predominantly at low surface loadings. The critical surface density of Fe varies with the mineral substrate as well as the aqueous Fe precursor. Fe impregnated on TiO2 exhibits markedly higher activity than its Al2O3 and SiO2 counterparts. The speciation of interfacial Fe is analyzed with diffuse reflectance UV-vis analysis and interpretation of the data in the context of benzoic oxidation rates suggests that the surface activity of the solids for ·OH generation correlates strongly with the isolated (i.e., mononuclear) Fe species. Therefore, iron dispersed on mineral colloids is a significant form of reactive iron surfaces in the aquatic environment.

  13. Fe-Impregnated Mineral Colloids for Peroxide Activation: Effects of Mineral Substrate and Fe Precursor.

    PubMed

    Li, Yue; Machala, Libor; Yan, Weile

    2016-02-01

    Heterogeneous iron species at the mineral/water interface are important catalysts for the generation of reactive oxygen species at circumneutral pH. One significant pathway leading to the formation of such species arises from deposition of dissolved iron onto mineral colloids due to changes in redox conditions. This study investigates the catalytic properties of Fe impregnated on silica, alumina, and titania nanoparticles (as prototypical mineral colloids). Fe impregnation was carried out by immersing the mineral nanoparticles in dilute Fe(II) or Fe(III) solutions at pH 6 and 3, respectively, in an aerobic environment. The uptake of iron per unit surface area follows the order of nTiO2 > nAl2O3 > nSiO2 for both types of Fe precursors. Impregnation of mineral particles in Fe(II) solutions results in predominantly Fe(III) species due to efficient surface-mediated oxidation. The catalytic activity of the impregnated solids to produce hydroxyl radical (·OH) from H2O2 decomposition was evaluated using benzoic acid as a probe compound under dark conditions. Invariably, the rates of benzoic acid oxidation with different Fe-laden particles increase with the surface density of Fe until a critical density above which the catalytic activity approaches a plateau, suggesting active Fe species are formed predominantly at low surface loadings. The critical surface density of Fe varies with the mineral substrate as well as the aqueous Fe precursor. Fe impregnated on TiO2 exhibits markedly higher activity than its Al2O3 and SiO2 counterparts. The speciation of interfacial Fe is analyzed with diffuse reflectance UV-vis analysis and interpretation of the data in the context of benzoic oxidation rates suggests that the surface activity of the solids for ·OH generation correlates strongly with the isolated (i.e., mononuclear) Fe species. Therefore, iron dispersed on mineral colloids is a significant form of reactive iron surfaces in the aquatic environment. PMID:26713453

  14. Blockade of cannabinoid 1 receptor improves GLP-1R mediated insulin secretion in mice.

    PubMed

    González-Mariscal, Isabel; Krzysik-Walker, Susan M; Kim, Wook; Rouse, Michael; Egan, Josephine M

    2016-03-01

    The cannabinoid 1 receptor (CB1) is an important regulator of energy metabolism. Reports of in vivo and in vitro studies give conflicting results regarding its role in insulin secretion, possibly due to circulatory factors, such as incretins. We hypothesized that this receptor may be a regulator of the entero-insular axis. We found that despite lower food consumption and lower body weight postprandial GLP-1 plasma concentrations were increased in CB1(-/-) mice compared to CB1(+/+) mice administered a standard diet or high fat/sugar diet. Upon exogenous GLP-1 treatment, CB1(-/-) mice had increased glucose-stimulated insulin secretion. In mouse insulinoma cells, cannabinoids reduced GLP-1R-mediated intracellular cAMP accumulation and subsequent insulin secretion. Importantly, such effects were also evident in human islets, and were prevented by pharmacologic blockade of CB1. Collectively, these findings suggest a novel mechanism in which endocannabinoids are negative modulators of incretin-mediated insulin secretion. PMID:26724516

  15. Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue

    PubMed Central

    Durymanov, Mikhail O; Slastnikova, Tatiana A; Kuzmich, Alexey I; Khramtsov, Yuri V; Ulasov, Alexey V; Rosenkranz, Andrey A1; Egorov, Sergey Y; Sverdlov, Eugene D; Sobolev, Alexander S

    2013-01-01

    Targeted sodium-iodide symporter (NIS) gene transfer can be considered as a promising approach for diagnostics of specific types of cancer. For this purpose we used targeted polyplexes based on PEI–PEG–MC1SP block-copolymer containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (MC1R) overexpressed on melanoma cells. Targeted polyplexes demonstrated enhanced NIS gene transfer compared to non-targeted (lacking MC1SP) ones in vitro. Using dorsal skinfold chamber and intravital microscopy we evaluated accumulation and microdistribution of quantum dot-labeled polyplexes in tumor and normal subcutaneous tissues up to 4 hours after intravenous injection. Polyplexes demonstrated significantly higher total accumulation in tumor tissue in comparison with subcutaneous ones (control). Targeted and non-targeted polyplexes extravasated and penetrated into the tumor tissue up to 20 μm from the vessel walls. In contrast, in normal subcutaneous tissue polyplexes penetrated less than 5 μm from the vessel walls with the level of extravasated polyplexes 400-fold less than in tumor. Accumulated polyplexes in tumor tissue caused NIS gene expression. Subsequent 123I- intravenous injection resulted in 6.8 ± 1.1 and 4.5 ± 0.8 % ID/g (p < 0.001) iodide accumulation in tumors in the case of targeted and non-targeted polyplexes, respectively, as was shown using SPECT/CT. PMID:24075405

  16. The Optical Field Angle Distortion Calibration of HST Fine Guidance Sensors 1R and 3

    NASA Technical Reports Server (NTRS)

    McArthur, B.; Benedict, G. F.; Jefferys, W. H.; Nelan, E.

    2006-01-01

    To date five OFAD (Optical Field Angle Distortion) calibrations have been performed with a star field in M35, four on FGS3 and one on FGS1, all analyzed by the Astrometry Science Team. We have recently completed an improved FGS1R OFAD calibration. The ongoing Long Term Stability Tests have also been analyzed and incorporated into these calibrations, which are time-dependent due to on-orbit changes in the FGS. Descriptions of these tests and the results of our OFAD modeling are given. Because all OFAD calibrations use the same star field, we calibrate FGS 1 and FGS 3 simultaneously. This increases the precision of our input catalog,resulting in an improvement in both the FGS 1 and FGS 3 calibrations. A redetermination of the proper motions,using 12 years of HST data has significantly improved our calibration. Residuals to our OFAD modeling indicate that FGS 1 will provide astrometry superior to FGS 3 by approx. 20%. Past and future FGS astrometric science supported by these calibrations is briefly reviewed.

  17. First passage times in M2[X ]|G |1 |R queue with hysteretic overload control policy

    NASA Astrophysics Data System (ADS)

    Pechinkin, Alexander V.; Razumchik, Rostislav R.; Zaryadov, Ivan S.

    2016-06-01

    One of the reported approaches towards the solution of overload problem in networks of SIP servers is the implementation of multi-level hysteretic control of arrivals in SIP servers. Each level, being the parameter of the policy, specifies operation mode of SIP server i.e. it implicitly indicates what SIP server must do with the arriving packets. The choice of parameters' values is not guided by standards and is usually left for the network owner. In general, all operation modes of the considered policy can be grouped into two groups: normal mode (when all arriving packets are accepted) and congested mode (when part or all arriving packets are being dropped). Such grouping may serve as the criteria for choosing parameters' values of the policy: pick those values which minimize SIP server sojourn time in congested mode. In this short note we propose some analytical results which facilitate the solution of stated minimization problem. The considered mathematical model of SIP server is the queueing system M2[X ]|G |1 |R with batch arrivals and bi-level hysteretic control policy, which specifies three operation modes: normal (customers both flows are accepted), overload (only customers from one flow are accepted), discard (customers from both flows are blocked/lost)). The switching between modes can occur only on service completions. Analytical method allowing computation of stationary sojourn times in different operation modes (as well as first passage times between modes) is presented in brief. Numerical example is given.

  18. Alternative 5' exons and differential splicing regulate expression of protein 4.1R isoforms with distinct n-termini

    SciTech Connect

    Parra, Marilyn K.; Gee, Sherry L.; Koury, Mark J.; Mohandas, Narla; Conboy, John G.

    2003-03-25

    Among the alternative pre-mRNA splicing events that characterize protein 4.1R gene expression, one involving exon 2' plays a critical role in regulating translation initiation and N-terminal protein structure. Exon 2' encompasses translation initiation site AUG1 and is located between alternative splice acceptor sites at the 5' end of exon 2; its inclusion or exclusion from mature 4.1R mRNA regulates expression of longer or shorter isoforms of 4.1R protein, respectively. The current study reports unexpected complexity in the 5' region of the 4.1R gene that directly affects alternative splicing of exon 2'. Three mutually exclusive alternative 5' exons, designated 1A, 1B, and 1C, were identified far upstream of exon 2 in both mouse and human genomes; all three are associated with strong transcriptional promoters in the flanking genomic sequence. Importantly, exons 1A and 1B splice differentially with respect to exon 2', generating transcripts with different 5' ends and distinct N-terminal protein coding capacity. Exon 1A-type transcripts splice so as to exclude exon 2' and therefore utilize the downstream AUG2 for translation of 80kD 4.1R protein, whereas exon 1B transcripts include exon 2' and initiate at AUG1 to synthesize 135kD isoforms. RNA blot analyses revealed that 1A transcripts increase in abundance in late erythroblasts, consistent with the previously demonstrated upregulation of 80kD 4.1R during terminal erythroid differentiation. Together these results suggest that synthesis of structurally distinct 4.1R protein isoforms in various cell types is regulated by a novel mechanism requiring coordination between upstream transcription initiation events and downstream alternative splicing events.

  19. Secretome of transmissible Pseudomonas aeruginosa AES-1R grown in a cystic fibrosis lung-like environment.

    PubMed

    Scott, Nichollas E; Hare, Nathan J; White, Melanie Y; Manos, Jim; Cordwell, Stuart J

    2013-12-01

    Pseudomonas aeruginosa is the predominant cause of mortality in patients with cystic fibrosis (CF). We examined the secretome of an acute, transmissible CF P. aeruginosa (Australian epidemic strain 1-R; AES-1R) compared with laboratory-adapted PAO1. Culture supernatant proteins from rich (LB) and minimal (M9) media were compared using 2-DE and 2DLC-MS/MS, which revealed elevated abundance of PasP protease and absence of AprA protease in AES-1R. CF lung-like artificial sputum medium (ASMDM) contains serum and mucin that generally preclude proteomics of secreted proteins. ASMDM culture supernatants were subjected to 2DLC-MS/MS, which allowed the identification of 57 P. aeruginosa proteins, and qualitative spectral counting was used to estimate relative abundance. AES-1R-specific AES_7139 and PasP were more abundant in AES-1R ASMDM culture supernatants, while AprA could only be identified in PAO1. Relative quantitation was performed using selected reaction monitoring. Significantly elevated levels of PasP, LasB, chitin-binding protein (CbpD), and PA4495 were identified in AES-1R ASMDM supernatants. Quantitative PCR showed elevated pasP in AES-1R during early (18 h) ASMDM growth, while no evidence of aprA expression could be observed. Genomic screening of CF isolates revealed aes_7139 was present in all AES-1 and one pair of sequential nonepidemic isolates. Secreted proteins may be crucial in aiding CF-associated P. aeruginosa to establish infection and for adaptation to the CF lung. PMID:23991618

  20. IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas

    PubMed Central

    Huang, Xin; Park, Haein; Greene, Joseph; Zhou, Sophia X.; Albert, Catherine M.; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V.; Loeb, David M.; Cairo, Mitchell S.; Zhou, Xianzheng

    2015-01-01

    Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients. PMID:26173023

  1. Identification of six novel PTH1R mutations in families with a history of primary failure of tooth eruption.

    PubMed

    Risom, Lotte; Christoffersen, Line; Daugaard-Jensen, Jette; Hove, Hanne Dahlgaard; Andersen, Henriette Skovgaard; Andresen, Brage Storstein; Kreiborg, Sven; Duno, Morten

    2013-01-01

    Primary Failure of tooth Eruption (PFE) is a non-syndromic disorder which can be caused by mutations in the parathyroid hormone receptor 1 gene (PTH1R). Traditionally, the disorder has been identified clinically based on post-emergent failure of eruption of permanent molars. However, patients with PTH1R mutations will not benefit from surgical and/or orthodontic treatment and it is therefore clinically important to establish whether a given failure of tooth eruption is caused by a PTH1R defect or not. We analyzed the PTH1R gene in six patients clinically diagnosed with PFE, all of which had undergone surgical and/or orthodontic interventions, and identified novel PTH1R mutations in all. Four of the six mutations were predicted to abolish correct mRNA maturation either through introduction of premature stop codons (c.947C>A and c.1082G>A), or by altering correct mRNA splicing (c.544-26_544-23del and c.989G>T). The latter was validated by transfection of minigenes. The six novel mutations expand the mutation spectrum for PFE from eight to 14 pathogenic mutations. Loss-of-function mutations in PTH1R are also associated with recessively inherited Blomstrand chondrodysplasia. We compiled all published PTH1R mutations and identified a mutational overlap between Blomstrand chondrodysplasia and PFE. The results suggest that a genetic approach to preclinical diagnosis will have important implication for surgical and orthodontic treatment of patients with failure of tooth eruption.

  2. IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.

    PubMed

    Huang, Xin; Park, Haein; Greene, Joseph; Pao, James; Mulvey, Erin; Zhou, Sophia X; Albert, Catherine M; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V; Loeb, David M; Cairo, Mitchell S; Zhou, Xianzheng

    2015-01-01

    Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients. PMID:26173023

  3. Mn-SOD Upregulation by Electroacupuncture Attenuates Ischemic Oxidative Damage via CB1R-Mediated STAT3 Phosphorylation.

    PubMed

    Sun, Sisi; Chen, Xiyao; Gao, Yang; Liu, Zhaoyu; Zhai, Qian; Xiong, Lize; Cai, Min; Wang, Qiang

    2016-01-01

    Electroacupuncture (EA) pretreatment elicits the neuroprotective effect against cerebral ischemic injury through cannabinoid receptor type 1 receptor (CB1R). In current study, we aimed to investigate whether the signal transducer and activator of transcription 3 (STAT3) and manganese superoxide dismutase (Mn-SOD) were involved in the antioxidant effect of EA pretreatment through CB1R. At 2 h after EA pretreatment, focal cerebral ischemic injury was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice. The expression of Mn-SOD in the penumbra was assessed by Western blot and immunoflourescent staining at 2 h after reperfusion. In the presence or absence of Mn-SOD small interfering RNA (siRNA), the neurological deficit score, the infarct volume, the terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling (TUNEL) staining, and oxidative stress were evaluated. Furthermore, the Mn-SOD protein expression and phosphorylation of STAT3 at Y705 were also determined in the presence and absence of CB1R antagonists (AM251, SR141716) and CB1R agonists (arachidonyl-2-chloroethylamide (ACEA), WIN 55,212-2). EA pretreatment upregulated the Mn-SOD protein expression and Mn-SOD-positive neuronal cells at 2 h after reperfusion. EA pretreatment also attenuated oxidative stress, inhibited cellular apoptosis, and induced neuroprotection against ischemic damage, whereas these beneficial effects of EA pretreatment were reversed by knockdown of Mn-SOD. Mn-SOD upregulation and STAT3 phosphorylation by EA pretreatment were abolished by two CB1R antagonists, while pretreatment with two CB1R agonists increased the expression of Mn-SOD and phosphorylation level of STAT3. Mn-SOD upregulation by EA attenuates ischemic oxidative damage through CB1R-mediated STAT3 phosphorylation in stroke mice, which may represent one new mechanism of EA pretreatment-induced neuroprotection against cerebral ischemia.

  4. Insulin deficiency induces rat renal mesangial cell dysfunction via activation of IGF-1/IGF-1R pathway

    PubMed Central

    Kong, Ya-li; Shen, Yang; Ni, Jun; Shao, De-cui; Miao, Nai-jun; Xu, Jin-lan; Zhou, Li; Xue, Hong; Zhang, Wei; Wang, Xiao-xia; Lu, Li-min

    2016-01-01

    Aim: Diabetic nephropathy is one of the major complications of diabetes and the major cause of end-stage renal disease. In this study we investigated the insulin deficiency (ID) induced changes in renal mesangial cells (MCs) and in the kidney of STZ-induced diabetic rats. Methods: Cultured rat renal MCs were incubated in ID media. Cell proliferation was analyzed using BrdU incorporation assay. The expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), phosphorylated IGF-1R, fibronectin, and collagen IV was determined with Western blot analysis. STZ-induced diabetic rats were treated with an IGF-1R antagonist picropodophyllin (PPP, 20 mg·kg−1·d−1, po) for 8 weeks. After the rats were euthanized, plasma and kidneys were collected. IGF-1 levels in renal cortex were measured with RT-PCR or ELISA. The morphological changes in the kidneys were also examined. Results: Incubation in ID media significantly increased cell proliferation, the synthesis of fibronectin and collagen IV, and the expression of IGF-1 and IGF-1R and phosphorylated IGF-1R in renal MCs. Pretreatment of the cells with PPP (50 nmol/L) blocked ID-induced increases in cell proliferation and the synthesis of fibronectin and collagen IV; knockdown of IGF-1R showed a similar effect as PPP did. In contrast, treatment of the cells with IGF-1 (50 ng/mL) exacerbated ID-induced increases in cell proliferation. In the kidneys of diabetic rats, the expression of IGF-1, IGF-1R and phosphorylated IGF-1R were significantly elevated. Treatment of diabetic rats with PPP did not lower the blood glucose levels, but significantly suppressed the expression of TGF-β, fibronectin and collagen IV in the kidneys, the plasma levels of urinary nitrogen and creatinine, and the urinary protein excretion. Conclusion: Insulin deficiency increases the expression of IGF-1 and IGF-1R in renal MCs and the kidney of diabetic rats, which contributes to the development of diabetic nephropathy. PMID

  5. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.

    PubMed

    Rademakers, Rosa; Baker, Matt; Nicholson, Alexandra M; Rutherford, Nicola J; Finch, NiCole; Soto-Ortolaza, Alexandra; Lash, Jennifer; Wider, Christian; Wojtas, Aleksandra; DeJesus-Hernandez, Mariely; Adamson, Jennifer; Kouri, Naomi; Sundal, Christina; Shuster, Elizabeth A; Aasly, Jan; MacKenzie, James; Roeber, Sigrun; Kretzschmar, Hans A; Boeve, Bradley F; Knopman, David S; Petersen, Ronald C; Cairns, Nigel J; Ghetti, Bernardino; Spina, Salvatore; Garbern, James; Tselis, Alexandros C; Uitti, Ryan; Das, Pritam; Van Gerpen, Jay A; Meschia, James F; Levy, Shawn; Broderick, Daniel F; Graff-Radford, Neill; Ross, Owen A; Miller, Bradley B; Swerdlow, Russell H; Dickson, Dennis W; Wszolek, Zbigniew K

    2011-12-25

    Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.

  6. Interleukin-1β Upregulates Functional Expression of Neurokinin-1 Receptor (NK-1R) via NF-κB in Astrocytes

    PubMed Central

    GUO, CHANG-JIANG; DOUGLAS, STEVEN D.; GAO, ZHIYONG; WOLF, BRYAN A.; GRINSPAN, JUDITH; LAI, JIAN-PING; RIEDEL, ERIC; HO, WEN-ZHE

    2014-01-01

    Cytokines and neuropeptides are modulators of neuroimmunoregulation in the central nervous system (CNS). The interaction of these modulators may have important implications in CNS diseases. We investigated whether interleukin-1β (IL-1β) modulates the expression of neurokinin-1 receptor (NK-1R), the primary receptor for substance P (SP), a potent neuropeptide in the CNS. IL-1β upregulated NK-1R expression in human astroglioma cells (U87 MG) and primary rat astrocytes at both mRNA and protein levels. IL-1β treatment of U87 MG cells and primary rat astrocytes led to an increase in cytosolic Ca2+ in response to SP stimulation, indicating that IL-1β-induced NK-1R is functional. CP-96,345, a specific non-peptide NK-1R antagonist, inhibited SP-induced rise of [Ca2+]i in the astroglioma cells. Investigation of the mechanism responsible for IL-1β action revealed that IL-1β has the ability of activating nuclear factor-κb (NF-κB). Caffeic acid phenethyl ester (CAPE), a specific inhibitor of NF-κB activation, not only abrogated IL-1β-induced NF-κB promoter activation, but also blocked IL-1β-mediated induction of NK-1R gene expression. These findings provide additional evidence that there is a biological interaction between IL-1β and the neuropeptide SP in the CNS, which may have important implications in the inflammatory diseases in the CNS. PMID:15390113

  7. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration

    PubMed Central

    Martino, Mikaël M.; Maruyama, Kenta; Kuhn, Gisela A.; Satoh, Takashi; Takeuchi, Osamu; Müller, Ralph; Akira, Shizuo

    2016-01-01

    Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1β which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3β/β-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications. PMID:27001940

  8. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration.

    PubMed

    Martino, Mikaël M; Maruyama, Kenta; Kuhn, Gisela A; Satoh, Takashi; Takeuchi, Osamu; Müller, Ralph; Akira, Shizuo

    2016-03-22

    Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1β which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3β/β-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications.

  9. Genetics and evolution of plumage color in Crested Ibis: Analysis of the melanocortin-1 receptor (MC1R).

    PubMed

    Yang, J; Liu, X; Zhang, J; Qing, B; Lu, B

    2015-01-01

    The melanocortin-1-recepter gene (MC1R), an important regulator in melanin synthesis, may cause different plumage color patterns in birds: gain-of-function mutations lead to the synthesis of eumelanin, whereas loss-of-function mutations help to generate pheomelanin synthesis. We had chosen MC1R as a candidate gene for the depigmentation of crested ibis, cloned and sequenced the crested ibis MC1R gene the first time. The crested ibis MC1R sequence, highly conserved with other birds during evolution, had seven transmembrane domains which played an indispensable function through evolution. We did not found any substitution on this sequence among all the sample individuals. The phylogenetic tree showed that crested ibis separated early in the evolution of birds. TYR, TYRP1, TYRP2 and MC1R were expressed in blood and the expression of the four genes showed no significant difference (p>0.05) between normal and albinism individuals, and this result demonstrated that melanic pigments are not involved in the production of red pigmentation in birds. Further study of the crested ibis albinism should focus on analyzing carotenoid-based genes. PMID:26314199

  10. ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors

    PubMed Central

    Zhang, Wei; Wang, Guangzhi; Yao, Kun; Wang, Zhiliang; Li, Guanzhang; Qian, Zenghui; Li, Yongli; Jiang, Tao; Jiang, Chuanlu

    2016-01-01

    Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. Malignant astrocytic tumors such as glioblastoma (GBM) are the most lethal intracranial tumors. However, the clinical practicability and significance of molecular parameters for the diagnostic and prognostic prediction of astrocytic tumors is still limited. In this study, we detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and observed the association of IDH1-R132H with ATRX and Ki-67 expression. There was a strong association between ATRX loss and IDH1-R132H (p<0.0001). However, Ki-67 high expression restricted in the tumors with IDH1-R132H negative (p=0.0129). Patients with IDH1-R132H positive or ATRX loss astrocytic tumors had a longer progressive- free survival (p<0.0001, p=0.0044, respectively). High Ki-67 expression was associated with shorter PFS in patients with astrocytic tumors (p=0.002). Then we characterized three prognostic subgroups of astrocytic tumors (referred to as A1, A2 and A3). The new model demonstrated a remarkable separation of the progression interval in the three molecular subgroups and the distribution of patients’ age in the A1-A2-A3 model was also significant different. This model will aid predicting the overall survival and progressive time of astrocytic tumors’ patients. PMID:27713914

  11. Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor

    PubMed Central

    Assadi-Porter, Fariba M.; Maillet, Emeline L.; Radek, James T.; Quijada, Jeniffer; Markley, John L.; Max, Marianna

    2010-01-01

    The sweet protein brazzein activates the human sweet receptor, a heterodimeric G-protein coupled receptor (GPCR) composed of subunits T1R2 and T1R3. In order to elucidate the key amino acid(s) responsible for this interaction, we mutated residues in brazzein and each of the two subunits of the receptor. The effects of brazzein mutations were assayed by a human taste panel and by an in vitro assay involving receptor subunits expressed recombinantly in human embryonic kidney cells; the effects of the receptor mutations were assayed by the in vitro assay. We mutated surface residues of brazzein at three putative interaction sites: Site 1 (Loop43), Site 2 (N- and C-terminus and adjacent Glu36, Loop33), and Site 3 (Loop9–19). Basic residues in Site 1 and acidic residues in Site 2 were essential for positive responses from each assay. Mutation of Y39A (Site 1) greatly reduced positive responses. A bulky side chain at position 54 (Site 2), rather than a side chain with hydrogen bonding potential, was required for positive responses as was the presence of the native disulfide bond in Loop 9–19 (Site 3). Results from mutagenesis and chimeras of the receptor indicated that brazzein interacts with both T1R2 and T1R3 and that the Venus fly trap module of T1R2 is important for brazzein agonism. With one exception, all mutations of receptor residues at putative interaction sites predicted by wedge models failed to yield the expected decrease in the brazzein response. The exception, hT1R2:R217A-hT1R3, which contained a substitution in lobe 2 at the interface between the two subunits, exhibited a small selective decrease in brazzein activity. However, because the mutation was found to increase the positive cooperativity of binding by multiple ligands proposed to bind both T1R subunits (brazzein, monellin, and sucralose) but not those that bind to a single subunit (neotame and cyclamate), we suggest that this site in involved in subunit-subunit interaction rather than direct

  12. Effect of complete protein 4.1R deficiency on ion transportproperties of murine erythrocytes

    SciTech Connect

    Rivera, Alicia; De Franceschi, Lucia; Peters, Luanne L.; Gascard,Philippe; Mohandas, Narla; Brugnara, Carlo

    2006-06-02

    Moderate hemolytic anemia, abnormal erythrocyte morphology(spherocytosis), and decreased membrane stability are observed in micewith complete deficiency of all erythroid protein 4.1 protein isoforms(4.1-/-; Shi TS et al., J. Clin. Invest. 103:331,1999). We have examinedthe effects of erythroid protein 4.1 (4.1R) deficiency on erythrocytecation transport and volume regulation. 4.1-/- mice exhibited erythrocytedehydration that was associated with reduced cellular K and increased Nacontent. Increased Na permeability was observed in these mice, mostlymediated by Na/H exchange with normal Na-K pump and Na-K-2Cl cotransportactivities. The Na/H exchange of 4.1-/- erythrocytes was markedlyactivated by exposure to hypertonic conditions (18.2+- 3.2 in 4.1 -/- vs.9.8 +- 1.3 mmol/1013 cell x h in control mice), with an abnormaldependence on osmolarity, (K0.5=417 +- 42 in 4.1 -/- vs. 460 +- 35 mOsmin control mice) suggestive of an up-regulated functional state. Whilethe affinity for internal protons was not altered (K0.5= 489.7 +- 0.7 vs.537.0+- 0.56 nM in control mice), the Vmax of the H-induced Na/H exchangeactivity was markedly elevated in 4.1-/- erythrocytes (Vmax 91.47Moderatehemolytic anemia, abnormal erythrocyte morphology (spherocytosis), anddecreased membrane stability are observed in mice with completedeficiency of all erythroid protein 4.1 protein isoforms (4.1-/-; Shi TSet al., J. Clin. Invest. 103:331,1999). We have examined the effects oferythroid protein 4.1 (4.1R) deficiency on erythrocyte cation transportand volume regulation. 4.1-/- mice exhibited erythrocyte dehydration thatwas associated with reduced cellular K and increased Na content.Increased Na permeability was observed in these mice, mostly mediated byNa/H exchange with normal Na-K pump and Na-K-2Cl cotransport activities.The Na/H exchange of 4.1-/- erythrocytes was markedly activated byexposure to hypertonic conditions (18.2 +- 3.2 in 4.1 -/- vs. 9.8 +- 1.3mmol/1013 cell x h in control mice), with an

  13. Beneficial behavioral, neurochemical and molecular effects of 1-(R)-aminoindan in aged mice.

    PubMed

    Badinter, Felix; Amit, Tamar; Bar-Am, Orit; Youdim, Moussa B H; Weinreb, Orly

    2015-12-01

    Previous neuroprotective studies demonstrated that 1-(R)-aminoindan (AI), which is the major metabolite of the anti-Parkinsonian drug rasagiline, possesses beneficial pharmacological effects in various cell culture and animal models of neurodegeneration. The present study was aimed at investigating the possible neuroprotective effects of AI on cognitive impairments and neurochemical alterations in aged mice. Our findings provide evidence that following chronic systemic treatment with AI (5 mg/kg; daily; 3 months) of aged mice (24 months old), the compound exerted a significant positive impact on neuropsychiatric functions and cognitive behavior deficits, assessed in a variety of tasks (spatial learning and memory retention, working memory, learning abilities and nest building behavior) and produced an antidepressant-like effect. In addition, chronic AI treatment significantly enhanced expression levels of neurotrophins, including brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), tyrosine kinase- B (Trk-B) receptor and synaptic plasticity markers, such as synapsin-1 and growth-associated protein-43 (GAP-43) in the striatum and hippocampus in aged mice. Our results also indicate that AI treatment up-regulated the expression levels of the pro-survival Bcl-2 mRNA, increased the anti-apoptotic index Bcl-2/Bax and enhanced the activity of the antioxidant enzyme catalase in the brain of aged mice. These effects of AI were also confirmed in aged rats (24 months old). Altogether, the present findings indicate that AI can induce neuroprotective effects on age-related alterations in neurobehavioral functions and exerts neurotrophic up-regulatory and anti-apoptotic properties in aged animals. PMID:26087462

  14. The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus.

    PubMed

    Sauter, Kristin A; Bouhlel, M Amine; O'Neal, Julie; Sester, David P; Tagoh, Hiromi; Ingram, Richard M; Pridans, Clare; Bonifer, Constanze; Hume, David A

    2013-01-01

    The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element.

  15. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.

    PubMed

    Ries, Carola H; Cannarile, Michael A; Hoves, Sabine; Benz, Jörg; Wartha, Katharina; Runza, Valeria; Rey-Giraud, Flora; Pradel, Leon P; Feuerhake, Friedrich; Klaman, Irina; Jones, Tobin; Jucknischke, Ute; Scheiblich, Stefan; Kaluza, Klaus; Gorr, Ingo H; Walz, Antje; Abiraj, Keelara; Cassier, Philippe A; Sica, Antonio; Gomez-Roca, Carlos; de Visser, Karin E; Italiano, Antoine; Le Tourneau, Christophe; Delord, Jean-Pierre; Levitsky, Hyam; Blay, Jean-Yves; Rüttinger, Dominik

    2014-06-16

    Macrophage infiltration has been identified as an independent poor prognostic factor in several cancer types. The major survival factor for these macrophages is macrophage colony-stimulating factor 1 (CSF-1). We generated a monoclonal antibody (RG7155) that inhibits CSF-1 receptor (CSF-1R) activation. In vitro RG7155 treatment results in cell death of CSF-1-differentiated macrophages. In animal models, CSF-1R inhibition strongly reduces F4/80(+) tumor-associated macrophages accompanied by an increase of the CD8(+)/CD4(+) T cell ratio. Administration of RG7155 to patients led to striking reductions of CSF-1R(+)CD163(+) macrophages in tumor tissues, which translated into clinical objective responses in diffuse-type giant cell tumor (Dt-GCT) patients.

  16. Anti-ETAR and anti-AT1R autoantibodies are elevated in patients with endstage cystic fibrosis.

    PubMed

    Budding, K; van de Graaf, E A; Hoefnagel, T; Kwakkel-van Erp, J M; van Kessel, D A; Dragun, D; Hack, C E; Otten, H G

    2015-01-01

    Autoantibodies against endothelin-1 type A receptor (ETAR) are present in systemic sclerosis complicated by lung fibrosis and pulmonary hypertension. As increased serum levels and local overproduction of endothelin-1 in the airways are reported in cystic fibrosis (CF) patients, we reasoned that anti-ETAR antibodies could be prevalent in endstage CF patients prior to lung transplantation (LTx). Also, ETAR autoantibodies are frequently associated with autoantibodies against the angiotensin II type 1 receptor (AT1R). We analyzed the presence of anti-ETAR and anti-AT1R autoantibodies in 43 LTx patients (chronic obstructive pulmonary disease (COPD), n=20; CF, n=13; interstitial lung disease (ILD), n=1). We observed overall higher anti-ETAR and anti-AT1R autoantibody titers in sera taken prior to LTx in the CF patient group as compared to COPD. No difference was found in autoantibody levels between patients with CF versus ILD. In sera taken post-LTx we found the same difference in anti-ETAR and anti-AT1R autoantibody titers between patients with CF versus COPD. No difference was found in antibody titers between sera taken prior to or 6 months after LTx. There was no association between autoantibody levels and other relevant demographic parameters, and we found no association between autoantibody titers and the development of the bronchiolitis obliterans syndrome. Both autoantibody titers were strongly correlated. We hypothesize that due to prolonged exposure to bacterial infection, increased levels of AT1R and ETAR result in a deregulated immune response causing autoantibody formation. Further research is expedient to elucidate the occurrence of autoantibodies against ETAR and AT1R and their role in disease progression.

  17. Loss of both CSF1R (FMS) alleles in patients with myelodysplasia and a chromosome 5 deletion

    SciTech Connect

    Boultwood, J.; Rack, K.; Buckle, V.J.; Wainscoat, J.S. ); Kelly, S. ); Madden, J.; Oscier, D.G. ); Sakaguchi, A.Y.; Wang, Lingmei )

    1991-07-15

    A high proportion of patients with myelodysplasia show characteristic karyotypic abnormalities in bone marrow cells. The most distinctive of the myelodysplastic syndromes is the 5q- syndrome characterized by refractory anemia, poorly lobulated megakaryocytes, and an interstitial deletion of the long arm of chromosome 5 (5q deletion) as the sole karyotypic abnormality. Recently, several genes encoding hemopoietic growth factors and receptors, have been localized to the long arm of chromosome 5, and there has been much speculation that deletion of one or more of these genes may be critical to the pathogenesis of the associated myeloid disorders. One candidate gene is CSF1R. The authors have carried out a molecular examination of the CSF1R, both on the 5q- chromosome and on the apparently normal homologous chromsome 5, in 10 patients with myelodysplasia and a 5q deletion. They have found, using restriction fragment length polymorphism analysis and gene dosage experiments, that all 10 patients showed deletion of CSF1R. The homozygous CSF1R loss has been confirmed in 2 patients by an in situ hybridization technique comparing the signal in affected cells to that in control sex-mismatched cells on the same slides. This loss of one CSF1R allele, together with loss in some cells of the remaining allele on the homologous chromsome 5, in patients with myelodysplasia indicates that this is a region of critical gene loss on 5q. The loss of the hemopoietic growth factor receptor gene CSF1R may be important in the pathogenesis of human myeloid leukemia.

  18. A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins.

    PubMed<