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Sample records for 1r camphorylsulphonyl oxaziridine impregnated

  1. Synthesis of Dihydrobenzisoxazoles by the [3+2] Cycloaddition of Arynes and Oxaziridines

    PubMed Central

    Kivrak, Arif; Larock, Richard C.

    2010-01-01

    Dihydrobenzisoxazoles are readily prepared in good yields by the [3+2] cycloaddition of oxaziridines and arynes. The reaction involves an unusual cleavage of the C-O bond of the oxaziridine and tolerates a variety of substituents on the oxaziridine and the o-(trimethylsilyl)aryl triflate to form aryl-, heteroaryl-, alkyl- and naphthyl-substituted dihydrobenzisoxazoles. The resulting halogen-substituted dihydrobenzisoxazoles are readily elaborated to more complex products using palladium-catalyzed crossing-coupling processes. PMID:20936802

  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.

  3. Electrophilic amination of amino acids with N-Boc-oxaziridines: efficient preparation of N-orthogonally diprotected hydrazino acids and piperazic acid derivatives.

    PubMed

    Hannachi, Jean-Christophe; Vidal, Joëlle; Mulatier, Jean-Christophe; Collet, André

    2004-04-02

    A general two-step preparation of enantiopure N(alpha),N(beta)-orthogonally diprotected alpha-hydrazino acids 1 is developed on a multigram scale. The key reaction is the efficient electrophilic amination of N-benzyl amino acids 6 with N-Boc-oxaziridine 7 and accommodates various functional groups encountered in side chains of amino acids. The cyclic 2,3,4,5-tetrahydro-3-pyridazine carboxylic acid (piperazic acid) derivatives 2 and 3 or the cyclic 3,4-dihydro-3-pyrazolecarboxylate 4 are conveniently prepared from glutamic acid or aspartic acid via orthogonally diprotected alpha-hydrazino acids 1m and 1n.

  4. Metabolism-dependent mutagenicity of a compound containing a piperazinyl indazole motif: Role of a novel p450-mediated metabolic reaction involving a putative oxaziridine intermediate.

    PubMed

    Chen, Hao; Murray, Joel; Kornberg, Brian; Dethloff, Lloyd; Rock, David; Nikam, Sham; Mutlib, Abdul E

    2006-10-01

    Compound 1a (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperazin-1-yl]-propyl}-3,3-dimethyl-1,3-dihydro-indol-2-one) was mutagenic to Salmonella typhimurium TA98 in the presence of rat liver S9 subcellular fraction. The metabolism of 1a in rat liver S9 or microsomes demonstrated that it underwent a P450-mediated N-deindazolation (loss of indazole ring) as a predominant metabolic pathway. To investigate a possible link between metabolism and mutagenicity, a structural analogue 1b (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperidin-1-yl]-propyl}-3,3-dimethyl-1,3-dihydro-indol-2-one), the cleaved product 2a (6-chloro-3,3-dimethyl-5-(3-piperazin-1-yl-propyl)-1,3-dihydro-indol-2-one), and the core motif 3a (3-piperazinyl indazole) were evaluated in the Ames assay. It was found that 1b was not mutagenic to Salmonella typhimurium TA98 in the absence or presence of a metabolic activating system. In contrast to 1a, 1b did not undergo the metabolic cleavage (loss of indazole ring). Marginal mutagenicity of 2a to TA98 was observed with rat liver S9, whereas 3a was shown to be a promutagen. It was further demonstrated that 1a inactivated P450 3A, the principle enzyme catalyzing the N-deindazolation reaction, in an NADPH-, time-, and concentration-dependent manner. The kinetics of inactivation was characterized by a K(I) of 8.1 microM and k(inact) of 0.114 min(-1). The differences in mutagenicity between 1a and 1b suggest that a chemical bond extending from the 3-position of the indazole to a heteroatom (as part of another cyclic ring) is a prerequisite for the toxicity. The metabolic process leading to the elimination of the indazole from the rest of the molecule apparently plays a key role in causing mutagenicity. It is postulated that the N-deindazolation of 1a proceeds via an oxaziridine intermediate, the formation of which is indirectly inferred from the presence of benzoic acid in microsomal incubations. Benzoic acid is thought to be derived from the hydrolysis of 3-indazolone, an

  5. 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.

  6. 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)

  7. Apparatus Impregnates Weak Fibers

    NASA Technical Reports Server (NTRS)

    Stanfield, Clarence E.; Wilson, Maywood L.

    1989-01-01

    Low-cost apparatus developed for use in conventional drum winding machine to impregnate fibrous materials having very low tensile strengths. Fiber fitted onto freely-spinning unwinding creel. Unwinds from creel between two tension bars onto guide spools, aligns fiber so properly enters sealed reservoir of resin. Stainless-steel metering die at entrance to reservoir aligns fiber and seals reservoir. Beneficial results obtained by use of reservoir made of polyethylene. Composite material made from resin matrices reinforced by fibers have great potential for solving challenging and often critical problems in design of spacecraft, space structures, and terrestrial structures.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Refractory-metal compound impregnation of polytetrafluoroethylene

    NASA Technical Reports Server (NTRS)

    Leibecki, H. F.

    1969-01-01

    Process impregnates polytetrafluoroethylene /PTFE/ with rhenium or molybdenum compounds. The refractory metals impregnated PTFE combines chemical inertness with electrical conductivity. They are useful for electro-chemical cells, chemical processing equipment, catalysts, electrostatic charge removal, RF gasketing, and cable shielding.

  13. Beneficiation of natural aggregates by polymer impregnation

    SciTech Connect

    Webster, R.P.; Fontana, J.J.

    1980-09-01

    The use of polymer impregnation as a means of upgrading natural aggregates has been investigated. The effect of polymer impregnation on the physical and mechanical properties was evaluated in a series of tests performed using four aggregates of varying quality. The strength of concrete cast with polymer impregnated coarse aggregate was also tested. Two monomer systems were used in the investigation; a methyl methacrylate-based system and a styrene-based system. In general, significant improvements in the physical and mechanical properties of each of the four aggregates resulted from polymer impregnation. The strength of concrete cast with impregnated aggregates varied, being increased in some cases and decreased in others.

  14. Antifungal activity of antimicrobial-impregnated devices.

    PubMed

    Darouiche, R O; Mansouri, M D; Kojic, E M

    2006-04-01

    The in-vitro and in-vivo efficacy against Candida albicans and Candida krusei of devices impregnated with chlorhexidine and chloroxylenol was examined. The impregnated devices produced large zones of inhibition against both organisms (mean size, 39 mm and 38 mm, respectively). In a rabbit model in which segments of silicone catheters were placed percutaneously, non-impregnated devices were twice as likely as impregnated devices to become colonised with either C. albicans or C. krusei. Impregnated devices also had significantly lower colony counts of C. albicans (58 vs. 1361 CFU; p 0.008) and C. krusei (19 vs. 764 CFU; p 0.008).

  15. FGS1r AMA Re-Optimization

    NASA Astrophysics Data System (ADS)

    Nelan, Edmund

    2007-07-01

    This proposal re-optimizes FGS1r interferometric performance {S-curves} by adjustment of the instrument's AMA. This will imporve the FGS1r angular resolution in Transfer Mode while imporving the reliability of Position Mode observations. Observations of close binaries {separations ranging from 12 to 20 mas} and all stars fainter than V=15 will benefit from this re-optimization. Moreover, this re-optimization will return FGS1r to the commissioning state that was deemed optimal for operating it as a guider in 1997.

  16. THE ENZYMATIC NATURE OF C'1r

    PubMed Central

    Naff, George B.; Ratnoff, Oscar D.

    1968-01-01

    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. PMID:5675434

  17. FGS1r, HST's Interferometer That Can

    NASA Astrophysics Data System (ADS)

    Nelan, E.; Makidon, R.; Nagel, L.

    1999-05-01

    The Hubble Space Telescope's Fine Guidance Sensor #1r (FGS1r) offers observing capabilities unmatched by either ground-based interferometers or space-based imaging systems, including those aboard HST. In high angular resolution mode, FGS1r can detect binary systems and measure the separation, position angle, and relative brightness of the components for stars separated by as little as 10 mas and system magnitudes as faint as mv=15. In astrometric mode, FGS1r can measure the relative positions of objects (including binary systems) distributed across its 69**2 amin FOV with a per observation precision of 1mas over a dynamic range of 3 < mv < 17, thereby achieving sub-mas relative astrometry for multi-epoch observing programs. The FGS has also been used as 40hz photometer to temporally resolve a flare on an M dwarf and to observe the occultation of a star by the moon Triton. In this paper we present examples for each of these capabilities and compare FGS results to those of ground-based interferometers, astrometric observing facilities, and to HST's own WFPC2 imager. Astronomers can learn more about what the FGS can do by visiting our web site at the URL listed below. STScI is operated by AURA for NASA.

  18. GLP-1R Agonists Modulate Enteric Immune Responses Through the Intestinal Intraepithelial Lymphocyte GLP-1R.

    PubMed

    Yusta, Bernardo; Baggio, Laurie L; Koehler, Jacqueline; Holland, Dianne; Cao, Xiemin; Pinnell, Lee J; Johnson-Henry, Kathene C; Yeung, William; Surette, Michael G; Bang, K W Annie; Sherman, Philip M; Drucker, Daniel J

    2015-07-01

    Obesity and diabetes are characterized by increased inflammation reflecting disordered control of innate immunity. We reveal a local intestinal intraepithelial lymphocyte (IEL)-GLP-1 receptor (GLP-1R) signaling network that controls mucosal immune responses. Glp1r expression was enriched in intestinal IEL preparations and copurified with markers of Tαβ and Tγδ IELs, the two main subsets of intestinal IELs. Exendin-4 increased cAMP accumulation in purified IELs and reduced the production of cytokines from activated IELs but not from splenocytes ex vivo. These actions were mimicked by forskolin, absent in IELs from Glp1r(-/-) mice, and attenuated by the GLP-1R agonist exendin (9-39) consistent with a GLP-1R-dependent mechanism of action. Furthermore, Glp1r(-/-) mice exhibited dysregulated intestinal gene expression, an abnormal representation of microbial species in feces, and enhanced sensitivity to intestinal injury following administration of dextran sodium sulfate. Bone marrow transplantation using wild-type C57BL/6 donors normalized expression of multiple genes regulating immune function and epithelial integrity in Glp1r(-/-) recipient mice, whereas acute exendin-4 administration robustly induced the expression of genes encoding cytokines and chemokines in normal and injured intestine. Taken together, these findings define a local enteroendocrine-IEL axis linking energy availability, host microbial responses, and mucosal integrity to the control of innate immunity.

  19. Polytetrafluoroethylene-Impregnated Anodization For Aluminum

    NASA Technical Reports Server (NTRS)

    Danford, Merlin D.

    1990-01-01

    Technical memorandum describes experiments on ability of two commercial coatings and of standard hard anodization to protect aluminum against corrosion. Both commercial coatings, Polylube and Tufram, polytetrafluoroethylene-impregnated anodizations. Standard hard-anodized coating found to provide greatest protection.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Effects of Weathering on Impregnated Charcoal Performance.

    DTIC Science & Technology

    1981-09-01

    4 A mixture of elemental iodine (0.5 wt.%) and an S" activated carbon (BC Type 177) from coconut shells was heated (6.70 C/min) in a flow of purified...Penetration of 1 3 1 ICH3 at 21°C for new (not used) Coconut Shell Commercial Carbons (impregnated) With and Without Prehumidification...Mixture of Elemental Iodine and Non-impregnated Coconut Activated Carbon . (Note: Y coordinate is logarithmic)... 87 29. Formation of Organic Iodides

  5. 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.

  6. Synthesis of the supported catalysts by co-impregnation and sequential impregnation methods

    NASA Astrophysics Data System (ADS)

    Dwi Nugrahaningtyas, Khoirina; Hidayat, Yuniawan; Patiha; Prihastuti, Nina; Yelvi, Brigitta; Umami Nur Kalimah, Riza

    2017-02-01

    The non-sulfide catalysts Co-Mo/USY were prepared with three different methods, i.e. co-impregnation and two sequential impregnation procedures. The phases of the synthesized materials and their composition were characterized with X-ray diffraction. Furthermore, the X-ray diffraction patterns were analyzed using Le Bail methods with Rietica software. Finally, an overview of the substitution effect of cobalt and molybdenum on the metal content and acidity of the catalyst were also investigated.

  7. Kisspeptin/KISS1R System in Breast Cancer.

    PubMed

    Cvetković, Donna; Babwah, Andy V; Bhattacharya, Moshmi

    2013-09-26

    Kisspeptins (KP), peptide products of the kisspeptin-1 (KISS1) gene are the endogenous ligands for a G protein-coupled receptor (GPCR) - KP receptor (KISS1R). KISS1R couples to the Gαq/11 signaling pathway. KISS1 is a metastasis suppressor gene and the KP/KISS1R signaling has anti-metastatic and tumor-suppressant effects in numerous human cancers. On the other hand, recent studies indicate that KP/KISS1R pathway plays detrimental roles in breast cancer. In this review, we summarize recent developments in the understanding of the mechanisms regulating KP/KISS1R signaling in breast cancer metastasis.

  8. 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.

  9. Impregnating magnetic components with MDA free epoxy

    SciTech Connect

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

    1995-08-01

    This paper describes the use of {open_quotes}Formula 456{close_quotes} 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.

  10. 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

  11. 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.

  12. The 1/r1/r singularity in weakly nonlinear fracture mechanics

    NASA Astrophysics Data System (ADS)

    Bouchbinder, Eran; Livne, Ariel; Fineberg, Jay

    2009-09-01

    Material failure by crack propagation essentially involves a concentration of large displacement-gradients near a crack's tip, even at scales where no irreversible deformation and energy dissipation occurs. This physical situation provides the motivation for a systematic gradient expansion of general nonlinear elastic constitutive laws that goes beyond the first order displacement-gradient expansion that is the basis for linear elastic fracture mechanics (LEFM). A weakly nonlinear fracture mechanics theory was recently developed by considering displacement-gradients up to second order. The theory predicts that, at scales within a dynamic lengthscale ℓ from a crack's tip, significant logr displacements and 1/r displacement-gradient contributions arise. Whereas in LEFM the 1/r singularity generates an unbalanced force and must be discarded, we show that this singularity not only exists but is also necessary in the weakly nonlinear theory. The theory generates no spurious forces and is consistent with the notion of the autonomy of the near-tip nonlinear region. The J-integral in the weakly nonlinear theory is also shown to be path-independent, taking the same value as the linear elastic J-integral. Thus, the weakly nonlinear theory retains the key tenets of fracture mechanics, while providing excellent quantitative agreement with measurements near the tip of single propagating cracks. As ℓ is consistent with lengthscales that appear in crack tip instabilities, we suggest that this theory may serve as a promising starting point for resolving open questions in fracture dynamics.

  13. L-Theanine elicits umami taste via the T1R1 + T1R3 umami taste receptor.

    PubMed

    Narukawa, Masataka; Toda, Yasuka; Nakagita, Tomoya; Hayashi, Yukako; Misaka, Takumi

    2014-06-01

    L-Theanine is a unique amino acid present in green tea. It elicits umami taste and has a considerable effect on tea taste and quality. We investigated L-theanine activity on the T1R1 + T1R3 umami taste receptor. L-Theanine activated T1R1 + T1R3-expressing cells and showed a synergistic response with inosine 5'-monophosphate. The site-directed mutagenesis analysis revealed that L-theanine binds to L-amino acid binding site in the Venus flytrap domain of T1R1. This study shows that L-theanine elicits an umami taste via T1R1 + T1R3.

  14. Screening of allergic components mediated by H(1)R in homoharringtonine injection through H(1)R/CMC-HPLC/MS.

    PubMed

    Guo, Ying; Han, Shengli; Cao, Jingjing; Liu, Qi; Zhang, Tao

    2014-12-01

    It has been reported that the histamine H1 receptor (H(1)R) gene is up-regulated in patients with allergic rhinitis and H(1)R expression level strongly correlates with the severity of allergy symptoms. Drugs for therapy should avoid allergy symptoms, especially for patients with over-expressed H(1)R. Therefore, screening of the components which could induce H(1)R activation is urgently needed for drug safety evaluation. Homoharringtonine injection is a preparation for acute nonlymphocytic leukemia, which is approved by China Food and Drug Administration (CFDA) and US Food and Drug Administration. However, severely adverse reactions often occur with intravenous injection of the preparation. In present study, an H(1)R/CMC model was applied for capturing membrane retained components which could induce H(1)R activation. Retention components were enriched and analyzed by H(1)R/CMC-HPLC/MS. Homoharringtonine was recognized, separated and identified in homoharringtonine injection. Ca(2+) flux assay and p-IP3R expression founded that homoharringtonine retained by the H1 R/CMC model increased phosphorylation of IP3R and promoted cytosolic free Ca(2+) elevation in a dose-dependent manner which further verified the activity of homoharringtonine in activating the H1 R. In conclusion, homoharringtonine was screened and identified as a potential allergic factor. This provides an indication that a patient with over-expressed H1 R should be aware of possible allergic reaction when applying homoharringtonine injection.

  15. Thermocapillary motion on lubricant-impregnated surfaces

    NASA Astrophysics Data System (ADS)

    Bjelobrk, Nada; Girard, Henri-Louis; Bengaluru Subramanyam, Srinivas; Kwon, Hyuk-Min; Quéré, David; Varanasi, Kripa K.

    2016-10-01

    We show that thermocapillary-induced droplet motion is markedly enhanced when using lubricant-impregnated surfaces as compared to solid substrates. These surfaces provide weak pinning, which makes them ideal for droplet transportation and specifically for water transportation. Using a lubricant with viscosity comparable to that of water and temperature gradients as low as 2 K/mm, we observe that drops can propel at 6.5 mm/s, that is, at least 5 times quicker than reported on conventional substrates. Also in contrast with solids, the liquid nature of the different interfaces makes it possible to predict quantitatively the thermocapillary Marangoni force (and velocity) responsible for the propulsion.

  16. 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.

  17. 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.

  18. Kisspeptin/KISS1R System in Breast Cancer

    PubMed Central

    Cvetković, Donna; Babwah, Andy V.; Bhattacharya, Moshmi

    2013-01-01

    Kisspeptins (KP), peptide products of the kisspeptin-1 (KISS1) gene are the endogenous ligands for a G protein-coupled receptor (GPCR) - KP receptor (KISS1R). KISS1R couples to the Gαq/11 signaling pathway. KISS1 is a metastasis suppressor gene and the KP/KISS1R signaling has anti-metastatic and tumor-suppressant effects in numerous human cancers. On the other hand, recent studies indicate that KP/KISS1R pathway plays detrimental roles in breast cancer. In this review, we summarize recent developments in the understanding of the mechanisms regulating KP/KISS1R signaling in breast cancer metastasis. PMID:24155777

  19. Boron impregnation treatment of Eucalyptus grandis wood.

    PubMed

    Dhamodaran, T K; Gnanaharan, R

    2007-08-01

    Eucalyptus grandis is suitable for small timber purposes, but its wood is reported to be non-durable and difficult to treat. Boron compounds being diffusible, and the vacuum-pressure impregnation (VPI) method being more suitable for industrial-scale treatment, the possibility of boron impregnation of partially dry to green timber was investigated using a 6% boric acid equivalent (BAE) solution of boric acid and borax in the ratio 1:1.5 under different treatment schedules. It was found that E. grandis wood, even in green condition, could be pressure treated to desired chemical dry salt retention (DSR) and penetration levels using 6% BAE solution. Up to a thickness of 50mm, in order to achieve a DSR of 5 kg/m(3) boron compounds, the desired DSR level as per the Indian Standard for perishable timbers for indoor use, it was found that neither the moisture content of wood nor the treatment schedule posed any problem as far as the treatability of E. grandis wood was concerned.

  20. Red hair is the null phenotype of MC1R.

    PubMed

    Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

    2008-08-01

    The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

  1. 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.

  2. 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.

  3. Post FGS1r AMA Adjustment, OFAD Re-Calibration

    NASA Astrophysics Data System (ADS)

    Nelan, Edmund

    2009-07-01

    The FGS1r AMA was adjusted in January 22, 2009 to restore the morphology of the FGS S-curves to near ideal. While this significantly improved FGS1r's angular resolution, it also changed the instrument's geometric distortion at a level that unacceptably impairs its astrometric performance. To mitigate this problem, this proposal uses FGS1r in POS mode to observe OAFD stars in M35 with six HST orbits at a variety of orientations {75 deg to 113 deg} and translations of the FGS FOV. The observations will obtain the relative positions of the selected stars with 1 mas precision. Comparing the observed positions to the OFAD catalog, which gives the undistorted relative positions of the same stars to an accuracy of 1 mas, the geometric distortion in FGS1r will be re-calibrated.

  4. 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.

  5. 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.

  6. Tobramycin-impregnated methylmethacrylate for mandible reconstruction.

    PubMed

    Goode, R L; Reynolds, B N

    1992-02-01

    Reconstruction of the mandible to restore continuity following resection is described in four cases using a tobramycin-impregnated methylmethacrylate implant fabricated at the time of surgery. Methylmethacrylate has excellent biocompatibility and strength and has been used in surgery for over 20 years. The technique uses readily available materials and is similar in concept to reconstruction with a metal plate. Potential advantages are: (1) the presence of a potent antibiotic within the implant that is released over a period of months to minimize postoperative infection and (2) the capability of the material to accurately fit any defect, either when used alone or in combination with a plate or rod. Three of the four patients whom we present are doing well; one implant became exposed following postoperative radiotherapy and had to be removed.

  7. The germline-enriched Ppp1r36 promotes autophagy

    PubMed Central

    Zhang, Qinghua; Gao, Maomao; Zhang, Ying; Song, Ying; Cheng, Hanhua; Zhou, Rongjia

    2016-01-01

    Spermatogenesis is a highly regulated process during which haploid sperm cells are generated. Although autophagy is involved in the spermatogenesis process, the molecular pathways and regulations of autophagy in germ cell development remain elusive. Here, we showed that Ppp1r36, a regulatory subunit of protein phosphatase 1, is expressed during gonadal development, mainly in testes during spermatogenesis. Autophagy protein LC3 (microtubule associated protein 1 light chain 3), especially its active form LC3-II, had a similar expression pattern to Ppp1r36. Moreover, LC3-II level and puncta analysis showed that autophagy is up-regulated around 21 dpp (day postpartum) in postnatal testis, indicating a potential role of autophagy during the first wave of spermatogenesis. We demonstrated that Ppp1r36 promotes autophagosome formation upon starvation induction. Further autophagy flux analysis using a tandem fluorescent indicator, mCherry-GFP-LC3, confirmed that Ppp1r36 participated in autophagy. We further determined that Ppp1r36 is associated with Atg16L1 (autophagy related 16-like 1) in autophagy of starvation induction. Thus, our results uncover a potential role of the regulatory subunit Ppp1r36 of protein phosphatase 1 in enhancing autophagy during spermatogenesis. PMID:27098880

  8. MC1R signaling. Intracellular partners and pathophysiological implications.

    PubMed

    Herraiz, Cecilia; Garcia-Borron, Jose C; Jiménez-Cervantes, Celia; Olivares, Conchi

    2017-03-01

    The melanocortin-1 receptor (MC1R) preferentially expressed in melanocytes is best known as a key regulator of the synthesis of epidermal melanin pigments. Its paracrine stimulation by keratinocyte-derived melanocortins also activates DNA repair pathways and antioxidant defenses to build a complex, multifaceted photoprotective response. Many MC1R actions rely on cAMP-dependent activation of two transcription factors, MITF and PGC1α, but pleiotropic MC1R signaling also involves activation of mitogen-activated kinases and AKT. MC1R partners such as β-arrestins, PTEN and the E3 ubiquitin ligase MGRN1 differentially regulate these pathways. The MC1R gene is complex and polymorphic, with frequent variants associated with skin phenotypes and increased cancer risk. We review current knowledge of signaling from canonical MC1R, its splice isoforms and natural polymorphic variants. Recently discovered intracellular targets and partners are also discussed, to highlight the diversity of mechanisms that may contribute to normal and pathological variation of pigmentation and sensitivity to solar radiation-induced damage. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.

  9. Drug loading of foldable commercial intraocular lenses using supercritical impregnation.

    PubMed

    Bouledjouidja, A; Masmoudi, Y; Sergent, M; Trivedi, V; Meniai, A; Badens, E

    2016-03-16

    The drug delivery through intraocular lenses (IOLs) allows the combination of cataract surgery act and postoperative treatment in a single procedure. In order to prepare such systems, "clean" supercritical CO2 processes are studied for loading commercial IOLs with ophthalmic drugs. Ciprofloxacin (CIP, an antibiotic) and dexamethasone 21-phosphate disodium (DXP, an anti-inflammatory drug) were impregnated into foldable IOLs made from poly-2-hydroxyethyl methacrylate (P-HEMA). A first pre-treatment step was conducted in order to remove absorbed conditioning physiological solution. Supercritical impregnations were then performed by varying the experimental conditions. In order to obtain transparent IOLs and avoid the appearance of undesirable foaming, it was necessary to couple slow pressurization and depressurization phases during supercritical treatments. The impregnation yields were determined through drug release studies. For both drugs, release studies show deep and reproducible impregnation for different diopters. For the system P-HEMA/CIP, a series of impregnations was performed to delimit the experimental range at two pressures (80 and 200 bar) in the presence or absence of ethanol as a co-solvent for two diopters (+5.0 D and +21.0 D). Increase in pressure in the absence of a co-solvent resulted in improved CIP impregnation. The addition of ethanol (5 mol%) produced impregnation yields comparable to those obtained at 200 bar without co-solvent. A response surface methodology based on experimental designs was used to study the influence of operating conditions on impregnation of IOLs (+21.0 D) in the absence of co-solvent. Two input variables with 5 levels each were considered; the pressure (80-200 bar) and the impregnation duration (30-240 min). CIP impregnation yields ranging between 0.92 and 3.83 μg CIP/mg IOL were obtained from these experiments and response surface indicated the pressure as a key factor in the process. The DXP impregnation in P-HEMA was

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

    2017-02-01

    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.

  15. 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

  16. 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.

  17. 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.

  18. 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…

  19. 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…

  20. FLOS-1R and FLOD-1R Single- and Double-Precision Floating Point Packages for the LINC,

    DTIC Science & Technology

    floating point package for the LINC. The present revision corrects an error in the Add routine, requires fewer memory locations, and is slightly faster than the original program. The functional description of Flod-1R is exactly identical to that of the original program FLOD. Since the original report also described a matching single-precision floating point package, FLOS, the report also describes FLOS. Although FLOS has not been revised, it is given the revised name FLOS-1R in this report. (Modified author

  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. 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.

  3. 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.

  4. 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

    2016-05-09

    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.

  5. 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.

  6. 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).

  7. Fog-harvesting potential of lubricant-impregnated electrospun nanomats.

    PubMed

    Lalia, Boor Singh; Anand, Sushant; Varanasi, Kripa K; Hashaikeh, Raed

    2013-10-22

    Hydrophobic PVDF-HFP nanowebs were fabricated by a facile electrospinning method and proposed for harvesting fog from the atmosphere. A strong adhesive force between the surface and a water droplet has been observed, which resists the water being shed from the surface. The water droplets on the inhomogeneous nanomats showed high contact angle hysteresis. The impregnation of nanomats with lubricants (total quartz oil and Krytox 1506) decreased the contact angle hysteresis and hence improved the roll off of water droplets on the nanomat surface. It was found that water droplets of 5 μL size (diameter = 2.1 mm) and larger roll down on an oil-impregnated surface, held vertically, compared to 38 μL (diameter = 4.2 mm) on a plain nanoweb. The contact angle hysteresis decreased from ~95 to ~23° with the Krytox 1506 impregnation.

  8. Liquefaction of coal impregnated with catalyst during preswelling

    SciTech Connect

    Brannan, C.J.; Curtis, C.W.; Cronauer, D.C.

    1994-12-31

    The effect of impregnating coal with slurry phase catalysts during solvent preswelling on coal conversion was investigated. Black Thunder subbituminous coal which was either untreated or pretreated with aqueous SO{sub 2} was used. The coal was placed into the swelling solvents, THF, methanol or isopropanol, for 96 hr prior to liquefaction. Slurry phase catalysts, Mo naphthenate, Molyvan L and Ni octoate, were introduced into the swelling solvents; catalyst uptake by coal was 90 to 95% of the catalyst introduced. Coal conversions of these impregnated coals were obtained at 410{degrees}C in reaction solvents of 1-methylnaphthalene, coal-derived V1074, and dihydroanthracene, and were compared to those obtained with swelled and nonswelled coals. The swelling solvent and the SO{sub 2} pretreatment affected the amount of coal conversion obtained. Coal conversions achieved with impregnated coals were somewhat less than those achieved when the catalyst was added directly to the reactor.

  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. Starch-modified magnetite nanoparticles for impregnation into cartilage

    NASA Astrophysics Data System (ADS)

    Soshnikova, Yulia M.; Roman, Svetlana G.; Chebotareva, Natalia A.; Baum, Olga I.; Obrezkova, Mariya V.; Gillis, Richard B.; Harding, Stephen E.; Sobol, Emil N.; Lunin, Valeriy V.

    2013-11-01

    The paper presents preparation and characterization of starch-modified Fe3O4 nanoparticles (NPs) in aqueous dispersion after impregnation into healthy and damaged types of cartilage. We show that starch-modified dispersion has a narrower size distribution than a non-stabilized one. The average hydrodynamic radius of magnetite NPs in a dispersion used for impregnation into cartilage is (48 ± 1) nm with the width of the distribution from 5 to 200 nm. We investigate stability of aqueous magnetite NPs dispersions during storage and with increase in temperature (up to 70 °C). We find that polydisperse magnetite NPs can penetrate into cartilage and the size and concentration of impregnated particles depend on the organization of the tissue structure. The results confirm the possibility of application of magnetite NPs in diagnostics and laser treatment of degenerative cartilage deceases.

  11. The design of CY-1R night vision helmet

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Chang, Benkang

    2004-05-01

    In this paper, the research intention and design principle of CY-1R night vision helmet are explained which fills the gaps in active-passive combined night vision field in our country. The structure, composition, mechanism and overall performance of the goggle are analyzed. It is a new type device consisting of laser illuminator system, special optical system and high performance low-level-light intensifier. Based on these characteristics, the sensitivity of the system is high and the image observed is very clear. Taking advantage of it, we can complete the military operation under any atrocious weather conditions.

  12. Field evaluation of bednets impregnated with deltamethrin for malaria control.

    PubMed

    Wu, N; Qin, L; Liao, G; Zhou, W; Geng, W; Shi, Y; Tan, Y; Zhao, K

    1993-12-01

    Trials were undertaken in a hypoendemic area of malaria in an area bordering Vietnam, in Napo County of Guangxi Zhuang Autonomous Region, China. The aim was to compare the relative cost effectiveness of DDT residual spraying and of bednets impregnated with deltamethrin in the malaria control program. The trials were divided into three subgroups: (1) two farming areas and one coal mining area with a total population > 20,000, where the trial consisted of mass bednets impregnated with deltamethrin 15 mg/m2 net surface once a year, (2) one farming area with a population of approximately 3,600 where DDT residual spraying at 2g/m2 was carried out twice a year in May and August; (3) one farming area and one coal mining village with a population of > 4,000 were used as a control. The malaria vector population consisted mainly of Anopheles minimus and An. anthropophagus with a small contribution from An. sinensis. After bednets were impregnated with deltamethrin the mosquitos resting on the surface of the bednets decreased significantly, although there was less effect on the total vector population. The results showed that malaria incidence decreased significantly both in areas where impregnated bednets were used and in areas where residual spraying was undertaken. The positive IFAT rates of residents who slept under impregnated bednets decreased significantly in farming areas, especially in that area where bednet impregnation as a vector control measure had been undertaken for two years, but there was no change in the IFAT rate in DDT sprayed or control areas.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. 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.

  14. 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.

  15. Exposure to creosote in the impregnation and handling of impregnated wood.

    PubMed

    Heikkilä, P R; Hämeilä, M; Pyy, L; Raunu, P

    1987-10-01

    The major components of vapors and polycyclic aromatic hydrocarbons in particulate matter were identified and quantified in two creosote impregnation plants and in the handling of treated wood. The vapors were collected on XAD-2 resin (recovery in the range of 82-102%) and analyzed by gas chromatography. Particulate polycyclic aromatic hydrocarbons were collected on glass fiber filters and analyzed with high-pressure liquid chromatography with a fluorescence detector. The main components of the vapors were naphthalene, methyl naphthalenes, indene, phenol, and its methyl homologues, benzothiophene, diphenyl, acenaphthene and fluorene. The exposure of the workers to vapors varied between 0.1 and 11 mg/m3. The concentrations of particulate polycyclic aromatic hydrocarbons varied between 0.2 and 46 micrograms/m3. The benzo(a)pyrene concentration was under 0.03 micrograms/m3, except in manual metal-arc welding and in the boring of railroad ties, where it was 0.24-0.89 micrograms/m3. In the measurement of creosote vapors, naphthalene could be used as an indicator agent.

  16. 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.

  17. 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.

  18. 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…

  19. 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

  20. 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.

  1. 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 900 times.

  2. An X-Ray Photoelectron Spectroscopy (XPS) Study of Activated Carbons Impregnated with some Organocopper Complexes,

    DTIC Science & Technology

    1993-10-01

    AD-A282 721 l lllllll a Dfene Defence nationals AN X.RAY PHOTOELECTRON SPECTROSCOPY (XPS) STUDY OF ACTIVATED CARBONS IMPREGNATED WITH SOME... ammoniacal solution as a carrier into which all impregnants (except TEDA) were dissolved. Without a suitable carrier, and with the inherent low vapor...and will not be repeated here. All five complexes were synthesized at DREO using known methods. 2 2.2 IMPREGNATING PROCEDURES Two impregnating

  3. Modification of oil palm wood using acetylation and impregnation process

    NASA Astrophysics Data System (ADS)

    Subagiyo, Lambang; Rosamah, Enih; Hesim

    2017-03-01

    The purpose of this study is chemical modification by process of acetylation and impregnation of oil palm wood to improve the dimensional stability. Acetylation process aimed at substituting the hydroxyl groups in a timber with an acetyl group. By increasing the acetyl groups in wood is expected to reduce the ability of wood to absorb water vapor which lead to the dimensions of the wood becomes more stable. Studies conducted on oil palm wood (Elaeis guineensis Jacq) by acetylation and impregnation method. The results showed that acetylated and impregnated wood oil palm (E. guineensis Jacq) were changed in their physical properties. Impregnation with coal ashfly provide the greatest response to changes in weight (in wet conditions) and after conditioning (dry) with the average percentage of weight gain of 198.16% and 66.41% respectively. Changes in volume indicates an increase of volume in the wet condition (imbibition) with the coal ashfly treatment gave highest value of 23.04 %, whereas after conditioning (dry) the highest value obtained in the treatment of gum rosin:ethanol with a volume increase of 13:44%. The highest changes of the density with the coal ashfly impregnation in wet condition (imbibition) in value of 142.32% and after conditioning (dry) of 57.87%. The result of reduction in water absorption (RWA) test showed that in the palm oil wood samples most stable by using of gum rosin : ethanol of 0.97%, whereas the increase in oil palm wood dimensional stability (ASE) is the best of 59.42% after acetylation with Acetic Anhydride: Xylene.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Two Droplets Burning Side by Side on MSL-1R

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The Fiber-Supported Droplet Combustion (FSDC) experiment team got more than twice as many burns have been completed as were originally scheduled for STS-95. This image was taken July 12, 1997, MET:10/08:13 (approximate). As shown here, scientists were able to burn two droplets side by side, more closely mimicking behavior of burning fuel in an engine. This shows ignition of a single drop that subsequently burned while a fan blew through the chamber, giving the scientists data on burning with convection, but no buoyancy -- an important distinction when you're trying to solve a problem by breaking it into parts. FSDC-2 studied fundamental phenomena related to liquid fuel droplet combustion in air. Pure fuels and mixtures of fuels were burned as isolated single and dual droplets with and without forced air convection. The FSDC guest investigator was Forman Williams, University of California, San Diego. The experiment was part of the space research investigations conducted during the Microgravity Science Laboratory-1R mission (STS-94, July 1-17 1997). Advanced combustion experiments will be a part of investigations plarned for the International Space Station. (200KB JPEG, 1171 x 1319 pixels; downlinked video, higher quality not available) The MPG from which this composite was made is available at http://mix.msfc.nasa.gov/ABSTRACTS/MSFC-0300177.html.

  9. 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.

  10. 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.

  11. Low solids content, coal tar based impregnating pitch

    SciTech Connect

    Chu, A.S.; Bart, E.F.; Cook, G.R.; Horbachewski, D.M.

    1987-05-12

    A method is described of obtaining a coal tar based impregnant pitch characterized by having a sulfur content of less than 0.5 weight percent and a quinoline insoluble, QI, content of less than about 0.5 percent and enhanced impregnation property. This method comprises: selecting coal tar oil feedstock having: (1) a distillation residue at 355/sup 0/C > 30 weight percent; and (2) a QI < 0.5 weight percent; heating the feedstock to a temperature of between about 150/sup 0/C and 390/sup 0/C; and oxidizing and stripping the feedstock until: an ASTM D-3104-77 softening point between about 90/sup 0/C and 150/sup 0/C; a coking value of at least 45 weight percent according to ASTM D-2416-73; and a flashpoint of at least 200/sup 0/C according to ASTM D92-72 are obtained.

  12. 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.

  13. Effectiveness of Commercially-Available Antibiotic-Impregnated Implants

    DTIC Science & Technology

    2006-08-01

    were tested for tuberculosis, brucellosis and Q fever, and were healthy prior to the study. Study design. The goats were randomised into four...impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no...for the care and use of laboratory animals. Twenty-nine castrated male Spanish goats with a mean weight of 48.1 kg ( SD 0.68) were used. All

  14. 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.

  15. Surrogate nits impregnated with white piedra--a case report.

    PubMed

    Ghorpade, A

    2004-07-01

    White piedral spores packed inside empty pedicular nits were accidentally found on microscopic examination in a 42-year-old Indian woman who presented with hair loss. The diagnosis of piedra was confirmed on culture. She responded to topical 2% miconazole nitrate solution and manual removal of the nits. This is the first case report of pedicular nits found to be impregnated with spores of white piedra.

  16. 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.

  17. 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.

  18. Stannic chloride impregnated chitosan for defluoridation of water.

    PubMed

    Kahu, Shashikant; Shekhawat, Anita; Saravanan, D; Jugade, Ravin

    2017-03-01

    Chitosan, a potent amino polysaccharide, has been impregnated with Sn(IV) chloride for effective adsorption of fluoride from water. The Sn(IV) chloride impregnated chitosan was synthesized using microwave assisted technique. The material was thoroughly characterized using FTIR, SEM, EDX and XRD. The increase in surface area and pore volume has been revealed from BET studies. Enhanced thermal stability of this material was ascertained by TGA-DTA studies. This Sn(IV) chloride impregnated chitosan(Sn-Ch) has been exploited for its defluoridation property. Various parameters like pH, amount of adsorbent, adsorption time etc have been optimized to achieve maximum defluoridation efficiency. Under optimum conditions, Sn-Ch was found to have adsorption capacity of 17. 63mg/g. The equilibrium studies showed that the data fits well with Freundlich isotherm model. Thermodynamics and kinetics parameters have been evaluated. The material has been applied for the defluoridation of real water sample. It was found to be recyclable material and can be regenerated and reused multiple times adding a greener dimension.

  19. Liquid-impregnated porous polypropylene surfaces for liquid repellency.

    PubMed

    Brown, Philip S; Bhushan, Bharat

    2017-02-01

    Polypropylene is a popular plastic material used in consumer packaging. It would be desirable if such plastic containers were liquid repellent and not so easily fouled by their contents. Superomniphobic surfaces typically work by keeping the fouling liquid in a metastable state, with trapped pockets of air between the substrate and the liquid. An alternative method with greater long-term stability utilizes liquid-impregnated surfaces, where the liquid being repelled slides over an immiscible liquid immobilized on a porous surface. Here, we report a method for creating porous polypropylene surfaces amenable to liquid-impregnation. A solvent-nonsolvent polypropylene solution was deposited at high temperature to achieve the necessary porosity. Such surfaces were further functionalized with fluorosilane and dipped in the lubricating liquid to result in a durable, liquid-repellent surface. It is believed these liquid-impregnated surfaces will be more industrially viable than previous examples due to the ease of fabrication and their durability. These surfaces were found to exhibit repellency towards water, oils, shampoo, and laundry detergent with extremely low tilt angles due to the smooth liquid-liquid contact between the lubricating liquid and the liquid being repelled.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Characterization of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia.

    PubMed

    Shimomura-Kuroki, Junko; Farooq, Muhammad; Sekimoto, Tsuneo; Amizuka, Norio; Shimomura, Yutaka

    2016-05-09

    Parathyroid hormone and parathyroid hormone-related peptide (PTHrP), and its receptor (PTH1R) play an important role in differentiation of bone and cartilage in the developing stages. Constitutive dimers of PTH1R are believed to be dissociated by ligand binding, and monomeric PTH1R is capable of activating G protein. Jansen type metaphyseal chondrodysplasia is caused by missense mutations in PTH1R, which are constitutively active even without the presence of the ligands. However, the underlying pathomechanisms remained largely unknown. In this study, we have attempted to further characterize a PTH1R missense mutation H223R responsible for Jansen type metaphyseal chondrodysplasia. cDNAs encoding wild-type (Wt)- and H223R mutant (Mut)-PTH1R were transfected into HEK293T cells, and as a consequence of western blots, both the Wt- and Mut-PTH1R proteins showed several fragments between 55 and 65 kDa in size, while the patterns of N-glycosylation were distinct between them. Then we hypothesized that the Mut-PTH1R might physically interact with the Wt-PTH1R, leading to affect the downstream cAMP accumulation. Co-immunoprecipitation assays clearly showed that interaction occurred not only between the Wt-PTH1R themselves, but also between the Wt- and Mut-PTH1R. Furthermore, we performed CRE reporter assays to investigate cAMP accumulation. Constitutive, ligand-independent cAMP accumulation was observed in HEK293T cells expressing the Mut-PTH1R. Interestingly, there was a statistically lower constitutive activity in HEK293T cells co-expressing the Wt- and Mut-PTH1R proteins. Summarizing, it seems likely that Mut-PTH1R may be, at least in part, co-localized with Wt-PTH1R by forming a heterodimer, leading to affect the function to each other.

  5. Decreased expression of IDH1-R132H correlates with poor survival in gastrointestinal cancer

    PubMed Central

    Li, Jieying; Huang, Jianfei; Huang, Fang; Jin, Qing; Zhu, Huijun; Wang, Xudong; Chen, Meng

    2016-01-01

    Isocitrate dehydrogenase (IDH1) is an NADP-dependent enzyme that catalyzes the decarboxylation of isocitrate to alpha-ketoglutarate. The IDH1-R132H mutation predicts a better clinical outcome for glioma patients, and the expression of IDH1-R132H correlates with a favorable outcome in patients with brain tumors. Here, we investigated IDH1-R132H expression in both gastric (n=526) and colorectal (n=399) tissues by performing immunohistochemistry analyses on tissue microarrays. We also tested whether IDH1-R132H expression correlated with various clinical parameters. In both gastric and colorectal cancer, expression of IDH1-R132H was associated with tumor stage. Patients with low IDH1-R132H expression had a poor overall survival. Our data indicate that IDH1-R132H expression could be used as a predictive marker of prognosis for patients with gastrointestinal cancer. PMID:27655638

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

    PubMed

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

    2007-12-19

    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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Marking excision margins of surgical specimens by silver impregnation.

    PubMed

    Feit, J

    2005-07-01

    Marking excision margins of surgical specimens by silver impregnation has several advantages over commonly used Indian ink: during the slicing the tissue preserves its natural color, the staining is permanent, and the pigment does not smudge over cutting surfaces. The pigment is clearly visible in tissue sections. The tissue specimen is shortly dipped into a 10% water solution of argent nitrate (AgNO3 with HNO3). After slicing, the tissue specimens are developed in common black & white developer for several seconds and paraffin processed as usual. The method is suitable for formaldehyde fixed as well as fresh tissue specimens.

  15. Separation of uranium on polyurethane foam impregnated with trioctylphosphine oxide

    SciTech Connect

    Korkisch, J.; Steffan, I.

    1983-01-01

    A method is described for the quantitative separation of uranium from practically all other elements in 1M hydrochloric acid solution containing ascorbic acid. From such a solution uranium is retained selectively by a column containing open-cell polyurethane foam impregnated with tri-n-octylphosphine oxide (TOPO). The uranium together with TOPO is eluted with ethanol and then it is adsorbed on a column of Dowex 1 anion exchange resin from a HCl-organic solvent system. Uranium is eluted with 1M hydrochloric acid. 5 tables.

  16. Alkali impregnated teflon as a filter for atmospheric SO 2 PIXE analysis

    NASA Astrophysics Data System (ADS)

    Matsuda, Yatsuka; Cahill, Thomas A.

    1985-02-01

    In order to collect SO 2 gas on a stretched Teflon filter impregnated with an alkali solution for a PIXE analysis, an impregnation method has been developed. In this article, the following points are presented. a) It has been found to be necessary to replace the air trapped in filter pores by methanol, and then to replace the methanol by an alkali solution, b) The resistance for air flow through an impregnated Teflon filter is not high and it has been checked that an ordinary pump can be used for the air sampling with the impregnated filter, with the usual flow rate aerosol sampling, c) The impurity levels of the reagents used for impregnants were small enough for sulfur analysis, d) The collection efficiencies of the impregnants, 20%NaOH + 10%glycerin and 20%NaOH + 10%TEA, which are the most suitable ones, did not decrease with flow rate in the range of 0-10 {1}/{min} per filter of 25 mm in diameter. A cross check experiment on the collection of ambient SO 2 gas with the three kinds of filter (A: 5%NaOH + 5%glycerin impregnated Whatman-41 filter, B: 20%NaOH + 10%TEA coated Nuclepore filter, C: 20%NaOH + 10%TEA impregnated stretched Teflon filter) was done. The results showed a satisfactory tolerance for the practical use of Teflon impregnated filter.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Impregnation of tubular self-assemblies into dextran hydrogels.

    PubMed

    Sun, Guoming; Chu, Chih-Chang

    2010-02-16

    Amine groups are the building units of proteins. The incorporation of amine groups into polyethylene glycol diacrylate (PEGDA) hydrogel through dextran-allyl isocyanate-ethylamine (Dex-AE) enhances sustained protein release by introducing effective interactions. To investigate such an interaction effect and to improve protein release, we impregnated self-assembled tubular structures from dextran-bromoethylamine (Dex-BH) and dextran-chloroacetic acid (Dex-CA) into Dex-AE/PEGDA hydrogel. The morphology data obtained from scanning electron microscopy (SEM) reveal that pure PEGDA hydrogel had no effect on the distribution of the self-assembled tubules; the introduction of Dex-AE brought about the dispersion of these tubules, and an increase in Dex-AE content led to more evenly distributed structures. Moreover, the implantation of the self-assembled tubules had no distinct effect on the swelling capacity of the hybrid self-assembly embedded hydrogels. The in vitro albumin release study was carried out in a pH 7.4 buffer solution; the results show that the implantation of the self-assembly into the hydrogels reduced the burst release and prolonged the protein release time. These findings demonstrate that the impregnation of tubular self-assembly into hydrogel makes the hybrid hydrogel an excellent protein delivery system.

  2. Impact properties of shear thickening fluid impregnated foams

    NASA Astrophysics Data System (ADS)

    Soutrenon, M.; Michaud, V.

    2014-03-01

    Concentrated colloidal suspensions of silica particles in polyethylene glycol exhibit a shear thickening behavior: above a critical shear rate in a confined environment, they show a steep increase of viscosity. This reversible transition from a low to a high viscosity state is associated with a large energy absorption that could be harnessed for impact protection. As these suspensions are liquid at rest, however, shear thickening fluids (STFs) are difficult to use in practical applications. Furthermore, their specific rheological properties exist within a narrow range of concentration, so they tend to disappear when the material is in contact with air and humidity. In this work, a soft foam scaffold was impregnated with STF to provide a three-dimensional shape to the assembly at rest, while a silicone was cast around it to serve as a physical barrier to the external environment. A method to quickly impregnate the foam was proposed. Impact tests were carried out on the STF/foam/silicone composite pads using a free fall impact tower. Compared to rubber or pure silicone, larger energy absorptions, up to 85%, were observed, which could be repeated for multiple impacts. The transmitted shock waves were also reduced, showing the potential of this system for impact protection of structures.

  3. 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.

  4. 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

  5. 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.

  6. Hyperglycemia-induced GLP-1R downregulation causes RPE cell apoptosis.

    PubMed

    Kim, Dong-Il; Park, Min-Jung; Choi, Joo-Hee; Lim, Seul-Ki; Choi, Hak-Jong; Park, Soo-Hyun

    2015-02-01

    Glucagon-like peptide-1 receptor (GLP-1R) is closely associated with the onset of diabetes and its complications. However, its roles in diabetic retinopathy are unknown. Retinal pigment epithelial (RPE) cells are a crucial component of the outer blood-retina barrier and their death is related to the progression of diabetic retinopathy. Thus, we examined the pathophysiological role of GLP-1R in RPE cell apoptosis. We found that GLP-1R expression was lower in the isolated neuroretina and RPE cells of streptozotocin-treated rats than in vehicle-treated rats. High-glucose treatment also decreased GLP-1R expression in a human RPE cell line (ARPE-19 cells). GLP-1R was silenced in ARPE-19 cells, in order to elucidate the pathophysiological roles of GLP-1R. This increased intracellular reactive oxygen species (ROS) generation and activated p53-mediated Bax promoter and endoplasmic reticulum (ER) stress signaling. We also found that GLP-1R knockdown-mediated p53 expression was regulated by ER stress. Interestingly, antioxidant treatment and peroxiredoxin 1 (Prx1) overexpression attenuated GLP-1R knockdown-induced ER stress signaling and p53 expression. Finally, to confirm that GLP-1R activation has protective effects, ARPE-19 cells were treated with exendin-4, a synthetic GLP-1R agonist. This attenuated high-glucose-induced ROS generation, ER stress signaling, and p53 expression. Collectively, these results indicated that hyperglycemia decreases GLP-1R expression in RPE cells. Such a decrease generates intracellular ROS, which increases ER stress-mediated p53 expression, and subsequently causes apoptosis by increasing Bax promoter activity. Our data suggested that regulation of GLP-1R expression is a promising approach for the treatment of diabetic retinopathy.

  7. The MC1R gene in the guppy (Poecilia reticulata): Genotypic and phenotypic polymorphisms

    PubMed Central

    2011-01-01

    Background The guppy (Poecilia reticulata) is an important model organism for studying sexual selection; male guppies have complex and conspicuous pigmentation, and female guppies exhibit preferences for males with specific color spots. Understanding the genetic basis underlying pigmentation variation in the guppy is important for exploring the factors causing the maintenance of color polymorphism in wild populations. Findings We focused on the melanic black pigmentation of guppies, and examined genetic variations in the melanocortin 1 receptor (MC1R) gene because variation in this gene is known to contribute to polymorphism of melanin pigmentation in several animal species. The complete coding sequence of the guppy MC1R gene was determined, and two different MC1R alleles (963 and 969 bp) were found in wild populations. Ornamental strain guppies with a 963-bp MC1R tended to show less black pigmentation than those with a 969-bp MC1R, although the association between MC1R genotype and black pigmentation disappeared in the F2 offspring. Conclusions The guppy MC1R gene showed variation in the five wild Trinidadian populations we examined, and these populations also differed in terms of allele frequencies. We identified a significant association between black pigmentation and MC1R genotype in fish obtained from aquarium shops. However, the results from F2 families suggest that there are other genes that modify the effects of the MC1R gene. PMID:21294861

  8. Novel mutations in PTH1R associated with primary failure of eruption and osteoarthritis.

    PubMed

    Frazier-Bowers, S A; Hendricks, H M; Wright, J T; Lee, J; Long, K; Dibble, C F; Bencharit, S

    2014-02-01

    Autosomal dominant mutations in PTH1R segregate with primary failure of eruption (PFE), marked by clinical eruption failure of adult teeth without mechanical obstruction. While the diagnosis of PFE conveys a poor dental prognosis, there are no reports of PFE patients who carry PTH1R mutations and exhibit any other skeletal problems. We performed polymerase chain reaction-based mutational analysis of the PTH1R gene to determine the genetic contribution of PTH1R in 10 families with PFE. Sequence analysis of the coding regions and intron-exon boundaries of the PTH1R gene in 10 families (n = 54) and 7 isolated individuals revealed 2 novel autosomal dominant mutations in PTH1R (c.996_997insC and C.572delA) that occur in the coding region and result in a truncated protein. One family showed incomplete penetrance. Of 10 families diagnosed with PFE, 8 did not reveal functional (nonsynonymous) mutations in PTH1R; furthermore, 4 families and 1 sporadic case carried synonymous single-nucleotide polymorphisms. Five PFE patients in 2 families carried PTH1R mutations and presented with osteoarthritis. We propose that the autosomal dominant mutations of PTH1R that cause PFE may also be associated with osteoarthritis; a dose-dependent model may explain isolated PFE and osteoarthritis in the absence of other known symptoms in the skeletal system.

  9. Phenoxy herbicides and fibrates potently inhibit the human chemosensory receptor subunit T1R3

    PubMed Central

    Maillet, Emeline L.; Margolskee, Robert F.; Mosinger, Bedrich

    2009-01-01

    We show that phenoxy-auxin herbicides and lipid-lowering fibrates inhibit human but not rodent T1R3. T1R3 as a co-receptor in taste cells responds to sweet compounds and amino-acids; in endocrine cells of gut and pancreas T1R3 contributes to glucose sensing. Thus, certain effects of fibrates in treating hyperlipidemia and type II diabetes may be via actions on T1R3. Likewise, phenoxy-herbicides may have adverse metabolic effects in humans that would have gone undetected in studies on rodents. PMID:19817384

  10. Endothelial IL-1R1 is a critical mediator of EAE pathogenesis

    PubMed Central

    Li, Qiming; Powell, Nicole; Zhang, Hao; Belevych, Natalya; Ching, San; Chen, Qun; Sheridan, John; Whitacre, Caroline; Quan, Ning

    2010-01-01

    Interleukin-1 (IL-1) has been implicated in the disease progression of multiple sclerosis (MS). In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), the induction of disease is significantly attenuated in mice lacking the type I IL-1 receptor (IL-1R1). In this study, we created a transgenic mouse (eIL-1R1 kd) in which IL-1R1 expression is knocked down specifically in endothelial cells. Induction of EAE in eIL-1R1 kd mice results in a decrease in incidence, severity and delayed onset of EAE. In addition, eIL-1R1 kd mice show significant decrease in VCAM-1 expression and diminished CD45+ and CD3+ infiltrating leukocytes in the spinal cord in animals challenged with EAE. Further, IL-1 and IL-23 stimulate IL-17 production by splenocytes from both wild type and the eIL-1R1 kd animals. Similarly, IL-1 and IL-23 synergistically stimulate splenocytes proliferation in these two strains of animals. After immunization with MOG79–96, although eIL-1R1 kd mice displayed greatly reduced clinical scores, their splenocytes produced IL-17 and proliferated in response to a second MOG challenge, similar to wild type animals. These findings indicate a critical role for endothelial IL-1R1 in mediating the pathogenesis of EAE, and describe a new model that can be used to study endothelial IL-1R1. PMID:20854891

  11. PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist.

    PubMed

    Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Jensen, Robert T; Takayanagi, Ryoichi

    2014-01-01

    There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation

  12. Gefitinib resistance in HCC mahlavu cells: upregulation of CD133 expression, activation of IGF-1R signaling pathway, and enhancement of IGF-1R nuclear translocation.

    PubMed

    Bodzin, Adam S; Wei, Zhengyu; Hurtt, Reginald; Gu, Tina; Doria, Cataldo

    2012-07-01

    Hepatocellular carcinoma (HCC) is the major form of primary liver cancer which accounts for more than half million deaths annually worldwide. While the incidence of HCC is still on the rise, options of treatment are limited and the overall survival rate is poor. The acquisition of cancer drug resistance remains one of the key hurdles to successful treatment. Clearly, a thorough understanding of the underlying mechanisms is needed for new strategies to design novel treatments and/or to improve the current therapies. In the present study, we examined the expression of cancer stem cell (CSC) marker CD133, the activation of insulin-like growth factor 1 receptor (IGF-1R) signaling, and the nuclear translocation of IGF-1R in HCC Mahlavu cells under the treatment of gefitinib, a cancer drug that inhibits epidermal growth factor receptor (EGFR) pathway. Our results demonstrated that Mahlavu cells exhibited strong gefitinib resistance and the CD133 expression level was dramatically increased (from 3.88% to 32%) after drug treatment. In addition, the gefitinib treated cells displayed increased levels of phosphorylation in IGF-1R and Akt, indicating the intensified activation of this cancer-associated signaling pathway. Moreover, we revealed that IGF-1R underwent nuclear translocation in gefitinib treated cells using confocal microscopy. The IGF-1R nuclear translocation was enhanced under gefitinib treatment and appeared in a dose-dependent manner. Our findings suggest that increased IGF-1R nuclear translocation after gefitinib treatment may contribute to the drug resistance and IGF1-R activation, which might also associate with the upregulation of CD133 expression.

  13. 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

  14. 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

  15. 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 Section 529.1003 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1003 Flurogestone acetate-impregnated vaginal sponge. (a) Specifications. Each vaginal...

  16. 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 Section 529.1003 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1003 Flurogestone acetate-impregnated vaginal sponge. (a) Specifications. Each vaginal...

  17. 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 Section 529.1003 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1003 Flurogestone acetate-impregnated vaginal sponge. (a) Specifications. Each vaginal...

  18. 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 ...

  19. Preparation of sulfurized powdered activated carbon from waste tires using an innovative compositive impregnation process.

    PubMed

    Yuan, Chung-Shin; Lin, Hsun-Yu; Wu, Chun-Hsin; Liu, Ming-Han; Hung, Chung-Hsuang

    2004-07-01

    The objective of this study is to develop an innovative compositive impregnation process for preparing sulfurized powdered activated carbon (PAC) from waste tires. An experimental apparatus, including a pyrolysis and activation system and a sulfur (S) impregnation system, was designed and applied to produce sulfurized PAC with a high specific surface area. Experimental tests involved the pyrolysis, activation, and sulfurization of waste tires. Waste-tire-derived PAC (WPAC) was initially produced in the pyrolysis and activation system. Experimental results indicated that the Brunauer-Emmett-Teller (BET) surface area of WPAC increased, and the average pore radius of WPAC decreased, as water feed rate and activation time increased. In this study, a conventional direct impregnation process was used to prepare the sulfurized PAC by impregnating WPAC with sodium sulfide (Na2S) solution. Furthermore, an innovative compositive impregnation process was developed and then compared with the conventional direct impregnation process. Experimental results showed that the compositive impregnation process produced the sulfurized WPAC with high BET surface area and a high S content. A maximum BET surface area of 886 m2/g and the S content of 2.61% by mass were obtained at 900 degrees C and at the S feed ratio of 2160 mg Na2S/g C. However, the direct impregnation process led to a BET surface area of sulfurized WPAC that decreased significantly as the S content increased.

  20. Kl-impregnated Oyster Shells as a Solid Catalyst for Soybean Oil Transesterificaton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research on inexpensive and green catalysts is needed for economical production of biodiesel. The goal of the research was to test KI-impregnated oyster shell as a solid catalyst for transesterification of soybean oil. Specific objectives were to characterize KI-impregnated oyster shell, determine t...

  1. 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.

  2. 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.

  3. Surface cooled, vacuum impregnated superconducting magnet systems: Design, construction, applications

    NASA Astrophysics Data System (ADS)

    Dam, Jacobus Adrianus Maria; Pieterman, Karel

    The design and construction of three superconducting magnet systems for applications in the fields of medical imaging, plasma physics and nuclear physics are described. All three systems have vacuum impregnated, intrinsically stable coils with cooling at the outer surfaces of the winding package with liquid helium, and are all coupled in some way to closed cycle cooling systems. General theories are discussed. The techniques used in both the design and the construction of the different magnet systems, are given. The use of numerical methods for the calculation of thermal and mechanical properties of superconducting coil systems, is emphasized. The experimental results obtained with the Delft magnetic resonance imaging system are described and examples of images showing sagittal sections of the human head, successfully produced with this system, are given.

  4. 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.

  5. 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.

  6. Antimicrobial activity of silver nanoparticles impregnated wound dressing

    NASA Astrophysics Data System (ADS)

    Shinde, V. V.; Jadhav, P. R.; Patil, P. S.

    2013-06-01

    In this work, silver nanoparticles were synthesized by simple wet chemical reduction method. The silver nitrate was reduced by Sodium borohydride used as reducing agent and Poly (vinyl pyrrolidone) (PVP) as stabilizing agent. The formation of silver nanoparticles was evaluated by UV-visible spectroscope and transmission electron microscope (TEM). Absorption spectrum consist two plasmon peaks at 410 and 668 nm revels the formation of anisotropic nanoparticles confirmed by TEM. The formation of silver nanoparticles was also evidenced by dynamic light scattering (DLS) study. DLS showed polydisperse silver nanoparticles with hydrodynamic size 32 nm. Protecting mechanism of PVP was manifested by FT-Raman study. Silver nanoparticles were impregnated into wound dressing by sonochemical method. The Kirby-Bauer disc diffusion methods were used for antimicrobial susceptibility testing. The antimicrobial activity of the samples has been tested against gram-negative bacterium Escherichia coli and gram-positive bacterium Staphylococcus aureus.

  7. SILVER IMPREGNATION OF ULTRATHIN SECTIONS FOR ELECTRON MICROSCOPY

    PubMed Central

    Marinozzi, Vittorio

    1961-01-01

    A new procedure is described for silver impregnation of thin sections for electron microscopy. Sections of various tissues, fixed in OsO4 and embedded in methacrylate, were treated with an ammoniacal silver solution, directly or after oxidation with periodic acid or hydrogen peroxide. After OsO4 fixation all cellular membranous systems exhibit a primary argentaffinity probably due to the reduction of ammoniacal silver solution by the reduced osmium bound to unsaturated lipids. Bleaching the sections with hydrogen peroxide removes the argentaffinity of protoplasmic structures. Treatment of the sections with periodic acid results in decreased argentaffinity of protoplasmic components while the argentaffinity of metaplasmic structures is greatly enhanced. The latter procedure appears particularly useful for enhancing the contrast of basement membranes. PMID:13766855

  8. 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.

  9. 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.

  10. 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.

  11. Mechanical behavior of silica nanoparticle-impregnated Kevlar fabrics

    NASA Astrophysics Data System (ADS)

    Dong, Zhaoxu

    Plain woven Kevlar fabrics are widely used as body protection materials. The present study investigated the impact performance of five styles of Kevlar fabrics K310, K706, K720, K745 and K779 from Hexcel. The fabrics are different in many aspects, i.e., weight per square meter, yarn counts, yarn size, Kevlar fiber type, friction and breaking strength. Silica nanoparticles were impregnated into the fabric to enhance the ballistic impact performance. The fabric impregnated with nanoparticles exhibit significant enhancement in impact performance over their neat counterparts. Fabrics experience large deformation under impact. More or less yarn pull-out was observed on all the fabrics. The in-plane yarn pull-out force has good correlation to the impact performance: fabrics with higher pull-out force performed better in impact tests. A two-dimensional finite element model was proposed to simulate the single yarn pull-out procedure and predict the maximum pull-out force. The most important fabric features are included in this model: yarn count, yarn size, fabric thickness, yarn waviness, fiber modulus, fiber diameter and coefficients of friction et al. The numerical results show good agreement with the experimentally measured pull-out forces. To understand the impact process, a constitutive model was developed to characterize the nonlinear anisotropic properties of the fabric in large deformation. The nanoparticles largely increase the shear stiffness, while only slightly affect the tension behavior along warp and weft yarn directions. This constitutive model was incorporated in the commercial FEA software ABAQUS through the user-defined material subroutine and used to simulate deformations with various loads. Finally the out-of-plane yarn pull-out force was predicted from the in-plane yarn pull-out results using finite element method and the proposed constitutive model.

  12. Epithelial IL-1R2 acts as a homeostatic regulator during remission of ulcerative colitis

    PubMed Central

    Mora-Buch, R; Dotti, I; Planell, N; Calderón-Gómez, E; Jung, P; Masamunt, M C; Llach, J; Ricart, E; Batlle, E; Panés, J; Salas, A

    2016-01-01

    Ulcerative colitis (UC) is a chronic intestinal inflammatory disease that may undergo periods of activity followed by remission. We aimed to identify the endogenous regulatory mechanisms that may promote disease remission. Transcriptional and protein analysis of the intestinal mucosa revealed that the IL-1 decoy receptor, interleukin-1 receptor type 2 (IL1R2), was upregulated in remission compared with active UC and controls. We identified epithelial cells as being responsible for increased IL-1R2 production during remission. Expression of IL1R2 was negatively regulated by Wnt/beta-catenin signals in colonic crypts or epithelial stem cell cultures; accordingly, epithelial stem cells upregulated IL-1R2 upon differentiation. Blocking IL-1R2 in isolated colonic crypt cultures of UC patients in remission and T-cell cultures stimulated with biopsy supernatant from UC patients in remission boosted IL-1β-dependent production of inflammation-related cytokines. Finally, IL1R2 transcription was significantly lower in patients that relapsed during a 1-year follow-up period compared with those in endoscopic remission. Collectively, our results reveal that the IL-1/IL-1R2 axis is differentially regulated in the remitting intestinal mucosa of UC patients. We hypothesize that IL-1R2 in the presence of low concentrations of IL-1β may act locally as a regulator of intestinal homeostasis. PMID:26530134

  13. Tethered Satellite System (TSS) Dynamics Assessments and Analysis, TSS-1R Post Flight Data Evaluation

    NASA Technical Reports Server (NTRS)

    Glaese, John R.

    1996-01-01

    The purpose of this report is to document the analysis performed on the TSS-1R telemetry data after the flight. These analysis addressed the tether dynamics of TSS-1r. The telemetry data was provided in a CD-ROM format. The data contained on the CD-ROM was selected from available Satellite and orbiter MSID's.

  14. IGF1R signaling acts on the anagen to catagen transition in the hair cycle.

    PubMed

    Castela, Mathieu; Linay, Fabien; Roy, Edwige; Moguelet, Philippe; Xu, Jie; Holzenberger, Martin; Khosrotehrani, Kiarash; Aractingi, Selim

    2017-01-17

    Insulin like growth factor 1 (IGF1) is important for skin development and homeostasis. However, overexpression and inactivation studies have produced variable findings regarding its role in hair follicle (HF) biology. Here, we studied a conditional and inducible knockout of the IGF1 receptor (IGF1R) in keratin 15-expressing bulge cells. Deletion of IGF1R after the development of the skin appendages in K15-IGF1R(KO) mice showed no abnormalities in epidermal homeostasis. Numbers of bulge cells were lower in K15-IGF1R(KO) mice than in controls, without consequences on wound healing, at least in young mice. K15-IGF1R(KO) HFs entered anagen phase earlier than controls and showed a delay in the anagen/catagen switch. The expression of BMP-4 mRNA was inhibited in HFs from K15-IGF1R(KO) . MED1 transcription was impaired in the epidermis of K15-IGF1R(KO) mice. These findings suggest that IGF1R controls the hair cycle, partly through BMP-4 activation. This article is protected by copyright. All rights reserved.

  15. Disruption of the melanin-concentrating hormone receptor 1 (MCH1R) affects thyroid function.

    PubMed

    Chung, Shinjae; Liao, Xiao-Hui; Di Cosmo, Caterina; Van Sande, Jacqueline; Wang, Zhiwei; Refetoff, Samuel; Civelli, Olivier

    2012-12-01

    Melanin-concentrating hormone (MCH) is a peptide produced in the hypothalamus and the zona incerta that acts on one receptor, MCH receptor 1 (MCH1R), in rodents. The MCH system has been implicated in the regulation of several centrally directed physiological responses, including the hypothalamus-pituitary-thyroid axis. Yet a possible direct effect of the MCH system on thyroid function has not been explored in detail. We now show that MCH1R mRNA is expressed in thyroid follicular cells and that mice lacking MCH1R [MCH1R-knockout (KO)] exhibit reduced circulating iodothyronine (T(4), free T(4), T(3), and rT(3)) levels and high TRH and TSH when compared with wild-type (WT) mice. Because the TSH of MCH1R-KO mice displays a normal bioactivity, we hypothesize that their hypothyroidism may be caused by defective thyroid function. Yet expression levels of the genes important for thyroid hormones synthesis or secretion are not different between the MCH1R-KO and WT mice. However, the average thyroid follicle size of the MCH1R-KO mice is larger than that of WT mice and contained more free and total T(4) and T(3) than the WT glands, suggesting that they are sequestered in the glands. Indeed, when challenged with TSH, the thyroids of MCH1R-KO mice secrete lower amounts of T(4). Similarly, secretion of iodothyronines in the plasma upon (125)I administration is significantly reduced in MCH1R-KO mice. Therefore, the absence of MCH1R affects thyroid function by disrupting thyroid hormone secretion. To our knowledge, this study is the first to link the activity of the MCH system to the thyroid function.

  16. 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

  17. EXPRESSION OF IGF1R IN NORMAL BREAST TISSUE AND SUBSEQUENT RISK OF BREAST CANCER

    PubMed Central

    Tamimi, Rulla M.; Colditz, Graham A.; Wang, Yihong; Collins, Laura C.; Hu, Rong; Rosner, Bernard; Irie, Hanna Y.; Connolly, James L.; Schnitt, Stuart J.

    2011-01-01

    Introduction The growth hormone and insulin-like growth factor (IGF) axis plays an essential role in the growth and development of the mammary gland. IGF1 and IGF1 receptor (IGF1R) may also play a role in the early transformation of mammary cells. Methods Using a nested case-control design, we examined the association between IGF1R expression in normal breast tissue from benign biopsies and subsequent risk of breast cancer within the Nurses’ Health Study. We constructed tissue microarrays (TMAs) containing normal terminal ductal lobular units (TDLUs) from benign breast biopsies. Immunostains for IGF1R were performed on sections cut from the TMAs. A total of 312 women had evaluable IGF1R staining in normal TDLUs; 75 subsequently developed breast cancer (cases) and 237 did not (controls). The epithelial cells in the normal TDLUs were scored for both cytoplasmic and membrane staining for IGF1R. Results Cytoplasmic IGF1R expression was positively associated with subsequent risk of breast cancer (OR=2.47, 95% CI 1.41–4.33). Women whose TDLU epithelial cells showed little or no membrane expression of IGF1R but high levels of cytoplasmic IGF1R were at the highest breast cancer risk and were 15 times more likely to develop subsequent breast cancer when compared with women who had little or no membrane or cytoplasmic IGF1R expression in their TDLU epithelial cells (OR=15.9, 95% CI 3.6–69.8). Conclusion In this study, IGF1R expression patterns in epithelial cells of normal TDLUs in benign breast biopsies were associated with an increased risk of subsequent breast cancer. Additional studies to confirm these findings are necessary. PMID:21197570

  18. RF9 Acts as a KISS1R Agonist In Vivo and In Vitro.

    PubMed

    Min, Le; Leon, Silvia; Li, Huan; Pinilla, Leonor; Carroll, Rona S; Tena-Sempere, Manuel; Kaiser, Ursula B

    2015-12-01

    RF9, a reported antagonist of the mammalian gonadotropin-inhibitory hormone receptor, stimulates gonadotropin secretion in mammals. Recent studies have suggested that the stimulatory effect of RF9 on gonadotropin secretion relies on intact kisspeptin receptor (KISS1R) signaling, but the underlying mechanisms remain to be elucidated. Using Chinese Hamster Ovary cells stably transfected with KISS1R, we show that RF9 binds specifically to KISS1R, with a Kd of 1.6 × 10(-5)M, and stimulates an increase in intracellular calcium and inositol phosphate accumulation in a KISS1R-dependent manner, with EC50 values of 3.0 × 10(-6)M and 1.6 × 10(-7)M, respectively. RF9 also stimulated ERK phosphorylation, with a time course similar to that of kisspeptin-10. RFRP-3, the putative endogenous ligand for NPFFR1, did not stimulate inositol phosphate accumulation or pERK, nor did it alter responses to of kisspeptin-10 or RF9. In agreement with these in vitro data, we found that RF9 stimulated a robust LH increase in Npffr1(-/-) mice, similar to that in wild-type littermates, whereas the stimulatory effect of RF9 was markedly reduced in Kiss1r(-/-) and double Kiss1r(-/-)/Npfrr1(-/-) mice. The stimulatory effect of RF9 on LH secretion was restored by the selective rescue of Kiss1r expression in GnRH neurons, in Kiss1r(-/-T) mice. Taken together, our study demonstrates that RF9 acts primarily as a KISS1R agonist, but not as an allosteric modulator, to stimulate LH secretion. Our findings raise questions regarding the utility of RF9 for assessing NPFF1R function and de-emphasize a predominant role of this signaling system in central regulation of reproduction.

  19. Functional variation of MC1R alleles from red-haired individuals.

    PubMed

    Healy, E; Jordan, S A; Budd, P S; Suffolk, R; Rees, J L; Jackson, I J

    2001-10-01

    Red hair in humans is associated with variant alleles of the alphaMSH receptor gene, MC1R. Loss of MC1R function in other mammals results in red or yellow hair pigmentation. We show that a mouse bacterial artificial chromosome (BAC) which contains Mc1r will efficiently rescue loss of Mc1r in transgenic mice, and that overexpression of the receptor suppresses the effect of the endogenous antagonist, agouti protein. We engineered the BAC to replace the mouse coding region with the human MC1R sequence and used this in the transgenic assay. The human receptor also efficiently rescued Mc1r deficiency, and in addition, appeared to be completely resistant to the effects of agouti, suggesting agouti protein may not play a role in human pigmentary variation. Three human variant alleles account for 60% of all cases of red hair. We engineered each of these in turn into the BAC and find that they have reduced, but not completely absent, function in transgenic mice. Comparison of the phenotypes of alphaMSH-deficient mice and humans in conjunction with this data suggests that red hair may not be the null phenotype of MC1R.

  20. 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.

  1. More functional V1R genes occur in nest-living and nocturnal terricolous mammals.

    PubMed

    Wang, Guodong; Shi, Peng; Zhu, Zhouhai; Zhang, Ya-ping

    2010-07-12

    Size of the vomeronasal type 1 receptor (V1R) gene repertoire may be a good indicator for examining the relationship between animal genomes and their environmental niche specialization, especially the relationship between ecological factors and the molecular evolutionary history of the sensory system. Recently, Young et al. (Young JM, Massa HF, Hsu L, Trask BJ. 2009. Extreme variability among mammalian V1R gene families. Genome Res.) concluded that no single ecological factor could explain the extreme variability of the V1R gene repertoire in mammalian genomes. In contrast, we found a significant positive correlation between the size and percentage of intact V1R genes in 32 species that represent the phylogenetic diversity of terricolous mammals and two ecological factors: spatial activity and rhythm activity. Nest-living species possessed a greater number of intact V1R genes than open-living species, and nocturnal terricolous mammals tended to possess more intact V1R genes than did diurnal species. Moreover, our analysis reveals that the evolutionary mechanisms underlying these observations likely resulted from the rapid gene birth and accelerated amino acid substitutions in nest-living and nocturnal mammals, likely a functional requirement for exploiting narrow, dark environments. Taken together, these results reveal how adaptation to divergent circadian rhythms and spatial activity were manifested at the genomic scale. Size of the V1R gene family might have indicated how this gene family adapts to ecological factors.

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

    PubMed

    Wang, Peng-Fei; Liu, Ning; Song, Hong-Wang; Yao, Kun; Jiang, Tao; Li, Shou-Wei; Yan, Chang-Xiang

    2016-05-24

    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.

  3. The Astrometric Calibration of Hubble Space Telescope Fine Guidance Sensor 1r - Fringe Tracking

    NASA Astrophysics Data System (ADS)

    Benedict, G. F.; McArthur, B. E.; Nelan, E. P.; Jefferys, W. H.

    2001-05-01

    We report on our progress towards an astrometric calibration of Fine Guidance Sensor 1r, installed during an HST refurbishment mission a few years ago. The calibration of this space-based interferometer will complete the commissioning of FGS1r as a sub-milliarcsecond astrometric science instrument for Cycle 10 and all future HST cycles, and permit the final reduction and analysis of ~100 orbits of FGS1r data acquired by a variety of GO programs during HST Cycles 8 and 9. These calibration data were secured in December 2000. We map the optical field angle distortions of FGS1r to facilitate the goal of millisecond of arc precision astrometry for FGS1r's fringe tracking (Position) mode. Our results will populate the FGS1r calibration database and will be available to all FGS GOs through the use of STScI's calibration pipeline. A second result will be an improved M35 calibration field, one that takes into account proper motions in the catalog. This will allow for more accurate monitoring of the FGS1r plate scale and distortions during future HST cycles.

  4. 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.

  5. Preparation of iron-impregnated granular activated carbon for arsenic removal from drinking water.

    PubMed

    Chang, Qigang; Lin, Wei; Ying, Wei-chi

    2010-12-15

    Granular activated carbon (GAC) was impregnated with iron through a new multi-step procedure using ferrous chloride as the precursor for removing arsenic from drinking water. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) analysis demonstrated that the impregnated iron was distributed evenly on the internal surface of the GAC. Impregnated iron formed nano-size particles, and existed in both crystalline (akaganeite) and amorphous iron forms. Iron-impregnated GACs (Fe-GACs) were treated with sodium hydroxide to stabilize iron in GAC and impregnated iron was found very stable at the common pH range in water treatments. Synthetic arsenate-contaminated drinking water was used in isotherm tests to evaluate arsenic adsorption capacities and iron use efficiencies of Fe-GACs with iron contents ranging from 1.64% to 12.13% (by weight). Nonlinear regression was used to obtain unbiased estimates of Langmuir model parameters. The arsenic adsorption capacity of Fe-GAC increased significantly with impregnated iron up to 4.22% and then decreased with more impregnated iron. Fe-GACs synthesized in this study exhibited higher affinity for arsenate as compared with references in literature and shows great potential for real implementations.

  6. Electrophoretic protein analysis for the identification of doubled haploid 1A-1R, 1B-1R wheat-rye double translocation lines and for the assessment of their genetic stability.

    PubMed

    Vahl, U; Müller, G; Böhme, T

    1993-06-01

    Eighteen available doubled haploid wheat lines with a cytologically proven 1A-1R, 1B-1R double translocation, which where derived via anther culture from four crosses of the 1A-1R wheat-rye translocation cv "Amigo" with several 1B-1R wheat-rye translocation forms, were subjected to electrophoretic seed protein analysis. Besides, the five parents used in the crosses and some other wheat cultivars and doubled haploid lines (19 with a 1B-1R single translocation, 10 with a 1A-1R translocation and 7 without any 1R translocation) were also included in the investigation. It was found that the gliadin patterns visualized after SDS polyacrylamide gel electrophoresis of alcohol-soluble seed protein extracts can differentiate not only 1B-1R and 1A-1R translocation forms from wheats without any 1R-translocation chromosome, but also 1B-1R and 1A-1R wheats from each other. Moreover, 1A-1R, 1B-1R double translocation lines can be distinguished as well due to characteristic differences revealed between 1A-1R and 1B-1R translocation forms. Thus, all of tested dh1- and dh2-grains of the double translocation lines showed the expected doublet: the 1A-1R translocation ("Amigo")-typical rye band and the 1B-1R translocation ("Kawkas")-typical rye band. Consequently, gliadin patterns estimated after SDS electrophoresis may be used as markers for the fast detection of the desired 1A-1R, 1B-1R double translocation forms among 1A-1R single translocation lines, 1B-1R single translocation lines and lines without any 1R-translocation in the progenies of appropriate crosses. Furthermore, by means of gliadin tests on the dh2-generation the excellent stability of the double translocation 1A-1R, 1B-1R during more than one propagation phase has been proven. Estimations of high-molecular weight (HMW) glutenin subunits coded by 1A and 1B chromosomes are compatible with the double translocation constitution. A few deviating results can be explained by crossing-over events. Seed protein analysis

  7. 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

  8. 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

  9. Effect of nanoparticles on charge transport in nanofluid-impregnated pressboard

    NASA Astrophysics Data System (ADS)

    Du, Yuefan; Lv, Yuzhen; Li, Chengrong; Chen, Mutian; Zhong, Yuxiang; Zhang, Shengnan; Zhou, You

    2012-06-01

    Transformer pressboard impregnated in mineral oil modified by nanoparticles (nanofluid) exhibits substantially higher AC and DC breakdown voltage than that of the pure oil-impregnated pressboard (OP). Charge transport and decay characteristics of both pressboards were measured by pulse electroacoustic technique. It reveals that nanofluid-impregnated pressboard (NP) has a more uniform internal electric field and a higher charge decay rate compared to OP, which is caused by an increase of shallow trap density in NP related to the difference of internal structures, based on the test results of thermally stimulated current and Fourier transformed infra-red spectroscopy.

  10. A silver impregnation method for nervous tissue suitable for routine use with mounted sections.

    PubMed

    Loots, J M; Loots, G P; Joubert, W S

    1977-03-01

    A simple, reliable silver impregnation method for nervous tissue is described for tissues fixed in various fixatives including formalin, Bouin, and Susa. Sections are impregnated in a solution containing 1 g Protargol, 2 ml of a 1% Cu(NO3)2 solution, 2 ml of a 1% AgNO3 solution, and 2-4 drops 30% H2O2 in 100 ml distilled water. Sections are impregnated 2-5 days at 37 C and thereafter reduced in a hydroquinone-formalin solution. This is followed by gold toning and subsequent reduction, dehydration and mounting. This method has been found to be very reliable and selective.

  11. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24145216

  13. Salmonella typhimurium A1-R and Cell-Cycle Decoy Therapy of Cancer.

    PubMed

    Hoffman, Robert M; Yano, Shuya

    2016-01-01

    Cancer cells in G0/G1 are resistant to cytotoxic chemotherapy agents which kill only cycling cancer cells. Salmonella typhimurium A1-R (S. typhimurium A1-R) decoyed cancer cells in monolayer culture and in tumor spheres to cycle from G0/G1 to S/G2/M, as demonstrated by fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging. S. typhimurium A1-R targeted FUCCI-expressing subcutaneous tumors, and tumors growing on the liver, growing in nude mice and also decoyed quiescent cancer cells, which were the majority of the cells in the tumors, to cycle from G0/G1 to S/G2/M. The S. typhimurium A1-R-decoyed cancer cells became sensitive to cytotoxic agents.

  14. 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.

  15. 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.

  16. The melanocortin 1 receptor (MC1R): more than just red hair.

    PubMed

    Rees, J L

    2000-06-01

    The melanocortin 1 receptor, a seven pass transmembrane G protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. Activating mutations, in animals at least, lead to enhanced eumelanin synthesis. In man, a number of loss-of-function mutations in the MC1R have been described. The majority of red-heads (red-haired persons) are compound heterozygotes or homozygotes for up to five frequent loss-of-function mutations. A minority of redheads are, however, only heterozygote. The MC1R is, therefore, a major determinant of sun sensitivity and a genetic risk factor for melanoma and non-melanoma skin cancer. Recent work suggests that the MC1R also shows a clear heterozygote effect on skin type, with up to 30% of the population harbouring loss-of-function mutations. Activating mutations of the MC1R in man have not been described. The MC1R is particularly informative and a tractable gene for studies of human evolution and migration. In particular, study of the MC1R may provide insights into the lightening of skin colour observed in most European populations. The world wide pattern of MC1R diversity is compatible with functional constraint operating in Africa, whereas the greater allelic diversity seen in non-African populations is consistent with neutral predictions rather than selection. Whether this conclusion is as a result of weakness in the statistical testing procedures applied, or whether it will be seen in other pigment genes will be of great interest for studies of human skin colour evolution.

  17. Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma

    PubMed Central

    Lian, Jianpo; Wang, Xiaojing; Ning, Guang; Wang, Weiqing; Zhu, Yu

    2016-01-01

    Purpose Adrenocortical carcinoma (ACC) is a rare tumor with very poor prognosis and no effective treatment. The aim of this study was to explore a novel therapy co-targeting EGFR and IGF1R in vitro and vivo. Methods The expression of EGFR and IGF1R were evaluated in a series of adrenocortical tumors by immunohistochemistry. Cell viability of ACC cell lines H295R and SW13 were determined by MTT assay after treatment with the combination of EGFR inhibitor Erlotinib and IGF1R inhibitor NVP-AEW541. Apoptosis was assessed by flow cytometry. The mechanism within intracellular signaling pathways was analyzed by Western blot. Mice bearing human ACC xenografts were treated with Erlotinib and NVP-AEW541, and the effects on tumour growth were assessed. Results Our results show a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. Conclusions In conclusion, coinhibition therapy targeting EGFR and IGF1R may be considerable for treatment of ACC in the future. PMID:27105537

  18. 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

  19. 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

  20. 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

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

    PubMed

    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

    2015-06-01

    Melanocortin-1 receptor (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 Genes, Environment, and Melanoma 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 caused by 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. In addition, we evaluated haplotypes involving polymorphisms near the Agouti signaling protein gene (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 (hazard ratio (HR) = 0.60; 95% confidence interval (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.

  2. 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.

  3. Inherited variation at MC1R and histological characteristics of primary melanoma.

    PubMed

    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.

  4. Enhanced condensation on lubricant-impregnated nanotextured surfaces.

    PubMed

    Anand, Sushant; Paxson, Adam T; Dhiman, Rajeev; Smith, J David; Varanasi, Kripa K

    2012-11-27

    Nanotextured superhydrophobic surfaces have received significant attention due to their ability to easily shed liquid drops. However, water droplets have been shown to condense within the textures of superhydrophobic surfaces, impale the vapor pockets, and strongly pin to the surface. This results in poor droplet mobility and degrades condensation performance. In this paper, we show that pinning of condensate droplets can be drastically reduced by designing a hierarchical micro-nanoscale texture on a surface and impregnating it with an appropriate lubricant. The choice of lubricant must take into account the surface energies of all phases present. A lubricant will cloak the condensate and inhibit growth if the spreading coefficient is positive. If the lubricant does not fully wet the solid, we show how condensate-solid pinning can be reduced by proper implementation of nanotexture. On such a surface, condensate droplets as small as 100 μm become highly mobile and move continuously at speeds that are several orders of magnitude higher than those on identically textured superhydrophobic surfaces. This remarkable mobility produces a continuous sweeping effect that clears the surface for fresh nucleation and results in enhanced condensation.

  5. Auger spectroscopy investigations of various types of impregnated cathodes

    NASA Astrophysics Data System (ADS)

    Brion, D.; Tonnerre, J. C.; Shroff, A. M.

    The formation of a complete oxygen and barium monolayer on a tungsten surface has been followed by Auger spectroscopy. At 1300 K, the coverage for an S-type cathode is approximatively half of a monolayer. The surface composition and the state of oxidation of barium are studied and their variations are also observed as a function of the temperature on new cathodes and on cathodes after long operation time. The decrease of surface barium concentration and the important increase in the oxidation of barium lead to an increase of the work function. Between 1100 and 1500 K, the activation energy for the rate of coverage variation of barium is relatively low (0.15 eV). It has been found that when aluminum is present at the surface of impregnated cathodes, it modifies the chemical environment of the barium atoms and leads frequently to the increase of barium coverage. During activation of M-type cathodes, tungsten diffuses towards the surface. For osmium films having a thickness between 3000 and 15000 Å, the surface composition after activation is near to 35% tungsten. The barium concentration is 20% higher compared to an S-type cathode while the oxygen concentration is slightly lower. The oxidation state of barium is about the same for both cathode types.

  6. Impregnated-electrode-type liquid metal ion source

    NASA Astrophysics Data System (ADS)

    Ishikawa, J.; Gotoh, Y.; Tsuji, H.; Takagi, T.

    We have developed an impregnated-electrode-type liquid metal ion source whose tip is a sintered-porous structure made of a refractory metal such as tungsten. By this structure the ratio of the liquid metal surface area facing the vacuum to the volume is low, which decreases useless metal evaporation from the surface. The maximum vapour pressure of the metal in operation for this ion source is 10 -1-10 0 Torr, which is 2-3 orders of magnitude higher than that for the needle type. Therefore, useful metal ions such as Ga +, Au +, Ag +, In +, Si 2+, Ge 2+, and Sb 2+ can be extracted from single element metals or alloys. The porous structure of the tip has also an effect on the positive control of the liquid metal flow rate to the tip head. Thus, a stable operation with a high current of a few hundreds of μA can be obtained together with a low current high brightness ion beam. Therefore, this ion source is suitable not only for microfocusing but also for a general use as a metal ion source.

  7. High activity redox catalysts synthesized by chemical vapor impregnation.

    PubMed

    Forde, Michael M; Kesavan, Lokesh; Bin Saiman, Mohd Izham; He, Qian; Dimitratos, Nikolaos; Lopez-Sanchez, Jose Antonio; Jenkins, Robert L; Taylor, Stuart H; Kiely, Christopher J; Hutchings, Graham J

    2014-01-28

    The use of precious metals in heterogeneous catalysis relies on the preparation of small nanoparticles that are stable under reaction conditions. To date, most conventional routes used to prepare noble metal nanoparticles have drawbacks related to surface contamination, particle agglomeration, and reproducibility restraints. We have prepared titania-supported palladium (Pd) and platinum (Pt) catalysts using a simplified vapor deposition technique termed chemical vapor impregnation (CVI) that can be performed in any standard chemical laboratory. These materials, composed of nanoparticles typically below 3 nm in size, show remarkable activity under mild conditions for oxidation and hydrogenation reactions of industrial importance. We demonstrate the preparation of bimetallic Pd-Pt homogeneous alloy nanoparticles by this new CVI method, which show synergistic effects in toluene oxidation. The versatility of our CVI methodology to be able to tailor the composition and morphology of supported nanoparticles in an easily accessible and scalable manner is further demonstrated by the synthesis of Pdshell-Aucore nanoparticles using CVI deposition of Pd onto preformed Au nanoparticles supported on titania (prepared by sol immobilization) in addition to the presence of monometallic Au and Pd nanoparticles.

  8. Multiple episodic evolution events in V1R receptor genes of East-African cichlids.

    PubMed

    Nikaido, Masato; Ota, Tomoki; Hirata, Tadashi; Suzuki, Hikoyu; Satta, Yoko; Aibara, Mitsuto; Mzighani, Semvua I; Sturmbauer, Christian; Hagino-Yamagishi, Kimiko; Okada, Norihiro

    2014-05-06

    Fish use olfaction to detect a variety of nonvolatile chemical signals, and thus, this sense is key to survival and communication. However, the contribution of the olfactory sense to social-especially reproductive-interactions in cichlids is still controversial. To obtain insights into this issue, we investigated the genes encoding V1Rs-possible candidates for reproductive pheromone receptors-among East-African cichlids. Interestingly, we found an excess of nonsynonymous over synonymous substitutions in four of six V1R genes in multiple cichlid lineages. First, we found that highly dimorphic V1R2 allele groups were shared among the cichlids inhabiting all East-African Great Lakes emerged through the episodic accumulation of the nonsynonymous substitutions prior to the radiation of the Lake Tanganyika species flock. We further detected such episodic events in V1R1 of the tribe Tropheini, and in V1R3 and V1R6 of the tribe Trematocarini. The excess of nonsynonymous substitutions in these examples were indicated as dN/dS > 1, which were all statistically significant by Fisher's exact test. Furthermore, we speculate that the amino acid changes in these episodic events are likely functional switch because they occurred in the putative ligand-binding pocket. Our finding of the occurrence of multiple episodic events and the unexpected gene diversity in one unique gene family is suggestive of the contribution of the V1R to the species diversification and the social interaction in cichlids.

  9. MC1R is a potent regulator of PTEN after UV exposure in melanocytes.

    PubMed

    Cao, Juxiang; Wan, Lixin; Hacker, Elke; Dai, Xiangpeng; Lenna, Stefania; Jimenez-Cervantes, Celia; Wang, Yongjun; Leslie, Nick R; Xu, George X; Widlund, Hans R; Ryu, Byungwoo; Alani, Rhoda M; Dutton-Regester, Ken; Goding, Colin R; Hayward, Nicholas K; Wei, Wenyi; Cui, Rutao

    2013-08-22

    The individuals carrying melanocortin-1 receptor (MC1R) variants, especially those associated with red hair color, fair skin, and poor tanning ability (RHC trait), are more prone to melanoma; however, the underlying mechanism is poorly defined. Here, we report that UVB exposure triggers phosphatase and tensin homolog (PTEN) interaction with wild-type (WT), but not RHC-associated MC1R variants, which protects PTEN from WWP2-mediated degradation, leading to AKT inactivation. Strikingly, the biological consequences of the failure of MC1R variants to suppress PI3K/AKT signaling are highly context dependent. In primary melanocytes, hyperactivation of PI3K/AKT signaling leads to premature senescence; in the presence of BRAF(V600E), MC1R deficiency-induced elevated PI3K/AKT signaling drives oncogenic transformation. These studies establish the MC1R-PTEN axis as a central regulator for melanocytes' response to UVB exposure and reveal the molecular basis underlying the association between MC1R variants and melanomagenesis.

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

    PubMed

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

    2016-06-08

    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 [Nle(4), D-Phe(7)]-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.

  11. UBE3A regulates MC1R expression: a link to hypopigmentation in Angelman syndrome.

    PubMed

    Low, Daren; Chen, Ken-Shiung

    2011-10-01

    Angelman syndrome (AS) is a neurogenetic disorder caused by the lack of functional ubiquitin-protein ligase E3A (UBE3A) that acts as an E3 ligase in the ubiquitin-proteosomal degradation pathway and/or as a transcriptional coactivator. Besides neurological deficit, hypopigmentation is another phenotype associated with AS patients currently attributed to the hemizygosity of the type II oculocutaneous albinism (OCA2) gene. Here we show that the melanocortin-1-receptor (MC1R) is down-regulated in the skin of the Ube3a((-/-)) mice. Luciferase-reporter assay shows that UBE3A is able to induce MC1R promoter activity. Using chromatin immunoprecipitation assay, Ube3a was observed to be physically associated with the Mc1r promoter. Deletion of the E box/SP1 element in the MC1R minimal promoter abolishes the ability of UBE3A to elevate MC1R promoter-luciferase reporter activity. Ube3a((-/-)) mice also show relative skin hypopigmentation. These results demonstrate that UBE3A plays a role in MC1R transcriptional regulation which can contribute to the development of hypopigmentation in AS patients.

  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. 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.

  14. Polishing is made cheaper by disposable diamond-impregnated abrasive cloth

    NASA Technical Reports Server (NTRS)

    Harper, F. J.

    1972-01-01

    Diamond impregnated abrasive cloth eliminated expensive diamond pastes and was economically disposed of to avoid contamination. Cloth was spunbonded nylon, but any napless fabric could be used. Cloth was sprayed with diamond abrasive gel.

  15. Cost/benefit analysis of chlorhexidine-silver sulfadiazine-impregnated venous catheters for femoral access.

    PubMed

    Lorente, Leonardo; Lecuona, María; Jiménez, Alejandro; Lorenzo, Lisset; Diosdado, Sara; Marca, Lucía; Mora, María L

    2014-10-01

    Sixty-four patients with chlorhexidine-silver sulfadiazine-impregnated catheters had a lower rate of catheter-related bloodstream infection and lower central venous catheter-related costs per catheter day than 190 patients with a standard catheter.

  16. 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.

  17. Study of use of ultrasound technology to prepare polymer-impregnated concrete

    SciTech Connect

    Han Wu; Brooman, E.W. )

    1993-05-01

    Low intensity ultrasound waves (20 kHz, 0.19 to 0.57 W/cm[sup 2] based on concrete area) have been applied to enhance the efficiency of impregnating a monomer into hardened concrete, without prior drying, for subsequent in situ polymerization. It was found that methyl methacrylate could be impregnated into partly air-dried Portland cement concrete, without removing the free water in the specimen, to approximately 80% of the depth of that into a similar, previously oven-dried specimen. A systematic study has been carried out to assess the relationship between impregnation depth and the following parameters: ultrasound energy density, impregnation time, gap distance between the ultrasound horn and the specimen surface, and the applied DC voltage gradient. The results of the experiments and a proposed mechanism for the ultrasound enhancement are presented in this paper.

  18. Radiation-curable impregnants for the consolidation of wooden finds and art objects

    NASA Astrophysics Data System (ADS)

    Schaudy, R.

    During the last decade a large number of radiation-curable monomers and oligomers have been investigated in order to determine whether they are suitable for the impregnation and consolidation of porous materials, especially of old wooden objects like archaeological finds, farmer's tools, furniture or art objects. Criteria for suitability are mainly the viscosity of the impregnant, curing behaviour, shrinkage upon curing, hardness and elasticity of the cured product, compatibility with the wood matrix and ageing properties. Selected impregnants have been applied to standardized sound and artificially decayed wood, and the interaction has been studied. Apparently the properties of the consolidated wood can only to a limited extent be derived from the behaviour of the pure polymeric material. Predictions are therefore difficult. Some selected impregnants have been applied to archaeological and ethnological objects with good success.

  19. 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.

  20. Lipid raft-regulated IGF-1R activation antagonizes TRAIL-induced apoptosis in gastric cancer cells.

    PubMed

    Xu, Ling; Qu, Xiujuan; Hu, Xuejun; Zhu, Zhitu; Li, Ce; Li, Enze; Ma, Yanju; Song, Na; Liu, Yunpeng

    2013-11-29

    Gastric cancer cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and the resistance mechanism is not fully understood. In human gastric cancer MGC803 and BGC823 cells, TRAIL induces insulin-like growth factor-1 receptor (IGF-1R) pathway activation. Treatment with IGF-1R inhibitor OSI-906 or small interfering RNAs against IGF-1R, prevents IGF-1R pathway activation and increases TRAIL-induced apoptosis. The TRAIL-induced IGF-1R pathway activation is promoted by IGF-1R translocation into lipid rafts. Moreover, the translocation of IGF-1R into lipid rafts is regulated by Casitas B-lineage lymphoma b (Cbl-b). Taken together, TRAIL-induced IGF-1R activation antagonizes TRAIL-induced apoptosis by Cbl-b-regulated distribution of IGF-1R in lipid rafts.

  1. 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.

  2. Impregnated Metal-Organic Frameworks for the Removal of Toxic Industrial Chemicals

    DTIC Science & Technology

    2008-11-01

    with various chemicals for enhanced reactivity. Specifically, MOF-5 (IRMOF- l ) was impregnated with citric acid, copper acetate, copper oxide, and...177, MOF-199, and ZIF-8 and provided recommendations for future material syntheses . The present report describes an initial effort aimed at...PROCESS 2.1 Materials MOF-5 (IRMOF-1) was synthesized at UCLA and subsequently sent to Guild Associates, Inc. (Dublin, Ohio) for impregnation. The

  3. 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.

  4. Carbonization of heavy metal impregnated sewage sludge oriented towards potential co-disposal.

    PubMed

    Dou, Xiaomin; Chen, Dezhen; Hu, Yuyan; Feng, Yuheng; Dai, Xiaohu

    2017-01-05

    Sewage sludge (SS) is adopted as a stabilizer to immobilize externally impregnated heavy metals through carbonization oriented towards the co-disposal of SS and some hazardous wastes. Firstly Cu and Pb were impregnated into SS to ascertain the impregnating capacity and leaching behaviours of heavy metals in the resulting sewage sludge char (SSC). Meanwhile, scanning electron microscopy (SEM) and X-ray diffraction (XRD) were employed to detect the heavy metal phase in the SSC. The results showed that within 400-800°C and an impregnating concentration ≨0.5wt%, more than 90% of the externally impregnated Cu and Pb were remained in the SSC and immobilized. And higher temperatures helped produce non-hazardous SSC. In addition, SEM and XRD analyses revealed that externally impregnated heavy metals could be converted into stable forms and evenly distributed throughout the SSC. In the second step municipal solid waste incineration fly ash (FA) was kneaded into SS and subjected to carbonization; it has been proved that the heavy metals in FA can be well immobilized in the resulting char when FA: SS mass ratio is 1:5. Those results show that sewage sludge can be co-carbonized with wastes contaminated with heavy metals to achieve co-disposal.

  5. The effect of silver impregnation of surgical scrub suits on surface bacterial contamination.

    PubMed

    Freeman, A I; Halladay, L J; Cripps, P

    2012-06-01

    Silver-impregnated fabrics are widely used for their antibacterial and antifungal effects, including for clinical clothing such as surgical scrub suits (scrubs). This study investigated whether silver impregnation reduces surface bacterial contamination of surgical scrubs during use in a veterinary hospital. Using agar contact plates, abdominal and lumbar areas of silver-impregnated nylon or polyester/cotton scrubs were sampled for surface bacterial contamination before (0 h) and after 4 and 8h of use. The number of bacterial colonies on each contact plate was counted after 24 and 48 h incubation at 37°C. Standard basic descriptive statistics and mixed-effects linear regression were used to investigate the association of possible predictors of the level of bacterial contamination of the scrubs with surface bacterial counts. Silver-impregnated scrubs had significantly lowered bacterial colony counts (BCC) at 0 h compared with polyester/cotton scrubs. However, after 4 and 8h of wear, silver impregnation had no effect on BCC. Scrub tops with higher BCC at 0 h had significantly higher BCC at 4 and 8h, suggesting that contamination present at 0 h persisted during wear. Sampling from the lumbar area was associated with lower BCC at all three time points. Other factors (contamination of the scrub top with a medication/drug, restraint of patients, working in the anaesthesia recovery area) also affected BCC at some time points. Silver impregnation appeared to be ineffective in reducing bacterial contamination of scrubs during use in a veterinary hospital.

  6. 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

  7. Functional evaluation of a PTSD-associated genetic variant: estradiol regulation and ADCYAP1R1

    PubMed Central

    Mercer, K B; Dias, B; Shafer, D; Maddox, S A; Mulle, J G; Hu, P; Walton, J; Ressler, K J

    2016-01-01

    Posttraumatic stress disorder (PTSD) affects 5–10% percent of the US adult population with a higher prevalence among women compared with men. Although it remains unclear how biological sex associates with susceptibility to PTSD, one mechanism may involve a role for estrogen in a gene by environment interaction. We previously demonstrated a sex-dependent association between the pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) and PTSD, where carriers of a C allele at single-nucleotide polymorphism (SNP) rs2267735 within the PAC1 receptor gene (ADCYAP1R1) have increased symptoms of PTSD. This SNP is located within a predicted estrogen response element (ERE), which regulates gene transcription when bound to estradiol (E2) activated estrogen receptor alpha (ERα). In the current study, we examined E2 regulation of ADCYAP1R1 in vitro, in cell culture, and in vivo in mice and humans. We find in mice that fear conditioning and E2 additively increase ADCYAP1R1 expression. In vitro, we show that E2/ERα binds to the ADCYAP1R1 ERE, with less efficient binding to an ERE containing the C allele of rs2267735. In women with low serum E2, the CC genotype associates with lower ADCYAP1R1 expression, which further associates with higher PTSD symptoms. These findings lead to a model in which E2 induces the expression of ADCYAP1R1 through binding of ERα at the ERE as an adaptive response to stress. Inhibition of E2/ERα binding to the ERE containing the rs2267735 risk allele results in reduced expression of ADCYAP1R1, diminishing estrogen regulation as an adaptive stress response and increasing risk for PTSD. PMID:27959335

  8. Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway.

    PubMed

    Digiacomo, Graziana; Tusa, Ignazia; Bacci, Marina; Cipolleschi, Maria Grazia; Dello Sbarba, Persio; Rovida, Elisabetta

    2016-09-02

    Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and β1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.

  9. Suppression of homologous recombination sensitizes human tumor cells to IGF-1R inhibition.

    PubMed

    Lodhia, Kunal A; Gao, Shan; Aleksic, Tamara; Esashi, Fumiko; Macaulay, Valentine M

    2015-06-15

    Inhibition of type 1 IGF receptor (IGF-1R) sensitizes to DNA-damaging cancer treatments, and delays repair of DNA double strand breaks (DSBs) by non-homologous end-joining and homologous recombination (HR). In a recent screen for mediators of resistance to IGF-1R inhibitor AZ12253801, we identified RAD51, required for the strand invasion step of HR. These findings prompted us to test the hypothesis that IGF-1R-inhibited cells accumulate DSBs formed at endogenous DNA lesions, and depend on residual HR for their repair. Indeed, initial experiments showed time-dependent accumulation of γH2AX foci in IGF-1R -inhibited or -depleted prostate cancer cells. We then tested effects of suppressing HR, and found that RAD51 depletion enhanced AZ12253801 sensitivity in PTEN wild-type prostate cancer cells but not in cells lacking functional PTEN. Similar sensitization was induced in prostate cancer cells by depletion of BRCA2, required for RAD51 loading onto DNA, and in BRCA2(-/-) colorectal cancer cells, compared with isogenic BRCA2(+/-) cells. We also assessed chemical HR inhibitors, finding that RAD51 inhibitor BO2 blocked RAD51 focus formation and sensitized to AZ12253801. Finally, we tested CDK1 inhibitor RO-3306, which impairs HR by inhibiting CDK1-mediated BRCA1 phosphorylation. R0-3306 suppressed RAD51 focus formation consistent with HR attenuation, and sensitized prostate cancer cells to IGF-1R inhibition, with 2.4-fold reduction in AZ12253801 GI50 and 13-fold reduction in GI80. These data suggest that responses to IGF-1R inhibition are enhanced by genetic and chemical approaches to suppress HR, defining a population of cancers (PTEN wild-type, BRCA mutant) that may be intrinsically sensitive to IGF-1R inhibitory drugs.

  10. 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

  11. 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.

  12. Not another type of potato: MC1R and the russet coloration of Burmese cats.

    PubMed

    Gustafson, N A; Gandolfi, B; Lyons, L A

    2017-02-01

    The Burmese is a breed of domestic cat that originated in Southeast Asia and was further developed in the United States. Variants in melanocortin 1 receptor (MC1R) causes common coat colour phenotypes in a variety of mammalian species but only limited colour variation in the domestic cat. Known as the extension (E) locus, melanocortin 1 receptor (MC1R) interacts with the agouti locus to produce the eumelanin and pheomelanin pigments. Recently, a novel reddish coloration, which is termed russet, was identified in the Burmese cat breed. Because this russet Burmese coloration changes with aging, MC1R was suggested as candidate gene. The similar colouration in specific lineages of Norwegian Forest cat known as amber (e) (c.250G>A; p.Asp84Asn) was excluded for this Burmese phenotype. The complete 954-bp coding region of MC1R was directly sequenced in russet Burmese and suspected carriers. A 3-bp deletion (c.439_441del) associated with the deletion of a phenyalanine (p.Phe146del) in the protein sequence was identified. All russet coloured cats were homozygous for the variant, and all obligate carriers were heterozygous, confirming that the deletion segregated concordantly with colouring in Burmese cats from the New Zealand foundation lineage. The variant was not identified in 442 cats from 26 different breeds and random-bred cats. Twenty-six Burmese from the USA did not have the variant. This MC1R variant defines a unique coloration and the second breed-specific MC1R variant in cats. The interactions of the two recessive feline MC1R alleles (E  >  e, e(r) ) is unknown.

  13. RF9 Acts as a KISS1R Agonist In Vivo and In Vitro

    PubMed Central

    Min, Le; Leon, Silvia; Li, Huan; Pinilla, Leonor; Carroll, Rona S.; Tena-Sempere, Manuel

    2015-01-01

    RF9, a reported antagonist of the mammalian gonadotropin-inhibitory hormone receptor, stimulates gonadotropin secretion in mammals. Recent studies have suggested that the stimulatory effect of RF9 on gonadotropin secretion relies on intact kisspeptin receptor (KISS1R) signaling, but the underlying mechanisms remain to be elucidated. Using Chinese Hamster Ovary cells stably transfected with KISS1R, we show that RF9 binds specifically to KISS1R, with a Kd of 1.6 × 10−5M, and stimulates an increase in intracellular calcium and inositol phosphate accumulation in a KISS1R-dependent manner, with EC50 values of 3.0 × 10−6M and 1.6 × 10−7M, respectively. RF9 also stimulated ERK phosphorylation, with a time course similar to that of kisspeptin-10. RFRP-3, the putative endogenous ligand for NPFFR1, did not stimulate inositol phosphate accumulation or pERK, nor did it alter responses to of kisspeptin-10 or RF9. In agreement with these in vitro data, we found that RF9 stimulated a robust LH increase in Npffr1−/− mice, similar to that in wild-type littermates, whereas the stimulatory effect of RF9 was markedly reduced in Kiss1r−/− and double Kiss1r−/−/Npfrr1−/− mice. The stimulatory effect of RF9 on LH secretion was restored by the selective rescue of Kiss1r expression in GnRH neurons, in Kiss1r−/−T mice. Taken together, our study demonstrates that RF9 acts primarily as a KISS1R agonist, but not as an allosteric modulator, to stimulate LH secretion. Our findings raise questions regarding the utility of RF9 for assessing NPFF1R function and de-emphasize a predominant role of this signaling system in central regulation of reproduction. PMID:26418326

  14. 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.

  15. 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.

  16. Zinc enrichment of whole potato tuber by vacuum impregnation.

    PubMed

    Erihemu; Hironaka, Kazunori; Koaze, Hiroshi; Oda, Yuji; Shimada, Kenichiro

    2015-04-01

    Zinc is a nutritionally essential truce element, and thus zinc deficiency (ZD) severely affects human health. More than 25% of the world's population is at risk of ZD. This study was initiated to examine the use of the vacuum impregnation (VI) technique for enriching zinc content of whole potatoes; the effect of vacuum time, restoration time, steam-cooking and storage at 4 °C on the zinc content of VI whole potatoes was evaluated. Whole potato tubers were immersed in a 9 g/100 g zinc (zinc gluconate) solution. Vacuum pressure of 1,000 Pa was applied for 0-120 min, and atmospheric pressure restoration for 0-4 h. Experimental results showed that the zinc content of VI potatoes increased with vacuum and restoration time. Moreover, VI-cooked unpeeled or peeled potatoes had 63-94 times and 47-75 times higher zinc contents than un-VI-cooked unpeeled or peeled potatoes, respectively. The world daily potato consumption (86 g) of the VI-cooked unpeeled and peeled potatoes provided adult men with 130-148% and 100-135% of the recommended daily allowance (RDA) of zinc, respectively. Also, the daily potato consumption of the unpeeled and peeled potatoes supplied adult women with 178-203% and 137-185% of the RDA level, respectively. In addition, the VI potatoes had 40 times higher zinc contents through 30 days of storage at 4 °C, compared with un-VI-treated potatoes. This study indicated that VI treatment of whole potatoes was useful for enriching the zinc content.

  17. 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

  18. 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.

  19. CysLT1R Antagonists Inhibit Tumor Growth in a Xenograft Model of Colon Cancer

    PubMed Central

    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 p21WAF/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. PMID:24039952

  20. Genetic variation of the bronze locus (MC1R) in turkeys from Southern Brazil.

    PubMed

    Corso, Josmael; Hepp, Diego; Ledur, Mônica C; Peixoto, Jane O; Fagundes, Nelson J R; Freitas, Thales R O

    2017-03-20

    Domestic turkeys present several color phenotypes controlled by at least five genetic loci, but only one of these has been identified precisely: the bronze locus, which turned out to be the melanocortin-1 receptor (MC1R) gene. MC1R variation is important for breeders interested in maintaining or developing different color varieties. In this study, we sequenced most of the MC1R gene from 16 White Holland (the main commercial turkey variety) and 19 pigmented turkeys from southern Brazil with two purposes. The first was to describe the MC1R diversity in White Holland turkeys, which may serve as reservoirs of genetic diversity at this locus. The second was to test whether the traditional color classification used by Brazilian breeders is related to previously known MC1R alleles. White Holland turkeys had four different haplotypes corresponding to the bronze (b+) and black-winged bronze (b1) alleles. Pigmented turkeys also had four haplotypes corresponding to the b+ and b1 alleles, but different haplotypes represent the most common b+ allele in these two groups. The black (B) allele was absent from our samples. Overall, our results suggest that white and pigmented individuals form two different populations, and that the traditional color classification used by Brazilian breeders cannot accurately predict the genotypes at the bronze locus.

  1. Targeting the IGF-1R: The Tale of the Tortoise and the Hare

    PubMed Central

    Crudden, Caitrin; Girnita, Ada; Girnita, Leonard

    2015-01-01

    The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the development and maintenance of cancer. Since the first links between growth factor receptors and oncogenes were noted over three decades ago, targeting the IGF-1R has been of great interest. This review follows the progress from inception through intense pharmaceutical development, disappointing clinical trials and recent updates to the signaling paradigm. In light of major developments in signaling understanding and activation complexities, we examine reasons for failure of first line targeting approaches. Recent findings include the fact that the IGF-1R can signal in the absence of the ligand, in the absence of kinase activity, and utilizes components of the GPCR system. With recognition of the unappreciated complexities that this first wave of targeting approaches encountered, we advocate re-recognition of IGF-1R as a valid target for cancer treatment and look to future directions, where both research and pharmaceutical strengths can lend themselves to finally unearthing anti-IGF-1R potential. PMID:25964779

  2. IGF1R levels in the brain negatively correlate with longevity in 16 rodent species.

    PubMed

    Azpurua, Jorge; Yang, Jiang-Nan; Van Meter, Michael; Liu, Zhengshan; Kim, Julie; Lobo Ladd, Aliny A B; Coppi, Antonio Augusto; Gorbunova, Vera; Seluanov, Andrei

    2013-04-01

    The insulin/insulin-like growth factor signaling (IIS) pathway is a major conserved regulator of aging. Nematode, fruit fly and mouse mutants with reduced IIS signaling exhibit extended lifespan. These mutants are often dwarfs leading to the idea that small body mass correlates with longevity within species. However, when different species are compared, larger animals are typically longer-lived. Hence, the role of IIS in the evolution of life history traits remains unresolved. Here we used comparative approach to test whether IGF1R signaling changes in response to selection on lifespan or body mass and whether specific tissues are involved. The IGF1R levels in the heart, lungs, kidneys, and brains of sixteen rodent species with highly diverse lifespans and body masses were measured via immunoblot after epitope conservation analysis. We report that IGF1R levels display strong negative correlation with maximum lifespan only in brain tissue and no significant correlations with body mass for any organ. The brain-IGF1R and lifespan correlation holds when phylogenetic non-independence of data-points is taken into account. These results suggest that modulation of IGF1R signaling in nervous tissue, but not in the peripheral tissues, is an important factor in the evolution of longevity in mammals.

  3. α-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes

    PubMed Central

    Dalziel, Martin; Kolesnichenko, Marina; das Neves, Ricardo Pires; Iborra, Francisco; Goding, Colin; Furger, André

    2011-01-01

    Alternative splicing enables higher eukaryotes to increase their repertoire of proteins derived from a restricted number of genes. However, the possibility that functional diversity may also be augmented by splicing between adjacent genes has been largely neglected. Here, we show that the human melanocortin 1 receptor (MC1R) gene, a critical component of the facultative skin pigmentation system, has a highly complex and inefficient poly(A) site which is instrumental in allowing intergenic splicing between this locus and its immediate downstream neighbour tubulin-β-III (TUBB3). These transcripts, which produce two distinct protein isoforms localizing to the plasma membrane and the endoplasmic reticulum, seem to be restricted to humans as no detectable chimeric mRNA could be found in MC1R expressing mouse melanocytes. Significantly, treatment with the MC1R agonist α-MSH or activation of the stress response kinase p38-MAPK, both key molecules associated with ultraviolet radiation dermal insult and subsequent skin tanning, result in a shift in expression from MC1R in favour of chimeric MC1R-TUBB3 isoforms in cultured melanocytes. We propose that these chimeric proteins serve to equip melanocytes with novel cellular phenotypes required as part of the pigmentation response. PMID:21071418

  4. Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation

    PubMed Central

    Farabaugh, Susan M.; Boone, David N.; Lee, Adrian V.

    2015-01-01

    Insulin-like growth factor (IGF) signaling is fundamental for growth and survival. A large body of evidence (laboratory, epidemiological, and clinical) implicates the exploitation of this pathway in cancer. Up to 50% of breast tumors express the activated form of the type 1 insulin-like growth factor receptor (IGF1R). Breast cancers are categorized into subtypes based upon hormone and ERRB2 receptor expression and/or gene expression profiling. Even though IGF1R influences tumorigenic phenotypes and drug resistance across all breast cancer subtypes, it has specific expression and function in each. In some subtypes, IGF1R levels correlate with a favorable prognosis, while in others it is associated with recurrence and poor prognosis, suggesting different actions based upon cellular and molecular contexts. In this review, we examine IGF1R expression and function as it relates to breast cancer subtype and therapy-acquired resistance. Additionally, we discuss the role of IGF1R in stem cell maintenance and lineage differentiation and how these cell fate influences may alter the differentiation potential and cellular composition of breast tumors. PMID:25964777

  5. Sequence variation in the Mc1r gene for a group of polymorphic snakes.

    PubMed

    Cox, Christian L; Rabosky, Alison R Davis; Chippindale, Paul T

    2013-01-25

    Studying the genetic factors underlying phenotypic traits can provide insight into dynamics of selection and molecular basis of adaptation, but this goal can be difficult for non-model organisms without extensive genomic resources. However, sequencing candidate genes for the trait of interest can facilitate the study of evolutionary genetics in natural populations. We sequenced the melanocortin-1 receptor (Mc1r) to study the genetic basis of color polymorphism in a group of snake species with variable black banding, the genera Sonora, Chilomeniscus, and Chionactis. Mc1r is an important gene in the melanin synthesis pathway and is associated with ecologically important variation in color pattern in birds, mammals, and other squamate reptiles. We found that Mc1r nucleotide sequence was variable and that within our focal Sonora species, there are both fixed and heterozygous nucleotide substitutions that result in an amino acid change and selection analyses indicated that Mc1r sequence was likely under purifying selection. However, we did not detect any statistical association with the presence or absence of black bands. Our results agree with other studies that have found no role for sequence variation in Mc1r and highlight the importance of comparative data for studying the phenotypic associations of candidate genes.

  6. 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.

  7. 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.

  8. IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma

    PubMed Central

    2013-01-01

    Background High-grade osteosarcoma is an aggressive tumor most often developing in the long bones of adolescents, with a second peak in the 5th decade of life. Better knowledge on cellular signaling in this tumor may identify new possibilities for targeted treatment. Methods We performed gene set analysis on previously published genome-wide gene expression data of osteosarcoma cell lines (n=19) and pretreatment biopsies (n=84). We characterized overexpression of the insulin-like growth factor receptor (IGF1R) signaling pathways in human osteosarcoma as compared with osteoblasts and with the hypothesized progenitor cells of osteosarcoma – mesenchymal stem cells. This pathway plays a key role in the growth and development of bone. Since most profound differences in mRNA expression were found at and upstream of the receptor of this pathway, we set out to inhibit IR/IGF1R using OSI-906, a dual inhibitor for IR/IGF1R, on four osteosarcoma cell lines. Inhibitory effects of this drug were measured by Western blotting and cell proliferation assays. Results OSI-906 had a strong inhibitory effect on proliferation of 3 of 4 osteosarcoma cell lines, with IC50s below 100 nM at 72 hrs of treatment. Phosphorylation of IRS-1, a direct downstream target of IGF1R signaling, was inhibited in the responsive osteosarcoma cell lines. Conclusions This study provides an in vitro rationale for using IR/IGF1R inhibitors in preclinical studies of osteosarcoma. PMID:23688189

  9. Trans-activation of TRPV1 by D1R in mouse dorsal root ganglion neurons.

    PubMed

    Lee, Dong Woo; Cho, Pyung Sun; Lee, Han Kyu; Lee, Sang Hoon; Jung, Sung Jun; Oh, Seog Bae

    2015-10-02

    TRPV1, a ligand-gated ion channel expressed in nociceptive sensory neurons is modulated by a variety of intracellular signaling pathways. Dopamine is a neurotransmitter that plays important roles in motor control, cognition, and pain modulation in the CNS, and acts via a variety of dopamine receptors (D1R-D5R), a class of GPCRs. Although nociceptive sensory neurons express D1-like receptors, very little is known about the effect of dopamine on TRPV1 in the peripheral nervous system. Therefore, in this study, we examined the effects of D1R activation on TRPV1 in mouse DRG neurons using Ca(2+) imaging and immunohistochemical analysis. The D1R agonist SKF-38393 induced reproducible Ca(2+) responses via Ca(2+) influx through TRPV1 rather than Ca(2+) mobilization from intracellular Ca(2+) stores. Immunohistochemical analysis revealed co-expression of D1R and TRPV1 in mouse DRG neurons. The PLC-specific inhibitor blocked the SKF-38393-induced Ca(2+) response, whereas the PKC, DAG lipase, AC, and PKA inhibitors had no effect on the SKF-38393-induced Ca(2+) response. Taken together, our results suggest that the SKF-38393-induced Ca(2+) response results from the direct activation of TRPV1 by a PLC/DAG-mediated membrane-delimited pathway. These results provide evidence that the trans-activation of TRPV1 following D1R activation may contribute to the modulation of pain signaling in nociceptive sensory neurons.

  10. Kisspeptin and KISS1R: a critical pathway in the reproductive system.

    PubMed

    Gianetti, Elena; Seminara, Stephanie

    2008-09-01

    In 2003, three groups around the world simultaneously discovered that KISS1R (GPR54) is a key gatekeeper of sexual maturation in both mice and men. Developmental changes in the expression of the ligand for KISS1R, kisspeptin, support its critical role in the pubertal transition. In addition, kisspeptin, a powerful stimulus of GNRH-induced gonadotropin secretion and may modulate both positive and negative sex steroid feedback effects at the hypothalamic level. Genetic studies in humans have revealed both loss-of-function and gainof-function mutations in patients with idiopathic hypogonadotropic hypogonadism and precocious puberty respectively. This review examines the kisspeptin/KISS1R pathway in the reproductive system.

  11. 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

  12. MC1R variants affect the expression of melanocortin and melanogenic genes and the association between melanocortin genes and coloration.

    PubMed

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

    2017-01-01

    The melanocortin-1 receptor (MC1R) gene influences coloration by altering the expression of genes acting downstream in the melanin synthesis. MC1R belongs to the melanocortin system, a genetic network coding for the ligands that regulate MC1R and other melanocortin receptors controlling different physiological and behavioural traits. The impact of MC1R variants on these regulatory melanocortin genes was never considered, even though MC1R mutations could alter the influence of these genes on coloration (e.g. by decreasing MC1R response to melanocortin ligands). Using barn owl growing feathers, we investigated the differences between MC1R genotypes in the (co)expression of six melanocortin and nine melanogenic-related genes and in the association between melanocortin gene expression and phenotype (feather pheomelanin content). Compared to the MC1R rufous allele, responsible for reddish coloration, the white allele was not only associated with an expected lower expression of melanogenic-related genes (TYR, TYRP1, OCA2, SLC45A2, KIT, DCT) but also with a lower MC1R expression and a higher expression of ASIP, the MC1R antagonist. More importantly, the expression of PCSK2, responsible for the maturation of the MC1R agonist, α-melanocyte-stimulating hormone, was positively related to pheomelanin content in MC1R white homozygotes but not in individuals carrying the MC1R rufous allele. These findings indicate that MC1R mutations not only alter the expression of melanogenic-related genes but also the association between coloration and the expression of melanocortin genes upstream of MC1R. This suggests that MC1R mutations can modulate the regulation of coloration by the pleiotropic melanocortin genes, potentially decoupling the often-observed associations between coloration and other phenotypes.

  13. 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.

  14. MC1R variants, melanoma and red hair color phenotype: a meta-analysis.

    PubMed

    Raimondi, Sara; Sera, Francesco; Gandini, Sara; Iodice, Simona; Caini, Saverio; Maisonneuve, Patrick; Fargnoli, Maria Concetta

    2008-06-15

    Melanocortin-1-receptor (MC1R) is one of the major genes that determine skin pigmentation. MC1R variants were suggested to be associated with red hair, fair skin, and an increased risk of melanoma. We performed a meta-analysis on the association between the 9 most studied MC1R variants (p.V60L, p.D84E, p.V92M, p.R142H, p.R151C, p.I155T, p.R160W, p.R163Q and p.D294H) and melanoma and/or red hair, fair skin phenotype. Eleven studies on MC1R and melanoma, and 9 on MC1R and phenotype were included in the analysis. The 7 variants p.D84E, p.R142H, p.R151C, p.I155T, p.R160W, p. R163Q and p.D294H were significantly associated with melanoma development, with ORs (95%CI) ranging from 1.42 (1.09-1.85) for p.R163Q to 2.45 (1.32-4.55) for p.I155T. The MC1R variants p.R160W and p.D294H were associated both with red hair and fair skin, while p.D84E, p.R142H, and p.R151C were strongly associated with red hair only- ORs (95%CI) ranged from 2.99 (1.51-5.91) for p.D84E to 8.10 (5.82-11.28) for p.R151C. No association with melanoma or phenotype was found for p.V60L and p.V92M variants. In conclusion this meta-analysis provided evidence that some MC1R variants are associated both with melanoma and phenotype, while other are only associated with melanoma development. These results suggest that MC1R variants could play a role in melanoma development both via pigmentary and non-pigmentary pathways.

  15. 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

  16. 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

  17. PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling

    PubMed Central

    Kollert, Sina; Rukoyatkina, Natalia; Sturm, Julia; Gambaryan, Stepan; Stellzig-Eisenhauer, Angelika; Meyer-Marcotty, Philipp; Eigenthaler, Martin; Wischmeyer, Erhard

    2016-01-01

    Aim Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. Materials and Methods In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE. The effects on activation of PTH-regulated intracellular signaling pathways were analyzed by ELISA and Western immunoblotting. Differential effects of wild type and mutated PTH1R on TRESK ion channel regulation were analyzed by electrophysiological recordings in Xenopus laevis oocytes. Results In HEK293 cells, activation of PTH1R wild type increases cAMP and in response activates cAMP-stimulated protein kinase as detected by phosphorylation of the vasodilator stimulated phosphoprotein (VASP). In contrast, the PTH1R mutants are functionally inactive and mutant PTH1R/Gly452Glu has a dominant negative effect on the signaling of PTH1R wild type. Confocal imaging revealed that wild type PTH1R is expressed on the cell surface, whereas PTH1R/Gly452Glu mutant is mostly retained inside the cell. Furthermore, in contrast to wild type PTH1R which substantially augmented K+ currents of TRESK channels, coupling of mutated PTH1R to TRESK channels was completely abolished. Conclusions PTH1R mutations affect intracellular PTH-regulated signaling in vitro. In patients with primary failure of tooth eruption defective signaling of PTH1R mutations is suggested to occur in dento-alveolar cells and thus may lead to impaired tooth movement. PMID:27898723

  18. 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.

  19. 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.

  20. Elemental mercury adsorption on sulfur-impregnated porous carbon - a review.

    PubMed

    Reddy, K Suresh Kumar; Shoaibi, Ahmed Al; Srinivasakannan, C

    2014-01-01

    The presence of elemental mercury in wellhead natural gas is an important industrial problem, since even low levels of mercury can damage cryogenic aluminium heat exchangers and other plant equipment. Mercury present in the natural gas stream will also dramatically shorten the useful life of precious metal catalysts. The present work reviews the overall process of elemental mercury removal in practice using non-regenerative adsorbents (e.g. sulfur-impregnated porous carbon), addressing the various influencing parameters such as the method of sulfur impregnation, the impregnation temperature, the sulfur to carbon ratio, the impregnation time, the impact of flue gas constituents, the effect of processing temperature, and the nature of any carbon-containing functional groups present. The distribution of elemental sulfur is found to be the key to developing an effective adsorbent, rather than quantity of sulfur impregnated. Modifying or developing an adsorbent for elemental mercury removal from natural gas needs a detail physical and chemical characteristics assessment of the adsorbent.

  1. Sorption and desorption of chromate by wood shavings impregnated with iron or aluminum oxide.

    PubMed

    Kuo, S; Bembenek, R

    2008-09-01

    This study examined the impregnation of hybrid poplar shavings with Fe or Al oxide and their reactivity with Cr(VI). The shavings were impregnated with an average of 1.24+/-0.18 mmol Fe g(-1) or 1.51+/-0.17 mmol Al g(-1), and the impregnated Fe or Al oxide was highly amorphous. Capacity of Cr(VI) sorption by impregnated shavings was high and rate of the sorption was rapid. While the freshly sorbed Cr on the Fe oxide-shavings was readily desorbed in 0.1M NaOH, nine weeks of ageing reduced the desorbability to only 6.5% of the sorbed Cr. Extraction with 0.1M NaOH remained feasible to recover most sorbed Cr from the Al oxide-shavings over the same ageing period. Impregnation of the shavings with Fe or Al oxide turns the wood waste into a product for removing Cr(VI) or other oxyanions from wastewater.

  2. Impacts of amount of impregnated iron in granular activated carbon on arsenate adsorption capacities and kinetics.

    PubMed

    Chang, Qigang; Lin, Wei; Ying, Wei-Chi

    2012-06-01

    Iron-impregnated granular activated carbons (Fe-GAC) can remove arsenic effectively from water. In this study, Fe-GACs with iron content of 1.64 to 28.90% were synthesized using a new multi-step procedure for the investigation of effects of iron amount on arsenic adsorption capacities and kinetics. Langmuir model satisfactorily fit arsenic adsorption on Fe-GACs. The maximum arsenic adsorption capacity (q(m)) increased significantly with iron impregnation and reached 1,867 to 1,912 microg/g with iron content of 9.96 to 13.59%. Further increase of iron content (> 13.59%) caused gradual decrease of q(m). It was found that the amount of impregnated iron showed little impact on the affinity for arsenate. Kinetic study showed that the amount of impregnated iron affected the arsenic intraparticle diffusion rate greatly. The pseudo-second-order kinetic model fit arsenic adsorption kinetics on Fe-GACs better than the pseudo-first-order model. The arsenic adsorption rate increased with increasing of iron content from 1.64% to 13.59%, and then decreased with more impregnated iron (13.59 to 28.90%).

  3. An extended lookup table of cloud detection for MTSAT-1R

    NASA Astrophysics Data System (ADS)

    Chen, Wuhan; Zhong, Bo; Li, Weisheng; Wu, Shanlong; Yu, Shanshan

    2014-11-01

    Cloud detection is a key work for the estimation of solar radiation from remote sensing. Particularly, the detection of thin cirrus cloud and the edges of thicker cloud is critical and difficult. To obtain accurate estimates of cloud cover of MTSAT-1R image, we propose an effective cloud detection algorithm for improving the detection of thin cirrus cloud and the edges of thicker cloud. Using the brightness temperature difference (BTD) and lookup table to identify cloud-free and cloud-filled pixels is not sufficient for MTSAT-1R data on the region of China. Therefore, a new lookup table (LUT) is made by extending the original one. On the basis of the exiting method, in order to apply to the MTSAT-1R satellite data in China region, we expand the scope of the latitude and extend the applicable scope of satellite zenith angle. We change the interpolation method from linear mode to nonlinear mode. The evaluation results indicate that our proposed method is effective for the cirrus and the edges of thicker cloud detection of MTSAT-1R in China region.

  4. MC1R, eumelanin and pheomelanin: their role in determining the susceptibility to skin cancer.

    PubMed

    Nasti, Tahseen H; Timares, Laura

    2015-01-01

    Skin pigmentation is due to the accumulation of two types of melanin granules in the keratinocytes. Besides being the most potent blocker of ultraviolet radiation, the role of melanin in photoprotection is complex. This is because one type of melanin called eumelanin is UV absorbent, whereas the other, pheomelanin, is photounstable and may even promote carcinogenesis. Skin hyperpigmentation may be caused by stress or exposure to sunlight, which stimulates the release of α-melanocyte stimulating hormone (α-MSH) from damaged keratinocytes. Melanocortin 1 receptor (MC1R) is a key signaling molecule on melanocytes that responds to α-MSH by inducing expression of enzymes responsible for eumelanin synthesis. Persons with red hair have mutations in the MC1R causing its inactivation; this leads to a paucity of eumelanin production and makes red-heads more susceptible to skin cancer. Apart from its effects on melanin production, the α-MSH/MC1R signaling is also a potent anti-inflammatory pathway and has been shown to promote antimelanoma immunity. This review will focus on the role of MC1R in terms of its regulation of melanogenesis and influence on the immune system with respect to skin cancer susceptibility.

  5. A clinicopathological analysis of KISS1 and KISS1R expression in colorectal cancer.

    PubMed

    Kostakis, Ioannis D; Agrogiannis, George; Vaiopoulos, Aristeidis G; Mylona, Eleni; Patsouris, Efstratios; Kouraklis, Gregory; Koutsilieris, Michael

    2015-07-01

    Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 111 patients with colorectal adenocarcinoma. KISS1 expression was much higher in the normal than in the malignant colonic mucosa. Regarding malignant tissues, KISS1 levels were higher in larger tumors, in stage III and IV cancers, in cancers with lymph node metastasis and in tumors located in the distal part of the large intestine. Patients with greater KISS1 levels had worse prognosis. No KISS1R expression was detected in normal or malignant tissues or in liver metastases. KISS1 expression is reduced during the malignant transformation of the colonic mucosa. However, larger and advanced colorectal cancers express more KISS1, without reaching the former normal levels, and increased KISS1 levels are associated with worse prognosis. Finally, neither the normal nor the malignant colonic epithelial cells produce KISS1R.

  6. Structural definition of the F-actin-binding THATCH domain from HIP1R.

    PubMed

    Brett, Tom J; Legendre-Guillemin, Valerie; McPherson, Peter S; Fremont, Daved H

    2006-02-01

    Huntingtin-interacting protein-1 related (HIP1R) has a crucial protein-trafficking role, mediating associations between actin and clathrin-coated structures at the plasma membrane and trans-Golgi network. Here, we characterize the F-actin-binding region of HIP1R, termed the talin-HIP1/R/Sla2p actin-tethering C-terminal homology (THATCH) domain. The 1.9-A crystal structure of the human HIP1R THATCH core reveals a large sequence-conserved surface patch created primarily by residues from the third and fourth helices of a unique five-helix bundle. Point mutations of seven contiguous patch residues produced significant decreases in F-actin binding. We also show that THATCH domains have a conserved C-terminal latch capable of oligomerizing the core, thereby modulating F-actin engagement. Collectively, these results establish a framework for investigating the links between endocytosis and actin dynamics mediated by THATCH domain-containing proteins.

  7. Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus.

    PubMed

    Shughrue, P J; Lane, M V; Merchenthaler, I

    1996-11-01

    GLP-1 has been shown to dramatically reduce food intake in fasted rats and is thought to exert its effects by modulating neuronal function in the hypothalamus. To date, little is known about the distribution of GLP1-R and its mRNA in the rodent hypothalamus. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of GLP1-R mRNA in the rat hypothalamus. The results of these studies revealed an extensive distribution of GLP1-R mRNA throughout the rostral-caudal extent of the hypothalamus; with a dense accumulation of labeled cells in the supraoptic, paraventricular, and arcuate nuclei. Additional labeled cells were also detected in medial and lateral preoptic areas, periventricular nucleus, ventral division of the bed nucleus of the stria terminalis, lateral hypothalamus, and dorsomedial nucleus. The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of GLP1-R mRNA in the rat hypothalamus. In addition, this morphological data provides important information about the neuronal systems modulated by GLP-1 and their potential role in feeding behavior.

  8. 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

  9. Association study of human VN1R1 pheromone receptor gene alleles and gender.

    PubMed

    Mitropoulos, Constantinos; Papachatzopoulou, Adamantia; Menounos, Panagiotis G; Kolonelou, Christina; Pappa, Magda; Bertolis, George; Gerou, Spiros; Patrinos, George P

    2007-01-01

    Pheromones are water-soluble chemicals that elicit neuroendocrine and physiological changes, while they also provide information about gender within individuals of the same species. VN1R1 is the only functional pheromone receptor in humans. We have undertaken a large mutation screening approach in 425 adult individuals from the Hellenic population to investigate whether the allelic differences, namely alleles 1a and 1b present in the human VN1R1 gene, are gender specific. Here we show that both VN1R1 1a and 1b alleles are found in chromosomes of both male and female subjects at frequency of 26.35% and 73.65%, respectively. Given the fact that those allelic differences potentially cause minor changes in the protein conformation and its transmembrane domains, as simulated by the TMHMM software, our data suggest that the allelic differences in the human VN1R1 gene are unlikely to be associated with gender and hence to contribute to distinct gender-specific behavior.

  10. Genetic Variations of the KISS1R Gene in Korean Girls with Central Precocious Puberty

    PubMed Central

    2017-01-01

    The timing of puberty onset varies greatly among individuals, and much of this variation is modulated by genetic factors. This study aimed to identify the kisspeptin receptor (KISS1R) gene variations and to investigate the associations between these variations and central precocious puberty (CPP). Korean girls with CPP (n = 194) and their healthy controls (n = 99) were included in this study. The entire coding region and the exon-intron boundaries (exon 1 through 5) of the KISS1R gene were directly sequenced. Seven polymorphisms were identified in the KISS1R gene. A missense change c.1091T>A, and an intron variant c.738+64G>T showed significantly higher allele frequencies in CPP patients than in controls (c.1091T>A: 30.7% vs. 22.2%, P = 0.031; c.738+64G>T: 45.6% vs. 35.9%, P = 0.023). The missense variant (c.1091T>A) was a nonsynonymous polymorphism that induces amino acid substitution of p.Leu364His. The haplotype CAGTGTC was detected more frequently in the CPP group (P = 0.042). The sequence variants of the KISS1R gene can be inducible factors in the development of CPP. The association between sequence variants and CPP should be validated by further evidence obtained from larger samples of children with CPP. PMID:27914139

  11. Genetic analysis of MC1R variants in Chinese Han patients with sporadic Parkinson's disease.

    PubMed

    He, Sihan; Tan, Ting; Song, Zhi; Yuan, Lamei; Deng, Xiong; Ni, Bin; Chen, Yong; Deng, Hao

    2016-01-12

    Parkinson's disease (PD, OMIM 168600) is a neurodegenerative disorder featured by degeneration of melanin-positive dopaminergic neurons. Epidemiologic studies have suggested that PD and malignant melanoma (MM) might share common genetic components. Recently, the p.R160W variant in the melanocortin 1 receptor gene (MC1R, OMIM 155555), a risk factor for MM, has been identified to be associated with PD in Spanish population. To explore whether the MC1R variants are associated with sporadic PD in Chinese population, we designed a case-control comparison study and studied three variants, including rs3212366 (p.F196L), rs33932559 (p.I120T) and rs34090186 (p.R67Q), in the MC1R gene in 512 Chinese Han patients with sporadic PD and 512 age, gender and ethnicity matched normal controls. For rs3212366, only the TT genotype was identified in both PD and control cohorts. For variants rs33932559 and rs34090186, we did not identify any statistically significant difference in either genotypic distribution or allelic distribution between the PD cohort and control cohort, and in addition, we did not identify any related haplotype that would either increase the risk for PD or play a protective role against PD. Our data suggest that none of the three variants of the MC1R gene and related haplotypes be associated with sporadic form of PD in Chinese Han population from Mainland China.

  12. 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.

  13. HST's Fine Guidance Sensor 1R, The Resolving Power of this Optimized Space Based Interferometer.

    NASA Astrophysics Data System (ADS)

    Lupie, O.; Nelan, E.; Nagel, L.; Makidon, R.; Franz, O.; Wasserman, L.

    1998-05-01

    The Fine Guidance Sensor is a white light shearing interferometer which is sensitive to the tilt of the wavefront presented to its Koesters Prisms. If the wavefront is planar, the instrument is remarkably insensitive to large shifts (3mm) of the pupil on the face of the prisms. However, in the presence of HST's spherically aberrated wavefront, any internal misalignment of the instrument which leads to small ( 0.3mm) displacements of the pupil at the Koesters Prism rapidly degrades the interferometer's fringe visibility and morphology. FGS1r, installed in HST during the Second Servicing Mission, benefits from an articulating mirror (FF3) which can be adjusted to recenter the pupil on the Koesters Prisms to optimize the interferometer's performance. We report the results of an on-orbit test, using the optimized FGS1r, to measure the angular separation of the components of the binary system ADS11300. In this test, the roll angle of HST was varied so that the projected angular separation of the binary's components along FGS1r's X axis ranged from 6 to 20 mas. We discuss the class of science observations for which this instrument is best suited and STScI's consideration of offering FGS1r as a science instrument in cycle 8. Updated information about the FGSs can be found at http://www.stsci.edu/ftp/instrument_news/fgs/html/TOPfgs.html.

  14. Post FGS1r AMA-Adjustment: OFAD Check and Alignment Calibration, 2008

    NASA Astrophysics Data System (ADS)

    Lallo, Matthew

    2007-07-01

    The FGS1 AMA optimization proposal {11963} leaves the AMA mirror in a new position, which shifts the FGS1r FOV relative to FGS2r and FGS3 and has the potential to change the FGS1r OFAD solution. This proposal will use the astrometric open cluster NGC 5617 to check for 1 mas size changes in the OFAD and to establish the new alignment of FGS1r relative to FGS2r and FGS3 to a precision of approximately 25 mas. The OFAD check requires 4 HST orbits before, and 4 HST orbits after, the AMA adjustment. Each orbit observes the same stars in NGC 5617 with FGS1r in POS mode. The alignment aspect of this proposal uses data from these same orbits. The ICRS positions of the relevant stars are taken from the UCAC catalog, but the proper motions taken from the "special guide star plate ZZZT" provided by Yale University. We chose guide stars in FGS2r and FGS3, and astrometry targets that are common to GSC2, UCAC, and ZZZT. Each visit uses a unique guide star pair, so that all the visits taken together have guide stars spanning the guider FGSs FOV.

  15. 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

  16. Isocitrate dehydrogenase 1 R132H mutation is not detected in angiocentric glioma.

    PubMed

    Raghunathan, Aditya; Olar, Adriana; Vogel, Hannes; Parker, John R; Coventry, Susan C; Debski, Robert; Albarracin, Constance T; Aldape, Kenneth D; Cahill, Daniel P; Powell, Suzanne Z; Fuller, Gregory N

    2012-08-01

    Mutations of isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (R132H), have been described in World Health Organization grade II and III diffuse gliomas and secondary glioblastoma. Immunohistochemistry using a mouse monoclonal antibody has a high specificity and sensitivity for detecting IDH1 R132H mutant protein in sections from formalin-fixed, paraffin-embedded tissue. Angiocentric glioma (AG), a unique neoplasm with mixed phenotypic features of diffuse glioma and ependymoma, has recently been codified as a grade I neoplasm in the 2007 World Health Organization classification of central nervous system tumors. The present study was designed to evaluate IDH1 R132H protein in AG. Three cases of AG were collected, and the diagnoses were confirmed. Expression of mutant IDH1 R132H protein was determined by immunohistochemistry on representative formalin-fixed, paraffin-embedded sections using the antihuman mouse monoclonal antibody IDH1 R132H (Dianova, Hamburg, Germany). Known IDH1 mutation-positive and IDH1 wild-type cases of grade II to IV glioma served as positive and negative controls. All 3 patients were male, aged 3, 5, and 15 years, with intra-axial tumors in the right posterior parietal-occipital lobe, right frontal lobe, and left frontal lobe, respectively. All 3 cases showed characteristic morphologic features of AG, including a monomorphous population of slender bipolar cells that diffusely infiltrated cortical parenchyma and ensheathed cortical blood vessels radially and longitudinally. All 3 cases were negative for the presence of IDH1 R132H mutant protein (0/3). All control cases showed appropriate reactivity. IDH1 R132H mutation has been described as a common molecular signature of grade II and III diffuse gliomas and secondary glioblastoma; however, AG, which exhibits some features of diffuse glioma, has not been evaluated. The absence of mutant IDH1 R132H protein expression in AG

  17. Nucleotide diversity of the melanocortin 1 receptor gene (MC1R) in the gayal (Bos frontalis).

    PubMed

    Xi, Dongmei; Liu, Qing; Huo, Yinqiang; Sun, Yongke; Leng, Jing; Gou, Xiao; Mao, Huaming; Deng, Weidong

    2012-07-01

    The melanocortin 1 receptor gene (MC1R) plays a crucial role in determining coat colour of mammals. To investigate the relationship of polymorphism of the MC1R with coat colour in gayal, the coding sequence (CDS), and the 5'- and 3'-untranslated regions (UTR) of the MC1R were sequenced from 63 samples from the gayal and compared with the sequences of the MC1R from other ruminant species. A sequence of 1,136 bp including the whole CDS (954 bp) and parts of the 5'- and 3'-UTR (164 and 18 bp, respectively) of the gayal MC1R was obtained. A total of nine single nucleotide polymorphisms (SNPs) including four SNPs (c.-129T>C, c.-127A>C, c.-106C>T, c.-1G>A) in the 5'-UTR and five SNPs (c.201C>T, c.583C>T, c.663T>C, c.871A>G and c.876T>C) in the CDS were detected, revealing high genetic diversity. Three novel coding SNPs including c.201C>T, c.583C>T and c.876T>C, which have not been reported previously in bovid species, were retrieved. Within five coding SNPs, c.201C>T, c.663T>C and c.876T>C were silent mutations, while c.583C>T and c.871A>G were mis-sense mutations, resulting in changes in the amino acids located in the fifth (p.L195F) and seventh (p.T291A) transmembrane regions, respectively. The alignment of amino acid sequences was found to be very similar to those for other bovid species. It was demonstrated, using the functional effect prediction, that the p.T291A amino acid replacement could have an effect on MC1R protein function but not for the p.L195F substitution. Using phylogenetic analyses it was revealed that the gayal has a close genetic relationship with the yak. However, three classical bovine MC1R loci the E (D), E (+) and e were not retrieved in the gayal, indicating other genes or factors could affect coat colour in this species.

  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. Sigma-1R agonist improves motor function and motoneuron survival in ALS mice.

    PubMed

    Mancuso, Renzo; Oliván, Sara; Rando, Amaya; Casas, Caty; Osta, Rosario; Navarro, Xavier

    2012-10-01

    Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1(G93A) mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1(G93A) animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca(2+) influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.

    PubMed

    Wauson, Eric M; Guerra, Marcy L; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M; Cobb, Melanie H

    2015-08-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that G(I) is not central to either pathway. Although glucagon-like peptide 1, an agonist for a G(s-)coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca(2+) entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective G(q) inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for G(q). Inhibition of G(12/13) by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways.

  6. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells

    PubMed Central

    Wauson, Eric M.; Guerra, Marcy L.; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M.

    2015-01-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that Gi is not central to either pathway. Although glucagon-like peptide 1, an agonist for a Gs-coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca2+ entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective Gq inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for Gq. Inhibition of G12/13 by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways. PMID:26168033

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Adsorption of indoor toxic gas by ionic liquid impregnated activated carbons

    NASA Astrophysics Data System (ADS)

    Rahman, Noraisyah Azeezah Abdul; Leveque, Jean Marc; Mutalib, Mohamed Ibrahim Abdul; Ghani, Noraini Abdul; Thangarajoo, Nanthinie; Mazlan, Faizureen Afzal; Farooq, Amjad; Irfan, Naseem; Duclaux, Laurent; Reinert, Laurence; Ondarts, Michel

    2016-11-01

    Butylpyridinium thiocyanate [BuPyr]SCN ionic liquid was synthesized by metathesis and characterized. NMR spectrum has shown the [BuPyr] cation while FTIR has shown the SCN anion peak which confirms the structure of the synthesized ionic liquid. The ionic liquid was impregnated on activated carbon in order to enhance performance of sulfur dioxide adsorption compared to the non-impregnated raw activated carbon. Two types of activated carbons were used; activated carbon cylindrical granules and cloth. Different percentages of ionic liquid loading (1%, 10% and 20%) were applied. The capacity of the adsorbent for treatment of 10 ppm and 50 ppm SO2 was determined by breakthrough curve analysis whereby optimum breakthrough time was obtained. [BuPyr]SCN impregnated on activated carbon cloth have shown higher adsorption performance.

  12. 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.

  13. 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.

  14. 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

  15. Elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro.

    PubMed

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2016-11-01

    OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro. SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls). PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.

  16. The effect of silver impregnation of surgical scrub suits on surface bacterial contamination

    PubMed Central

    Freeman, A.I.; Halladay, L.J.; Cripps, P.

    2012-01-01

    Silver-impregnated fabrics are widely used for their antibacterial and antifungal effects, including for clinical clothing such as surgical scrub suits (scrubs). This study investigated whether silver impregnation reduces surface bacterial contamination of surgical scrubs during use in a veterinary hospital. Using agar contact plates, abdominal and lumbar areas of silver-impregnated nylon or polyester/cotton scrubs were sampled for surface bacterial contamination before (0 h) and after 4 and 8 h of use. The number of bacterial colonies on each contact plate was counted after 24 and 48 h incubation at 37 °C. Standard basic descriptive statistics and mixed-effects linear regression were used to investigate the association of possible predictors of the level of bacterial contamination of the scrubs with surface bacterial counts. Silver-impregnated scrubs had significantly lowered bacterial colony counts (BCC) at 0 h compared with polyester/cotton scrubs. However, after 4 and 8 h of wear, silver impregnation had no effect on BCC. Scrub tops with higher BCC at 0 h had significantly higher BCC at 4 and 8 h, suggesting that contamination present at 0 h persisted during wear. Sampling from the lumbar area was associated with lower BCC at all three time points. Other factors (contamination of the scrub top with a medication/drug, restraint of patients, working in the anaesthesia recovery area) also affected BCC at some time points. Silver impregnation appeared to be ineffective in reducing bacterial contamination of scrubs during use in a veterinary hospital. PMID:22015140

  17. Comparison of sorption behavior of Th(IV) and U(VI) on modified impregnated resin containing quinizarin with that conventional prepared impregnated resin.

    PubMed

    Hosseini, Mohammad Saeid; Hosseini-Bandegharaei, Ahmad

    2011-06-15

    This paper reports the results obtained by studying the ion-exchange properties of a new solvent impregnated resin (SIR), which was prepared by impregnation of quinizarin (1,4-dihydroxyanthraquinone, QNZ) on Amberlite XAD-16 after nitration of the benzene rings present in its structure. The sorption behavior of Th(IV) and U(VI) on/in the modified SIR was compared with that of the SIR prepared via the conventional method. It was observed that sorption capacity and sorption rate of the modified SIR are significantly greater than the conventional one. The modified SIR was then applied to the extraction of Th(IV) and U(VI) ions at the presence of many co-existence metal ions. The results obtained denote on successful application of this new SIR to analysis of natural water samples spiked to Th(IV) and U(VI) ions.

  18. Synthesis of hybrid organic-inorganic perovskite platelets by vacuum impregnation

    NASA Astrophysics Data System (ADS)

    Manthina, Venkata; Agrios, Alexander G.

    2016-11-01

    In perovskite solar cells and optoelectronics, perovskite film morphology controls the performance of the device. Various methods have been developed to control the morphology and coverage of the perovskite films. In this article platelet type perovskite morphlogy was synthesized using low temperature vacuum impregnation of the perovskite solution CH3NH3PbI3 resulting in complete coverage on TiO2 film. Vacuum impregnation synthesis of perovskites has the advantage of low cost and low temperature which faciliates application in flexible electronics and solar cells.

  19. Out-of-Plane Self-Propulsion of Droplets on Heated Lubricant-Impregnated Surfaces

    NASA Astrophysics Data System (ADS)

    Dash, Susmita; de Ruiter, Jolet; Varanasi, Kripa

    2016-11-01

    In this work, we investigate droplet motion on lubricant-impregnated surfaces that are stable at high temperatures. Water droplets on such surfaces demonstrate in-plane hopping motion and out-of-plane self-propulsion at temperatures far below the typical Leidenfrost temperatures. While the in-plane motion of the droplet is on the order of 10 mm/s, the droplet is propelled vertically upwards at a velocity of approximately 200 mm/s. We present the mechanics underlying this behavior of droplets, which is specific to lubricant-impregnated surfaces.

  20. The Experimental Analysis on the Thermal and Electrical Characteristics of Impregnating Materials for Superconducting Magnets

    NASA Astrophysics Data System (ADS)

    Yang, Seong Eun; Kweon Bae, Duck; Kang, Hyoungku; Ahn, Min Cheol; Park, Dong Keun; Seok, Bok-Yeol; Myoung Jang, Ho; Kuk Ko, Tae

    2006-06-01

    In recent years, a development of Coated Conductor (CC) that is a called the second generation superconductor tape is opened out. Therefore a commercialization of superconducting power equipments will be realized presently. To realize a commercialization, it is necessary to develop a stable superconducting magnet. A superconducting magnet has to keep thermal stability as well as electrical stability. In this paper, thermal conductivity of impregnating materials, epoxy compounds, was measured at 65K, 77K, 100K and 200K. Dielectric Strength of superconducting magnet modeled electrode system with impregnating materials was also analyzed. Stycast blue/catalyst 23LV is good materials to apply to the superconducting magnets.

  1. 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.

  2. An X-Ray Photoelectron Spectroscopy (XPS) Study of Activated Carbons Impregnated with Some Organocopper Complexes

    DTIC Science & Technology

    1993-10-01

    preparation of ASC/T carbon involved using an aqueous ammoniacal solution as a carrier into which all impregnants (except TEDA) were dissolved. Without a...routes to these complexes have been described (1), and will not be repeated here. All five complexes were synthesized at DREO using known methods.’ 2...earlier report (2) that fresh Whetlerite (a carbon which has been impregnated with an ammoniacal solution containing CrO3 , (NH4 ) 2CO3 and CuCO3 "Cu(OH

  3. 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.

  4. A modification of the chronic tartrate silver impregnation technique for block impregnation of the central nervous system and paraffin wax embedding.

    PubMed

    Abadía-Fenoll, F; Ostos Garrido, M V; López-Lendínez, J L; Carmona Martos, R

    1985-03-01

    This paper describes a block silver impregnation technique for the CNS. The procedure, which is quite simple, yields highly consistent and reproducible results. After fixation during 6-10 days in 10% saline formaldehyde, 4 mm thick blocks of brain are treated with chromic anhydride and sodium potassium tartrate solution for 4 days. After this period the specimens are rinsed in 0.75% silver nitrate solution to which 8-10 drops of pyridine per 100 ml of solution have been added. This is followed by impregnation for 4 days at 37 degrees C in silver nitrate-pyridine solution identical to that used in the previous rinsing step. The impregnated blocks are reduced during 20-26 h in 1% pyrogallol to which 6 ml commercial formaldehyde per 100 ml of solution have been added, followed by dehydration in dioxan and paraffin embedding. Sections no thicker than 30 microns are then cut for histological study. This fundamentally neurofibrillar method reveals: neuronal somata and their processes; synaptic structures; fibre bundles; and cell nuclei and nucleoli.

  5. Immunohistochemical localisation of cholinergic muscarinic receptor subtype 1 (M1r) in the guinea pig and human enteric nervous system.

    PubMed

    Harrington, A M; Hutson, J M; Southwell, B R

    2007-07-01

    Little is known regarding the location of cholinergic muscarinic receptor 1 (M1r) in the ENS, even though physiological data suggest that M1rs are central to cholinergic neurotransmission. This study localised M1rs in the ENS of the guinea pig ileum and human colon using fluorescence immunohistochemistry and RT-PCR in human colon. Double labelling using antibodies against neurochemical markers was used to identify neuron subytpes bearing M1r. M1r immunoreactivity (IR) was present on neurons in the myenteric and submucosal ganglia. The two antibodies gave similar M1r-IR patterns and M1r-IR was abolished upon antibody preabsorption. M1r-IR was present on cholinergic and nNOS-IR nerve cell bodies in both guinea pig and human myenteric neurons. Presynaptic M1r-IR was present on NOS-IR and VAChT-IR nerve fibres in the circular muscle in the human colon. In the submucosal ganglia, M1r-IR was present on a population of neurons that contained cChAT-IR, but did not contain NPY-IR or calretinin-IR. M1r-IR was present on endothelial cells of blood vessels in the submucosal plexus. The localisation of M1r-IR in the guinea pig and human ENS shown in this study agrees with physiological studies. M1r-IR in cholinergic and nitrergic neurons and nerve fibres indicate that M1rs have a role in both cholinergic and nitrergic transmission. M1r-IR present in submucosal neurons suggests a role in mediating acetylcholine's effect on submucosal sensory and secretomotor/vasodilator neurons. M1r-IR present on blood vessel endothelial cells suggests that M1rs may also mediate acetylcholine's direct effect on vasoactivation.

  6. Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells.

    PubMed

    Kojima, Itaru; Nakagawa, Yuko; Hamano, Kunihisa; Medina, Johan; Li, Longfei; Nagasawa, Masahiro

    2015-01-01

    Subunits of the sweet taste receptors T1R2 and T1R3 are expressed in pancreatic β-cells. Compared with T1R3, mRNA expression of T1R2 is considerably lower. At the protein level, expression of T1R2 is undetectable in β-cells. Accordingly, a major component of the sweet taste-sensing receptor in β-cells may be a homodimer of T1R3 rather than a heterodimer of T1R2/T1R3. Inhibition of this receptor by gurmarin or deletion of the T1R3 gene attenuates glucose-induced insulin secretion from β-cells. Hence the T1R3 homodimer functions as a glucose-sensing receptor (GSR) in pancreatic β-cells. When GSR is activated by the T1R3 agonist sucralose, elevation of intracellular ATP concentration ([ATP]i) is observed. Sucralose increases [ATP]i even in the absence of ambient glucose, indicating that sucralose increases [ATP]i not simply by activating glucokinase, a rate-limiting enzyme in the glycolytic pathway. In addition, sucralose augments elevation of [ATP]i induced by methylsuccinate, suggesting that sucralose activates mitochondrial metabolism. Nonmetabolizable 3-O-methylglucose also increases [ATP]i and knockdown of T1R3 attenuates elevation of [ATP]i induced by high concentration of glucose. Collectively, these results indicate that the T1R3 homodimer functions as a GSR; this receptor is involved in glucose-induced insulin secretion by activating glucose metabolism probably in mitochondria.

  7. MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas.

    PubMed

    Liboutet, Muriel; Portela, Marc; Delestaing, Gisèle; Vilmer, Catherine; Dupin, Nicolas; Gorin, Isabelle; Saiag, Philippe; Lebbé, Céleste; Kerob, Delphine; Dubertret, Louis; Grandchamp, Bernard; Basset-Seguin, Nicole; Soufir, Nadem

    2006-07-01

    In this study, we assessed the role of melanocortin 1 receptor (MC1R) variants and of two patched (PTCH) polymorphisms (c.3944C>T (P1315L), insertion 18 bp IVS1-83) as risk factors for basal cell carcinoma (BCC) in the French population. The population investigated comprised 126 BCC patients who were enrolled on the basis of specific criteria (multiple and/or familial BCC and/or onset before the age of 40 years and/or association with another tumor)--and 151 controls matched for ethnicity, age, and sex. MC1R variants appeared as a moderate risk factor for BCC (odds ratio (OR) for one and two variants, 2.17 [1.28-3.68] and 7.72 [3.42-17.38], respectively), independently of pigmentation characteristics (OR = 2.53 [1.34-4.8]). Interestingly, in addition to the predictable red hair color (RHC) alleles, two non-RHC alleles (V60L and V92M) were also closely associated with BCC risk (OR 3.21 [1.91-5.38] and 2.87 [1.5-5.48], respectively), which differs from the situation in the Celtic population. In addition, the PTCH c.3944C/C genotype was also associated with BCC risk (OR 1.94 [1.2-3.1]), especially in the subgroup of patients with multiple tumors (OR 2.16 [1.3-3.6]). Thus, our data show that MC1R and PTCH variants are associated with BCC risk in the French population. We further suggest that assessing MC1R and PTCH status could be useful, combined with the assessment of clinical risk factors, in identifying high-risk patients to be targeted for prevention or more rigorous surveillance.

  8. The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders.

    PubMed

    Johnson, M Brittany; Young, Ada D; Marriott, Ian

    2016-01-01

    The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson's disease, Alzheimer's disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical in preserving normal CNS functions. The neuropeptide substance P is produced at high levels within the CNS and its selective receptor, the neurokinin 1 receptor (NK-1R), is abundantly expressed by neurons and is present on glial cell types including microglia and astrocytes. In addition to its functions as a neurotransmitter in the perception of pain and its essential role in gut motility, this tachykinin is widely recognized to exacerbate inflammation at peripheral sites including the skin, gastrointestinal tract and the lungs. Recently, a number of studies have identified a role for substance P and NK-1R interactions in neuroinflammation and described the ability of this neuropeptide to alter the immune functions of activated microglia and astrocytes. In this review article, we describe the expression of substance P and its receptor by resident CNS cells, and we discuss the ability of this neuropeptide to exacerbate the inflammatory responses of glia and immune cells that are recruited to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions.

  9. The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders

    PubMed Central

    Johnson, M. Brittany; Young, Ada D.; Marriott, Ian

    2017-01-01

    The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical in preserving normal CNS functions. The neuropeptide substance P is produced at high levels within the CNS and its selective receptor, the neurokinin 1 receptor (NK-1R), is abundantly expressed by neurons and is present on glial cell types including microglia and astrocytes. In addition to its functions as a neurotransmitter in the perception of pain and its essential role in gut motility, this tachykinin is widely recognized to exacerbate inflammation at peripheral sites including the skin, gastrointestinal tract and the lungs. Recently, a number of studies have identified a role for substance P and NK-1R interactions in neuroinflammation and described the ability of this neuropeptide to alter the immune functions of activated microglia and astrocytes. In this review article, we describe the expression of substance P and its receptor by resident CNS cells, and we discuss the ability of this neuropeptide to exacerbate the inflammatory responses of glia and immune cells that are recruited to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions. PMID:28101005

  10. 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.

  11. IDH1 R132H mutation in a pilocytic astrocytoma: a case report

    PubMed Central

    Behling, Felix; Steinhilber, Julia; Tatagiba, Marcos; Bisdas, Sotirios; Schittenhelm, Jens

    2015-01-01

    We present the case of a 72-year old female with a right cerebellar pilocytic astrocytoma WHO grade I with an Isocitrate dehydrogenase 1 (IDH1) R132H mutation. The patient is recurrence-free 6 years after the initial diagnosis. Only one single case with strikingly similar clinicopathological features has been reported before. Otherwise, IDH1/2 mutations are not seen in pilocytic astrocytomas. The clinical implications of these findings are discussed. PMID:26617931

  12. Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R signaling.

    PubMed

    Cheng, Shujie; Castillo, Victor; Eliaz, Isaac; Sliva, Daniel

    2015-01-01

    Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis.

  13. Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling.

    PubMed

    Lai, Jinsheng; Chen, Fuqiong; Chen, Jing; Ruan, Guoran; He, Mengying; Chen, Chen; Tang, Jiarong; Wang, Dao Wen

    2017-03-14

    Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro.

  14. Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R signaling

    PubMed Central

    CHENG, SHUJIE; CASTILLO, VICTOR; ELIAZ, ISAAC; SLIVA, DANIEL

    2015-01-01

    Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis. PMID:25846316

  15. Regulatory Role of IL-1R8 in Immunity and Disease

    PubMed Central

    Molgora, Martina; Barajon, Isabella; Mantovani, Alberto; Garlanda, Cecilia

    2016-01-01

    Interleukin-1 receptor family members (ILRs) and toll-like receptors (TLRs) are characterized by the presence of a conserved intracellular domain and the toll-IL-1resistance (TIR) domain and are key players in immunity and inflammation. ILR and TLR signaling is tightly regulated at different levels. All cell types of the innate immune system express ILRs and TLRs. In addition, IL-1 family members are emerging as key players in the differentiation and function of innate and adaptive lymphoid cells. IL-1R8, also known as TIR8 or SIGIRR, is a fringe member of the ILR family and acts as a negative regulator of ILR and TLR signaling, which dampens ILR- and TLR-mediated cell activation. IL-1R8 is a component of the receptor recognizing human IL-37. Here, we summarize our current understanding of the structure and function of IL-1R8, focusing on its role in different pathological conditions, ranging from infectious and sterile inflammation to autoimmunity and cancer-related inflammation. PMID:27148268

  16. 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.

  17. 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.

  18. Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling

    PubMed Central

    Lai, Jinsheng; Chen, Fuqiong; Chen, Jing; Ruan, Guoran; He, Mengying; Chen, Chen; Tang, Jiarong; Wang, Dao Wen

    2017-01-01

    Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro. PMID:28290552

  19. The Relationship between MC1R Mutation and Plumage Color Variation in Pigeons

    PubMed Central

    Ran, Jin-Shan; You, Xiao-Yan; Jin, Jie; Zhou, Yu-Guang; Wang, Ye; Lan, Dan; Ren, Peng

    2016-01-01

    The polymorphisms of MC1R gene play a crucial role in coat color variation in mammals; however, the relationship is still unclear in pigeons. In this study, we sequenced 741 bp fragment of the MC1R for 39 individuals with five plumage color patterns (gray plumage, n = 12; black plumage, n = 9; white plumage, n = 3; spotted plumage, n = 12; red plumage, n = 3). A total of three single nucleotide polymorphisms (SNPs) were detected, including G199A, G225A, and A466G, which subsequently determined four haplotypes (H1–H4). Among them, H1 is the predominant haplotype. Association analysis revealed that H1 and H3 were significantly associated with the black plumage trait (P < 0.05), while the H4 was significantly associated with gray plumage trait (P < 0.05). Furthermore, only diplotype H1H1 was significantly associated with black and gray traits of pigeons. Collectively, our study suggested an association between genetic variation of MC1R and plumage color in pigeon. PMID:27957493

  20. α-Bisabolol Inhibits Invasiveness and Motility in Pancreatic Cancer Through KISS1R Activation.

    PubMed

    Uno, Masanori; Kokuryo, Toshio; Yokoyama, Yukihiro; Senga, Takeshi; Nagino, Masato

    2016-02-01

    α-Bisabolol is a plant-derived, oily sesquiterpene alcohol that induces apoptosis of various cancer cells. We previously reported the antiproliferative effects of α-bisabolol on pancreatic cancer cell lines using in vitro and in vivo experiments. However, the effects of α-bisabolol on tumor invasiveness and motility are still unknown. In this study, demonstrated that α-bisabolol suppressed the invasiveness and motility of a pancreatic cancer cell line. Although Early growth response 1 (EGR1) was involved in antiproliferative effects of α-bisabolol, it had no relationship with the inhibitory effect of α-bisabolol on cellular invasiveness and motility. Polymerase chain reaction analysis revealed that α-bisabolol induced Kisspeptin 1 receptor (KISS1R) in pancreatic cancer cell lines. The inhibition of KISS1R weakened the inhibitory effect of α-bisabolol on invasiveness of pancreatic cancer cells. The results also implied that the inhibitory effects of α-bisabolol on tumor invasiveness and motility are at least partly associated with the activation of KISS1R. However, there is a possibility that other molecular mechanisms of α-bisabolol regulate invasiveness and motility in pancreatic cancer cells. Further investigations are necessary to clarify the precise mechanisms of α-bisabolol activity for clinical application as a novel treatment for pancreatic cancer.

  1. Mutations in MC1R gene determine black coat color phenotype in Chinese sheep.

    PubMed

    Yang, Guang-Li; Fu, Dong-Li; Lang, Xia; Wang, Yu-Tao; Cheng, Shu-Ru; Fang, Su-Li; Luo, Yu-Zhu

    2013-01-01

    The melanocortin receptor 1 (MC1R) plays a central role in regulation of animal coat color formation. In this study, we sequenced the complete coding region and parts of the 5'- and 3'-untranslated regions of the MC1R gene in Chinese sheep with completely white (Large-tailed Han sheep), black (Minxian Black-fur sheep), and brown coat colors (Kazakh Fat-Rumped sheep). The results showed five single nucleotide polymorphisms (SNPs): two non-synonymous mutations previously associated with coat color (c.218 T>A, p.73 Met>Lys. c.361 G>A, p.121 Asp>Asn) and three synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu. c.735 C>T, p.245 Ile>Ile). Meanwhile, all mutations were detected in Minxian Black-fur sheep. However, the two nonsynonymous mutation sites were not in all studied breeds (Large-tailed Han, Small-tailed Han, Gansu Alpine Merino, and China Merino breeds), all of which are in white coat. A single haplotype AATGT (haplotype3) was uniquely associated with black coat color in Minxian Black-fur breed (P = 9.72E - 72, chi-square test). The first and second A alleles in this haplotype 3 represent location at 218 and 361 positions, respectively. Our results suggest that the mutations of MC1R gene are associated with black coat color phenotype in Chinese sheep.

  2. MC1R gene variants and sporadic malignant melanoma susceptibility in the Canary Islands population.

    PubMed

    Córdoba-Lanús, Elizabeth; Hernández-Jiménez, José G; Medina-Coello, Chaxiraxi; Espinoza-Jiménez, Adriana; González, Ana; Rodríguez-Pérez, María-Del-Cristo; Carretero-Hernández, Gregorio; Almeida, Pablo; Suárez-Hernández, José; Perera-Molinero, Antonio; Fernández-de-Misa, Ricardo

    2014-01-01

    Several MC1R variants are associated with increased risk of malignant melanoma (MM) in a variety of populations. We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. Overall, 1,046 Caucasian individuals were included in the study. A thousand of them were genotyped for MC1R variants: 509 were sporadic MM patients and 491 were healthy control subjects from general population. The analysis was adjusted for age, sex, hair colour, eye colour, skin phototype and ancestry. We found that carriers of the R151C and R163Q variants were at an increased risk for melanoma OR 2.76 (1.59-4.78) and OR 5.62 (2.54-12.42), respectively. The risk of carrying RHC variants was 3.04 (1.90-4.86). Current study confirms the increased MM risk for R151C carriers. It also supports the association between R163Q variant and MM risk in the population on the Canary Islands, as opposed to reported on northern populations. These results highlight the importance of the sample population selection in this kind of studies.

  3. Genetic variation of chicken MC1R gene in different plumage colour populations.

    PubMed

    Guo, X L; Li, X L; Li, Y; Gu, Z L; Zheng, C S; Wei, Z H; Wang, J S; Zhou, R Y; Li, L H; Zheng, H Q

    2010-12-01

    1. Genetic variation in the chicken MC1R gene was analysed through bioinformatic methods after polymerase chain reaction (PCR) amplification and sequencing of the coding region of MC1R gene from 5 different populations with 4 plumage colours (black, grey plumage with black spots, yellow plumage with black spots, red). 2. A total of 11 novel variations were detected in Hebei chickens, of which 8 were non-synonymous. Allele distribution analysis showed that the wild-type e(+) (Brown Leghorn) allele was mainly found in Hy-Line Brown and Lohmann Brown, the dominant Extended black E(AY220304) allele was mainly found in Hebei chicken with black plumage, whereas the Buttercup (e(bc)) allele was rare. 3. Nucleotide diversity (π) within each colour strain of Hebei chickens (0·0047-0·0052) was significantly greater than that of Hy-Line Brown (0·0024) or Lohmann Brown (0·0043). 4. The results indicate that there is abundant polymorphism in the MC1R gene, especially in Hebei chicken, which was associated with its rich plumage colour diversity.

  4. Improving expression of recombinant human IGF-1 using IGF-1R knockout CHO cell lines.

    PubMed

    Romand, Sandrine; Jostock, Thomas; Fornaro, Mara; Schmidt, Joerg; Ritter, Anett; Wilms, Burkhard; Laux, Holger

    2016-05-01

    Chinese Hamster Ovary (CHO) cells are widely used for the large-scale production of recombinant biopharmaceuticals. However, attempts to express IGF-1 (a mutated human Insulin-like growth factor 1 Ea peptide (hIGF-1Ea mut)) in CHO cells resulted in poor cell growth and low productivity (0.1-0.2 g/L). Human IGF-1 variants negatively impacted CHO cell growth via the IGF-1 receptor (IGF-1R). Therefore knockout (KO) of the IGF-1R gene in two different CHO cell lines as well as knockdown (KD) of IGF-1R in one CHO cell line were performed. These cell line engineering approaches decreased significantly the hIGF-1 mediated cell growth inhibition and increased productivity of both KO CHO cell lines as well as of the KD CHO cell line. A productivity increase of 10-fold at pool level and sevenfold at clone level was achieved, resulting in a titer of 1.3 g/L. This data illustrate that cell line engineering approaches are powerful tools to improve the yields of recombinant proteins which are difficult to produce in CHO cells.

  5. In Vivo Imaging of GLP-1R with a Targeted Bimodal PET/Fluorescence Imaging Agent

    PubMed Central

    2015-01-01

    Accurate visualization and quantification of β-cell mass is critical for the improved understanding, diagnosis, and treatment of both type 1 diabetes (T1D) and insulinoma. Here, we describe the synthesis of a bimodal imaging probe (PET/fluorescence) for imaging GLP-1R expression in the pancreas and in pancreatic islet cell tumors. The conjugation of a bimodal imaging tag containing a near-infrared fluorescent dye, and the copper chelator sarcophagine to the GLP-1R targeting peptide exendin-4 provided the basis for the bimodal imaging probe. Conjugation was performed via a novel sequential one-pot synthetic procedure including 64Cu radiolabeling and copper-catalyzed click-conjugation. The bimodal imaging agent 64Cu-E4-Fl was synthesized in good radiochemical yield and specific activity (RCY = 36%, specific activity: 141 μCi/μg, >98% radiochemical purity). The agent showed good performance in vivo and ex vivo, visualizing small xenografts (<2 mm) with PET and pancreatic β-cell mass by phosphor autoradiography. Using the fluorescent properties of the probe, we were able to detect individual pancreatic islets, confirming specific binding to GLP-1R and surpassing the sensitivity of the radioactive label. The use of bimodal PET/fluorescent imaging probes is promising for preoperative imaging and fluorescence-assisted analysis of patient tissues. We believe that our procedure could become relevant as a protocol for the development of bimodal imaging agents. PMID:24856928

  6. Effect of impregnation phases on the performance of Ni-based anodes for low temperature solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Liu, Zhangbo; Ding, Dong; Liu, Beibei; Guo, Weiwei; Wang, Wendong; Xia, Changrong

    2011-10-01

    Impregnated nanoparticles are very effective in improving the electrochemical performance of solid oxide fuel cell (SOFC) anodes possibly due to the extension of reaction sites and/or the enhancement of catalytic activity. In this work, samaria-doped ceria (SDC), pure ceria, samaria, and alumina oxides impregnated Ni-based anodes are fabricated to compare the site extending and the catalytic effects. Except for alumina, the impregnation of the other three nano-sized oxides could substantially enhance the performance of the anodes for the hydrogen oxidation reactions. Moreover, single cells with CeO2 and Sm2O3 impregnated anodes could exhibit as great performance as those with SDC impregnated anodes. When the impregnation loading reached the optimal value, 1.7 mmol cm-3, these cells exhibit very high performance, with peak power densities around 750 mW cm-2. The high performance of CeO2 and Sm2O3 impregnated anodes demonstrates that the improved performance are mainly attributed to the significantly improved electrochemical activities of the anodes, but not to the extension of triple-phase-boundary, and wet impregnation is indeed an alternative and effective technique to introduce these nano-sized catalytic active oxides into the anode configuration of SOFCs to enhance cell performance, stability and reliability.

  7. Antibiotic Impregnated Bone Cement for the Treatment of Osteomelitis and Severe Open Fractures: Expanded Options for Surgeons

    DTIC Science & Technology

    2008-06-01

    Impregnated Bone Cement for the treatment of Osteomelitis and Severe Open Fractures: Expanded Options for Surgeons PRINCIPAL INVESTIGATOR: CDR...34Antibiotic Impregnated Bone Cement for the treatment of Osteomelitis 5b. GRANT NUMBER W81XWH-07-1-0221 and Severe Open Fractures: Expanded Options for

  8. An example of designed multiple ligands spanning protein classes: dual MCH-1R antagonists/DPPIV inhibitors.

    PubMed

    Gattrell, William T; Sambrook Smith, Colin P; Smith, Alun J

    2012-04-01

    A ligand-based approach to identify potential starting points for a dual MCH-1R antagonist/DPPIV inhibitor medicinal chemistry program was undertaken. Potential ligand pairs were identified by analysis of MCH-1R and DPPIV in vitro data. A highly targeted synthetic effort lead to the discovery of pyridone 11, a dual MCH-1R antagonist/DPPIV inhibitor with selectivity over DPP8 and DPP9.

  9. 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

  10. Resistance of constructional steel to fracture in hydrogen impregnation and hydrogen sulfide cracking

    SciTech Connect

    Savchenkov, E.A.

    1986-01-01

    This article discusses the resistance of constructional steel to fracture in hydrogen impregnation and hydrogen sulfide cracking. The greater the hydrogen concentration at the crack tip, the lower the failure stress intensity factor. The relationship of the new parameter of hydrogen resistance and the equations of decohesion of the hydrogen impregnated metal is revealed in analysis of the threshold stresses of hydrogen sulfide cracking. The quantitative rules and criteria of fracture of hydrogen impregnated steel established show that the activity of hydrogen, creating ''hydrogen stresses'' and adsorption effects, has primary significance. Results presented show that the harmful influence of hydrogen may be neutralized by selection of appropriate alloying and methods of treatment of the steel to reduce the activity of hydrogen and under certain conditions to even obtain a positive effect from hydrogen impregnation. The author outlines several conclusions and shows that the criterion of failure of constructional steels in hydrogen embrittlement may be represented in clear form through the probability of decohesion, the hydrogen activity and the original crack resistance.

  11. 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

  12. Impregnation method for detecting annual laminations in sediment cores: An overview

    NASA Astrophysics Data System (ADS)

    Boës, Xavier; Fagel, Nathalie

    2005-08-01

    Annually laminated sediments can provide an absolute time scale (by varve counting) and a high-resolution palaeoclimate information (from varve thickness). Both types of information may be directly measured from sediment core surfaces. In this paper, we stress that varve counting and varve thickness measurements derived from fresh core surfaces could not systematically reveal the internal sedimentary structure, even if assisted by high resolution image analysis. We present an example of a homogeneous sediment core for which the varves were only observable after core impregnation and polishing steps. Because the impregnation methods are not yet standardized, the aim of this paper is to give an updated review of the methodology. In this review, we present the major critical points during impregnation steps. In particular, we focus on all of the post-treatment sediment disturbances that can alter the laminated micro-structure and, consequently, varve measurements. Finally, we propose a modified impregnation protocol, especially adapted for tracking varved intervals in long cores.

  13. 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.

  14. Effect of two cleaning processes for bone allografts on gentamicin impregnation and in vitro antibiotic release.

    PubMed

    Coraça-Huber, D C; Hausdorfer, J; Fille, M; Steidl, M; Nogler, M

    2013-06-01

    Bone allografts are a useful and sometimes indispensable tool for the surgeon to repair bone defects. Microbial contamination is a major reason for discarding allografts from bone banks. To improve the number of safe allografts, we suggest chemical cleaning of the grafts followed by antibiotic impregnation. Comparison of two chemical cleaning processes for bone allografts aiming for antibiotic impregnation and consequently delivery rates in vitro. Bone chips of 5-10 mm were prepared from human femoral heads. Two cleaning methods (cleaning A and cleaning B) based on solutions containing hydrogen peroxide, paracetic acid, ethanol and biological detergent were carried out and compared. After the cleaning processes, the bone chips were impregnated with gentamicin. Bacillus subtilis bioassay was used to determine the gentamicin release after intervals of 1-7 days. Differences were compared with non-parametric Mann-Whitney U tests. The zones of inhibition obtained from the bone grafts cleaned with both cleaning processes were similar between the groups. The concentration of the released antibiotic was decreasing gradually over time, following a similar pattern for both groups. The cleaning procedure A as well as the cleaning procedure B for bone allografts allowed the impregnation with gentamicin powder in the same concentrations in both groups. The delivery of gentamicin was similar for both groups. Both cleaning procedures were easy to be carried out, making them suitable for routine use at the bone banks.

  15. Effects of impregnated metal ions on air/CO2-gasification of woody biomass.

    PubMed

    Hurley, Scott; Li, Hanning; Xu, Chunbao Charles

    2010-12-01

    Several impregnated metal ions (Fe (III), Co (II), Ni (II), and Ru (IV)) and a raw iron ore (natural limonite) were examined as catalysts for gasification of pine sawdust in air/CO(2) at 700 and 800 degrees C. The yields of char and tar both increased with increasing CO(2) content in the feed gas. All the impregnated metal ions, in particular Ni (II), Co (II) and Ru (IV), were very effective for promoting biomass gasification in CO(2), leading to greatly reduced yields of tar and char accompanied by significantly enhanced formation of CO and H(2). At 800 degrees C, the impregnation of Fe (III), Ni (II), Co (II) or Ru (IV) led to almost complete conversion of the solid biomass into gas/liquid products, producing an extremely low char yield (<1-4 wt.%), and a very high yield of combustible gas (from 51.7 wt.% for Fe to 84 wt.% for Ru). The tar yield reduced from 32.1 wt.% without catalyst to 19-27 wt.% with the impregnated metal ions.

  16. 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.

  17. 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.

  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. Effect of TEPA loading on the physicochemical properties of Si-MCM-41 by impregnation method

    NASA Astrophysics Data System (ADS)

    Ahmed, Sohail; Ramli, Anita; Yusup, Suzana

    2012-09-01

    Si-MCM-41 with highly ordered hexagonal pore arrangement was synthesized hydrothermally at 100 °C. The calcined Si-MCM-41 was then modified with Tetraethylenepentamine (TEPA) using impregnation method. By impregnation method calcined Si-MCM-41 was modified with 10, 20, 30, 40 and 50% (w/w) of Tetraethylenpentamine (TEPA). The physicochemical properties were studied by characterizing these samples with FTIR, TGA, XRD, and CHNS analysis. Results showed that Si-MCM-41 successfully modified with TEPA by impregnation method. FTIR results showed that all the characteristic peaks of Si-MCM-41 i.e. 794, 1080 and 1230 cm-1 were existed after modification which means that mesoporous frame work remain intact. TGA analysis showed that TEPA impregnated Si-MCM-41 samples have thermal stability in the range of 140 - 500 δC. XRD results showed that intensity of the peaks reduced as the Si-MCM-41 modified with TEPA, this showed that TEPA molecules attached in the pores and on the surface. CHNS analysis confirmed the presence of carbon and nitrogen in the modified samples due to presence of Tetraethylenepentamine.

  20. 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.

  1. 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...

  2. 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

  3. IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine phosphatase activity.

    PubMed

    Gan, Yujun; Zhang, Yue; Buckels, Ashiya; Paterson, Andrew J; Jiang, Jing; Clemens, Thomas L; Zhang, Zhong-Yin; Du, Keyong; Chang, Yingzi; Frank, Stuart J

    2013-11-01

    GH is a potent anabolic and metabolic factor that binds its cell surface receptor (GHR), activating the GHR-associated tyrosine kinase, Janus kinase 2, which phosphorylates and activates the latent transcription factor, signal transducer and activator of transcription 5 (STAT5). Some GH actions are mediated by the elaboration of IGF-1, which exerts effects by binding and activating the heterotetrameric tyrosine kinase growth factor receptor, IGF-1R. In addition to this GH-GHR-IGF-1-IGF-1R scheme, we have demonstrated in primary osteoblasts and in islet β-cells that then deletion or silencing of IGF-1R results in diminished GH-induced STAT5 phosphorylation, suggesting that the presence of IGF-1R may facilitate GH signaling. In this study, we explore potential roles for protein tyrosine phosphatase activity in modulating GH-induced signaling, comparing conditions in which IGF-1R is present or diminished. We confirm that in mouse primary osteoblasts harboring loxP sites flanking the IGF-1R gene, infection with an adenovirus that expresses the Cre recombinase results in IGF-1R deletion and diminished acute GH-induced STAT5 phosphorylation. Furthermore, we present a new model of IGF-1R silencing, in which expression of short hairpin RNA directed at IGF-1R greatly reduces IGF-1R abundance in LNCaP human prostate cancer cells. In both models, treatment with a chemical inhibitor of protein tyrosine phosphatase-1B (PTP-1B), but not one of src homology region 2 domain-containing phosphotase-1 (SHP-1) and SHP-2, reverses the loss of GH-induced STAT5 phosphorylation in cells lacking IGF-1R but has no effect in cells with intact IGF-1R. Furthermore, expression of either a dominant-negative PTP-1B or the PTP-1B-interacting inhibitory protein, constitutive photomorphogenesis 1, also rescues acute GH-induced STAT5 signaling in IGF-1R-deficient cells but has no effect in IGF-1R replete cells. By expressing a substrate-trapping mutant PTP-1B, we demonstrate that tyrosine

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. CHLORHEXIDINE-IMPREGNATED DRESSING FOR PREVENTION OF CATHETER-RELATED BLOODSTREAM INFECTION: A META-ANALYSIS

    PubMed Central

    Safdar, Nasia; O’Horo, John C.; Ghufran, Aiman; Bearden, Allison; Didier, Maria Eugenia; Chateau, Dan; Maki, Dennis G.

    2014-01-01

    Background Catheter related bloodstream infections (CRBSI) are associated with significant morbidity and mortality and effective methods for their prevention are needed. Objective To assess the efficacy of a chlorhexidine-impregnated dressing for prevention of central venous catheter-related colonization and CRBSI using meta-analysis. Data Sources Multiple computerized database searches supplemented by manual searches including relevant conference proceedings. Study Selection Randomized controlled trials (RCT) evaluating the efficacy of a chlorhexidine-impregnated dressing compared with conventional dressings for prevention of catheter colonization and CRBSI. Data Extraction Data were extracted on patient and catheter characteristics and outcomes. Data Synthesis Pooled estimates of the relative risk (RR) and 95% confidence intervals (CI) were obtained using the DerSimonian and Laird random effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was assessed using the Cochran Q statistic and I2. Subgroup analyses were used to explore heterogeneity. Results Nine RCTs met the inclusion criteria. Use of a chlorhexidine-impregnated dressing resulted in a reduced incidence of CRBSI (random effects RR 0.57, 95% CI 0.42–0.79, P=0.002). The incidence of catheter colonization was also markedly reduced in the chlorhexidine-impregnated dressing group (random effects RR 0.51, 95% CI 0.39–0.67, P< 0.001). There was significant benefit for prevention of catheter colonization and CRBSI, including arterial catheters used for hemodynamic monitoring. Other than in low birth weight infants, adverse effects were rare and minor. Conclusions Our analysis shows that a chlorhexidine-impregnated dressing is beneficial in preventing catheter colonization and, more importantly, CRBSI and warrants routine use in patients at high risk of CRBSI and CVC or arterial catheter colonization in ICUs. PMID:24674924

  10. Visualising impregnated chitosan in Pinus radiata early wood cells using light and scanning electron microscopy.

    PubMed

    Singh, Adya P; Singh, Tripti; Rickard, Catherine L

    2010-04-01

    Chitosan, a deacetylated product of an abundant naturally occurring biopolymer chitin, has been used in a range of applications, particularly in food and health areas, as an antimicrobial agent. In the work reported here Pinus radiata wood was impregnated with chitosan as an environmentally compatible organic biocide (Eikenes et al., 2005a,b) to protect wood against wood deteriorating microorganisms and to thus prolong the service life of wooden products. We developed sample preparation techniques targeted to visualise impregnated chitosan within wood tissues using light microscope and field-emission scanning electron microscope (FE-SEM). Sections were viewed with the light microscope without staining with a dye as well as after staining with the dye toluidine blue. Light microscopy was also undertaken on sections that had been stained with 1% aqueous osmium tetroxide (OsO(4)). For SEM observations, the sections were treated with OsO(4) and then examined with the FE-SEM, first in the secondary electron imaging mode (SEI) and then in the backscattered electron imaging (BEI) mode, imaging the same areas of a section in both SEI and BEI modes. The preparation techniques employed and the combined use of light and scanning electron microscopy provided valuable complementary information, revealing that chitosan had penetrated into the cavities (cell lumens, intercellular spaces) of all sizes present within wood tissues and had also impregnated early wood cell walls. The information obtained is discussed in relation to its importance in further development of chitosan formulations and refinement of impregnation technologies to optimise chitosan impregnation into and distribution within wood tissues as well as in assessing chitosan efficacy.

  11. Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice.

    PubMed

    Sclafani, Anthony; Glass, Damien S; Margolskee, Robert F; Glendinning, John I

    2010-12-01

    Most mammals prefer the sweet taste of sugars, which is mediated by the heterodimeric T1R2+T1R3 taste receptor. Sugar appetite is also enhanced by the post-oral reinforcing actions of the nutrient in the gut. Here, we examined the contribution of gut T1R3 (either alone or as part of the T1R3+T1R3 receptor) to post-oral sugar reinforcement using a flavor-conditioning paradigm. We trained mice to associate consumption of a flavored solution (CS+) with intragastric (IG) infusions of a sweetener, and a different flavored solution (CS-) with IG infusions of water (23 h/day); then, we measured preference in a CS+ vs. CS- choice test. In experiment 1, we predicted that if activation of gut T1R3 mediates sugar reinforcement, then IG infusions of a nutritive (sucrose) or nonnutritive (sucralose) ligand for this receptor should condition a preference for the CS+ in B6 wild-type (WT) mice. While the mice that received IG sucrose infusions developed a strong preference for the CS+, those that received IG sucralose infusions developed a weak avoidance of the CS+. In experiment 2, we used T1R3 knockout (KO) mice to examine the necessity of gut T1R2+T1R3 receptors for conditioned flavor preferences. If intact gut T1R3 (or T1R2+T1R3) receptors are necessary for flavor-sugar conditioning, then T1R3 KO mice should not develop a sugar-conditioned flavor preference. We found that T1R3 KO mice, like WT mice, acquired a strong preference for the CS+ paired with IG sucrose infusions. The KO mice were also like WT mice in avoiding a CS+ flavor paired with IG sucralose infusions These findings provide clear evidence that gut T1R3 receptors are not necessary for sugar-conditioned flavor preferences or sucralose-induced flavor avoidance in mice.

  12. IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin

    PubMed Central

    O'Flanagan, Ciara H.; O'shea, Sandra; Lyons, Amy; Fogarty, Fionola M.; McCabe, Nuala; Kennedy, Richard D.; O'Connor, Rosemary

    2016-01-01

    The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition. These included ATM and Ataxia Telangiectasia and RAD3-related kinase (ATR). We also observed a clear induction of DDR in cells that were exposed to IGF-1R TKIs (BMS-754807 and OSI-906) as indicated by accumulation of γ-H2AX, and phosphorylated Chk1. Combination of the IGF-1R/IR TKIs with an ATR kinase inhibitor VE-821 resulted in additive to synergistic cytotoxicity compared to either drug alone. In MCF-7 cells with stably acquired resistance to the IGF-1R TKI (MCF-7-R), DNA damage was also observed, and again, dual inhibition of the ATR kinase and IGF-1R/IR kinase resulted in synergistic cytotoxicity. Interestingly, dual inhibition of ATR and IGF-1R was more effective in MCF-7-R cells than parental cells. IGF-1R TKIs also potentiated the effects of cisplatin in a panel of breast cancer cell lines. Overall, our findings identify induction of DDR by IGF-1R kinase inhibition as a rationale for co-targeting the IGF-1R with ATR kinase inhibitors or cisplatin, particularly in cells with acquired resistance to TKIs. PMID:27472395

  13. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

    PubMed Central

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-01-01

    Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

  14. PRR repeats in the intracellular domain of KISS1R are important for its export to cell membrane.

    PubMed

    Chevrier, Lucie; de Brevern, Alexandre; Hernandez, Eva; Leprince, Jérome; Vaudry, Hubert; Guedj, Anne Marie; de Roux, Nicolas

    2013-06-01

    Inactivating mutations of KISS-1 receptor (KISS1R) have been recently described as a rare cause of isolated hypogonadotropic hypogonadism transmitted as a recessive trait. Few mutations have been described, and the structure-function relationship of KISS1R remains poorly understood. Here, we have taken advantage of the discovery of a novel mutation of KISS1R to characterize the structure and function of an uncommon protein motif composed of 3 proline-arginine-arginine (PRR) repeats located within the intracellular domain. A heterozygous insertion of 1 PRR repeat in-frame with 3 PRR repeats leading to synthesis of a receptor bearing 4 PRR repeats (PRR-KISS1R) was found in the index case. Functional analysis of PRR-KISS1R showed a decrease of the maximal response to kisspeptin stimulation, associated to a lower cell surface expression without modification of total expression. PRR-KISS1R exerts a dominant negative effect on the synthesis of the wild-type (WT)-KISS1R. This effect was due to the nature of inserted residues but also to the difference of the length of the intracellular domain between PRR-KISS1R and WT-KISS1R. A molecular dynamic analysis showed that the additional PRR constrained this arginine-rich region into a polyproline type II helix. Altogether, this study shows that a heterozygous insertion in KISS1R may lead to hypogonadotropic hypogonadism by a dominant negative effect on the WT receptor. An additional PRR repeat into a proline-arginine-rich motif can dramatically changed the conformation of the intracellular domain of KISS1R and its probable interaction with partner proteins.

  15. 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.

  16. A local formulation of lattice Wess-Zumino model with exact U(1)R symmetry

    NASA Astrophysics Data System (ADS)

    Kikukawa, Yoshio; Suzuki, Hiroshi

    2005-02-01

    A lattice Wess-Zumino model is formulated on the basis of Ginsparg-Wilson fermions. In perturbation theory, our formulation is equivalent to the formulation by Fujikawa and Ishibashi and by Fujikawa. Our formulation is, however, free from a singular nature of the latter formulation due to an additional auxiliary chiral supermultiplet on a lattice. The model posssesses an exact U(1)R symmetry as a supersymmetric counterpart of the Lüscher lattice chiral U(1) symmetry. A restration of the supersymmetric Ward-Takahashi identity in the continuum limit is analyzed in renormalized perturbation theory. In the one-loop level, a supersymmetric continuum limit is ensured by suitably adjusting a coefficient of a single local term tilde F*tilde F. The non-renormalization theorem holds to this order of perturbation theory. In higher orders, on the other hand, coefficents of local terms with dimension <= 4 that are consistent with the U(1)R symmetry have to be adjusted for a supersymmetric continuum limit. The origin of this complexicity in higher-order loops is clarified on the basis of the Reisz power counting theorem. Therefore, from a view point of supersymmetry, the present formulation is not quite better than a lattice Wess-Zumino model formulated by using Wilson fermions, although a number of coefficients which require adjustment is much less due to the exact U(1)R symmetry. We also comment on an exact non-linear fermionic symmetry which corresponds to the one studied by Bonini and Feo; an existence of this exact symmetry itself does not imply a restoration of supersymmetry in the continuum limit without any adjustment of parameters.

  17. 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.

  18. Loss of Ntrk2/Kiss1r signaling in oocytes causes premature ovarian failure.

    PubMed

    Dorfman, Mauricio D; Garcia-Rudaz, Cecilia; Alderman, Zefora; Kerr, Bredford; Lomniczi, Alejandro; Dissen, Gregory A; Castellano, Juan Manuel; Garcia-Galiano, David; Gaytan, Francisco; Xu, Baoji; Tena-Sempere, Manuel; Ojeda, Sergio R

    2014-08-01

    Neurotrophins (NTs), once believed to be neural-specific trophic factors, are now known to also provide developmental cues to non-neural cells. In the ovary, NTs contribute to both the formation and development of follicles. Here we show that oocyte-specific deletion of the Ntrk2 gene that encodes the NTRK2 receptor (NTRK2) for neurotrophin-4/5 and brain-derived neurotrophic factor (BDNF) results in post-pubertal oocyte death, loss of follicular organization, and early adulthood infertility. Oocytes lacking NTRK2 do not respond to gonadotropins with activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mediated signaling. Before puberty, oocytes only express a truncated NTRK2 form (NTRK2.T1), but at puberty full-length (NTRK2.FL) receptors are rapidly induced by the preovulatory gonadotropin surge. A cell line expressing both NTRK2.T1 and the kisspeptin receptor (KISS1R) responds to BDNF stimulation with activation of Ntrk2 expression only if kisspeptin is present. This suggests that BDNF and kisspeptin that are produced by granulosa cells (GCs) of periovulatory follicles act in concert to mediate the effect of gonadotropins on Ntrk2 expression in oocytes. In keeping with this finding, the oocytes of NTRK2-intact mice fail to respond to gonadotropins with increased Ntrk2 expression in the absence of KISS1R. Our results demonstrate that the preovulatory gonadotropin surge promotes oocyte survival at the onset of reproductive cyclicity by inducing oocyte expression of NTRK2.FL receptors that set in motion an AKT-mediated survival pathway. They also suggest that gonadotropins activate NTRK2.FL expression via a dual communication pathway involving BDNF and kisspeptin produced in GCs and their respective receptors NTRK2.T1 and KISS1R expressed in oocytes.

  19. Certifying the SMOV4 FGS AMA Stars with FGS1r

    NASA Astrophysics Data System (ADS)

    Nelan, Edmund

    2007-07-01

    This proposal observes the candidate SMOV4 "AMA stars" prior to SM4 to certify which of them are unresolved point sources, and hence is an appropriate AMA target. Each target is to be observed in a 1-orbit visit using FGS1r in its highy angular resolution Transfer mode with two exposures. Exposure 1 utilizes a 0.8" scan path with 20 scans which will provide high S/N for the detection of binariy down to ~12 mas, while the second exposure utilizes a 6" scan path to provide sensitivity to putative wide companions.

  20. Design of CY-1R binocular goggle with two intensifier tubes

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Chang, Benkang

    2003-11-01

    In this paper, the present status and developing tendency of night vision device of helmet are reviewed. The research intention and design principle of CY-1R night vision goggle are explained which fills the gaps in active-passive combined night vision field in our country. The structure, composition, mechanism and overall performance of the goggle are analyzed. Based on these characteristics, the sensitivity of the system is high and the image observed is very clear. Taking advantage of it, we can complete the military operation under any atrocious weather conditions.

  1. KISS1R signaling promotes invadopodia formation in human breast cancer cell via β-arrestin2/ERK.

    PubMed

    Goertzen, Cameron G; Dragan, Magdalena; Turley, Eva; Babwah, Andy V; Bhattacharya, Moshmi

    2016-03-01

    Kisspeptins (KPs), peptide products of the KISS1 gene are endogenous ligands for the kisspeptin receptor (KISS1R), a G protein-coupled receptor. In numerous cancers, KISS1R signaling plays anti-metastatic roles. However, we have previously shown that in breast cancer cells lacking the estrogen receptor (ERα), kisspeptin-10 stimulates cell migration and invasion by cross-talking with the epidermal growth factor receptor (EGFR), via a β-arrestin-2-dependent mechanism. To further define the mechanisms by which KISS1R stimulates invasion, we determined the effect of down-regulating KISS1R expression in triple negative breast cancer cells. We found that depletion of KISS1R reduced their mesenchymal phenotype and invasiveness. We show for the first time that KISS1R signaling induces invadopodia formation and activation of key invadopodia proteins, cortactin, cofilin and membrane type I matrix metalloproteases (MT1-MMP). Moreover, KISS1R stimulated invadopodia formation occurs via a new pathway involving a β-arrestin2 and ERK1/2-dependent mechanism, independent of Src. Taken together, our findings suggest that targeting the KISS1R signaling axis might be a promising strategy to inhibit invasiveness and metastasis.

  2. 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

  3. 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

  4. Do polymorphisms in the TAS1R1 gene contribute to broader differences in human taste intensity?

    PubMed

    Rawal, Shristi; Hayes, John E; Wallace, Margaret R; Bartoshuk, Linda M; Duffy, Valerie B

    2013-10-01

    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.

  5. Test design description, Volume 1B, Part 2; FSP-1R FFTF test assembly (HF191A): Revision

    SciTech Connect

    McWethy, L.M.

    1989-07-01

    The principal objective of the FSP-1 test series is to provide the required fuel behavior data needed for fuel modeling and data on the performance of Reference Flight System prototypic cladding and liners at goal burnup. The test series includes two reconstitutions, designated FSP-1R and FSP-1RR, respectively. The irradiation times specified are: 150 equivalent full power days (EFPDs) for the initial FSP-1, 300 EFPDs for FSP-1R, and 400 EFPDs for FSP-1RR. A TDD-IB, part 1 document was issued to specify the design and fabrication requirements for fuel pins in the FSP-1R test. This TDD-IB, Part 2 document will specify the requirements for encapsulation of the FSP-1R fuel pins and fabrication of the FSP-1R test assembly. 6 figs., 5 tabs.

  6. 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

  7. 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.

  8. Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

    PubMed Central

    Liu, Chun-Hua; Gong, Zheng; Liang, Zong-Lai; Liu, Zhi-Xin; Yang, Fan; Sun, Yu-Jing; Ma, Ming-Liang; Wang, Yi-Jing; Ji, Chao-Ran; Wang, Yu-Hong; Wang, Mei-Jie; Cui, Fu-Ai; Lin, Amy; Zheng, Wen-Shuai; He, Dong-Fang; Qu, Chang-xiu; Xiao, Peng; Liu, Chuan-Yong; Thomsen, Alex R. B.; Joseph Cahill, Thomas; Kahsai, Alem W.; Yi, Fan; Xiao, Kun-Hong; Xue, Tian; Zhou, Zhuan; Yu, Xiao; Sun, Jin-Peng

    2017-01-01

    Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes. PMID:28181498

  9. The TSS-1R Results - the Physics of Current Collection in Magnetized Plasmas Revised

    NASA Astrophysics Data System (ADS)

    Papadopoulos, Konstantinos

    1996-11-01

    The Tethered Satellite System (TSS-1R) was deployed from the space shuttle "Columbia" (STS-75 Mission) on February 24, 1996. The satellite was deployed to a distance of 19.7 km above the shuttle. The system operated nominally over its deployment phase which lasted 5.5 hours. A defect in the tether insulation inside the orbiter caused a local discharge which led to a tether break. Data collected before and during the break revealed a host of new physics phenomena concerning the current collection by charged bodies in space moving at orbital velocities. The maximum EMF observed during the mission was 3.8 kV and the maximum current exceeded 1A. Power generation of several kW's was demonstrated. The current collected was significantly larger than expected by space charged limited flow in magnetized and even unmagnetized plasmas. For example the 1A current was collected with less than 1 kV potential instead of the 20 kV given by previous theories. The presentation will review the fascinating results of the TSS-1R and will discuss the ongoing physics analysis of the observed phenomena. *In collaboration with A. Drobot and C.L. Chang of SAIC.

  10. Allelic variants of IL1R1 gene associate with severe hand osteoarthritis

    PubMed Central

    2010-01-01

    Background In search for genes predisposing to osteoarthritis (OA), several genome wide scans have provided evidence for linkage on 2q. In this study we targeted a 470 kb region on 2q11.2 presenting the locus with most evidence for linkage to severe OA of distal interphalangeal joints (DIP) in our genome wide scan families. Methods We genotyped 32 single nucleotide polymorphisms (SNPs) in this 470 kb region comprising six genes belonging to the interleukin 1 superfamily and monitored for association with individual SNPs and SNP haplotypes among severe familial hand OA cases (material extended from our previous linkage study; n = 134), unrelated end-stage bilateral primary knee OA cases (n = 113), and population based controls (n = 436). Results Four SNPs in the IL1R1 gene, mapping to a 125 kb LD block, provided evidence for association with hand OA in family-based and case-control analysis, the strongest association being with SNP rs2287047 (p-value = 0.0009). Conclusions This study demonstrates an association between severe hand OA and IL1R1 gene. This gene represents a highly relevant biological candidate since it encodes protein that is a known modulator of inflammatory processes associated with joint destruction and resides within a locus providing consistent evidence for linkage to hand OA. As the observed association did not fully explain the linkage obtained in the previous study, it is plausible that also other variants in this genome region predispose to hand OA. PMID:20353565

  11. Evolution of the melanocortin-1 receptor gene (MC1R) in chamois (Rupicapra spp.).

    PubMed

    Pérez, Trinidad; Essler, Sabine; Palacios, Borja; Albornoz, Jesús; Domínguez, Ana

    2013-06-01

    The taxonomy of chamois and the effects of historical and evolutionary events on its diversification are still under discussion given that different morphological and genetic features presented partially discordant views. One of the morphological features that differentiate the two currently considered species, Rupicapra pyrenaica (southern chamois) and R. rupicapra (northern chamois) is coat color pattern. The melanocortin-1 receptor gene (MC1R) is related with differences in coloration in different mammals and was analyzed here in a sample of 25 chamois covering the 10 subspecies recognized, three in R. pyrenaica, (parva, pyrenaica and ornata) and seven in R. rupicapra (cartusiana, rupicapra, tatrica, carpatica, balcanica, asiatica and caucasica). Comparison with other caprinae showed that the MC1R gene has evolved under strong purifying selection. Three well differentiated haplotypes were identified: one shared by the seven subspecies of R. rupicapra, other common to the two Iberian chamois, both of the species R. pyrenaica, and a third haplotype, basal in the phylogenetic tree, unique to the subspecies from the Apennines, R. pyrenaica ornata. This pattern of variation, with three conspicuous clades, concurs with previous findings on microsatellites and mtDNA and argues in favor of the old classifications that distinguished the species R. ornata.

  12. 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.

  13. 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.

  14. 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.

  15. MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA.

    PubMed

    Dagan, Efrat; Gershoni-Baruch, Ruth; Khatib, Ihab; Mori, Adi; Brik, Riva

    2010-03-01

    PFAPA is a periodic fever disease, of unknown etiology, characterized by aphthous stomatitis, pharyngitis and cervical adenitis. To inquire whether genes implicated in other auto-inflammatory diseases might be involved in its pathogenesis, predominant mutations in the genes causing familial Mediterranean fever, TNF receptor-associated periodic fever syndrome, Crohn's disease and Muckel-Wells syndrome were analyzed in PFAPA patients. Patients (n = 57) with PFAPA, according to previously published criteria were recruited, at the Meyer Children Hospital during 2006-2007. Clinical information was complemented during physicians-parents encounter. Predominant mutations in MEFV, TNF1rA, CARD15/NOD2 and NLRP3 genes were tested. Mean age at diagnosis was 30.64 +/- 16.4 months. Boys (n = 33; 58%) were diagnosed earlier than girls (n = 21; 42%) at 26.18 +/- 13.83 and 36.41 +/- 18.32 months, respectively (P = 0.05). Fifteen patients (27%) carried an MEFV mutation; two patients (3.6%) a CARD15 mutation, one patient (1.8%) a variance in TNF1rA and another had both an MEFV and a CARD15 mutation. Clinical symptoms were equally manifested in carriers and non-carriers. The high carrier rate of MEFV mutations in our PFAPA cases compares well with that of the general population in Israel. It is debated whether MEFV mutations, when mediated by the presence of additional modifiers, may expose a transient fever condition, namely PFAPA.

  16. 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

  17. Parallel changes in neuronal AT1R and GRK5 expression following exercise training in heart failure.

    PubMed

    Haack, Karla K V; Engler, Christopher W; Papoutsi, Evlampia; Pipinos, Iraklis I; Patel, Kaushik P; Zucker, Irving H

    2012-08-01

    Although exercise training (ExT) is an important therapeutic strategy for improving quality of life in patients with chronic heart failure (CHF), the central mechanisms by which ExT is beneficial are not well understood. The angiotensin II type 1 receptor (AT1R) plays a pivotal role in the development of CHF and is upregulated in a number of tissues owing, in part, to transcription factor nuclear factor kappa B (NF-κB). In addition, AT1R is marked for internalization and recycling via G-protein-coupled receptor kinase (GRK) phosphorylation. Because previous studies have shown that the beneficial effects of ExT in CHF rely on a reduction in angiotensin II, we hypothesized ExT would decrease AT1R, GRK5, and NF-κB protein expression in the paraventricular nucleus and rostral ventrolateral medulla of CHF rats. Following infarction by coronary artery ligation, animals were exercised 4 weeks postsurgery on a treadmill at a final speed of 25 miles per minute for 60 minutes, 5 days per week for 6 weeks. Western blot analysis of paraventricular nucleus and rostral ventrolateral medulla micropunches revealed an upregulation of AT1R, GRK5, and NF-κB in the infarcted group that was reversed by ExT. Furthermore, the relative expression of phosphorylated AT1R and AT1R/GRK5 physical association was increased in the CHF sedentary group and reversed by ExT. Overexpression of GRK5 in cultured CATH.a neurons blunted angiotensin II-mediated upregulation of AT1R and NF-κB; conversely, silencing of GRK5 exacerbated angiotensin II-mediated AT1R and NF-κB upregulation. Taken together, increased GRK5 may regulate AT1R expression in CHF, and ExT mitigates AT1R and its pathway components.

  18. 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

  19. Ethanol Exposure Induces Neonatal Neurodegeneration by Enhancing CB1R Exon1 Histone H4K8 Acetylation and Up-regulating CB1R Function causing Neurobehavioral Abnormalities in Adult Mice

    PubMed Central

    Subbanna, Shivakumar; Nagre, Nagaraja N.; Umapathy, Nagavedi S.; Pace, Betty S.

    2015-01-01

    Background: Ethanol exposure to rodents during postnatal day 7 (P7), which is comparable to the third trimester of human pregnancy, induces long-term potentiation and memory deficits. However, the molecular mechanisms underlying these deficits are still poorly understood. Methods: In the present study, we explored the potential role of epigenetic changes at cannabinoid type 1 (CB1R) exon1 and additional CB1R functions, which could promote memory deficits in animal models of fetal alcohol spectrum disorder. Results: We found that ethanol treatment of P7 mice enhances acetylation of H4 on lysine 8 (H4K8ace) at CB1R exon1, CB1R binding as well as the CB1R agonist-stimulated GTPγS binding in the hippocampus and neocortex, two brain regions that are vulnerable to ethanol at P7 and are important for memory formation and storage, respectively. We also found that ethanol inhibits cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation and activity-regulated cytoskeleton-associated protein (Arc) expression in neonatal and adult mice. The blockade or genetic deletion of CB1Rs prior to ethanol treatment at P7 rescued CREB phosphorylation and Arc expression. CB1R knockout mice exhibited neither ethanol-induced neurodegeneration nor inhibition of CREB phosphorylation or Arc expression. However, both neonatal and adult mice did exhibit enhanced CREB phosphorylation and Arc protein expression. P7 ethanol-treated adult mice exhibited impaired spatial and social recognition memory, which were prevented by the pharmacological blockade or deletion of CB1Rs at P7. Conclusions: Together, these findings suggest that P7 ethanol treatment induces CB1R expression through epigenetic modification of the CB1R gene, and that the enhanced CB1R function induces pCREB, Arc, spatial, and social memory deficits in adult mice. PMID:25609594

  20. Co-Targeting IGF-1R and Autophagy Enhances the Effects of Cell Growth Suppression and Apoptosis Induced by the IGF-1R Inhibitor NVP-AEW541 in Triple-Negative Breast Cancer Cells

    PubMed Central

    Shao, Nan; Shi, Yawei; Liu, Ruiming; Li, Wen; Lin, Yin; Wang, Shenming

    2017-01-01

    Background Triple-negative breast cancer (TNBC) is the most intractable type of breast cancer, and there is a lack of effective targeted therapy. Insulin-like growth factor-1 receptor (IGF-1R) is reportedly a potential target for TNBC treatment. However, satisfying treatment outcomes in breast cancer patients have yet to be achieved with IGF-1R-targeted agents. Methods To confirm whether inhibiting IGF-1R could induce autophagy, we detected autophagy-related proteins by western blotting and immunofluorescence staining of LC3-II. The IGF-1R inhibitor NVP-AEW541, autophagy inhibitor 3-methyladenine (3-MA) and Atg7 small interfering RNA (siRNA) were used to further investigate the effects of autophagy induced by IGF-1R inhibition in TNBC cells. The CCK8 assay, EdU assay, apoptosis and cell cycle analyses were applied to test cell function after treatment. Results NVP-AEW541 markedly induced autophagy in TNBC cells by increasing the levels of the autophagy-related protein Beclin-1 and the LC3-II/LC-I ratio and reducing the selective autophagy substrate p62. Joint application of 3-MA or Atg7 siRNA enhanced the cell growth inhibition and apoptosis effects of NVP-AEW541 by arresting cells at G1/G0 phase and increasing Bax expression and decreasing that of Bcl-2. Conclusion Targeting IGF-1R in TNBC induces cell-protective autophagy, thereby weakening the therapeutic effect of agents directed toward IGF-1R. Our findings reveal that combined use autophagy-disrupting agents can enhance the therapeutic efficacy of IGF-1R inhibitors in TNBC cells and may provide a valuable treatment strategy for IGF-1R inhibitor-based therapies for TNBC and other IGF-1 signaling-associated tumors. PMID:28046018

  1. Thermal-mechanical properties of epoxy-impregnated Bi-2212/Ag composite

    DOE PAGES

    Li, Pei; Wang, Yang; Fermi National Accelerator Lab.; ...

    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

  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

    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.

  3. 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.

  4. 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.

  5. A method for impregnating nylon transfer membranes with leucocrystal violet for enhancing and lifting bloody impressions.

    PubMed

    Michaud, Amy L; Brun-Conti, Leanora

    2004-05-01

    The objective of this research project was to demonstrate a quick and easy method for impregnating nylon transfer membranes with leucocrystal violet (LCV) for the purpose of lifting and enhancing impressions made in blood. A stamp that would simulate fine detail found in fingerprints or footwear was used to create impressions on a variety of substrates. Four different LCV formulations were tested to determine the effectiveness of the prepared membranes in lifting and enhancing the impressions. Further investigation involved the feasibility of using the LCV membranes in the field by studying the shelf life and storage of the impregnated membranes and the longevity of the lifted impressions. One of the formations studied demonstrated superior lifting and enhancing capabilities, as well as a prolonged shelf life and a resilience of the lifted impressions, thus proving LCV to be an extremely valuable technique.

  6. Influence of gas composition of the modulus of elasticity of gas-impregnated anthracites

    SciTech Connect

    Vinokurova, E.B.; Ketslakh, A.I.

    1986-07-01

    A study of the elastic properties of anthracites under strain and high gas pressure is described. The tests were made on Class I and II anthracites after exposure to helium, nitrogen, methane, carbon dioxide, and a mixture of these gases similar in composition to that of natural gas in worked anthracite strata. Each test sample was loaded in air at atmospheric pressure, and then subjected to vacuum treatment and impregnated with gas. Tables show strain on samples in air at atmospheric pressure in helium, nitrogen, methane and gas mixtures, and values of modulus of elasticity for anthracite in various gases. It was shown that impregnation with carbon dioxide under pressure has a destructive influence on the anthracite. The presence of 1.5% of carbon dioxide in a gas is sufficient to cause a reduction in the modulus of elasticity. During the working of a stratum, the consequential change in the gas content also alters the mechanical properties of the anthracite.

  7. Partial discharge measurements on a high voltage direct current mass impregnated paper cable

    SciTech Connect

    Jeroense, M.J.P.; Kreuger, F.H.

    1996-12-31

    Partial discharge measurement has been a good tool for the quality assurance of cables under alternating voltage. With the growing interest in High Voltage Direct Current cables it seems therefore logical to extend this technique for use at direct voltage. The paper describes this technique as used on a HVDC cable with mass impregnated paper. The different phases of operation (no load, full load, cooling phase, etc.) are characterized by a different discharge behavior. Special attention is given to the dangerous cooling phase. Models have been developed which can explain the discharge patterns that were measured. This paper gives an insight in the electrical behavior of a HVDC cable with mass impregnated paper insulation.

  8. Basic technology for 6Li enrichment using an ionic-liquid impregnated organic membrane

    NASA Astrophysics Data System (ADS)

    Hoshino, Tsuyoshi; Terai, Takayuki

    2011-10-01

    The tritium needed as a fuel for fusion reactors is produced by the neutron capture reaction of lithium-6 ( 6Li) in tritium breeding materials. However, natural Li contains only about 7.6 at.% 6Li. In this paper, a new lithium isotope separation technique using an ionic-liquid impregnated organic membrane is proposed. In order to separate and concentrate lithium isotopes, only lithium ions are able to move through the membrane by electrodialysis between the cathode and the anode in lithium solutions. Preliminary experiments of lithium isotope separation were conducted using this phenomenon. Organic membranes impregnated with TMPA-TFSI and PP13-TFSI as ionic liquids were prepared, and the relationship between the 6Li separation coefficient and the applied electrodialytic conditions was evaluated using them. The results showed that the 6Li isotope separation coefficient in this method (about 1.1-1.4) was larger than that in the mercury amalgam method (about 1.06).

  9. 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.

  10. Adsorption of congo red by chitosan hydrogel beads impregnated with carbon nanotubes.

    PubMed

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

    2010-03-01

    The adsorption performance of chitosan (CS) hydrogel beads was investigated after multiwalled carbon nanotubes (MWCNTs) impregnation for the removal of congo red (CR) as an anionic dye. The study of the adsorption capacity of CS/CNT beads as a function of the CNT concentration indicated that 0.01% CNT impregnation was the most useful for enhancing the adsorption capacity. The sulfur (%) in the CS/CNT beads measured by energy dispersive X-ray (EDX) was 2.5 times higher than that of normal CS beads after CR adsorption. Equilibrium adsorption isotherm data of the CS/CNT beads exhibited better fit to the Langmuir isotherm model than to the Freundlich isotherm model, and the heterogeneity factor (n) value of the CS/CNT beads calculated from the Sips isotherm model was close to unity (0.98). The maximum adsorption capacity of CS/CNT beads obtained from the Langmuir model was 450.4 mg g(-1).

  11. 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.

  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. Capture of carbon dioxide by amine-impregnated as-synthesized MCM-41.

    PubMed

    Wei, Jianwen; Liao, Lei; Xiao, Yu; Zhang, Pei; Shi, Yao

    2010-01-01

    The novel carbon dioxide (CO2) adsorbents with a high capture efficiency were prepared through impregnating the as-synthesized MCM-41 with three kinds of amines, namely diethylenetriamine (DETA), triethylenetetramine (TETA) and 2-amino-2-methyl-1-propanol (AMP). The resultant samples were characterized by small angle X-ray diffraction and low temperature N2 adsorption. The synthesis way not only saves the energy or extractor to remove the template but also is environmentally friendly due to the absence of the potential pollutants such as toluene. CO2 capture was investigated in a dynamic packed column. The sample impregnated by TETA showed the highest adsorption capacity, approximately 2.22 mmol/g at 60 degrees C due to its highest amino-groups content among the three amines. The CO2 adsorption behavior was also investigated with the deactivation model, which showed an excellent prediction for the breakthrough curves.

  15. Long-Lasting Permethrin-Impregnated Clothing Protects against Mosquito Bites in Outdoor Workers

    PubMed Central

    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.

    2015-01-01

    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. PMID:26195460

  16. 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.

  17. 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.

  18. Boron removal from aqueous solutions by activated carbon impregnated with salicylic acid.

    PubMed

    Celik, Z Ceylan; Can, B Z; Kocakerim, M Muhtar

    2008-03-21

    In this study, the removal of boric acid from aqueous solution by activated carbon impregnated with salicylic acid was studied in batch system. pH, adsorbent amount, initial boron concentration, temperature, shaking rate and salicylic acid film thickness were chosen as parameters. Boron removal efficiencies increased with increasing adsorbent amount, temperature and pH, decreasing initial boron concentration. As thickness of salicylic acid film on activated carbon becomes thin up to 0.088nm, the efficiency increased, and then, the efficiency decreased with becoming thinner than 0.088nm of salicylic acid film. Shaking rate was no effect on removal efficiency. In result, it was determined that the use of salicylic acid as an impregnant for activated carbon led to the increase of the amount of boron adsorbed. A lactone ring, being the most appropriate conformation, forms between boric acid and -COOH and -OH groups of salicylic acid.

  19. Genetic variation within coat color genes of MC1R and ASIP in Chinese brownish red Tibetan pigs.

    PubMed

    Mao, Huirong; Ren, Jun; Ding, Nengshui; Xiao, Shijun; Huang, Lusheng

    2010-12-01

    Melanocortin receptor 1 (MC1R) and agouti signaling protein (ASIP) are two major genes affecting coat color phenotypes in mammals, and inactivation mutations in the MC1R gene are responsible for red coat color in European pig breeds. Conversely, the gain-of-function ASIP mutations block MC1R signaling and lead to the production of red pheomelanin. Chinese Tibetan pigs have three types of coat color phenotypes, including brownish red, solid black and black with patches of brownish red and white. Herein, we investigated variations of the MC1R and ASIP genes in Tibetan pigs. The results showed that the brownish red Tibet pig had the dominant black MC1R allele (E(D1)). No loss-of-function mutation in MC1R responsible for red coat color in European breeds was observed in this breed. No causal mutation for the red coat color phenotype was found in the coding sequence of the ASIP gene. A novel missense mutation c.157G > A was firstly identified in exon 2 of ASIP, which was further genotyped in 285 pigs from five Chinese breeds and three Western breeds having different coat color phenotypes. Nearly all pigs were GG homozygotes. In conclusion, no functional variant responsible for brownish red coloration was found in the coding region of MC1R and ASIP in Tibetan pigs.

  20. KISS1R induces invasiveness of estrogen receptor-negative human mammary epithelial and breast cancer cells.

    PubMed

    Cvetkovic, Donna; Dragan, Magdalena; Leith, Sean J; Mir, Zuhaib M; Leong, Hon S; Pampillo, Macarena; Lewis, John D; Babwah, Andy V; Bhattacharya, Moshmi

    2013-06-01

    Kisspeptins (KPs), peptide products of the KISS1 metastasis-suppressor gene, are endogenous ligands for a G protein-coupled receptor (KISS1R). KISS1 acts as a metastasis suppressor in numerous human cancers. However, recent studies have demonstrated that an increase in KISS1 and KISS1R expression in patient breast tumors correlates with higher tumor grade and metastatic potential. We have shown that KP-10 stimulates invasion of estrogen receptor α (ERα)-negative MDA-MB-231 breast cancer cells via transactivation of the epidermal growth factor receptor (EGFR). Here, we report that either KP-10 treatment of ERα-negative nonmalignant mammary epithelial MCF10A cells or expression of KISS1R in MCF10A cells induced a mesenchymal phenotype and stimulated invasiveness. Similarly, exogenous expression of KISS1R in ERα-negative SKBR3 breast cancer cells was sufficient to trigger invasion and induced extravasation in vivo. In contrast, KP-10 failed to transactivate EGFR or stimulate invasiveness in the ERα-positive MCF7 and T47D breast cancer cells. This suggested that ERα negatively regulates KISS1R-dependent breast cancer cell migration, invasion, and EGFR transactivation. In support of this, we found that these KP-10-induced effects were ablated upon exogenous expression of ERα in the MDA-MB-231 cells, by down-regulating KISS1R expression. Lastly, we have identified IQGAP1, an actin cytoskeletal binding protein as a novel binding partner of KISS1R, and have shown that KISS1R regulates EGFR transactivation in breast cancer cells in an IQGAP1-dependent manner. Overall, our data strongly suggest that the ERα status of mammary cells dictates whether KISS1R may be a novel clinical target for treating breast cancer metastasis.

  1. Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy

    PubMed Central

    Ulanet, Danielle B.; Ludwig, Dale L.; Kahn, C. Ronald; Hanahan, Douglas

    2010-01-01

    The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. Surprisingly, preclinical trials with an inhibitory monoclonal antibody to IGF-1R did not significantly impact tumor growth, prompting us to investigate the involvement of IR. The levels of IR were found to be significantly up-regulated during multistep progression from hyperplastic lesions to islet tumors. Its functional involvement was revealed by genetic disruption of the IR gene in the oncogene-expressing pancreatic β cells, which resulted in reduced tumor burden accompanied by increased apoptosis. Notably, the IR knockout tumors now exhibited sensitivity to anti–IGF-1R therapy; similarly, high IR to IGF-1R ratios demonstrably conveyed resistance to IGF-1R inhibition in human breast cancer cells. The results predict that elevated IR signaling before and after treatment will respectively manifest intrinsic and adaptive resistance to anti–IGF-1R therapies. PMID:20457905

  2. MiR-143 and MiR-145 Regulate IGF1R to Suppress Cell Proliferation in Colorectal Cancer

    PubMed Central

    Wang, Nan; Zhang, Suyang; Yan, Xin; Feng, Hui; Pang, Wenjing; Wang, Yanbo; Wang, Xueliang; Fu, Zhen; Liu, Yanqing; Zhao, Chihao; Zhang, Junfeng; Zhang, Chen-Yu; Zen, Ke; Chen, Xi; Wang, Yalei

    2014-01-01

    Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane receptor that is activated by insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors and plays an important role in colorectal cancer etiology and progression. In this study, we used bioinformatic analyses to search for miRNAs that potentially target IGF1R. We identified specific target sites for miR-143 and miR-145 (miR-143/145) in the 3′-untranslated region (3′-UTR) of the IGF1R gene. These miRNAs are members of a cluster of miRNAs that have been reported to exhibit tumor suppressor activity. Consistent with the bioinformatic analyses, we identified an inverse correlation between miR-143/145 levels and IGF1R protein levels in colorectal cancer tissues. By overexpressing miR-143/145 in Caco2, HT29 and SW480 colorectal cancer cells, we experimentally validated that miR-143/145 directly recognizes the 3′-UTR of the IGF1R transcript and regulates IGF1R expression. Furthermore, the biological consequences of the targeting of IGF1R by miR-143/145 were examined by cell proliferation assays in vitro. We demonstrated that the repression of IGF1R by miR-143/145 suppressed the proliferation of Caco2 cells. Taken together, our findings provide evidence for a role of the miR-143/145 cluster as a tumor suppressor in colorectal cancer through the inhibition of IGF1R translation. PMID:25474488

  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. 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.

  5. CysLT1R downregulation reverses intracerebroventricular streptozotocin-induced memory impairment via modulation of neuroinflammation in mice.

    PubMed

    Ghosh, Arijit; Chen, Fang; Wu, Feng; Tang, Su-Su; Hu, Mei; Long, Yan; Sun, Hong-Bin; Kong, Ling-Yi; Hong, Hao

    2017-02-06

    Our previous studies showed that cysteinyl leukotrienes receptor 1 (CysLT1R) is upregulated in amyloid-β (Aβ)-induced neurotoxicity and that administration of CysLT1R antagonists such as pranlukast or montelukast can ameliorate memory impairment in mice. In the current study, we sought to explore the role of CysLT1R in intracerebroventricular streptozotocin (STZ-ICV)-induced mouse model of memory impairment and neuroinflammation through shRNA-mediated knockdown of CysLT1R and also its pharmacological blockade by pranlukast. ICR mice were infused with STZ (3.0mg/kg) by a single bilateral stereotaxic ICV microinjection followed by administration of CysLT1R-shRNA (intra-hippocampal) or pranlukast (intragastric, IG). After 21days, a set of behavioral and biochemical tests were performed in order to assess the degree of memory impairment and neuroinflammation in mice. STZ-infused mice spent less time in the target quadrant of Morris water maze test and took more time to find the shock-free arm in modified Y-maze test, which were rescued in the CysLT1R-knockdowned or pranlukast-treated mice. STZ-induced memory impairment was also accompanied by an elevated level of hippocampal CysLT1R, microglial activation, increased IL-1β, and TNF-α. Such elevation of these factors was found to be mediated through the classical NF-κB pathway and administration of CysLT1R-shRNA or pranlukast for 21days reversed all these parameters, suggesting a role of CysLT1R in STZ-induced memory deficit and neuroinflammation.

  6. 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.

  7. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents.

    PubMed

    van den Brink, Willem; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; van der Laan, Jan Willem

    2017-04-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes.

  8. 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

  9. Permanent antibiotic impregnated intramedullary nail in diabetic limb salvage: a case report and literature review.

    PubMed

    Woods, Jason B; Lowery, Nicholas J; Burns, Patrick R

    2012-01-01

    Managing complications after attempted hind foot and ankle arthrodesis with intramedullary nail fixation is a challenge. This situation becomes more problematic in the patient with diabetes mellitus and multiple comorbidities. Infection and subsequent osteomyelitis can be a devastating, limb threatening complication associated with these procedures. The surgeon must manage both the infectious process and the skeletal instability concurrently. This article provides a literature review and detailed management strategies for a modified technique of employing antibiotic impregnated polymethylmethacrylate-coated intramedullary nailing.

  10. 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.

  11. 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.

  12. 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.

  13. Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial

    PubMed Central

    Kroeger, Axel; Avila, Elci Villegas; Morison, Linda

    2002-01-01

    Objective To measure the impact on transmission of leishmaniasis of curtains impregnated with insecticide. Design Cluster randomised controlled trial: household interview survey, observational study of people's behaviour, entomological study with light trap captures of sandflies inside houses. Setting 14 urban sectors in Trujillo, Venezuela. Participants 2913 inhabitants of 569 houses. Intervention Sectors were paired according to their 12 month cumulative incidence of cutaneous leishmaniasis, one sector in each pair was randomly allocated to receive polyester curtains impregnated with lambdacyhalothrin (intervention group) while the other sector received curtains without insecticide or no curtains (control groups). After 12 months a follow up household survey was conducted. Main outcome measures Reduction in abundance of sandflies indoors and 12 month incidence of clinical cases of cutaneous leishmaniasis. Results Transmission of cutaneous leishmaniasis occurred mainly in the domestic setting, with the incidence over 12 months of 4%. The mean number of sandflies per trap per night was 16. After follow up the 12 month incidence of cutaneous leishmaniasis was 0% in the intervention group and 8% in the six pairs in the control group that received unimpregnated curtains (mean difference 8, 95% confidence interval 4.22 to 11.78; P=0.001). There were significantly fewer sandflies in the intervention group (2 v 15, mean difference 13 sandflies per trap; 9 to 17; P<0.001). Conclusion Curtains impregnated with insecticide provide a high degree of protection against indoor transmission of cutaneous leishmaniasis. What is already known on this topicThe transmission of cutaneous leishmaniasis is increasingly in urban and domestic settingsHouse spraying, space spraying, and insecticide treated material reduce the number of vectorsWhat this paper addsPyrethroid impregnated curtains can considerably reduce the incidence rate of cutaneous leishmaniasis in areas where indoor

  14. 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 (...

  15. Antibiotic-impregnated beads for the treatment of aortic graft infection.

    PubMed

    Healy, Aaron H; Reid, Bruce B; Allred, Bryce D; Doty, John R

    2012-03-01

    Infection of a prosthetic graft after replacement of the ascending aorta is an uncommon but life-threatening complication of surgery. We report the use of antibiotic-impregnated calcium sulfate beads in a patient with ascending aortic graft infection to provide localized, high-dose therapy to the infected region. Perigraft placement of antibiotic beads provides an alternative method for the treatment of aortic graft infection.

  16. Clinical and laboratory experience with heparin-impregnated silicone shunts for carotid endarterectomy.

    PubMed

    Piepgras, D G; Sundt, T M

    1976-11-01

    Our experience with use of a Silastic shunt for carotid endarterectomy is reviewed briefly, and the complication of shunt thrombosis despite intraoperative administration of heparin is noted. Of obvious importance are the reduction of blood flow and the possibility of embolization caused by accumulating thrombus. Shunt thrombosis has been abolished by the use of heparin-impregnated Silastic shunts. In experiments in dogs, such heparin-treated shunts showed greater thromboresistance than did untreated shunts.

  17. Determination of the Impregnant Concentrations on ASC Type Charcoal. A Magnetic Susceptibility Study

    DTIC Science & Technology

    1987-10-01

    chloropicrin etc., before and after adsorption on the diamagnetic charcoal prepared from coconut shell . However, the conclusions drawn from these... activation analysis for 55 elements was performed on two charcoal samples, namely the BPL and the CAL-1048, both supplied directly from Calgon Carbon ...of Neutron Activation Analysis on the BPL- Charcoal (Coal-Based, No Impregnants)................2424 TABLE B-2: Result of Neutron Activation Analysis

  18. Current collection at the shuttle orbiter during TSS-1R high voltage charging

    NASA Astrophysics Data System (ADS)

    Agüero, V. M.; Williams, S. D.; Gilchrist, B. E.; Krause, L. Habash; Thompson, D. C.; Raitt, W. J.; Burke, W. J.; Gentile, L. C.

    We compare measurements of collected currents and Space Shuttle Orbiter potentials, taken during the Tethered Satellite System (TSS) missions, with predictions of a numerical model. The model assumes thin potential sheaths about the Orbiter and contributions from both ram and thermal currents. It was originally developed to explain the smaller than expected Orbiter charging detected throughout the first TSS mission (TSS-1). During periods of the TSS reflight (TSS-1R) when the Orbiter potential was > -100 V the model effectively described current collection. Deviations from model predictions appeared at more negative potentials. These indicate bounds of applicability for the model and the growing importance of unaccounted physical processes. Data acquired near the time of the tether break suggest that additional current during the break was carried by secondary ions created in collisions between surface-generated electrons and ambient neutrals within the Orbiter's high-voltage sheath.

  19. Chromosome mapping of the owl monkey CSF1R and IL5 genes.

    PubMed

    Ma, N S; Lin, K C

    1992-08-01

    We mapped the owl monkey colony-stimulating factor 1 receptor (CSF1R) locus to the proximal region of chromosome 3q of karyotype VI(K-VI) and karyotype V(K-V) and the interleukin 5 (IL5) locus to the mid-region of chromosome 3q(K-VI) and 19q(K-IV) using a combination of Southern hybridization of somatic cells and in situ chromosomal hybridization methodologies. The findings support the proposed evolution of owl monkey chromosome 3(K-VI) from a fusion of two smaller structures, the homologs of chromosomes 6 and 19 (K-IV). The data also indicate genomic conservation of the HSA 5q23-q35 segment in the higher primates.

  20. 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

  1. 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.

  2. 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.

  3. Congenital erythropoietic porphyria linked to GATA1-R216W mutation: challenges for diagnosis.

    PubMed

    Di Pierro, Elena; Russo, Roberta; Karakas, Zeynep; Brancaleoni, Valentina; Gambale, Antonella; Kurt, Ismail; Winter, S Stuart; Granata, Francesca; Czuchlewski, David Rodriguez; Langella, Concetta; Iolascon, Achille; Cappellini, Maria Domenica

    2015-06-01

    Congenital erythropoietic porphyria (CEP) is a rare genetic disease that is characterized by a severe cutaneous photosensitivity causing unrecoverable deformities, chronic hemolytic anemia requiring blood transfusion program, and by fatal systemic complications. A correct and early diagnosis is required to develop a management plan that is appropriate to the patient's needs. Recently only one case of X-linked CEP had been reported, describing the trans-acting GATA1-R216W mutation. Here, we have characterized two novel X-linked CEP patients, both with misleading hematological phenotypes that include dyserythropoietic anemia, thrombocytopenia, and hereditary persistence of fetal hemoglobin. We compare the previously reported case to ours and propose a diagnostic paradigm for this variant of CEP. Finally, a correlation between phenotype variability and the presence of modifier mutations in loci related to disease-causing gene is described.

  4. 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.

  5. 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.

  6. Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists.

    PubMed

    Tripathi, Trivendra; Shahid, Mohammad; Khan, Haris M; Negi, Mahendra Pal Singh; Siddiqui, Mashiatullah; Khan, Rahat A

    2010-01-01

    The present study was designed to delineate the immunomodulatory role of histamine receptors (H1R and H2R) and their antibody generation in a rabbit model. Six groups containing 18 rabbits each received either vehicle (sterile distilled water, 1 ml/kg x b.i.d), histamine (100 μg/kg x b.i.d.), H1R agonist (HTMT, 10 μg/kg x b.i.d.), H2R agonist (amthamine, 10 μg/kg x b.i.d.), H1R antagonist (pheniramine, 10 mg/kg x b.i.d.) or H2R antagonist (ranitidine, 10 mg/kg x b.i.d.). All animals were subsequently immunized with an intravenous injection of sheep red blood cells (SRBC). Estimations of total serum immunoglobulins (Igs), immunoglobulin M (IgM) and immunoglobulin G (IgG) were performed by ELISA and hemagglutination assay (HA) at days 0 (pre-immunization), 7, 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed similar production of Igs, IgM and IgG but the results were found comparatively more significant by ELISA as opposed to HA. Results showed that histamine could influence a detectable antibody response to SRBC early (i.e., at day 7), which lasted until day 58. Immunomodulatory processes showed suppression of an Ig generation in the H1R-antagonist group with enhancement in the H2R-antagonist group. The H1R-agonist group showed an increased Ig production in comparison to the H2R-agonist group. The IgM production was inhibited in the H1R-antagonist group as compared to the H2R-antagonist group, and it was also suppressed in H1R-agonist group as compared to H2R-agonist group. IgG production was inhibited in the H1R-antagonist group as opposed to the H2R-antagonist group. In contrast, the H1R-agonist group increased IgG production as compared to the H2R-agonist group. All the results were found to be statistically significant (p < 0.05 or p < 0.01). In conclusion, histamine and its receptor (H1R and H2R) agonists enhance antibody production by triggering the histamine receptors (H1R and H2R), and both the H1R antagonist and the H2R antagonist

  7. Identification of a uniquely expanded V1R (ORA) gene family in the Japanese grenadier anchovy (Coilia nasus).

    PubMed

    Zhu, Guoli; Tang, Wenqiao; Wang, Liangjiang; Wang, Cong; Wang, Xiaomei

    A number of studies have suggested that olfaction plays an important role in fish migration. Fish use several distinct families of olfactory receptors to detect environmental odorants, including MORs (main olfactory receptors), V1Rs (vomeronasal type-1 receptors), V2Rs (vomeronasal type-2 receptors), TAARs (trace amine-associated receptors), and FPRs (formyl peptide receptors). The V1Rs have been reported to detect pheromones, and a pheromone hypothesis for the spawning migration of anadromous fish has been proposed. Examining whether Coilia nasus relies on V1R-mediated olfaction for spawning migration is important for understanding the molecular basis of spawning migration behavior. Here, we explored the V1R gene family in anadromous C. nasus. Six V1R genes previously reported in other teleost fish were successfully identified. Interestingly, we detected the largest V1R repertoire in teleost fish from C. nasus and identified a species-specific expansion event of V1R3 gene that has previously been detected as single-copy genes in other teleost fish. The V1R loci were found to be populated with repetitive sequences, especially in the expanded V1R3 genes. Additionally, the divergence of V1R3 genetic structures in different populations of C. nasus indicates the copy number variation (CNV) in V1R3 gene among individuals of C. nasus. Most of the putative C. nasus V1R genes were expressed primarily in the olfactory epithelium, consistent with the role of the gene products as functional olfactory receptors. Significant differences in the expression levels of V1R genes were detected between the anadromous and non-anadromous C. nasus. This study represents a first step in the elucidation of the olfactory communication system of C. nasus at the molecular level. Our results indicate that some V1R genes may be involved in the spawning migration of C. nasus, and the study provides new insights into the spawning migration and genome evolution of C. nasus.

  8. Synthesis and characterization of silver-nanoparticle-impregnated fiberglass and utility in water disinfection

    NASA Astrophysics Data System (ADS)

    Nangmenyi, Gordon; Yue, Zhongren; Mehrabi, Sharifeh; Mintz, Eric; Economy, James

    2009-12-01

    A number of researchers have deployed silver (Ag) nanoparticles through a number of techniques on various substrates including carbon, zeolites and polymers for water disinfection applications. However, Ag impregnated on an inorganic fiberglass surface through a simple electroless process was only recently reported for the first time. Fiberglass impregnated with Ag nanoparticles displays superior performance over carbon-based silver support systems but little is known about the factors that affect the architecture of the system, its interfacial properties and its consequent bactericidal activity. In this study, Ag content and particle size on a fiberglass substrate were manipulated by adjusting the AgNO3 concentration, immersion time, temperature, solution pH and reduction temperature. The reduction chemistry of the Ag-nanoparticle-impregnated fiberglass is described and supported with thermal gravimetric analysis (TGA) and photoelectron spectroscopy (XPS) measurements. The Ag content along with the particle size and particle size distribution were characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS) and x-ray diffraction (XRD). The Ag content on the fiberglass mats ranged from 0.04 to 4.7 wt% Ag/g-fiber with a size distribution of 10-900 nm under standard processing conditions. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze the Ag desorption from the fiberglass substrate, while the bactericidal properties were evaluated against Escherichia coli (E. coli).

  9. 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.

  10. 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.

  11. Antimicrobial-impregnated catheters for the prevention of catheter-related bloodstream infections.

    PubMed

    Lorente, Leonardo

    2016-05-04

    Central venous catheters are commonly used in critically ill patients. Such catheterization may entail mechanical and infectious complications. The interest in catheter-related infection lies in the morbidity, mortality and costs that it involved. Numerous contributions have been made in the prevention of catheter-related infection and the current review focuses on the possible current role of antimicrobial impregnated catheters to reduce catheter-related bloodstream infections (CRBSI). There is evidence that the use of chlorhexidine-silver sulfadiazine (CHSS), rifampicin-minocycline, or rifampicin-miconazol impregnated catheters reduce the incidence of CRBSI and costs. In addition, there are some clinical circumstances associated with higher risk of CRBSI, such as the venous catheter access and the presence of tracheostomy. Current guidelines for the prevention of CRBSI recommended the use of a CHSS or rifampicin-minocycline impregnated catheter in patients whose catheter is expected to remain in place > 5 d and if the CRBSI rate has not decreased after implementation of a comprehensive strategy to reduce it.

  12. 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.

  13. Theoretical impact of insecticide-impregnated school uniforms on dengue incidence in Thai children.

    PubMed

    Massad, Eduardo; Amaku, Marcos; Antonio Bezerra Coutinho, Francisco; Kittayapong, Pattamaporn; Wilder-Smith, Annelies

    2013-01-01

    Background Children carry the main burden of morbidity and mortality caused by dengue. Children spend a considerable amount of their day at school; hence strategies that reduce human-mosquito contact to protect against the day-biting habits of Aedes mosquitoes at schools, such as insecticide-impregnated uniforms, could be an effective prevention strategy. Methodology We used mathematical models to calculate the risk of dengue infection based on force of infection taking into account the estimated proportion of mosquito bites that occur in school and the proportion of school time that children wear the impregnated uniforms. Principal findings The use of insecticide-impregnated uniforms has efficacy varying from around 6% in the most pessimistic estimations, to 55% in the most optimistic scenarios simulated. Conclusions Reducing contact between mosquito bites and human hosts via insecticide-treated uniforms during school time is theoretically effective in reducing dengue incidence and may be a valuable additional tool for dengue control in school-aged children. The efficacy of this strategy, however, is dependent on the compliance of the target population in terms of proper and consistent wearing of uniforms and, perhaps more importantly, the proportion of bites inflicted by the Aedes population during school time.

  14. Characterization of (Th,U)O 2 fuel pellets made by impregnation technique

    NASA Astrophysics Data System (ADS)

    Kutty, T. R. G.; Nair, M. R.; Sengupta, P.; Basak, U.; Kumar, Arun; Kamath, H. S.

    2008-02-01

    Impregnation technique is an attractive alternative for manufacturing highly radiotoxic 233U bearing thoria based mixed oxide fuel pellets, which are remotely treated in hot cell or shielded glove-box facilities. This technique is being investigated to fabricate the fuel for the forthcoming Indian Advanced Heavy Water Reactor (AHWR). In the impregnation process, porous ThO 2 pellets are prepared in an unshielded facility which are then impregnated with 1.5 molar uranyl nitrate solution in a shielded facility. The resulting composites are dried and denitrated at 500 °C and then sintered in reducing/oxidizing atmosphere to obtain high density (Th,U)O 2 pellets. In this work, the densification behaviour of ThO 2-2% UO 2 and ThO 2-4% UO 2 pellets was studied in reducing and oxidizing atmospheres using a high temperature dilatometer. Densification was found to be larger in air than in Ar-8% H 2. The characterization of the sintered pellets was made by optical microscopy, scanning electron microscopy (SEM) and electron probe microanalysis (EPMA). The grain structure of ThO 2-2% UO 2 and ThO 2-4% UO 2 pellets was uniform. The EPMA data confirmed that the uranium concentration was slightly higher at the periphery of the pellet than that at the centre.

  15. Unmodified versus caustics-impregnated carbons for control of hydrogen sulfide emissions from sewage treatment plants

    SciTech Connect

    Bandosz, T.J.; Bagreev, A.; Adib, F.; Turk, A.

    2000-03-15

    Unmodified and caustic-impregnated carbons were compared as adsorbents for hydrogen sulfide in the North River Water Pollution Control Plant in New York City over a period of 2 years. The carbons were characterized using accelerated H{sub 2}S breakthrough capacity tests, sorption of nitrogen, potentiometric titration, and thermal analysis. The accelerated laboratory tests indicate that the initial capacity of caustic-impregnated carbons exceeds that of unmodified carbon, but the nature of real-life challenge streams, particularly their lower H{sub 2}S concentrations, nullifies this advantage. As the caustic content of the impregnated carbon is consumed, the situation reverses, and the unmodified carbon becomes more effective. When the concentration of H{sub 2}S is low, the developed surface area and pore volume along with the affinity to retain water create a favorable environment for dissociative adsorption of hydrogen sulfide and its oxidation to elemental sulfur, S{sup 4+}, and S{sup 6+}. In the case of the caustic carbon, the catalytic impact of the carbon surface is limited, and its good performance lasts only while active base is present. The results also show the significant differences in performance of unmodified carbons due to combined effects of their porosity and surface chemistry.

  16. Solvent-impregnated agarose gel liquid phase microextraction of polycyclic aromatic hydrocarbons in water.

    PubMed

    Loh, Saw Hong; Sanagi, Mohd Marsin; Wan Ibrahim, Wan Aini; Hasan, Mohamed Noor

    2013-08-09

    A new microextraction procedure termed agarose gel liquid phase microextraction (AG-LPME) combined with gas chromatography-mass spectrometry (GC-MS) was developed for the determination of selected polycyclic aromatic hydrocarbons (PAHs) in water. The technique utilized an agarose gel disc impregnated with the acceptor phase (1-octanol). The extraction procedure was performed by allowing the solvent-impregnated agarose gel disc to tumble freely in the stirred sample solution. After extraction, the agarose gel disc was removed and subjected to centrifugation to disrupt its framework and to release the impregnated solvent, which was subsequently withdrawn and injected into the GC-MS for analysis. Under optimized extraction conditions, the new method offered high enrichment factors (89-177), trace level LODs (9-14ngL(-1)) and efficient extraction with good relative recoveries in the range of 93.3-108.2% for spiked drinking water samples. AG-LPME did not exhibit any problems related to solvent dissolution, and it provided high extraction efficiencies that were comparable to those of hollow fiber liquid phase microextraction (HF-LPME) and significantly higher than those of agarose film liquid phase microextraction (AF-LPME). This technique employed a microextraction format and utilized an environmentally compatible solvent holder that supported the green chemistry concept.

  17. Steam pretreatment of Saccharum officinarum L. bagasse by adding of impregnating agents for advanced bioethanol production.

    PubMed

    Verardi, A; Blasi, A; De Bari, I; Calabrò, V

    2016-12-01

    The main byproduct of the sugarcane industry, Saccharum officinarum L. bagasse (sugarcane bagasse, SCB), is widely used as lignocellulose biomass for bio-ethanol (EtOH) production. In this research study, SCB was pretreated by steam explosion (SE) method using two different impregnating agents: sulfur dioxide (SD) and hydrogen peroxide (HP). As matter of fact, the use of impregnating agents improves the performance of SE method, increasing the concentrations of fermentable sugars after enzymatic saccharification, and decreasing the inhibitor compounds produced during the steam pretreatment step. The aim of this study was to investigate and compare the use of the two impregnating agents in various SE-conditions in order to optimize pretreatment parameters. For every pretreatment condition, it has been evaluated: concentration of fermentable sugars, glucose and xylose yields, and the effects of the inhibitor compounds on enzymatic hydrolysis step. The obtained results allow to improve the efficiency of the whole process of bio-EtOH synthesis enhancing the amount of fermentable sugars produced and the eco-sustainability of the whole process. Indeed, the optimization of steam pretreatment leads to a reduction of energy requirements and to a lower environmental impact.

  18. 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.

  19. DGEBF epoxy blends for use in the resin impregnation of extremely large composite parts

    DOE PAGES

    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

  20. 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.

  1. Antimicrobial-impregnated catheters for the prevention of catheter-related bloodstream infections

    PubMed Central

    Lorente, Leonardo

    2016-01-01

    Central venous catheters are commonly used in critically ill patients. Such catheterization may entail mechanical and infectious complications. The interest in catheter-related infection lies in the morbidity, mortality and costs that it involved. Numerous contributions have been made in the prevention of catheter-related infection and the current review focuses on the possible current role of antimicrobial impregnated catheters to reduce catheter-related bloodstream infections (CRBSI). There is evidence that the use of chlorhexidine-silver sulfadiazine (CHSS), rifampicin-minocycline, or rifampicin-miconazol impregnated catheters reduce the incidence of CRBSI and costs. In addition, there are some clinical circumstances associated with higher risk of CRBSI, such as the venous catheter access and the presence of tracheostomy. Current guidelines for the prevention of CRBSI recommended the use of a CHSS or rifampicin-minocycline impregnated catheter in patients whose catheter is expected to remain in place > 5 d and if the CRBSI rate has not decreased after implementation of a comprehensive strategy to reduce it. PMID:27152256

  2. 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.

  3. Adsorption of Neutral Red onto Mn-impregnated activated carbons prepared from Typha orientalis.

    PubMed

    Zhang, Jian; Shi, Qianqian; Zhang, Chenglu; Xu, Jingtao; Zhai, Bing; Zhang, Bo

    2008-12-01

    Activated carbon was prepared from an inexpensive and renewable carbon source, Typha orientalis, by H(3)PO(4) activation and then impregnated with different Mn salts and tested for its Neutral Red (NR) adsorption capacities. The amount of Mn impregnated in the activated carbon was influenced by the anion species. Impregnation with Mn decreased the surface area, changed the pore size and crystal structure, and introduced more acidic functional groups such as carboxyl, lactone and phenol groups. The optimum adsorption performance for all the activated carbons was obtained at pH 3.7, Mn-Carbon dose of 0.100g/100ml solution and contact time 4.5h. The adsorption isotherms fit the Langmuir isotherm equation. The kinetic data followed the pseudo-second-order model. The thermodynamic parameters indicated that the processes were spontaneous and endothermic. According to these results, the prepared Mn modified activated carbons are promising adsorbents for the removal of Neutral Red from wastewater.

  4. 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.

  5. Use of Antibiotic-Impregnated Absorbable Beads and Tissue Coverage of Complex Wounds.

    PubMed

    White, Terris L; Culliford, Alfred T; Zomaya, Martin; Freed, Gary; Demas, Christopher P

    2016-11-01

    The treatment of complex wounds is commonplace for plastic surgeons. Standard management is debridement of infected and devitalized tissue and systemic antibiotic therapy. In cases where vital structures are exposed within the wound, coverage is obtained with the use of vascularized tissue using both muscle and fasciocutaneous flaps. The use of nondissolving polymethylmethacrylate and absorbable antibiotic-impregnated beads has been shown to deliver high concentrations of antibiotics with low systemic levels of the same antibiotic. We present a multicenter retrospective review of all cases that used absorbable antibiotic-impregnated beads for complex wound management from 2003 to 2013. A total of 104 cases were investigated, flap coverage was used in 97 cases (93.3%). Overall, 15 patients (14.4%) required reoperation with the highest groups involving orthopedic wounds and sternal wounds. The advantages of using absorbable antibiotic-impregnated beads in complex infected wounds have been demonstrated with minimal disadvantages. The utilization of these beads is expanding to a variety of complex infectious wounds requiring high concentrations of local antibiotics.

  6. Efficacy of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with osteomyelitis.

    PubMed

    Kelly, Kristi R; Kapatkin, Amy R; Zwingenberger, Allison L; Christe, Kari L

    2012-08-01

    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.

  7. Carbon molecular sieves from carbon cloth: Influence of the chemical impregnant on gas separation properties

    NASA Astrophysics Data System (ADS)

    Rodríguez-Blanco, G.; Giraldo, L.; Moreno-Piraján, J. C.

    2010-06-01

    Carbon materials with molecular sieve properties (CMS) were prepared by pyrolysis of cotton fabrics by chemical activation procedures. To evaluate the changes in the chemical and textural properties, the impregnants AlCl 3, ZnCl 2 and H 3PO 4 were used at 1123 K. The materials were characterized using adsorption of nitrogen and carbon dioxide, TPD, and immersion calorimetry in C 6H 6. Adsorption kinetics of O 2, N 2, CO 2, CH 4, C 3H 8 and C 3H 6 were measured in all the prepared materials to determine their behaviour as molecular sieves. The results confirm that the chemical used as impregnant has a significant effect on the resulting CMS separation properties. All materials exhibit microporosity and low oxygen surface group contents; however, the sample impregnated with zinc chloride, with an immersion enthalpy value of 66.4 J g -1 in benzene, exhibits the best performance in the separation of CH 4-CO 2 and C 3H 8-C 3H 6 at 273 K.

  8. 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

  9. Bio-inspired surfactant assisted nano-catalyst impregnation of Solid-Oxide Fuel Cell (SOFC) electrodes

    SciTech Connect

    Ozmen, Ozcan; Zondlo, John W.; Lee, Shiwoo; 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).

  10. Preparation of gold- and chlorine-impregnated bead-type activated carbon for a mercury sorbent trap.

    PubMed

    Song, Young Cheol; Lee, Tai Gyu

    2016-12-01

    This study aimed to develop a mercury (Hg) adsorption trap, which can be used to measure the concentration of elemental Hg in emissions from a Hg discharge facility, and evaluate its adsorption efficiency. The Hg spiking efficiency was compared by impregnating metallic and halogen materials that have high affinity for Hg into activated carbon (AC) to determine an accurate spiking method for Hg on AC. The Hg spiking efficiency was compared according to the type and content of the impregnated substances. AC impregnated with Cl and Au had a 15-20% higher Hg spiking efficiency compared to virgin AC. For Au impregnation at weight ratios of 0-20 wt% of adsorbent, spiking efficiencies of over 97% were observed under certain conditions. The Hg adsorption properties of the above adsorbent were determined experimentally, and the results were used to test the adsorption performance of Hg adsorption traps.

  11. 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-...

  12. Identification and characterization of two members of a novel class of the interleukin-1 receptor (IL-1R) family. Delineation of a new class of IL-1R-related proteins based on signaling.

    PubMed

    Born, T L; Smith, D E; Garka, K E; Renshaw, B R; Bertles, J S; Sims, J E

    2000-09-29

    Two novel members of the interleukin-1 receptor (IL-1R) family, identified by homology searches of human genomic sequence data bases, are described. The genes have been named according to their structural features: TIGIRR-1 (three immunoglobulin domain-containing IL-1 receptor-related) and TIGIRR-2. TIGIRR-2 has recently been identified as causing mental retardation when mutated (Carrie, A., Jun, L., Bienvenu, T., Vinet, M. C., McDonell, N., Couvert, P., Zemni, R., Cardona, A., Van Buggenhout, G., Frints, S., Hamel, B., Moraine, C., Ropers, H. H., Strom, T., Howell, G. R., Whittaker, A., Ross, M. T., Kahn, A., Fryns, J. P., Beldjord, C., Marynen, P., and Chelly, J. (1999) Nat. Genet. 23, 25-31) and called IL1RAPL, a name we will also use henceforth. Neither receptor alone was able to mediate transcriptional activation of NF-kappaB in response to IL-1alpha, IL-1beta, or IL-18. In order to begin to elucidate the function of these and other orphan IL-1R family members, we have developed a functional assay utilizing a panel of chimeric receptors containing the extracellular and transmembrane domains of either type I IL-1R or IL-1R accessory protein (AcP) coupled to the cytoplasmic domains of all family members. Coexpression of each IL-1R chimera with each AcP chimera and an NF-kappaB-responsive reporter demonstrated that the cytoplasmic domains could be classified as IL-1R-like, AcP-like, or neither. Any IL-1R-like cytoplasmic domain could cooperate with any AcP-like cytoplasmic domain. The TIGIRR-1 and IL1RAPL cytoplasmic domains, however, were unable to signal as either IL-1R-like or AcP-like components, suggesting that they function as a new class of receptors within this family.

  13. Uptake and release of fluoride from fluoride-impregnated chewing sticks (miswaks) in vitro and in vivo.

    PubMed

    Baeshen, H A; Kjellberg, H; Lingström, P; Birkhed, D

    2008-01-01

    The purpose was to investigate the uptake and release of fluoride (F) from F-impregnated chewing sticks (miswaks). In the first series, 3-cm-long pieces were impregnated in 1, 2, 3 and 4% NaF solutions for 3 h, 1 day and 3 days (10 pieces/test). There was a dose-response effect with respect to both impregnation time and the concentration of the F solution. In the second and third series, totally 40 miswak pieces were impregnated in 3% NaF for 1 day and 3 days; the outer layer (bark) was separated from the inner spongy part (pulp) and analyzed separately. F was released from both parts, but somewhat more was released from the bark than from the pulp; a plateau was reached at around 30 min. In vivo, 9 healthy subjects used three products for 2 min in a crossover design: (1) a miswak impregnated in 3% NaF for 1 day, (2) a miswak impregnated in 3% NaF for 3 days, and (3) 1 g of F toothpaste (containing 1,450 ppm F as NaF) on a toothbrush. The highest F concentration at the approximal area was obtained after using the miswak impregnated in 3% NaF for 3 days compared with the other products (p < 0.05 or p < 0.01). To conclude, NaF-impregnated miswaks produced a rapid release of F in vitro as well as in vivo and may be an interesting vehicle for home care use for caries prevention in countries where they are used regularly.

  14. Investigation of the metabolic consequences of impregnating spinach leaves with trehalose and applying a pulsed electric field.

    PubMed

    Dymek, Katarzyna; Panarese, Valentina; Herremans, Els; Cantre, Dennis; Schoo, Rick; Toraño, Javier Sastre; Schluepmann, Henriette; Wadso, Lars; Verboven, Pieter; Nicolai, Bart M; Dejmek, Petr; Gómez Galindo, Federico

    2016-12-01

    The impregnation of leafy vegetables with cryoprotectants using a combination of vacuum impregnation (VI) and pulsed electric fields (PEF) has been proposed by our research group as a method of improving their freezing tolerance and consequently their general quality after thawing. In this study, we have investigated the metabolic consequences of the combination of these unit operations on spinach. The vacuum impregnated spinach leaves showed a drastic decrease in the porosity of the extracellular space. However, at maximum weight gain, randomly located air pockets remained, which may account for oxygen-consuming pathways in the cells being active after VI. The metabolic activity of the impregnated leaves showed a drastic increase that was further enhanced by the application of PEF to the impregnated tissue. Impregnating the leaves with trehalose by VI led to a significant accumulation of trehalose-6-phosphate (T6P), however, this was not further enhanced by PEF. It is suggested that the accumulation of T6P in the leaves may increase metabolic activity, and increase tissue resistance to abiotic stress.

  15. Fe-Impregnated Mineral Colloids for Peroxide Activation: Effects of Mineral Substrate and Fe Precursor.

    PubMed

    Li, Yue; Machala, Libor; Yan, Weile

    2016-02-02

    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.

  16. The MC1R melanoma risk variant p.R160W is associated with Parkinson disease.

    PubMed

    Tell-Marti, Gemma; Puig-Butille, Joan Anton; Potrony, Miriam; Badenas, Celia; Milà, Montserrat; Malvehy, Josep; Martí, María José; Ezquerra, Mario; Fernández-Santiago, Rubén; Puig, Susana

    2015-05-01

    Epidemiological studies have reported the co-occurrence of Parkinson disease (PD) and melanoma. Common genetic variants in the MC1R (melanocortin 1 receptor) gene, which determines skin and hair color, are associated with melanoma. Here we investigated whether genetic variants in MC1R modulate the risk of PD by sequencing the entire gene in 870 PD patients and 736 controls ascertained from Spain. We found that the MC1R variant p.R160W (rs1805008) is marginally associated with PD (odds ratio = 2.10, gender- and age-adjusted p = 0.009, Bonferroni-corrected p = 0.063). Our results suggest that MC1R genetic variants modulate the risk of PD disease in the Spanish population.

  17. A melanin-independent interaction between Mc1r and Met signalling pathways is required for HGF-dependent melanoma

    PubMed Central

    Wolnicka-Glubisz, Agnieszka; Strickland, Faith M.; Wielgus, Albert; Anver, Miriam; Merlino, Glenn; De Fabo, Edward C.; Noonan, Frances P.

    2014-01-01

    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. PMID:24975581

  18. Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma?

    PubMed Central

    Dolley-Hitze, T; Jouan, F; Martin, B; Mottier, S; Edeline, J; Moranne, O; Le Pogamp, P; Belaud-Rotureau, M-A; Patard, J-J; Rioux-Leclercq, N; Vigneau, C

    2010-01-01

    Background: The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors. Methods: Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT–PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS). Results: A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT–PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118, respectively). Conclusion: Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy. PMID:21102591

  19. 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.

  20. 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

  1. Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants.

    PubMed

    Ozola, Aija; Azarjana, Kristīne; Doniņa, Simona; Proboka, Guna; Mandrika, Ilona; Petrovska, Ramona; Cēma, Ingrīda; Heisele, Olita; Eņģele, Ludmila; Streinerte, Baiba; Pjanova, Dace

    2013-03-01

    To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, P<0.001). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% CI 2.15-7.38, P<0.001) that of carriers of one variant (OR 1.98, 95% CI 1.26-3.11, P=0.003). After stratification according to the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.

  2. Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r.

    PubMed Central

    Arlaud, G J; Willis, A C; Gagnon, J

    1987-01-01

    The amino acid sequence of human C1r A chain was determined, from sequence analysis performed on fragments obtained from C1r autolytic cleavage, cleavage of methionyl bonds, tryptic cleavages at arginine and lysine residues, and cleavages by staphylococcal proteinase. The polypeptide chain has an N-terminal serine residue and contains 446 amino acid residues (Mr 51,200). The sequence data allow chemical characterization of fragments alpha (positions 1-211), beta (positions 212-279) and gamma (positions 280-446) yielded from C1r autolytic cleavage, and identification of the two major cleavage sites generating these fragments. Position 150 of C1r A chain is occupied by a modified amino acid residue that, upon acid hydrolysis, yields erythro-beta-hydroxyaspartic acid, and that is located in a sequence homologous to the beta-hydroxyaspartic acid-containing regions of Factor IX, Factor X, protein C and protein Z. Sequence comparison reveals internal homology between two segments (positions 10-78 and 186-257). Two carbohydrate moieties are attached to the polypeptide chain, both via asparagine residues at positions 108 and 204. Combined with the previously determined sequence of C1r B chain [Arlaud & Gagnon (1983) Biochemistry 22, 1758-1764], these data give the complete sequence of human C1r. PMID:3036070

  3. HUMAN GRK4γ142V VARIANT PROMOTES AT1R-MEDIATED HYPERTENSION VIA RENAL HDAC1 INHIBITION

    PubMed Central

    Wang, Zheng; Zeng, Chunyu; Villar, Van Anthony M.; Chen, Shi-You; Konkalmatt, Prasad; Wang, Xiaoyan; Asico, Laureano D.; Jones, John E.; Yang, Yu; Sanada, Hironobu; Felder, Robin A.; Eisner, Gilbert M.; Weir, Matthew R.; Armando, Ines; Jose, Pedro A.

    2015-01-01

    The influence of a single gene on the etiology of essential hypertension may be difficult to ascertain, unless the gene interacts with other genes that are germane to blood pressure regulation. G protein-coupled receptor kinase type 4 (GRK4) is one such gene. We have reported that the expression of its variant hGRK4γ142V in mice results in hypertension due to impaired dopamine D1 receptor (D1R). Signaling through D1R and angiotensin II type I receptor (AT1R) reciprocally modulates renal sodium excretion and blood pressure. Here, we demonstrate the ability of the hGRK4γ142V to increase the expression and activity of the AT1R. We show that hGRK4γ142V phosphorylates histone deacetylase type 1 and promotes its nuclear export to the cytoplasm, resulting in increased AT1R expression and greater pressor response to angiotensin II. AT1R blockade and the deletion of the Agtr1a gene normalize the hypertension in hGRK4γ142V mice. These findings illustrate the unique role of GRK4 by targeting receptors with opposite physiological activity for the same goal of maintaining blood pressure homeostasis, and thus making the GRK4 a relevant therapeutic target to control blood pressure. PMID:26667412

  4. 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.

  5. Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX).

    PubMed

    Hiroshima, Yukihiko; Zhao, Ming; Maawy, Ali; Zhang, Yong; Katz, Matthew H G; Fleming, Jason B; Uehara, Fuminari; Miwa, Shinji; Yano, Shuya; Momiyama, Masashi; Suetsugu, Atsushi; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2014-07-01

    The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purpose of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control (P = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans's criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.

  6. Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R).

    PubMed

    Yang, Dehua; de Graaf, Chris; Yang, Linlin; Song, Gaojie; Dai, Antao; Cai, Xiaoqing; Feng, Yang; Reedtz-Runge, Steffen; Hanson, Michael A; Yang, Huaiyu; Jiang, Hualiang; Stevens, Raymond C; Wang, Ming-Wei

    2016-06-17

    The glucagon-like peptide-1 receptor (GLP-1R) belongs to the secretin-like (class B) family of G protein-coupled receptors. Members of the class B family are distinguished by their large extracellular domain, which works cooperatively with the canonical seven-transmembrane (7TM) helical domain to signal in response to binding of various peptide hormones. We have combined structure-based site-specific mutational studies with molecular dynamics simulations of a full-length model of GLP-1R bound to multiple peptide ligand variants. Despite the high sequence similarity between GLP-1R and its closest structural homologue, the glucagon receptor (GCGR), nearly half of the 62 stably expressed mutants affected GLP-1R in a different manner than the corresponding mutants in GCGR. The molecular dynamics simulations of wild-type and mutant GLP-1R·ligand complexes provided molecular insights into GLP-1R-specific recognition mechanisms for the N terminus of GLP-1 by residues in the 7TM pocket and explained how glucagon-mimicking GLP-1 mutants restored binding affinity for (GCGR-mimicking) GLP-1R mutants. Structural analysis of the simulations suggested that peptide ligand binding mode variations in the 7TM binding pocket are facilitated by movement of the extracellular domain relative to the 7TM bundle. These differences in binding modes may account for the pharmacological differences between GLP-1 peptide variants.

  7. 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.

  8. MC1R, the cAMP pathway and the response to solar UV: Extending the horizon beyond pigmentation

    PubMed Central

    García-Borrón, Jose C; Abdel-Malek, Zalfa; Jiménez-Cervantes, Celia

    2014-01-01

    Summary 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. PMID:24807163

  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. Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue.

    PubMed

    Durymanov, Mikhail O; Slastnikova, Tatiana A; Kuzmich, Alexey I; Khramtsov, Yuri V; Ulasov, Alexey V; Rosenkranz, Andrey A; Egorov, Sergey Y; Sverdlov, Eugene D; Sobolev, Alexander S

    2013-12-01

    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 h 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 not more than 3 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 (123)I(-) 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.

  11. Interaction of MC1R and PMEL alleles on solid coat colors in Highland cattle.

    PubMed

    Schmutz, Sheila M; Dreger, Dayna L

    2013-02-01

    Six solid colors occur in Highland cattle: black, dun, silver dun and red, yellow, and white. These six coat colors are explained by a non-epistatic interaction of the genotypes at the MC1R and PMEL genes. A three base pair deletion in the PMEL gene leading to the deletion of a leucine from the signal peptide is observed in dilute-colored Highland cattle (c.50_52delTTC, p.Leu18del). The mutant PMEL allele acts in a semi-dominant manner. Dun Galloway cattle also have one copy of the deletion allele, and silver dun Galloway cattle have two copies. The presence of two adjacent leucine residues at the site of this deletion is highly conserved in human, horse, mouse and chicken as well as in cattle with undiluted coat colors. Highland and Galloway cattle thus exhibit a similar dose-dependent dilution effect based on the number of PMEL :c.50_51delTTC alleles, as Charolais cattle with PMEL :c.64G>A alleles. The PMEL :c.64G>A allele was not found in Highland or Galloway cattle.

  12. Application of polymerase chain reaction based on ITS1 rDNA to speciate Eimeria.

    PubMed

    Jenkins, M C; Miska, K; Klopp, S

    2006-03-01

    A method was developed to recover Eimeria spp. oocysts directly from poultry litter and determine which species of Eimeria were present using polymerase chain reaction (PCR) based on the ITS1 rDNA sequence. The species composition of Eimeria oocysts was also compared before and after propagation in susceptible chickens to determine if the relative proportion of each species changed after expansion. In samples from two broiler operations, ITS1-PCR was able to detect Eimeria spp. oocysts recovered from litter, with Eimeria acervulina, Eimeria maxima, and Eimeria praecox being the predominant species present therein. Although Eimeria tenella was found in one sample, the other species--Eimeria brunetti, Eimeria necatrix, and Eimeria mitis-were not detected. The species composition as determined by ITS1-PCR did not appear to appreciably alter after expansion in susceptible chickens. The described method represents a rapid means for determining the major Eimeria species in a poultry operation and may be helpful in choosing a particular live oocyst vaccine formulation to protect chickens against coccidiosis.

  13. 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

  14. 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.

  15. Bose-Einstein condensates with attractive 1/r interaction: The case of self-trapping

    SciTech Connect

    Papadopoulos, I.; Wagner, P.; Wunner, G.; Main, J.

    2007-11-15

    Amplifying on a proposal by O'Dell et al. for the realization of Bose-Einstein condensates of neutral atoms with attractive 1/r interaction, we point out that the instance of self-trapping of the condensate, without an external trap potential, is physically best understood by introducing appropriate 'atomic' units. This reveals a remarkable scaling property: the physics of the condensate depends only on the two parameters N{sup 2}a/a{sub u} and {gamma}/N{sup 2}, where N is the particle number, a the scattering length, a{sub u} the 'Bohr' radius, and {gamma} the trap frequency in atomic units. We calculate accurate numerical results for self-trapping wave functions and potentials, and for energies, sizes, and peak densities, and compare with previous variational results. We point out the existence of a second solution of the extended Gross-Pitaevskii equation for negative scattering lengths, with and without trapping potential, which is born together with the ground state in a tangent bifurcation. This indicates the existence of an unstable collectively excited state of the condensate for negative scattering lengths.

  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. Caustics of 1/r{sup n} binary gravitational lenses: from galactic haloes to exotic matter

    SciTech Connect

    Bozza, V.; Melchiorre, C. E-mail: cmelchiorre@unisa.it

    2016-03-01

    We investigate the caustic topologies for binary gravitational lenses made up of two objects whose gravitational potential declines as 1/r{sup n}. With n<1 this corresponds to power-law dust distributions like the singular isothermal sphere. The n>1 regime can be obtained with some violations of the energy conditions, one famous example being the Ellis wormhole. Gravitational lensing provides a natural arena to distinguish and identify such exotic objects in our Universe. We find that there are still three topologies for caustics as in the standard Schwarzschild binary lens, with the main novelty coming from the secondary caustics of the close topology, which become huge at higher n. After drawing caustics by numerical methods, we derive a large amount of analytical formulae in all limits that are useful to provide deeper insight in the mathematics of the problem. Our study is useful to better understand the phenomenology of galaxy lensing in clusters as well as the distinct signatures of exotic matter in complex systems.

  18. Trypsin resistance of a decapeptide KISS1R agonist containing an Nω-methylarginine substitution.

    PubMed

    Asami, Taiji; Nishizawa, Naoki; Ishibashi, Yoshihiro; Nishibori, Kimiko; Horikoshi, Yasuko; Matsumoto, Hirokazu; Ohtaki, Tetsuya; Kitada, Chieko

    2012-10-15

    Metastin/kisspeptin is an amidated peptide with 54 amino acid residues isolated from human placental tissues as a ligand of the orphan G-protein-coupled receptor KISS1R that is expressed throughout the central nervous system and in a variety of endocrine and gonadal tissues. Compared to the full-length metastin protein, the N-terminal truncated peptide metastin(45-54) has 3-10 times higher receptor affinity and enhanced ability to increase intracellular calcium concentration which is essential for activation of protein kinases involved in intracellular signaling in a number of pathways that affect reproduction and cell migration. However, metastin(45-54) is rapidly inactivated in serum. In this study, we designed and synthesized a number of metastin(45-54) analogs and evaluated their agonistic activity and trypsin resistance. Among analogs with substitutions of arginine at position 53, N(ω)(-)methylarginine analog 8 showed 3-fold more potent agonistic activity compared with metastin(45-54). Furthermore, analog 8 was shown to resist trypsin cleavage between positions 53 and 54. This substitution may be useful in the development of other Arg-containing peptides for which the avoidance of cleavage is desired.

  19. 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.

  20. Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome.

    PubMed

    Falik-Zaccai, Tzipora C; Barsheshet, Yiftah; Mandel, Hanna; Segev, Meital; Lorber, Avraham; Gelberg, Shachaf; Kalfon, Limor; Ben Haroush, Shani; Shalata, Adel; Gelernter-Yaniv, Liat; Chaim, Sarah; Raviv Shay, Dorith; Khayat, Morad; Werbner, Michal; Levi, Inbar; Shoval, Yishay; Tal, Galit; Shalev, Stavit; Reuveni, Eli; Avitan-Hersh, Emily; Vlodavsky, Eugene; Appl-Sarid, Liat; Goldsher, Dorit; Bergman, Reuven; Segal, Zvi; Bitterman-Deutsch, Ora; Avni, Orly

    2017-03-01

    Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients' fibroblasts and PPP1R13L-knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l-knocked down murine cardiomyocytes and hearts of Ppp1r13l-deficient mice. The hypersensitivity to lipopolysaccharide was NF-κB-dependent, and its inducible binding activity to promoters of pro-inflammatory cytokine genes was elevated in patients' fibroblasts. RNA sequencing of Ppp1r13l-knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13l-deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal-recessive cardio-cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.

  1. 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

  2. Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures.

    PubMed

    Xapelli, Sara; Agasse, Fabienne; Sardà-Arroyo, Laura; Bernardino, Liliana; Santos, Tiago; Ribeiro, Filipa F; Valero, Jorge; Bragança, José; Schitine, Clarissa; de Melo Reis, Ricardo A; Sebastião, Ana M; Malva, João O

    2013-01-01

    The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca(2+)]i) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.

  3. 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.

  4. Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role during Repair Kinetics after Selective Club Cell Ablation

    PubMed Central

    López, Icíar P.; Piñeiro-Hermida, Sergio; Pais, Rosete S.; Torrens, Raquel; Hoeflich, Andreas; Pichel, José G.

    2016-01-01

    Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice, and revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury. PMID:27861515

  5. On the reactive adsorption of ammonia on activated carbons modified by impregnation with inorganic compounds.

    PubMed

    Bandosz, Teresa J; Petit, Camille

    2009-10-15

    Ammonia adsorption was studied under dynamic conditions, at room temperature, on activated carbons of different origins (coal-based, wood-based and coconut-shell-based carbons) before and after their impregnation with various inorganic compounds including metal chlorides, metal oxides and polycations. The role of humidity was evaluated by running tests in both dry and moist conditions. Adsorbents were analyzed before and after exposure to ammonia by thermal analyses, sorption of nitrogen, potentiometric titration, X-ray diffraction and FTIR spectroscopy. Results of breakthrough tests show significant differences in terms of adsorption capacity depending on the parent carbon, the impregnates and the experimental conditions. It is found that surface chemistry governs ammonia adsorption on the impregnated carbons. More precisely, it was demonstrated that a proper combination of the surface pH, the strength, type and amount of functional groups present on the adsorbents' surface is a key point in ammonia uptake. Water can have either positive or negative effects on the performance of adsorbents. It can enhance NH(3) adsorption capacity since it favors ammonia dissolution and thus enables reaction between ammonium ions and carboxylic groups from the carbons' surface. On the other hand, water can also reduce the performance from the strength of adsorption standpoint. It promotes dissolution of ammonia and that ammonia is first removed from the system when the adsorbent bed is purged with air. Ammonia, besides adsorption by van der Waals forces and dissolution in water, is also retained on the surface via reactive mechanisms such as acid-base reactions (Brønsted and Lewis) or complexation. Depending on the materials used and the experimental conditions, 6-47% ammonia adsorbed is strongly retained on the surface even when the bed is purged with air.

  6. High-performance anode-supported solid oxide fuel cell with impregnated electrodes

    NASA Astrophysics Data System (ADS)

    Osinkin, D. A.; Bogdanovich, N. M.; Beresnev, S. M.; Zhuravlev, V. D.

    2015-08-01

    The 61%NiO + 39%Zr0.84Y0.16O1.92 (NiO-YSZ) and 56%NiO + 44%Zr0.83Sc0.16Ce0.01O1.92 (NiO-CeSSZ) composite powders have been prepared using two-steps and one-step combustion synthesis, respectively. The Ni-YSZ anode substrate with a low level of electrical resistance (less than 1 mOhm cm) and porosity of about 53% in the reduced state was fabricated. The functional layer of the anode with the high level of electrochemical activity was made of NiO-CeSSZ. The single anode-supported solid oxide fuel cell with the bi-layer Ni-cermet anode, Zr0.84Sc0.16O1.92 film electrolyte and the Pt + 3% Zr0.84Y0.16O1.92 cathode was fabricated. The power density and the U-I curves of the fuel cell at initial state and after impregnation of the cathode and anode by praseodymium and cerium oxides, respectively, have been measured at different temperatures. The maximum of power density of the initial fuel cell was 0.35 W cm-2 at conditions of wet hydrogen (air) supply to the anode (cathode) at 900 °C. After the electrodes were impregnated, the value of power density increased by seven times and was approximately 2.4 W cm-2 at 0.6 V. It was suggested that after the electrodes impregnation the polarization resistance of the fuel cell was determined by the gas diffusion in the supported anode.

  7. Fabrication and Characterization of Polycarbonate Polyurethane (PCPU) Nanofibers Impregnated with Nanofillers

    NASA Astrophysics Data System (ADS)

    Katakam, Hruday chand

    Polycarbonate polyurethane (PCPU) has been studied as a novel polymer impregnated with nanoparticles for improved mechanical, thermal and adhesion properties. This study investigates the synthesis of polycarbonate polyurethane (PCPU) polymeric nanofiber membranes by the process of electrospinning. This study further examines all the parameters associated with electrospinning a novel PCPU polymeric solution impregnated with nanofillers, such as nanoparticles, to produce fiber membranes. Tetrahydrofuran (THF) and N, N dimethylformamide (DMF) are used as solvents to dissolve PCPU polymer. One percent (1%) of nanofillers like silver and silica nanoparticles are added to PCPU polymer solution to investigate the impact on polymer solution properties, which in turn affects the fiber formation. Process parameters are studied by evaluating the impact each parameter has on the fiber formation. PCPU polymer concentrations of three polymer solutions (PCPU, PCPU + 1% silver and PCPU + 1% silica) with the appropriate solvent mixture ratio are achieved to produce polymeric fiber membranes with minimal bead formation. Polymeric nanofiber membranes of PCPU, PCPU + 1% silver and PCPU + 1% silica are produced using THF/DMF: 70/30 (V/V) solvent mixture. The polymeric nanofiber membranes obtained are characterized by using a scanning electron microscopy, rotational viscometer, tensiometer, contact angle measurement device, fourier transform infrared spectroscopy (FTIR). A comparative life cycle assessment (LCA) is performed to evaluate environmental impacts associated with solvents in the process of producing PCPU polymeric nanofiber membranes. The LCA is completed to gauge the potential impacts PCPU nanofiber membranes may have when utilized for various applications. This study discusses the successful production and characterization of good quality (no beading) polymeric nanofiber membranes of PCPU and novel composites of PCPU + 1% silver and PCPU + 1% silica. This two dimensional

  8. Microwave application on air drying of apple (var. Granny Smith). The influence of vacuum impregnation pretreatment

    NASA Astrophysics Data System (ADS)

    Martin Esparza, Maria Eugenia

    Combined hot air-microwave drying has been studied on apple (var. Granny Smith), with and without vacuum impregnation (VI) pretreatment with isotonic solution, respect to kinetics, microstructural and final quality items. In order to reach this objective, a drier has been designed and built, that allows to control and to register all the variables which take place during the drying process. Thermal and dielectric properties, that are very important characteristics when studying heat and mass transfer phenomena that occur during the combined drying process, have been related to temperature and/or moisture content throughout empirical equations. It could be observed that all these properties decreased with product moisture content. Respect to dielectric properties, a relationship among water binding forms to food structure and water molecules relaxation frequency has been found. On the other hand, the effect of drying treatment conditions (air rate, drying temperature, sample thickness and incident microwave power) on the drying rate, from an empirical model based on diffusional mechanisms with two kinetic parameters (k1 and k2), both function of the incident microwave power, has been studied. Microwave application to air drying implied a notable decrease on drying time, the higher the applied power the higher the reduction. Microstructural study by Cryo-Sem revealed fast water vaporization taking place when microwaves are applied. Vacuum impregnation did not implied an additional advantage for combined drying as drying rate was similar to that of NIV samples. Finally, it has been studied the influence of process conditions on the color and mechanical properties of the dried product (IV and NIV). Vacuum impregnation implied an increase on the fracture resistance and less purity and tone angle. Microwave application induced product browning with respect to air drying (tone decreased and purity increased).

  9. On the reactive adsorption of ammonia on activated carbons modified by impregnation with inorganic compounds

    SciTech Connect

    Bandosz, T.J.; Petit, C.

    2009-10-15

    Ammonia adsorption was studied under dynamic conditions, at room temperature, on activated carbons of different origins (coal-based, wood-based and coconut-shell-based carbons) before and after their impregnation with various inorganic compounds including metal chlorides, metal oxides and polycations. The role of humidity was evaluated by running tests in both dry and moist conditions. Adsorbents were analyzed before and after exposure to ammonia by thermal analyses, sorption of nitrogen, potentiometric titration, X-ray diffraction and FTIR spectroscopy. Results of breakthrough tests show significant differences in terms of adsorption capacity depending on the parent carbon, the impregnates and the experimental conditions. It is found that surface chemistry governs ammonia adsorption on the impregnated carbons. More precisely, it was demonstrated that a proper combination of the surface pH, the strength, type and amount of functional groups present on the adsorbents' surface is a key point in ammonia uptake. Water can have either positive or negative effects on the performance of adsorbents. It can enhance NH{sub 3} adsorption capacity since it favors ammonia dissolution and thus enables reaction between ammonium ions and carboxylic groups from the carbons' surface. On the other hand, water can also reduce the performance from the strength of adsorption standpoint. It promotes dissolution of ammonia and that ammonia is first removed from the system when the adsorbent bed is purged with air. Ammonia, besides adsorption by van der Waals forces and dissolution in water, is also retained on the surface via reactive mechanisms such as acid-base reactions (Bronsted and Lewis) or complexation. Depending on the materials used and the experimental conditions, 6-47% ammonia adsorbed is strongly retained on the surface even when the bed is purged with air.

  10. Adsorption of low concentration phosphine in yellow phosphorus off-gas by impregnated activated carbon.

    PubMed

    Wang, Xueqian; Ning, Ping; Shi, Yan; Jiang, Ming

    2009-11-15

    In order to utilize high concentration CO comprehensively, impregnated activated carbon sorbent and the catalytic oxidation reaction for PH(3) were investigated in this study. Carbon was impregnated with HCl, KNO(3), or hexanediol. The activated carbon modified by 7% (mass fraction) HCl could enhance the adsorption purification ability significantly. Raising the reaction temperature or increasing the oxygen content of the gas can improve the purification efficiency. The structure of the materials after modification was determined using nitrogen adsorption. The modification decreased the volume of pores smaller than 2 nm in diameter with the most noticeable change occurring in the micropores ranging from 0.3 nm to 1.5 nm in diameter. Decreases in micropore volume accounted for 87% of the total pore volume change. After the adsorption, the surface areas decreased 28%, 29% of which was due to decreased micropore surface. HCl significantly increased the performance of carbon as a PH(3) adsorbent when HCl impregnation was applied whereas the effects of other materials used in this study were much less pronounced. HCl present in the small pores probably acted as a catalyst for oxygen activation that caused PH(3) oxidation. As a result of this process, H(3)PO(4) and P(4)O(10) were formed, strongly adsorbed, and present in the small pores ranging from 0.3 nm to 1.5 nm. In conclusion, this study provides evidence that CO from industrial off-gas can be purified and used as the raw material for a broader range of products.

  11. 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

  12. MTSAT-1R satellite-based overshooting top detection and relationship to precipitation intensity

    NASA Astrophysics Data System (ADS)

    Li, Fu-ning; Yu, Fan

    2014-11-01

    Both satellite-based 11-um infrared window channel brightness temperature (IRW BT) and 6-7-um water vapor minus IRW BT difference (WV-IRW BTD) have been widely used in detection of convective overshooting top (OT). In this paper, considering a significant negative correlation between WV-IRW BTD and IRW BT (<0.7 in 93.07% cases) but a banded distribution, a combined parameter named weighted BTD (WBTD) is constructed for convective OT detection, which offers an improvement over the WV-IRW BTD technique. With this method, MTSAT-1R satellite data and ground station precipitation data during July to September in 2010 in east China are used to research the relationship between OT occurrence and precipitation, also to study the variations of precipitation intensity (PI) and mean WBTD (WBTD_M) during the evolution of convective clouds. The results show that (1) 58.2% of the analyzed OT cases appear a certain rainfall and 46.32% of these precipitation events record over 1mm/10min PI; (2) in all recorded over 1mm/10min precipitation events, OT occurrence probability in the corresponding region is 12.55%, greater probability happens in higher PI, in over 10mm/10min cases, the probability rises to 34%; (3) study in ten groups of strong convective clouds shows a positive correlation (up to 0.9) between WBTD_OI and PI; OT occurrence probability in cloud area is great when convection develops to a strong phase, while very small even no OTs in the early and late of convection.

  13. Variation of macrophage tropism among HIV-1 R5 envelopes in brain and other tissues.

    PubMed

    Peters, Paul J; Dueñas-Decamp, Maria J; Sullivan, W Matthew; Clapham, Paul R

    2007-03-01

    Human immunodeficiency virus (HIV)-positive individuals frequently suffer from progressive encephelopathy, which is characterized by sensory neuropathy, sensory myelopathy, and dementia. Our group and others have reported the presence of highly macrophage-tropic R5 variants of HIV-1 in brain tissue of patients with neurological complications. These variants are able to exploit low amounts of CD4 and/or CCR5 for infection and potentially confer an expanded tropism for any cell types that express low CD4 and/or CCR5. In contrast to the brain-derived envelopes, we found that envelopes from lymph node tissue, blood, or semen were predominantly non-macrophage-tropic and required high amounts of CD4 for infection. Nevertheless, where tested, the non-macrophage-tropic envelopes conferred efficient replication in primary CD4(+) T-cell cultures. Determinants of R5 macrophage tropism appear to involve changes in the CD4 binding site, although further unknown determinants are also involved. The variation of R5 envelopes also affects their sensitivity to inhibition by ligands and entry inhibitors that target CD4 and CCR5. In summary, HIV-1 R5 viruses vary extensively in macrophage tropism. In the brain, highly macrophage-tropic variants may represent neurotropic or neurovirulent viruses. In addition, variation in R5 macrophage tropism may also have implications (1) for transmission, depending on what role macrophages or cells that express low CD4 and/or CCR5 play in the establishment of infection in a new host, and (2) for pathogenesis and depletion of CD4(+) T cells (i.e., do highly macrophage-tropic variants confer a broader tropism among CD4(+) T-cell populations late in disease and contribute to their depletion?).

  14. 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.

  15. Design, synthesis, and biological evaluation of novel investigational nonapeptide KISS1R agonists with testosterone-suppressive activity.

    PubMed

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

    2013-11-14

    Metastin/kisspeptin is a 54 amino acid peptide ligand of the KISS1R receptor and is a critical regulator of GnRH secretion. The N-terminally truncated peptide, metastin(45-54), possesses a 10-fold higher receptor-binding affinity than full-length metastin and agonistic KISS1R activity but is rapidly inactivated in rodent plasma. We have developed a decapeptide analog [D-Tyr(45),D-Trp(47),azaGly(51),Arg(Me)(53)]metastin(45-54) with improved serum stability compared with metastin(45-54) but with decreased KISS1R agonistic activity. Amino acid replacements at positions 45-47 led to an enhancement of KISS1R agonistic activity and metabolic stability. N-terminal truncation resulted in a stable nonapeptide, [D-Tyr(46),D-Pya(4)(47),azaGly(51),Arg(Me)(53)]metastin(46-54), compound 26, which displayed KISS1R binding affinities comparable to metastin(45-54) and had improved serum stability. Compound 26 reduced plasma testosterone in male rats and is the first short-length metastin analog to possess testosterone suppressive activities. Compound 26 has led to the elucidation of investigational analogs TAK-683 and TAK-448, both of which have undergone clinical evaluation for hormone-dependent diseases such as prostate cancer.

  16. MiRNA-181b suppresses IGF-1R and functions as a tumor suppressor gene in gliomas.

    PubMed

    Shi, Zhu-Mei; Wang, Xie-Feng; Qian, Xu; Tao, Tao; Wang, Lin; Chen, Qiu-Dan; Wang, Xi-Rui; Cao, Lei; Wang, Ying-Yi; Zhang, Jun-Xia; Jiang, Tao; Kang, Chun-Sheng; Jiang, Bing-Hua; Liu, Ning; You, Yong-Ping

    2013-04-01

    MicroRNAs (miRNAs) are single-stranded, 18- to 23-nt RNA molecules that function as regulators of gene expression. Previous studies have shown that microRNAs play important roles in human cancers, including gliomas. Here, we found that expression levels of miR-181b were decreased in gliomas, and we identified IGF-1R as a novel direct target of miR-181b. MiR-181b overexpression inhibited cell proliferation, migration, invasion, and tumorigenesis by targeting IGF-1R and its downstream signaling pathways, PI3K/AKT and MAPK/ERK1/2. Overexpression of IGF-1R rescued the inhibitory effects of miR-181b. In clinical specimens, IGF-1R was overexpressed, and its protein levels were inversely correlated with miR-181b expression. Taken together, our results indicate that miR-181b functions in gliomas to suppress growth by targeting the IGF-1R oncogene and that miR-181b may serve as a novel therapeutic target for gliomas.

  17. 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.

  18. Assessment of gene expression levels of proopiomelanocortin (POMC) and melanocortin-1 receptor (MC1R) in vitiligo.

    PubMed

    Nagui, Noha A; Mahmoud, Sara B; Abdel Hay, Rania M; Hassieb, May M; Rashed, Laila A

    2015-10-06

    Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non-lesional skin of patients and from the non-sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real-time polymerase chain reaction. Both factors were significantly lower in lesional than non-lesional skin and controls, while they were significantly higher in non-lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non-lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non-lesional levels of POMC, as well as between the lesional and non-lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.

  19. Pigmentation in Black-boned sheep (Ovis aries): association with polymorphism of the MC1R gene.

    PubMed

    Deng, W D; Shu, W; Yang, S L; Shi, X W; Mao, H M

    2009-03-01

    Variations in vertebrate skin and hair color are due to varied amounts of eumelanin (brown/black) and phaeomelanin (red/yellow) produced by the melanocytes. The melanocortin 1 receptor (MC1R) is a regulator of eumelanin and phaeomelanin production in the melanocytes, and MC1R mutations causing coat color changes are known in many vertebrates. We have sequenced the entire coding region of the MC1R gene in Black-boned, Nanping indigenous and Romney Marsh sheep populations and found two silent mutation sites of A12G and G144C, respectively. PCR-RFLP of G144C showed that frequency of allele G in Black-boned, Nanping indigenous and Romney Marsh sheep was 0.818, 0.894 and 0, respectively. Sheep with GG genotype had significantly higher (P < 0.05) tyrosinase activity than sheep with CC genotype in the all investigated samples. Moreover, there was significant effect of MC1R genotype on coat color, suggesting that MC1R gene could affect coat color but not black traits. There would be merit in further studies using molecular techniques to elucidate the cause of black traits in these Black-boned sheep.

  20. 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

    2015-08-28

    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.

  1. CD99 triggering induces methuosis of Ewing sarcoma cells through IGF-1R/RAS/Rac1 signaling

    PubMed Central

    Manara, Maria Cristina; Terracciano, Mario; Mancarella, Caterina; Sciandra, Marika; Guerzoni, Clara; Pasello, Michela; Grilli, Andrea; Zini, Nicoletta; Picci, Piero; Colombo, Mario P.; Morrione, Andrea; Scotlandi, Katia

    2016-01-01

    CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis. This process, which is not detected in CD99-expressing normal mesenchymal cells, is inhibited by disruption of the IGF-1R signaling, whereas enhanced by IGF-1 stimulation. Induction of IGF-1R/RAS/Rac1 was also observed in the EWS xenografts that respond to anti-CD99 mAb, further supporting the role of the IGF/RAS/Rac1 axis in the hyperstimulation of macropinocytosis and selective death of EWS cells. Thus, we describe a vulnerability of EWS cells, including those resistant to standard chemotherapy, to a treatment with anti-CD99 mAb, which requires IGF-1R/RAS signaling but bypasses the need for their direct targeting. Overall, we propose CD99 targeting as new opportunity to treat EWS patients resistant to canonical apoptosis-inducing agents. PMID:27835596

  2. Sucrose-conditioned flavor preferences in sweet ageusic T1r3 and Calhm1 knockout mice.

    PubMed

    Sclafani, Anthony; Marambaud, Philippe; Ackroff, Karen

    2014-03-14

    The present study compared the ability of sweet ageusic T1r3 knockout (KO) and Calhm1 KO mice to acquire preferences for a sucrose-paired flavor as well as for unflavored sucrose. The KO and wildtype (WT) mice were given 24-h one-bottle access to 8% sucrose containing one flavor CS+, e.g., grape) and to water containing a different flavor (CS-, e.g., cherry) over 4 training days. In subsequent two-bottle tests with the flavors in water only, the T1r3 KO and Calhm1 KO mice, like WT mice, preferred the CS+ to the CS-. After training with flavored solutions, both KO groups also preferred unflavored 8% sucrose to water although Calhm1 KO mice required more sugar experience to match the preference of the T1r3 KO mice. These findings demonstrate that Calhm1 KO mice, like T1r3 KO mice and WT mice, are sensitive to the post-oral preference conditioning actions of sucrose and can discriminate sugar from water. Yet, despite their acquired sucrose preferences, the Calhm1 KO and T1r3 KO mice consumed only half as much sugar per day as did WT mice. Thus, sweet taste signaling elements are not needed in the gut for sugar conditioning, but sweet taste signaling in the mouth is essential for the full expression of sugar appetite.

  3. Photoperiodic regulation of melatonin membrane receptor (MT1R) expression and steroidogenesis in testis of adult golden hamster, Mesocricetus auratus.

    PubMed

    Mukherjee, Arun; Haldar, Chandana

    2014-11-01

    Photoperiodic modulation of melatonin membrane receptor (MT1R) expression in testis has never been reported for any seasonal breeder. Thus, the aim of the present study was to investigate the expression dynamics of MT1R in testis and its interaction with testicular steroidogenesis in a long-day breeder, Mesocricetus auratus. Hamsters were exposed to different photoperiodic conditions i.e. critical- (CP; 12.5L:11.5D); short-day- (SD; 8L:16D) and long-day- (LD; 16L:8D) for 10 weeks wherein testicular steroidogenesis, local melatonin synthesis and the expression of MT1R were analyzed. SD induced melatonin suppressed testicular steroidogenesis as evident from regressed testicular histoarchitecture, decreased expression of AR, StAR, LH-R, P₄₅₀SCC and enzyme activities of 3β- and 17β-HSD. Differential photoperiodic regulation of MT1R expression in testis suggests its involvement in photoperiodic signal transduction for seasonal adjustment of reproduction. Increased S-NAT (Serotonin N-acetyl transferase) activity and local testicular melatonin under SD condition suggest an inhibitory effect of the local melatonergic system on testicular steroidogenesis. Completely opposite responses were recorded for all the parameters analyzed when hamsters were exposed to CP or LD conditions. In conclusion, we may suggest that photoperiod via regulating circulatory and local melatonin level as well as MT1R expression in testes fine tunes the steroidogenesis and thereby, the reproductive status of male golden hamster.

  4. Factors affecting the retention of methyl iodide by iodide-impregnated carbon

    SciTech Connect

    Hyder, M.L.; Malstrom, R.A.

    1990-12-31

    Iodide-impregnated activated carbon that had been in use for up to 30 months was studied to characterize those factors that affect its interaction with and retention of methyl iodide. Humidity and competing organic sorbents were observed to decrease the residence time of the methyl iodide on the carbon bed. Additionally, changes in the effective surface area and the loss of iodide from the surface are both important in determining the effectiveness of the carbon for retaining radioactive iodine from methyl iodide. A simple model incorporating both factors gave a fairly good fit to the experimental data.

  5. Factors affecting the retention of methyl iodide by iodide-impregnated carbon

    SciTech Connect

    Hyder, M.L.; Malstrom, R.A.

    1990-01-01

    Iodide-impregnated activated carbon that had been in use for up to 30 months was studied to characterize those factors that affect its interaction with and retention of methyl iodide. Humidity and competing organic sorbents were observed to decrease the residence time of the methyl iodide on the carbon bed. Additionally, changes in the effective surface area and the loss of iodide from the surface are both important in determining the effectiveness of the carbon for retaining radioactive iodine from methyl iodide. A simple model incorporating both factors gave a fairly good fit to the experimental data.

  6. Prevention of hydrocephalus shunt catheter colonisation in vitro by impregnation with antimicrobials.

    PubMed Central

    Bayston, R; Grove, N; Siegel, J; Lawellin, D; Barsham, S

    1989-01-01

    A process is described by which hydrocephalus shunt catheters can be impregnated with antimicrobials. The processed catheters showed antimicrobial activity at their surfaces for long periods and could be sterilised by autoclaving. When tested in vitro in a model of catheter colonisation using large challenge doses of Staphylococcus epidermidis and prolonged perfusion, some antimicrobials failed to protect against colonisation whereas others protected against one or two challenges. A combination of rifampicin and clindamycin gave best results, protecting against three successive challenges over a 28 day perfusion period. Resistant organisms did not develop. The process is likely to be useful in prevention of hydrocephalus shunt infection. Images PMID:2732730

  7. Synthesis and characterization of high-stability solvent-impregnated resins

    SciTech Connect

    Alexandratos, S.D.; Ripperger, K.P.

    1998-12-01

    A copolymer comprised of glycidyl methacrylate and N,N-methylenebis(acrylamide) has been defined that can be used to coat solvent-impregnated resins (SIRs). Vinyl groups on the surface of a cross-linked macroporous support were used to anchor the polar copolymer to the surface of the bead. The coated SIR containing di(2-ethylhexyl)phosphoric acid maintained a high level of metal ion complexation (96% Cu(II)) over five cycles while the uncoated SIR dropped from 93% to 11% Cu(II) complexed in three cycles.

  8. A model for the impregnated cathode emission behaviour under ion bombardment

    NASA Astrophysics Data System (ADS)

    Schipper, D. J.; Steeghs, M. H. G.

    1985-12-01

    The electron current emitted by a cathode in the saturation region decrease if the cathode is exposed to ion bombardment. The change in surface coverage with barium (oxide) is used in the model to describe the current behaviour. The steady state current reached (equilibrium current) depends on the gas pressure. The experimental results can be explained in terms of the model and the parameters are determined. The temperature dependence of the barium supply rate for an S-and M-type impregnated cathode are determined.

  9. Use of insecticide-impregnated bed nets in Gambian primary health care: economic aspects.

    PubMed Central

    MacCormack, C. P.; Snow, R. W.; Greenwood, B. M.

    1989-01-01

    Village-wide use of permethrin-impregnated bed nets, compared with placebo-treated nets, has reduced clinical attacks of malaria by 63% in the Gambia. Costs were calculated for nets made by local tailors and for their treatment with insecticide in the villages, as well as for targeted chemoprophylaxis and back-up treatment for fever, in a comprehensive malaria control strategy through primary health care. The villagers' preferences for bed net fabrics and willingness to pay for them, and their preferences for various items of expenditure by ranked order, age group, and sex are given. Ethnic differences in the use of bed nets are also discussed. PMID:2743540

  10. Electrochemical impregnation and cycle life of lightweight nickel electrodes for nickel-hydrogen cells

    NASA Technical Reports Server (NTRS)

    Britton, Doris L.

    1990-01-01

    Development of a high specific energy nickel electrode is the main goal of the lightweight nickel electrode program at NASA-Lewis. The approach was to improve the nickel electrode by continuing combined in-house and contract efforts to develop a more efficient and lighter weight electrode for the nickel-hydrogen cell. Lightweight plaques are used as conductive supports for the nickel hydroxide active material. These plaques are commercial products that are fabricated into nickel electrodes by electrochemically impregnating them with active material. The electrodes are life cycle tested in a low earth orbit regime at 40 and 80 percent depths-of-discharge.

  11. Electrochemical impregnation and cycle life of lightweight nickel electrodes for nickel-hydrogen cells

    NASA Technical Reports Server (NTRS)

    Britton, Doris L.

    1990-01-01

    Development of a high specific energy nickel electrode is the main goal of the lightweight nickel electrode program at NASA-Lewis. The approach was to improve the nickel electrode by continuing combined in-house and contract efforts to develop a more efficient and lighter weight electrode for the nickel-hydrogen cell. Lightweight plaques are used as conductive supports for the nickel hydroxide active material. These plaques are commercial products that are fabricated into nickel electrodes by electrochemically impregnating them with active material. The electrodes are life cycle tested in a low Earth orbit regime at 40 and 80 percent depths-of-discharge.

  12. Mathematical modelling of the steam explosion treatment process for pre-impregnated lignocellulosic material

    NASA Astrophysics Data System (ADS)

    Prosvirnikov, D. B.; Ziatdinova, D. F.; Timerbaev, N. F.; Saldaev, V. A.; Gilfanov, K. H.

    2016-04-01

    The article analyses the physical picture of the process of steam explosion treatment of pre-impregnated lignocellulosic material, on the basis of which a mathematical modelling of the process is done. The mathematical modelling is represented in the form of differential equations with boundary conditions. The obtained mathematical description allows identifying the degree of influence of various factors on the kinetics of the process and producing a rational selection of operating parameters for the considered processes in terms of the set of application tasks.

  13. Gentamicin-impregnated collagen sponge for preventing sternal wound infection after cardiac surgery

    PubMed Central

    Targońska, Sylwia; Stążka, Janusz; Kozioł-Montewka, Maria

    2014-01-01

    The frequency of sternal wound infection (SWI) after cardiac surgery ranges from 0.5% to 8% and is associated with significant morbidity, mortality, and treatment cost. Perioperative antibiotic prophylaxis is not sufficient to fully prevent the contamination of the surgical access site. One of the most effective methods for the prevention of wound infection seems to be the use of gentamicin-impregnated collagen sponge, which is successfully used in abdominal and orthopedic surgery. Surgically implantable topical antibiotics can reduce wound infection in cardiac patients as well, but the efficacy of SWI prevention in cardiac surgery still raises many questions. PMID:26336388

  14. Gentamicin-impregnated collagen sponge for preventing sternal wound infection after cardiac surgery.

    PubMed

    Kozioł, Małgorzata; Targońska, Sylwia; Stążka, Janusz; Kozioł-Montewka, Maria

    2014-03-01

    The frequency of sternal wound infection (SWI) after cardiac surgery ranges from 0.5% to 8% and is associated with significant morbidity, mortality, and treatment cost. Perioperative antibiotic prophylaxis is not sufficient to fully prevent the contamination of the surgical access site. One of the most effective methods for the prevention of wound infection seems to be the use of gentamicin-impregnated collagen sponge, which is successfully used in abdominal and orthopedic surgery. Surgically implantable topical antibiotics can reduce wound infection in cardiac patients as well, but the efficacy of SWI prevention in cardiac surgery still raises many questions.

  15. Response of zooplankton and phytoplankton communities to creosote-impregnated Douglas fir pilings in freshwater microcosms.

    PubMed

    Sibley, P K; Harris, M L; Bestari, K T; Steele, T A; Robinson, R D; Gensemer, R W; Day, K E; Solomon, K R

    2004-07-01

    Creosote has been used extensively as an industrial wood preservative for the protection of marine pilings, railway ties, and utility poles and is a common source of polycyclic aromatic hydrocarbons (PAHs) into aquatic environments. At present, there is little information by which to judge the potential for creosote leached from impregnated pilings to cause toxicity to biota in aquatic environments. The objective of the current study was to assess the effects of creosote on zooplankton and phytoplankton populations in freshwater microcosms in relation to changes in the concentration and composition of PAHs leached from creosote-impregnated Douglas fir pilings during an 83-day exposure period. The study consisted of single microcosms containing one half, one, two, three, four, and six treated pilings. Two microcosms that received untreated pilings were used as controls. The total surface area of pilings in each microcosm was normalized by adding the appropriate number of untreated pilings. Samples were collected periodically between -14 and 83 days pre- and postexposure to determine aqueous concentrations of 15 priority PAHs and to assess the response of zooplankton and phytoplankton communities. Plankton community response to creosote was analyzed using principle responses curves. Peak aqueous concentrations of sigmaPAH occur