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Sample records for stabilizer ketotifen fumarate

  1. Interaction of Ketotifen Fumarate with Anhydrous Theophylline in ...

    African Journals Online (AJOL)

    Purpose: The purpose of the present study was to investigate interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH. Methods: By using Job's continuous-variation analysis and Ardon's spectrophotomeric methods, the values of stability constants of theophylline with ketotifen ...

  2. Interaction of Ketotifen Fumarate with Anhydrous Theophylline in ...

    African Journals Online (AJOL)

    HP

    Theophylline in Simulated Gastric and Intestinal Media and Effect on ... However, following theophylline interaction with ketotifen, stability constant was < 1 at gastric pH (0.4 and 2.0) ..... from pH as low as stomach acid (pH 0.4 to 3) to as high ...

  3. Potentiometric Determination of Ketotifen Fumarate in Pharmaceutical Preparations and Urine Using Carbon Paste and PVC Membrane Selective Electrodes

    Directory of Open Access Journals (Sweden)

    Eman Y. Z. Frag

    2011-01-01

    Full Text Available This study compares between unmodified carbon paste (CPE; the paste has no ion pair and polyvinyl chloride (PVC membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF, where sodium tetraphenylborate (NaTPB was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10−7 to 10−2 mol L−1. The electrodes show Nernstian slope value of 52.51±0.20 and 51.51±0.25 mV decade−1 for CPE and PVC membrane electrodes at 30∘C, respectively. The potential is nearly stable over the pH range 3.0–6.0 and 2.0–7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets, and biological fluid (urine. The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of 98.97±0.53 and 98.62±0.74 with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.

  4. Potentiometric determination of ketotifen fumarate in pharmaceutical preparations and urine using carbon paste and PVC membrane selective electrodes.

    Science.gov (United States)

    Frag, Eman Y Z; Mohamed, Gehad G; Khalil, Mohamed M; Hwehy, Mohammad M A

    2011-01-01

    This study compares between unmodified carbon paste (CPE; the paste has no ion pair) and polyvinyl chloride (PVC) membrane selective electrodes that were used in potentiometric determination of ketotifen fumarate (KTF), where sodium tetraphenylborate (NaTPB) was used as titrant. The performance characteristics of these sensors were evaluated according to IUPAC recommendations which reveal a fast, stable, and linear response for KTF over the concentration range of 10(-7) to 10(-2) mol L(-1). The electrodes show Nernstian slope value of 52.51 ± 0.20 and 51.51 ± 0.25 mV decade(-1) for CPE and PVC membrane electrodes at 30°C, respectively. The potential is nearly stable over the pH range 3.0-6.0 and 2.0-7.0 for CPE and PVC membrane electrodes, respectively. Selectivity coefficient values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. The electrodes responses at different temperatures were also studied, and long operational lifetime of 12 and 5 weeks for CPE and PVC membrane electrodes, respectively, were found. These are used for determination of ketotifen fumarate using potentiometric titration, calibration, and standard addition methods in pure samples, its pharmaceutical preparations (Zaditen tablets), and biological fluid (urine). The direct potentiometric determination of KTF using the proposed sensors gave recoveries % of 98.97 ± 0.53 and 98.62 ± 0.74 with RSD 1.42 and 0.63% for CPE and PVC membrane selective electrodes, respectively. Validation of the method shows suitability of the proposed sensors for use in quality control assessment of KTF. The obtained results were in a good agreement with those obtained using the reported spectrophotometric method.

  5. Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

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    Asuka Baba

    2016-01-01

    Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

  6. Generic selection criteria for safety and patient benefit [V]: Comparing the pharmaceutical properties and patient usability of original and generic nasal spray containing ketotifen fumarate.

    Science.gov (United States)

    Wada, Yuko; Ami, Shyoko; Nozawa, Mitsuru; Goto, Miho; Shimokawa, Ken-Ichi; Ishii, Fumiyoshi

    The pH, osmotic pressure (cryoscopy), viscosity, squeeze force, spray angle, and spraying frequency of nasal spray containing ketotifen fumarate (1 brand-name product and 8 generic products) were measured. Based on the results of pH measurement, all products were weakly acidic (4.0 to 5.1). For all products, the osmotic pressure ratio to physiological saline was approximately 1. The viscosity of various products ranged from approximately 1.0 to 1.5 mPa·s. The spray angle of drug solution differed among the products: minimum, 46 degrees (Sawai and Fusachol); and maximum, 68.7 degrees (Sekiton). In particular, TOA, Sawai, Fusachol, and TYK showed significantly smaller angles compared to Zaditen (brand-name product). Container properties varied among the products: minimum squeeze force, 19.0 N (Sekiton); and maximum squeeze force, 43.1 N (Sawai). Based on these results, although all the above products are identical in dosage form and active ingredient, the differences in pharmaceutical properties, such as container operations and drug-solution spraying/attachment, may markedly influence patients' subjective opinions.

  7. Comparing the effects of ketotifen fumarate eye drops and ketotifen oral pills on symptom severity and quality of life in patients with allergic rhinitis: a double-blind randomized clinical trial.

    Science.gov (United States)

    Akhavan, Asghar; Karimi-Sari, Hamidreza; Khosravi, Mohammad Hossein; Arefzadeh, Esmaeil; Yavarahmadi, Mohammadhosein

    2015-05-01

    Allergic rhinitis is a chronic inflammatory disease of nasal mucosa. Previous studies have shown the therapeutic effects of ketotifen eye drops on allergic conjunctivitis and rhinitis patients. This study was designed to compare the effects of ketotifen drops and oral ketotifen pills on symptoms and quality of life in allergic rhinitis patients. In this double-blind randomized clinical trial, patients with mild allergic rhinitis who were referred to the allergy clinic of Baqiyatallah Hospital from March to April 2014 were randomly allocated to 2 groups; the first group received ketotifen drops (1 drop every 12 hours) with placebo pills (2 pills daily), and the second group received placebo eye drops with ketotifen pills for 4 weeks. Symptoms (sneezing, runny nose, itching, and nasal obstruction) severity were examined and Rhinitis Quality of Life Questionnaire (RQLQ) scores were evaluated in the second and fourth weeks. A total of 140 patients were evaluated in 2 groups. The mean age was 30.33 years. There were no significant differences in demographic data between the groups (p > 0.05). Both groups showed a significant improvement in rhinorrhea, nasal congestion, nasal itching, coughing, sneezing, RQLQ, and nasal smear eosinophil percent compared to baseline amounts (p < 0.05). Improvements were significantly more in the drops group (p < 0.05). Because of the absence of systemic complications in ketotifen eye drops in patients with allergic rhinitis and their easy availability in Iran, using this medication instead of systemic therapies is suggested. Nevertheless, more studies are required to evaluate the long-term effects of using this drug and the recurrence rate of symptoms. © 2015 ARS-AAOA, LLC.

  8. Comparison of preservative-free ketotifen fumarate and preserved olopatadine hydrochloride eye drops in the treatment of moderate to severe seasonal allergic conjunctivitis.

    Science.gov (United States)

    Mortemousque, B; Bourcier, T; Khairallah, M; Messaoud, R; Brignole-Baudouin, F; Renault, D; Rebika, H; Brémond-Gignac, D

    2014-01-01

    To compare preservative-free ketotifen 0.025% ophthalmic solution to olopatadine 0.1% ophthalmic solution in with the treatment of seasonal allergic conjunctivitis (SAC) in clinical practice. This was a comparative, randomised, investigator-masked, pilot clinical study in adult patients with documented history of SAC and presenting with moderate to severe itching and conjunctival hyperemia. Eligible patients initiated either ketotifen or olopatadine treatment at a dose of one drop twice daily for 28days. The resolution of ocular signs and symptoms was assessed on day 7 and day 28. Itching was also assessed within 15minutes following the first instillation (day 0). Conjunctival impression cytology was performed at each visit to assess the evolution of ICAM-1 expression (day 0, 7 and 28). Seventy-five patients were randomised (ketotifen: 38 patients; olopatadine: 37 patients). At day 28, the composite score for primary criteria (itching, tearing, and conjunctival hyperemia) improved from 6.8±1.2 to 0.9±1.0 in the Ketotifen group, without statistically significant difference between treatment groups (P=0.67). There was no relevant difference between treatment groups in other efficacy parameters, except a trend for a more rapid resolution of conjunctival hyperemia in the Ketotifen group. Both drugs were well tolerated, with a trend for a better tolerability reported by patients on ketotifen compared to those on olopatadine at day 7 (P=0.054). A rapid and comparable improvement in SAC was achieved after 28days of treatment with both preservative-free ketotifen and preserved olopatadine ophthalmic solutions, with a slightly better ocular tolerance with unpreserved ketotifen 0.025% eye drops. Copyright © 2013. Published by Elsevier Masson SAS.

  9. Quantification of fumarate and investigation of endogenous and exogenous fumarate stability in rat plasma by LC-MS/MS.

    Science.gov (United States)

    Shi, Yao; Tse, Susanna; Rago, Brian; Yapa, Udeni; Li, Fumin; Fast, Douglas M

    2016-04-01

    Fumaric acid is a commonly used excipient in pharmaceutical products. It is not known if its presence may lead to fluctuation of endogenous fumarate levels. An LC-MS/MS method was developed and validated to quantify fumarate in support of a toxicokinetics study. Stability evaluation showed that endogenous fumarate was stable for 6 h at room temperature, while exogenously added fumaric acid was converted to malate within 1 h due to the presence of fumarase. Citric acid, a fumarase inhibitor, prevented the conversion of added fumaric acid in rat plasma. The method was validated in citric acid stabilized rat plasma using a surrogate matrix approach. A discrepancy in stability was observed between endogenous fumarate and exogenously added fumaric acid.

  10. The effect of ketotifen on inflammatory markers in allergic conjunctivitis: an open, uncontrolled study

    Directory of Open Access Journals (Sweden)

    Gagliardi Julio

    2003-01-01

    Full Text Available Abstract Background The efficacy and safety of ketotifen eye drop treatment in allergic conjunctivitis (AC management is perfectly known by several studies, but the mechanism of action at the biochemical levels is poorly understood so we decided to perform an open, uncontrolled study in order to investigate the effect of the topical administration of ketotifen fumarate 0.05% on biochemical markers of inflammation on conjunctival cells in patients with AC. Methods Nineteen patients with symptoms and signs of AC (itching, discharge, burning, redness, increase in the watery discharge, swelling and follicles and with a history of allergy were prescribed with two daily instillation of one drop of eyewash ketotifen fumarate 0,05% in both eyes during thirty days. They were studied by measuring clinical and immunologic parameters. Results Ketotifen fumarate treatment significantly reduced the total symptoms and signs score for each patient as well as each symptoms and signs at all time points compared with day 0 (p Conclusion Ketotifen besides the well-known effect in reducing signs and symptoms of AC significantly diminished production of eotaxin and expression of CD29 by epithelial cells in patients with seasonal AC.

  11. Development and Validation of a Stability-Indicating LC-UV Method ...

    African Journals Online (AJOL)

    Keywords: Ketotifen, Cetirizine, Stability indicating method, Stressed conditions, Validation. Tropical ... in biological fluids [13] are also reported. Stability indicating HPLC method is reported for ketotifen where drug is ..... paracetamol, cetirizine.

  12. Effects of ketotifen on human lymphocytes in vitro and in vivo

    NARCIS (Netherlands)

    Petrasch, S.; van Tits, L. J.; Motulsky, H. J.; Brodde, O. E.; Michel, M. C.

    1993-01-01

    The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen-

  13. A Validated Stability Indicating RP-HPLC Method for the Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Pharmaceutical Dosage Form

    Science.gov (United States)

    Runja, Chinnalalaiah; Ravi Kumar, Pigili; Avanapu, Srinivasa Rao

    2016-01-01

    A new simple, rapid stability indicating assay method has been developed and validated for the determination of emtricitabine, tenofovir disoproxil fumarate, elvitegravir and cobicistat using reverse-phase high-performance liquid chromatography in their pharmaceutical dosage form. The chromatographic separation was performed on an ODS column (250 × 4.6 mm, 5 µm) using mobile phase A (potassium dihydrogen orthophosphate, pH adjusted to 2.5) and mobile phase B (acetonitrile) in the ratio of 55:45% v/v at a flow rate of 1 mL/min. The analytes were detected at 250 nm. The method was found to be linear in the concentration range of 2–12 µg/mL for EMT, 3–18 µg/mL for TNDF, 1.5–9 µg/mL for ELV and COB, with the coefficient value (R2) of >0.9990. The accuracy was measured via recovery studies and found to be acceptable, and the percentage recoveries were found in the range of 99.93–100.08 ± 0.5%. Forced degradation studies were also conducted, and the drugs were subjected to various stress conditions such as acid hydrolysis, base hydrolysis, oxidative, photolytic and thermal degradation. The proposed method was successfully validated and applied for the quantitative estimation of these drugs in both bulk and tablet dosage forms. PMID:26865655

  14. Ketotifen, a mast cell blocker improves sperm motility in asthenospermic infertile men

    Directory of Open Access Journals (Sweden)

    Nasrin Saharkhiz

    2013-01-01

    Full Text Available Aim: This study aimed to evaluate the efficacy of ketotifen on sperm motility of asthenospermic infertile men. Setting and Design: It is a prospective study designed in vivo. Materials and Methods: In this interventional experimental study, a total of 40 infertile couples with asthenospermic infertility factor undergoing assisted reproductive technology (ART cycles were enrolled. The couples were randomly assigned to one of two groups at the starting of the cycle. In control group (n = 20, the men did not receive Ketotifen, while in experiment group (n = 20, the men received oraly ketotifen (1 mg Bid for 2 months. Semen analysis, under optimal circumferences, was obtained prior to initiation of treatment. The second semen analysis was done 2-3 weeks after stopped ketotifen treatment and sperm motility was defined. Clinical pregnancy was identified as the presence of a fetal sac by vaginal ultrasound examination. Statistical Analysis Used: All data are expressed as the mean ± standard error of mean (SEM. t test was used for comparing the data of the control and treated groups. Results: The mean sperm motility increased significantly (from 16.7% to 21.4% after ketotifen treatment (P < 0.001. This sperm motility improvement was more pronounced in the primary infertility cases (P < 0.003. The rate of pregnancy was 12.5% in infertile couples that their men receiving 1 mg/twice a day ketotifen. In 52% of infertile men′s semen, the percentage of sperm motility was increased from 5% to 35% and this sperm motility improvement was also observed in 33% of necrospermia (0% motility cases. Conclusion: These results suggest that ketotifen may represent as a novel therapeutic approach to improve sperm motility in the infertile men with cause of asthenospermia or necrospermia.

  15. Fumaric acid production by fermentation

    NARCIS (Netherlands)

    Roa Engel, C.A.; Straathof, A.J.J.; Zijlmans, T.W.; Van Gulik, W.M.; Van der Wielen, L.A.M.

    2008-01-01

    Abstract The potential of fumaric acid as a raw material in the polymer industry and the increment of cost of petroleum-based fumaric acid raises interest in fermentation processes for production of this compound from renewable resources. Although the chemical process yields 112% w/w fumaric acid

  16. 21 CFR 172.350 - Fumaric acid and salts of fumaric acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Fumaric acid and salts of fumaric acid. 172.350... HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.350 Fumaric acid and salts of fumaric acid. Fumaric acid and its calcium, ferrous, magnesium, potassium, and sodium salts may be safely used...

  17. Protective effect of ketotifen and disodium cromoglycate against bronchoconstriction induced by aspirin, benzoic acid or tartrazine in intolerant asthmatics.

    Science.gov (United States)

    Wüthrich, B

    1979-01-01

    Oral challenge tests with acetylsalicylic acid, tartrazine or benzoic acid were performed in 7 intolerant asthmatic patients after a 3-day treatment with either orally taken ketotifen (1 mg twice daily) or inhaled disodium cromoglycate (20 mg four times daily) at random. Protection was noted with ketotifen in 5, with DSCG in 3 patients. On the evaluation of the mean percentage of the maximum decline in the forced expiratory volume in 1 sec (FEV1) only ketotifen afforded significant protection statistically (p less than 0.05). All the intolerant asthmatics studies showed, as an immunological abnormity, a slight, but significant decrease of the C1-inhibitor levels. Moreover, in three out of these the alpha 1-antitrypsin serum values were under the lower normal range.

  18. Hydrothermal synthesis and crystal structure of a new lanthanum(III coordination polymer with fumaric acid

    Directory of Open Access Journals (Sweden)

    Hayet Anana

    2015-05-01

    Full Text Available The title compound, poly[diaquatris(μ4-but-2-enedioato(μ2-but-2-enedioic aciddilanthanum(III], [La2(C4H2O43(C4H4O4(H2O2]n, was synthesized by the reaction of lanthanum chloride pentahydrate with fumaric acid under hydrothermal conditions. The asymmetric unit comprises an LaIII cation, one and a half fumarate dianions (L2−, one a half-molecule of fumaric acid (H2L and one coordinated water molecule. Each LaIII cation has the same nine-coordinate environment and is surrounded by eight O atoms from seven distinct fumarate moieties, including one protonated fumarate unit and one water molecule in a distorted tricapped trigonal–prismatic environment. The LaO8(H2O polyhedra centres are edge-shared through three carboxylate bridges of the fumarate ligand, forming chains in three dimensions to construct the MOF. The crystal structure is stabilized by O—H...O hydrogen-bond interactions between the coordinated water molecule and the carboxylate O atoms, and also between oxygen atoms of fumaric acid

  19. Diseño de una formulación de ketotifeno 0,025 % colirio Design of a Ketotifen formula: 0.025 % eyedrops

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    Yenilen Troche Concepción

    2010-06-01

    Full Text Available El colirio de ketotifeno se indica para aliviar los signos y síntomas de las conjuntivitis alérgicas, por ser este un potente antihistamínico H1 que muestra cierta capacidad para inhibir la liberación de histamina y otros mediadores en mastocitos. El objetivo del presente trabajo consistió en realizar el desarrollo tecnológico del colirio de ketotifeno 0,025 %, de producción nacional teniendo en cuenta que es un medicamento muy utilizado en la "Operación Milagro", en la cual participa la República de Cuba, para lo que se hace un diseño y los estudios de preformulación. Se estudió además, las especificaciones de calidad de la formulación seleccionada, la estabilidad del producto y el tiempo de vigencia de este. Se realizó el estudio de estabilidad acelerado y por vida de estante, para lo cual se emplearon 3 lotes del producto a escala piloto. El colirio resultó estable física, química y microbiológicamente envasado en frascos de polietileno de baja densidad, por espacio de 12 meses a temperatura ambienteThe Ketotifen eyedrops is prescribed to relieve the signs and symptoms of allergic conjunctivitis due to it is a powerful H1 antihistaminic with certain ability to inhibit the histamine release and other mediators in the case of mast cells. The aim of present paper was to perform the technological development of 0.025 % eyedrops Ketotifen of national production considering that it is a drug very used in the "Operación Milagro" with participation of the Republic of Cuba and with its own design and the pre-formula. Also, we studied the selected formula specifications, the product stability and its expiry date. An accelerated stability study was conducted and by shelf life using 3 batches of pilot scale product. The eyedrops was physically, chemically and microbiologically stable when it is bottling in low-density polyethylene flasks during 12 months at room temperature.

  20. Emtricitabine/tenofovir disoproxil fumarate.

    Science.gov (United States)

    2004-01-01

    Gilead Sciences is developing a fixed-dose co-formulation of two of its reverse transcriptase inhibitors, emtricitabine [Emtriva] and tenofovir disoproxil fumarate [Viread], for once-daily dosing in combination with other antiretrovirals for the treatment of HIV infection. Each co-formulated tablet will contain 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine. Emtricitabine [Emtriva] is a nucleoside reverse transcriptase inhibitor (NRTI) with demonstrated potent activity against HIV and hepatitis B virus (HBV). It was first approved in the US by the FDA in July 2003 and is indicated for adults aged > or =18 years. Safety and effectiveness in paediatric patients have not been established. In antiretroviral-treatment-experienced patients, the use of emtricitabine may be considered for adults with HIV strains that are expected to be susceptible to the drug as assessed by genotypic or phenotypic testing. The recommended dose of emtricitabine is one 200 mg capsule daily, with or without food. In the European Union, emtricitabine is indicated in combination with other antiretroviral agents for the treatment of HIV in adults and children, where it is also licensed as an oral 10 mg/mL solution. The oral solution is for use in infants older than 4 months, children and patients unable to swallow hard capsules, and patients with renal impairment who require dose reduction. Tenofovir disoproxil fumarate [Viread] is a nucleotide reverse transcriptase inhibitor that is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients. The drug was first approved in the US in October 2001, followed by further approvals in the European Union, Australia, Iceland, Brazil, Canada and Switzerland. The drug has been launched in all these countries. In February 2003, the EMEA's advisory committee adopted a positive opinion to extend the indication of tenofovir disoproxil fumarate in all 15 member states to

  1. Ketotifen Ophthalmic

    Science.gov (United States)

    ... class of medications called antihistamines. It works by blocking histamine, a substance in the body that causes ... the remaining fingers of that hand against your face. While looking up, gently squeeze the dropper so ...

  2. Aluminium fumarate and CPO-27(Ni) MOFs: Characterization and thermodynamic analysis for adsorption heat pump applications

    International Nuclear Information System (INIS)

    Elsayed, Eman; AL-Dadah, Raya; Mahmoud, Saad; Elsayed, Ahmed; Anderson, Paul A.

    2016-01-01

    Highlights: • CPO-27(Ni) and aluminium fumarate were investigated for adsorption heating, cooling and desalination applications. • Both MOFs have high potential in adsorption applications. • The optimum desorption temperature for the CPO-27(Ni) is higher than 90 °C, and for aluminium fumarate, it is 55–70 °C. • CPO-27(Ni) outperforms aluminium fumarate at low evaporation temperature (5 °C). • Aluminium fumarate outperforms CPO-27(Ni) at high evaporation temperature (20 °C). - Abstract: Metal-organic framework (MOF) materials are new porous materials with high surface area, pore size and volume, and tunable pore geometry thus providing high adsorption capacity. Currently, limited MOF materials with high water adsorption capabilities and hydrothermal stability are available on a large scale. Two MOF materials, namely CPO-27(Ni) and aluminium fumarate, have been identified to have a high hydrothermal stability, high water uptake of 0.47 g_H_2_O_.g_a_d_s"−"1 and 0.53 g_H_2_O_.g_a_d_s"−"1 at a relative pressure of 0.9 and are commercially available. This work aims to measure the water adsorption characteristics of these two MOF materials in terms of isotherms, kinetics and cyclic stability. Also the thermodynamic cycle performance of such materials based on their equilibrium adsorption data was investigated under different operating conditions for various adsorption applications such as heating, cooling and water desalination. Results showed that the CPO-27(Ni)/water pair outperformed the aluminium fumarate/water pair at low evaporation temperatures (5 °C) and high desorption temperatures (≥90 °C), while the aluminium fumarate/water pair was more suitable for applications requiring high evaporation temperature (20 °C) and/or low desorption temperature (70 °C).

  3. Fumar o no fumar, en restoranes, hoteles y cantinas

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    Francisco Javier López-Antuñano

    2002-01-01

    Full Text Available Con el objetivo de revisar la información sobre los efectos adversos de fumar tabaco y de la exposición al humo del tabaco en el ambiente (HTA, se revisó la base de MEDLINE para identificar citas relevantes. Los efectos adversos a la salud, de la exposición al HTA, son daños ocupacionales significativos para los trabajadores de los servicios de alimentación. Se han demostrado altos niveles de sustancias mutagénicas en el aire ambiental de restoranes y en la orina de los trabajadores, así como la exposición al 3-aminofenil, un carcinógeno asociado con la hemoglobina. La mejor manera de proteger a estos trabajadores es reducir el consumo de tabaco en restoranes, hoteles, cantinas y tabernas. En trabajadores de restoranes es evidente el incremento del riesgo de cáncer pulmonar atribuible a la exposición al HTA.A MEDLINE search was conducted to identify relevant references, to review the information on adverse effects of tobacco smoking and environmental tobacco smoke (ETS. Occupational exposure to ETS causes significant damages to food industry workers. High levels of mutagenic substances have been demonstrated in restaurant air as well as in the urine samples from those workers. Exposition to 3-aminophenyl, a hemoglobine-associated carcinogen. The best way to protect these workers is the reduction of tobacco smoking in restaurants, hotels, bars and taverns. In restaurant workers, ETS attributable risk for lung cancer is evident.

  4. Preparation of polymer blends from glycerol, fumaric acid and of poly(ethylene terephthalate) (PET) recycled

    International Nuclear Information System (INIS)

    Medeiros, Marina A.O.; Guimaraes, Danilo H.; Brioude, Michel M.; Jose, Nadia M.; Prado, Luis A.S. de A.

    2011-01-01

    Polymer blends based on recycled poly(ethylene terephthalate) (PET) and poly(glycerol fumarate) polyesters were prepared in different PET concentrations. The PET powder was dispersed during the poly(glycerol fumarate) synthesis at 260 deg C. The resulting blends were characterized by X-ray diffraction. The thermal stability of the materials was evaluated by thermogravimetric analysis and differential scanning calorimetry. The morphology was studies by scanning electron microscopy. The blends were clearly immiscible. The possibility of (interfacial) compatibilization of the PET domains, caused by transesterification reactions between PET and glycerol were discussed. (author)

  5. Fumaric Acid Production: A Biorefinery Perspective

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    Victor Martin-Dominguez

    2018-05-01

    Full Text Available The increasing scarcity of fossil raw materials, together with the need to develop new processes and technology based on renewable sources, and the need to dispose of an increasing amount of biomass-derived waste, have boosted the concept of biorefineries. Both 1G and 2G biorefineries are focused on the obtention of biofuels, chemicals, materials, food and feed from biomass, a renewable resource. Fumaric acid, and most compounds involved in the Kreb cycle, are considered key platform chemicals, not only for being acidulants and additives in the food industry, but also for their prospective use as monomers. This review is focused on the biotechnological processes based on fungi, mainly of the Rhizopus genus, whose main product is fumaric acid, on the process conditions, the bioreactors and modes of operation and on the purification of the acid once it is produced.

  6. Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

    Science.gov (United States)

    Muir, J F; Bertin, L; Georges, D

    1992-11-01

    We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

  7. Malate and fumarate extend lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Clare B Edwards

    Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

  8. Footwear contact dermatitis from dimethyl fumarate.

    Science.gov (United States)

    Švecová, Danka; Šimaljakova, Maria; Doležalová, Anna

    2013-07-01

    Dimethyl fumarate (DMF) is an effective inhibitor of mold growth. In very low concentrations, DMF is a potent sensitizer that can cause severe allergic contact dermatitis (ACD). It has been identified as the agent responsible for furniture contact dermatitis in Europe. The aim of this study was to evaluate patients in Slovakia with footwear ACD associated with DMF, with regard to clinical manifestations, patch test results, and results of chemical analysis of their footwear. Nine patients with suspected footwear contact dermatitis underwent patch testing with the following allergens: samples of their own footwear, commercial DMF, the European baseline, shoe screening, textile and leather dye screening, and industrial biocides series. The results were recorded according to international guidelines. The content of DMF in footwear and anti-mold sachets was analyzed using gas chromatography and mass spectrometry. Acute ACD was observed in nine Caucasian female patients. All patients developed delayed sensitization, as demonstrated by positive patch testing using textile footwear lining. Seven patients were patch tested with 0.1% DMF, and all seven were positive. Chemical analysis of available footwear showed that DMF was present in very high concentrations (25-80 mg/Kg). Dimethyl fumarate is a new footwear allergen and was responsible for severe ACD in our patients. To avoid an increase in the number of cases, the already approved European preventive measures should be accepted and commonly employed. © 2013 The International Society of Dermatology.

  9. Development and Validation of a Stability-Indicating LC-UV Method ...

    African Journals Online (AJOL)

    Development and Validation of a Stability-Indicating LC-UV Method for Simultaneous Determination of Ketotifen and Cetirizine in Pharmaceutical Dosage Forms. ... 5 μm) using an isocratic mobile phase that consisted of acetonitrile and 10 mM disodium hydrogen phosphate buffer (pH 6.5) in a ratio of 45:55 % v/v at a flow ...

  10. Fumaric acid production by Rhizopus oryzae and its facilitated ...

    African Journals Online (AJOL)

    Anupreet

    2014-03-05

    Mar 5, 2014 ... Currently, fumaric acid is produced from petroleum based derivative maleic ... best possible option that came up for the strip phase was an alkaline medium. .... Future directions of membrane gas separation technology. Indus.

  11. Identification, characterization, and high-performance liquid chromatography quantification of process-related impurities in vonoprazan fumarate.

    Science.gov (United States)

    Liu, Lei; Cao, Na; Ma, Xingling; Xiong, Kaihe; Sun, Lili; Zou, Qiaogen

    2016-04-01

    High-performance liquid chromatography analysis of vonoprazan fumarate, a novel proton pump inhibitor drug revealed six impurities. These were identified by liquid chromatography with mass spectrometry. Further, the structures of the impurities were confirmed by synthesis followed by characterization by mass spectrometry, NMR spectroscopy, and infrared spectroscopy. On the basis of these data and knowledge of the synthetic scheme of vonoprazan fumarate, the previously unknown impurity was identified as 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methyldimethylamine, which is a new compound. The possible mechanisms by which these impurities were formed were also discussed. A high-performance liquid chromatography method was optimized in order to separate, selectively detect, and quantify all process-related impurities of vonoprazan fumarate. The presented method has been validated in terms of linearity, limits of detection, and quantification, and response factors and, therefore, is highly suitable for routine analysis of vonoprazan fumarate related substances as well as stability studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Branch retinal vein occlusion associated with quetiapine fumarate

    Directory of Open Access Journals (Sweden)

    Siang Lim

    2011-08-01

    Full Text Available Abstract Background To report a case of branch retinal vein occlusion in a young adult with bipolar mood disorder treated with quetiapine fumarate. Case Presentation A 29 years old gentleman who was taking quetiapine fumarate for 3 years for bipolar mood disorder, presented with sudden vision loss. He was found to have a superior temporal branch retinal vein occlusion associated with hypercholesterolemia. Conclusion Atypical antipsychotic drugs have metabolic side effects which require regular monitoring and prompt treatment.

  13. Solution thermodynamics of valnemulin hydrogen fumarate in different pure solvents

    International Nuclear Information System (INIS)

    Ouyang, Jinbo; Wang, Jingkang; Huang, Xin; Bao, Ying; Wang, Yongli; Yin, Qiuxiang; Liu, Ailing; Li, Xudong; Hao, Hongxun

    2015-01-01

    Highlights: • The solubility of valnemulin hydrogen fumarate in five pure solvents was experimentally determined. • The solubility data were correlated by Wilson model, NRTL model and UNIQUAC model. • Mixing thermodynamic properties of valnemulin hydrogen fumarate in five pure solvents were calculated. - Abstract: Solubility of valnemulin hydrogen fumarate in five pure solvents was determined within temperature range of (278.15 to 323.15) K by a gravimetric method. The results show that the solubility of valnemulin hydrogen fumarate in tested pure solvents increases with the increasing temperature. The solubility values were correlated by the Wilson model, NRTL model and UNIQUAC model. The UNIQUAC volume parameter, area parameter, and Wilson liquid molar volume parameter of valnemulin hydrogen fumarate were estimated by the group contribution method. It was found that the correlated results are in good agreement with the experimental results. Furthermore, the mixing thermodynamic properties of valnemulin hydrogen fumarate in solutions, including the mixing Gibbs energy, the mixing enthalpy and entropy, were determined by using the Wilson model and the experimental solubility results.

  14. Reconstruction of cytosolic fumaric acid biosynthetic pathways in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Xu Guoqiang

    2012-02-01

    Full Text Available Abstract Background Fumaric acid is a commercially important component of foodstuffs, pharmaceuticals and industrial materials, yet the current methods of production are unsustainable and ecologically destructive. Results In this study, the fumarate biosynthetic pathway involving reductive reactions of the tricarboxylic acid cycle was exogenously introduced in S. cerevisiae by a series of simple genetic modifications. First, the Rhizopus oryzae genes for malate dehydrogenase (RoMDH and fumarase (RoFUM1 were heterologously expressed. Then, expression of the endogenous pyruvate carboxylase (PYC2 was up-regulated. The resultant yeast strain, FMME-001 ↑PYC2 + ↑RoMDH, was capable of producing significantly higher yields of fumarate in the glucose medium (3.18 ± 0.15 g liter-1 than the control strain FMME-001 empty vector. Conclusions The results presented here provide a novel strategy for fumarate biosynthesis, which represents an important advancement in producing high yields of fumarate in a sustainable and ecologically-friendly manner.

  15. Effects of dimethyl fumarate on neuroprotection and immunomodulation

    Directory of Open Access Journals (Sweden)

    Albrecht Philipp

    2012-07-01

    Full Text Available Abstract Background Neuronal degeneration in multiple sclerosis has been linked to oxidative stress. Dimethyl fumarate is a promising novel oral therapeutic option shown to reduce disease activity and progression in patients with relapsing-remitting multiple sclerosis. These effects are presumed to originate from a combination of immunomodulatory and neuroprotective mechanisms. We aimed to clarify whether neuroprotective concentrations of dimethyl fumarate have immunomodulatory effects. Findings We determined time- and concentration-dependent effects of dimethyl fumarate and its metabolite monomethyl fumarate on viability in a model of endogenous neuronal oxidative stress and clarified the mechanism of action by quantitating cellular glutathione content and recycling, nuclear translocation of transcription factors, and the expression of antioxidant genes. We compared this with changes in the cytokine profiles released by stimulated splenocytes measured by ELISPOT technology and analyzed the interactions between neuronal and immune cells and neuronal function and viability in cell death assays and multi-electrode arrays. Our observations show that dimethyl fumarate causes short-lived oxidative stress, which leads to increased levels and nuclear localization of the transcription factor nuclear factor erythroid 2-related factor 2 and a subsequent increase in glutathione synthesis and recycling in neuronal cells. Concentrations that were cytoprotective in neuronal cells had no negative effects on viability of splenocytes but suppressed the production of proinflammatory cytokines in cultures from C57BL/6 and SJL mice and had no effects on neuronal activity in multi-electrode arrays. Conclusions These results suggest that immunomodulatory concentrations of dimethyl fumarate can reduce oxidative stress without altering neuronal network activity.

  16. Molecular Pathways: Fumarate Hydratase-Deficient Kidney Cancer: Targeting the Warburg Effect in Cancer

    Science.gov (United States)

    Linehan, W. Marston; Rouault, Tracey A.

    2015-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid cycle (TCA) enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer levels of AMPK, a cellular energy sensor, are decreased; resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of HIF1α, and increased expression of genes such as vascular endothelial growth factor (VEGF) and GLUT1 to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, LDH-A, the anti-oxidant response pathway, the heme oxygenase pathway and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the metabolic basis of a rare cancer such as fumarate hydratase

  17. Synthesis and characterization of unsatured polyesters from the reaction of glycerol with fumaric acid

    International Nuclear Information System (INIS)

    Medeiros, Marina A.O.; Brioude, Michel M.; Agrela, Sara P.; Rosa, Leandro O.S.; Jose, Nadia M.; Prado, Luis A.S.A.

    2009-01-01

    The biodiesel production from vegetable oils has been encouraged by the Brazilian Federal Government, since biodiesel is a renewable fuel. The utilization of glycerol (by-product of biodiesel production) has gained importance, since it corresponds to 30 wt-% of the produced biodiesel. In this context, the present work aims at preparing and characterizing polymers based on glycerol, which could have an application. In this way, the production of biodiesel could be further stimulated. Unsaturated polyesters were preparing by esterification of glycerol with fumaric acid. The reaction mixture was heated up to 240 deg C. After the polymerization was complete, the material was cast onto Teflon molds. The materials were characterized by Infrared Spectroscopy, X-ray diffraction. The thermal stability was evaluated by thermogravimetric analysis and differential scanning calorimetry. The materials showed thermal stability comparable to alkyd thermoset derived from maleic anhydride and glycerol. (author)

  18. In vitro pharmacokinetics of anti-psoriatic fumaric acid esters

    NARCIS (Netherlands)

    N.H.R. Litjens (Nicolle); E. van Strijen (Elizabeth); C. van Gulpen (Co); H. Mattie (Herman); J.T. van Dissel (Jaap); H.B. Thio (Bing); P.H. Nibbering (Peter)

    2004-01-01

    textabstractBackground: Psoriasis is a chronic inflammatory skin disease that can be successfully treated with a mixture of fumaric acid esters (FAE) formulated as enteric-coated tablets for oral use. These tablets consist of dimethylfumarate (DMF) and salts of monoethylfumarate (MEF) and its main

  19. 21 CFR 522.84 - Beta-aminopropionitrile fumarate.

    Science.gov (United States)

    2010-04-01

    ... use in breeding animals since the effects on fertility, pregnancy, or fetal health have not been... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Beta-aminopropionitrile fumarate. 522.84 Section 522.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  20. Solubility of fumaric acid and its monosodium salt

    NARCIS (Netherlands)

    Roa Engel, C.A.; Horst, J.H. ter; Pieterse, M.; Wielen, L.A.M. van der; Straathof, A.J.J.

    2013-01-01

    Fumaric acid is a dicarboxylic acid applied in food industry and in some polymers. Currently, its fermentative production from renewable resources is receiving much attention, and crystallization is used to recover it. To determine the window of operation for crystallization from multicomponent

  1. Fumaric acid production by Rhizopus oryzae and its facilitated ...

    African Journals Online (AJOL)

    Anupreet

    2014-03-05

    Mar 5, 2014 ... membrane' setup for a 'fumaric acid' source, with toluene as organic membrane and sodium hydroxide as strip phase. The liquid ... polymer films can be extended to include liquids. They are defined as Liquid .... Membrane solutions were prepared by dissolution of trioctylamine. (TOA) (Fluka A.G. ...

  2. Synthesis and characterization of thermoplastic copolyester elastomers modified with fumaric moieties

    Directory of Open Access Journals (Sweden)

    JASNA DJONLAGIC

    2001-03-01

    Full Text Available A series of poly(ether-esters derived from dimethyl terephthalate (DMT, dimethyl fumarate (DMF, 1,4-butandiol (BD and poly(tetramethylene oxide (PTMO,Mn = 1000 g/mol was synthesized in a two stage process involving transesterification and polycondensation in the melt. The mole ratio of the starting components was selected to result in copolymers with a constant hard:soft segment wieght ratio (56:44. The amount of DMF was 10 mol %, referred to the total amount of the esters used. The synthesis was optimized in terms of both the concentration of catalyst, tetra-n-butyl-titanate, Ti(OBu4 and thermal stabilizer N,N’-diphenyl-p-phenylenediamine, DPPD, as well as the temperature. The composition and structure of the synthesized poly(ether-esters were characterized by 1H-NMR. The number average molecular weights of the polymers calculated from the 1H-NMR spectra were compared with the corresponding values of the inherent viscosity (hinh in m-cresol and the complex dynamic viscosity (h *. The effect of the content of fumaric residues on the thermal properties of the synthesized copolyesters was also investigated using differential scanning calorimetry (DSC and thermal gravimetric analysis (TGA.

  3. Comparative proteomics of Rhizopus delemar ATCC 20344 unravels the role of amino acid catabolism in fumarate accumulation

    OpenAIRE

    Odoni, Dorett I.; Tamayo-Ramos, Juan A.; Sloothaak, Jasper; van Heck, Ruben G.A.; Martins dos Santos, Vitor A.P.; de Graaff, Leo H.; Suarez-Diez, Maria; Schaap, Peter J.

    2017-01-01

    The filamentous fungus Rhizopus delemar naturally accumulates relatively high amounts of fumarate. Although the culture conditions that increase fumarate yields are well established, the network underlying the accumulation of fumarate is not yet fully understood. We set out to increase the knowledge about fumarate accumulation in R. delemar. To this end, we combined a transcriptomics and proteomics approach to identify key metabolic pathways involved in fumarate production in R. delemar, and ...

  4. S Sensors: Fumarate-Based fcu-MOF Thin Film Grown on a Capacitive Interdigitated Electrode

    KAUST Repository

    Yassine, Omar

    2016-10-31

    Herein we report the fabrication of an advanced sensor for the detection of hydrogen sulfide (H2S) at room temperature, using thin films of rare-earth metal (RE)-based metal-organic framework (MOF) with underlying fcu topology. This unique MOF-based sensor is made via the insitu growth of fumarate-based fcu-MOF (fum-fcu-MOF) thin film on a capacitive interdigitated electrode. The sensor showed a remarkable detection sensitivity for H2S at concentrations down to 100ppb, with the lower detection limit around 5ppb. The fum-fcu-MOF sensor exhibits a highly desirable detection selectivity towards H2S vs. CH4, NO2, H2, and C7H8 as well as an outstanding H2S sensing stability as compared to other reported MOFs. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

    Science.gov (United States)

    Deegan, Alexander Paul; Kirby, Brian; Rogers, Sarah; Crotty, Tom Bernard; McDonnell, Timonthy John

    2010-10-01

      We present the case of a 49-year old male who presented with dyspnoea, cough, weight loss, night sweats and general malaise. He had been on treatment with oral fumaric acid esters (FAE, Fumaderm®; Biogen Idec GmbH, Ismaning, Germany) for 6 months.   Report of a case.   His chest X-ray showed patchy infiltrates in the left upper lobe which failed to resolve under empiric antibiotic therapy. A computed tomography of thorax revealed bilateral, mostly peripheral foci of consolidation with air bronchograms. Transbronchial biopsies showed a pattern of organising pneumonia (OP).   Therapy with oral prednisolone (40 mg/day) resulted in a rapid clinical and radiological improvement. An association of FAE and OP has not previously been reported. Please cite this paper as: Deegan AP, Kirby B, Rogers S, Crotty TB and McDonnell TJ. Organising pneumonia associated with fumaric acid ester treatment for psoriasis. © 2010 Blackwell Publishing Ltd.

  6. Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

    LENUS (Irish Health Repository)

    Deegan, Alexander Paul

    2012-02-01

    INTRODUCTION: We present the case of a 49-year old male who presented with dyspnoea, cough, weight loss, night sweats and general malaise. He had been on treatment with oral fumaric acid esters (FAE, Fumaderm(R); Biogen Idec GmbH, Ismaning, Germany) for 6 months. METHODS: Report of a case. RESULTS: His chest X-ray showed patchy infiltrates in the left upper lobe which failed to resolve under empiric antibiotic therapy. A computed tomography of thorax revealed bilateral, mostly peripheral foci of consolidation with air bronchograms. Transbronchial biopsies showed a pattern of organising pneumonia (OP). CONCLUSIONS: Therapy with oral prednisolone (40 mg\\/day) resulted in a rapid clinical and radiological improvement. An association of FAE and OP has not previously been reported. Please cite this paper as: Deegan AP, Kirby B, Rogers S, Crotty TB and McDonnell TJ. Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

  7. The emerging role of fumarate as an oncometabolite

    International Nuclear Information System (INIS)

    Yang, Ming; Soga, Tomoyoshi; Pollard, Patrick J.; Adam, Julie

    2012-01-01

    The drive to understand how altered cellular metabolism and cancer are linked has caused a paradigm shift in the focus of cancer research. The discovery of a mutated metabolic enzyme, isocitrate dehydrogenase 1, that leads to accumulation of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence that dysfunctional metabolism plays an important role in oncogenesis. Striking parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumor suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumors. Loss of FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our studies have questioned the role of HIF and have highlighted other candidate mechanisms, in particular the non-enzymatic modification of cysteine residues (succination) that could lead to disruption or loss of protein functions, dysfunctional cell metabolism and cell signaling. Here, we discuss the evidence for proposing fumarate as an onco-metabolite.

  8. Tratamientos para dejar de fumar, disponibles en México

    Directory of Open Access Journals (Sweden)

    Sansores Raúl H

    2002-01-01

    Full Text Available Objetivo. Describir las estrategias terapéuticas disponibles para ayudar a los fumadores a dejar de fumar. Material y métodos. Estudio realizado en el Instituto Nacional de Enfermedades Respiratorias, México. Se hizo una revisión en Medline con el encabezado de meta-análisis y se consultó el Cochrane Library, de 1990 a 2001. Resultados. La farmacoterapia muestra una buena probabilidad promedio de éxito para dejar de fumar expresada como una relación entre el medicamento activo y el placebo (índice de 39, 78, 79, 117 y 119% para los chicles de nicotina, los parches de nicotina, el bupropión, el inhalador de nicotina y el spray nasal de nicotina, respectivamente. El éxito de la terapia conductual puede ser buena (RM=3.8, sin embargo, se requiere más investigación. Conclusiones. Se hace énfasis en la necesidad de combinar la terapia cognitivo-conductual con el uso de fármacos, así como la combinación de éstos entre sí para incrementar las posibilidades de éxito para dejar de fumar.

  9. Comparative proteomics of Rhizopus delemar ATCC 20344 unravels the role of amino acid catabolism in fumarate accumulation

    Directory of Open Access Journals (Sweden)

    Dorett I. Odoni

    2017-03-01

    Full Text Available The filamentous fungus Rhizopus delemar naturally accumulates relatively high amounts of fumarate. Although the culture conditions that increase fumarate yields are well established, the network underlying the accumulation of fumarate is not yet fully understood. We set out to increase the knowledge about fumarate accumulation in R. delemar. To this end, we combined a transcriptomics and proteomics approach to identify key metabolic pathways involved in fumarate production in R. delemar, and propose that a substantial part of the fumarate accumulated in R. delemar during nitrogen starvation results from the urea cycle due to amino acid catabolism.

  10. Preparation of polymer blends from glycerol, fumaric acid and of poly(ethylene terephthalate) (PET) recycled; Preparacao de blendas polimericas a partir do glicerol, acido fumarico e do politereftalato de etileno (PET) pos consumo

    Energy Technology Data Exchange (ETDEWEB)

    Medeiros, Marina A.O.; Guimaraes, Danilo H.; Brioude, Michel M.; Jose, Nadia M. [Instituto de Quimica, Universidade Federal da Bahia, Salvador, BA (Brazil); Prado, Luis A.S. de A. [Institut fuer Kunststoffe und Verbundwerkstoffe - Technische Universitaet Hamburg-Harburg, Hamburg (Germany)

    2011-07-01

    Polymer blends based on recycled poly(ethylene terephthalate) (PET) and poly(glycerol fumarate) polyesters were prepared in different PET concentrations. The PET powder was dispersed during the poly(glycerol fumarate) synthesis at 260 deg C. The resulting blends were characterized by X-ray diffraction. The thermal stability of the materials was evaluated by thermogravimetric analysis and differential scanning calorimetry. The morphology was studies by scanning electron microscopy. The blends were clearly immiscible. The possibility of (interfacial) compatibilization of the PET domains, caused by transesterification reactions between PET and glycerol were discussed. (author)

  11. Tratamientos para dejar de fumar, disponibles en México

    Directory of Open Access Journals (Sweden)

    Raúl H Sansores

    2002-01-01

    Full Text Available Objetivo. Describir las estrategias terapéuticas disponibles para ayudar a los fumadores a dejar de fumar. Material y métodos. Estudio realizado en el Instituto Nacional de Enfermedades Respiratorias, México. Se hizo una revisión en Medline con el encabezado de meta-análisis y se consultó el Cochrane Library, de 1990 a 2001. Resultados. La farmacoterapia muestra una buena probabilidad promedio de éxito para dejar de fumar expresada como una relación entre el medicamento activo y el placebo (índice de 39, 78, 79, 117 y 119% para los chicles de nicotina, los parches de nicotina, el bupropión, el inhalador de nicotina y el spray nasal de nicotina, respectivamente. El éxito de la terapia conductual puede ser buena (RM=3.8, sin embargo, se requiere más investigación. Conclusiones. Se hace énfasis en la necesidad de combinar la terapia cognitivo-conductual con el uso de fármacos, así como la combinación de éstos entre sí para incrementar las posibilidades de éxito para dejar de fumar.Objective. To describe smoking cessation therapies available in Mexico. Material and Methods. Literature review of meta-analysis, controlled clinical trials, and behavioral therapy studies. Results. Smoking cessation pharmacotherapy interventions showed a good chance of success on average, expressed as the ratio of the active drug vs. placebo cessation therapy outcomes (ratios of 39, 78, 79, 117, and 119%, for nicotine chewing gum, bupropion, nicotine patch, inhaler, and nicotine nasal spray, respectively. Behavioral therapy showed satisfactory results, (OR= 3.8 however, more research is needed to establish its effectiveness. Conclusions. Emphasis is made on the need to combine behavioral therapy with pharmacotherapy, to increase the likelihood of successful smoking cessation.

  12. Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma

    DEFF Research Database (Denmark)

    Ylisaukko-oja, Sanna K.; Cybulski, Cezary; Lehtonen, Rainer

    2006-01-01

    Germline mutations in the fumarate hydratase (FH) gene were recently shown to predispose to the dominantly inherited syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is characterized by benign leiomyomas of the skin and the uterus, renal cell carcinoma, and uterine...... leiomyosarcoma. The aim of this study was to identify new families with FH mutations, and to further examine the tumor spectrum associated with FH mutations. FH germline mutations were screened from 89 patients with RCC, skin leiomyomas or ovarian tumors. Subsequently, 13 ovarian and 48 bladder carcinomas were...

  13. Fumaric acid production in Saccharomyces cerevisiae by simultaneous use of oxidative and reductive routes.

    Science.gov (United States)

    Xu, Guoqiang; Chen, Xiulai; Liu, Liming; Jiang, Linghuo

    2013-11-01

    In this study, the simultaneous use of reductive and oxidative routes to produce fumaric acid was explored. The strain FMME003 (Saccharomyces cerevisiae CEN.PK2-1CΔTHI2) exhibited capability to accumulate pyruvate and was used for fumaric acid production. The fum1 mutant FMME004 could produce fumaric acid via oxidative route, but the introduction of reductive route derived from Rhizopus oryzae NRRL 1526 led to lower fumaric acid production. Analysis of the key factors associated with fumaric acid production revealed that pyruvate carboxylase had a low degree of control over the carbon flow to malic acid. The fumaric acid titer was improved dramatically when the heterologous gene RoPYC was overexpressed and 32 μg/L of biotin was added. Furthermore, under the optimal carbon/nitrogen ratio, the engineered strain FMME004-6 could produce up to 5.64 ± 0.16 g/L of fumaric acid. These results demonstrated that the proposed fermentative method is efficient for fumaric acid production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Fabrication and in vitro degradation of porous fumarate-based polymer/alumoxane nanocomposite scaffolds for bone tissue engineering.

    NARCIS (Netherlands)

    Mistry, A.S.; Cheng, S.H.; Yeh, T.; Christenson, E.; Jansen, J.A.; Mikos, A.G.

    2009-01-01

    In this work, the fabrication and in vitro degradation of porous fumarate-based/alumoxane nanocomposites were evaluated for their potential as bone tissue engineering scaffolds. The biodegradable polymer poly (propylene fumarate)/propylene fumarate-diacrylate (PPF/PF-DA), a macrocomposite composed

  15. Comparative proteomics of Rhizopus delemar ATCC 20344 unravels the role of amino acid catabolism in fumarate accumulation

    NARCIS (Netherlands)

    Odoni, Dorett I.; Tamayo-Ramos, Juan A.; Sloothaak, Jasper; Heck, van Ruben; Martins dos Santos, Vitor A.P.; Graaff, de Leo H.; Suarez-Diez, Maria; Schaap, Peter J.

    2017-01-01

    The filamentous fungus Rhizopus delemar naturally accumulates relatively high amounts of fumarate. Although the culture conditions that increase fumarate yields are well established, the network underlying the accumulation of fumarate is not yet fully understood. We set out to increase the

  16. Tissue Engineering Bionanocomposites Based on Poly(propylene fumarate

    Directory of Open Access Journals (Sweden)

    Ana M. Diez-Pascual

    2017-06-01

    Full Text Available Poly(propylene fumarate (PPF is a linear and unsaturated copolyester based on fumaric acid that has been widely investigated for tissue engineering applications in recent years due to its tailorable mechanical performance, adjustable biodegradability and exceptional biocompatibility. In order to improve its mechanical properties and spread its range of practical applications, novel approaches need to be developed such as the incorporation of fillers or polymer blending. Thus, PPF-based bionanocomposites reinforced with different amounts of single-walled carbon nanotubes (SWCNT, multi-walled carbon nanotubes (MWCNT, graphene oxide nanoribbons (GONR, graphite oxide nanoplatelets (GONP, polyethylene glycol-functionalized graphene oxide (PEG-GO, polyethylene glycol-grafted boron nitride nanotubes (PEG-g-BNNTs and hydroxyapatite (HA nanoparticles were synthesized via sonication and thermal curing, and their morphology, biodegradability, cytotoxicity, thermal, rheological, mechanical and antibacterial properties were investigated. An increase in the level of hydrophilicity, biodegradation rate, stiffness and strength was found upon increasing nanofiller loading. The nanocomposites retained enough rigidity and strength under physiological conditions to provide effective support for bone tissue formation, showed antibacterial activity against Gram-positive and Gram-negative bacteria, and did not induce toxicity on human dermal fibroblasts. These novel biomaterials demonstrate great potential to be used for bone tissue engineering applications.

  17. Mast cell stabilization decreases cardiomyocyte and LV function in dogs with isolated mitral regurgitation.

    Science.gov (United States)

    Pat, Betty; Killingsworth, Cheryl; Chen, Yuanwen; Gladden, James D; Walcott, Greg; Powell, Pamela C; Denney, Thomas; Gupta, Himanshu; Desai, Ravi; Tillson, Michael; Dillon, A Ray; Dell'italia, Louis J

    2010-09-01

    Mast cells are increased in isolated mitral regurgitation (MR) in the dog and may mediate extracellular matrix loss and left ventricular (LV) dilatation. We tested the hypothesis that mast cell stabilization would attenuate LV remodeling and improve function in the MR dog. MR was induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were obtained at baseline and after 4 months of MR and magnetic resonance imaging (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end-diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3-dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum time-varying elastance was significantly depressed in MR and MR + MCS dogs. Furthermore, cardiomyocyte fractional shortening was decreased in MR versus normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro administration of ketotifen to normal cardiomyocytes also significantly decreased fractional shortening and calcium transients. Chronic mast cell stabilization did not attenuate eccentric LV remodeling or collagen loss in MR. However, MCS therapy had a detrimental effect on LV function because of a direct negative inotropic effect on cardiomyocyte function. Published by Elsevier Inc.

  18. Stabilization

    Directory of Open Access Journals (Sweden)

    Muhammad H. Al-Malack

    2016-07-01

    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  19. Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

    Science.gov (United States)

    Guitart, Amelie V; Panagopoulou, Theano I; Villacreces, Arnaud; Vukovic, Milica; Sepulveda, Catarina; Allen, Lewis; Carter, Roderick N; van de Lagemaat, Louie N; Morgan, Marcos; Giles, Peter; Sas, Zuzanna; Gonzalez, Marta Vila; Lawson, Hannah; Paris, Jasmin; Edwards-Hicks, Joy; Schaak, Katrin; Subramani, Chithra; Gezer, Deniz; Armesilla-Diaz, Alejandro; Wills, Jimi; Easterbrook, Aaron; Coman, David; So, Chi Wai Eric; O'Carroll, Donal; Vernimmen, Douglas; Rodrigues, Neil P; Pollard, Patrick J; Morton, Nicholas M; Finch, Andrew; Kranc, Kamil R

    2017-03-06

    Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1 / Hoxa9 -driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation. © 2017 Guitart et al.

  20. The Epi-TAF for Tenofovir Disoproxil Fumarate?

    Science.gov (United States)

    Walensky, Rochelle P; Horn, Tim H; Paltiel, A David

    2016-04-01

    Approximately 84% of human immunodeficiency virus (HIV)-infected US residents on antiretroviral therapy currently receive some form of tenofovir disoproxil fumarate (TDF) as part of their HIV treatment regimen. The TDF analogue tenofovir alafenamide (TAF) has demonstrated equal efficacy but with decreased renal injury and bone mineral density loss compared with TDF. We examine how much more society ought to be willing to pay for TAF over TDF, in exchange for its improved toxicity profile. Using cost-effectiveness methods, we find that current conditions warrant an annual premium of up to $1000 over the average wholesale price (AWP) of TDF. Once generic coformulations of tenofovir/lamivudine become accessible, however, the appropriate premium for TAF will likely merit a downward adjustment, using generic TDF-based costs as the benchmark. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  1. USE OF DIMETHYL FUMARATE IN THE TREATMENT OF MULTIPLE SCLEROSIS: CLINICAL AND ECONOMIC ANALYSIS

    Directory of Open Access Journals (Sweden)

    V. R. Mkrtchyan

    2016-01-01

    Full Text Available The paper presents a review of an update on the comparative pharmacoeconomic analysis of using dimethyl fumarate in the treatment of multiple sclerosis (MS in European countries. A pharmacoeconomic evaluation was made to study the use of first-line oral dimethyl fumarate versus another first-line oral teriflunomide in the treatment of MS in the Russian Federation (for 1 year and second-line natalizumab and fingolimod. Among first-line oral drugs, dimethyl fumarate was shown to be superior to teriflunomide in a cost-effectiveness ratio and to be slightly ahead of the MS-modifying drugs (MSMDs  and the second-line drugs natalizumab and fingolimod. According to clinical and economic indicators, dimethyl fumarate is the drug of choise among other MSMDs in the treatment of MS.

  2. Purification of Polymer-Grade Fumaric Acid from Fermented Spent Sulfite Liquor

    Directory of Open Access Journals (Sweden)

    Diogo Figueira

    2017-04-01

    Full Text Available Fumaric acid is a chemical building block with many applications, namely in the polymer industry. The fermentative production of fumaric acid from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. The use of existing industrial side-streams as raw-materials within biorefineries potentially enables production costs competitive against current chemical processes, while preventing the use of refined sugars competing with food and feed uses and avoiding purposely grown crops requiring large areas of arable land. However, most industrial side streams contain a diversity of molecules that will add complexity to the purification of fumaric acid from the fermentation broth. A process for the recovery and purification of fumaric acid from a complex fermentation medium containing spent sulfite liquor (SSL as a carbon source was developed and is herein described. A simple two-stage precipitation procedure, involving separation unit operations, pH and temperature manipulation and polishing through the removal of contaminants with activated carbon, allowed for the recovery of fumaric acid with 68.3% recovery yield with specifications meeting the requirements of the polymer industry. Further, process integration opportunities were implemented that allowed minimizing the generation of waste streams containing fumaric acid, which enabled increasing the yield to 81.4% while keeping the product specifications.

  3. Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

    Science.gov (United States)

    Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

    2018-04-01

    Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

  4. Interaction and miscibility study of fumarate-based macromers with chitosan

    International Nuclear Information System (INIS)

    Hashemi Doulabi, Azadehsadat; Mirzadeh, Hamid; Imani, Mohammad

    2013-01-01

    This work is aimed to prepare Chitosan/Poly(ethylene glycol fumarate) (Ch/PEGF) blend films and to determine blend miscibility of the two polymers as a function of molecular interactions between Ch and PEGF. The blend films are prepared in various ratios (0/100 to 100/0) by the conventional solution-casting method. Interactions occurring in the blends are investigated and probed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic mechanical thermal analysis (DMTA). FTIR and XRD analyses reveal the existence of newly-formed hydrogen bond interactions between Ch and PEGF. The influence of Ch/PEGF blend ratio on thermal properties of the blend systems is discussed especially considering thermal stability. The results indicate that both melting point and crystallinity of PEGF component in the blends depend on the composition of the blends. The obtained results of FTIR, DSC, and XRD analyses suggest that the partially protonated amine groups of Ch interacts with the hydroxyl groups of PEGF and thus partial miscibility are occurred. The results are confirmed with polarized microscopy observations. It is shown that although weak hydrogen bonding exists between the polymers functional groups; the blends are partially miscible. Highlights: ► Miscibility of Ch/PEGF blends is evaluated as a function of molecular interactions. ► We explore the relationship between blend ratio of films and miscibility behavior. ► Chitosan chains can affect and disturb original crystalline structures of PEGF. ► Thermal stability of the blend films is discussed. ► These analyses suggest the blends are partially miscible

  5. Dimethyl sulfoxyde diethyl fumarate solution for high dose dosimetry

    International Nuclear Information System (INIS)

    Al-Kassiri, H.; Kattan, M.; Daher, Y.

    2007-06-01

    Dosimetric characterization of diethyl fumarate DEF in dimethyl sulfoxyde DMSO solution has been studied spectrophotometrically for possible application at high dose radiation dosimetry in the range (0-225 kGy). The absorption spectra of irradiated solution showed broad absorption bands between (325-400 nm) with a shoulder at 332 nm. The absorption increases as the dose is increased. Absorbance at 332 nm were measured and plotted against absorbed dose. Linear relationship and good response were found between absorbed dose and absorbance of 20% DEF concentration in the range (0-225 kGy) at the wave length, and linearity up to 250 kGy of absorbance at 332 nm .Good dose rate independence was observed in the range (14-33 kGy/h). The effect of post irradiation storage in darkness and indirect daylight conditions were not found to influence the absorption up to 700 h after irradiation. The effect of irradiation temperature within the range (0 to 60 centigrade degree) on the dosimetry performance was discussed.(author)

  6. The release characteristics of a model protein from self-assembled succinimide-terminated poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, Angel E; He Xuezhong; Xu Weijie; Jabbari, Esmaiel [Biomimetic Materials and Tissue Engineering Laboratories, Department of Chemical Engineering, University of South Carolina, SC 29208, Columbia (United States)], E-mail: jabbari@engr.sc.edu

    2008-08-13

    Lactide-co-glycolide-based functionalized nanoparticles (NPs), because of their high surface areas for conjugation and biodegradability, are attractive as carriers for stabilization and sustained delivery of therapeutic agents and protein drugs. The objective of this work was to compare the release characteristics of model molecules encapsulated in NPs produced from poly(lactide-co-glycolide fumarate) (PLGF) macromer with those of model molecules conjugated to NPs produced from succinimide (NHS)-terminated PLGF-NHS macromer. Poly(lactide fumarate) (PLAF), PLGF and poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromers were synthesized by condensation polymerization. The hydroxyl end-groups of PLAF and PLGF macromers were reacted with N,N{sup '}-disuccinimidyl carbonate (DSC) to produce succinimide-terminated PLAF-NHS and PLGF-NHS macromers. The macromers were self-assembled by dialysis to form NPs. The amphiphilic PLEOF macromer was used as the surfactant to stabilize the NPs in the process of self-assembly. 1-(2-pyridylazo)-2-naphthol (PAN) was used as a model small molecule for encapsulation in PLAF or PLGF NPs and bovine serum albumin (BSA) was used as a model protein for conjugation to PLAF-NHS and PLGF-NHS NPs. The profile of release of the encapsulated PAN from PLAF and PLGF NPs was non-linear and consisted of a burst release followed by a period of sustained release. The release profile for BSA, conjugated to PLAF-NHS and PLGF-NHS NPs, was linear up to complete degradation of the NPs. PLGF and PLAF NPs degraded in 15 and 28 days, respectively, while PLGF-NHS and PLAF-NHS NPs degraded in 25 and 38 days, which demonstrated that the release was dominated by erosion of the matrix. PLAF-NHS and PLGF-NHS NPs are potentially useful as carriers for sustained in situ release of protein drugs.

  7. Structural and biochemical analyses reveal insights into covalent flavinylation of the Escherichia coli Complex II homolog quinol:fumarate reductase

    Energy Technology Data Exchange (ETDEWEB)

    Starbird, C.A.; Maklashina, Elena; Sharma, Pankaj; Qualls-Histed, Susan; Cecchini, Gary; Iverson, T.M. (VA); (UCSF); (Vanderbilt)

    2017-06-14

    The Escherichia coli Complex II homolog quinol:fumarate reductase (QFR, FrdABCD) catalyzes the interconversion of fumarate and succinate at a covalently attached FAD within the FrdA subunit. The SdhE assembly factor enhances covalent flavinylation of Complex II homologs, but the mechanisms underlying the covalent attachment of FAD remain to be fully elucidated. Here, we explored the mechanisms of covalent flavinylation of the E. coli QFR FrdA subunit. Using a ΔsdhE E. coli strain, we show that the requirement for the assembly factor depends on the cellular redox environment. We next identified residues important for the covalent attachment and selected the FrdAE245 residue, which contributes to proton shuttling during fumarate reduction, for detailed biophysical and structural characterization. We found that QFR complexes containing FrdAE245Q have a structure similar to that of the WT flavoprotein, but lack detectable substrate binding and turnover. In the context of the isolated FrdA subunit, the anticipated assembly intermediate during covalent flavinylation, FrdAE245 variants had stability similar to that of WT FrdA, contained noncovalent FAD, and displayed a reduced capacity to interact with SdhE. However, small-angle X-ray scattering (SAXS) analysis of WT FrdA cross-linked to SdhE suggested that the FrdAE245 residue is unlikely to contribute directly to the FrdA-SdhE protein-protein interface. We also found that no auxiliary factor is absolutely required for flavinylation, indicating that the covalent flavinylation is autocatalytic. We propose that multiple factors, including the SdhE assembly factor and bound dicarboxylates, stimulate covalent flavinylation by preorganizing the active site to stabilize the quinone-methide intermediate.

  8. Preparation and Performance of Poly(butyl fumarate-Based Material for Potential Application in LED Encapsulation

    Directory of Open Access Journals (Sweden)

    Liang Wang

    2017-02-01

    Full Text Available A UV-curable poly(butyl fumarate (PBF/poly(propylene fumarate-diacrylate (PPF-DA hybrid material with good performance for LED encapsulation is introduced in the paper. They have been prepared by radical polymerization using PBF and PPF-DA macromers with a UV curing system. PBF and PPF-DA were characterized by Fourier-transform infrared (FT-IR and H-nuclear magnetic resonance (1H NMR. The thermal behavior, optical and mechanical properties of the material were examined by thermogravimetric analysis (TGA, differential scanning calorimetry (DSC, ultraviolet-visible spectroscopy (UV–vis, and a material testing system mechanical testing machine, respectively. The results indicated that the hybrid material has a suitable refractive index (n = 1.537 and high transmittance (99.64% in visible range before/after thermal aging. With the increasing of the double bond ratio from 0.5 to 2, the water absorption ratios of the prepared encapsulation material were 1.22%, 1.87% and 2.88%, respectively. The mechanical property experiments showed that bonding strength was in the range of 1.86–3.40 MPa, tensile-shear strength ranged from 0.84 MPa to 1.57 MPa, and compression strength was in the range of 5.10–27.65 MPa. The cured PBF/PPF-DA hybrid material can be used as a light-emitting diode (LED encapsulant, owing to its suitable refractive index, high transparency, excellent thermal stability, lower water absorption, and good mechanical properties.

  9. Fumaric acid production using renewable resources from biodiesel and cane sugar production processes.

    Science.gov (United States)

    Papadaki, Aikaterini; Papapostolou, Harris; Alexandri, Maria; Kopsahelis, Nikolaos; Papanikolaou, Seraphim; de Castro, Aline Machado; Freire, Denise M G; Koutinas, Apostolis A

    2018-04-13

    The microbial production of fumaric acid by Rhizopus arrhizus NRRL 2582 has been evaluated using soybean cake from biodiesel production processes and very high polarity (VHP) sugar from sugarcane mills. Soybean cake was converted into a nutrient-rich hydrolysate via a two-stage bioprocess involving crude enzyme production via solid state fermentations (SSF) of either Aspergillus oryzae or R. arrhizus cultivated on soybean cake followed by enzymatic hydrolysis of soybean cake. The soybean cake hydrolysate produced using crude enzymes derived via SSF of R. arrhizus was supplemented with VHP sugar and evaluated using different initial free amino nitrogen (FAN) concentrations (100, 200, and 400 mg/L) in fed-batch cultures for fumaric acid production. The highest fumaric acid concentration (27.3 g/L) and yield (0.7 g/g of total consumed sugars) were achieved when the initial FAN concentration was 200 mg/L. The combination of VHP sugar with soybean cake hydrolysate derived from crude enzymes produced by SSF of A. oryzae at 200 mg/L initial FAN concentration led to the production of 40 g/L fumaric acid with a yield of 0.86 g/g of total consumed sugars. The utilization of sugarcane molasses led to low fumaric acid production by R. arrhizus, probably due to the presence of various minerals and phenolic compounds. The promising results achieved through the valorization of VHP sugar and soybean cake suggest that a focused study on molasses pretreatment could lead to enhanced fumaric acid production.

  10. Mitochondrial fumarate reductase as a target of chemotherapy: from parasites to cancer cells.

    Science.gov (United States)

    Sakai, Chika; Tomitsuka, Eriko; Esumi, Hiroyasu; Harada, Shigeharu; Kita, Kiyoshi

    2012-05-01

    Recent research on respiratory chain of the parasitic helminth, Ascaris suum has shown that the mitochondrial NADH-fumarate reductase system (fumarate respiration), which is composed of complex I (NADH-rhodoquinone reductase), rhodoquinone and complex II (rhodoquinol-fumarate reductase) plays an important role in the anaerobic energy metabolism of adult parasites inhabiting hosts. The enzymes in these parasite-specific pathways are potential target for chemotherapy. We isolated a novel compound, nafuredin, from Aspergillus niger, which inhibits NADH-fumarate reductase in helminth mitochondria at nM order. It competes for the quinone-binding site in complex I and shows high selective toxicity to the helminth enzyme. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep indicating that mitochondrial complex I is a promising target for chemotherapy. In addition to complex I, complex II is a good target because its catalytic direction is reverse of succinate-ubiquionone reductase in the host complex II. Furthermore, we found atpenin and flutolanil strongly and specifically inhibit mitochondrial complex II. Interestingly, fumarate respiration was found not only in the parasites but also in some types of human cancer cells. Analysis of the mitochondria from the cancer cells identified an anthelminthic as a specific inhibitor of the fumarate respiration. Role of isoforms of human complex II in the hypoxic condition of cancer cells and fetal tissues is a challenge. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Variations of 57Fe hyperfine parameters in medicaments containing ferrous fumarate and ferrous sulfate

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Novikov, E. G.; Dubiel, S. M.; Semionkin, V. A.

    2010-01-01

    Several commercially available medicaments containing ferrous fumarate (FeC 4 H 2 O 4 ) and ferrous sulfate (FeSO 4 ), as a source of ferrous iron, were studied using a high velocity resolution Mössbauer spectroscopy. A comparison of the 57 Fe hyperfine parameters revealed small variations for the main components in both medicaments indicating some differences in the ferrous fumarates and ferrous sulfates. It was also found that all spectra contained additional minor components probably related to ferrous and ferric impurities or to partially modified main components.

  12. Variations of {sup 57}Fe hyperfine parameters in medicaments containing ferrous fumarate and ferrous sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru; Novikov, E. G. [Ural Federal University (The former Ural State Technical University-UPI), Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Dubiel, S. M. [AGH University of Science and Technology, Faculty of Physics and Computer Science (Poland); Semionkin, V. A. [Ural Federal University (The former Ural State Technical University-UPI), Faculty of Physical Techniques and Devices for Quality Control (Russian Federation)

    2010-04-15

    Several commercially available medicaments containing ferrous fumarate (FeC{sub 4}H{sub 2}O{sub 4}) and ferrous sulfate (FeSO{sub 4}), as a source of ferrous iron, were studied using a high velocity resolution Moessbauer spectroscopy. A comparison of the {sup 57}Fe hyperfine parameters revealed small variations for the main components in both medicaments indicating some differences in the ferrous fumarates and ferrous sulfates. It was also found that all spectra contained additional minor components probably related to ferrous and ferric impurities or to partially modified main components.

  13. Studies on biodegradable and crosslinkable poly(castor oil fumarate)/poly(propylene fumarate) composite adhesive as a potential injectable biomaterial.

    Science.gov (United States)

    Mitha, M K; Jayabalan, M

    2009-12-01

    Biodegradable hydroxyl terminated-poly(castor oil fumarate) (HT-PCF) and poly(propylene fumarate) (HT-PPF) resins were synthesized as an injectable and in situ-cross linkable polyester resins for orthopedic applications. An injectable adhesive formulation containing this resin blend, N-vinyl pyrrolidone (NVP), hydroxy apatite, free radical initiator and accelerator was developed. The Composite adhesives containing the ratio of resin blend and NVP, 2.1:1.5, 2.1:1.2 and 2.1:1.0 set fast with tolerable exothermic temperature as a three dimensionally cross linked toughened material. Crosslink density and mechanical properties of the crosslinked composite increase with increase of NVP. The present crosslinked composite has hydrophilic character and cytocompatibility with L929 fibroblast cells.

  14. Design of sustained release pellets of ferrous fumarate using cow ghee as hot-melt coating agent.

    Science.gov (United States)

    Sakarkar, Dinesh M; Dorle, Avinash K; Mahajan, Nilesh Manoharrao; Sudke, Suresh Gendappa

    2013-07-01

    The objective of the present study was to design ferrous fumarate (FF) sustained release (SR) pellets using of cow ghee (CG) as an important hot-melt coating (HMC) agent. The pellets were coated by HMC technique using CG and ethyl cellulose composition by conventional coating pan without the use of spray system. FF formulated as pellets and characterized with regard to the drug content and physico-chemical properties. Stability studies were carried out on the optimized formulation for a period of 6 months at 40 ± 2°C and 75 ± 5% relative humidity. Pellets with good surface morphology and smooth texture confirmed by stereo micrographs. HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating. In-vitro release from pellets at a given level of coating and for present pellet size was dependent upon the physico-chemical property of the drug and mostly aqueous solubility of the drug. The selection of optimized FF formulation was confirmed by comparing percent cumulative drug release with theoretical release profile. Formulation F2 had difference factor (f 1) and similarity factor (f 2) values was found to be 5 and 66 respectively. F2 showed SR of drug for 8 h with cumulative per cent release of 98.03 ± 4.49%. Release kinetics indicates approximately zero order release pattern. HMC pellets were stable during the course of stability study. By means of HMC using CG and ethyl cellulose, SR pellets containing FF were successfully prepared.

  15. Poly [[tetraaquatris(monomethylfumarato)strontium(II)] monomethyl fumarate] at 120 K

    DEFF Research Database (Denmark)

    Ståhl, Kenny; Andersen, Jens Enevold Thaulov; Nilsson, Henrik

    2006-01-01

    The title compound, {[Sr2(C5H5O4)3(H2O)4](C5H5O4)}n, crystallizes with three methyl fumarate ions and four water molecules coordinating the two independent strontium(II) ions. The coordination polyhedra are interconnected by edge-sharing to form chains, which are connected by hydrogen bonds...

  16. Two Approaches to the Synthesis of Dimethyl Fumarate That Demonstrate Fundamental Principles of Organic Chemistry

    Science.gov (United States)

    Love, Brian E.; Bennett, Lisa J.

    2017-01-01

    Two experiments are described which lead to the preparation of dimethyl fumarate, a compound currently used in the treatment of multiple sclerosis. Preparation of a compound with "real-world" applications is believed to increase student interest in the experiment. One experiment involves the isomerization of dimethyl maleate to the…

  17. Fumarate Production by Torulopsis glabrata: Engineering Heterologous Fumarase Expression and Improving Acid Tolerance.

    Directory of Open Access Journals (Sweden)

    Xiulai Chen

    Full Text Available Fumarate is a well-known biomass building block compound. However, the poor catalytic efficiency of fumarase is one of the major factors preventing its widespread production. To address this issue, we selected residues 159HPND162 of fumarase from Rhizopus oryzae as targets for site-directed mutagenesis based on molecular docking analysis. Twelve mutants were generated and characterized in detail. Kinetic studies showed that the Km values of the P160A, P160T, P160H, N161E, and D162W mutants were decreased, whereas Km values of H159Y, H159V, H159S, N161R, N161F, D162K, and D162M mutants were increased. In addition, all mutants displayed decreased catalytic efficiency except for the P160A mutant, whose kcat/Km was increased by 33.2%. Moreover, by overexpressing the P160A mutant, the engineered strain T.G-PMS-P160A was able to produce 5.2 g/L fumarate. To further enhance fumarate production, the acid tolerance of T.G-PMS-P160A was improved by deleting ade12, a component of the purine nucleotide cycle, and the resulting strain T.G(△ade12-PMS-P160A produced 9.2 g/L fumarate. The strategy generated in this study opens up new avenues for pathway optimization and efficient production of natural products.

  18. The Campylobacter jejuni RacRS system regulates fumarate utilization in a low oxygen environment

    NARCIS (Netherlands)

    van der Stel, Anne-Xander; van Mourik, Andries; Heijmen-van Dijk, Linda; Parker, Craig T; Kelly, David J; van de Lest, Chris H A; van Putten, Jos P M; Wosten, Marc

    2015-01-01

    The natural environment of the human pathogen Campylobacter jejuni is the gastrointestinal tract of warm-blooded animals. In the gut, the availability of oxygen is limited; therefore, less efficient electron acceptors such as nitrate or fumarate are used by C. jejuni. The molecular mechanisms that

  19. Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: A case series

    NARCIS (Netherlands)

    D.M.W. Balak (Deepak); J.N.B. Bavinck (Jan Nico Bouwes); De Vries, A.P.J. (Aiko P. J.); Hartman, J. (Jenny); Martino Neumann, H.A. (Hendrik A.); R. Zietse (Bob); H.B. Thio (Bing)

    2016-01-01

    textabstractBackground: Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced

  20. UV and γ-ray resistance of poly(N-methylmaleimide-alt-isobutene) and poly(diisopropyl fumarate) as transparent polymer films

    Science.gov (United States)

    Imaizumi, Ryota; Furuta, Masakazu; Okamura, Haruyuki; Matsumoto, Akikazu

    2017-09-01

    UV and γ-ray resistance of transparent polymers obtained by radical polymerization of maleic and fumaric acid derivatives, i.e., an alternating copolymer of N-methylmaleimide and isobutene (PMI) and poly(diisopropyl fumarate) (PDiPF), was investigated. Transmittance in UV and visible regions of these polymers were examined after UV irradiation and compared with the results for poly(methyl methacrylate) (PMMA) and polycarbonate (PC) as conventional transparent polymers. The order of stability toward UV irradiation was PMMA≈PDiPF>PMI>>PC, deduced from changes in the transmittance of 380 nm light. Tensile mechanical properties, such as elastic modulus, maximum strength, and elongation values of PMI, PDiPF, and PMMA were also investigated after UV and γ-radiation. UV irradiation induced the side chain scission of PMI and PDiPF via Norrish I type reaction as well as crosslinking by combination between formed polymer radicals, leading to deterioration in their optical and mechanical properties. γ-radiation induced significant changes in molecular weight and mechanical properties of the polymers. In conclusion, PMI exhibited unchanged mechanical properties and PDiPF maintained its high transparency under various irradiation conditions.

  1. Preparation and evaluation of poly(caprolactone fumarate nanoparticles containing doxorubicin HCl

    Directory of Open Access Journals (Sweden)

    N Shokri

    2011-03-01

    Full Text Available Background and the purpose of the study: Biodegradable Poly(caprolactone fumarate (PCLF has been used as bioresorbable sutures. In this study, doxorubicin HCl (Dox loaded PCLF nanoparticles were prepared and characterized.  Materials and methods: PCLFs were synthesized by polycondensation of PCL diols (Mws of 530, 1250 and 2000 with fumaryl chloride. The degradation of PCLF in NaOH, water and phosphate buffer saline (PBS, was determined in terms of Mw. Nanoparticles (NPs were prepared by two methods. In microemulsion polymerization method, dichloromethane containing PCLF and photoinitiator were combined with the water containing surfactants and then placed under light for crosslinking. In nanoprecipitation method, the organic solvent containing PCLF was poured into the stirring water. The effect of several variables concentration of PCLF, poly vinyl alcohol (PVA, Dox and Trypan blue (Trb and the Mw of PCLF and PVA on NP size and loading were evaluated. Results: PCLF 530, 1250 and 2000 in PBS or water were not degrade over 28 days. Nanoprecipitaion method gave spherical (revealed by SEM images stable NPs of about 225 with narrow size distribution and a zeta potential of -43 mV. The size of NP increased significantly with increase in Mw or concentration of PCLF. Although PVA was not necessary for formation of NPs but decreased the NP size. Dox loading and EE were 2.5-6.8% and 15-20%, respectively. Increasing the drug concentration, increased the drug loading (DL and NP size. The entrapment efficiency (EE for Trb ranged from 1% for PCLF530 to 6% for PCLF2000. An increase in PCLF concentration resulted in an increase in EE. Dox and Trb release showed a burst followed by 80% and 78% release during 3 and 4 days respectively.                                                                                                           

  2. Fumaric acid: an overlooked form of fixed carbon in Arabidopsis and other plant species

    International Nuclear Information System (INIS)

    Chia, D.W.; Yoder, T.J.; Reiter, W.D.; Gibson, S.I.

    2000-01-01

    Photoassimilates are used by plants for production of energy, as carbon skeletons and in transport of fixed carbon between different plant organs. Many studies have been devoted to characterizing the factors that. regulate photoassimilate concentrations in different plant species. Most studies examining photoassimilate concentrations in C(sub 3) plants have focused on analyzing starch and soluble sugars. However, work presented here demonstrates that a number of C(sub 3) plants, including the popular model organism Arabidopsis thaliana (L.) Heynh., and agriculturally important plants, such as soybean[Glycine ma (L.) Merr.], contain significant quantities of furnaric acid. In fact, furnaric acid can accumulate to levels of several mg per g fresh weight in A-abidopsis leaves, often exceeding starch and soluble sugar levels. Furnaric acid is a component of the tricarboxylic acid cycle and, like starch and soluble sugars, can be metabolized to yield energy and carbon skeletons for production of other compounds. Fumaric acid concentrations increase with plant age and light intensity in Arabidopsis leaves. Arabidopsis phloem exudates contain significant quantities of fumaric acid, raising the possibility that fumaric acid may function in carbon transport

  3. An experimental screen for quinoline/fumaric acid salts and co-crystals

    DEFF Research Database (Denmark)

    Beko, S. L.; Schmidt, M. U.; Bond, A. D.

    2012-01-01

    . Characterised products include the previously published 1 : 1 salt, C9H8N+center dot C4H3O4-, and a new 2 : 1 quinoline/fumaric acid co-crystal, (C9H7N)(2)center dot C4H4O4. Attempts to influence the crystallisation outcome by addition of 6-methylquinoline yielded a second co-crystal, also with an inherent 2......An experimental screen has been carried out for salts and co-crystals of quinoline (C9H7N) and fumaric acid (C4H4O4), including solution-based co-crystallisation from a variety of solvents, solvent-assisted and solvent-free co-grinding, and direct co-crystallisation of the starting materials...... : 1 quinoline/fumaric acid ratio, as a solid solution containing ca. 75% 6-methylquinoline and 25% quinoline. The corresponding co-crystal with pure 6-methylquinoline, (C10H9N)(2)center dot C4H4O4, was prepared, but the analogous structure with pure quinoline could not be obtained. Energy minimisation...

  4. Fumaric acid: an overlooked form of fixed carbon in Arabidopsis and other plant species

    Energy Technology Data Exchange (ETDEWEB)

    Chia, D.W.; Yoder, T.J.; Reiter, W.D.; Gibson, S.I.

    2000-10-01

    Photoassimilates are used by plants for production of energy, as carbon skeletons and in transport of fixed carbon between different plant organs. Many studies have been devoted to characterizing the factors that. regulate photoassimilate concentrations in different plant species. Most studies examining photoassimilate concentrations in C{sub 3} plants have focused on analyzing starch and soluble sugars. However, work presented here demonstrates that a number of C{sub 3} plants, including the popular model organism Arabidopsis thaliana (L.) Heynh., and agriculturally important plants, such as soybean [Glycine ma (L.) Merr.], contain significant quantities of furnaric acid. In fact, furnaric acid can accumulate to levels of several mg per g fresh weight in A-abidopsis leaves, often exceeding starch and soluble sugar levels. Furnaric acid is a component of the tricarboxylic acid cycle and, like starch and soluble sugars, can be metabolized to yield energy and carbon skeletons for production of other compounds. Fumaric acid concentrations increase with plant age and light intensity in Arabidopsis leaves. Arabidopsis phloem exudates contain significant quantities of fumaric acid, raising the possibility that fumaric acid may function in carbon transport.

  5. Fumarate Hydratase Deletion in Pancreatic β Cells Leads to Progressive Diabetes

    Directory of Open Access Journals (Sweden)

    Julie Adam

    2017-09-01

    Full Text Available We explored the role of the Krebs cycle enzyme fumarate hydratase (FH in glucose-stimulated insulin secretion (GSIS. Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice appear normal for 6–8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+]i elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D. The impaired GSIS in islets from diabetic Fh1βKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D.

  6. Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

    Science.gov (United States)

    Suneetha, A; Raja Rajeswari, K

    2016-04-15

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via

  7. Forced degradation of mometasone furoate and development of two RP-HPLC methods for its determination with formoterol fumarate or salicylic acid

    Directory of Open Access Journals (Sweden)

    Ramzia I. El-Bagary

    2016-05-01

    Full Text Available Two simple, selective and precise stability-indicating reversed-phase liquid chromatographic methods were developed and validated for the determination of mometasone furoate in two binary mixtures, with formoterol fumarate (Mixture 1 and salicylic acid (Mixture 2. Also, a forced degradation study of mometasone furoate was carried out including acid and alkali hydrolysis, oxidation, thermal and photo-degradation. For mixture 1, the method was based on isocratic elution using a mobile phase consisting of (Acetonitrile: 3 mM Sodium lauryl sulfate (60:40, v/v at a flow rate of 1 ml min−1. Quantitation was achieved applying dual wavelength detection where mometasone furoate and its degradation products were detected at 247 nm and formoterol fumarate and its degradation product were detected at 214 nm at 30 °C. For mixture 2 and for the forced degradation study, separation was based on isocratic elution of mometasone furoate, its degradation products and salicylic acid on a reversed phase C8 column using a mobile phase consisting of acetonitrile:water:methanol:glacial acetic acid (60:30:10:0.1, v/v at a flow rate of 2 mL min−1. Quantitation was achieved with UV detection at 240 nm. In addition, products from alkaline forced degradation of mometasone furoate were verified by LC–MS. Linearity, accuracy and precision were found to be acceptable over the concentration range of 10–800 μg mL−1 and 5–60 μg mL−1 for mometasone furoate and formoterol fumarate, respectively and over the concentration range of 5–320 μg mL−1 and 20–1280 μg mL−1 for mometasone furoate and salicylic acid, respectively. The two proposed methods could be successfully applied for the routine analysis of the studied drugs in their pharmaceutical preparations without any preliminary separation step.

  8. Effects of irradiation and fumaric acid treatment on the inactivation of Listeria monocytogenes and Salmonella typhimurium inoculated on sliced ham

    International Nuclear Information System (INIS)

    Song, Hyeon-Jeong; Lee, Ji-Hye; Song, Kyung Bin

    2011-01-01

    To examine the effects of fumaric acid and electron beam irradiation on the inactivation of foodborne pathogens in ready-to-eat meat products, sliced ham was inoculated with Listeria monocytogenes and Salmonella typhimurium. The inoculated ham slices were treated with 0.5% fumaric acid or electron beam irradiation at 2 kGy. Fumaric acid treatment reduced the populations of L. monocytogenes and S. typhimurium by approximately 1 log CFU/g compared to control populations. In contrast, electron beam irradiation decreased the populations of S. typhimurium and L. monocytogenes by 3.78 and 2.42 log CFU/g, respectively. These results suggest that electron beam irradiation is a better and appropriate technique for improving the microbial safety of sliced ham. - Highlights: → We compare irradiation and fumaric acid treatment on the inactivation of pathogens. → We examine changes in the populations of L. monocytogenes and S. typhimurium. → Irradiation at 2 kGy is more effective in sliced ham than fumaric acid treatment. → Low-dose irradiation can improve the microbial safety of sliced ham during storage.

  9. Effects of irradiation and fumaric acid treatment on the inactivation of Listeria monocytogenes and Salmonella typhimurium inoculated on sliced ham

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hyeon-Jeong; Lee, Ji-Hye [Department of Food Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Song, Kyung Bin, E-mail: kbsong@cnu.ac.kr [Department of Food Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2011-11-15

    To examine the effects of fumaric acid and electron beam irradiation on the inactivation of foodborne pathogens in ready-to-eat meat products, sliced ham was inoculated with Listeria monocytogenes and Salmonella typhimurium. The inoculated ham slices were treated with 0.5% fumaric acid or electron beam irradiation at 2 kGy. Fumaric acid treatment reduced the populations of L. monocytogenes and S. typhimurium by approximately 1 log CFU/g compared to control populations. In contrast, electron beam irradiation decreased the populations of S. typhimurium and L. monocytogenes by 3.78 and 2.42 log CFU/g, respectively. These results suggest that electron beam irradiation is a better and appropriate technique for improving the microbial safety of sliced ham. - Highlights: > We compare irradiation and fumaric acid treatment on the inactivation of pathogens. > We examine changes in the populations of L. monocytogenes and S. typhimurium. > Irradiation at 2 kGy is more effective in sliced ham than fumaric acid treatment. > Low-dose irradiation can improve the microbial safety of sliced ham during storage.

  10. Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV.

    Science.gov (United States)

    Khan, Arshad Bashir; Thakur, Ram Sharnagat

    2018-03-01

    To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF). It may provide pre-exposure prophylaxis for women against HIV. TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr's index, Hausner ratio, angle of repose, post compression parameters such as color, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies. Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague-Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40 ± 2 °C and 75 ± 5% RH for six months. C1 was selected as the best formulation due to better swelling index (65.93% at 24 h), prolonged release of 100.62% cumulative drug release (CDR) at 24 h, superior mucoadhesion force (35.93 × 10 2 dynes/cm 2 ) and retention time (16 h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.

  11. Studies on potential effects of fumaric acid on rumen microbial fermentation, methane production and microbial community.

    Science.gov (United States)

    Riede, Susanne; Boguhn, Jeannette; Breves, Gerhard

    2013-01-01

    The greenhouse gas methane (CH4) contributes substantially to global climate change. As a potential approach to decrease ruminal methanogenesis, the effects of different dosages of fumaric acid (FA) on ruminal microbial metabolism and on the microbial community (archaea, bacteria) were studied using a rumen simulation technique (RUSITEC). FA acts as alternative hydrogen acceptor diverting 2H from methanogenesis of archaea towards propionate formation of bacteria. Three identical trials were conducted with 12 fermentation vessels over a period of 14 days. In each trial, four fermentation vessels were assigned to one of the three treatment groups differing in FA dosage: low fumaric acid (LFA), high fumaric acid (HFA) and without FA (control). FA was continuously infused with the buffer. Grass silage and concentrate served as substrate. FA led to decreases in pH and to higher production rates of total short chain fatty acids (SCFA) mediated by increases in propionate for LFA of 1.69 mmol d(-1) and in propionate and acetate production for HFA of 4.49 and 1.10 mmol d(-1), respectively. Concentrations of NH3-N, microbial crude protein synthesis, their efficiency, degradation of crude nutrients and detergent fibre fraction were unchanged. Total gas and CH4 production were not affected by FA. Effects of FA on structure of microbial community by means of single strand conformation polymorphism (SSCP) analyses could not be detected. Given the observed increase in propionate production and the unaffected CH4 production it can be supposed that the availability of reduction equivalents like 2H was not limited by the addition of FA in this study. It has to be concluded from the present study that the application of FA is not an appropriate approach to decrease the ruminal CH4 production.

  12. [Preparation and application on compound excipient of sodium stearyl fumarate and plasdone S-630].

    Science.gov (United States)

    Jiang, Yan-Rong; Zhang, Zhen-Hai; Jia, Xiao-Bin

    2013-01-01

    The compound excipient containing sodium stearyl fumarate and plasdone S-630 was prepared by applying spray drying method. The basic physical properties of compound excipient were studied by solubility test, scanning electron microscope, differential scanning calorimeter, X-ray diffraction and Fourier transform infra-red spectroscopy. The effect of compound excipient on moisture absorption and ferulic acid in vitro dissolution of spray drying power of angelica were investigated. The results showed that the chemical constituents of compound excipient did not change before and after spray drying. The water soluble compound excipient can improve significantly moisture absorption and has application prospect.

  13. In-situ IR monitoring of the formation of Zr-fumarate MOF

    CSIR Research Space (South Africa)

    Ren, Jianwei

    2017-05-01

    Full Text Available monitoring of the formation of Zr-fumarate MOF Authors: Jianwei Ren, Nicholas M. Musyoka, Henrietta W. Langmi, Brian C. North, Mkhulu Mathe, Wan Pang, Mingjie Wang, Joseph Walker PII: S0169-4332(17)30296-9 DOI: http://dx.doi.org/doi:10.1016/j.apsusc.2017....01.271 Reference: APSUSC 35066 To appear in: APSUSC Received date: 21-9-2016 Revised date: 20-1-2017 Accepted date: 25-1-2017 Please cite this article as: Jianwei Ren, Nicholas M.Musyoka, Henrietta W.Langmi, Brian C.North, Mkhulu Mathe, Wan Pang, Mingjie Wang...

  14. Fumarate to Malate Conversion in Infarcted Porcine Heart – a Pilot Study

    DEFF Research Database (Denmark)

    Søvsø Szocska Hansen, Esben; Tougaard, Rasmus Stilling; Nielsen, Per Mose

    2017-01-01

    Hyperpolarized MR may be a key tool for investigation cardiac metabolism and cardiac treatment response. [1,4- 13C2]Fumarate is an emerging and interesting candidate for measuring and visualizing cardiac injury after ischemia. In this study we showed an initial step for imaging cardiac cell death...... in a large animal model with [1,4- 13C2]malate. The [1,4- 13C2]malate signal correlated well with increased 13C-lactate signal and 13C-alanine absence. Overall, this shows increased metabolism in the infarcted area and ongoing necrosis....

  15. Anaerobic α-Amylase Production and Secretion with Fumarate as the Final Electron Acceptor in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Liu, Zihe; Österlund, Tobias; Hou, Jin

    2013-01-01

    In this study, we focus on production of heterologous α-amylase in the yeast Saccharomyces cerevisiae under anaerobic conditions. We compare the metabolic fluxes and transcriptional regulation under aerobic and anaerobic conditions, with the objective of identifying the final electron acceptor...... reticulum are transferred to fumarate as the final electron acceptor. This model is supported by findings that the addition of fumarate under anaerobic (but not aerobic) conditions improves cell growth, specifically in the α-amylase-producing strain, in which it is not used as a carbon source. Our results...... provide a model for the molecular mechanism of anaerobic protein secretion using fumarate as the final electron acceptor, which may allow for further engineering of yeast for improved protein secretion under anaerobic growth conditions....

  16. Effects of irradiation and fumaric acid treatment on the inactivation of Listeria monocytogenes and Salmonella typhimurium inoculated on sliced ham

    Science.gov (United States)

    Song, Hyeon-Jeong; Lee, Ji-Hye; Song, Kyung Bin

    2011-11-01

    To examine the effects of fumaric acid and electron beam irradiation on the inactivation of foodborne pathogens in ready-to-eat meat products, sliced ham was inoculated with Listeria monocytogenes and Salmonella typhimurium. The inoculated ham slices were treated with 0.5% fumaric acid or electron beam irradiation at 2 kGy. Fumaric acid treatment reduced the populations of L. monocytogenes and S. typhimurium by approximately 1 log CFU/g compared to control populations. In contrast, electron beam irradiation decreased the populations of S. typhimurium and L. monocytogenes by 3.78 and 2.42 log CFU/g, respectively. These results suggest that electron beam irradiation is a better and appropriate technique for improving the microbial safety of sliced ham.

  17. Effect of sodium lauryl sulfate-fumaric Acid coupled addition on the in vitro rumen fermentation with special regard to methanogenesis.

    Science.gov (United States)

    Abdl-Rahman, M A; Sawiress, F A R; Abd El-Aty, A M

    2010-01-01

    The aim of the current study was to evaluate the effect of sodium lauryl sulfate-fumaric acid coupled addition on in vitro methangenesis and rumen fermentation. Evaluation was carried out using in vitro gas production technique. Ruminal contents were collected from five steers immediately after slaughtering and used for preparation of inoculums of mixed rumen microorganisms. Rumen fluid was then mixed with the basal diet of steers and used to generate four treatments, negative control (no additives), sodium lauryl sulfate (SLS) treated, fumaric acid treated, and SLS-fumaric acid coupled addition treated. The results revealed that, relative to control, efficiency in reduction of methanogenesis was as follows: coupled addition > SLS-addition > fumaric acid addition. Both SLS-addition and SLS-fumaric acid coupled addition demonstrated a decremental effect on ammonia nitrogen (NH(3)-N), total short chain volatile fatty acids (SCVFAs) concentrations and the amount of substrate degraded, and an increment effect on microbial mass and microbial yield (Y(ATP)). Nevertheless, fumaric acid did not alter any of the previously mentioned parameters but induced a decremental effect on NH(3)-N. Furthermore, both fumaric acid and SLS-fumaric acid coupled addition increased propionate at the expense of acetate and butyrate, while, defaunation increased acetate at the expense of propionate and butyrate. The pH value was decreased by all treatments relative to control, while, cellulase activity did not differ by different treatments. The current study can be promising strategies for suppressing ruminal methane emissions and improving ruminants feed efficiency.

  18. Utilization of dimethyl fumarate and related molecules for treatment of multiple sclerosis, cancer, and other diseases

    Directory of Open Access Journals (Sweden)

    Azzam Maghazachi

    2016-07-01

    Full Text Available Several drugs have been approved for treatment of multiple sclerosis. Dimethyl fumarate (DMF is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF, a related compound has not been examined in greater details although it has the potential as a therapeutic drug for multiple sclerosis and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species. However, other mechanisms have also been described which include effects on monocytes, dendritic cells, T cells, and natural killer cells. It is also reported that DMF might be useful for treating psoriasis, asthma, aggressive breast cancers, hematopoeitic tumors, inflammatory bowel disease, intracerebral hemorrhage, osteoarthritis, chronic pancreatitis, and retinal ischemia. In this article we will touch on some of these diseases with an emphasis on the effects of DMF and MMF on various immune cells.

  19. Fumaric acid production in Saccharomyces cerevisiae by in silico aided metabolic engineering.

    Directory of Open Access Journals (Sweden)

    Guoqiang Xu

    Full Text Available Fumaric acid (FA is a promising biomass-derived building-block chemical. Bio-based FA production from renewable feedstock is a promising and sustainable alternative to petroleum-based chemical synthesis. Here we report on FA production by direct fermentation using metabolically engineered Saccharomyces cerevisiae with the aid of in silico analysis of a genome-scale metabolic model. First, FUM1 was selected as the target gene on the basis of extensive literature mining. Flux balance analysis (FBA revealed that FUM1 deletion can lead to FA production and slightly lower growth of S. cerevisiae. The engineered S. cerevisiae strain obtained by deleting FUM1 can produce FA up to a concentration of 610±31 mg L(-1 without any apparent change in growth in fed-batch culture. FT-IR and (1H and (13C NMR spectra confirmed that FA was synthesized by the engineered S. cerevisiae strain. FBA identified pyruvate carboxylase as one of the factors limiting higher FA production. When the RoPYC gene was introduced, S. cerevisiae produced 1134±48 mg L(-1 FA. Furthermore, the final engineered S. cerevisiae strain was able to produce 1675±52 mg L(-1 FA in batch culture when the SFC1 gene encoding a succinate-fumarate transporter was introduced. These results demonstrate that the model shows great predictive capability for metabolic engineering. Moreover, FA production in S. cerevisiae can be efficiently developed with the aid of in silico metabolic engineering.

  20. An Iterative O-Methyltransferase Catalyzes 1,11-Dimethylation of Aspergillus fumigatus Fumaric Acid Amides.

    Science.gov (United States)

    Kalb, Daniel; Heinekamp, Thorsten; Schieferdecker, Sebastian; Nett, Markus; Brakhage, Axel A; Hoffmeister, Dirk

    2016-10-04

    S-adenosyl-l-methionine (SAM)-dependent methyltransfer is a common biosynthetic strategy to modify natural products. We investigated the previously uncharacterized Aspergillus fumigatus methyltransferase FtpM, which is encoded next to the bimodular fumaric acid amide synthetase FtpA. Structure elucidation of two new A. fumigatus natural products, the 1,11-dimethyl esters of fumaryl-l-tyrosine and fumaryl-l-phenylalanine, together with ftpM gene disruption suggested that FtpM catalyzes iterative methylation. Final evidence that a single enzyme repeatedly acts on fumaric acid amides came from an in vitro biochemical investigation with recombinantly produced FtpM. Size-exclusion chromatography indicated that this methyltransferase is active as a dimer. As ftpA and ftpM homologues are found clustered in other fungi, we expect our work will help to identify and annotate natural product biosynthesis genes in various species. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Polypropylene fumarate/phloroglucinol triglycidyl methacrylate blend for use as partially biodegradable orthopaedic cement.

    Science.gov (United States)

    Jayabalan, M; Thomas, V; Rajesh, P N

    2001-10-01

    Polypropylene fumarate/phloroglucinol triglycidyl methacrylate oligomeric blend-based bone cement was studied. Higher the percentage of phloroglucinol triglycidyl methacrylate, lesser the setting time. An optimum setting time could be arrived with 50:50 blend composition of the two oligomers. Composite cement of 50:50 blend prepared with hydroxyapatite granules of particle size 125 microm binds bovine rib bones. The tensile strength of this adhesive bond was found to be 1.11 kPa. The thermal studies suggest the onset of cross-linking reaction in the cured blend if the blend is heated. The absence of softening endotherm in the cured blend shows the thermosetting-like amorphous nature of blend system, which may restrict the changes in creep properties. The in vitro biodegradation studies reveal possible association of calcium ions with negatively charged units of degrading polymer chain resulting in slow down of degradation. Relatively slow degradation was observed in Ringer's solution. The study reveals the potential use of polypropylene fumarate/phloroglucinol triglycidyl methacrylate as partially degradable polymeric cement for orthopaedic applications.

  2. Dimethyl Fumarate

    Science.gov (United States)

    ... memory, or awareness that leads to confusion and personality changes extreme tiredness, loss of appetite, pain in ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  3. Degradation and biocompatibility of a poly(propylene fumarate)-based/alumoxane nanocomposite for bone tissue engineering.

    NARCIS (Netherlands)

    Mistry, A.S.; Mikos, A.G.; Jansen, J.A.

    2007-01-01

    In this work, we evaluated the in vitro cytotoxicity and in vivo biocompatibility of a novel poly(propylene fumarate) (PPF)-based/alumoxane nanocomposite for bone tissue engineering applications. The incorporation of functionalized alumoxane nanoparticles into the PPF-based polymer was previously

  4. Evaluation of the binding interaction between bovine serum albumin and dimethyl fumarate, an anti-inflammatory drug by multispectroscopic methods

    Science.gov (United States)

    Jattinagoudar, Laxmi; Meti, Manjunath; Nandibewoor, Sharanappa; Chimatadar, Shivamurti

    2016-03-01

    The information of the quenching reaction of bovine serum albumin with dimethyl fumarate is obtained by multi-spectroscopic methods. The number of binding sites, n and binding constants, KA were determined at different temperatures. The effect of increasing temperature on Stern-Volmer quenching constants (KD) indicates that a dynamic quenching mechanism is involved in the interaction. The analysis of thermodynamic quantities namely, ∆H° and ∆S° suggested hydrophobic forces playing a major role in the interaction between dimethyl fumarate and bovine serum albumin. The binding site of dimethyl fumarate on bovine serum albumin was determined by displacement studies, using the site probes viz., warfarin, ibuprofen and digitoxin. The determination of magnitude of the distance of approach for molecular interactions between dimethyl fumarate and bovine serum albumin is calculated according to the theory of Förster energy transfer. The CD, 3D fluorescence spectra, synchronous fluorescence measurements and FT-IR spectral results were indicative of the change in secondary structure of the protein. The influence of some of the metal ions on the binding interaction was also studied.

  5. Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds.

    NARCIS (Netherlands)

    Holland, T.A.; Bodde, E.W.H.; Baggett, L.S.; Tabata, Y.; Mikos, A.G.; Jansen, J.A.

    2005-01-01

    In this study, hydrogel scaffolds, based on the polymer oligo(poly(ethylene glycol) fumarate) (OPF), were implanted into osteochondral defects in the rabbit model. Scaffolds consisted of two layers-a bottom, bone forming layer and a top, cartilage forming layer. Three scaffold formulations were

  6. Structure of fumarate hydratase from Rickettsia prowazekii, the agent of typhus and suspected relative of the mitochondria

    International Nuclear Information System (INIS)

    Phan, Isabelle; Subramanian, Sandhya; Olsen, Christian; Edwards, Thomas E.; Guo, Wenjin; Zhang, Yang; Van Voorhis, Wesley C.; Stewart, Lance J.; Myler, Peter J.

    2011-01-01

    Fumarate hydratase is an enzyme of the tricarboxylic acid cycle, one of the metabolic pathways characteristic of the mitochondria. The structure of R. prowazekii class II fumarate hydratase is reported at 2.4 Å resolution and is compared with the available structure of the human homolog. Rickettsiae are obligate intracellular parasites of eukaryotic cells that are the causative agents responsible for spotted fever and typhus. Their small genome (about 800 protein-coding genes) is highly conserved across species and has been postulated as the ancestor of the mitochondria. No genes that are required for glycolysis are found in the Rickettsia prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in both. A 2.4 Å resolution crystal structure of R. prowazekii fumarate hydratase, an enzyme catalyzing the third step of the tricarboxylic acid cycle pathway that ultimately converts phosphoenolpyruvate into succinyl-CoA, has been solved. A structure alignment with human mitochondrial fumarate hydratase highlights the close similarity between R. prowazekii and mitochondrial enzymes

  7. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis

    OpenAIRE

    Glidden, David; Grant, Robert; Mulligan, Kathleen; Solomon, MM; Lama, JR; Glidden, DV; McMahan, V; Liu, AY; Vicente, J; Veloso, VG; Mayer, KH; Chariyalertsak, S

    2014-01-01

    Objective: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. Design and methods: The Iniciativa Profilaxis Pre-Exposición (iP

  8. Algunas Consideraciones Relativas al Hábito de Fumar en los Hospitales

    Directory of Open Access Journals (Sweden)

    José Felix Patiño Restrepo

    1986-12-01

    Full Text Available

    El cigarrillo constituye el problema de salud más grave que enfrenta la sociedad moderna. El hábito de fumar resulta en elevadas tasas de morbilidad y está plenamente comprobado que disminuye notoriamente la expectativa de vida por el desarrollo de cáncer pulmonar, enfermedad pulmonar obstructiva crónica, enfermedad coronaria del corazón y una variedad de neoplasias malignas y de enfermedades vasculares.

    La medicina, la enfermería y las profesiones afines de la salud tienen como propósito y como misión promover la salud. Los hospitales son instituciones dedicadas al mantenimientoy la recuperación de la salud, y el personal que labora en ellos está totalmente comprometido contal objetivo.

    Los empleados que trabajan en los hospitales, pero especialmente los pacientes y sus familiares, tienen el sagrado derecho a respirar un ambiente no contaminado. Si los hospitales permiten que se pueda fumar en sus instalacionesy, especialmente, si permiten que sus empleados fumen, deben entonces estar preparados para asumirla responsabilidad por la incomodidad o el daño quepuedan ocurrir a los empleados, pacientes, familiares yvisitantes que encuentren un ambiente contaminado.

    Fumar es realmente incompatible con una profesión de salud. Significa una contradicción ante los postulados que gobiernan las actividades de los trabajadores de la salud, representa un mal ejemplo para el público y significa una actitud irresponsable que, según algunos observadores, raya en la falta de ética profesional. Sin embargo,se debe aceptar que en los hospitales hay personal profesional y técnico que fuma. Algunas personas jóvenes han iniciado el hábito hace poco tiempo, probablemente bajo una condición de sorprendente ignorancia;otras de mayor edad, conocen las implicaciones nocivas pero encuentran muy difícil suspender el arraigado hábito.Los primeros probablemente podrán sobreponerse; los segundos deberán abstenerse, por lo menos

  9. Intestinal Bacterial Flora that Compete on the Haem Precursor Iron Fumarate in Iron Deficiency Anemia Cases

    Directory of Open Access Journals (Sweden)

    Selim, S. A. H.

    2012-06-01

    Full Text Available Aims: The study focused on finding if there is any possible relation between the intestinal bacterial population quantitative and qualitative and the deficiency of the most important iron compounds as haem precursors. Methodology and Results: Blood complete picture and stool analyses were done to 750 volunteer cases whom were asked for these analyses by their physicians. Analyses proved that 560 cases representing 75.2 % were anemic as the RBC(s based on counts of the total studied cases of less than 263 x 104 and the haemoglobin amount ranged between 7.2 and 11.3 g/dl, while the remainder 24.8 % of the volunteer sample was not anemic. A high male/female ratio ofanemic cases, 1:27 was also documented. Considering that all the studied stool samples should be completely free from any parasites or any other anemia-related diseases was a priority. Bacteriological analysis of stool samples of the anemic cases resulted in the detection of high counts of total viable bacteria, exceeded 42 x 109 cfu/g, while it was never more than 26 x 106 cfu/g and decreased to 4 x 106 cfu/g in many cases in this study. Identifying of the 361 bacterial isolates, were found to belong to 12 genera and 19 species, 6 of them; Pseudomonas putrefaciens, Micrococcus luteus, Erysipelothrix rhusiopathiae, Bacillus megaterium, Bacillus pumilus and Bacillus coagulans , were found and in high counts in the stool samples of only anemic cases. The ability of these isolates to compete for iron compounds such as ferrous fumarate alone or with glucose and phytate as activators or inhibitors to these abilities was investigated. Results proved 11 species out of the 19 identified species are capable to use and compete on ferrous fumarate as a haemprecursor. Sensitivity test for the representatives of the 19 species and 6 of the most commonly used antibiotics in the Egyptian pharmacy, using standard disc method, revealed variable susceptibilities of almost all of them to more than one of

  10. Fabrication and in vitro degradation of porous fumarate-based polymer/alumoxane nanocomposite scaffolds for bone tissue engineering.

    Science.gov (United States)

    Mistry, Amit S; Cheng, Stacy H; Yeh, Tiffany; Christenson, Elizabeth; Jansen, John A; Mikos, Antonios G

    2009-04-01

    In this work, the fabrication and in vitro degradation of porous fumarate-based/alumoxane nanocomposites were evaluated for their potential as bone tissue engineering scaffolds. The biodegradable polymer poly (propylene fumarate)/propylene fumarate-diacrylate (PPF/PF-DA), a macrocomposite composed of PPF/PF-DA and boehmite microparticles, and a nanocomposite composed of PPF/PF-DA and surface-modified alumoxane nanoparticles were used to fabricate porous scaffolds by photo-crosslinking and salt-leaching. Scaffolds then underwent 12 weeks of in vitro degradation in phosphate buffered saline at 37 degrees C. The presence of boehmite microparticles and alumoxane nanoparticles in the polymer inhibited scaffold shrinkage during crosslinking. Furthermore, the incorporation of alumoxane nanoparticles into the polymer limited salt-leaching, perhaps due to tighter crosslinking within the nanocomposite. Analysis of crosslinking revealed that the acrylate and overall double bond conversions in the nanocomposite were higher than in the PPF/PF-DA polymer alone, though these differences were not significant. During 12 weeks of in vitro degradation, the nanocomposite lost 5.3% +/- 2.4% of its mass but maintained its compressive mechanical properties and porous architecture. The addition of alumoxane nanoparticles into the fumarate-based polymer did not significantly affect the degradation of the nanocomposite compared with the other materials in terms of mass loss, compressive properties, and porous structure. These results demonstrate the feasibility of fabricating degradable nanocomposite scaffolds for bone tissue engineering by photo-crosslinking and salt-leaching mixtures of fumarate-based polymers, alumoxane nanoparticles, and salt microparticles. Copyright 2008 Wiley Periodicals, Inc.

  11. Representações sociais do comportamento de fumar em adolescentes de 13 anos

    Directory of Open Access Journals (Sweden)

    S. Fraga

    2011-01-01

    Full Text Available Resumo: Objectivo: O objectivo deste estudo foi identificar em adolescentes, através de uma abordagem qualitativa, as representações sociais sobre o comportamento de fumar. Métodos: Foram realizadas trinta entrevistas semi-estruturadas por entrevistadores treinados, gravadas com a permissão dos participantes após explicação detalhada do processo de entrevista. Depois da transcrição do conteúdo de cada entrevista, a informação foi sintetizada em cada questão principal e foi realizada uma análise de conteúdo conceptual. A análise foi realizada por dois dos autores, e os conflitos foram resolvidos por uma terceira pessoa. Resultados: Os adolescentes sugeriram diferentes explicações para o comportamento de fumar das pessoas em geral e dos adolescentes. Enquanto que fumar para os primeiros estava mais relacionado com a dependência, na adolescência pretendia melhorar o estatuto entre os colegas e ser uma forma de manter as relações sociais. Os adolescentes estavam conscientes das implicações graves do tabagismo para a saúde, mas eles só referiram efeitos a longo prazo, sem percepcionarem consequências durante a adolescência. Verificámos também que tinham dificuldades em indicar potenciais medidas preventivas orientadas para os adolescentes. Conclusão: Este estudo aponta para a importância dos pares como agentes de socialização do consumo do tabaco, e mostra a importância de campanhas anti-tabagismo neste grupo etário com ênfase nas consequências do tabagismo na adolescência. Abstract: Objective: The purpose of this study was to identify adolescents’ social representations on smoking using a qualitative approach. Methods: Thirty semi-structured interviews were conducted by trained interviewers. The interviews were recorded with participant's permission after our comprehensive explanation of the interview process. After transcript

  12. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K.

    2015-01-01

    production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led......Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities...... of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact...

  13. A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia

    Directory of Open Access Journals (Sweden)

    Julie Adam

    2013-05-01

    Full Text Available The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH, predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target.

  14. Methanol Reforming over Cobalt Catalysts Prepared from Fumarate Precursors: TPD Investigation

    Directory of Open Access Journals (Sweden)

    Eftichia Papadopoulou

    2016-02-01

    Full Text Available Temperature-programmed desorption (TPD was employed to investigate adsorption characteristics of CH3OH, H2O, H2, CO2 and CO on cobalt-manganese oxide catalysts prepared through mixed Co-Mn fumarate precursors either by pyrolysis or oxidation and oxidation/reduction pretreatment. Pyrolysis temperature and Co/Mn ratio were the variable synthesis parameters. Adsorption of methanol, water and CO2 was carried out at room temperature. Adsorption of H2 and H2O was carried out at 25 and 300 °C. Adsorption of CO was carried out at 25 and 150 °C. The goal of the work was to gain insight on the observed differences in the performance of the aforementioned catalysts in methanol steam reforming. TPD results indicated that activity differences are mostly related to variation in the number density of active sites, which are able to adsorb and decompose methanol.

  15. Tetrabutylammonium Bromide Media Aza-Michael Addition of 1,2,3,6-Tetrahydrophthalimide to Symmetrical Fumaric Esters and Acrylic Esters under Solvent-Free Conditions

    Directory of Open Access Journals (Sweden)

    Mohammadreza Zamanloo

    2010-10-01

    Full Text Available The aza-Michael addition of 1,2,3,6-tetrahydrophthalimide with symmetrical fumaric esters has been performed efficiently in a solvent-free system at 100 °C and using 1,4-diazabicyclo[2.2.2]octane (DABCO as a base in the presence of tetrabutylammonium bromide (TBAB. The products were obtained in good to high yields within 2.5-7.0 h. This reaction worked well on linear alkyl fumarates and was not effective with nonlinear alkyl fumarates. Although the reaction was also applicable to acrylates such as n-butyl acrylate, methacrylates and crotonates were not suitable Michael acceptors for this reaction.

  16. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety?

    Science.gov (United States)

    Hill, Andrew; Hughes, Sophie L; Gotham, Dzintars; Pozniak, Anton L

    2018-04-01

    Higher plasma tenofovir concentrations are associated with higher risks of renal and bone adverse events. The pharmacokinetic boosters ritonavir (RTV) and cobicistat (COBI) significantly increase plasma area under the curve (AUC) concentrations of tenofovir disoproxil fumarate (TDF), by 25-37%. When combined with RTV or COBI, the dose of tenofovir alafenamide (TAF) is lowered from 25 mg to 10 mg daily, but the TDF dose is maintained at 300 mg daily. To assess the differences in safety and efficacy between tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) in regimens with and without the pharmacokinetic boosters RTV and COBI. A PubMed/Embase search inclusive of dates up to 17 July 2017 identified 11 randomised head-to-head trials (8111 patients) of TDF versus TAF. The Mantel-Haenszel method was used to calculate pooled risk differences and 95% confidence intervals using random-effects models. A pre-defined sub-group analysis compared TAF with TDF, either when boosted with RTV or COBI, or when unboosted. Nine clinical trials compared TAF and TDF for treatment of HIV-1 and two were for hepatitis B treatment. The eleven clinical trials documented 4574 patients with boosting RTV or COBI in both arms, covering 7198 patient-years of follow-up. Some 3537 patients received unboosted regimens, totalling 3595 patient-years of follow-up. Boosted TDF-treated patients showed borderline lower HIV RNA suppression TAF and unboosted TDF. TDF boosted with RTV or COBI was associated with higher risks of bone and renal adverse events, and lower HIV RNA suppression rates, compared with TAF. By contrast, when ritonavir and cobicistat were not used, there were no efficacy differences between TAF and TDF, and marginal differences in safety. The health economic value of TAF versus low-cost generic TDF may be limited when these drugs are used without cobicistat or ritonavir.

  17. Fixed dose darunavir boosted with cobicistat combined with emtricitabine and tenofovir alafenamide fumarate.

    Science.gov (United States)

    Cevik, Muge; Orkin, Chloe

    2018-07-01

    In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes. These findings led to two subsequent international phase III double-blind randomized controlled trials; AMBER and EMERALD. In the (treatment naïve) AMBER study, D/C/F/TAF FDC was noninferior to component regimen F/TDF + darunavir/cobicistat with favorable bone and renal outcomes at week 48. In the EMERALD study (switch study for virologically suppressed patients), D/C/F/TAF showed noninferior efficacy to F/TDF and boosted protease inhibitor (bPI) regimen at week 48 also with favorable renal and bone outcomes. No virological failure was observed, and no resistance to TDF or darunavir emerged in either study. In clinical trials, D/C/F/TAF FDC demonstrated excellent, noninferior virological efficacy, maintained a high genetic barrier and conferred the additional safety benefits of TAF. As the first one pill, once daily, protease inhibitor-based regimen, D/C/F/TAF FDC offers a new option for the treatment of HIV infection.

  18. Effect of dimethyl fumarate on heme oxygenase-1 expression in experimental allergic encephalomyelitis in rats

    Directory of Open Access Journals (Sweden)

    Kaja Kasarełło

    2017-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmunological disease leading to neurodegeneration. The etiology of the disease remains unknown, which strongly impedes the development of effective therapy. Most MS treatments focus on modulating the activity of the immune system. Dimethyl fumarate (DMF exerts a broad spectrum of action, such as modulating immune cell differentiation towards anti-inflammatory subtypes, influencing cytokine production, regulating immune cell migration into the central nervous system, and activating intracellular antioxidant mechanisms. It is well established that activation of the nuclear factor E2 (Nrf2-dependent pathway, leading to expression of the second-phase antioxidant enzymes, is influenced by DMF. In our experiments we used female Lewis rats in an animal model of MS – experimental allergic encephalomyelitis (EAE. The rats were fed with dimethyl fumarate to test the expression of heme oxygenase-1 (HO-1, one of the second-phase antioxidant enzymes, at specific time points of the symptomatic phases of the disease: on the first day of the occurrence of clinical symptoms (10th day post immunization, DPI; at the peak of clinical symptoms (14th DPI; and at the end of the relapse (21st DPI. The results showed that HO-1 expression, at both the mRNA and protein level, is influenced by DMF administration only at the very beginning of the symptomatic phase of EAE, and not at the peak of clinical symptoms, nor at the end of the relapse. This indicates that the regulation of the Nrf2-dependent antioxidant pathway by DMF occurs at a certain time interval (early EAE/MS and strongly underlines the importance of the earliest introduction of the therapy to the patient.

  19. Prevention of Posttraumatic Contractures with Ketotifen (PERK)

    Science.gov (United States)

    2017-10-01

    Disability Arm, Shoulder, Hand; Oxford Elbow Score; radiographs; reoperation 2 – 52 weeks post-randomization. Military Benefit and Clinical Impact: A...disengagement from the project for more than three months, or a 25 percent reduction in his or her time devoted to the project. d. The inclusion of direct...FINAL_OES_English_UK_Sample-1 Disability of the Arm, Shoulder and Hand (DASH) Questionnaire Case Report Forms, 1.0, July 24, 2017 PERK II Protocol V1.0 20170731, 1.0

  20. FILM MATERIALS WITH TIAMULIN FUMARATE ON THE BASIS OF POLYURETHANEUREAS, WHICH CONTAINING IN THE STRUCTURE FRAGMENTS OF A COPOLYMER OF N-VINYLPYRROLIDONE WITH VINYL ALCOHOL

    Directory of Open Access Journals (Sweden)

    T. V. Rudenchyk

    2016-10-01

    Full Text Available A series of hydrophilic film materials with tiamulin fumarate based on polyurethaneureas  (PUU which contain in its structure fragments of the copolymer N-vinylpyrrolidone and  vinyl alcohol at various ratios of components. The structure of the obtained polymer materials  was investigated by the method of IR-spectroscopy. It was established that immobilization of tiamulin fumarate occurs due to physical bonds. The introduction of the tiamulin fumarate in to PUU leads to increased physical and mechanical properties which are within the 3,0-7,3 MPa. Polymeric materials with tiamulin fumarate synthesized at ratio GMDA to VP-VA as 70 to 30 characterized by most high values of strength (7.3 MPa and the relative elongation at break (100% and can be offered for medical and biological tests.

  1. Effect of Sodium Lauryl Sulfate-Fumaric Acid Coupled Addition on the In Vitro Rumen Fermentation with Special Regard to Methanogenesis

    Directory of Open Access Journals (Sweden)

    M. A. Abdl-Rahman

    2010-01-01

    Full Text Available The aim of the current study was to evaluate the effect of sodium lauryl sulfate-fumaric acid coupled addition on in vitro methangenesis and rumen fermentation. Evaluation was carried out using in vitro gas production technique. Ruminal contents were collected from five steers immediately after slaughtering and used for preparation of inoculums of mixed rumen microorganisms. Rumen fluid was then mixed with the basal diet of steers and used to generate four treatments, negative control (no additives, sodium lauryl sulfate (SLS treated, fumaric acid treated, and SLS-fumaric acid coupled addition treated. The results revealed that, relative to control, efficiency in reduction of methanogenesis was as follows: coupled addition > SLS-addition > fumaric acid addition. Both SLS-addition and SLS-fumaric acid coupled addition demonstrated a decremental effect on ammonia nitrogen (NH3–N, total short chain volatile fatty acids (SCVFAs concentrations and the amount of substrate degraded, and an increment effect on microbial mass and microbial yield (YATP. Nevertheless, fumaric acid did not alter any of the previously mentioned parameters but induced a decremental effect on NH3–N. Furthermore, both fumaric acid and SLS-fumaric acid coupled addition increased propionate at the expense of acetate and butyrate, while, defaunation increased acetate at the expense of propionate and butyrate. The pH value was decreased by all treatments relative to control, while, cellulase activity did not differ by different treatments. The current study can be promising strategies for suppressing ruminal methane emissions and improving ruminants feed efficiency.

  2. Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and review of the literature.

    Science.gov (United States)

    Zouboulis, Christos C; Lippert, Undine; Karagiannidis, Ioannis

    2014-01-01

    Sarcoidosis is a rare, systemic disease that is characterized by the formation of granulomas in various organs, including the skin. As the etiology remains unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old female patient with progressive, multi-organ sarcoidosis who had a complete clinical improvement of the skin lesions, a moderate reduction in pulmonary opacities on chest X-ray, a marked subjective improvement in general status and pulmonary efficiency and a marked reduction in serum angiotensin-converting enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric acid esters. The present case and similar reports in the literature highlight the probable efficacy of fumaric acid esters in the treatment of sarcoidosis and other non-infectious, granulomatous diseases. © 2014 S. Karger AG, Basel.

  3. Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model.

    Science.gov (United States)

    Morrison, Juliet; Rathore, Abhay P S; Mantri, Chinmay K; Aman, Siti A B; Nishida, Andrew; St John, Ashley L

    2017-09-15

    There are no approved therapeutics for the treatment of dengue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors. DENV infections can lead to vascular complications, hemorrhage, and shock due to the ability of DENV to infect a variety of immune and nonimmune cell populations. Increasingly, studies have implicated the host response as a major contributor to severe disease. Inflammatory products of various cell types, including responding T cells, mast cells (MCs), and infected monocytes, can contribute to immune pathology. In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection strongly induced metabolic dysregulation, complement signaling, and inflammation. DENV also affected the immune cell content of the spleen and liver, enhancing NK, NKT, and CD8 + T cell activation. The MC-stabilizing drug ketotifen reversed many of these responses without suppressing memory T cell formation and induced additional changes in the transcriptome and immune cell composition of the spleen, consistent with reduced inflammation. This study provides a global transcriptional map of immune activation in DENV target organs of an immunocompetent host and supports the further development of targeted immunomodulatory strategies to treat DENV disease. IMPORTANCE Dengue virus (DENV), which causes febrile illness, is transmitted by mosquito vectors throughout tropical and subtropical regions of the world. Symptoms of DENV infection involve damage to blood vessels and, in rare cases, hemorrhage and shock. Currently, there are no targeted therapies to treat DENV infection, but it is thought that drugs that target the host immune response may be effective in limiting symptoms that result from excessive inflammation. In this study, we measured the host transcriptional response to infection in multiple DENV target organs

  4. Urinary β2 microglobulin can predict tenofovir disoproxil fumarate-related renal dysfunction in HIV-1-infected patients who initiate tenofovir disoproxil fumarate-containing antiretroviral therapy.

    Science.gov (United States)

    Nishijima, Takeshi; Kurosawa, Takuma; Tanaka, Noriko; Kawasaki, Yohei; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

    2016-06-19

    In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. A single-center observational study. The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model. A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR. Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.

  5. Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod-Intravaginal Rings Protects Macaques from Multiple SHIV Exposures

    OpenAIRE

    Srinivasan, Priya; Moss, John A.; Gunawardana, Manjula; Churchman, Scott A.; Yang, Flora; Dinh, Chuong T.; Mitchell, James M.; Zhang, Jining; Fanter, Rob; Miller, Christine S.; Butkyavichene, Irina; McNicholl, Janet M.; Smith, Thomas J.; Baum, Marc M.; Smith, James M.

    2016-01-01

    Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravagina...

  6. Time Course-Dependent Methanogenic Crude Oil Biodegradation: Dynamics of Fumarate Addition Metabolites, Biodegradative Genes, and Microbial Community Composition

    Directory of Open Access Journals (Sweden)

    Courtney R. A. Toth

    2018-01-01

    Full Text Available Biodegradation of crude oil in subsurface petroleum reservoirs has adversely impacted most of the world's oil, converting this resource to heavier forms that are of lower quality and more challenging to recover. Oil degradation in deep reservoir environments has been attributed to methanogenesis over geological time, yet our understanding of the processes and organisms mediating oil transformation in the absence of electron acceptors remains incomplete. Here, we sought to identify hydrocarbon activation mechanisms and reservoir-associated microorganisms that may have helped shape the formation of biodegraded oil by incubating oilfield produced water in the presence of light (°API = 32 or heavy crude oil (°API = 16. Over the course of 17 months, we conducted routine analytical (GC, GC-MS and molecular (PCR/qPCR of assA and bssA genes, 16S rRNA gene sequencing surveys to assess microbial community composition and activity changes over time. Over the incubation period, we detected the formation of transient hydrocarbon metabolites indicative of alkane and alkylbenzene addition to fumarate, corresponding with increases in methane production and fumarate addition gene abundance. Chemical and gene-based evidence of hydrocarbon biodegradation under methanogenic conditions was supported by the enrichment of hydrocarbon fermenters known to catalyze fumarate addition reactions (e.g., Desulfotomaculum, Smithella, along with syntrophic bacteria (Syntrophus, methanogenic archaea, and several candidate phyla (e.g., “Atribacteria”, “Cloacimonetes”. Our results reveal that fumarate addition is a possible mechanism for catalyzing the methanogenic biodegradation of susceptible saturates and aromatic hydrocarbons in crude oil, and we propose the roles of community members and candidate phyla in our cultures that may be involved in hydrocarbon transformation to methane in crude oil systems.

  7. The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: A potential contributor to progressive multifocal leukoencephalopathy risk.

    Science.gov (United States)

    Khatri, Bhupendra O; Garland, Jeffery; Berger, Joseph; Kramer, John; Sershon, Lisa; Olapo, Tayo; Sesing, Jean; Dukic, Mary; Rehn, Eileen

    2015-07-01

    Dimethyl fumarate (Tecfidera™) is an effective therapy for relapsing forms of multiple sclerosis (MS). Our study suggests that this drug may have immunosuppressive properties evidenced by significant sustained reduction in CD8 lymphocyte counts and, to a lesser extent, CD4 lymphocyte counts. This observation is relevant in light of the recent case of progressive multifocal leukoencephalopathy in a patient receiving this drug. Copyright © 2015. Published by Elsevier B.V.

  8. Development of an Amperometric Biosensor Platform for the Combined Determination of L-Malic, Fumaric, and L-Aspartic Acid.

    Science.gov (United States)

    Röhlen, Désirée L; Pilas, Johanna; Schöning, Michael J; Selmer, Thorsten

    2017-10-01

    Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD + ) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM -1 (L-malate biosensor) and 0.4 μA mM -1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0-10.0 mM with a sensitivity of 0.09 μA mM -1 . The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.

  9. In vitro study of a new biodegradable nanocomposite based on poly propylene fumarate as bone glue

    Energy Technology Data Exchange (ETDEWEB)

    Shahbazi, S.; Moztarzadeh, F. [Department of Medical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Sadeghi, G. Mir Mohamad [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Jafari, Y., E-mail: y.j.arisman@gmail.com [Department of Analytical Chemistry, Faculty of Chemistry, University of Kashan, Kashan (Iran, Islamic Republic of)

    2016-12-01

    A novel poly propylene fumarate (PPF)-based glue which is reinforced by nanobioactive glass (NBG) particles and promoted by hydroxyethyl methacrylate (HEMA) as crosslinker agent, was developed and investigated for bone-to-bone bonding applications. In-vitro bioactivity, biodegradability, biocompatibility, and bone adhesion were tested and the results have verified that it can be used as bone glue. In an in-vitro condition, the prepared nanocomposite (PPF/HEMA/NBG) showed improved adhesion to wet bone surfaces. The combined tension and shear resistance between two wet bone surfaces was measured, and its maximum value was 9 ± 59 MPa. To investigate the bioactivity and biodegradability of the nanocomposite, it has been immersed in simulated body fluid (SBF). After 14 days exposure to SBF, a hydroxyapatite (HA) layer formed on the surface of the composite confirms the bioactivity of this material. In the XRD pattern of the nanocomposite surface, the HA characteristic diffraction peak at θ = 26 and 31.8 were observed. Also, by monitoring the weight change after 8 weeks immersion in SBF, the mass loss was about 16.46 wt%. It has been confirmed that this nanocomposite is a biodegradable material. Also, bioactivity and biodegradability of nanocomposite have been proved by SEM images. It has been showed that by using NBG particles and HEMA precursor, mechanical properties increased significantly. The ultimate tensile strength (UTS) of nanocomposite which contains 20% NBG and the ratio of 70/30 wt% PPF/HEMA (PHB.732) was approximately 62 MPa, while the UTS in the pure PPF/HEMA was about 32 MPa. High cell viability in this nanocomposite (MTT assays, 85–95%) can be attributed to the NBG nature which contains calcium phosphate and is similar to physiological environment. Furthermore, it possesses biomineralization and biodegradation which significantly affected by impregnation of hydrophilic HEMA in the PPF-based polymeric matrix. The results indicated that the new

  10. TITRIMETRIC AND SENSITIVE SPECTRO-PHOTOMETRIC METHODS FOR THE ASSAY OF QUETIAPINE FUMARATE IN PHARMACEUTICAL FORMULATIONS

    Directory of Open Access Journals (Sweden)

    Nagaraju Rajendraprasad

    2011-03-01

    Full Text Available Quetiapine fumarate (QTF is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2, and dopamine type 2 (D2 receptors. Titrimetric and spectrophotometric assay of quetiapine fumarate (QTF using perchloric acid and acetic acid as reagents are described. The first method (method A is a non-aqueous titrimetric method and is based on the titration of QTF in glacial acetic acid with 0.01 M acetous perchloric acid using crystal violet as indicator. In the second method (method B, QTF has been measured in 0.1M acetic acid spectrophotometrically at a wavelength of 222 nm. The titri¬metric method was applicable over the range of 2.0–20.0 mg of QTF. The reac¬tion stoichiometry of 1:3 is obtained which served as the basis for calculation. In spectrophotometry, Beer’s law was obeyed over the concentration range of 1.25–15.0 µg mL-1. The linear regression equation of the calibration graph was A = 0.0115 + 0.0673c with a regression coefficient (r of 0.9986 (n = 7. The apparent molar absorptivity was calculated to be 4.25104 L mol-1cm-1 and the Sandell sensitivity was 0.0145 µg cm-2. The limits of detection (LOD and quantification (LOQ calculated as per the ICH guidelines were 0.07 and 0.21 µg mL-1, respectively. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different levels of QTF. The intra-day and inter-day relative standard deviation (%RSD were in the range of 0.99–2.88 and 1.65–2.32%, for method A and B, respectively, with an acceptable percentage relative error (%RE < 2%. The methods were successfully applied to the determination of QTF in two different brands of tablets with good accuracy and precision and without detectable interference by excipients. The methods have demonstrated to be simple and easy to apply in routine usage and do not need any costly instrumentation. Therefore, the proposed procedures are advantageous and can be

  11. Shoe contact dermatitis from dimethyl fumarate: clinical manifestations, patch test results, chemical analysis, and source of exposure.

    Science.gov (United States)

    Giménez-Arnau, Ana; Silvestre, Juan Francisco; Mercader, Pedro; De la Cuadra, Jesus; Ballester, Isabel; Gallardo, Fernando; Pujol, Ramón M; Zimerson, Erik; Bruze, Magnus

    2009-11-01

    The methyl ester form of fumaric acid named dimethyl fumarate (DMF) is an effective mould-growth inhibitor. Its irritating and sensitizing properties were demonstrated in animal models. Recently, DMF has been identified as responsible for furniture contact dermatitis in Europe. To describe the clinical manifestations, patch test results, shoe chemical analysis, and source of exposure to DMF-induced shoe contact dermatitis. Patients with suspected shoe contact dermatitis were studied in compliance with the Declaration of Helsinki. Patch test results obtained with their own shoe and the European baseline series, acrylates and fumaric acid esters (FAE), were recorded according to international guidelines. The content of DMF in shoes was analysed with gas chromatography and mass spectrometry. Acute, immediate irritant contact dermatitis and non-immunological contact urticaria were observed in eight adults and two children, respectively. All the adult patients studied developed a delayed sensitization demonstrated by a positive patch testing to DMF Global preventive measures for avoiding contact with DMF are necessary.

  12. ¿Mejora la entrevista motivacional la eficacia del tratamiento psicológico para dejar de fumar?

    Directory of Open Access Journals (Sweden)

    Bárbara Piñeiro

    2014-01-01

    Full Text Available Distintos estudios muestran que cuando se utiliza la entrevista motivacional (EM añadida a un tratamiento estándar, con el objetivo de aumentar la motivación, mejoran los resultados del tratamiento. El objetivo del presente estudio fue analizar si los fumadores que reciben una intervención con EM antes de un tratamiento psicológico cognitivo conductual para dejar de fumar mejoran la adherencia y la eficacia del tratamiento y reducen la recaída en los seguimientos, en comparación con fumadores que únicamente reciben un tratamiento psicológico cognitivo conductual para dejar de fumar. Se comparó en 58 fumadores (46.6% hombres y 53.4% mujeres la eficacia de añadir o no EM a un tratamiento psicológico para dejar de fumar. El grupo experimental recibió 2 sesiones de EM antes del comienzo de las 6 sesiones del tratamiento psicológico, mientras que el grupo de control recibió únicamente las 6 sesiones del tratamiento. Los resultados no mostraron diferencias estadísticamente significativas entre los 2 grupos en la adherencia al tratamiento, resultados al final del tratamiento y en los seguimientos a los 6 y 12 meses. Concluimos que la intervención con EM no produce mejores resultados en comparación con la aplicación de un tratamiento psicológico cognitivo conductual solo.

  13. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    Science.gov (United States)

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Hydrogen-Bonded Networks Along and Bifurcation of the E-Pathway in Quinol: Fumarate Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Herzog, Elena; Gu, Wei; Juhnke, Hanno D.; Haas, Alexander H.; Mantele, Werner; Simon, Jorg; Helms, Volkhard H.; Lancaster , C. Roy D.

    2012-09-19

    The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu- C180 and heme bD ring C (bD-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the bD-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the bD-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bD ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori.

  15. Extrusion-based 3D printing of poly(propylene fumarate) scaffolds with hydroxyapatite gradients

    Science.gov (United States)

    Trachtenberg, Jordan E.; Placone, Jesse K.; Smith, Brandon T.; Fisher, John P.; Mikos, Antonios G.

    2017-01-01

    The primary focus of this work is to present the current challenges of printing scaffolds with concentration gradients of nanoparticles with an aim to improve the processing of these scaffolds. Furthermore, we address how print fidelity is related to material composition and emphasize the importance of considering this relationship when developing complex scaffolds for bone implants. The ability to create complex tissues is becoming increasingly relevant in the tissue engineering community. For bone tissue engineering applications, this work demonstrates the ability to use extrusion-based printing techniques to control the spatial deposition of hydroxyapatite (HA) nanoparticles in a 3D composite scaffold. In doing so, we combined the benefits of synthetic, degradable polymers, such as poly(propylene fumarate) (PPF), with osteoconductive HA nanoparticles that provide robust compressive mechanical properties. Furthermore, the final 3D printed scaffolds consisted of well-defined layers with interconnected pores, two critical features for a successful bone implant. To demonstrate a controlled gradient of HA, thermogravimetric analysis was carried out to quantify HA on a per-layer basis. Moreover, we non-destructively evaluated the tendency of HA particles to aggregate within PPF using micro-computed tomography (µCT). This work provides insight for proper fabrication and characterization of composite scaffolds containing particle gradients and has broad applicability for future efforts in fabricating complex scaffolds for tissue engineering applications. PMID:28125380

  16. Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems.

    Science.gov (United States)

    Ueda, H; Hacker, M C; Haesslein, A; Jo, S; Ammon, D M; Borazjani, R N; Kunzler, J F; Salamone, J C; Mikos, A G

    2007-12-01

    This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery. Copyright 2007 Wiley Periodicals, Inc.

  17. Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

    Directory of Open Access Journals (Sweden)

    Daniel Ken Inaoka

    2015-07-01

    Full Text Available Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM. In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

  18. Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

    Science.gov (United States)

    Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

    2015-07-07

    Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

  19. Dimethyl fumarate contact dermatitis of the foot: an increasingly widespread disease.

    Science.gov (United States)

    D'Erme, Angelo Massimiliano; Bassi, Andrea; Lotti, Torello; Gola, Massimo

    2012-01-01

    Dimethyl fumarate (DMF) has been recognized as an extremely potent irritant and sensitizer found in sachets inside furniture. The first skin manifestations were correlated to contact with sofas, chairs, and other furniture. In these last years, some papers have reported a development of allergic contact dermatitis on the foot caused by DMF present in high concentration in shoes made in China. We report the case of a 37-year-old woman who presented with severe eczema on the foot shortly after having bought a new pair of shoes. The diagnosis was performed by patch tests with DMF in several dilutions, with pieces of internal and external parts of the shoes, and by chemical analysis of the shoes. In the last three years, goods containing DMF increased diffusely despite the augmentation on global preventive measures by Europe. Therefore, new cases of contact dermatitis could be dependent on DMF, and it is of note that this allergen is not included in most series for patch testing. © 2011 The International Society of Dermatology.

  20. Carbamazepine-Fumaric Acid Co-Crystal Screening Using Solution Based Method

    Directory of Open Access Journals (Sweden)

    Abd Rahim Syarifah

    2016-01-01

    Full Text Available Co-crystals is a multi-component system which connected by non-covalent interactions, present physically as a solid form under ambient conditions. Nowadays, co-crystal has becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ and fumaric acid (FUM co-crystal former (CCF using non-stoichiometric method (addition of CBZ to CCF saturated solution and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD, Differential Scanning Calorimetry (DSC and Fourier Transform Infrared (FT-IR. The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method where no crystal was found precipitate. The findings from this study revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvent systems.

  1. Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention.

    Science.gov (United States)

    Mugwanya, Kenneth K; Baeten, Jared M

    2016-01-01

    Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.

  2. Demand for and availability of online support to stop smoking Soporte en línea para parar de fumar Suporte online para parar de fumar

    Directory of Open Access Journals (Sweden)

    Beatriz Helena Carlini

    2012-12-01

    Full Text Available OBJECTIVES: Estimate the frequency of online searches on the topic of smoking and analyze the quality of online resources available to smokers interested in giving up smoking. METHODS: Search engines were used to revise searches and online resources related to stopping smoking in Brazil in 2010. The number of searches was determined using analytical tools available on Google Ads; the number and type of sites were determined by replicating the search patterns of internet users. The sites were classified according to content (advertising, library of articles and other. The quality of the sites was analyzed using the Smoking Treatment Scale- Content (STS-C and the Smoking Treatment Scale - Rating (STS-R. RESULTS: A total of 642,446 searches was carried out. Around a third of the 113 sites encountered were of the 'library' type, i.e. they only contained articles, followed by sites containing clinical advertising (18.6 and professional education (10.6. Thirteen of the sites offered advice on quitting directed at smokers. The majority of the sites did not contain evidence-based information, were not interactive and did not have the possibility of communicating with users after the first contact. Other limitations we came across were a lack of financial disclosure as well as no guarantee of privacy concerning information obtained and no distinction made between editorial content and advertisements. CONCLUSIONS: There is a disparity between the high demand for online support in giving up smoking and the scarcity of quality online resources for smokers. It is necessary to develop interactive, customized online resources based on evidence and random clinical testing in order to improve the support available to Brazilian smokers.OBJETIVO: Estimar la frecuencia de búsquedas en línea sobre tabaquismo y analizar la calidad de los recursos en línea de apoyo para fumadores interesados en parar de fumar. MÉTODOS: Revisión de búsquedas y recursos en l

  3. Growth of Campylobacter incubated aerobically in fumarate-pyruvate media or media supplemented with dairy, meat, or soy extracts and peptones.

    Science.gov (United States)

    Hinton, Arthur

    2016-09-01

    The ability of Campylobacter to grow aerobically in media supplemented with fumarate-pyruvate or with dairy, meat, or soy extracts or peptones was examined. Optical densities (OD) of Campylobacter cultured in basal media, media supplemented with fumarate-pyruvate or with 1.0, 2.5, 5.0, or 7.5% beef extract was measured. Growth was also compared in media supplemented with other extracts or peptones. Finally, cfu/mL of Campylobacter recovered from basal media or media supplemented with fumarate-pyruvate, casamino acids, beef extract, soytone, or beef extract and soytone was determined. Results indicated that OD of cultures grown in media supplemented with fumarate-pyruvate or with 5.0 or 7.5% beef extract were higher than OD of isolates grown in basal media or media supplemented with lower concentrations of beef extract. Highest OD were produced by isolates grown in media supplemented with beef extract, peptone from meat, polypeptone, proteose peptone, or soytone. Also, more cfu/mL were recovered from media with fumarate-pyruvate, beef extract, soytone, or beef extract-soytone than from basal media or media with casamino acids. Findings indicate that media supplemented with organic acids, vitamins, and minerals and media supplemented with extracts or peptones containing these metabolites can support aerobic growth of Campylobacter. Published by Elsevier Ltd.

  4. Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF).

    Science.gov (United States)

    De Clercq, Erik

    2016-11-01

    Tenofovir alafenamide (TAF) can be considered a new prodrug of tenofovir (TFV), as successor of tenofovir disoproxil fumarate (TDF). It is in vivo as potent against human immunodeficiency virus (HIV) at a 30-fold lower dose (10mg) than TDF (300mg). TAF has been approved in November 2015 (in the US and EU), as a single-tablet regimen (STR) containing 150mg elvitegravir (E), 150mg cobicistat (C), 200mg emtricitabine [(-)FTC] (F) and 10mg TAF, marketed as Genvoya®, on 01 March 2016 in the US as an STR containing 25mg rilpivirine (R), 200mg F and 25mg TAF, marketed as Odefsey®, and on 4 April 2016 in the US, as an STR containing 200mg F and 25mg TAF, marketed as Descovy®, for the treatment of HIV infections. STR combinations containing TAF and emtricitabine could be paired with a range of third agents, for example, darunavir and cobicistat. TAF has a much lower risk of kidney toxicity or bone density changes than TDF, and also offers long-term potential in the pre-exposure prophylaxis (PrEP) of HIV infections. TAF is specifically accumulated in lymphatic tissue, and in the liver, and hence also holds great potential for the treatment of hepatitis B virus (HBV) infections. Akin to TDF, TAF is converted intracellularly to TFV. Its active diphosphate metabolite (TFVpp) is targeted at the RNA-dependent DNA polymerase (reverse transcriptase) of either HIV or HBV. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells

    Science.gov (United States)

    Bennett Saidu, Nathaniel Edward; Bretagne, Marie; Mansuet, Audrey Lupo; Just, Pierre-Alexandre; Leroy, Karen; Cerles, Olivier; Chouzenoux, Sandrine; Nicco, Carole; Damotte, Diane; Alifano, Marco; Borghese, Bruno; Goldwasser, François; Batteux, Frédéric; Alexandre, Jérôme

    2018-01-01

    KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells. This effect was observed in patient-derived cancer cell lines harbouring a G12V KRAS mutation, compared with cell lines without such a mutation. In addition, KRAS*G12V over-expression in the human Caco-2 colon cancer cell line significantly promoted DMF-induced cell death, as well as DMF-induced- reactive oxygen species (ROS) formation and -glutathione (GSH) depletion. Moreover, in contrast to malignant cells, our data confirms that the same concentration of DMF has no significant cytotoxic effects on non-tumorigenic human ARPE-19 retinal epithelial, murine 3T3 fibroblasts and primary mice bone marrow cells; but is rather associated with NRF2 activation, decreased ROS and increased GSH levels. Furthermore, DJ-1 down-regulation experiments showed that this protein does not play a protective role against NRF2 in non-tumorigenic cells, as it does in malignant ones. This, interestingly, could be at the root of the differential effect of DMF observed between malignant and non-tumorigenic cells. Our results suggest for the first time that the dependence on NRF2 observed in mutated KRAS malignant cells makes them more sensitive to the cytotoxic effect of DMF, which thus opens up new prospects for the therapeutic applications of DMF. PMID:29507676

  6. Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells.

    Science.gov (United States)

    Bennett Saidu, Nathaniel Edward; Bretagne, Marie; Mansuet, Audrey Lupo; Just, Pierre-Alexandre; Leroy, Karen; Cerles, Olivier; Chouzenoux, Sandrine; Nicco, Carole; Damotte, Diane; Alifano, Marco; Borghese, Bruno; Goldwasser, François; Batteux, Frédéric; Alexandre, Jérôme

    2018-02-06

    KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells. This effect was observed in patient-derived cancer cell lines harbouring a G12V KRAS mutation, compared with cell lines without such a mutation. In addition, KRAS*G12V over-expression in the human Caco-2 colon cancer cell line significantly promoted DMF-induced cell death, as well as DMF-induced- reactive oxygen species (ROS) formation and -glutathione (GSH) depletion. Moreover, in contrast to malignant cells, our data confirms that the same concentration of DMF has no significant cytotoxic effects on non-tumorigenic human ARPE-19 retinal epithelial, murine 3T3 fibroblasts and primary mice bone marrow cells; but is rather associated with NRF2 activation, decreased ROS and increased GSH levels. Furthermore, DJ-1 down-regulation experiments showed that this protein does not play a protective role against NRF2 in non-tumorigenic cells, as it does in malignant ones. This, interestingly, could be at the root of the differential effect of DMF observed between malignant and non-tumorigenic cells. Our results suggest for the first time that the dependence on NRF2 observed in mutated KRAS malignant cells makes them more sensitive to the cytotoxic effect of DMF, which thus opens up new prospects for the therapeutic applications of DMF.

  7. Characterization of lymphopenia in patients with MS treated with dimethyl fumarate and fingolimod.

    Science.gov (United States)

    Nakhaei-Nejad, Maryam; Barilla, David; Lee, Chieh-Hsin; Blevins, Gregg; Giuliani, Fabrizio

    2018-03-01

    Lymphopenia is a common occurrence of disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). The aim of this study was to dissect the prevalence of various lymphocyte subsets in patients with RRMS treated with 2 DMTs commonly associated with lymphopenia, dimethyl fumarate (DMF), and fingolimod (FTY). Multicolor flow cytometry and multiplex assays were used to identify up to 50 lymphocyte subpopulations and to examine the expression of multiple cytokines in selected patients. We compared patients untreated (NT) or treated with FTY or DMF who did (DMF-L) or did not (DMF-N) develop lymphopenia. All FTY patients developed lymphopenia in both T-cell and B-cell compartments. CD41 T cells were more affected by this treatment than CD81 cells. In the B-cell compartment, the CD271IgD2 subpopulation was reduced. T cells but not B cells were significantly reduced in DMF-L. However, within the B cells, CD271 cells were significantly lower. Both CD41 and CD81 subpopulations were reduced in DMF-L. Within the remaining CD41 and CD81 compartments, there was an expansion of the naive subpopulation and a reduction of the effector memory subpopulation. Unactivated lymphocyte from DMF-L patients had significantly higher levels of interferon-γ, interleukin (IL)-12, IL-2, IL-4, IL-6, and IL-1β compared with DMF-N. In plasma, TNFβ was significantly higher in DMF-N and DMF-L compared with NT, whereas CCL17 was significantly higher in DMF-L compared with NT and DMF-N. This study shows that different treatments can target different lymphocyte compartments and suggests that lymphopenia can induce compensatory mechanisms to maintain immune homeostasis.

  8. Update on extended release quetiapine fumarate in schizophrenia and bipolar disorders

    Directory of Open Access Journals (Sweden)

    El-Khalili N

    2012-11-01

    Full Text Available Nizar El-KhaliliAlpine Clinic, Lafayette, IN, USAAbstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR and as an extended release (XR formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse, the treatment of bipolar disorder (manic and depressive episodes, and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS. The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation

  9. Digital micromirror device (DMD)-based 3D printing of poly(propylene fumarate) scaffolds.

    Science.gov (United States)

    Mott, Eric J; Busso, Mallory; Luo, Xinyi; Dolder, Courtney; Wang, Martha O; Fisher, John P; Dean, David

    2016-04-01

    Our recent investigations into the 3D printing of poly(propylene fumarate) (PPF), a linear polyester, using a DMD-based system brought us to a resin that used titanium dioxide (TiO2) as an ultraviolet (UV) filter for controlling cure depth. However, this material hindered the 3D printing process due to undesirable lateral or "dark" curing (i.e., in areas not exposed to light from the DMD chip). Well known from its use in sunscreen, another UV filter, oxybenzone, has previously been used in conjunction with TiO2. In this study we hypothesize that combining these two UV filters will result in a synergistic effect that controls cure depth and avoids dark cure. A resin mixture (i.e., polymer, initiator, UV filters) was identified that worked well. The resin was then further characterized through mechanical testing, cure testing, and cytotoxicity testing to investigate its use as a material for bone tissue engineering scaffolds. Results show that the final resin eliminated dark cure as shown through image analysis. Mechanically the new scaffolds proved to be far weaker than those printed from previous resins, with compressive strengths of 7.8 ± 0.5 MPa vs. 36.5 ± 1.6 MPa, respectively. The new scaffolds showed a 90% reduction in elastic modulus and a 74% increase in max strain. These properties may be useful in tissue engineering applications where resorption is required. Initial cytotoxicity evaluation was negative. As hypothesized, the use of TiO2 and oxybenzone showed synergistic effects in the 3D printing of PPF tissue engineering scaffolds. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Foamed oligo(poly(ethylene glycol)fumarate) hydrogels as versatile prefabricated scaffolds for tissue engineering.

    Science.gov (United States)

    Henke, Matthias; Baumer, Julia; Blunk, Torsten; Tessmar, Joerg

    2014-03-01

    Radically cross-linked hydrogels are frequently used as cell carriers due to their excellent biocompatibility and their tissue-like mechanical properties. Through frequent investigation, PEG-based polymers such as oligo(poly(ethylene glycol)fumarate [OPF] have proven to be especially suitable as cell carriers by encapsulating cells during hydrogel formation. In some cases, NaCl or biodegradable gelatin microparticles were added prior to cross-linking in order to provide space for the proliferating cells, which would otherwise stay embedded in the hydrogel matrix. However, all of these immediate cross-linking procedures involve time consuming sample preparation and sterilization directly before cell culture and often show notable swelling after their preparation. In this study, ready to use OPF-hydrogel scaffolds were prepared by gas foaming, freeze drying, individual packing into bags and subsequent γ-sterilization. The scaffolds could be stored and used "off-the-shelf" without any need for further processing prior to cell culture. Thus the handling was simplified and the sterility of the cell carrier was assured. Further improvement of the gel system was achieved using a two component injectable system, which may be used for homogenous injection molding in order to create individually shaped three dimensional scaffolds. In order to evaluate the suitability of the scaffolds for tissue engineering, constructs were seeded with juvenile bovine chondrocytes and cultured for 28 days. Cross-sections of the respective constructs showed an intense and homogenous red staining of GAG with safranin O, indicating a homogenous cell distribution within the scaffolds and the production of substantial amounts of GAG-rich matrix. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Metabolic reprogramming for producing energy and reducing power in fumarate hydratase null cells from hereditary leiomyomatosis renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Youfeng Yang

    Full Text Available Fumarate hydratase (FH-deficient kidney cancer undergoes metabolic remodeling, with changes in mitochondrial respiration, glucose, and glutamine metabolism. These changes represent multiple biochemical adaptations in glucose and fatty acid metabolism that supports malignant proliferation. However, the metabolic linkages between altered mitochondrial function, nucleotide biosynthesis and NADPH production required for proliferation and survival have not been elucidated. To characterize the alterations in glycolysis, the Krebs cycle and the pentose phosphate pathways (PPP that either generate NADPH (oxidative or do not (non-oxidative, we utilized [U-(13C]-glucose, [U-(13C,(15N]-glutamine, and [1,2- (13C2]-glucose tracers with mass spectrometry and NMR detection to track these pathways, and measured the oxygen consumption rate (OCR and extracellular acidification rate (ECAR of growing cell lines. This metabolic reprogramming in the FH null cells was compared to cells in which FH has been restored. The FH null cells showed a substantial metabolic reorganization of their intracellular metabolic fluxes to fulfill their high ATP demand, as observed by a high rate of glucose uptake, increased glucose turnover via glycolysis, high production of glucose-derived lactate, and low entry of glucose carbon into the Krebs cycle. Despite the truncation of the Krebs cycle associated with inactivation of fumarate hydratase, there was a small but persistent level of mitochondrial respiration, which was coupled to ATP production from oxidation of glutamine-derived α-ketoglutarate through to fumarate. [1,2- (13C2]-glucose tracer experiments demonstrated that the oxidative branch of PPP initiated by glucose-6-phosphate dehydrogenase activity is preferentially utilized for ribose production (56-66% that produces increased amounts of ribose necessary for growth and NADPH. Increased NADPH is required to drive reductive carboxylation of α-ketoglutarate and fatty acid

  12. Percepción de los estudiantes de enfermería en cuanto al comportamiento de fumar en México

    OpenAIRE

    Francisco Cruz Vazquez; Sandra Cristina Pillon; Maria Teresa Cuamatzi

    2004-01-01

    El estudio tiene como objetivo evaluar el comportamiento de fumar y la percepción de los factores que influeyen en ese comportamiento, entre estudiantes del primer año de Licenciatura en enfermería. Fueron entrevistado 36 alumnos del primer año de graduación en enfermería. Siendo 18 (50%) fumadores, con edad media de 23,5 años; 75% del sexo femenino en cuanto al patron de consumo estos fuman de 2 a 6 cigarrillos al dia, empezaron a fumar en media con 15 años. En cuanto a la per...

  13. The Anti-Inflammatory Effects of Dimethyl Fumarate in Astrocytes Involve Glutathione and Haem Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Shao Xia Lin

    2011-03-01

    Full Text Available DMF (dimethyl fumarate exerts anti-inflammatory and prometabolic effects in a variety of cell types, and a formulation (BG-12 is being evaluated for monotherapy in multiple sclerosis patients. DMF modifies glutathione (GSH levels that can induce expression of the anti-inflammatory protein HO-1 (haem oxygenase-1. In primary astrocytes and C6 glioma cells, BG-12 dose-dependently suppressed nitrite production induced by either LI [LPS (lipopolysaccharide at 1 μg/ml plus IFNγ (interferon γ at 20 units/ml] or a mixture of proinflammatory cytokines, with greater efficacy in C6 cells. BG-12 reduced NOS2 (nitric oxide synthase 2 mRNA levels and activation of a NOS2 promoter, reduced nuclear levels of NF-κB (nuclear factor κB p65 subunit and attenuated loss of |κBα (inhibitory κBα in both cell types, although with greater effects in astrocytes. In astrocytes, LI decreased mRNA levels for GSHr (GSH reductase and GCL (c-glutamylcysteine synthetase, and slightly suppressed GSHs (GSH synthetase mRNAs. Co-treatment with BG-12 prevented those decreased and increased levels above control values. In contrast, LI reduced GSHp (GSH peroxidase and GCL in C6 cells, and BG-12 had no effect on those levels. BG-12 increased nuclear levels of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2, an inducer of GSH-related enzymes, in astrocytes but not C6 cells. In astrocytes, GSH was decreased by BG-12 at 2 h and increased at 24 h. Prior depletion of GSH using buthionine-sulfoximine increased the ability of BG-12 to reduce nitrites. In astrocytes, BG-12 increased HO-1 mRNA levels and effects on nitrite levels were blocked by an HO-1 inhibitor. These results demonstrate that BG-12 suppresses inflammatory activation in astrocytes and C6 glioma cells, but with distinct mechanisms, different dependence on GSH and different effects on transcription factor activation.

  14. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

    Science.gov (United States)

    Ke, Weixia; Zhang, Chi; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

    2016-11-01

    Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. For Chinese chronic hepatitis B patients, ETV is still the most cost

  15. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

    Directory of Open Access Journals (Sweden)

    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  16. Studies on Poly(propylene fumarate-co-caprolactone diol Thermoset Composites towards the Development of Biodegradable Bone Fixation Devices

    Directory of Open Access Journals (Sweden)

    M. Jayabalan

    2009-01-01

    Full Text Available The effect of reinforcement in the cross-linked poly(propylene fumarate-co-caprolactone diol thermoset composites based on Kevlar fibres and hydroxyapatite was studied. Cross-linked poly(propylene fumarate-co-caprolactone diol was also studied without any reinforcement for comparison. The reinforcing fibre acts as a barrier for the curing reaction leading to longer setting time and lesser cross-link density. The fibre and HA reinforced composites have almost the same compressive strength. Nonreinforced material undergoes greater degree of swelling. Among the reinforced materials, the hydroxyapatite reinforced composite has a much higher swelling percentage than the fibre reinforced one. The studies on in vitro degradation of the cured materials reveal hydrolytic degradation in Ringer's solution and PBS medium during aging. All the three materials are found to swell initially in Ringer's solution and PBS medium during aging and then undergo gradual degradation. Compression properties of these cross-linked composites increase with aging; HA reinforced composite has the highest compressive strength and compressive modulus, whereas the aged fibre-reinforced composite has the least compressive strength and modulus.

  17. Studies on Poly(propylene fumarate-co-caprolactone diol) Thermoset Composites towards the Development of Biodegradable Bone Fixation Devices.

    Science.gov (United States)

    Jayabalan, M

    2009-01-01

    The effect of reinforcement in the cross-linked poly(propylene fumarate-co-caprolactone diol) thermoset composites based on Kevlar fibres and hydroxyapatite was studied. Cross-linked poly(propylene fumarate-co-caprolactone diol) was also studied without any reinforcement for comparison. The reinforcing fibre acts as a barrier for the curing reaction leading to longer setting time and lesser cross-link density. The fibre and HA reinforced composites have almost the same compressive strength. Nonreinforced material undergoes greater degree of swelling. Among the reinforced materials, the hydroxyapatite reinforced composite has a much higher swelling percentage than the fibre reinforced one. The studies on in vitro degradation of the cured materials reveal hydrolytic degradation in Ringer's solution and PBS medium during aging. All the three materials are found to swell initially in Ringer's solution and PBS medium during aging and then undergo gradual degradation. Compression properties of these cross-linked composites increase with aging; HA reinforced composite has the highest compressive strength and compressive modulus, whereas the aged fibre-reinforced composite has the least compressive strength and modulus.

  18. Development and application of an exchange model for anisotropic water diffusion in the microporous MOF aluminum fumarate

    Science.gov (United States)

    Splith, Tobias; Fröhlich, Dominik; Henninger, Stefan K.; Stallmach, Frank

    2018-06-01

    Diffusion of water in aluminum fumarate was studied by means of pulsed field gradient (PFG) nuclear magnetic resonance (NMR). Due to water molecules exchanging between the intracrystalline anisotropic pore space and the isotropic intercrystalline void space the model of intracrystalline anisotropic diffusion fails to describe the experimental PFG NMR data at high observation times. Therefore, the two-site exchange model developed by Kärger is extended to the case of exchange between an anisotropic and an isotropic site. This extended exchange model is solved by numerical integration. It describes the experimental data very well and yields values for the intracrystalline diffusion coefficient and the mean residence times of the respective sites. Further PFG NMR studies were performed with coatings consisting of small aluminum fumarate crystals, which are used in adsorptive heat transformation applications. The diffusion coefficients of water in the small crystal coating are compared to the values expected from the extended two-site exchange model and from the model of long-range diffusion.

  19. Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice

    NARCIS (Netherlands)

    Hanson, Julien; Gille, Andreas; Zwykiel, Sabrina; Lukasova, Martina; Clausen, Björn E.; Ahmed, Kashan; Tunaru, Sorin; Wirth, Angela; Offermanns, Stefan

    2010-01-01

    The antidyslipidemic drug nicotinic acid and the antipsoriatic drug monomethyl fumarate induce cutaneous flushing through activation of G protein-coupled receptor 109A (GPR109A). Flushing is a troublesome side effect of nicotinic acid, but may be a direct reflection of the wanted effects of

  20. Rumen microbial response in production of CLA and methane to safflower oil in association with fish oil or/and fumarate.

    Science.gov (United States)

    Li, Xiang Z; Long, Rui J; Yan, Chang G; Lee, Hong G; Kim, Young J; Song, Man K

    2011-06-01

    Supplementation effect of fish oil and/or fumarate on production of conjugated linoleic acid (CLA) and methane by rumen microbes was examined when incubated with safflower oil. One hundred and twenty milligrams of safflower oil (SO), safflower oil with 24 mg fish oil (SOFO), safflower oil with 24 mmol/L fumarate (SOFA), or safflower oil with 24 mg fish oil and 24 mmol/L fumarate (SOFOFA) were added to the 90 mL culture solution. The culture solution was also made without any supplements (control). The SOFA and SOFOFA increased pH and propionate (C3) compared to other treatments from 3 h incubation time. An accumulated amount of total methane (CH(4) ) for 12 h incubation was decreased by all the supplements compared to control. The concentrations of c9,t11CLA for all the incubation times were increased in the treatments of SOFO, SOFA and SOFOFA compared to SO. The highest concentration of c9,t11CLA was observed from SOFOFA among all the treatments at all incubation times. Overall data indicate that supplementation of combined fumarate and/or fish oil when incubated with safflower oil could depress CH(4) generation and increase production of C(3) and CLA under the condition of current in vitro study. © 2011 The Authors; Animal Science Journal © 2011 Japanese Society of Animal Science.

  1. Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B : A European multicenter study

    NARCIS (Netherlands)

    Si-Ahmed, Si-Nafa; Pradat, Pierre; Zoutendijk, Roeland; Buti, Maria; Mallet, Vincent; Cruiziat, Claire; Deterding, Katja; Dumortier, Jerome; Bailly, Francois; Esteban, Rafael; Wedemeyer, Heiner; Janssen, Harry L.; Zoulim, Fabien

    2011-01-01

    Background and aims: The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in

  2. Dietary inclusion of diallyl disulfide, yucca powder, calcium fumarate, an extruded linseed product, or medium-chain fatty acids does not affect methane production in lactating dairy cows

    NARCIS (Netherlands)

    Zijderveld, van S.M.; Dijkstra, J.; Perdok, H.B.; Newbold, J.R.; Gerrits, W.J.J.

    2011-01-01

    Two similar experiments were conducted to assess the effect of diallyl disulfide (DADS), yucca powder (YP), calcium fumarate (CAFU), an extruded linseed product (UNSAT), or a mixture of capric and caprylic acid (MCFA) on methane production, energy balance, and dairy cow performance. In experiment 1,

  3. Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

    Science.gov (United States)

    Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

  4. Preservation of acidified cucumbers with a natural preservative combination of fumaric acid and allyl isothiocyanate that target lactic acid bacteria and yeasts

    Science.gov (United States)

    Without the addition of preservative compounds cucumbers acidified with 150 mM acetic acid with pH adjusted to 3.5 typically undergo fermentation by lactic acid bacteria. Fumaric acid (20 mM) inhibited growth of Lactobacillus plantarum and the lactic acid bacteria present on fresh cucumbers, but sp...

  5. Omics-based approaches reveal phospholipids remodeling of Rhizopus oryzae responding to furfural stress for fumaric acid-production from xylose.

    Science.gov (United States)

    Pan, Xinrong; Liu, Huanhuan; Liu, Jiao; Wang, Cheng; Wen, Jianping

    2016-12-01

    In order to relieve the toxicity of furfural on Rhizopus oryzae fermentation, the molecular mechanism of R. oryzae responding to furfural stress for fumaric acid-production was investigated by omics-based approaches. In metabolomics analysis, 29 metabolites including amino acid, sugars, polyols and fatty acids showed significant changes for maintaining the basic cell metabolism at the cost of lowering fumaric acid production. To further uncover the survival mechanism, lipidomics was carried out, revealing that phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and polyunsaturated acyl chains might be closely correlated with R. oryzae's adapting to furfural stress. Based on the above omics analysis, lecithin, inositol and soybean oil were exogenously supplemented separately with an optimized concentration in the presence of furfural, which increased fumaric acid titer from 5.78g/L to 10.03g/L, 10.05g/L and 12.13g/L (increased by 73.5%, 73.8% and 110%, respectively). These findings provide a methodological guidance for hemicellulose-fumaric acid development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Preparation of hydrolytic liquid from dried distiller's grains with solubles and fumaric acid fermentation by Rhizopus arrhizus RH 7-13.

    Science.gov (United States)

    Liu, Huan; Yue, Xuemin; Jin, Yuhan; Wang, Meng; Deng, Li; Wang, Fang; Tan, Tianwei

    2017-10-01

    Fumaric acid production from lignocellulosic materials is an alternative chemicals production system. This work investigated the suitable conditions for hydrolysis of dried distiller's grains with solubles (DDGS). The hydrolytic liquid was subsequently used for the production of fumaric acid. After optimizing the hydrolysis conditions, the most suitable concentration of H 2 SO 4 (2%), hydrolysis temperature (120 °C), hydrolysis time (100min) and solid/liquid ratio (1:10) were obtained. The yield of monosaccharides reached 258 mg/g DDGS and 15.88 g/L glucose, 7.53 g/L xylose and 2.35 g/L arabinose were obtained in unprocessed hydrolytic liquid. The furfural inhibitor in the hydrolytic liquid was also detected and the yield of it was reducing progressively in the pretreatment process. The ferment ability of the hydrolytic liquid from DDGS was tested through the process of fumaric acid production by Rhizopus arrhizus RH 7-13. The unprocessed hydrolytic liquid was not appropriate for the fermentation process. The yield of fumaric acid from the concentrated processed hydrolytic liquid reached 18.93 g/L, which was close to the yield of fermenting 80 g/L glucose. This result indicated that the commonly used carbon resource glucose could to some extent be replaced by processed hydrolytic liquid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Cytotoxicity of Paclitaxel in biodegradable self-assembled core-shell poly(lactide-co-glycolide ethylene oxide fumarate) nanoparticles.

    Science.gov (United States)

    He, Xuezhong; Ma, Junyu; Mercado, Angel E; Xu, Weijie; Jabbari, Esmaiel

    2008-07-01

    Biodegradable core-shell polymeric nanoparticles (NPs), with a hydrophobic core and hydrophilic shell, are developed for surfactant-free encapsulation and delivery of Paclitaxel to tumor cells. Poly (lactide-co-glycolide fumarate) (PLGF) and Poly (lactide-fumarate) (PLAF) were synthesized by condensation polymerization of ultra-low molecular weight poly(L: -lactide-co-glycolide) (ULMW PLGA) with fumaryl chloride (FuCl). Similarly, poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromer was synthesized by reacting ultra-low molecular weight poly(L: -lactide) (ULMW PLA) and PEG with FuCl. The blend PLGF/PLEOF and PLAF/PLEOF macromers were self-assembled into NPs by dialysis. The NPs were characterized with respect to particle size distribution, morphology, and loading efficiency. The physical state and miscibility of Paclitaxel in NPs were characterized by differential scanning calorimetry. Tumor cell uptake and cytotoxicity of Paclitaxel loaded NPs were measured by incubation with HCT116 human colon carcinoma cells. The distribution of NPs in vivo was assessed with Apc(Min/+)mouse using infrared imaging. PLEOF macromer, due to its amphiphilic nature, acted as a surface active agent in the process of self-assembly which produced core-shell NPs with PLGF/PLAF and PLEOF macromers as the core and shell, respectively. The encapsulation efficiency ranged from 70 to 56% and it was independent of the macromer but decreased with increasing concentration of Paclitaxel. Most of the PLGF and PLAF NPs degraded in 15 and 28 days, respectively, which demonstrated that the release was dominated by hydrolytic degradation and erosion of the matrix. As the concentration of Paclitaxel was increased from 0 to 10, and 40 mug/ml, the viability of HCT116 cells incubated with free Paclitaxel decreased from 100 to 65 and 40%, respectively, while those encapsulated in PLGF/PLEOF NPs decreased from 93 to 54 and 28%. Groups with Paclitaxel loaded NPs had higher cytotoxicity compared to

  8. Development and Validation of UV Spectrophotometric Method For Determination of Bisoprolol Fumarate in Bulk and Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    Shahinaz Mohammed

    2017-10-01

    Full Text Available In this study a simple, accurate and precise UV- spectrophotometric method was developed for the estimation of bisoprolol fumarate (BF in bulk and tablet dosage form. The method was based on measurement of absorbance of BF aqueous solution at 225 nm. Validation was conducted in accordance to ICH guidelines. The calibration curve was linear in the concentration range 5.0-30.0 µg/mL with correlation coefficient not less than 0.996. The limit of detection and limit of quantification were 0.22 μg/ml and 0.66 μg/ml, respectively. Intraday and intermediate precision of the developed method were reflected by the low RSD% values (1.19 and 0.854, respectively. The recovery percentage was 100.6 ± 0.6%, n=3. The proposed method was applied for the assay of BF in three different brands.

  9. Tenofovir Disoproxil Fumarate Fails to Prevent HIV Acquisition or the Establishment of a Viral Reservoir: Two Case Reports.

    Science.gov (United States)

    Fox, Julie; Brady, Michael; Alexander, Hannah; Davies, Olubanke; Robinson, Nicola; Pace, Mathew; Else, Laura; Cason, John; Khoo, Saye; Back, David; Fidler, Sarah; Frater, John

    2016-03-01

    The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention. The World Health Organization recently recommended Truvada(®) (Gilead Sciences, Inc.) or tenofovir disoproxil fumarate (TDF) for high-risk individuals, with limited data for single-agent TDF PrEP in men who have sex with men (MSM). We report two cases of TDF PrEP failure in MSM who had received long-term TDF for hepatitis B infection and had therapeutic levels of drug immediately after HIV acquisition. Rapid antiretroviral intensification at diagnosis of acute HIV infection failed to limit immune dysfunction or prevent the establishment of a viral reservoir.

  10. Inhibition of fumarate reductase in Leishmania major and L. donovani by chalcones

    DEFF Research Database (Denmark)

    Chen, M; Zhai, L; Christensen, S B

    2001-01-01

    Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity...... of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major...... promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4'-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4'-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. major...

  11. Studies on biodegradation of crosslinked hydroxy terminated-poly(proplyene fumarate) and formation of scaffold for orthopedic applications.

    Science.gov (United States)

    Shalumon, K T; Jayabalan, M

    2009-12-01

    Biodegradation of crosslinked-hydroxy terminated-poly(proplyene fumarate) (X-HTPPF) has been studied in simulated physiological media to assess the formation of porous scaffold structure for bone growth and remodeling in load bearing orthopedic applications. Variation in crosslink density and surface hydrophilicity of X-HTPPF are observed due to non-stoichiometric mass of reacting partners. These variations influence absorption of the medium and biodegradation during aging. Though the initial absorption of medium is relatively higher with the crosslinked polymer (PNVP1) having 63.6% HT-PPF and 36.4% comonomer n-vinyl pyrrolidone (NVP) during the initial period of aging, the weight loss due to subsequent degradation with time is relatively lesser. PNVP1 undergo slow degradation with formation of fibril structure on the surface. The present crosslinked material PNVP1 is a candidate for the load bearing orthopedic applications.

  12. Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

    Directory of Open Access Journals (Sweden)

    Singh D

    2017-10-01

    Full Text Available Dave Singh,1 Massimo Corradi,2 Monica Spinola,3 Alberto Papi,4 Omar S Usmani,5 Mario Scuri,3 Stefano Petruzzelli,3 Jørgen Vestbo1 1Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 2Department of Medicine and Surgery, University of Parma, Parma, Italy; 3Chiesi Farmaceutici SpA, Parma, Italy; 4Department of Medical Sciences, Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; 5National Heart and Lung Institute, Imperial College London, London, UK Abstract: The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs, long-acting beta2 agonists (LABAs, and long-acting muscarinic antagonists (LAMAs has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff/formoterol fumarate (6 µg/puff/glycopyrronium bromide (12.5 µg/puff has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide

  13. Hábito de fumar en la adolescencia al nivel comunitario Smoking in adolescence at a community level

    Directory of Open Access Journals (Sweden)

    Neiza Álvarez Valdés

    2007-09-01

    Full Text Available Considerándose la adolescencia como la etapa más susceptible a desarrollar una adicción y observándose un incremento de los adolescentes fumadores en el área de salud, se propone caracterizar el hábito de fumar en los adolescentes atendidos por un Grupo Básico de Trabajo del Policlínico “Marcio Manduley”, en el año 2006, a través de un estudio descriptivo de índole transversal en el que se investiga a 402 adolescentes de entre 11 y 14 años de edad que cumplen con los criterios de inclusión y exclusión. Se utiliza como principal instrumento la Encuesta Mundial sobre Tabaquismo en Jóvenes (GYTS 2001, donde se clasifican los adolescentes en fumadores y no fumadores, se estima una prevalencia de 14,2 % de fumadores, con predominio del sexo masculino y de la edad de 13 años. Se destaca la adquisición de la droga (cigarro en tiendas o vendedores callejeros y su consumo en los hogares. Se constata una alta exposición al humo del tabaco ambiental, así como un elevado índice de familiares fumadores que conviven con los escolares. Se clasifican los fumadores activos, en su mayoría, en bajos dependientes físicos, y con alta motivación por dejar de fumar. Se concluye que el hábito de fumar en la adolescencia es un problema de salud de alta prevalencia en la población estudiada, por lo que se hace necesaria una activa participación social y comunitaria, teniendo en cuenta que la atención integral al adolescente constituye un eslabón medular en el equilibrio de la salud comunitaria.Considering adolescence like the more susceptible stage to develop addiction, and washing an increment of smoker adolescents in health area, we propose to characterize smoking in adolescent seen in Basic Work Group of “Marcio Manduley” Polyclinic in 2006, by means of a descriptive and transversal study made in 402 adolescent aged between 11 y 14, fulfilling inclusion and exclusion criteria. We used the main instrument, World Survey on Nicotinism

  14. Fumaric Acid Esters Can Block Pro-Inflammatory Actions of Human CRP and Ameliorate Metabolic Disturbances in Transgenic Spontaneously Hypertensive Rats

    Czech Academy of Sciences Publication Activity Database

    Šilhavý, Jan; Zídek, Václav; Mlejnek, Petr; Landa, Vladimír; Šimáková, Miroslava; Strnad, Hynek; Oliyarnyk, O.; Škop, V.; Kazdová, L.; Kurtz, T.; Pravenec, Michal

    2014-01-01

    Roč. 9, č. 7 (2014), e101906 E-ISSN 1932-6203 R&D Projects: GA MZd(CZ) NT14325; GA MŠk(CZ) LH12061; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fumaric acid esters * C-reactive protein * transgenic * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  15. Cable Stability

    Energy Technology Data Exchange (ETDEWEB)

    Bottura, L [European Organization for Nuclear Research, Geneva (Switzerland)

    2014-07-01

    Superconductor stability is at the core of the design of any successful cable and magnet application. This chapter reviews the initial understanding of the stability mechanism, and reviews matters of importance for stability such as the nature and magnitude of the perturbation spectrum and the cooling mechanisms. Various stability strategies are studied, providing criteria that depend on the desired design and operating conditions.

  16. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection.

    Science.gov (United States)

    Agarwal, Kosh; Brunetto, Maurizia; Seto, Wai Kay; Lim, Young-Suk; Fung, Scott; Marcellin, Patrick; Ahn, Sang Hoon; Izumi, Namiki; Chuang, Wan-Long; Bae, Ho; Sharma, Manoj; Janssen, Harry L A; Pan, Calvin Q; Çelen, Mustafa Kemal; Furusyo, Norihiro; Shalimar, Dr; Yoon, Ki Tae; Trinh, Huy; Flaherty, John F; Gaggar, Anuj; Lau, Audrey H; Cathcart, Andrea L; Lin, Lanjia; Bhardwaj, Neeru; Suri, Vithika; Mani Subramanian, G; Gane, Edward J; Buti, Maria; Chan, Henry L Y

    2018-04-01

    Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials. In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population. At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference -2.2% (95% CI -8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients receiving TAF and TDF (90% vs. 91%, respectively, adjusted difference -0.6% (95% CI -7.0 to 5.8%; p = 0.84). In both studies the proportions of patients with alanine aminotransferase above the upper limit of normal at baseline, who had normal alanine aminotransferase at week 96 of treatment, were significantly higher in patients receiving TAF than in those receiving TDF. In the pooled safety population, patients receiving TAF had significantly smaller decreases in bone mineral density than those receiving TDF in the hip (mean % change -0.33% vs. -2.51%; p TAF remained as effective as TDF, with continued improved renal and bone safety, two years after the initiation of treatment. Clinicaltrials.gov number: NCT01940471 and NCT01940341. At week 96 of two ongoing studies comparing the efficacy and safety of tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B patients, TAF continues to be as effective as TDF with continued

  17. Hábito de fumar: Repercusión sobre el aparato cardiovascular Smoking: Repercussion on the cardiovascular system

    Directory of Open Access Journals (Sweden)

    Alejandro Fadragas Fernández

    2005-08-01

    Full Text Available Nos propusimos revisar la literatura más actualizada, para dar a conocer la magnitud de este nocivo hábito, alarmados ante la terrible realidad de saber que el tabaco causa 1 muerte cada 10 s, según un informe publicado recientemente por la Organización Mundial de la Salud. El tabaquismo provoca 3 500 000 muertes anuales y ocasiona enfermedades cardiovasculares y cerebrovasculares. El objetivo de esta revisión bibliográfica es realizar una actualización de este tema, haciendo mayor énfasis en la repercusión del hábito de fumar en el aparato cardiovascular. Como resultado de esta revisión encontramos que el hábito de fumar constituye un factor de riesgo de enfermedades cardiovasculares, donde las lesiones ateroscleróticas se presentan en un porcentaje elevado de los pacientes que fallecen por esta causa, y es a su vez, factor importante en la aparición de otras enfermedades, como son: la hipertensión arterial, la cardiopatía isquémica y las enfermedades cerebrovasculares.Summary We propose ourselves to review the most updated literature to make known the magnitude of this harmful habit, alarmed by the terrible reality to know that tobbaco causes a death per 10 s, according to a report recently published by the World Health Organization. Smoking produces 3 500 000 deaths a year and brings about cardiovascular and cerebrovascular diseases. The purpose of this bibliographic review is to update this topic, making emphasis on the repercussion of smoking on the cardiovascular system. As a result of this review, we found that smoking is a risk factor for cardiovascular diseases, where the atherosclerotic lesions are present in an elevated percentage of the patients dying for this cause, and that it is at the same time an important factor in the appearance of other diseases, such as arterial hypertension, ischemic heart disease and cerebrovascular diseases.

  18. Complex effect of lignocellulosic biomass pretreatment with 1-butyl-3-methylimidazolium chloride ionic liquid on various aspects of ethanol and fumaric acid production by immobilized cells within SSF.

    Science.gov (United States)

    Dotsenko, Anna S; Dotsenko, Gleb S; Senko, Olga V; Stepanov, Nikolay A; Lyagin, Ilya V; Efremenko, Elena N; Gusakov, Alexander V; Zorov, Ivan N; Rubtsova, Ekaterina A

    2018-02-01

    The pretreatment of softwood and hardwood samples (spruce and hornbeam wood) with 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) was undertaken for further simultaneous enzymatic saccharification of renewable non-food lignocellulosic biomass and microbial fermentation of obtained sugars to ethanol and fumaric acid. A multienzyme cocktail based on cellulases and yeast or fungus cells producing ethanol and fumaric acid were the main objects of [Bmim]Cl influence studies. A complex effect of lignocellulosic biomass pretreatment with [Bmim]Cl on various aspects of the process (both action of cellulases and microbial conversion of hydrolysates to target products) was revealed. Positive effects of the pretreatment with [Bmim]Cl included decreasing the lignin content in the biomass, and increasing the effectiveness of enzymatic hydrolysis and microbial transformation of pretreated biomass. Immobilized cells of both yeasts and fungi possessed improved productive characteristics in the biotransformation of biomass pretreated with [Bmim]Cl to ethanol and fumaric acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Comparative evaluation of Compritol® HD5 ATO with Sodium Stearyl Fumarate and PEG 6000 as amphiphilic, hydrodispersible pharmaceutical lubricants

    Directory of Open Access Journals (Sweden)

    Chhanda Kapadia

    2017-03-01

    Full Text Available Hydrophobic lubricants are commonly used to reduce the frictional forces generated during tableting but impart a hydrophobic film on the surface of the powder or granules. This negatively affects the performance properties of the resultant tablets by slowing disintegration and dissolution, which is especially problematic in the case of orally disintegrating tablets. In the present study a comparative evaluation of the lubricant capacity of Compritol® HD5 ATO was performed with commonly used amphiphilic lubricants, sodium stearyl fumarate and PEG 6000. The effect of concentration and mixing time of Compritol® HD5 ATO with the granulation, on material flow properties, tablet ejection force, hardness, disintegration time and rate of dissolution of paracetamol tablets was evaluated. The physical properties of the lubricants such as crystallinity, wettability, thermal behaviour and surface area were also measured. Compritol® HD5 ATO is crystalline, hydrodispersible and thermostable. It reduced the tablet ejection force, the desired hardness range was obtained at significantly lower compression forces and no significant effect of lubricant mixing time and concentration on the hardness and disintegration time of the tablets was observed when compared with Sodium stearyl fumarate and PEG 6000. Compritol® HD5 ATO was found to be an as effective a lubricant for a fast disintegrating paracetamol formulation containing microcrystalline cellulose, lactose and PVP prepared by wet granulation in comparison with sodium stearyl fumarate and PEG 6000.

  20. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Directory of Open Access Journals (Sweden)

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  1. Reformulating Polycaprolactone Fumarate to Eliminate Toxic Diethylene Glycol: Effects of Polymeric Branching and Autoclave Sterilization on Material Properties

    Science.gov (United States)

    Runge, M. Brett; Wang, Huan; Spinner, Robert J; Windebank, Anthony J; Yaszemski, Michael J.

    2011-01-01

    Polycaprolactone fumarate (PCLF) is a cross-linkable derivate of polycaprolactone diol that has been shown to be an effective nerve conduit material that supports regeneration across segmental nerve defects and has warranted future clinical trials. Degradation of the previously studied PCLF (PCLFDEG) releases toxic small molecules of diethylene glycol used as the initiator for the synthesis of polycaprolactone diol. In an effort to eliminate this toxic degradation product we present a strategy for the synthesis of PCLF from either propylene glycol (PCLFPPD) or glycerol (PCLFGLY). PCLFPPD is linear and resembles the previously studied PCLFDEG, while PCLFGLY is branched and exhibits dramatically different material properties. The synthesis and characterization of their thermal, rheological, and mechanical properties are reported. The results show that the linear PCLFPPD has material properties similar to the previously studied PCLFDEG. The branched PCLFGLY exhibits dramatically lower crystalline properties resulting in lower rheological and mechanical moduli, and is therefore a more compliant material. In addition, the question of an appropriate FDA approvable sterilization method is addressed. This study shows that autoclave sterilization on PCLF materials is an acceptable sterilization method for cross-linked PCLF and has minimal effect on the PCLF thermal and mechanical properties. PMID:21911087

  2. Fabrication of high flux and antifouling mixed matrix fumarate-alumoxane/PAN membranes via electrospinning for application in membrane bioreactors

    Science.gov (United States)

    Moradi, Golshan; Zinadini, Sirus; Rajabi, Laleh; Dadari, Soheil

    2018-01-01

    The nanofibrous Polyacrylonitrile (PAN) membranes embedded with fumarate-alumoxane (Fum-A) nanoparticles were prepared via electrospinning technique as high flux and antifouling membranes for membrane bioreactor (MBR) applications. The effect of Fum-A nanoparticles on membrane morphology, surface hydrophilicity, pure water flux, effluent turbidity and the antifouling property was investigated. Fum-A is a carboxylate-alumoxane nanoparticle covered by extra hydroxyl and carboxylate groups on its surface. By embedding Fum-A nanoparticles into the spinning solution, the surface hydrophilicity and pure water flux of the resulted membranes were improved. The smooth surface of fibers at the low amount of nanoparticles and the agglomeration of nanoparticles at their high concentration were shown in SEM images of the membranes surface. The energy dispersive spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) analysis of the prepared Fum-A/PAN membrane confirmed the presence of carboxylate and hydroxyl functional groups of Fum-A nanoparticles on the surface of the Fum-A nanoparticles containing membrane. The results obtained from the filtration of activated sludge suspension revealed that by addition of a low amount of Fum-A nanoparticles, the irreversible fouling was significantly decreased due to the higher hydrophilicity. The Fum-A/PAN membranes showed superior permeate flux and antifouling properties compared to bare electrospun PAN membrane. Finally, 2 wt.% Fum-A/PAN membrane exhibited the highest FRR of 96% and the lowest irreversible fouling of 4% with excellent durability of antifouling property during twenty repeated activated sludge filtrations.

  3. Role of Nuclear Factor (Erythroid-Derived 2-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Anna Hammer

    2017-12-01

    Full Text Available To date, the intracellular signaling pathways involved in dendritic cell (DC function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2-like 2 (Nrf2 has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE, as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role. We explore the role of Nrf2 in DC function, and DC-mediated T cell responses during T cell-mediated autoimmunity of the central nervous system using genetic ablation and pharmacological activation in mice and men to corroborate our data in a translational setting. In murine and human DCs, monomethyl fumarate induced Nrf2 signaling inhibits DC maturation and DC-mediated T cell proliferation by reducing inflammatory cytokine production and expression of costimulatory molecules. In contrast, Nrf2-deficient DCs generate more activated T helper cells (Th1/Th17 but fewer regulatory T cells and foster T cell proliferation. Transfer of DCs with Nrf2 activation during active EAE reduces disease severity and T cell infiltration. Our data demonstrate that Nrf2 signaling modulates autoimmunity in murine and human systems via inhibiting DC maturation and function thus shedding further light on the mechanism of action of antioxidative stress pathways in antigen-presenting cells.

  4. Determination of clemastine hydrogen fumarate, desloratadine, losartan potassium and moxepril HCl through binary complex formation with eosin

    Directory of Open Access Journals (Sweden)

    Soad S. Abd El-Hay

    2016-09-01

    Full Text Available A simple and sensitive spectrophotometric method has been established for the determination of clemastine hydrogen fumarate (I, desloratadine (II, losartan potassium(III and moxepril HCl(IV based on binary complex formation with eosin. The method does not involve solvent extraction through the use of a non-ionic surfactant (methylcellulose. The color of the produced complex was measured at 552, 549 nm for (I, (II while was measured at 540 nm for (III and (IV. Appropriate conditions were established for the color reaction between eosin and the studied drugs to obtain maximum sensitivity. Under the proposed conditions, the method is applicable over concentration range of 1.25–11.25, 0.31–2.81, 2.5–20 and 1.25–15 μg/ml for (I, (II, (III and (IV, respectively. The molar absorptivity (ε, sandell sensitivity, detection (LOD and quantitation limits (LOQ are calculated. Unlike other reported ion-pair techniques, the suggested methods have the advantage of being applicable for the determination of the four drugs in their pharmaceutical dosage forms without prior extraction with excellent recoveries.

  5. Spray drying of budesonide, formoterol fumarate and their composites-II. Statistical factorial design and in vitro deposition properties.

    Science.gov (United States)

    Tajber, L; Corrigan, O I; Healy, A M

    2009-02-09

    The aim of this study was to investigate the effect of changing spray drying parameters on the production of a budesonide/formoterol fumarate 100:6 (w/w) composite. The systems were spray dried as solutions from 95% ethanol/5% water (v/v) using a Büchi 191-Mini Spray Dryer. A 2(5-1) factorial design study was undertaken to assess the consequence of altering spray drying processing variables on particle characteristics. The processing parameters that were studied were inlet temperature, spray drier airflow rate, pump rate, aspirator setting and feed concentration. Each batch of the resulting powder was characterised in terms of thermal and micromeritic properties as well as an in vitro deposition by twin impinger analysis. Overall, the parameter that had the greatest influence on each response investigated was production yield - airflow (higher airflow giving greater yields), median particle size - airflow (higher airflow giving smaller particle sizes) and Carr's compressibility index - feed concentration (lower feed concentration giving smaller Carr's indices). A six- to seven-fold difference in respirable fraction can be observed by changing the spray drying process parameters. The co-spray dried composite system which displayed best in vitro deposition characteristics, showed a 2.6-fold increase in respirable fraction in the twin impinger experiments and better dose uniformity compared with the physical mix of micronised powders.

  6. Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women.

    Science.gov (United States)

    Mugwanya, Kenneth K; John-Stewart, Grace; Baeten, Jared

    2017-07-01

    In settings where HIV is prevalent in heterosexual populations, pregnancy and postpartum breastfeeding periods can be associated with substantial HIV acquisition risk. Pre-exposure prophylaxis (PrEP) with daily oral tenofovir disoproxil fumarate (TDF)/emtricitabine is an attractive HIV prevention option for women who are lactating but data are limited on its safety during the lactation period. Areas covered: We provide a concise synthesis and summary of current evidence on the safety of TDF-based PrEP during breastfeeding. We conducted a review, searching Pubmed database and major PrEP conferences for primary studies with TDF-based PrEP exposure during postpartum breastfeeding. Expert opinion: TDF-based oral PrEP is an effective female-controlled HIV prevention option. There is evidence supporting the safety of TDF use for infant outcomes during breastfeeding in antiretroviral treatment regimens for HIV and hepatitis B virus, and more limited, but consistently safe, data from use of TDF as PrEP. The potential for risk is arguably outweighed for at-risk individuals by HIV prevention benefits, including indirect protection to the infant as a result of preventing HIV in the breastfeeding mother. As PrEP delivery is scaled up in heterosexual populations in high HIV prevalence settings and for at-risk persons in other settings, implementation science studies can provide a framework to increase the accrual of safety, acceptability, and use data related to PrEP during lactation.

  7. Impaired Malate and Fumarate Accumulation Due to the Mutation of the Tonoplast Dicarboxylate Transporter Has Little Effects on Stomatal Behavior.

    Science.gov (United States)

    Medeiros, David B; Barros, Kallyne A; Barros, Jessica Aline S; Omena-Garcia, Rebeca P; Arrivault, Stéphanie; Sanglard, Lílian M V P; Detmann, Kelly C; Silva, Willian Batista; Daloso, Danilo M; DaMatta, Fábio M; Nunes-Nesi, Adriano; Fernie, Alisdair R; Araújo, Wagner L

    2017-11-01

    Malate is a central metabolite involved in a multiplicity of plant metabolic pathways, being associated with mitochondrial metabolism and playing significant roles in stomatal movements. Vacuolar malate transport has been characterized at the molecular level and is performed by at least one carrier protein and two channels in Arabidopsis ( Arabidopsis thaliana ) vacuoles. The absence of the Arabidopsis tonoplast Dicarboxylate Transporter (tDT) in the tdt knockout mutant was associated previously with an impaired accumulation of malate and fumarate in leaves. Here, we investigated the consequences of this lower accumulation on stomatal behavior and photosynthetic capacity as well as its putative metabolic impacts. Neither the stomatal conductance nor the kinetic responses to dark, light, or high CO 2 were highly affected in tdt plants. In addition, we did not observe any impact on stomatal aperture following incubation with abscisic acid, malate, or citrate. Furthermore, an effect on photosynthetic capacity was not observed in the mutant lines. However, leaf mitochondrial metabolism was affected in the tdt plants. Levels of the intermediates of the tricarboxylic acid cycle were altered, and increases in both light and dark respiration were observed. We conclude that manipulation of the tonoplastic organic acid transporter impacted mitochondrial metabolism, while the overall stomatal and photosynthetic capacity were unaffected. © 2017 American Society of Plant Biologists. All Rights Reserved.

  8. Methanogenic paraffin degradation proceeds via alkane addition to fumarate by 'Smithella' spp. mediated by a syntrophic coupling with hydrogenotrophic methanogens.

    Science.gov (United States)

    Wawrik, Boris; Marks, Christopher R; Davidova, Irene A; McInerney, Michael J; Pruitt, Shane; Duncan, Kathleen E; Suflita, Joseph M; Callaghan, Amy V

    2016-09-01

    Anaerobic microbial biodegradation of recalcitrant, water-insoluble substrates, such as paraffins, presents unique metabolic challenges. To elucidate this process, a methanogenic consortium capable of mineralizing long-chain n-paraffins (C28 -C50 ) was enriched from San Diego Bay sediment. Analysis of 16S rRNA genes indicated the dominance of Syntrophobacterales (43%) and Methanomicrobiales (26%). Metagenomic sequencing allowed draft genome assembly of dominant uncultivated community members belonging to the bacterial genus Smithella and the archaeal genera Methanoculleus and Methanosaeta. Five contigs encoding homologs of the catalytic subunit of alkylsuccinate synthase (assA) were detected. Additionally, mRNA transcripts for these genes, including a homolog binned within the 'Smithella' sp. SDB genome scaffold, were detected via RT-PCR, implying that paraffins are activated via 'fumarate addition'. Metabolic reconstruction and comparison with genome scaffolds of uncultivated n-alkane degrading 'Smithella' spp. are consistent with the hypothesis that syntrophically growing 'Smithella' spp. may achieve reverse electron transfer by coupling the reoxidation of ETFred to a membrane-bound FeS oxidoreductase functioning as an ETF:menaquinone oxidoreductase. Subsequent electron transfer could proceed via a periplasmic formate dehydrogenase and/or hydrogenase, allowing energetic coupling to hydrogenotrophic methanogens such as Methanoculleus. Ultimately, these data provide fundamental insight into the energy conservation mechanisms that dictate interspecies interactions salient to methanogenic alkane mineralization. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

    Directory of Open Access Journals (Sweden)

    Sharvil Patil

    2017-11-01

    Full Text Available BCS class III drugs suffer from a drawback of low permeability even though they have high aqueous solubility. The objective of current work was to screen the suitability of glyceryl monooleate (GMO/Pluronic F127 cubic phase liquid crystals precursors for permeation enhancement and in turn the bioavailability of tenofovir disoproxil fumarate (TDF, a BCS class III drug. Spray-drying method was used for preparation of TDF loaded liquid crystal precursors (LCP consisting of GMO/Pluronic F127 and lactose monohydrate with an ability to in situ transform into stable cubic phases upon hydration. The quality by design (QbD approach (Factorial design was used for batch optimization. Spherical TDF loaded LCP as revealed by scanning electron microscopy photographs when hydrated and analyzed by small angle X-ray scattering confirmed formation of cubic phase. Differential scanning calorimetry and X-ray diffraction studies confirmed the molecular dispersion of TDF in polymer matrix and also suggested the conversion of TDF from crystalline to amorphous form. In vitro TDF release from prepared LCP showed controlled drug release over a period of 10 h. Further ex vivo studies revealed permeation enhancing activity of prepared LCP, which was highest when tested in presence of digestive enzyme extract. Thus, formulation of stable liquid crystal powder precursor can serve as an alternative for designing oral delivery system for drugs with low permeability.

  10. The synthesis and the spectroscopic, thermal, and structural properties of the M2[(fumarate)Ni(CN)4]·2(1,4-Dioxane) clathrate (M = Co, Ni, Cd and Hg)

    Science.gov (United States)

    Kartal, Zeki; Yavuz, Abdülkerim

    2018-03-01

    In this study, the clathrates of fumarate-tetracyanonickel-dioxane, given by the formula M2[(fumarate)Ni(CN)4]·2(1,4-Dioxane) (M = Co, Ni, Cd and Hg), have been obtained for the first time through chemical methods. These clathrates have been characterized by elemental, thermal, FT-IR, and FT-Raman spectroscopies. The parameters of structures of clathrates have been determined by X-ray powder diffraction. The thermal behaviors of these clathrates have been also investigated by thermo-gravimetric analysis (TGA), differential thermal analysis (DTA), and derivative thermal gravimetric analysis (DTG) in the range of 20-900 °C. X-ray powder diffraction data have been recorded at ambient temperature in the 2θ range 5-50°. The FT-IR and FT-Raman spectra of clathrates have been recorded in the region of 4000-400 cm-1 and 4000-100 cm-1, respectively. The results of the spectral and thermal analyses of the newly synthesized clathrates of fumarate-tetracyanonickel-dioxane suggest that these clathrates are new examples of the Hofmann-type dioxane clathrates. In our study, the Hofmann-type dioxane clathrates, which are formed by bounding electrons of oxygen-donor atoms of fumarate ion ligand molecule to transition metal atoms, consist of the corrugated |M-Ni(CN)4|∞ polymeric layers, which are held in parallel through the chain of (-M-fumarate-M-).

  11. Spectrophotometric determination of quetiapine fumarate in pharmaceuticals and human urine by two charge-transfer complexation reactions

    Directory of Open Access Journals (Sweden)

    Vinay K.B.

    2012-01-01

    Full Text Available Two simple, rapid and accurate spectrophotometric procedures are proposed for the determination of quetiapine fumarate (QTF in pharmaceuticals and in spiked human urine. The methods are based on charge transfer complexation reactions of free base form of the drug (quetiapine, QTP, as n-electron donor (D, with either p-chloranilic acid (p-CAA (method A or 2,3-dichloro-5,6-dicyanoquinone (DDQ (method B as π-acceptors (A. The coloured charge transfer complexes produced exhibit absorption maxima at 520 and 540 nm, in method A and method B, respectively. The experimental conditions such as reagent concentration, reaction solvent and time have been carefully optimized to achieve the maximum sensitivity. Beer’s law is obeyed over the concentration ranges of 8.0 - 160 and 4.0 - 80.0 μg ml-1, for method A and method B, respectively. The calculated molar absorptivity values are 1.77 × 103 and 4.59 × 103 l mol-1cm-1, respectively, for method A and method B. The Sandell sensitivity values, limits of detection (LOD and quantification (LOQ have also been reported. The stoichiometry of the reaction in both cases was accomplished adopting the limiting logarithmic method and was found to be 1: 2 (D: A. The accuracy and precision of the methods were evaluated on intra-day and inter-day basis. The proposed methods were successfully applied for the determination of QTF in pharmaceutical formulations and spiked human urine.

  12. Effect of Cobicistat on Tenofovir Disoproxil Fumarate (TDF): What Is True for TAF May Also Be True for TDF.

    Science.gov (United States)

    Cattaneo, Dario; Minisci, Davide; Baldelli, Sara; Mazzali, Cristina; Giacomelli, Andrea; Milazzo, Laura; Meraviglia, Paola; Resnati, Chiara; Rizzardini, Giuliano; Clementi, Emilio; Galli, Massimo; Gervasoni, Cristina

    2018-01-01

    The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting. HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons. Patients were given TDF with protease inhibitors/ritonavir (n = 212), non-nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation. Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out.

  13. Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients With Chronic HBV Infection.

    Science.gov (United States)

    Seto, Wai-Kay; Asahina, Yasuhiro; Brown, Todd T; Peng, Cheng-Yuan; Stanciu, Carol; Abdurakhmanov, Dzhamal; Tabak, Fehmi; Nguyen, Tuan T; Chuang, Wan-Long; Inokuma, Tetsuro; Ikeda, Fusao; Santantonio, Teresa Antonia; Habersetzer, François; Ramji, Alnoor; Lau, Audrey H; Suri, Vithika; Flaherty, John F; Wang, Hongyuan; Gaggar, Anuj; Subramanian, G Mani; Mukewar, Shrikant; Brunetto, Maurizia R; Fung, Scott; Chan, Henry Lik-Yuen

    2018-06-19

    Long-term use of tenofovir disoproxil fumarate (TDF) reduces bone mineral density (BMD). Tenofovir alafenamide (TAF), a new prodrug of tenofovir, has shown non-inferior efficacy to TDF in patients with chronic hepatitis B virus (HBV) infection, with improved bone effects at 48 weeks. We performed a randomized trial to evaluate the bone safety of TAF compared with TDF over 2 years, assessing baseline risk factors for bone loss, were evaluated after 2 years of treatment. In a double-blind study, hepatitis B e antigen (HBeAg)-positive patients (n=873) and HBeAg-negative patients (n=425) were randomly assigned (2:1) to groups given TAF (25 mg, n=866) or TDF (300 mg, n=432) once daily. We assessed bone safety, including hip and spine BMD, using dual-energy X-ray absorptiometry and measured changes in serum markers of bone turnover over 96 weeks. At baseline, treatment groups were well matched. At week 96, patients receiving TAF had significantly smaller decreases in hip BMD (mean reduction of 0.33%) than patients receiving TDF (mean reduction of 2.51%) (PTAF vs reduction of 2.57% in patients receiving TDF) (PTAF and TDF groups increased at week 96 compared to week 48 (PTAF group had minimal changes in markers of bone turnover by 12 weeks of treatment, but the TDF group had significant changes, compared to baseline. Risk factors for bone loss had fewer effects in patients receiving TAF than TDF at week 96. In double-blind randomized trials, we found that after 2 years of treatment, patients receiving TAF had continued improvements in bone safety compared with patients receiving TDF. Clinicaltrial.gov no: NCT01940471 and NCT01940341. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

    Science.gov (United States)

    Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

    2015-01-01

    Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

  15. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.

    Science.gov (United States)

    Solomon, Marc M; Lama, Javier R; Glidden, David V; Mulligan, Kathleen; McMahan, Vanessa; Liu, Albert Y; Guanira, Juan Vicente; Veloso, Valdilea G; Mayer, Kenneth H; Chariyalertsak, Suwat; Schechter, Mauro; Bekker, Linda-Gail; Kallás, Esper Georges; Burns, David N; Grant, Robert M

    2014-03-27

    Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons. The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft-Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy. There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: -2.4 vs. -1.1 ml/min; P=0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P=0.02), and resolved after stopping pre-exposure prophylaxis (mean change: -0.1 vs. 0.0 ml/min; P=0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy. In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.

  16. Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).

    Science.gov (United States)

    Kempen, Diederik H R; Lu, Lichun; Kim, Choll; Zhu, Xun; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

    2006-04-01

    The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study

  17. Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children.

    Science.gov (United States)

    Hazra, Rohan; Balis, Frank M; Tullio, Antonella N; DeCarlo, Ellen; Worrell, Carol J; Steinberg, Seth M; Flaherty, John F; Yale, Kitty; Poblenz, Marianne; Kearney, Brian P; Zhong, Lijie; Coakley, Dion F; Blanche, Stephane; Bresson, Jean Louis; Zuckerman, Judith A; Zeichner, Steven L

    2004-01-01

    Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the geometric mean maximum concentration (C(max)) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng. h/ml and was significantly higher than the AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with tenofovir DF at 300 mg.

  18. Impact of fumaric acid esters on cardiovascular risk factors and depression in psoriasis: a prospective pilot study.

    Science.gov (United States)

    Schmieder, Astrid; Poppe, Manuel; Hametner, Christian; Meyer-Schraml, Hanna; Schaarschmidt, Marthe-Lisa; Findeisen, Peter; Benoit, Sandrine; Bauer, Boris; Schmid, Sybille; Goebeler, Matthias; Goerdt, Sergij; Ludwig-Peitsch, Wiebke K

    2015-07-01

    Patients with psoriasis have an increased risk of cardiovascular disease that is partly attributable to chronic systemic inflammation. The aim of our prospective pilot study was to investigate the impact of fumaric acid esters (FAE), a first-line systemic antipsoriatic treatment in Germany, on cardiovascular risk parameters. Participants with moderate-to-severe psoriasis from the University Medical Center Mannheim and the University Hospital Würzburg were treated with FAE for 16 weeks according to standard dosage recommendations. Disease severity, life quality and depression scores as well as biomarkers of inflammation, lipid and glucose metabolism were assessed prior to initiation of FAE and after 16 weeks. Out of 39 participants recruited, 27 completed the study. 44% of all participants and 63% of those completing the 16-week treatment achieved PASI 50 response and 27 or 37% PASI 75 response. Clinical improvement was paralleled by significant improvement in quality of life, high treatment satisfaction and significant reduction of depressive symptoms. Adverse events, most frequently mild gastrointestinal complaints, flush and lymphocytopenia occurred in 89%. FAE did not modify glucose metabolism or inflammatory parameters substantially. However, a highly significant increase in serum levels of the atheroprotective cytokine adiponectin was noted after 16 weeks (median 4.7 vs. 8.9 µg/ml; p = 0.0002). Our study demonstrates a significant beneficial impact of FAE on adiponectin, indicating a potential cardioprotective effect. It will be interesting to verify this finding in larger cohorts and to assess the long-term influence of FAE on cardiovascular risk and disease.

  19. Effects of fumaric acid supplementation on methane production and rumen fermentation in goats fed diets varying in forage and concentrate particle size.

    Science.gov (United States)

    Li, Zongjun; Liu, Nannan; Cao, Yangchun; Jin, Chunjia; Li, Fei; Cai, Chuanjiang; Yao, Junhu

    2018-01-01

    In rumen fermentation, fumaric acid (FA) could competitively utilize hydrogen with methanogenesis to enhance propionate production and suppress methane emission, but both effects were diet-dependent. This study aimed to explore the effects of FA supplementation on methanogenesis and rumen fermentation in goats fed diets varying in forage and concentrate particle size. Four rumen-cannulated goats were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments: low or high ratio of forage particle size: concentrate particle size (Fps:Cps), without or with FA supplementation (24 g/d). Fps:Cps was higher in the diet with chopped alfalfa hay plus ground corn than in that with ground alfalfa hay plus crushed corn. Both increasing dietary Fps:Cps and FA supplementation shifted ruminal volatile fatty acid (VFA) patterns toward more propionate and less acetate in goats. An interaction between dietary Fps:Cps and FA supplementation was observed for the ratio of acetate to propionate (A:P), which was more predominant when FA was supplemented in the low-Fps:Cps diet. Methane production was reduced by FA, and the reduction was larger in the low-Fps:Cps diet (31.72%) than in the high-Fps:Cps diet (17.91%). Fumaric acid decreased ruminal total VFA concentration and increased ruminal pH. No difference was found in ruminal DM degradation of concentrate or alfalfa hay by dietary Fps:Cps or FA. Goats presented a lower ruminal methanogen abundance with FA supplementation and a higher B. fibrisolvens abundance with high dietary Fps:Cps. Adjusting dietary Fps:Cps is an alternative dietary model for studying diet-dependent effects without changing dietary chemical composition. Fumaric acid supplementation in the low-Fps:Cps diet showed greater responses in methane mitigation and propionate increase.

  20. Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Qin Wang

    2015-06-01

    Full Text Available Multiple sclerosis (MS is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS. Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12 is an oral formulation of the fumaric acid esters (FAE, containing the active metabolite dimethyl fumarate (DMF. Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF on mouse and rat neural stem/progenitor cells (NPCs and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2 treatment. In addition, utilizing the reactive oxygen species (ROS assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2 at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1. Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS.

  1. Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Jan Šilhavý

    Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

  2. The outer membrane protein Omp35 affects the reduction of Fe(III, nitrate, and fumarate by Shewanella oneidensis MR-1

    Directory of Open Access Journals (Sweden)

    Myers Charles R

    2004-06-01

    Full Text Available Abstract Background Shewanella oneidensis MR-1 uses several electron acceptors to support anaerobic respiration including insoluble species such as iron(III and manganese(IV oxides, and soluble species such as nitrate, fumarate, dimethylsulfoxide and many others. MR-1 has complex branched electron transport chains that include components in the cytoplasmic membrane, periplasm, and outer membrane (OM. Previous studies have implicated a role for anaerobically upregulated OM electron transport components in the use of insoluble electron acceptors, and have suggested that other OM components may also contribute to insoluble electron acceptor use. In this study, the role for an anaerobically upregulated 35-kDa OM protein (Omp35 in the use of anaerobic electron acceptors was explored. Results Omp35 was purified from the OM of anaerobically grown cells, the gene encoding Omp35 was identified, and an omp35 null mutant (OMP35-1 was isolated and characterized. Although OMP35-1 grew on all electron acceptors tested, a significant lag was seen when grown on fumarate, nitrate, and Fe(III. Complementation studies confirmed that the phenotype of OMP35-1 was due to the loss of Omp35. Despite its requirement for wild-type rates of electron acceptor use, analysis of Omp35 protein and predicted sequence did not identify any electron transport moieties or predicted motifs. OMP35-1 had normal levels and distribution of known electron transport components including quinones, cytochromes, and fumarate reductase. Omp35 is related to putative porins from MR-1 and S. frigidimarina as well as to the PorA porin from Neisseria meningitidis. Subcellular fraction analysis confirmed that Omp35 is an OM protein. The seven-fold anaerobic upregulation of Omp35 is mediated post-transcriptionally. Conclusion Omp35 is a putative porin in the OM of MR-1 that is markedly upregulated anaerobically by a post-transcriptional mechanism. Omp35 is required for normal rates of growth on Fe

  3. Studies on chemically crosslinkable carboxy terminated-poly(propylene fumarate-co-ethylene glycol)-acrylamide hydrogel as an injectable biomaterial

    International Nuclear Information System (INIS)

    Kallukalam, B C; Jayabalan, M; Sankar, V

    2009-01-01

    Carboxy terminated-poly(propylene fumarate)-co-ethylene glycol) (CT-PPF-co-PEG) was prepared and set into crosslinked hydrogel material with acrylamide. The setting studies reveal that this copolymer system can be used as an injectable material. The hydrogel material exhibits a higher degree of swelling, good mechanical strength and flexibility. The hydrogel favours adhesion of L929 fibroblast cells without proliferation on the surface. However, cardiac fibroblast cells (isolated from new born rat (Wistar) hearts) adhere and proliferate on the hydrogel due to the formation of synergistic hydrophilic-hydrophobic surface-by-surface reorganization.

  4. Synthesis and characterization of biodegradable poly (ethylene glycol) and poly (caprolactone diol) end capped poly (propylene fumarate) cross linked amphiphilic hydrogel as tissue engineering scaffold material.

    Science.gov (United States)

    Krishna, Lekshmi; Jayabalan, Muthu

    2009-12-01

    Biodegradable poly (caprolactone diol-co-propylene fumarate-co-ethylene glycol) amphiphilic polymer with poly (ethylene glycol) and poly (caprolactone diol) chain ends (PCL-PPF-PEG) was prepared. PCL-PPF-PEG undergoes fast setting with acrylamide (aqueous solution) by free radical polymerization and produces a crosslinked hydrogel. The cross linked and freeze-dried amphiphilic material has porous and interconnected network. It undergoes higher degree of swelling and water absorption to form hydrogel with hydrophilic and hydrophobic domains at the surface and appreciable tensile strength. The present hydrogel is compatible with L929 fibroblast cells. PCL-PPF-PEG/acrylamide hydrogel is a candidate scaffold material for tissue engineering applications.

  5. Studies on chemically crosslinkable carboxy terminated-poly(propylene fumarate-co-ethylene glycol)-acrylamide hydrogel as an injectable biomaterial

    Energy Technology Data Exchange (ETDEWEB)

    Kallukalam, B C; Jayabalan, M [Polymer Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695 012 (India); Sankar, V, E-mail: muthujayabalan@rediffmail.co [Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695 012 (India)

    2009-02-15

    Carboxy terminated-poly(propylene fumarate)-co-ethylene glycol) (CT-PPF-co-PEG) was prepared and set into crosslinked hydrogel material with acrylamide. The setting studies reveal that this copolymer system can be used as an injectable material. The hydrogel material exhibits a higher degree of swelling, good mechanical strength and flexibility. The hydrogel favours adhesion of L929 fibroblast cells without proliferation on the surface. However, cardiac fibroblast cells (isolated from new born rat (Wistar) hearts) adhere and proliferate on the hydrogel due to the formation of synergistic hydrophilic-hydrophobic surface-by-surface reorganization.

  6. Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

    Directory of Open Access Journals (Sweden)

    Suzuki F

    2014-06-01

    Full Text Available Fumitaka Suzuki,1,2 Hitomi Sezaki,1 Norio Akuta,1 Yoshiyuki Suzuki,1 Yusuke Kawamura,1 Tetsuya Hosaka,1 Masahiro Kobayashi,1 Satoshi Saitoh,1 Yasuji Arase,1 Kenji Ikeda,1 Mariko Kobayashi,3 Sachiyo Watahiki,3 Rie Mineta,3 Yukiko Suzuki,3 Hiromitsu Kumada1 1Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 2Okinaka Memorial Institute for Medical Research, Tokyo, Japan; 3Research Institute for Hepatology, Toranomon Branch Hospital, Kawasaki, Japan Abstract: Tenofovir disoproxil fumarate (TDF is widely used to treat hepatitis B virus (HBV patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV, against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg, whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out. Keywords: hepatitis B virus, resistant

  7. Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective.

    Science.gov (United States)

    Dakin, Helen; Sherman, Morris; Fung, Scott; Fidler, Carrie; Bentley, Anthony

    2011-12-01

    Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe. Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers. A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide-naive patients with compensated cirrhosis; and lamivudine-resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum. First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85-9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43,758 and $Can48,015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost

  8. Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

    Science.gov (United States)

    Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

    2018-06-01

    Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

  9. Ligament Tissue Engineering Using a Novel Porous Polycaprolactone Fumarate Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells Grown in Platelet Lysate.

    Science.gov (United States)

    Wagner, Eric R; Bravo, Dalibel; Dadsetan, Mahrokh; Riester, Scott M; Chase, Steven; Westendorf, Jennifer J; Dietz, Allan B; van Wijnen, Andre J; Yaszemski, Michael J; Kakar, Sanjeev

    2015-11-01

    Surgical reconstruction of intra-articular ligament injuries is hampered by the poor regenerative potential of the tissue. We hypothesized that a novel composite polymer "neoligament" seeded with progenitor cells and growth factors would be effective in regenerating native ligamentous tissue. We synthesized a fumarate-derivative of polycaprolactone fumarate (PCLF) to create macro-porous scaffolds to allow cell-cell communication and nutrient flow. Clinical grade human adipose tissue-derived human mesenchymal stem cells (AMSCs) were cultured in 5% human platelet lysate (PL) and seeded on scaffolds using a dynamic bioreactor. Cell growth, viability, and differentiation were examined using metabolic assays and immunostaining for ligament-related markers (e.g., glycosaminoglycans [GAGs], alkaline phosphatase [ALP], collagens, and tenascin-C). AMSCs seeded on three-dimensional (3D) PCLF scaffolds remain viable for at least 2 weeks with proliferating cells filling the pores. AMSC proliferation rates increased in PL compared to fetal bovine serum (FBS) (p ligament and tenogenic growth factor fibroblast growth factor 2 (FGF-2), especially when cultured in the presence of PL (p engineering and ligament regeneration.

  10. Evaluation of Potential Drug–Drug Interaction Between Delayed‐Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women

    Science.gov (United States)

    Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I.

    2017-01-01

    Abstract Delayed‐release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti‐inflammatory and neuroprotective properties. This 2‐period crossover study was conducted to evaluate the potential for drug–drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty‐six healthy women were enrolled; 32 completed the study. After the lead‐in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration–time curve over the dosing interval and peak plasma concentration contained within the 0.8–1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol–based OCs may be used with DMF without dose modification. PMID:28783872

  11. Percepción de los estudiantes de enfermería en cuanto al comportamiento de fumar en México

    Directory of Open Access Journals (Sweden)

    Francisco Cruz Vazquez

    2004-01-01

    Full Text Available El estudio tiene como objetivo evaluar el comportamiento de fumar y la percepción de los factores que influeyen en ese comportamiento, entre estudiantes del primer año de Licenciatura en enfermería. Fueron entrevistado 36 alumnos del primer año de graduación en enfermería. Siendo 18 (50% fumadores, con edad media de 23,5 años; 75% del sexo femenino en cuanto al patron de consumo estos fuman de 2 a 6 cigarrillos al dia, empezaron a fumar en media con 15 años. En cuanto a la percepción de los alumnos, los fumadores se consideran más tímidos e inseguros que los no fumadores; 56% de éstos tienen un familiar fumador y perciben que estos tienen mayor riesgo de enfermar que los no fumadores. El grupo de amigos, el exceso de tareas y trabajo son fuertes influenciadores. Concluimos que el asunto es de extrema importancia, campañas educativas de ámbito preventivo en todos los niveles educacionales deben ser desarrollados además de la inserción de este tema en los currículos

  12. Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

    Science.gov (United States)

    Zhu, Bing; Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I

    2017-11-01

    Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  13. UM ESTUDO DE CASO SOBRE O FUMO, O USO DOS CACHIMBOS E AS PRÁTICAS DE FUMAR ENTRE OS MBYÁ-GUARANI (RS

    Directory of Open Access Journals (Sweden)

    Roberta Pôrto Marques

    2012-06-01

    Full Text Available Este artigo trata de uma pesquisa acerca dos cachimbos utilizados entre grupos indígenas Mbyá-Guarani de aldeias próximas à cidade de Porto Alegre, Rio Grande do Sul. Com o intuito de estudar o uso do fumo e as práticas do fumar – nos cachimbos (petynguá – se buscou, através da prática etnográfica, perceber de que maneira e em que medida se dá esse uso e o que ele significa para tais grupos. Traz-se, ainda, referências em trabalhos etnográficos acerca do uso do fumo entre outras etnias ameríndias, a fim de proporcionar certo entendimento de tal temática, no sentido de reforçar a valorização da prática de fumar como parte fundamental da sociocosmologia de muitos grupos ameríndios.

  14. Anaerobic respiratory growth of Vibrio harveyi, Vibrio fischeri and Photobacterium leiognathi with trimethylamine N-oxide, nitrate and fumarate: ecological implications.

    Science.gov (United States)

    Proctor, L M; Gunsalus, R P

    2000-08-01

    Two symbiotic species, Photobacterium leiognathi and Vibrio fischeri, and one non-symbiotic species, Vibrio harveyi, of the Vibrionaceae were tested for their ability to grow by anaerobic respiration on various electron acceptors, including trimethylamine N-oxide (TMAO) and dimethylsulphoxide (DMSO), compounds common in the marine environment. Each species was able to grow anaerobically with TMAO, nitrate or fumarate, but not with DMSO, as an electron acceptor. Cell growth under microaerophilic growth conditions resulted in elevated levels of TMAO reductase, nitrate reductase and fumarate reductase activity in each strain, whereas growth in the presence of the respective substrate for each enzyme further elevated enzyme activity. TMAO reductase specific activity was the highest of all the reductases. Interestingly, the bacteria-colonized light organs from the two squids, Euprymna scolopes and Euprymna morsei, and the light organ of the ponyfish, Leiognathus equus, also had high levels of TMAO reductase enzyme activity, in contrast to non-symbiotic tissues. The ability of these bacterial symbionts to support cell growth by respiration with TMAO may conceivably eliminate the competition for oxygen needed for both bioluminescence and metabolism.

  15. A spectroscopic and surface microhardness study of enamel exposed to beverages supplemented with ferrous fumarate and ferrous sulfate. A randomized in vitro trial.

    Science.gov (United States)

    Xavier, Arun M; Rai, Kavita; Hegde, Amitha M; Shetty, Suchetha

    2016-06-01

    To compare the efficacy between supplementing ferrous fumarate and ferrous sulfate to carbonated beverages by recording the in vitro mineral loss and surface microhardness (SMH) changes in human enamel. 120 enamel blocks each (from primary and permanent teeth) were uniformly prepared and the initial SMH was recorded. These enamel specimens were equally divided (n = 60) for their respective beverage treatment in Group 1 (2 mmol/L ferrous sulfate) and Group 2 (2 mmol/L ferrous fumarate). Each group was further divided into three subgroups as Coca-Cola, Sprite and mineral water (n= 10). The specimens were subjected to three repetitive cycles of respective treatment for a 5-minute incubation period, equally interspaced by 5-minute storage in artificial saliva. The calcium and phosphate released after each cycle were analyzed spectrophotometrically and the final SMH recorded. The results were tested using student's t-test, one-way ANOVA and Wilcoxon signed rank test (P Coca-Cola (P < 0.005).

  16. Stabilizing Niger

    DEFF Research Database (Denmark)

    Hahonou, Eric Komlavi

    international intervention in Niger. Their main objective is to secure their own strategic, economic and political interests by strengthening the Nigerien authorities through direct intervention and capacity building activities. For western states reinforcing state security institutions and stabilizing elite...

  17. Sentidos sobre o hábito de fumar para mulheres participantes de grupo de tabagistas Significados acerca del fumar para las mujeres participantes en un grupo de fumadores Meanings about smoking for women participant in a group for smokers

    Directory of Open Access Journals (Sweden)

    Neusa da Silva Eckerdt

    2010-06-01

    Full Text Available O objetivo deste estudo foi conhecer sentidos produzidos sobre o tabagismo por mulheres participantes de um grupo para tabagistas em Florianópolis, SC, Brasil. O grupo foi composto por sete participantes. Utilizou-se a entrevista estruturada, com cinco questões abertas. O referencial teórico foi construcionismo social. Como conclusão, encontrou-se dois eixos temáticos: 1 cigarro no ciclo vital da mulher 2 expectativas em relação ao tratamento. Os repertórios utilizados para descrever o início do consumo na adolescência incluíram glamour, charme, independência e aceitação pelos pares, enquanto aqueles utilizados para descrever a manutenção do consumo na idade adulta incluíram ansiedade, depressão e recurso para lidar com o estresse diário. Quanto às expectativas em relação ao tratamento, acreditam que o contato com pessoas que vivenciam as mesmas dificuldades, em relação à interrupção do consumo e sonhos de uma vida saudável, seria motivador. O tratamento oferecido para tabagistas deve explorar estratégias para que as mulheres alcancem o que desejam com o consumo de cigarro.El objetivo de este estudio fue conocer el significado, sobre el fumar, declarado por mujeres que participaban en un grupo de fumadores en Florianópolis, estado de Santa Catarina, Brasil. Participaron siete fumadores. Se utilizó entrevistas estructuradas con cinco preguntas abiertas. El marco teórico fue el construccionismo social. Dos temas fueran detectados: 1 Los cigarrillos en el ciclo de vida de la mujer 2 Expectativas en relación al tratamiento. Los repertorios utilizados para describir el inicio del consumo, en la adolescencia, incluyen: glamour, encanto, independencia y el ser aceptado entre iguales; y los utilizados para describir el mantenimiento del consumo en la edad adulta incluyen: ansiedad, depresión y el uso como recurso para lidiar con el estrés diario. En cuanto a las expectativas para el tratamiento, creen que ayudaría el

  18. Decline in bone mass with tenofovir disoproxil fumarate/emtricitabine is associated with hormonal changes in the absence of renal impairment when used by HIV uninfected adolescent boys and young men for HIV pre-exposure

    Science.gov (United States)

    Background. We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity. Methods. In a study of daily TDF/emtricitabine (FTC) pre-exposure prophylaxis (PrEP) in HIV uninfected young men who have sex with men, we measured ch...

  19. The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels

    KAUST Repository

    Tong, Winghang; Sourbier, Carole; Kovtunovych, Gennadiy; Jeong, Suhyoung; Vira, Manish A.; Ghosh, Manik Chandra; Romero, Vladimir Valera; Sougrat, Rachid; Vaulont, Sophie; Viollet, Benoî t; Kim, Yeongsang; Lee, Sunmin; Trepel, Jane B.; Srinivasan, Ramaprasad; Bratslavsky, Gennady; Yang, Youfeng; Linehan, William Marston; Rouault, Tracey A.

    2011-01-01

    Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels lead to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells. © 2011 Elsevier Inc.

  20. The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels

    KAUST Repository

    Tong, Winghang

    2011-09-01

    Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels lead to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells. © 2011 Elsevier Inc.

  1. Macroeconomic stability

    DEFF Research Database (Denmark)

    Jespersen, Jesper

    2004-01-01

    It is demonstrated that full employment and sustainable development not necessarily are conflicting goals. On the other hand macroeconomic stability cannot be obtained without a deliberate labour sharing policy and a shift in the composition of private consumption away from traditional material...

  2. Stabilized superconductors

    International Nuclear Information System (INIS)

    Wong, J.

    1975-01-01

    The stable, high field, high current composite wire comprises multiple filaments in a depleted bronze matrix, each filament comprising a type II superconducting, beta-tungsten structure, intermetallic compound layer jacketing and metallurgically bonded to a stabilizing copper core, directly or via an intermediate layer of refractory metal

  3. Ligament Tissue Engineering Using a Novel Porous Polycaprolactone Fumarate Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells Grown in Platelet Lysate

    Science.gov (United States)

    Wagner, Eric R.; Bravo, Dalibel; Dadsetan, Mahrokh; Riester, Scott M.; Chase, Steven; Westendorf, Jennifer J.; Dietz, Allan B.; van Wijnen, Andre J.; Yaszemski, Michael J.

    2015-01-01

    Purpose: Surgical reconstruction of intra-articular ligament injuries is hampered by the poor regenerative potential of the tissue. We hypothesized that a novel composite polymer “neoligament” seeded with progenitor cells and growth factors would be effective in regenerating native ligamentous tissue. Methods: We synthesized a fumarate-derivative of polycaprolactone fumarate (PCLF) to create macro-porous scaffolds to allow cell–cell communication and nutrient flow. Clinical grade human adipose tissue-derived human mesenchymal stem cells (AMSCs) were cultured in 5% human platelet lysate (PL) and seeded on scaffolds using a dynamic bioreactor. Cell growth, viability, and differentiation were examined using metabolic assays and immunostaining for ligament-related markers (e.g., glycosaminoglycans [GAGs], alkaline phosphatase [ALP], collagens, and tenascin-C). Results: AMSCs seeded on three-dimensional (3D) PCLF scaffolds remain viable for at least 2 weeks with proliferating cells filling the pores. AMSC proliferation rates increased in PL compared to fetal bovine serum (FBS) (p < 0.05). Cells had a low baseline expression of ALP and GAG, but increased expression of total collagen when induced by the ligament and tenogenic growth factor fibroblast growth factor 2 (FGF-2), especially when cultured in the presence of PL (p < 0.01) instead of FBS (p < 0.05). FGF-2 and PL also significantly increased immunostaining of tenascin-C and collagen at 2 and 4 weeks compared with human fibroblasts. Summary: Our results demonstrate that AMSCs proliferate and eventually produce a collagen-rich extracellular matrix on porous PCLF scaffolds. This novel scaffold has potential in stem cell engineering and ligament regeneration. PMID:26413793

  4. Dimethyl Fumarate Inhibits the Nuclear Factor κB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein.

    Science.gov (United States)

    Kastrati, Irida; Siklos, Marton I; Calderon-Gierszal, Esther L; El-Shennawy, Lamiaa; Georgieva, Gergana; Thayer, Emily N; Thatcher, Gregory R J; Frasor, Jonna

    2016-02-12

    In breast tumors, activation of the nuclear factor κB (NFκB) pathway promotes survival, migration, invasion, angiogenesis, stem cell-like properties, and resistance to therapy--all phenotypes of aggressive disease where therapy options remain limited. Adding an anti-inflammatory/anti-NFκB agent to breast cancer treatment would be beneficial, but no such drug is approved as either a monotherapy or adjuvant therapy. To address this need, we examined whether dimethyl fumarate (DMF), an anti-inflammatory drug already in clinical use for multiple sclerosis, can inhibit the NFκB pathway. We found that DMF effectively blocks NFκB activity in multiple breast cancer cell lines and abrogates NFκB-dependent mammosphere formation, indicating that DMF has anti-cancer stem cell properties. In addition, DMF inhibits cell proliferation and significantly impairs xenograft tumor growth. Mechanistically, DMF prevents p65 nuclear translocation and attenuates its DNA binding activity but has no effect on upstream proteins in the NFκB pathway. Dimethyl succinate, the inactive analog of DMF that lacks the electrophilic double bond of fumarate, is unable to inhibit NFκB activity. Also, the cell-permeable thiol N-acetyl l-cysteine, reverses DMF inhibition of the NFκB pathway, supporting the notion that the electrophile, DMF, acts via covalent modification. To determine whether DMF interacts directly with p65, we synthesized and used a novel chemical probe of DMF by incorporating an alkyne functionality and found that DMF covalently modifies p65, with cysteine 38 being essential for the activity of DMF. These results establish DMF as an NFκB inhibitor with anti-tumor activity that may add therapeutic value in the treatment of aggressive breast cancers. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite

    Energy Technology Data Exchange (ETDEWEB)

    Jayabalan, M; Shalumon, K T; Mitha, M K [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Division, BMT Wing, Thiruvananthapuram 695 012, Kerala (India); Ganesan, K; Epple, M, E-mail: muthujayabalan@rediffmail.co [University of Duisburg-Essen, Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), Universitaetsstr. 5-7, 45117 Essen (Germany)

    2010-04-15

    The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite.

  6. The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite.

    Science.gov (United States)

    Jayabalan, M; Shalumon, K T; Mitha, M K; Ganesan, K; Epple, M

    2010-04-01

    The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite.

  7. The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite

    International Nuclear Information System (INIS)

    Jayabalan, M; Shalumon, K T; Mitha, M K; Ganesan, K; Epple, M

    2010-01-01

    The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite.

  8. Preparation, physical characterization, and stability of Ferrous-Chitosan microcapsules using different iron sources

    Science.gov (United States)

    Handayani, Noer Abyor; Luthfansyah, M.; Krisanti, Elsa; Kartohardjono, Sutrasno; Mulia, Kamarza

    2017-11-01

    Dietary modification, supplementation and food fortification are common strategies to alleviate iron deficiencies. Fortification of food is an effective long-term approach to improve iron status of populations. Fortification by adding iron directly to food will cause sensory problems and decrease its bioavailability. The purpose of iron encapsulation is: (1) to improve iron bioavailability, by preventing oxidation and contact with inhibitors and competitors; and (2) to disguise the rancid aroma and flavor of iron. A microcapsule formulation of two suitable iron compounds (iron II fumarate and iron II gluconate) using chitosan as a biodegradable polymer will be very important. Freeze dryer was also used for completing the iron microencapsulation process. The main objective of the present study was to prepare and characterize the iron-chitosan microcapsules. Physical characterization, i.e. encapsulation efficiency, iron loading capacity, and SEM, were also discussed in this paper. The stability of microencapsulated iron under simulated gastrointestinal conditions was also investigated, as well. Both iron sources were highly encapsulated, ranging from 71.5% to 98.5%. Furthermore, the highest ferrous fumarate and ferrous gluconate loaded were 1.9% and 4.8%, respectively. About 1.04% to 9.17% and 45.17% to 75.19% of Fe II and total Fe, were released in simulated gastric fluid for two hours and in simulated intestinal fluid for six hours, respectively.

  9. Before Stabilization

    DEFF Research Database (Denmark)

    Plesner, Ursula; Horst, Maja

    2013-01-01

    of the communication about innovations in information and communication technology (ICT), and to contribute to an understanding of how different visions promise particular future configurations of workflows, communication processes, politics, economic models and social relations. Hereby, the paper adds...... to the literature on the relationship between ICTs and organizing, but with a distinct focus on innovation communication and distributed innovation processes taking place before ICTs are stabilized, issues which cannot be captured by studies of diffusion and adaptation of new ICTs within single organizations....

  10. A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report

    OpenAIRE

    Suttels, Veronique; Florence, Eric; Leys, John; Vekemans, Marc; Van den Ende, Jef; Vlieghe, Erika; Kenyon, Chris

    2015-01-01

    Introduction We present what we believe to be the first case in the literature of rhabdomyolysis-induced renal failure caused by a probable drug interaction between elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) and pravastatin/fenofibrate. Case presentation A 68-year old Caucasian man presented with progressive pain in both legs two weeks after commencing treatment with EVG/COBI/FTC/TDF. He was found to have biochemical evidence of rhabdomyolysis and a...

  11. Determinantes do hábito de fumar e de seu abandono durante a gestação em localidade urbana na região sul do Brasil

    Directory of Open Access Journals (Sweden)

    Iná S. Halal

    1993-04-01

    Full Text Available Foi realizado um estudo transversal, com 873 gestantes que freqüentaram o pré-natal em Pelotas (RS, em 1989-90, com o objetivo de investigar possíveis fatores de risco e fatores prognósticos para o tabagismo durante a gravidez. A prevalência no início da gravidez foi de 40,8%. O hábito de fumar da mãe da gestante e do marido e a baixa escolaridade da mulher estiveram associados com o risco de fumar no início da gravidez. O tabagismo do marido esteve associado com um aumento de cerca de duas vezes nesse risco. A taxa de abandono até a 15ª-22ª semana gestacional foi de 35,6%. A renda familiar, o hábito de fumar da mãe da gestante e do companheiro, a idade de início, duração e intensidade do hábito da mulher estiveram associados com a interrupção durante a gravidez. Os resultados acima permaneceram após ajuste para fatores de confusão, através de análise estratificada.

  12. The search for equality: representations of the smoking act among adolescent women En búsqueda de la igualdad: representaciones del acto de fumar en mujeres adolescentes Em busca da igualdade: representações do ato de fumar em mulheres adolescentes

    Directory of Open Access Journals (Sweden)

    J. Adriana Sánchez Martínez

    2008-08-01

    Full Text Available This study aimed to discover the representations of the smoking habit in both non-smoking and smoking female adolescents from a high school in Querétaro, Mexico. It is a qualitative research, carried out with 14 female adolescents in 2005. A semi-structured interview and a socioeconomic survey were used to collect data. Results evidenced adolescents know the biomedical discourse, which proposes that smoking causes serious consequences to health. However, there are other symbolic reasons that influence its use such as the search for equality and image, since they think men find smoking women more attractive and mature. Peer pressure represents an important factor for women to smoke by validating its practice and minimizing its effects to the body.El objetivo de este estudio fue conocer las representaciones del acto de fumar en mujeres adolescentes fumadoras y no fumadoras de una institución de educación media superior en el estado de Querétaro, México. Es una investigación cualitativa realizada en el 2005 con 14 mujeres adolescentes. Como instrumento de recogida de información se utilizó una entrevista semi-estructurada y un cuestionario de datos sociodemográficos. Los resultados señalan que las adolescentes conocen el discurso biomédico que plantea que fumar trae graves consecuencias en el organismo, pero hay otras razones simbólicas que inciden en el consumo, tales como la búsqueda de la igualdad con los hombres y la imagen, ya que consideran que para los hombres una mujer que fuma es atractiva y tiene un grado más alto de madurez. El grupo social ejerce una influencia muy importante para que las mujeres fumen al validar la práctica y minimizar los daños en el organismo.O objetivo deste estudo foi conhecer as representações do ato de fumar em mulheres adolescentes, tanto fumantes quanto não fumantes, de uma instituição de Educação Superior no Estado de Querétaro, México. Trata-se de uma investigação qualitativa

  13. Superior Efficacy and Improved Renal and Bone Safety After Switching from a Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through 96 Weeks of Treatment.

    Science.gov (United States)

    DeJesus, Edwin; Haas, Bernard; Segal-Maurer, Sorana; Ramgopal, Moti N; Mills, Anthony; Margot, Nicolas; Liu, Ya-Pei; Makadzange, Tariro; McCallister, Scott

    2018-04-01

    We previously demonstrated superior efficacy and safety advantages in HIV-infected, virologically suppressed adults switched to a regimen containing tenofovir alafenamide (TAF) as compared with those remaining on a tenofovir disoproxil fumarate (TDF) regimen through week 48. We now report long-term data through week 96. In this randomized, active-controlled, multicenter, open-label, noninferiority trial (ClinicalTrials.gov No. NCT01815736), we randomized virologically suppressed (HIV-1 RNA TAF group or to continue one of four TDF-containing regimens (TDF group) for 96 weeks. We evaluated efficacy (HIV-1 RNA TAF n = 959, TDF n = 477). At week 96, TAF was superior to TDF in virologic efficacy, with 93% on TAF and 89% on TDF having HIV-1 RNA TAF versus TDF continued through week 96 (p TAF group versus TDF through week 96 (p TAF group as compared with one case in the TDF group. Switching to EVG/COBI/FTC/TAF (E/C/F/TAF) was associated with statistically significant efficacy and safety advantages over remaining on a standard-of-care TDF-based regimen.

  14. Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

    Science.gov (United States)

    Weisenseel, Peter; Reich, Kristian; Griemberg, Wiebke; Merten, Katharina; Gröschel, Christine; Gomez, Natalie Nunez; Taipale, Kirsi; Bräu, Beate; Zschocke, Ina

    2017-02-01

    Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm ® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  15. Washington y Ginebra llegan a Buenos Aires: notas sobre la historia del hábito de fumar y su medicalización

    Directory of Open Access Journals (Sweden)

    Diego Armus

    2015-03-01

    Full Text Available Durante gran parte del siglo XX tanto los gobiernos civiles como los militares no encontraron en el tabaquismo un tema prioritario. Recién en la última década del siglo el movimiento internacional contra el cigarrillo, liderado por la Organización Mundial de la Salud, organizaciones norteamericanas y académicos, empezó a tener algún impacto en la escena política argentina. Fue en ese contexto que un nuevo grupo profesional logró impulsar la constitución de un amplio bloque político antitabaco. En ese proceso, el voluntarismo centrado en programas individuales para dejar de fumar que había marcado gran parte de las iniciativas del siglo XX, terminó desplazado por políticas públicas destinadas a producir ambientes libres de humo y a combatir la exposición pasiva al humo de tabaco ajeno.

  16. Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2.

    Science.gov (United States)

    Hu, Xinyue; Rajesh, Mohanraj; Zhang, Jian; Zhou, Shanshan; Wang, Shudong; Sun, Jian; Tan, Yi; Zheng, Yang; Cai, Lu

    2018-05-01

    Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Nachega, Jean B; Uthman, Olalekan A; Mofenson, Lynne M; Anderson, Jean R; Kanters, Steve; Renaud, Francoise; Ford, Nathan; Essajee, Shaffiq; Doherty, Meg C; Mills, Edward J

    2017-09-01

    There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants. We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The risk ratio (RR) for associations was pooled using a fixed-effects model. Seventeen studies met the study inclusion criteria. We found that the rate of preterm (14 days) (RR = 0.65; 95% CI: 0.23 to 1.85), but increased neonatal mortality (age <14 days) risk (RR = 5.64, 95% CI: 1.70 to 18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age 1 year. TDF-based ART in pregnancy seems generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.

  18. Maternal Tenofovir Disoproxil Fumarate Use During Pregnancy Is Not Associated With Adverse Perinatal Outcomes Among HIV-infected East African Women: A Prospective Study.

    Science.gov (United States)

    Pintye, Jillian; Baeten, Jared M; Celum, Connie; Mugo, Nelly; Ngure, Kenneth; Were, Edwin; Bukusi, Elizabeth A; John-Stewart, Grace; Heffron, Renee A

    2017-12-19

    Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and pre-exposure prophylaxis regimens. We evaluated the relationship between adverse perinatal outcomes and prenatal TDF use. Longitudinal data were analyzed from human immunodeficiency virus (HIV)-infected women who became pregnant during 2 HIV prevention studies conducted among HIV-serodiscordant couples in Kenya and Uganda. Pregnancies included were singleton, not terminated by an induced abortion, and had documented 3-drug ART use. Multivariate generalized estimating equation models were used to determine the association of prenatal TDF and perinatal outcomes. The most frequent ART regimens were TDF/3TC/EFV (39%) and AZT/3TC/NVP (34%); 49% of pregnancies had prenatal TDF exposure and 6% used a protease inhibitor. Neonatal death, preterm birth, and pregnancy loss occurred in 2%, 8%, and 12% of pregnancies, respectively. No differences were observed between pregnancies with and without exposure to TDF in the frequency of pregnancy loss (adjusted prevalence rate ratio [aPRR] 1.19, P = .8) or neonatal death (aPRR 0.68, P = .6). Preterm birth occurred less frequently among pregnancies exposed to TDF (aPRR, 0.34, P = .02). Maternal TDF use did not adversely affect perinatal outcomes. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  19. 4f-4f absorption spectral analysis of complexation of Pr(IlI) and Nd(IlI) with fumaric acid and maleic acid in different solvents

    International Nuclear Information System (INIS)

    Singh, Th. David; Taru Taru, T.; Nimita, L.; Singh, N. Rajmuhon

    2008-01-01

    Full text: Dimensions to lanthanide co-ordination chemistry in solution become a new age with the increase use of lanthanides as PROBES in the exploration of the structural function of biomolecular reactions. Absorption difference and comparative absorption spectrophotometric studies involving 4f-4f transitions for the complexation of Pr(III)/Nd(lIl) with fumaric acid and maleic acid have been carried out in CH 3 OH,CH 3 CN, dioxane and DMF. The small chemical and structural differences due to the ligands and solvents are shown to produce significant red shift and variation in the intensities of observed 4f-4f absorption bands. The variation in the spectral energy parameters - Slater Condon (F K ), Lande spin orbit coupling constant (ζ 4f ), nephelauxetic ratio (β), bonding parameter (b 1/2 ) and percent covalency (δ) are calculated and correlated with binding of the ligands with Pr(III)/Nd(III). In addition to this experimentally calculated oscillator strengths (P) and calculated values of Judd-Ofelt electric dipole intensity parameters, T λ (λ=2,4,6) are discussed for different 4f-4f transitions in different experimental conditions to discuss the nature of bonding between Ln(lIl) and ligands. The participation of π-electron density of ligands with complexation is also discussed

  20. "Application of Box-Behnken design for optimization and development of quetiapine fumarate loaded chitosan nanoparticles for brain delivery via intranasal route* ".

    Science.gov (United States)

    Shah, Brijesh; Khunt, Dignesh; Misra, Manju; Padh, Harish

    2016-08-01

    The objective of the present investigation was to optimize and develop quetiapine fumarate (QF) loaded chitosan nanoparticles (QF-NP) by ionic gelation method using Box-Behnken design. Three independent variables viz., X1-Concentration of chitosan, X2-Concentration of sodium tripolyphosphate and X3-Volume of sodium tripolyphosphate were taken to investigate their effect on dependent variables (Y1-Size, Y2-PDI and Y3-%EE). Optimized formula of QF-NP was selected from the design space which was further evaluated for physicochemical, morphological, solid state characterization, nasal diffusion and in-vivo distribution for brain targeting following non-invasive intranasal administration. The average particle size, PDI, %EE and nasal diffusion were found to be 131.08±7.45nm, 0.252±0.064, 89.93±3.85% and 65.24±5.26% respectively. Neither toxicity nor structural damage on nasal mucosa was observed upon histopathological examination. Significantly higher brain/blood ratio and 2 folds higher nasal bioavailability in brain with QF-NP in comparison to drug solution following intranasal administration revealed preferential nose to brain transport bypassing blood-brain barrier and prolonged retention of QF at site of action suggesting superiority of chitosan as permeability enhancer. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The Fumarate Reductase of Bacteroides thetaiotaomicron, unlike That of Escherichia coli, Is Configured so that It Does Not Generate Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Zheng Lu

    2017-01-01

    Full Text Available The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS.

  2. Neurological syndrome in an HIV-prevention trial participant randomized to daily tenofovir disoproxil fumarate (300 mg and emtricitabine (200 mg in Bondo, Kenya

    Directory of Open Access Journals (Sweden)

    Owino F

    2013-11-01

    Full Text Available Fredrick Owino,1 Justin Mandala,2 Julie Ambia,3 Kawango Agot,1 Lut Van Damme2 1Impact Research and Development Organization, Kisumu, Kenya; 2Department of Global Health, Population, and Nutrition, FHI 360, Washington, DC, USA; 3KAVI-Institute of Clinical Research, University of Nairobi, Nairobi, Kenya Abstract: Side effects of antiretroviral drug use by HIV-positive patients have been extensively studied; however, there are limited data on the side effects of antiretroviral drugs used as an HIV prophylaxis among healthy, HIV-negative individuals. Here we report on an unusual neuropathy in a 24-year-old participant in the FEM-PrEP trial. This was a Phase III randomized, double blind, placebo-controlled trial to test the safety and effectiveness of tenofovir disoproxil fumarate (300 mg and emtricitabine (200 mg (TDF-FTC to prevent HIV. At the eighth week of taking TDF-FTC with moderate adherence, the participant complained of mild paresthesiae, numbness, and a tingling sensation in her upper limbs that was associated with pain and cold. After an additional 4 days, she developed a disabling weakness of her upper limbs and tremors in her hands. The study product was discontinued, and within 2 weeks she was free of all symptoms. One month after restarting the drug, she complained of posture-dependent numbness of her upper limbs. Results of clinical and neurological exams, laboratory tests, and magnetic resonance imaging are described here. Keywords: pre-exposure prophylaxis, toxic neuropathy, NRTI

  3. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2013-09-01

    In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

  4. Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.

    Science.gov (United States)

    Porter, Danielle P; Toma, Jonathan; Tan, Yuping; Solberg, Owen; Cai, Suqin; Kulkarni, Rima; Andreatta, Kristen; Lie, Yolanda; Chuck, Susan K; Palella, Frank; Miller, Michael D; White, Kirsten L

    2016-02-01

    Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance

  5. Formulation development and optimization of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF 300 mg FDC tablets by D-optimal mixture design

    Directory of Open Access Journals (Sweden)

    Prosper Tibalinda

    2016-12-01

    Full Text Available The usage of fixed dose combination (FDC tablets of Lamivudine and Tenofovir Disoproxil Fumarate (TDF is increasing due to increased incidences of HIV/Hepatitis B and HIV/TB co-infections. This is likely to increase the financial crisis due to limited resources for funding procurement of ready-made products from the pharmaceuticals manufacturing leading countries. Therefore, production of local oral tablets containing Lamivudine and TDF FDC is inevitable. Lamivudine 300 mg/TDF 300 mg tablets were developed and optimized by D-optimal mixture design and produced by direct compression technique. Twenty trial formulations with independent variables, including PVP-CL 1–12.00%, PVP-K30 1–10.00%, starch-1500 2.5–12.5% and Avicel-PH102 2–19.25% were prepared by direct compression technique. The formulations were assessed on assay, dissolution, friability, weight variation and disintegration time. It was found that assay ranged from 98.13–101.95% for Lamivudine, 98.25–102.84 for TDF, both were within the in-house assay specification of 95 to 105%. Dissolution at single point was above 80% for Lamivudine 93.96–100.55% and 95.85–103.15% for TDF, disintegration time was between 1.92–66.33 min and friability 0.06–12.56%. Out of twenty formulation trials, eight formulations had all parameters in proven acceptable range. On optimization, one formulation with independent variables, PVP-CL 5.67%, PVP-K30 1.00%, Starch-1500 5.76% was selected. The optimized formulation was comparable to the reference product on the market with similarity factor (f2 and difference factor (f1 within the acceptable range for both Lamivudine and TDF.

  6. Economic impact of new active substance status on EU payers' budgets: example of dimethyl fumarate (Tecfidera(®)) for multiple sclerosis.

    Science.gov (United States)

    Toumi, Mondher; Jadot, Guy

    2014-01-01

    Recently, collaboration between regulators and payers was set up and was mainly focused on evidence generation along product clinical development. However, neither the regulatory path nor the new active substance status (NASs) was considered. Granting NASs will provide the product with 8 years of data protection and 2 years of market exclusivity during which no generic could enter the market. To review the economic impact (for payers) of NASs granted by the European Medicines Agency (EMA) for dimethyl fumarate (DMF), developed by Biogen and approved for multiple sclerosis (MS) as Tecfidera(®) on 3 February 2014. We reviewed the available DMF-containing products and identified their indication and price through relevant databases and official Web sites. The economic impact of Tecfidera(®) on payers' budgets was calculated assuming NASs was or was not granted. The forecast was identified in Datamonitor. Results identified four products already containing DMF as the main or unique active substance. This would have potentially prevented Tecfidera(®) from being granted NASs. The EMA Committee for Medicinal Products for Human Use (CHMP) denied Tecfidera(®) NASs and, following a company appeal, reversed its position opening as polemic. The impact of that decision has been evaluated at €7 to €10 billion over a 10-year period. NASs is a critical decision because it does have a major budget impact for payers, and it prevents generic competition. Current European Union (EU) regulations on that topic are unclear and open up too many interpretations thus distorting fair trade and affecting payers' bills. Greater clarity and more stringent rules are required to prevent mistrust of this EMA decision.

  7. Effects of liarozole fumarate (R85246) in combination with tamoxifen on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model

    International Nuclear Information System (INIS)

    Goss, Paul E; Strasser-Weippl, Kathrin; Qi, Shangle; Hu, Haiqing

    2007-01-01

    Liarozole fumarate (liarozole – R85246) is a novel compound with characteristics of both aromatase inhibitor (AI) and a retinoic acid metabolism blocking agent (RAMBA). Our objective was to determine the effects of liarozole alone or in combination with tamoxifen on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, as well as on the uterus in ovariectomized immature rats. (1) Tumor burden experiments: Animals bearing one or more tumors greater than 10 mm in diameter were treated for 56 consecutive days with 20 mg/kg or 80 mg/kg of liarozole by oral gavage, tamoxifen 100 μg/kg by subcutaneous injection, or a combination of liarozole and tamoxifen. At the end of the treatment period, total cumulative tumor volume as well as retinoic acid levels were measured. (2) Uterotrophic assay and proliferation experiments: 21-day-old ovariectomized (OVX) Sprague-Dawley rats were treated with 20 mg/kg or 80 mg/kg of liarozole by oral gavage, tamoxifen 1 mg/kg by subcutaneous injection, and combination of both for 4 consecutive days. At the end of the treatment period, uterine weight, epithelial lining cell height and indices of proliferation cell nuclear antigen (PCNA) were measured. The tumor burden experiments in rats bearing estrogen receptor (ER) positive mammary tumours showed that liarozole has a marked anti-tumour effect. In combination with tamoxifen, liarozole had neither an additive nor an antagonistic effect. However, liarozole markedly reduced the uterotrophic effects induced by tamoxifen. Liarozole's antitumor effects on ER positive mammary tumors and its protective effect on the uterus merit further studies to confirm its clinical value in combination with tamoxifen in ER positive postmenopausal breast cancer. Liarozole and other retinomimetics might also be suitable chemoprevention drugs in combination with tamoxifen because of their favorable toxicity profile

  8. Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre-exposure prophylaxis.

    Science.gov (United States)

    Koenig, H C; Mounzer, K; Daughtridge, G W; Sloan, C E; Lalley-Chareczko, L; Moorthy, G S; Conyngham, S C; Zuppa, A F; Montaner, L J; Tebas, P

    2017-07-01

    Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre-exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real-time adherence monitoring. We developed and validated a urine assay to measure tenofovir (TFV) to objectively monitor adherence to PrEP. We developed a urine assay using high-performance liquid chromatography coupled to tandem mass spectrometry with high sensitivity/specificity for TFV that allowed us to determine TFV concentrations in log 10 categories between 0 and 10 000 ng/mL. We validated the assay in three cohorts: (1) HIV-positive subjects with undetectable viral loads on a TDF/FTC-based regimen, (2) healthy HIV-negative subjects who received a single dose of TDF/FTC, and (3) HIV-negative subjects receiving daily TDF/FTC as PrEP for 24 weeks. The urine assay detected TFV with greater sensitivity than plasma-based measures and with a window of measurements within 7 days of the last TDF/FTC dose. Based on the urine log-linear clearance after the last dose and its concordance with all detectable plasma levels, a urine TFV concentration > 1000 ng/mL was identified as highly predictive of the presence of TFV in plasma at > 10 ng/mL. The urine assay was able to distinguish high and low adherence patterns within the last 48 h (> 1000 ng/mL versus 10-1000 ng/mL), as well as nonadherence (< 10 ng/mL) extended over at least 1 week prior to measurement. We provide proof of concept that a semiquantitative urine assay measuring levels of TFV could be further developed into a point-of-care test and be a useful tool to monitor adherence to PrEP. © 2017 British HIV Association.

  9. The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.

    Science.gov (United States)

    Hamed, Rania; AlJanabi, Reem; Sunoqrot, Suhair; Abbas, Aiman

    2017-08-01

    The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel ® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol ® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel ® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel ® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.

  10. Cuanta más psicología, mejor: eficacia para dejar de fumar de la terapia cognitiva conductual intensiva y de los parches de nicotina combinados con terapia cognitiva conductual intensiva y menos intensiva

    OpenAIRE

    Fernández Arias, Ignacio Gabino; García-Vera, María Paz; Sanz, Jesús

    2014-01-01

    Para comparar la eficacia para dejar de fumar de la terapia cognitiva conductual intensiva (TCC/I), la TCC/I con parches de nicotina (TCC/I+PN) y la terapia cognitiva conductual no intensiva con parches de nicotina (TCC/NI+PN) se realizó un estudio experimental de medidas repetidas con 235 fumadores adultos asignados aleatoriamente a uno de esos tres tratamientos. Entre los pacientes que completaron el tratamiento (n = 152) la TCC/I+PN mostró tasas de abstinencia a los 6 meses y al año, mayor...

  11. Plutonium inventories for stabilization and stabilized materials

    Energy Technology Data Exchange (ETDEWEB)

    Williams, A.K.

    1996-05-01

    The objective of the breakout session was to identify characteristics of materials containing plutonium, the need to stabilize these materials for storage, and plans to accomplish the stabilization activities. All current stabilization activities are driven by the Defense Nuclear Facilities Safety Board Recommendation 94-1 (May 26, 1994) and by the recently completed Plutonium ES&H Vulnerability Assessment (DOE-EH-0415). The Implementation Plan for accomplishing stabilization of plutonium-bearing residues in response to the Recommendation and the Assessment was published by DOE on February 28, 1995. This Implementation Plan (IP) commits to stabilizing problem materials within 3 years, and stabilizing all other materials within 8 years. The IP identifies approximately 20 metric tons of plutonium requiring stabilization and/or repackaging. A further breakdown shows this material to consist of 8.5 metric tons of plutonium metal and alloys, 5.5 metric tons of plutonium as oxide, and 6 metric tons of plutonium as residues. Stabilization of the metal and oxide categories containing greater than 50 weight percent plutonium is covered by DOE Standard {open_quotes}Criteria for Safe Storage of Plutonium Metals and Oxides{close_quotes} December, 1994 (DOE-STD-3013-94). This standard establishes criteria for safe storage of stabilized plutonium metals and oxides for up to 50 years. Each of the DOE sites and contractors with large plutonium inventories has either started or is preparing to start stabilization activities to meet these criteria.

  12. Trapped particle stability for the kinetic stabilizer

    Science.gov (United States)

    Berk, H. L.; Pratt, J.

    2011-08-01

    A kinetically stabilized axially symmetric tandem mirror (KSTM) uses the momentum flux of low-energy, unconfined particles that sample only the outer end-regions of the mirror plugs, where large favourable field-line curvature exists. The window of operation is determined for achieving magnetohydrodynamic (MHD) stability with tolerable energy drain from the kinetic stabilizer. Then MHD stable systems are analysed for stability of the trapped particle mode. This mode is characterized by the detachment of the central-cell plasma from the kinetic-stabilizer region without inducing field-line bending. Stability of the trapped particle mode is sensitive to the electron connection between the stabilizer and the end plug. It is found that the stability condition for the trapped particle mode is more constraining than the stability condition for the MHD mode, and it is challenging to satisfy the required power constraint. Furthermore, a severe power drain may arise from the necessary connection of low-energy electrons in the kinetic stabilizer to the central region.

  13. Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.

    Science.gov (United States)

    Nkhoma, Ella T; Rosenblatt, Lisa; Myers, Joel; Villasis-Keever, Angelina; Coumbis, John

    2016-01-01

    Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs). This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs). We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD -3.96; 95% CI: -7.31, -1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD -3.85; 95% CI: -5.02, -2.78). In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower

  14. Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants.

    Science.gov (United States)

    Paganini, Daniela; Uyoga, Mary A; Cercamondi, Colin I; Moretti, Diego; Mwasi, Edith; Schwab, Clarissa; Bechtler, Salome; Mutuku, Francis M; Galetti, Valeria; Lacroix, Christophe; Karanja, Simon; Zimmermann, Michael B

    2017-10-01

    Background: Whether consumption of prebiotics increases iron absorption in infants is unclear. Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+NaFeEDTA) in Kenyan infants. Design: Infants ( n = 50; aged 6-14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto-oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as 57 FeFum+Na 58 FeEDTA or ferrous sulfate ( 54 FeSO 4 ). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixed-effects models. Results: There was a significant group-by-compound interaction on iron absorption ( P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO 4 in the Fe group were 11.6% (IQR: 6.9-19.9%) and 20.3% (IQR: 14.2-25.7%), respectively, ( P iron absorption was greater from the FeFum+NaFeEDTA ( P = 0.047) in the Fe+GOS group but not from the FeSO 4 ( P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO 4 was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time-by-group interaction on Bifidobacterium spp. ( P = 0.008) and Lactobacillus / Pediococcus / Leuconostoc spp. ( P = 0.018); Lactobacillus / Pediococcus / Leuconostoc spp. decreased in the Fe group ( P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group ( P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH ( P iron absorption by 62

  15. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC tumor syndrome and congenital fumarase deficiency

    Directory of Open Access Journals (Sweden)

    Tomlinson Ian PM

    2008-03-01

    Full Text Available Abstract Background Fumarate hydratase (HGNC approved gene symbol – FH, also known as fumarase, is an enzyme of the tricarboxylic acid (TCA cycle, involved in fundamental cellular energy production. First described by Zinn et al in 1986, deficiency of FH results in early onset, severe encephalopathy. In 2002, the Multiple Leiomyoma Consortium identified heterozygous germline mutations of FH in patients with multiple cutaneous and uterine leiomyomas, (MCUL: OMIM 150800. In some families renal cell cancer also forms a component of the complex and as such has been described as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839. The identification of FH as a tumor suppressor was an unexpected finding and following the identification of subunits of succinate dehydrogenase in 2000 and 2001, was only the second description of the involvement of an enzyme of intermediary metabolism in tumorigenesis. Description The FH mutation database is a part of the TCA cycle gene mutation database (formerly the succinate dehydrogenase gene mutation database and is based on the Leiden Open (source Variation Database (LOVD system. The variants included in the database were derived from the published literature and annotated to conform to current mutation nomenclature. The FH database applies HGVS nomenclature guidelines, and will assist researchers in applying these guidelines when directly submitting new sequence variants online. Since the first molecular characterization of an FH mutation by Bourgeron et al in 1994, a series of reports of both FH deficiency patients and patients with MCUL/HLRRC have described 107 variants, of which 93 are thought to be pathogenic. The most common type of mutation is missense (57%, followed by frameshifts & nonsense (27%, and diverse deletions, insertions and duplications. Here we introduce an online database detailing all reported FH sequence variants. Conclusion The FH mutation database strives to systematically

  16. Tenofovir disoproxil fumarate monotherapy for nucleos(tide analogue-naïve and nucleos(tide analogue-experienced chronic hepatitis B patients

    Directory of Open Access Journals (Sweden)

    Sang Kyung Jung

    2015-03-01

    Full Text Available Background/AimsThis study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF monotherapy in nucleos(tide analogue (NA-naive and NA-experienced chronic hepatitis B (CHB patients.MethodsCHB patients treated with TDF monotherapy (300 mg/day for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks.ResultsIn total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis were included. Sixty-two patients were nucleos(tide (NA-naïve, and 74 patients had prior NA therapy (NA-exp group, and 31 patients in the NA-exp group had lamivudine (LAM-resistance (LAM-R group. The baseline serum hepatitis B virus (HBV DNA level was 4.9±2.3 log IU/mL (mean±SD, and was higher in the NA-naïve group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P<0.01. The complete virological response (CVR rate at week 48 in the NA-naïve group (71.4% did not differ significantly from those in the NA-exp (71.3% and LAM-R (66.1% groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898, while the CVR rate did not differ with the NA experience.ConclusionsTDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.

  17. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Wang G

    2014-01-01

    Full Text Available Gang Wang,1 Alexander McIntyre,2 Willie R Earley,3 Shane R Raines,3 Hans Eriksson4 1Beijing Anding Hospital, Capital Medical University, Beijing, People's Republic of China; 2Department of Psychiatry, Penticton Regional Hospital, Penticton, BC, Canada; 3AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 4AstraZeneca R&D, Södertälje, Sweden Objectives: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder (MDD. Patients and methods: This was a 10-week (8-week active treatment/2-week post-treatment randomized, double-blind, placebo- and active-controlled study (D1448C00004. Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement and remission (score ≤8; Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results: A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346] versus placebo (-15.61. There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37. Mixed-model repeated

  18. Cuanta más psicología, mejor: eficacia para dejar de fumar. De la terapia cognitiva conductual intensiva y de los parches de nicotina combinados con terapia cognitiva conductual intensiva y menos intensiva

    Directory of Open Access Journals (Sweden)

    Ignacio Gabino Fernández Arias

    2014-01-01

    Full Text Available Para comparar la eficacia para dejar de fumar de la terapia cognitiva conductual intensiva (TCC/I, la TCC/I con parches de nicotina (TCC/I+PN y la terapia cognitiva conductual no intensiva con parches de nicotina (TCC/NI+PN se realizó un estudio experimental de medidas repetidas con 235 fumadores adultos asignados aleatoriamente a uno de esos tres tratamientos. Entre los pacientes que completaron el tratamiento (n= 152 la TCC/I+PN mostró tasas de abstinencia a los 6 meses y al año, mayores que la TCC/NI+PN, mientras que la TCC/I mostró tasas de abstinencia que no eran significativamente diferentes de las de los otros dos tratamientos. Estos resultados sugieren que los parches de nicotina se deberían utilizar siempre con una terapia cognitiva conductual lo más intensiva posible y que la utilización de esta última terapia en solitario debería gozar de mayor relevancia en las guías clínicas para dejar de fumar.

  19. Stability of Dolos Slopes

    DEFF Research Database (Denmark)

    Brorsen, Michael; Burcharth, Hans F.; Larsen, Torben

    The stability of dolos armour blocks against wave attack has been investigated in wave model studies.......The stability of dolos armour blocks against wave attack has been investigated in wave model studies....

  20. Stability of parallel flows

    CERN Document Server

    Betchov, R

    2012-01-01

    Stability of Parallel Flows provides information pertinent to hydrodynamical stability. This book explores the stability problems that occur in various fields, including electronics, mechanics, oceanography, administration, economics, as well as naval and aeronautical engineering. Organized into two parts encompassing 10 chapters, this book starts with an overview of the general equations of a two-dimensional incompressible flow. This text then explores the stability of a laminar boundary layer and presents the equation of the inviscid approximation. Other chapters present the general equation

  1. The BWR Stability Issue

    International Nuclear Information System (INIS)

    D'Auria, F.

    2008-01-01

    The purpose of this paper is to supply general information about Boiling Water Reactor (BWR) stability. The main concerned topics are: phenomenological aspects, experimental database, modelling features and capabilities, numerical models, three-dimensional modelling, BWR system performance during stability, stability monitoring and licensing aspects.

  2. Determinacion de la configuracion E-Z de los acidos Fumarico y Maleico. Un experimento orientado a incentivar el desarrollo de la investigacion cientifica en alumnos de Pregrado Determination of the E-Z fumaric and maleic acids configuration. An experiment designed to develop scientific research abilities in undergraduates students

    Directory of Open Access Journals (Sweden)

    Carlos Bustos

    2000-08-01

    Full Text Available In this work we intend to eliminate the idea that laboratory exercises seem like cookbooks. That is, exercises shall be presented as a problematic situation. Based on observation and experimentation, the students should determine the E-Z configuration of maleic and fumaric acids. The basis of this laboratory exercise is the acid-catalyzed isomerization of maleic acid to fumaric acid. Students are given the starting material, reagents and the experimental procedure. They are told that the starting material is a dicarboxylic acid containing a C=C double bond of formula C4H4O4. Students determine melting points, solubilities, acidity and chromatographic patterns for both the starting material and the product, so that a configuration of each acid can be proposed. This type of experiment yields excellent results, because the students are left to deduce that maleic acid is less stable than fumaric acid. Additionally, they conclude that maleic acid is the "Z" isomer and fumaric acid is the "E" isomer. Finally, this laboratory exercise allows the students to develop simultaneously their critical-thinking skills with the respective laboratory techniques and not to see chemistry as recipes to be followed.

  3. Escala Razões para Fumar da Universidade de São Paulo: um novo instrumento para avaliar a motivação para fumar University of São Paulo Reasons for Smoking Scale: a new tool for the evaluation of smoking motivation

    Directory of Open Access Journals (Sweden)

    Elisa Sebba Tosta de Souza

    2010-12-01

    Full Text Available OBJETIVO: Desenvolver uma nova escala voltada para a avaliação da motivação para fumar, incorporando questões do 68-item Wisconsin Inventory of Smoking Dependence Motives (WISDM-68, Inventário Wisconsin dos Motivos de Dependência ao Fumo, de 68 itens na Modified Reasons for Smoking Scale (MRSS. Escala Razões para Fumar Modificada. MÉTODOS: Nove questões do WISDM-68 relativas à associação estreita, exposição a gatilhos/processos associativos e controle de peso foram incorporadas às 21 questões da MRSS. Um total de 311 fumantes (214 homens; idade média = 37,6 ± 10,8 anos; média de cigarros consumidos ao dia = 15,0 ± 9,2 responderam a nova escala, o Fagerström Test for Nicotine Dependence (FTND, Teste de Fagerström para Dependência de Nicotina e outras questões. Empregamos a análise fatorial exploratória para determinar a estrutura fatorial da escala. A influência de algumas características clínicas nos escores da solução fatorial final foi também avaliada. RESULTADOS: A análise fatorial revelou uma solução com 21 questões agrupadas em nove fatores: dependência, prazer de fumar, redução da tensão, estimulação, automatismo, manuseio, tabagismo social, controle de peso e associação estreita. Para a escala como um todo, o coeficiente alfa de Cronbach foi de 0,83. As mulheres exibiram maiores escores para dependência, redução da tensão, manuseio, controle de peso e associação estreita do que os homens. Os escores do FTND correlacionaram-se positivamente com dependência, redução da tensão, estimulação, automatismo, tabagismo social e associação estreita. O número de cigarros fumados ao dia se associou com dependência, redução da tensão, estimulação, automatismo, associação estreita e manuseio. Os níveis de CO exalado mostraram associações positivas com dependência, automatismo e associação estreita. CONCLUSÕES: A nova escala fornece um quadro aceitável dos fatores motivacionais

  4. Feedback stabilization initiative

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes.

  5. Feedback stabilization initiative

    International Nuclear Information System (INIS)

    1997-06-01

    Much progress has been made in attaining high confinement regimes in magnetic confinement devices. These operating modes tend to be transient, however, due to the onset of MHD instabilities, and their stabilization is critical for improved performance at steady state. This report describes the Feedback Stabilization Initiative (FSI), a broad-based, multi-institutional effort to develop and implement methods for raising the achievable plasma betas through active MHD feedback stabilization. A key element in this proposed effort is the Feedback Stabilization Experiment (FSX), a medium-sized, national facility that would be specifically dedicated to demonstrating beta improvement in reactor relevant plasmas by using a variety of MHD feedback stabilization schemes

  6. RCRA facility stabilization initiative

    International Nuclear Information System (INIS)

    1995-02-01

    The RCRA Facility Stabilization Initiative was developed as a means of implementing the Corrective Action Program's management goals recommended by the RIS for stabilizing actual or imminent releases from solid waste management units that threaten human health and the environment. The overall goal of stabilization is to, as situations warrant, control or abate threats to human health and/or the environment from releases at RCRA facilities, and/or to prevent or minimize the further spread of contamination while long-term remedies are pursued. The Stabilization initiative is a management philosophy and should not be confused with stabilization technologies

  7. Association of Stability Parameters and Yield Stability of Sesame ...

    African Journals Online (AJOL)

    Association of Stability Parameters and Yield Stability of Sesame ( Sesamum ... Information on phenotypic stability is useful for the selection of crop varieties as well as for ... as an alternative to parametric stability measurements is important.

  8. Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results.

    Science.gov (United States)

    Arribas, José R; Thompson, Melanie; Sax, Paul E; Haas, Bernhard; McDonald, Cheryl; Wohl, David A; DeJesus, Edwin; Clarke, Amanda E; Guo, Susan; Wang, Hui; Callebaut, Christian; Plummer, Andrew; Cheng, Andrew; Das, Moupali; McCallister, Scott

    2017-06-01

    In 2 double-blind phase 3 trials, 1733 antiretroviral-naive adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs 80.0% having HIV-1 RNA TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P TAF vs 4 for TDF. There were greater increases in lipids with TAF vs TDF, with no difference in the total cholesterol to high-density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety.

  9. INFLUENCIA DEL HÁBITO DE FUMAR SOBRE EL CONSUMO DE ALIMENTOS Y EL ESTILO DE VIDA EN ESTUDIANTES DE LA FACULTAD DE CIENCIAS DE LA PONTIFICIA UNIVERSIDAD JAVERIANA

    Directory of Open Access Journals (Sweden)

    Martha Díaz Perilla

    2003-06-01

    Full Text Available La presente investigación fue realizada para establecer la relación entre el hábito de fumar, el consumo de alimentos y el estilo de vida en estudiantes de la Facultad de Ciencias de la Pontificia Universidad Javeriana de Bogotá.El estudio fue de tipo descriptivo de corte transversal, en el cual participaron 130 sujetos seleccionados aleatoriamente del total de estudiantes de la Facultad de Ciencias. Para el análisis estadístico de las variables cuantitativas se utilizaron las pruebas Z y t y pani las variables cualitativas la prueba Chi 2, con un nivel de significancia p 0.05, mientras que el antecedente personal de obesidad (p = 0.03 y el consumo de bebidas alcohólicas (p = 0.009 sí lo estaban. De igual forma se observó que los fumadores tienen un consumo superior de energía (13% así como de grasa total (3.8% , grasa saturada (2.5% y colesterol (18.9%. Las mayores asociaciones que se encontraron con el hábito de fumar fueron el bajo consumo de frutas (p = 2.53x1Q-6 y de verduras (p = 5.8 x10·4. Por otro lado, se determinó que menos del 50% de los fumadores manifestaron cambio en el sabor de los alimentos. En conclusión, los fumadores pueden tener más posibilidades de padecer alguna enfermedad cardiovasculár por presentar más factores de riesgo, así como hábitos alimentarios poco saludables como el alto consumo de energía, grasa total, saturada y colesterol y el bajo consumo de frutas y verduras.

  10. Stability of Hyperthermophilic Proteins

    DEFF Research Database (Denmark)

    Stiefler-Jensen, Daniel

    stability by randomly generate mutants and lengthy screening processes to identify the best new mutants. However, with the increase in available genomic sequences of thermophilic or hyperthermophilic organisms a world of enzymes with intrinsic high stability are now available. As these organisms are adapted...... to life at high temperatures so are their enzymes, as a result the high stability is accompanied by low activity at moderate temperatures. Thus, much effort had been put into decoding the mechanisms behind the high stability of the thermophilic enzymes. The hope is to enable scientist to design enzymes...... in the high stability of hyperthermophilic enzymes. The thesis starts with an introduction to the field of protein and enzyme stability with special focus on the thermophilic and hyperthermophilic enzymes and proteins. After the introduction three original research manuscripts present the experimental data...

  11. Are Stabilization Programs Expansionary?

    OpenAIRE

    Federico Echenique; Alvaro Forteza

    1997-01-01

    The empirical evidence presented in this paper casts serious doubts on the by now widely accepted "stylized facts" of the exchange rate based stabilization programs (ERBS) as they are stated in Kiguel and Liviatan (1992) and in Végh (1992). Even though the ERBS programs were associated with output booms, no evidence of booms provoked by the stabilization programs is found. Rather, exogenous capital inflows to Latin America seem to have caused both the output booms and the stabilization progra...

  12. Internet Addiction: Stability and Change

    Science.gov (United States)

    Huang, Chiungjung

    2010-01-01

    This longitudinal study examined five indices of stability and change in Internet addiction: structural stability, mean-level stability, differential stability, individual-level stability, and ipsative stability. The study sample was 351 undergraduate students from end of freshman year to end of junior year. Convergent findings revealed stability…

  13. Microwave stability at transition

    International Nuclear Information System (INIS)

    Holt, J.A.; Colestock, P.L.

    1995-05-01

    The question of microwave stability at transition is revisited using a Vlasov approach retaining higher order terms in the particle dynamics near the transition energy. A dispersion relation is derived which can be solved numerically for the complex frequency in terms of the longitudinal impedance and other beam parameters. Stability near transition is examined and compared with simulation results

  14. Beam stabilization at SPEAR

    International Nuclear Information System (INIS)

    Corbett, J.

    1996-01-01

    The SPEAR storage ring began routine synchrotron radiation operation with a dedicated injector in 1990. Since then, a program to improve beam stability has steadily progressed. This paper, based on a seminar given at a workshop on storage ring optimization (1995 SRI conference) reviews the beam stability program for SPEAR. copyright 1996 American Institute of Physics

  15. Visual attention and stability

    NARCIS (Netherlands)

    Mathot, Sebastiaan; Theeuwes, Jan

    2011-01-01

    In the present review, we address the relationship between attention and visual stability. Even though with each eye, head and body movement the retinal image changes dramatically, we perceive the world as stable and are able to perform visually guided actions. However, visual stability is not as

  16. Electrode stabilizing materials

    Science.gov (United States)

    Amine, Khalil; Abouimrane, Ali; Moore, Jeffrey S.; Odom, Susan A.

    2015-11-03

    An electrolyte includes a polar aprotic solvent; an alkali metal salt; and an electrode stabilizing compound that is a monomer, which when polymerized forms an electrically conductive polymer. The electrode stabilizing compound is a thiophene, a imidazole, a anilines, a benzene, a azulene, a carbazole, or a thiol. Electrochemical devices may incorporate such electrolytes.

  17. Homological stabilizer codes

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Jonas T., E-mail: jonastyleranderson@gmail.com

    2013-03-15

    In this paper we define homological stabilizer codes on qubits which encompass codes such as Kitaev's toric code and the topological color codes. These codes are defined solely by the graphs they reside on. This feature allows us to use properties of topological graph theory to determine the graphs which are suitable as homological stabilizer codes. We then show that all toric codes are equivalent to homological stabilizer codes on 4-valent graphs. We show that the topological color codes and toric codes correspond to two distinct classes of graphs. We define the notion of label set equivalencies and show that under a small set of constraints the only homological stabilizer codes without local logical operators are equivalent to Kitaev's toric code or to the topological color codes. - Highlights: Black-Right-Pointing-Pointer We show that Kitaev's toric codes are equivalent to homological stabilizer codes on 4-valent graphs. Black-Right-Pointing-Pointer We show that toric codes and color codes correspond to homological stabilizer codes on distinct graphs. Black-Right-Pointing-Pointer We find and classify all 2D homological stabilizer codes. Black-Right-Pointing-Pointer We find optimal codes among the homological stabilizer codes.

  18. Stabilized radiographic scanning agent

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1979-01-01

    A stable composition useful in preparation of technetium-99m-based radiographic scanning agents has been developed. The composition contains a stabilizing amount of gentisate stabilizer selected from gentisic acid and its soluble pharmaceutically-acceptable salts and esthers. (E.G.)

  19. Problems support economic stability

    OpenAIRE

    Tkach, Ivan

    2012-01-01

    . The article is devoted to summarizing the approaches to the classification of the stability of the state's economy, identifying the main characteristics, and offers the author's vision for the classification of the stability of the economy of the state under various conditions of operation.

  20. Stability of multihypernuclear objects

    International Nuclear Information System (INIS)

    Ikram, M.; Rather, Asloob A.; Usmani, A.A.; Patra, S.K.

    2016-01-01

    In present work, we analyze the stability of multi-hypernuclear objects having higher content of strangeness. The aim of this work is to test the stability of such objects which might be produced in heavy-ion reactions. Studies of such type of systems might have great implication to nuclear-astrophysics

  1. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  2. Stability of Organic Nanowires

    DEFF Research Database (Denmark)

    Balzer, F.; Schiek, M.; Wallmann, I.

    2011-01-01

    The morphological stability of organic nanowires over time and under thermal load is of major importance for their use in any device. In this study the growth and stability of organic nanowires from a naphthyl end-capped thiophene grown by organic molecular beam deposition is investigated via ato...

  3. The statistical stability phenomenon

    CERN Document Server

    Gorban, Igor I

    2017-01-01

    This monograph investigates violations of statistical stability of physical events, variables, and processes and develops a new physical-mathematical theory taking into consideration such violations – the theory of hyper-random phenomena. There are five parts. The first describes the phenomenon of statistical stability and its features, and develops methods for detecting violations of statistical stability, in particular when data is limited. The second part presents several examples of real processes of different physical nature and demonstrates the violation of statistical stability over broad observation intervals. The third part outlines the mathematical foundations of the theory of hyper-random phenomena, while the fourth develops the foundations of the mathematical analysis of divergent and many-valued functions. The fifth part contains theoretical and experimental studies of statistical laws where there is violation of statistical stability. The monograph should be of particular interest to engineers...

  4. Dispersal and metapopulation stability

    Directory of Open Access Journals (Sweden)

    Shaopeng Wang

    2015-10-01

    Full Text Available Metapopulation dynamics are jointly regulated by local and spatial factors. These factors may affect the dynamics of local populations and of the entire metapopulation differently. Previous studies have shown that dispersal can stabilize local populations; however, as dispersal also tends to increase spatial synchrony, its net effect on metapopulation stability has been controversial. Here we present a simple metapopulation model to study how dispersal, in interaction with other spatial and local processes, affects the temporal variability of metapopulations in a stochastic environment. Our results show that in homogeneous metapopulations, the local stabilizing and spatial synchronizing effects of dispersal cancel each other out, such that dispersal has no effect on metapopulation variability. This result is robust to moderate heterogeneities in local and spatial parameters. When local and spatial dynamics exhibit high heterogeneities, however, dispersal can either stabilize or destabilize metapopulation dynamics through various mechanisms. Our findings have important theoretical and practical implications. We show that dispersal functions as a form of spatial intraspecific mutualism in metapopulation dynamics and that its effect on metapopulation stability is opposite to that of interspecific competition on local community stability. Our results also suggest that conservation corridors should be designed with appreciation of spatial heterogeneities in population dynamics in order to maximize metapopulation stability.

  5. Life raft stabilizer

    Science.gov (United States)

    Radnofsky, M. I.; Barnett, J. H., Jr.; Harrison, F. L.; Marak, R. J. (Inventor)

    1973-01-01

    An improved life raft stabilizer for reducing rocking and substantially precluding capsizing is discussed. The stabilizer may be removably attached to the raft and is defined by flexible side walls which extend a considerable depth downwardly to one another in the water. The side walls, in conjunction with the floor of the raft, form a ballast enclosure. A weight is placed in the bottom of the enclosure and water port means are provided in the walls. Placement of the stabilizer in the water allows the weighted bottom to sink, producing submerged deployment thereof and permitting water to enter the enclosure through the port means, thus forming a ballast for the raft.

  6. Gravity stabilizes itself

    International Nuclear Information System (INIS)

    Chakraborty, Sumanta; SenGupta, Soumitra

    2017-01-01

    We show that a possible resolution to the stabilization of an extra spatial dimension (radion) can be obtained solely in the context of gravitational dynamics itself without the necessity of introducing any external stabilizing field. In this scenario the stabilized value of the radion field gets determined in terms of the parameters appearing in the higher curvature gravitational action. Furthermore, the mass of the radion field and its coupling to the standard model fields are found to be in the weak scale implying possible signatures in the TeV scale colliders. Some resulting implications are also discussed. (orig.)

  7. Gravity stabilizes itself

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sumanta; SenGupta, Soumitra [Indian Association for the Cultivation of Science, Department of Theoretical Physics, Kolkata (India)

    2017-08-15

    We show that a possible resolution to the stabilization of an extra spatial dimension (radion) can be obtained solely in the context of gravitational dynamics itself without the necessity of introducing any external stabilizing field. In this scenario the stabilized value of the radion field gets determined in terms of the parameters appearing in the higher curvature gravitational action. Furthermore, the mass of the radion field and its coupling to the standard model fields are found to be in the weak scale implying possible signatures in the TeV scale colliders. Some resulting implications are also discussed. (orig.)

  8. Stability of matter

    International Nuclear Information System (INIS)

    Thirring, W.

    1985-01-01

    Basing on quantum mechanics and the simple Hamiltonian consisting of kinetic energy and Coulomb potential, heuristic arguments and estimates are used to guess the essential stability properties of many-particle systems. In view of applications in astrophysics, gravitation as a second potential and thermodynamic arguments are added. The guesses thus obtained are confronted with known exact results. The connection between the stabilities against explosion and against implosion, and thermodynamic stability is considered. In systems with a particle number larger than approx= 10 54 (corresponding to the Jupiter mass) gravitational energy prevails over the electrostatic energy and determines the history of a star. Negative specific heat accompanies life and death of a star. Finally the role of stability and instability in the universe for life is outlined. (G.Q.)

  9. Factores asociados con la intención de fumar y el inicio del hábito tabáquico en escolares: resultados del estudio ESFA en Barcelona

    Directory of Open Access Journals (Sweden)

    Nebot M.

    2002-01-01

    Full Text Available Objetivo: Describir los factores asociados con el consumo de tabaco y la intención de fumar en el futuro en una muestra representativa de escolares de primer curso de educación secundaria en Barcelona. Sujetos y métodos: Se seleccionaron 37 escuelas al azar para participar en la evaluación de un programa europeo de prevención del tabaquismo (European Smoking prevention Frame Approach, proyecto ESFA. En estas escuelas 1.041 alumnos de primer curso de Enseñanza Secundaria Obligatoria (ESO contestaron a un cuestionario diseñado por la Universidad de Maastricht para estudiar las actitudes y conductas relacionadas con diversos comportamientos, incluyendo el consumo de tabaco. Resultados: El 9,8% de los chicos y el 12,6% de las chicas manifestaron fumar de forma regular u ocasional. Entre los no fumadores, un 61,4% de los chicos y un 73,3% de las chicas declararon tener intención de fumar en el futuro. En los chicos, los determinantes del consumo son la norma social (odds ratio [OR] = 2,5; intervalo de confianza [IC] del 95%, 1,2-5,2, el consumo de tabaco por parte de los hermanos (OR = 2,4; IC del 95%, 1,1-5,2, las actitudes contrarias al consumo (OR = 0,3; IC del 95%, 0,1-0,6, la práctica de deporte en el tiempo libre (OR = 0,3; IC del 95%, 0,1-0,7 y el dinero semanal disponible (OR = 3,2; IC del 95%, 1,5-6,8, mientras que la intención únicamente se asoció de forma significativa a las actitudes contrarias (OR = 0,3; IC del 95%, 0,2-0,5. Para las chicas, el consumo se asoció a la presión (OR = 2,5; IC del 95%, 1,2-5,0 y el consumo (OR = 6,0; IC del 95%, 2,4-15,4 por parte de los amigos, y las actitudes contrarias (OR = 0,2; IC del 95%, 0,1-0,4, mientras que la intención se halla asociada a las actitudes contrarias (OR = 0,4; IC del 95%, 0,2-0,6 y pasar tiempo libre en la calle (OR = 2,1; IC del 95%, 1,3-3,5. Conclusiones: Los resultados corroboran la necesidad de abordar simultáneamente los distintos factores relacionados con el

  10. Progress on plutonium stabilization

    International Nuclear Information System (INIS)

    Hurt, D.

    1996-01-01

    The Defense Nuclear Facilities Safety Board has safety oversight responsibility for most of the facilities where unstable forms of plutonium are being processed and packaged for interim storage. The Board has issued recommendations on plutonium stabilization and has has a considerable influence on DOE's stabilization schedules and priorities. The Board has not made any recommendations on long-term plutonium disposition, although it may get more involved in the future if DOE develops plans to use defense nuclear facilities for disposition activities

  11. Structural Stability and Vibration

    DEFF Research Database (Denmark)

    Wiggers, Sine Leergaard; Pedersen, Pauli

    This book offers an integrated introduction to the topic of stability and vibration. Strikingly, it describes stability as a function of boundary conditions and eigenfrequency as a function of both boundary conditions and column force. Based on a post graduate course held by the author at the Uni...... and their derivation, thus stimulating them to write interactive and dynamic programs to analyze instability and vibrational modes....

  12. Automatic Fiscal Stabilizers

    Directory of Open Access Journals (Sweden)

    Narcis Eduard Mitu

    2013-11-01

    Full Text Available Policies or institutions (built into an economic system that automatically tend to dampen economic cycle fluctuations in income, employment, etc., without direct government intervention. For example, in boom times, progressive income tax automatically reduces money supply as incomes and spendings rise. Similarly, in recessionary times, payment of unemployment benefits injects more money in the system and stimulates demand. Also called automatic stabilizers or built-in stabilizers.

  13. Soil stabilization 1982

    Science.gov (United States)

    Barenberg, E. J.; Thompson, M. R.; Tayabji, S. D.; Nussbaum, P. J.; Ciolko, A. T.

    Seven papers cover the following areas: design, construction and performance of lime, fly ash, and slag pavement; evaluation of heavily loaded cement stabilized bases; coal refuse and fly ash compositions; potential highway base course materials; lime soil mixture design considerations for soils of southeastern United States; short term active soil property changes caused by injection of lime and fly ash; soil cement for use in stream channel grade stabilization structures; and reaction products of lime treated southeastern soils.

  14. Investigations of slope stability

    Energy Technology Data Exchange (ETDEWEB)

    Nonveiller, E.

    1979-01-01

    The dynamics of slope slides and parameters for calculating slope stability is discussed. Two types of slides are outlined: rotation slide and translation slide. Slide dynamics are analyzed according to A. Heim. A calculation example of a slide which occurred at Vajont, Yugoslavia is presented. Calculation results differ from those presented by Ciabatti. For investigation of slope stability the calculation methods of A.W. Bishop (1955), N. Morgenstern and M. Maksimovic are discussed. 12 references

  15. PFP solution stabilization

    International Nuclear Information System (INIS)

    Aftanas, B.L.

    1996-01-01

    This Functional Design Criteria (FDC) addresses remediation of the plutonium-bearing solutions currently in inventory at the Plutonium Finishing Plant (PFP). The recommendation from the Environmental Impact Statement (EIS) is that the solutions be treated thermally and stabilized as a solid for long term storage. For solutions which are not discardable, the baseline plan is to utilize a denitration process to stabilize the solutions prior to packaging for storage

  16. METHOD FOR STABILIZING KLYSTRONS

    Science.gov (United States)

    Magnuson, D.W.; Smith, D.F.

    1959-04-14

    High-frequency oscillators for the generation of microwaves, particularly a system for stabilizing frequency-modulated klystron oscillators of the reflex type, are described. The system takos advantage of the fact that a change in oscillator frequency will alter the normal phase displacement between the cavity and its modulator, creating an error voltage which is utilized to regulate the frequency of the oscillator and stabilize it.

  17. Cyber Deterrence and Stability

    Energy Technology Data Exchange (ETDEWEB)

    Goychayev, Rustam [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carr, Geoffrey A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Weise, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Donnelly, David A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clements, Samuel L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Benz, Jacob M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rodda, Kabrena E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bartholomew, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McKinnon, Archibald D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Andres, Richard B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2017-09-30

    Throughout the 20th and early 21st centuries, deterrence and arms control have been cornerstones of strategic stability between the superpowers. However, the weaponization of the cyber realm by State actors and the multipolar nature of cyber conflict now undermines that stability. Strategic stability is the state in which nations believe that if they act aggressively to undermine U.S. national interests and the post-World War II liberal democratic order, the consequences will outweigh the benefits. The sense of lawlessness and lack of consequences in the cyber realm embolden States to be more aggressive in taking actions that undermine stability. Accordingly, this paper examines 1) the role of deterrence and arms control in securing cyber stability, and 2) the limitations and challenges associated with these traditional national security paradigms as applied to this emerging threat domain. This paper demonstrates that many 20th-century deterrence and arms control concepts are not particularly applicable in the cyber realm. However, they are not entirely irrelevant. The United States can distill lessons learned from this rich deterrence and arms control experience to develop and deploy a strategy to advance cyber stability.

  18. Prevalencia del habito de fumar en jóvenes y sus padres: asociaciones relevantes con educacion y ocupación Prevalência do hábito de fumar em jovens e seus pais: associações de importância com educação e ocupação Prevalence of smoking in young people and their parents: important assocations with education and occupation

    Directory of Open Access Journals (Sweden)

    Leonor Poletto

    1991-10-01

    Full Text Available Con el objetivo de conocer la prevalencia del hábito de fumar cigarrillos en los jóvenes, se estudiaron muestras aleatorias de varones de 18 años y de estudiantes universitarios de medicina y de economía, los que respondieron un cuestionario referido al hábito, escolaridad y ocupación propias y de sus padres, así como sus opiniones y motivaciones. La prevalencia del hábito fue mayor en los varones en ambas generaciones, en los estudiantes de medicina que en los de economía, y en los padres con nivel universitario. Se encontró asociación entre el hábito de los jóvenes de la problación general con el de sus padres (pCom o objetivo de conhecer a prevalência de hábito de fumar cigarros entre os jovens, estudaram-se amostras aleatórias de homens de 18 anos e de estudantes universitários de medicina e de economia, que responderam um questionário sobre o hábito, escolaridade e ocupação, próprios e de seus pais. A prevalência do hábito de fumar foi maior nos homens de ambas as gerações, nos estudantes de medicina, que nos de economia, e nos pais com educação universitária. Achou-se associação entre o hábito dos jovens representativos da população geral (p Rosario, with a million inhabitants, is the second major urban concentration in Argentina and serves as the commercial and industrial center for a large area. In view of the lack of information on the present prevalence of smoking in this area as for the country as a whole, a study was performed on random samples of young people and university students of medicine and economics, as well as on their parents. Information was obtained on their life smoking habits, education and occupation. The prevalence of the habit was higher: a in men, both in the youngsters and their parents; b in medical students than in those of the economic sciences; c in parents with university education. The smoking habit of these subjects and parents was highly associated (p < 0.001 in the

  19. Stabilization of compactible waste

    International Nuclear Information System (INIS)

    Franz, E.M.; Heiser, J.H. III; Colombo, P.

    1990-09-01

    This report summarizes the results of series of experiments performed to determine the feasibility of stabilizing compacted or compactible waste with polymers. The need for this work arose from problems encountered at disposal sites attributed to the instability of this waste in disposal. These studies are part of an experimental program conducted at Brookhaven National Laboratory (BNL) investigating methods for the improved solidification/stabilization of DOE low-level wastes. The approach taken in this study was to perform a series of survey type experiments using various polymerization systems to find the most economical and practical method for further in-depth studies. Compactible dry bulk waste was stabilized with two different monomer systems: styrene-trimethylolpropane trimethacrylate (TMPTMA) and polyester-styrene, in laboratory-scale experiments. Stabilization was accomplished by wetting or soaking compactible waste (before or after compaction) with monomers, which were subsequently polymerized. Three stabilization methods are described. One involves the in-situ treatment of compacted waste with monomers in which a vacuum technique is used to introduce the binder into the waste. The second method involves the alternate placement and compaction of waste and binder into a disposal container. In the third method, the waste is treated before compaction by wetting the waste with the binder using a spraying technique. A series of samples stabilized at various binder-to-waste ratios were evaluated through water immersion and compression testing. Full-scale studies were conducted by stabilizing two 55-gallon drums of real compacted waste. The results of this preliminary study indicate that the integrity of compacted waste forms can be readily improved to ensure their long-term durability in disposal environments. 9 refs., 10 figs., 2 tabs

  20. Intervenciones para dejar de fumar en México: análisis de disponibilidad a pagar por un método efectivo de cesación Smoking cessation interventions in Mexico: analysis of the willingness to pay for an effective method to quit

    Directory of Open Access Journals (Sweden)

    Edson E Serván-Mori

    2012-06-01

    Full Text Available OBJETIVO: Identificar factores socioeconómicos, demográficos, historia de tabaquismo y contextuales asociados con el deseo de dejar de fumar, estimar la disponibilidad a pagar (DAP por tratamientos de cesación tabáquica (TCT efectivos, e identificar sus factores asociados. MATERIAL Y MÉTODOS: Mediante la Encuesta Global de Tabaquismo en Adultos, México 2009, caracterizamos a 1 626 fumadores. Modelos logit y de regresión lineal múltiple permitieron identificar factores asociados con el deseo de dejar de fumar y la DAP. RESULTADOS: 82.2% de los fumadores que no deseaban dejar de fumar fueron hombres. Entre quienes deseaban dejar de fumar, 49.8% fumaba diariamente y reportó más de 16 años de fumar, 57% manifestó intentos previos de cesación y 10% conocer centros de ayuda. La DAP promedio fue 2 708 MXN, destacando diferencias por nivel socioeconómico y educativo. CONCLUSIONES: Se contribuye al diseño de estrategias de cesación diferenciadas, propiciando mejoras en la respuesta del sistema de salud al combate del tabaquismo en México.OBJECTIVE: To identify environmental, demographic and socioeconomic factors associated with the desire to quit, estimate the willingness to pay (WTP for smoking cessation treatments (SCT and to identify associated factors with this valuation. MATERIALS AND METHODS: Using the Global Adult Tobacco Survey, Mexico 2009, we characterized 1 626 smokers. Logistic and multiple lineal regression models allowed to identify associated factors with the desire to quit and the WTP for SCT. RESULTS: 82.2 % of the current smokers who did not want to quit were men. Between those who wanted to quit, 49.8 % had been consuming tobacco every day, for more than 16 years, 57 % had made cessation attempts in the past, and around 10% knew about the existence of centers to help quit smoking. Average WTP was 2 708 Mexican pesos (MXP, with differences by educational and socioeconomic levels. CONCLUSIONS: This evidence supports

  1. An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

    2015-04-30

    Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Stabilizing weighted complex networks

    International Nuclear Information System (INIS)

    Xiang Linying; Chen Zengqiang; Liu Zhongxin; Chen Fei; Yuan Zhuzhi

    2007-01-01

    Real networks often consist of local units which interact with each other via asymmetric and heterogeneous connections. In this paper, the V-stability problem is investigated for a class of asymmetric weighted coupled networks with nonidentical node dynamics, which includes the unweighted network as a special case. Pinning control is suggested to stabilize such a coupled network. The complicated stabilization problem is reduced to measuring the semi-negative property of the characteristic matrix which embodies not only the network topology, but also the node self-dynamics and the control gains. It is found that network stabilizability depends critically on the second largest eigenvalue of the characteristic matrix. The smaller the second largest eigenvalue is, the more the network is pinning controllable. Numerical simulations of two representative networks composed of non-chaotic systems and chaotic systems, respectively, are shown for illustration and verification

  3. Hydrodynamic and hydromagnetic stability

    CERN Document Server

    Chandrasekhar, S

    1981-01-01

    Dr. Chandrasekhar's book received high praise when it first appeared in 1961 as part of Oxford University Press' International Series of Monographs on Physics. Since then it has been reprinted numerous times in its expensive hardcover format. This first lower-priced, sturdy paperback edition will be welcomed by graduate physics students and scientists familiar with Dr. Chandrasekhar's work, particularly in light of the resurgence of interest in the Rayleigh-Bénard problem. This book presents a most lucid introduction to the Rayleigh-Bénard problem: it has also been applauded for its thorough, clear coverage of the theory of instabilities causing convection. Dr. Chandrasekhar considers most of the typical problems in hydromagnetic stability, with the exception of viscous shear flow; a specialized domain deserving a book unto itself. Contents include: Rotation; Stability of More General Flows; Bénard Problem; Gravitational Equilibrium and Instability; Stability of a Magnetic Field; Thermal Instability of a L...

  4. Magnet stability and reproducibility

    CERN Document Server

    Marks, N

    2010-01-01

    Magnet stability and reproducibility have become increasingly important as greater precision and beams with smaller dimension are required for research, medical and other purpose. The observed causes of mechanical and electrical instability are introduced and the engineering arrangements needed to minimize these problems discussed; the resulting performance of a state-of-the-art synchrotron source (Diamond) is then presented. The need for orbit feedback to obtain best possible beam stability is briefly introduced, but omitting any details of the necessary technical equipment, which is outside the scope of the presentation.

  5. Progress on plutonium stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Hurt, D. [Defense Nuclear Facilities Safety Board, Washington, DC (United States)

    1996-05-01

    The Defense Nuclear Facilities Safety Board has safety oversight responsibility for most of the facilities where unstable forms of plutonium are being processed and packaged for interim storage. The Board has issued recommendations on plutonium stabilization and has has a considerable influence on DOE`s stabilization schedules and priorities. The Board has not made any recommendations on long-term plutonium disposition, although it may get more involved in the future if DOE develops plans to use defense nuclear facilities for disposition activities.

  6. Stability of dynamical systems

    CERN Document Server

    Liao, Xiaoxin; Yu, P 0

    2007-01-01

    The main purpose of developing stability theory is to examine dynamic responses of a system to disturbances as the time approaches infinity. It has been and still is the object of intense investigations due to its intrinsic interest and its relevance to all practical systems in engineering, finance, natural science and social science. This monograph provides some state-of-the-art expositions of major advances in fundamental stability theories and methods for dynamic systems of ODE and DDE types and in limit cycle, normal form and Hopf bifurcation control of nonlinear dynamic systems.ʺ Presents

  7. Magnetohydrodynamic stability of tokamaks

    CERN Document Server

    Zohm, Hartmut

    2014-01-01

    This book bridges the gap between general plasma physics lectures and the real world problems in MHD stability. In order to support the understanding of concepts and their implication, it refers to real world problems such as toroidal mode coupling or nonlinear evolution in a conceptual and phenomenological approach. Detailed mathematical treatment will involve classical linear stability analysis and an outline of more recent concepts such as the ballooning formalism. The book is based on lectures that the author has given to Master and PhD students in Fusion Plasma Physics. Due its strong lin

  8. Stability of loess

    Science.gov (United States)

    Lutenegger, A.J.; Hallberg, G.R.

    1988-01-01

    Lutenegger, A.J. and Hallberg, G.R., 1988. Stability of loess. Eng. Geol., 25: 247-261. The natural stability of loess soils can be related to fundamental geotechnical properties such as Atterberg limits, water content and void ratio. Field observations of unstable conditions in loess deposits in the upper midwest, U.S.A. show relationships between instability and the in situ moisture content and the liquidity index of the loess. Unstable loess can attain natural moisture contents equal to, or greater than, its liquid limit. Implications of these observations for applied engineering works are described. ?? 1988.

  9. Stability of heterodyne terahertz receivers

    NARCIS (Netherlands)

    Kooi, J.W.; Baselmans, J.J.A.; Baryshev, A.; Schieder, R.; Hajenius, M.; Gao, J.R.; Klapwijk, T.M.; Voronov, B.; Gol'tsman, G.

    2006-01-01

    In this paper we discuss the stability of heterodyne terahertz receivers based on small volume NbN phonon cooled hot electron bolometers (HEBs). The stability of these receivers can be broken down in two parts: the intrinsic stability of the HEB mixer and the stability of the local oscillator (LO)

  10. stabilized lateritic soil

    African Journals Online (AJOL)

    user

    this work to optimize the amount of bagasse ash content in cement-stabilized lateritic soil. Geometric .... can handle or consider all the properties involved at the same time to ...... Bearig Ratio of Used oil contaminated Lateritic soils” Nigerian ...

  11. Stability of mixing layers

    Science.gov (United States)

    Tam, Christopher; Krothapalli, A

    1993-01-01

    The research program for the first year of this project (see the original research proposal) consists of developing an explicit marching scheme for solving the parabolized stability equations (PSE). Performing mathematical analysis of the computational algorithm including numerical stability analysis and the determination of the proper boundary conditions needed at the boundary of the computation domain are implicit in the task. Before one can solve the parabolized stability equations for high-speed mixing layers, the mean flow must first be found. In the past, instability analysis of high-speed mixing layer has mostly been performed on mean flow profiles calculated by the boundary layer equations. In carrying out this project, it is believed that the boundary layer equations might not give an accurate enough nonparallel, nonlinear mean flow needed for parabolized stability analysis. A more accurate mean flow can, however, be found by solving the parabolized Navier-Stokes equations. The advantage of the parabolized Navier-Stokes equations is that its accuracy is consistent with the PSE method. Furthermore, the method of solution is similar. Hence, the major part of the effort of the work of this year has been devoted to the development of an explicit numerical marching scheme for the solution of the Parabolized Navier-Stokes equation as applied to the high-seed mixing layer problem.

  12. Stabilized chromium oxide film

    Science.gov (United States)

    Garwin, Edward L.; Nyaiesh, Ali R.

    1988-01-01

    Stabilized air-oxidized chromium films deposited on high-power klystron ceramic windows and sleeves having a thickness between 20 and 150.ANG. are useful in lowering secondary electron emission yield and in avoiding multipactoring and window failure due to overheating. The ceramic substrate for the film is chosen from alumina, sapphire or beryllium oxide.

  13. Ractor stability monitor

    International Nuclear Information System (INIS)

    Takeuchi, Yutaka.

    1991-01-01

    A stability monitor for a BWR type reactor determines the index of stability by statistic processing of signals from an average power region monitor or the like, but it takes much time and the reliability thereof is not always high. Then, parameters such as reactor core power are measured on every sampling periods as observation data and pretreatments such as normalization are applied successively, to obtain monitored amount and store them successively. Differentiation coefficient relative to time are calculated by using the observed amount at present and that one sample period before, to evaluate on a phasal plane using the amount of observation and the differentiation coefficient with time on the axes of coordinate. As a result, information relative to the stability can be represented accurately, thereby enabling to monitor the stability at a high accuracy. Further, judgement for the condition considering the amplitude is conducted upon oscillation, thereby enabling to conduct control operation certainly. The operation in a region where it has been limited under great caution can be conducted appropriately and safely, enabling to conduct controlled operation of excellent economical property. (N.H.)

  14. Economical stabilized scintillation detector

    International Nuclear Information System (INIS)

    Anshakov, O.M.; Chudakov, V.A.; Gurinovich, V.I.

    1983-01-01

    An economical scintillation detector with the stabilization system of an integral type is described. Power consumed by the photomultiplier high-voltage power source is 40 mW, energy resolution is not worse than 9%. The given detector is used in a reference detector of a digital radioisotope densimeter for light media which is successfully operating for several years

  15. Stability through cycles

    NARCIS (Netherlands)

    E.A. de Groot (Bert); Ph.H.B.F. Franses (Philip Hans)

    2006-01-01

    textabstractEconomic variables like GDP growth, employment, interest rates and consumption show signs of cyclical behavior. Many variables display multiple cycles, with lengths ranging in between 5 to even up to 100 years. We argue that multiple cycles can be associated with long-run stability of

  16. Moral Hazard and Stability

    DEFF Research Database (Denmark)

    Tumennasan, Norovsambuu

    2014-01-01

    not form. Formally, we study the team formation problem in which the agents’ efforts are not verifiable and the size of teams does not exceed quota r . We show that if the team members cannot make transfers, then moral hazard affects stability positively in a large class of games. For example, a stable...

  17. Watt steam governor stability

    Science.gov (United States)

    Denny, Mark

    2002-05-01

    The physics of the fly-ball governor, introduced to regulate the speed of steam engines, is here analysed anew. The original analysis is generalized to arbitrary governor geometry. The well-known stability criterion for the linearized system breaks down for large excursions from equilibrium; we show approximately how this criterion changes.

  18. Axisymmetric annular curtain stability

    International Nuclear Information System (INIS)

    Ahmed, Zahir U; Khayat, Roger E; Maissa, Philippe; Mathis, Christian

    2012-01-01

    A temporal stability analysis was carried out to investigate the stability of an axially moving viscous annular liquid jet subject to axisymmetric disturbances in surrounding co-flowing viscous gas media. We investigated in this study the effects of inertia, surface tension, the gas-to-liquid density ratio, the inner-to-outer radius ratio and the gas-to-liquid viscosity ratio on the stability of the jet. With an increase in inertia, the growth rate of the unstable disturbances is found to increase. The dominant (or most unstable) wavenumber decreases with increasing Reynolds number for larger values of the gas-to-liquid viscosity ratio. However, an opposite tendency for the most unstable wavenumber is predicted for small viscosity ratio in the same inertia range. The surrounding gas density, in the presence of viscosity, always reduces the growth rate, hence stabilizing the flow. There exists a critical value of the density ratio above which the flow becomes stable for very small viscosity ratio, whereas for large viscosity ratio, no stable flow appears in the same range of the density ratio. The curvature has a significant destabilizing effect on the thin annular jet, whereas for a relatively thick jet, the maximum growth rate decreases as the inner radius increases, irrespective of the surrounding gas viscosity. The degree of instability increases with Weber number for a relatively large viscosity ratio. In contrast, for small viscosity ratio, the growth rate exhibits a dramatic dependence on the surface tension. There is a small Weber number range, which depends on the viscosity ratio, where the flow is stable. The viscosity ratio always stabilizes the flow. However, the dominant wavenumber increases with increasing viscosity ratio. The range of unstable wavenumbers is affected only by the curvature effect. (paper)

  19. Surface-stabilized gold nanocatalysts

    Science.gov (United States)

    Dai, Sheng [Knoxville, TN; Yan, Wenfu [Oak Ridge, TN

    2009-12-08

    A surface-stabilized gold nanocatalyst includes a solid support having stabilizing surfaces for supporting gold nanoparticles, and a plurality of gold nanoparticles having an average particle size of less than 8 nm disposed on the stabilizing surfaces. The surface-stabilized gold nanocatalyst provides enhanced stability, such as at high temperature under oxygen containing environments. In one embodiment, the solid support is a multi-layer support comprising at least a first layer having a second layer providing the stabilizing surfaces disposed thereon, the first and second layer being chemically distinct.

  20. Bunched beam longitudinal stability

    International Nuclear Information System (INIS)

    Baartman, R.

    1991-05-01

    Instabilities driven by narrow-band impedances can be stabilized by Landau damping arising from the synchrotron frequency spread due to the nonlinearity of the rf wave-form. We calculate stability diagrams for various phase space distributions. We find that distributions without tails are unstable in the 'negative mass' regime (inductive impedance below transition or capacitive impedance above transition). We also find that longitudinal instability thresholds of the (usually neglected) higher order radial modes are lower than expected. For example, the next to lowest dipole mode has a lower threshold than the lowest sextupole mode even though the latter has the larger growth rate in the absence of Landau damping. (Author) 5 refs., 5 figs

  1. Gross xenon stability

    International Nuclear Information System (INIS)

    Lewins, J.D.; Wilson, P.P.H.

    1997-01-01

    The effect of xenon in thermal reactors on steady operation is generally destabilizing. Illustrating this involves the study of appropriate transfer functions, which may be conveniently displayed in three ways: as Bode, Nyquist, and root-locus diagrams. The three forms allow different aspects to be highlighted. These are illustrated for the effect of xenon with allowance not only for the stabilizing effect of the direct yield in fission but also to show the consequences of neglecting the time dependence due to the thermal capacity of the reactor. With careful interpretation, all these forms give an interpretation of stability that is consistent with direct evaluation and promote the understanding of the onset of gross oscillations in power

  2. Hillslope hydrology and stability

    Science.gov (United States)

    Lu, Ning; Godt, Jonathan

    2012-01-01

    Landslides are caused by a failure of the mechanical balance within hillslopes. This balance is governed by two coupled physical processes: hydrological or subsurface flow and stress. The stabilizing strength of hillslope materials depends on effective stress, which is diminished by rainfall. This book presents a cutting-edge quantitative approach to understanding hydro-mechanical processes across variably saturated hillslope environments and to the study and prediction of rainfall-induced landslides. Topics covered include historic synthesis of hillslope geomorphology and hydrology, total and effective stress distributions, critical reviews of shear strength of hillslope materials and different bases for stability analysis. Exercises and homework problems are provided for students to engage with the theory in practice. This is an invaluable resource for graduate students and researchers in hydrology, geomorphology, engineering geology, geotechnical engineering and geomechanics and for professionals in the fields of civil and environmental engineering and natural hazard analysis.

  3. Marital stability and repartnering

    DEFF Research Database (Denmark)

    Martins, Mariana V; Costa, Patrício; Peterson, Brennan D

    2014-01-01

    a second union have higher initial levels of stress in their original relationship and higher changes in stress levels over the course of treatments. These findings suggest that high infertility-related stress levels before entering fertility treatment can negatively affect the stability of marital......OBJECTIVE: To compare the trajectories of infertility-related stress between patients who remain in the same relationship and patients who repartner. DESIGN: Longitudinal cohort study using latent growth modeling. SETTING: Fertility centers. PATIENT(S): Childless men and women evaluated before...... starting a new cycle of fertility treatment and observed for a 5-year period of unsuccessful treatments. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Marital stability and infertility-related stress. RESULT(S): The majority of patients (86%) remained with their initial partner, but 14% of participants...

  4. Second region of stability

    International Nuclear Information System (INIS)

    Greene, J.M.; Chance, M.S.

    1980-10-01

    A new type of axisymmetric magnetohydrodynamic equilibrium is presented. It is characterized by a region of pressure and safety factor variation with a short scale length imposed as a perturbation. The equilibrium consistent with these profile variations can be calculated by means of an asymptotic expansion. The flexibility obtained by generating such equilibria allows for a close examination of the mechanisms that are relevant to ballooning instabilities - ideal MHD modes with large toroidal mode number. The so-called first and second regions of stability against these modes are seen well within the limits of validity of the asymptotic expansion. It appears that the modes must be localized in regions with small values of the local shear of the magnetic field. The second region of stability occurs where the local shear is large throughout the range where the magnetic field line curvature is destabilizing

  5. Noise Enhanced Stability

    International Nuclear Information System (INIS)

    Spagnolo, B.; Agudov, N.V.; Dubkov, A.A.

    2004-01-01

    The noise can stabilize a fluctuating or a periodically driven metastable state in such a way that the system remains in this state for a longer time than in the absence of white noise. This is the noise enhanced stability phenomenon, observed experimentally and numerically in different physical systems. After shortly reviewing all the physical systems where the phenomenon was observed, the theoretical approaches used to explain the effect are presented. Specifically the conditions to observe the effect in systems: (a) with periodical driving force, and (b) with random dichotomous driving force, are discussed. In case (b) we review the analytical results concerning the mean first passage time and the nonlinear relaxation time as a function of the white noise intensity, the parameters of the potential barrier, and of the dichotomous noise. (author)

  6. Limits of Nuclear Stability

    CERN Document Server

    Nerlo-Pomorska, B; Kleban, M

    2003-01-01

    The modern version of the liquid-drop model (LSD) is compared with the macroscopic part of the binding energy evaluated within the Hartree-Fock- Bogoliubov procedure with the Gogny force and the relativistic mean field theory. The parameters of a liquid-drop like mass formula which approximate on the average the self-consistent results are compared with other models. The limits of nuclear stability predicted by these models are discussed.

  7. Base Stability of Aminocyclopropeniums

    Science.gov (United States)

    2017-11-01

    PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) US Army Research Laboratory Weapons and Materials Research Directorate (ATTN: RDRL-WMM-G) 2800 Powder...Mill Road Adelphi, MD 20783-1138 8. PERFORMING ORGANIZATION REPORT NUMBER ARL-TR-8204 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES...fuel cells to test their utility in anion exchange membranes. While the aminocyclopropeniums showed poor base stability, the cyclopropenium cation

  8. Stability of Ignition Transients

    OpenAIRE

    V.E. Zarko

    1991-01-01

    The problem of ignition stability arises in the case of the action of intense external heat stimuli when, resulting from the cut-off of solid substance heating, momentary ignition is followed by extinction. Physical pattern of solid propellant ignition is considered and ignition criteria available in the literature are discussed. It is shown that the above mentioned problem amounts to transient burning at a given arbitrary temperature distribution in the condensed phase. A brief survey...

  9. Entropy-Stabilized Oxides

    Science.gov (United States)

    2015-09-29

    antiferroelectrics. Phys. Rev. Lett. 110, 017603 (2013). 22. Cantor , B., Chang, I., Knight, P. & Vincent, A. Microstructural development in equiatomic...Science 345, 1153–1158 (2014). 24. Gali, A. & George , E. Tensile properties of high- and medium-entropy alloys. Intermetallics 39, 74–78 (2013). 25...148–153 (2014). 26. Otto, F., Yang, Y., Bei, H. & George , E. Relative effects of enthalpy and entropy on the phase stability of equiatomic high-entropy

  10. Advanced Tokamak Stability Theory

    Science.gov (United States)

    Zheng, Linjin

    2015-03-01

    The intention of this book is to introduce advanced tokamak stability theory. We start with the derivation of the Grad-Shafranov equation and the construction of various toroidal flux coordinates. An analytical tokamak equilibrium theory is presented to demonstrate the Shafranov shift and how the toroidal hoop force can be balanced by the application of a vertical magnetic field in tokamaks. In addition to advanced theories, this book also discusses the intuitive physics pictures for various experimentally observed phenomena.

  11. Taxation and political stability

    OpenAIRE

    Estrada, Fernando; Mutascu, Mihai; Tiwari, Aviral

    2011-01-01

    The present study is, in particular, an attempt to test the relationship between tax level and political stability by using some economic control variables and to see the relationship among government effectiveness, corruption, and GDP. For the purpose, we used the Vector Autoregression (VAR) approach in the panel framework, using a country-level panel data from 59 countries for the period 2002 to 2008. The salient features of this model are: (a) simplicity is based on a limited number of var...

  12. Taxation and political stability

    OpenAIRE

    Mutascu, Mihai; Tiwari, Aviral; Estrada, Fernando

    2011-01-01

    The present study is, in particular, an attempt to test the relationship between tax level and political stability by using some economic control variables and to see the relationship among government effectiveness, corruption, and GDP. For the purpose, we used the Vector Autoregression (VAR) approach in the panel framework, using a country-level panel data from 59 countries for the period 2002 to 2008. The salient features of this model are: (a) simplicity is based on a limited number of ...

  13. Determining postural stability

    Science.gov (United States)

    Lieberman, Erez (Inventor); Forth, Katharine E. (Inventor); Paloski, William H. (Inventor)

    2011-01-01

    A method for determining postural stability of a person can include acquiring a plurality of pressure data points over a period of time from at least one pressure sensor. The method can also include the step of identifying a postural state for each pressure data point to generate a plurality of postural states. The method can include the step of determining a postural state of the person at a point in time based on at least the plurality of postural states.

  14. Oxidative stability of polyaniline

    Czech Academy of Sciences Publication Activity Database

    Stejskal, Jaroslav; Exnerová, Milena; Morávková, Zuzana; Trchová, Miroslava; Hromádková, Jiřina; Prokeš, J.

    2012-01-01

    Roč. 97, č. 6 (2012), s. 1026-1033 ISSN 0141-3910 R&D Projects: GA ČR GA202/09/1626; GA ČR GAP205/12/0911 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : polyaniline * nanotubes * oxidation stability Subject RIV: BK - Fluid Dynamics Impact factor: 2.770, year: 2012

  15. Stabilized power constant alimentation

    International Nuclear Information System (INIS)

    Roussel, L.

    1968-06-01

    The study and realization of a stabilized power alimentation variable from 5 to 100 watts are described. In order to realize a constant power drift of Lithium compensated diodes, we have searched a 1 per cent precision of regulation and a response time minus than 1 sec. Recent components like Hall multiplicator and integrated amplifiers give this possibility and it is easy to use permutable circuits. (author) [fr

  16. Extrap interchange stability

    International Nuclear Information System (INIS)

    Scheffel, J.

    1989-05-01

    This is a non-linear MHD study of Extrap interchange stability. The closed-line stability criterion d(pgγ)/dψ ≥ 0 is used for fully 2-D numerical calculations of marginally stable equilibria. It is found that Extrap has a stabilzing effect on these modes. The reason for this is that q = Ιdl/B diverges towards the separatrix, which forms a boundary for the pinch. Consequently, in comparison with the 1-D Z-pinch, the Extrap octupole field allows steeper pressure profile in the boundary region. This stabilizing effect is shown to diminish in equilibria with an externally imposed axial magnetic field. It is also shown how the shape of the plasma cross-section depends on the relative direction of plasma current and external rod currents, when the current density j is finite on the boundary. Unfavourable curvature and higher values of j at the boundary are obtained in the case of parallel currents. Only when j vanishes at the separatrix, the cross-section can be truly square-shaped. The type of singularity of q at the separatrix is derived, as well as criteria for j to become singular

  17. Uranium mill tailings stabilization

    International Nuclear Information System (INIS)

    Hartley, J.N.; Koehmstedt, P.L.; Esterl, D.J.; Freeman, H.D.

    1980-02-01

    Uranium mill tailings pose a potential radiation health hazard to the public. Therefore, stabilization or disposal of these tailings in a safe and environmentally sound way is needed to minimize radon exhalation and other environmental hazards. One of the most promising concepts for stabilizing U tailings is the use of asphalt emulsion to contain radon and other hazardous materials within uranium tailings. This approach is being investigated at the Pacific Northwest Laboratory. Results of these studies indicate that a radon flux reduction of greater than 99% can be obtained using either a poured-on/sprayed-on seal (3.0 to 7.0 mm thick) or an admixture seal (2.5 to 12.7 cm thick) containing about 18 wt % residual asphalt. A field test was carried out in June 1979 at the Grand Junction tailings pile in order to demonstrate the sealing process. A reduction in radon flux ranging from 4.5 to greater than 99% (76% average) was achieved using a 15.2-cm (6-in.) admix seal with a sprayed-on top coat. A hydrostatic stabilizer was used to apply the admix. Following compaction, a spray coat seal was applied over the admix as the final step in construction of a radon seal. Overburden was applied to provide a protective soil layer over the seal. Included in part of the overburden was a herbicide to prevent root penetration

  18. Improved roof stabilization technologies

    International Nuclear Information System (INIS)

    Ebadian, M.A.

    1998-01-01

    Decontamination and decommissioning (D and D) activities require that personnel have access to all areas of structures, some of which are more than 40 years old. In many cases, these structures have remained in a standby condition for up to 10 years; few preventative maintenance activities have been performed on them because of lack of funding or a defined future plan of action. This situation has led to deteriorated building conditions, resulting in potential personnel safety hazards. In addition, leaky roofs allow water to enter the buildings, which can cause the spread of contamination and increase building deterioration, worsening the already unsafe working conditions. To ensure worker safety and facilitate building dismantlement, the assessment of roof stabilization techniques applicable to US Department of Energy (DOE) structures has become an important issue. During Fiscal year 1997 (FY97), a comprehensive reliability-based model for the structural stabilization analysis of roof system in complex structures was developed. The model consists of three major components: a material testing method, a deterministic structural computer model, and a reliability-based optimization, and probabilistic analyses of roof structures can be implemented. Given site-specific needs, this model recommends the most appropriate roof stabilization system. This model will give not only an accurate evaluation of the existing roof system in complex structures, but it will also be a reliable method to aid the decision-making process. This final report includes in its appendix a Users' Manual for the Program of Deterministic and Reliability Analysis of Roof Structures

  19. Stability of boson stars

    International Nuclear Information System (INIS)

    Gleiser, M.

    1988-01-01

    Boson stars are gravitationally bound, spherically symmetric equilibrium configurations of cold, free, or interacting complex scalar fields phi. As these equilibrium configurations naturally present local anisotropy, it is sensible to expect departures from the well-known stability criteria for fluid stars. With this in mind, I investigate the dynamical instability of boson stars against charge-conserving, small radial perturbations. Following the method developed by Chandrasekhar, a variational base for determining the eigenfrequencies of the perturbations is found. This approach allows one to find numerically an upper bound for the central density where dynamical instability occurs. As applications of the formalism, I study the stability of equilibrium configurations obtained both for the free and for the self-interacting [with V(phi) = (λ/4)chemical bondphichemical bond 4 ] massive scalar field phi. Instabilities are found to occur not for the critical central density as in fluid stars but for central densities considerably higher. The departure from the results for fluid stars is sensitive to the coupling λ; the higher the value of λ, the more the stability properties of boson stars approach those of a fluid star. These results are linked to the fractional anisotropy at the radius of the configuration

  20. Heterotic moduli stabilization

    International Nuclear Information System (INIS)

    Cicoli, M.; De Alwis, S.; Colorado Univ., Boulder, CO; Westphal, A.

    2013-04-01

    We perform a systematic analysis of moduli stabilization for weakly coupled heterotic string theory compactified on smooth Calabi-Yau three-folds. We focus on both supersymmetric and supersymmetry breaking vacua of generic (0,2) compactifications obtained by minimising the total (F+D)-term scalar potential. After reviewing how to stabilise all the geometric moduli in a supersymmetric way by including fractional fluxes, non-perturbative and threshold effects, we show that the inclusion of α' corrections leads to new de Sitter or nearly Minkowski vacua which break supersymmetry spontaneously. The minimum lies at moderately large volumes of all the geometric moduli, at perturbative values of the string coupling and at the right phenomenological value of the GUT gauge coupling. However the structure of the heterotic 3-form flux used for complex structure moduli stabilization does not contain enough freedom to tune the superpotential. This results in the generic prediction of high-scale supersymmetry breaking around the GUT scale. We finally provide a dynamical derivation of anisotropic compactifications with stabilized moduli which allow for perturbative gauge coupling unification around 10 16 GeV.

  1. Heterotic moduli stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Cicoli, M. [Bologna Univ. (Italy). Dipt. Fisica ed Astronomia; INFN, Bologna (Italy); Adbus Salam ICTP, Trieste (Italy); De Alwis, S. [Adbus Salam ICTP, Trieste (Italy); Colorado Univ., Boulder, CO (United States). UCB 390 Physics Dept.; Westphal, A. [DESY Hamburg (Germany). Theory Group

    2013-04-15

    We perform a systematic analysis of moduli stabilization for weakly coupled heterotic string theory compactified on smooth Calabi-Yau three-folds. We focus on both supersymmetric and supersymmetry breaking vacua of generic (0,2) compactifications obtained by minimising the total (F+D)-term scalar potential. After reviewing how to stabilise all the geometric moduli in a supersymmetric way by including fractional fluxes, non-perturbative and threshold effects, we show that the inclusion of {alpha}' corrections leads to new de Sitter or nearly Minkowski vacua which break supersymmetry spontaneously. The minimum lies at moderately large volumes of all the geometric moduli, at perturbative values of the string coupling and at the right phenomenological value of the GUT gauge coupling. However the structure of the heterotic 3-form flux used for complex structure moduli stabilization does not contain enough freedom to tune the superpotential. This results in the generic prediction of high-scale supersymmetry breaking around the GUT scale. We finally provide a dynamical derivation of anisotropic compactifications with stabilized moduli which allow for perturbative gauge coupling unification around 10{sup 16} GeV.

  2. Vibrational stability of graphene

    Directory of Open Access Journals (Sweden)

    Yangfan Hu

    2013-05-01

    Full Text Available The mechanical stability of graphene as temperature rises is analyzed based on three different self-consistent phonon (SCP models. Compared with three-dimensional (3-D materials, the critical temperature Ti at which instability occurs for graphene is much closer to its melting temperature Tm obtained from Monte Carlo simulation (Ti ≃ 2Tm, K. V. Zakharchenko, A. Fasolino, J. H. Los, and M. I. Katsnelson, J. Phys. Condens. Matter 23, 202202. This suggests that thermal vibration plays a significant role in melting of graphene while melting for 3-D materials is often dominated by topologic defects. This peculiar property of graphene derives from its high structural anisotropy, which is characterized by the vibrational anisotropic coefficient (VAC, defined upon its Lindermann ratios in different directions. For any carbon based material with a graphene-like structure, the VAC value must be smaller than 5.4 to maintain its stability. It is also found that the high VAC value of graphene is responsible for its negative thermal expansion coefficient at low temperature range. We believe that the VAC can be regarded as a new criterion concerning the vibrational stability of any low-dimensional (low-D materials.

  3. Factors associated to smoking habit among older adults (The Bambuí Health and Aging Study Fatores associados ao hábito de fumar entre idosos (Projeto Bambuí

    Directory of Open Access Journals (Sweden)

    Sérgio Viana Peixoto

    2005-10-01

    Full Text Available OBJECTIVE: To describe the characteristics and associated factors of the smoking habit among older adults. METHODS: A population-based study was carried out comprising 1,606 (92.2% older adults (>60 years old living in the Bambuí town, Southeastern Brazil in 1997. Data was obtained by means of interview and socio-demographic factors, health status, physical functioning, use of healthcare services and medication were considered. The multiple multinomial logistic regression was used to assess independent associations between smoking habits (current and former smokers and the exploratory variables. RESULTS: The prevalence of current and past smoking was 31.4% and 40.2% among men, and 10.3% and 11.2% among women, respectively (p80 years and schooling (>8 years and positive association with poor health perception and not being married. Among women, independent and negative associations with current smoking were observed for age (75-79 and >80 years and schooling (4-7 and >8 years. CONCLUSIONS: Smoking was a public health concern among older adults in the studied community, particularly for men. Yet, in a low schooling population, a slightly higher level was a protective factor against smoking for both men and women. Programs for reducing smoking in the elderly population should take these findings into consideration.OBJETIVO: Descrever as características e fatores associados ao hábito de fumar em uma população idosa. MÉTODOS: Estudo de base populacional realizado com 1.606 (92,2% idosos (>60 anos residentes na cidade de Bambuí, Estado de Minas Gerais, em 1997. As variáveis estudadas foram: fatores sociodemográficos, condições de saúde, função física, uso de serviço de saúde e de medicamentos. Os dados foram coletados por meio de entrevista. A regressão logística multinomial foi utilizada para avaliar associações independentes entre o hábito de fumar (atual e passado e as variáveis exploratórias. RESULTADOS: A prevalência de

  4. Glycosylation and thermodynamic versus kinetic stability of horseradish peroxidase

    DEFF Research Database (Denmark)

    Tams, J.W.; Welinder, Karen G.

    1998-01-01

    Glycoprotein stability, glycoprotein unfolding, horseradish peroxidase, thermodynamic stability, kinetik stability......Glycoprotein stability, glycoprotein unfolding, horseradish peroxidase, thermodynamic stability, kinetik stability...

  5. Epidemiología del tabaquismo en los estudiantes de ciencias de la salud Epidemiologia do hábito de fumar em estudantes de ciências da saúde Tobacco use in health-science students

    Directory of Open Access Journals (Sweden)

    Andres Prat-Marin

    1994-04-01

    Full Text Available Las características del hábito tabáquico en los estudiantes de la División de Ciencias de la Salud de la Universidad de Barcelona han sido estudiadas en este trabajo. Durante el Curso Académico 1988-89, 382 alumnos han sido entrevistados individualmente en relación al tabaquismo, mediante el cuestionario utilizado habitualmente por el Departamento de Sanidad y Segundad Social de la Generalidad de Cataluña (España, con las modificaciones más oportunas para este colectivo específico. Asimismo se ha recogido información relacionada con la influencia de los estudios universitarios en el hábito de fumar, la autorización de la publicidad y la eficacia de los programas y campañas de lucha antitabaco desarrollados por las Administraciones públicas. La prevalencia de tabaquismo ha sido del 40,8% (29,8% de fumadores habituales y 11% de fumadores ocasionales. Hay que remarcar que los estudios relacionados con la salud no parecen influir de forma destacada en el hábito de los estudiantes, siendo el entorno cultural y social los factores que tienen un papel más determinante en este sentido. Como conclusión final señalar que, para disminuir la prevalencia de tabaquismo en este importante colectivo, hay que instaurar programas educativos a nivel de la escolarización pre-universitaria (bachillerato unificado polivalente y curso de orientación universitaria, e introducir modificaciones en los futuros planes de estudio de las profesiones sanitarias, de manera que los contenidos relacionados con el tabaco sean más motivadores para los alumnos.Foram estudadas as características do habito de fumar nos estudantes de ciências da saúde da Universidade de Barcelona. Durante o ano letivo 1988-89 foram entrevistados 382 alunos em relação ao uso do fumo, por meio de questionário rotinamente utilizado por um Departamento daquela Universidade, no qual foram efetuadas modificações pertinentes ao grupo estudado. Foram obtidas informa

  6. Convergent systems vs. incremental stability

    NARCIS (Netherlands)

    Rüffer, B.S.; Wouw, van de N.; Mueller, M.

    2013-01-01

    Two similar stability notions are considered; one is the long established notion of convergent systems, the other is the younger notion of incremental stability. Both notions require that any two solutions of a system converge to each other. Yet these stability concepts are different, in the sense

  7. Elements of magnetohydrodynamic stability theory

    International Nuclear Information System (INIS)

    Spies, G.O.

    1976-11-01

    The nonlinear equations of ideal magnetohydrodynamics are discussed along with the following topics: (1) static equilibrium, (2) strict linear theory, (3) stability of a system with one degree of freedom, (4) spectrum and variational principles in magnetohydrodynamics, (5) elementary proof of the modified energy principle, (6) sufficient stability criteria, (7) local stability, and (8) normal modes

  8. Control of locomotor stability in stabilizing and destabilizing environments.

    Science.gov (United States)

    Wu, Mengnan/Mary; Brown, Geoffrey; Gordon, Keith E

    2017-06-01

    To develop effective interventions targeting locomotor stability, it is crucial to understand how people control and modify gait in response to changes in stabilization requirements. Our purpose was to examine how individuals with and without incomplete spinal cord injury (iSCI) control lateral stability in haptic walking environments that increase or decrease stabilization demands. We hypothesized that people would adapt to walking in a predictable, stabilizing viscous force field and unpredictable destabilizing force field by increasing and decreasing feedforward control of lateral stability, respectively. Adaptations in feedforward control were measured using after-effects when fields were removed. Both groups significantly (pfeedforward adaptions to increase control of lateral stability. In contrast, in the destabilizing field, non-impaired subjects increased movement variability (p0.05). When the destabilizing field was removed, increases in movement variability persisted (pfeedforward decreases in resistance to perturbations. Published by Elsevier B.V.

  9. Arctic Submarine Slope Stability

    Science.gov (United States)

    Winkelmann, D.; Geissler, W.

    2010-12-01

    Submarine landsliding represents aside submarine earthquakes major natural hazard to coastal and sea-floor infrastructure as well as to coastal communities due to their ability to generate large-scale tsunamis with their socio-economic consequences. The investigation of submarine landslides, their conditions and trigger mechanisms, recurrence rates and potential impact remains an important task for the evaluation of risks in coastal management and offshore industrial activities. In the light of a changing globe with warming oceans and rising sea-level accompanied by increasing human population along coasts and enhanced near- and offshore activities, slope stability issues gain more importance than ever before. The Arctic exhibits the most rapid and drastic changes and is predicted to change even faster. Aside rising air temperatures, enhanced inflow of less cooled Atlantic water into the Arctic Ocean reduces sea-ice cover and warms the surroundings. Slope stability is challenged considering large areas of permafrost and hydrates. The Hinlopen/Yermak Megaslide (HYM) north of Svalbard is the first and so far only reported large-scale submarine landslide in the Arctic Ocean. The HYM exhibits the highest headwalls that have been found on siliciclastic margins. With more than 10.000 square kilometer areal extent and app. 2.400 cubic kilometer of involved sedimentary material, it is one of the largest exposed submarine slides worldwide. Geometry and age put this slide in a special position in discussing submarine slope stability on glaciated continental margins. The HYM occurred 30 ka ago, when the global sea-level dropped by app. 50 m within less than one millennium due to rapid onset of global glaciation. It probably caused a tsunami with circum-Arctic impact and wave heights exceeding 130 meters. The HYM affected the slope stability field in its neighbourhood by removal of support. Post-megaslide slope instability as expressed in creeping and smaller-scaled slides are

  10. Cosmic baldness and stability

    Energy Technology Data Exchange (ETDEWEB)

    Panchapakesan, N.; Lohiya, D.

    1985-04-01

    The stability of the de Sitter metric and the relevance of the initial state of a domain which approaches a de Sitter universe asymptotically are investigated analytically, adapting the one-dimensional wave equation with effective potential derived by Khanal and Panchapakesan (1981), for the perturbations of the de Sitter-Schwarzschild metric, to the de Sitter case. It is demonstrated that initial nonspherical perturbations do not increase exponentially with time but rather decay, the frozen modes exponentially and the backscattered perturbations of finite angular momentum l as t to the -(2l - l). It is concluded that the cosmic horizon is stable and has no hair. 14 references.

  11. Rotation, Stability and Transport

    Energy Technology Data Exchange (ETDEWEB)

    Connor, J. W.

    2007-07-01

    Tokamak plasmas can frequently exhibit high levels of rotation and rotation shear. This can usually be attributed to various sources: injection of momentum, e.g. through neutral beams, flows driven by plasma gradients or torques resulting from non-ambipolar particle loss; however, the source sometimes remains a mystery, such as the spontaneous rotation observed in Ohmic plasmas. The equilibrium rotation profile is given by the balance of these sources with transport and other losses; the edge boundary conditions can play an important role in determining this profile . Such plasma rotation, particularly sheared rotation, is predicted theoretically to have a significant influence on plasma behaviour. In the first place, sonic flows can significantly affect tokamak equilibria and neoclassical transport losses. However, the influence of rotation on plasma stability and turbulence is more profound. At the macroscopic level it affects the behaviour of the gross MHD modes that influence plasma operational limits. This includes sawteeth, the seeding of neoclassical tearing modes, resistive wall modes and the onset of disruptions through error fields, mode locking and reconnection. At the microscopic level it has a major effect on the stability of ballooning modes, both ideal MHD and drift wave instabilities such as ion temperature gradient (ITG) modes. In the non-linear state, as unstable drift waves evolve into turbulent structures, sheared rotation also tears apart eddies, thereby reducing the resulting transport. There is considerable experimental evidence for these effects on both MHD stability and plasma confinement. In particular, the appearance of improved confinement modes with transport barriers, such as edge H-mode barriers and internal transport barriers (ITBs) appears to correlate well with the presence of sheared plasma rotation. This talk will describe the theory underlying some of these phenomena involving plasma rotation, on both macroscopic and microscopic

  12. Stability of Streamer Chamber

    Science.gov (United States)

    Wada, Toshiaki; Ogawa, Masato; Takahashi, Kaoru; Sugiyama, Tsunetoshi; Kobayashi, Shigeharu; Kohno, Hirobumi

    1982-08-01

    The quality of tracks obtained from a streamer chamber is studied through the measurement of the streamer brightness. The stability of streamer tracks depends on the value of the high voltage applied and its shape. By using a single conical-type spark gap as the pulse shaper, stable brightness of the streamer tracks is attained. The data on the streamer brightness are compared with the result by Bulos et al. and it is found that the brightness is more strongly affected by field parameters than in their result.

  13. Stability of streamer chamber

    International Nuclear Information System (INIS)

    Wada, Toshiaki; Ogawa, Masato; Takahashi, Kaoru; Sugiyama, Tsunetoshi; Kobayashi, Shigeharu; Kohno, Hirobumi.

    1982-01-01

    The quality of tracks obtained from a streamer chamber is studied through the measurement of the streamer brightness. The stability of streamer tracks depends on the value of the high voltage applied and its shape. By using a single conical-type spark gap as the pulse shaper, stable brightness of the streamer tracks is attained. The data on the streamer brightness are compared with the result by Bulos et al. and it is found that the brightness is more strongly affected by field parameters than in their result. (author)

  14. Radion cosmology and stabilization

    International Nuclear Information System (INIS)

    Chakraborty, Sumanta; SenGupta, Soumitra

    2014-01-01

    We solve the Einstein equation in five-dimensional space-time for Randall-Sundrum Brane world model with time dependent radion field to study the variation of brane scale factor with time. We have shown that as the radion field decreases with time compactifying the extra dimension, the scale factor increases exponentially with time leading to an inflationary scenario. We have also proposed a time dependent generalization of the Goldberger-Wise moduli stabilization mechanism to explain the time evolution of the radion field to reach a stable value, after which the scale factor on the brane exits from inflationary expansion. (orig.)

  15. Stability of heterodyne terahertz receivers

    OpenAIRE

    Kooi, J. W.; Baselmans, J. J. A.; Baryshev, A.; Schieder, R.; Hajenius, M.; Gao, J. R.; Klapwijk, T. M.; Voronov, B.; Gol'tsman, G.

    2006-01-01

    In this paper we discuss the stability of heterodyne terahertz receivers based on small volume NbN phonon cooled hot electron bolometers (HEBs). The stability of these receivers can be broken down in two parts: the intrinsic stability of the HEB mixer and the stability of the local oscillator (LO) signal injection scheme. Measurements show that the HEB mixer stability is limited by gain fluctuations with a 1/f spectral distribution. In a 60 MHz noise bandwidth this results in an Allan varian...

  16. Polymer Thin Film Stabilization.

    Science.gov (United States)

    Costa, A. C.; Oslanec, R.; Composto, R. J.; Vlcek, P.

    1998-03-01

    We study the dewetting dynamics of thin polystyrene (PS) films deposited on silicon oxide surfaces using optical (OM) and atomic force (AFM) microscopes. Quantitative analysis of the hole diameter as a function of annealing time at 175^oC shows that blending poly(styrene-block-methyl-methacrylate) (PS-b-PMMA) with PS acts to dramatically slow down the dewetting rate and even stops holes growth before they impinge. AFM studies show that the hole floor is smooth for a pure PS film but contains residual polymer for the blend. At 5% vol., a PS-b-PMMA with high molar mass and low PMMA is a more effective stabilizing agent than a low molar mass/high PMMA additive. The optimum copolymer concentration is 3% vol. beyond which film stability doesn't improve. Although dewetting is slowed down relative to pure PS, PS/PS-b-PMMA bilayers dewet at a faster rate than blends having the same overall additive concentration.

  17. Gender and family stability

    Directory of Open Access Journals (Sweden)

    2001-02-01

    Full Text Available The increasing trend of partnership disruption among families with children in recent decades has been accompanied by substantial changes in traditional gender roles in industrialized countries. Yet, relatively little is known about the effects of changing gender relations on family stability in the European context. In this paper, we study such gender influences at the familial and societal level in Sweden and Hungary between the mid-1960s and the early 1990s. We focus on the disruption of the first parental union (i.e. the union in which a couple's first child was born. Our analysis is based on data extracted from the Swedish and Hungarian Fertility and Family Surveys of 1992/93. We use the method of hazard regression. The results suggest (i that the establishment of the dual-earner family model influences family stability only if it is accompanied by some changes in traditional gender relations within the family, and (ii that women's and men's labor-market behavior have different effects in spite of the relatively long history of women's (also mothers' labor-force participation in both Sweden and Hungary.

  18. Stability of cascade search

    Energy Technology Data Exchange (ETDEWEB)

    Fomenko, Tatiana N [M. V. Lomonosov Moscow State University, Faculty of Computational Mathematics and Cybernetics, Moscow (Russian Federation)

    2010-10-22

    We find sufficient conditions on a searching multi-cascade for a modification of the set of limit points of the cascade that satisfy an assessing inequality for the distance from each of these points to the initial point to be small, provided that the modifications of the initial point and the initial set-valued functionals or maps used to construct the multi-cascade are small. Using this result, we prove the stability (in the above sense) of the cascade search for the set of common pre-images of a closed subspace under the action of n set-valued maps, n{>=}1 (in particular, for the set of common roots of these maps and for the set of their coincidences). For n=2 we obtain generalizations of some results of A. V. Arutyunov; the very statement of the problem comes from a recent paper of his devoted to the study of the stability of the subset of coincidences of a Lipschitz map and a covering map.

  19. Containment vessel stability analysis

    International Nuclear Information System (INIS)

    Harstead, G.A.; Morris, N.F.; Unsal, A.I.

    1983-01-01

    The stability analysis for a steel containment shell is presented herein. The containment is a freestanding shell consisting of a vertical cylinder with a hemispherical dome. It is stiffened by large ring stiffeners and relatively small longitudinal stiffeners. The containment vessel is subjected to both static and dynamic loads which can cause buckling. These loads must be combined prior to their use in a stability analysis. The buckling loads were computed with the aid of the ASME Code case N-284 used in conjunction with general purpose computer codes and in-house programs. The equations contained in the Code case were used to compute the knockdown factors due to shell imperfections. After these knockdown factors were applied to the critical stress states determined by freezing the maximum dynamic stresses and combining them with other static stresses, a linear bifurcation analysis was carried out with the aid of the BOSOR4 program. Since the containment shell contained large penetrations, the Code case had to be supplemented by a local buckling analysis of the shell area surrounding the largest penetration. This analysis was carried out with the aid of the NASTRAN program. Although the factor of safety against buckling obtained in this analysis was satisfactory, it is claimed that the use of the Code case knockdown factors are unduly conservative when applied to the analysis of buckling around penetrations. (orig.)

  20. High beta and second stability region transport and stability analysis

    International Nuclear Information System (INIS)

    1991-01-01

    This document describes ideal and resistive MHD studies of high-beta plasmas and of the second stability region. Significant progress is reported on the resistive stability properties of high beta poloidal ''supershot'' discharges. For these studies initial profiles were taken from the TRANSP code which is used extensively to analyze experimental data. When an ad hoc method of removing the finite pressure stabilization of tearing modes is implemented it is shown that there is substantial agreement between MHD stability computation and experiment. In particular, the mode structures observed experimentally are consistent with the predictions of the resistive MHD model. We also report on resistive stability near the transition to the second region in TFTR. Tearing modes associated with a nearby infernal mode may explain the increase in MHD activity seen in high beta supershots and which impede the realization of Q∼1. We also report on a collaborative study with PPPL involving sawtooth stabilization with ICRF

  1. Food Fortification Stability Study

    Science.gov (United States)

    Sirmons, T.; Cooper, M.; Douglas, G.

    2017-01-01

    NASA has established the goal of traveling beyond low-Earth orbit and extending manned exploration to Mars. The length of proposed Mars missions and the lack of resupply missions increases the importance of nutritional content in the food system, which will need a five-year shelf life. The purpose of this research is to assess the stability of vitamin supplementation in traditionally processed spaceflight foods. It is expected that commercially available fortification nutrients will remain stable through a long duration exploration mission at sufficient levels if compatible formulation, processing, and storage temperatures are achieved. Five vitamins (vitamin E, vitamin K, pantothenic acid, folic acid, and thiamin) were blended into a vitamin premix (DSM, Freeport, TX) such that the vitamin concentration per serving equaled 25% of the recommended daily intake after two years of ambient storage. Four freeze-dried foods (Scrambled Eggs, Italian Vegetables, Potatoes Au Gratin, Noodles and Chicken) and four thermo-stabilized foods (Curry Sauce with Vegetables, Chicken Noodle Soup, Grilled Pork Chop, Rice with Butter) were produced, with and without the vitamin premix, to assess the impact of the added fortification on color and taste and to determine the stability of supplemental vitamins in spaceflight foods. The addition of fortification to spaceflight foods did not greatly alter the organoleptic properties of most products. In most cases, overall acceptability scores remained above 6.0 (minimum acceptable score) following six months and one year of low-temperature storage. Likewise, the color of fortified products appears to be preserved over one year of storage. The only exceptions were Grilled pork Chop and Chicken Noodle Soup whose individual components appeareddegrade rapidly over one year of storage. Finally, most vitamins appeared to be stable during long-term storage. The only exception was thiamin, which degraded rapidly during the first year of storage at

  2. Food Fortification Stability Study

    Science.gov (United States)

    Abdulmalik, T. O.; Cooper, M. R.; Douglas, G. L.

    2015-01-01

    NASA has established the goal of traveling beyond low-Earth orbit and extending manned exploration to Mars. The extended length of a Mars mission, along with the lack of resupply missions increases the importance of nutritional content in the food system. The purpose of this research is to assess the stability of vitamin supplementation in traditionally processed spaceflight foods. It is expected that commercially available fortificants will remain stable through long-duration missions if proper formulation, processing, and storage temperatures are all achieved. Five vitamins (vitamin E, vitamin K, pantothenic acid, folic acid, and thiamin) were blended into a vitamin premix (DSM, Freeport, TX); premixes were formulated to be compatible with current processing techniques (retort or freeze-dried), varied water activities (high or low), and packaging material. The overall goal of this process is to provide 25% of the recommended daily intake of each vitamin (per serving), following processing and two years of ambient storage. Four freeze-dried foods (Scrambled Eggs, Italian Vegetables, Potatoes Au Gratin, Noodles and Chicken) and four thermostabilized foods (Curry Sauce with Vegetables, Chicken Noodle Soup, Grilled Pork Chop, Rice with Butter) were produced (with and without the vitamin premix), to assess the impact of the added fortificant on color and taste, and to determine the stability of supplemental vitamins in spaceflight foods. The use of fortification in spaceflight foods appears to be a plausible mitigation step to inadequate nutrition. This is due to the ease of vitamin addition as well as the sustainability of the premixes through initial processing steps. Postprocessing analysis indicated that vitamin fortification with this premix did not immediately impact organoleptic properties of the food. At this stage, the largest hurdle to fortification is the preciseness to which vitamins can be added; the total amount of vitamins required for production is 10

  3. Insulin structure and stability.

    Science.gov (United States)

    Brange, J; Langkjoer, L

    1993-01-01

    Insulin is composed of 51 amino acids in two peptide chains (A and B) linked by two disulfide bonds. The three-dimensional structure of the insulin molecule (insulin monomer), essentially the same in solution and in solid phase, exists in two main conformations. These differ in the extent of helix in the B chain which is governed by the presence of phenol or its derivatives. In acid and neutral solutions, in concentrations relevant for pharmaceutical formulation, the insulin monomer assembles to dimers and at neutral pH, in the presence of zinc ions, further to hexamers. Many crystalline modifications of insulin have been identified but only those with the hexamer as the basic unit are utilized in preparations for therapy. The insulin hexamer forms a relatively stable unit but some flexibility remains within the individual molecules. The intrinsic flexibility at the ends of the B chain plays an important role in governing the physical and chemical stability of insulin. A variety of chemical changes of the primary structure (yielding insulin derivatives), and physical modifications of the secondary to quaternary structures (resulting in "denaturation," aggregation, and precipitation) are known to affect insulin and insulin preparations during storage and use (Fig. 8). The tendency of insulin to undergo structural transformation resulting in aggregation and formation of insoluble insulin fibrils has been one of the most intriguing and widely studied phenomena in relation to insulin stability. Although the exact mechanism of fibril formation is still obscure, it is now clear that the initial step is an exposure of certain hydrophobic residues, normally buried in the three-dimensional structure, to the surface of the insulin monomer. This requires displacement of the COOH-terminal B-chain residues from their normal position which can only be accomplished via monomerization of the insulin. Therefore, most methods stabilizing insulin against fibrillation share the

  4. Long-term stability of sodium caseinate-stabilized nanoemulsions.

    Science.gov (United States)

    Yerramilli, Manispuritha; Ghosh, Supratim

    2017-01-01

    Oil-in-water (5 wt%) nanoemulsions were prepared with different concentration (2.5-10 wt%) of sodium caseinate as a sole emulsifier and their long-term storage stability was investigated for 6 months. Previous studies associated with sodium caseinate looked only into nanoemulsion formation; hence the challenges with long-term stability were not addressed. All nanoemulsions displayed an average droplet size sodium caseinate-stabilized nanoemulsions.

  5. Transient stability index for online stability assessment and contingency evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ribbens-Pavella, M; Murthy, P G; Horward, J L; Carpentier, J L

    1982-04-01

    An on-line methodology is proposed for assessing the robustness of a power system from the point of view of transient stability, and a scalar expression, the transient stability index, is accordingly derived. The reliability and sensitivity of this index are tested by means of simulations for a number of power system cases. The index is shown to be appropriate for online stability assessment, contingency evaluation and preventive control. 14 refs.

  6. Exploiting sequence and stability information for directing nanobody stability engineering.

    Science.gov (United States)

    Kunz, Patrick; Flock, Tilman; Soler, Nicolas; Zaiss, Moritz; Vincke, Cécile; Sterckx, Yann; Kastelic, Damjana; Muyldermans, Serge; Hoheisel, Jörg D

    2017-09-01

    Variable domains of camelid heavy-chain antibodies, commonly named nanobodies, have high biotechnological potential. In view of their broad range of applications in research, diagnostics and therapy, engineering their stability is of particular interest. One important aspect is the improvement of thermostability, because it can have immediate effects on conformational stability, protease resistance and aggregation propensity of the protein. We analyzed the sequences and thermostabilities of 78 purified nanobody binders. From this data, potentially stabilizing amino acid variations were identified and studied experimentally. Some mutations improved the stability of nanobodies by up to 6.1°C, with an average of 2.3°C across eight modified nanobodies. The stabilizing mechanism involves an improvement of both conformational stability and aggregation behavior, explaining the variable degree of stabilization in individual molecules. In some instances, variations predicted to be stabilizing actually led to thermal destabilization of the proteins. The reasons for this contradiction between prediction and experiment were investigated. The results reveal a mutational strategy to improve the biophysical behavior of nanobody binders and indicate a species-specificity of nanobody architecture. This study illustrates the potential and limitations of engineering nanobody thermostability by merging sequence information with stability data, an aspect that is becoming increasingly important with the recent development of high-throughput biophysical methods. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Energy balance and stability

    International Nuclear Information System (INIS)

    Hammer, R.

    1982-01-01

    The energy balance of the outer atmospheres of solarlike stars is discussed. The energy balance of open coronal regions is considered, discussing the construction and characteristics of models of such regions in some detail. In particular, the temperature as a function of height is considered, as are the damping length dependence of the global energy balance in the region between the base of the transition region and the critical point, and the effects of changing the amount of coronal heating, the stellar mass, and the stellar radius. Models of coronal loops are more briefly discussed. The chromosphere is then included in the discussion of the energy balance, and the connection between global energy balance and global thermal stability is addressed. The observed positive correlations between the chromospheric and coronal energy losses and the pressure of the transition region is qualitatively explained

  8. HMD symbol stabilization concepts

    Science.gov (United States)

    Newman, Richard L.; Greeley, Kevin W.

    1995-05-01

    Helmet-mounted displays (HMDs) present flight, navigation, and weapon information in the pilot's line of sight. The HMD was developed to allow the pilot to retain aircraft and weapon information while looking off boresight. Symbol stabilization is a key issue for HMDs. In current equipment, the lack of compensation for pilot head motion creates excessive workload during hovering and nap-of-the-earth flight. This high workload translates into excessive training requirements. At the same time, misleading symbology makes interpretation of the height of obstructions impossible. A set of standardized coordinate transformations are necessary for the development of HMD symbology and the control laws. Part of the problem is there is no agreed upon set of definitions or descriptions for how HMD symbols are driven to compensate for pilot head motion. A candidate set of coordinate definitions is proposed to address this issue.

  9. IMPROVED ROOF STABILIZATION TECHNOLOGIES

    International Nuclear Information System (INIS)

    Ebadian, M.A.

    1999-01-01

    Many U.S. Department of Energy (DOE) remediation sites have performed roof repair and roof replacement to stabilize facilities prior to performing deactivation and decommissioning (D and D) activities. This project will review the decision criteria used by these DOE sites, along with the type of repair system used for each different roof type. Based on this information, along with that compiled from roofing experts, a decision-making tool will be generated to aid in selecting the proper roof repair systems. Where appropriate, innovative technologies will be reviewed and applied to the decision-making tool to determine their applicability. Based on the results, applied research and development will be conducted to develop a method to repair these existing roofing systems, while providing protection for the D and D worker in a cost-efficient manner

  10. IMPROVED ROOF STABILIZATION TECHNOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    M.A. Ebadian, Ph.D.

    1999-01-01

    Many U.S. Department of Energy (DOE) remediation sites have performed roof repair and roof replacement to stabilize facilities prior to performing deactivation and decommissioning (D&D) activities. This project will review the decision criteria used by these DOE sites, along with the type of repair system used for each different roof type. Based on this information, along with that compiled from roofing experts, a decision-making tool will be generated to aid in selecting the proper roof repair systems. Where appropriate, innovative technologies will be reviewed and applied to the decision-making tool to determine their applicability. Based on the results, applied research and development will be conducted to develop a method to repair these existing roofing systems, while providing protection for the D and D worker in a cost-efficient manner.

  11. Stabilizing motor fuels

    Energy Technology Data Exchange (ETDEWEB)

    1935-07-12

    Motor fuel is stabilized by adding less than 2% of a tar fraction from peat, coal, torbanite or shale, said fraction containing sufficient constituents boiling between 200 and 325/sup 0/C, to inhibit gum formation. Low-temperature coal-tar fractions are specified. The preferred boiling ranges are from 225 or 250/sup 0/ to 275/sup 0/C. In examples, the quantity added was 0.01%. The fuel may be a cracked distillate of gasoline boiling-point range or containing gasoline, and may contain relatively large proportions of di- and tri-olefines. The material added to the fuel may be (1) the tar fraction itself; (2) its alkali-soluble constituents; (3) its acid-soluble constituents; (4) a mixture of (2) and (3); (5) a blend of (2), (3) or (4) with a normal tar fraction; (6) the residue after extraction with alkali; (7) the residue after extraction with acid and alkali.

  12. Stability in designer gravity

    International Nuclear Information System (INIS)

    Hertog, Thomas; Hollands, Stefan

    2005-01-01

    We study the stability of designer gravity theories, in which one considers gravity coupled to a tachyonic scalar with anti-de Sitter (AdS) boundary conditions defined by a smooth function W. We construct Hamiltonian generators of the asymptotic symmetries using the covariant phase space method of Wald et al and find that they differ from the spinor charges except when W = 0. The positivity of the spinor charge is used to establish a lower bound on the conserved energy of any solution that satisfies boundary conditions for which W has a global minimum. A large class of designer gravity theories therefore have a stable ground state, which the AdS/CFT correspondence indicates should be the lowest energy soliton. We make progress towards proving this by showing that minimum energy solutions are static. The generalization of our results to designer gravity theories in higher dimensions involving several tachyonic scalars is discussed

  13. [Lumbar stabilization exercises].

    Science.gov (United States)

    Vásquez-Ríos, Jorge Rodrigo; Nava-Bringas, Tania Inés

    2014-01-01

    Exercise is the intervention with the highest level of evidence on efficacy for treatment of chronic low back pain, with a higher benefit in terms of pain and function compared to any other intervention. A wide variety of exercises programs have been designed; however, "lumbar stabilization exercises" have become increasingly popular among clinicians who are in contact with spine diseases. However, there is controversy regarding the adequate prescription and there are multiple protocols. The aim of this literature review is to analyze the information about these exercises to promote better decision-making among clinicians and design the best program for each patient. We found the program an essential tool in the treatment of low back pain in both therapeutic and preventive phases.

  14. CONSIDERATIONS REGARDING FINANCIAL STABILITY

    Directory of Open Access Journals (Sweden)

    MERCEA PATRICIA AMALIA

    2018-02-01

    target digital coin concepts, use in distributed real-time payment systems of blockchain technologology, artificial intelligence, and information security. However, a large number of economists admit that the current crisis has emphasized the overcoming of the limits of (mainstream economics and its implications in the field of financial regulation and the sphere of monetary policy that should focus not only on price stability, but also on financial stability. In other words, the banks, the financial institutions must be obliged to hold a minimal countercyclical capital and mandatory reserves that should be large enough to cope with the turmoil generated by the decrease of the asset prices and the liquidity risk. In macroprudential policy, the “shadow banking system” (investment banks, hedge funds, private equity funds must also be included.Last but not least, the central banks have to cooperate with the other categories of systemic risk managers: Financial Stability Oversight Council-FSOC (USA, European Systemic Risk Board-ESRB (EU, Financial Policy Committee-FPC (Great Britain, National Committee for Financial Stability-CNSF (Romania.

  15. Stabilizing Pentacene By Cyclopentannulation.

    Science.gov (United States)

    Bheemireddy, Sambasiva R; Ubaldo, Pamela C; Rose, Peter W; Finke, Aaron D; Zhuang, Junpeng; Wang, Lichang; Plunkett, Kyle N

    2015-12-21

    A new class of stabilized pentacene derivatives with externally fused five-membered rings are prepared by means of a key palladium-catalyzed cyclopentannulation step. The target compounds are synthesized by chemical manipulation of a partially saturated 6,13-dibromopentacene precursor that can be fully aromatized in a final step through a DDQ-mediated dehydrogenation reaction (DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The new 1,2,8,9-tetraaryldicyclopenta[fg,qr]pentacene derivatives have narrow energy gaps of circa 1.2 eV and behave as strong electron acceptors with lowest unoccupied molecular orbital energies between -3.81 and -3.90 eV. Photodegradation studies reveal the new compounds are more photostable than 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. From Crisis to Stability

    DEFF Research Database (Denmark)

    Ban, Cornel; Seabrooke, Leonard

    governance institution, and makes a number of concrete recommendations. To make the ESM accountable, more transparency is in order, about where decisions are taken and who calls the shots. Is it the ESM, the Eurogroup, the Commission, or a coalition of Member States? Our report launch attempts to answer......The European Stability Mechanism (ESM) was created to save the euro from collapse. But the Eurozone’s bailout fund is not actually an EU institution. This has a series of knock-on effects, making it difficult to hold the ESM to EU standards as regards transparency, legal review by the CJEU......, but also access to documents regulation and accountability vis-à-vis the European Parliament, the Court of Auditors and Anti-Fraud Office. Transparency International EU’s in-depth study of the governance and accountability of the ESM provides the first comprehensive analysis of the newest European economic...

  17. Complementarity and stability conditions

    Directory of Open Access Journals (Sweden)

    Howard Georgi

    2017-08-01

    Full Text Available We discuss the issue of complementarity between the confining phase and the Higgs phase for gauge theories in which there are no light particles below the scale of confinement or spontaneous symmetry breaking. We show with a number of examples that even though the low energy effective theories are the same (and trivial, discontinuous changes in the structure of heavy stable particles can signal a phase transition and thus we can sometimes argue that two phases which have different structures of heavy particles that cannot be continuously connected and thus the phases cannot be complementary. We discuss what this means and suggest that such “stability conditions” can be a useful physical check for complementarity.

  18. Parabolized stability equations

    Science.gov (United States)

    Herbert, Thorwald

    1994-01-01

    The parabolized stability equations (PSE) are a new approach to analyze the streamwise evolution of single or interacting Fourier modes in weakly nonparallel flows such as boundary layers. The concept rests on the decomposition of every mode into a slowly varying amplitude function and a wave function with slowly varying wave number. The neglect of the small second derivatives of the slowly varying functions with respect to the streamwise variable leads to an initial boundary-value problem that can be solved by numerical marching procedures. The PSE approach is valid in convectively unstable flows. The equations for a single mode are closely related to those of the traditional eigenvalue problems for linear stability analysis. However, the PSE approach does not exploit the homogeneity of the problem and, therefore, can be utilized to analyze forced modes and the nonlinear growth and interaction of an initial disturbance field. In contrast to the traditional patching of local solutions, the PSE provide the spatial evolution of modes with proper account for their history. The PSE approach allows studies of secondary instabilities without the constraints of the Floquet analysis and reproduces the established experimental, theoretical, and computational benchmark results on transition up to the breakdown stage. The method matches or exceeds the demonstrated capabilities of current spatial Navier-Stokes solvers at a small fraction of their computational cost. Recent applications include studies on localized or distributed receptivity and prediction of transition in model environments for realistic engineering problems. This report describes the basis, intricacies, and some applications of the PSE methodology.

  19. Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

    Science.gov (United States)

    Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

    2017-12-01

    To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

  20. New image-stabilizing system

    Science.gov (United States)

    Zhao, Yuejin

    1996-06-01

    In this paper, a new method for image stabilization with a three-axis image- stabilizing reflecting prism assembly is presented, and the principle of image stabilization in this prism assembly, formulae for image stabilization and working formulae with an approximation up to the third power are given in detail. In this image-stabilizing system, a single chip microcomputer is used to calculate value of compensating angles and thus to control the prism assembly. Two gyroscopes act as sensors from which information of angular perturbation is obtained, three stepping motors drive the prism assembly to compensate for the movement of image produced by angular perturbation. The image-stabilizing device so established is a multifold system which involves optics, mechanics, electronics and computer.

  1. The stability of some asteroids

    International Nuclear Information System (INIS)

    Vicente, R.O.

    1983-01-01

    The utilization of two different stability criteria, namely, Hill's modified stability criterium and the method of surface of section, has been employed for asteroid orbits. The idea is to compute different criteria of stability for the same asteroids in order to compare the results and see the practical interest of the computations for researches about evolutionary trends of individual asteroids, groups and families of asteroids. (Auth.)

  2. Superconductor stability 90: A review

    International Nuclear Information System (INIS)

    Dresner, L.

    1990-01-01

    This paper reviews some recent developments in the field of stability of superconductors. The main topics dealt with are hydrodynamic phenomena in cable-in-conduit superconductors, namely, multiple stability, quench pressure, thermal expulsion, and thermal hydraulic quenchback, traveling normal zones in large, composite conductors, such as those intended for SMES, and the stability of vapor-cooled leads made of high-temperature superconductors. 31 refs., 5 figs

  3. Demand Uncertainty and Price Stabilization

    OpenAIRE

    E. Kwan Choi; Stanley R. Johnson

    1987-01-01

    Price stabilization is an important policy goal of government intervention in competitive markets. These policies are primarily directed at raising producer income and stabilizing market prices at levels acceptable to consumers and producers (Fox 1956, Turnovsky 1978, Newbery and Stiglitz 1979). Many of the stabilization policy results have been developed from the study of agricultural commodity markets. In these markets, prices tend to be highly variable due to uncertain and inelastic supply...

  4. Strengthening Strategic Stability with Russia

    Science.gov (United States)

    2017-01-01

    political stabil - ity. From the current Russian perspective, both of these compo- nents were thrown out of balance in the 1990s, creating instability ...part of the United States in the early 2000s, stra- tegic stability was replaced with instability and military- political defeats for Russia.27...overall strategic balance of the world political system.8 (As discussed later, the official Russian definition of strategic stability is broadening in

  5. Motivos que contribuem para indivíduos de uma escola de nível superior tornarem-se ou não tabagistas Motivación para fumar en la comunidad de una escuela de enfermería de educación superior Motivation for smoking in the community of a high education nursing school

    Directory of Open Access Journals (Sweden)

    Stephani Amanda Lukasewicz Ferreira

    2011-06-01

    Full Text Available Estudo transversal que objetivou identificar motivos que contribuem para indivíduos de uma escola de nível superior tornarem-se ou não tabagistas. Os dados foram coletados em 2009, em questionários específicos, analisados estatisticamente. A amostra foi de 426 sujeitos, destes 21 (5% fumantes, 26 (6,1% ex-fumantes e 376 (88,9% não-fumantes. A principal motivação dos fumantes para cessar o tabagismo são os problemas de saúde advindos do cigarro e dentre os fatores que dificultam esse processo está a dependência à nicotina. Ex-fumantes dizem que questões emocionais e o prazer causado pelo cigarro podem fazê-los voltar a fumar, e se mantém em abstinência por estarem determinados a não querer fumar. Não-fumantes relatam não gostarem do cigarro, seu cheiro e fumaça. Os motivos para ser ou não tabagista podem subsidiar a realização de ações de educação em saúde, com vistas a coibir o início e promover a sua cessação.Estudio transversal con objetivo de identificar razones que contribuyen a individuos de una escuela de enseñanza superior se convierten en fumadores o no. Los datos fueron recolectados en 2009, en cuestionarios, análisis estadístico. La muestra fue de 426 sujetos, de estos 21(5% fumadores, 26(6,1% ex-fumadores y 376(88,9% no-fumadores. La principal motivación de fumadores a dejar de fumar son problemas de salud derivados del cigarrillo y entre los factores que obstaculizan este proceso es la dependencia de la nicotina. Ex-fumadores dicen que cuestiones emocional y placer causado por lo cigarrillo puede hacer que empiecen a fumar de nuevo, y mantiene la abstinencia ya que están decididos a no querer fumar. Los no-fumadores reportan que no les gusta el humo y olor del cigarrillo. Las razones de ser o no fumador puede apoyar la aplicación de acciones de educación para la salud, destinado a frenar el inicio y promover su cese.Cross-sectional study that aimed to identify motives that contribute to people

  6. Sea surface stability parameters

    International Nuclear Information System (INIS)

    Weber, A.H.; Suich, J.E.

    1978-01-01

    A number of studies dealing with climatology of the Northwest Atlantic Ocean have been published in the last ten years. These published studies have dealt with directly measured meteorological parameters, e.g., wind speed, temperature, etc. This information has been useful because of the increased focus on the near coastal zone where man's activities are increasing in magnitude and scope, e.g., offshore power plants, petroleum production, and the subsequent environmental impacts of these activities. Atmospheric transport of passive or nonpassive material is significantly influenced by the turbulence structure of the atmosphere in the region of the atmosphere-ocean interface. This research entails identification of the suitability of standard atmospheric stability parameters which can be used to determine turbulence structure; the calculation of these parameters for the near-shore and continental shelf regions of the U.S. east coast from Cape Hatteras to Miami, Florida; and the preparation of a climatology of these parameters. In addition, a climatology for average surface stress for the same geographical region is being prepared

  7. PROFITABILITY AND FINANCIAL STABILITY

    Directory of Open Access Journals (Sweden)

    CĂRUNTU CONSTANTIN

    2011-09-01

    Full Text Available The business activity allows identifying two categories of flows: flows of results and cash flows. Flows affect the income and expenses, participating in training result, the company's profitability. Financial flows involved in their formation both monetary items (which drive the monetary input or output and thus implies a cash flow, and non-cash items (affecting the result, without leading to a cash flow. Are equally identifiable cash flows that do not involve an immediate effect on the outcome or effect on the result equivalent to that spread on the treasury. Financial equilibrium in a general manner evokes the idea of harmony between different elements of a system, which in finance is harmonization of resources with the needs. Financial equilibrium can be defined by the company's ability to secure payment of its proceeds without interruption to current liabilities incurred in implementing its object of activity or tax laws, so it can avoid the risk of bankruptcy. Maintaining financial stability is the essential condition of survival of the enterprise, financial and balanced assessment must take into account the concrete conditions of the occurrence of default.

  8. Cryostatic stability equation

    International Nuclear Information System (INIS)

    Sydoriak, S.G.

    1976-01-01

    Although criteria for cryostatic stability of superconducting magnets cooled by pool boiling of liquid helium have been widely discussed the same cannot be said for magnets cooled by natural convection or forced flow boiling in channels. Boiling in narrow channels is shown to be qualitatively superior to pool boiling because the recovery heat flux equals the breakaway flux for narrow channels, whereas the two are markedly different in pool boiling. A second advantage of channel boiling is that it is well understood and calculable; pool peak nucleate boiling heat flux has been adequately measured only for boiling from the top of an immersed heated body. Peak boiling from the bottom is much less and (probably) depends strongly on the extent of the bottom surface. Equations are presented by which one can calculate the critical boiling heat flux for parallel wall vertical channels subject to either natural convection or forced flow boiling, with one or both walls heated. The one-heated-wall forced flow equation is discussed with regard to design of a spiral wound solenoid (pancake magnet) having a slippery insulating tape between the windings

  9. Hydrocode subcycling stability

    International Nuclear Information System (INIS)

    Hicks, D.L.

    1981-01-01

    The method of artificial viscosity was originally designed by von Neumann and Richtmyer for calculating the propagation of waves in materials that were hydrodynamic and rate-independent (e.g., ideal gas law). However, hydrocodes (such as WONDY) based on this method continue to expand their repertoire of material laws even unto material laws that are rate-dependent (e.g., Maxwell's material law). Restrictions on the timestep required for stability with material laws that are rate-dependent can be considerably more severe than restrictions of the Courant-Friedrichs-Lewy (CFL) type that are imposed in these hydrocodes. These very small timesteps can make computations very expensive. An alternative is to go ahead and integrate the conservation laws with the usual CFL timestep while subcycling (integrating with a smaller timestep) the integration of the stress-rate equation. If the subcycling is done with a large enough number of subcycles (i.e., with a small enough subcycle timestep), then the calculation is stable. Specifically, the number of subcycles must be one greater than the ratio of the CFL timestep to the relaxation time of the material

  10. Test Room Stability Plan

    International Nuclear Information System (INIS)

    1993-01-01

    This plan documents the combination of designs, installations, programs, and activities that ensures that the underground excavations at the Waste Isolation Pilot Plant (WIPP), in which transuranic (TRU) waste may be emplaced during the Test Phase, will remain sufficiently stable and safe during that time. The current ground support systems installed at the WIPP are the result of over ten years of data collection from hundreds of geomechanical instruments and thousands of hours of direct observation of the changing conditions of the openings. In addition, some of the world's most respected experts on salt rock mechanics have provided input in the design process and concurrence on the suitability of the final design. The general mine rockbolt pattern and the ground support system for the test rooms are designed to specifically address the fracture and deformation geometries observed today at the WIPP. After an introductory chapter, this plan describes the general underground design, then proceeds to an account of general ground support performance, and finally focuses on the details of the special test room ground support systems. One such system already installed in Room 1, Panel 1, is described in comprehensive detail. Other test rooms in Panel 1, whether full-size or smaller, will be equipped with systems that ensure stability to the same or equivalent extent. They will benefit from the experience gained in the first test room, which in turn benefitted from the data and knowledge accumulated during previous stages (e.g., the Site and Preliminary Design Validation program) of the project

  11. Stability and Change

    Directory of Open Access Journals (Sweden)

    April K. Clark

    2014-03-01

    Full Text Available Ever since Stouffer began to measure political tolerance a half century ago, multiple studies have shown that a number of social, psychological, and political characteristics play a significant role in influencing whether individuals want to extend civil liberties to fringe groups. However, less is known about the stability of tolerance attitudes over an individual’s lifetime. To address this problem, our research draws on a national U.S. multiple-generation, four-wave panel study stretching from 1965 to 1997. The intuitive appeal of the approach used in this study is to advance theoretical accounts for variations in political intolerance irrespective of generational placement, life cycle, and differences in the political context. Specifically, the panel design encourages an effort to examine the relative impact of the social, political, and psychological predictors on intolerance over time and across the same individuals, and to assess the consequences of how changes in these determinants affect some of our most fundamental hypotheses about the origins of these attitudes.

  12. Stabilized thermally compensated mirror

    International Nuclear Information System (INIS)

    Dunn, C. III; Tobin, R.D.; Bergstreser, N.E.; Heinz, T.A.

    1975-01-01

    A thermally compensated mirror is described that is formed by a laminated structure. The structure is comprised of a front plate having a reflective front surface and having a plurality of grooves formed in the rear surface for conducting coolant fluid in heat exchanging relation with said reflective surface, a rear plate having coolant inlet and coolant outlet openings extending therethrough, a minimum temperature plate interposed between said front and rear plates and formed with a plurality of coolant distribution passageways coupled to receive coolant fluid from said coolant inlet and oriented to distribute said coolant fluid in a manner to establish a minimum temperature plane parallel to said reflective surface, a temperature stabilization plate interposed between said front plate and said minimum temperature plate and formed with a plurality of coolant distribution channels coupled to receive said coolant fluid after said coolant fluid has passed in heat exchanging relation with said reflective surface and oriented to distribute said coolant fluid in a manner to establish a uniform temperature plane parallel to said reflective surface, and means for circulating said coolant fluid through said structure in a predetermined path. (U.S.)

  13. Ferrocyanide tank waste stability

    International Nuclear Information System (INIS)

    Fowler, K.D.

    1993-01-01

    Ferrocyanide wastes were generated at the Hanford Site during the mid to late 1950s as a result of efforts to create more tank space for the storage of high-level nuclear waste. The ferrocyanide process was developed to remove 137 CS from existing waste and newly generated waste that resulted from the recovery of valuable uranium in Hanford Site waste tanks. During the course of research associated with the ferrocyanide process, it was recognized that ferrocyanide materials, when mixed with sodium nitrate and/or sodium nitrite, were capable of violent exothermic reaction. This chemical reactivity became an issue in the 1980s, when safety issues associated with the storage of ferrocyanide wastes in Hanford Site tanks became prominent. These safety issues heightened in the late 1980s and led to the current scrutiny of the safety issues associated with these wastes, as well as current research and waste management programs. Testing to provide information on the nature of possible tank reactions is ongoing. This document supplements the information presented in Summary of Single-Shell Tank Waste Stability, WHC-EP-0347, March 1991 (Borsheim and Kirch 1991), which evaluated several issues. This supplement only considers information particular to ferrocyanide wastes

  14. Polycarbonate radiolytic degradation and stabilization

    International Nuclear Information System (INIS)

    Araujo, E.S. de

    1994-01-01

    Polycarbonate Durolon, useful for medical supplies fabrication, is submitted to gamma radiation for sterilization purposes. Scissions in main chain occur, in carbonyl groups, producing molecular degradations and yellowness. The radiolytic stabilization is obtained through additive to the polymer. In this work some degradation and stabilization aspects are presented. (L.C.J.A.). 7 refs, 7 figs, 2 tabs

  15. Interval stability for complex systems

    Science.gov (United States)

    Klinshov, Vladimir V.; Kirillov, Sergey; Kurths, Jürgen; Nekorkin, Vladimir I.

    2018-04-01

    Stability of dynamical systems against strong perturbations is an important problem of nonlinear dynamics relevant to many applications in various areas. Here, we develop a novel concept of interval stability, referring to the behavior of the perturbed system during a finite time interval. Based on this concept, we suggest new measures of stability, namely interval basin stability (IBS) and interval stability threshold (IST). IBS characterizes the likelihood that the perturbed system returns to the stable regime (attractor) in a given time. IST provides the minimal magnitude of the perturbation capable to disrupt the stable regime for a given interval of time. The suggested measures provide important information about the system susceptibility to external perturbations which may be useful for practical applications. Moreover, from a theoretical viewpoint the interval stability measures are shown to bridge the gap between linear and asymptotic stability. We also suggest numerical algorithms for quantification of the interval stability characteristics and demonstrate their potential for several dynamical systems of various nature, such as power grids and neural networks.

  16. Stability of Randomly Switched Diffusions

    DEFF Research Database (Denmark)

    Schiøler, Henrik; Leth, John-Josef; Gholami, Mehdi

    2012-01-01

    This paper provides a sufficient criterion for ε-moment stability (boundedness) and ergodicity for a class of systems comprising a finite set of diffusions among which switching is governed by a continuous time Markov chain. Stability/instability properties for each separate subsystem are assumed...

  17. A Remark on Dilaton Stabilization

    CERN Document Server

    Dvali, Gia; Dvali, Gia; Kakushadze, Zurab

    1998-01-01

    Dilaton stabilization may occur in a theory based on a single asymptotically free gauge group with matter due to an interplay between quantum modification of the moduli space and tree-level superpotential. We present a toy model where such a mechanism is realized. Dilaton stabilization in this mechanism tends to occur at strong coupling values unless some unnatural adjustment of parameters is involved.

  18. Vibrations and Stability: Solved Problems

    DEFF Research Database (Denmark)

    Thomsen, Jon Juel

    Worked out solutions for exercise problems in J. J. Thomsen 'Vibrations and Stability: Advanced Theory, Analysis, and Tools', Springer, Berlin - Heidelberg, 2003.......Worked out solutions for exercise problems in J. J. Thomsen 'Vibrations and Stability: Advanced Theory, Analysis, and Tools', Springer, Berlin - Heidelberg, 2003....

  19. Stability of Polymer Solar Cells

    DEFF Research Database (Denmark)

    Jørgensen, Mikkel; Norrman, Kion; Gevorgyan, Suren

    2012-01-01

    Organic photovoltaics (OPVs) evolve in an exponential manner in the two key areas of efficiency and stability. The power conversion efficiency (PCE) has in the last decade been increased by almost a factor of ten approaching 10%. A main concern has been the stability that was previously measured ...

  20. Exponential Stabilization of Underactuated Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Pettersen, K.Y.

    1996-12-31

    Underactuated vehicles are vehicles with fewer independent control actuators than degrees of freedom to be controlled. Such vehicles may be used in inspection of sub-sea cables, inspection and maintenance of offshore oil drilling platforms, and similar. This doctoral thesis discusses feedback stabilization of underactuated vehicles. The main objective has been to further develop methods from stabilization of nonholonomic systems to arrive at methods that are applicable to underactuated vehicles. A nonlinear model including both dynamics and kinematics is used to describe the vehicles, which may be surface vessels, spacecraft or autonomous underwater vehicles (AUVs). It is shown that for a certain class of underactuated vehicles the stabilization problem is not solvable by linear control theory. A new stability result for a class of homogeneous time-varying systems is derived and shown to be an important tool for developing continuous periodic time-varying feedback laws that stabilize underactuated vehicles without involving cancellation of dynamics. For position and orientation control of a surface vessel without side thruster a new continuous periodic feedback law is proposed that does not cancel any dynamics, and that exponentially stabilizes the origin of the underactuated surface vessel. A further issue considered is the stabilization of the attitude of an AUV. Finally, the thesis discusses stabilization of both position and attitude of an underactuated AUV. 55 refs., 28 figs.

  1. Project Management Plan Solution Stabilization

    Energy Technology Data Exchange (ETDEWEB)

    SATO, P.K.

    1999-08-31

    This plan presents the overall objectives, description, justification and planning for the Plutonium Finishing Plant (PFP) Solutions Stabilization subproject. The intent of this plan is to describe how this project will be managed and integrated with other facility stabilization and deactivation activities. This plan supplements the overall integrated plan presented in the Integrated Project Management Plan (IPMP) for the Plutonium Finishing Plant Stabilization and Deactivation Project, HNF-3617. This project plan is the top-level definitive project management document for the PFP Solution Stabilization subproject. It specifies the technical, schedule, requirements and the cost baselines to manage the execution of the Solution Stabilization subproject. Any deviations to the document must be authorized through the appropriate change control process.

  2. Project Management Plan Solution Stabilization

    International Nuclear Information System (INIS)

    SATO, P.K.

    1999-01-01

    This plan presents the overall objectives, description, justification and planning for the Plutonium Finishing Plant (PFP) Solutions Stabilization subproject. The intent of this plan is to describe how this project will be managed and integrated with other facility stabilization and deactivation activities. This plan supplements the overall integrated plan presented in the Integrated Project Management Plan (IPMP) for the Plutonium Finishing Plant Stabilization and Deactivation Project, HNF-3617. This project plan is the top-level definitive project management document for the PFP Solution Stabilization subproject. It specifies the technical, schedule, requirements and the cost baselines to manage the execution of the Solution Stabilization subproject. Any deviations to the document must be authorized through the appropriate change control process

  3. Magnetohydodynamics stability of compact stellarators

    International Nuclear Information System (INIS)

    Fu, G.Y.; Ku, L.P.; Cooper, W.A.; Hirshman, S.H.

    2000-01-01

    Recent stability results of external kink modes and vertical modes in compact stellarators are presented. The vertical mode is found to be stabilized by externally generated poloidal flux. A simple stability criterion is derived in the limit of large aspect ratio and constant current density. For a wall at infinite distance from the plasma, the amount of external flux needed for stabilization is given by Fi = (k2 minus k)=(k2 + 1), where k is the axisymmetric elongation and Fi is the fraction of the external rotational transform. A systematic parameter study shows that the external kink mode in QAS can be stabilized at high beta (approximately 5%) without a conducting wall by magnetic shear via 3D shaping. It is found that external kinks are driven by both parallel current and pressure gradient. The pressure contributes significantly to the overall drive through the curvature term and the Pfirsch-Schluter current

  4. Dispersion stability of thermal nanofluids

    Directory of Open Access Journals (Sweden)

    Fan Yu

    2017-10-01

    Full Text Available Thermal nanofluids, the engineered fluids with dispersed functional nanoparticles, have exhibited extraordinary thermophysical properties and added functionalities, and thus have enabled a broad range of important applications. The poor dispersion stability of thermal nanofluids, however, has been considered as a long-existing issue that limits their further development and practical application. This review overviews the recent efforts and progresses in improving the dispersion stability of thermal nanofluids such as mechanistic understanding of dispersion behavior of nanofluids, examples of both water-based and oil-based nanofluids, strategies to stabilize nanofluids, and characterization techniques for dispersion behavior of nanofluids. Finally, on-going research needs, and possible solutions to research challenges and future research directions in exploring stably dispersed thermal nanofluids are discussed. Keywords: Thermal nanofluids, Dispersion, Aggregation, Electrostatic stabilization, Steric stabilization

  5. Phase stabilities at a glance: Stability diagrams of nickel dipnictides

    International Nuclear Information System (INIS)

    Bachhuber, F.; Rothballer, J.; Weihrich, R.; Söhnel, T.

    2013-01-01

    In the course of the recent advances in chemical structure prediction, a straightforward type of diagram to evaluate phase stabilities is presented based on an expedient example. Crystal structures and energetic stabilities of dipnictides NiPn 2 (Pn = N, P, As, Sb, Bi) are systematically investigated by first principles calculations within the framework of density functional theory using the generalized gradient approximation to treat exchange and correlation. These dipnictides show remarkable polymorphism that is not yet understood systematically and offers room for the discovery of new phases. Relationships between the concerned structures including the marcasite, the pyrite, the arsenopyrite/CoSb 2 , and the NiAs 2 types are highlighted by means of common structural fragments. Electronic stabilities of experimentally known and related AB 2 structure types are presented graphically in so-called stability diagrams. Additionally, competing binary phases are taken into consideration in the diagrams to evaluate the stabilities of the title compounds with respect to decomposition. The main purpose of the stability diagrams is the introduction of an image that enables the estimation of phase stabilities at a single glance. Beyond that, some of the energetically favored structure types can be identified as potential new phases

  6. Stability of superconductor

    International Nuclear Information System (INIS)

    Wada, Hitoshi; Takeuchi, Takao; Kuroda, Tsuneo

    2000-01-01

    To evaluate the stability of superconductors, we constructed a measurement system of the critical current density Jr property as function of temperature, magnetic strength, azimuth of magnetic field and distortion. LabView program automatically controlled the magnetic field, temperature, rotational displacement, load, multimeter and sample source in the system. The superconducting critical surface of Nb 3 Al wire was prepared by two methods: a low temperature diffusion method and a phase transformation method. Nb 3 Al prepared by two methods proved the temperature scaling law of magnetic pinning force density and parameters for fitting the pinning model were introduced. The tailing of Jc-T curve at the high temperature side was generated by pinning property of magnetic flux line. On measurement of AC magnetic susceptibility, a primary stack (JR filament) of RIT Nb 3 Al wire prepared by phase transformation connected electrically and the size corresponded to the effective core size, so that, large n value was shown in spite of high temperature treatment and it showed good distortion resistance. Nb 3 Al wire prepared by low temperature diffusion method indicated large anisotropy of Bc 2 and Jc in the rectangular wire. On V 3 Ga, the temperature scaling law of magnetic field was not established and it was observed the effective grain boundary pinning at the low magnetic field and the other pinning mechanism of which magnetic flux line synchronized in the high temperature field. The specific magnetic azimuth dependency showed in the neighborhood of the parallel magnetic field. Jc indicated the positive dependence of temperature in the peak magnetic field. Jc of Bi oxides tape conductor was measured and the results showed the magnetic field was governed by magnetic field dependence on the c axis direction. (S.Y.)

  7. Quantifying Stability in Complex Networks: From Linear to Basin Stability

    Science.gov (United States)

    Kurths, Jürgen

    The human brain, power grids, arrays of coupled lasers and the Amazon rainforest are all characterized by multistability. The likelihood that these systems will remain in the most desirable of their many stable states depends on their stability against significant perturbations, particularly in a state space populated by undesirable states. Here we claim that the traditional linearization-based approach to stability is in several cases too local to adequately assess how stable a state is. Instead, we quantify it in terms of basin stability, a new measure related to the volume of the basin of attraction. Basin stability is non-local, nonlinear and easily applicable, even to high-dimensional systems. It provides a long-sought-after explanation for the surprisingly regular topologies of neural networks and power grids, which have eluded theoretical description based solely on linear stability. Specifically, we employ a component-wise version of basin stability, a nonlinear inspection scheme, to investigate how a grid's degree of stability is influenced by certain patterns in the wiring topology. Various statistics from our ensemble simulations all support one main finding: The widespread and cheapest of all connection schemes, namely dead ends and dead trees, strongly diminish stability. For the Northern European power system we demonstrate that the inverse is also true: `Healing' dead ends by addition of transmission lines substantially enhances stability. This indicates a crucial smart-design principle for tomorrow's sustainable power grids: add just a few more lines to avoid dead ends. Further, we analyse the particular function of certain network motifs to promote the stability of the system. Here we uncover the impact of so-called detour motifs on the appearance of nodes with a poor stability score and discuss the implications for power grid design. Moreover, it will be shown that basin stability enables uncovering the mechanism for explosive synchronization and

  8. New stability and stabilization for switched neutral control systems

    International Nuclear Information System (INIS)

    Xiong Lianglin; Zhong Shouming; Ye Mao; Wu Shiliang

    2009-01-01

    This paper concerns stability and stabilization issues for switched neutral systems and presents new classes of piecewise Lyapunov functionals and multiple Lyapunov functionals, based on which, two new switching rules are introduced to stabilize the neutral systems. One switching rule is designed from the solution of the so-called Lyapunov-Metzler linear matrix inequalities. The other is based on the determination of average dwell time computed from a new class of linear matrix inequalities (LMIs). And then, state-feedback control is derived for the switched neutral control system mainly based on the state switching rules. Finally, three examples are given to demonstrate the effectiveness of the proposed method.

  9. Stability of yttria-stabilized zirconia during pyroprocessing tests

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun-Young, E-mail: eychoi@kaeri.re.kr; Lee, Jeong; Lee, Sung-Jai; Kim, Sung-Wook; Jeon, Sang-Chae; Cho, Soo Haeng; Oh, Seung Chul; Jeon, Min Ku; Lee, Sang Kwon; Kang, Hyun Woo; Hur, Jin-Mok

    2016-07-15

    In this study, the feasibility of yttria-stabilized zirconia (YSZ) was investigated for use as a ceramic material, which can be commonly used for both electrolytic reduction and electrorefining. First, the stability of YSZ in salts for electrolytic reduction and electrorefining was examined. Then, its stability was demonstrated by a series of pyroprocessing tests, such as electrolytic reduction, LiCl distillation, electrorefining, and LiCl−KCl distillation, using a single stainless steel wire mesh basket containing fuel and YSZ. A single basket was used by its transportation from one test to subsequent tests without the requirements for unloading.

  10. Stability of dispersions in polar organic media. I. Electrostatic stabilization

    NARCIS (Netherlands)

    Rooy, N. de; Bruyn, P.L. de; Overbeek, J.Th.G.

    Electrostatically stabilized sols of silver, silver iodide, α-goethite, and copper phthalocyanine in methanol, ethanol, isopropanol, and acetone have been prepared and characterized. Coagulation concentrations with electrolytes of various charge numbers have been determined in water, in organic

  11. Stability indicators in network reconstruction.

    Directory of Open Access Journals (Sweden)

    Michele Filosi

    Full Text Available The number of available algorithms to infer a biological network from a dataset of high-throughput measurements is overwhelming and keeps growing. However, evaluating their performance is unfeasible unless a 'gold standard' is available to measure how close the reconstructed network is to the ground truth. One measure of this is the stability of these predictions to data resampling approaches. We introduce NetSI, a family of Network Stability Indicators, to assess quantitatively the stability of a reconstructed network in terms of inference variability due to data subsampling. In order to evaluate network stability, the main NetSI methods use a global/local network metric in combination with a resampling (bootstrap or cross-validation procedure. In addition, we provide two normalized variability scores over data resampling to measure edge weight stability and node degree stability, and then introduce a stability ranking for edges and nodes. A complete implementation of the NetSI indicators, including the Hamming-Ipsen-Mikhailov (HIM network distance adopted in this paper is available with the R package nettools. We demonstrate the use of the NetSI family by measuring network stability on four datasets against alternative network reconstruction methods. First, the effect of sample size on stability of inferred networks is studied in a gold standard framework on yeast-like data from the Gene Net Weaver simulator. We also consider the impact of varying modularity on a set of structurally different networks (50 nodes, from 2 to 10 modules, and then of complex feature covariance structure, showing the different behaviours of standard reconstruction methods based on Pearson correlation, Maximum Information Coefficient (MIC and False Discovery Rate (FDR strategy. Finally, we demonstrate a strong combined effect of different reconstruction methods and phenotype subgroups on a hepatocellular carcinoma miRNA microarray dataset (240 subjects, and we

  12. Field investigation of keyblock stability

    International Nuclear Information System (INIS)

    Yow, J.L. Jr.

    1985-04-01

    Discontinuities in a rock mass can intersect an excavation surface to form discrete blocks (keyblocks) which can be unstable. This engineering problem is divided into two parts: block identification, and evaluation of block stability. One stable keyblock and thirteen fallen keyblocks were observed in field investigations at the Nevada Test Site. Nine blocks were measured in detail sufficient to allow back-analysis of their stability. Measurements included block geometry, and discontinuity roughness and compressive strength. Back-analysis correctly predicted stability or failure in all but two cases. These two exceptions involved situations that violated the stress assumptions of the stability calculations. Keyblock faces correlated well with known joint set orientations. The effect of tunnel orientation on keyblock frequency was apparent. Back-analysis of physical models successfully predicted block pullout force for two-dimensional models of unit thickness. Two-dimensional (2D) and three-dimensional (3D) analytic models for the stability of simple pyramidal keyblocks were examined. Calculated stability is greater for 3D analyses than for 2D analyses. Calculated keyblock stability increases with larger in situ stress magnitudes, larger lateral stress ratios, and larger shear strengths. Discontinuity stiffness controls block displacement more strongly than it does stability itself. Large keyblocks are less stable than small ones, and stability increases as blocks become more slender. Rock mass temperature decreases reduce the confining stress magnitudes and can lead to failure. The pattern of stresses affecting each block face explains conceptually the occurrence of pyramidal keyblocks that are truncated near their apex

  13. Radiochemical stability of radiopharmaceutical preparations

    International Nuclear Information System (INIS)

    Martins, Patricia de A.; Silva, Jose L. da; Ramos, Marcelo P.S.; Oliveira, Ideli M. de; Felgueiras, Carlos F.; Herrerias, Rosana; Zapparoli Junior, Carlos L.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.

    2011-01-01

    The 'in vitro' stability studies of the radiopharmaceutical preparations are an essential requirement for routine practice in nuclear medicine and are an important parameter for evaluating the quality, safety and efficacy required for the sanitary registration of pharmaceutical products. Several countries have published guidelines for the evaluation of pharmaceutical stability. In Brazil, the stability studies should be conducted according to the Guide for Conducting Stability Studies published in the Resolution-RE n. 1, of 29th July 2005. There are also for radiopharmaceutical products, two specific resolutions: RDC-63 regulates the Good Manufacturing Practices for Radiopharmaceuticals and RDC-64 provides the Registration of Radiopharmaceuticals, both published on the 18th December 2009. The radiopharmaceutical stability is defined as the time during which the radioisotope can be safely used for the intended purpose. The radiochemical stability can be affected by a variety of factors, including storage temperature, amount of radioactivity, radioactive concentration, presence or absence of antioxidants or other stabilizing agents. The radiochemical stability studies must be established under controlled conditions determined by the effective use of the product. The aim of this work was to evaluate the radiochemical stability of labeled molecules with 131 I, 123 I, 153 Sm, 18 F, 51 Cr, 177 Lu and 111 In as well as 67 Ga and 201 Tl radiopharmaceuticals. Radiochemical purity was evaluated after production and in the validity period, with the maximum activity and in the recommended storage conditions. The analyses were carried out by thin-layer silica gel plate, paper chromatography and gel chromatography. The experimental results showed to be in accordance with the specified limits for all the analysed products. (author)

  14. Sludge Stabilization Campaign blend plan

    International Nuclear Information System (INIS)

    De Vries, M.L.

    1994-01-01

    This sludge stabilization blend plan documents the material to be processed and the order of processing for the FY95 Sludge Stabilization Campaign. The primary mission of this process is to reduce the inventory of unstable plutonium bearing sludge. The source of the sludge is residual and glovebox floor sweepings from the production of material at the Plutonium Finishing Plant (PFP). The reactive sludge is currently being stored in various gloveboxes at PFP. There are two types of the plutonium bearing material that will be thermally stabilized in the muffle furnace: Plutonium Reclamation Facility (PRF) sludge and Remote Mechanical C (RMC) Line material

  15. Plutonium stabilization and packaging system

    International Nuclear Information System (INIS)

    1996-01-01

    This document describes the functional design of the Plutonium Stabilization and Packaging System (Pu SPS). The objective of this system is to stabilize and package plutonium metals and oxides of greater than 50% wt, as well as other selected isotopes, in accordance with the requirements of the DOE standard for safe storage of these materials for 50 years. This system will support completion of stabilization and packaging campaigns of the inventory at a number of affected sites before the year 2002. The package will be standard for all sites and will provide a minimum of two uncontaminated, organics free confinement barriers for the packaged material

  16. Unemployment and Subsequent Employment Stability

    DEFF Research Database (Denmark)

    Wulfgramm, Melike; Fervers, Lukas

    2015-01-01

    Recent labour market reforms in Europe have been aimed at activating non-employed people and shortening unemployment duration. While this should indisputably be a central policy aim, the exclusive focus on quick re-employment neglects the importance of its quality and stability. Therefore......, this paper analyses the effect of labour market policy on re-employment stability in Europe. Combining EU-SILC longitudinal survey data with macro-data on labour market policy, we conduct multi-level survival analysis. Empirical evidence suggests that countries with more generous unemployment insurance......, and their positive effect on re-employment stability on the other hand....

  17. Stability analysis and stabilization strategies for linear supply chains

    Science.gov (United States)

    Nagatani, Takashi; Helbing, Dirk

    2004-04-01

    Due to delays in the adaptation of production or delivery rates, supply chains can be dynamically unstable with respect to perturbations in the consumption rate, which is known as “bull-whip effect”. Here, we study several conceivable production strategies to stabilize supply chains, which is expressed by different specifications of the management function controlling the production speed in dependence of the stock levels. In particular, we will investigate, whether the reaction to stock levels of other producers or suppliers has a stabilizing effect. We will also demonstrate that the anticipation of future stock levels can stabilize the supply system, given the forecast horizon τ is long enough. To show this, we derive linear stability conditions and carry out simulations for different control strategies. The results indicate that the linear stability analysis is a helpful tool for the judgement of the stabilization effect, although unexpected deviations can occur in the non-linear regime. There are also signs of phase transitions and chaotic behavior, but this remains to be investigated more thoroughly in the future.

  18. MATLAB Stability and Control Toolbox Trim and Static Stability Module

    Science.gov (United States)

    Kenny, Sean P.; Crespo, Luis

    2012-01-01

    MATLAB Stability and Control Toolbox (MASCOT) utilizes geometric, aerodynamic, and inertial inputs to calculate air vehicle stability in a variety of critical flight conditions. The code is based on fundamental, non-linear equations of motion and is able to translate results into a qualitative, graphical scale useful to the non-expert. MASCOT was created to provide the conceptual aircraft designer accurate predictions of air vehicle stability and control characteristics. The code takes as input mass property data in the form of an inertia tensor, aerodynamic loading data, and propulsion (i.e. thrust) loading data. Using fundamental nonlinear equations of motion, MASCOT then calculates vehicle trim and static stability data for the desired flight condition(s). Available flight conditions include six horizontal and six landing rotation conditions with varying options for engine out, crosswind, and sideslip, plus three take-off rotation conditions. Results are displayed through a unique graphical interface developed to provide the non-stability and control expert conceptual design engineer a qualitative scale indicating whether the vehicle has acceptable, marginal, or unacceptable static stability characteristics. If desired, the user can also examine the detailed, quantitative results.

  19. The Brazilian smoker: a survey in the largest cities of Brazil Fatores associados ao hábito de fumar do brasileiro: um estudo nas maiores cidades do país

    Directory of Open Access Journals (Sweden)

    Emérita Sátiro Opaleye

    2012-03-01

    verificar associação com o hábito de fumar. RESULTADOS: De 7.921 entrevistados, 16,4% relataram uso diário de cigarros. A prevalência de uso entre os gêneros foi semelhante, embora as mulheres tenham relatado idade de início de uso superior e menores quantidades por dia. Quase 65% dos fumantes manifestaram interesse em abandonar ou reduzir o hábito. As principais características sociodemográficas associadas ao tabagismo foram: idade adulta (30 a 59 anos, desemprego, menor escolaridade e menor poder aquisitivo. O uso abusivo de álcool também se mostrou associado ao fumo. CONCLUSÕES: Os achados sugerem características socioeconômicas desfavorecidas implicadas em maior vulnerabilidade ao tabagismo no Brasil. Houve um elevado relato de fumantes interessados em abandonar ou reduzir o hábito. Os dados apontam fatores sociodemográficos que devem ser considerados na elaboração de políticas de prevenção e tratamento.

  20. Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial

    Directory of Open Access Journals (Sweden)

    Tashkin DP

    2012-02-01

    Full Text Available Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Sibabrata Banerjee5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR USA; 4Fundación Salud Bosque, Bogota, Colombia; 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ USABackground: A clinical trial of mometasone furoate/formoterol fumarate (MF/F administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD investigated the efficacy and safety of a fixed-dose combination of MF/F.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1 over 0–12 hours (AUC0–12 FEV1 with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ], symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.Results: Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007. Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV1 data were collected >2 days after the last

  1. Determinantes do hábito de fumar e de seu abandono durante a gestação em localidade urbana na região sul do Brasil Determining factors related to smoking and its abandonment during pregnancy in an urban locality in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Iná S. Halal

    1993-04-01

    Full Text Available Foi realizado um estudo transversal, com 873 gestantes que freqüentaram o pré-natal em Pelotas (RS, em 1989-90, com o objetivo de investigar possíveis fatores de risco e fatores prognósticos para o tabagismo durante a gravidez. A prevalência no início da gravidez foi de 40,8%. O hábito de fumar da mãe da gestante e do marido e a baixa escolaridade da mulher estiveram associados com o risco de fumar no início da gravidez. O tabagismo do marido esteve associado com um aumento de cerca de duas vezes nesse risco. A taxa de abandono até a 15ª-22ª semana gestacional foi de 35,6%. A renda familiar, o hábito de fumar da mãe da gestante e do companheiro, a idade de início, duração e intensidade do hábito da mulher estiveram associados com a interrupção durante a gravidez. Os resultados acima permaneceram após ajuste para fatores de confusão, através de análise estratificada.A cross-sectional study of 873 pregnant women attending a prenatal care clinic was undertaken in Pelotas (Southern Brazil, over a one-year period (1989-90 for the purpose of identifying possible risk and prognostic factors for smoking during pregnancy. The prevalence of smoking at the beginning of pregnancy was 40.8%. The smoking habits of the woman's mother and partner, as well as her educational level, were associated with smoking at the beginning of pregnancy. Smoking in the partner was associated with an approximately two-fold increase in the risk of smoking. The smoking interruption rate, until the 15th-22nd gestational week, was of 35.6%. Family income, smoking habits of woman's mother and partner, age at starting, duration and intensity of the woman's habit were all associated with the interruption during pregnancy. The above results were not affected by adjustment for confounding variables made through stratified analysis.

  2. Linear stability of tearing modes

    International Nuclear Information System (INIS)

    Cowley, S.C.; Kulsrud, R.M.; Hahm, T.S.

    1986-05-01

    This paper examines the stability of tearing modes in a sheared slab when the width of the tearing layer is much smaller than the ion Larmor radius. The ion response is nonlocal, and the quasineutrality retains its full integal form. An expansion procedure is introduced to solve the quasineutrality equation in powers of the width of the tearing layer over the ion Larmor radius. The expansion procedure is applied to the collisionless and semi-collisional tearing modes. The first order terms in the expansion we find to be strongly stabilizing. The physics of the mode and of the stabilization is discussed. Tearing modes are observed in experiments even though the slab theory predicts stability. It is proposed that these modes grow from an equilibrium with islands at the rational surfaces. If the equilibrium islands are wider than the ion Larmor radius, the mode is unstable when Δ' is positive

  3. Feedback stabilization of plasma instabilities

    International Nuclear Information System (INIS)

    Cap, F.F.

    1977-01-01

    This paper reviews the theoretical and experimental aspects of feedback stabilization. After giving an outline of a general theoretical model for electrostatic instabilities the author provides a theoretical analysis of the suppression of various types of instability. Experiments which have been carried out on the feedback stabilization of various types of plasma instability are reported. An extensive list of references is given. (B.R.H.)

  4. Reliability criteria for voltage stability

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Carson W; Silverstein, Brian L [Bonneville Power Administration, Portland, OR (United States)

    1994-12-31

    In face of costs pressures, there is need to allocate scare resources more effectively in order to achieve voltage stability. This naturally leads to development of probabilistic criteria and notions of rick management. In this paper it is presented a discussion about criteria for long term voltage stability limited to the case in which the time frames are topically several minutes. (author) 14 refs., 1 fig.

  5. Dynamic Stability of Maglev Systems,

    Science.gov (United States)

    1992-04-01

    AD-A259 178 ANL-92/21 Materials and Components Dynamic Stability of Technology Division Materials and Components Maglev Systems Technology Division...of Maglev Systems Y. Cai, S. S. Chen, and T. M. Mulcahy Materials and Components Technology Division D. M. Rote Center for Transportation Research...of Maglev System with L-Shaped Guideway ......................................... 6 3 Stability of M aglev System s

  6. Laccases stabilization with phosphatidylcholine liposomes

    OpenAIRE

    Martí, M.; Zille, Andrea; Paulo, Artur Cavaco; Parra, J. L.; Coderch, L.

    2012-01-01

    In recent years, there has been an upsurge of interest in enzyme treatment of textile fibres. Enzymes are globular proteins whose catalytic function is due to their three dimensional structure. For this reason, stability strategies make use of compounds that avoid dismantling or distorting protein 3D structures. This study is concerned with the use of microencapsulation techniques to optimize enzyme stabilization. Laccases were embedded in phophatidylcholine liposomes and their encaps...

  7. Market liquidity and financial stability.

    OpenAIRE

    Crockett, A.

    2008-01-01

    Stability in financial institutions and in financial markets are closely intertwined. Banks and other financial institutions need liquid markets through which to conduct risk management. And markets need the back-up liquidity lines provided by financial institutions. Market liquidity depends not only on objective, exogenous factors, but also on endogenous market dynamics. Central banks responsible for systemic stability need to consider how far their traditional responsibility for the health ...

  8. Stability measures in arid ecosystems

    Science.gov (United States)

    Nosshi, M. I.; Brunsell, N. A.; Koerner, S.

    2015-12-01

    Stability, the capacity of ecosystems to persist in the face of change, has proven its relevance as a fundamental component of ecological theory. Here, we would like to explore meaningful and quantifiable metrics to define stability, with a focus on highly variable arid and semi-arid savanna ecosystems. Recognizing the importance of a characteristic timescale to any definition of stability, our metrics will be focused scales from annual to multi-annual, capturing different aspects of stability. Our three measures of stability, in increasing order of temporal scale, are: (1) Ecosystem resistance, quantified as the degree to which the system maintains its mean state in response to a perturbation (drought), based on inter-annual variability in Normalized Difference Vegetation Index (NDVI). (2) An optimization approach, relevant to arid systems with pulse dynamics, that models vegetation structure and function based on a trade off between the ability to respond to resource availability and avoid stress. (3) Community resilience, measured as species turnover rate (β diversity). Understanding the nature of stability in structurally-diverse arid ecosystems, which are highly variable, yields theoretical insight which has practical implications.

  9. Stability of Pharmaceuticals in Space

    Science.gov (United States)

    Nguyen, Y-Uyen

    2009-01-01

    Stability testing is a tool used to access shelf life and effects of storage conditions for pharmaceutical formulations. Early research from the International Space Station (ISS) revealed that some medications may have degraded while in space. This potential loss of medication efficacy would be very dangerous to Crew health. The aim of this research project, Stability of Pharmacotherapeutic Compounds, is to study how the stability of pharmaceutical compounds is affected by environmental conditions in space. Four identical pharmaceutical payload kits containing medications in different dosage forms (liquid for injection, tablet, capsule, ointment and suppository) were transported to the ISS aboard a Space Shuttle. One of the four kits was stored on that Shuttle and the other three were stored on the ISS for return to Earth at various time intervals aboard a pre-designated Shuttle flight. The Pharmacotherapeutics laboratory used stability test as defined by the United States Pharmacopeia (USP), to access the degree of degradation to the Payload kit medications that may have occurred during space flight. Once these medications returned, the results of stability test performed on them were compared to those from the matching ground controls stored on Earth. Analyses of the results obtained from physical and chemical stability assessments on these payload medications will provide researchers additional tools to promote safe and efficacious medications for space exploration.

  10. High beta and second stability region transport and stability analysis

    International Nuclear Information System (INIS)

    Hughes, M.H.; Phillps, M.W.; Todd, A.M.M.; Krishnaswami, J.; Hartley, R.

    1992-09-01

    This report describes ideal and resistive studies of high-beta plasmas and of the second stability region. Emphasis is focused on ''supershot'' plasmas in TFIR where MHD instabilities are frequently observed and which spoil their confinement properties. Substantial results are described from the analysis of these high beta poloidal plasmas. During these studies, initial pressure and safety factor profiles were obtained from the TRANSP code, which is used extensively to analyze experimental data. Resistive MBD stability studies of supershot equilibria show that finite pressure stabilization of tearing modes is very strong in these high βp plasmas. This has prompted a detailed re-examination of linear tearing mode theory in which we participated in collaboration with Columbia University and General Atomics. This finite pressure effect is shown to be highly sensitive to small scale details of the pressure profile. Even when an ad hoc method of removing this stabilizing mechanism is implemented, however, it is shown that there is only superficial agreement between resistive MBD stability computation and the experimental data. While the mode structures observed experimentally can be found computationally, there is no convincing correlation with the experimental observations when the computed results are compared with a large set of supershot data. We also describe both the ideal and resistive stability properties of TFIR equilibria near the transition to the second region. It is shown that the highest β plasmas, although stable to infinite-n ideal ballooning modes, can be unstable to the so called ''infernal'' modes associated with small shear. The sensitivity of these results to the assumed pressure and current density profiles is discussed. Finally, we describe results from two collaborative studies with PPPL. The first involves exploratory studies of the role of the 1/1 mode in tokamaks and, secondly, a study of sawtooth stabilization using ICRF

  11. Subgrade stabilization alternatives to lime and cement.

    Science.gov (United States)

    2010-04-15

    This project involved four distinct research activities, (1) the influence of temperature on lime-stabilized soils, (2) the influence of temperature on cement-stabilized soils (3) temperature modeling of stabilized subgrade and (4) use of calcium chl...

  12. Use of soil stabilizers on highway shoulders.

    Science.gov (United States)

    2005-01-01

    This study evaluated soil additives as stabilizers for aggregate and topsoil shoulders. Its purpose was to determine (1) the effect soil stabilizers have on the strength and stability of soil shoulders, and (2) the costs and benefits of using stabili...

  13. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  14. Phase stability in yttria-stabilized zirconia from first principles

    Energy Technology Data Exchange (ETDEWEB)

    Carbogno, Christian; Scheffler, Matthias [Materials Department, University of California, Santa Barbara, CA (United States); Fritz-Haber-Institut der Max-Planck-Gesellschaft, Berlin (Germany); Levi, Carlos G.; Van de Walle, Chris G. [Materials Department, University of California, Santa Barbara, CA (United States)

    2012-07-01

    Zirconia based ceramics are of pivotal importance for a variety of industrial technologies, e.g., for thermal barrier coatings in gas and airplane turbines. Naturally, the stability of such coatings at elevated temperatures plays a critical role in these applications. It is well known that an aliovalent doping of tetragonal ZrO{sub 2} with yttria, which induces oxygen vacancies due to charge conservation, increases its thermodynamic stability. However, the atomistic mechanisms that determine the phase stability of such yttria-stabilized Zirconia (YSZ) coatings are not yet fully understood. In this work, we use density functional theory calculations to assess the electronic structure of the different YSZ polymorphs at various levels of doping. With the help of population analysis schemes, we are able to unravel the intrinsic mechanisms that govern the interaction in YSZ and that can so explain the relative stabilities of the various polymorphs. We critically compare our results to experimental measurements and discuss the implications of our findings with respect to other oxides.

  15. Measuring Stability and Security in Iraq

    National Research Council Canada - National Science Library

    2006-01-01

    .... The first section of the report, Stability and Security in Iraq, describes trends and progress towards meeting goals for political stability, strengthening economic activity, and achieving a stable...

  16. Compressible stability of growing boundary layers using parabolized stability equations

    Science.gov (United States)

    Chang, Chau-Lyan; Malik, Mujeeb R.; Erlebacher, Gordon; Hussaini, M. Y.

    1991-01-01

    The parabolized stability equation (PSE) approach is employed to study linear and nonlinear compressible stability with an eye to providing a capability for boundary-layer transition prediction in both 'quiet' and 'disturbed' environments. The governing compressible stability equations are solved by a rational parabolizing approximation in the streamwise direction. Nonparallel flow effects are studied for both the first- and second-mode disturbances. For oblique waves of the first-mode type, the departure from the parallel results is more pronounced as compared to that for the two-dimensional waves. Results for the Mach 4.5 case show that flow nonparallelism has more influence on the first mode than on the second. The disturbance growth rate is shown to be a strong function of the wall-normal distance due to either flow nonparallelism or nonlinear interactions. The subharmonic and fundamental types of breakdown are found to be similar to the ones in incompressible boundary layers.

  17. High beta and second stability region transport and stability analysis

    International Nuclear Information System (INIS)

    1990-01-01

    This document summarizes progress made on the research of high beta and second region transport and stability. In the area second stability region studies we report on an investigation of the possibility of second region access in the center of TFTR ''supershots.'' The instabilities found may coincide with experimental observation. Significant progress has been made on the resistive stability properties of high beta poloidal ''supershot'' discharges. For these studies profiles were taken from the TRANSP transport analysis code which analyzes experimental data. Invoking flattening of the pressure profile on mode rational surfaces causes tearing modes to persist into the experimental range of interest. Further, the experimental observation of the modes seems to be consistent with the predictions of the MHD model. In addition, code development in several areas has proceeded

  18. Matlab Stability and Control Toolbox: Trim and Static Stability Module

    Science.gov (United States)

    Crespo, Luis G.; Kenny, Sean P.

    2006-01-01

    This paper presents the technical background of the Trim and Static module of the Matlab Stability and Control Toolbox. This module performs a low-fidelity stability and control assessment of an aircraft model for a set of flight critical conditions. This is attained by determining if the control authority available for trim is sufficient and if the static stability characteristics are adequate. These conditions can be selected from a prescribed set or can be specified to meet particular requirements. The prescribed set of conditions includes horizontal flight, take-off rotation, landing flare, steady roll, steady turn and pull-up/ push-over flight, for which several operating conditions can be specified. A mathematical model was developed allowing for six-dimensional trim, adjustable inertial properties, asymmetric vehicle layouts, arbitrary number of engines, multi-axial thrust vectoring, engine(s)-out conditions, crosswind and gyroscopic effects.

  19. Stability Analysis and Stabilization of Miduk Heap Leaching Structure, Iran

    Directory of Open Access Journals (Sweden)

    Mehdi Amini

    2013-06-01

    Full Text Available To construct copper heap leaching structures, a stepped heap of ore is placed over an isolated sloping surface and then washed with sulphuric acid. The isolated bed of such a heap consists of some natural and geosynthetic layers. Shear strength parameters between these layers are low, so they form the possible sliding surfaces of the heaps. Economic and environmental considerations call for studying such slides. In this study, firstly, results of the laboratory tests carried on the materials of the heap leaching structures bed are presented. Then, the instability mechanisms of such structures are investigated and proper approaches are summarized for their stabilization. Finally, stability of the Miduk copper heap is evaluated as a case history, and appropriate approaches and their effects are discussed for its stabilization.

  20. Can the UN Stabilize Mali? Towards a UN Stabilization Doctrine?

    Directory of Open Access Journals (Sweden)

    Arthur Boutellis

    2015-06-01

    Full Text Available Almost two years after the deployment of the United Nations Multidimensional Integrated Stabilization Mission in Mali (MINUSMA in July 2013, the increasing number of asymmetric terrorist attacks targeting UN peacekeepers – in the context of a drawn-out peace process – has raised a number of questions in Mali, the sub-region, and in New York, over the relevance and adequacies of MINUSMA’s mandate and capabilities. It also raises a broader issue, of whether the consent-based UN peacekeeping tool is appropriate and can be effective in carrying out stabilization mandates in such a context and what doctrine such operations should be based on. The UN is indeed under increasing pressure from host countries and some African troop-contributing countries to go on the offensive. Member States have also increasingly recognized terrorism and organized crime as a strategic threat, and while opposed to the UN directly engaging in counterterrorism (CT operations, some may wish to see the UN playing a greater stabilization role following the January 2013 French military intervention in Mali. However, little guidance and means have been given so far to UN missions for dealing with such threats and implementing effective stabilization mandates. The High-Level Panel on Peace Operations, which recently released its report, noted that the usage of the term “stabilization” by the UN requires clarification. This article analyses the complex and evolving nature of threats in northern Mali and implications for MINUSMA and describes the military and political tools – including mediation – so far available within and outside the UN. The article concludes that the UN is bound to move towards stabilization when and if deployed in contexts such as Mali’s if it wants to remain relevant. However, such a move should be based on an overarching UN stabilization doctrine and context-specific UN-wide stabilization strategies which are first and foremost political

  1. Development of emotional stability scale

    Directory of Open Access Journals (Sweden)

    M Chaturvedi

    2010-01-01

    Full Text Available Background: Emotional stability remains the central theme in personality studies. The concept of stable emotional behavior at any level is that which reflects the fruits of normal emotional development. The study aims at development of an emotional stability scale. Materials and Methods: Based on available literature the components of emotional stability were identified and 250 items were developed, covering each component. Two-stage elimination of items was carried out, i.e. through judges′ opinions and item analysis. Results: Fifty items with highest ′t′ values covering 5 dimensions of emotional stability viz pessimism vs. optimism, anxiety vs. calm, aggression vs. tolerance., dependence vs. autonomy., apathy vs. empathy were retained in the final scale. Reliability as checked by Cronbach′s alpha was .81 and by split half method it was .79. Content validity and construct validity were checked. Norms are given in the form of cumulative percentages. Conclusion: Based on the psychometric principles a 50 item, self-administered 5 point Lickert type rating scale was developed for measurement of emotional stability.

  2. Stabilizing effect of epoxidized sunflower oil as a secondary stabilizer for Ca/Hg stabilized PVC

    Directory of Open Access Journals (Sweden)

    2008-01-01

    Full Text Available Unsaturated triglyceride oil sunflower was epoxidized and characterized by chemical and spectroscopic methods. Epoxidized sunflower oil (ESO was used as an organic thermal co-stabilizer for rigid poly(vinyl chloride (PVC in the presence of tricalcium dicitrate (Ca3(C6H5O72 and mercury (II acetate (Hg(CH3COO2. The thermo-oxidative degradation of PVC was studied in the presence of these ternary stabilizer systems at 170, 180, 190 and 200°C in N2 atmosphere. The effects of metal carboxylate combination Ca/Hg in the absence and in the presence of epoxidized sunflower oil on static heat treatment of PVC have been studied. The formation of polyene sequences was investigated by UV-visible and FT-IR spectroscopy and by comparing viscosity data obtained in the presence and in the absence of the additives. It was found that the additives retard the rate of degradation and reduce the extent of polymer chain scission associated with the thermal degradation of poly(vinyl chloride. Synergistic effects were found when stabilizer was blended in 50:50 weight ratios with either. It was found that ESO exerted a stabilizing effect on the degradation of PVC. The activation energy for degraded PVC in absence of stabilizers was 38.6 kJ•mol–1 and in the presence of Ca/Hg and Ca/Hg/ESO were 53.3 and 64.7 kJ•mol–1 respectively. In order of compare the efficiency of the epoxidized sunflower oil with these metal soap stabilizers, thermal stabilities were evaluated on the basis of evolved hydrogen chloride determined by conductometry technique and degree of discoloration are discussed.

  3. Nonlinear stability of supersonic jets

    Science.gov (United States)

    Tiwari, S. N. (Principal Investigator); Bhat, T. R. S. (Principal Investigator)

    1996-01-01

    The stability calculations made for a shock-free supersonic jet using the model based on parabolized stability equations are presented. In this analysis the large scale structures, which play a dominant role in the mixing as well as the noise radiated, are modeled as instability waves. This model takes into consideration non-parallel flow effects and also nonlinear interaction of the instability waves. The stability calculations have been performed for different frequencies and mode numbers over a range of jet operating temperatures. Comparisons are made, where appropriate, with the solutions to Rayleigh's equation (linear, inviscid analysis with the assumption of parallel flow). The comparison of the solutions obtained using the two approaches show very good agreement.

  4. Secular stability of rotating stars

    International Nuclear Information System (INIS)

    Imamura, J.N.; Friedman, J.L.; Durisen, R.H.

    1984-01-01

    In this work, we calculate the secular stability limits of rotating polytropes to nonaxisymmetric perturbations of low m. We consider polytropic indices ranging from 1 to 3 and several angular momentum distributions. Results are most conveniently presented in terms of the t-parameter, defined as the ratio of the rotational kinetic energy to the absolute value of the gravitational energy of the fluid. Previous work on polytropes considered only the m = 2 mode, which is unstable for values of the t-parameter greater than 0.14 +- 0.01 for the n values n = 1.5 and 3 and the angular momentum distributions tested (see Durisen and Imamura 1981). The GRR secular stability limit of the m = 2 mode for the Maclaurin spheroids (n = O) was determined by Chandrasekhar (1970). GRR stability limits of higher m modes for the Maclaurin spheroids were located approximately by Comins (1979a,b) and more precisely by Friedman (1983)

  5. Chemical stabilization of graphite surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Bistrika, Alexander A.; Lerner, Michael M.

    2018-04-03

    Embodiments of a device, or a component of a device, including a stabilized graphite surface, methods of stabilizing graphite surfaces, and uses for the devices or components are disclosed. The device or component includes a surface comprising graphite, and a plurality of haloaryl ions and/or haloalkyl ions bound to at least a portion of the graphite. The ions may be perhaloaryl ions and/or perhaloalkyl ions. In certain embodiments, the ions are perfluorobenzenesulfonate anions. Embodiments of the device or component including stabilized graphite surfaces may maintain a steady-state oxidation or reduction surface current density after being exposed to continuous oxidation conditions for a period of at least 1-100 hours. The device or component is prepared by exposing a graphite-containing surface to an acidic aqueous solution of the ions under oxidizing conditions. The device or component can be exposed in situ to the solution.

  6. Ash Stabilization Campaign Blend Plan

    International Nuclear Information System (INIS)

    Winstead, M.L.

    1995-01-01

    This Stabilization Blend Plan documents the material to be processed and the processing order for the FY95 Ash Stabilization Campaign. The primary mission of this process is to reduce the inventory of unstable plutonium bearing ash. The source of the ash is from Rocky Flats and the 232-Z incinerator at the Plutonium Finishing Plant (PFP). The ash is currently being stored in Room 235B and Vault 174 in building 234-5Z. The sludge is to be thermally stabilized in a glovebox in room 230A of the 234-5Z building and material handling for the process will be done in room 230B of the same building. The campaign is scheduled for approximately 12--16 weeks. A total of roughly 4 kg of Pu will be processed

  7. Gold nanoparticles stabilized by chitosan

    International Nuclear Information System (INIS)

    Geraldes, Adriana N.; Oliveira, Maria Jose A.; Silva, Andressa A. da; Leal, Jessica; Batista, Jorge G.S.; Lugao, Ademar B.

    2015-01-01

    In our laboratory has been growing the interest in studying gold nanoparticles and for this reason, the aim of this work is report the first results of the effect of chitosan as stabilizer in gold nanoparticle formulation. AuNPs were synthesized by reducing hydrogen tetrachloroaurate (HAuCl 4 ) using NaBH 4 or gamma irradiation (25kGy) as reduction agent. The chitosan (3 mol L -1 ) was added at 0.5; 1.0 and 1.5 mL. The gold nanoparticles were characterized by UV-Vis absorption spectroscopy, X-ray diffraction (XRD) and Transmission electron microscopy (TEM). Their physical stability was determined using a UV-Vis spectrophotometer over one week during storage at room temperature. Absorption measurements indicated that the plasmon resonance wavelength appears at a wavelength around 530 nm. Has been observed that Chitosan in such quantities were not effective in stabilizing the AuNPs. (author)

  8. Stability and stabilization of linear systems with saturating actuators

    CERN Document Server

    Tarbouriech, Sophie; Gomes da Silva Jr, João Manoel; Queinnec, Isabelle

    2011-01-01

    Gives the reader an in-depth understanding of the phenomena caused by the more-or-less ubiquitous problem of actuator saturation. Proposes methods and algorithms designed to avoid, manage or overcome the effects of actuator saturation. Uses a state-space approach to ensure local and global stability of the systems considered. Compilation of fifteen years' worth of research results.

  9. Intrinsic stability of technical superconductors

    International Nuclear Information System (INIS)

    Veringa, H.J.

    1981-10-01

    For the operation of technical superconductors under high current density conditions, the superconducting wires composing high current cables should be intrinsically stabilized. In this report the various important stability criteria are derived and investigated on their validity. An experimental set up is made to check the occurrence of magnetic instabilities if the different applicable criteria are violated. It is found that the observed instabilities can be predicted on the basis of the model given in this report. Production of high current cables based upon composites made by the ECN technique seems to be possible. (Auth.)

  10. Theory of hot particle stability

    International Nuclear Information System (INIS)

    Berk, H.L.; Wong, H.V.; Tsang, K.T.

    1986-10-01

    The investigation of stabilization of hot particle drift reversed systems to low frequency modes has been extended to arbitrary hot beta, β/sub H/ for systems that have unfavorable field line curvature. We consider steep profile equilibria where the thickness of the pressure drop, Δ, is less than plasma radius, r/sub p/. The analysis describes layer modes which have mΔ/r/sub p/ 2/3. When robust stability conditions are fulfilled, the hot particles will have their axial bounce frequency less than their grad-B drift frequency. This allows for a low bounce frequency expansion to describe the axial dependence of the magnetic compressional response

  11. Hydraulic Stability of Accropode Armour

    DEFF Research Database (Denmark)

    Jensen, T.; Burcharth, H. F.; Frigaard, Peter

    The present report describes the hydraulic model tests of Accropode armour layers carried out at the Hydraulics Laboratory at Aalborg University from November 1995 through March 1996. The objective of the model tests was to investigate the hydraulic stability of Accropode armour layers...... with permeable core (crushed granite with a gradation of 5-8 mm). The outcome of this study is described in "Hydraulic Stability of Single-Layer Dolos and Accropode Armour Layers" by Christensen & Burcharth (1995). In January/February 1996, Research Assistant Thomas Jensen carried out a similar study...

  12. FINANCIAL STABILITY OF ISLAMIC AND CONVENTIONAL BANKS IN BANGLADESH: REVISITING STABILITY MEASURES AND ANALYZING STABILITY BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Md Enayet Hossain

    2018-03-01

    Full Text Available This study intends to assess the relative financial stability of Islamic banks in Bangladesh using three different Z-Scores as financial stability measures, based on a sample of 29 listed commercial banks (23 conventional and 6 Islamic in Bangladesh over the period 2005-2016. Apart from the existing measure of financial stability, Z-Score, the paper contributes to the literature by developing an alternative Z-Score based on bank’s loan portfolio infection ratio. We first use pair-wise comparison and find that Islamic banks are financially more stable in two stability measures i.e. Z-Score (based on Capital Adequacy Ratio and Z-Score (based on Infection Ratio. We then perform static (random effects and dynamic (GMM panel data analysis. By controlling for bank-specific, industry-specific and macroeconomic variables in the regressions, we find that Islamic banks are financially more stable in 2 panel regressions of Z-Score (based on Infection Ratio. We also find that the presence of Islamic banks increases the stability of all banks in the system including their conventional peers.

  13. Nuclear reactor core stabilizing arrangement

    International Nuclear Information System (INIS)

    Jabsen, F.S.

    1976-01-01

    A nuclear reactor core stabilizing arrangement is described wherein a plurality of actuators, disposed in a pattern laterally surrounding a group of elongated fuel assemblies, press against respective contiguous fuel assemblies on the periphery of the group to reduce the clearance between adjacent fuel assemblies thereby forming a more compacted, vibration resistant core structure. 7 claims, 4 drawing figures

  14. Homological stability of diffeomorphism groups

    DEFF Research Database (Denmark)

    Berglund, Alexander; Madsen, Ib Henning

    2013-01-01

    In this paper we prove a stability theorem for block diffeomorphisms of 2d -dimensional manifolds that are connected sums of S d ×S d . Combining this with a recent theorem of S. Galatius and O. Randal-Williams and Morlet’s lemma of disjunction, we determine the homology of the classifying space ...

  15. Material stabilization characterization management plan

    International Nuclear Information System (INIS)

    GIBSON, M.W.

    1999-01-01

    This document presents overall direction for characterization needs during stabilization of SNM at the Plutonium Finishing Plant (PFP). Technical issues for needed data and equipment are identified. Information on material categories and links to vulnerabilities are given. Comparison data on the material categories is discussed to assist in assessing the relative risks and desired processing priority

  16. Extrap L-1 experimental stability

    International Nuclear Information System (INIS)

    Brunsell, P.; Hellblom, G.; Karlsson, P.; Mazur, S.; Nordlund, P.; Scheffel, J.

    1990-01-01

    In the Extrap scheme a Z-pinch is stabilized by imposing a strongly inhomogeneous octupole magnetic field. This field is generated by four conductor rods, each carrying equal currents I v antiparallel to the plasma current I p itself. Theoretically, interchange stability is improved by the magnetic field, as well as long-wavelength kinks due to induced currents in the plasma and in the rods. Short wavelength kinks are, as in the 1-D pinch, stabilized by FLR and viscous-resistive effects. We have performed a set of experiments in the linear Extrap L-1 device (length 40 cm, plasma radius a 2 cm, rod distance 3 cm) in order to determine optimal performance in terms of confined current (5-20 kA) and stability during the discharge length (80 μs; of the order 100 Alfven times). In this paper we summarize our results from two types of experiments; with and without external axial magnetic field. The results are compared with theory in the final paragraph. (author) 5 figs

  17. Postmortem stability of Ebola virus.

    Science.gov (United States)

    Prescott, Joseph; Bushmaker, Trenton; Fischer, Robert; Miazgowicz, Kerri; Judson, Seth; Munster, Vincent J

    2015-05-01

    The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus-infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks.

  18. Numerical Computation of Detonation Stability

    KAUST Repository

    Kabanov, Dmitry

    2018-06-03

    Detonation is a supersonic mode of combustion that is modeled by a system of conservation laws of compressible fluid mechanics coupled with the equations describing thermodynamic and chemical properties of the fluid. Mathematically, these governing equations admit steady-state travelling-wave solutions consisting of a leading shock wave followed by a reaction zone. However, such solutions are often unstable to perturbations and rarely observed in laboratory experiments. The goal of this work is to study the stability of travelling-wave solutions of detonation models by the following novel approach. We linearize the governing equations about a base travelling-wave solution and solve the resultant linearized problem using high-order numerical methods. The results of these computations are postprocessed using dynamic mode decomposition to extract growth rates and frequencies of the perturbations and predict stability of travelling-wave solutions to infinitesimal perturbations. We apply this approach to two models based on the reactive Euler equations for perfect gases. For the first model with a one-step reaction mechanism, we find agreement of our results with the results of normal-mode analysis. For the second model with a two-step mechanism, we find that both types of admissible travelling-wave solutions exhibit the same stability spectra. Then we investigate the Fickett’s detonation analogue coupled with a particular reaction-rate expression. In addition to the linear stability analysis of this model, we demonstrate that it exhibits rich nonlinear dynamics with multiple bifurcations and chaotic behavior.

  19. STABILITY SYSTEMS VIA HURWITZ POLYNOMIALS

    Directory of Open Access Journals (Sweden)

    BALTAZAR AGUIRRE HERNÁNDEZ

    2017-01-01

    Full Text Available To analyze the stability of a linear system of differential equations  ẋ = Ax we can study the location of the roots of the characteristic polynomial pA(t associated with the matrix A. We present various criteria - algebraic and geometric - that help us to determine where the roots are located without calculating them directly.

  20. Stabilities of MHD rotational discontinuities

    International Nuclear Information System (INIS)

    Wang, S.

    1984-11-01

    In this paper, the stabilities of MHD rotational discontinuities are analyzed. The results show that the rotational discontinuities in an incompressible magnetofluid are not always stable with respect to infinitesimal perturbation. The instability condition in a special case is obtained. (author)

  1. Strategic delegation improves cartel stability

    NARCIS (Netherlands)

    Han, M.A.

    2010-01-01

    Fershtman and Judd (1987) and Sklivas (1987) show how strategic delegation in the one-shot Cournot game reduces firm profits. However, with infinitely repeated interaction, strategic delegation allows for an improvement in cartel stability compared to the infinitely repeated standard Cournot game,

  2. Stability of solubilized benzodiazepine receptors

    NARCIS (Netherlands)

    Janssen, M.J; Ensing, K; de Zeeuw, R.A

    1997-01-01

    According to the observations of other researchers, benzodiazepine receptors solubilized with sodium deoxycholate are unstable, but stability can be improved by exchanging deoxycholate for Triton X-100. In our experiments we conclude that the choice of detergent is not the restrictive factor for the

  3. Stability of charged thin shells

    International Nuclear Information System (INIS)

    Eiroa, Ernesto F.; Simeone, Claudio

    2011-01-01

    In this article we study the mechanical stability of spherically symmetric thin shells with charge, in Einstein-Maxwell and Einstein-Born-Infeld theories. We analyze linearized perturbations preserving the symmetry, for shells around vacuum and shells surrounding noncharged black holes.

  4. Sludge stabilization operability test report

    International Nuclear Information System (INIS)

    Lewis, W.S.

    1994-01-01

    Document provides the results of the Operability Test Procedure performed to test the operability of the HC-21C thermal stabilization process for sludge. The OTP assured all equipment functioned properly and established the baseline temperature profile for glovebox HC-21C

  5. Morphology stabilization of heterogeneous blends

    International Nuclear Information System (INIS)

    1980-01-01

    A heterogeneous elastomer blend is described, consisting of at least two elastomer components which are cross-linkable by irradiation and having a stabilized morphology formed by subjecting the blend to high energy radiation to a point from below to slightly above the gel dose of the blend. (author)

  6. Stability of Functional Differential Equations

    CERN Document Server

    Lemm, Jeffrey M

    1986-01-01

    This book provides an introduction to the structure and stability properties of solutions of functional differential equations. Numerous examples of applications (such as feedback systrems with aftereffect, two-reflector antennae, nuclear reactors, mathematical models in immunology, viscoelastic bodies, aeroautoelastic phenomena and so on) are considered in detail. The development is illustrated by numerous figures and tables.

  7. Hydrodynamic stability and stellar oscillations

    Indian Academy of Sciences (India)

    in 1961, is a standard reference on linear stability theory. It gives a ... perturbations about the equilibrium state are constants and the x, y, t dependence of the ..... anism was proposed for the formation of X-ray binaries in globular clusters. They.

  8. MHD stability of tandem mirrors

    International Nuclear Information System (INIS)

    Poulsen, P.; Molvik, A.; Shearer, J.

    1982-01-01

    The TMX-Upgrade experiment was described, and the manner in which various plasma parameters could be affected was discussed. The initial analysis of the MHD stability of the tandem mirror was also discussed, with emphasis on the negative tandem configuration

  9. Numerical Computation of Detonation Stability

    KAUST Repository

    Kabanov, Dmitry

    2018-01-01

    Then we investigate the Fickett’s detonation analogue coupled with a particular reaction-rate expression. In addition to the linear stability analysis of this model, we demonstrate that it exhibits rich nonlinear dynamics with multiple bifurcations and chaotic behavior.

  10. The Stability of Galaxy Disks

    NARCIS (Netherlands)

    Westfall, K. B.; Andersen, D. R.; Bershady, M. A.; Martinsson, T. P. K.; Swaters, R. A.; Verheijen, M. A. W.; Seigar, M.S.; Treuthardt, P.

    2014-01-01

    We calculate the stellar surface mass density (Σ*) and two-component (gas+stars) disk stability (QRW) for 25 late-type galaxies from the DiskMass Survey. These calculations are based on fits of a dynamical model to our ionized-gas and stellar kinematic data performed using a Markov Chain Monte Carlo

  11. Rudder roll stabilization for ships

    NARCIS (Netherlands)

    van Amerongen, J.; van der Klugt, P.G.M.; van Nauta lemke, H.R.

    1990-01-01

    This paper describes the design of an autopilot for rudder roll stabilization for ships. This autopilot uses the rudder not only for course keeping but also for reduction of the roll. The system has a series of properties which make the controller design far from straightforward: the process has

  12. Transverse stability of Kawahara solitons

    DEFF Research Database (Denmark)

    Karpman, V.I.

    1993-01-01

    The transverse stability of the planar solitons described by the fifth-order Korteweg-de Vries equation (Kawahara solitons) is studied. It is shown that the planar solitons are unstable with respect to bending if the coefficient at the fifth-derivative term is positive and stable if it is negative...

  13. Translational Influence on Messenger Stability

    DEFF Research Database (Denmark)

    Eriksen, Mette

    -termination to be a global phenomena in gene regulation. The influence of codon usage in the early coding region on messenger stability was examined, in order to establish how fast or slow the ribosome has to decode the sequence for it to protect the messenger from degradation. The experiments demonstrated that very fast...

  14. Stability of the plasma sheath

    International Nuclear Information System (INIS)

    Franklin, R.N.

    1979-12-01

    The stability of a collisionless sheath joined to a plasma in the presence of secondary emission of electrons from the sheath boundary is examined in the fluid approximation. Instability is unlikely to occur under floating conditions but if significant currents flow corresponding to increased wall-plasma potentials the system can go unstable. (author)

  15. Molecular laser stabilization for LISA

    Science.gov (United States)

    Halloin, Hubert; Acef, Ouali; Argence, Berengere; Jeannin, Olivier; Prat, Pierre; de Vismes, Eden; Plagnol, Eric; Brillet, Alain; Mondin, Linda; Berthon, Jacques; Turazza, Oscar

    2017-11-01

    The expected performance of LISA relies on two main technical challenges: the ability for the spacecrafts to precisely follow the free-flying masses and the outstanding precision of the phase shift measurement. This latter constraint requires frequency stabilized lasers and efficient numerical algorithms to account for the redundant, delayed noise propagation, thus cancelling laser phase noise by many orders of magnitude (TDI methods). Recently involved in the technical developments for LISA, the goal of our team at APC (France) is to contribute on these two subjects: frequency reference for laser stabilization and benchtop simulation of the interferometer. In the present design of LISA, two stages of laser stabilization are used (not accounting for the "post-processed" TDI algorithm): laser pre-stabilization on a frequency reference and lock on the ultra stable distance between spacecrafts (arm-locking). While the foreseen (and deeply studied) laser reference consists of a Fabry-Perot cavity, other techniques may be suitable for LISA or future metrology missions. In particular, locking to a molecular reference (namely iodine in the case of the LISA Nd:YAG laser) is an interesting alternative. It offers the required performance with very good long-term stability (absolute frequency reference) though the reference can be slightly tuned to account for arm-locking. This technique is currently being investigated by our team and optimized for LISA (compactness, vacuum compatibility, ease of use and initialization, etc.). A collaboration with a French laboratory (the SYRTE) had been started aiming to study a second improved technique consisting in inserting the iodine cell in a Fabry-Perot cavity. Ongoing results and prospects to increase the performance of the system are presented in the present article.

  16. Protein stability: a crystallographer’s perspective

    International Nuclear Information System (INIS)

    Deller, Marc C.; Kong, Leopold; Rupp, Bernhard

    2016-01-01

    An understanding of protein stability is essential for optimizing the expression, purification and crystallization of proteins. In this review, discussion will focus on factors affecting protein stability on a somewhat practical level, particularly from the view of a protein crystallographer. Protein stability is a topic of major interest for the biotechnology, pharmaceutical and food industries, in addition to being a daily consideration for academic researchers studying proteins. An understanding of protein stability is essential for optimizing the expression, purification, formulation, storage and structural studies of proteins. In this review, discussion will focus on factors affecting protein stability, on a somewhat practical level, particularly from the view of a protein crystallographer. The differences between protein conformational stability and protein compositional stability will be discussed, along with a brief introduction to key methods useful for analyzing protein stability. Finally, tactics for addressing protein-stability issues during protein expression, purification and crystallization will be discussed

  17. Protein stability: a crystallographer’s perspective

    Energy Technology Data Exchange (ETDEWEB)

    Deller, Marc C., E-mail: mdeller@stanford.edu [Stanford University, Shriram Center, 443 Via Ortega, Room 097, MC5082, Stanford, CA 94305-4125 (United States); Kong, Leopold [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Building 8, Room 1A03, 8 Center Drive, Bethesda, MD 20814 (United States); Rupp, Bernhard [k.-k. Hofkristallamt, 91 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

    2016-01-26

    An understanding of protein stability is essential for optimizing the expression, purification and crystallization of proteins. In this review, discussion will focus on factors affecting protein stability on a somewhat practical level, particularly from the view of a protein crystallographer. Protein stability is a topic of major interest for the biotechnology, pharmaceutical and food industries, in addition to being a daily consideration for academic researchers studying proteins. An understanding of protein stability is essential for optimizing the expression, purification, formulation, storage and structural studies of proteins. In this review, discussion will focus on factors affecting protein stability, on a somewhat practical level, particularly from the view of a protein crystallographer. The differences between protein conformational stability and protein compositional stability will be discussed, along with a brief introduction to key methods useful for analyzing protein stability. Finally, tactics for addressing protein-stability issues during protein expression, purification and crystallization will be discussed.

  18. Electrochemical stabilization of clayey ground

    Science.gov (United States)

    Rzhanitzin, B.A.; Sokoloff, V.P.

    1947-01-01

    Recently developed new methods of stabilization of weak grounds (e.g. the silicate treatment) are based on injection of chemical solutions into the ground. Such methods are applicable accordingly only to the kinds of ground that have the coefficient of filtration higher than 2 meters per 24 hours and permit penetration of the chemical solutions under pressure. This limit, however, as it is shown by our experience in construction, excludes a numerous and an important class of grounds, stabilization of which is indispensable in many instances. For example, digging of trenches and pits in clayey, silty, or sandy ground shows that all these types act like typical "floaters" (sluds? -S) in the presence of the ground water pressure. There were several instances in the canalization of the city of Moskow where the laying of trenches below the ground water level has led to extreme difficulties with clayey and silty ground. Similar examples could be cited in mining, engineering hydrology, and railroad construction. For these reasons, the development of methods of stabilizing such difficult types of ground has become an urgent problem of our day. In 1936, the author began his investigations, at the ground Stabilization Laboratory of VODGEO Institute, with direct electrical current as the means of stabilization of grounds. Experiments had shown that a large number of clayey types, following passage of direct electrical current, undergoes a transformation of its physico-chemical properties. It was established that the (apparent -S) density of the ground is substantially increased in consequence of the application of direct electrical current. The ground loses also its capacity to swell and to soften in water. Later, after a more detailed study of the physico-chemical mechanism of the electrical stabilization, it became possible to develop the method so as to make it applicable to sandy and silty as well as to clayey ground. By this time (1941, S.), the method has already been

  19. Interfacial stability with mass and heat transfer

    International Nuclear Information System (INIS)

    Hsieh, D.Y.

    1977-07-01

    A simplified formulation is presented to deal with interfacial stability problems with mass and heat transfer. For Rayleigh-Taylor stability problems of a liquid-vapor system, it was found that the effect of mass and heat transfer tends to enhance the stability of the system when the vapor is hotter than the liquid, although the classical stability criterion is still valid. For Kelvin-Holmholtz stability problems, however, the classical stability criterion was found to be modified substantially due to the effect of mass and heat transfer

  20. Straightening: existence, uniqueness and stability

    Science.gov (United States)

    Destrade, M.; Ogden, R. W.; Sgura, I.; Vergori, L.

    2014-01-01

    One of the least studied universal deformations of incompressible nonlinear elasticity, namely the straightening of a sector of a circular cylinder into a rectangular block, is revisited here and, in particular, issues of existence and stability are addressed. Particular attention is paid to the system of forces required to sustain the large static deformation, including by the application of end couples. The influence of geometric parameters and constitutive models on the appearance of wrinkles on the compressed face of the block is also studied. Different numerical methods for solving the incremental stability problem are compared and it is found that the impedance matrix method, based on the resolution of a matrix Riccati differential equation, is the more precise. PMID:24711723

  1. Enzyme stabilization for pesticide degradation

    Energy Technology Data Exchange (ETDEWEB)

    Rivers, D.B.; Frazer, F.R. III; Mason, D.W.; Tice, T.R.

    1988-01-01

    Enzymes offer inherent advantages and limitations as active components of formulations used to decontaminate soil and equipment contaminated with toxic materials such as pesticides. Because of the catalytic nature of enzymes, each molecule of enzyme has the potential to destroy countless molecules of a contaminating toxic compound. This degradation takes place under mild environmental conditions of pH, temperature, pressure, and solvent. The basic limitation of enzymes is their degree of stability during storage and application conditions. Stabilizing methods such as the use of additives, covalent crosslinking, covalent attachment, gel entrapment, and microencapsulation have been directed developing an enzyme preparation that is stable under extremes of pH, temperature, and exposure to organic solvents. Initial studies were conducted using the model enzymes subtilisin and horseradish peroxidase.

  2. Oxidative stability of marine phospholipids

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline Pascale

    Many studies have shown that marine phospholipids (MPL) provide more advantages than fish oil. They have better bioavailability, better resistance towards oxidation and higher content of eicosapentaenoic acids (EPA) and docosahexaenoic acids (DHA) than oily triglycerides (fish oil). The objective...... of this study is to investigate the oxidative and hydrolytic stability of MPL. In addition, this study also investigates the effect of chemical composition of MPL and Maillard reaction (interaction between lipids oxidation products with the residue of amino acids) on MPL emulsions’ stability. Firstly, MPL were...... was further investigated through measurement of secondary volatile compounds by Solid Phase Microextraction at several time intervals. On the other hand, the Maillard reaction was investigated through the measurement of color changes and pyrrole content before and after 32 days storage. Preliminary result...

  3. Stability of Boolean multilevel networks.

    Science.gov (United States)

    Cozzo, Emanuele; Arenas, Alex; Moreno, Yamir

    2012-09-01

    The study of the interplay between the structure and dynamics of complex multilevel systems is a pressing challenge nowadays. In this paper, we use a semiannealed approximation to study the stability properties of random Boolean networks in multiplex (multilayered) graphs. Our main finding is that the multilevel structure provides a mechanism for the stabilization of the dynamics of the whole system even when individual layers work on the chaotic regime, therefore identifying new ways of feedback between the structure and the dynamics of these systems. Our results point out the need for a conceptual transition from the physics of single-layered networks to the physics of multiplex networks. Finally, the fact that the coupling modifies the phase diagram and the critical conditions of the isolated layers suggests that interdependency can be used as a control mechanism.

  4. FINANCIAL STABILITY - A THEORETICAL APPROACH

    Directory of Open Access Journals (Sweden)

    Maria Vasilescu

    2012-03-01

    Full Text Available Central banks have become poles of stability and decisive factors of globalization. Financialstability represents a national issue, a public asset, that requires both an intervention of public judicious authoritiesand their cooperation with private sector. Given the integration of financial markets during the last decades in bothdeveloped and developing countries, as direct result of globalization, liberalization and deregulation processes, andthe high degree of innovation they felt over time, a shift in market participants’ perceptions on the importance ofstable financial systems in economic growth arose. The global context characterized by the interdependence ofmarkets and institutions, emergence of new techniques and instruments, increasing international capital flowsstressed the new meanings of the analysis of financial stability.

  5. Macroprudential policy and financial stability

    Directory of Open Access Journals (Sweden)

    Bogdan CHIRIACESCU

    2013-02-01

    Full Text Available This paper tries a conceptual framing of the issue of financial stability in economic theory and also to identify solutions to address episodes of financial instability. An essential reference is Minsky's financial instability hypothesis, which argues that a fundamental feature of the financial system is that it swings between robustness and fragility and these pendulum swings are an integral part of the process that generates the business cycle. Studies show that the effects of banking crises on economic activity are important both in magnitude and duration. Recently, macroprudential policy stood out as a central pillar in promoting financial stability in a broad sense. Regarding specific objectives of macroprudential policy, the prevalent vision refers to limiting systemic risk and macroeconomic costs of financial crises, but there are also important nuances.

  6. Bifurcation routes and economic stability

    Czech Academy of Sciences Publication Activity Database

    Vošvrda, Miloslav

    2001-01-01

    Roč. 8, č. 14 (2001), s. 43-59 ISSN 1212-074X R&D Projects: GA ČR GA402/00/0439; GA ČR GA402/01/0034; GA ČR GA402/01/0539 Institutional research plan: AV0Z1075907 Keywords : macroeconomic stability * foreign investment phenomenon * the Hopf bifurcation Subject RIV: AH - Economics

  7. Water-stabilized plasma generators

    Czech Academy of Sciences Publication Activity Database

    Hrabovský, Milan

    1998-01-01

    Roč. 70, č. 6 (1998), s. 1157-1162 ISSN 0033-4545 R&D Projects: GA ČR GA102/95/0592; GA ČR GV106/96/K245 Institutional research plan: CEZ:AV0Z2043910 Keywords : thermal plasma, plasma torch, water-stabilized plasma Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.677, year: 1998

  8. Stabilization of superconducting dry solenoids

    International Nuclear Information System (INIS)

    Urata, M.; Maeda, H.

    1989-01-01

    Premature quenches in superconducting solenoids, wound with Formvar coated NbTi conductors, have been studied. Some model coils were tested wound with various winding tensions. The experimental results are discussed considering the calculated stress distribution for coil winding, cool-down to liquid helium temperature, and energization at 4.2 K. /Some mechanisms of premature quenches are classified by the winding tension. Some stabilization methods are presented based on these quench mechanisms

  9. Mao-Gilles Stabilization Algorithm

    OpenAIRE

    Jérôme Gilles

    2013-01-01

    Originally, the Mao-Gilles stabilization algorithm was designed to compensate the non-rigid deformations due to atmospheric turbulence. Given a sequence of frames affected by atmospheric turbulence, the algorithm uses a variational model combining optical flow and regularization to characterize the static observed scene. The optimization problem is solved by Bregman Iteration and the operator splitting method. The algorithm is simple, efficient, and can be easily generalized for different sce...

  10. Mao-Gilles Stabilization Algorithm

    Directory of Open Access Journals (Sweden)

    Jérôme Gilles

    2013-07-01

    Full Text Available Originally, the Mao-Gilles stabilization algorithm was designed to compensate the non-rigid deformations due to atmospheric turbulence. Given a sequence of frames affected by atmospheric turbulence, the algorithm uses a variational model combining optical flow and regularization to characterize the static observed scene. The optimization problem is solved by Bregman Iteration and the operator splitting method. The algorithm is simple, efficient, and can be easily generalized for different scenarios involving non-rigid deformations.

  11. PATRIMONIAL ANALYSIS OF FINANCIAL STABILITY

    Directory of Open Access Journals (Sweden)

    GABRIELA CORINA SLUSARIUC

    2011-01-01

    Full Text Available Patrimonial analysis of financial stability is realized with the help of some indicator determined on the balance: working capital; required working capital and net treasury. These indicators are determined and presented in evolution at two companies with different situations, and there are given conclusions and suggestions concerning achieving and maintaining the financial equilibrium or initiating corrective measures in time, before the imbalance would take irrecoverable forms.

  12. Morocco; Financial System Stability Assessment

    OpenAIRE

    International Monetary Fund

    2003-01-01

    The Financial System Stability Assessment of Morocco reviews the reform program that is aimed at establishing a modern, market-oriented financial system that optimizes the mobilization of savings and the allocation of financial resources. It reviews the modernization of the banking sector and the development of competition within the sector, development of financial markets, and removal of constraints on financial system activity. It also provides reports on the Observance of Standards and Co...

  13. Capacity Markets and Market Stability

    International Nuclear Information System (INIS)

    Stauffer, Hoff

    2006-01-01

    The good news is that market stability can be achieved through a combination of longer-term contracts, auctions for far enough in the future to permit new entry, a capacity management system, and a demand curve. The bad news is that if and when stable capacity markets are designed, the markets may seem to be relatively close to where we started - with integrated resource planning. Market ideologues will find this anathema. (author)

  14. political stability and tax power

    OpenAIRE

    Estrada, Fernando

    2013-01-01

    The present study is, in particular, an attempt to test the relationship between tax level and political stability by using some economic control variables and to see the relationship among government effectiveness, corruption, and GDP. For the purpose, we used the Vector Autoregression (VAR) approach in the panel framework, using a country-level panel data from 59 countries for the period 2002 to 2008. The salient features of this model are: (a) simplicity is based on a limited number of var...

  15. Stabilization of gasoline from shale

    Energy Technology Data Exchange (ETDEWEB)

    Benedetti, L

    1929-03-14

    A process is described of stabilizing gasoline from shale, consisting in treating by agitating the gasoline freshly distilled from shale oil with 1.5 percent of its weight of sulfuric acid diluted to more than 10 times its volume, after which separating the pyridine, then treating by agitating with sulfuric acid which treatment separates the unsaturated hydrocarbons and finally treating by agitating with 1.5 percent of its weight of saturated caustic soda solution and washing with water.

  16. Furfural stability in various conditions

    OpenAIRE

    Oreiro Muzas, Olaya

    2011-01-01

    The topic of this thesis is the study of the furfural stability to determine the influence of some conditions in furfural degradation. The aim of the study is to decrease furfural degradation and thus improve furfural yield in furfural production. The thesis consists of a literature review and laboratory experiments. Attention has been paid to the furfural description and properties as well as the background of the research and traditional methods to produce furfural. In the experiments, w...

  17. Thermal stability of titanate nanotubes

    Czech Academy of Sciences Publication Activity Database

    Králová, Daniela; Kužel, R.; Kovářová, Jana; Dybal, Jiří; Šlouf, Miroslav

    2009-01-01

    Roč. 16, 2a (2009), s. 41-43 ISSN 1211-5894. [Struktura - Colloquium of Czech and Slovak Crystallographic Association. Hluboká nad Vltavou, 22.06.2009-25.06.2009] R&D Projects: GA ČR GA203/07/0717; GA AV ČR KAN200520704 Institutional research plan: CEZ:AV0Z40500505 Keywords : titanate nanotubes * thermal stability Subject RIV: CD - Macromolecular Chemistry

  18. Nigeria; Financial Sector Stability Assessment

    OpenAIRE

    International Monetary Fund

    2013-01-01

    This Financial Sector Stability Assessment on Nigeria discusses the macroeconomic performance and structure of the financial system. Although Nigerian economy experienced both domestic and external shocks in recent years, the economy continued to grow rapidly, achieving more than 7 percent growth each year since 2009. The performance of financial institutions has begun to improve, though some of the emergency anti-crisis measures continue to be in place. However, the regulatory and supervisor...

  19. Canada; Financial Sector Stability Assessment

    OpenAIRE

    International Monetary Fund

    2014-01-01

    This report discusses key findings of the Financial Sector Stability Assessment on Canada. Canada’s financial system successfully navigated the global financial crisis, and stress tests suggest that major financial institutions would continue to be resilient to credit, liquidity, and contagion risks arising from a severe stress scenario. Elevated housing prices and high household debt remain an area of concern, though targeted prudential and macroprudential measures are proving to be effectiv...

  20. Stability diagram of colliding beams

    CERN Document Server

    Buffat, X; Mounet, N; Pieloni, T

    2014-01-01

    The effect of the beam-beam interactions on the stability of impedance mode is discussed. The detuning is evaluated by the means of single particle tracking in arbitrarily complex collision configurations, including lattice non-linearities, and used to numerically evaluate the dispersion integral. This approach also allows the effect of non-Gaussian distributions to be considered. Distributions modified by the action of external noise are discussed.