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Sample records for topical nicotinamide modulates

  1. Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide

    International Nuclear Information System (INIS)

    Gensler, H.L.

    1997-01-01

    Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosuppression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We previously showed a correlation between the inhibition of photoimmunosuppression and prevention of photocarcinogenesis by dl-alpha-tocopherol, tannic acid, or alpha-difluoro methylornithine. The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 micromoles of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppresion. UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximatety 6.2 x 10(5) J/m(2) in the passive transfer assays and 1.09 x 10(6) J/m(2) in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation

  2. A case of vesicular cutaneous lupus erythematosus in a Border collie successfully treated with topical tacrolimus and nicotinamide-tetracycline.

    Science.gov (United States)

    Lehner, Georg M; Linek, Monika

    2013-12-01

    Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period. © 2013 ESVD and ACVD.

  3. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

    Science.gov (United States)

    Ratajczak, Joanna; Joffraud, Magali; Trammell, Samuel A J; Ras, Rosa; Canela, Núria; Boutant, Marie; Kulkarni, Sameer S; Rodrigues, Marcelo; Redpath, Philip; Migaud, Marie E; Auwerx, Johan; Yanes, Oscar; Brenner, Charles; Cantó, Carles

    2016-10-11

    NAD + is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD + precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD + synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD + synthesis from other NAD + precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD + . Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD + synthesis, explaining the overlapping metabolic effects observed with the two compounds.

  4. Nicotinamide induces mitochondrial-mediated apoptosis through oxidative stress in human cervical cancer HeLa cells.

    Science.gov (United States)

    Feng, Yi; Wang, Yonghua; Jiang, Chengrui; Fang, Zishui; Zhang, Zhiqiang; Lin, Xiaoying; Sun, Liwei; Jiang, Weiying

    2017-07-15

    Nicotinamide participates in energy metabolism and influences cellular redox status and modulates multiple pathways related with both cellular survival and death. Recent studies have shown that it induced proliferation inhibition and apoptosis in many cancer cells. However, little is known about the effects of nicotinamide on human cervical cancer cells. We aimed to evaluate the effects of the indicated concentrations nicotinamide on cell proliferation, apoptosis and redox-related parameters in HeLa cells and investigated the apoptotic mechanism. After the treatment of the indicated concentrations nicotinamide, HeLa cell proliferation was evaluated by the CCK-8 assay and the production of ROS (reactive oxygen species) was measured using 2',7'-Dichlorofluorescin diacetate. The apoptotic effect was confirmed by observing the cellular and nuclear morphologies with fluorescence microscope and apoptotic rate of HeLa cell apoptosis was measured by flow cytometry using Annexin-V method. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured the expression of apoptosis related genes using qRT-PCR and immunoblotting. Nicotinamide restrained the HeLa cell proliferation and significantly increased the accumulation of ROS and depletion of GSH at relatively high concentrations. Furthermore, nicotinamide promoted HeLa cell apoptosis via the intrinsic mitochondrial apoptotic pathway. Our study revealed that nicotinamide induced the apoptosis through oxidative stress and intrinsic mitochondrial apoptotic pathways in HeLa cell. The results emerge that nicotinamide may be an inexpensive, safe and promising therapeutic agent or a neoadjuvant chemotherapy for cervical cancer patients, as well useful to find new drugs for cervical cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Nicotinamide extends replicative lifespan of human cells.

    Science.gov (United States)

    Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

    2006-10-01

    We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

  6. Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans.

    Science.gov (United States)

    Vrablik, Tracy L; Huang, Li; Lange, Stephanie E; Hanna-Rose, Wendy

    2009-11-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a central molecule in cellular metabolism and an obligate co-substrate for NAD(+)-consuming enzymes, which regulate key biological processes such as longevity and stress responses. Although NAD(+) biosynthesis has been intensely studied, little analysis has been done in developmental models. We have uncovered novel developmental roles for a nicotinamidase (PNC), the first enzyme in the NAD(+) salvage pathway of invertebrates. Mutations in the Caenorhabditis elegans nicotinamidase PNC-1 cause developmental and functional defects in the reproductive system; the development of the gonad is delayed, four uterine cells die by necrosis and the mutant animals are egg-laying defective. The temporal delay in gonad development results from depletion of the salvage pathway product NAD(+), whereas the uv1 cell necrosis and egg-laying defects result from accumulation of the substrate nicotinamide. Thus, regulation of both substrate and product level is key to the biological activity of PNC-1. We also find that diet probably affects the levels of these metabolites, as it affects phenotypes. Finally, we identified a secreted isoform of PNC-1 and confirmed its extracellular localization and functional activity in vivo. We demonstrate that nicotinamide phosphoribosyltransferase (Nampt), the equivalent enzyme in nicotinamide recycling to NAD(+) in vertebrates, can functionally substitute for PNC-1. As Nampt is also secreted, we postulate an evolutionarily conserved extracellular role for NAD(+) biosynthetic enzymes during development and physiology.

  7. Nicotinamide pharmacokinetics in humans and mice

    International Nuclear Information System (INIS)

    Horsman, M.R.; Hoyer, M.; Overgaard, J.; Honess, D.J.; Dennis, A.F.

    1993-01-01

    Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed to female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half-lives were not dose-dependent. The average peak plasma concentration of 160 μg/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours. (author)

  8. Evaluation of nicotinamide microemulsion on the skin penetration enhancement.

    Science.gov (United States)

    Boonme, Prapaporn; Boonthongchuay, Chalida; Wongpoowarak, Wibul; Amnuaikit, Thanaporn

    2016-01-01

    This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4 °C and room temperature (≈30 ± 2 °C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.

  9. 21 CFR 573.625 - Menadione nicotinamide bisulfite.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Menadione nicotinamide bisulfite. 573.625 Section 573.625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... ANIMALS Food Additive Listing § 573.625 Menadione nicotinamide bisulfite. The food additive may be safely...

  10. Nicotinamide exacerbates hypoxemia in ventilator-induced lung injury independent of neutrophil infiltration.

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    Heather D Jones

    Full Text Available Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3 directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury.We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε.Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice.Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the

  11. Nicotinamide -Methyltransferase in Health and Cancer

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    David B Ramsden

    2017-06-01

    Full Text Available Over the past decade, the roles of nicotinamide N -methyltransferase and its product 1-methyl nicotinamide have emerged from playing merely minor roles in phase 2 xenobiotic metabolism as actors in some of the most important scenes of human life. In this review, the structures of the gene, messenger RNA, and protein are discussed, together with the role of the enzyme in many of the common cancers that afflict people today.

  12. The NAD(+) precursor nicotinamide riboside decreases exercise performance in rats.

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    Kourtzidis, Ioannis A; Stoupas, Andreas T; Gioris, Ioannis S; Veskoukis, Aristidis S; Margaritelis, Nikos V; Tsantarliotou, Maria; Taitzoglou, Ioannis; Vrabas, Ioannis S; Paschalis, Vassilis; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-01-01

    Nicotinamide adenine dinucleotide (NAD(+)) and its phosphorylated form (NADP(+)) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD(+) and NADP(+) precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide riboside administration (an NAD(+) precursor) affects exercise performance. Eighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide riboside at a dose of 300 mg/kg body weight/day for 21 days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test. The nicotinamide riboside group showed a tendency towards worse physical performance by 35 % compared to the control group at the final 10 % load (94 ± 53 s for the nicotinamide riboside group and 145 ± 59 s for the control group; P = 0.071). Our results do not confirm the previously reported ergogenic effect of nicotinamide riboside. The potentially negative effect of nicotinamide riboside administration on physical performance may be attributed to the pleiotropic metabolic and redox properties of NAD(+) and NADP(+).

  13. Nicotinamide riboside kinase structures reveal new pathways to NAD+.

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    Wolfram Tempel

    2007-10-01

    Full Text Available The eukaryotic nicotinamide riboside kinase (Nrk pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+ by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

  14. Structural Basis of Substrate Recognition in Human Nicotinamide N-Methyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Yi; Sartini, Davide; Pozzi, Valentina; Wilk, Dennis; Emanuelli, Monica; Yee, Vivien C. (Case Western); (Politecnica Valencia)

    2012-05-02

    Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide, pyridines, and other analogues using S-adenosyl-L-methionine as donor. NNMT plays a significant role in the regulation of metabolic pathways and is expressed at markedly high levels in several kinds of cancers, presenting it as a potential molecular target for cancer therapy. We have determined the crystal structure of human NNMT as a ternary complex bound to both the demethylated donor S-adenosyl-L-homocysteine and the acceptor substrate nicotinamide, to 2.7 {angstrom} resolution. These studies reveal the structural basis for nicotinamide binding and highlight several residues in the active site which may play roles in nicotinamide recognition and NNMT catalysis. The functional importance of these residues was probed by mutagenesis. Of three residues near the nicotinamide's amide group, substitution of S201 and S213 had no effect on enzyme activity while replacement of D197 dramatically decreased activity. Substitutions of Y20, whose side chain hydroxyl interacts with both the nicotinamide aromatic ring and AdoHcy carboxylate, also compromised activity. Enzyme kinetics analysis revealed k{sub cat}/K{sub m} decreases of 2-3 orders of magnitude for the D197A and Y20A mutants, confirming the functional importance of these active site residues. The mutants exhibited substantially increased K{sub m} for both NCA and AdoMet and modestly decreased k{sub cat}. MD simulations revealed long-range conformational effects which provide an explanation for the large increase in K{sub m}(AdoMet) for the D197A mutant, which interacts directly only with nicotinamide in the ternary complex crystal structure.

  15. 4-Hydroxy-3-methoxybenzaldehyde–nicotinamide (1/1

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    Fiona N.-F. How

    2011-12-01

    Full Text Available In the title compound, C6H6N2O·C8H8O3, an equimolar co-crystal of nicotinamide and vanillin, the aromatic ring and the amide fragment of the nicotinamide molecule make a dihedral angle of 32.6 (2°. The vanillin molecule is almost planar, with an r.m.s. deviation for all non-H atoms of 0.0094 Å. The vaniline and nicotinamide aromatic rings are nearly coplanar, the dihedral angle between them being 3.20 (9°. In the crystal, the two components are linked through N—H...O and O—H...N hydrogen bonds into chains along the a axis. The chains are connected via C—H...O interactions, forming a three-dimensional polymeric structure.

  16. Characterization of CobB kinetics and inhibition by nicotinamide.

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    Julia Gallego-Jara

    Full Text Available Lysine acetylation has emerged as a global protein regulation system in all domains of life. Sirtuins, or Sir2-like enzymes, are a family of histone deacetylases characterized by their employing NAD+ as a co-substrate. Sirtuins can deacetylate several acetylated proteins, but a consensus substrate recognition sequence has not yet been established. Product inhibition of many eukaryotic sirtuins by nicotinamide and its analogues has been studied in vitro due to their potential role as anticancer agents. In this work, the kinetics of CobB, the main Escherichia coli deacetylase, have been characterized. To our knowledge, this is the first kinetic characterization of a sirtuin employing a fully acetylated and natively folded protein as a substrate. CobB deacetylated several acetyl-CoA synthetase acetylated lysines with a single kinetic rate. In addition, in vitro nicotinamide inhibition of CobB has been characterized, and the intracellular nicotinamide concentrations have been determined under different growth conditions. The results suggest that nicotinamide can act as a CobB regulator in vivo. A nicotinamidase deletion strain was thus phenotypically characterized, and it behaved similarly to the ΔcobB strain. The results of this work demonstrate the potential regulatory role of the nicotinamide metabolite in vivo.

  17. Characterization of CobB kinetics and inhibition by nicotinamide.

    Science.gov (United States)

    Gallego-Jara, Julia; Écija Conesa, Ana; de Diego Puente, Teresa; Lozano Terol, Gema; Cánovas Díaz, Manuel

    2017-01-01

    Lysine acetylation has emerged as a global protein regulation system in all domains of life. Sirtuins, or Sir2-like enzymes, are a family of histone deacetylases characterized by their employing NAD+ as a co-substrate. Sirtuins can deacetylate several acetylated proteins, but a consensus substrate recognition sequence has not yet been established. Product inhibition of many eukaryotic sirtuins by nicotinamide and its analogues has been studied in vitro due to their potential role as anticancer agents. In this work, the kinetics of CobB, the main Escherichia coli deacetylase, have been characterized. To our knowledge, this is the first kinetic characterization of a sirtuin employing a fully acetylated and natively folded protein as a substrate. CobB deacetylated several acetyl-CoA synthetase acetylated lysines with a single kinetic rate. In addition, in vitro nicotinamide inhibition of CobB has been characterized, and the intracellular nicotinamide concentrations have been determined under different growth conditions. The results suggest that nicotinamide can act as a CobB regulator in vivo. A nicotinamidase deletion strain was thus phenotypically characterized, and it behaved similarly to the ΔcobB strain. The results of this work demonstrate the potential regulatory role of the nicotinamide metabolite in vivo.

  18. pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

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    Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

    2018-05-04

    The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

  19. Cyclic voltammetric response of nicotinic acid and nicotinamide on a polycrystalline gold electrode

    International Nuclear Information System (INIS)

    Wang Xiaoxia; Yang Nianjun; Wan Qijin

    2006-01-01

    The oxidation of nicotinic acid and nicotinamide on a polycrystalline gold electrode occurred at almost same potentials but their reduction did at different peak potentials. The redox reaction mechanisms of nicotinic acid and nicotinamide were rationalized by the formation/disappearance of the new nitrogen-oxygen bonds in the pyridine rings by means of cyclic voltammetry and bulk electrolysis. The anodic currents of nicotinic acid and nicotinamide were controlled by diffusion, while the cathodic ones by adsorption. The difference in the cathodic peak potentials of nicotinic acid and nicotinamide on the polycrystalline gold electrode is attributed to the effect of the electron densities of remote substituents on the pyridine rings. The cathodic peak currents at about 0.20 V were linear with their concentrations in the range of 2.4 mM to 2.7 μM and 2.4 mM to 3.3 μM with detection limits of 0.27 and 0.33 μM for nicotinic acid and nicotinamide, respectively. Voltammetry was then adopted for the selective monitoring the content of nicotinic acid and nicotinamide in pharmaceuticals

  20. Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

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    Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

    2009-06-19

    NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

  1. European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Gale, E A M; Bingley, P J; Emmett, C L

    2004-01-01

    with a pseudorandom number generator and we used size balanced blocks of four and stratified by age and national group. Primary outcome was development of diabetes, as defined by WHO criteria. Analysis was done on an intention-to-treat basis. FINDINGS: There was no difference in the development of diabetes between...... secretion. INTERPRETATION: Large-scale controlled trials of interventions designed to prevent the onset of type 1 diabetes are feasible, but nicotinamide was ineffective at the dose we used.......BACKGROUND: Results of studies in animals and human beings suggest that type 1 diabetes is preventable. Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair enzyme poly-ADP-ribose polymerase and prevention of beta-cell NAD depletion. We aimed...

  2. Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

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    Adrian C Williams

    2017-04-01

    Full Text Available Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

  3. Deracemization of Axially Chiral Nicotinamides by Dynamic Salt Formation with Enantiopure Dibenzoyltartaric Acid (DBTA

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    Fumitoshi Yagishita

    2013-11-01

    Full Text Available Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of enantiopure DBTA as a chiral auxiliary. The axial chirality generated by dynamic salt formation was retained for a long period after dissolving the chiral salt in solution even after removal of the chiral acid. The rate of racemization of nicotinamides could be controlled based on the temperature and solvent properties, and that of the salts was prolonged compared to free nicotinamides, as the molecular structure of the pyridinium ion in the salts was different from that of acid-free nicotinamides.

  4. Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

    International Nuclear Information System (INIS)

    Vaca, Pilar; Berna, Genoveva; Araujo, Raquel; Carneiro, Everardo M.; Bedoya, Francisco J.; Soria, Bernat; Martin, Franz

    2008-01-01

    The poly(ADP-ribose) polymerase (PARP) inhibitor, nicotinamide, induces differentiation and maturation of fetal pancreatic cells. In addition, we have previously reported evidence that nicotinamide increases the insulin content of cells differentiated from embryonic stem (ES) cells, but the possibility of nicotinamide acting as a differentiating agent on its own has never been completely explored. Islet cell differentiation was studied by: (i) X-gal staining after neomycin selection; (ii) BrdU studies; (iii) single and double immunohistochemistry for insulin, C-peptide and Glut-2; (iv) insulin and C-peptide content and secretion assays; and (v) transplantation of differentiated cells, under the kidney capsule, into streptozotocin (STZ)-diabetic mice. Here we show that undifferentiated mouse ES cells treated with nicotinamide: (i) showed an 80% decrease in cell proliferation; (ii) co-expressed insulin, C-peptide and Glut-2; (iii) had values of insulin and C-peptide corresponding to 10% of normal mouse islets; (iv) released insulin and C-peptide in response to stimulatory glucose concentrations; and (v) after transplantation into diabetic mice, normalized blood glucose levels over 7 weeks. Our data indicate that nicotinamide decreases ES cell proliferation and induces differentiation into insulin-secreting cells. Both aspects are very important when thinking about cell therapy for the treatment of diabetes based on ES cells

  5. Radiotherapy and chemotherapy with or without carbogen and nicotinamide in inoperable biopsy-proven glioblastoma multiforme

    International Nuclear Information System (INIS)

    Simon, Jean-Marc; Noeel, Georges; Chiras, Jacques; Khe, H.-X.; Delattre, Jean-Yves; Baillet, Francois; Mazeron, Jean-Jacques

    2003-01-01

    Background: Nicotinamide and carbogen have been shown to enhance the radiation effect in tumour models. Purpose: Prospective evaluation of the toxicity and efficacy of carbogen and nicotinamide with external beam radiotherapy in the management of inoperable glioblastoma. Patients and methods: From April 1995 to December 1997, 33 patients with inoperable biopsy-proven glioblastoma multiforme (GBM) were enrolled in a phase II trial, to undergo radiotherapy (59.4 Gy in 1.8 Gy/fraction), intra-arterial cerebral chemotherapy (ACNU 100 mg/m 2 , three cycles), carbogen breathing (15 l/min), and nicotinamide (85 mg/kg). This experimental group was compared to a control group of 38 patients with inoperable GBM treated with radiotherapy and three cycles of nitrosourea-based chemotherapy from January 1990 to March 1995, in our institution. Results: In the experimental group, carbogen breathing was well tolerated, but only 51.5% of patients completed daily nicotinamide over the 6.5-week treatment period. Nausea and vomiting were the most frequent side effects of nicotinamide. No significant difference in overall survival was observed among the two treatment groups: median survival times were 36.7 and 35.3 weeks for patients treated with carbogen and nicotinamide, and for those treated in the control group, respectively. Conclusion: The association of carbogen and nicotinamide with radiotherapy is feasible, but tolerable only in 51.5% of patients with GBM. Carbogen and nicotinamide did not appear to modify the evolution of glioblastoma

  6. Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma.

    Science.gov (United States)

    Williams, Pete A; Harder, Jeffrey M; John, Simon W M

    2017-12-01

    Mitochondrial dysfunction may be an important, if not essential, component of human glaucoma. Using transcriptomics followed by molecular and neurobiological techniques, we have recently demonstrated that mitochondrial dysfunction within retinal ganglion cells is an early feature in the DBA/2J mouse model of inherited glaucoma. Guided by these findings, we discovered that the retinal level of nicotinamide adenine dinucleotide (NAD, a key molecule for mitochondrial health) declines in an age-dependent manner. We hypothesized that this decline in NAD renders retinal ganglion cells susceptible to damage during periods of elevated intraocular pressure. To replete NAD levels in this glaucoma, we administered nicotinamide (the amide of vitamin B3). At the lowest dose tested, nicotinamide robustly protected from glaucoma (~70% of eyes had no detectable glaucomatous neurodegeneration). At this dose, nicotinamide had no influence on intraocular pressure and so its effect was neuroprotective. At the highest dose tested, 93% of eyes had no detectable glaucoma. This represents a ~10-fold decrease in the risk of developing glaucoma. At this dose, intraocular pressure still became elevated but there was a reduction in the degree of elevation showing an additional benefit. Thus, nicotinamide is unexpectedly potent at preventing this glaucoma and is an attractive option for glaucoma therapeutics. Our findings demonstrate the promise for both preventing and treating glaucoma by interventions that bolster metabolism during increasing age and during periods of elevated intraocular pressure. Nicotinamide prevents age-related declines in NAD (a decline that occurs in different genetic contexts and species). NAD precursors are reported to protect from a variety of neurodegenerative conditions. Thus, nicotinamide may provide a much needed neuroprotective treatment against human glaucoma. This manuscript summarizes human data implicating mitochondria in glaucoma, and argues for studies to

  7. Protein Engineering for Nicotinamide Coenzyme Specificity in Oxidoreductases: Attempts and Challenges.

    Science.gov (United States)

    Chánique, Andrea M; Parra, Loreto P

    2018-01-01

    Oxidoreductases are ubiquitous enzymes that catalyze an extensive range of chemical reactions with great specificity, efficiency, and selectivity. Most oxidoreductases are nicotinamide cofactor-dependent enzymes with a strong preference for NADP or NAD. Because these coenzymes differ in stability, bioavailability and costs, the enzyme preference for a specific coenzyme is an important issue for practical applications. Different approaches for the manipulation of coenzyme specificity have been reported, with different degrees of success. Here we present various attempts for the switching of nicotinamide coenzyme preference in oxidoreductases by protein engineering. This review covers 103 enzyme engineering studies from 82 articles and evaluates the accomplishments in terms of coenzyme specificity and catalytic efficiency compared to wild type enzymes of different classes. We analyzed different protein engineering strategies and related them with the degree of success in inverting the cofactor specificity. In general, catalytic activity is compromised when coenzyme specificity is reversed, however when switching from NAD to NADP, better results are obtained. In most of the cases, rational strategies were used, predominantly with loop exchange generating the best results. In general, the tendency of removing acidic residues and incorporating basic residues is the strategy of choice when trying to change specificity from NAD to NADP, and vice versa . Computational strategies and algorithms are also covered as helpful tools to guide protein engineering strategies. This mini review aims to give a general introduction to the topic, giving an overview of tools and information to work in protein engineering for the reversal of coenzyme specificity.

  8. Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

    Science.gov (United States)

    Nirmal, J; Singh, S B; Biswas, N R; Thavaraj, V; Azad, R V; Velpandian, T

    2013-01-01

    Purpose We hypothesize organic cation transporters (OCT) may have a potential role in determining the pharmacokinetics and toxicity of organic cation drugs applied topically. Hence, in the present in vivo study, we attempted to evaluate the role of OCT in modulating the transport of its substrates after topical application. Methods New Zealand albino rabbits of either sex were used. Transcorneal penetration of OCT substrates tetraethylammonium and metformin after single instillation was evaluated in the absence and presence of OCT blockers (quinidine and atropine). Aqueous humor (AH) samples were collected through paracentesis amounting to 70–100 μl under topical anesthesia at various time intervals. The samples were subjected for estimation of both substrate as well as blocker concentrations using liquid chromatography mass spectrometry. Results Topical pre-treatment (30 min before substrate) of OCT blockers significantly decreased the transcorneal penetration of OCT substrates after single topical administration. The levels of blockers reaching AH in the presence of substrates were also modulated at 60 min after its administration as compared with its control. Conclusion OCT are functionally active in the uptake of their substrates from tear to AH. Therefore, OCT in the corneal epithelium may be positioned from apical to basolateral. When administering their substrates/blockers topically, both may be competing for OCT for their uptake across the cornea, thereby decreasing the corneal penetration. Hence OCT can have a potential pharmacokinetic role in modulating the ocular bioavailability of their substrates administered topically, which are used as ocular therapeutics. PMID:23846373

  9. Concentrations of Nicotinamide in Plasma by RP-HPLC With Fluorescence Detection

    Directory of Open Access Journals (Sweden)

    Pan Zhipeng

    2016-01-01

    Full Text Available The purpose of this study is to establish a new method for detecting nicotinamide concentration in plasma. In the experiment, the high performance liquid chromatography (HPLC method was used, with a fluorescence detector. The nicotinamide in the plasma was first converted to N1- methylnicotinamide, then reacted with acetophenone under certain conditions to produce fluorescent derivatives for testing. The method is a kind of highly sensitive detection, of which the lower limit is 10 ng/mL, the recovery rate is between 92.75% and 105.13%, and the relative standard deviation (RSD is between 3.76% and 4.43%. The results showed that this measurement method is accurate, sensitive and rapid. It meets the requirements of the experiment, and applies to the detection of nicotinamide concentration in plasma.

  10. Cocrystal of Ibuprofen–Nicotinamide: Solid-State Characterization and In Vivo Analgesic Activity Evaluation

    Directory of Open Access Journals (Sweden)

    Yori Yuliandra

    2018-06-01

    Full Text Available Ibuprofen is classified as a BCS class II drug which has low solubility and high permeability. We conducted the formation of the cocrystalline phase of ibuprofen with coformer nicotinamide to increase its solubility. The purpose of this study was to characterize the solid state of cocrystalline phase of ibuprofen-nicotinamide, determine the solubility, and evaluate its in vivo analgesic activity. The cocrystal of ibuprofen-nicotinamide was prepared by a slow evaporation method. The solid-state characterization was conducted by powder X-ray diffraction (PXRD analysis, differential thermal analysis (DTA, and scanning electron microscopy (SEM. To investigate the in vivo analgesic activity, 28 male Swiss-Webster mice were injected with acetic acid 0.5% following oral administration of intact ibuprofen, physical mixture, and its cocrystalline phase with nicotinamide (equivalent to 26 mg/kg ibuprofen. The number of writhes was counted, and pain inhibition was calculated. All data were analyzed with one-way ANOVA followed by Duncan’s Multiple Range Test (95% confidence interval. The results revealed that a new cocrystalline phase was successfully formed. The solubility testing showed that the cocrystal formation enhanced the solubility significantly as compared with the physical mixture and intact ibuprofen. A significant increase in the analgesic activity of cocrystal ibuprofen-nicotinamide was also confirmed.

  11. Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features.

    Science.gov (United States)

    Weiss, Ronald; Schilling, Erik; Grahnert, Anja; Kölling, Valeen; Dorow, Juliane; Ceglarek, Uta; Sack, Ulrich; Hauschildt, Sunna

    2015-11-01

    The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features. © The Author(s) 2015.

  12. Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma.

    Directory of Open Access Journals (Sweden)

    Orit Itzhaki

    Full Text Available Vasculogenic mimicry (VM describes functional vascular channels composed only of tumor cells and its presence predicts poor prognosis in melanoma patients. Inhibition of this alternative vascularization pathway might be of clinical importance, especially as several anti-angiogenic therapies targeting endothelial cells are largely ineffective in melanoma. We show the presence of VM structures histologically in a series of human melanoma lesions and demonstrate that cell cultures derived from these lesions form tubes in 3D cultures ex vivo. We tested the ability of nicotinamide, the amide form of vitamin B3 (niacin, which acts as an epigenetic gene regulator through unique cellular pathways, to modify VM. Nicotinamide effectively inhibited the formation of VM structures and destroyed already formed ones, in a dose-dependent manner. Remarkably, VM formation capacity remained suppressed even one month after the complete withdrawal of Nicotimamid. The inhibitory effect of nicotinamide on VM formation could be at least partially explained by a nicotinamide-driven downregulation of vascular endothelial cadherin (VE-Cadherin, which is known to have a central role in VM. Further major changes in the expression profile of hundreds of genes, most of them clustered in biologically-relevant clusters, were observed. In addition, nicotinamide significantly inhibited melanoma cell proliferation, but had an opposite effect on their invasion capacity. Cell cycle analysis indicated moderate changes in apoptotic indices. Therefore, nicotinamide could be further used to unravel new biological mechanisms that drive VM and tumor progression. Targeting VM, especially in combination with anti-angiogenic strategies, is expected to be synergistic and might yield substantial anti neoplastic effects in a variety of malignancies.

  13. Big Brains, Meat, Tuberculosis, and the Nicotinamide Switches: Co-Evolutionary Relationships with Modern Repercussions?

    Directory of Open Access Journals (Sweden)

    Adrian C. Williams

    2013-01-01

    Full Text Available Meat-eating was a game changer for human evolution. We suggest that the limiting factors for expanding brains earlier were scarcities of nicotinamide and tryptophan. In humans and some other omnivores, lack of meat causes these deficiencies. Nicotinamide adenine dinucleotide (NADH is necessary to synthesize adenosine triphosphate (ATP via either glycolysis or via the mitochondrial respiratory chain. NAD consumption is also necessary for developmental and repair circuits. Inadequate supplies result in “de-evolutionary” brain atrophy, as seen with pellagra. If trophic nicotinamide/tryptophan was a “prime mover” in building bigger brains, back-up mechanisms should have evolved. One strategy may be to recruit extra gut symbionts that produce NADH precursors or export nicotinamide (though this may cause diarrhea. We propose a novel supplier TB that co-evolved early, which did not originally and does not now inevitably cause disease. TB has highly paradoxical immunology for a pathogen, and secretes and is inhibited by nicotinamide and its analogue, isoniazid. Sharp declines in TB and diarrhea correlated with increased meat intake in the past, suggesting that dietary vitamin B 3 and tryptophan deficiencies (also associated with poor cognition and decreased lifespans are still common where meat is unaffordable.

  14. Modulation of glucose uptake in adipose tissue by nitric oxide ...

    Indian Academy of Sciences (India)

    Madhu

    ion-dependent breakdown and trans-nitrosation reactions are ... [McGrowder D, Ragoobirsingh D and Brown P 2006 Modulation of glucose uptake in adipose tissue by nitric oxide-generating ... Briefly, nicotinamide (Sigma Chemical Co.,.

  15. A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments

    International Nuclear Information System (INIS)

    Kjellen, E.; Joiner, M.C.; Collier, J.M.; Johns, H.; Rojas, A.

    1991-01-01

    The ability of normobaric oxygen and carbogen (95 percent O 2 + 5 percent CO 2 ) combined with nicotinamide to enhance the radiosensitivity of two rodent adenocarcinomas and of mouse skin and kidneys was compared with the effects of radiation in air and without the drug. A comparison of the results in tumors and normal tissues showed that significant therapeutic benefit was obtained with normobaric oxygen and carbogen combined with nicotinamide. Toxic side effects of the treatment are unlikely, as prolonged administration of nicotinamide is well tolerated in man. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumor radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment. (author). 45 refs.; 4 fig.; 4 tabs

  16. New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD+ salvage from nicotinamide

    Science.gov (United States)

    2014-01-01

    Background In an effort to reconstitute the NAD+ synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD+de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD+de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD+ metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD+ biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD+ salvage pathway from nicotinamide. Results Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Conclusions Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD+ salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD+ salvage pathway might be significant in some bacteria lacking NAD+de novo and NAD+ salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD+. However, this speculation needs to be experimentally tested. PMID:24506841

  17. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.

    Science.gov (United States)

    Anderson, Rozalyn M; Bitterman, Kevin J; Wood, Jason G; Medvedik, Oliver; Sinclair, David A

    2003-05-08

    Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

  18. Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

    International Nuclear Information System (INIS)

    Jonsson, G.G.; Kjellen, E.; Pero, R.W.; Cameron, R.

    1985-01-01

    Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. The authors have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. The data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors

  19. Biosynthesis of NAD from nicotinic acid and nicotinamide by resting cells of Arthrobacter globiformis

    International Nuclear Information System (INIS)

    Kuwahara, Masaaki

    1978-01-01

    Isotopically labeled nicotinic acid and nicotinamide were incorporated into the metabolites of nicotinic acid-dependent pathway (Preiss-Handler pathway) of the NAD biosynthesis by resting cells of Arthrobacter globiformis. Azaserine and adenosine markedly stimulated the accumulation of NAD in the cells. Radioactive nicotinic acid and nicotinamide were also incorporated into an unknown compound when the cells were incubated in the presence of azaserine. Cell-free extract of the organism showed the NAD synthetase activity, which required ammonium ion and ATP for the amidation of deamido-NAD. Adenosine inhibited the enzyme activity. The organism possessed nicotinamidase, suggesting deamidation is the first step in the biosynthesis of NAD from nicotinamide. The activity was inhibited by NAD, NADP and NMN. (auth.)

  20. Simvastatin-nicotinamide co-crystal: design, preparation and ...

    African Journals Online (AJOL)

    Purpose: To improve the solubility of simvastatin (SV) by co-crystallization using nicotinamide (Nic) as co-crystal agent (co-former). Methods: In silico molecular modeling of Nic counter to SV were investigated using Auto Dock 4.2. Cocrystal of Nic-SV was obtained by solvent evaporation (SE) using an equimolar ratio of Nic ...

  1. Different effects of histone deacetylase inhibitors nicotinamide and trichostatin A (TSA) in C17.2 neural stem cells.

    Science.gov (United States)

    Wang, Haifeng; Cheng, Hua; Wang, Kai; Wen, Tieqiao

    2012-11-01

    Histone deacetylase inhibitors are involved in proliferation, apoptosis, cell cycle, mRNA transcription, and protein expression in various cells. However, the molecular mechanism underlying such functions is still not fully clear. In this study, we used C17.2 neural stem cell (NSC) line as a model to evaluate the effects of nicotinamide and trichostatin A (TSA) on cell characteristics. Results show that nicotinamide and TSA greatly inhibit cell growth, lead to cell morphology changes, and effectively induce cell apoptosis in a dose-dependent manner. Western blot analyses confirmed that nicotinamide significantly decreases the expression of bcl-2 and p38. Further insight into the molecular mechanisms shows the suppression of phosphorylation in eukaryotic initiation factor 4E-binding protein 1 (4EBP1) by nicotinamide, whereas, an increased expression of bcl-2 and p38 and phosphorylation of 4EBP1 by TSA. However, both nicotinamide and TSA significantly increase the expression of cytochrome c (cyt c). These results strongly suggest that bcl-2, p38, cyt c, and p-4EBP1 could suppress proliferation and induce apoptosis of C17.2 NSCs mediated by histone deacetylase inhibitors, nicotinamide and TSA, involving different molecular mechanisms.

  2. 21 CFR 172.315 - Nicotinamide-ascorbic acid complex.

    Science.gov (United States)

    2010-04-01

    ... 172.315 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.315 Nicotinamide-ascorbic acid complex...

  3. S-Adenosyl-L-Homocysteine Hydrolase Inhibition by a Synthetic Nicotinamide Cofactor Biomimetic

    Directory of Open Access Journals (Sweden)

    Lyn L. Kailing

    2018-03-01

    Full Text Available S-adenosyl-L-homocysteine (SAH hydrolases (SAHases are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD+ as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB are a promising tool to modulate SAHase activity. In the present in vitro study, we investigated 10 synthetic truncated NAD+ analogs against a SAHase from the root-nodulating bacterium Bradyrhizobium elkanii. Among this set of analogs, one was identified to inhibit the SAHase in both directions. Isothermal titration calorimetry (ITC and crystallography experiments suggest that the inhibitory effect is not mediated by a direct interaction with the protein. Neither the apo-enzyme (i.e., deprived of the natural cofactor, nor the holo-enzyme (i.e., in the NAD+-bound state were found to bind the inhibitor. Yet, enzyme kinetics point to a non-competitive inhibition mechanism, where the inhibitor acts on both, the enzyme and enzyme-SAH complex. Based on our experimental results, we hypothesize that the NCB inhibits the enzyme via oxidation of the enzyme-bound NADH, which may be accessible through an open molecular gate, leaving the enzyme stalled in a configuration with oxidized cofactor, where the reaction intermediate can be neither converted nor released. Since the reaction mechanism of SAHase is quite uncommon, this kind of inhibition could be a viable pharmacological route, with a low risk of off-target effects. The NCB presented in this work could be used as a template for the development of more potent SAHase inhibitors.

  4. A Rapid and Efficient Assay for the Characterization of Substrates and Inhibitors of Nicotinamide N-Methyltransferase

    NARCIS (Netherlands)

    van Haren, Matthijs J; Sastre Torano, Javier; Sartini, Davide; Emanuelli, Monica; Parsons, Richard B; Martin, Nathaniel I

    2016-01-01

    Nicotinamide N-methyltransferase (NNMT) is one of the most abundant small molecule methyltransferases in the human body and is primarily responsible for the N-methylation of the nicotinamide (vitamin B3). Employing the cofactor S-adenosyl-l-methionine, NNMT transfers a methyl group to the pyridine

  5. [The influence of fasting, of a hyperprotein diet and of nicotinamide on hepatic L-threonine deaminase].

    Science.gov (United States)

    Aleo, M F; Casella, A; Marinello, E

    1981-09-15

    The induction of L-threonine deaminase, following nicotinamide injection has been studied: the effect of fasting and of hyperproteic diet have been also taken in consideration. Maximal induction is observed after 5 days hyperproteic diet, and is additional only with nicotinamide treatment. Results are interpreted assuming a different hepatic content and behavior of multiple forms of the enzyme.

  6. Validity And Practicality of Experiment Integrated Guided Inquiry-Based Module on Topic of Colloidal Chemistry for Senior High School Learning

    Science.gov (United States)

    Andromeda, A.; Lufri; Festiyed; Ellizar, E.; Iryani, I.; Guspatni, G.; Fitri, L.

    2018-04-01

    This Research & Development study aims to produce a valid and practical experiment integrated guided inquiry based module on topic of colloidal chemistry. 4D instructional design model was selected in this study. Limited trial of the product was conducted at SMAN 7 Padang. Instruments used were validity and practicality questionnaires. Validity and practicality data were analyzed using Kappa moment. Analysis of the data shows that Kappa moment for validity was 0.88 indicating a very high degree of validity. Kappa moments for the practicality from students and teachers were 0.89 and 0.95 respectively indicating high degree of practicality. Analysis on the module filled in by students shows that 91.37% students could correctly answer critical thinking, exercise, prelab, postlab and worksheet questions asked in the module. These findings indicate that the integrated guided inquiry based module on topic of colloidal chemistry was valid and practical for chemistry learning in senior high school.

  7. A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

    Science.gov (United States)

    Crinó, A; Schiaffini, R; Ciampalini, P; Suraci, M C; Manfrini, S; Visalli, N; Matteoli, M C; Patera, P; Buzzetti, R; Guglielmi, C; Spera, S; Costanza, F; Fioriti, E; Pitocco, D; Pozzilli, P

    2005-08-01

    A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be

  8. Effects of radiosensitising agent nicotinamide on relative tissue perfusion and kidney junction in C3H mice

    International Nuclear Information System (INIS)

    Honess, D.J.; Bleehen, N.M.

    1993-01-01

    Nicotinamide is an effective radiosensitiser of murine tumours, functioning by improving tumour perfusion by decreasing the proportion of intermittently closed capillaries. The effect of nicotinamide on relative tissue perfusion of RIF-1 tumour and normal skin, muscle, lung, liver, kidney and spleen were investigated using the 86 Rb extraction technique. A dose of 1000 mg/kg was shown to have transient effects on tumour, skin and lung perfusion but to have sustained effects on muscle (a drop to 80% of control), liver, kidney and spleen (with increased ranging from 165% to 280% of control) from 0.5 to 4 h after treatment i.e. during the period of maximum radiosensitisation. These increases were evident at doses as low as 100 mg/kg. The data suggest that the radiosensitisation induced by nicotinamide in the mouse may be associated with these perfusion changes. Nicotinamide was also shown to have a substantial inhibitory effect on renal function, inhibiting 51 CrEDTA clearance by a factor (± 2 SE) of 2.56 ± 0.19 and 125 I-iodohippurate clearance by a factor of 2.07 ± 0.45 at 1000 mg/kg. These effects were shown to be dose-related, and to be evident at doses from 400 mg/kg upwards. This suggests that nicotinamide potentiation of co-administered cytotoxic agents may be mediated by reduced renal clearance of the cytotoxic drug, thus increasing the plasma half-life. (author)

  9. Increasing NAD Synthesis in Muscle via Nicotinamide Phosphoribosyltransferase Is Not Sufficient to Promote Oxidative Metabolism*

    Science.gov (United States)

    Frederick, David W.; Davis, James G.; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A.; Nakamaru-Ogiso, Eiko; Baur, Joseph A.

    2015-01-01

    The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. PMID:25411251

  10. Validation of diffuse correlation spectroscopy sensitivity to nicotinamide-induced blood flow elevation in the murine hindlimb using the fluorescent microsphere technique

    Science.gov (United States)

    Proctor, Ashley R.; Ramirez, Gabriel A.; Han, Songfeng; Liu, Ziping; Bubel, Tracy M.; Choe, Regine

    2018-03-01

    Nicotinamide has been shown to affect blood flow in both tumor and normal tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was used as a simple intervention to test the sensitivity of noninvasive diffuse correlation spectroscopy (DCS) to changes in blood flow in the murine left quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard fluorescent microsphere (FM) technique for validation. The nicotinamide dose-response experiment showed that relative blood flow measured by DCS increased following treatment with 500- and 1000-mg / kg nicotinamide. The DCS and FM technique comparison showed that blood flow index measured by DCS was correlated with FM counts quantified by image analysis. The results of this study show that DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left quadriceps femoris. Additionally, the results of the comparison were consistent with similar studies in higher-order animal models, suggesting that mouse models can be effectively employed to investigate the utility of DCS for various blood flow measurement applications.

  11. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT inhibition on human cancer cells.

    Directory of Open Access Journals (Sweden)

    Vladimir Tolstikov

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer and HCT-116 (colorectal cancer cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA, and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  12. Clinical study of 89Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms

    International Nuclear Information System (INIS)

    Liu Yajie; Wang Shubin; Guo Yiling; Chen Zuowei; Zhang Yingnan

    2005-01-01

    Objective: To evaluate the curative effect and side effects of 89 Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms. Methods: Ninety-seven patients were divided into 4 groups respectively: group A, 89 Sr + nicotinamide + carbogen (24 patients); group B, 89 Sr + nicotinamide(22 patients); group C, 89 Sr + carbogen (25 patients); group D, 89 Sr, (26 patients). 89 SrCl was intravenously injected at a dose of 1.48-2.22 MBq/kg. Nicotinamide was taken orally 1 hour before 89 SrCl injection, 6 g/day, tid, d1-d5. Aspiration of carbogen(95%O 2 + 5%CO 2 ) gases, 6 L/min, 10 minutes, qd, d1-d5. Results: The effective rate of pain control and QOL improvement in A group were higher than in groups B, C and D (91.7% VS 77.3%, 76.0% and 69.2%, P=0.048). The lesions assessed by SPECT imaging in every group was not significantly different at three months after treatment. I to II degree toxic effect on bone marrow appeared in every group and there were no significantly inter-group differences. Conclusions: Combinative therapy using 89 Sr + nicotinamide + carbogen is more effective to treat multiple metastatic bone pain and for improvement of QOL. The side effects are not increased. (authors)

  13. Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

    International Nuclear Information System (INIS)

    Horsman, M.

    1996-01-01

    Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

  14. Analytical Method Validation and Determination of Pyridoxine, Nicotinamide, and Caffeine in Energy Drinks Using Thin Layer Chromatography-Densitometry

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    Florentinus Dika Octa Riswanto

    2015-03-01

    Full Text Available Food supplement which contains vitamins and stimulants such as caffeine were classified as energy drink. TLC-densitometry method was chosen to determine the pyridoxine, nicotinamide, and caffeine in the energy drink sample. TLC plates of silica gel 60 F254 was used as the stationary phase and methanol : ethyl acetate : ammonia 25% (134:77:10 was used as the mobile phase. The correlation coefficient for each pyridoxine, nicotinamide, and caffeine were 0.9982, 0.9997, and 0.9966, respectively. Detection and quantitation limits of from the three analytes were 4.05 and 13.51 µg/mL; 13.15 and 43.83 µg/mL; 5.43 and 18.11 µg/mL, respectively. The recovery of pyridoxine, nicotinamide, and caffeine were within the required limit range of 95-105%. The percent of RSD were below the limit value of 5.7% for caffeine and nicotinamide and 8% for pyridoxine. The content amount of pyridoxine in the sample 1 and 2 were 33.59 ± 0.981 and 30.29 ± 2.061 µg/mL, respectively. The content amount of nicotinamide in the sample 1 and 2 were 106.53 ± 3.521 and 98.20 ± 3.648 µg/mL, respectively. The content amount of caffeine in the sample 1 and 2 were 249.50 ± 5.080 and 252.80 ± 2.640 µg/mL, respectively. Robustness test results showed that the most optimal method conditions should be applied for the analysis.

  15. Congenital malformations in embryos of female mice exposed to alcohol and nicotinamide

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    Natasha Soares Simões dos Santos

    2009-03-01

    Full Text Available Objective: To compare the incidence of congenital malformations among the offspring of female mice exposed to alcohol or alcohol plus nicotinamide. Methods: Three groups of pregnant C57BL/6J mice were studied; G1 received alcohol (5 g/kg in saline solution (20% - vol/vol; G2 received nicotinamide, 50 mg/ml associated to alcohol; and G3, only saline solution; all by intraperitoneal injection on the seventh day of pregnancy. The animals were killed in a CO2 chamber on day 18 of pregnancy. The intrauterine content was assessed and the number of complete and reabsorbed fetuses was counted. The complete fetuses had their weight and crown-rump length measured and malformations were identified. Rresults: G1 showed the highest number of malformations: micrognathia, low set ears, hypertrophic nose, scoliosis, and atrophy of the lower and upper limbs. Weight was significantly different among the groups (p = 0.0139, and in G1 it was below average as compared to G3 (p = 0.3133. As for length, the lowest values were found in G2 and G3 showed the highest ones. There was a significant difference among the groups (p = 0.0145. Cconclusions: Ethanol, when administered to pregnant mice was teratogenic. However, length of G1 fetuses was, in average, higher than that of other groups. Nicotinamide decreased the number of malformations and may be a possible protector against alcohol effects.

  16. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats.

    Science.gov (United States)

    Madkor, Hafez R; Mansour, Sherif W; Ramadan, Gamal

    2011-04-01

    Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)-nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80-97 %, P diabetic rats by increasing the production of insulin (26-37 %), enhancing the antioxidant defence system (31-52 %, especially GSH) and decreasing lipid peroxidation (60-97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10-23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.

  17. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects.

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    Smedts, Huberdina P M; Rakhshandehroo, Maryam; Verkleij-Hagoort, Anna C; de Vries, Jeanne H M; Ottenkamp, Jaap; Steegers, Eric A P; Steegers-Theunissen, Régine P M

    2008-10-01

    With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism. To investigate associations between the maternal dietary intake of fats, riboflavin and nicotinamide, and CHD risk in the offspring. A case-control family study was conducted in 276 mothers of a child with a CHD comprising of 190 outflow tract defects (OTD) and 86 non-outflow tract defects (non-OTD) and 324 control mothers of a non-malformed child. Mothers filled out general and food frequency questionnaires at 16 months after the index-pregnancy, as a proxy of the habitual food intake in the preconception period. Nutrient intakes (medians) were compared between cases and controls by Mann-Whitney U test. Odds ratios (OR) for the association between CHDs and nutrient intakes were estimated in a logistic regression model. Case mothers, in particular mothers of a child with OTD, had higher dietary intakes of saturated fat, 30.9 vs. 29.8 g/d; P riboflavin and nicotinamide were lower in mothers of a child with an OTD than in controls (1.32 vs. 1.41 mg/d; P riboflavin (riboflavin and nicotinamide seems to contribute to CHD risk, in particular OTDs.

  18. Generation of 1:1 Carbamazepine:Nicotinamide cocrystals by spray drying.

    Science.gov (United States)

    Patil, Shashank P; Modi, Sameer R; Bansal, Arvind K

    2014-10-01

    The present study investigates the potential of spray drying as a technique for generation of pharmaceutical cocrystals. Carbamazepine-Nicotinamide cocrystal (CNC) was chosen as model cocrystal system for this study. Firstly, CNC was generated using liquid assisted grinding and used for generation of phase solubility diagram (PSD) and ternary phase diagram (TPD). Both PSD and TPD were carefully evaluated for phase behavior of CNC when equilibrated with solvent. The undersaturated region with respect to CNC, as depicted by TPD, was selected as target region to initiate cocrystallization experiments. Various points in this region, representative of different compositions of Carbamazepine, Nicotinamide and CNC, were selected and spray drying was carried out. The spray dried product was characterized for solid state properties and was compared with CNC generated by liquid assisted grinding. Spray drying successfully generated CNC of similar quality as those generated by liquid assisted grinding. Moreover, there was no significant impact of process variables on formation of CNC. Spray drying, owing to its simplicity and industrial scalability, can be a promising method for large scale cocrystal generation. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Pyridine nucleotide cycle of Salmonella typhimurium: isolation and characterization of pncA, pncB, and pncC mutants and utilization of exogenous nicotinamide adenine dinucleotide.

    Science.gov (United States)

    Foster, J W; Kinney, D M; Moat, A G

    1979-03-01

    Mutants of Salmonella typhimurium LT-2 deficient in nicotinamidase activity (pncA) or nicotinic acid phosphoribosyltransferase activity (pncB) were isolated as resistant to analogs of nicotinic acid and nicotinamide. Information obtained from interrupted mating experiments placed the pncA gene at 27 units and the pncB gene at 25 units on the S. typhimurium LT-2 linkage map. A major difference in the location of the pncA gene was found between the S. typhimurium and Escherichia coli linkage maps. The pncA gene is located in a region in which there is a major inversion of the gene order in S. typhimurium as compared to that in E. coli. Growth experiments using double mutants blocked in the de novo pathway to nicotinamide adenine dinucleotide (NAD) (nad) and in the pyridine nucleotide cycle (pnc) at either the pncA or pncB locus, or both, have provided evidence for the existence of an alternate recycling pathway in this organism. Mutants lacking this alternate cycle, pncC, have been isolated and mapped via cotransduction at 0 units. Utilization of exogenous NAD was examined through the use of [14C]carbonyl-labeled NAD and [14C]adenine-labeled NAD. The results of these experiments suggest that NAD is degraded to nicotinamide mononucleotide at the cell surface. A portion of this extracellular nicotinamide mononucleotide is then transported across the cell membrane by nicotinamide mononucleotide glycohydrolase and degraded to nicotinamide in the process. The remaining nicotinamide mononucleotide accumulates extracellularly and will support the growth of nadA pncB mutants which cannot utilize the nicotinamide resulting from the major pathway of NAD degradation. A model is presented for the utilization of exogenous NAD by S. typhimurium LT-2.

  20. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

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    Benjamin C Thompson

    Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  1. Cleavage of nicotinamide adenine dinucleotide by the ribosome-inactivating protein from Momordica charantia.

    Science.gov (United States)

    Vinkovic, M; Dunn, G; Wood, G E; Husain, J; Wood, S P; Gill, R

    2015-09-01

    The interaction of momordin, a type 1 ribosome-inactivating protein from Momordica charantia, with NADP(+) and NADPH has been investigated by X-ray diffraction analysis of complexes generated by co-crystallization and crystal soaking. It is known that the proteins of this family readily cleave the adenine-ribose bond of adenosine and related nucleotides in the crystal, leaving the product, adenine, bound to the enzyme active site. Surprisingly, the nicotinamide-ribose bond of oxidized NADP(+) is cleaved, leaving nicotinamide bound in the active site in the same position but in a slightly different orientation to that of the five-membered ring of adenine. No binding or cleavage of NADPH was observed at pH 7.4 in these experiments. These observations are in accord with current views of the enzyme mechanism and may contribute to ongoing searches for effective inhibitors.

  2. Interactive effects of salinity stress and nicotinamide on physiological and biochemical parameters of Faba bean plant

    International Nuclear Information System (INIS)

    Abdelhamid, Magdi T; Sadak, Mervat Sh; Schmidhalter, Urs; El Saady, Abdel Kareem M.

    2013-01-01

    A possible survival strategy for plants under saline conditions is to use some compounds that could alleviate the salt stress effect. One of these compounds is nicotinamide (vitamin B3/niacin). The effect of exogenous application of nicotinamide with different concentrations (0,200 or 400 mg l-1) on faba bean (Vicia faba L.) plant grown at different NaCl levels (0,50 or 100 mM) was investigated in the wire house of the National Research Centre, Cairo, Egypt. Salinity stress significantly reduced the photosynthetic pigments, polysaccharides, total carbohydrates, total-N contents of shoot, plant height, leaves number, fresh and dry weights of shoot, seed yield, total carbohydrates and total crude protein of the yielded seeds compared with those of the control plants. In contrast, salinity induced marked increases in sucrose, total soluble sugars, total free amino acids, proline, lipid peroxidation product (MDA) and some oxidative enzymes (polyphenol-oxidase and peroxidase). Also, salinity stress increased Na+ contents with the decreases of other macro and micro elements contents (P, K+, Mg_2+, Ca_2+, Fe_2+, Mn_2+, Zn_2+ and Cu_2+) of shoots and the yielded seeds of faba bean. Foliar spraying of nicotinamide alleviated the adverse effects of salinity stress through increased the photosynthetic pigments, polysaccharides, total carbohydrates, total N concentration of shoot, plant height, leaves number, fresh and dry weights of shoot, and seed yield as well as, sucrose, total soluble sugars, total free amino acids and proline, compared with those of the corresponding salinity levels, while decreased lipid peroxidation product as malondialdehyde (MDA) and the oxidative enzymes (polyphenol oxidase and peroxidase enzymes). Nicotinamide inhibited the uptake of Na+ and accelerated the accumulation of P, K+, Mg_2+, Ca_2+, Fe_2+, Mn_2+, Zn_2+ and Cu_2+ concentrations in the shoots of salt stressed plants and enhanced total carbohydrate and total crude protein percentage and

  3. L-glutamine supplementation prevents the development of experimental diabetic cardiomyopathy in streptozotocin-nicotinamide induced diabetic rats.

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    Sachin L Badole

    Full Text Available The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg. Nicotinamide (100 mg/kg, i.p. was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o., II: diabetic control (distilled water, 10 ml/kg, p.o., III: L-glutamine (500 mg/kg, p.o. and IV: L-glutamine (1000 mg/kg, p.o.. All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

  4. Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity.

    Science.gov (United States)

    Gallo, Christopher M; Smith, Daniel L; Smith, Jeffrey S

    2004-02-01

    The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone deacetylase (HDAC) that functions in transcriptional silencing and longevity. The NAD(+) salvage pathway protein, Npt1, regulates Sir2-mediated processes by maintaining a sufficiently high intracellular NAD(+) concentration. However, another NAD(+) salvage pathway component, Pnc1, modulates silencing independently of the NAD(+) concentration. Nicotinamide (NAM) is a by-product of the Sir2 deacetylase reaction and is a natural Sir2 inhibitor. Pnc1 is a nicotinamidase that converts NAM to nicotinic acid. Here we show that recombinant Pnc1 stimulates Sir2 HDAC activity in vitro by preventing the accumulation of NAM produced by Sir2. In vivo, telomeric, rDNA, and HM silencing are differentially sensitive to inhibition by NAM. Furthermore, PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, life span, and Hst1-mediated transcriptional repression. Finally, we show that stress suppresses the inhibitory effect of NAM through the induction of PNC1 expression. Pnc1, therefore, positively regulates Sir2-mediated silencing and longevity by preventing the accumulation of intracellular NAM during times of stress.

  5. Modulation of cortical activity during comprehension of familiar and unfamiliar text topics in speed reading and speed listening.

    Science.gov (United States)

    Buchweitz, Augusto; Mason, Robert A; Meschyan, Gayane; Keller, Timothy A; Just, Marcel Adam

    2014-12-01

    Brain activation associated with normal and speeded comprehension of expository texts on familiar and unfamiliar topics was investigated in reading and listening. The goal was to determine how brain activation and the comprehension processes it reflects are modulated by comprehension speed and topic familiarity. Passages on more familiar topics differentially activated a set of areas in the anterior temporal lobe and medial frontal gyrus, areas often associated with text-level integration processes, which we interpret to reflect integration of previous knowledge with the passage content. Passages presented at the faster presentation resulted in more activation of a network of frontal areas associated with strategic and working-memory processes (as well as visual or auditory sensory-related regions), which we interpret to reflect maintenance of local coherence among briefly available passage segments. The implications of this research is that the brain system for text comprehension adapts to varying perceptual and knowledge conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.

    Science.gov (United States)

    Ye, Yong-Hao; Ma, Liang; Dai, Zhi-Cheng; Xiao, Yu; Zhang, Ying-Ying; Li, Dong-Dong; Wang, Jian-Xin; Zhu, Hai-Liang

    2014-05-07

    Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.

  7. Nicotinamide supplementation phenocopies SIR2 inactivation by modulating carbon metabolism and respiration during yeast chronological aging.

    Science.gov (United States)

    Orlandi, Ivan; Pellegrino Coppola, Damiano; Strippoli, Maurizio; Ronzulli, Rossella; Vai, Marina

    2017-01-01

    Nicotinamide (NAM), a form of vitamin B 3 , is a byproduct and noncompetitive inhibitor of the deacetylation reaction catalyzed by Sirtuins. These represent a family of evolutionarily conserved NAD + -dependent deacetylases that are well-known critical regulators of metabolism and aging and whose founding member is Sir2 of Saccharomyces cerevisiae. Here, we investigated the effects of NAM supplementation in the context of yeast chronological aging, the established model for studying aging of postmitotic quiescent mammalian cells. Our data show that NAM supplementation at the diauxic shift results in a phenocopy of chronologically aging sir2Δ cells. In fact, NAM-supplemented cells display the same chronological lifespan extension both in expired medium and extreme Calorie Restriction. Furthermore, NAM allows the cells to push their metabolism toward the same outcomes of sir2Δ cells by elevating the level of the acetylated Pck1. Both these cells have the same metabolic changes that concern not only anabolic pathways such as an increased gluconeogenesis but also respiratory activity in terms both of respiratory rate and state of respiration. In particular, they have a higher respiratory reserve capacity and a lower non-phosphorylating respiration that in concert with a low burden of superoxide anions can affect positively chronological aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Nicotinamide dependence of uropathogenic Escherichia coli UTI89 and application of nadB as a neutral insertion site.

    Science.gov (United States)

    Li, Zhaoli; Bouckaert, Julie; Deboeck, Francine; De Greve, Henri; Hernalsteens, Jean-Pierre

    2012-03-01

    NAD and NADP are ubiquitous in the metabolism of Escherichia coli K-12. NAD auxotrophy can be rendered by mutation in any of the three genes nadB, nadA and nadC. The nadB and nadA genes were defined as antivirulence loci in Shigella spp., as a mutation (mainly in nadB) disrupting the synthesis of quinolinate is required for virulence. Uropathogenic E. coli (UPEC) isolates from acute cystitis patients, exhibiting nicotinamide auxotrophy, were of serotype O18 : K1 : H7. E. coli UTI89, the model uropathogenic and O18 : K1 : H7 strain, requires nicotinamide or quinolinate for growth. A mutation in the nadB gene, encoding L-aspartate oxidase, was shown to be responsible for the nicotinamide requirement of UTI89. This was further confirmed by complementation of UTI89 with a recombinant plasmid harbouring the nadB gene of E. coli K-12. An Ala28Val point mutant of the recombinant plasmid failed to support the growth of UTI89 in minimal medium. This proves that the Ala28Val mutation in the NadB gene of UTI89 completely impedes de novo synthesis of nicotinamide. In spontaneous prototrophic revertants of UTI89, the nadB gene has a Val28Ala mutation. Both analyses implicate that the nicotinamide auxotrophy of UTI89 is caused by a single Ala28Val mutation in NadB. We showed that the same mutation is also present in other NAD auxotrophic E. coli O18 strains. No significant differences were observed between the virulence of isogenic NAD auxotrophic and prototrophic strains in the murine ascending urinary tract infection model. Considering these data, we applied the nadB locus as a neutral site for DNA insertions in the bacterial chromosome. We successfully restored the parental phenotype of a fimH mutant by inserting fimH, with a synthetic em7 promoter, into the nadB gene. This neutral insertion site is of significance for further research on the pathogenicity of UPEC.

  9. Meat Intake and the Dose of Vitamin B – Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

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    Lisa J Hill

    2017-05-01

    Full Text Available Meat and vitamin B 3 – nicotinamide – intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by ‘welcoming’ gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B 3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives may be driven by positive ‘meat transitions’. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B 3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress.

  10. Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and Subsequent Neurodegeneration in the Developing Mouse Cerebellum.

    Science.gov (United States)

    Ieraci, Alessandro; Herrera, Daniel G

    2018-06-01

    Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable. In this study, we investigated the effects of nicotinamide on ethanol-induced neuronal cell death in the developing cerebellum. Subcutaneous administration of ethanol in postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1 followed by a massive neurodegeneration in the developing cerebellum. Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol-induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but not caspase-3 activation or ethanol-induced neurodegeneration in the developing cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in the developing cerebellum, suggesting that nicotinamide might be a promising and safe neuroprotective agent for treating FASD and other neurodegenerative disorders in the developing brain that shares similar cell death pathways.

  11. Rho-kinase inhibitor and nicotinamide adenine dinucleotide phosphate oxidase inhibitor prevent impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats.

    Science.gov (United States)

    Iida, Hiroki; Iida, Mami; Takenaka, Motoyasu; Fukuoka, Naokazu; Dohi, Shuji

    2008-06-01

    We previously reported that acute cigarette smoking can cause a dysfunction of endothelium-dependent vasodilation in cerebral vessels, and that blocking the angiotensin II (Ang II) type 1 (AT1) receptor with valsartan prevented this impairment. Our aim was to investigate the effects of a Rho-kinase inhibitor (fasudil) and a Nicotinamide Adenine Dinucleotide PHosphate (NADPH) oxidase inhibitor (apocynin) on smoking-induced endothelial dysfunction in cerebral arterioles. In Sprague-Dawley rats, we used a closed cranial window preparation to measure changes in pial vessel diameters following topical acetylcholine (ACh) before smoking. After one-minute smoking, we again examined the arteriolar responses to ACh. Finally, after intravenous fasudil or apocynin pre-treatment we re-examined the vasodilator responses to topical ACh (before and after cigarette smoking). Under control conditions, cerebral arterioles were dose-dependently dilated by topical ACh (10(-6) M and 10(-5) M). One hour after a one-minute smoking (1 mg-nicotine cigarette), 10(-5) M ACh constricted cerebral arterioles. However, one hour after a one-minute smoking, 10(-5) M ACh dilated cerebral pial arteries both in the fasudil pre-treatment and the apocynin pre-treatment groups, responses that were significantly different from those obtained without fasudil or apocynin pre-treatment. Thus, inhibition of Rho-kinase and NADPH oxidase activities may prevent the above smoking-induced impairment of endothelium-dependent vasodilation.

  12. Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

    Science.gov (United States)

    Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

    2016-11-01

    Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

  13. Formation of nicotinamide ribose diphosphate ribose, a new metabolite of the NAD pathway, by growing mycelium of Aspergillus niger

    International Nuclear Information System (INIS)

    Kuwahara, Masaaki

    1976-01-01

    A new step of NAD metabolism was shown in Aspergillus niger. Radioactive nicotinic acid and nicotinamide were incorporated into nicotinamide ribose diphosphate ribose (NAm-RDPR), which had been isolated from the culture filtrate. Its content in the culture medium increased with an increase of culture time, and this compound was proved to be a terminal metabolite in the NAD pathway. The experimental results also showed that the Preiss-Handler pathway and the NAD cycling system function in the NAD biosynthesis in A. niger. A part of the radioactive precursors was also incorporated into an unknown compound. (auth.)

  14. Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Kuo-Ping Shen

    2018-03-01

    Full Text Available This study examined the effects of eugenosedin-A (Eu-A in a streptozotocin (STZ/nicotinamide-induced rat model of type II diabetes mellitus (T2DM. Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1 RD group, normal rats fed a regular diet (RD, (2 DM group, T2DM rats fed a high-fat diet, and (3 Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day. After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK in liver and skeletal muscle and decreased protein expression of insulin receptor (IR, insulin receptor substrate-1 (IRS-1, IRS-2, AMP-activated protein kinase (AMPK, glucose transporter-4 (GLUT-4, glucokinase (GCK, and peroxisome proliferator-activated receptor γ (PPAR-γ. STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

  15. Uptake of [14C]nicotinic acid and [14C]nicotinamide by Bordetella pertussis

    International Nuclear Information System (INIS)

    McPheat, W.L.; Wardlaw, A.C.

    1980-01-01

    Bordetella pertussis has an absolute requirement for either nicotinic acid (NA) or nicotinamide (ND), both being equally effective in supporting growth. The results of an investigation to compare the rates of uptake of NA and ND, to determine the influence of factors such as energy source and temperature on uptake, and to measure the Ksub(m) and Vsub(max) values are reported. (Auth.)

  16. Hormones and Antibiotics in Nature: A Laboratory Module Designed to Broaden Undergraduate Perspectives on Typically Human-Centered Topics

    Directory of Open Access Journals (Sweden)

    Carolyn F. Weber

    2014-07-01

    Full Text Available Bringing discovery-based research into undergraduate laboratory courses increases student motivation and learning gains over traditional exercises that merely teach technique or demonstrate well-documented phenomena. Laboratory experiences are further enhanced when they are designed to challenge student perspectives on topics relevant to their lives. To this end, a laboratory module on antibiotics and hormones, which are generally discussed in the context of human health, was developed for students to explore the multifaceted roles of antibiotics and hormones in nature (e.g. interspecies communication via reading primary scientific literature and performing discovery-based experiments. The main objective of this module was to increase the general biological literacy of students as determined by their ability to connect the Five Core Concepts of Biological Literacy (American Association for the Advancement of Science, Vision and Change in Undergraduate Education: A Call to Action, 2011 to the topics “hormones” and “antibiotics” in pre- and postmodule surveys. After discussing unpublished research findings, cell biology students performed experiments demonstrating that: 1 fungi may promote fern growth via hormone production, 2 novel bacterial isolates in the genus Streptomyces produce antifungal compounds, and 3 subinhibitory antibiotic concentrations may enhance soil bacterial growth. The third finding provided evidence supporting a hypothesis framed in a scientific article that students read and discussed. Student perspectives on premodule surveys focused on roles of hormones and antibiotics in the human body (e.g. development, fighting infection, but their broadened postmodule perspectives encompassed the roles of these molecules in organismal communication and possibly the evolution of multicellularity.

  17. Density and viscosity study of nicotinic acid and nicotinamide in dilute aqueous solutions at and around the temperature of the maximum density of water

    International Nuclear Information System (INIS)

    Dhondge, Sudhakar S.; Dahasahasra, Prachi N.; Paliwal, Lalitmohan J.; Deshmukh, Dinesh W.

    2014-01-01

    Highlights: • Volumetric and transport behaviour of aqueous solutions of important vitamins are reported. • Various interactions of nicotinic acid and nicotinamide with water have been reported. • The temperature dependence of interactions between solute and solvent is discussed. • The study indicates that nicotinamide is more hydrated as compared to nicotinic acid. - Abstract: In the present study, we report experimental densities (ρ) and viscosities (η) of aqueous solutions of nicotinic acid and nicotinamide within the concentration range (0 to 0.1) mol · kg −1 at T = (275.15, 277.15 and 279.15) K. These parameters are then used to obtain thermodynamic and transport functions such as apparent molar volume of solute (V ϕ ), limiting apparent molar volume of solute (V ϕ 0 ), limiting apparent molar expansivity of solute (E ϕ 0 ), coefficient of thermal expansion (α ∗ ), Jones–Dole equation viscosity A, B and D coefficients, temperature derivative of B coefficient i.e. (dB/dT) and hydration number (n H ), etc. The activation parameters of viscous flow for the binary mixtures have been determined and discussed in terms of Eyring’s transition state theory. These significant parameters are helpful to study the structure promoting or destroying tendency of solute and various interactions present in (nicotinic acid + water) and (nicotinamide + water) binary mixtures

  18. Combined experimental and computational studies of pyrazinamide and nicotinamide in the context of crystal engineering and thermodynamics

    DEFF Research Database (Denmark)

    Jarzembska, Katarzyna N.; Hoser, Anna Agnieszka; Kamiński, Radosław

    2014-01-01

    and computational analysis of the β form of pyrazinamide and α form of nicotinamide. Static electron density distribution is obtained through application of Hansen and Coppens multipolar formalism, and further analyzed via Baders quantum theory of atoms in molecules (QTAIM). Geometrical and electron density...

  19. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects

    NARCIS (Netherlands)

    Smedts, H.P.M.; Rakhshandehroo, M.; Verkleij-Hagoort, A.C.; Vries, de J.H.M.; Ottenkamp, J.; Steegers, E.A.P.; Steegers-Theunissen, R.P.M.

    2008-01-01

    With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism.

  20. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects

    NARCIS (Netherlands)

    Smedts, Huberdina P. M.; Rakhshandehroo, Maryam; Verkleij-Hagoort, Anna C.; de Vries, Jeanne H. M.; Ottenkamp, Jaap; Steegers, Eric A. P.; Steegers-Theunissen, Régine P. M.

    2008-01-01

    BACKGROUND: With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid

  1. Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu Xiang; Pham, Tien Q.; Berghofer, Paula; Chapman, Janette; Greguric, Ivan; Mitchell, Peter; Mattner, Filomena; Loc' h, Christian [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia); Katsifis, Andrew [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia)], E-mail: akx@ansto.gov.au

    2008-10-15

    Introduction: A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. Methods: [{sup 123}I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. Results: The iodonicotinamides displayed low-affinity binding for {sigma}{sub 1}-{sigma}{sub 2} receptors (K{sub i}>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[{sup 123}I]iodonicotinamide ([{sup 123}I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ({approx}8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [{sup 123}I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [{sup 123}I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [{sup 123}I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. Conclusion: These findings suggest that [{sup 123}I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.

  2. The B vitamins nicotinamide (B3) and riboflavin (B2) stimulate metamorphosis in larvae of the deposit-feeding polychaete Capitella teleta: implications for a sensory ligand-gated ion channel.

    Science.gov (United States)

    Burns, Robert T; Pechenik, Jan A; Biggers, William J; Scavo, Gia; Lehman, Christopher

    2014-01-01

    Marine sediments can contain B vitamins, presumably incorporated from settled, decaying phytoplankton and microorganisms associated with decomposition. Because B vitamins may be advantageous for the energetically intensive processes of metamorphosis, post-metamorphic growth, and reproduction, we tested several B vitamins to determine if they would stimulate larvae of the deposit-feeding polychaete Capitella teleta to settle and metamorphose. Nicotinamide and riboflavin individually stimulated larvae of C. teleta to settle and metamorphose, generally within 1-2 hours at nicotinamide concentrations as low as 3 µM and riboflavin concentrations as low as 50 µM. More than 80% of the larvae metamorphosed within 30 minutes at a nicotinamide concentration of 7 µM. The pyridine channel agonist pyrazinecarboxamide also stimulated metamorphosis at very low concentrations. In contrast, neither lumichrome, thiamine HCl, pyridoxine HCl, nor vitamin B12 stimulated larvae of C. teleta to metamorphose at concentrations as high as 500 µM. Larvae also did not metamorphose in response to either nicotinamide or pyrazinecarboxamide in calcium-free seawater or with the addition of 4-acetylpyridine, a competitive inhibitor of the pyridine receptor. Together, these results suggest that larvae of C. teleta are responding to nicotinamide and riboflavin via a chemosensory pyridine receptor similar to that previously reported to be present on crayfish chela and involved with food recognition. Our data are the first to implicate B vitamins as possible natural chemical settlement cues for marine invertebrate larvae.

  3. The B Vitamins Nicotinamide (B3) and Riboflavin (B2) Stimulate Metamorphosis in Larvae of the Deposit-Feeding Polychaete Capitella teleta: Implications for a Sensory Ligand-Gated Ion Channel

    Science.gov (United States)

    Burns, Robert T.; Pechenik, Jan A.; Biggers, William J.; Scavo, Gia; Lehman, Christopher

    2014-01-01

    Marine sediments can contain B vitamins, presumably incorporated from settled, decaying phytoplankton and microorganisms associated with decomposition. Because B vitamins may be advantageous for the energetically intensive processes of metamorphosis, post-metamorphic growth, and reproduction, we tested several B vitamins to determine if they would stimulate larvae of the deposit-feeding polychaete Capitella teleta to settle and metamorphose. Nicotinamide and riboflavin individually stimulated larvae of C. teleta to settle and metamorphose, generally within 1–2 hours at nicotinamide concentrations as low as 3 µM and riboflavin concentrations as low as 50 µM. More than 80% of the larvae metamorphosed within 30 minutes at a nicotinamide concentration of 7 µM. The pyridine channel agonist pyrazinecarboxamide also stimulated metamorphosis at very low concentrations. In contrast, neither lumichrome, thiamine HCl, pyridoxine HCl, nor vitamin B12 stimulated larvae of C. teleta to metamorphose at concentrations as high as 500 µM. Larvae also did not metamorphose in response to either nicotinamide or pyrazinecarboxamide in calcium-free seawater or with the addition of 4-acetylpyridine, a competitive inhibitor of the pyridine receptor. Together, these results suggest that larvae of C. teleta are responding to nicotinamide and riboflavin via a chemosensory pyridine receptor similar to that previously reported to be present on crayfish chela and involved with food recognition. Our data are the first to implicate B vitamins as possible natural chemical settlement cues for marine invertebrate larvae. PMID:25390040

  4. Topical Melatonin for Treatment of Androgenetic Alopecia

    OpenAIRE

    Fischer, Tobias W; Tr?eb, Ralph M; H?nggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-01-01

    Background: In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. Materials and Methods: One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardise...

  5. YCL047C/POF1 is a novel nicotinamide mononucleotide adenylyltransferase (NMNAT) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kato, Michiko; Lin, Su-Ju

    2014-05-30

    NAD(+) is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD(+) pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared with wild type, suggesting that POF1 plays an important role in NR/NAD(+) metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleotide adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD(+) levels and decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contributes to the regulation of NAD(+) homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD(+) metabolism in higher eukaryotes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT)

    Energy Technology Data Exchange (ETDEWEB)

    Curtin, Michael L.; Heyman, H. Robin; Clark, Richard F.; Sorensen, Bryan K.; Doherty, George A.; Hansen, T. Matthew; Frey, Robin R.; Sarris, Kathy A.; Aguirre, Ana L.; Shrestha, Anurupa; Tu, Noah; Woller, Kevin; Pliushchev, Marina A.; Sweis, Ramzi F.; Cheng, Min; Wilsbacher, Julie L.; Kovar, Peter J.; Guo, Jun; Cheng, Dong; Longenecker, Kenton L.; Raich, Diana; Korepanova, Alla V.; Soni, Nirupama B.; Algire, Mikkel A.; Richardson, Paul L.; Marin, Violeta L.; Badagnani, Ilaria; Vasudevan, Anil; Buchanan, F.Greg; Maag, David; Chiang, Gary G.; Tse, Chris; Michaelides, Michael R. (AbbVie)

    2017-08-01

    Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed.

  7. Nicotinamide and carbogen: relationship between pO2 and radiosensitivity in three tumour lines

    International Nuclear Information System (INIS)

    Martin, L.M.; Thomas, C.D.; Guichard, M.

    1994-01-01

    The effects of carbogen breathing, nicotinamide injection and their combination on tumour radiosensitivity were correlated with changes in tumour O 2 tension to determine the relationship between radiosensitivity and measured pO 2 . The radiosensitivity (in vivo-in vitro colony assay) and O 2 tension (computerized pO 2 histograph KIMOC 6650) of two human xenografted tumours (HRT18 and NA11 +) and one murine tumour (EMT6) were measured under similar experimental conditions. (author)

  8. Topics in nonlinear wave theory with applications

    International Nuclear Information System (INIS)

    Tracy, E.R.

    1984-01-01

    Selected topics in nonlinear wave theory are discussed, and applications to the study of modulational instabilities are presented. A historical survey is given of topics relating to solitons and modulational problems. A method is then presented for generating exact periodic and quasi-periodic solutions to several nonlinear wave equations, which have important physical applications. The method is then specialized for the purposes of studying the modulational instability of a plane wave solution of the nonlinear Schroedinger equation, an equation with general applicability in one-dimensional modulational problems. Some numerical results obtained in conjunction with the analytic study are presented. The analytic approach explains the recurrence phenomena seen in the numerical studies, and the numerical work of other authors. The method of solution (related to the inverse scattering method) is then analyzed within the context of Hamiltonian dynamics where it is shown that the method can be viewed as simply a pair of canonical transformations. The Abel Transformation, which appears here and in the work of other authors, is shown to be a special form of Liouville's transformation to action-angle variables. The construction of closed form solutions of these nonlinear wave equations, via the solution of Jacobi's inversion problem, is surveyed briefly

  9. Development of Chemistry Triangle Oriented Module on Topic of Reaction Rate for Senior High School Level Grade XI Chemistry Learning.

    Science.gov (United States)

    Sari, D. R.; Hardeli; Bayharti

    2018-04-01

    This study aims to produce chemistry triangle oriented module on topic of reaction rate, and to reveal the validity and practicality level of the generated module. The type of research used is EducationalDesign Research (EDR) with development model is Plompmodel. This model consists of three phases, which are preliminary research, prototyping phase, and assessment phase. The instrument used in this research is questionnaire validity and practicality. The data of the research were analyzed by using Kappa Cohen formula. The chemistry triangle oriented module validation sheet was given to 5 validators consisting of 3 chemistry lecturers and 2 high school chemistry teachers, while the practicality sheet was given to 2 chemistry teachers, 6 students of SMAN 10 Padang grade XII MIA 5 on the small groupevaluation and 25 students of SMAN 10 Padang grade XII MIA 6 on the field test. Based on the questionnaire validity analysis, the validity level of the module is very high with the value of kappa moment 0.87. The level of practicality based on teacher questionnaire response is very high category with a kappa moment value 0.96. Based on the questionnaire of student responses on small group evaluation, the level of practicality is very high category with a kappa moment 0.81, and the practicality is very high category with kappa moment value 0.83 based on questionnaire of student response on field test.

  10. 1H NMR analysis of complexation of hydrotropic agents nicotinamide and caffeine with aromatic biologically active molecules in aqueous solution

    Science.gov (United States)

    Lantushenko, Anastasia O.; Mukhina, Yulia V.; Veselkov, Kyrill A.; Davies, David B.; Veselkov, Alexei N.

    2004-07-01

    NMR spectroscopy has been used to elucidate the molecular mechanism of solubilization action of hydrotropic agents nicotinamide (NA) and caffeine (CAF). Hetero-association of NA with riboflavine-mononucleotide (FMN) and CAF with low soluble in aqueous solution synthetic analogue of antibiotic actinomycin D, actinocyl-bis-(3-dimethylaminopropyl) amine (Actill), has been investigated by 500 MHz 1H NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts have been analysed in terms of a statistical-thermodynamic model of indefinite self- and heteroassociation of aromatic molecules. The obtained results enable to conclude that NA-FMN and CAF-Actill intermolecular complexes are mainly stabilized by the stacking interactions of the aromatic chromophores. Hetero-association of the investigated molecules plays an important role in solubilization of aromatic drugs by hydrotropic agents nicotinamide and caffeine.

  11. Nicotinamide adenosine dinucleotide level in dimethylsulfate-treated or UV-irradiated mouse epidermis

    International Nuclear Information System (INIS)

    Balard, B.; Giacomoni, P.U.

    1989-01-01

    The level of nicotinamide (NAD) has been determined in the epidermis of 30 mice. Its value is 0.63+-0.15 μg/mg protein. Upon treatment with dimethylsulfate (DMS), the level of NAD drops in a dosedependent fashion. This diminution is reversible when low doses of DMS are used. Upon irradiation with ultraviolet light, the level of NAD drops in the irradiated epidermis, the treshold of saturation being below 1200 J/m 2 . There is also a drop in the level of NAD in the epidermis protected against irradiation with a black rubber sheet. (author). 17 refs.; 6 figs.; 1 tab

  12. Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland

    International Nuclear Information System (INIS)

    Xiang, Bin; Han, Lichi; Wang, Xinyue; Tang, Ling; Li, Kailiang; Li, Xiuxiu; Zhao, Xibo; Xia, Miaomiao; Zhou, Xixi; Zhang, Fuyin; Liu, Ke Jian

    2016-01-01

    Purpose: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology. However, the regulatory events of NAMPT in response to the irradiated salivary gland are unknown. Methods and Materials: The cell viability of primary cultured submandibular gland cells was determined using the PrestoBlue assay. NAMPT expression was measured using reverse transcriptase polymerase chain reaction and Western blotting in vitro and in vivo. Silent information regulator 1 (SIRT1) and phosphorylated Akt protein levels were examined by Western blotting. The cellular locations of NAMPT and SIRT1 were detected by immunohistochemistry. NAMPT promoter activity was assessed using the luciferase reporter gene assay. Results: NAMPT was mainly distributed in the cytoplasm of granular convoluted tubule cells and ductal cells in normal submandibular glands. mRNA and protein expression of NAMPT was downregulated after radiation but upregulated with phenylephrine pretreatment both in vivo and in vitro. Moreover, the protein expression of phosphorylated Akt and SIRT1 was decreased in irradiated glands, and phenylephrine pretreatment restored the expression of both. SIRT1 was mainly located in the cell nucleus and cytoplasm in the normal submandibular gland. Phenylephrine dramatically enhanced the expression of SIRT1, which was significantly reduced by radiation. Furthermore, phenylephrine induced a marked increase of NAMPT promoter activity. Conclusions: These findings reveal the regulatory mechanisms of NAMPT expression

  13. Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Bin, E-mail: xiangbin72@163.com [Laboratory of Oral and Maxillofacial Disease, Second Hospital of Dalian Medical University, Dalian (China); Han, Lichi [Department of Oral Medicine and Medical Research Center of Medical College, Dalian University, Dalian (China); Wang, Xinyue [Laboratory of Oral and Maxillofacial Disease, Second Hospital of Dalian Medical University, Dalian (China); Tang, Ling [Life Sciences and Technology College, Dalian University, Dalian (China); Li, Kailiang [Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian (China); Li, Xiuxiu [Department of Oral Medicine and Medical Research Center of Medical College, Dalian University, Dalian (China); Zhao, Xibo [Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian (China); Xia, Miaomiao [Department of Oral Medicine and Medical Research Center of Medical College, Dalian University, Dalian (China); Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico (United States); Zhang, Fuyin [Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian (China); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico (United States)

    2016-11-01

    Purpose: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology. However, the regulatory events of NAMPT in response to the irradiated salivary gland are unknown. Methods and Materials: The cell viability of primary cultured submandibular gland cells was determined using the PrestoBlue assay. NAMPT expression was measured using reverse transcriptase polymerase chain reaction and Western blotting in vitro and in vivo. Silent information regulator 1 (SIRT1) and phosphorylated Akt protein levels were examined by Western blotting. The cellular locations of NAMPT and SIRT1 were detected by immunohistochemistry. NAMPT promoter activity was assessed using the luciferase reporter gene assay. Results: NAMPT was mainly distributed in the cytoplasm of granular convoluted tubule cells and ductal cells in normal submandibular glands. mRNA and protein expression of NAMPT was downregulated after radiation but upregulated with phenylephrine pretreatment both in vivo and in vitro. Moreover, the protein expression of phosphorylated Akt and SIRT1 was decreased in irradiated glands, and phenylephrine pretreatment restored the expression of both. SIRT1 was mainly located in the cell nucleus and cytoplasm in the normal submandibular gland. Phenylephrine dramatically enhanced the expression of SIRT1, which was significantly reduced by radiation. Furthermore, phenylephrine induced a marked increase of NAMPT promoter activity. Conclusions: These findings reveal the regulatory mechanisms of NAMPT expression

  14. Deficits in discrimination after experimental frontal brain injury are mediated by motivation and can be improved by nicotinamide administration.

    Science.gov (United States)

    Vonder Haar, Cole; Maass, William R; Jacobs, Eric A; Hoane, Michael R

    2014-10-15

    One of the largest challenges in experimental neurotrauma work is the development of models relevant to the human condition. This includes both creating similar pathophysiology as well as the generation of relevant behavioral deficits. Recent studies have shown that there is a large potential for the use of discrimination tasks in rats to detect injury-induced deficits. The literature on discrimination and TBI is still limited, however. The current study investigated motivational and motor factors that could potentially contribute to deficits in discrimination. In addition, the efficacy of a neuroprotective agent, nicotinamide, was assessed. Rats were trained on a discrimination task and motivation task, given a bilateral frontal controlled cortical impact TBI (+3.0 AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI resulted in large deficits in discrimination and motivation. No deficits were observed on gross motor measures; however, the vehicle group showed impairments in fine motor control. Both injured groups were impaired on the reference memory MWM, but only nicotinamide-treated rats were impaired on the working memory MWM. Nicotinamide administration improved performance on discrimination and motivation measures. Experiment 2 evaluated retraining on the discrimination task and suggested that motivation may be a large factor underlying discrimination deficits. Retrained rats improved considerably on the discrimination task. The tasks evaluated in this study demonstrate robust deficits and may improve the detection of pharmaceutical effects by being very sensitive to pervasive cognitive deficits that occur after frontal TBI.

  15. Special Attachments. Module 19.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special attachments, one in a series dealing with industrial sewing machines, their attachments, and operation, covers four topics: gauges; cording attachment; zipper foot; and hemming, shirring, and binding. For each topic these components are provided: an introduction, directions, an objective, learning activities, student…

  16. Special Operation. Module 20.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special operations, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: topstitching and mitering. For each topic these components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a check-out…

  17. Health Occupations Module. The Integumentary System.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the integumentary system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, objectives (e.g., list and describe the types of glands formed in the skin, and explain the…

  18. The influence of nalidixic acid and nicotinamide of the radiation-induced cytogenetic injury to hexaploid wheat varities contrast by radioresistance

    International Nuclear Information System (INIS)

    Selezneva, E.M.; Sarapul'tsev, B.I.

    1990-01-01

    Nalidixic acid modifies the cytogenetic injury when only applied to seeds of a radiosensitive variety, Moskovskaya 35. The radioprotective effect of nicotinamide on both radiosensitive and radioresistant hexaploid wheat varities is observed being dependent on the extent which the genetic apparatus is impaired

  19. Affirmative Action. Module Number 16. Work Experience Program Modules. Coordination Techniques Series.

    Science.gov (United States)

    Shawhan, Carl; Morley, Ray

    This self-instructional module, the last in a series of 16 on techniques for coordinating work experience programs, deals with affirmative action. Addressed in the module are the following topics: the nature of affirmative action legislation and regulations, the role of the teacher-coordinator as a resource person for affirmative action…

  20. Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 regulates axon integrity in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Amy N Hicks

    Full Text Available Using transposon-mediated gene-trap mutagenesis, we have generated a novel mouse mutant termed Blad (Bloated Bladder. Homozygous mutant mice die perinatally showing a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass. Wild type and heterozygote mice appear normal. Using PCR, we identified a transposon insertion site in the first intron of Nmnat2 (Nicotinamide mononucleotide adenyltransferase 2. Nmnat2 is expressed predominantly in the brain and nervous system and has been linked to the survival of axons. Expression of this gene is undetectable in Nmnat2(blad/blad mutants. Examination of the brains of E18.5 Nmnat2(blad/blad mutant embryos did not reveal any obvious morphological changes. In contrast, E18.5 Nmnat2(blad/blad homozygotes showed an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion (DRG. In addition, facial motoneuron numbers were severely reduced, and there was virtually a complete absence of axons in the hind limb. Our observations suggest that during embryogenesis, Nmnat2 plays an important role in axonal growth or maintenance. It appears that in the absence of Nmnat2, major target organs and tissues (e.g., muscle are not functionally innervated resulting in perinatal lethality. In addition, neither Nmnat1 nor 3 can compensate for the loss of Nmnat2. Whilst there have been recent suggestions that Nmnat2 may be an endogenous modulator of axon integrity, this work represents the first in vivo study demonstrating that Nmnat2 is involved in axon development or survival in a mammal.

  1. Influence of Sodium Lauryl Sulfate and Tween 80 on Carbamazepine–Nicotinamide Cocrystal Solubility and Dissolution Behaviour

    OpenAIRE

    Ke Wang; Ning Qiao; Mingzhong Li

    2013-01-01

    The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine–nicotinamide (CBZ–NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ–NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ–NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated...

  2. The human heart and the circulatory system as an interesting interdisciplinary topic in lessons of physics and biology

    International Nuclear Information System (INIS)

    Volná, M; Látal, F; Kubínek, R; Richterek, L

    2014-01-01

    Many topics which are closely related can be found in the national curriculum of the Czech Republic for physics and biology. One of them is the heart and the circulatory system in the human body. This topic was examined cross curriculum, a teaching module was created and the topic was chosen for our research. The task was to determine if the students of bachelor study are aware of connections between physics and biology within this topic and whether we can help them effectively to describe the corresponding physics phenomena in the human body connected, for example, with a heart attack or with the measurement of blood pressure. In this paper, the heart and the circulatory system are presented as suitable topics for an interdisciplinary teaching module which includes both theoretical and experimental parts. The module was evaluated by a group of first-year undergraduate students of physics at the Faculty of Science, Palacký University. The acquired knowledge was compared with another control group through a test. The highest efficiency of the module was evaluated on the basis of questions that covered the calculation problems. (paper)

  3. Expose Mechanical Engineering Students to Biomechanics Topics

    Science.gov (United States)

    Shen, Hui

    2011-01-01

    To adapt the focus of engineering education to emerging new industries and technologies nationwide and in the local area, a biomechanics module has been developed and incorporated into a mechanical engineering technical elective course to expose mechanical engineering students at ONU (Ohio Northern University) to the biomedical engineering topics.…

  4. Topical melatonin for treatment of androgenetic alopecia.

    Science.gov (United States)

    Fischer, Tobias W; Trüeb, Ralph M; Hänggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-10-01

    In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second hair count test and hair pull test. FIVE CLINICAL STUDIES SHOWED POSITIVE EFFECTS OF A TOPICAL MELATONIN SOLUTION IN THE TREATMENT OF AGA IN MEN AND WOMEN WHILE SHOWING GOOD TOLERABILITY: (1) Pharmacodynamics under once-daily topical application in the evening showed no significant influence on endogenous serum melatonin levels. (2) An observational study involving 30 men and women showed a significant reduction in the degree of severity of alopecia after 30 and 90 days (P melatonin solution can be considered as a treatment option in androgenetic alopecia.

  5. Medical Terminology: Suffixes. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (suffixes) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three learning experiences. The first two learning…

  6. Health Occupations Module. The Skeletal System--I.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, three objectives (e.g., define the skeletal system and list its functions), and three learning…

  7. Health Occupations Module. The Skeletal System--II.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, two objectives (e.g., list the types of joints and movements, and give examples), and two learning…

  8. The Buttonhole Machine. Module 13.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the bottonhole machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: performing special operations on the buttonhole machine (parts and purpose) and performing special operations on the buttonhole machine (gauged buttonholes). For each topic these components are…

  9. Pharmacokinetics of pirfenidone after topical administration in rabbit eye.

    Science.gov (United States)

    Sun, Guoying; Lin, Xianchai; Zhong, Hua; Yang, Yangfan; Qiu, Xuan; Ye, Chengtian; Wu, Kaili; Yu, Minbin

    2011-01-01

    Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum agent that has an inhibition effect on the proliferation, migration, and collagen contraction of human Tenon's fibroblasts, and thus modulating the wound healing process of glaucoma filtering surgical site. This study investigated the pharmacokinetics of topically administered pirfenidone (0.5%) in rabbit eyes. Pirfenidone solution (50 μl) was instilled into the rabbit's conjunctival sac. The rabbits were quickly sacrificed at 2, 5, 8, 10, 15, 20, 30, 60, 90, and 120 min after the administration and ocular tissues were obtained. The concentrations of pirfenidone in conjunctiva, sclera, cornea, aqueous humor, and vitreous were determined by high performance liquid chromatography. After topical administration, there was wide distribution and fast clearance of pirfenidone among the various ocular tissues. The mean maximum concentrations (C(max)) of pirfenidone in cornea, conjunctiva, sclera, aqueous humor, and vitreous were 9.64 mg/g, 9.62 mg/g, 2.13 mg/g, 34.88 mg/l and 0.52 mg/l, respectively. The half-life for these tissues was 18.26, 34.16, 15.71, 70.91, and 39.48 min, respectively. Measurable concentrations of pirfenidone are achieved in ocular tissues after topical application in rabbit model. Topical administration of pirfenidone may be an effective approach for modulation of wound healing responses in glaucoma filtration surgical site.

  10. Hyperthermophilic Archaeon Thermococcus kodakarensis Utilizes a Four-Step Pathway for NAD+ Salvage through Nicotinamide Deamination.

    Science.gov (United States)

    Hachisuka, Shin-Ichi; Sato, Takaaki; Atomi, Haruyuki

    2018-06-01

    Many organisms possess pathways that regenerate NAD + from its degradation products, and two pathways are known to salvage NAD + from nicotinamide (Nm). One is a four-step pathway that proceeds through deamination of Nm to nicotinic acid (Na) by Nm deamidase and phosphoribosylation to nicotinic acid mononucleotide (NaMN), followed by adenylylation and amidation. Another is a two-step pathway that does not involve deamination and directly proceeds with the phosphoribosylation of Nm to nicotinamide mononucleotide (NMN), followed by adenylylation. Judging from genome sequence data, the hyperthermophilic archaeon Thermococcus kodakarensis is supposed to utilize the four-step pathway, but the fact that the adenylyltransferase encoded by TK0067 recognizes both NMN and NaMN also raises the possibility of a two-step salvage mechanism. Here, we examined the substrate specificity of the recombinant TK1676 protein, annotated as nicotinic acid phosphoribosyltransferase. The TK1676 protein displayed significant activity toward Na and phosphoribosyl pyrophosphate (PRPP) and only trace activity with Nm and PRPP. We further performed genetic analyses on TK0218 (quinolinic acid phosphoribosyltransferase) and TK1650 (Nm deamidase), involved in de novo biosynthesis and four-step salvage of NAD + , respectively. The ΔTK0218 mutant cells displayed growth defects in a minimal synthetic medium, but growth was fully restored with the addition of Na or Nm. The ΔTK0218 ΔTK1650 mutant cells did not display growth in the minimal medium, and growth was restored with the addition of Na but not Nm. The enzymatic and genetic analyses strongly suggest that NAD + salvage in T. kodakarensis requires deamination of Nm and proceeds through the four-step pathway. IMPORTANCE Hyperthermophiles must constantly deal with increased degradation rates of their biomolecules due to their high growth temperatures. Here, we identified the pathway that regenerates NAD + from nicotinamide (Nm) in the

  11. Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.

    Science.gov (United States)

    Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael

    2018-03-06

    The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD + , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD + nor NADP + was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects. Published by Elsevier Inc.

  12. Problematic topics in first-year mathematics: lecturer and student views

    Science.gov (United States)

    Ní Shé, Caitríona; Mac an Bhaird, Ciarán; Ní Fhloinn, Eabhnat; O'Shea, Ann

    2017-07-01

    In this paper we report on the outcomes of two surveys carried out in higher education institutions of Ireland; one of students attending first-year undergraduate non-specialist mathematics modules and another of their lecturers. The surveys aimed to identify the topics that these students found difficult, whether they had most difficulty with the concepts or procedures involved in the topics, and the resources they used to overcome these difficulties. In this paper we focus on the mathematical concepts and procedures that students found most difficult. While there was agreement between students and lecturers on certain problematic topics, this was not uniform across all topics, and students rated their conceptual understanding higher than their ability to do questions, in contrast to lecturers' opinions.

  13. Liquid crystals: a new topic in physics for undergraduates

    International Nuclear Information System (INIS)

    Pavlin, Jerneja; Čepič, Mojca; Vaupotič, Nataša

    2013-01-01

    This paper presents a teaching module about liquid crystals. Since liquid crystals are linked to everyday student experiences and are also a topic of current scientific research, they are an excellent candidate for a modern topic to be introduced into education. We show that liquid crystals can provide a pathway through several fields of physics such as thermodynamics, optics and electromagnetism. We discuss what students should learn about liquid crystals and what physical concepts they should know before considering them. In the presentation of the teaching module, which consists of a lecture and experimental work in a chemistry and physics laboratory, we focus on experiments on phase transitions, polarization of light, double refraction and colours. A pilot evaluation of the module was performed among pre-service primary school teachers who have no special preference for natural sciences. The evaluation shows that the module is very efficient in transferring knowledge. A prior study showed that the informally obtained pre-knowledge on liquid crystals of the first-year students from several different fields of study was negligible. Since social science students are the least interested in natural sciences, it can be expected that students in any study programme will on average achieve at least as good qualitative knowledge of phenomena related to liquid crystals as the group involved in the pilot study. (paper)

  14. Model theory and modules

    CERN Document Server

    Prest, M

    1988-01-01

    In recent years the interplay between model theory and other branches of mathematics has led to many deep and intriguing results. In this, the first book on the topic, the theme is the interplay between model theory and the theory of modules. The book is intended to be a self-contained introduction to the subject and introduces the requisite model theory and module theory as it is needed. Dr Prest develops the basic ideas concerning what can be said about modules using the information which may be expressed in a first-order language. Later chapters discuss stability-theoretic aspects of module

  15. TOPICS-B, Neutron and Gamma Cross-Sections Library Handling in FIDO Format

    International Nuclear Information System (INIS)

    Wasastjerna, Frej

    2003-01-01

    1 - Description of program or function: The program is intended to manipulate working format neutron and/or gamma cross section libraries, carrying out such operations as mixing materials, deleting unneeded groups, inserting response cross sections or whatever the user may require. It has been designed to make it easy to include new modules to cope with new requirements. The cross section libraries involved should preferably be in ANISN format, but if they are not, this too can be handled by adding new modules as needed. This program is intended to supersede TOPICS (NEA-1406). TOPICS was intended for interactive use, but experience has shown that using it is somewhat difficult. Therefore it was redesigned for batch use (the input is written to a file and the program is then run using that file, instead of reading input directly from the keyboard). 2 - Method of solution: Each required operation is performed by a separate module (a set of subprograms). 3 - Restrictions on the complexity of the problem: Essentially none, variable dimensioning is used. However, TOPICS-B is not intended to be applied to basic nuclear data libraries (such as the ENDF/B series) or to flexible format libraries (e.g., the VITAMIN series). It is intended only for working format libraries like the BUGLE series

  16. Pnc1p-mediated nicotinamide clearance modifies the epigenetic properties of rDNA silencing in Saccharomyces cerevisiae.

    Science.gov (United States)

    McClure, Julie M; Gallo, Christopher M; Smith, Daniel L; Matecic, Mirela; Hontz, Robert D; Buck, Stephen W; Racette, Frances G; Smith, Jeffrey S

    2008-10-01

    The histone deacetylase activity of Sir2p is dependent on NAD(+) and inhibited by nicotinamide (NAM). As a result, Sir2p-regulated processes in Saccharomyces cerevisiae such as silencing and replicative aging are susceptible to alterations in cellular NAD(+) and NAM levels. We have determined that high concentrations of NAM in the growth medium elevate the intracellular NAD(+) concentration through a mechanism that is partially dependent on NPT1, an important gene in the Preiss-Handler NAD(+) salvage pathway. Overexpression of the nicotinamidase, Pnc1p, prevents inhibition of Sir2p by the excess NAM while maintaining the elevated NAD(+) concentration. This growth condition alters the epigenetics of rDNA silencing, such that repression of a URA3 reporter gene located at the rDNA induces growth on media that either lacks uracil or contains 5-fluoroorotic acid (5-FOA), an unusual dual phenotype that is reminiscent of telomeric silencing (TPE) of URA3. Despite the similarities to TPE, the modified rDNA silencing phenotype does not require the SIR complex. Instead, it retains key characteristics of typical rDNA silencing, including RENT and Pol I dependence, as well as a requirement for the Preiss-Handler NAD(+) salvage pathway. Exogenous nicotinamide can therefore have negative or positive impacts on rDNA silencing, depending on the PNC1 expression level.

  17. Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes.

    Science.gov (United States)

    Ziamajidi, Nasrin; Nasiri, Abolfazl; Abbasalipourkabir, Roghayeh; Sadeghi Moheb, Somayeh

    2017-12-01

    Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia. The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ) + nicotinamide-induced diabetes. Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ + nicotinamide-induced diabetes that received a single dose of STZ (65 mg/kg) and nicotinamide (110 mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2 g/kg/d, gavage), and normal rats that received garlic (2 g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats. The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p garlic-treated diabetic rats compared with diabetic rats (p garlic, it was close to the normal level (p garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.

  18. A novel twist on molecular interactions between thioredoxin and nicotinamide adenine dinucleotide phosphate-dependent thioredoxin reductase

    DEFF Research Database (Denmark)

    Kirkensgaard, Kristine Groth; Hägglund, Per; Shahpiri, Azar

    2013-01-01

    The ubiquitous disulfide reductase thioredoxin (Trx) regulates several important biological processes such as seed germination in plants. Oxidized cytosolic Trx is regenerated by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase (NTR) in a multistep transfer...... dinucleotide (FAD)-binding domain of HvNTR2 to strongly affect the interaction with Trx. In particular, Trp42 and Met43 play key roles for recognition of the endogenous HvTrxh2. Trx from Arabidopsis thaliana is also efficiently recycled by HvNTR2 but turnover in this case appears to be less dependent...

  19. Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

    2011-01-01

    The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker...... for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant.......0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors....

  20. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  1. Quantum model for electro-optical amplitude modulation.

    Science.gov (United States)

    Capmany, José; Fernández-Pousa, Carlos R

    2010-11-22

    We present a quantum model for electro-optic amplitude modulation, which is built upon quantum models of the main photonic components that constitute the modulator, that is, the guided-wave beamsplitter and the electro-optic phase modulator and accounts for all the different available modulator structures. General models are developed both for single and dual drive configurations and specific results are obtained for the most common configurations currently employed. Finally, the operation with two-photon input for the control of phase-modulated photons and the important topic of multicarrier modulation are also addressed.

  2. Place Value. Fundamentals of Occupational Mathematics. Module 1.

    Science.gov (United States)

    Engelbrecht, Nancy; And Others

    This module is the first in a series of 12 learning modules designed to teach occupational mathematics. Designed for improving machine shop technology skills, this module begins with an introduction to the topic. Blocks of informative material and rules are followed by examples and practice problems. The solutions to the practice problems are…

  3. The Adsorption of Calmoduline via Nicotinamide Immobilized Poly(HEMA-GMA Cryogels

    Directory of Open Access Journals (Sweden)

    Kadir Erol

    2016-12-01

    Full Text Available The separation and purification methods for the isolation of an important biomolecule calmoduline protein is extremely important. Among these methods, the adsorption technique is extremely popular, and the cryogels as adsorbents with the macro porous structure and interconnected flow channels cryogel they have are preferred in this field. In this study, the adsorption of calmoduline via Ca(II immobilized poly (2-hydroxyethyl methacrylate-glycidyl methacrylate, poly (HEMA-GMA, cryogels through changing interaction time, calmoduline initial concentration and temperature conditions. For the characterization of cryogels, the swelling test, Fourier Transform Infrared (FT-IR Spectroscopy, Scanning Electron Microscopy (SEM, surface area (BET, elemental analysis and ICP-OES methods were performed. Nicotinamide molecule was used as Ca (II chelating agent and the adsorption capacity of the cryogels was estimated as 1.812 mg calmoduline / g cryogel. The adsorption models of the adsorption reaction were examined by the Langmuir and Freundlich isotherm models and was determined to be more appropriate for Langmuir isotherm model.

  4. Development of a simple and efficient method for assaying cytidine monophosphate sialic acid synthetase activity using an enzymatic reduced nicotinamide adenine dinucleotide/oxidized nicotinamide adenine dinucleotide converting system.

    Science.gov (United States)

    Fujita, Akiko; Sato, Chihiro; Münster-Kühnel, Anja-K; Gerardy-Schahn, Rita; Kitajima, Ken

    2005-02-01

    A new reliable method to assay the activity of cytidine monophosphate sialic acid (CMP-Sia) synthetase (CSS) has been developed. The activation of sialic acids (Sia) to CMP-Sia is a prerequisite for the de novo synthesis of sialoglycoconjugates. In vertebrates, CSS has been cloned from human, mouse, and rainbow trout, and the crystal structure has been resolved for the mouse enzyme. The mouse and rainbow trout enzyme have been compared with respect to substrate specificity, demonstrating that the mouse enzyme exhibits a pronounced specificity for N-acetylneuraminic acid (Neu5Ac), while the rainbow trout CSS is equally active with either of three Sia species, Neu5Ac, N-glycolylneuraminic acid (Neu5Gc), and deaminoneuraminic acid (KDN). However, molecular details that explain the pronounced substrate specificities are unknown. Understanding the catalytic mechanisms of these enzymes is of major importance, since CSSs play crucial roles in cellular sialylation patterns and thus are potential drug targets in a number of pathophysiological situations. The availability of the cDNAs and the obtained structural data enable rational approaches; however, these efforts are limited by the lack of a reliable high-throughput assay system. Here we describe a new assay system that allows product quantification in a reduced nicotinamide adenine dinucleotide (NADH)-dependent color reaction. The activation reaction catalyzed by CSS, CTP+Sia-->CMP-Sia+pyrophosphate, was evaluated by a consumption of Sia, which corresponds to that of NADH on the following two successive reactions: (i) Sia-->pyruvate+ManNAc (or Man), catalyzed by a sialic acid lyase (SAL), and (ii) pyruvate+NADH-->lactate+oxidized nicotinamide adenine dinucleotide (NAD+), catalyzed by a lactate dehydrogenase (LDH). Consumption of NADH can be photometrically monitored on a microtiter plate reader for a number of test samples at the same time. Furthermore, based on the quantification of CSS used in the SAL/LDH assay

  5. Assess Student Performance: Skills. Second Edition. Module D-4 of Category D--Instructional Evaluation. Professional Teacher Education Module Series.

    Science.gov (United States)

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This module, one of a series of 127 performance-based teacher education learning packages focusing upon specific professional competencies of vocational education teachers, deals with assessing student performance of psychomotor skills. Included in the module are learning experiences that address the following topics: important considerations…

  6. A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

    2010-01-01

    Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitam...

  7. Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease.

    Science.gov (United States)

    Watson, Alanna; Nong, Zengxuan; Yin, Hao; O'Neil, Caroline; Fox, Stephanie; Balint, Brittany; Guo, Linrui; Leo, Oberdan; Chu, Michael W A; Gros, Robert; Pickering, J Geoffrey

    2017-06-09

    The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage, but their capacities decline with age and stress. Recently, cellular production of nicotinamide adenine dinucleotide (NAD + ) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown. To determine whether a Nampt-NAD + control system exists within the aortic media and is required for aortic health. Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between SMC NAMPT content and aortic diameter. To determine whether a Nampt-NAD + control system in SMCs impacts aortic integrity, mice with Nampt -deficient SMCs were generated. SMC- Nampt knockout mice were viable but with mildly dilated aortas that had a 43% reduction in NAD + in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection. SMCs were not apoptotic but displayed senescence associated-ß-galactosidase activity and upregulated p16, indicating premature senescence. Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks, and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible on resupplying NAD + with nicotinamide riboside. Remarkably, we discovered unrepaired DNA strand breaks in SMCs within the human ascending aorta, which were specifically enriched in SMCs with low NAMPT. NAMPT promoter analysis revealed CpG hypermethylation within the dilated human thoracic aorta and in SMCs cultured from these tissues, which inversely correlated with NAMPT expression. The aortic media depends on an intrinsic NAD + fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy. © 2017 American Heart

  8. Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

    International Nuclear Information System (INIS)

    Martin del Campo, Julia S.; Patino, Rodrigo

    2011-01-01

    Research highlights: → The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. → A spectrophotometric method is proposed for kinetic and thermodynamic analysis. → The pH and the temperature influences are reported on physical chemical properties. → Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD ox ) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD ox as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, Δ f G o = -1784 ± 5 kJ mol -1 .

  9. Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

    Energy Technology Data Exchange (ETDEWEB)

    Martin del Campo, Julia S. [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico); Patino, Rodrigo, E-mail: rtarkus@mda.cinvestav.mx [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico)

    2011-04-20

    Research highlights: {yields} The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. {yields} A spectrophotometric method is proposed for kinetic and thermodynamic analysis. {yields} The pH and the temperature influences are reported on physical chemical properties. {yields} Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD{sub ox}) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD{sub ox} as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, {Delta}{sub f}G{sup o} = -1784 {+-} 5 kJ mol{sup -1}.

  10. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

    OpenAIRE

    Tsung-Han Yang; Hsien-Tsung Yao; Meng-Tsan Chiang

    2015-01-01

    Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with...

  11. Combination of hydrotropic nicotinamide with nanoparticles for enhancing tacrolimus percutaneous delivery

    Directory of Open Access Journals (Sweden)

    Pan W

    2016-08-01

    Full Text Available Wenhui Pan, Mengyao Qin, Guoguang Zhang, Yueming Long, Wenyi Ruan, Jingtong Pan, Zushuai Wu, Tao Wan, Chuanbin Wu, Yuehong Xu Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Tacrolimus (FK506, an effective immunosuppressant for treating inflammatory skin diseases, hardly penetrates into and through the skin owing to its high hydrophobicity and molecular weight. The aim of this study was to develop a hybrid system based on nicotinamide (NIC and nanoparticles (NPs encapsulating FK506, such as FK506–NPs–NIC, for facilitating percutaneous delivery, which exploited virtues of both NIC and NPs to obtain the synergetic effect. Solubility and percutaneous permeation studies were carried out. The results showed that NIC could increase the solubility and permeability of FK506 and that 20% (w/v NIC presented higher FK506 permeability and was thus chosen as the hydrotropic solution to solubilize FK506 and prepare FK506–NPs–NIC. Hyaluronic acid (HA was chemically conjugated with cholesterol (Chol to obtain amphiphilic conjugate of HA–Chol, which self-assembled NPs in 20% NIC solution containing FK506. The particle size, zeta potential, and morphology of NPs were characterized. The encapsulation efficiency and in vitro percutaneous permeation of NPs were evaluated in the presence and absence of NIC. The results demonstrated that hydrotropic solubilizing FK506 was readily encapsulated into NPs with a higher encapsulation efficiency of 79.2%±4.2%, and the combination of NPs with NIC exhibited a significantly synergistic effect on FK506 deposition within the skin (2.39±0.53 µg/cm2 and penetration through the skin (13.38±2.26 µg/cm2. The effect of the combination of NPs with NIC on drug permeation was further visualized by confocal laser scanning microscope through in vivo permeation studies, and the results confirmed that NPs–NIC synergistically enhanced

  12. Instructor's Guide for Human Development Student Modules.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This instructor's guide is designed for use with an accompanying set of 61 student learning modules on human development. Included among the topics covered in the individual modules are the following: consumer and homemaking education (health and nutrition, personal appearance and grooming, puberty, menstruation, the human reproductive system,…

  13. Topical use of dexpanthenol: a 70th anniversary article.

    Science.gov (United States)

    Proksch, Ehrhardt; de Bony, Raymond; Trapp, Sonja; Boudon, Stéphanie

    2017-12-01

    Approximately 70 years ago, the first topical dexpanthenol-containing formulation (Bepanthen™ Ointment) has been developed. Nowadays, various topical dexpanthenol preparations exist, tailored according to individual requirements. Topical dexpanthenol has emerged as frequently used formulation in the field of dermatology and skin care. Various studies confirmed dexpanthenol's moisturizing and skin barrier enhancing potential. It prevents skin irritation, stimulates skin regeneration and promotes wound healing. Two main directions in the use of topical dexpanthenol-containing formulations have therefore been pursued: as skin moisturizer/skin barrier restorer and as facilitator of wound healing. This 70th anniversary paper reviews studies with topical dexpanthenol in skin conditions where it is most frequently used. Although discovered decades ago, the exact mechanisms of action of dexpanthenol have not been fully elucidated yet. With the adoption of new technologies, new light has been shed on dexpanthenol's mode of action at the molecular level. It appears that dexpanthenol increases the mobility of stratum corneum molecular components which are important for barrier function and modulates the expression of genes important for wound healing. This review will update readers on recent advances in this field.

  14. Enzymatic synthesis of 13N-β-nicotinamide adenine dinucleotide

    International Nuclear Information System (INIS)

    Lambrecht, R.H.D.; Slegers, G.; Claeys, A.; Vandecasteele, C.

    1985-01-01

    Nitrogen-13-labelled β-nicotinamide adenine dinucleotide ( 13 N-NAD) is an interesting new compound for positron emission tomography. A semi-automatic production method is developed that yields a solution of 13 N-NAD of radiopharmaceutical quality, suitable for human intravenous administration. The 13 N-NAD is prepared enzymatically in one step from cyclotron-produced 13 NH 3 and nicotinic acid adenine dinucleotide (deamido-NAD). The enzyme NAD synthetase (E.C. 6.3.1.5), catalysing this reaction, is extracted and purified from Escherichia coli. The purified enzyme is immobilized by glutaraldehyde coupling to γ-aminopropylsilane-coated porous glass beads. The enzyme-loaded glass beads are packed in a column. The kinetic properties of the column are optimized. For synthetizing 13 N-NAD, the mixture of co-factors and substrates, containing 13 NH 3 , is pumped over the enzyme column. The unreacted 13 NH 3 is separated from 13 N-NAD by on-line passage over a cation exchanger. After passing over a millipore filter, a sterile solution of radiochemically pure 13 N-NAD is obtained, containing 70 mCi in 10 mL. The total synthesis time is 10 minutes. The specific activity is about 120 mCi/μmol at EOB. Quality control includes sterility and pyrogen tests, HPLC and HPTLC analysis. (author)

  15. Virtual Library Effluent Volume to Soil Disposal Sites Module Specification; TOPICAL

    International Nuclear Information System (INIS)

    M. A. deLamare

    2001-01-01

    This document provides the design specifications for each of the modules identified in the Virtual Library. The design specifications include design logic, input and output specifications, validation, and error handling

  16. Millwright Apprenticeship. Related Training Modules. 8.1-8.5 Turbines.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains five modules covering turbines. The modules provide information on the following topics: types, components, and auxiliaries of steam turbines; operation and maintenance of steam turbines; and gas turbines. Each module consists…

  17. Gas Metal Arc Welding. Welding Module 5. Instructor's Guide.

    Science.gov (United States)

    Missouri Univ., Columbia. Instructional Materials Lab.

    This guide is intended to assist vocational educators in teaching an eight-unit module in gas metal arc welding. The module is part of a welding curriculum that has been designed to be totally integrated with Missouri's Vocational Instruction Management System. The following topics are covered in the module: safety and testing, gas metal arc…

  18. Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

    Directory of Open Access Journals (Sweden)

    Avital Beig

    2016-10-01

    Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

  19. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

    Science.gov (United States)

    Beig, Avital; Lindley, David; Miller, Jonathan M.; Agbaria, Riad; Dahan, Arik

    2016-01-01

    Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure. PMID:27826241

  20. Diaquabis(4-bromobenzoato-κObis(nicotinamide-κN1copper(II

    Directory of Open Access Journals (Sweden)

    Hacali Necefoğlu

    2011-07-01

    Full Text Available The asymmetric unit of the title mononuclear CuII complex, [Cu(C7H4BrO22(C6H6N2O2(H2O2], contains one half-molecule, the CuII atom being located on an inversion center. The unit cell contains two nicotinamide (NA, two 4-bromobenzoate (PBB ligands and two coordinated water molecules. The four O atoms in the equatorial plane around the CuII ion form a slightly distorted square-planar arrangement, while the slightly distorted octahedral coordination is completed by the two N atoms of the NA ligands in the axial positions. The dihedral angle between the carboxylate group and the adjacent benzene ring is 22.17 (16°, while the pyridine ring and the benzene ring are oriented at a dihedral angle of 82.80 (6°. In the crystal, N—H...O, O—H...O and C—H...O hydrogen bonds link the molecules into a three-dimensional network. A weak C—H...π interaction is also observed.

  1. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

    Science.gov (United States)

    Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

    2017-03-07

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

  2. Induced modules over group algebras

    CERN Document Server

    Karpilovsky, Gregory

    1990-01-01

    In 1898 Frobenius discovered a construction which, in present terminology, associates with every module of a subgroup the induced module of a group. This construction proved to be of fundamental importance and is one of the basic tools in the entire theory of group representations.This monograph is designed for research mathematicians and advanced graduate students and gives a picture of the general theory of induced modules as it exists at present. Much of the material has until now been available only in research articles. The approach is not intended to be encyclopedic, rather each topic is

  3. Problematic Topics in First-Year Mathematics: Lecturer and Student Views

    Science.gov (United States)

    Ní Shé, Caitríona; Mac an Bhaird, Ciarán; Ní Fhloinn, Eabhnat; O'Shea, Ann

    2017-01-01

    In this paper we report on the outcomes of two surveys carried out in higher education institutions of Ireland; one of students attending first-year undergraduate non-specialist mathematics modules and another of their lecturers. The surveys aimed to identify the topics that these students found difficult, whether they had most difficulty with the…

  4. The kinetic analysis of the N-methylation of 4-phenylpyridine by nicotinamide N-methyltransferase: Evidence for a novel mechanism of substrate inhibition.

    Science.gov (United States)

    van Haren, Matthijs J; Thomas, Martin G; Sartini, Davide; Barlow, David J; Ramsden, David B; Emanuelli, Monica; Klamt, Fábio; Martin, Nathaniel I; Parsons, Richard B

    2018-03-13

    The N-methylation of 4-phenylpyridine produces the neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+). We investigated the kinetics of 4-phenylpyridine N-methylation by nicotinamide N-methyltransferase (NNMT) and its effect upon 4-phenylpyridine toxicity in vitro. Human recombinant NNMT possessed 4-phenylpyridine N-methyltransferase activity, with a specific activity of 1.7 ± 0.03 nmol MPP+ produced/h/mg NNMT. Although the K m for 4-phenylpyridine was similar to that reported for nicotinamide, its k cat of 9.3 × 10 -5  ± 2 × 10 -5  s -1 and specificity constant, k cat /K m , of 0.8 ± 0.8 s -1  M -1 were less than 0.15% of the respective values for nicotinamide, demonstrating that 4-phenylpyridine is a poor substrate for NNMT. At low (N-methylation was competitively inhibited by dimethylsulphoxide, with a K i of 34 ± 8 mM. At high (>2.5 mM) substrate concentration, enzyme activity followed substrate inhibition kinetics, with a K i of 4 ± 1 mM. In silico molecular docking suggested that 4-phenylpyridine binds to the active site of NNMT in two non-redundant poses, one a substrate binding mode and the other an inhibitory mode. Finally, the expression of NNMT in the SH-SY5Y cell-line had no effect cell death, viability, ATP content or mitochondrial membrane potential. These data demonstrate that 4-phenylpyridine N-methylation by NNMT is unlikely to serve as a source of MPP+. The possibility for competitive inhibition by dimethylsulphoxide should be considered in NNMT-based drug discovery studies. The potential for 4-phenylpyridine to bind to the active site in two binding orientations using the same active site residues is a novel mechanism of substrate inhibition. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet

    NARCIS (Netherlands)

    Shi, W.; Hegeman, M.A.; Dartel, van D.A.M.; Tang, J.; Suarez, M.; Swarts, H.; Hee, van der B.; Arola, L.; Keijer, J.

    2017-01-01

    Scope: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined

  6. Dense module enumeration in biological networks

    Science.gov (United States)

    Tsuda, Koji; Georgii, Elisabeth

    2009-12-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  7. Dense module enumeration in biological networks

    International Nuclear Information System (INIS)

    Tsuda, Koji; Georgii, Elisabeth

    2009-01-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  8. Topics and topic prominence in two sign languages

    NARCIS (Netherlands)

    Kimmelman, V.

    2015-01-01

    In this paper we describe topic marking in Russian Sign Language (RSL) and Sign Language of the Netherlands (NGT) and discuss whether these languages should be considered topic prominent. The formal markers of topics in RSL are sentence-initial position, a prosodic break following the topic, and

  9. Stationary Engineers Apprenticeship. Related Training Modules. 12.1-12.9. Boilers.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with boilers. Addressed in the individual instructional packages included in the module are the following topics: firetube and watertube boilers; boiler construction; procedures for operating and cleaning boilers; and boiler fittings,…

  10. Stationary Engineers Apprenticeship. Related Training Modules. 20.1-23.1 Miscellaneous.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with miscellaneous job skills needed by persons working in power plants. Addressed in the individual instructional packages included in the module are the following topics: transformers, circuit protection, construction of foundations…

  11. Online Video Modules for Improvement in Student Learning

    Science.gov (United States)

    Lancellotti, Matthew; Thomas, Sunil; Kohli, Chiranjeev

    2016-01-01

    The objective of this teaching innovation was to incorporate a comprehensive set of short online video modules covering key topics from the undergraduate principles of marketing class, and to evaluate its effectiveness in improving student learning. A quasiexperimental design was used to compare students who had access to video modules with a…

  12. Stationary Engineers Apprenticeship. Related Training Modules. 15.1-15.5 Turbines.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with turbines. addressed in the individual instructional packages included in the module are the following topics: types and components of steam turbines, steam turbine auxiliaries, operation and maintenance of steam turbines, and gas…

  13. Stationary Engineers Apprenticeship. Related Training Modules. 16.1-16.5 Combustion.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with combustion. Addressed in the individual instructional packages included in the module are the following topics: the combustion process, types of fuel, air and flue gases, heat transfer during combustion, and wood combustion. Each…

  14. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

    Science.gov (United States)

    Airhart, Sophia E; Shireman, Laura M; Risler, Linda J; Anderson, Gail D; Nagana Gowda, G A; Raftery, Daniel; Tian, Rong; Shen, Danny D; O'Brien, Kevin D

    2017-01-01

    The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

  15. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR and its effects on blood NAD+ levels in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sophia E Airhart

    Full Text Available The co-primary objectives of this study were to determine the human pharmacokinetics (PK of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+ levels.Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR, improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials.In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed.Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss were observed for both NR (p = 0.03 and NAD+ (p = 0.001; the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008.Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

  16. Topical Imiquimod in the Treatment of Conjunctival Actinic Keratosis.

    Science.gov (United States)

    Rowlands, Megan A; Giacometti, Joseph N; Servat, Javier; Materin, Miguel A; Levin, Flora

    Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.

  17. Medical Terminology: Latin Words/Abbreviations; Special Signs and Symbols. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (using Latin words/abbreviations; special signs and symbols) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three…

  18. Medical Terminology: Using Some Common Prefixes, Suffixes, and Roots. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (using common prefixes, suffixes, and root words) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three learning…

  19. The generation of myricetin-nicotinamide nanococrystals by top down and bottom up technologies.

    Science.gov (United States)

    Liu, Mingyu; Hong, Chao; Li, Guowen; Ma, Ping; Xie, Yan

    2016-09-30

    Myricetin-nicotinamide (MYR-NIC) nanococrystal preparation methods were developed and optimized using both top down and bottom up approaches. The grinding (top down) method successfully achieved nanococrystals, but there were some micrometer range particles and aggregation. The key consideration of the grinding technology was to control the milling time to determine a balance between the particle size and distribution. In contrast, a modified bottom up approach based on a solution method in conjunction with sonochemistry resulted in a uniform MYR-NIC nanococrystal that was confirmed by powder x-ray diffraction, scanning electron microscopy, dynamic light scattering, and differential scanning calorimeter, and the particle dissolution rate and amount were significantly greater than that of MYR-NIC cocrystal. Notably, this was a simple method without the addition of any non-solvent. We anticipate our findings will provide some guidance for future nanococrystal preparation as well as its application in both chemical and pharmaceutical area.

  20. The Chainstitch Machine. Module 18.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the chainstitch machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the chainstitch machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and…

  1. Special topics in infrared interferometry. [Michelson interferometer development

    Science.gov (United States)

    Hanel, R. A.

    1985-01-01

    Topics in IR interferometry related to the development of a Michelson interferometer are treated. The selection and reading of the signal from the detector to the analog to digital converter is explained. The requirements for the Michelson interferometer advance speed are deduced. The effects of intensity modulation on the interferogram are discussed. Wavelength and intensity calibration of the interferometer are explained. Noise sources (Nyquist or Johnson noise, phonon noise), definitions of measuring methods of noise, and noise measurements are presented.

  2. Millwright Apprenticeship. Related Training Modules. 7.1-7.9 Boilers.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains nine modules covering boilers. The modules provide information on the following topics: fire and water tube types of boilers, construction, fittings, operation, cleaning, heat recovery systems, instruments and controls, and…

  3. Influence of Sodium Lauryl Sulfate and Tween 80 on Carbamazepine–Nicotinamide Cocrystal Solubility and Dissolution Behaviour

    Science.gov (United States)

    Li, Mingzhong; Qiao, Ning; Wang, Ke

    2013-01-01

    The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine–nicotinamide (CBZ–NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ–NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ–NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ–NIC cocrystal but they had totally opposite effects on the IDR of the CBZ–NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ–NIC cocrystal while Tween 80 decreased its IDR. PMID:24300560

  4. Influence of Sodium Lauryl Sulfate and Tween 80 on Carbamazepine–Nicotinamide Cocrystal Solubility and Dissolution Behaviour

    Directory of Open Access Journals (Sweden)

    Ke Wang

    2013-10-01

    Full Text Available The influence of the surfactants of sodium lauryl sulfate (SLS and Tween 80 on carbamazepine–nicotinamide (CBZ–NIC cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ–NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR of the CBZ–NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ–NIC cocrystal but they had totally opposite effects on the IDR of the CBZ–NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ–NIC cocrystal while Tween 80 decreased its IDR.

  5. Influence of sodium lauryl sulfate and tween 80 on carbamazepine-nicotinamide cocrystal solubility and dissolution behaviour.

    Science.gov (United States)

    Li, Mingzhong; Qiao, Ning; Wang, Ke

    2013-10-11

    The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine-nicotinamide (CBZ-NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ-NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ-NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ-NIC cocrystal but they had totally opposite effects on the IDR of the CBZ-NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ-NIC cocrystal while Tween 80 decreased its IDR.

  6. Nicotinamide starvation and inhibition of poly(ADP-Ribose) synthesis enhance the induced mutation in Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Okada, Gensaku; Kaneko, Ichiro; Mitsui, Hideki.

    1987-01-01

    The effects of nicotinamide (NA) deficiency and added NA and 3-aminobenzamide (3AB) on the cytotoxicity and the induction of mutations in Chinese hamster V79-14 cells were investigated. In NA deficiency the addition of NA (up to 4 mM) and 3AB (up to 7.5 mM) was not cytotoxic. The presence of NA prior to exposure to mitomycin C (MMC) or γ-rays produced a dose-dependent increase in the relative cloning ability of DNA-damaged cells. The lethality of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was significantly potentiated by pre-treatment with 5 mM 3AB, but no potentiation by 3AB was observed for MMC, ultraviolet (UV)-B light, or γ-rays. Among cells pre-cultured in NA-free medium there were increased frequencies of mutations at both the hypoxanthineguanine phosphoribosyltransferase (HGPRT) and the adenine phosphoribosyltransferase (APRT) loci following DNA damage. The enhancing effect by NA deficiency was time-dependent. Incubation with NA prior to DNA damage produced a significant reduction in the frequency of mutations. The addition of 3AB to the nicotinamide adenine dinucleotide (NAD + )-depleted cell cultures before or after the DNA damage also strongly increased the frequency of induced mutations, with increasing concentrations of 3AB up to 5 mM, but the frequency was reduced at higher concentrations. The interaction between NA deficiency and the addition of 3AB appears to act synergistically on mutation induction. A correlation was observed between the potential of inhibiting poly (ADP-ribose) polymerase and the enhancement of mutation frequency. (author)

  7. Millwright Apprenticeship. Related Training Modules. 1.1-1.8 Safety.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains eight modules covering safety. The modules provide information on the following topics: general safety, hand tool safety, power tool safety, fire safety, hygiene, safety and electricity, types of fire and fire prevention, and…

  8. Transportation life cycle assessment (LCA) synthesis : life cycle assessment learning module series.

    Science.gov (United States)

    2015-03-12

    The Life Cycle Assessment Learning Module Series is a set of narrated, self-advancing slideshows on : various topics related to environmental life cycle assessment (LCA). This research project produced the first 27 of such modules, which : are freely...

  9. Recent progress in GeSi electro-absorption modulators

    International Nuclear Information System (INIS)

    Chaisakul, Papichaya; Marris-Morini, Delphine; Rouifed, Mohamed-Said; Coudevylle, Jean-René; Roux, Xavier Le; Edmond, Samson; Vivien, Laurent; Frigerio, Jacopo; Chrastina, Daniel; Isella, Giovanni

    2014-01-01

    Electro-absorption from GeSi heterostructures is receiving growing attention as a high performance optical modulator for short distance optical interconnects. Ge incorporation with Si allows strong modulation mechanism using the Franz–Keldysh effect and the quantum-confined Stark effect from bulk and quantum well structures at telecommunication wavelengths. In this review, we discuss the current state of knowledge and the on-going challenges concerning the development of high performance GeSi electro-absorption modulators. We also provide feasible future prospects concerning this research topic. (review)

  10. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2–4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    International Nuclear Information System (INIS)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2–4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2–4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2–4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  11. Pharmacokinetics of pirfenidone after topical administration in rabbit eye

    OpenAIRE

    Sun, Guoying; Lin, Xianchai; Zhong, Hua; Yang, Yangfan; Qiu, Xuan; Ye, Chengtian; Wu, Kaili; Yu, Minbin

    2011-01-01

    Purpose Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum agent that has an inhibition effect on the proliferation, migration, and collagen contraction of human Tenon’s fibroblasts, and thus modulating the wound healing process of glaucoma filtering surgical site. This study investigated the pharmacokinetics of topically administered pirfenidone (0.5%) in rabbit eyes. Methods Pirfenidone solution (50 μl) was instilled into the rabbit’s conjunctival sac. The rabbits were...

  12. Outreach Education Modules on Space Sciences in Taiwan

    Science.gov (United States)

    Lee, I.-Te; Tiger Liu, Jann-Yeng; Chen, Chao-Yen

    2013-04-01

    The Ionospheric Radio Science Laboratory (IRSL) at Institute of Space Science, National Central University in Taiwan has been conducting a program for public outreach educations on space science by giving lectures, organizing camps, touring exhibits, and experiencing hand-on experiments to elementary school, high school, and college students as well as general public since 1991. The program began with a topic of traveling/living in space, and was followed by space environment, space mission, and space weather monitoring, etc. and a series of course module and experiment (i.e. experiencing activity) module was carried out. For past decadal, the course modules have been developed to cover the space environment of the Sun, interplanetary space, and geospace, as well as the space technology of the rocket, satellite, space shuttle (plane), space station, living in space, observing the Earth from space, and weather observation. Each course module highlights the current status and latest new finding as well as discusses 1-3 key/core issues/concepts and equip with 2-3 activity/experiment modules to make students more easily to understand the topics/issues. Meanwhile, scientific camps are given to lead students a better understanding and interesting on space science. Currently, a visualized image projecting system, Dagik Earth, is developed to demonstrate the scientific results on a sphere together with the course modules. This system will dramatically improve the educational skill and increase interests of participators.

  13. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes.

    Science.gov (United States)

    Ahangarpour, Akram; Oroojan, Ali Akbar; Heidari, Hamid; Ghaedi, Ehsan; Taherkhani, Reza

    2015-01-01

    Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice. In this experimental study, 56 adult male Naval Medical Research Institute (NMRI) mice (30-35 g) were randomly divided into seven groups: control, diabetes, diabetes + glibenclamide (0.25 mg/kg), diabetes + extract (200 or 300 mg/kg), and extract (200 or 300 mg/kg). Diabetes was induced with intraperitoneal injection of nicotinamide (NA) and streptozotocin (STZ). Twenty-four hours after the last extract and drug administration, serum samples, testes, and cauda epididymis were removed immediately for experimental assessment. Body weight, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels, and sperm count (P lappa plant has an effect on the health of the reproductive system in order to improve diabetic conditions.

  14. Fieldcrest Cannon Workplace Literacy Modules for Supervisors. Alabama Partnership for Training.

    Science.gov (United States)

    Alabama State Dept. of Education, Montgomery.

    This packet contains eight learning modules developed for use in Fieldcrest Cannon workplace literacy classes for supervisors. The modules cover the following topics: (1) coaching/communication; (2) coaching/communication and motivation; (3) communication skills; (4) training/coaching; (5) time management; (6) policy and procedures; (7) safety;…

  15. Learning about Teaching the Extracurricular Topic of Nanotechnology as a Vehicle for Achieving a Sustainable Change in Science Education

    Science.gov (United States)

    Blonder, Ron; Mamlok-Naaman, Rachel

    2016-01-01

    This study focused on teachers' transfer of a variety of teaching methods from a teaching module on nanotechnology, which is an example of a topic outside the science curriculum, to teaching topics that are part of the chemistry curriculum. Nanotechnology is outside the science curriculum, but it was used in this study as a means to carry out a…

  16. Effect of tetrahydrocurcumin on lipid peroxidation and lipids in streptozotocin-nicotinamide-induced diabetic rats.

    Science.gov (United States)

    Murugan, Pidaran; Pari, Leelavinothan

    2006-08-01

    Hyperlipidaemia is an associated complication of diabetes mellitus. We recently reported that tetrahydrocurcumin lowered the blood glucose in diabetic rats. In the present study, we have investigated the effect of tetrahydrocurcumin, one of the active metabolites of curcumin on lipid profile and lipid peroxidation in streptozotocin-nicotinamide-induced diabetic rats. Tetrahydrocurcumin 80 mg/kg body weight was administered orally to diabetic rats for 45 days, resulted a significant reduction in blood glucose and significant increase in plasma insulin in diabetic rats, which proved its antidiabetic effect. Tetrahydrocurcumin also caused a significant reduction in lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) and lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in serum and tissues, suggesting its role in protection against lipid peroxidation and its antihyperlipidemic effect. Tetrahydrocurcumin showed a better effect when compared with curcumin. Results of the present study indicate that tetrahydrocurcumin showed antihyperlipidaemic effect in addition to its antidiabetic effect in type 2 diabetic rats.

  17. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin

    Directory of Open Access Journals (Sweden)

    Nisma Mujahid

    2017-06-01

    Full Text Available The presence of dark melanin (eumelanin within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in “redhaired” Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk.

  18. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.

    Science.gov (United States)

    Mujahid, Nisma; Liang, Yanke; Murakami, Ryo; Choi, Hwan Geun; Dobry, Allison S; Wang, Jinhua; Suita, Yusuke; Weng, Qing Yu; Allouche, Jennifer; Kemeny, Lajos V; Hermann, Andrea L; Roider, Elisabeth M; Gray, Nathanael S; Fisher, David E

    2017-06-13

    The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Wound healing modulators in a tracheoplasty canine model.

    Science.gov (United States)

    Olmos-Zúñiga, J Raúl; Hernández-Jiménez, Claudia; Díaz-Martínez, Emmanuel; Jasso-Victoria, Rogelio; Sotres-Vega, Avelina; Gaxiola-Gaxiola, Miguel O; Villalba-Caloca, Jaime; Baltazares-Lipp, Matilde; Santillán-Doherty, Patricio; Santibáñez-Salgado, J Alfredo

    2007-01-01

    Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.

  20. Effect of aqueous bark extract of Garuga pinnata Roxb. in streptozotocin-nicotinamide induced type-II diabetes mellitus.

    Science.gov (United States)

    Shirwaikar, Annie; Rajendran, K; Barik, Rakesh

    2006-09-19

    A study was undertaken to evaluate the antihyperglycemic activity of aqueous extract of bark of Garuga pinnata Roxb. (Burseraceae). The various parameters studied included fasting blood sugar levels, serum lipid levels, liver glycogen content, serum insulin level and glycated hemoglobin in diabetic and normal rats. Streptozotocin-nicotinamide was used to induce type-II diabetes mellitus. Treatment with the extract at two dose levels showed a significant increase in the liver glycogen and serum insulin level and a significant decrease in fasting blood glucose and glycated hemoglobin levels. The total cholesterol and serum triglycerides levels were also significantly reduced and the HDL cholesterol levels were significantly increased upon treatment with the extract thus proving the potent antidiabetic property of the plant.

  1. The Knife Machine. Module 15.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the knife machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the knife machine (a single needle or multi-needle machine which sews and cuts at the same time). These components are provided: an introduction, directions, an objective,…

  2. Topical tags vs non-topical tags : Towards a bipartite classification?

    NARCIS (Netherlands)

    Basile, Valerio; Peroni, Silvio; Tamburini, Fabio; Vitali, Fabio

    2015-01-01

    In this paper we investigate whether it is possible to create a computational approach that allows us to distinguish topical tags (i.e. talking about the topic of a resource) and non-topical tags (i.e. describing aspects of a resource that are not related to its topic) in folksonomies, in a way that

  3. Topic Space: Rapid Prototyping a Mobile Augmented Reality Recommendation App

    Directory of Open Access Journals (Sweden)

    Jim Hahn

    2015-10-01

    Full Text Available With funding from an Institute of Museum and Library Services (IMLS Sparks! Ignition Grant, researchers from the University of Illinois Library designed and tested a mobile recommender app with augmented reality features. By embedding open source optical character recognition software into a “Topic Space” module, the augmented reality app can recognize call numbers on a book in the library and suggest relevant items that are not shelved nearby. Topic Space can also show users items that are normally shelved in the starting location but that are currently checked out. Using formative UX methods, grant staff shaped app interface and functionality through early user testing. This paper reports results of UX testing; a redesigned mobile interface, and provides considerations on the future development of personalized recommendation functionality.

  4. Integrating STEM education through Project-Based Inquiry Learning (PIL) in topic space among year one pupils

    Science.gov (United States)

    Ng, Chee Hoe; Adnan, M.

    2018-01-01

    This research aims to investigate the effect of integrating STEM education through Project-based Inquiry Learning (PIL) and the users of the STEM modules which consists of five projects on topic Space in Year One Mathematics Syllabus in Kurikulum Standard Sekolah Rendah (KSSR) of Malaysia. STEM education in primary school focuses on the introduces and awareness of students about the importance of STEM education. The projects in STEM modules are covering the different ethnic cultures in Malaysia. The modules are designed using the four phases in PIL. Concepts and the explanation of STEM education on each project are emphasized and provided in the modules so the teachers able to carry out the projects by using the modules. By using the modules in primary Mathematics, the students and teachers will be more understanding on how to integrate the Mathematics’ concepts in STEM education.

  5. Getting Down to Business: Travel Agency, Module 9. [Student Guide]. Entrepreneurship Training Components.

    Science.gov (United States)

    Rassen, Rachel L.

    This module on owning and operating a travel agency is one of 36 modules in a series on entrepreneurship. The introduction tells the student what topics will be covered and suggests other modules to read in related occupations. Each unit includes student goals, a case study, and a discussion of the unit subject matter. Learning activities are…

  6. Commutative algebra constructive methods finite projective modules

    CERN Document Server

    Lombardi, Henri

    2015-01-01

    Translated from the popular French edition, this book offers a detailed introduction to various basic concepts, methods, principles, and results of commutative algebra. It takes a constructive viewpoint in commutative algebra and studies algorithmic approaches alongside several abstract classical theories. Indeed, it revisits these traditional topics with a new and simplifying manner, making the subject both accessible and innovative. The algorithmic aspects of such naturally abstract topics as Galois theory, Dedekind rings, Prüfer rings, finitely generated projective modules, dimension theory of commutative rings, and others in the current treatise, are all analysed in the spirit of the great developers of constructive algebra in the nineteenth century. This updated and revised edition contains over 350 well-arranged exercises, together with their helpful hints for solution. A basic knowledge of linear algebra, group theory, elementary number theory as well as the fundamentals of ring and module theory is r...

  7. The Button Sew Machine. Module 12.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the button sew machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the button sew machine. These components are provided: an introduction, direction, an objective, learning activities, student information, a student self-check, and a…

  8. The Zig Zag Machine. Module 14.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the zig zag machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the zig zag machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a…

  9. The Bar Tack Machine. Module 16.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the bar tack machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the bar tack machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a…

  10. A rapid microwave induced synthesis of [carboxyl-14C]-nicotinic acid (vitamin B3) and [carbonyl-14C]-nicotinamide using K14CN

    International Nuclear Information System (INIS)

    Ravi, S.; Mathew, K.M.; Sivaprasad, N.

    2008-01-01

    Microwave assisted direct aromatic substitution of 3-bromopyridine with K 14 CN as the cyanide source and catalytic amount of tetrabutylammonium bromide afforded [3- 14 C]-cyanopyridine 3 in 90% yield. Microwave assisted hydrolysis of 3 with a mixture of concentrated hydrochloric acid and propionic acid afforded [carboxyl- 14 C]-nicotinic acid in 95% yield whereas microwave assisted hydrolysis of 3 with a mixture of concentrated sulfuric acid and propionic acid afforded [carbonyl- 14 C]-nicotinamide in 85% yield. (author)

  11. Ultrasound assisted combined molecularly imprinted polymer for selective extraction of nicotinamide in human urine and milk samples: Spectrophotometric determination and optimization study.

    Science.gov (United States)

    Asfaram, Arash; Ghaedi, Mehrorang; Dashtian, Kheibar

    2017-01-01

    Ultrasound-assisted dispersive solid phase microextraction followed by UV-vis spectrophotometer (UA-DSPME-UV-vis) was designed for extraction and preconcentration of nicotinamide (vitamin B 3 ) by HKUST-1 metal organic framework (MOF) based molecularly imprinted polymer (MIP). This new material was characterized by FTIR and FE-SEM techniques. The preliminary Plackett-Burman design was used for screening and subsequently the central composite design justifies significant terms and possible construction of mathematical equation which give the individual and cooperative contribution of variables like HKUST-1-MOF-NA-MIP mass, sonication time, temperature, eluent volume, pH and vortex time. Accordingly the optimum condition was set as: 2.0mg HKUST-1-MOF-NA-MIP, 200μL eluent and 5.0min sonication time in center points other variables were determined as the best conditions to reach the maximum recovery of the analyte. The UA-DSPME-UV-vis method performances like excellent linearity (LR), limits of detection (LOD), limits of quantification of 10-5000μgL -1 with R 2 of 0.99, LOD (1.96ngmL -1 ), LOQ (6.53μgL -1 ), respectively show successful and accurate applicability of the present method for monitoring analytes with within- and between-day precision of 0.96-3.38%. The average absolute recoveries of the nicotinamide extracted from the urine, milk and water samples were 95.85-101.27%. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Engine Performance (Section C: Emission Control Systems). Auto Mechanics Curriculum Guide. Module 3. Instructor's Guide.

    Science.gov (United States)

    Rains, Larry

    This engine performance (emission control systems) module is one of a series of competency-based modules in the Missouri Auto Mechanics Curriculum Guide. Topics of this module's five units are: positive crankcase ventilation (PCV) and evaporative emission control systems; exhaust gas recirculation (EGR); air injection and catalytic converters;…

  13. EkSTEMiT Learning Module and Inculcation of Inventive Thinking

    Directory of Open Access Journals (Sweden)

    Norhaslinda Abdul Samad

    2017-10-01

    Full Text Available The young generation of today must be prepared with the knowledge and skills necessary to be able to compete globally thus boosting economic growth and prosperity. Therefore, students should not only be equipped with knowledge but they are in need of the “21st century skills”, which is the top priority and one of the main education agenda goals today. As one of the domains in the 21st century skills, inventive thinking includes elements of flexibility, self-regulation, curiosity, creativity, risk taking, higher order thinking and reasoning. In order to inculcate inventive thinking for students, the EkSTEMiT Learning Module was developed for the topic Electrochemistry; one of the most difficult topics to learn among students. EkSTEMiT Learning Module was developed based on the STEM (Science, Technology, Engineering and Mathematics integrated model. Thus, this paper will discuss the conceptual framework underlying the development of EkSTEMiT Learning Module with descriptions of learning activities designed for Electrochemistry.

  14. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes

    OpenAIRE

    AHANGARPOUR, Akram; OROOJAN, Ali Akbar; HEIDARI, Hamid; GHAEDI, Ehsan; TAHERKHANI, Reza

    2015-01-01

    Background: Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice.

  15. Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells

    Directory of Open Access Journals (Sweden)

    Qian Li

    2017-04-01

    Full Text Available Background: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM to S-adenosylhomocysteine (SAH. However, the role of NNMT in nickel-induced histone methylation remains unclear. Methods: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2 for 72 h or 200 μM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9 mono-, di-, and trimethylation and NNMT protein levels were measured by western blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen-activated protein kinase 3 (MAP2K3 and dickkopf1 (DKK1, were determined by qPCR analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+ to reduced NAD (NADH and SAM/SAH ratio were determined. Results: Exposure of BEAS-2B cells to nickel increased H3K9 dimethylation (H3K9me2, suppressed the expressions of H3K9me2-associated genes (MAP2K3 and DKK1, and induced NNMT repression at both the protein and mRNA levels. Furthermore, over-expression of NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio. Additionally, the NADH oxidant phenazine methosulfate (PMS not only reversed the nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2. Conclusions: These findings indicate that the repression of NNMT may underlie nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.

  16. Changing the Topic. Topic Position in Ancient Greek Word Order

    NARCIS (Netherlands)

    Allan, R.J.

    2014-01-01

    Ancient Greek, topics can be expressed as intra-clausal constituents but they can also precede or follow the main clause as extra-clausal constituents. Together, these various topic expressions constitute a coherent system of complementary pragmatic functions. For a comprehensive account of topic

  17. Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial

    DEFF Research Database (Denmark)

    Bingley, P J; Gale, E A M; Reimers, Jesper Irving

    2006-01-01

    of development of diabetes within 5 years varied according to age, relationship to the proband, positivity for IAA, IA-2A and GADA, number and combination of islet antibodies, HLA class II genotype, baseline glucose tolerance, and first-phase insulin secretion, but not gender or incidence of childhood type 1...... of additional antibody markers, but not antibody type or genotype. Individuals diabetes within 5 years and these combined criteria identified 81% of the cases in the whole cohort. CONCLUSIONS/INTERPRETATION: We suggest that screening......AIMS/HYPOTHESIS: To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)-positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabetes Intervention Trial. METHODS...

  18. Evaluation of a personal and professional development module in an undergraduate medical curriculum in India

    Directory of Open Access Journals (Sweden)

    Ramnarayan Komattil

    2016-03-01

    Full Text Available The study aimed at evaluating the personal and professional development (PPD module in the undergraduate medical curriculum in Melaka Manipal Medical College, India. PPD hours were incorporated in the curriculum. A team of faculty members and a faculty coordinator identified relevant topics and students were introduced to topics such as medical humanities, leadership skills, communication skills, ethics, professional behavior, and patient narratives. The module was evaluated using a prevalidated course feedback questionnaire which was administered to three consecutive batches of students from March 2011 to March 2013. To analyze faculty perspectives, one to one in-depth interviews and focus group discussions were conducted by the coordinators with faculty members who conducted the PPD classes. Analysis of the course feedback form revealed that majority (80% of students agreed that the module was well prepared and was "highly relevant" to the profession. Faculty found the topics new and interdisciplinary and there was a sense of sharing responsibility and workload by the faculty. PPD modules are necessary components of the curriculum and help to mould students while they are still acquiescent as they assume their roles as doctors of the future.

  19. Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

    Directory of Open Access Journals (Sweden)

    Bing Zhao

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.

  20. Plumbing. Building Maintenance. Module III. Instructor's Guide.

    Science.gov (United States)

    Brunk, Art

    This curriculum guide, one of six modules keyed to the building maintenance competency profile developed by industry and education professionals, provides materials for a plumbing procedures unit of seven lessons. Lesson topics are: safety procedures, joining pipes, water systems, fixtures and appliances, maintenance and repair, drainage systems,…

  1. Redox Modulations, Antioxidants, and Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Erik A. Fraunberger

    2016-01-01

    Full Text Available Although antioxidants, redox modulations, and neuropsychiatric disorders have been widely studied for many years, the field would benefit from an integrative and corroborative review. Our primary objective is to delineate the biological significance of compounds that modulate our redox status (i.e., reactive species and antioxidants as well as outline their current role in brain health and the impact of redox modulations on the severity of illnesses. Therefore, this review will not enter into the debate regarding the perceived medical legitimacy of antioxidants but rather seek to clarify their abilities and limitations. With this in mind, antioxidants may be interpreted as natural products with significant pharmacological actions in the body. A renewed understanding of these often overlooked compounds will allow us to critically appraise the current literature and provide an informed, novel perspective on an important healthcare issue. In this review, we will introduce the complex topics of redox modulations and their role in the development of select neuropsychiatric disorders.

  2. Phase-Modulated Optical Communication Systems

    CERN Document Server

    Ho, Keang-Po

    2005-01-01

    Fiber-optic communication systems have revolutionized our telecommunication infrastructures – currently, almost all telephone land-line, cellular, and internet communications must travel via some form of optical fibers. In these transmission systems, neither the phase nor frequency of the optical signal carries information – only the intensity of the signal is used. To transmit more information in a single optical carrier, the phase of the optical carrier must be explored. As a result, there is renewed interest in phase-modulated optical communications, mainly in direct-detection DPSK signals for long-haul optical communication systems. When optical amplifiers are used to maintain certain signal level among the fiber link, the system is limited by amplifier noises and fiber nonlinearities. Phase-Modulated Optical Communication Systems surveys this newly popular area, covering the following topics: The transmitter and receiver for phase-modulated coherent lightwave systems Method for performance analysis o...

  3. TOPICAL REVIEW: Metallo-supramolecular modules as a paradigm for materials science

    Directory of Open Access Journals (Sweden)

    Dirk G Kurth

    2008-01-01

    Full Text Available Metal ion coordination in discrete or extended metallo-supramolecular assemblies offers ample opportunity to fabricate and study devices and materials that are equally important for fundamental research and new technologies. Metal ions embedded in a specific ligand field offer diverse thermodynamic, kinetic, chemical, physical and structural properties that make these systems promising candidates for active components in functional materials. A key challenge is to improve and develop methodologies for placing these active modules in suitable device architectures, such as thin films or mesophases. This review highlights recent developments in extended, polymeric metallo-supramolecular systems and discrete polyoxometalates with an emphasis on materials science.

  4. Dunnione ameliorates cisplatin ototoxicity through modulation of NAD(+) metabolism.

    Science.gov (United States)

    Kim, Hyung-Jin; Pandit, Arpana; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon; Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young; Kwak, Tae Hwan; Choe, Seong-Kyu; Park, Raekil; So, Hong-Seob

    2016-03-01

    Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD(+) levels in cisplatin-mediated ototoxicity. We provide evidence that the decreases in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) polymerase-1 (PARP-1) activation and microRNA-34a levels through cisplatin-mediated p53 activation aggravate the associated ototoxicity. Furthermore, we show that the induction of cellular NAD(+) levels using dunnione, which targets intracellular NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Ultracompact, High-Speed Field-Effect Optical Modulators (Research Topic 4.2 Optoelectronics)

    Science.gov (United States)

    2017-11-29

    surface charge for a given gate voltage. Third, two MIC structures are designed back-to-back to double the field-induced charge, simultaneously on top...metal-oxide-semiconductor structure, inversion (of carriers into holes), is less likely to occur. Figure 1. Illustration of the working modes of the...between the two gold layers. See Fig. 2(a). Two MIM plasmonic waveguides simultaneously exist in our modulator. The left side one is an Au-HfO2-ITO

  6. Freshman Health Topics

    Science.gov (United States)

    Hovde, Karen

    2011-01-01

    This article examines a cluster of health topics that are frequently selected by students in lower division classes. Topics address issues relating to addictive substances, including alcohol and tobacco, eating disorders, obesity, and dieting. Analysis of the topics examines their interrelationships and organization in the reference literature.…

  7. SirT1 confers hypoxia-induced radioresistance via the modulation of c-Myc stabilization on hepatoma cells

    International Nuclear Information System (INIS)

    Xie Yuexia; Zhang Jianghong; Shao Chunlin; Xu Yanwu

    2012-01-01

    Intratumoral hypoxia is an important contributory factor to tumor cell resistance to radiotherapy. SirT1, a nicotinamide adenine dinucleotide (NAD + )-dependent histone/protein deacetylase, has been linked to the decrease of radiation-induced DNA damage and seems to be critical for cancer therapy. The purpose of this study was to investigate the role of SirT1 in hypoxia-induced radiation response on hepatoma cells. It was found that the administration with resveratrol, a putative SirT1 activator, enhanced the resistance of HepG2 cells against radiation-induced DNA damage of MN formation under hypoxia condition; while nicotinamide, a well-known SirT1 inhibitor, sensitized this radiation damage. Nevertheless, pretreatment of cells with 10058-F4, a specific inhibitor of c-Myc, almost eliminated the nicotinamide-induced radiosensitive effect. Further studies revealed that resveratrol inhibited c-Myc protein accumulation via up-regulation of SirT1 expression and deacetylase activity, and this loss of c-Myc protein was abolished by inhibiting its degradation in the presence of MG132, a potent inhibitor of proteasome. In contrast, nicotinamide attenuated c-Myc protein degradation induced by radiation under hypoxia through inhibition of SirT1 deacetylase activity. Our findings suggest that SirT1 could serve as a novel potent target of radiation-induced DNA damage and thus as a potential strategy to advance the efficiency of radiation therapy in hepatoma entities. (author)

  8. Topical glucocorticoids and the skin-mechanisms of action: an update

    Directory of Open Access Journals (Sweden)

    A. Ahluwalia

    1998-01-01

    Full Text Available The topical glucocorticoids (GCs represent the treatment of choice for many types of inflammatory dermatoses. Despite the extensive use of this class of drugs as first line therapy the mechanism of their action is uncertain. It is clear that the multiplicity of actions of the topical GCs is an important facet of their scope in the treatment of dermal disorders. The aim of this update is to review past and current theories regarding how these agents might work. Current understanding of the molecular mechanism s of GC action has advanced significantly over the past decade with the realisation that multiple systems are responsible for transduction of GC effects at a molecular level. The two primary modes of action are via interaction directly with DNA or indirectly through modulation of specific transcription factors: the endpoint in both cases being modulation of specific protein synthesis. Both of these mechanisms will be discussed. In particular this review will concentrate on the possibility that a GC-inducible protein, termed lipocortin 1, may have a significant role to play in the anti-inflammatory actions of these drugs. Additionally it has become apparent that several inflammatory enzymes induced in inflamm ation are sites of inhibitory action of the GCs, and the possibility that this occurs in the skin will be discussed paying particular attention to the inducible phospholipase A2, nitric oxide synthase and cyclooxygenase systems.

  9. Undergraduate teaching modules featuring geodesy data applied to critical social topics (GETSI: GEodetic Tools for Societal Issues)

    Science.gov (United States)

    Pratt-Sitaula, B. A.; Walker, B.; Douglas, B. J.; Charlevoix, D. J.; Miller, M. M.

    2015-12-01

    The GETSI project, funded by NSF TUES, is developing and disseminating teaching and learning materials that feature geodesy data applied to critical societal issues such as climate change, water resource management, and natural hazards (serc.carleton.edu/getsi). It is collaborative between UNAVCO (NSF's geodetic facility), Mt San Antonio College, and Indiana University. GETSI was initiated after requests by geoscience faculty for geodetic teaching resources for introductory and majors-level students. Full modules take two weeks but module subsets can also be used. Modules are developed and tested by two co-authors and also tested in a third classroom. GETSI is working in partnership with the Science Education Resource Center's (SERC) InTeGrate project on the development, assessment, and dissemination to ensure compatibility with the growing number of resources for geoscience education. Two GETSI modules are being published in October 2015. "Ice mass and sea level changes" includes geodetic data from GRACE, satellite altimetry, and GPS time series. "Imaging Active Tectonics" has students analyzing InSAR and LiDAR data to assess infrastructure earthquake vulnerability. Another three modules are in testing during fall 2015 and will be published in 2016. "Surface process hazards" investigates mass wasting hazard and risk using LiDAR data. "Water resources and geodesy" uses GRACE, vertical GPS, and reflection GPS data to have students investigating droughts in California and the High Great Plains. "GPS, strain, and earthquakes" helps students learn about infinitesimal and coseismic strain through analysis of horizontal GPS data and includes an extension module on the Napa 2014 earthquake. In addition to teaching resources, the GETSI project is compiling recommendations on successful development of geodesy curricula. The chief recommendations so far are the critical importance of including scientific experts in the authorship team and investing significant resources in

  10. Evaluating topic models with stability

    CSIR Research Space (South Africa)

    De Waal, A

    2008-11-01

    Full Text Available Topic models are unsupervised techniques that extract likely topics from text corpora, by creating probabilistic word-topic and topic-document associations. Evaluation of topic models is a challenge because (a) topic models are often employed...

  11. The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the medulla oblongata, spinal cord, cranial and spinal nerves of frog, Microhyla ornata.

    Science.gov (United States)

    Jadhao, Arun G; Biswas, Saikat P; Bhoyar, Rahul C; Pinelli, Claudia

    2017-04-01

    Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) enzymatic activity has been reported in few amphibian species. In this study, we report its unusual localization in the medulla oblongata, spinal cord, cranial nerves, spinal nerves, and ganglions of the frog, Microhyla ornata. In the rhombencephalon, at the level of facial and vagus nerves, the NADPH-d labeling was noted in the nucleus of the abducent and facial nerves, dorsal nucleus of the vestibulocochlear nerve, the nucleus of hypoglossus nerve, dorsal and lateral column nucleus, the nucleus of the solitary tract, the dorsal field of spinal grey, the lateral and medial motor fields of spinal grey and radix ventralis and dorsalis (2-10). Many ependymal cells around the lining of the fourth ventricle, both facial and vagus nerves and dorsal root ganglion, were intensely labeled with NADPH-d. Most strikingly the NADPH-d activity was seen in small and large sized motoneurons in both medial and lateral motor neuron columns on the right and left sides of the brain. This is the largest stained group observed from the caudal rhombencephalon up to the level of radix dorsalis 10 in the spinal cord. The neurons were either oval or elongated in shape with long processes and showed significant variation in the nuclear and cellular diameter. A massive NADPH-d activity in the medulla oblongata, spinal cord, and spinal nerves implied an important role of this enzyme in the neuronal signaling as well as in the modulation of motor functions in the peripheral nervous systems of the amphibians. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Topical report review status

    International Nuclear Information System (INIS)

    1997-08-01

    This report provides industry with procedures for submitting topical reports, guidance on how the U.S. Nuclear Regulatory Commission (NRC) processes and responds to topical report submittals, and an accounting, with review schedules, of all topical reports currently accepted for review schedules, of all topical reports currently accepted for review by the NRC. This report will be published annually. Each sponsoring organization with one or more topical reports accepted for review copies

  13. Do diosgenin ameliorate urinary bladder toxic effect of ...

    African Journals Online (AJOL)

    SWEET

    2012-01-26

    Jan 26, 2012 ... experimental animal models? ... BSO doses using a Swiss albino mouse model. Toxicity modulation ... bladder inflammation induced by CP in rats and mice .... 0.1 ml NADPH (nicotinamide adenine dinucleotide phosphate.

  14. Mode change design for capacity modulation in reciprocating compressor

    International Nuclear Information System (INIS)

    Bae, Young Ju; Kim, Jin Kook; Kim, Jong Bong; Chang, Young June

    2008-01-01

    Due to environmental issues, the development of low energy consumption products has become one of the main topics in the home appliance industry. The energy consumption of a refrigerator depends on the efficiency of its compressor as well as on the refrigerator cycle design, such as the capacity modulation. This study features the design of a novel capacity modulation reciprocating compressor, i.e., two-step capacity modulation (TCM). In a TCM compressor, capacity modulation is achieved by changing the dead volume in the cylinder. Instead of a concentric sleeve, an eccentric sleeve is used to change the dead volume for the clockwise and counterclockwise rotation of a motor. For stable capacity modulation, a new latching system with a key, a spring, and an eccentric sleeve is introduced, and the mode change reliability is verified by dynamic analysis

  15. Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.H.; Shetty, A.S.

    1977-01-01

    Kynureninase-type (L-kynurenine hydrolase, EC 3.7.1.3) activity has been found to be present in the livers of fish, amphibia, reptiles, and birds. In addition to past information concerning this enzyme activity in mammalian liver, it is now clear that all the major classes of vertebrates carry a highly specialized kynureninase-type enzyme, which we have termed a hydroxykynureninase. To compare the reactivities of these enzymes with L-kynurenine and L-3-hydroxykynurenine, ratios of tau values (K/sub m//V) were used. Based on this comparison, the bacterium Pseudomonas fluorescens carries the most efficient kynureninase, whereas the amphibian Xenopus laevis has the most efficient hydroxykynurenase. In these two cases, the ratio of tau values differs by a factor of 38,000. It is hypothesized that the tryptophan-to-nicotinamide adenine dinucleotide biosynthetic pathway evolved from a catabolic system of enzymes, and that the differences observed in the kynureninase-type enzymes between lower and higher organisms reflect the specialization of the function of these enzymes from a strictly catabolic role to an anabolic one during the course of evolution.

  16. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  17. Preclinical evidence of mitochondrial nicotinamide adenine dinucleotide as an effective alarm parameter under hypoxia

    Science.gov (United States)

    Shi, Hua; Sun, Nannan; Mayevsky, Avraham; Zhang, Zhihong; Luo, Qingming

    2014-01-01

    Early detection of tissue hypoxia in the intensive care unit is essential for effective treatment. Reduced nicotinamide adenine dinucleotide (NADH) has been suggested to be the most sensitive indicator of tissue oxygenation at the mitochondrial level. However, no experimental evidence comparing the kinetics of changes in NADH and other physiological parameters has been provided. The aim of this study is to obtain the missing data in a systematic and reliable manner. We constructed four acute hypoxia models, including hypoxic hypoxia, hypemic hypoxia, circulatory hypoxia, and histogenous hypoxia, and measured NADH fluorescence, tissue reflectance, cerebral blood flow, respiration, and electrocardiography simultaneously from the induction of hypoxia until death. We found that NADH was not always the first onset parameter responding to hypoxia. The order of responses was mainly affected by the cause of hypoxia. However, NADH reached its alarm level earlier than the other monitored parameters, ranging from several seconds to >10 min. As such, we suggest that the NADH can be used as a hypoxia indicator, although the exact level that should be used must be further investigated. When the NADH alarm is detected, the body still has a chance to recover if appropriate and timely treatment is provided.

  18. Syntacticized topics in Kurmuk

    DEFF Research Database (Denmark)

    Andersen, Torben

    2015-01-01

    This article argues that Kurmuk, a little-described Western Nilotic language, is characterized by a syntacticized topic whose grammatical relation is variable. In this language, declarative clauses have as topic an obligatory preverbal NP which is either a subject, an object or an adjunct....... The grammatical relation of the topic is expressed by a voice-like inflection of the verb, here called orientation. While subject-orientation is morphologically unmarked, object-oriented and adjunct-oriented verbs are marked by a subject suffix or by a suffix indicating that the topic is not subject, and adjunct......-orientation differs from object-orientation by a marked tone pattern. Topic choice largely reflects information structure by indicating topic continuity. The topic also plays a crucial role in relative clauses and in clauses with contrastive constituent focus, in that objects and adjuncts can only be relativized...

  19. Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

    KAUST Repository

    Rose, Nicholas D.; Regan, John M.

    2015-01-01

    © 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD+, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP+, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

  20. Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

    KAUST Repository

    Rose, Nicholas D.

    2015-12-01

    © 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD+, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP+, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

  1. Masonry Procedures. Building Maintenance. Module V. Instructor's Guide.

    Science.gov (United States)

    Eck, Francis

    This curriculum guide, one of six modules keyed to the building maintenance competency profile developed by industry and education professionals, provides materials for a masonry procedures unit containing eight lessons. Lesson topics are masonry safety practices; set forms; mix concrete; patch and/or repair concrete; pour and finish concrete; mix…

  2. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.

    Science.gov (United States)

    Neelakantan, Harshini; Vance, Virginia; Wetzel, Michael D; Wang, Hua-Yu Leo; McHardy, Stanton F; Finnerty, Celeste C; Hommel, Jonathan D; Watowich, Stanley J

    2018-01-01

    There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors. Membrane permeability of NNMT inhibitors was characterized using parallel artificial membrane permeability and Caco-2 cell assays. Selectivity was tested against structurally-related methyltransferases and nicotinamide adenine dinucleotide (NAD + ) salvage pathway enzymes. Effects of NNMT inhibitors on lipogenesis and intracellular levels of metabolites, including NNMT reaction product 1-methylnicotianamide (1-MNA) were evaluated in cultured adipocytes. Effects of a potent NNMT inhibitor on obesity measures and plasma lipid were assessed in diet-induced obese mice fed a high-fat diet. Methylquinolinium scaffolds with primary amine substitutions displayed high permeability from passive and active transport across membranes. Importantly, methylquinolinium analogues displayed high selectivity, not inhibiting related SAM-dependent methyltransferases or enzymes in the NAD + salvage pathway. NNMT inhibitors reduced intracellular 1-MNA, increased intracellular NAD + and S-(5'-adenosyl)-l-methionine (SAM), and suppressed lipogenesis in adipocytes. Treatment of diet-induced obese mice systemically with a potent NNMT inhibitor significantly reduced body weight and white adipose mass, decreased adipocyte size, and lowered plasma total cholesterol levels. Notably, administration of NNMT inhibitors did not impact total food intake nor produce any observable adverse effects. These results support development of small molecule NNMT inhibitors as therapeutics to

  3. Broadening Student Perspectives on Marketing Research Ethics: Development and Applications of a Teaching Module

    Science.gov (United States)

    Handlin, Amy

    2012-01-01

    This paper describes an ethics module developed by the author to engage marketing research students during the fall semester, when they are bombarded by political polls. The module matches ethically questionable polling practices to similarly troubling practices in marketing research. The goals are to show that ethical principles are not topic- or…

  4. Retailing. Instructor's Guide Sheets and Instructor's Package, Modules R 1-45. Competency-Based Education.

    Science.gov (United States)

    Kentucky State Dept. of Education, Frankfort.

    This package contains instructor's guide sheets and student task assignment sheets for Modules R 1-45 of the competency-based curriculum in retailing developed for use in secondary and postsecondary schools in Kentucky. Some of the topics covered in the modules include the following: retailing--past, present, and future; retailing occupations;…

  5. Topical Drugs for Pain Relief

    Directory of Open Access Journals (Sweden)

    Anjali Srinivasan

    2015-03-01

    Full Text Available Topical therapy helps patients with oral and perioral pain problems such as ulcers, burning mouth syndrome, temporomandibular disorders, neuromas, neuropathies and neuralgias. Topical drugs used in the field of dentistry are topical anaesthetics, topical analgesics, topical antibiotics and topical corticosteroids. It provides symptomatic/curative effect. Topical drugs are easy to apply, avoids hepatic first pass metabolism and more sites specific. But it can only be used for medications that require low plasma concentrations to achieve a therapeutic effect.

  6. Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation.

    Science.gov (United States)

    Mathers, Alicia R; Carey, Cara D; Killeen, Meaghan E; Salvatore, Sonia R; Ferris, Laura K; Freeman, Bruce A; Schopfer, Francisco J; Falo, Louis D

    2018-02-01

    Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid (OA-NO 2 ), an exemplary nitro-fatty acid, inhibit skin inflammation in a model of allergic contact dermatitis (ACD). Given the nitration of unsaturated fatty acids during metabolic and inflammatory processes and the growing use of fatty acids in topical formulations, we sought to further study the effect of nitro-fatty acids on cutaneous inflammation. To accomplish this, the effect of topically applied OA-NO 2 on skin inflammation was evaluated using established murine models of contact hypersensitivity (CHS). In contrast to the effects of subcutaneously injected OA-NO 2 , topical OA-NO 2 potentiated hapten-dependent inflammation inducing a sustained neutrophil-dependent inflammatory response characterized by psoriasiform histological features, increased angiogenesis, and an inflammatory infiltrate that included neutrophils, inflammatory monocytes, and γδ T cells. Consistent with these results, HPLC-MS/MS analysis of skin from psoriasis patients displayed a 56% increase in nitro-conjugated linoleic acid (CLA-NO 2 ) levels in lesional skin compared to non-lesional skin. These results suggest that nitro-fatty acids in the skin microenvironment are products of cutaneous inflammatory responses and, in high local concentrations, may exacerbate inflammatory skin diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Development of an e-Learning Research Module Using Multimedia Instruction Approach.

    Science.gov (United States)

    Kowitlawakul, Yanika; Chan, Moon Fai; Tan, Sharon Swee Lin; Soong, Alan Swee Kit; Chan, Sally Wai Chi

    2017-03-01

    Students nowadays feel more comfortable with new technologies, which increase their motivation and, as a result, improve their academic performance. In the last two decades, the use of information communication technology has been increasing in many disciplines in higher education. Online learning or e-learning has been used and integrated into the curriculum around the world. A team of nursing faculty and educational technology specialists have developed an e-learning research module and integrate it into the nursing curriculum. The aim was to assist master of nursing and postgraduate nursing students in developing their research knowledge before and throughout their enrollment in the research course. This e-learning module includes interactive multimedia such as audiovisual presentation, graphical theme, animation, case-based learning, and pretest and posttest for each topic area. The module focuses on three main topic areas: (1) basic research principles (for review), (2) quantitative method, and (3) qualitative method. The e-learning module is an innovative use of the information and communication technology to enhance student engagement and learning outcomes in a local context. This article discusses the development journey, piloting process, including the variety of evaluation perspectives, and the ways in which the results influenced the e-learning resource before its wider distribution.

  8. Topical N-acetylcysteine reduces interleukin-1-alpha in tear fluid after laser subepithelial keratectomy.

    Science.gov (United States)

    Urgancioglu, Berrak; Bilgihan, Kamil; Engin, Doruk; Cirak, Meltem Yalinay; Hondur, Ahmet; Hasanreisoglu, Berati

    2009-01-01

    To evaluate the effect of topical N-acetylcysteine (NAC) on interleukin 1-alpha (IL-1alpha) levels in tear fluid after myopic laser subepithelial keratectomy (LASEK) and its possible role in modulating corneal wound healing. Twenty-six eyes of 13 patients who underwent myopic LASEK were divided into 2 groups. Group 1 (n=10 eyes) was used as a control group. All patients received topical lomefloxacin and dexamethasone postoperatively. Additionally, patients in Group 2 received topical NAC for 1 month postoperatively. Tear fluid samples were collected with microcapillary tubes preoperatively, on the first and on the fifth postoperative day, and the release of IL-1alpha in tear fluid was calculated. Haze grading and confocal microscopic examination were performed at 1 and 3 months postoperatively. The mean IL-1-alpha release values were 0.285-/+0.159 pg/min in Group 1 and 0.235-/+0.142 pg/min in Group 2 preoperatively. In Group 1, the values were 0.243-/+0.155 pg/min on day 1 and 0.164-/+0.125 pg/min on day 5. In Group 2, the mean IL-1alpha release values were 0.220-/+0.200 pg/min on day 1 and 0.080-/+0.079 pg/min on day 5. The difference between the groups was significant only for day 5 (p0.05). NAC seems to have an additive effect to steroids in suppressing IL-1alpha levels in tear fluid and may be clinically advantageous in modulating corneal wound healing during the early postoperative period after LASEK.

  9. Development of active learning modules in pharmacology for small group teaching.

    Science.gov (United States)

    Tripathi, Raakhi K; Sarkate, Pankaj V; Jalgaonkar, Sharmila V; Rege, Nirmala N

    2015-01-01

    Current teaching in pharmacology in undergraduate medical curriculum in India is primarily drug centered and stresses imparting factual knowledge rather than on pharmacotherapeutic skills. These skills would be better developed through active learning by the students. Hence modules that will encourage active learning were developed and compared with traditional methods within the Seth GS Medical College, Mumbai. After Institutional Review Board approval, 90 second year undergraduate medical students who consented were randomized into six sub-groups, each with 15 students. Pre-test was administered. The three sub-groups were taught a topic using active learning modules (active learning groups), which included problems on case scenarios, critical appraisal of prescriptions and drug identification. The remaining three sub-groups were taught the same topic in a conventional tutorial mode (tutorial learning groups). There was crossover for the second topic. Performance was assessed using post-test. Questionnaires with Likert-scaled items were used to assess feedback on teaching technique, student interaction and group dynamics. The active and tutorial learning groups differed significantly in their post-test scores (11.3 ± 1.9 and 15.9 ± 2.7, respectively, P active learning session as interactive (vs. 37/90 students in tutorial group) and enhanced their understanding vs. 56/90 in tutorial group), aroused intellectual curiosity (47/90 students of active learning group vs. 30/90 in tutorial group) and provoked self-learning (41/90 active learning group vs. 14/90 in tutorial group). Sixty-four students in the active learning group felt that questioning each other helped in understanding the topic, which was the experience of 25/90 students in tutorial group. Nevertheless, students (55/90) preferred tutorial mode of learning to help them score better in their examinations. In this study, students preferred an active learning environment, though to pass examinations, they

  10. Dermatitis herpetiformis intolerant to dapsone in Aids

    Directory of Open Access Journals (Sweden)

    Krishna K

    1999-01-01

    Full Text Available A 35-year-old man with AIDS and pulmonary tuberculosis presented with lesions suggestive of dermatitis herpetiformis and intolerance to dapsone. He was managed successfully with a combination of nicotinamide 200 mg/day and indomethacin 75 mg/day, topical steroids and gluten free diet.

  11. Topical report review status

    International Nuclear Information System (INIS)

    1982-08-01

    A Topical Report Review Status is scheduled to be published semi-annually. The primary purpose of this document is to provide periodic progress reports of on-going topical report reviews, to identify those topical reports for which the Nuclear Regulatory Commission (NRC) staff review has been completed and, to the extent practicable, to provide NRC management with sufficient information regarding the conduct of the topical report program to permit taking whatever actions deemed necessary or appropriate. This document is also intended to be a source of information to NRC Licensing Project Managers and other NRC personnel regarding the status of topical reports which may be referenced in applications for which they have responsibility. This status report is published primarily for internal NRC use in managing the topical report program, but is also used by NRC to advise the industry of report review status

  12. Topical report review status

    International Nuclear Information System (INIS)

    1983-01-01

    A Topical Report Review Status is scheduled to be published semi-annually. The primary purpose of this document is to provide periodic progress reports of on-going topical report reviews, to identify those topical reports for which the Nuclear Regulatory Commission (NRC) staff review has been completed and, to the extent practicable, to provide NRC management with sufficient information regarding the conduct of the topical report program to permit taking whatever actions deemed necessary or appropriate. This document is also intended to be a source of information to NRC Licensing Project Managers and other NRC personnel regarding the status of topical reports which may be referenced in applications for which they have responsibility. This status report is published primarily for internal NRC use in managing the topical report program, but is also used by NRC to advise the industry of report review status

  13. What Patients Can Tell Us: Topic Analysis for Social Media on Breast Cancer.

    Science.gov (United States)

    Tapi Nzali, Mike Donald; Bringay, Sandra; Lavergne, Christian; Mollevi, Caroline; Opitz, Thomas

    2017-07-31

    Social media dedicated to health are increasingly used by patients and health professionals. They are rich textual resources with content generated through free exchange between patients. We are proposing a method to tackle the problem of retrieving clinically relevant information from such social media in order to analyze the quality of life of patients with breast cancer. Our aim was to detect the different topics discussed by patients on social media and to relate them to functional and symptomatic dimensions assessed in the internationally standardized self-administered questionnaires used in cancer clinical trials (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core 30 [QLQ-C30] and breast cancer module [QLQ-BR23]). First, we applied a classic text mining technique, latent Dirichlet allocation (LDA), to detect the different topics discussed on social media dealing with breast cancer. We applied the LDA model to 2 datasets composed of messages extracted from public Facebook groups and from a public health forum (cancerdusein.org, a French breast cancer forum) with relevant preprocessing. Second, we applied a customized Jaccard coefficient to automatically compute similarity distance between the topics detected with LDA and the questions in the self-administered questionnaires used to study quality of life. Among the 23 topics present in the self-administered questionnaires, 22 matched with the topics discussed by patients on social media. Interestingly, these topics corresponded to 95% (22/23) of the forum and 86% (20/23) of the Facebook group topics. These figures underline that topics related to quality of life are an important concern for patients. However, 5 social media topics had no corresponding topic in the questionnaires, which do not cover all of the patients' concerns. Of these 5 topics, 2 could potentially be used in the questionnaires, and these 2 topics corresponded to a total of 3.10% (523

  14. 75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2010-05-12

    .... FDA-2010-N-0002] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... are treated with a topical solution of ivermectin. DATES: This rule is effective May 12, 2010. FOR... ANADA 200-340 for PRIVERMECTIN (ivermectin), a topical solution used on cattle to control infestations...

  15. Women's Health Topics

    Science.gov (United States)

    ... Information by Audience For Women Women's Health Topics Women's Health Topics Share Tweet Linkedin Pin it More sharing options Linkedin Pin it Email Print National Women's Health Week May 13 - 19, 2018 Join us ...

  16. Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas.

    Science.gov (United States)

    Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

    2011-04-01

    The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant lymphomas (diffuse large B-cell lymphoma, follicular B-cell lymphoma, Hodgkin's lymphoma and peripheral T-cell lymphoma). The expression of NAMPT was generally high in the more aggressive malignant lymphomas, with >80% strong expression, whereas the expression in the more indolent follicular lymphoma (FL) was significantly lower (>75% moderate or low expression, p = 0.0002). NAMPT was very highly expressed in Hodgkin Reed-Sternberg cells in Hodgkin's lymphoma. NAPRT expression was more varied (p > 0.0001) with 30-50% low expression except for Hodgkin's lymphoma where 85% displayed low expression (p = 0.0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors. © 2011 The Authors. APMIS © 2011 APMIS.

  17. Pengembangan Modul Pembelajaran Fisika Berbasis Problem Based Learning (PBL pada Materi Gelombang Bunyi untuk Siswa SMA Kelas XII

    Directory of Open Access Journals (Sweden)

    Tri Anita Nur Hasanah

    2017-03-01

    Full Text Available The 2013 curriculum emphasizes on Scientific Approach taht tie topic with real context. Either learning model that leads to Scientific Approach that is Problem Based Learning (PBL. So that need to prepare appropriate teaching material to support learning model PBL one of them module independent teaching topic for learners. The aim of these research is describe the Learning Module which is developed that is physic learning module based on PBL of the topic sound wave for senior high school grade XII and examine its feasibility. This development research used 4-D Thiagarajan with modified model. This research has been done in three stages such as define, design, and develop which are restricted until the limited try out. The data collection is used questionnaire. The module validation by 4 validators and limited try out to 10 students. The result of research drawn that material aspect is 3,59 with the suitable criterion, presentation aspect is 3,9 with the suitable criterion, language aspect is 3,41 with the suitable criterion, and the limited try out result got 3,6 with an appropriate criterion. In conclusion, physic learning module based on PBL in sound wave material for senior high school grade XII is applicable. Keywords: Physic Learning Module, Problem Based Learning (PBL, Topic sound wave Pada kurikulum 2013 menekankan pada Scientific Approach yang mengaitkan materi dengan konteks dunia nyata. Salah satu model pembelajaran yang mengarah ke Scientific Approach yaitu Problem Based Learning (PBL. Sehingga perlu dipersiapkan bahan ajar yang tepat untuk mendukung model pembelajaran PBL salah satunya modul yang merupakan bahan ajar mandiri bagi peserta didik. Tujuan penelitian ini adalah mendeskripsikan pengembangan modul yaitu modul pembelajaran fisika berbasis PBL pada materi Gelombang Bunyi untuk siswa SMA kelas XII dan menguji kelayakannya.Penelitian pengembangan menggunakan model 4-D Thiagarajan yang sudah di modifikasi. Penelitian ini

  18. Crystal structure of trans-diaquabis(4-cyanobenzoato-κObis(nicotinamide-κN1cobalt(II

    Directory of Open Access Journals (Sweden)

    Gülçin Şefiye Aşkın

    2015-05-01

    Full Text Available In the title complex, [Co(C8H4NO22(C6H6N2O2(H2O2], the CoII atom is located on an inversion centre and is coordinated by two 4-cyanobenzoate (CNB anions, two nicotinamide (NA ligands and two water molecules. The four O atoms in the equatorial plane form a slightly distorted square-planar arrangement, while the slightly distorted octahedral coordination sphere is completed by the two N atoms of the NA ligands in the axial positions. The dihedral angle between the carboxylate group and the adjacent benzene ring is 22.11 (15°, while the pyridine and benzene rings are oriented at a dihedral angle of 89.98 (5°. In the crystal, intermolecular N—H...O and O—H...O hydrogen bonds link the molecules, enclosing R22(8 and R44(8 ring motifs, forming layers parallel to (100. The layers are linked via C—H...O and C—H...N hydrogen bonds, resulting in a three-dimensional network. A weak C—H...π interaction is also observed.

  19. Enhancement of in vivo Radiosensitization by Combination with Pentoxifylline and Nicotinamide

    International Nuclear Information System (INIS)

    Lee, In Tae; Cho, Moon June

    1991-01-01

    Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the O2 release from RBC. Nicotinamide (N4) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the the FSa II murine fibrosarcoma by oxygenation the hypoxic cells. We observed a significantly enhanced radiation-induced growth delay of the FSa II tumors by PENTO-NA. Thus the enhancement ration was between 2.5 and 2.8 in growth delay assay. The TCD 50 of control tumors was about 57 Gy, but that of PENTO-NA treated tumors was about 32 Gy. The TCD50 was modified by a factor of 1.8. We also observed that PENTO+NA, changes in tumor blood flow and intratumor pO2 were measured using laser Doppler flowmetry and O2 microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+NA. Furthermore, we also found that PENTO+NA significantly increased intratumor pO2 from 8 to 19 mmHg. We concluded that PENTO+NA was far more effective than NA alone or PENTO alone. The increase in the response of tumor in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted

  20. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Stephan Menzel

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP and nicotinamide adenine dinucleotide (NAD+ are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies – single domain antibodies derived from heavy chain antibodies that naturally occur in camelids – display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  1. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity.

    Science.gov (United States)

    Menzel, Stephan; Schwarz, Nicole; Haag, Friedrich; Koch-Nolte, Friedrich

    2018-01-01

    Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD + is converted by CD38, CD203 and other ecto-enzymes to the Ca 2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  2. Modulation of DNA binding by gene-specific transcription factors.

    Science.gov (United States)

    Schleif, Robert F

    2013-10-01

    The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

  3. Human-competitive automatic topic indexing

    CERN Document Server

    Medelyan, Olena

    2009-01-01

    Topic indexing is the task of identifying the main topics covered by a document. These are useful for many purposes: as subject headings in libraries, as keywords in academic publications and as tags on the web. Knowing a document’s topics helps people judge its relevance quickly. However, assigning topics manually is labor intensive. This thesis shows how to generate them automatically in a way that competes with human performance. Three kinds of indexing are investigated: term assignment, a task commonly performed by librarians, who select topics from a controlled vocabulary; tagging, a popular activity of web users, who choose topics freely; and a new method of keyphrase extraction, where topics are equated to Wikipedia article names. A general two-stage algorithm is introduced that first selects candidate topics and then ranks them by significance based on their properties. These properties draw on statistical, semantic, domain-specific and encyclopedic knowledge. They are combined using a machine learn...

  4. Emergency Victim Care. A Training Manual for Emergency Medical Technicians. Module 3--Anatomy and Physiology. Revised.

    Science.gov (United States)

    Ohio State Dept. of Education, Columbus. Div. of Vocational Education.

    This student manual, the third in a set of 14 modules, is designed to train emergency medical technicians (EMTs) in Ohio. The module contains one section covering the following topics: general anatomical terms, the body cavities and contents, the integumentary system, the skeletal system, the muscular system, the nervous system, the respiratory…

  5. Assessing Advanced High School and Undergraduate Students' Thinking Skills: The Chemistry--From the Nanoscale to Microelectronics Module

    Science.gov (United States)

    Dori, Yehudit Judy; Dangur, Vered; Avargil, Shirly; Peskin, Uri

    2014-01-01

    Chemistry students in Israel have two options for studying chemistry: basic or honors (advanced placement). For instruction in high school honors chemistry courses, we developed a module focusing on abstract topics in quantum mechanics: Chemistry--From the Nanoscale to Microelectronics. The module adopts a visual-conceptual approach, which…

  6. Topic Visualization and Survival Analysis

    OpenAIRE

    Wang, Ping Jr

    2017-01-01

    Latent semantic structure in a text collection is called a topic. In this thesis, we aim to visualize topics in the scientific literature and detect active or inactive research areas based on their lifetime. Topics were extracted from over 1 million abstracts from the arXiv.org database using Latent Dirichlet Allocation (LDA). Hellinger distance measures similarity between two topics. Topics are determined to be relevant if their pairwise distances are smaller than the threshold of Hellinger ...

  7. GeneTopics - interpretation of gene sets via literature-driven topic models

    Science.gov (United States)

    2013-01-01

    Background Annotation of a set of genes is often accomplished through comparison to a library of labelled gene sets such as biological processes or canonical pathways. However, this approach might fail if the employed libraries are not up to date with the latest research, don't capture relevant biological themes or are curated at a different level of granularity than is required to appropriately analyze the input gene set. At the same time, the vast biomedical literature offers an unstructured repository of the latest research findings that can be tapped to provide thematic sub-groupings for any input gene set. Methods Our proposed method relies on a gene-specific text corpus and extracts commonalities between documents in an unsupervised manner using a topic model approach. We automatically determine the number of topics summarizing the corpus and calculate a gene relevancy score for each topic allowing us to eliminate non-specific topics. As a result we obtain a set of literature topics in which each topic is associated with a subset of the input genes providing directly interpretable keywords and corresponding documents for literature research. Results We validate our method based on labelled gene sets from the KEGG metabolic pathway collection and the genetic association database (GAD) and show that the approach is able to detect topics consistent with the labelled annotation. Furthermore, we discuss the results on three different types of experimentally derived gene sets, (1) differentially expressed genes from a cardiac hypertrophy experiment in mice, (2) altered transcript abundance in human pancreatic beta cells, and (3) genes implicated by GWA studies to be associated with metabolite levels in a healthy population. In all three cases, we are able to replicate findings from the original papers in a quick and semi-automated manner. Conclusions Our approach provides a novel way of automatically generating meaningful annotations for gene sets that are directly

  8. Fieldcrest Cannon, Inc. Advanced Technical Preparation. Statistical Process Control (SPC). Safety Section: Modules 1-3. Instructor Book.

    Science.gov (United States)

    Averitt, Sallie D.

    These three modules, which were developed for use by instructors in a manufacturing firm's advanced technical preparation program, contain the materials required to present the safety section of the plant's adult-oriented, job-specific competency-based training program. The 3 modules contain 12 lessons on the following topics: lockout/tagout…

  9. Phenylacetic acid co-crystals with acridine, caffeine, isonicotinamide and nicotinamide: Crystal structures, thermal analysis, FTIR spectroscopy and Hirshfeld surface analysis

    Science.gov (United States)

    Amombo Noa, Francoise M.; Jacobs, Ayesha

    2017-07-01

    Co-crystals of phenylacetic acid (PAA) with acridine (ACR), caffeine (CAF), isonicotinamide (INM) and nicotinamide (NAM) have been successfully prepared and characterised by single crystal X-ray diffraction, FTIR spectroscopy, thermal analysis and Hirshfeld surface analysis. The ACR, INM and NAM co-crystals with PAA exhibit the carboxylic acid-pyridine heterosynthon. Furthermore the amide-amide supramolecular homosynthon is observed in the PAA co-crystals with INM and NAM as well as Nsbnd H⋯O interactions between the acid and the respective base. The CAF co-crystal exhibits hydrogen bonding between the imidazole nitrogen and the COOH group of the PAA. The compounds demonstrate different stoichiometries; for PAA·ACR and PAA·INM a 1:1 ratio is displayed, a 2:1 in 2PAA·CAF and a 2:2 in the case of 2PAA·2NAM.

  10. Identifying Effective Design Features of Technology-Infused Inquiry Learning Modules: A Two-Year Study of Students' Inquiry Abilities

    Science.gov (United States)

    Hsu, Ying-Shao; Fang, Su-Chi; Zhang, Wen-Xin; Hsin-Kai, Wu; Wu, Pai-Hsing; Hwang, Fu-Kwun

    2016-01-01

    The two-year study aimed to explore how students' development of different inquiry abilities actually benefited from the design of technology-infused learning modules. Three learning modules on the topics of seasons, environmental issues and air pollution were developed to facilitate students' inquiry abilities: questioning, planning, analyzing,…

  11. Fluorimetric study of the interaction between nicotinamide adenine dinucleotide phosphate and tetracycline-europium complex and its application

    International Nuclear Information System (INIS)

    Peng Qian; Hou Faju; Ge Xiaoxia; Jiang Chongqiu; Gong Shubo

    2005-01-01

    A new spectrofluorimetric method was developed for the determination of trace amount of nicotinamide adenine dinucleotide phosphate (NADP). Using europium (Eu 3+ )-tetracycline (TC) complex as a fluorescent probe, in the buffer solution of pH 7.60. NADP can remarkably enhance the fluorescence intensity of the Eu 3+ -TC complex at λ = 612 nm and the enhanced fluorescence intensity of Eu 3+ ion is in proportion to the concentration of NADP. Optimum conditions for the determination of NADP were also investigated. The dynamic range for the determination of NADP is 4.4 x 10 -7 to 2.2 x 10 -6 mol l -1 with detection limit of 6.9 x 10 -8 mol l -1 . This method is simple, practical and relatively free interference from coexisting substances and can be successfully applied to determination of NADP in synthetic water samples and in serum samples. Moreover, the enhancement mechanisms of the fluorescence intensity in the Eu 3+ -TC system and the Eu 3+ -TC-NADP system have been also discussed

  12. Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide.

    Science.gov (United States)

    Nurliyani; Harmayani, Eni; Sunarti

    2015-01-01

    The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (pkefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (pkefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (pkefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells.

  13. Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    2017-01-01

    Full Text Available Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

  14. Formulation of Multiple Choice Questions as a Revision Exercise at the End of a Teaching Module in Biochemistry

    Science.gov (United States)

    Bobby, Zachariah; Radhika, M. R.; Nandeesha, H.; Balasubramanian, A.; Prerna, Singh; Archana, Nimesh; Thippeswamy, D. N.

    2012-01-01

    The graduate medical students often get less opportunity for clarifying their doubts and to reinforce their concepts after lecture classes. Assessment of the effect of MCQ preparation by graduate medical students as a revision exercise on the topic "Mineral metabolism." At the end of regular teaching module on the topic "Mineral metabolism,"…

  15. Comparing the efficacy of multimedia modules with traditional textbooks for learning introductory physics content

    Science.gov (United States)

    Stelzer, Timothy; Gladding, Gary; Mestre, José P.; Brookes, David T.

    2009-02-01

    We compared the efficacy of multimedia learning modules with traditional textbooks for the first few topics of a calculus-based introductory electricity and magnetism course. Students were randomly assigned to three groups. One group received the multimedia learning module presentations, and the other two received the presentations via written text. All students were then tested on their learning immediately following the presentations as well as 2weeks later. The students receiving the multimedia learning modules performed significantly better on both tests than the students experiencing the text-based presentations.

  16. Procurement Service launches new eLearning module

    CERN Multimedia

    2015-01-01

    The Procurement Service has launched a training module covering “Procurement of supplies at CERN up to 200,000 CHF” in the form of an eLearning, accessible to all users involved in the procurement process. A long version (30 minutes) and a short version (10 minutes) are now available via this link.   The objectives of this eLearning module are as follows: To improve users' knowledge of the Procurement Rules to facilitate the successful completion of a DAI. This will ensure their DAI is processed as quickly as possible; To decrease the number of single tender requests and to avoid non compliant procurement practices such as the fragmentation of requirements into smaller orders. The eLearning module in its short version covers a range of topics, including the role of the technical officer, estimation of order amount (and the subsequent procedure to follow) and preparation and completion of the DAI form. The longer version also includes useful informati...

  17. Health Topic XML File Description

    Science.gov (United States)

    ... this page: https://medlineplus.gov/xmldescription.html Health Topic XML File Description: MedlinePlus To use the sharing ... information categories assigned. Example of a Full Health Topic Record A record for a MedlinePlus health topic ...

  18. Children at risk of diabetes type 1. Treatment with acetyl-L-carnitine plus nicotinamide - case reports.

    Science.gov (United States)

    Fernandez, Ivana Cristina; Del Carmen Camberos, María; Passicot, Gisel Anabel; Martucci, Lucía Camila; Cresto, Juan Carlos

    2013-01-01

    Abstract Objectives: The aim was to evaluate the treatment with acetyl-L-carnitine (50 mg/kg/day) and nicotinamide (25 mg/kg/day) in children at risk of type 1 diabetes. This treatment was effective and harmless in experimental type 1 diabetes in mice. Nine out of seventy healthy participants of the type 1 diabetes risk study were treated. They were typified for diabetes with HLA-DQB1 and positive autoantibodies. Children with a first peak of insulin response ≤48 µU were randomly distributed in control and treated patients. Children evolution was followed with an intravenous glucose tolerance test. Control children were treated when was another risk parameter was added. During their evolution all children were treated. Treatment periods differ (range: 120-16 months) because children began treatment at different times. During the treatment 4 patients recovered their parameters and the medication was suspended; 2 patients continued the treatment with favorable evolution. Two children evolved slowly with normal growth and development. One girl became diabetic because she was treated late. In children at risk, this treatment delays the development or remits the evolution of type 1 diabetes.

  19. Nicotinamide-NAD sequence: redox process and related behavior, behavior and properties of intermediate and final products

    International Nuclear Information System (INIS)

    Elving, P.J.; Schmakel, C.O.; Santhanam, K.S.V.

    1976-01-01

    Illustrations of the application of analytical chemical techniques to the study of chemical phenomena are given. In particular, electrochemical techniques and methodology and, to a lesser extent, spectrophotometry were used to investigate the solution behavior, adsorption, redox processes including coupled chemical reactions, and allied aspects of biologically significant compounds and of their intermediate and final redox products, e.g., the behavior of the free radicals produced by initial one-electron processes. This approach is illustrated by the consideration of the behavior in aqueous and nonaqueous media of a sequence of compounds ranging from nicotinamide (3-carbamoylpyridine) to NAD + and NADP + ; the latter compounds function as coenzymes for the pyridinoproteins which are principal components in the Krebs citric acid cycle and in the electron transport chain in biological redox reactions. The discussion is presented under the following section headings: interpretation of electrochemical behavior; mechanistic patterns; kinetic aspects of charge-transfer and chemical reactions; correlation with theoretically calculated parameters; and, mechanisms of biological oxidation-reduction reactions. The use of pulse radiolysis, chronopotentiometric, and cyclic voltammetric methods in studies on free radical dimerization rates is reviewed in the discussion of the kinetic aspects of charge-transfer and chemical reactions. (188 references)

  20. CLIC Quadrupole Module final report

    CERN Document Server

    Artoos, K; Mainaud-Durand, H

    2013-01-01

    Future Linear colliders will need particle beam sizes in the nanometre range. The beam also needs to be stable all along the beam line. The CLIC Main Beam Quadrupole (MBQ) module has been defined and studied. It is meant as a test stand for stabilisation and pre-alignment with a MB Quadrupole. The main topic that has been tackled concerns the Quadrupole magnet stabilisation to 1nm at 1Hz. This is needed to obtain the desired CLIC luminosity of 2.1034 cm-2m-1. The deliverable was demonstrated by procuring a MBQ and by stabilising a powered and cooled CLIC MBQ quadrupole. In addition, the stabilisation system has to be compatible with the pre-alignment procedures. Pre-alignment movement resolution has been demonstrated to 1m. The last step is the combined test of stability with a quadrupole on a CLIC Module with the pre-alignment.

  1. Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice.

    Science.gov (United States)

    Ahangarpour, Akram; Heidari, Hamid; Junghani, Majid Salehizade; Absari, Reza; Khoogar, Mehdi; Ghaedi, Ehsan

    2017-10-01

    Type 2 diabetes often leads to dislipidemia and abnormal activity of hepatic enzymes. The purpose of this study was to evaluate the antidiabetic and hypolipidemic properties of Rhus coriaria ( R. coriaria ) seed extrac on nicotinamide-streptozotocin induced type 2 diabetic mice. In this experimental study, 56 male Naval Medical Research Institute mice (30-35 g) were randomly separated into seven groups: control, diabetic group, diabetic mice treated with glibenclamide (0.25 mg/kg, as standard antidiabetic drug) or R. coriaria seed extract in doses of 200 and 300 mg/kg, and control groups received these two doses of extract orally for 28 days. Induction of diabetes was done by intraperitoneal injection of nicotinamide and streptozotocin. Ultimately, body weight of mice, blood levels of glucose, insulin, hepatic enzymes, leptin, and lipid profile were assayed. After induction of type 2 diabetes, level of glucose, cholesterol, low density lipoprotein, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase increased and level of insulin and high density lipoprotein decreased remarkably. Administration of both doses of extract decreased level of glucose and cholesterol significantly in diabetic mice. LDL level decreased in treated group with dose of 300 mg/kg of the extract. Although usage of the extract improved level of other lipid profiles, insulin and hepatic enzymes, changes weren't significant. This study showed R. coriaria seeds administration has a favorable effect in controlling some blood parameters in type 2 diabetes. Therefore it may be beneficial in the treatment of diabetes.

  2. Identifying Topics in Microblogs Using Wikipedia.

    Science.gov (United States)

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail.

  3. Regulatory Information By Topic

    Science.gov (United States)

    EPA develops and enforces regulations that span many environmental topics, from acid rain reduction to wetlands restoration. Each topic listed below may include related laws and regulations, compliance enforcement information, policies guidance

  4. Head to head comparison of short-term treatment with the NAD+ precursor nicotinamide mononucleotide (NMN and six weeks of exercise in obese female mice

    Directory of Open Access Journals (Sweden)

    Golam Mezbah Uddin

    2016-08-01

    Full Text Available Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD+. Recent studies have shown that NAD+ levels can be increased by using the NAD+ precursor, nicotinamide mononucleotide (NMN leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across 5 interventions: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group. After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 minutes, 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight was injected (i.p. daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD+ levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD+ only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

  5. Identifying Topics in Microblogs Using Wikipedia.

    Directory of Open Access Journals (Sweden)

    Ahmet Yıldırım

    Full Text Available Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA, propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision and other observations from the study are discussed in detail.

  6. Dynamic changes in nicotinamide pyridine dinucleotide content in normal human epidermal keratinocytes and their effect on retinoic acid biosynthesis

    International Nuclear Information System (INIS)

    Pinkas-Sarafova, Adriana; Markova, N.G.; Simon, M.

    2005-01-01

    The function of many enzymes that regulate metabolism and transcription depends critically on the nicotinamide pyridine dinucleotides. To understand the role of NAD(P)(H) in physiology and pathophysiology, it is imperative to estimate both their amount and ratios in a given cell type. In human epidermis and in cultured epidermal keratinocytes, we found that the total dinucleotide content is in the low millimolar range. The dinucleotide pattern changes during proliferation and maturation of keratinocytes in culture. Differences in the concentrations of NAD(P)(H) of 1.5- to 12-fold were observed. This resulted in alteration of the NAD(P)H/NAD(P) ratio, which could impact the differential regulation of both transcriptional and metabolic processes. In support of this notion, we provide evidence that the two-step oxidation of retinol to retinoic acid, a nuclear hormone critical for epidermal homeostasis, can be regulated by the relative physiological amounts of the pyridine dinucleotides

  7. Dressings and topical agents for treating pressure ulcers.

    Science.gov (United States)

    Westby, Maggie J; Dumville, Jo C; Soares, Marta O; Stubbs, Nikki; Norman, Gill

    2017-06-22

    Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers. Such a review would ideally help people with pressure ulcers and health professionals assess the best treatment options. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents. To assess the effects of dressings and topical agents for healing pressure ulcers in any care setting. We aimed to examine this evidence base as a whole, determining probabilities that each treatment is the best, with full assessment of uncertainty and evidence quality. In July 2016 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. Published or unpublished randomised controlled trials (RCTs) comparing the effects of at least one of the following interventions with any other intervention in the treatment of pressure ulcers (Stage 2 or above): any dressing, or any topical agent applied directly

  8. Differential Topic Models.

    Science.gov (United States)

    Chen, Changyou; Buntine, Wray; Ding, Nan; Xie, Lexing; Du, Lan

    2015-02-01

    In applications we may want to compare different document collections: they could have shared content but also different and unique aspects in particular collections. This task has been called comparative text mining or cross-collection modeling. We present a differential topic model for this application that models both topic differences and similarities. For this we use hierarchical Bayesian nonparametric models. Moreover, we found it was important to properly model power-law phenomena in topic-word distributions and thus we used the full Pitman-Yor process rather than just a Dirichlet process. Furthermore, we propose the transformed Pitman-Yor process (TPYP) to incorporate prior knowledge such as vocabulary variations in different collections into the model. To deal with the non-conjugate issue between model prior and likelihood in the TPYP, we thus propose an efficient sampling algorithm using a data augmentation technique based on the multinomial theorem. Experimental results show the model discovers interesting aspects of different collections. We also show the proposed MCMC based algorithm achieves a dramatically reduced test perplexity compared to some existing topic models. Finally, we show our model outperforms the state-of-the-art for document classification/ideology prediction on a number of text collections.

  9. Topic Model for Graph Mining.

    Science.gov (United States)

    Xuan, Junyu; Lu, Jie; Zhang, Guangquan; Luo, Xiangfeng

    2015-12-01

    Graph mining has been a popular research area because of its numerous application scenarios. Many unstructured and structured data can be represented as graphs, such as, documents, chemical molecular structures, and images. However, an issue in relation to current research on graphs is that they cannot adequately discover the topics hidden in graph-structured data which can be beneficial for both the unsupervised learning and supervised learning of the graphs. Although topic models have proved to be very successful in discovering latent topics, the standard topic models cannot be directly applied to graph-structured data due to the "bag-of-word" assumption. In this paper, an innovative graph topic model (GTM) is proposed to address this issue, which uses Bernoulli distributions to model the edges between nodes in a graph. It can, therefore, make the edges in a graph contribute to latent topic discovery and further improve the accuracy of the supervised and unsupervised learning of graphs. The experimental results on two different types of graph datasets show that the proposed GTM outperforms the latent Dirichlet allocation on classification by using the unveiled topics of these two models to represent graphs.

  10. Analyses of Research Topics in the Field of Informetrics Based on the Method of Topic Modeling

    OpenAIRE

    Sung-Chien Lin

    2014-01-01

    In this study, we used the approach of topic modeling to uncover the possible structure of research topics in the field of Informetrics, to explore the distribution of the topics over years, and to compare the core journals. In order to infer the structure of the topics in the field, the data of the papers published in the Journal of Informetricsand Scientometrics during 2007 to 2013 are retrieved from the database of the Web of Science as input of the approach of topic modeling. The results ...

  11. Analyses of Research Topics in the Field of Informetrics Based on the Method of Topic Modeling

    Directory of Open Access Journals (Sweden)

    Sung-Chien Lin

    2014-07-01

    Full Text Available In this study, we used the approach of topic modeling to uncover the possible structure of research topics in the field of Informetrics, to explore the distribution of the topics over years, and to compare the core journals. In order to infer the structure of the topics in the field, the data of the papers published in the Journal of Informetricsand Scientometrics during 2007 to 2013 are retrieved from the database of the Web of Science as input of the approach of topic modeling. The results of this study show that when the number of topics was set to 10, the topic model has the smallest perplexity. Although data scopes and analysis methodsare different to previous studies, the generating topics of this study are consistent with those results produced by analyses of experts. Empirical case studies and measurements of bibliometric indicators were concerned important in every year during the whole analytic period, and the field was increasing stability. Both the two core journals broadly paid more attention to all of the topics in the field of Informetrics. The Journal of Informetricsput particular emphasis on construction and applications ofbibliometric indicators and Scientometrics focused on the evaluation and the factors of productivity of countries, institutions, domains, and journals.

  12. Topical treatments of skin pain: a general review with a focus on hidradenitis suppurativa with topical agents.

    Science.gov (United States)

    Scheinfeld, Noah

    2014-07-15

    Hidradenitis Supprurativa (HS) is a painful chronic follicular disease. Few papers have addressed pain control for this debilitating condition. Possible topical agents include tricyclic antidepressants, opioids, anticonvulsants, NSAIDs, NMDA receptor antagonists, local anesthetics and other agents. The first line agents for the topical treatment of the cutaneous pain of HS are diclonefac gel 1% and liposomal xylocaine 4% and 5% cream or 5% ointment. The chief advantage of topical xylocaine is that is quick acting i.e. immediate however with a limited duration of effect 1-2 hours. The use of topical ketamine, which blocks n-methyl-D-aspartate receptors in a non-competitive fashion, might be a useful tool for the treatment of HS pain. Topical doxepin, which available in a 5% commercially preparation (Zonalon®) , makes patients drowsy and is not useful for controlling the pain of HS . Doxepin is available in a 3% or 3.3% concentration (which causes less drowsiness) from compounding pharmacies and can be used in compounded analgesic preparations with positive effect. Topical doxepin is preferred over use of topical amitriptyline because topical doxepin is more effective. Nevertheless, topical amitriptyline increase of the tactile and mechanical nociceptive thresholds and can be used for topical pain control in compound mixture of analgesics . Gabapentin and pregablin can also be used compounded with other agents in topical analgesic preparations with positive topical anesthetic effect. Capsaicin is not useful for topical treatment of the pain of HS. Sometimes compounded of anesthetics medications such as ketamine 10%, bupivacaine 1%, diclofenac 3%, doxepin 3% or 3.3%, and gabapentin 6% can extend the duration of effect so that medication only needs to be used 2 or 3 times a day. Still in my experience the easiest to get and most patient requested agent is topical diclonefac 1% gel.

  13. Topical steroid-damaged skin

    Directory of Open Access Journals (Sweden)

    Anil Abraham

    2014-01-01

    Full Text Available Topical steroids, commonly used for a wide range of skin disorders, are associated with side effects both systemic and cutaneous. This article aims at bringing awareness among practitioners, about the cutaneous side effects of easily available, over the counter, topical steroids. This makes it important for us as dermatologists to weigh the usefulness of topical steroids versus their side effects, and to make an informed decision regarding their use in each individual based on other factors such as age, site involved and type of skin disorder.

  14. Mental Mechanisms for Topics Identification

    Directory of Open Access Journals (Sweden)

    Louis Massey

    2014-01-01

    Full Text Available Topics identification (TI is the process that consists in determining the main themes present in natural language documents. The current TI modeling paradigm aims at acquiring semantic information from statistic properties of large text datasets. We investigate the mental mechanisms responsible for the identification of topics in a single document given existing knowledge. Our main hypothesis is that topics are the result of accumulated neural activation of loosely organized information stored in long-term memory (LTM. We experimentally tested our hypothesis with a computational model that simulates LTM activation. The model assumes activation decay as an unavoidable phenomenon originating from the bioelectric nature of neural systems. Since decay should negatively affect the quality of topics, the model predicts the presence of short-term memory (STM to keep the focus of attention on a few words, with the expected outcome of restoring quality to a baseline level. Our experiments measured topics quality of over 300 documents with various decay rates and STM capacity. Our results showed that accumulated activation of loosely organized information was an effective mental computational commodity to identify topics. It was furthermore confirmed that rapid decay is detrimental to topics quality but that limited capacity STM restores quality to a baseline level, even exceeding it slightly.

  15. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial.

    Science.gov (United States)

    Morgulis, Yuri; Kumar, Rakesh K; Lindeman, Robert; Velan, Gary M

    2012-05-28

    e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group's evaluation of the module was overwhelmingly positive. A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  16. Performance And Radiation Hardness Of The Atlas/sct Detector Module

    CERN Document Server

    Eklund, L

    2003-01-01

    The ATLAS experiment is a general purpose experiment being constructed at the Large Hadron Collider (LHC) at FERN, Geneva. ATLAS is designed to exploit the full physics potential of LHC, in particular to study topics concerning the Higgs mechanism, Super-symmetry and CP violation. The cross sections for the processes under study are extremely small, requiring very high luminosity colliding beams. The Semiconductor Tracker (SCT) is an essential part of the Inner Detector tracking system of ATLAS. The active elements of the SCT is 4088 detector modules, tiled on four barrel cylinders and eighteen endcap disks. As a consequence of the high luminosity, the detector modules will operate in a harsh radiation environment. This thesis describes work concerning radiation hardness, beam test performance and methods for production testing of detector modules. The radiation hardness studies have been focused on the electrical performance of the front-end ASIC and the detector module. The results have identified features ...

  17. (Solid + liquid) phase diagram for (indomethacin + nicotinamide)-methanol or methanol/ethyl acetate mixture and solubility behavior of 1:1 (indomethacin + nicotinamide) co-crystal at T = (298.15 and 313.15) K

    International Nuclear Information System (INIS)

    Sun, Xiaowei; Yin, Qiuxiang; Ding, Suping; Shen, Zhiming; Bao, Ying; Gong, Junbo; Hou, Baohong; Hao, Hongxun; Wang, Yongli; Wang, Jingkang; Xie, Chuang

    2015-01-01

    Highlights: • Ternary phase diagrams of (IMC + NCT)-methanol or methanol/ethyl acetate mixture at T = (298.15 and 313.15) K were measured. • The effects of temperature and introduced ethyl acetate on solid phase stability were discussed. • Solubility of (IMC + NCT) cocrystals was first correlated using a model considering solubility product and complexation. • Solubility of (IMC + NCT) cocrystals as a function of co-former concentration was evaluated. - Abstract: (Solid + liquid) equilibrium data for indomethacin (IMC) and nicotinamide (NCT) in both methanol (MeOH) and methanol/ethyl acetate (EA) mixture were determined using a static method at T = (298.15 and 313.15) K under atmospheric pressure. The 1:1 (IMC + NCT) co-crystal and IMC·MeOH were found in both systems under conditions investigated. The solubility of the 1:1 (IMC + NCT) co-crystal was correlated using a mathematical model consisting of both solubility product and a complexation process. Solubility of (IMC + NCT) co-crystals as a function of co-former (NCT) concentration was evaluated. It was found that temperature has a significant effect on the formation of methanol solvate in the systems investigated. Solvate formation could be suppressed either by increasing temperature or using solvent mixtures. Additionally, the solvent mixture could level out the solubility differences between IMC and NCT, resulting in larger and more symmetric regions for the (IMC + NCT) co-crystal, which would be helpful to the development of the co-crystallization process for the 1:1 (IMC + NCT) co-crystal

  18. Topical Treatment of Degenerative Knee Osteoarthritis.

    Science.gov (United States)

    Meng, Zengdong; Huang, Rongzhong

    2018-01-01

    This article reviews topical management strategies for degenerative osteoarthritis (OA) of the knee. A search of Pubmed, Embase and the Cochrane library using MeSH terms including "topical," "treatment," "knee" and "osteoarthritis" was carried out. Original research and review articles on the effectiveness and safety, recommendations from international published guidelines and acceptability studies of topical preparations were included. Current topical treatments included for the management of knee OA include topical nonsteroidal anti-inflammatory drugs, capsaicin, salicylates and physical treatments such as hot or cold therapy. Current treatment guidelines recommend topical nonsteroidal anti-inflammatory drugs as an alternative and even first-line therapy for OA management, especially among elderly patients. Guidelines on other topical treatments vary, from recommendations against their use, to in favor as alternative or simultaneous therapy, especially for patients with contraindications to other analgesics. Although often well-tolerated and preferred by many patients, clinical care still lags in the adoption of topical treatments. Aspects of efficacy, safety and patient quality of life data require further research. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  19. Correlated Topic Vector for Scene Classification.

    Science.gov (United States)

    Wei, Pengxu; Qin, Fei; Wan, Fang; Zhu, Yi; Jiao, Jianbin; Ye, Qixiang

    2017-07-01

    Scene images usually involve semantic correlations, particularly when considering large-scale image data sets. This paper proposes a novel generative image representation, correlated topic vector, to model such semantic correlations. Oriented from the correlated topic model, correlated topic vector intends to naturally utilize the correlations among topics, which are seldom considered in the conventional feature encoding, e.g., Fisher vector, but do exist in scene images. It is expected that the involvement of correlations can increase the discriminative capability of the learned generative model and consequently improve the recognition accuracy. Incorporated with the Fisher kernel method, correlated topic vector inherits the advantages of Fisher vector. The contributions to the topics of visual words have been further employed by incorporating the Fisher kernel framework to indicate the differences among scenes. Combined with the deep convolutional neural network (CNN) features and Gibbs sampling solution, correlated topic vector shows great potential when processing large-scale and complex scene image data sets. Experiments on two scene image data sets demonstrate that correlated topic vector improves significantly the deep CNN features, and outperforms existing Fisher kernel-based features.

  20. Topical treatment of psoriasis: questionnaire results on topical therapy accessibility and influence of body surface area on usage.

    Science.gov (United States)

    Iversen, L; Lange, M M; Bissonette, R; Carvalho, A V E; van de Kerkhof, P C; Kirby, B; Kleyn, C E; Lynde, C W; van der Walt, J M; Wu, J J

    2017-07-01

    Topical treatment of mild to moderate psoriasis is first-line treatment and exhibits varying degrees of success across patient groups. Key factors influencing treatment success are physician topical treatment choice (high efficacy, low adverse events) and strict patient adherence. Currently, no formalized, international consensus guidelines exist to direct optimal topical treatment, although many countries have national guidelines. To describe and analyse cross-regional variations in the use and access of psoriasis topical therapies. The study was conducted as an observational cross-sectional study. A survey was distributed to dermatologists from the International Psoriasis Council (IPC) to assess topical therapy accessibility in 26 countries and to understand how body surface area (BSA) categories guide clinical decisions on topical use. Variation in the availability of tars, topical retinoids, dithranol and balneotherapy was reported. The vast majority of respondents (100% and 88.4%) used topical therapy as first-line monotherapy in situations with BSA 10%, the number of respondents who prescribe topical therapy decreased considerably. In addition, combination therapy of a topical drug and a systemic drug was frequently reported when BSA measured >10%. This physician survey provides new evidence on topical access and the influence of disease severity on topical usage in an effort to improve treatment strategies on a global level. © 2017 European Academy of Dermatology and Venereology.

  1. Reversal of endothelial dysfunction in aorta of streptozotocin-nicotinamide-induced type-2 diabetic rats by S-Allylcysteine.

    Science.gov (United States)

    Brahmanaidu, Parim; Uddandrao, V V Sathibabu; Sasikumar, Vadivukkarasi; Naik, Ramavat Ravindar; Pothani, Suresh; Begum, Mustapha Sabana; Rajeshkumar, M Prasanna; Varatharaju, Chandrasekar; Meriga, Balaji; Rameshreddy, P; Kalaivani, A; Saravanan, Ganapathy

    2017-08-01

    Dietary measures and plant-based therapies as prescribed by native systems of medicine have gained attraction among diabetics with claims of efficacy. The present study investigated the effects of S-Allylcysteine (SAC) on body weight gain, glucose, insulin, insulin resistance, and nitric oxide synthase in plasma and argininosuccinate synthase (AS) and argininosuccinate lyase (ASL), lipid peroxides and antioxidant enzymes in aorta of control and streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Changes in body weight, glucose, insulin, insulin resistance, and antioxidant profiles of aorta and mRNA expressions of nitric oxide synthase, AS, and ASL were observed in experimental rats. SAC (150 mg/kg b.w) showed its therapeutic effects similar to gliclazide in decreasing glucose, insulin resistance, lipid peroxidation, and increasing body weight; insulin, antioxidant enzymes, and mRNA levels of nitric oxide synthase, argininosuccinate synthase, and argininosuccinate lyase genes in STZ-NA rats. Histopathologic studies also revealed the protective nature of SAC on aorta. In conclusion, garlic and its constituents mediate the anti-diabetic potential through mitigating hyperglycemic status, changing insulin resistance by alleviating endothelial dysregulation in both plasma and tissues.

  2. Simple experiments with a thermoelectric module

    International Nuclear Information System (INIS)

    Kraftmakher, Yaakov

    2005-01-01

    The Seebeck and Peltier effects are explored with a commercially available thermoelectric module and a data-acquisition system. Five topics are presented: (i) thermoelectric heating and cooling, (ii) the Seebeck coefficient, (iii) efficiency of a thermoelectric generator, (iv) the maximum temperature difference provided by a thermoelectric cooler and (v) the Peltier coefficient and the coefficient of performance. Using a data-acquisition system, the measurements are carried out in a reasonably short time. It is shown how to deduce quantities important for the theory and applications of thermoelectric devices

  3. Topical botulinum toxin.

    Science.gov (United States)

    Collins, Ashley; Nasir, Adnan

    2010-03-01

    Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.

  4. Development Of Electronic Digestive System Module For Effective Teaching And Learning

    Directory of Open Access Journals (Sweden)

    Liman Aminu Doko

    2017-07-01

    Full Text Available The digestive system hence digestion of food is usually one of the topics taught at the secondary and tertiary levels of education. Often this topic is taught using teaching aid in the form of diagrams or charts drawn on plane papers. The inanimate nature of these teaching aid employed makes learning less interesting and comprehension difficult. This paper presents the design and construction of a semi animated digestive module with remote control that visualizes the movement and process of food digestion in the body. Basically the system consists of carved wooden digestive organs with light emitting diodes LEDs carefully fixed on the path of digestion. A remote control is also built to aid remote access to the module. These LEDs start to blink indicating swallowing from the mouth down to the anus illustrating the process of digestion which also involves the production of enzymes. A comparison of with the improved teaching aid will make conventional types showed that it aroused student interest during teaching and learning process. It also reduced too much abstract explanation. Thus making teaching more efficient.

  5. Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells.

    Science.gov (United States)

    Greenhouse, W V; Lehninger, A L

    1977-11-01

    Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.

  6. Studies of yeast cell oxygenation and energetics by laser fluorometry of reduced nicotinamide adenine dinucleotide

    Science.gov (United States)

    Pan, Fu-shih; Chen, Stephen; Mintzer, Robert A.; Chen, Chin-Tu; Schumacker, Paul

    1991-03-01

    It is of fundamental importance for biological scientists to assess cellular energetics. Under aerobic conditions, the tricarboxylic acid cycle (TCA cycle) is coupled with the mitochondrial electron cascade pathway to provide the cell with energy. The nicotinamide adenine dinucleotide-conjugated pair (NAD and NADH) is the coenzyme in numerous important biomedical reactions which include several important dehydrogenase reactions in the TCA cycle. Based on Le Chatelier's principle, NADH will accumulate when this energy production mechanism is impaired. The relative amounts of NAD and NADH in a cell are defined as the redox state of the cell (Williamson et.al. 1967) which provides a valuable index of cellular energetics. The sum of the amounts of NAD and NADH in a cell may be assumed to be constant during a finite time; therefore, a reliable means of measuring the NADH concentration would provide us with a useful indicator of tissue viability. Traditionally, the quantities of NADH and NAD may be measured by chemical assay methods. We can avoid these tediois analyses by exploiting the significant difference between the ultraviolet absorption spectra of this redox pair. However, because of the opacity of biological samples and the interference of other biochemicals that also absorb ultraviolet radiation, measurement of NADH and NAD+ concentrations in vivo by absorption spectroscopy is not feasible.

  7. Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Obesity in Chinese Han Male College Students

    Directory of Open Access Journals (Sweden)

    Qiong Zhou

    2017-01-01

    Full Text Available Some reports have shown that nicotinamide N-methyltransferase (NNMT is associated with the body mass index (BMI and energy metabolism. Here we explored the association between NNMT gene polymorphisms and obesity. The subjects were recruited from male Chinese Han college student. 289 of them (19 ≤ body fat percentage (BF% were selected as the high body fat group (HBFG, 494 of them (3 ≤ BF% < 13.5 were selected as the low body fat group (LBFG, and then a case-control study (fat versus thin was carried out to explore the association between the NNMT gene polymorphism and the body composition using tagSNPs method. A tagSNP (rs10891644 in NNMT gene was found significantly associated with the body composition (P<0.0026. At this locus, the BF% for the genotype GT, TT, and GG were 14.56±8.35, 13.47±8.11, and 12.42±7.50, respectively, and the differences between the GT and the GG + TT were highly significant (P<0.01; the ORadjusted value of the GT versus (GG + TT was 1.716 (Padjusted=0.002, 95% CI = 1.240–2.235. Therefore, the variation of the tagSNP, rs10891644, is significantly associated with obesity and the GT carriers are the susceptible population.

  8. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

    Science.gov (United States)

    Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

    2014-09-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%). We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

  9. Life Span Extension and Neuronal Cell Protection by Drosophila Nicotinamidase*S⃞

    OpenAIRE

    Balan, Vitaly; Miller, Gregory S.; Kaplun, Ludmila; Balan, Karina; Chong, Zhao-Zhong; Li, Faqi; Kaplun, Alexander; VanBerkum, Mark F. A.; Arking, Robert; Freeman, D. Carl; Maiese, Kenneth; Tzivion, Guri

    2008-01-01

    The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone ...

  10. Coformer selection based on degradation pathway of drugs: a case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals.

    Science.gov (United States)

    Gao, Yuan; Gao, Jing; Liu, Ziling; Kan, Hongliang; Zu, Hui; Sun, Wanjin; Zhang, Jianjun; Qian, Shuai

    2012-11-15

    Adefovir dipivoxil (AD) is a bis(pivaloyloxymethyl) prodrug of adefovir with chemical stability problem. It undergoes two degradation pathways including hydrolysis and dimerization during storage. Pharmaceutical cocrystallization exhibits a promising approach to enhance aqueous solubility as well as physicochemical stability. In this study we attempted to prepare and investigate the physiochemical properties of AD cocrystals, which were formed with two coformers having different acidity and alkalinity (weakly acidic saccharin (SAC) and weakly basic nicotinamide (NCT)). The presence of different coformer molecules along with AD resulted in altered physicochemical properties. AD-SAC cocrystal showed great improvement in solubility and chemical stability, while AD-NCT did not. Several potential factors giving rise to different solid-state properties were summarized. Different coformers resulted in different cocrystal formation, packing style and hydrogen bond formation. This study could provide the coformer selection strategy based on degradation pathways for some unstable drugs in pharmaceutical cocrystal design. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. The human amygdaloid complex: a cytologic and histochemical atlas using Nissl, myelin, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining.

    Science.gov (United States)

    Sims, K S; Williams, R S

    1990-01-01

    We examined the distribution of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase enzyme activity in the human amygdala using histochemical techniques. Both methods revealed compartments of higher or lower enzyme activity, in cells or neuropil, which corresponded to the nuclear subdivisions of the amygdala as defined with classical Nissl and myelin methods. The boundaries between the histochemical compartments were usually so sharp that the identification of these nuclear subdivisions was enhanced. There was also variation of staining intensity within many of the nuclear subdivisions, such as the lateral and central nuclei, anterior amygdaloid area and the intercalated groups. This histochemical difference corresponded to more subtle differences in Nissl and myelin staining patterns, and suggests further structural subdivisions of potential functional significance. We present a revised scheme of anatomical parcellation of the human amygdala based upon serial analysis with all four techniques. Our expectation is that this will allow the delineation of a clearer homology between the cytoarchitectonic subdivisions of the human amygdala and those of experimental animals.

  12. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Directory of Open Access Journals (Sweden)

    Ivyna Pau Ni Bong

    2016-11-01

    Full Text Available Multiple myeloma (MM is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM phosphoribosyltransferase (NAMPT and lysosomal trafficking regulator (LYST genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05. NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05. Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01. Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.

  13. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study

    Science.gov (United States)

    Bong, Ivyna Pau Ni; Ng, Ching Ching; Fakiruddin, Shaik Kamal; Lim, Moon Nian; Zakaria, Zubaidah

    2016-01-01

    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the fprotein expression in unctions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM. PMID:27754828

  14. Recent advances in topical anesthesia

    Science.gov (United States)

    2016-01-01

    Topical anesthetics act on the peripheral nerves and reduce the sensation of pain at the site of application. In dentistry, they are used to control local pain caused by needling, placement of orthodontic bands, the vomiting reflex, oral mucositis, and rubber-dam clamp placement. Traditional topical anesthetics contain lidocaine or benzocaine as active ingredients and are used in the form of solutions, creams, gels, and sprays. Eutectic mixtures of local anesthesia cream, a mixture of various topical anesthetics, has been reported to be more potent than other anesthetics. Recently, new products with modified ingredients and application methods have been introduced into the market. These products may be used for mild pain during periodontal treatment, such as scaling. Dentists should be aware that topical anesthetics, although rare, might induce allergic reactions or side effects as a result of an overdose. Topical anesthetics are useful aids during dental treatment, as they reduce dental phobia, especially in children, by mitigating discomfort and pain. PMID:28879311

  15. Discriminative Relational Topic Models.

    Science.gov (United States)

    Chen, Ning; Zhu, Jun; Xia, Fei; Zhang, Bo

    2015-05-01

    Relational topic models (RTMs) provide a probabilistic generative process to describe both the link structure and document contents for document networks, and they have shown promise on predicting network structures and discovering latent topic representations. However, existing RTMs have limitations in both the restricted model expressiveness and incapability of dealing with imbalanced network data. To expand the scope and improve the inference accuracy of RTMs, this paper presents three extensions: 1) unlike the common link likelihood with a diagonal weight matrix that allows the-same-topic interactions only, we generalize it to use a full weight matrix that captures all pairwise topic interactions and is applicable to asymmetric networks; 2) instead of doing standard Bayesian inference, we perform regularized Bayesian inference (RegBayes) with a regularization parameter to deal with the imbalanced link structure issue in real networks and improve the discriminative ability of learned latent representations; and 3) instead of doing variational approximation with strict mean-field assumptions, we present collapsed Gibbs sampling algorithms for the generalized relational topic models by exploring data augmentation without making restricting assumptions. Under the generic RegBayes framework, we carefully investigate two popular discriminative loss functions, namely, the logistic log-loss and the max-margin hinge loss. Experimental results on several real network datasets demonstrate the significance of these extensions on improving prediction performance.

  16. Topical anesthesia

    Directory of Open Access Journals (Sweden)

    Mritunjay Kumar

    2015-01-01

    Full Text Available Topical anesthetics are being widely used in numerous medical and surgical sub-specialties such as anesthesia, ophthalmology, otorhinolaryngology, dentistry, urology, and aesthetic surgery. They cause superficial loss of pain sensation after direct application. Their delivery and effectiveness can be enhanced by using free bases; by increasing the drug concentration, lowering the melting point; by using physical and chemical permeation enhancers and lipid delivery vesicles. Various topical anesthetic agents available for use are eutectic mixture of local anesthetics, ELA-max, lidocaine, epinephrine, tetracaine, bupivanor, 4% tetracaine, benzocaine, proparacaine, Betacaine-LA, topicaine, lidoderm, S-caine patch™ and local anesthetic peel. While using them, careful attention must be paid to their pharmacology, area and duration of application, age and weight of the patients and possible side-effects.

  17. Problematic topic transitions in dysarthric conversation.

    Science.gov (United States)

    Bloch, Steven; Saldert, Charlotta; Ferm, Ulrika

    2015-01-01

    This study examined the nature of topic transition problems associated with acquired progressive dysarthric speech in the everyday conversation of people with motor neurone disease. Using conversation analytic methods, a video collection of five naturally occurring problematic topic transitions was identified, transcribed and analysed. These were extracted from a main collection of over 200 other-initiated repair sequences and a sub-set of 15 problematic topic transition sequences. The sequences were analysed with reference to how the participants both identified and resolved the problems. Analysis revealed that topic transition by people with dysarthria can prove problematic. Conversation partners may find transitions problematic not only because of speech intelligibility but also because of a sequential disjuncture between the dysarthric speech turn and whatever topic has come prior. In addition the treatment of problematic topic transition as a complaint reveals the potential vulnerability of people with dysarthria to judgements of competence. These findings have implications for how dysarthria is conceptualized and how specific actions in conversation, such as topic transition, might be suitable targets for clinical intervention.

  18. 76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2011-12-29

    .... FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... solution of ivermectin. DATES: This rule is effective December 29, 2011. FOR FURTHER INFORMATION CONTACT... ANADA 200-318 for [[Page 81807

  19. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Morgulis Yuri

    2012-05-01

    Full Text Available Abstract Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  20. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Science.gov (United States)

    2012-01-01

    Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines. PMID:22640463

  1. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

    OpenAIRE

    Deng-Fu Yang; Jeng-Woei Lee; Hsin-Ming Chen; Yih-Chih Hsu

    2014-01-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Methods: Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical A...

  2. Topical immunomodulators in dermatology

    Directory of Open Access Journals (Sweden)

    Khandpur Sujay

    2004-04-01

    Full Text Available Topical immunomodulators are agents that regulate the local immune response of the skin. They are now emerging as the therapy of choice for several immune-mediated dermatoses such as atopic dermatitis, contact allergic dermatitis, alopecia areata, psoriasis, vitiligo, connective tissue disorders such as morphea and lupus erythematosus, disorders of keratinization and several benign and malignant skin tumours, because of their comparable efficacy, ease of application and greater safety than their systemic counterparts. They can be used on a domiciliary basis for longer periods without aggressive monitoring. In this article, we have discussed the mechanism of action, common indications and side-effects of the commonly used topical immunomodulators, excluding topical steroids. Moreover, newer agents, which are still in the experimental stages, have also been described. A MEDLINE search was undertaken using the key words "topical immunomodulators, dermatology" and related articles were also searched. In addition, a manual search for many Indian articles, which are not indexed, was also carried out. Wherever possible, the full article was reviewed. If the full article could not be traced, the abstract was used.

  3. Recent Advances In Topical Therapy In Dermatology

    Directory of Open Access Journals (Sweden)

    Mohan Thappa Devinder

    2003-01-01

    Full Text Available With changing times various newer topical agents are introduced in the field of dermatology. Tacrolimus and pimecrolimus are immunisuppressants, which are effective topically and are tried in the management of atopic dermatitis as well as other disorders including allergic contact dermatitis, atrophic lichen planus, pyoderma gangrenosum. Imiquimod, an immune response modifier, is presently in use for genital warts but has potentials as anti- tumour agent and in various other dermatological conditions when used topically. Tazarotene is a newer addition to the list of topical reginoids, which is effective in psoriasis and has better effect in combination with calcipotriene, phototherapy and topical costicosteroids. Tazarotene and adapelene are also effective in inflammatory acne. Calcipotriol, a vitamin D analogue has been introduced as a topical agent in the treatment of psoriasis. Steroid components are also developed recently which will be devoid of the side effects but having adequate anti-inflammatory effect. Topical photodynamic therapy has also a wide range of use in dermatology. Newer topical agents including cidofovir, capsaicin, topical sensitizers, topical antifungal agents for onychomycosis are also of use in clinical practice. Other promising developments include skin substitutes and growth factors for wound care.

  4. CD73 Protein as a Source of Extracellular Precursors for Sustained NAD+ Biosynthesis in FK866-treated Tumor Cells*

    Science.gov (United States)

    Grozio, Alessia; Sociali, Giovanna; Sturla, Laura; Caffa, Irene; Soncini, Debora; Salis, Annalisa; Raffaelli, Nadia; De Flora, Antonio; Nencioni, Alessio; Bruzzone, Santina

    2013-01-01

    NAD+ is mainly synthesized in human cells via the “salvage” pathways starting from nicotinamide, nicotinic acid, or nicotinamide riboside (NR). The inhibition with FK866 of the enzyme nicotinamide phosphoribosyltransferase (NAMPT), catalyzing the first reaction in the “salvage” pathway from nicotinamide, showed potent antitumor activity in several preclinical models of solid and hematologic cancers. In the clinical studies performed with FK866, however, no tumor remission was observed. Here we demonstrate that low micromolar concentrations of extracellular NAD+ or NAD+ precursors, nicotinamide mononucleotide (NMN) and NR, can reverse the FK866-induced cell death, this representing a plausible explanation for the failure of NAMPT inhibition as an anti-cancer therapy. NMN is a substrate of both ectoenzymes CD38 and CD73, with generation of NAM and NR, respectively. In this study, we investigated the roles of CD38 and CD73 in providing ectocellular NAD+ precursors for NAD+ biosynthesis and in modulating cell susceptibility to FK866. By specifically silencing or overexpressing CD38 and CD73, we demonstrated that endogenous CD73 enables, whereas CD38 impairs, the conversion of extracellular NMN to NR as a precursor for intracellular NAD+ biosynthesis in human cells. Moreover, cell viability in FK866-treated cells supplemented with extracellular NMN was strongly reduced in tumor cells, upon pharmacological inhibition or specific down-regulation of CD73. Thus, our study suggests that genetic or pharmacologic interventions interfering with CD73 activity may prove useful to increase cancer cell sensitivity to NAMPT inhibitors. PMID:23880765

  5. Topic Modeling of Hierarchical Corpora /

    OpenAIRE

    Kim, Do-kyum

    2014-01-01

    The sizes of modern digital libraries have grown beyond our capacity to comprehend manually. Thus we need new tools to help us in organizing and browsing large corpora of text that do not require manually examining each document. To this end, machine learning researchers have developed topic models, statistical learning algorithms for automatic comprehension of large collections of text. Topic models provide both global and local views of a corpus; they discover topics that run through the co...

  6. Testosterone Topical

    Science.gov (United States)

    ... not apply any testosterone topical products to your penis or scrotum or to skin that has sores, ... are severe or do not go away: breast enlargement and/or pain decreased sexual desire acne depression ...

  7. Credibility improves topical blog post retrieval

    NARCIS (Netherlands)

    Weerkamp, W.; de Rijke, M.

    2008-01-01

    Topical blog post retrieval is the task of ranking blog posts with respect to their relevance for a given topic. To improve topical blog post retrieval we incorporate textual credibility indicators in the retrieval process. We consider two groups of indicators: post level (determined using

  8. Topic prominence in Chinese EFL learners’ interlanguage

    Directory of Open Access Journals (Sweden)

    Shaopeng Li

    2014-01-01

    Full Text Available The present study aims to investigate the general characteristics of topicprominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from a discourse perspective. Topic structures mainly appear in Chinese discourse in the form of topic chains (Wang, 2002; 2004. The research target are the topic chain, which is the main topic-prominent structure in Chinese discourse, and zero anaphora, which is the most common topic anaphora in the topic chain. Two important findings emerged from the present study. First, the characteristics of Chinese topic chains are transferrable to the interlanguage of Chinese EFL learners, thus resulting in overgeneralization of the zero anaphora. Second, the interlanguage discourse of Chinese EFL learners reflects a change of the second language acquisition process from topic-prominence to subject-prominence, thus lending support to the discourse transfer hypothesis.

  9. Intensity-modulated three-dimensional conformal radiotherapy

    International Nuclear Information System (INIS)

    Mohan, Radhe

    1996-01-01

    Optimized intensity-modulated treatments one of the important advances in photon radiotherapy. Intensity modulation provides a greatly increased control over dose distributions. Such control can be maximally exploited to achieve significantly higher levels of conformation to the desired clinical objectives using sophisticated optimization techniques. Safe, rapid and efficient delivery of intensity-modulated treatments has become feasible using a dynamic multi-leaf collimator under computer control. The need for all other field shaping devices such as blocks, wedges and compensators is eliminated. Planning and delivery of intensity-modulated treatments is amenable to automation and development of class solutions for each treatment site and stage which can be implemented not only at major academic centers but on a wide scale. A typical treatment involving as many as 10 fields can be delivered in times shorter than much simpler conventional treatments. The main objective of the course is to give an overview of the current state of the art of planning and delivery methods of intensity-modulated treatments. Specifically, the following topics will be covered using representative optimized plans and treatments: 1. A typical procedure for planning and delivering an intensity-modulated treatment. 2. Quantitative definition of criteria (i.e., the objective function) of optimization of intensity-modulated treatments. Clinical relevance of objectives and the dependence of the quality of optimized intensity-modulated plans upon whether the objectives are stated purely in terms of simple dose or dose-volume criteria or whether they incorporate biological indices. 3. Importance of the lateral transport of radiation in the design of intensity-modulated treatments. Impact on dose homogeneity and the optimum choice of margins. 4. Use of intensity-modulated treatments in escalation of tumor dose for the same or lower normal tissue dose. Fractionation of intensity-modulated treatments

  10. Intensity-modulated three-dimensional conformal radiotherapy

    International Nuclear Information System (INIS)

    Mohan, Radhe

    1997-01-01

    Optimized intensity-modulated treatments one of the important advances in photon radiotherapy. Intensity modulation provides a greatly increased control over dose distributions. Such control can be maximally exploited to achieve significantly higher levels of conformation to the desired clinical objectives using sophisticated optimization techniques. Safe, rapid and efficient delivery of intensity-modulated treatments has become feasible using a dynamic multi-leaf collimator under computer control. The need for all other field shaping devices such as blocks, wedges and compensators is eliminated. Planning and delivery of intensity-modulated treatments is amenable to automation and development of class solutions for each treatment site and stage which can be implemented not only at major academic centers but on a wide scale. A typical treatment involving as many as 10 fields can be delivered in times shorter than much simpler conventional treatments. The main objective of the course is to give an overview of the current state of the art of planning and delivery methods of intensity-modulated treatments. Specifically, the following topics will be covered using representative optimized plans and treatments: 1. A typical procedure for planning and delivering an intensity-modulated treatment. 2. Quantitative definition of criteria (i.e., the objective function) of optimization of intensity-modulated treatments. Clinical relevance of objectives and the dependence of the quality of optimized intensity-modulated plans upon whether the objectives are stated purely in terms of simple dose or dose-volume criteria or whether they incorporate biological indices. 3. Importance of the lateral transport of radiation in the design of intensity-modulated treatments. Impact on dose homogeneity and the optimum choice of margins. 4. Use of intensity-modulated treatments in escalation of tumor dose for the same or lower normal tissue dose. Fractionation of intensity-modulated treatments

  11. Topical report review status: Volume 10

    International Nuclear Information System (INIS)

    1996-03-01

    This report provides industry with procedures for submitting topical reports, guidance on how the U.S. Nuclear Regulatory Commission (NRC) processes and responds to topical report submittals, and an accounting, with review schedules, of all topical reports currently accepted for review by the NRC. This report is published annually

  12. Design and production of various fusion proteins of the nicotinamide/nicotinate mononucleotide adenilil transferase (NMNAT of Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Carlos Alfonso Nieto Clavijo

    2017-09-01

    Full Text Available Recombinant proteins have become useful tools in biochemistry research. During their production, however, inclusion bodies (IB appear, on the one hand, due to the high expression rate from the recombinant plasmids, which have high efficiency promoters, and, on the other hand, intrinsic characteristics of the expressed protein. Furhtermore, the nicotinamide/nicotinate mononucleotide adenilyl transferase (NMNAT is a central protein in NAD(H+ biosynthesis, an essential cofactor in cell metabolism, and in protozoon parasite has been studied. To study the NMNAT protein of these parasites, their recombinant version in E. coli has been expressed, getting a great quantity of IB as a by-product. To increase the solubility of the protein, the coding sequence of the NMNAT enzyme of Plasmodium falciparum was cloned in different expression plasmids which were subsequently transformed into E. coli BL21(DE3 expression strain. The solubility of the recombinant proteins was assessed and the one with the highest presence in the soluble fraction was subsequently purified and its enzyme activity was determined. The recombinant protein with a MBP (maltose-binding protein tag showed an increased solubility and purity.

  13. Effect of a mixture of caffeine and nicotinamide on the solubility of vitamin (B2) in aqueous solution.

    Science.gov (United States)

    Evstigneev, M P; Evstigneev, V P; Santiago, A A Hernandez; Davies, D B

    2006-05-01

    The effect of caffeine (CAF) and nicotinamide (NMD) on the solubility of a vitamin B2 derivative (FMN) has been evaluated for mixtures containing either a single hydrotrope (CAF or NMD) or the two hydrotropes simultaneously. A model for analysis of ternary systems, which takes into account all possible complexes between the molecules, has been developed and tested with experimental NMR data on the three-component mixture FMN-CAF-NMD. The results indicate that special attention should be given to the concentration of a hydrotropic agent used to enhance the solubility of a particular drug. A decrease in the efficacy of solubility of the vitamin on addition of large amounts of hydrotropic agent is expected in the two-component systems due to the increased proportion of self-association of the hydrotrope. It is found that a mixture of two hydrotropic agents leads to an increase in the solubility of the vitamin in three-component compared to the two-component system. Rather than using just one hydrotropic agent, it is proposed that a strategy for optimising the solubility of aromatic drugs is to use a mixture of hydrotropic agents.

  14. Chiropractic: MedlinePlus Health Topic

    Science.gov (United States)

    ... for back pain (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Chiropractic updates by ... ENCYCLOPEDIA Chiropractic care for back pain Related Health Topics Back Pain Complementary and Integrative Medicine National Institutes ...

  15. Diets: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Mediterranean diet (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Diets updates by ... foods Diet-busting foods Mediterranean diet Related Health Topics Child Nutrition DASH Eating Plan Diabetic Diet Nutrition ...

  16. Colonoscopy: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Virtual colonoscopy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Colonoscopy updates by ... Colonoscopy Colonoscopy discharge Sigmoidoscopy Virtual colonoscopy Related Health Topics Colonic Diseases Colonic Polyps Colorectal Cancer National Institutes ...

  17. Dialysis: MedlinePlus Health Topic

    Science.gov (United States)

    ... access for hemodialysis (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Dialysis updates by ... for hemodialysis Show More Show Less Related Health Topics Creatinine Kidney Cysts Kidney Failure Peritoneal Disorders National ...

  18. Menopause: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish What is Menopause? (National Institute on Aging) Topic Image MedlinePlus Email Updates Get Menopause updates by ... test Menopause Types of hormone therapy Related Health Topics Hormone Replacement Therapy Menstruation Premature Ovarian Failure National ...

  19. Vaginitis: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Vulvovaginitis - overview (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Vaginitis updates by ... Vaginitis test - wet mount Vulvovaginitis - overview Related Health Topics Trichomoniasis Vaginal Diseases Yeast Infections Other Languages Find ...

  20. Second quantization, projective modules, and local gauge invariance

    Energy Technology Data Exchange (ETDEWEB)

    Selesnick, S A [Missouri Univ., St. Louis (USA)

    1983-01-01

    Bundles and bundle structures have gained wide currency in modern approaches to certain topics in quantum physics, significant applications appearing in connection with gauge theories, theories of geometric quantization, and in numerous other contexts. It is argued that such structures can already be discerned in the most elementary notions of second quantization. An examination of the methods traditionally used by physicists in dealing quantum mechanically with systems exhibiting an infinite number of degrees of freedom reveals the implicit use of module structures over algebras of functions. By making these structures explicit and adapting some results of perturbation theory an association between bare particles and finitely generated projective modules is arrived at. In particular, rank one modules emerge naturally, for algebraic reasons, as the appropriate descriptors of bosons in this association. As a first application of the formalism the existence of phononlike excitations in general many-fermion systems is shown. When these ideas are further specialized (local) gauge theoretical notions arise in a natural way out of a consideration of the bundles.

  1. Topical Acne Treatments and Pregnancy

    Science.gov (United States)

    Topical Acne Treatments In every pregnancy, a woman starts out with a 3-5% chance of having a baby ... This sheet talks about whether exposure to topical acne treatments may increase the risk for birth defects ...

  2. Symbiosis: Rich, Exciting, Neglected Topic

    Science.gov (United States)

    Rowland, Jane Thomas

    1974-01-01

    Argues that the topic of symbiosis has been greatly neglected and underemphasized in general-biology textbooks. Discusses many types and examples of symbiosis, and provides an extensive bibliography of the literature related to this topic. (JR)

  3. Solar modulation of galactic cosmic rays: techniques and applications

    International Nuclear Information System (INIS)

    Perko, J.S.

    1984-01-01

    This thesis covers four topics in the theory of interplanetary cosmic-ray propagation: the first part involves the time-dependent, spherically-symmetric, solar modulation of galactic cosmic rays. A numerical technique was introduced for the solution of this problem. A model for the solar cycle variation in cosmic-ray intensity illustrated this method using enhanced particle scattering regions. The second section contains an attempt to explain recent observations which show that cosmic-ray electrons are returning to higher intensities, characteristic of solar minimum, faster than cosmic-ray protons of about the same energy, the reverse of the previous eleven-year cycle. The third section involves the solar modulation of galactic antiprotons. Using a steady-state, spherically-symmetric, numerical modulation code, a solution that reasonably fits the observed 1980 galactic proton spectrum at 1 AU implied that the modulation used for the data interpretation has been significantly underestimated. The final section contains a spherically-symmetric steady-state calculation of the effects of a strong termination shock in the heliosphere. In the end, high-energy particles cooling down in the upstream solar wind overwhelmed any accelerated low-energy particles

  4. Prediabetes:MedlinePlus Health Topic

    Science.gov (United States)

    ... in Spanish Prediabetes (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Prediabetes updates by ... Glucose tolerance test - non-pregnant Prediabetes Related Health Topics A1C Diabetes Diabetes in Children and Teens Diabetes ...

  5. Diabetes: MedlinePlus Health Topic

    Science.gov (United States)

    ... High blood sugar (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Diabetes updates by ... ketones test Show More Show Less Related Health Topics A1C Blood Sugar Diabetes and Pregnancy Diabetes Complications ...

  6. Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide

    Science.gov (United States)

    Harmayani, Eni; Sunarti

    2015-01-01

    The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells. PMID:26877646

  7. Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating SIRT1 activity and antioxidant gene expression in mouse cells.

    Science.gov (United States)

    Khaidizar, Fiqri D; Nakahata, Yasukazu; Kume, Akira; Sumizawa, Kyosuke; Kohno, Kenji; Matsui, Takaaki; Bessho, Yasumasa

    2017-12-01

    Senescent cells accumulate in tissues of aged animals and deteriorate tissue functions. The elimination of senescent cells from aged mice not only attenuates progression of already established age-related disorders, but also extends median lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD + salvage pathway, has shown a protective effect on cellular senescence of human primary cells. However, it still remains unclear how NAMPT has a protective impact on aging in vitro and in vivo. In this study, we found that primary mouse embryonic fibroblast (MEF) cells undergo progressive decline of NAMPT and NAD + contents during serial passaging before becoming senescent. Furthermore, we showed that constitutive Nampt over-expression increases cellular NAD + content and delays cellular senescence of MEF cells in vitro. We further found that constitutive Nampt over-expression increases SIRT1 activity, increases the expression of antioxidant genes, superoxide dismutase 2 and catalase and promotes resistance against oxidative stress. These findings suggest that Nampt over-expression in MEF cells delays cellular senescence by the mitigation of oxidative stress via the upregulation of superoxide dismutase 2 and catalase gene expressions by SIRT1 activation. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  8. Tracking topic birth and death in LDA.

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Andrew T.; Robinson, David Gerald

    2011-09-01

    Most topic modeling algorithms that address the evolution of documents over time use the same number of topics at all times. This obscures the common occurrence in the data where new subjects arise and old ones diminish or disappear entirely. We propose an algorithm to model the birth and death of topics within an LDA-like framework. The user selects an initial number of topics, after which new topics are created and retired without further supervision. Our approach also accommodates many of the acceleration and parallelization schemes developed in recent years for standard LDA. In recent years, topic modeling algorithms such as latent semantic analysis (LSA)[17], latent Dirichlet allocation (LDA)[10] and their descendants have offered a powerful way to explore and interrogate corpora far too large for any human to grasp without assistance. Using such algorithms we are able to search for similar documents, model and track the volume of topics over time, search for correlated topics or model them with a hierarchy. Most of these algorithms are intended for use with static corpora where the number of documents and the size of the vocabulary are known in advance. Moreover, almost all current topic modeling algorithms fix the number of topics as one of the input parameters and keep it fixed across the entire corpus. While this is appropriate for static corpora, it becomes a serious handicap when analyzing time-varying data sets where topics come and go as a matter of course. This is doubly true for online algorithms that may not have the option of revising earlier results in light of new data. To be sure, these algorithms will account for changing data one way or another, but without the ability to adapt to structural changes such as entirely new topics they may do so in counterintuitive ways.

  9. Topics in lightwave transmission systems

    CERN Document Server

    Li, Tingye

    1991-01-01

    Topics in Lightwave Transmission Systems is a second volume of a treatise on optical fiber communications that is devoted to the science, engineering, and application of information transmission via optical fibers. The first volume, published in 1985, dealt exclusively with fiber fabrication. The present volume contains topics that pertain to subsystems and systems. The book contains five chapters and begins with discussions of transmitters and receivers, which are basic to systems now operating in the field. Subsequent chapters cover topics relating to coherent systems: frequency and phase m

  10. The development of form two mathematics i-Think module (Mi-T2)

    Science.gov (United States)

    Yao, Foo Jing; Abdullah, Mohd Faizal Nizam Lee; Tien, Lee Tien

    2017-05-01

    This study aims to develop a training module i-THINK Mathematics Form Two (Mi-T2) to increase the higher-order thinking skills of students. The Mi-T2 training module was built based on the Sidek Module Development Model (2001). Constructivist learning theory, cognitive learning theory, i-THINK map and higher order thinking skills were the building blocks of the module development. In this study, researcher determined the validity and reliability of Mi-T2 module. The design being used in this study was descriptive study. To determine the needs of Mi-T2 module, questionnaires and literature review were used to collect data. When the need of the module was determined, the module was built and a pilot study was conducted to test the reliability of the Mi-T2 module. The pilot study was conducted at a secondary school in North Kinta, Perak. A Form Two class was selected to be the sample study through clustered random sampling. The pilot study was conducted for two months and one topic had been studied. The Mi-T2 module was evaluated by five expert panels to determine the content validity of the module. The instruments being used in the study were questionnaires about the necessity of the Mi-T2 module for guidance, questionnaires about the validity of the module and questionnaires concerning the reliability of the module. Statistical analysis was conducted to determine the validity and reliability coefficients of the Mi-T2 module. The content validity of Mi-T2 module was determined by Cohen's Kappa's (1968) agreement coefficient and the reliability of Mi-T2 module was determined by Cronbach Alpha's value scale. The content validity of Mi-T2 module was 0.89 and the Cronbach Alpha's value of Mi-T2 module was 0.911.

  11. Module for Interns in Medical Ethics: A Developmental Diegesis.

    Science.gov (United States)

    Mahajan, Rajiv; Goyal, Parmod Kumar; Sidhu, Tanvir Kaur; Kaur, Upinder; Kaur, Sandeep; Gupta, Vitull

    2017-12-01

    Media report is rife with incidences of doctor-patients' conflict, and this partly is due to communication gap and unethical practices being adopted by the doctors. Our regular curriculum fails to impart any training in ethical issues in patient care. Imparting training to students in these soft-skills is the need of the hour. To develop a module for interns in medical ethics (MIME) in patient care, validate it and pilot run the module for standardization. After conducting faculty development workshop in curriculum designing and three rounds of Delphi with alumni, a module in medical ethics was developed and peer validated. The questionnaire for pilot run, questionnaire for future use of module delivery and pre- and post-test were also peer validated. The module was delivered to 17 interns as pilot run in the form of 4 days' workshop. After pilot run, the module was standardized to 10 broad topics and 3 days' workshop. The questionnaire for future delivery of module in regular routine was also validated during pilot run. Twenty-five faculty members participated in 1 day faculty development workshop and 59 alumni completed three rounds of Delphi. After peer review by five experts, a module of 11 broad areas was developed and was pilot run on 17 interns. Based on the feedback from pilot run, a standardized, validated 18 h teaching MIME in patient care was developed. Pilot study proves that curriculum innovation in the form of medical ethics training to interns; when as undergraduate students, they actively participate in patient care under supervision will go a long way in inculcating soft skills like ethics, compassion and communication in them.

  12. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial

    NARCIS (Netherlands)

    Koeneman, M. M.; Kruse, Arnold-Jan; Kooreman, L. F. S.; zur Hausen, Axel; Hopman, Anton H N; Sep, S. J. S.; Van Gorp, T.; Slangen, B. F. M.; van Beekhuizen, H. J.; de Sande, Michiel A. J. van; Gerestein, Cornelis G.; Nijman, H. W.; Kruitwagen, R. F. M. P.

    2017-01-01

    The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia

  13. Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.

    Science.gov (United States)

    Lozoya, Oswaldo A; Martinez-Reyes, Inmaculada; Wang, Tianyuan; Grenet, Dagoberto; Bushel, Pierre; Li, Jianying; Chandel, Navdeep; Woychik, Richard P; Santos, Janine H

    2018-04-18

    Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle. We find that this program also increases DNA methylation, which occurs primarily in the genes that are differentially expressed. Maintenance of mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation in the context of mtDNA loss rescues methionine salvage and polyamine synthesis and prevents changes in DNA methylation and gene expression but does not affect serine/folate metabolism or transsulfuration. This work provides a novel mechanistic link between mitochondrial function and epigenetic regulation of gene expression that involves polyamine and methionine metabolism responding to changes in the tricarboxylic acid (TCA) cycle. Given the implications of these findings, future studies across different physiological contexts and in vivo are warranted.

  14. Influence of tetrahydrocurcumin on tail tendon collagen contents and its properties in rats with streptozotocin-nicotinamide-induced type 2 diabetes.

    Science.gov (United States)

    Pari, Leelavinothan; Murugan, Pidaran

    2007-12-01

    Changes in the structural and functional properties of collagen caused by advanced glycation might be of importance for the etiology of late-stage complications in diabetics. Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin, exhibiting many of the same physiological and pharmacological activities of curcumin and in some systems may exert greater antioxidant activity than curcumin. In diabetic rats, hydroxyproline and collagen content as well as its degree of cross-linking were increased, as shown by increased extent of glycation, collagen-linked fluorescence, neutral salt collagen, and decreased acid and pepsin solubility. Administration of THC for 45 days to diabetic rats significantly reduced the accumulation and cross-linking of collagen. The effects of THC were comparable with those of curcumin. In conclusion, administration of THC had a positive influence on the content of collagen and its properties in streptozotocin- and nicotinamide-induced diabetic rats. THC was found to be more effective than curcumin.

  15. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

    Science.gov (United States)

    Camacho-Pereira, Juliana; Tarragó, Mariana G; Chini, Claudia C S; Nin, Veronica; Escande, Carlos; Warner, Gina M; Puranik, Amrutesh S; Schoon, Renee A; Reid, Joel M; Galina, Antonio; Chini, Eduardo N

    2016-06-14

    Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Deep Unfolding for Topic Models.

    Science.gov (United States)

    Chien, Jen-Tzung; Lee, Chao-Hsi

    2018-02-01

    Deep unfolding provides an approach to integrate the probabilistic generative models and the deterministic neural networks. Such an approach is benefited by deep representation, easy interpretation, flexible learning and stochastic modeling. This study develops the unsupervised and supervised learning of deep unfolded topic models for document representation and classification. Conventionally, the unsupervised and supervised topic models are inferred via the variational inference algorithm where the model parameters are estimated by maximizing the lower bound of logarithm of marginal likelihood using input documents without and with class labels, respectively. The representation capability or classification accuracy is constrained by the variational lower bound and the tied model parameters across inference procedure. This paper aims to relax these constraints by directly maximizing the end performance criterion and continuously untying the parameters in learning process via deep unfolding inference (DUI). The inference procedure is treated as the layer-wise learning in a deep neural network. The end performance is iteratively improved by using the estimated topic parameters according to the exponentiated updates. Deep learning of topic models is therefore implemented through a back-propagation procedure. Experimental results show the merits of DUI with increasing number of layers compared with variational inference in unsupervised as well as supervised topic models.

  17. Aberration compensation using a spatial light modulator LCD

    International Nuclear Information System (INIS)

    Amezquita, R; Rincon, O; Torres, Y M

    2011-01-01

    The dynamic correction of aberrations introduced in optical systems have been a widely discussed topic in the past 10 years. Adaptive optics is the most important developed field where the Shack-Hartmann sensors and deformable mirrors are used for the measurement and correction of wavefronts. In this paper, an interferometric set-up which uses a Spatial Light Modulator (SLM) as an active element is proposed. Using this SLM a procedure for the compensation of all phase aberrations present in the experimental setup is shown.

  18. Bimatoprost Topical

    Science.gov (United States)

    ... not use a cotton swab or any other brush or applicator to apply topical bimatoprost.To use the solution, follow these steps: Wash your hands and face thoroughly with soap and water. Be sure that all makeup is removed. Do not let the tip of ...

  19. Topics in quantum field theory

    NARCIS (Netherlands)

    Dams, C.J.F.

    2006-01-01

    In this PhD-thesis some topics in quantum field theory are considered. The first chapter gives a background to these topics. The second chapter discusses renormalization. In particular it is shown how loop calculations can be performed when using the axial gauge fixing. Fermion creation and

  20. Nicotinamide impairs entry into and exit from meiosis I in mouse oocytes.

    Science.gov (United States)

    Riepsamen, Angelique; Wu, Lindsay; Lau, Laurin; Listijono, Dave; Ledger, William; Sinclair, David; Homer, Hayden

    2015-01-01

    Following exit from meiosis I, mammalian oocytes immediately enter meiosis II without an intervening interphase, accompanied by rapid reassembly of a bipolar spindle that maintains condensed chromosomes in a metaphase configuration (metaphase II arrest). Here we study the effect of nicotinamide (NAM), a non-competitive pan-sirtuin inhibitor, during meiotic maturation in mouse oocytes. Sirtuins are a family of seven NAD+-dependent deacetylases (Sirt1-7), which are involved in multiple cellular processes and are emerging as important regulators in oocytes and embryos. We found that NAM significantly delayed entry into meiosis I associated with delayed accumulation of the Cdk1 co-activator, cyclin B1. GVBD was also inhibited by the Sirt2-specific inhibitor, AGK2, and in a very similar pattern to NAM, supporting the notion that as in somatic cells, NAM inhibits sirtuins in oocytes. NAM did not affect subsequent spindle assembly, chromosome alignment or the timing of first polar body extrusion (PBE). Unexpectedly, however, in the majority of oocytes with a polar body, chromatin was decondensed and a nuclear structure was present. An identical phenotype was observed when flavopiridol was used to induce Cdk1 inactivation during late meiosis I prior to PBE, but not if Cdk1 was inactivated after PBE when metaphase II arrest was already established, altogether indicating that NAM impaired establishment rather than maintenance of metaphase II arrest. During meiosis I exit in NAM-treated medium, we found that cyclin B1 levels were lower and inhibitory Cdk1 phosphorylation was increased compared with controls. Although activation of the anaphase-promoting complex-Cdc20 (APC-Cdc20) occurred on-time in NAM-treated oocytes, Cdc20 levels were higher in very late meiosis I, pointing to exaggerated APC-Cdc20-mediated proteolysis as a reason for lower cyclin B1 levels. Collectively, therefore, our data indicate that by disrupting Cdk1 regulation, NAM impairs entry into meiosis I and

  1. Learning topic models by belief propagation.

    Science.gov (United States)

    Zeng, Jia; Cheung, William K; Liu, Jiming

    2013-05-01

    Latent Dirichlet allocation (LDA) is an important hierarchical Bayesian model for probabilistic topic modeling, which attracts worldwide interest and touches on many important applications in text mining, computer vision and computational biology. This paper represents the collapsed LDA as a factor graph, which enables the classic loopy belief propagation (BP) algorithm for approximate inference and parameter estimation. Although two commonly used approximate inference methods, such as variational Bayes (VB) and collapsed Gibbs sampling (GS), have gained great success in learning LDA, the proposed BP is competitive in both speed and accuracy, as validated by encouraging experimental results on four large-scale document datasets. Furthermore, the BP algorithm has the potential to become a generic scheme for learning variants of LDA-based topic models in the collapsed space. To this end, we show how to learn two typical variants of LDA-based topic models, such as author-topic models (ATM) and relational topic models (RTM), using BP based on the factor graph representations.

  2. Should carbogen and nicotinamide be given throughout the full course of fractionated radiotherapy regimens?

    International Nuclear Information System (INIS)

    Rojas, A.M.; Johns, H.; Fiat, P.R.

    1993-01-01

    Tumor radiosensitization with carbogen and nicotinamide (CON) was compared when both agents were given throughout fractionated radiotherapy with the sensitization observed when administered with only half of the fractions. The effect of overall treatment time on the local control of tumors irradiated in air or with CON was also investigated. Local tumor control of a rodent adenocarcinoma, CaNT, was studied using eight different 20-fraction x-ray regimens. An overall time of either 10 or 20 days was used and CON was given with all, the first half or last half of the treatment. Relative to air, all six sensitizer combinations gave a large and significant increase in sensitization (p much-lt 0.00001). Enhancement ratios were 1.9 and 2.1 when CON was given with all 20 fractions in either 10 or 20 days, respectively. For both overall times, enhancement ratios were reduced by 15-25% when CON was given with only half of the fractions. In air, reducing the treatment time from 20 to 10 days gave a small but significant decrease in the isoeffective doses. When CON was administered with either all or part of a schedule, varying the treatment time had little or no effect on local tumor control. No toxic side-effects were encountered when the sensitizers were administered 10 or 20 times, either once or twice per day. CON is an effective and non-toxic tumor radiosensitizer. In CaNT tumors, a significantly greater effect is seen when CON is given with every fraction of the schedule. The sensitizers reduced or abolished the sparing effect of overall time. 22 refs., 1 fig., 2 tabs

  3. Nonlinear modulation near the Lighthill instability threshold in 2+1 Whitham theory

    Science.gov (United States)

    Bridges, Thomas J.; Ratliff, Daniel J.

    2018-04-01

    The dispersionless Whitham modulation equations in 2+1 (two space dimensions and time) are reviewed and the instabilities identified. The modulation theory is then reformulated, near the Lighthill instability threshold, with a slow phase, moving frame and different scalings. The resulting nonlinear phase modulation equation near the Lighthill surfaces is a geometric form of the 2+1 two-way Boussinesq equation. This equation is universal in the same sense as Whitham theory. Moreover, it is dispersive, and it has a wide range of interesting multi-periodic, quasi-periodic and multi-pulse localized solutions. For illustration the theory is applied to a complex nonlinear 2+1 Klein-Gordon equation which has two Lighthill surfaces in the manifold of periodic travelling waves. This article is part of the theme issue `Stability of nonlinear waves and patterns and related topics'.

  4. Bare quantifier fronting as contrastive topicalization

    Directory of Open Access Journals (Sweden)

    Ion Giurgea

    2015-11-01

    Full Text Available I argue that indefinites (in particular bare quantifiers such as ‘something’, ‘somebody’, etc. which are neither existentially presupposed nor in the restriction of a quantifier over situations, can undergo topicalization in a number of Romance languages (Catalan, Italian, Romanian, Spanish, but only if the sentence contains “verum” focus, i.e. focus on a high degree of certainty of the sentence. I analyze these indefinites as contrastive topics, using Büring’s (1999 theory (where the term ‘S-topic’ is used for what I call ‘contrastive topic’. I propose that the topic is evaluated in relation to a scalar set including generalized quantifiers such as {lP $x P(x, lP MANYx P(x, lP MOSTx P(x, lP “xP(x} or {lP $xP(x, lP P(a, lP P(b …}, and that the contrastive topic is the weakest generalized quantifier in this set. The verum focus, which is part of the “comment” that co-occurs with the “Topic”, introduces a set of alternatives including degrees of certainty of the assertion. The speaker asserts that his claim is certainly true or highly probable, contrasting it with stronger claims for which the degree of probability is unknown. This explains the observation that in downward entailing contexts, the fronted quantified DPs are headed by ‘all’ or ‘many’, whereas ‘some’, small numbers or ‘at least n’ appear in upward entailing contexts. Unlike other cases of non-specific topics, which are property topics, these are quantifier topics: the topic part is a generalized quantifier, the comment is a property of generalized quantifiers. This explains the narrow scope of the fronted quantified DP.

  5. Osmolarity as a contributing factor in topical drug delivery

    Science.gov (United States)

    Funke, Claire; Szeri, Andrew J.

    2017-11-01

    Gels and dissolvable solids are drug delivery platforms being evaluated for application of active pharmaceutical ingredients, termed microbicides, which act topically against infection by sexually transmitted HIV. In previous work, we have investigated how dilution by naturally produced fluid from the vaginal mucosa affects drug transport into the vaginal wall. We expand on this work by no longer assuming a constant flux and instead developing a relation for fluid transport based on osmolarity - thus allowing fluid to pass both into and out of epithelial cells. This relation shows that varying the osmolarity of the applied solution can have a significant effect on the amount of drug delivered to its target while holding the applied amount constant. This effect is modulated by a dimensionless group that relates the rates of solute and solvent transport. Ultimately, our goal is to develop a tool to understand better how to manipulate solution osmolarity in order to improve drug delivery within safety parameters for mucosal tissue.

  6. Resources for Topics in Architecture.

    Science.gov (United States)

    Van Noate, Judith, Comp.

    This guide for conducting library research on topics in architecture or on the work of a particular architect presents suggestions for utilizing four categories of resources: books, dictionaries and encyclopedias, indexes, and a periodicals and series list (PASL). Two topics are researched as examples: the contemporary architect Richard Meier, and…

  7. Web directories as topical context

    NARCIS (Netherlands)

    Kaptein, R.; Kamps, J.; Aly, R.; Hauff, C.; den Hamer, I.; Hiemstra, D.; Huibers, T.; de Jong, F.

    2009-01-01

    In this paper we explore whether the Open Directory (or DMOZ) can be used to classify queries into topical categories on different levels and whether we can use this topical context to improve retrieval performance. We have set up a user study to let test persons explicitly classify queries into

  8. Multi-equilibrium property of metabolic networks: SSI module

    Directory of Open Access Journals (Sweden)

    Chen Luonan

    2011-06-01

    Full Text Available Abstract Background Revealing the multi-equilibrium property of a metabolic network is a fundamental and important topic in systems biology. Due to the complexity of the metabolic network, it is generally a difficult task to study the problem as a whole from both analytical and numerical viewpoint. On the other hand, the structure-oriented modularization idea is a good choice to overcome such a difficulty, i.e. decomposing the network into several basic building blocks and then studying the whole network through investigating the dynamical characteristics of the basic building blocks and their interactions. Single substrate and single product with inhibition (SSI metabolic module is one type of the basic building blocks of metabolic networks, and its multi-equilibrium property has important influence on that of the whole metabolic networks. Results In this paper, we describe what the SSI metabolic module is, characterize the rates of the metabolic reactions by Hill kinetics and give a unified model for SSI modules by using a set of nonlinear ordinary differential equations with multi-variables. Specifically, a sufficient and necessary condition is first given to describe the injectivity of a class of nonlinear systems, and then, the sufficient condition is used to study the multi-equilibrium property of SSI modules. As a main theoretical result, for the SSI modules in which each reaction has no more than one inhibitor, a sufficient condition is derived to rule out multiple equilibria, i.e. the Jacobian matrix of its rate function is nonsingular everywhere. Conclusions In summary, we describe SSI modules and give a general modeling framework based on Hill kinetics, and provide a sufficient condition for ruling out multiple equilibria of a key type of SSI module.

  9. Link-topic model for biomedical abbreviation disambiguation.

    Science.gov (United States)

    Kim, Seonho; Yoon, Juntae

    2015-02-01

    The ambiguity of biomedical abbreviations is one of the challenges in biomedical text mining systems. In particular, the handling of term variants and abbreviations without nearby definitions is a critical issue. In this study, we adopt the concepts of topic of document and word link to disambiguate biomedical abbreviations. We newly suggest the link topic model inspired by the latent Dirichlet allocation model, in which each document is perceived as a random mixture of topics, where each topic is characterized by a distribution over words. Thus, the most probable expansions with respect to abbreviations of a given abstract are determined by word-topic, document-topic, and word-link distributions estimated from a document collection through the link topic model. The model allows two distinct modes of word generation to incorporate semantic dependencies among words, particularly long form words of abbreviations and their sentential co-occurring words; a word can be generated either dependently on the long form of the abbreviation or independently. The semantic dependency between two words is defined as a link and a new random parameter for the link is assigned to each word as well as a topic parameter. Because the link status indicates whether the word constitutes a link with a given specific long form, it has the effect of determining whether a word forms a unigram or a skipping/consecutive bigram with respect to the long form. Furthermore, we place a constraint on the model so that a word has the same topic as a specific long form if it is generated in reference to the long form. Consequently, documents are generated from the two hidden parameters, i.e. topic and link, and the most probable expansion of a specific abbreviation is estimated from the parameters. Our model relaxes the bag-of-words assumption of the standard topic model in which the word order is neglected, and it captures a richer structure of text than does the standard topic model by considering

  10. Unsupervised topic discovery by anomaly detection

    OpenAIRE

    Cheng, Leon

    2013-01-01

    Approved for public release; distribution is unlimited With the vast amount of information and public comment available online, it is of increasing interest to understand what is being said and what topics are trending online. Government agencies, for example, want to know what policies concern the public without having to look through thousands of comments manually. Topic detection provides automatic identification of topics in documents based on the information content and enhances many ...

  11. Topical cyclosporine for atopic keratoconjunctivitis.

    Science.gov (United States)

    González-López, Julio J; López-Alcalde, Jesús; Morcillo Laiz, Rafael; Fernández Buenaga, Roberto; Rebolleda Fernández, Gema

    2012-09-12

    Atopic keratoconjunctivitis (AKC) is a chronic ocular surface non-infectious inflammatory condition that atopic dermatitis patients may suffer at any time point in the course of their dermatologic disease and is independent of its degree of severity. AKC is usually not self resolving and it poses a higher risk of corneal injuries and severe sequelae. Management of AKC should prevent or treat corneal damage. Although topical corticosteroids remain the standard treatment for patients with AKC, prolonged use may lead to complications. Topical cyclosporine A (CsA) may improve AKC signs and symptoms, and be used as a corticosteroid sparing agent. To determine the efficacy and gather evidence on safety from randomised controlled trials (RCTs) of topical CsA in patients with AKC. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to July 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en), the IFPMA Clinical Trials Portal (http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm) and Web of Science Conference Proceedings Citation Index- Science (CPCI-S). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 July 2012. We also handsearched the following conference proceedings: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, International Council of Opthalmology and Societas

  12. 21 CFR 868.5170 - Laryngotracheal topical anesthesia applicator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Laryngotracheal topical anesthesia applicator. 868... topical anesthesia applicator. (a) Identification. A laryngotracheal topical anesthesia applicator is a device used to apply topical anesthetics to a patient's laryngotracheal area. (b) Classification. Class...

  13. Topical therapy of atopic dermatitis: controversies from Hippocrates to topical immunomodulators.

    Science.gov (United States)

    Tilles, Gérard; Wallach, Daniel; Taïeb, Alain

    2007-02-01

    Although atopic dermatitis can be treated efficiently, there is still much controversy about the risk/benefit ratio of both topical corticosteroids and topical immunomodulators. Conflicting data may be found about the usefulness of bathing, diet regulation, and other therapeutic interventions. These controversies result in part from the persistence of Hippocratic doctrines in modern medical thinking. Humoralist and diathetic doctrines, as they pertain to eczema, are reviewed. The paradoxical worsening of oozing and the deadly hazards of hospitalization before the era of antibiotics are brought to mind. We hope that this historical review will improve the understanding of current controversies and help dermatologists to manage patients with atopic dermatitis and other chronic skin diseases.

  14. Simulation-Visualization and Self-Assessment Modules' Capabilities in Structural Analysis Course Including Survey Analysis Results

    Science.gov (United States)

    Kadiam, Subhash Chandra Bose S. V.; Mohammed, Ahmed Ali; Nguyen, Duc T.

    2010-01-01

    In this paper, we describe an approach to analyze 2D truss/Frame/Beam structures under Flash-based environment. Stiffness Matrix Method (SMM) module was developed as part of ongoing projects on a broad topic "Students' Learning Improvements in Science, Technology, Engineering and Mathematics (STEM) Related Areas" at Old Dominion…

  15. Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics

    Science.gov (United States)

    Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network. PMID:20810955

  16. Mathematical biology modules based on modern molecular biology and modern discrete mathematics.

    Science.gov (United States)

    Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

  17. THE EFFECTIVENESS OF A VIRTUAL FIELD TRIP (VFT MODULE IN LEARNING BIOLOGY

    Directory of Open Access Journals (Sweden)

    Norbaizura HARIS

    2015-07-01

    Full Text Available Virtual Field Trip is a computer aided module of science developed to study the Colonisation and Succession in Mangrove Swamps, as an alternative to the real field trip in Form for Biology. This study is to identify the effectiveness of the Virtual Field Trip (VFT module towards the level of achievement in the formative test for this topic. This study was conducted to 60 students employing a quasi-experimental design involving a treatment group taught using the VFT module and a control group who were taught using conventional methods. Analysis into the effectiveness of the virtual module was done descriptively, followed by inferential analysis involving the two-way ANOVA. The results showed significant differences in the mean scores of pre and post achievement between students taught using VFT and students who were taught using conventional methods for objective, structure and essay type questions. The study concluded that teaching and learning by using the VFT module, integrated with ICT, has a positive impact on student achievement whencompared to conventional methods. This study focuses on the use of the VFT recognizing that teachers are often unable to conduct a real field trip on location.

  18. Topic Time Series Analysis of Microblogs

    Science.gov (United States)

    2014-10-01

    may be distributed more globally. Tweets on a specific topic that cluster spatially, temporally or both might be of interest to analysts, marketers ...of $ and @, with the latter only in the case that it is the only character in the token (the @ symbol is significant in its usage by Instagram in...is generated by Instagram . Topic 80, Distance: 143.2101 Top words: 1. rawr 2. ˆ0ˆ 3. kill 4. jurassic 5. dinosaur Analysis: This topic is quite

  19. Topic modelling in the information warfare domain

    CSIR Research Space (South Africa)

    De Waal, A

    2013-11-01

    Full Text Available for interesting and relevant topics. The objectives of this paper is to describe topic modelling, put it in context as a useful IW technique and illustrate its use with two examples. They discuss several applications of topic modelling in the safety and security...

  20. Signal-enhanced electrochemiluminescence immunosensor based on synergistic catalysis of nicotinamide adenine dinucleotide hydride and silver nanoparticles.

    Science.gov (United States)

    Wang, Guangjie; Jin, Feng; Dai, Nan; Zhong, Zhaoyang; Qing, Yi; Li, Mengxia; Yuan, Ruo; Wang, Dong

    2012-03-01

    A new metal-organic nanocomposite with synergistic catalysis function was prepared and developed to construct an electrochemiluminescence (ECL) immunosensor for ultrasensitive detection of tumor biomarker CA125. Silver nanoparticles (AgNPs) and nicotinamide adenine dinucleotide hydride (NADH) that can participate and catalyze the ECL reaction of Ru(bpy)(3)(2+) were employed as the metal component and the organic component to synthesize the metal-organic nanocomposite of NADH-AgNPs (NA). The novel ECL immunosensor was assembled via Ru(bpy)(3)(2+)-doped silica nanoparticles (Ru-SiO(2)) modified electrode with the NA as immune labels. First, the chitosan-suspended Ru-SiO(2) nanoparticles were cast on the gold electrode surface to immobilize the ECL probes of Ru(bpy)(3)(2+) and link gold nanoparticles. Then, the primary antibodies were loaded onto the modified electrode via the gold sulfhydryl covalent binding. After immunobinding the analytes of antigen, NA-attached secondary antibodies could be captured as a sandwich type on the electrode. Finally, based on the circularly synergistic catalysis by the silver and NADH for the solid-phase ECL of Ru(bpy)(3)(2+), the proposed immunosensor sensed the concentration of antigen. The synergistic ECL catalysis of metal-organic nanocomposite amplified response signal and pushed the detection limit down to 0.03 U ml(-1), which initiated a new ECL labeling field and has great significance for ECL immunoassays. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress.

    Science.gov (United States)

    Yu, Tao; Wang, Yong-Tao; Chen, Pan; Li, Yu-Hua; Chen, Yi-Xin; Zeng, Hang; Yu, Ai-Ming; Huang, Min; Bi, Hui-Chang

    2015-01-01

    Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. © 2015 S. Karger AG, Basel.

  2. Effects of Nicotinamide N-Methyltransferase on PANC-1 Cells Proliferation, Metastatic Potential and Survival Under Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Tao Yu

    2015-01-01

    Full Text Available Background: Aberrant expression of Nicotinamide N-methyltransferase (NNMT has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Methods: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. Results: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. Conclusions: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.

  3. Task-Driven Comparison of Topic Models.

    Science.gov (United States)

    Alexander, Eric; Gleicher, Michael

    2016-01-01

    Topic modeling, a method of statistically extracting thematic content from a large collection of texts, is used for a wide variety of tasks within text analysis. Though there are a growing number of tools and techniques for exploring single models, comparisons between models are generally reduced to a small set of numerical metrics. These metrics may or may not reflect a model's performance on the analyst's intended task, and can therefore be insufficient to diagnose what causes differences between models. In this paper, we explore task-centric topic model comparison, considering how we can both provide detail for a more nuanced understanding of differences and address the wealth of tasks for which topic models are used. We derive comparison tasks from single-model uses of topic models, which predominantly fall into the categories of understanding topics, understanding similarity, and understanding change. Finally, we provide several visualization techniques that facilitate these tasks, including buddy plots, which combine color and position encodings to allow analysts to readily view changes in document similarity.

  4. Inferring modules from human protein interactome classes

    Directory of Open Access Journals (Sweden)

    Chaurasia Gautam

    2010-07-01

    Full Text Available Abstract Background The integration of protein-protein interaction networks derived from high-throughput screening approaches and complementary sources is a key topic in systems biology. Although integration of protein interaction data is conventionally performed, the effects of this procedure on the result of network analyses has not been examined yet. In particular, in order to optimize the fusion of heterogeneous interaction datasets, it is crucial to consider not only their degree of coverage and accuracy, but also their mutual dependencies and additional salient features. Results We examined this issue based on the analysis of modules detected by network clustering methods applied to both integrated and individual (disaggregated data sources, which we call interactome classes. Due to class diversity, we deal with variable dependencies of data features arising from structural specificities and biases, but also from possible overlaps. Since highly connected regions of the human interactome may point to potential protein complexes, we have focused on the concept of modularity, and elucidated the detection power of module extraction algorithms by independent validations based on GO, MIPS and KEGG. From the combination of protein interactions with gene expressions, a confidence scoring scheme has been proposed before proceeding via GO with further classification in permanent and transient modules. Conclusions Disaggregated interactomes are shown to be informative for inferring modularity, thus contributing to perform an effective integrative analysis. Validation of the extracted modules by multiple annotation allows for the assessment of confidence measures assigned to the modules in a protein pathway context. Notably, the proposed multilayer confidence scheme can be used for network calibration by enabling a transition from unweighted to weighted interactomes based on biological evidence.

  5. Topical Session on Materials Management

    International Nuclear Information System (INIS)

    2002-01-01

    At its second meeting, in Paris, 5-7 December 2001, the WPDD held two topical sessions on the D and D Safety Case and on the Management of Materials from D and D, respectively. This report documents the topical session on the management of materials. Presentations during the topical session covered key aspects of the management of materials and meant to provide an exchange of information and experience, including: Experience and lessons learnt from VLLW and non-radioactive material management in Spain and Germany with special attention to recycling (How specific solutions came about? Are there 'generic' examples for wider adoption?); Risk assessment of recycling and non-recycling: a CPD study; Waste acceptance issues within different national contexts (What constraints are there on the waste receiving body and what flexibility can the latter have? What constraints does this impose on D and D implementers? What about wastes are without current solution? What needs to be done? What about large items and 'difficult' waste in general?); Radiological characterisation of materials during decommissioning, particularly difficult situations - large volumes, large items,.. wastes, heterogeneous streams (What examples of established practice? What are the approaches or aspects that set the regulatory requirements? How can the flow rates be large but the answers acceptable? How much is needed to be known for later action, e. g., disposal, release, protection of worker, etc.); Radiological characterisation of buildings as they stand, in order to allow conventional demolition (What are strategies for optimisation of characterisation? How much needs to be known to take action later? e.g. for storage, disposal, release, cost estimation and ALARA? What needs to be done in advance and after decommissioning/dismantling?). At the end of each presentation time was allotted for discussion of the paper. Integral to the Topical Session was a facilitated plenary discussion on the topical

  6. Topical steroid addiction in atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Fukaya M

    2014-10-01

    Full Text Available Mototsugu Fukaya,1 Kenji Sato,2 Mitsuko Sato,3 Hajime Kimata,4 Shigeki Fujisawa,5 Haruhiko Dozono,6 Jun Yoshizawa,7 Satoko Minaguchi8 1Tsurumai Kouen Clinic, Nagoya, 2Department of Dermatology, Hannan Chuo Hospital, Osaka, 3Sato Pediatric Clinic, Osaka, 4Kimata Hajime Clinic, Osaka, 5Fujisawa Dermatology Clinic, Tokyo, 6Dozono Medical House, Kagoshima, 7Yoshizawa Dermatology Clinic, Yokohama, 8Department of Dermatology, Kounosu Kyousei Hospital, Saitama, Japan Abstract: The American Academy of Dermatology published a new guideline regarding topical therapy in atopic dermatitis in May 2014. Although topical steroid addiction or red burning skin syndrome had been mentioned as possible side effects of topical steroids in a 2006 review article in the Journal of the American Academy of Dermatology, no statement was made regarding this illness in the new guidelines. This suggests that there are still controversies regarding this illness. Here, we describe the clinical features of topical steroid addiction or red burning skin syndrome, based on the treatment of many cases of the illness. Because there have been few articles in the medical literature regarding this illness, the description in this article will be of some benefit to better understand the illness and to spur discussion regarding topical steroid addiction or red burning skin syndrome. Keywords: topical steroid addiction, atopic dermatitis, red burning skin syndrome, rebound, corticosteroid, eczema

  7. Operation and maintenance cost data for residential photovoltaic modules/panels

    Science.gov (United States)

    Oster, J. R., Jr.; Zaremski, D. R., Jr.; Albert, E. M.; Hawkins, S. L.

    1980-01-01

    Costs associated with the operation and maintenance of residential photovoltaic modules and arrays are studied. Six basic topics related to operation and maintenance to photovoltaic arrays are investigated: maintenance; cleaning; panel replacement; gasket repair/replacement; wiring repair/replacement; and termination repair/replacement. The effects of the mounting types (rack mount, stand off mount, direct mount and integral mount) and the installation/replacement type (sequential, partial interruption and independent) are identified and described. Methods of reducing maintenance costs are suggested.

  8. Eye Wear: MedlinePlus Health Topic

    Science.gov (United States)

    ... When You Exercise (National Institute on Aging) - PDF Topic Image MedlinePlus Email Updates Get Eye Wear updates by email What's this? GO Related Health Topics Refractive Errors National Institutes of Health The primary ...

  9. 21 CFR 524.1193 - Ivermectin topical solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin topical solution. 524.1193 Section 524...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1193 Ivermectin topical solution. (a) Specifications. Each milliliter (mL) of solution contains 5 milligrams of...

  10. Eosinophilic Esophagitis: MedlinePlus Health Topic

    Science.gov (United States)

    ... Esophagitis (EoE) (American Academy of Allergy, Asthma, and Immunology) Also in Spanish Latest News Eosinophilic Esophagitis May ... Pediatric and Adolescent Patients (American College of Gastroenterology) Topic Image Related Health Topics Eosinophilic Disorders Esophagus Disorders ...

  11. Female Infertility: MedlinePlus Health Topic

    Science.gov (United States)

    ... Prolactin blood test (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Female Infertility updates ... Serum progesterone Show More Show Less Related Health Topics Assisted Reproductive Technology Infertility Male Infertility National Institutes ...

  12. Mobility Aids: MedlinePlus Health Topic

    Science.gov (United States)

    ... Mobility Problems (AGS Foundation for Health in Aging) Topic Image MedlinePlus Email Updates Get Mobility Aids updates ... standing and walking Using a cane Related Health Topics Assistive Devices Other Languages Find health information in ...

  13. Genetic Testing: MedlinePlus Health Topic

    Science.gov (United States)

    ... Your Family's Health (National Institutes of Health) - PDF Topic Image MedlinePlus Email Updates Get Genetic Testing updates ... testing and your cancer risk Karyotyping Related Health Topics Birth Defects Genetic Counseling Genetic Disorders Newborn Screening ...

  14. Folic Acid: MedlinePlus Health Topic

    Science.gov (United States)

    ... acid in diet (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Folic Acid updates ... acid - test Folic acid in diet Related Health Topics Vitamins National Institutes of Health The primary NIH ...

  15. Pneumococcal Infections: MedlinePlus Health Topic

    Science.gov (United States)

    ... Prevention, Immunization Action Coalition) - PDF Also in Spanish Topic Image MedlinePlus Email Updates Get Pneumococcal Infections updates ... ray Meningitis - pneumococcal Sputum gram stain Related Health Topics Meningitis Pneumonia Sepsis Sinusitis Streptococcal Infections National Institutes ...

  16. Wilms' Tumor: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Wilms tumor (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Wilms Tumor updates ... ENCYCLOPEDIA After chemotherapy - discharge Wilms tumor Related Health Topics Kidney Cancer National Institutes of Health The primary ...

  17. Child Safety: MedlinePlus Health Topic

    Science.gov (United States)

    ... injuries in children (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Child Safety updates ... safety Preventing head injuries in children Related Health Topics Infant and Newborn Care Internet Safety Motor Vehicle ...

  18. Pneumocystis Infections: MedlinePlus Health Topic

    Science.gov (United States)

    ... Pneumocystis jiroveci pneumonia (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Pneumocystis Infections updates ... GO MEDICAL ENCYCLOPEDIA Pneumocystis jiroveci pneumonia Related Health Topics HIV/AIDS HIV/AIDS and Infections Pneumonia National ...

  19. Collapsed Lung: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Pneumothorax - infants (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Collapsed Lung updates ... Lung surgery Pneumothorax - slideshow Pneumothorax - infants Related Health Topics Chest Injuries and Disorders Lung Diseases Pleural Disorders ...

  20. Male Infertility: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Testicular biopsy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Male Infertility updates ... analysis Sperm release pathway Testicular biopsy Related Health Topics Assisted Reproductive Technology Female Infertility Infertility National Institutes ...

  1. Healthy Aging: MedlinePlus Health Topic

    Science.gov (United States)

    ... Aging National Institute on Aging Also in Spanish Topic Image MedlinePlus Email Updates Get Healthy Aging updates ... 65 Health screening - women - over 65 Related Health Topics Exercise for Seniors Nutrition for Seniors Seniors' Health ...

  2. Psoriatic Arthritis: MedlinePlus Health Topic

    Science.gov (United States)

    ... Handouts Psoriatic arthritis (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Psoriatic Arthritis updates ... this? GO MEDICAL ENCYCLOPEDIA Psoriatic arthritis Related Health Topics Arthritis Psoriasis National Institutes of Health The primary ...

  3. Hip Replacement: MedlinePlus Health Topic

    Science.gov (United States)

    ... invasive hip replacement (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hip Replacement updates ... replacement - precautions Minimally invasive hip replacement Related Health Topics Hip Injuries and Disorders National Institutes of Health ...

  4. Platelet Disorders: MedlinePlus Health Topic

    Science.gov (United States)

    ... Thromobocytopenia - drug-induced (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Platelet Disorders updates ... Willebrand disease Show More Show Less Related Health Topics Bleeding Disorders Blood Clots Blood Count Tests Blood ...

  5. Cardiac Rehabilitation: MedlinePlus Health Topic

    Science.gov (United States)

    ... in Spanish Electrocardiogram (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Cardiac Rehabilitation updates ... How to take your pulse Pulse Related Health Topics Heart Attack Heart Diseases How to Prevent Heart ...

  6. Cardiac Arrest: MedlinePlus Health Topic

    Science.gov (United States)

    ... Handouts Cardiac arrest (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Cardiac Arrest updates ... this? GO MEDICAL ENCYCLOPEDIA Cardiac arrest Related Health Topics Arrhythmia CPR Pacemakers and Implantable Defibrillators National Institutes ...

  7. Kawasaki Disease: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Kawasaki disease (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Kawasaki Disease updates ... GO MEDICAL ENCYCLOPEDIA Electrocardiogram Kawasaki disease Related Health Topics Vasculitis National Institutes of Health The primary NIH ...

  8. Diabetic Diet: MedlinePlus Health Topic

    Science.gov (United States)

    ... Sweeteners - sugar substitutes (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Diabetic Diet updates ... you have diabetes Sweeteners - sugar substitutes Related Health Topics Blood Sugar Diabetes Diabetes in Children and Teens ...

  9. Infection Control: MedlinePlus Health Topic

    Science.gov (United States)

    ... Staph infections - hospital (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Infection Control updates ... infections when visiting Staph infections - hospital Related Health Topics Hepatitis HIV/AIDS MRSA National Institutes of Health ...

  10. Hearing Aids: MedlinePlus Health Topic

    Science.gov (United States)

    ... for hearing loss (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hearing Aids updates ... MEDICAL ENCYCLOPEDIA Devices for hearing loss Related Health Topics Cochlear Implants Hearing Disorders and Deafness National Institutes ...

  11. Kidney Tests: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Total protein (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Kidney Tests updates ... hour volume Show More Show Less Related Health Topics Kidney Cancer Kidney Diseases National Institutes of Health ...

  12. Ischemic Stroke: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Thrombolytic therapy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Ischemic Stroke updates ... cardiogenic embolism Stroke - slideshow Thrombolytic therapy Related Health Topics Hemorrhagic Stroke Stroke Stroke Rehabilitation National Institutes of ...

  13. Pulmonary Rehabilitation: MedlinePlus Health Topic

    Science.gov (United States)

    ... Handouts Postural drainage (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Pulmonary Rehabilitation updates ... this? GO MEDICAL ENCYCLOPEDIA Postural drainage Related Health Topics Lung Diseases National Institutes of Health The primary ...

  14. Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors

    Directory of Open Access Journals (Sweden)

    Sadrerafi K

    2018-04-01

    Full Text Available Keivan Sadrerafi, Emilia O Mason, Mark W Lee Jr Department of Chemistry, University of Missouri, Columbia, MO, USA Purpose: Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl-7-(4′-(trans-3″-(3‴-pyridylacrylamidobutyl-1,7-dicarbadodecaborane (hm-MC4-PPEA, was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt. Nampt has been shown to be upregulated in most cancers and is a promising target for the treatment of many different types of cancers, including breast cancers. Patients and methods: To increase the selectivity of hm-MC4-PPEA toward cancer cells, three prodrugs were synthesized with different hydrolyzable linkers: ester, carbonate, and carbamate. Using click chemistry a fluorophore was attached to these prodrugs to act as a model for our conjugation strategy and to serve as an aid for prodrug stability studies. The stabilities of these drug conjugates were tested in phosphate-buffered saline (PBS at normothermia (37°C using three different pH levels, 5.5, 7.5, and 9.5, as well as in horse serum at physiological pH. The stability of each was monitored using reversed-phase HPLC equipped with both diode array and fluorescence detection. The inhibitory activity of hm-MC4-PPEA was also measured using a commercially available colorimetric assay. The biological activities of the drug conjugates as well as those of the free drug (hm-MC4-PPEA, were evaluated using the MTT assay against the human breast cancer cell lines T47D and MCF7, as well as the noncancerous, transformed, Nampt-dependent human breast epithelium cell line 184A1.Results: hm-MC4-PPEA showed to be a potent inhibitor of recombinant Nampt activity, exhibiting an IC50 concentration of 6.8 nM. The prodrugs showed great stability towards hydrolytic degradation under neutral, mildly acidic and mildly basic conditions. The carbamate prodrug also showed to be stable in rat serum. However, the carbonate and the ester prodrug

  15. Antibiotic Resistance: MedlinePlus Health Topic

    Science.gov (United States)

    ... GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Health Topics → Antibiotic Resistance URL of this page: https://medlineplus.gov/antibioticresistance. ...

  16. Module theory, extending modules and generalizations

    CERN Document Server

    Tercan, Adnan

    2016-01-01

    The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

  17. Modules to enhance smart lighting education

    Science.gov (United States)

    Bunch, Robert M.; Joenathan, Charles; Connor, Kenneth; Chouikha, Mohamed

    2012-10-01

    Over the past several years there has been a rapid advancement in solid state lighting applications brought on by the development of high efficiency light emitting diodes. Development of lighting devices, systems and products that meet the demands of the future lighting marketplace requires workers from many disciplines including engineers, scientists, designers and architects. The National Science Foundation has recognized this fact and established the Smart Lighting Engineering Research Center that promotes research leading to smart lighting systems, partners with industry to enhance innovation and educates a diverse, world-class workforce. The lead institution is Rensselaer Polytechnic Institute with core partners Boston University and The University of New Mexico. Outreach partners include Howard University, Morgan State University, and Rose-Hulman Institute of Technology. Because of the multidisciplinary nature of advanced smart lighting systems workers often have little or no formal education in basic optics, lighting and illumination. This paper describes the initial stages of the development of self-contained and universally applicable educational modules that target essential optics topics needed for lighting applications. The modules are intended to be easily incorporated into new and existing courses by a variety of educators and/or to be used in a series of stand-alone, asynchronous training exercises by new graduate students. The ultimate goal of this effort is to produce resources such as video lectures, video presentations of students-teaching-students, classroom activities, assessment tools, student research projects and laboratories integrated into learning modules. Sample modules and resources will be highlighted. Other outreach activities such as plans for coursework, undergraduate research, design projects, and high school enrichment programs will be discussed.

  18. Madness and the movies: an undergraduate module for medical students.

    Science.gov (United States)

    Datta, Vivek

    2009-06-01

    Films featuring psychiatrists, psychiatry and the mentally ill abound, for better or for worse. The use of cinema in postgraduate psychiatry training has been gaining increasing acceptability, but its potential for use in undergraduate psychiatry has received little attention in the literature. This paper reports on the rationale behind, and medical students' responses to a special study module for third year medical students at King's College London, which utilized movies to highlight the significance of the social, cultural and historical context in shaping representations of mental illness, psychiatry, and psychiatrists. Medical students were very receptive to the use of film as an educational tool and able to understand both the benefits and limitations. They found the module enjoyable, and subjectively rated their knowledge of psychiatric topics and the history of psychiatry as significantly improved. The results presented are course feedback from medical students (n = 8) who completed the module. Although our findings provide provisional support for the use of film as an educational tool in undergraduate psychiatry, more systematic research is needed to delineate the potential role of cinema in undergraduate psychiatric education.

  19. Large-Scale Topic Detection and Language Model Adaptation

    National Research Council Canada - National Science Library

    Seymore, Kristie

    1997-01-01

    .... We have developed a language model adaptation scheme that takes apiece of text, chooses the most similar topic clusters from a set of over 5000 elemental topics, and uses topic specific language...

  20. Depletion of NAD pool contributes to impairment of endothelial progenitor cell mobilization in diabetes.

    Science.gov (United States)

    Wang, Pei; Yang, Xi; Zhang, Zheng; Song, Jie; Guan, Yun-Feng; Zou, Da-Jin; Miao, Chao-Yu

    2016-06-01

    The impaired mobilization of endothelial progenitor cells (EPCs) from bone marrow (BM) critically contributes to the diabetes-associated vascular complications. Here, we investigated the relationship between the nicotinamide phosphoribosyltransferase (NAMPT)-controlled nicotinamide adenine dinucleotide (NAD) metabolism and the impaired mobilization of BM-derived EPCs in diabetic condition. The NAMPT-NAD pool in BM and BM-derived EPCs in wild-type (WT) and diabetic db/db mice was determined. Nicotinamide, a natural substrate for NAD biosynthesis, was administrated for 2weeks in db/db mice to examine the influence of enhancing NAD pool on BM and blood EPCs number. The modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein in BM were measured using immunoblotting. The EPCs intracellular NAMPT level and NAD concentration, as well as the blood EPCs number, were compared between 9 healthy people and 16 patients with type 2 diabetes mellitus (T2DM). The T2DM patients were treated with nicotinamide for two weeks and then the blood EPCs number was determined. Moreover, the association between blood EPCs numbers and EPCs intracellular NAD(+)/NAMPT protein levels in 21 healthy individuals was determined. We found that NAD concentration and NAMPT expression in BM and BM-derived EPCs of db/db mice were significantly lower than those in WT mice BM. Enhancing NAD pool not only increased the EPCs intracellular NAD concentration and blood EPCs number, but also improved post-ischemic wound healing and blood reperfusion in db/db mice with hind-limb ischemia model. Enhancing NAD pool rescued the impaired modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein levels in db/db mice BM upon hind-limb ischemia. In addition, enhancing NAD pool significantly inhibited PARP and caspase-3 activates in db/db mice BM. The intracellular NAMPT-NAD pool was positively associated with blood

  1. Quantum mechanics II advanced topics

    CERN Document Server

    Rajasekar, S

    2015-01-01

    Quantum Mechanics II: Advanced Topics uses more than a decade of research and the authors’ own teaching experience to expound on some of the more advanced topics and current research in quantum mechanics. A follow-up to the authors introductory book Quantum Mechanics I: The Fundamentals, this book begins with a chapter on quantum field theory, and goes on to present basic principles, key features, and applications. It outlines recent quantum technologies and phenomena, and introduces growing topics of interest in quantum mechanics. The authors describe promising applications that include ghost imaging, detection of weak amplitude objects, entangled two-photon microscopy, detection of small displacements, lithography, metrology, and teleportation of optical images. They also present worked-out examples and provide numerous problems at the end of each chapter.

  2. Topical application of hemostatic paste

    Directory of Open Access Journals (Sweden)

    Mohammad Mizanur Rahman

    2017-02-01

    Full Text Available As a measure to control minor surgical bleeding, surgeons usually depend on a number of hemostatic aids. Topical use of bovine thrombin is a widely used procedure to arrest such minor bleeding. A 35 year old male sergeant of Bangladesh Air Force presented with repeated development of hematoma in his left thigh without any history of trauma or previous history of bleeding. Critical analysis of the patient’s history, routine and sophisticated hematological investigations revealed that the patient developed anti-thrombin antibody following the application of hemostatic paste in the tooth socket five years back during minor dental procedure to stop ignorable bleeding episodes. Therefore, topical use of hemostatic glue/paste or bovine thrombin should be avoided to desist minor bleeding as recombinant human thrombin is now available for topical use.

  3. Earth System Science Education Modules

    Science.gov (United States)

    Hall, C.; Kaufman, C.; Humphreys, R. R.; Colgan, M. W.

    2009-12-01

    The College of Charleston is developing several new geoscience-based education modules for integration into the Earth System Science Education Alliance (ESSEA). These three new modules provide opportunities for science and pre-service education students to participate in inquiry-based, data-driven experiences. The three new modules will be discussed in this session. Coastal Crisis is a module that analyzes rapidly changing coastlines and uses technology - remotely sensed data and geographic information systems (GIS) to delineate, understand and monitor changes in coastal environments. The beaches near Charleston, SC are undergoing erosion and therefore are used as examples of rapidly changing coastlines. Students will use real data from NASA, NOAA and other federal agencies in the classroom to study coastal change. Through this case study, learners will acquire remotely sensed images and GIS data sets from online sources, utilize those data sets within Google Earth or other visualization programs, and understand what the data is telling them. Analyzing the data will allow learners to contemplate and make predictions on the impact associated with changing environmental conditions, within the context of a coastal setting. To Drill or Not To Drill is a multidisciplinary problem based module to increase students’ knowledge of problems associated with nonrenewable resource extraction. The controversial topic of drilling in the Arctic National Wildlife Refuge (ANWR) examines whether the economic benefit of the oil extracted from ANWR is worth the social cost of the environmental damage that such extraction may inflict. By attempting to answer this question, learners must balance the interests of preservation with the economic need for oil. The learners are exposed to the difficulties associated with a real world problem that requires trade-off between environmental trust and economic well-being. The Citizen Science module challenges students to translate scientific

  4. Aerodynamics of wind turbines emerging topics

    CERN Document Server

    Amano, R S

    2014-01-01

    Focusing on Aerodynamics of Wind Turbines with topics ranging from Fundamental to Application of horizontal axis wind turbines, this book presents advanced topics including: Basic Theory for Wind turbine Blade Aerodynamics, Computational Methods, and Special Structural Reinforcement Technique for Wind Turbine Blades.

  5. SETI: A good introductory physics topic

    Science.gov (United States)

    Hobson, Art

    1997-04-01

    If America is to achieve the science literacy that is essential to industrialized democracy, all students must study such topics as scientific methodology, pseudoscience, ozone depletion, and global warming. My large-enrollment liberal-arts physics course covers the great principles of physics along with several such philosophical and societal topics. It is easy to include the interdisciplinary context of physics in courses for non-scientists, because these courses are flexible, conceptual, and taught to students whose interests span a broad range. Students find these topics relevant and fascinating, leading to large enrollments by non-scientists even in courses labeled ''physics.'' I will discuss my approach to teaching the search for extra-terrestrial intelligence (SETI), a topic with lots of good physics and with connections to scientific methodology and pseudoscience. A textbook for this kind of course has been published, Physics: Concepts and Connections (Prentice-Hall, 1995).

  6. Affinity between information retrieval system and search topic

    International Nuclear Information System (INIS)

    Ebinuma, Yukio

    1979-01-01

    Ten search profiles are tested on the INIS system at the Japan Atomic Energy Research Institute. The results are plotted on recall-precision chart ranging from 100% recall to 100% precision. The curves are not purely systems-dependent nor search-dependent, and are determined substantially by the ''affinity'' between the system and the search topic. The curves are named ''Affinity curves of search topics with information retrieval systems'', and hence retrieval affinity factors are derived. They are obtained not only for individual search topics but also for averages in the system. By such a quantitative examination, the difference of affinity among search topics in a given system, that of the same search topic among various systems, and that of systems to the same group of search topics can be compared reasonably. (author)

  7. Analyzing the history of Cognition using Topic Models.

    Science.gov (United States)

    Cohen Priva, Uriel; Austerweil, Joseph L

    2015-02-01

    Very few articles have analyzed how cognitive science as a field has changed over the last six decades. We explore how Cognition changed over the last four decades using Topic Models. Topic Models assume that every word in every document is generated by one of a limited number of topics. Words that are likely to co-occur are likely to be generated by a single topic. We find a number of significant historical trends: the rise of moral cognition, eyetracking methods, and action, the fall of sentence processing, and the stability of development. We introduce the notion of framing topics, which frame content, rather than present the content itself. These framing topics suggest that over time Cognition turned from abstract theorizing to more experimental approaches. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Topics of Bioengineering in Wikipedia

    Directory of Open Access Journals (Sweden)

    Vassia Atanassova

    2009-10-01

    Full Text Available The present report aims to give a snapshot of how topics from the field of bioengineering (bioinformatics, bioprocess systems, biomedical engineering, biotechnology, etc. are currently covered in the free electronic encyclopedia Wikipedia. It also offers insights and information about what Wikipedia is, how it functions, how and when to cite Wikipedian articles, if necessary. Several external wikis, devoted to topics of bioengineering, are also listed and reviewed.

  9. Updates of Topical and Local Anesthesia Agents.

    Science.gov (United States)

    Boyce, Ricardo A; Kirpalani, Tarun; Mohan, Naveen

    2016-04-01

    As described in this article, there are many advances in topical and local anesthesia. Topical and local anesthetics have played a great role in dentistry in alleviating the fears of patients, eliminating pain, and providing pain control. Many invasive procedures would not be performed without the use and advances of topical/local anesthetics. The modern-day dentist has the responsibility of knowing the variety of products on the market and should have at least references to access before, during, and after treatment. This practice ensures proper care with topical and local anesthetics for the masses of patients entering dental offices worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Teaching calculus using module based on cooperative learning strategy

    Science.gov (United States)

    Arbin, Norazman; Ghani, Sazelli Abdul; Hamzah, Firdaus Mohamad

    2014-06-01

    The purpose of the research is to evaluate the effectiveness of a module which utilizes the cooperative learning for teaching Calculus for limit, derivative and integral. The sample consists of 50 semester 1 students from the Science Programme (AT 16) Sultan Idris Education University. A set of questions of related topics (pre and post) has been used as an instrument to collect data. The data is analyzed using inferential statistics involving the paired sample t-test and the independent t-test. The result shows that students have positive inclination towards the modulein terms of understanding.

  11. Anesthesia: A Topic for Interdisciplinary Study.

    Science.gov (United States)

    Labianca, Dominick A.; Reeves, William J.

    1977-01-01

    Describes an interdisciplinary approach for teaching the topic of anesthesia as one aspect of a chemistry-oriented course for nonscience majors which focuses on timely topics such as the energy crisis and drugs. Historical treatment with the examination of literature is emphasized in teaching. (HM)

  12. Efficacy, tolerability and consumer acceptability of terbinafine topical spray versus terbinafine topical solution: a phase IIa, randomised, observer-blind, comparative study.

    Science.gov (United States)

    Brown, Marc; Evans, Charles; Muddle, Andrew; Turner, Rob; Lim, Sian; Reed, Jessica; Traynor, Matt

    2013-10-01

    Tinea pedis is one of the world's most prevalent dermatophyte infections. MedSpray™ tinea pedis 1 % w/w (topical spray) is a novel, easy-to-use propellant-based spray formulation containing 1 % w/w terbinafine, requiring no manipulation at the site of infection. This is in contrast to the only formulation currently approved in Europe for single application (none are approved in the USA for single use), which is Lamisil(®) Once 1 % w/w (topical solution), containing 1 % w/w terbinafine hydrochloride, which requires manipulation on the affected area. The aim of this study was to evaluate the efficacy, tolerability and consumer acceptability of a topical spray versus a topical solution in the treatment of tinea pedis. This study is a phase IIa, randomised, observer-blind, non-inferiority comparative study of the topical spray compared with the topical solution over a 12-week study period. The study was conducted at Bioskin GmbH, Hamburg and Berlin. Patients (n = 120) who presented with the presence of interdigital tinea pedis caused by dermatophytes on one or both feet were enrolled in the study. Patients were randomly assigned between the two treatment groups. Either the topical spray or the topical solution was administered by the study nurse and consisted of a single application (equivalent to 20 mg of terbinafine per foot) on day 1 of the study. No further applications were made for the duration of the study. The hypothesis formulated before commencement of the study was that the topical spray would prove to be non-inferior to the topical solution. Efficacy assessments, including clinical signs and symptoms, mycology and microscopy were performed at baseline and 1, 6 and 12 weeks after treatment. The rate of mycological cure at week 1 was statistically equivalent for both treatments. There was a significant reduction in the overall clinical score as assessed by the Physician's Global Assessment of signs and symptoms for both treatment groups. The topical

  13. Topical thrombin-related corneal calcification.

    Science.gov (United States)

    Kiratli, Hayyam; Irkeç, Murat; Alaçal, Sibel; Söylemezoğlu, Figen

    2006-09-01

    To report a highly unusual case of corneal calcification after brief intraoperative use of topical thrombin. A 44-year-old man underwent sclerouvectomy for ciliochoroidal leiomyoma, during which 35 UNIH/mL lyophilized bovine thrombin mixed with 9 mL of diluent containing 1500 mmol/mL calcium chloride was used. From the first postoperative day, corneal and anterior lenticular capsule calcifications developed, and corneal involvement slightly enlarged thereafter. A year later, 2 corneal punch biopsies confirmed calcification mainly in the Bowman layer. Topical treatment with 1.5% ethylenediaminetetraacetic acid significantly restored corneal clarity. Six months later, a standard extracapsular cataract extraction with intraocular lens placement improved visual acuity to 20/60. This case suggests that topical thrombin drops with elevated calcium concentrations may cause acute corneal calcification in Bowman layer and on the anterior lens capsule.

  14. Independent learning modules enhance student performance and understanding of anatomy.

    Science.gov (United States)

    Serrat, Maria A; Dom, Aaron M; Buchanan, James T; Williams, Alison R; Efaw, Morgan L; Richardson, Laura L

    2014-01-01

    Didactic lessons are only one part of the multimodal teaching strategies used in gross anatomy courses today. Increased emphasis is placed on providing more opportunities for students to develop lifelong learning and critical thinking skills during medical training. In a pilot program designed to promote more engaged and independent learning in anatomy, self-study modules were introduced to supplement human gross anatomy instruction at Joan C. Edwards School of Medicine at Marshall University. Modules use three-dimensional constructs to help students understand complex anatomical regions. Resources are self-contained in portable bins and are accessible at any time. Students use modules individually or in groups in a structured self-study format that augments material presented in lecture and laboratory. Pilot outcome data, measured by feedback surveys and examination performance statistics, suggest that the activity may be improving learning in gross anatomy. Positive feedback on both pre- and post-examination surveys showed that students felt the activity helped to increase their understanding of the topic. In concordance with student perception, average examination scores on module-related laboratory and lecture questions were higher in the two years of the pilot program compared with the year before its initiation. Modules can be fabricated on a modest budget using minimal resources, making implementation practical for smaller institutions. Upper level medical students assist in module design and upkeep, enabling continuous opportunities for vertical integration across the curriculum. This resource offers a feasible mechanism for enhancing independent and lifelong learning competencies, which could be a valuable complement to any gross anatomy curriculum. © 2014 American Association of Anatomists.

  15. Red algae (Gelidium amansii reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

    Directory of Open Access Journals (Sweden)

    Tsung-Han Yang

    2015-12-01

    Full Text Available Gelidium amansii (GA is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1 rats without diabetes fed a high-fat diet (control group; (2 rats with diabetes fed a high-fat diet; (3 rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4 rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes.

  16. In-line monitoring of cocrystallization process and quantification of carbamazepine-nicotinamide cocrystal using Raman spectroscopy and chemometric tools

    Science.gov (United States)

    Soares, Frederico L. F.; Carneiro, Renato L.

    2017-06-01

    A cocrystallization process may involve several molecular species, which are generally solid under ambient conditions. Thus, accurate monitoring of different components that might appear during the reaction is necessary, as well as quantification of the final product. This work reports for the first time the synthesis of carbamazepine-nicotinamide cocrystal in aqueous media with a full conversion. The reactions were monitored by Raman spectroscopy coupled with Multivariate Curve Resolution - Alternating Least Squares, and the quantification of the final product among its coformers was performed using Raman spectroscopy and Partial Least Squares regression. The slurry reaction was made in four different conditions: room temperature, 40 °C, 60 °C and 80 °C. The slurry reaction at 80 °C enabled a full conversion of initial substrates into the cocrystal form, using water as solvent for a greener method. The employment of MCR-ALS coupled with Raman spectroscopy enabled to observe the main steps of the reactions, such as drug dissolution, nucleation and crystallization of the cocrystal. The PLS models gave mean errors of cross validation around 2.0 (% wt/wt), and errors of validation between 2.5 and 8.2 (% wt/wt) for all components. These were good results since the spectra of cocrystals and the physical mixture of the coformers present some similar peaks.

  17. Topics in the Journal of Counseling Psychology, 1963-2015.

    Science.gov (United States)

    Oh, JungSu; Stewart, Alan E; Phelps, Rosemary E

    2017-11-01

    Historical trends in a scientific field should be apparent in the changing content of journal articles over time. Using a topic modeling approach, a statistical method for quantifying the thematic content of text, 70 topics were extracted from the abstracts of 3,603 articles published in the Journal of Counseling Psychology from 1963 to 2015. After examining interpretability of 70 topics derived from the model, 64 meaningful topics and their trends were named. In addition, the authors also classified some of the related topics into 4 categories-counseling process and outcome, multiculturalism, research methodology, and vocational psychology. Counseling process and outcome related topics have decreased recently, while topics relating to multiculturalism and diversity have shown increasing trends. The authors also discussed trends that were observed and tried to account for the changing frequencies of some important research topics within these categories. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Influence of number of topics, topic duration, and curricular focus on biology achievement of Population 3 TIMSS countries

    Science.gov (United States)

    Hodges, Eddie Louis

    The purposes of this study were to determine if a relationship exists between biology achievement and (1) number of topics, (2) topic duration, (3) curricular focus, and (4) science achievement using TIMSS data from Population 3---the final year of secondary school. Students included in this study were subsets of the 55,675 students from 22 countries who participated in the science literacy portion of TIMSS at the Population 3 level (IEA, 1997). The sample included in this study for the four research questions were comprised of between (1) 17,769 and 37,794 students from 15 countries, (2) 17,769 and 37,794 students from 15 countries, (3) 21,715 and 46,458 students from 18 countries, and (4) 19,518 and 46,458 students from 18 countries, respectively. A Pearson's product moment correlation was used to determine whether a relationship exists between the number of biology topics addressed by intended national science curricula and mean student achievement on selected items by country. No statistically significant correlation was found by country between biology achievement and number of topics. To determine whether a relationship exists between the topic duration of biology topics addressed by released, biology-oriented, Population 3 Science Literacy items and student achievement on those items, a Pearson's product moment correlation was also used. A statistically significant correlation between biology achievement and topic duration for only one topic (Interdependence of Life) was found at the .05 level of significance. A possible relationship between the degree of curricular focus of Population 3 TIMSS countries and student achievement on selected items by country was evaluated using a Pearson's product moment correlation. No statistically significant correlation by country between biology achievement and degree of curricular focus was found. A Pearson's product moment correlation was used to determine whether a relationship exists between science literacy

  19. Syntheses, crystal structures and spectroscopic properties of copper(II)-tetracyanometallate(II) complexes with nicotinamide and isonicotinamide ligands

    Science.gov (United States)

    Sayın, Elvan; Kürkçüoğlu, Güneş Süheyla; Yeşilel, Okan Zafer; Hökelek, Tuncer

    2015-09-01

    Four new one dimensional (1D) cyanide complexes, namely {[Cu(NH3)4(μ-na)][M‧(CN)4]}n and {[Cu(NH3)2(ina)2M‧(μ-CN)2(CN)2]}n (M‧(II) = Pd (1 and 3) or Pt (2 and 4), na:nicotinamide and ina:isonicotinamide) have been synthesized and characterized by elemental, spectral (FT-IR and Raman), and thermal (TG, DTG and DTA) analyses. The crystal structures of complexes 1-3 have been determined by single crystal X-ray diffraction technique. In complexes 1 and 2, na ligand is coordinated to the adjacent Cu(II) ions as a bridging ligand, giving rise to 1D linear cationic chain and the [M‧(CN)4]2- anionic complex acts as a counter ion. Complexes 3 and 4 are also 1D linear chain in which two cyanide ligands bridged neighboring M‧(II) and Cu(II) ions, while ina ligand is coordinated Cu(II) ion through nitrogen atom of pyridine ring. In the complexes, the Cu(II) ions adopt distorted octahedral geometries, while M‧(II) ions are four coordinated with four carbon atoms from cyanide ligands in square-planar geometries. The adjacent chains are further stacked through intermolecular hydrogen bond, Nsbnd Hṡṡṡπ, Csbnd H⋯M‧ and M‧⋯π interactions to form 3D supramolecular networks. Vibration assignments are given for all the observed bands. In addition, thermal stabilities of the compounds are also discussed.

  20. Extracting Hot spots of Topics from Time Stamped Documents

    Science.gov (United States)

    Chen, Wei; Chundi, Parvathi

    2011-01-01

    Identifying time periods with a burst of activities related to a topic has been an important problem in analyzing time-stamped documents. In this paper, we propose an approach to extract a hot spot of a given topic in a time-stamped document set. Topics can be basic, containing a simple list of keywords, or complex. Logical relationships such as and, or, and not are used to build complex topics from basic topics. A concept of presence measure of a topic based on fuzzy set theory is introduced to compute the amount of information related to the topic in the document set. Each interval in the time period of the document set is associated with a numeric value which we call the discrepancy score. A high discrepancy score indicates that the documents in the time interval are more focused on the topic than those outside of the time interval. A hot spot of a given topic is defined as a time interval with the highest discrepancy score. We first describe a naive implementation for extracting hot spots. We then construct an algorithm called EHE (Efficient Hot Spot Extraction) using several efficient strategies to improve performance. We also introduce the notion of a topic DAG to facilitate an efficient computation of presence measures of complex topics. The proposed approach is illustrated by several experiments on a subset of the TDT-Pilot Corpus and DBLP conference data set. The experiments show that the proposed EHE algorithm significantly outperforms the naive one, and the extracted hot spots of given topics are meaningful. PMID:21765568

  1. A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor

    DEFF Research Database (Denmark)

    Olesen, Uffe Høgh; Thougaard, Annemette V; Jensen, Peter Buhl

    2010-01-01

    Inhibitor of nicotinamide phosphoribosyltransferase APO866 is a promising cancer drug currently in phase II clinical trials in oncology. Here, we present a strategy for increasing the therapeutic potential of APO866 through the rescue of normal tissues by coadministration of nicotinic acid (Vitamin...... B(3)). We examined the toxicity profile of APO866 in B6D2F1 mice and the effect of oral administration of nicotinic acid on tissue toxicity. Nicotinic acid (50 mg/kg) protects mice from death and severe toxicity from an APO866 dose (60 mg/kg) four times the monotherapy maximum tolerated dose (15 mg....../kg). In a panel of six cancer cell lines, we find that three (including ML-2 cells) are protected by nicotinic acid in vitro, whereas the cytotoxicity of APO866 remains unaffected in the remaining three (including A2780 cells). A selective biomarker for the protection by nicotinic acid was subsequently identified...

  2. Topics in supergravity and string theory

    International Nuclear Information System (INIS)

    Eastaugh, A.G.

    1987-01-01

    The first topic covered in this dissertation concerns the harmonic expansion technique and its application to the dimensional compactification of higher dimensional supergravity. A simple example is given to explain the method and then the method is applied to the problem of obtaining the mass spectrum of the squashed seven-sphere compactification of eleven dimensional supergravity. The second topic concerns the application of Fujikawa's method of anomaly calculation to the calculation of the critical dimension of various string models. The third topic is a study and explicit calculation of the Fock space representation of the vertex in Witten's formulation of the interacting open bosonic string field theory

  3. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    Directory of Open Access Journals (Sweden)

    David R Lionberger

    2010-11-01

    Full Text Available David R Lionberger1, Michael J Brennan21Southwest Orthopedic Group, Houston, TX, USA; 2Department of Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs, diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9. In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs. The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions

  4. Topics in modern differential geometry

    CERN Document Server

    Verstraelen, Leopold

    2017-01-01

    A variety of introductory articles is provided on a wide range of topics, including variational problems on curves and surfaces with anisotropic curvature. Experts in the fields of Riemannian, Lorentzian and contact geometry present state-of-the-art reviews of their topics. The contributions are written on a graduate level and contain extended bibliographies. The ten chapters are the result of various doctoral courses which were held in 2009 and 2010 at universities in Leuven, Serbia, Romania and Spain.

  5. Key Topics in Sports Medicine

    OpenAIRE

    2006-01-01

    Key Topics in Sports Medicine is a single quick reference source for sports and exercise medicine. It presents the essential information from across relevant topic areas, and includes both the core and emerging issues in this rapidly developing field. It covers: 1) Sports injuries, rehabilitation and injury prevention, 2) Exercise physiology, fitness testing and training, 3) Drugs in sport, 4) Exercise and health promotion, 5) Sport and exercise for special and clinical populations, 6) The ps...

  6. Irreducible Specht modules are signed Young modules

    OpenAIRE

    Hemmer, David J.

    2005-01-01

    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  7. Salicylic Acid Topical

    Science.gov (United States)

    ... the package label for more information.Apply a small amount of the salicylic acid product to one or two small areas you want to treat for 3 days ... know that children and teenagers who have chicken pox or the flu should not use topical salicylic ...

  8. Topical report review status. Volume 9, No. 1

    International Nuclear Information System (INIS)

    1995-02-01

    This report provides industry with procedures for submitting topical reports, guidance on how the US Nuclear Regulatory Commission (NRC) processes and responds to topical report submittals, and an accounting, with review schedules, of all topical reports currently accepted for review by the NRC. This report is published semiannually

  9. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch.

    Science.gov (United States)

    Lionberger, David R; Brennan, Michael J

    2010-11-10

    The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978-2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5-1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical-chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions.

  10. Construction of Context-Based Module: How OLED can be used as a Context in High School Chemistry Instruction

    Science.gov (United States)

    Anugrah, I. R.; Mudzakir, A.; Sumarna, O.

    2017-09-01

    Teaching materials used in Indonesia generally just emphasize remembering skill so that the students’ science literacy is low. Innovation is needed to transform traditional teaching materials so that it can stimulate students’ science literacy, one of which is by context-based approach. This study focused on the construction of context-based module for high school using Organic Light-Emitting Diode (OLED) topics. OLED was chosen because it is an up-to-date topic and relevant to real life. This study used Model of Educational Reconstruction (MER) to reconstruct science content structure about OLED through combining scientist’s perspectives with student’s preconceptions and national curriculum. Literature review of OLED includes its definition, components, characteristics and working principle. Student’s preconceptions about OLED are obtained through interviews. The result shows that student’s preconceptions have not been fully similar with the scientist’s perspective. One of the reasons is that some of the related Chemistry concepts are too complicated. Through curriculum analysis, Chemistry about OLED that are appropriate for high school are Bohr’s atomic theory, redox and organic chemistry including polymers and aromatics. The OLED context and its Chemistry concept were developed into context-based module by adapting science literacy-based learning. This module is expected to increase students’ science literacy performance.

  11. Topical treatment of psoriasis: questionnaire results on topical therapy accessibility and influence of body surface area on usage

    NARCIS (Netherlands)

    Iversen, L.; Lange, M.M. De; Bissonette, R.; Carvalho, A.V.E.; Kerkhof, P.C.M. van de; Kirby, B.; Kleyn, C.E.; Lynde, C.W.; Walt, J.M. van der; Wu, J.J.

    2017-01-01

    BACKGROUND: Topical treatment of mild to moderate psoriasis is first-line treatment and exhibits varying degrees of success across patient groups. Key factors influencing treatment success are physician topical treatment choice (high efficacy, low adverse events) and strict patient adherence.

  12. Hot topics: Signal processing in acoustics

    Science.gov (United States)

    Gaumond, Charles F.

    2005-09-01

    Signal processing in acoustics is a multidisciplinary group of people that work in many areas of acoustics. We have chosen two areas that have shown exciting new applications of signal processing to acoustics or have shown exciting and important results from the use of signal processing. In this session, two hot topics are shown: the use of noiselike acoustic fields to determine sound propagation structure and the use of localization to determine animal behaviors. The first topic shows the application of correlation on geo-acoustic fields to determine the Greens function for propagation through the Earth. These results can then be further used to solve geo-acoustic inverse problems. The first topic also shows the application of correlation using oceanic noise fields to determine the Greens function through the ocean. These results also have utility for oceanic inverse problems. The second topic shows exciting results from the detection, localization, and tracking of marine mammals by two different groups. Results from detection and localization of bullfrogs are shown, too. Each of these studies contributed to the knowledge of animal behavior. [Work supported by ONR.

  13. Topical Valproate Solution for Hair Growth

    Directory of Open Access Journals (Sweden)

    Anil Kakunje

    2018-05-01

    Full Text Available Valproate is used regularly in the treatment of various seizure disorders, bipolar disorder, migraine prophylaxis and off label in many other conditions. Alopecia or hair loss is cosmetic side effect of oral valproate administration. Hair loss with valproate is diffused, non-scarring and dose related. A large number of drugs may interfere with the hair cycle and produce hair loss. We have only a few drugs like Minoxidil, Finasteride used for hair regeneration and both have its own side effects and limitations. In contrast to oral ingestions of valproate causing hair loss, early experiments with topical Valproic acid cream showed hair regeneration. Valproic acid cream is currently unavailable in the market, alternatively, we do have valproate and divalproex solutions available in various strengths which have a potential to be used topically for hair regeneration. The side effects and cost of topical valproate solution could be much less than the available options in the market. Valproate solution topically has the potential to be used for hair growth.

  14. Evaluating topic model interpretability from a primary care physician perspective.

    Science.gov (United States)

    Arnold, Corey W; Oh, Andrea; Chen, Shawn; Speier, William

    2016-02-01

    Probabilistic topic models provide an unsupervised method for analyzing unstructured text. These models discover semantically coherent combinations of words (topics) that could be integrated in a clinical automatic summarization system for primary care physicians performing chart review. However, the human interpretability of topics discovered from clinical reports is unknown. Our objective is to assess the coherence of topics and their ability to represent the contents of clinical reports from a primary care physician's point of view. Three latent Dirichlet allocation models (50 topics, 100 topics, and 150 topics) were fit to a large collection of clinical reports. Topics were manually evaluated by primary care physicians and graduate students. Wilcoxon Signed-Rank Tests for Paired Samples were used to evaluate differences between different topic models, while differences in performance between students and primary care physicians (PCPs) were tested using Mann-Whitney U tests for each of the tasks. While the 150-topic model produced the best log likelihood, participants were most accurate at identifying words that did not belong in topics learned by the 100-topic model, suggesting that 100 topics provides better relative granularity of discovered semantic themes for the data set used in this study. Models were comparable in their ability to represent the contents of documents. Primary care physicians significantly outperformed students in both tasks. This work establishes a baseline of interpretability for topic models trained with clinical reports, and provides insights on the appropriateness of using topic models for informatics applications. Our results indicate that PCPs find discovered topics more coherent and representative of clinical reports relative to students, warranting further research into their use for automatic summarization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Topics on continua

    CERN Document Server

    Macias, Sergio

    2005-01-01

    Specialized as it might be, continuum theory is one of the most intriguing areas in mathematics. However, despite being popular journal fare, few books have thoroughly explored this interesting aspect of topology. In Topics on Continua, Sergio Macías, one of the field's leading scholars, presents four of his favorite continuum topics: inverse limits, Jones's set function T, homogenous continua, and n-fold hyperspaces, and in doing so, presents the most complete set of theorems and proofs ever contained in a single topology volume. Many of the results presented have previously appeared only in research papers, and some appear here for the first time. After building the requisite background and exploring the inverse limits of continua, the discussions focus on Professor Jones''s set function T and continua for which T is continuous. An introduction to topological groups and group actions lead to a proof of Effros''s Theorem, followed by a presentation of two decomposition theorems. The author then offers an...

  16. Topical cholesterol in clofazimine induced ichthyosis

    Directory of Open Access Journals (Sweden)

    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  17. Topical antibiotic monotherapy prescribing practices in acne vulgaris.

    Science.gov (United States)

    Hoover, William D; Davis, Scott A; Fleischer, Alan B; Feldman, Steven R

    2014-04-01

    The aim of this study is to evaluate the frequency of dosing topical antibiotics as monotherapy in the treatment of acne vulgaris, and physician specialty prescribing these medications. This study is a retrospective review of all visits with a sole diagnosis of acne vulgaris (ICD-9-CM code 706.1) found on the National Ambulatory Medical Care Survey (NAMCS) in 1993-2010. We recorded the number of visits surveyed where acne vulgaris was the sole diagnosis, number of visits where topical antibiotics were the only treatment prescribed, and the specialty of physician in each encounter. Topical erythromycin or clindamycin were the sole medication prescribed in 0.81% of the visits recorded, with 60% of these prescriptions arising from dermatologists and 40% from non-dermatologists. The trend of prescribing topical antibiotic monotherapy is declining (p acnes to topical antibiotic regimens has led to the need to re-evaluate the use of topical antibiotics in the treatment of acne vulgaris. While the rate of topical antibiotic monotherapy is declining, their use should be reserved for situations where the direct need for antibiotics arises. If a clinician feels that antibiotics are a necessary component to acne therapy, they should be used as part of a combination regimen.

  18. Development of oxybutynin chloride topical gel for overactive bladder

    Directory of Open Access Journals (Sweden)

    Lucente VR

    2011-04-01

    Full Text Available Vincent R Lucente1, David R Staskin2, Elise De31Institute of Female Pelvic Medicine and Reconstructive Surgery, Allentown, PA, USA; 2Division of Urology, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA, USA; 3Urological Institute of Northeastern New York, Albany, NY, USAAbstract: Overactive bladder (OAB is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo

  19. Signed Young Modules and Simple Specht Modules

    OpenAIRE

    Danz, Susanne; Lim, Kay Jin

    2015-01-01

    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  20. Baby Health Checkup: MedlinePlus Health Topic

    Science.gov (United States)

    ... Know (Centers for Disease Control and Prevention) - PDF Topic Image MedlinePlus Email Updates Get Baby Health Checkup ... GO MEDICAL ENCYCLOPEDIA Well-child visits Related Health Topics Childhood Immunization Common Infant and Newborn Problems Infant ...

  1. Laser Eye Surgery: MedlinePlus Health Topic

    Science.gov (United States)

    ... corneal surgery - discharge (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Laser Eye Surgery ... surgery - what to ask your doctor Related Health Topics Refractive Errors National Institutes of Health The primary ...

  2. Child Mental Health: MedlinePlus Health Topic

    Science.gov (United States)

    ... events and children (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Child Mental Health ... in childhood Traumatic events and children Related Health Topics Bullying Child Behavior Disorders Mental Disorders Mental Health ...

  3. Bone Marrow Transplantation: MedlinePlus Health Topic

    Science.gov (United States)

    ... marrow transplant - discharge (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Bone Marrow Transplantation ... transplant - slideshow Graft-versus-host disease Related Health Topics Bone Marrow Diseases Stem Cells National Institutes of ...

  4. Nutrition for Seniors: MedlinePlus Health Topic

    Science.gov (United States)

    ... America) National Institute on Aging Also in Spanish Topic Image MedlinePlus Email Updates Get Nutrition for Seniors updates by email What's this? GO Related Health Topics Nutrition Seniors' Health National Institutes of Health The ...

  5. Blood Count Tests: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish WBC count (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Blood Count Tests ... WBC count Show More Show Less Related Health Topics Bleeding Disorders Blood Laboratory Tests National Institutes of ...

  6. Hormone Replacement Therapy: MedlinePlus Health Topic

    Science.gov (United States)

    ... of hormone therapy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hormone Replacement Therapy ... Estrogen overdose Types of hormone therapy Related Health Topics Menopause National Institutes of Health The primary NIH ...

  7. Topics in millimeter wave technology

    CERN Document Server

    Button, Kenneth

    1988-01-01

    Topics in Millimeter Wave Technology, Volume 1 presents topics related to millimeter wave technology, including fin-lines and passive components realized in fin-lines, suspended striplines, suspended substrate microstrips, and modal power exchange in multimode fibers. A miniaturized monopulse assembly constructed in planar waveguide with multimode scalar horn feeds is also described. This volume is comprised of five chapters; the first of which deals with the analysis and synthesis techniques for fin-lines as well as the various passive components realized in fin-line. Tapers, discontinuities,

  8. Meteorological Instrumentation and Measurements Open Resource Training Modules for Undergraduate and Graduate Education

    Science.gov (United States)

    Rockwell, A.; Clark, R. D.; Stevermer, A.

    2017-12-01

    The National Center for Atmospheric Research Earth Observing Laboratory, Millersville University and The COMET Program are collaborating to produce a series of nine online modules on the the topic of meteorological instrumentation and measurements. These interactive, multimedia educational modules can be integrated into undergraduate and graduate meteorology courses on instrumentation, measurement science, and observing systems to supplement traditional pedagogies and enhance blended instruction. These freely available and open-source training tools are designed to supplement traditional pedagogies and enhance blended instruction. Three of the modules are now available and address the theory and application of Instrument Performance Characteristics, Meteorological Temperature Instrumentation and Measurements, and Meteorological Pressure Instrumentation and Measurements. The content of these modules is of the highest caliber as it has been developed by scientists and engineers who are at the forefront of the field of observational science. Communicating the availability of these unique and influential educational resources with the community is of high priority. These modules will have a profound effect on the atmospheric observational sciences community by fulfilling a need for contemporary, interactive, multimedia guided education and training modules integrating the latest instructional design and assessment tools in observational science. Thousands of undergraduate and graduate students will benefit, while course instructors will value a set of high quality modules to use as supplements to their courses. The modules can serve as an alternative to observational research training and fill the void between field projects or assist those schools that lack the resources to stage a field- or laboratory-based instrumentation experience.

  9. Thin-film-based CdTe photovoltaic module characterization: measurements and energy prediction improvement.

    Science.gov (United States)

    Lay-Ekuakille, A; Arnesano, A; Vergallo, P

    2013-01-01

    Photovoltaic characterization is a topic of major interest in the field of renewable energy. Monocrystalline and polycrystalline modules are mostly used and, hence characterized since many laboratories have data of them. Conversely, cadmium telluride (CdTe), as thin-film module are, in some circumstances, difficult to be used for energy prediction. This work covers outdoor testing of photovoltaic modules, in particular that regarding CdTe ones. The scope is to obtain temperature coefficients that best predict the energy production. A First Solar (K-275) module has been used for the purposes of this research. Outdoor characterizations were performed at Department of Innovation Engineering, University of Salento, Lecce, Italy. The location of Lecce city represents a typical site in the South Italy. The module was exposed outdoor and tested under clear sky conditions as well as under cloudy sky ones. During testing, the global-inclined irradiance varied between 0 and 1500 W/m(2). About 37,000 I-V characteristics were acquired, allowing to process temperature coefficients as a function of irradiance and ambient temperature. The module was characterized by measuring the full temperature-irradiance matrix in the range from 50 to 1300 W/m(2) and from -1 to 40 W/m(2) from October 2011 to February 2012. Afterwards, the module energy output, under real conditions, was calculated with the "matrix method" of SUPSI-ISAAC and the results were compared with the five months energy output data of the same module measured with the outdoor energy yield facility in Lecce.

  10. Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

    Science.gov (United States)

    Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

    2006-07-01

    Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

  11. Crystal structure and Hirshfeld surface analysis of aqua-bis-(nicotinamide-κN)bis-(4-sulfamoylbenzoato-κO1)copper(II).

    Science.gov (United States)

    Hökelek, Tuncer; Yavuz, Vijdan; Dal, Hakan; Necefoğlu, Hacali

    2018-01-01

    In the crystal of the title complex, [Cu(C 7 H 6 NO 4 S) 2 (C 6 H 6 N 2 O) 2 (H 2 O)], the Cu II cation and the O atom of the coordinated water mol-ecule reside on a twofold rotation axis. The Cu II ion is coordinated by two carboxyl-ate O atoms of the two symmetry-related 4-sulfamoylbenzoate (SB) anions and by two N atoms of the two symmetry-related nicotinamide (NA) mol-ecules at distances of 1.978 (2) and 2.025 (3) Å, respectively, forming a slightly distorted square-planar arrangement. The distorted square-pyramidal coordination environment is completed by the water O atom in the axial position at a distance of 2.147 (4) Å. In the crystal, the mol-ecules are linked via O-H⋯O and N-H⋯O hydrogen bonds with R 2 2 (8) and R 2 2 (18) ring motifs, forming a three-dimensional architecture. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯O/O⋯H (42.2%), H⋯H (25.7%) and H⋯C/C⋯H (20.0%) inter-actions.

  12. Transferable Training Modules: Building Environmental Education Opportunities With and for Mexican Community Health Workers (Promotores de Salud).

    Science.gov (United States)

    Ramírez, Denise Moreno; Vea, Lourdes; Field, James A; Baker, Paul B; Gandolfi, A Jay; Maier, Raina M

    Community health workers (promotores de salud) have the ability to empower communities to mitigate negative health outcomes. Current training efforts in environmental topics are lacking. This project addressed this gap by developing 4 transferable training modules on environmental health. By applying a series of surveys, interviews, and trainings, we evaluated their relevance. Partners provided favorable feedback for 3 of the 4 modules. It was also learned that the development method could be improved by engaging technically trained promotores de salud in the role of co-creators. This project has implications for environmental justice communities as it can lessen information disparities.

  13. Topical report review status. Volume 7, No. 2

    International Nuclear Information System (INIS)

    1984-11-01

    Purpose of this document is to provide periodic progress reports of on-going topical report reviews, to identify those topical reports for which the NRC staff review has been completed and those which are under review and to provide NRC management with sufficient information regarding the conduct of the topical report program to permit taking whatever actions are deemed necessary or appropriate. This document is also intended to be a source of information to NRC Licensing Project Managers and other NRC personnel regarding the status of topical reports which may be referenced in applications for which they have responsibility

  14. Development and Evaluation of Topical Gabapentin Formulations

    Science.gov (United States)

    Alcock, Natalie; Hiom, Sarah; Birchall, James C.

    2017-01-01

    Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. PMID:28867811

  15. Selected topics in nuclear structure

    Energy Technology Data Exchange (ETDEWEB)

    Solov` ev, V G; Gromov, K Ya; Malov, L A; Shilov, V M

    1994-12-31

    The Fourth International Conference on selected topics in nuclear structure was held at Dubna in July 1994 on recent experimental and theoretical investigations in nuclear structure. Topics discussed were the following: nuclear structure at low-energy excitations (collective quasiparticle phenomena, proton-neutron interactions, microscopic and phenomenological theories of nuclear structure; nuclear structure studies with charged particles). heavy ions, neutrons and photons; nuclei at high angular momenta and superdeformation, structure and decay properties of giant resonances, charge-exchange resonances and {beta}-decay; semiclassical approach of large amplitude collective motion and structure of hot nuclei.

  16. Topics in current aerosol research

    CERN Document Server

    Hidy, G M

    1971-01-01

    Topics in Current Aerosol Research deals with the fundamental aspects of aerosol science, with emphasis on experiment and theory describing highly dispersed aerosols (HDAs) as well as the dynamics of charged suspensions. Topics covered range from the basic properties of HDAs to their formation and methods of generation; sources of electric charges; interactions between fluid and aerosol particles; and one-dimensional motion of charged cloud of particles. This volume is comprised of 13 chapters and begins with an introduction to the basic properties of HDAs, followed by a discussion on the form

  17. Selected topics in nuclear structure

    International Nuclear Information System (INIS)

    Solov'ev, V.G.; Gromov, K.Ya.; Malov, L.A.; Shilov, V.M.

    1994-01-01

    The Fourth International Conference on selected topics in nuclear structure was held at Dubna in July 1994 on recent experimental and theoretical investigations in nuclear structure. Topics discussed were the following: nuclear structure at low-energy excitations (collective quasiparticle phenomena, proton-neutron interactions, microscopic and phenomenological theories of nuclear structure; nuclear structure studies with charged particles. heavy ions, neutrons and photons; nuclei at high angular momenta and superdeformation, structure and decay properties of giant resonances, charge-exchange resonances and β-decay; semiclassical approach of large amplitude collective motion and structure of hot nuclei

  18. Topical Antibacterials and Global Challenges on Resistance ...

    African Journals Online (AJOL)

    skin infections can be easily treated with topical antibacterial medication that is available over the counter or by ... infection in minor cut or burn, eyes and ear infection [5]. .... Sensitive/dry skin ... includes both oral and topical antibiotics, but.

  19. Topical phenytoin for treating pressure ulcers.

    Science.gov (United States)

    Hao, Xiang Yong; Li, Hong Ling; Su, He; Cai, Hui; Guo, Tian Kang; Liu, Ruifeng; Jiang, Lei; Shen, Yan Fei

    2017-02-22

    Pressure ulcers are common in clinical practice and pose a significant health problem worldwide. Apart from causing suffering to patients, they also result in longer hospital stays and increase the cost of health care. A variety of methods are used for treating pressure ulcers, including pressure relief, patient repositioning, biophysical strategies, nutritional supplementation, debridement, topical negative pressure, and local treatments including dressings, ointments and creams such as bacitracin, silver sulphadiazine, neomycin, and phenytoin. Phenytoin is a drug more commonly used in the treatment of epilepsy, but may play an important role in accelerating ulcer healing. To assess the effects of topical phenytoin on the rate of healing of pressure ulcers of any grade, in any care setting. In September 2016, we searched the following electronic databases to identify relevant randomized clinical trials: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid Embase; and EBSCO CINAHL Plus. We handsearched conference proceedings from the European Pressure Ulcer Advisory Panel, European Wound Management Association and the Tissue Viability Society for all available years. We searched the references of the retrieved trials to identify further relevant trials. We also searched clinical trials registries to identify ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting. We included all randomized controlled trials (RCTs) addressing the effects (both benefits and harms) of topical phenytoin on the healing of pressure ulcers of any grade compared with placebo or alternative treatments or no therapy, irrespective of blinding, language, and publication status. Two review authors independently selected studies, extracted information on participants, interventions, methods and results and assessed risk of bias using

  20. Quadrature amplitude modulation from basics to adaptive trellis-coded turbo-equalised and space-time coded OFDM CDMA and MC-CDMA systems

    CERN Document Server

    Hanzo, Lajos

    2004-01-01

    "Now fully revised and updated, with more than 300 pages of new material, this new edition presents the wide range of recent developments in the field and places particular emphasis on the family of coded modulation aided OFDM and CDMA schemes. In addition, it also includes a fully revised chapter on adaptive modulation and a new chapter characterizing the design trade-offs of adaptive modulation and space-time coding." "In summary, this volume amalgamates a comprehensive textbook with a deep research monograph on the topic of QAM, ensuring it has a wide-ranging appeal for both senior undergraduate and postgraduate students as well as practicing engineers and researchers."--Jacket.

  1. Topics in Finance Part VII--Dividend Policy

    Science.gov (United States)

    Laux, Judy

    2011-01-01

    This series inspects the major topics in finance, reviewing the roles of stockholder wealth maximization, the risk-return tradeoff, and agency conflicts. The current article, devoted to dividend policy, also reviews the topic as presented in textbooks and the literature.

  2. Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle.

    Science.gov (United States)

    Gameiro, Paulo A; Laviolette, Laura A; Kelleher, Joanne K; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-05-03

    Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of α-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)(+) cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)(+) ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle.

  3. Topics in Nuclear Astrophysics

    International Nuclear Information System (INIS)

    Chung, K.C.

    1982-01-01

    Some topics in nuclear astrophysics are discussed, e.g.: highly evolved stellar cores, stellar evolution (through the temperature analysis of stellar surface), nucleosynthesis and finally the solar neutrino problem. (L.C.) [pt

  4. Performance of 7-cells Dye Sensitized Solar Module in Z-type Series Interconnection

    Science.gov (United States)

    Nur Anggraini, Putri; Muliani, Lia; Maulani Nursam, Natalita; Hidayat, Jojo

    2018-01-01

    Dye sensitized solar cells (DSSC) is becoming attractive research topic as third generation solar cells technology since it provides clean energy and low cost fabrication. In this study, DSSC was fabricated into module scale, which is important for practical applications. The module was prepared in sandwich structure consisting of TiO2 working electrode and Pt counter electrode on conductive substrate with an area of 100 mm x 100 mm, which was distributed into seven active cells. TiO2 paste was deposited on FTO glass as working electrode with a size of 10 mm x 98 mm per unit cell by screen printing method. Each cell was connected in Z-type series that able to produce high voltage. I - V measurement was applied in two methods consisting of laboratory testing using sun simulator under 500 W/m2 of illumination and outdoor testing using a digital multimeter under direct sunlight. The result shows that DSSC module has photoconversion efficiency of 1.08% and 1.17% for laboratory and outdoor testing, respectively. The module was also tested in three different times to monitor its stability performance.

  5. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide.

    Science.gov (United States)

    Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

    2015-12-01

    Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes. Copyright © 2015. Published by Elsevier B.V.

  6. Case Of Iatrogenic Cushing's Syndrome By Topical Triamcinolone.

    Science.gov (United States)

    Zil-E-Ali, Ahsan; Janjua, Omer Hanif; Latif, Aiza; Aadil, Muhammad

    2018-01-01

    Cushing's syndrome is a collection of signs and symptoms due to hypercortisolism. Prolong use of topical steroid may cause this syndrome and suppression of hypothalamic and pituitary function, however such events are more common with oral and parenteral route. There are very few cases of Cushing's syndrome with a topical application amongst which triamcinolone is the rarest drug. We report a case of 11-year-old boy is presented who developed Cushing's disease by topical application. The child had body rashes for which the caregiver consulted a local quack, a topical cream of triamcinolone was prescribed. After application for three months, the patient became obese and developed a moon-like face. A thorough biochemical workup and diagnostic test for Cushing's disease was done to confirm. The following case report a dramatic example of development of the syndrome from chronic topical application of the least potent corticosteroid.

  7. Interpretable Topic Features for Post-ICU Mortality Prediction.

    Science.gov (United States)

    Luo, Yen-Fu; Rumshisky, Anna

    2016-01-01

    Electronic health records provide valuable resources for understanding the correlation between various diseases and mortality. The analysis of post-discharge mortality is critical for healthcare professionals to follow up potential causes of death after a patient is discharged from the hospital and give prompt treatment. Moreover, it may reduce the cost derived from readmissions and improve the quality of healthcare. Our work focused on post-discharge ICU mortality prediction. In addition to features derived from physiological measurements, we incorporated ICD-9-CM hierarchy into Bayesian topic model learning and extracted topic features from medical notes. We achieved highest AUCs of 0.835 and 0.829 for 30-day and 6-month post-discharge mortality prediction using baseline and topic proportions derived from Labeled-LDA. Moreover, our work emphasized the interpretability of topic features derived from topic model which may facilitates the understanding and investigation of the complexity between mortality and diseases.

  8. Exploring Topic Structure: Coherence, Diversity and Relatedness

    NARCIS (Netherlands)

    J. He (Jiyin)

    2011-01-01

    htmlabstractThe use of topical information has long been studied in the context of information retrieval. For example, grouping search results into topical categories enables more effective information presentation to users, while grouping documents in a collection can lead to efficient information

  9. topicmodels: An R Package for Fitting Topic Models

    Directory of Open Access Journals (Sweden)

    Bettina Grun

    2011-05-01

    Full Text Available Topic models allow the probabilistic modeling of term frequency occurrences in documents. The fitted model can be used to estimate the similarity between documents as well as between a set of specified keywords using an additional layer of latent variables which are referred to as topics. The R package topicmodels provides basic infrastructure for fitting topic models based on data structures from the text mining package tm. The package includes interfaces to two algorithms for fitting topic models: the variational expectation-maximization algorithm provided by David M. Blei and co-authors and an algorithm using Gibbs sampling by Xuan-Hieu Phan and co-authors.

  10. Topical Research: Africa.

    Science.gov (United States)

    Lynn, Karen

    This lesson plan can be used in social studies, language arts, or library research. The instructional objective is for students to select a topic of study relating to Africa, write a thesis statement, collect information from media sources, and develop a conclusion. The teacher may assign the lesson for written or oral evaluation. The teacher…

  11. Topic structure affects semantic integration: evidence from event-related potentials.

    Science.gov (United States)

    Yang, Xiaohong; Chen, Xuhai; Chen, Shuang; Xu, Xiaoying; Yang, Yufang

    2013-01-01

    This study investigated whether semantic integration in discourse context could be influenced by topic structure using event-related brain potentials. Participants read discourses in which the last sentence contained a critical word that was either congruent or incongruent with the topic established in the first sentence. The intervening sentences between the first and the last sentence of the discourse either maintained or shifted the original topic. Results showed that incongruent words in topic-maintained discourses elicited an N400 effect that was broadly distributed over the scalp while those in topic-shifted discourses elicited an N400 effect that was lateralized to the right hemisphere and localized over central and posterior areas. Moreover, a late positivity effect was only elicited by incongruent words in topic-shifted discourses, but not in topic-maintained discourses. This suggests an important role for discourse structure in semantic integration, such that compared with topic-maintained discourses, the complexity of discourse structure in topic-shifted condition reduces the initial stage of semantic integration and enhances the later stage in which a mental representation is updated.

  12. Anti-inflammatory activity of Punica granatum L. (Pomegranate) rind extracts applied topically to ex vivo skin.

    Science.gov (United States)

    Houston, David M J; Bugert, Joachim; Denyer, Stephen P; Heard, Charles M

    2017-03-01

    Coadministered pomegranate rind extract (PRE) and zinc (II) produces a potent virucidal activity against Herpes simplex virus (HSV); however, HSV infections are also associated with localised inflammation and pain. Here, the objective was to determine the anti-inflammatory activity and relative depth penetration of PRE, total pomegranate tannins (TPT) and zinc (II) in skin, ex vivo. PRE, TPT and ZnSO 4 were dosed onto freshly excised ex vivo porcine skin mounted in Franz diffusion cells and analysed for COX-2, as a marker for modulation of the arachidonic acid inflammation pathway, by Western blotting and immunohistochemistry. Tape stripping was carried out to construct relative depth profiles. Topical application of PRE to ex vivo skin downregulated expression of COX-2, which was significant after just 6h, and maintained for up to 24h. This was achieved with intact stratum corneum, proving that punicalagin penetrated skin, further supported by the depth profiling data. When PRE and ZnSO 4 were applied together, statistically equal downregulation of COX-2 was observed when compared to the application of PRE alone; no effect followed the application of ZnSO 4 alone. TPT downregulated COX-2 less than PRE, indicating that tannins alone may not be entirely responsible for the anti-inflammatory activity of PRE. Punicalagin was found throughout the skin, in particular the lower regions, indicating appendageal delivery as a significant route to the viable epidermis. Topical application of TPT and PRE had significant anti-inflammatory effects in ex vivo skin, confirming that PRE penetrates the skin and modulates COX-2 regulation in the viable epidermis. Pomegranates have potential as a novel approach in ameliorating the inflammation and pain associated with a range of skin conditions, including cold sores and herpetic stromal keratitis. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Diclofenac Topical (osteoarthritis pain)

    Science.gov (United States)

    ... gel (Voltaren) is used to relieve pain from osteoarthritis (arthritis caused by a breakdown of the lining ... Diclofenac topical liquid (Pennsaid) is used to relieve osteoarthritis pain in the knees. Diclofenac is in a ...

  14. Diclofenac Topical (actinic keratosis)

    Science.gov (United States)

    ... topical gel (Solaraze) is used to treat actinic keratosis (flat, scaly growths on the skin caused by ... The way diclofenac gel works to treat actinic keratosis is not known.Diclofenac is also available as ...

  15. Digital Social Network Mining for Topic Discovery

    Science.gov (United States)

    Moradianzadeh, Pooya; Mohi, Maryam; Sadighi Moshkenani, Mohsen

    Networked computers are expanding more and more around the world, and digital social networks becoming of great importance for many people's work and leisure. This paper mainly focused on discovering the topic of exchanging information in digital social network. In brief, our method is to use a hierarchical dictionary of related topics and words that mapped to a graph. Then, with comparing the extracted keywords from the context of social network with graph nodes, probability of relation between context and desired topics will be computed. This model can be used in many applications such as advertising, viral marketing and high-risk group detection.

  16. Development and Evaluation of Topical Gabapentin Formulations

    Directory of Open Access Journals (Sweden)

    Christopher J. Martin

    2017-08-01

    Full Text Available Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w gabapentin 0.75% (w/w Carbopol® hydrogels containing 5% (w/w DMSO or 70% (w/w ethanol and a compounded 10% (w/w gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.

  17. Antimicrobial topical agents used in the vagina.

    Science.gov (United States)

    Frey Tirri, Brigitte

    2011-01-01

    Vaginally applied antimicrobial agents are widely used in the vagina in women with lower genital tract infections. An 'antimicrobial' is a general term that refers to a group of drugs that are effective against bacteria, fungi, viruses and protozoa. Topical treatments can be prescribed for a wide variety of vaginal infections. Many bacterial infections, such as bacterial vaginosis, desquamative inflammatory vaginitis or, as some European authors call it, aerobic vaginitis as well as infection with Staphylococcus aureus or group A streptococci, may be treated in this way. Candida vulvovaginitis is a fungal infection that is very amenable to topical treatment. The most common viral infections which can be treated with topical medications are condylomata acuminata and herpes simplex. The most often encountered protozoal vaginitis, which is caused by Trichomonas vaginalis, may be susceptible to topical medications, although this infection is treated systemically. This chapter covers the wide variety of commonly used topical antimicrobial agents for these diseases and focuses on the individual therapeutic agents and their clinical efficacy. In addition, potential difficulties that can occur in practice, as well as the usage of these medications in the special setting of pregnancy, are described in this chapter. Copyright © 2011 S. Karger AG, Basel.

  18. Improvement of Nicotinic Acid and Nicotinamide Analysis in Meats and Meat Products by HPLC and LC-MS/MS with Solid-Phase Extraction.

    Science.gov (United States)

    Hiki, Asako; Yamajima, Yukiko; Uematsu, Yoko

    2016-01-01

    A method for nicotinic acid (NA) and nicotinamide (NAA) analysis in meats was developed. NA and NAA were extracted from meats or meat products with metaphosphate aqueous solution. The extract was cleaned up with an Oasis MCX cartridge. The cartridge was washed with 2% acetic acid (v/v) and acetic acid-methanol solution. NA and NAA were eluted with ammonia-methanol solution. NA and NAA in the eluate were chromatographed on a Scherzo SM-C18 (3.0×150 mm, 3.0 μm) column with 20 mmol/L ammonium acetate containing 0.1% acetic acid-acetonitrile (97 : 3) as a mobile phase and were monitored at 261 nm. Quantification was performed by LC and LC-MS/MS. Calibration curves showed high linearity (correlation coefficient>0.998) between 1-25 μg/mL for LC and LC-MS/MS. Recoveries were 84-108% (CV≦5.8%) by HPLC and 79-105% (CV≦9.0%) by LC-MS/MS. The limit of quantitation for NA was 0.005-0.01 g/kg and that for NAA was 0.01-0.02 g/kg.

  19. Validity and Practitality of Acid-Base Module Based on Guided Discovery Learning for Senior High School

    Science.gov (United States)

    Yerimadesi; Bayharti; Jannah, S. M.; Lufri; Festiyed; Kiram, Y.

    2018-04-01

    This Research and Development(R&D) aims to produce guided discovery learning based module on topic of acid-base and determine its validity and practicality in learning. Module development used Four D (4-D) model (define, design, develop and disseminate).This research was performed until development stage. Research’s instruments were validity and practicality questionnaires. Module was validated by five experts (three chemistry lecturers of Universitas Negeri Padang and two chemistry teachers of SMAN 9 Padang). Practicality test was done by two chemistry teachers and 30 students of SMAN 9 Padang. Kappa Cohen’s was used to analyze validity and practicality. The average moment kappa was 0.86 for validity and those for practicality were 0.85 by teachers and 0.76 by students revealing high category. It can be concluded that validity and practicality was proven for high school chemistry learning.

  20. Vodcasts and active-learning exercises in a "flipped classroom" model of a renal pharmacotherapy module.

    Science.gov (United States)

    Pierce, Richard; Fox, Jeremy

    2012-12-12

    To implement a "flipped classroom" model for a renal pharmacotherapy topic module and assess the impact on pharmacy students' performance and attitudes. Students viewed vodcasts (video podcasts) of lectures prior to the scheduled class and then discussed interactive cases of patients with end-stage renal disease in class. A process-oriented guided inquiry learning (POGIL) activity was developed and implemented that complemented, summarized, and allowed for application of the material contained in the previously viewed lectures. Students' performance on the final examination significantly improved compared to performance of students the previous year who completed the same module in a traditional classroom setting. Students' opinions of the POGIL activity and the flipped classroom instructional model were mostly positive. Implementing a flipped classroom model to teach a renal pharmacotherapy module resulted in improved student performance and favorable student perceptions about the instructional approach. Some of the factors that may have contributed to students' improved scores included: student mediated contact with the course material prior to classes, benchmark and formative assessments administered during the module, and the interactive class activities.

  1. Influence of input matrix representation on topic modelling performance

    CSIR Research Space (South Africa)

    De Waal, A

    2010-11-01

    Full Text Available Topic models explain a collection of documents with a small set of distributions over terms. These distributions over terms define the topics. Topic models ignore the structure of documents and use a bag-of-words approach which relies solely...

  2. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2014-09-02

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

  3. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

    Directory of Open Access Journals (Sweden)

    Deng-Fu Yang

    2014-09-01

    Conclusion: We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT.

  4. A Data-Based Approach to Discovering Multi-Topic Influential Leaders.

    Directory of Open Access Journals (Sweden)

    Xing Tang

    Full Text Available Recently, increasing numbers of users have adopted microblogging services as their main information source. However, most of them find themselves drowning in the millions of posts produced by other users every day. To cope with this, identifying a set of the most influential people is paramount. Moreover, finding a set of related influential users to expand the coverage of one particular topic is required in real world scenarios. Most of the existing algorithms in this area focus on topology-related methods such as PageRank. These methods mine link structures to find the expected influential rank of users. However, because they ignore the interaction data, these methods turn out to be less effective in social networks. In reality, a variety of topics exist within the information diffusing through the network. Because they have different interests, users play different roles in the diffusion of information related to different topics. As a result, distinguishing influential leaders according to different topics is also worthy of research. In this paper, we propose a multi-topic influence diffusion model (MTID based on traces acquired from historic information. We decompose the influential scores of users into two parts: the direct influence determined by information propagation along the link structure and indirect influence that extends beyond the restrictions of direct follower relationships. To model the network from a multi-topical viewpoint, we introduce topic pools, each of which represents a particular topic information source. Then, we extract the topic distributions from the traces of tweets, determining the influence propagation probability and content generation probability. In the network, we adopt multiple ground nodes representing topic pools to connect every user through bidirectional links. Based on this multi-topical view of the network, we further introduce the topic-dependent rank (TD-Rank algorithm to identify the multi-topic

  5. A Data-Based Approach to Discovering Multi-Topic Influential Leaders.

    Science.gov (United States)

    Tang, Xing; Miao, Qiguang; Yu, Shangshang; Quan, Yining

    2016-01-01

    Recently, increasing numbers of users have adopted microblogging services as their main information source. However, most of them find themselves drowning in the millions of posts produced by other users every day. To cope with this, identifying a set of the most influential people is paramount. Moreover, finding a set of related influential users to expand the coverage of one particular topic is required in real world scenarios. Most of the existing algorithms in this area focus on topology-related methods such as PageRank. These methods mine link structures to find the expected influential rank of users. However, because they ignore the interaction data, these methods turn out to be less effective in social networks. In reality, a variety of topics exist within the information diffusing through the network. Because they have different interests, users play different roles in the diffusion of information related to different topics. As a result, distinguishing influential leaders according to different topics is also worthy of research. In this paper, we propose a multi-topic influence diffusion model (MTID) based on traces acquired from historic information. We decompose the influential scores of users into two parts: the direct influence determined by information propagation along the link structure and indirect influence that extends beyond the restrictions of direct follower relationships. To model the network from a multi-topical viewpoint, we introduce topic pools, each of which represents a particular topic information source. Then, we extract the topic distributions from the traces of tweets, determining the influence propagation probability and content generation probability. In the network, we adopt multiple ground nodes representing topic pools to connect every user through bidirectional links. Based on this multi-topical view of the network, we further introduce the topic-dependent rank (TD-Rank) algorithm to identify the multi-topic influential users

  6. Interactional Organization and Topic Control in Conciliation Hearings

    Directory of Open Access Journals (Sweden)

    Wânia Terezinha Ladeira

    2011-07-01

    Full Text Available We analyse discursive topic in talk-in-interaction within the institutional setting of three conciliation hearings held in a kind of small claims court for consumption conflict resolution. This research is based on Interactional Sociolinguistics and Conversation Analysis theories. The analysis shows that the participants of those meetings have asymmetric rights regarding the choice of discussion topics. Thus, the mediator is the one who has the right to suggest and control the discursive topics of the conversation. This topic control is the most important institutional procedure that can cause a reduction in accusations and adjacent replies. Consequently, the chance of mediators achieving their institutional task of reaching an agreement between parts in conflict is increased.

  7. The use of compound topical anesthetics: a review.

    Science.gov (United States)

    Kravitz, Neal D

    2007-10-01

    The author reviewed the history of, federal regulations regarding, risks of and adverse drug reactions of five compound topical anesthetics: tetracaine, adrenaline/epinephrine and cocaine (TAC); lidocaine, adrenaline/epinephrine and tetracaine (LET); lidocaine, tetracaine and phenylephrine (TAC 20 percent Alternate); lidocaine, prilocaine and tetracaine (Profound); and lidocaine, prilocaine, tetracaine and phenylephrine with thickeners (Profound PET). The author reviewed clinical trials, case reports, descriptive articles, and U.S. Food and Drug Administration (FDA) regulations and recent public advisory warnings regarding the federal approval of and risks associated with the use of compound topical anesthetics. Compound topical anesthetics are neither FDA-regulated nor -unregulated. Some compounding pharmacies bypass the new FDA drug approval process, which is based on reliable scientific data and ensures that a marketed drug is safe, effective, properly manufactured and accurately labeled. Two deaths have been attributed to the lay use of compound topical anesthetics. In response, the FDA has announced the strengthening of its efforts against unapproved drug products. Compound topical anesthetics may be an effective alternative to local infiltration for some minimally invasive dental procedures; however, legitimate concerns exist in regard to their safety. Until they become federally regulated, compound topical anesthetics remain unapproved drug products whose benefits may not outweigh their risks for dental patients.

  8. Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

    Directory of Open Access Journals (Sweden)

    Mao-Qiang Man

    2012-01-01

    Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.

  9. Engaging students in geodesy: A quantitative InSAR module for undergraduate tectonics and geophysics classes

    Science.gov (United States)

    Taylor, H.; Charlevoix, D. J.; Pritchard, M. E.; Lohman, R. B.

    2013-12-01

    In the last several decades, advances in geodetic technology have allowed us to significantly expand our knowledge of processes acting on and beneath the Earth's surface. Many of these advances have come as a result of EarthScope, a community of scientists conducting multidisciplinary Earth science research utilizing freely accessible data from a variety of instruments. The geodetic component of EarthScope includes the acquisition of synthetic aperture radar (SAR) images, which are archived at the UNAVCO facility. Interferometric SAR complements the spatial and temporal coverage of GPS and allows monitoring of ground deformation in remote areas worldwide. However, because of the complex software required for processing, InSAR data are not readily accessible to most students. Even with these challenges, exposure at the undergraduate level is important for showing how geodesy can be applied in various areas of the geosciences and for promoting geodesy as a future career path. Here we present a module focused on exploring the tectonics of the western United States using InSAR data for use in undergraduate tectonics and geophysics classes. The module has two major objectives: address topics concerning tectonics in the western U.S. including Basin and Range extension, Yellowstone hotspot activity, and creep in southern California, and familiarize students with how imperfect real-world data can be manipulated and interpreted. Module questions promote critical thinking skills and data literacy by prompting students to use the information given to confront and question assumptions (e.g. 'Is there a consistency between seismic rates and permanent earthquake deformation? What other factors might need to be considered besides seismicity?'). The module consists of an introduction to the basics of InSAR and three student exercises, each focused on one of the topics listed above. Students analyze pre-processed InSAR data using MATLAB, or an Excel equivalent, and draw on GPS and

  10. Knowledge-Based Topic Model for Unsupervised Object Discovery and Localization.

    Science.gov (United States)

    Niu, Zhenxing; Hua, Gang; Wang, Le; Gao, Xinbo

    Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object instances from a given image collection without any supervision. Previous work has attempted to tackle this problem with vanilla topic models, such as latent Dirichlet allocation (LDA). However, in those methods no prior knowledge for the given image collection is exploited to facilitate object discovery. On the other hand, the topic models used in those methods suffer from the topic coherence issue-some inferred topics do not have clear meaning, which limits the final performance of object discovery. In this paper, prior knowledge in terms of the so-called must-links are exploited from Web images on the Internet. Furthermore, a novel knowledge-based topic model, called LDA with mixture of Dirichlet trees, is proposed to incorporate the must-links into topic modeling for object discovery. In particular, to better deal with the polysemy phenomenon of visual words, the must-link is re-defined as that one must-link only constrains one or some topic(s) instead of all topics, which leads to significantly improved topic coherence. Moreover, the must-links are built and grouped with respect to specific object classes, thus the must-links in our approach are semantic-specific , which allows to more efficiently exploit discriminative prior knowledge from Web images. Extensive experiments validated the efficiency of our proposed approach on several data sets. It is shown that our method significantly improves topic coherence and outperforms the unsupervised methods for object discovery and localization. In addition, compared with discriminative methods, the naturally existing object classes in the given image collection can be subtly discovered, which makes our approach well suited for realistic applications of unsupervised object discovery.Unsupervised object discovery and localization is to discover some dominant object classes and localize all of object

  11. Topic Prominence in Chinese EFL Learners' Interlanguage

    Science.gov (United States)

    Li, Shaopeng; Yang, Lianrui

    2014-01-01

    The present study aims to investigate the general characteristics of topicprominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from a discourse perspective. Topic structures mainly appear in Chinese discourse in the form of topic chains (Wang, 2002; 2004). The…

  12. Evaluation of the glycemic effect of Ceratonia siliqua pods (Carob on a streptozotocin-nicotinamide induced diabetic rat model

    Directory of Open Access Journals (Sweden)

    Mousa A. Qasem

    2018-05-01

    Full Text Available Background Ceratonia siliqua pods (carob have been nominated to control the high blood glucose of diabetics. In Yemen, however, its antihyperglycemic activity has not been yet assessed. Thus, this study evaluated the in vitro inhibitory effect of the methanolic extract of carob pods against α-amylase and α-glucosidase and the in vivo glycemic effect of such extract in streptozotocin-nicotinamide induced diabetic rats. Methods 2,2-diphenyl-1-picrylhydrazyl (DPPH and Ferric reducing antioxidant power assay (FRAP were applied to evaluate the antioxidant activity of carob. In vitro cytotoxicity of carob was conducted on human hepatocytes (WRL68 and rat pancreatic β-cells (RIN-5F. Acute oral toxicity of carob was conducted on a total of 18 male and 18 female Sprague-Dawley (SD rats, which were subdivided into three groups (n = 6, namely: high and low dose carob-treated (CS5000 and CS2000, respectively as well as the normal control (NC receiving a single oral dose of 5,000 mg kg−1 carob, 2,000 mg kg−1 carob and 5 mL kg−1 distilled water for 14 days, respectively. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, creatinine and urea were assessed. Livers and kidneys were harvested for histopathology. In vitro inhibitory effect against α-amylase and α-glucosidase was evaluated. In vivo glycemic activity was conducted on 24 male SD rats which were previously intraperitoneally injected with 55 mg kg−1 streptozotocin (STZ followed by 210 mg kg−1nicotinamide to induce type 2 diabetes mellitus. An extra non-injected group (n = 6 was added as a normal control (NC. The injected-rats were divided into four groups (n = 6, namely: diabetic control (D0, 5 mg kg−1glibenclamide-treated diabetic (GD, 500 mg kg−1 carob-treated diabetic (CS500 and 1,000 mg kg−1 carob-treated diabetic (CS1000. All groups received a single oral daily dose of their treatment for 4 weeks. Body weight, fasting blood

  13. A Discourse Perspective of Topic-prominence in Chinese EFL Learners’ Interlanguage

    Directory of Open Access Journals (Sweden)

    Shaopeng Li

    2014-07-01

    Full Text Available The present study aims to investigate the general characteristics of topic-prominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from the discourse perspective. We have selected as the research target “topic chain” which is the main topic-prominent structure in Chinese discourse and “zero anaphora” which is the most common topic anaphor of topic chain. Topic structures mainly appear in Chinese discourse in the form of “topic chain” (Wang, 2002; 2004. Actually, in the event of a topic chain, research on topic structures should go into the typical range of discourse. Two important findings were yielded by the present study. First, the characteristics of Chinese topic chain are transferrable to the interlanguage of Chinese EFL learners, thus resulting in overgeneralization of zero anaphora; second, interlanguage discourse of Chinese EFL learners reflects the characteristics of a second language acquisition process from topic-prominence to subject-prominence, thus lending support to the discourse transfer hypothesis.

  14. Topical reports on Louisiana salt domes

    International Nuclear Information System (INIS)

    1983-09-01

    The Institute for Environmental Studies at Louisiana State University conducted research into the potential use of Louisiana salt domes for disposal of nuclear waste material. Topical reports generated in 1981 and 1982 related to Vacherie and Rayburn's domes are compiled and presented, which address palynological studies, tiltmeter monitoring, precise releveling, saline springs, and surface hydrology. The latter two are basically a compilation of references related to these topics. Individual reports are abstracted

  15. Data Mining Thesis Topics in Finland

    OpenAIRE

    Bajo Rouvinen, Ari

    2017-01-01

    The Theseus open repository contains metadata about more than 100,000 thesis publications from the different universities of applied sciences in Finland. Different data mining techniques were applied to the Theseus dataset to build a web application to explore thesis topics and degree programmes using different libraries in Python and JavaScript. Thesis topics were extracted from manually annotated keywords by the authors and curated subjects by the librarians. During the project, the quality...

  16. Selected topics in e+e- physics

    International Nuclear Information System (INIS)

    Sau Lan Wu

    1981-01-01

    Selected topics of recent experimental results from the high-energy electron-positron storage rings are presented. The topics include some of the tau and charm physics from SPEAR, the upsilon physics from DORIS and CESR, and the γγ physics and quark and gluon physics from the PLUTO and TASSO Collaborations at PETRA. Related data from the JADE and MARK J Collaborations at PETRA are discussed in separated papers at this school. (orig.)

  17. Weyl modules, demazure modules, KR-modules, crystals, fusion products and limit constructions

    OpenAIRE

    Fourier, G.; Littelmann, P.

    2007-01-01

    We study finite dimensional representations of current algebras, loop algebras and their quantized versions. For the current algebra of a simple Lie algebra of type {\\tt ADE}, we show that Kirillov-Reshetikhin modules and Weyl modules are in fact all Demazure modules. As a consequence one obtains an elementary proof of the dimension formula for Weyl modules for the current and the loop algebra. Further, we show that the crystals of the Weyl and the Demazure module are the same up to some addi...

  18. An overview of topic modeling and its current applications in bioinformatics.

    Science.gov (United States)

    Liu, Lin; Tang, Lin; Dong, Wen; Yao, Shaowen; Zhou, Wei

    2016-01-01

    With the rapid accumulation of biological datasets, machine learning methods designed to automate data analysis are urgently needed. In recent years, so-called topic models that originated from the field of natural language processing have been receiving much attention in bioinformatics because of their interpretability. Our aim was to review the application and development of topic models for bioinformatics. This paper starts with the description of a topic model, with a focus on the understanding of topic modeling. A general outline is provided on how to build an application in a topic model and how to develop a topic model. Meanwhile, the literature on application of topic models to biological data was searched and analyzed in depth. According to the types of models and the analogy between the concept of document-topic-word and a biological object (as well as the tasks of a topic model), we categorized the related studies and provided an outlook on the use of topic models for the development of bioinformatics applications. Topic modeling is a useful method (in contrast to the traditional means of data reduction in bioinformatics) and enhances researchers' ability to interpret biological information. Nevertheless, due to the lack of topic models optimized for specific biological data, the studies on topic modeling in biological data still have a long and challenging road ahead. We believe that topic models are a promising method for various applications in bioinformatics research.

  19. Design and discovery of thioether and nicotinamide containing sorafenib analogues as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2.

    Science.gov (United States)

    Sun, Shaofeng; He, Zuopeng; Huang, Mindong; Wang, Ningning; He, Zongzhong; Kong, Xiangkai; Yao, Jianwen

    2018-04-03

    New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-Raf V600E and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-Raf V600E and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC 50 of 21 nM, 27 nM and 17 nM, B-Raf V600E with IC 50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC 50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Mitigation of PID in commercial PV modules using current interruption method

    Science.gov (United States)

    Bora, Birinchi; Oh, Jaewon; Tatapudi, Sai; Sastry, Oruganty S.; Kumar, Rajesh; Prasad, Basudev; Tamizhmani, Govindasamy

    2017-08-01

    Potential-induced degradation (PID) is known to have a very severe effect on the reliability of PV modules. PID is caused due to the leakage of current from the cell circuit to the grounded frame under humid conditions of high voltage photovoltaic (PV) systems. There are multiple paths for the current leakage. The most dominant leakage path is from the cell to the frame through encapsulant, glass bulk and glass surface. This dominant path can be prevented by interrupting the electrical conductivity at the glass surface. In our previous works related to this topic, we demonstrated the effectiveness of glass surface conductivity interruption technique using one-cell PV coupons. In this work, we demonstrate the effectiveness of this technique using a full size commercial module susceptible to PID. The interruption of surface conductivity of the commercial module was achieved by attaching a narrow, thin flexible glass strips, from Corning, called Willow Glass on the glass surface along the inner edges of the frame. The flexible glass strip was attached to the module glass surface by heating the glass strip with an ionomer adhesive underneath using a handheld heat gun. The PID stress test was performed at 60°C and 85% RH for 96 hours at -600 V. Pre- and post-PID characterizations including I-V and electroluminescence were carried out to determine the performance loss and affected cell areas. This work demonstrates that the PID issue can be effectively addressed by using this current interruption technique. An important benefit of this approach is that this interruption technique can be applied after manufacturing the modules and after installing the modules in the field as well.