Sample records for antimycin a

  1. Analysis of antimycin A by reversed-phase liquid chromatography/nuclear magnetic-resonance spectrometry (United States)

    Ha, Steven T.K.; Wilkins, Charles L.; Abidi, Sharon L.


    A mixture of closely related streptomyces fermentation products, antimycin A, Is separated, and the components are identified by using reversed-phase high-performance liquid chromatography with directly linked 400-MHz proton nuclear magnetic resonance detection. Analyses of mixtures of three amino acids, alanine, glycine, and valine, are used to determine optimal measurement conditions. Sensitivity increases of as much as a factor of 3 are achieved, at the expense of some loss in chromatographic resolution, by use of an 80-μL NMR cell, Instead of a smaller 14-μL cell. Analysis of the antimycin A mixture, using the optimal analytical high performance liquid chromatography/nuclear magnetic resonance conditions, reveals it to consist of at least 10 closely related components.

  2. High-performance liquid chromatographic separation of subcomponents of antimycin A. (United States)

    Abidi, S L


    Using a reversed-phase high-performance liquid chromatographic (HPLC) technique, a mixture of antimycins A was separated into eight hitherto unreported subcomponents, A1a, A1b, A2a, A2b, A3a, A3b, A4a, and A4b. Although a base-line resolution of the known four major antimycins A1, A2, A3, and A4 was readily achieved with mobile phases containing acetate buffers, the separation of the new antibiotic subcomponents was highly sensitive to variation in mobile phase conditions. The type and composition of organic modifers, the nature of buffer salts, and the concentration of added electrolytes had profound effects on capacity factors, separation factors, and peak resolution values. Of the numerous chromatographic systems examined, a mobile phase consisting of methanol-water (70:30) and 0.005 M tetrabutylammonium phosphate at pH 3.0 yielded the most satisfactory results for the separation of the subcomponents. Reversed-phase gradient HPLC separation of the dansylated or methylated antibiotic compounds produced superior chromatographic characteristics and the presence of added electrolytes was not a critical factor for achieving separation. Differences in the chromatographic outcome between homologous and structural isomers were interpreted based on a differential solvophobic interaction rationale. Preparative reversed-phase HPLC under optimal conditions enabled isolation of pure samples of the methylated antimycin subcomponents for use in structural studies.

  3. Reversed-phase thin-layer chromatography of homologs of Antimycin-A and related derivatives (United States)

    Abidi, Sharon L.


    Using a reversed-phase high-performance liquid chromatographic (HPLC) technique, a mixture of antimycins A was separated into eight hitherto unreported subcomponents, Ala, Alb, A2a, A2b, A3a, A3b, A4a, and A4b. Although a base-line resolution of the known four major antimycins Al, A2, A3, and A4 was readily achieved with mobile phases containing acetate buffers, the separation of the new antibiotic subcomponents was highly sensitive to variation in mobile phase conditions. The type and composition of organic modifiers, the nature of buffer salts, and the concentration of added electrolytes had profound effects on capacity factors, separation factors, and peak resolution values. Of the numerous chromatographic systems examined, a mobile phase consisting of methanol-water (70:30) and 0.005 M tetrabutylammonium phosphate at pH 3.0 yielded the most satisfactory results for the separation of the subcomponents. Reversed-phase gradient HPLC separation of the dansylated or methylated antibiotic compounds produced superior chromatographic characteristics and the presence of added electrolytes was not a critical factor for achieving separation. Differences in the chromatographic outcome between homologous and structural isomers were interpretated based on a differential solvophobic interaction rationale. Preparative reversed-phase HPLC under optimal conditions enabled isolation of pure samples of the methylated antimycin subcomponents for use in structural studies.

  4. High-performance liquid-chromatographic separation of subcomponents of antimycin-A (United States)

    Abidi, S.L.


    Using a reversed-phase high-performance liquid chromatographic (HPLC) technique, a mixture of antimycins A was separated into eight hitherto unreported subcomponents, Ala, Alb, A2a, A2b, A3a, A3b, A4a, and A4b. Although a base-line resolution of the known four major antimycins Al, A2, A3, and A4 was readily achieved with mobile phases containing acetate buffers, the separation of the new antibiotic subcomponents was highly sensitive to variation in mobile phase conditions. The type and composition of organic modifiers, the nature of buffer salts, and the concentration of added electrolytes had profound effects on capacity factors, separation factors, and peak resolution values. Of the numerous chromatographic systems examined, a mobile phase consisting of methanol-water (70:30) and 0.005 M tetrabutylammonium phosphate at pH 3.0 yielded the most satisfactory results for the separation of the subcomponents. Reversed-phase gradient HPLC separation of the dansylated or methylated antibiotic compounds produced superior chromatographic characteristics and the presence of added electrolytes was not a critical factor for achieving separation. Differences in the chromatographic outcome between homologous and structural isomers were interpretated based on a differential solvophobic interaction rationale. Preparative reversed-phase HPLC under optimal conditions enabled isolation of pure samples of the methylated antimycin subcomponents for use in structural studies.

  5. Spermine binding to liver mitochondria deenergized by ruthenium red plus either FCCP or antimycin A. (United States)

    Dalla Via, L; Di Noto, V; Toninello, A


    Thermodynamic analysis of spermine binding to mitochondria treated with ruthenium red and deenergized with either FCCP or antimycin A confirms the presence of two polyamine binding sites, S1 and S2, both with monocoordination, as previously observed in energized mitochondria [Dalla Via et al., Biochim. Biophys. Acta 1284 (1996) 247-252]. Both sites undergo a marked change in binding capacity and binding affinity upon mitochondrial deenergization. This change is most likely responsible for the incomplete or delayed spermine-mediated inhibition of the permeability transition induced in deenergized mitochondria.

  6. The regulation and biosynthesis of antimycins

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    Ryan F. Seipke


    Full Text Available Antimycins (>40 members were discovered nearly 65 years ago but the discovery of the gene cluster encoding antimycin biosynthesis in 2011 has facilitated rapid progress in understanding the unusual biosynthetic pathway. Antimycin A is widely used as a piscicide in the catfish farming industry and also has potent killing activity against insects, nematodes and fungi. The mode of action of antimycins is to inhibit cytochrome c reductase in the electron transport chain and halt respiration. However, more recently, antimycin A has attracted attention as a potent and selective inhibitor of the mitochondrial anti-apoptotic proteins Bcl-2 and Bcl-xL. Remarkably, this inhibition is independent of the main mode of action of antimycins such that an artificial derivative named 2-methoxyantimycin A inhibits Bcl-xL but does not inhibit respiration. The Bcl-2/Bcl-xL family of proteins are over-produced in cancer cells that are resistant to apoptosis-inducing chemotherapy agents, so antimycins have great potential as anticancer drugs used in combination with existing chemotherapeutics. Here we review what is known about antimycins, the regulation of the ant gene cluster and the unusual biosynthetic pathway.

  7. A Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent

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    Chi-Tai Yeh


    Full Text Available Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs, was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA, was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress β-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate β-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

  8. Mitochondrial morphology and dynamics in Triticum aestivum roots in response to rotenone and antimycin A. (United States)

    Rakhmatullina, Daniya; Ponomareva, Anastasiya; Gazizova, Natalia; Minibayeva, Farida


    Mitochondria are dynamic organelles, capable of fusion and fission as a part of cellular responses to various signals, such as the shifts in the redox status of a cell. The mitochondrial electron transport chain (ETC.) is involved in the generation of reactive oxygen species (ROS), with complexes I and III contributing the most to this process. Disruptions of ETC. can lead to increased ROS generation. Here, we demonstrate the appearance of giant mitochondria in wheat roots in response to simultaneous application of the respiratory inhibitors rotenone (complex I of mitochondrial ETC.) and antimycin A (complex III of mitochondrial ETC.). The existence of such megamitochondria was temporary, and following longer treatment with inhibitors mitochondria resumed their conventional size and oval shape. Changes in mitochondrial morphology were accompanied with a decrease in mitochondrial potential and an unexpected increase in oxygen consumption. Changes in mitochondrial morphology and activity may result from the fusion and fission of mitochondria induced by the disruption of mitochondrial ETC. Results from experiments with the inhibitor of mitochondrial fission Mdivi-1 suggest that the retarded fission may facilitate plant mitochondria to appear in a fused shape. The processes of mitochondrial fusion and fission are involved in the regulation of the efficacy of the functions of the respiratory chain complexes and ROS metabolism during stresses. The changes in morphology of mitochondria, along with the changes in their functional activity, can be a part of the strategy of the plant adaptation to stresses.

  9. Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

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    Mohamad Hafizi Abu Bakar


    Full Text Available Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

  10. Binding of the Respiratory Chain Inhibitor Antimycin to theMitochondrial bc1 Complex: A New Crystal Structure Reveals an AlteredIntramolecular Hydrogen-Bonding Pattern

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    Huang, Li-shar; Cobessi, David; Tung, Eric Y.; Berry, Edward A.


    Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex.Structure-activity-relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28Angstrom resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cyt b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alpha-A helix.

  11. Bypasses of the antimycin a block of mitochondrial electron transport in relation to ubisemiquinone function. (United States)

    Alexandre, A; Lehninger, A L


    Two different bypasses around the antimycin block of electron transport from succinate to cytochrome c via the ubiquinol-cytochrome c oxidoreductase of intact rat liver mitochondria were analyzed, one promoted by N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and the other by 2,6-dichlorophenolindophenol (DCIP). Both bypasses are inhibited by myxothiazol, which blocks electron flow from ubiquinol to the Rieske iron-sulfur center, and by 2-hydroxy-3-undecyl-1,4-naphthoquinone, which inhibits electron flow from the iron-sulfur center to cytochrome c1. In the bypass promoted by TMPD its oxidized form (Wurster's blue) acts as an electron acceptor from some reduced component prior to the antimycin block, which by exclusion of other possibilities is ubisemiquinone. In the DCIP bypass its reduced form acts as an electron donor, by reducing ubisemiquinone to ubiquinol; reduced DCIP is regenerated again at the expense of either succinate or ascorbate. The observations described are consistent with and support current models of the Q cycle. Bypasses promoted by artificial electron carriers provide an independent approach to analysis of electron flow through ubiquinol-cytochrome c oxidoreductase.

  12. Determination of antimycin-A in water by liquid chromatographic/mass spectrometry: single-laboratory validation. (United States)

    Bernardy, Jeffry A; Hubert, Terrance D; Ogorek, Jacob M; Schmidt, Larry J


    An LC/MS method was developed and validated for the quantitative determination and confirmation of antimycin-A (ANT-A) in water from lakes or streams. Three different water sample volumes (25, 50, and 250 mL) were evaluated. ANT-A was stabilized in the field by immediately extracting it from water into anhydrous acetone using SPE. The stabilized concentrated samples were then transported to a laboratory and analyzed by LC/MS using negative electrospray ionization. The method was determined to have adequate accuracy (78 to 113% recovery), precision (0.77 to 7.5% RSD with samples > or = 500 ng/L and 4.8 to 17% RSD with samples < or = 100 ng/L), linearity, and robustness over an LOQ range from 8 to 51 600 ng/L.

  13. Determination of Antimycin-A in water by liquid chromatographic/mass spectrometry: single-laboratory validation (United States)

    Bernardy, Jeffry A.; Hubert, Terrance D.; Ogorek, Jacob M.; Schmidt, Larry J.


    An LC/MS method was developed and validated for the quantitative determination and confirmation of antimycin-A (ANT-A) in water from lakes or streams. Three different water sample volumes (25, 50, and 250 mL) were evaluated. ANT-A was stabilized in the field by immediately extracting it from water into anhydrous acetone using SPE. The stabilized concentrated samples were then transported to a laboratory and analyzed by LC/MS using negative electrospray ionization. The method was determined to have adequate accuracy (78 to 113% recovery), precision (0.77 to 7.5% RSD with samples ≥500 ng/L and 4.8 to 17% RSD with samples ≤100 ng/L), linearity, and robustness over an LOQ range from 8 to 51 600 ng/L.

  14. U.S.D.A. Forest Service environmental analysis report on the use of antimycin to rehabilitate lakes and streams (United States)

    US Fish and Wildlife Service, Department of the Interior — Report identifies characteristics of use of antimycin to destroy stickleback, chub, suckers and other competitors to salmon and dolly varden.

  15. Mechanisms involved in the inhibition of glycolysis by cyanide and antimycin A in Candida albicans and its reversal by hydrogen peroxide. A common feature in Candida species. (United States)

    Peña, Antonio; Sánchez, Norma Silvia; González-López, Omar; Calahorra, Martha


    In Candida albicans, cyanide and antimycin A inhibited K(+) transport, not only with ethanol-O2 as the substrate, but also with glucose. The reason for this was that they inhibited not only respiration, but also fermentation, decreasing ATP production. Measurements of oxygen levels in cell suspensions allowed identification of the electron pathways involved. NADH fluorescence levels increased in the presence of the inhibitors, indirectly indicating lower levels of NAD(+) and so pointing to glyceraldehyde-3-phosphate dehydrogenase as the limiting step responsible for the inhibition of glycolysis, which was confirmed by the levels of glycolytic intermediaries. The cyanide effect could be reversed by hydrogen peroxide, mainly due to an activity by which H2O2 can be reduced by electrons flowing from NADH through a pathway that can be inhibited by antimycin A, and appears to be a cytochrome c peroxidase. Therefore, the inhibition of glycolysis by the respiratory inhibitors seems to be due to the decreased availability of NAD(+), resulting in a decreased activity of glyceraldehyde-3-phosphate dehydrogenase. Compartmentalization of pyridine nucleotides in favor of the mitochondria can contribute to explaining the low fermentation capacity of C. albicans. Similar results were obtained with three C. albicans strains, Candida dubliniensis and, to a lower degree, Candida parapsilosis.

  16. All-atom molecular dynamics simulations reveal significant differences in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc1 complexes. (United States)

    Kokhan, Oleksandr; Shinkarev, Vladimir P


    Antimycin A is the most frequently used specific and powerful inhibitor of the mitochondrial respiratory chain. We used all-atom molecular dynamics (MD) simulations to study the dynamic aspects of the interaction of antimycin A with the Q(i) site of the bacterial and bovine bc(1) complexes embedded in a membrane. The MD simulations revealed considerable conformational flexibility of antimycin and significant mobility of antimycin, as a whole, inside the Q(i) pocket. We conclude that many of the differences in antimycin binding observed in high-resolution x-ray structures may have a dynamic origin and result from fluctuations of protein and antimycin between multiple conformational states of similar energy separated by low activation barriers, as well as from the mobility of antimycin within the Q(i) pocket. The MD simulations also revealed a significant difference in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc(1) complexes. The strong hydrogen bond between antimycin and conserved Asp-228 (bovine numeration) was observed to be frequently broken in the bacterial bc(1) complex and only rarely in the bovine bc(1) complex. In addition, the distances between antimycin and conserved His-201 and Lys-227 were consistently larger in the bacterial bc(1) complex. The observed differences could be responsible for a weaker interaction of antimycin with the bacterial bc(1) complex.

  17. Physiological Concentration of Exogenous Lactate Reduces Antimycin A Triggered Oxidative Stress in Intestinal Epithelial Cell Line IPEC-1 and IPEC-J2 In Vitro (United States)

    Kahlert, Stefan; Junnikkala, Sami; Renner, Lydia; Hynönen, Ulla; Hartig, Roland; Nossol, Constanze; Barta-Böszörményi, Anikó; Dänicke, Sven; Souffrant, Wolfgang-Bernhard; Palva, Airi; Rothkötter, Hermann-Josef; Kluess, Jeannette


    Weaning triggers an adaptation of the gut function including luminal lactate generation by lactobacilli, depending on gastrointestinal site. We hypothesized that both lactobacilli and lactate influence porcine intestinal epithelial cells. In vivo experiments showed that concentration of lactate was significantly higher in gastric, duodenal and jejunal chyme of suckling piglets compared to their weaned counterparts. In an in vitro study we investigated the impact of physiological lactate concentration as derived from the in vivo study on the porcine intestinal epithelial cells IPEC-1 and IPEC-J2. We detected direct adherence of lactobacilli on the apical epithelial surface and a modulated F-actin structure. Application of lactobacilli culture supernatant alone or lactate (25 mM) at low pH (pH 4) changed the F-actin structure in a similar manner. Treatment of IPEC cultures with lactate at near neutral pH resulted in a significantly reduced superoxide-generation in Antimycin A-challenged cells. This protective effect was nearly completely reversed by inhibition of cellular lactate uptake via monocarboxylate transporter. Lactate treatment enhanced NADH autofluorescence ratio (Fcytosol/Fnucleus) in non-challenged cells, indicating an increased availability of reduced nucleotides, but did not change the overall ATP content of the cells. Lactobacilli-derived physiological lactate concentration in intestine is relevant for alleviation of redox stress in intestinal epithelial cells. PMID:27054581

  18. Induction of the AOX1D Isoform of Alternative Oxidase in A. thaliana T-DNA Insertion Lines Lacking Isoform AOX1A Is Insufficient to Optimize Photosynthesis when Treated with Antimycin A

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    Inga Strodtkotter; Kollipara Padmasree; Challabathula Dinakar; Birgit Speth; Pamela S. Niazi; Joanna Wojtera; Ingo Voss; Phuc Thi Do; Adriano Nunes-Nesi; Alisdair R. Fernie; Vera Linke; Agepati S. Raghavendra; Renate Scheibe


    Plant respiration is characterized by two pathways for electron transfer to O2, namely the cytochrome path-way (CP) that is linked to ATP production, and the alternative pathway (AP), where electrons from ubiquinol are directly transferred to O2 via an alternative oxidase (AOX) without concomitant ATP production. This latter pathway is well suited to dispose of excess electrons in the light, leading to optimized photosynthetic performance. We have characterized T-DNA-insertion mutant lines of Arabidopsis thaliana that do not express the major isoform, AOXIA. In standard growth conditions, these plants did not show any phenotype, but restriction of electron flow through CP by antimycin A, which induces AOX1A expression in the wild-type, led to an increased expression of AOX1D in leaves of the aox1a-knockout mutant. Despite the increased presence of the AOX1D isoform in the mutant, antimycin A caused inhibition of photosyn-thesis, increased ROS, and ultimately resulted in amplified membrane leakage and necrosis when compared to the wild-type, which was only marginally affected by the inhibitor. It thus appears that AOX1D was unable to fully compensate for the loss of AOX1A when electron flow via the CP is restricted. A combination of inhibition studies, coupled to metabolite profiling and targeted expression analysis of the P-protein of glycine decarboxylase complex (GDC), suggests that the aox1a mutants attempt to increase their capacity for photorespiration. However, given their deficiency, it is intriguing that increase in expression neither of AOX1D nor of GDC could fully compensate for the lack of AOX1A to optimize pho-tosynthesis when treated with antimycin A. We suggest that the aox1a mutants can further be used to substantiate the current models concerning the influence of mitochondrial redox on photosynthetic performance and gene expression.

  19. Increased sensitivity of photosynthesis to antimycin A induced by inactivation of the chloroplast ndhB gene. Evidence for a participation of the NADH-dehydrogenase complex to cyclic electron flow around photosystem I. (United States)

    Joët, T; Cournac, L; Horvath, E M; Medgyesy, P; Peltier, G


    Tobacco (Nicotiana tabacum var Petit Havana) ndhB-inactivated mutants (ndhB-) obtained by plastid transformation (E.M. Horvath, S.O. Peter, T. Joët, D. Rumeau, L. Cournac, G.V. Horvath, T.A. Kavanagh, C. Schäfer, G. Peltier, P. MedgyesyHorvath [2000] Plant Physiol 123: 1337-1350) were used to study the role of the NADH-dehydrogenase complex (NDH) during photosynthesis and particularly the involvement of this complex in cyclic electron flow around photosystem I (PSI). Photosynthetic activity was determined on leaf discs by measuring CO2 exchange and chlorophyll fluorescence quenchings during a dark-to-light transition. In the absence of treatment, both non-photochemical and photochemical fluorescence quenchings were similar in ndhB- and wild type (WT). When leaf discs were treated with 5 microM antimycin A, an inhibitor of cyclic electron flow around PSI, both quenchings were strongly affected. At steady state, maximum photosynthetic electron transport activity was inhibited by 20% in WT and by 50% in ndhB-. Under non-photorespiratory conditions (2% O2, 2,500 microL x L(-1) CO2), antimycin A had no effect on photosynthetic activity of WT, whereas a 30% inhibition was observed both on quantum yield of photosynthesis assayed by chlorophyll fluorescence and on CO2 assimilation in ndhB-. The effect of antimycin A on ndhB- could not be mimicked by myxothiazol, an inhibitor of the mitochondrial cytochrome bc1 complex, therefore showing that it is not related to an inhibition of the mitochondrial electron transport chain but rather to an inhibition of cyclic electron flow around PSI. We conclude to the existence of two different pathways of cyclic electron flow operating around PSI in higher plant chloroplasts. One of these pathways, sensitive to antimycin A, probably involves ferredoxin plastoquinone reductase, whereas the other involves the NDH complex. The absence of visible phenotype in ndhB- plants under normal conditions is explained by the complement of these two

  20. Comparative kinetics of Qi site inhibitors of cytochrome bc1 complex: picomolar antimycin and micromolar cyazofamid. (United States)

    Li, Hui; Zhu, Xiao-Lei; Yang, Wen-Chao; Yang, Guang-Fu


    Antimycin and cyazofamid are specific inhibitors of the mitochondrial respiratory chain and bind to the Qi site of the cytochrome bc1 complex. With the aim to understand the detailed molecular inhibition mechanism of Qi inhibitors, we performed a comparative investigation of the inhibitory kinetics of them against the porcine bc1 complex. The results showed that antimycin is a slow tight-binding inhibitor of succinate-cytochrome c reductase (SCR) with Ki  = 0.033 ± 0.00027 nm and non-competitive inhibition with respect to cytochrome c. Cyazofamid is a classical inhibitor of SCR with Ki  = 12.90 ± 0.91 μm and a non-competitive inhibitor with respect to cytochrome c. Both of them show competitive inhibition with respect to substrate DBH2 . Further molecular docking and quantum mechanics calculations were performed. The results showed that antimycin underwent significant conformational change upon the binding. The energy barrier between the conformations in the crystal and in the binding pocket is ~13.63 kcal/mol. Antimycin formed an H-bond with Asp228 and two water-bridged H-bonds with Lys227 and His201, whereas cyazofamid formed only one H-bond with Asp228. The conformational change and the different hydrogen bonding network might account for why antimycin is a slow tight-binding inhibitor, whereas cyazofamid is a classic inhibitor.

  1. Inhibition of aldehyde dehydrogenase 2 activity enhances antimycin-induced rat cardiomyocytes apoptosis through activation of MAPK signaling pathway. (United States)

    Zhang, Peng; Xu, Danling; Wang, Shijun; Fu, Han; Wang, Keqiang; Zou, Yunzeng; Sun, Aijun; Ge, Junbo


    Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial-specific enzyme, has been proved to be involved in oxidative stress-induced cell apoptosis, while little is known in cardiomyocytes. This study was aimed at investigating the role of ALDH2 in antimycin A-induced cardiomyocytes apoptosis by suppressing ALDH2 activity with a specific ALDH2 inhibitor Daidzin. Antimycin A (40μg/ml) was used to induce neonatal cardiomyocytes apoptosis. Daidzin (60μM) effectively inhibited ALDH2 activity by 50% without own effect on cell apoptosis, and significantly enhanced antimycin A-induced cardiomyocytes apoptosis from 33.5±4.4 to 56.5±6.4% (Hochest method, pdaidzin treated cardiomyocytes compared to the cells treated with antimycin A alone. These findings indicated that modifying mitochondrial ALDH2 activity/expression might be a potential therapeutic option on reducing oxidative insults induced cardiomyocytes apoptosis.

  2. Antimycin-insensitive mutants of Candida utilis II. The effects of antimycin on Cytochrome b

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    Grimmelikhuijzen, C J; Marres, C A; Slater, Conor


    1. Cytochrome b-562 is more reduced in submitochondrial particles of mutant 28 during the aerobic steady-state respiration with succinate than in particles of the wild type. When anaerobiosis is reached, the reduction of cytochrome b is preceded by a rapid reoxidation in the mutnat. A similar reo...


    Institute of Scientific and Technical Information of China (English)

    江昇平; 田晓清; 廖丽; 杨桥; 陆亚男; 马丽艳; 陈波; 樊成奇


    极地微生物代谢产生芳香族硝基化合物、肽类、萜类等多种骨架类型的化学成分.为从北极放线菌中发现结构新颖、活性显著的小分子化合物,本研究采用Sephadex LH-20凝胶和半制备HPLC等柱层析分离纯化化合物手段,结合LC-MS、1H-和13C-NMR等波谱学数据和文献对比进行结构解析,从链霉菌Streptomycessp.604F提取物中分离鉴定出抗霉素Alb(1)、抗霉素A4a(2)、抗霉素A2a(3)、抗霉素A3a(4)、抗霉素Ala(5)以及伏尔加霉素(6)和8-脱氧伏尔加霉素(7)这7个化合物.化合物1-7是首次从北极海洋沉积物来源的微生物中发现,而且是首次从同一菌株中发现抗霉素A和伏尔加霉素这两类化合物.

  4. Extramitochondrial release of hydrogen peroxide from insect and mouse liver mitochondria using the respiratory inhibitors phosphine, myxothiazol, and antimycin and spectral analysis of inhibited cytochromes. (United States)

    Bolter, C J; Chefurka, W


    The fumigant insecticide phosphine (PH3) is known to inhibit cytochrome c oxidase in vitro. Inhibition of the respiratory chain at this site has been shown to stimulate the generation of superoxide radicals (O2-), which dismutate to form hydrogen peroxide (H2O2). This study was performed in order to investigate the production of H2O2 by mitochondria isolated from granary weevil (Sitophilus granarius) and mouse liver on exposure to PH3. Other respiratory inhibitors, antimycin, myxothiazol, and rotenone were used with insect mitochondria. Hydrogen peroxide was measured spectrophotometrically using yeast cytochrome c peroxidase as an indicator. Insect and mouse liver mitochondria, utilizing endogenous substrate, both produced H2O2 after inhibition by PH3. Insect organelles released threefold more H2O2 than did mouse organelles, when exposed to PH3. Production of H2O2 by PH3-treated insect mitochondria was increased significantly on addition of the substrate alpha-glycerophosphate. Succinate did not enhance H2O2 production, however, indicating that the H2O2 did not result from the autoxidation of ubiquinone. NAD(+)-linked substrates, malate and pyruvate also had no effect on H2O2 production, suggesting that NADH-dehydrogenase was not the source of H2O2. Data obtained using antimycin and myxothiazol, both of which stimulated the release of H2O2 from insect mitochondria, lead to the conclusion that glycerophosphate dehydrogenase is a source of H2O2. The effect of combining PH3, antimycin, and myxothiazol on cytochrome spectra in insect mitochondria was also recorded. It was observed that PH3 reduces cytochrome c oxidase but none of the other cytochromes in the electron transport chain. There was no movement of electrons to cytochrome b when insect mitochondria are inhibited with PH3. The spectral data show that the inhibitors interact with the respiratory chain in a way that would allow the production of H2O2 from the sites proposed previously.

  5. Genome Sequence of Streptomyces wadayamensis Strain A23, an Endophytic Actinobacterium from Citrus reticulata


    de Oliveira, Luciana G.; Tormet Gonzalez, Gabriela D; Samborsky, Markyian; Marcon, Joelma; Araujo, Welington L.; de Azevedo, João Lucio


    The actinobacterium Streptomyces wadayamensis A23 is an endophyte of Citrus reticulata that produces the antimycin and mannopeptimycin antibiotics, among others. The strain has the capability to inhibit Xylella fastidiosa growth. The draft genome of S. wadayamensis A23 has ~7.0 Mb and 6,006 protein-coding sequences, with a 73.5% G+C content.

  6. A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus.

    Directory of Open Access Journals (Sweden)

    Ryan F Seipke

    Full Text Available Attine ants are dependent on a cultivated fungus for food and use antibiotics produced by symbiotic Actinobacteria as weedkillers in their fungus gardens. Actinobacterial species belonging to the genera Pseudonocardia, Streptomyces and Amycolatopsis have been isolated from attine ant nests and shown to confer protection against a range of microfungal weeds. In previous work on the higher attine Acromyrmex octospinosus we isolated a Streptomyces strain that produces candicidin, consistent with another report that attine ants use Streptomyces-produced candicidin in their fungiculture. Here we report the genome analysis of this Streptomyces strain and identify multiple antibiotic biosynthetic pathways. We demonstrate, using gene disruptions and mass spectrometry, that this single strain has the capacity to make candicidin and multiple antimycin compounds. Although antimycins have been known for >60 years we report the sequence of the biosynthetic gene cluster for the first time. Crucially, disrupting the candicidin and antimycin gene clusters in the same strain had no effect on bioactivity against a co-evolved nest pathogen called Escovopsis that has been identified in ∼30% of attine ant nests. Since the Streptomyces strain has strong bioactivity against Escovopsis we conclude that it must make additional antifungal(s to inhibit Escovopsis. However, candicidin and antimycins likely offer protection against other microfungal weeds that infect the attine fungal gardens. Thus, we propose that the selection of this biosynthetically prolific strain from the natural environment provides A. octospinosus with broad spectrum activity against Escovopsis and other microfungal weeds.

  7. A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus. (United States)

    Seipke, Ryan F; Barke, Jörg; Brearley, Charles; Hill, Lionel; Yu, Douglas W; Goss, Rebecca J M; Hutchings, Matthew I


    Attine ants are dependent on a cultivated fungus for food and use antibiotics produced by symbiotic Actinobacteria as weedkillers in their fungus gardens. Actinobacterial species belonging to the genera Pseudonocardia, Streptomyces and Amycolatopsis have been isolated from attine ant nests and shown to confer protection against a range of microfungal weeds. In previous work on the higher attine Acromyrmex octospinosus we isolated a Streptomyces strain that produces candicidin, consistent with another report that attine ants use Streptomyces-produced candicidin in their fungiculture. Here we report the genome analysis of this Streptomyces strain and identify multiple antibiotic biosynthetic pathways. We demonstrate, using gene disruptions and mass spectrometry, that this single strain has the capacity to make candicidin and multiple antimycin compounds. Although antimycins have been known for >60 years we report the sequence of the biosynthetic gene cluster for the first time. Crucially, disrupting the candicidin and antimycin gene clusters in the same strain had no effect on bioactivity against a co-evolved nest pathogen called Escovopsis that has been identified in ∼30% of attine ant nests. Since the Streptomyces strain has strong bioactivity against Escovopsis we conclude that it must make additional antifungal(s) to inhibit Escovopsis. However, candicidin and antimycins likely offer protection against other microfungal weeds that infect the attine fungal gardens. Thus, we propose that the selection of this biosynthetically prolific strain from the natural environment provides A. octospinosus with broad spectrum activity against Escovopsis and other microfungal weeds.

  8. Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells: A novel technique for cell energy phenotyping

    DEFF Research Database (Denmark)

    Juul, Troels; Palm, Fredrik; Nielsen, Per Mose;


    ) C MR is suitable for cells isolated from kidney tissue, without prior cell culture. METHODS: Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system...

  9. Metabolomic Profiling and Genomic Study of a Marine Sponge-Associated Streptomyces sp.

    Directory of Open Access Journals (Sweden)

    Christina Viegelmann


    Full Text Available Metabolomics and genomics are two complementary platforms for analyzing an organism as they provide information on the phenotype and genotype, respectively. These two techniques were applied in the dereplication and identification of bioactive compounds from a Streptomyces sp. (SM8 isolated from the sponge Haliclona simulans from Irish waters. Streptomyces strain SM8 extracts showed antibacterial and antifungal activity. NMR analysis of the active fractions proved that hydroxylated saturated fatty acids were the major components present in the antibacterial fractions. Antimycin compounds were initially putatively identified in the antifungal fractions using LC-Orbitrap. Their presence was later confirmed by comparison to a standard. Genomic analysis of Streptomyces sp. SM8 revealed the presence of multiple secondary metabolism gene clusters, including a gene cluster for the biosynthesis of the antifungal antimycin family of compounds. The antimycin gene cluster of Streptomyces sp. SM8 was inactivated by disruption of the antimycin biosynthesis gene antC. Extracts from this mutant strain showed loss of antimycin production and significantly less antifungal activity than the wild-type strain. Three butenolides, 4,10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1, 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olide (2, and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (3 that had previously been reported from marine Streptomyces species were also isolated from SM8. Comparison of the extracts of Streptomyces strain SM8 and its host sponge, H. simulans, using LC-Orbitrap revealed the presence of metabolites common to both extracts, providing direct evidence linking sponge metabolites to a specific microbial symbiont.

  10. 40 CFR Appendix A to Part 355 - The List of Extremely Hazardous Substances and Their Threshold Planning Quantities (United States)


    ... Pentafluoride 500 500 1397-94-0 Antimycin A b 1,000 1,000/10,000 86-88-4 ANTU 100 500/10,000 1303-28-2 Arsenic... 500 814-49-3 Diethyl Chlorophosphate d 500 500 71-63-6 Digitoxin b 100 100/10,000 2238-07-5 Diglycidyl... Acetate 500 500/10,000 80-63-7 Methyl 2-Chloroacrylate 500 500 74-83-9 Methyl Bromide f 1,000 1,000...

  11. Characterization of cereulide synthetase, a toxin-producing macromolecular machine.

    Directory of Open Access Journals (Sweden)

    Diego A Alonzo

    Full Text Available Cereulide synthetase is a two-protein nonribosomal peptide synthetase system that produces a potent emetic toxin in virulent strains of Bacillus cereus. The toxin cereulide is a depsipeptide, as it consists of alternating aminoacyl and hydroxyacyl residues. The hydroxyacyl residues are derived from keto acid substrates, which cereulide synthetase selects and stereospecifically reduces with imbedded ketoreductase domains before incorporating them into the growing depsipeptide chain. We present an in vitro biochemical characterization of cereulide synthetase. We investigate the kinetics and side chain specificity of α-keto acid selection, evaluate the requirement of an MbtH-like protein for adenylation domain activity, assay the effectiveness of vinylsulfonamide inhibitors on ester-adding modules, perform NADPH turnover experiments and evaluate in vitro depsipeptide biosynthesis. This work also provides biochemical insight into depsipeptide-synthesizing nonribosomal peptide synthetases responsible for other bioactive molecules such as valinomycin, antimycin and kutzneride.

  12. Utilization of adenosine triphosphate in rat mast cells during histamine release induced by the ionophore A23187

    DEFF Research Database (Denmark)

    Johansen, Torben


    The role of endogenous adenosine triphosphate (ATP) in histamine release from rat mast cells induced by the ionophore A23187 in vitro has been studied. 2 The amount of histamine released by calcium from rat mast cells primed with the ionophore A23187 was dependent on the ATP content of the mast...... cells. 3 In aerobic experiments a drastic reduction in mast cell ATP content was found during the time when histamine release induced by A23187 takes place. 4 Anaerobic experiments were performed with metabolic inhibitors (antimycin A, oligomycin, and carbonyl cyanide p......-trifluorometroxyphenylnydrazone), which are known to block the energy-dependent calcium uptake by isolated mitochondria. The mast cell ATP content was reduced during A23187-induced histamine release under anaerobic conditions in the presence of glucose. This indicates an increased utilization of ATP during the release process. 5...

  13. Ascorbic acid is a key participant during the interactions between chloroplasts and mitochondria to optimize photosynthesis and protect against photoinhibition

    Indian Academy of Sciences (India)

    Saikrishna Talla; Khateef Riazunnisa; Lolla Padmavathi; Pidakala Rajsheel; Agepati S Raghavendra


    The possible role of L-ascorbate (AsA) as a biochemical signal during the interactions between photosynthesis and respiration was examined in leaf discs of Arabidopsis thaliana. AsA content was either decreased as in AsA-deficient vtc1 mutants or increased by treatment with L-galactono-1, 4-lactone (L-GalL, a precursor of AsA; EC In mutants, photosynthesis was extremely sensitive to both antimycin A (inhibitor of the cytochrome oxidase pathway [COX pathway]) and salicylhydroxamic acid (SHAM, inhibitor of the alternative pathway [AOX pathway]), particularly at high light conditions. Mitochondrial inhibitors lowered the ratio of reduced AsA to total AsA, at high light, indicating oxidative stress in leaf discs. Elevation of AsA by L-GalL decreased the sensitivity of photosynthesis at high light to antimycin A or SHAM, sustained photosynthesis at supraoptimal light and relieved the extent of photoinhibition. High ratios of reduced AsA to total AsA in L-GalL-treated leaf discs suggests that L-GalL lowers oxidative stress. The protection by L-GalL of photosynthesis against the mitochondrial inhibitors and photoinhibition was quite pronounced in vtc1 mutants. Our results suggest that the levels and redox state of AsA modify the pattern of modulation of photosynthesis by mitochondrial metabolism. The extent of the AOX pathway as a percentage of the total respiration in Arabidopsis mesophyll protoplasts was much higher in vtc1 than in wild type. We suggest that the role of AsA becomes pronounced at high light and/or when the AOX pathway is inhibited. While acknowledging the importance of the COX pathway, we hypothesize that AsA and the AOX pathway may complement each other to protect photosynthesis against photoinhibition.

  14. A broad distribution of the alternative oxidase in microsporidian parasites.

    Directory of Open Access Journals (Sweden)

    Bryony A P Williams


    Full Text Available Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of iron-sulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX, a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1 as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosomes.

  15. Existence of aa3-type ubiquinol oxidase as a terminal oxidase in sulfite oxidation of Acidithiobacillus thiooxidans. (United States)

    Sugio, Tsuyoshi; Hisazumi, Tomohiro; Kanao, Tadayoshi; Kamimura, Kazuo; Takeuchi, Fumiaki; Negishi, Atsunori


    It was found that Acidithiobacillus thiooxidans has sulfite:ubiquinone oxidoreductase and ubiquinol oxidase activities in the cells. Ubiquinol oxidase was purified from plasma membranes of strain NB1-3 in a nearly homogeneous state. A purified enzyme showed absorption peaks at 419 and 595 nm in the oxidized form and at 442 and 605 nm in the reduced form. Pyridine ferrohaemochrome prepared from the enzyme showed an alpha-peak characteristic of haem a at 587 nm, indicating that the enzyme contains haem a as a component. The CO difference spectrum of ubiquinol oxidase showed two peaks at 428 nm and 595 nm, and a trough at 446 nm, suggesting the existence of an aa(3)-type cytochrome in the enzyme. Ubiquinol oxidase was composed of three subunits with apparent molecular masses of 57 kDa, 34 kDa, and 23 kDa. The optimum pH and temperature for ubiquinol oxidation were pH 6.0 and 30 degrees C. The activity was completely inhibited by sodium cyanide at 1.0 mM. In contrast, the activity was inhibited weakly by antimycin A(1) and myxothiazol, which are inhibitors of mitochondrial bc(1) complex. Quinone analog 2-heptyl-4-hydoroxyquinoline N-oxide (HOQNO) strongly inhibited ubiquinol oxidase activity. Nickel and tungstate (0.1 mM), which are used as a bacteriostatic agent for A. thiooxidans-dependent concrete corrosion, inhibited ubiquinol oxidase activity 100 and 70% respectively.

  16. Enzymic analysis of NADPH metabolism in beta-lactam-producing Penicillium chrysogenum: presence of a mitochondrial NADPH dehydrogenase. (United States)

    Harris, Diana M; Diderich, Jasper A; van der Krogt, Zita A; Luttik, Marijke A H; Raamsdonk, Léonie M; Bovenberg, Roel A L; van Gulik, Walter M; van Dijken, Johannes P; Pronk, Jack T


    Based on assumed reaction network structures, NADPH availability has been proposed to be a key constraint in beta-lactam production by Penicillium chrysogenum. In this study, NADPH metabolism was investigated in glucose-limited chemostat cultures of an industrial P. chrysogenum strain. Enzyme assays confirmed the NADP(+)-specificity of the dehydrogenases of the pentose-phosphate pathway and the presence of NADP(+)-dependent isocitrate dehydrogenase. Pyruvate decarboxylase/NADP(+)-linked acetaldehyde dehydrogenase and NADP(+)-linked glyceraldehyde-3-phosphate dehydrogenase were not detected. Although the NADPH requirement of penicillin-G-producing chemostat cultures was calculated to be 1.4-1.6-fold higher than that of non-producing cultures, in vitro measured activities of the major NADPH-providing enzymes were the same. Isolated mitochondria showed high rates of antimycin A-sensitive respiration of NADPH, thus indicating the presence of a mitochondrial NADPH dehydrogenase that oxidises cytosolic NADPH. The presence of this enzyme in P. chrysogenum might have important implications for stoichiometric modelling of central carbon metabolism and beta-lactam production and may provide an interesting target for metabolic engineering.

  17. Identification of interacting partners of Human Mpv17-like protein with a mitigating effect of mitochondrial dysfunction through mtDNA damage. (United States)

    Iida, Reiko; Ueki, Misuzu; Yasuda, Toshihiro


    Human Mpv17-like protein (M-LPH) has been suggested to participate in mitochondrial function. In this study, we investigated the proteins that interact with M-LPH, and identified four: H2A histone family, member X (H2AX), ribosomal protein S14 (RPS14), ribosomal protein S3 (RPS3) and B-cell receptor-associated protein 31 (Bap31). Immunofluorescence and subcellular fractionation studies revealed that M-LPH is localized predominantly in the nucleus, to some extent in a subset of mitochondria, and marginally in the cytosol. Mitochondrial M-LPH appeared as punctate foci, and these were co-localized with a subset of mitochondrial transcription factor A (TFAM) and mtDNA, indicating that M-LPH is localized in or in close proximity to mitochondrial nucleoids. RNAi-mediated knockdown of M-LPH resulted in an increase of mtDNA damage and reduced the expression of mtDNA-encoded genes. A ROS inducer, antimycin A, caused an increase in both the number and size of the mitochondrial M-LPH foci, and these foci were co-localized with two enzymes, DNA polymerase γ (POLG) and DNA ligase III (LIG3), both involved in mtDNA repair. Furthermore, knockdown of M-LPH hampered mitochondrial localization of these enzymes. Taken together, these observations suggest that M-LPH is involved in the maintenance of mtDNA and protects cells from mitochondrial dysfunction.

  18. Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV. (United States)

    Diaz, Francisca; Enríquez, José Antonio; Moraes, Carlos T


    Mitochondrial respiratory complexes of the electron transport chain (CI, CIII, and CIV) can be assembled into larger structures forming supercomplexes. We analyzed the assembly/stability of respiratory complexes in mouse lung fibroblasts lacking the Rieske iron-sulfur protein (RISP knockout [KO]cells), one of the catalytic subunits of CIII. In the absence of RISP, most of the remaining CIII subunits were able to assemble into a large precomplex that lacked enzymatic activity. CI, CIV, and supercomplexes were decreased in the RISP-deficient cells. Reintroduction of RISP into KO cells restored CIII activity and increased the levels of active CI, CIV, and supercomplexes. We found that hypoxia (1% O(2)) resulted in increased levels of CI, CIV, and supercomplex assembly in RISP KO cells. In addition, treatment of control cells with different oxidative phosphorylation (OXPHOS) inhibitors showed that compounds known to generate reactive oxygen species (ROS) (e.g., antimycin A and oligomycin) had a negative impact on CI and supercomplex levels. Accordingly, a superoxide dismutase (SOD) mimetic compound and SOD2 overexpression provided a partial increase in supercomplex levels in the RISP KO cells. Our data suggest that the stability of CI, CIV, and supercomplexes is regulated by ROS in the context of defective oxidative phosphorylation.

  19. Mitochondrial Respiratory Chain Inhibitors Involved in ROS Production Induced by Acute High Concentrations of Iodide and the Effects of SOD as a Protective Factor

    Directory of Open Access Journals (Sweden)

    Lingyan Wang


    Full Text Available A major source of reactive oxygen species (ROS generation is the mitochondria. By using flow cytometry of the mitochondrial fluorescent probe, MitoSOX Red, western blot of mitochondrial ROS scavenger Peroxiredoxin (Prx 3 and fluorescence immunostaining, ELISA of cleaved caspases 3 and 9, and TUNEL staining, we demonstrated that exposure to 100 μM KI for 2 hours significantly increased mitochondrial superoxide production and Prx 3 protein expression with increased expressions of cleaved caspases 3 and 9. Besides, we indicated that superoxide dismutase (SOD at 1000 unit/mL attenuated the increase in mitochondrial superoxide production, Prx 3 protein expression, and lactate dehydrogenase (LDH release and improved the relative cell viability at 100 μM KI exposure. However, SOD inhibitor diethyldithiocarbamic acid (DETC (2 mM, Rotenone (0.5 μM, a mitochondrial complex I inhibitor, and Antimycin A (10 μM, a complex III inhibitor, caused an increase in mitochondrial superoxide production, Prx 3 protein expression, and LDH release and decreased the relative cell viability. We conclude that the inhibitors of mitochondrial respiratory chain complex I or III may be involved in oxidative stress caused by elevated concentrations of iodide, and SOD demonstrates its protective effect on the Fischer rat thyroid cell line (FRTL cells.

  20. Oxidative stress in duckweed (Lemna minor L.) induced by glyphosate: Is the mitochondrial electron transport chain a target of this herbicide? (United States)

    Gomes, Marcelo Pedrosa; Juneau, Philippe


    We investigated the physiological responses of Lemna minor plants exposed to glyphosate. The deleterious effects of this herbicide on photosynthesis, respiration, and pigment concentrations were related to glyphosate-induced oxidative stress through hydrogen peroxide (H2O2) accumulation. By using photosynthetic and respiratory electron transport chain (ETC) inhibitors we located the primary site of reactive oxygen species (ROS) production in plants exposed to 500 mg glyphosate l(-1). Inhibition of mitochondrial ETC Complex I by rotenone reduced H2O2 concentrations in glyphosate-treated plants. Complex III activity was very sensitive to glyphosate which appears to act much like antimycin A (an inhibitor of mitochondrial ETC Complex III) by shunting electrons from semiquinone to oxygen, with resulting ROS formation. Confocal evaluations for ROS localization showed that ROS are initially produced outside of the chloroplasts upon initial glyphosate exposure. Our results indicate that in addition to interfering with the shikimate pathway, glyphosate can induce oxidative stress in plants through H2O2 formation by targeting the mitochondrial ETC, which would explain its observed effects on non-target organisms.

  1. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease.

    Directory of Open Access Journals (Sweden)

    Shilpi Khare


    Full Text Available Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1 in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50 of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease.

  2. [Bioactivity of endophytic actinomycetes from medicinal plants and secondary metabolites from strain D62]. (United States)

    Liu, Ning; Zhang, Hui; Zheng, Wen; Huang, Ying; Wang, Hai-Bin


    It is believed that genetic recombination of the endophytes with the hosts that occurred in evolutionary time could result in some endophytes producing certain phytochemical originally characteristic of the host. Based on this widely accepted hypothesis, there have been increasing research efforts focused on screening for novel natural products from endophytes. In this study, antimicrobial and antitumor activities of 165 actinomycetes isolated from medicinal plants collected from Xishuangbanna were tested by agar diffusion method and WST-8 assay respectively. The results showed that over 42% of the isolates exhibited antagonism against pathogenic strains, and 54.5% displayed excellent inhibition against mouse melanoma cell line B16 or/and human alveolar epithelial cell line A549. These results are superior to those of soil actinomycetes, indicating tremendous potential of endophytic of actinomycetes for exploration. Six compounds that had both antimicrobial and antitumor activities were separated and purified from isolate Streptomyces sp. D62 by resin adsorption, silica-gel column and sephadex chromatography, etc. On the basis of spectral analyses, they were identified as antimycin A4a (1), antimycin A7a (2), antimycin A2a (3), antimycin A1a (4), 10-hydroxy-10-methyl-dodec-2-en-1,4-olide (5) and 6-(2-(4-aminophenyl)-2-oxoethyl)-3,5-dimethyl-tetrahydropyran-2-one(6), with the last one defined as a novel compound. Based on all these results, it is convinced that endophytic actinomycetes are a promising resource for bioactive natural product discovery.

  3. Kinetics of Molybdenum Reduction to Molybdenum Blue by Bacillus sp. Strain A.rzi

    Directory of Open Access Journals (Sweden)

    A. R. Othman


    Full Text Available Molybdenum is very toxic to agricultural animals. Mo-reducing bacterium can be used to immobilize soluble molybdenum to insoluble forms, reducing its toxicity in the process. In this work the isolation of a novel molybdate-reducing Gram positive bacterium tentatively identified as Bacillus sp. strain A.rzi from a metal-contaminated soil is reported. The cellular reduction of molybdate to molybdenum blue occurred optimally at 4 mM phosphate, using 1% (w/v glucose, 50 mM molybdate, between 28 and 30°C and at pH 7.3. The spectrum of the Mo-blue product showed a maximum peak at 865 nm and a shoulder at 700 nm. Inhibitors of bacterial electron transport system (ETS such as rotenone, sodium azide, antimycin A, and potassium cyanide could not inhibit the molybdenum-reducing activity. At 0.1 mM, mercury, copper, cadmium, arsenic, lead, chromium, cobalt, and zinc showed strong inhibition on molybdate reduction by crude enzyme. The best model that fitted the experimental data well was Luong followed by Haldane and Monod. The calculated value for Luong’s constants pmax, Ks, Sm, and n was 5.88 μmole Mo-blue hr−1, 70.36 mM, 108.22 mM, and 0.74, respectively. The characteristics of this bacterium make it an ideal tool for bioremediation of molybdenum pollution.

  4. A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets.

    Directory of Open Access Journals (Sweden)

    Jakob D Wikstrom

    Full Text Available BACKGROUND: The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets. METHODOLOGY/PRINCIPAL FINDINGS: The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets. CONCLUSIONS/SIGNIFICANCE: The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells.

  5. Estimation of the rate of energy production of rat mast cells in vitro

    DEFF Research Database (Denmark)

    Johansen, Torben


    Rat mast cells were treated with glycolytic and respiratory inhibitors. The rate of adenosine triphosphate depletion of cells incubated with both types of inhibitors and the rate of lactate produced in presence of antimycin A and glucose were used to estimate the rate of oxidative and glycolytic...

  6. Increased Na+/K(+)-pump activity and adenosine triphosphate utilization after compound 48/80-induced histamine secretion from rat mast cells

    DEFF Research Database (Denmark)

    Johansen, Torben; Praetorius, Birger Hans


    -production were measured by the bioluminescence technique (firefly lantern) and by measurement of the lactate production under anaerobic conditions (antimycin A, oligomycin), respectively. There was an increased requirement for ATP after the secretory response associated with an increased activity of the Na...

  7. Chemo-sensitization of fungal pathogens to antimicrobial agents using benzaldehyde analogs (United States)

    Activity of conventional antifungal agents, fludioxonil, strobilurin and antimycinA, which target the oxidative and osmotic stress response systems, was elevated by co-application of certain analogs of benzaldehyde. Fungal tolerance to 2,3-dihydroxybenzaldehyde or 2,3-dihydroxybenzoic acid was foun...

  8. Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

    Directory of Open Access Journals (Sweden)

    William Dott


    Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a

  9. Reactive oxygen species in unstimulated hemocytes of the pacific oyster Crassostrea gigas: a mitochondrial involvement.

    Directory of Open Access Journals (Sweden)

    Ludovic Donaghy

    Full Text Available The Pacific oyster Crassostrea gigas is a sessile bivalve mollusc whose homeostasis relies, at least partially, upon cells circulating in hemolymph and referred to as hemocytes. Oyster's hemocytes have been reported to produce reactive oxygen species (ROS, even in absence of stimulation. Although ROS production in bivalve molluscs is mostly studied for its defence involvement, ROS may also be involved in cellular and tissue homeostasis. ROS sources have not yet been described in oyster hemocytes. The objective of the present work was to characterize the ROS sources in unstimulated hemocytes. We studied the effects of chemical inhibitors on the ROS production and the mitochondrial membrane potential (Δψ(m of hemocytes. First, this work confirmed the specificity of JC-10 probe to measure Δψ(m in oyster hemocytes, without being affected by ΔpH, as reported in mammalian cells. Second, results show that ROS production in unstimulated hemocytes does not originate from cytoplasmic NADPH-oxidase, nitric oxide synthase or myeloperoxidase, but from mitochondria. In contrast to mammalian cells, incubation of hemocytes with rotenone (complex I inhibitor had no effect on ROS production. Incubation with antimycin A (complex III inhibitor resulted in a dose-dependent ROS production decrease while an over-production is usually reported in vertebrates. In hemocytes of C. gigas, the production of ROS seems similarly dependent on both Δψ(m and ΔpH. These findings point out differences between mammalian models and bivalve cells, which warrant further investigation about the fine characterization of the electron transfer chain and the respective involvement of mitochondrial complexes in ROS production in hemocytes of bivalve molluscs.

  10. Recombinant Bcl-xL attenuates vascular hyperpermeability in a rat model of hemorrhagic shock (United States)

    Tharakan, B; McNeal, SI; Hunter, FA; Sawant, DA; Smythe, WR; Childs, EW


    Following hemorrhagic shock (HS), vascular hyperpermeability, that is, the leakage of fluid, nutrients and proteins into the extravascular space occurs primarily due to the disruption of the endothelial cell–cell adherens junctional complex. Studies from our laboratory demonstrate that activation of the mitochondria-mediated ‘intrinsic’ apoptotic signaling cascade has a significant role in modulating HS-induced hyperpermeability. Here we report the novel use of recombinant Bcl-xL, an anti-apoptotic protein, to control HS-induced vascular hyperpermeability. Our results corroborate involvement of vascular hyperpermeability and apoptotic signaling. HS (the mean arterial pressure (MAP) was reduced to 40 mm Hg for 60 min followed by resuscitation to 90 mm Hg for 60 min) in rats resulted in vascular hyperpermeability as determined by intravital microscopy. Treatment of Bcl-xL (2.5 µg/ml of rat blood in non-lipid cationic polymer, i.v.) before, during and even after HS attenuated or reversed HS-induced vascular hyperpermeability significantly (P<0.05). Conversely, treatment using Bcl-xL inhibitors, 2-methoxy antimycin (2-OMeAA) and ABT 737, significantly increased vascular hyperpermeability compared with sham (P<0.05). Bcl-xL treatment also decreased the amount of fluid volume required to maintain a MAP of 90 mm Hg during resuscitation (P<0.05). HS resulted in an increased mitochondrial reactive oxygen species formation, reduction of ΔΨm, mitochondrial release of cytochrome c and significant activation of caspase-3 (P<0.05). All of these effects were significantly inhibited by Bcl-xL pre-treatment (P<0.05). Our results show that recombinant Bcl-xL is effective against HS-induced vascular hyperpermeability that appears to be mediated through the preservation of ΔΨm and subsequent prevention of caspase-3 activation. PMID:27042339

  11. Induction of mitochondrial alternative oxidase in response to a cell signal pathway down-regulating the cytochrome pathway prevents programmed cell death. (United States)

    Vanlerberghe, Greg C; Robson, Christine A; Yip, Justine Y H


    Treatment of tobacco (Nicotiana tabacum L. cv Petit Havana SR1) cells with cysteine (Cys) triggers a signal pathway culminating in a large loss of mitochondrial cytochrome (cyt) pathway capacity. This down-regulation of the cyt path likely requires events outside the mitochondrion and is effectively blocked by cantharidin or endothall, indicating that protein dephosphorylation is one critical process involved. Generation of reactive oxygen species, cytosolic protein synthesis, and Ca(2+) flux from organelles also appear to be involved. Accompanying the loss of cyt path is a large induction of alternative oxidase (AOX) protein and capacity. Induction of AOX allows the cells to maintain high rates of respiration, indicating that the lesion triggered by Cys is in the cyt path downstream of ubiquinone. Consistent with this, transgenic (AS8) cells unable to induce AOX (due to the presence of an antisense transgene) lose all respiratory capacity upon Cys treatment. This initiates in AS8 a programmed cell death pathway, as evidenced by the accumulation of oligonucleosomal fragments of DNA as the culture dies. Alternatively, wild-type cells remain viable and eventually recover their cyt path. Induction of AOX in response to a chemical inhibition of the cyt path (by antimycin A) is also dependent upon protein dephosphorylation and the generation of reactive oxygen species. Common events required for both down-regulation of the cyt path and induction of AOX may represent a mechanism to coordinate the biogenesis of these two electron transport paths. Such coordinate regulation may be necessary, not only to satisfy metabolic demands, but also to modulate the initiation of a programmed cell death pathway responsive to mitochondrial respiratory status.

  12. Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apoA-I from murine RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Allen Anne Marie


    Full Text Available Abstract Background Mitochondrial DNA damage, increased production of reactive oxygen species and progressive respiratory chain dysfunction, together with increased deposition of cholesterol and cholesteryl esters, are hallmarks of atherosclerosis. This study investigated the role of mitochondrial function in regulation of macrophage cholesterol efflux to apolipoprotein A-I, by the addition of established pharmacological modulators of mitochondrial function. Methods Murine RAW 264.7 macrophages were treated with a range of concentrations of resveratrol, antimycin, dinitrophenol, nigericin and oligomycin, and changes in viability, cytotoxicity, membrane potential and ATP, compared with efflux of [3H]cholesterol to apolipoprotein (apo A-I. The effect of oligomycin treatment on expression of genes implicated in macrophage cholesterol homeostasis were determined by quantitative polymerase chain reaction, and immunoblotting, relative to the housekeeping enzyme, Gapdh, and combined with studies of this molecule on cholesterol esterification, de novo lipid biosynthesis, and induction of apoptosis. Significant differences were determined using analysis of variance, and Dunnett’s or Bonferroni post t-tests, as appropriate. Results The positive control, resveratrol (24 h, significantly enhanced cholesterol efflux to apoA-I at concentrations ≥30 μM. By contrast, cholesterol efflux to apoA-I was significantly inhibited by nigericin (45%; ppAbca1 mRNA. Oligomycin treatment did not affect cholesterol biosynthesis, but significantly inhibited cholesterol esterification following exposure to acetylated LDL, and induced apoptosis at ≥30 μM. Finally, oligomycin induced the expression of genes implicated in both cholesterol efflux (Abca1, Abcg4, Stard1 and cholesterol biosynthesis (Hmgr, Mvk, Scap, Srebf2, indicating profound dysregulation of cholesterol homeostasis. Conclusions Acute loss of mitochondrial function, and in particular Δψm, reduces

  13. A possible role of oxidative stress in the switch mechanism of the cell death mode from apoptosis to necrosis--studies on rho0 cells. (United States)

    Wochna, Agnieszka; Niemczyk, Edyta; Kurono, Chieko; Masaoka, Makoto; Kedzior, Jakub; Słomińska, Ewa; Lipiński, Marcin; Wakabayashi, Takashi


    Apoptosis is induced not only during morphogenesis and embryogenesis but also under various pathological conditions, especially related to oxidative stress. Apoptotic cells are phagocytized by neighboring cells while necrotic cells cause local and general reactions sometimes lethal to our bodies. Data have been accumulated to demonstrate that the switch of the cell death mode from apoptosis to necrosis does occur. However, detailed mechanisms involved in the switch mechanism remain unsolved although decreases in the intracellular level of ATP and a burst in the cellular level of reactive oxygen species (ROS) have been proposed. Recently, we have shown that the population of apoptotic cells reaches maximum in human osteosarcoma 143B cells treated for 6h with menadione (MEN) while necrotic cells become predominant at 9h of the treatment. In the present study we have attempted to clarify the role of cellular ATP in the switch mechanism using rho(0) cells derived from human osteosarcoma rho+ cells. Results are summarized as follows: (1) Apoptotic and necrotic changes in rho(0) cells are much faster than rho+ cells after the treatment with MEN. (2) Cellular level of ATP in rho(0) cells remains essentially in the same level before and after the MEN-treatment while intracellular levels of superoxide continuously increase after the MEN-treatment. (3) rho+ cells treated with MEN in the presence of antimycin A plus oligomycin show similar changes to those of MEN-treated rho(0) cells. (4) MEN-induced increases in the cellular level of superoxide are distinctly suppressed by inhibitors of NADPH oxidase. These results suggest that the intracellular level of superoxide may be a key factor directly related to the switch mechanism from apoptosis to necrosis, and that decreases in cellular level of ATP accelerate both apoptotic and necrotic changes of the cells.

  14. Decreased Pasteur effect in platelets of aged individuals. (United States)

    D'Aurelio, M; Merlo Pich, M; Catani, L; Sgarbi, G L; Bovina, C; Formiggini, G; Parenti Castelli, G; Baum, H; Tura, S; Lenaz, G


    We have investigated the mitochondrial energy state in human platelets of young (19-30 years old) and aged individuals (65-87 years old) exploiting the Pasteur effect, i.e. stimulation of lactate production by incubation of the purified platelets with the mitochondrial respiratory chain inhibitor, antimycin A. This assay allows the determination of mitochondrial function with respect to glycolysis, and the ratio of mitochondrial adenosine triphosphate (ATP) to glycolytic ATP. A significant increase of basal, non-stimulated lactate production and decrease of the stimulation by antimycin A were observed in the older individuals, suggesting that the impairment of oxidative phosphorylation detectable in post-mitotic tissues of aged individuals can be observed also in easily collectable blood cells.

  15. Regulation of cyclic photophosphorylation during ferredoxin-mediated electron transport. Effect of DCMU and the NADPH/NADP/sup +/ ratio

    Energy Technology Data Exchange (ETDEWEB)

    Hosler, J.P.; Yocum, C.F.


    Addition of ferredoxin to isolated thylakoid membranes reconstitutes electron transport from water to NADP and to O/sub 2/ (the Mehler reaction). This electron flow is coupled to ATP synthesis, and both cyclic and noncyclic electron transport drive photophosphorylation. Under conditions where the NADPH/NADP/sup +/ ratio is varied, as is the amount of ATP synthesis due to cyclic activity is also varied, as is the amount of cyclic activity which is sensitive to antimycin A. Partial inhibition of photosystem II activity with DCMU (which affects reduction of electron carriers of the interphotosystem chain) also affects the level of cyclic activity. The results of these experiments indicate that two modes of cyclic electron transfer activity, which differ in their antimycin A sensitivity, can operate in the thylakoid membrane. Regulation of these activities can occur at the level of ferredoxin and is governed by the NADPH/NADP ratio.

  16. Inhibition of oxidative phosphorylation for enhancing citric acid production by Aspergillus niger


    Wang, Lu; Zhang, Jianhua; Cao, Zhanglei; Wang, Yajun; Gao, Qiang; Zhang, Jian; Wang, Depei


    Background The spore germination rate and growth characteristics were compared between the citric acid high-yield strain Aspergillus niger CGMCC 5751 and A. niger ATCC 1015 in media containing antimycin A or DNP. We inferred that differences in citric acid yield might be due to differences in energy metabolism between these strains. To explore the impact of energy metabolism on citric acid production, the changes in intracellular ATP, NADH and NADH/NAD+ were measured at various fermentation s...

  17. Bioactivity of endophytic actinomycetes from medicinal plants and secondary metabolites from strain D62%药用植物内生放线菌的生物活性及菌株D62的代谢产物分析

    Institute of Scientific and Technical Information of China (English)

    刘宁; 张辉; 郑文; 黄英; 王海彬; 雒文军


    利用琼脂移块法及WST-8法分别对分离自西双版纳药用植物的165株内生放线菌进行了抗菌、抗肿瘤活性测定.结果显示,超过42%的菌株对病原菌表现出拮抗活性,且对病原真菌的总体拮抗活性明显强于土壤放线菌;78%的菌株表现出抗肿瘤活性,且大部分菌株(54.5%)具有强抗肿瘤活性.选取其中对真菌及肿瘤细胞均有高抑制活性的菌株D62,并对其次生代谢产物进行了进一步的研究,共分离得6个化合物,分别是Antimycin A4a(1),Antimycin A7a(2)、Antimycin A2a(3)、Antimycin A1a(4)、10-hydroxy-10-methyl-dodec-2-en-1,4-olide(5)及6-(2-(4-aminophenyl)-2-oxoethyl)-3,5-dimethyl-tetrahydropyran-2-one(6),其中化合物6为新化合物.以上结果表明药用植物内生放线菌作为一类新的微生物资源具有很好的开发潜力.

  18. Influence of growth regulators and respiration inhibitors on dark transformation of phytochrome in coleoptiles of oat seedlings

    Directory of Open Access Journals (Sweden)

    Jan Kopcewicz


    Full Text Available Irradiation with red light leads to the formation of an unstable, undergoing gradual destruction, physiologically active PFR form of phytochrome in the coleoptiles of oat seedlings. Growth substances: IAA, GA3, kinetin, ABA, ethrel as well acetylcholine do not influence the nature and rate of phytochrome dark transformation. Inhibitors of energy-producing processes such as KCN, 2,4-DNP, DCCD and antimycin A inhibit the process of dark destruction of the PFR form of phytochrome.

  19. Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria. (United States)

    Turrens, J F; Alexandre, A; Lehninger, A L


    Much evidence indicates that superoxide is generated from O2 in a cyanide-sensitive reaction involving a reduced component of complex III of the mitochondrial respiratory chain, particularly when antimycin A is present. Although it is generally believed that ubisemiquinone is the electron donor to O2, little experimental evidence supporting this view has been reported. Experiments with succinate as electron donor in the presence of antimycin A in intact rat heart mitochondria, which contain much superoxide dismutase but little catalase, showed that myxothiazol, which inhibits reduction of the Rieske iron-sulfur center, prevented formation of hydrogen peroxide, determined spectrophotometrically as the H2O2-peroxidase complex. Similarly, depletion of the mitochondria of their cytochrome c also inhibited formation of H2O2, which was restored by addition of cytochrome c. These observations indicate that factors preventing the formation of ubisemiquinone also prevent H2O2 formation. They also exclude ubiquinol, which remains reduced under these conditions, as the reductant of O2. Since cytochrome b also remains fully reduced when myxothiazol is added to succinate- and antimycin A-supplemented mitochondria, reduced cytochrome b may also be excluded as the reductant of O2. These observations, which are consistent with the Q-cycle reactions, by exclusion of other possibilities leave ubisemiquinone as the only reduced electron carrier in complex III capable of reducing O2 to O2-.

  20. Strong Pasteur effect in rabbit corneal endothelium preserves fluid transport under anaerobic conditions. (United States)

    Riley, M V; Winkler, B S


    1. The hydration and transparency of the mammalian cornea are maintained by a metabolically dependent fluid transport system located in the endothelial cell layer. The purpose of the study was to determine whether this pump activity is dependent upon aerobic or anaerobic metabolism. 2. The ability of the cornea, superfused in vitro with a bicarbonate-Ringer solution containing glucose and adenosine, to maintain normal hydration (thickness) when respiration is inhibited has been examined in intact and de-epithelialized preparations and correlated with glycolytic activity and cellular concentrations of ATP. 3. In respiring intact and de-epithelialized corneas thickness was maintained for periods up to 5 h during superfusion with the control Ringer solution. 4. KCN (10(-3) M) or antimycin A (10(-6) M) caused the intact cornea to swell at 15 +/- 3 microns h-1, whereas the de-epithelialized tissue maintained normal thickness under these conditions. This swelling of the intact tissue appears to be due to the osmotic effect of increased epithelial lactate production under anaerobic conditions. 5. Pre-swollen de-epithelialized corneas deturgesced fully to original thickness at a rate of 43 +/- 7 microns h-1 under aerobic conditions, but with KCN or antimycin they deturgesced at only 65% of that rate and generally failed to return to their original thickness. 6. Ouabain (10(-4) M) caused de-epithelialized corneas to swell in the presence of KCN or antimycin, as it did under aerobic conditions, showing that maintenance of hydration or deturgescence are pump-dependent processes under both conditions. 7. Lactate production was markedly stimulated by KCN or antimycin in intact and de-epithelialized preparations, but not in the stroma alone. The magnitude of the Pasteur effect was calculated to be 5-fold in the endothelium and 2.5-fold in the epithelium. Ouabain inhibited anaerobic lactate production in the endothelium by 50%. 8. ATP content of the epithelium following 5 h

  1. Genetic localization of diuron- and mucidin-resistant mutants relative to a group of loci of the mitochondrial DNA controlling coenzyme QH2-cytochrome c reductase in Saccharomyces cerevisiae. (United States)

    Colson, A M; Slonimski, P P


    Diuron-resistance, DIU (Colson et al., 1977), antimycin-resistance, ANA (Michaelis, 1976; Burger et al., 1976), funiculosin-resistance, FUN (Pratje and Michaelis, 1977; Burger et al., 1977) and mucidin-resistance, MUC (Subik et al., 1977) are each coded by a pair of genetic loci on the mit DNA of S. cerevisiae. In the present paper, these respiratiory-competent, drug-resistant loci are localized relative to respiratory-deficient BOX mutants deficient in coenzyme QH2-cytochrome c reductase (Kotylak and Slonimski, 1976, 1977) using deletion and recombination mapping. Three drug-resistant loci possessing distinct mutated allelic forms are distinguished. DIU1 is allelic or closely linked to ANA2, FUN1 and BOX1; DIU2 is allelic or closely linked to ANA1, MUC1 and BOX4/5; MUC2 is allelic to BOX6. The high recombinant frequencies observed between the three loci (13% on the average for 33 various combinations analyzed) suggest the existence of either three genes coding for three distinct polypeptides or of a single gene coding for a single polypeptide but subdivided into three easily separable segments. The resistance of the respiratory-chain observed in vitro in the drug-resistant mutants and the allelism relationships between respiratory-competent, drug-resistant loci and coQH2-cyt c reductase deficient, BOX, loci strongly suggest that each of the three drug-resistant loci codes for a structural gene-product which is essential for the normal coQH2-cyt c reductase activity and is obviously a good candidate for a gene product of the drug-resistant loci mapped in this paper. Polypeptide length modifications of cytochrome b were observed in mutants deficient in the coQH2-cyt c red and localized at the BOX1, BOX4 and BOX6 genetic loci (Claisse et al., 1977, 1978) which are precisely the loci allelic to drug resistant mutants as shown in the present work. Taken together these two sets of data provide a strong evidence in favor of the idea that there exist three non contiguous

  2. Inhibition of membrane lipid peroxidation by a radical scavenging mechanism: a novel function for hydroxyl-containing ionophores. (United States)

    Grijalba, M T; Andrade, P B; Meinicke, A R; Castilho, R F; Vercesi, A E; Schreier, S


    In the present study we show that K+/H+ hydroxyl-containing ionophores lasalocid-A (LAS) and nigericin (NIG) in the nanomolar concentration range, inhibit Fe2+-citrate and 2,2'-azobis(2-amidinopropane) dihydrochloride (ABAP)-induced lipid peroxidation in intact rat liver mitochondria and in egg phosphatidylcholine (PC) liposomes containing negatively charged lipids--dicetyl phosphate (DCP) or cardiolipin (CL)--and KCl as the osmotic support. In addition, monensin (MON), a hydroxyl-containing ionophore with higher affinity for Na+ than for K+, promotes a similar effect when NaCl is the osmotic support. The protective effect of the ionophores is not observed when the osmolyte is sucrose. Lipid peroxidation was evidenced by mitochondrial swelling, antimycin A-insensitive O2 consumption, formation of thiobarbituric acid-reactive substances (TBARS), conjugated dienes, and electron paramagnetic resonance (EPR) spectra of an incorporated lipid spin probe. A time-dependent decay of spin label EPR signal is observed as a consequence of lipid peroxidation induced by both inductor systems in liposomes. Nitroxide destruction is inhibited by butylated hydroxytoluene, a known antioxidant, and by the hydroxyl-containing ionophores. In contrast, valinomycin (VAL), which does not possess alcoholic groups, does not display this protective effect. Effective order parameters (Seff), determined from the spectra of an incorporated spin label are larger in the presence of salt and display a small increase upon addition of the ionophores, as a result of the increase of counter ion concentration at the negatively charged bilayer surface. This condition leads to increased formation of the ion-ionophore complex, the membrane binding (uncharged) species. The membrane-incorporated complex is the active species in the lipid peroxidation inhibiting process. Studies in aqueous solution (in the absence of membranes) showed that NIG and LAS, but not VAL, decrease the Fe2+-citrate-induced production

  3. Low-dose methotrexate enhances cycling of highly anaplastic cancer cells (United States)

    Marzi, Ilaria; Olivotto, Massimo


    ABSTRACT We previously showed that cellular RedOx state governs the G1-S transition of AH130 hepatoma, a tumor spontaneously reprogrammed to the embryonic stem cell stage. This transition is impaired when the mithocondrial electron transport system is blocked by specific inhibitors (antimycin A) or the respiratory chain is saturated by adding to the cells high concentrations of pyruvate. The antimycin A or pyruvate block is removed by the addition of adequate concentrations of folate (F). This suggests that the G1-S transition of AH130 cells depends on a respiration-linked step of DNA synthesis related to folate metabolism. In the study reported here, we characterized the effects of methotrexate (MTX), an inhibitor of dihydofolate-reductase, on the G1-S transition of hepatoma cells, in the absence or the presence of exogenously added F, dihydrofolate (FH2) or tetrahydrofolate (FH4). MTX, at 1 μM or higher concentrations, inhibited G1-S transition. This inhibition was completely removed by exogenous folates. Surprisingly, 10 nM MTX stimulated G1-S transition. The addition of F, but not FH2 or FH4, significantly increased this effect. Furthermore, 10 nM MTX removed the block of the G1-S transition operated by antimycin A or pyruvate, an effect which was enhanced in the presence of F. Finally, the stimulatory effect of 10 nM MTX was inhibited in the presence of serine. Our findings indicated that, under certain conditions, MTX may stimulate, rather than inhibiting, the cycling of cancer cells exhibiting a stem cell-like phenotype, such as AH130 cells. This may impact the therapeutic use of MTX and of folates as supportive care. PMID:27841718

  4. Evaluation of cellular energetics by the pasteur effect in intact cardiomyoblasts and isolated perfused hearts. (United States)

    Muscari, Claudio; Gamberini, Chiara; Bonafe', Francesca; Giordano, Emanuele; Bianchi, Cristina; Lenaz, Giorgio; Caldarera, Claudio Marcello


    This work aims at exploring changes in cellular energetics by exploiting the Pasteur effect. We assumed that lactate overproduction arising from antimycin A-induced inhibition of mitochondrial respiration (delta-lactate = stimulated [lactate] -basal [lactate]) is indicative of the energy provided aerobically by the cell. Rat embryonal cardiomyocytes (H9c2), incubated with 2 micromol/L antimycin A, increased about 6 fold their lactate production in a manner linear with time and cell number. Antimycin A was also delivered to Langendorff-perfused rat hearts under control aerobic conditions or after 20 min-ischemia and 30 min-reperfusion. The test started at the end of each perfusion and lactate was measured into perfusate collected for further 25 min. A cardioplegic solution was also delivered during the test to exclude that lactate production was influenced by cardiac contraction. Control delta-lactate was 20.9 +/- 2.31 (S.E.M.) microg/mL and markedly decreased after reperfusion (7.66 +/- 0.51, p < 0.001), showing that energy production was impaired of about 70%. The determination of oxygen consumption by mitochondria isolated from reperfused hearts also suggested that the damage to the respiratory chain was similar to that evaluated by lactate overproduction (Respiratory Control Index: 75% lower than control, p < 0.001). Moreover, when delta-lactate was referred to the estimated cells which remained viable at the end of reperfusion (49.9%), it was 25% lower than control (p < 0.05). Therefore, we proposed this test as a tool for quantifying both physiological and pathological energetic modifications in living intact cardiomyocytes and in isolated and perfused hearts.

  5. Modification of the spectral properties of cytochrome b in mutants of Saccharomyces cerevisiae resistant to 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Mapping at two distinct genetic loci of the split mitochondrial gene of cytochrome b. (United States)

    Briquet, M; Goffeau, A


    The effects of five inhibitors of the cytochrome bc1 complex: 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), 2-n-heptyl-4-hydroxyquinoline-N-oxide (HpHOQnO), antimycin A, funiculosin and mucidin were measured in submitochondrial particles of strains of the yeast Saccharomyces cerevisiae belonging to two classes of diuron-resistant mutants Diu 1 and Diu 2 which are modified in different exons of the split mitochondrial gene of cytochrome b. 1. The oxidation of NADH and of cytochrome b-561 exhibits a similar resistance to diuron and HpHOQnO in Diu 1 and Diu 2 mutants. 2. No extra reduction of cytochrome b-561 and cytochrome b-565 is observed in the presence of diuron and HpHOQnO. 3. Both Diu 1 and Diu 2 mutants exhibit the red shift of cytochrome b-561 induced by concentrations of HpHOQno 2 -- 3-times higher than those required in the parental strains. 4. The spectral and respiratory effects of antimycin A, funiculosin and mucidin and generally similar in the diuron-resistant mutants and in their parental strains. However a cross-resistance between diuron and antimycin A is indicated in one Diu 2 mutant. 5. From the combined genetic and biochemical data it is concluded that the interaction of diuron and HpHOQnO with cytochrome b is mediated by at least two specific amino acids located apart in the central region of the apocytochrome b peptide coded by mitochondrial DNA. These two amino acids control tightly the extra reduction of cytochromes b-565 and b-561 as well as the flow of electrons through the bc1 complex. However the binding of HpHOQnO required for the expression of the red shift of cytochrome b-561 is only slightly affected by the diu-1 and diu-2 mutations.

  6. Ethacrynic acid inhibition of histamine release from rat mast cells: effect on cellular ATP levels and thiol groups

    DEFF Research Database (Denmark)

    Johansen, Torben


    The experiments concerned the effect of ethacrynic acid (0.5 mM) on the adenosine triphosphate (ATP) content of rat mast cells and the effect on histamine release induced by the ionophore A23187 (10 microM). Ethacrynic acid decreased the ATP level of the cells in presence of antimycin A and glucose...... as well as in presence of 2-deoxyglucose. A23187-induced histamine release was inhibited by ethacrynic acid, and this inhibition was completely reversed by dithiothreitol. These observations may indicate that ethacrynic acid inhibits glycolytic and respiratory energy production in rat mast cells...

  7. Terpenoid Metabolism in Plastids 1 (United States)

    Camara, Bilal; Bardat, Françoise; Dogbo, Odette; Brangeon, Judy; Monéger, René


    A technique for the isolation and the purification of Capsicum annum L. var. Yolo Wonder chromoplasts is described. The degree of purity of the isolated chromoplasts is greatly improved by the absence of MgCl2 in the extraction medium and in the gradient purification system, as shown by electron micrographs and the near absence of antimycin-insensitive NADH:cytochrome c reductase activity and succinate:cytochrome c reductase activity. Furthermore, phosphatidylserine was absent and the phosphatidylethanolamine content was reduced by a factor of 5 in these preparations, which were active in the synthesis of galactolipids, prenylquinones, and carotenoids. Images Fig. 1 PMID:16663194

  8. Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism

    DEFF Research Database (Denmark)

    Johansen, Torben


    The relation between anaphylactic histamine release and the adenosine triphosphate (ATP) content of the mast cells was studied. The cells were incubated with glycolytic (2-deoxyglucose) and respiratory inhibitors (antimycin A and oligomycin) in order to decrease the ATP content of the cells prior...... pretreated with 2-deoxyglucose. The release of histamine from these cells was reduced when respiratory inhibitors were added to the cell suspension 5 to 20 sec after exposure of the cells to antigen. This may indicate that the secretory process requires energy, and it seems necessary that energy should...... be produced as the release of histamine takes place....

  9. Cyanide-insensitive respiration in Acanthamoeba castellanii. Changes in sensitivity of whole cell respiration during exponential growth

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, S.W.; Lloyd, D.


    Respiration of Acanthamoeba castellanii shows varying sensitivity to cyanide during exponential growth in a medium containing proteose peptone, glucose and yeast extract. After 20 h growth, respiration was stimulated up to 40% by I mM-cyanide; sensitivity to cyanide then gradually increased until 90% inhibition of respiration was attained in late exponential phase cultures. Salicyl hydroxamic acid alone never stimulated or inhibited respiration by more than 20% but, when added together with cyanide, inhibition was always 70 to 100% from 3 h onward. Sensitivity to antimycin A was similar, but not identical to that shown to cyanide; when antimycin A was added together with salicyl hydroxamic acid, the inhibition was greater. Increased sensitivities to arsenite and malonate were also observed in late-exponential phase cultures. These changes in sensitivities were not associated with alterations in the growth medium since similar changes in sensitivity to inhibitors were observed during growth in conditioned medium. A rotenone-sensitive site is associated with cyanide-stimulated respiration and the results suggest that A. castellanii possesses a branched electron transport system.

  10. The involvement of cytochrome P450 peroxidase in the metabolic bioactivation of cumene hydroperoxide by isolated rat hepatocytes. (United States)

    Anari, M R; Khan, S; O'Brien, P J


    Organic hydroperoxides are believed to be primarily detoxified in cells by the GSH peroxidase/GSSG reductase system and activated to cytotoxic radical species by non-heme iron. However, organic hydroperoxides seem to be bioactivated by cytochrome P450 (P450) in isolated hepatocytes as various P450 (particularly P450 2E1) inhibitors inhibited cumene hydroperoxide (CumOOH) metabolism and attenuated subsequent cytotoxic effects including antimycin A-resistant respiration, lipid peroxidation, iron mobilization, ATP depletion, and cell membrane disruption. CumOOH metabolism was also faster in P450 1A-induced hepatocytes and was inhibited by the P450 1A inhibitor alpha-naphthoflavone. The ferric chelator deferoxamine also prevented cytotoxicity even after CumOOH had been metabolized but had no effect on CumOOH metabolism. This emphasizes the toxicological significance of the iron released following hydroperoxide metabolic activation by cytochrome P450. The radical trap, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), had no effect on CumOOH metabolism but prevented CumOOH-induced antimycin A-resistant respiration, lipid peroxidation, iron mobilization, and loss of membrane integrity. These results suggest that CumOOH is metabolically activated by some P450 enzymes (e.g., P450 2E1) in hepatocytes to form reactive radical metabolites or oxidants that cause lipid peroxidation and cytotoxicity.

  11. Effects of the thyroid hormone derivatives 3-iodothyronamine and thyronamine on rat liver oxidative capacity (United States)

    Venditti, P.; Napolitano, G.; Di Stefano, L.; Chiellini, G.; Zucchi, R.; Scanlan, T.S.; Di Meo, S.


    Thyronamines T0AM and T1AM are naturally occurring decarboxylated thyroid hormone derivatives. Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature. Since the mitochondrial energy-transduction apparatus is known to be a potential target of thyroid hormone and its derivatives, we investigated the in vitro effects of T0AM and T1AM on the rates of O2 consumption and H2O2 release by rat liver mitochondria. Hypothyroid animals were used because of the low levels of endogenous thyronamines. We found that both compounds are able to reduce mitochondrial O2 consumption and increase H2O2 release. The observed changes could be explained by a partial block, operated by thyronamines, at a site located near the site of action of antimycin A. This hypothesis was confirmed by the observation that thyronamines reduced the activity of Complex III where the site of antimycin action is located. Because thyronamines exerted their effects at concentrations comparable to those found in hepatic tissue, it is conceivable that they can affect in vivo mitochondrial O2 consumption and H2O2 production acting as modulators of thyroid hormone action. PMID:21664427

  12. Anti-Candida properties of urauchimycins from actinobacteria associated with trachymyrmex ants. (United States)

    Mendes, Thais D; Borges, Warley S; Rodrigues, Andre; Solomon, Scott E; Vieira, Paulo C; Duarte, Marta C T; Pagnocca, Fernando C


    After decades of intensive searching for antimicrobial compounds derived from actinobacteria, the frequency of isolation of new molecules has decreased. To cope with this concern, studies have focused on the exploitation of actinobacteria from unexplored environments and actinobacteria symbionts of plants and animals. In this study, twenty-four actinobacteria strains isolated from workers of Trachymyrmex ants were evaluated for antifungal activity towards a variety of Candida species. Results revealed that seven strains inhibited the tested Candida species. Streptomyces sp. TD025 presented potent and broad spectrum of inhibition of Candida and was selected for the isolation of bioactive molecules. From liquid shake culture of this bacterium, we isolated the rare antimycin urauchimycins A and B. For the first time, these molecules were evaluated for antifungal activity against medically important Candida species. Both antimycins showed antifungal activity, especially urauchimycin B. This compound inhibited the growth of all Candida species tested, with minimum inhibitory concentration values equivalent to the antifungal nystatin. Our results concur with the predictions that the attine ant-microbe symbiosis may be a source of bioactive metabolites for biotechnology and medical applications.

  13. Anti-Candida Properties of Urauchimycins from Actinobacteria Associated with Trachymyrmex Ants

    Directory of Open Access Journals (Sweden)

    Thais D. Mendes


    Full Text Available After decades of intensive searching for antimicrobial compounds derived from actinobacteria, the frequency of isolation of new molecules has decreased. To cope with this concern, studies have focused on the exploitation of actinobacteria from unexplored environments and actinobacteria symbionts of plants and animals. In this study, twenty-four actinobacteria strains isolated from workers of Trachymyrmex ants were evaluated for antifungal activity towards a variety of Candida species. Results revealed that seven strains inhibited the tested Candida species. Streptomyces sp. TD025 presented potent and broad spectrum of inhibition of Candida and was selected for the isolation of bioactive molecules. From liquid shake culture of this bacterium, we isolated the rare antimycin urauchimycins A and B. For the first time, these molecules were evaluated for antifungal activity against medically important Candida species. Both antimycins showed antifungal activity, especially urauchimycin B. This compound inhibited the growth of all Candida species tested, with minimum inhibitory concentration values equivalent to the antifungal nystatin. Our results concur with the predictions that the attine ant-microbe symbiosis may be a source of bioactive metabolites for biotechnology and medical applications.

  14. Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production. (United States)

    Ye, Junli; Jiang, Zhongxin; Chen, Xuehong; Liu, Mengyang; Li, Jing; Liu, Na


    Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation.

  15. Alternative respiration and fumaric acid production of Rhizopus oryzae. (United States)

    Gu, Shuai; Xu, Qing; Huang, He; Li, Shuang


    Under the conditions of fumaric acid fermentation, Rhizopus oryzae ME-F14 possessed at least two respiratory systems. The respiration of mycelia was partially inhibited by the cytochrome respiration inhibitor antimycin A or the alternative respiration inhibitor salicylhydroxamic acid and was completely inhibited in the presence of both antimycin A and salicylhydroxamic acid. During fumaric acid fermentation process, the activity of alternative respiration had a great correlation with fumaric acid productivity; both of them reached peak at the same time. The alternative oxidase gene, which encoded the mitochondrial alternative oxidase responsible for alternative respiration in R. oryzae ME-F14, was cloned and characterized in Escherichia coli. The activity of alternative respiration, the alternative oxidase gene transcription level, as well as the fumaric acid titer were measured under different carbon sources and different carbon-nitrogen ratios. The activity of alternative respiration was found to be comparable to the transcription level of the alternative oxidase gene and the fumaric acid titer. These results indicated that the activity of the alternative oxidase was regulated at the transcription stage under the conditions tested for R. oryzae ME-F14.

  16. Mitochondrial lipid peroxidation by cumene hydroperoxide and its prevention by succinate. (United States)

    Bindoli, A; Cavallini, L; Jocelyn, P


    Rat liver mitochondria form lipid hydroperoxides when they are incubated aerobically with cumene hydroperoxide. The rate of reaction is dependent on the initial concentration of the latter and involves the consumption of oxygen. Gradient-separated and cytochrome c-depleted mitochondria, mitoplasts and submitochondrial fractions also undergo this peroxidation. Mitochondrial lipid peroxidation by cumene hydroperoxide is strongly inhibited by SKF52A (an inhibitor of cytochrome P-450), by antioxidants and to a lesser extent by the enzymes superoxide dismutase and catalase. Conversely, rotenone and N-ethylmaleimide stimulate the reaction. Succinate protects against the lipid peroxidation and in some mitochondrial fractions the associated oxygen uptake is also inhibited. This protection by succinate is prevented by malonate but not by N-ethylmaleimide or antimycin. Lipid hydroperoxides present in previously peroxidised mitochondria are partly lost on reincubation with succinate and this reaction is also unaffected by N-ethylmaleimide but inhibited by both malonate and antimycin. The results suggest that reduction of mitochondrial ubiquinone may prevent the generation of lipid hydroperoxides but that their subsequent removal may require reduction at or beyond cytochrome b.

  17. Inhibition and stimulation of root respiration in pisum and plantago by hydroxamate : its consequences for the assessment of alternative path activity. (United States)

    de Visser, R; Blacquière, T


    The contribution of the alternative pathway in root respiration of Pisum sativum L. cv Rondo, Plantago lanceolata L., and Plantago major L. ssp major was determined by titration with salicylhydroxamate (SHAM) in the absence and presence of cyanide. SHAM completely inhibited the cyanide-resistant component of root respiration at 5 to 10 millimolar with an apparent K(i) of 600 micromolar. In contrast, SHAM enhanced pea root respiration by 30% at most, at concentrations below 15 millimolar. An unknown oxidase appeared to be responsible for this stimulation. Its maximum activity in the presence of low SHAM concentrations (1-5 millimolar) was 40% of control respiration rate in pea roots, since 25 millimolar SHAM resulted in 10% inhibition. In plantain roots, the maximum activity was found to be 15%. This hydroxamate-activated oxidase was distinct from the cytochrome path by its resistance to antimycin. The results of titrations with cyanide and antimycin indicated that high SHAM concentrations (up to 25 millimolar) block the hydroxamate-activated oxidase, but do not affect the cytochrome path and, therefore, are a reliable tool for estimating the activity of the alternative path in vivo. A considerable fraction of root respiration was mediated by the alternative path in plantain (45%) and pea (15%), in the latter because of the saturation of the cytochrome path.

  18. Differential effects of buffer pH on Ca2+-induced ROS emission with inhibited mitochondrial complex I and III

    Directory of Open Access Journals (Sweden)

    Daniel P Lindsay


    Full Text Available Excessive mitochondrial reactive oxygen species (ROS emission is a critical component in the etiolo-gy of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca2+, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complex I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rote-none, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore. These results indicate that ROS production by complex I and by III is differently affected by buffer pH and Ca2+ loading with mPTP opening. The study sug-gests that changes in the levels of cytosolic Ca2+ and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III.

  19. Iron deficiency induces changes in riboflavin secretion and the mitochondrial electron transport chain in hairy roots of Hyoscyamus albus. (United States)

    Higa, Ataru; Mori, Yuko; Kitamura, Yoshie


    Hyoscyamus albus hairy roots secrete riboflavin under Fe-deficient conditions. To determine whether this secretion was linked to an enhancement of respiration, both riboflavin secretion and the reduction of 2,3,5-triphenyltetrazolium chloride (TTC), as a measure of respiration activity, were determined in hairy roots cultured under Fe-deficient and Fe-replete conditions, with or without aeration. Appreciable TTC-reducing activity was detected at the root tips, at the bases of lateral roots and in internal tissues, notably the vascular system. TTC-reducing activity increased under Fe deficiency and this increase occurred in concert with riboflavin secretion and was more apparent under aeration. Riboflavin secretion was not apparent under Fe-replete conditions. In order to examine which elements of the mitochondrial electron transport chain might be involved, the effects of the respiratory inhibitors, barbiturate, dicoumarol, malonic acid, antimycin, KCN and salicylhydroxamic acid (SHAM) were investigated. Under Fe-deficient conditions, malonic acid affected neither root growth, TTC-reducing activity nor riboflavin secretion, whereas barbiturate and SHAM inhibited only root growth and TTC-reducing activity, respectively, and the other compounds variously inhibited growth and TTC-reducing activity. Riboflavin secretion was decreased, in concert with TTC-reducing activity, by dicoumarol, antimycin and KCN, but not by SHAM. In Fe-replete roots, all inhibitors which reduced riboflavin secretion in Fe-deficient roots showed somewhat different effects: notably, antimycin and KCN did not significantly inhibit TTC-reducing activity and the inhibition by dicoumarol was much weaker in Fe-replete roots. Combined treatment with KCN and SHAM also revealed that Fe-deficient and Fe-replete roots reduced TTC in different ways. A decrease in the Fe content of mitochondria in Fe-deficient roots was confirmed. Overall, the results suggest that, under conditions of Fe deficiency in H

  20. Anomalous cell wall synthesis in Mucor mucedo (L.) Fres. induced by some fungicides and other compounds related to the problem of dimorphism. (United States)

    Lyr, H; Casperson, G


    An anomalous cell wall thickening in Mucor mucedo is induced already within 60-120 min by some fungicides (etridiazol, chloroneb, pentachloronitrobenzene, dicloran, drazoxolon, biphenyl) as well as with a N2-atmosphere or high concentrations of glucose, but not with 2,4-dinitrophenol, chlorinated phenols, dichlofluanid and antimycin A. This effect seems to be identical to the change from the mycelial (M-) to the yeast (Y-) form in dimorphic fungi, which can be achieved by culture conditions as well as by addition of chemicals. The cause seems to be a specific, complex change in the metabolic state. A scheme of regulation is presented which explains most of the experimental results described till now.

  1. Screening for microbial metabolites affecting phenotype of Caenorhabditis elegans. (United States)

    Yamamuro, Daisuke; Uchida, Ryuji; Takahashi, Yoko; Masuma, Rokuro; Tomoda, Hiroshi


    Microbial samples, including our library of known microbial compounds (ca. 300) and microbial culture broths (ca. 9000), were screened for small molecules affecting the phenotype of Caenorhabditis elegans. As a result, seven known compounds were found to induce phenotypic abnormality of C. elegans. Staurosporine exhibited morphological defects in the vulva and tail of C. elegans, avermectin B1a exhibited hatching inhibition of starting eggs on day 1 at 25-100 µM and growth inhibition at 0.01-12.5 µM, siccanin and antimycin A inhibited the growth of C. elegans, and fluorouracil inhibited hatching of eggs newly spawned by adult C. elegans. Toromycin induced morphological defects in the intestine. 5-(4-Methoxyphenyl)-oxazole, isolated as a fungal metabolite for the first time, inhibited the hatching of eggs newly spawned by adult C. elegans.

  2. D-chiro-inositol affects accumulation of raffinose family oligosaccharides in developing embryos of Pisum sativum. (United States)

    Lahuta, Lesław B; Dzik, Tomasz


    Developing garden pea embryos are able to take up exogenously applied cyclitols: myo-inositol, which naturally occurs in pea, and two cyclitols absent in pea plants: d-chiro-inositol and d-pinitol. The competition in the uptake of cyclitols by pea embryo, insensitivity to glucose and sucrose, and susceptibility to inhibitor(s) of H(+)-symporters (e.g. CCCP and antimycin A) suggest that a common cyclitol transporter is involved. Both d-chiro-inositol and d-pinitol can be translocated through the pea plant to developing embryos. During seed maturation drying, they are used for synthesis of mainly mono-galactosides, such as fagopyritol B1 and galactosyl pinitol A. Accumulation of d-chiro-inositol (and formation of fagopyritols), but not d-pinitol, strongly reduces accumulation of verbascose, the main raffinose oligosaccharide in pea seeds. The reasons for the observed changes are discussed.

  3. Utilization of adenosine triphosphate in rat mast cells during and after secretion of histamine in response to compound 48/80

    DEFF Research Database (Denmark)

    Johansen, Torben


    The adenosine triphosphate (ATP) content of rat mast cells and their lactate production were measured during and after secretion of histamine induced by compound 48/80. Antimycin A and oligomycin were used to block oxidative ATP synthesis, and 2-deoxyglucose (2-DG) was used to block glycolytic ATP...... synthesis. Histamine secretion was completed after 10 sec. exposure of the cells to compound 48/80. During that time period there was an increased ATP-utilization of 0.15 pmol/10(3) cells. After completion of the secretory process there seemed to be an enhanced utilization of ATP of 0.40 pmol/10(3) cells....../min., which may be associated with recovery of the cells....

  4. Insulin resistance and the mitochondrial link. Lessons from cultured human myotubes

    DEFF Research Database (Denmark)

    Gaster, Michael


    In order to better understand the impact of reduced mitochondrial function for the development of insulin resistance and cellular metabolism, human myotubes were established from lean, obese, and T2D subjects and exposed to mitochondrial inhibitors, either affecting the electron transport chain...... lipid uptake. The metabolic phenotype during respiratory uncoupling resembled the above picture, except for an increase in glucose and palmitate oxidation. Antimycin A and oligomycin treatment induced insulin resistance at the level of glucose and palmitate uptake in all three study groups while......, at the level of glycogen synthesis, insulin resistance was only seen in lean myotubes. Primary insulin resistance in diabetic myotubes was significantly worsened at the level of glucose and lipid uptake. The present study is the first convincing data linking functional mitochondrial impairment per se...

  5. Glucose, Lactate and Glutamine but not Glutamate Support Depolarization-Induced Increased Respiration in Isolated Nerve Terminals

    DEFF Research Database (Denmark)

    Hohnholt, Michaela C; Andersen, Vibe H; Bak, Lasse K;


    and glycolytic rate in presence of different substrates. Mitochondrial function was tested by sequentially exposure of the synaptosomes to the ATP synthase inhibitor, oligomycin, the uncoupler FCCP (carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone) and the electron transport chain inhibitors rotenone...... and antimycin A. The synaptosomes exhibited intense respiratory activity using glucose as substrate. The FCCP-dependent respiration was significantly higher with 10 mM glucose compared to 1 mM glucose. Synaptosomes also readily used pyruvate as substrate, which elevated basal respiration, activity....... Synaptosomal respiration using glutamate and glutamine as substrates was significantly higher compared to basal respiration, whereas oligomycin-dependent and FCCP-induced respiration was lower compared to the responses obtained in the presence of glucose as substrate. We provide evidence that synaptosomes...

  6. Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface. (United States)

    Jinadasa, Tushare; Szabó, Elöd Z; Numat, Masayuki; Orlowski, John


    Strict regulation of intra- and extracellular pH is an important determinant of nervous system function as many voltage-, ligand-, and H(+)-gated cationic channels are exquisitely sensitive to transient fluctuations in pH elicited by neural activity and pathophysiologic events such as hypoxia-ischemia and seizures. Multiple Na(+)/H(+) exchangers (NHEs) are implicated in maintenance of neural pH homeostasis. However, aside from the ubiquitous NHE1 isoform, their relative contributions are poorly understood. NHE5 is of particular interest as it is preferentially expressed in brain relative to other tissues. In hippocampal neurons, NHE5 regulates steady-state cytoplasmic pH, but intriguingly the bulk of the transporter is stored in intracellular vesicles. Here, we show that NHE5 is a direct target for phosphorylation by the AMP-activated protein kinase (AMPK), a key sensor and regulator of cellular energy homeostasis in response to metabolic stresses. In NHE5-transfected non-neuronal cells, activation of AMPK by the AMP mimetic AICAR or by antimycin A, which blocks aerobic respiration and causes acidification, increased cell surface accumulation and activity of NHE5, and elevated intracellular pH. These effects were effectively blocked by the AMPK antagonist compound C, the NHE inhibitor HOE694, and mutation of a predicted AMPK recognition motif in the NHE5 C terminus. This regulatory pathway was also functional in primary hippocampal neurons, where AMPK activation of NHE5 protected the cells from sustained antimycin A-induced acidification. These data reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of hippocampal neurons during metabolic stress.

  7. On the location of the H+-extruding steps in site 2 of the mitochondrial electron transport chain. (United States)

    Alexandre, A; Galiazzo, F; Lehninger, A L


    The location of the H+-translocating reactions within energy-conserving Site 2 of the mitochondrial electron transport chain was evaluated from two sets of data. In the first, the H+/2e- ejection ratios and Ca2+/2e- uptake ratios were compared for electron flow from succinate dehydrogenase, whose active site is on the matrix side of the inner membrane and from glycerol phosphate dehydrogenase, whose active site is on the cytosolic side. In intact rat liver mitochondria both substrates yielded H+/2e- ejection ratios close to 4.0 and Ca2+/2e- uptake ratios close to 1.0 during antimycin-sensitive reduction of ferricyanide. With rat liver mitoplasts and ferricytochrome c as electron acceptor, both substrates again gave the same stoichiometric ratios. The second approach involved determination of the sidedness of H+ formation during electron flow from succinate to ferricyanide via bypass of the antimycin block of the cytochrome b.c1 complex provided by N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), under conditions in which the TMPD-TMPD+ couple does not act as a membrane-penetrating protonophore. Electron flow in this system was inhibited by 2-then-oyltrifluoroacetone, indicating that TMPD probably accepts electrons from ubiquinol. The 2 H+ formed in this system were not delivered into the matrix but appeared directly in the medium in the absence of a protonophore. To accommodate the available evidence on Site 2 substrates, it is concluded that the substrate hydrogens are first transferred to ubiquinone, 2 H+ per 2e then appear in the medium by protolytic dehydrogenation of a species of ubiquinol or ubiquinol-protein having the appropriate sidedness (designated Site 2A), and the other 2 H+ are translocated from the matrix to the medium on passage of 2e- through the cytochrome b x c1 complex (designated Site 2B).

  8. Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon. (United States)

    Herrero, A; Barja, G


    Basal (substrate alone) and maximum rates of H2O2 production, oxygen consumption and free radical leak in the respiratory chain were higher in heart mitochondria of the short-lived rat (4 years) than in the long-lived pigeon (35 years). This suggests that the low free radical production of pigeon heart mitochondria is due in part to both a low electron flow and a low percent leak of electrons out of sequence in the respiratory chain. Thenoyltrifluoroacetone did not increase H2O2 production with succinate either in rats or pigeons. Mitochondrial H2O2 production was higher with pyruvate/malate than with succinate in both animal species. Rotenone and antimycin A increased H2O2 production with pyruvate/malate to the maximum levels observed in each species. Addition of myxothiazol to antimycin A-treated mitochondria supplemented with pyruvate/malate decreased H2O2 production in both species. All the combinations of inhibitors added with pyruvate/malate resulted in higher rates of H2O2 production in rats than in pigeons. When succinate instead of pyruvate/malate was used as substrate, rotenone and thenoyltrifluoroacetone decreased mitochondrial H2O2 production in the rat and did not change it in the pigeon. The results indicate that Complexes I and III are the main H2O2 generators of heart mitochondria in rats and pigeons and that both Complexes are responsible for the low H2O2 production of the bird. p-Chloromercuribenzoate and ethoxyformic anhydride strongly inhibited the H2O2 production induced by rotenone with pyruvate/malate in both species. This suggests that the free radical generator of Complex I is located after the ferricyanide reduction site, between the ethoxyformic and the rotenone-sensitive sites.

  9. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen


    Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin-A

  10. Mitochondrial modulation of store-operated Ca(2+) entry in model cells of Alzheimer's disease. (United States)

    Ma, Tuo; Gong, Kai; Yan, Yufang; Song, Bo; Zhang, Xiufang; Gong, Yandao


    Mitochondrial malfunction and calcium dyshomeostasis are early pathological events considered as important features of the Alzheimer's disease (AD) brain. Recent studies have suggested mitochondrion as an active regulator of Ca(2+) signaling based on its calcium buffering capacity. Herein, we investigated the mitochondrial involvement in the modulation of store-operated calcium entry (SOCE) in neural 2a (N2a) transgenic AD model cells. Results showed that SOCE was significantly depressed in N2a cells transfected with wild-type human APP695 (N2a APPwt) compared with empty vector control (N2a WT) cells. Pharmacological manipulation with mitochondrial function blockers, such as FCCP, RuR, or antimycin A/oligomycin, could inhibit mitochondrial calcium handling, and then impair SOCE pathway in N2a WT cells. Furthermore, mitochondria of N2a APPwt cells exhibited more severe swelling in response to Ca(2+), which is an indication of mitochondrial membrane permeability transition (MPT), than the wild-type controls. Additionally, treatment with cyclosporin A, a potent inhibitor of cyclophilin D, which can block MPT, could significantly restore the attenuated SOCE in N2a APPwt cells. Therefore, inhibition of cyclophilin D might be a therapeutic strategy for Alzheimer's disease.

  11. Studies on the mechanism of synthesis of ethyl acetate in Kluyveromyces marxianus DSM 5422. (United States)

    Löser, Christian; Urit, Thanet; Keil, Peter; Bley, Thomas


    Kluyveromyces marxianus converts whey-borne sugar into ethyl acetate, an environmentally friendly solvent with many applications. K. marxianus DSM 5422 presumably synthesizes ethyl acetate from acetyl-SCoA. Iron limitation as a trigger for this synthesis is explained by a diminished aconitase and succinate dehydrogenase activity (both enzymes depend on iron) causing diversion of acetyl-SCoA from the tricarboxic acid cycle to ester synthesis. Copper limitation as another trigger for ester synthesis in this yeast refers to involvement of the electron transport chain (all ETC complexes depend on iron and complex IV requires copper). This hypothesis was checked by using several ETC inhibitors. Malonate was ineffective but carboxin partially inhibited complex II and initiated ester synthesis. Antimycin A and cyanide as complexes III and IV inhibitors initiated ester synthesis only at moderate levels while higher concentrations disrupted all respiration and caused ethanol formation. A restricted supply of oxygen (the terminal electron acceptor) also initiated some ester synthesis but primarily forced ethanol production. A switch from aerobic to anaerobic conditions nearly stopped ester synthesis and induced ethanol formation. Iron-limited ester formation was compared with anaerobic ethanol production; the ester yield was lower than the ethanol yield but a higher market price, a reduced number of process stages, a faster process, and decreased expenses for product recovery by stripping favor biotechnological ester production.

  12. Mitochondrial Malfunctioning, Proteasome Arrest and Apoptosis in Cancer Cells by Focused Intracellular Generation of Oxygen Radicals

    Directory of Open Access Journals (Sweden)

    Ilaria Postiglione


    Full Text Available Photofrin/photodynamic therapy (PDT at sub-lethal doses induced a transient stall in proteasome activity in surviving A549 (p53+/+ and H1299 (p53−/− cells as indicated by the time-dependent decline/recovery of chymotrypsin-like activity. Indeed, within 3 h of incubation, Photofrin invaded the cytoplasm and localized preferentially within the mitochondria. Its light activation determined a decrease in mitochondrial membrane potential and a reversible arrest in proteasomal activity. A similar result is obtained by treating cells with Antimycin and Rotenone, indicating, as a common denominator of this effect, the ATP decrease. Both inhibitors, however, were more toxic to cells as the recovery of proteasomal activity was incomplete. We evaluated whether combining PDT (which is a treatment for killing tumor cells, per se, and inducing proteasome arrest in the surviving ones with Bortezomib doses capable of sustaining the stall would protract the arrest with sufficient time to induce apoptosis in remaining cells. The evaluation of the mitochondrial membrane depolarization, residual proteasome and mitochondrial enzymatic activities, colony-forming capabilities, and changes in protein expression profiles in A549 and H1299 cells under a combined therapeutic regimen gave results consistent with our hypothesis.

  13. Different molecular mechanisms involved in spontaneous and oxidative stress-induced mitochondrial fragmentation in tripeptidyl peptidase-1 (TPP-1)-deficient fibroblasts (United States)

    Van Beersel, Guillaume; Tihon, Eliane; Demine, Stéphane; Hamer, Isabelle; Jadot, Michel; Arnould, Thierry


    NCLs (neuronal ceroid lipofuscinoses) form a group of eight inherited autosomal recessive diseases characterized by the intralysosomal accumulation of autofluorescent pigments, called ceroids. Recent data suggest that the pathogenesis of NCL is associated with the appearance of fragmented mitochondria with altered functions. However, even if an impairement in the autophagic pathway has often been evoked, the molecular mechanisms leading to mitochondrial fragmentation in response to a lysosomal dysfunction are still poorly understood. In this study, we show that fibroblasts that are deficient for the TPP-1 (tripeptidyl peptidase-1), a lysosomal hydrolase encoded by the gene mutated in the LINCL (late infantile NCL, CLN2 form) also exhibit a fragmented mitochondrial network. This morphological alteration is accompanied by an increase in the expression of the protein BNIP3 (Bcl2/adenovirus E1B 19 kDa interacting protein 3) as well as a decrease in the abundance of mitofusins 1 and 2, two proteins involved in mitochondrial fusion. Using RNAi (RNA interference) and quantitative analysis of the mitochondrial morphology, we show that the inhibition of BNIP3 expression does not result in an increase in the reticulation of the mitochondrial population in LINCL cells. However, this protein seems to play a key role in cell response to mitochondrial oxidative stress as it sensitizes mitochondria to antimycin A-induced fragmentation. To our knowledge, our results bring the first evidence of a mechanism that links TPP-1 deficiency and oxidative stress-induced changes in mitochondrial morphology. PMID:23249249

  14. Essentiality of respiratory activity for pentose utilization in thermotolerant yeast Kluyveromyces marxianus DMKU 3-1042. (United States)

    Lertwattanasakul, Noppon; Suprayogi; Murata, Masayuki; Rodrussamee, Nadchanok; Limtong, Savitree; Kosaka, Tomoyuki; Yamada, Mamoru


    By random integrative mutagenesis with a kanMX4 cassette in Kluyveromyces marxianus DMKU 3-1042, we obtained three mutants of COX15, ATP25 and CYC3 encoding a cytochrome oxidase assembly factor (singleton), a transcription factor required for assembly of the Atp9p subunit of mitochondrial ATP synthase and cytochrome c heme lyase, respectively, as mutants lacking growth capability on xylose and/or arabinose. They exhibited incapability of growth on non-fermentable carbon sources, such as acetate or glycerol, and thermosensitiveness. Their biomass formation in glucose medium was reduced, but ethanol yields were increased with a high ethanol level in the medium, compared to those of the parental strain. Experiments with respiratory inhibitors showed that cox15 and cyc3, but not atp25, were able to grow in glucose medium containing antimycin A and that the atp25 mutant was KCN-resistant. Activities of NADH and ubiquinol oxidases in membrane fractions of each mutant became a half of that of the parent and negligible, respectively, and their remaining NADH oxidase activities were found to be resistant to KCN. Absolute absorption spectral analysis revealed that the peak corresponding to a + a 3 was very small in atp25 and negligible in cox15 and cyc3. These findings suggest that the K. marxianus strain possesses an alternative KCN-resistant oxidase that is located between primary dehydrogenases and the ubiquinone pool and that the respiratory activity is essential for utilization of pentoses.

  15. Simultaneous Fluorescence and Phosphorescence Lifetime Imaging Microscopy in Living Cells. (United States)

    Jahn, Karolina; Buschmann, Volker; Hille, Carsten


    In living cells, there are always a plethora of processes taking place at the same time. Their precise regulation is the basis of cellular functions, since small failures can lead to severe dysfunctions. For a comprehensive understanding of intracellular homeostasis, simultaneous multiparameter detection is a versatile tool for revealing the spatial and temporal interactions of intracellular parameters. Here, a recently developed time-correlated single-photon counting (TCSPC) board was evaluated for simultaneous fluorescence and phosphorescence lifetime imaging microscopy (FLIM/PLIM). Therefore, the metabolic activity in insect salivary glands was investigated by recording ns-decaying intrinsic cellular fluorescence, mainly related to oxidized flavin adenine dinucleotide (FAD) and the μs-decaying phosphorescence of the oxygen-sensitive ruthenium-complex Kr341. Due to dopamine stimulation, the metabolic activity of salivary glands increased, causing a higher pericellular oxygen consumption and a resulting increase in Kr341 phosphorescence decay time. Furthermore, FAD fluorescence decay time decreased, presumably due to protein binding, thus inducing a quenching of FAD fluorescence decay time. Through application of the metabolic drugs antimycin and FCCP, the recorded signals could be assigned to a mitochondrial origin. The dopamine-induced changes could be observed in sequential FLIM and PLIM recordings, as well as in simultaneous FLIM/PLIM recordings using an intermediate TCSPC timing resolution.

  16. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

    Directory of Open Access Journals (Sweden)

    Ronald P. Haff


    Full Text Available Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA, a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2, tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.

  17. Brief exposure to carbon monoxide preconditions cardiomyogenic cells against apoptosis in ischemia-reperfusion

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    Kondo-Nakamura, Mihoko [Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Shintani-Ishida, Kaori, E-mail: [Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Uemura, Koichi; Yoshida, Ken-ichi [Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)


    We examined whether and how pretreatment with carbon monoxide (CO) prevents apoptosis of cardioblastic H9c2 cells in ischemia-reperfusion. Reperfusion (6 h) following brief ischemia (10 min) induced cytochrome c release, activation of caspase-9 and caspase-3, and apoptotic nuclear condensation. Brief CO pretreatment (10 min) or a caspase-9 inhibitor (Z-LEHD-FMK) attenuated these apoptotic changes. Ischemia-reperfusion increased phosphorylation of Akt at Ser472/473/474, and this was enhanced by CO pretreatment. A specific Akt inhibitor (API-2) blunted the anti-apoptotic effects of CO in reperfusion. In normoxic cells, CO enhanced O{sub 2}{sup -} generation, which was inhibited by a mitochondrial complex III inhibitor (antimycin A) but not by a NADH oxidase inhibitor (apocynin). The CO-enhanced Akt phosphorylation was suppressed by an O{sub 2}{sup -} scavenger (Tiron), catalase or a superoxide dismutase (SOD) inhibitor (DETC). These results suggest that CO pretreatment induces mitochondrial generation of O{sub 2}{sup -}, which is then converted by SOD to H{sub 2}O{sub 2}, and subsequent Akt activation by H{sub 2}O{sub 2} attenuates apoptosis in ischemia-reperfusion.

  18. Reduction of molybdate to molybdenum blue by Klebsiella sp. strain hkeem. (United States)

    Lim, H K; Syed, M A; Shukor, M Y


    A novel molybdate-reducing bacterium, tentatively identified as Klebsiella sp. strain hkeem and based on partial 16s rDNA gene sequencing and phylogenetic analysis, has been isolated. Strain hkeem produced 3 times more molybdenum blue than Serratia sp. strain Dr.Y8; the most potent Mo-reducing bacterium isolated to date. Molybdate was optimally reduced to molybdenum blue using 4.5 mM phosphate, 80 mM molybdate and using 1% (w/v) fructose as a carbon source. Molybdate reduction was optimum at 30 °C and at pH 7.3. The molybdenum blue produced from cellular reduction exhibited absorption spectrum with a maximum peak at 865 nm and a shoulder at 700 nm. Inhibitors of electron transport system such as antimycin A, rotenone, sodium azide, and potassium cyanide did not inhibit the molybdenum-reducing enzyme. Mercury, silver, and copper at 1 ppm inhibited molybdenum blue formation in whole cells of strain hkeem.

  19. Reduction of molybdate to molybdenum blue by Enterobacter sp. strain Dr.Y13. (United States)

    Shukor, M Y; Rahman, M F; Shamaan, N A; Syed, M A


    Extensive use of metals in various industrial applications has caused substantial environmental pollution. Molybdenum-reducing bacteria isolated from soils can be used to remove molybdenum from contaminated environments. In this work we have isolated a local bacterium with the capability to reduce soluble molybdate to the insoluble molybdenum blue. We studied several factors that would optimize molybdate reduction. Electron donor sources such as glucose, sucrose, lactose, maltose and fructose (in decreasing efficiency) supported molybdate reduction after 24 h of incubation with optimum glucose concentration for molybdate reduction at 1.5% (w/v). The optimum pH, phosphate and molybdate concentrations, and temperature for molybdate reduction were pH 6.5, 5.0, 25 to 50 mM and 37 degrees C, respectively. The Mo-blue produced by cellular reduction exhibited a unique absorption spectrum with a maximum peak at 865 nm and a shoulder at 700 nm. Metal ions such as chromium, cadmium, copper, silver and mercury caused approximately 73, 71, 81, 77 and 78% inhibition of the molybdenum-reducing activity, respectively. All of the respiratory inhibitors tested namely rotenone, azide, cyanide and antimycin A did not show any inhibition to the molybdenum-reducing activity suggesting components of the electron transport system are not responsible for the reducing activity. The isolate was tentatively identified as Enterobacter sp. strain Dr.Y13 based on carbon utilization profiles using Biolog GN plates and partial 16S rDNA molecular phylogeny.

  20. Molybdate Reduction to Molybdenum Blue by an Antarctic Bacterium

    Directory of Open Access Journals (Sweden)

    S. A. Ahmad


    Full Text Available A molybdenum-reducing bacterium from Antarctica has been isolated. The bacterium converts sodium molybdate or Mo6+ to molybdenum blue (Mo-blue. Electron donors such as glucose, sucrose, fructose, and lactose supported molybdate reduction. Ammonium sulphate was the best nitrogen source for molybdate reduction. Optimal conditions for molybdate reduction were between 30 and 50 mM molybdate, between 15 and 20°C, and initial pH between 6.5 and 7.5. The Mo-blue produced had a unique absorption spectrum with a peak maximum at 865 nm and a shoulder at 710 nm. Respiratory inhibitors such as antimycin A, sodium azide, potassium cyanide, and rotenone failed to inhibit the reducing activity. The Mo-reducing enzyme was partially purified using ion exchange and gel filtration chromatography. The partially purified enzyme showed optimal pH and temperature for activity at 6.0 and 20°C, respectively. Metal ions such as cadmium, chromium, copper, silver, lead, and mercury caused more than 95% inhibition of the molybdenum-reducing activity at 0.1 mM. The isolate was tentatively identified as Pseudomonas sp. strain DRY1 based on partial 16s rDNA molecular phylogenetic assessment and the Biolog microbial identification system. The characteristics of this strain would make it very useful in bioremediation works in the polar and temperate countries.

  1. Molybdate reduction to molybdenum blue by an Antarctic bacterium. (United States)

    Ahmad, S A; Shukor, M Y; Shamaan, N A; Mac Cormack, W P; Syed, M A


    A molybdenum-reducing bacterium from Antarctica has been isolated. The bacterium converts sodium molybdate or Mo⁶⁺ to molybdenum blue (Mo-blue). Electron donors such as glucose, sucrose, fructose, and lactose supported molybdate reduction. Ammonium sulphate was the best nitrogen source for molybdate reduction. Optimal conditions for molybdate reduction were between 30 and 50 mM molybdate, between 15 and 20°C, and initial pH between 6.5 and 7.5. The Mo-blue produced had a unique absorption spectrum with a peak maximum at 865 nm and a shoulder at 710 nm. Respiratory inhibitors such as antimycin A, sodium azide, potassium cyanide, and rotenone failed to inhibit the reducing activity. The Mo-reducing enzyme was partially purified using ion exchange and gel filtration chromatography. The partially purified enzyme showed optimal pH and temperature for activity at 6.0 and 20°C, respectively. Metal ions such as cadmium, chromium, copper, silver, lead, and mercury caused more than 95% inhibition of the molybdenum-reducing activity at 0.1 mM. The isolate was tentatively identified as Pseudomonas sp. strain DRY1 based on partial 16s rDNA molecular phylogenetic assessment and the Biolog microbial identification system. The characteristics of this strain would make it very useful in bioremediation works in the polar and temperate countries.

  2. Antioxidant properties of Neu2000 on mitochondrial free radicals and oxidative damage. (United States)

    Visavadiya, Nishant P; McEwen, Melanie L; Pandya, Jignesh D; Sullivan, Patrick G; Gwag, Byoung Joo; Springer, Joe E


    Neu2000 [2-hydroxy-5-(2,3,5,6-tetrafluoro-4 trifluoromethylbenzylamino) benzoic acid] is a dual-acting neuroprotective agent that functions both as a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and a free radical scavenger. In the present study, we investigated the scavenging activity of Neu2000 on various classes of reactive oxygen species and reactive nitrogen species (ROS/RNS) as well as its efficacy for reducing free radicals and oxidative stress/damage induced in spinal cord mitochondrial preparations. Neu2000 exerted scavenging activity against superoxide, nitric oxide, and hydroxyl radicals, and efficiently scavenged peroxynitrite. In the mitochondrial studies, Neu2000 markedly inhibited ROS/RNS and hydrogen peroxide levels following antimycin treatment. In addition, Neu2000 effectively scavenged hydroxyl radicals generated by iron(III)-ascorbate, reduced protein carbonyl formation mediated by hydroxyl radicals and peroxynitrite, and prevented glutathione oxidation caused by tert-butyl hydroperoxide in isolated mitochondria. Interestingly, incubation of isolated mitochondria with Neu2000 followed by centrifugation and removal of the supernatant also resulted in a concentration-dependent decrease in lipid peroxidation. This observation suggests that Neu2000 enters mitochondria to target free radicals or indirectly affects mitochondrial function in a manner that promotes antioxidant activity. The results of the present study demonstrate that Neu2000 possesses potent in vitro antioxidant activity due, most likely, to its active phenoxy group.

  3. Biochemical effects of the flavanol-rich lychee fruit extract on the melanin biosynthesis and reactive oxygen species. (United States)

    Hagiwara, Kazuya; Okura, Masae; Sumikawa, Yasuyuki; Hida, Tokimasa; Kuno, Atsushi; Horio, Yoshiyuki; Yamashita, Toshiharu


    An ingredient of fruit polyphenol, resveratrol, is known to have an inhibitory effect on melanogenesis. In order to examine the functional differences between resveratrol and other fruit polyphenols, we compared biochemical effects of a resveratrol-free polyphenol, flavanol-rich lychee fruit extract (FRLFE), with other phenolic compounds including resveratrol. FRLFE as well as hydroquinone and resveratrol suppressed growth of B16F1 melanoma cells more significantly than rhododendrol or arbutin. Resveratrol suppressed mushroom tyrosinase at the lowest concentration (23.0 μmol/L) among the compounds tested. FRLFE and hydroquinone suppressed tyrosinase at almost the same concentration (half maximal inhibitory concentration [IC50 ], 83.5 and 94.6 μmol/L, respectively), which was higher than rhododendrol, ascorbic acid and arbutin (IC50 , 245, 345 and 421 μmol/L, respectively). Western blot analysis revealed that although resveratrol decreased expressions of tyrosinase and tyrosinase-related protein 1, FRLFE did not affect their expressions. Both FRLFE and resveratrol suppressed antimycin A-mediated reactive oxygen species (ROS) production in melanocytic cells. Resveratrol-mediated ROS suppression was inhibited by nicotinamide, a SIRT1 inhibitor. However, FRLFE-mediated suppression was not affected by nicotinamide. Moreover, FRLFE directly decreased superoxide in vitro, as detected by superoxide dismutase-like scavenging activity assay. These results suggest that FRLFE can protect melanocytes from cytotoxicity caused by an excess amount of melanin and ROS in a different manner from resveratrol.

  4. Iron speciation in human cancer cells by K-edge total reflection X-ray fluorescence-X-ray absorption near edge structure analysis

    Energy Technology Data Exchange (ETDEWEB)

    Polgari, Zs. [Eoetvoes Lorand University, Institute of Chemistry, Department of Analytical Chemistry, Laboratory of Environmental Chemistry and Bioanalytics, P.O. Box 32, H-1518, Budapest (Hungary); Meirer, F. [Institute of Atomic and Subatomic Physics, Vienna University of Technology, Vienna (Austria); MiNALab, CMM-irst, Fondazione Bruno Kessler, Povo, Trento (Italy); Sasamori, S.; Ingerle, D. [Institute of Atomic and Subatomic Physics, Vienna University of Technology, Vienna (Austria); Pepponi, G. [MiNALab, CMM-irst, Fondazione Bruno Kessler, Povo, Trento (Italy); Streli, C. [Institute of Atomic and Subatomic Physics, Vienna University of Technology, Vienna (Austria); Rickers, K. [Hamburger Synchrotronstrahlungslabor at DESY, Hamburg (Germany); Reti, A.; Budai, B. [Department of Clinical Research, National Institute of Oncology, Budapest (Hungary); Szoboszlai, N. [Eoetvoes Lorand University, Institute of Chemistry, Department of Analytical Chemistry, Laboratory of Environmental Chemistry and Bioanalytics, P.O. Box 32, H-1518, Budapest (Hungary); Zaray, G., E-mail: [Eoetvoes Lorand University, Institute of Chemistry, Department of Analytical Chemistry, Laboratory of Environmental Chemistry and Bioanalytics, P.O. Box 32, H-1518, Budapest (Hungary)


    X-ray absorption near edge structure (XANES) analysis in combination with synchrotron radiation induced total reflection X-ray fluorescence (SR-TXRF) acquisition was used to determine the oxidation state of Fe in human cancer cells and simultaneously their elemental composition by applying a simple sample preparation procedure consisting of pipetting the cell suspension onto the quartz reflectors. XANES spectra of several inorganic and organic iron compounds were recorded and compared to that of different cell lines. The XANES spectra of cells, independently from the phase of cell growth and cell type were very similar to that of ferritin, the main Fe store within the cell. The spectra obtained after CoCl{sub 2} or NiCl{sub 2} treatment, which could mimic a hypoxic state of cells, did not differ noticeably from that of the ferritin standard. After 5-fluorouracil administration, which could also induce an oxidative-stress in cells, the absorption edge position was shifted toward higher energies representing a higher oxidation state of Fe. Intense treatment with antimycin A, which inhibits electron transfer in the respiratory chain, resulted in minor changes in the spectrum, resembling rather the N-donor Fe-{alpha},{alpha}'-dipyridyl complex at the oxidation energy of Fe(III), than ferritin. The incorporation of Co and Ni in the cells was followed by SR-TXRF measurements.

  5. Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle. (United States)

    Pardo-Andreu, Gilberto L; Cavalheiro, Renata A; Dorta, Daniel J; Naal, Zeki; Delgado, René; Vercesi, Aníbal E; Curti, Carlos


    Mangiferin acts as a strong antioxidant on mitochondria. However, when in the presence of Ca(2+), mangiferin elicits mitochondrial permeability transition (MPT), as evidenced by cyclosporin A-sensitive mitochondrial swelling. We now provide evidence, by means of electrochemical and UV-visible spectroscopical analysis, that Fe(III) coordinates with mangiferin. The resulting mangiferin-Fe(III) complex does not elicit MPT and prevents MPT by scavenging reactive oxygen species. Indeed, the complex protects mitochondrial membrane protein thiols and glutathione from oxidation. Fe(III) also significantly increases the ability of mangiferin to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical, as well as to display antioxidant activity toward antimycin A-induced H(2)O(2) production and t-butyl hydroperoxide-promoted membrane lipid peroxidation in mitochondria. We postulate that coordination with Fe(III) constitutes a potential protective mechanism toward the prooxidant action of mangiferin and other catechol-containing antioxidants regarding MPT induction. Potential therapeutic relevance of this finding for conditions of pathological iron overload is discussed.

  6. Effect of long-term cyanide exposure on cyanide-sensitive respiration and phosphate metabolism in the fungus Phycomyces blakesleeanus

    Directory of Open Access Journals (Sweden)

    Stanić Marina


    Full Text Available The effects of long-term exposure (5 h of Phycomyces blakesleeanus mycelium to 5 mM KCN on respiration and phosphate metabolites were tested. Exposure to cyanide, antimycin A and azide lead to a decrease in the activity of cyanide-sensitive respiration (CSR, and the ratio of core polyphosphates (PPc and inorganic phosphates (Pi, which is a good indicator of the metabolic state of a cell. After 5 h of incubation, the activity of CSR returned to control values. For this, the recovery of cytochrome c oxidase (COX was required. In addition, the PPc/Pi ratio started to recover shortly after initiation of COX recovery, but never reached control values. This led us to conclude that the regulation of polyphosphate (PPn levels in the cell is tightly coupled to respiratory chain functioning. In addition, acutely applied cyanide caused two different responses, observed by 31P NMR spectroscopy, that were probably mediated through the mechanism of glycolytic oscillations, triggered by the effect of cyanide on mitochondria. [Projekat Ministarstva nauke Republike Srbije, br. 173040

  7. Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems. (United States)

    El-Khoury, Riyad; Kaulio, Eveliina; Lassila, Katariina A; Crowther, Damian C; Jacobs, Howard T; Rustin, Pierre


    Mitochondrial dysfunction has been widely associated with the pathology of Alzheimer's disease, but there is no consensus on whether it is a cause or consequence of disease, nor on the precise mechanism(s). We addressed these issues by testing the effects of expressing the alternative oxidase AOX from Ciona intestinalis, in different models of AD pathology. AOX can restore respiratory electron flow when the cytochrome segment of the mitochondrial respiratory chain is inhibited, supporting ATP synthesis, maintaining cellular redox homeostasis and mitigating excess superoxide production at respiratory complexes I and III. In human HEK293-derived cells, AOX expression decreased the production of beta-amyloid peptide resulting from antimycin inhibition of respiratory complex III. Because hydrogen peroxide was neither a direct product nor substrate of AOX, the ability of AOX to mimic antioxidants in this assay must be indirect. In addition, AOX expression was able to partially alleviate the short lifespan of Drosophila models neuronally expressing human beta-amyloid peptides, whilst abrogating the induction of markers of oxidative stress. Our findings support the idea of respiratory chain dysfunction and excess ROS production as both an early step and as a pathologically meaningful target in Alzheimer's disease pathogenesis, supporting the concept of a mitochondrial vicious cycle underlying the disease.

  8. Protective effects of rilmenidine and AGN 192403 on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes. (United States)

    Choi, Dong-Hee; Kim, Dong-Hoon; Park, Yun-Gyu; Chun, Boe-Gwun; Choi, Sang-Hyun


    Oxidative stress and mitochondrial dysfunction are important aspects of pathogenesis, particularly in the brain, which is highly dependent on oxygen, and the protection of astrocytes is essential for neuroprotection. In this context, imidazoline drugs have been reported to be neuroprotective. Our recent study showed that imidazoline drugs, including guanabenz, inhibit the naphthazarin-induced oxidative cytotoxicity associated with lysosomal destabilization. We now report on a study into the protective effects of rilmenidine and AGN 192403, which have affinity for imidazoline-1 receptors, on the cytotoxicity induced by naphthazarin and inhibitors of mitochondrial respiration in astrocytes. Cytotoxicity was measured grossly by LDH release and by measuring changes in lysosomal membrane stability and features of mitochondrial membrane permeabilization. Naphthazarin-induced cytotoxicity was evidenced by the ordered development of lysosomal acridine orange relocation, decrease in mitochondrial potential, cytochrome c release, and caspase-9 activation, and was inhibited by guanabenz, rilmenidine, and AGN 192403. Antimycin A and rotenone induced mitochondrial dysfunction primarily, and their cytotoxicities were inhibited only by AGN 192403. Rilmenidine and guanabenz may have a lysosomal stabilizing effect, which underlies their protective effects. AGN 192403 might affect the mitochondrial cell death cascades, and had a novel protective effect on the cytotoxicity associated with mitochondrial dysfunction.

  9. Anoxic depolarization of hippocampal astrocytes: possible modulation by P2X7 receptors. (United States)

    Leichsenring, Anna; Riedel, Thomas; Qin, Ying; Rubini, Patrizia; Illes, Peter


    Current responses from CA1 neurons and stratum oriens astrocytes were recorded from hippocampal brain slices by means of the whole-cell patch-clamp technique. Anoxic depolarization (AD) was induced by an oxygen/glucose-deprived (OGD) medium also containing sodium iodoacetate and antimycin, in order to block glycolysis and oxidative phosphorylation, respectively. Anoxic depolarization has been reported to be due to the sudden increase of the extracellular K(+) concentration and the accompanying explosive rise in glutamate concentration. We asked ourselves whether the release of ATP activating P2X7 receptors is also involved in the AD. Although, the AD was evoked in absolute synchrony in neurons and astrocytes, and the NMDA receptor antagonistic AP-5 depressed these responses, neither the non-selective P2 receptor antagonist PPADS, nor the highly selective P2X7 receptor antagonist A438079 interfered with the AD or its delay time in neurons/astrocytes after inducing chemical hypoxia. However, A438079, but not PPADS increased in astrocytes the slow inward current observed in a hypoxic medium. It is concluded that ATP co-released with glutamate by hypoxic stimulation has only a minor function in the present brain slice system.

  10. Microscopic energy transfer spectroscopy to determine mitochondrial malfunction in human myotubes (United States)

    Gschwend, Michael H.; Strauss, Wolfgang S. L.; Brinkmeier, H.; Ruedel, R.; Steiner, Rudolf W.; Schneckenburger, Herbert


    A microscopic equipment is reported for examination of cellular autofluorescence and determination of energy transfer in vitro, which is proposed to be an appropriate tool to investigate mitochondrial malfunction. The method includes fluorescence microscopy combined with time-gated (nanosecond) fluorescence emission spectroscopy and is presently used to study mitochondrial metabolism of human myotube primary cultures Enzyme complexes of the respiratory chain, located at the inner mitochondrial membrane, were inhibited by various drugs, and fluorescence of the mitochondrial coenzyme nicotinamide adenine dinucleotide (NADH) as well as of the mitochondrial marker rhodamine 123 (R123) was examined. After inhibition of enzyme complex I (NADH-coenzyme Q reductase) by rotenone or enzyme complex III (coenzyme QH2-cytochrome c reductase) by antimycin a similar or increased NADH fluorescence was observed. In addition, energy transfer from excited states of NADH (energy donor) to R123 (energy acceptor) was deduced from a decrease of NADH fluorescence after coincubation with these inhibitors and R123. Application of microscopic energy transfer spectroscopy for diagnosis of congenital mitochondrial deficiencies is currently in preparation.

  11. Efflux of radioactive nucleotides from mouse pancreatic islets prelabelled with 2-/sup 3/H-adenosine

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, M.


    Cultured mouse pancreatic islets were prelabelled with 2-/sup 3/H-adenosine in order to monitor the efflux pattern of radioactivity and insulin. The outflow of radioactivity decreased continuously when the islets were perifused with glucose (1.67 mmol/l). When raising the glucose concentration to 16.7 mmol/l, there was a prompt inhibition of the radioactive efflux concomitant with an increased rate of insulin release. These effects were reversed when the high glucose challenge was withdrawn. Similar radioactive efflux patterns were obtained after addition of ..cap alpha..-ketoisocaproic acid, leucine or pyruvate to the perifusion medium, and also when the islets were challenged with high glucose concentrations in the absence of calcium. Both antimycin A and glipizide stimulated the efflux of radioactivity, although only the addition of glipizide was accompanied by a stimulation of the insulin release. Nucleotides constituted approximately 90% of the total effluent radioactivity. Decrease in the radioactive AMP and ADP efflux due to high glucose was furthermore found to be the cause of the observed inhibition of the total radioactive efflux. The changes in radioactive efflux induced by glucose probably reflect changes in the intracellular concentrations of AMP and ADP. It is concluded that no simple correlation exists between radioactive efflux and insulin release and that changes in the intracellular concentrations of nucleotides may be an early event in the stimulus-secretion coupling of glucose-induced insulin release.

  12. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain.

    Directory of Open Access Journals (Sweden)

    Piotr Bednarczyk

    Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

  13. Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu Qiuwei, E-mail:; Vu, Heather; Liu Liping; Wang, Ting-Chuan; Schaefer, William H. [Merck Research Laboratories (United States)


    Mitochondrial toxicity has been a serious concern, not only in preclinical drug development but also in clinical trials. In mitochondria, there are several distinct metabolic processes including fatty acid {beta}-oxidation, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS), and each process contains discrete but often intimately linked steps. Interruption in any one of those steps can cause mitochondrial dysfunction. Detection of inhibition to OXPHOS can be complicated in vivo because intermediate endogenous metabolites can be recycled in situ or circulated systemically for metabolism in other organs or tissues. Commonly used assays for evaluating mitochondrial function are often applied to ex vivo or in vitro samples; they include various enzymatic or protein assays, as well as functional assays such as measurement of oxygen consumption rate, membrane potential, or acidification rates. Metabolomics provides quantitative profiles of overall metabolic changes that can aid in the unraveling of explicit biochemical details of mitochondrial inhibition while providing a holistic view and heuristic understanding of cellular bioenergetics. In this paper, we showed the application of quantitative NMR metabolomics to in vitro myotube cells treated with mitochondrial toxicants, rotenone and antimycin A. The close coupling of the TCA cycle to the electron transfer chain (ETC) in OXPHOS enables specific diagnoses of inhibition to ETC complexes by discrete biochemical changes in the TCA cycle.

  14. Assay of mitochondrial functions by resazurin in vitro

    Institute of Scientific and Technical Information of China (English)

    Hai-xia ZHANG; Guan-hua DU; Jun-tian ZHANG


    AIM: To study the mechanism of resazurin as indicator of mitochondrial function and to develop a rapid and sensitive assay for measuring metabolic activity of isolated mitochondria from rat liver in vitro. METHODS: The screening was carried out on 96-well microtitre plates by monitoring fluorescence intensity of resazurin reduced by mitochondria. Experimental conditions were optimized and influences of several inhibitors on mitochondrial function were observed. RESULTS: Fluorescence intensity increased in a linear manner when the mitochondrial protein concentration from 5 to 50 μg protein per well was incubated with resazurin (5 μmol/L) during 230 min period at 37 ℃. Edetic acid could promote the reduction of resazurin in mitochondria. The fluorescence intensity decreased greatly after pretreatment with NaN3, antimycin A, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP),and oligomycin compared with the control. However, the typical complex I inhibitor, rotenone enhanced the fluorescence intensity without mitochondria. CONCLUSION: Using resazurin to determine mitochondrial function is sensitive, inexpensive and could be easily automated for high throughput screening.

  15. Evaluation of the electron transport chain inhibition and uncoupling of mitochondrial bioelectrocatalysis with antibiotics and nitro-based compounds

    Energy Technology Data Exchange (ETDEWEB)

    Arechederra, Marguerite N.; Fischer, Caitlin N.; Wetzel, David J. [Department of Chemistry, Saint Louis University, 3501 Laclede Ave., St. Louis, MO (United States); Minteer, Shelley D., E-mail: minteers@slu.ed [Department of Chemistry, Saint Louis University, 3501 Laclede Ave., St. Louis, MO (United States)


    Mitochondrial bioelectrocatalysis can be useful for sensing applications due to the unique metabolic pathways than can be selectively inhibited and uncoupled in mitochondria. This paper details the comparison of different inhibitors and nitro-containing explosive uncouplers in a mitochondria-catalyzed biofuel cell for self-powered explosive sensing. Previous research has reported inhibition of pyruvate oxidation at a mitochondria-modified electrode followed by nitroaromatic uncoupling of current and power. We have previously used oligomycin as the antibiotic and nitrobenzene as the uncoupler of the membrane in the mitochondria-catalyzed biofuel cell, but no comprehensive comparison of various mitochondria inhibitors or explosives has been performed. Results are discussed here for inhibitors targeting complex I, complex III, ATP synthases, adenine nucleotide transport and monocarboxylic acid transport. Reactivation with nitrobenzene was possible in the presence of these inhibitors: oligomycin, 3,3'-diindolylmethane, atractyloside, rotenone, {alpha}-cyano-4-hydroxy cinnamic acid and antimycin A. All eleven explosives studied, including: 2,4,6-trinitrotoluene (TNT) and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), caused uncoupling of the mitochondria function and could be detected by the biosensor.

  16. [Generation of superoxide radicals by the mitochondrial respiratory chain of isolated cardiomyocytes]. (United States)

    Kashkarov, K P; Vasil'eva, E V; Ruuge, E K


    Generation of superoxide radicals by the mitochondrial respiratory chain of cardiomyocites isolated from rat heart and treated with saponin was studied. The rate of O2- production was measured by electron paramagnetic resonance (EPR) spectroscopy using hydroxylamine TEMPONE-H as spin trap. A device has been constructed which provided permanent stirring of cardiomyocyte samples directly in the cavity and prevented cell aggregation. When substrates and antimycin A and/or rotenone are added, the radical production rate increased and reached its maximum in the presence of the both inhibitors. Superoxide dismutase as well as KCN suppressed the radical production, thus being suggestive of the generation of superoxide radicals in the bc1 complex, while the mechanism of O2- production is the same as was suggested for isolated mitochondria. The ratio between rates of O2- generation by isolated cardiomyocytes under various experimental conditions is in a good accord with corresponding parameter of isolated mitochondria. However, in the case of cardiomyocytes the absolute values of the O2- production rate are approximately twice as high as those in isolated mitochondria, presumably due to the partial damage of the mitochondrial respiratory chain during the isolation procedure.

  17. Mitochondrial respiratory pathways inhibition in Rhizopus oryzae potentiates activity of posaconazole and itraconazole via apoptosis.

    Directory of Open Access Journals (Sweden)

    Fazal Shirazi

    Full Text Available The incidence of mucormycosis has increased drastically in immunocompromised patients. Also the array of targets whose inhibition results in Mucorales death is limited. Recently, researchers identified mitochondria as important regulators of detoxification and virulence mechanisms in fungi. In this context, targeting the mitochondrial respiratory chain may provide a new platform for antifungal development. We hypothesized that targeting respiratory pathways potentiates triazoles activity via apoptosis. We found that simultaneous administration of antimycin A (AA and benzohydroxamate (BHAM, inhibitors of classical and alternative mitochondrial pathways respectively, resulted in potent activity of posaconazole (PCZ and itraconazole (ICZ against Rhizopus oryzae. We observed cellular changes characteristic of apoptosis in R. oryzae cells treated with PCZ or ICZ in combination with AA and BHAM. The fungicidal activity of this combination against R. oryzae was correlated with intracellular reactive oxygen species accumulation (ROS, phosphatidylserine externalization, mitochondrial membrane depolarization, and increased caspase like activity. DNA fragmentation and condensation assays also revealed apoptosis of R. oryzae cells. These apoptotic features were prevented by the addition of the ROS scavenger N-acetyl-cysteine. Taken together, these findings suggest that the use of PCZ or ICZ in combination with AA and BHAM makes R. oryzae exquisitely sensitive to treatment with triazoles via apoptosis. This strategy may serve as a new model for the development of improved or novel antifungal agents.

  18. Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts.

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    Aaron C-H Chen

    Full Text Available BACKGROUND: Despite over forty years of investigation on low-level light therapy (LLLT, the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we isolated murine embryonic fibroblasts (MEF from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm(2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. CONCLUSION: We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.

  19. In vitro reactive oxygen species production by mitochondria from the rabbitfish Siganus fuscessens livers and the effects of Irgarol-1051. (United States)

    Liang, Bo; Wang, Li; He, Tangtian; Liu, Wenhua; Li, Qi; Li, Mingfeng


    In this study, the mitochondria from the livers of Siganus fuscessens were exposed to the Irgarol-1051with or without respiratory chain inhibitors using succinate or malate as the substrate, and the effects on mitochondrial ROS production were tested. The mitochondrial ROS production was significantly enhanced by antimycin A with an increase of more than three folds but not by rotenone and NaN3, and this may suggest complex III is the major ROS-producing site. Irgarol-1051 treatments gave a somewhat contradictory result: this chemical can inhibit the mitochondrial ROS production but the inhibition decreased with the increase of doses. These contradictory data about Irgarol-1051 may be explained by the balance between the effects of inhibition through the opening of small-size pores and stimulation through blocking electron transfer, but the mechanism laid behind needs more evidence to support. As Irgarol-1051 was continuously used in antifouling and its bio-concentration factor is up to 160 in fish, the toxic effect of Irgarol-1051 on aquatic animals should be paid more attention to.

  20. The relationship between energy metabolism and the action of inhibitors of histamine release

    DEFF Research Database (Denmark)

    Garland, L G; Johansen, Torben


    1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol/l) and dicu......1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol...... of histamine release from mast cells incubated in glucose-free solution than in complete Tyrode solution (dose-ratio = 20). Like antimycin A (L MICRONMOL/L), PAPAVERINE (3 MICRONMOL/L) CAUSED A DEPLETION OF MAST CELL ATP that was greater in the absence (85%) than in the presence (25%) of extracellular glucose....... 4 These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis. 5 Inhibition of histamine release by dibutyryl...

  1. Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction. (United States)

    Resseguie, Emily A; Staversky, Rhonda J; Brookes, Paul S; O'Reilly, Michael A


    High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48 h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity.

  2. Energy-dependent intracellular translocation of proparathormone. (United States)

    Chu, L L; MacGregor, R R; Cohn, D V


    We previously suggested that after synthesis, proparathormone is transferred from rough endoplasmic reticulum to the Golgi region where its conversion to parathormone occurs. We have attempted to define more closely this transfer process. In the first type of study, bovine parathyroid slices were incubated with [3H]leucine for 10 min and then radioisotope labeling was restricted by addition of a large excess of nonradioactive leucine. Under these conditions, more than 90% of the initially labeled proparathormone was converted to parathormone in 40 min. Lowered temperature in the chase period markedly inhibited the conversion. Several chemical agents were employed individually in the chase period to examine their effect on the conversion process. Antimycin A, dinitrophenol, oligomycin, and anaerobiosis (N2) inhibited the conversion, whereas sodium flouride and cycloheximide had no effect. In the second type of study, parathyroid slices were incubated with [3H]leucine for the entire incubation period. Lowered temperature and inhibitors of energy metabolism and microtubular function all lengthened the interval (lag) between the initial synthesis of [3H]parathormone. Cycloheximide, Tris, and chloroquine decreased the rates of protein synthesis and conversion, respectively, but none had any effect on the lag. We interpret the lag to represent the time of transit for proparathormone from rough endoplasmic reticulum to the Golgi region. We conclude that this transfer process is independent of the synthesis of the prohormone and its conversion to the hormone. Moreover, this translocation requires metabolic energy and appears to be mediated by microtubules.

  3. Molecular cloning of alcohol dehydrogenase genes of the yeast Pichia stipitis and identification of the fermentative ADH. (United States)

    Passoth, V; Schäfer, B; Liebel, B; Weierstall, T; Klinner, U


    Two Pichia stipitis ADH genes (PsADH1 and PsADH2) were isolated by complementation of a Saccharomyces cerevisiae Adh(-)-mutant. The genes enabled the transformants to grow in the presence of antimycin A on glucose, to use ethanol as sole carbon source and made them sensitive to allylalcohol. The sequences of the genes showed similarities of 70-77% to sequences of ADH genes of Candida albicans, Kluyveromyces lactis, K. marxianus, and S. cerevisiae and about 60% homology to those of Schizosaccharomyces pombe and Aspergillus flavus. Southern hybridization experiments suggested that P. stipitis has only these two ADH genes. Both genes are located on the largest chromosome of P. stipitis. PsADH2 encodes for the ADH activity that is responsible for ethanol formation at oxygen limitation. The gene is regulated at the transcriptional level. Moreover, also in cells grown on ethanol, only PsADH2 transcript was found. PsADH1 transcript was detected under aerobic conditions on fermentable carbon sources.

  4. Effects of chitosan and oligochitosan on development and mitochondrial function of Rhizopus stolonifer. (United States)

    Robles-Martínez, Leobarda; Guerra-Sánchez, María Guadalupe; Hernández-Lauzardo, Ana Niurka; Pardo, Juan Pablo; Velázquez-del Valle, Miguel Gerardo


    The antifungal activities of chitosan and oligochitosan have been used to control postharvest decay of the fruits. The effect of chitosan and oligochitosan on mycelium growth, spore germination, and mitochondrial function of Rhizopus stolonifer was evaluated in order to establish a connection between fungus development and the main organelle in charge to provide energy to the cell. The mycelium growth of R. stolonifer was significantly reduced on minimum media amended with chitosan or oligochitosan. The highest antifungal indexes were obtained on media containing chitosan or oligochitosan at 2.0 mg ml(-1). Microscopic observation showed that chitosan and oligochitosan affected the spore germination and hyphae morphology. Both polymers increased oxygen consumption of R. stolonifer. Respiratory activity was restored with NADH in permeabilized treated and untreated cells, and was inhibited with rotenone and flavones. Complex III and IV were inhibited by antimycin A and cyanide, respectively, in treated and untreated cells. Chitosan and oligochitosan increased NADH dehydrogenase activity in isolated mitochondria. However, there were not changes in the cytochrome c oxidase and ATPase activities by effect of these polymers. These results suggest that both chitosan and oligochitosan affect the development of R. stolonifer and might be implicated in the mitochondrial dysfunction.

  5. Ceramide synthesis from free fatty acids in rat brain: function of NADPH and substrate specificity

    Energy Technology Data Exchange (ETDEWEB)

    Singh, I.


    At the subcellular level, the synthesis of ceramide from free lignoceric acid and sphingosine in brain required reconstituted enzyme system (particulate fraction, heat-stable and heat-labile factors) and pyridine nucleotide (NADPH). The mitochondrial electron transfer inhibitors (KCN and antimycin A), energy uncouplers (oligomycin and 2,4-dinitrophenol), and carboxyatractyloside, which prevents the transport of ATP and ADP through the mitochondrial wall, inhibit the synthesis of ceramide in the presence of NADPH but have very little effect in the presence of ATP. Similar to the synthesis of ceramide, the synthesis of ATP from NADPH and NADH by the particulate fraction also required cytoplasmic factors (heat-stable and heat-labile factors). Moreover, ATP, but not its analog (AMP-CH2-P-O-P), can replace NADPH, thus suggesting that the function of the pyridine nucleotide is to provide ATP for the synthesis of ceramide. The cytoplasmic factors were not required for the synthesis of ceramide in the presence of ATP. The maximum velocity for synthesis of ceramide from free fatty acids of different chain lengths (C16-C26) was bimodal, with maxima around stearic acid (C18) and behenic acid (C22). The relative rate of synthesis of ceramide parallels the relative distribution of these fatty acids in brain cerebrosides and sulfatides.

  6. Occurrence of the malate-aspartate shuttle in various tumor types. (United States)

    Greenhouse, W V; Lehninger, A L


    The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.

  7. Characterization of the respiratory chain of Helicobacter pylori

    DEFF Research Database (Denmark)

    Chen, M; Andersen, L P; Zhai, L


    The respiratory chain of Helicobacter pylori has been investigated. The total insensitivity of activities of NADH dehydrogenase to rotenone and of NADH-cytochrome c reductase to antimycin is indicative of the absence of the classical complex I of the electron transfer chain in this bacterium. NADPH...

  8. a

    Directory of Open Access Journals (Sweden)

    I. Pérez

    Full Text Available Fundamento: La solicitud de pruebas diagnósticas desde atención primaria presentan un aumento progresivo en el tiempo y una gran variabilidad interpersonal en su solicitud, que sugiere que se están aplicando servicios inefectivos. El objetivo es conocer las características de los demandantes de pruebas radiológicas (radiología general y ecografía y cuantificar las pruebas innecesarias en atención primaria. Material y métodos: Estudio descriptivo transversal sobre una muestra en cluster de 23 centros de salud de Navarra en el mes de marzo de 2004. Se diseña un cuestionario específico para cumplimentar por el médico solicitante de la prueba diagnóstica. Se realiza análisis multivariante mediante regresión logística para estudiar la asociación entre pruebas innecesarias y las otras variables de estudio. Resultados: Se realizan pruebas al 9 por mil de la población estudiada. La variabilidad interprofesional en la solicitud de pruebas oscila entre 0 y 33,3 por cada 1000 tarjetas sanitarias para la edad infantil. Los estudios radiológicos solicitados con mayor frecuencia fueron los óseos (48,9%, LC: 42,4-55,5. En el 63,2% de las solicitudes no se realizaron modificaciones en el tratamiento previo a la solicitud de la prueba y el 57 % (LC: 52,4-61,7 de las pruebas realizadas se solicitan para descartar patología. El 24,7% (LC: 17,1-29,2 son pruebas innecesarias y en el 15,2 % (LC:10,7-18,2 hubo presión del enfermo en la solicitud. En el análisis multivariante se observan diferencias significativas para Rx de tórax, cambios en el tratamiento y ser presionado por el enfermo. Tras ajustar por las otras variables, la solicitud de una prueba innecesaria es 12,55 veces mayor si el médico se siente presionado por el enfermo. Conclusiones: Debe analizarse la correcta indicación de la radiología, especialmente de la ósea, y se debe potenciar al radiólogo en la decisión última de realizar la prueba diagnóstica.

  9. A

    Directory of Open Access Journals (Sweden)

    Morteza Bahram


    Full Text Available We report on a new method for the preconcentration and microextraction of analytes from aqueous samples using a pH-sensitive hydrogel. It is referred to as semisolid–liquid dispersive microextraction (SSLDM and has the advantages of both dispersive liquid–liquid microextraction (DLLME and solid-phase extraction (SPE. The surface area of the droplets is large, so the equilibrium state is quickly reached. The high density of the gel facilitates phase separation, and disadvantages of existing methods are overcome in that there is no need for extraction and dispersive solvents (as in conventional DLLME and no need for desorption (as in SPE. The SSLDM method integrates sampling, extraction and concentration into one single and solvent-free step. The method was exemplarily applied to the preconcentration of malachite green (MG and crystal violet (CV which then were quantified by spectrophotometry. Specifically, poly (styrene-alt-maleic acid, a pH-sensitive hydrogel, was used to extract MG and CV from water samples. The linear analytical range is from 0.01 to 1 μmol L−1 for MG, and from 0.05 to 1 μmol L−1 for CV. The correlation coefficient for MG and CV is 0.999 and 0.993, respectively. The limit of detection for MG and CV is 0.011 and 0.014 μmol L−1, respectively.


    Directory of Open Access Journals (Sweden)

    Katyshev A.I.


    -cob* genetic construct with integrative properties. It contains the selective gene and the gene of interest under control of the 5'-regulatory regions of Arabidopsis orf262 gene and the tobacco cob gene. We used modified variant of the tobacco apocytochrome b gene as a gene for selection with the nucleotide substitution G128T (G43V which results in antimycin A resistance. The maize sod3.1 gene was used as a gene of interest. The construct was delivered into tobacco callus cells and leaf disks by biolistic method. The callus lines demonstrating the high growth rates in the presence of antimycin A in comparison with the non-transformed control lines were selected. PCR analysis of transformed callus lines revealed the presence of heterologous maize sod3.1 sequence and the integration of the construct elements in tobacco mitochondrial genome.

  11. Cytotoxic mechanisms of Zn{sup 2+} and Cd{sup 2+} involve Na{sup +}/H{sup +} exchanger (NHE) activation by ROS

    Energy Technology Data Exchange (ETDEWEB)

    Koutsogiannaki, Sophia [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Evangelinos, Nikolaos [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Koliakos, George [Department of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, P.O. Box 17034, 54124 Thessaloniki (Greece); Kaloyianni, Martha [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)]. E-mail:


    The signaling mechanism induced by cadmium (Cd) and zinc (Zn) in gill cells of Mytilus galloprovincialis was investigated. Both metals cause an increase in {center_dot}O{sub 2} {sup -} production, with Cd to be more potent (216 {+-} 15%) than Zn (150 {+-} 9.5%), in relation to control value (100%). The metals effect was reversed after incubation with the amiloride analogue, EIPA, a selective Na{sup +}/H{sup +} exchanger (NHE) inhibitor as well as in the presence of calphostin C, a protein kinase C (PKC) inhibitor. The heavy metals effect on {center_dot}O{sub 2} {sup -} production was mediated via the interaction of metal ions with {alpha}{sub 1}- and {beta}-adrenergic receptors, as shown after incubation with their respective agonists and antagonists. In addition, both metals caused an increase in intracellular pH (pHi) of gill cells. EIPA together with either metal significantly reduced the effect of each metal treatment on pHi. Incubation of gill cells with the oxidants rotenone, antimycin A and pyruvate caused a significant increase in pHi ({delta}pHi 0.830, 0.272 and 0.610, respectively), while in the presence of the anti-oxidant N-acetyl cysteine (NAC) a decrease in pHi ({delta}pHi -0.090) was measured, indicating that change in reactive oxygen species (ROS) production by heavy metals affects NHE activity. When rosiglitazone was incubated together with either heavy metal a decrease in O{sub 2} {sup -} production was observed. Our results show a key role of NHE in the signal transduction pathway induced by Zn and Cd in gill cells, with the involvement of ROS, PKC, adrenergic and PPAR-{gamma} receptors. In addition, differences between the two metals concerning NHE activation, O{sub 2} {sup -} production and interaction with adrenergic receptors were observed.

  12. Reconstitution of the anti-apoptotic Bcl-2 protein into lipid membranes and biophysical evidence for its detergent-driven association with the pro-apoptotic Bax protein.

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    Marcus Wallgren

    Full Text Available The anti-apoptotic B-cell CLL/lymphoma-2 (Bcl-2 protein and its counterpart, the pro-apoptotic Bcl-2-associated X protein (Bax, are key players in the regulation of the mitochondrial pathway of apoptosis. However, how they interact at the mitochondrial outer membrane (MOM and there determine whether the cell will live or be sentenced to death remains unknown. Competing models have been presented that describe how Bcl-2 inhibits the cell-killing activity of Bax, which is common in treatment-resistant tumors where Bcl-2 is overexpressed. Some studies suggest that Bcl-2 binds directly to and sequesters Bax, while others suggest an indirect process whereby Bcl-2 blocks BH3-only proteins and prevents them from activating Bax. Here we present the results of a biophysical study in which we investigated the putative interaction of solubilized full-length human Bcl-2 with Bax and the scope for incorporating the former into a native-like lipid environment. Far-UV circular dichroism (CD spectroscopy was used to detect direct Bcl-2-Bax-interactions in the presence of polyoxyethylene-(23-lauryl-ether (Brij-35 detergent at a level below its critical micelle concentration (CMC. Additional surface plasmon resonance (SPR measurements confirmed this observation and revealed a high affinity between the Bax and Bcl-2 proteins. Upon formation of this protein-protein complex, Bax also prevented the binding of antimycin A2 (a known inhibitory ligand of Bcl-2 to the Bcl-2 protein, as fluorescence spectroscopy experiments showed. In addition, Bcl-2 was able to form mixed micelles with Triton X-100 solubilized neutral phospholipids in the presence of high concentrations of Brij-35 (above its CMC. Following detergent removal, the integral membrane protein was found to have been fully reconstituted into a native-like membrane environment, as confirmed by ultracentrifugation and subsequent SDS-PAGE experiments.

  13. The metabolism of malate by cultured rat brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, M.C.; Tildon, J.T.; Couto, R.; Stevenson, J.H.; Caprio, F.J. (Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA))


    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

  14. Modulation of intracellular calcium waves and triggered activities by mitochondrial ca flux in mouse cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Zhenghang Zhao

    Full Text Available Recent studies have suggested that mitochondria may play important roles in the Ca(2+ homeostasis of cardiac myocytes. However, it is still unclear if mitochondrial Ca(2+ flux can regulate the generation of Ca(2+ waves (CaWs and triggered activities in cardiac myocytes. In the present study, intracellular/cytosolic Ca(2+ (Cai (2+ was imaged in Fluo-4-AM loaded mouse ventricular myocytes. Spontaneous sarcoplasmic reticulum (SR Ca(2+ release and CaWs were induced in the presence of high (4 mM external Ca(2+ (Cao (2+. The protonophore carbonyl cyanide p-(trifluoromethoxyphenylhydrazone (FCCP reversibly raised basal Cai (2+ levels even after depletion of SR Ca(2+ in the absence of Cao (2+ , suggesting Ca(2+ release from mitochondria. FCCP at 0.01 - 0.1 µM partially depolarized the mitochondrial membrane potential (Δψ m and increased the frequency and amplitude of CaWs in a dose-dependent manner. Simultaneous recording of cell membrane potentials showed the augmentation of delayed afterdepolarization amplitudes and frequencies, and induction of triggered action potentials. The effect of FCCP on CaWs was mimicked by antimycin A (an electron transport chain inhibitor disrupting Δψ m or Ru360 (a mitochondrial Ca(2+ uniporter inhibitor, but not by oligomycin (an ATP synthase inhibitor or iodoacetic acid (a glycolytic inhibitor, excluding the contribution of intracellular ATP levels. The effects of FCCP on CaWs were counteracted by the mitochondrial permeability transition pore blocker cyclosporine A, or the mitochondrial Ca(2+ uniporter activator kaempferol. Our results suggest that mitochondrial Ca(2+ release and uptake exquisitely control the local Ca(2+ level in the micro-domain near SR ryanodine receptors and play an important role in regulation of intracellular CaWs and arrhythmogenesis.

  15. The mitochondrial PPR protein LOVASTATIN INSENSITIVE 1 plays regulatory roles in cytosolic and plastidial isoprenoid biosynthesis through RNA editing. (United States)

    Tang, Jianwei; Kobayashi, Keiko; Suzuki, Masashi; Matsumoto, Shogo; Muranaka, Toshiya


    Unlike animals, plants synthesize isoprenoids via two pathways, the cytosolic mevalonate (MVA) pathway and the plastidial 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway. Little information is known about the mechanisms that regulate these complex biosynthetic networks over multiple organelles. To understand such regulatory mechanisms of the biosynthesis of isoprenoids in plants, we previously characterized the Arabidopsis mutant, lovastatin insensitive 1 (loi1), which is resistant to lovastatin and clomazone, specific inhibitors of the MVA and MEP pathways, respectively. LOI1 encodes a pentatricopeptide repeat (PPR) protein localized in mitochondria that is thought to have RNA binding ability and function in post-transcriptional regulation of mitochondrial gene expression. LOI1 belongs to the DYW subclass of PPR proteins, which is hypothesized to be correlated with RNA editing. As a result of analysis of RNA editing of mitochondrial genes in loi1, a defect in RNA editing of three genes, nad4, ccb203 and cox3, was identified in loi1. These genes are related to the respiratory chain. Wild type (WT) treated with some respiration inhibitors mimicked the loi1 phenotype. Interestingly, HMG-CoA reductase activity of WT treated with lovastatin combined with antimycin A, an inhibitor of complex III in the respiratory chain, was higher than that of WT treated with only lovastatin, despite the lack of alteration of transcript or protein levels of HMGR. These results suggest that HMGR enzyme activity is regulated through the respiratory cytochrome pathway. Although various mechanisms exist for isoprenoid biosynthesis, our studies demonstrate the novel possibility that mitochondrial respiration plays potentially regulatory roles in isoprenoid biosynthesis.

  16. Inhibition of the mitochondrial respiratory chain function abrogates quartz induced DNA damage in lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Li Hui [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Haberzettl, Petra [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Albrecht, Catrin [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Hoehr, Doris [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Knaapen, Ad M. [Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), University of Maastricht (Netherlands); Borm, Paul J.A. [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany); Hogeschool Zuyd Heerlen (Netherlands); Schins, Roel P.F. [Institut fuer umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Auf' m Hennekamp 50, D-40225 Duesseldorf (Germany)]. E-mail:


    Respirable quartz dust has been classified as a human carcinogen by the International Agency for Research on Cancer. The aim of our study was to investigate the mechanisms of DNA damage by DQ12 quartz in RLE-6TN rat lung epithelial type II cells (RLE). Transmission electron microscopy and flow-cytometry analysis showed a rapid particle uptake (30 min to 4 h) of quartz by the RLE cells, but particles were not found within the cell nuclei. This suggests that DNA strand breakage and induction of 8-hydroxydeoxyguanosine - as also observed in these cells during these treatment intervals - did not result from direct physical interactions between particles and DNA, or from short-lived particle surface-derived reactive oxygen species. DNA damage by quartz was significantly reduced in the presence of the mitochondrial inhibitors rotenone and antimycin-A. In the absence of quartz, these inhibitors did not affect DNA damage, but they reduced cellular oxygen consumption. No signs of apoptosis were observed by quartz. Flow-cytometry analysis indicated that the reduced DNA damage by rotenone was not due to a possible mitochondria-mediated reduction of particle uptake by the RLE cells. Further proof of concept for the role of mitochondria was shown by the failure of quartz to elicit DNA damage in mitochondria-depleted 143B (rho-0) osteosarcoma cells, at concentrations where it elicited DNA damage in the parental 143B cell line. In conclusion, our data show that respirable quartz particles can elicit oxidative DNA damage in vitro without entering the nuclei of type II cells, which are considered to be important target cells in quartz carcinogenesis. Furthermore, our observations indicate that such indirect DNA damage involves the mitochondrial electron transport chain function, by an as-yet-to-be elucidated mechanism.

  17. Alternative oxidase: distribution, induction, properties, structure, regulation, and functions. (United States)

    Rogov, A G; Sukhanova, E I; Uralskaya, L A; Aliverdieva, D A; Zvyagilskaya, R A


    The respiratory chain in the majority of organisms with aerobic type metabolism features the concomitant existence of the phosphorylating cytochrome pathway and the cyanide- and antimycin A-insensitive oxidative route comprising a so-called alternative oxidase (AOX) as a terminal oxidase. In this review, the history of AOX discovery is described. Considerable evidence is presented that AOX occurs widely in organisms at various levels of organization and is not confined to the plant kingdom. This enzyme has not been found only in Archaea, mammals, some yeasts and protists. Bioinformatics research revealed the sequences characteristic of AOX in representatives of various taxonomic groups. Based on multiple alignments of these sequences, a phylogenetic tree was constructed to infer their possible evolution. The ways of AOX activation, as well as regulatory interactions between AOX and the main respiratory chain are described. Data are summarized concerning the properties of AOX and the AOX-encoding genes whose expression is either constitutive or induced by various factors. Information is presented on the structure of AOX, its active center, and the ubiquinone-binding site. The principal functions of AOX are analyzed, including the cases of cell survival, optimization of respiratory metabolism, protection against excess of reactive oxygen species, and adaptation to variable nutrition sources and to biotic and abiotic stress factors. It is emphasized that different AOX functions complement each other in many instances and are not mutually exclusive. Examples are given to demonstrate that AOX is an important tool to overcome the adverse aftereffects of restricted activity of the main respiratory chain in cells and whole animals. This is the first comprehensive review on alternative oxidases of various organisms ranging from yeasts and protists to vascular plants.

  18. Ultrastructure and function of mitochondria in gametocytic stage of Plasmodium falciparum

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    Krungkrai J.


    Full Text Available Morphological properties of the mitochondrial organelles in the asexual and sexual gametocytic stages of Plasmodium falciparum have been analyzed and found to be markedly different. From in vitro cultures of both stages in human erythrocytes, it has been demonstrated that the asexual stages contained a defined double-membrane organelle having a few tubular-like cristae. The numbers of mitochondria in the gametocytes were found to be ~ 6 organelles per parasite, and they showed a greater density of the cristae than that of the asexual stage parasite. The organelles of the gametocytes were successfully purified by differential centrifugation following Percoll density gradient separation with the results of ~ 7 % yields and ~ 5 folds. The gametocytic organelles contained much more activities of mitochondrial electron transporting enzymes (i.e., cytochrome c reductase, cytochrome c oxidase than the asexual stage organelles. Mitochondrial function as measured by oxygen consumption were found to be different between these two stages organelles. Their rates of oxygen consumption were relatively low, as compared to those of human leukocyte and mouse liver mitochondria. In contrast to the coupled mammalian mitochondria, the gametocytic organelles were in the uncoupling state between oxidation and phosphorylation reactions during their respiration. However, they were sensitive to inhibitors of the electron transport system, e.g., antimycin A, cyanide. Our results suggest that the mitochondria of the gametocytic stages are metabolically active and still underdeveloped, although their inner membranes are extensively folded. The biochemical significance of the unique structure of the mitochondria in these developing stages in host erythrocytes remains to be elucidated.

  19. Role of mitochondria in the switch mechanism of the cell death mode from apoptosis to necrosis--studies on rho0 cells. (United States)

    Wochna, Agnieszka; Niemczyk, Edyta; Kurono, Chieko; Masaoka, Makoto; Majczak, Anna; Kedzior, Jakub; Slominska, Ewa; Lipinski, Marcin; Wakabayashi, Takashi


    Detailed mechanisms of the switch of the cell death mode from apoptosis to necrosis remain to be solved, although the intracellular level of ATP and that of free radicals have been postulated to be the major factors involved in the mechanisms. In the present study menadione (MEN)-induced cell injury processes were studied using rho0 cells derived from human osteosarcoma 143B cells and parental rho+ cells co-treated with inhibitors of electron transfer chain of mitochondria or oligomycin, an inhibitor of ATP synthesis. Treatment of rho+ cells with 100 microM MEN induced apoptosis, which reached the maximum at 6 h, and was followed by an abrupt decrease thereafter, while necrotic cells (NC) increased continuously when they were judged by Annexin V and PI double staining. On the other hand, MEN induced apoptotic and necrotic changes much faster in rho0 cells compared to rho+ cells. The frequency to find apoptotic cells (AP) in the former cells was distinctly smaller than that to find NC judged by Annexin V and PI double staining. Electron microscopically, a major population of rho0 cells treated with MEN for 6 h consisted of intermediate cells, and a small number of AP co-existed. At 9 h of the treatment intermediate cells were exclusively seen, and AP were hardly detected. When parental rho+ cells were treated with MEN in the presence of oligomycin or oligomycin plus antimycin A both apoptotic and necrotic changes of the cells were distinctly accelerated. The intracellular level of superoxide in rho0 cells continuously increased after the MEN treatment, whereas that of ATP remained distinctly low before and after the MEN treatment compared to that in rho+ cells. These data suggest that the intracellular level of superoxide may be a key factor controlling the switch from apoptosis to necrosis.

  20. Evidence for the role of cyclic electron flow in photoprotection for oxygen-evolving complex. (United States)

    Huang, Wei; Yang, Ying-Jie; Hu, Hong; Zhang, Shi-Bao; Cao, Kun-Fang


    Cyclic electron flow (CEF) alleviates PSII photo-inhibition under high light by at least two different mechanisms: one is liked to thermal energy dissipation (qE) and the other one is independent of qE. However, the latter mechanism is unclear. Because the photodamage to PSII primarily occurred at the oxygen-evolving complex (OEC), and the stability of OEC is dependent on proton gradient across thylakoid membrane (ΔpH), we hypothesize that the CEF-dependent generation of ΔpH can alleviate photodamage to OEC. To test this hypothesis, we determined the effects of antimycin A (AA), methyl viologen (MV), chloramphenicol (CM), nigericin (Nig) on PSII activity and the stability of OEC for leaves of a light-demanding tropical tree species Erythrophleum guineense by the analysis of OKJIP chlorophyll a fluorescence transient. After high light treatment, the stronger decrease in Fv/Fm in the AA-, CM-, MV-, and Nig-treated samples was accompanied with larger photo damage of OEC. The AA-treated samples significantly showed lower CEF activity than the H2O-treated samples. Although the AA-treated leaves significantly showed stronger PSII photo-inhibition and photo-damage of OEC compared to the H2O-treated leaves, the value of non-photochemical quenching did not differ between them. Therefore, CEF activity was partly inhibited in the AA-treated samples, and the stronger PSII photo-inhibition in the AA-treated leaves was independent of qE. Taking together, we propose a hypothesis that CEF-dependent generation of ΔpH under high light plays an important role in photoprotection for the OEC activity.

  1. Elucidation of Photoprotective Mechanisms of PSI Against Fluctuating Light photoinhibition. (United States)

    Kono, Masaru; Terashima, Ichiro


    It has been claimed that the cyclic electron flow around PSI (CEF-PSI) plays an important role in protection of PSI against fluctuating light photoinhibition. However, the photoprotective mechanism of PSI is not fully elucidated. Here, we examined the mechanism, using two CEF-PSI mutants of Arabidopsis thaliana, and antimycin A, an inhibitor of the PGR5 (proton gradient regulation 5)-mediated CEF-PSI. Dark-adapted leaves in these plants were illuminated in fluctuating light alternating between high light at 1,200 µmol m(-2) s(-1) and low light at 30 µmol m(-2) s(-1) every 2 min, and PSI and PSII parameters were simultaneously measured for 160 min with 830 nm absorption and Chl fluorescence, respectively. When CEF-PSI, especially PGR5-mediated CEF-PSI, did not operate, the acceptor-side limitation of PSI, Y(NA), increased stepwise, leading to marked PSI photoinhibition. The deficiency of CFE-PSI decreased not only the electron transport rate through PSI but also the donor-side limitation of PSI, Y(ND), in high light phases. These results showed that the large Y(ND), observed only when CEF-PSI operated, contributed to suppression of PSI photoinhibition. Taken together with our previous report that high Y(NA) was alleviated by the enhancement of CEF-PSI, a model for the protective mechanisms of PSI is proposed. In this model, both alleviation of Y(NA) and acceleration of Y(ND) are indispensable, and for realization of such a situation, regulation of the electron flows, especially the PGR5-mediated CEF-PSI, plays a key role. It is important for effective protection to regulate the balance of Y(ND) and Y(NA) through CEF-PSI.

  2. Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning. (United States)

    Leonard, Anthony P; Cameron, Robert B; Speiser, Jaime L; Wolf, Bethany J; Peterson, Yuri K; Schnellmann, Rick G; Beeson, Craig C; Rohrer, Bärbel


    Understanding the processes of mitochondrial dynamics (fission, fusion, biogenesis, and mitophagy) has been hampered by the lack of automated, deterministic methods to measure mitochondrial morphology from microscopic images. A method to quantify mitochondrial morphology and function is presented here using a commercially available automated high-content wide-field fluorescent microscopy platform and R programming-language-based semi-automated data analysis to achieve high throughput morphological categorization (puncta, rod, network, and large & round) and quantification of mitochondrial membrane potential. In conjunction with cellular respirometry to measure mitochondrial respiratory capacity, this method detected that increasing concentrations of toxicants known to directly or indirectly affect mitochondria (t-butyl hydroperoxide [TBHP], rotenone, antimycin A, oligomycin, ouabain, and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone [FCCP]), decreased mitochondrial networked areas in cultured 661w cells to 0.60-0.80 at concentrations that inhibited respiratory capacity to 0.20-0.70 (fold change compared to vehicle). Concomitantly, mitochondrial swelling was increased from 1.4- to 2.3-fold of vehicle as indicated by changes in large & round areas in response to TBHP, oligomycin, or ouabain. Finally, the automated identification of mitochondrial location enabled accurate quantification of mitochondrial membrane potential by measuring intramitochondrial tetramethylrhodamine methyl ester (TMRM) fluorescence intensity. Administration of FCCP depolarized and administration of oligomycin hyperpolarized mitochondria, as evidenced by changes in intramitochondrial TMRM fluorescence intensities to 0.33- or 5.25-fold of vehicle control values, respectively. In summary, this high-content imaging method accurately quantified mitochondrial morphology and membrane potential in hundreds of thousands of cells on a per-cell basis, with sufficient throughput for pharmacological

  3. The energy blockers 3-bromopyruvate and lonidamine: effects on bioenergetics of brain mitochondria. (United States)

    Macchioni, Lara; Davidescu, Magdalena; Roberti, Rita; Corazzi, Lanfranco


    Tumor cells favor abnormal energy production via aerobic glycolysis and show resistance to apoptosis, suggesting the involvement of mitochondrial dysfunction. The differences between normal and cancer cells in their energy metabolism provide a biochemical basis for developing new therapeutic strategies. The energy blocker 3-bromopyruvate (3BP) can eradicate liver cancer in animals without associated toxicity, and is a potent anticancer towards glioblastoma cells. Since mitochondria are 3BP targets, in this work the effects of 3BP on the bioenergetics of normal rat brain mitochondria were investigated in vitro, in comparison with the anticancer agent lonidamine (LND). Whereas LND impaired oxygen consumption dependent on any complex of the respiratory chain, 3BP was inhibitory to malate/pyruvate and succinate (Complexes I and II), but preserved respiration from glycerol-3-phosphate and ascorbate (Complex IV). Accordingly, although electron flow along the respiratory chain and ATP levels were decreased by 3BP in malate/pyruvate- and succinate-fed mitochondria, they were not significantly influenced from glycerol-3-phosphate- or ascorbate-fed mitochondria. LND produced a decrease in electron flow from all substrates tested. No ROS were produced from any substrate, with the exception of 3BP-induced H(2)O(2) release from succinate, which suggests an antimycin-like action of 3BP as an inhibitor of Complex III. We can conclude that 3BP does not abolish completely respiration and ATP synthesis in brain mitochondria, and has a limited effect on ROS production, confirming that this drug may have limited harmful effects on normal cells.

  4. Folate Deficiency Triggered Apoptosis of Synoviocytes: Role of Overproduction of Reactive Oxygen Species Generated via NADPH Oxidase/Mitochondrial Complex II and Calcium Perturbation. (United States)

    Hsu, Hung-Chih; Chang, Wen-Ming; Wu, Jin-Yi; Huang, Chin-Chin; Lu, Fung-Jou; Chuang, Yi-Wen; Chang, Pey-Jium; Chen, Kai-Hua; Hong, Chang-Zern; Yeh, Rang-Hui; Liu, Tsan-Zon; Chen, Ching-Hsein


    Despite a plethora of literature has documented that osteoarthritis (OA) is veritably associated with oxidative stress-mediated chondrocyte death and matrix degradation, yet the possible involvement of synoviocyte abnormality as causative factor of OA has not been thoroughly investigated. For this reason, we conduct the current studies to insight into how synoviocytes could respond to an episode of folate-deprived (FD) condition. First, when HIG-82 synoviocytes were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature mediated through FD-evoked overproduction of reactive oxygen species (ROS) and drastically released of cytosolic calcium (Ca2+) concentrations. Next, we uncovered that FD-evoked ROS overproduction could only be strongly suppressed by either mitochondrial complex II inhibitors (TTFA and carboxin) or NADPH oxidase (NOX) inhibitors (AEBSF and apocynin), but not by mitochondrial complex I inhibitor (rotenone) and mitochondrial complex III inhibitor (antimycin A). Interestingly, this selective inhibition of FD-evoked ROS by mitochondrial complex II and NOX inhibitors was found to correlate excellently with the suppression of cytosolic Ca2+ release and reduced the magnitude of the apoptotic TUNEL-positive cells. Taken together, we present the first evidence here that FD-triggered ROS overproduction in synoviocytes is originated from mitochondrial complex II and NOX. Both elevated ROS in tandem with cytosolic Ca2+ overload serve as final arbitrators for apoptotic lethality of synoviocytes cultivated under FD condition. Thus, folate supplementation may be beneficial to patients with OA.

  5. The upper and lower limits of the mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Stoichiometry of oxidative phosphorylation. (United States)

    Beavis, A D; Lehninger, A L


    Determination of the intrinsic or mechanistic P/O ratio of oxidative phosphorylation is difficult because of the unknown magnitude of leak fluxes. Applying a new approach developed to overcome this problem (see our preceding paper in this journal), the relationships between the rate of O2 uptake [( Jo)3], the net rate of phosphorylation (Jp), the P/O ratio, and the respiratory control ratio (RCR) have been determined in rat liver mitochondria when the rate of phosphorylation was systematically varied by three specific means. (a) When phosphorylation is titrated with carboxyatractyloside, linear relationships are observed between Jp and (Jo)3. These data indicate that the upper limit of the mechanistic P/O ratio is 1.80 for succinate and 2.90 for 3-hydroxybutyrate oxidation. (b) Titration with malonate or antimycin yields linear relationships between Jp and (Jo)3. These data give the lower limit of the mechanistic P/O ratio of 1.63 for succinate and 2.66 for 3-hydroxybutyrate oxidation. (c) Titration with a protonophore yields linear relationships between Jp, (Jo)3, and (Jo)4 and between P/O and 1/RCR. Extrapolation of the P/O ratio to 1/RCR = 0 yields P/O ratios of 1.75 for succinate and 2.73 for 3-hydroxybutyrate oxidation which must be equal to or greater than the mechanistic stoichiometry. When published values for the H+/O and H+/ATP ejection ratios are taken into consideration, these measurements suggest that the mechanistic P/O ratio is 1.75 for succinate oxidation and 2.75 for NADH oxidation.

  6. Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury.

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    Bhavya B Chandrika

    Full Text Available We examined whether endoplasmic reticulum (ER stress-induced autophagy provides cytoprotection from renal tubular epithelial cell injury due to oxidants and chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR injury in vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded protein response, upregulates ER chaperone Grp78, and activates the autophagy pathway in renal tubular epithelial cells in culture. Inhibition of ER stress-induced autophagy accelerated caspase-3 activation and cell death suggesting a pro-survival role of ER stress-induced autophagy. Compared to wild-type cells, autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation and cell death, a finding that further supports the cytoprotective role of ER stress-induced autophagy. Induction of autophagy by ER stress markedly afforded cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced autophagy or autophagy-deficient cells markedly enhanced cell death in response to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal epithelial cells in culture, tunicamycin triggered ER stress, markedly upregulated Grp78, and activated autophagy without impairing the autophagic flux. In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as evident from significant improvement in renal function and histology. Inhibition of autophagy by chloroquine markedly increased renal IR injury. These studies highlight beneficial impact of ER stress-induced autophagy in renal ischemia-reperfusion injury both in vitro and in vivo.

  7. Differential production of superoxide by neuronal mitochondria

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    Levin Leonard A


    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs, a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells. Results In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria. Conclusion RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.

  8. Computational modeling analysis of mitochondrial superoxide production under varying substrate conditions and upon inhibition of different segments of the electron transport chain. (United States)

    Markevich, Nikolai I; Hoek, Jan B


    A computational mechanistic model of superoxide (O2•-) formation in the mitochondrial electron transport chain (ETC) was developed to facilitate the quantitative analysis of factors controlling mitochondrial O2•- production and assist in the interpretation of experimental studies. The model takes into account all individual electron transfer reactions in Complexes I and III. The model accounts for multiple, often seemingly contradictory observations on the effects of ΔΨ and ΔpH, and for the effects of multiple substrate and inhibitor conditions, including differential effects of Complex III inhibitors antimycin A, myxothiazol and stigmatellin. Simulation results confirm that, in addition to O2•- formation in Complex III and at the flavin site of Complex I, the quinone binding site of Complex I is an additional superoxide generating site that accounts for experimental observations on O2•- production during reverse electron transfer. However, our simulation results predict that, when cytochrome c oxidase is inhibited during oxidation of succinate, ROS production at this site is eliminated and almost all superoxide in Complex I is generated by reduced FMN, even when the redox pressure for reverse electron transfer from succinate is strong. In addition, the model indicates that conflicting literature data on the kinetics of electron transfer in Complex III involving the iron-sulfur protein-cytochrome bL complex can be resolved in favor of a dissociation of the protein only after electron transfer to cytochrome bH. The model predictions can be helpful in understanding factors driving mitochondrial superoxide formation in intact cells and tissues.

  9. Ischemic proximal tubular injury primes mice to endotoxin-induced TNF-alpha generation and systemic release. (United States)

    Zager, R A; Johnson, Ali C M; Hanson, Sherry Y; Lund, Steve


    Endotoxemia (LPS) can exacerbate ischemic tubular injury and acute renal failure (ARF). The present study tested the following hypothesis: that acute ischemic damage sensitizes the kidney to LPS-mediated TNF-alpha generation, a process that can worsen inflammation and cytotoxicity. CD-1 mice underwent 15 min of unilateral renal ischemia. LPS (10 mg/kg iv), or its vehicle, was injected either 45 min before, or 18 h after, the ischemic event. TNF-alpha responses were gauged 2 h post-LPS injection by measuring plasma/renal cortical TNF-alpha and renal cortical TNF-alpha mRNA. Values were contrasted to those obtained in sham-operated mice or in contralateral, nonischemic kidneys. TNF-alpha generation by isolated mouse proximal tubules (PTs), and by cultured proximal tubule (HK-2) cells, in response to hypoxia-reoxygenation (H/R), oxidant stress, antimycin A (AA), or LPS was also assessed. Ischemia-reperfusion (I/R), by itself, did not raise plasma or renal cortical TNF-alpha or its mRNA. However, this same ischemic insult dramatically sensitized mice to LPS-mediated TNF-alpha increases in both plasma and kidney (approximately 2-fold). During late reperfusion, increased TNF-alpha mRNA levels also resulted. PTs generated TNF-alpha in response to injury. Neither AA nor LPS alone induced an HK-2 cell TNF-alpha response. However, when present together, AA+LPS induced approximately two- to fivefold increases in TNF-alpha/TNF-alpha mRNA. We conclude that modest I/R injury, and in vitro HK-2 cell mitochondrial inhibition (AA), can dramatically sensitize the kidney/PTs to LPS-mediated TNF-alpha generation and increases in TNF-alpha mRNA. That ischemia can "prime" tubules to LPS response(s) could have potentially important implications for sepsis syndrome, concomitant renal ischemia, and for the induction of ARF.

  10. Glucose, Lactate and Glutamine but not Glutamate Support Depolarization-Induced Increased Respiration in Isolated Nerve Terminals. (United States)

    Hohnholt, Michaela C; Andersen, Vibe H; Bak, Lasse K; Waagepetersen, Helle S


    Synaptosomes prepared from various aged and gene modified experimental animals constitute a valuable model system to study pre-synaptic mechanisms. Synaptosomes were isolated from whole brain and the XFe96 extracellular flux analyzer (Seahorse Bioscience) was used to study mitochondrial respiration and glycolytic rate in presence of different substrates. Mitochondrial function was tested by sequentially exposure of the synaptosomes to the ATP synthase inhibitor, oligomycin, the uncoupler FCCP (carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone) and the electron transport chain inhibitors rotenone and antimycin A. The synaptosomes exhibited intense respiratory activity using glucose as substrate. The FCCP-dependent respiration was significantly higher with 10 mM glucose compared to 1 mM glucose. Synaptosomes also readily used pyruvate as substrate, which elevated basal respiration, activity-dependent respiration induced by veratridine and the respiratory response to uncoupling compared to that obtained with glucose as substrate. Also lactate was used as substrate by synaptosomes but in contrast to pyruvate, mitochondrial lactate mediated respiration was comparable to respiration using glucose as substrate. Synaptosomal respiration using glutamate and glutamine as substrates was significantly higher compared to basal respiration, whereas oligomycin-dependent and FCCP-induced respiration was lower compared to the responses obtained in the presence of glucose as substrate. We provide evidence that synaptosomes are able to use besides glucose and pyruvate also the substrates lactate, glutamate and glutamine to support their basal respiration. Veratridine was found to increase respiration supported by glucose, pyruvate, lactate and glutamine and FCCP was found to increase respiration supported by glucose, pyruvate and lactate. This was not the case when glutamate was the only energy substrate.

  11. Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in murine precision cut lung slices

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    Goldenberg Anna


    Full Text Available Abstract Background Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV which serves to match lung perfusion to ventilation. The underlying mechanisms are not fully resolved yet. The major vascular segment contributing to HPV, the intra-acinar artery, is mostly located in that part of the lung that cannot be selectively reached by the presently available techniques, e.g. hemodynamic studies of isolated perfused lungs, recordings from dissected proximal arterial segments or analysis of subpleural vessels. The aim of the present study was to establish a model which allows the investigation of HPV and its underlying mechanisms in small intra-acinar arteries. Methods Intra-acinar arteries of the mouse lung were studied in 200 μm thick precision-cut lung slices (PCLS. The organisation of the muscle coat of these vessels was characterized by α-smooth muscle actin immunohistochemistry. Basic features of intra-acinar HPV were characterized, and then the impact of reactive oxygen species (ROS scavengers, inhibitors of the respiratory chain and Krebs cycle metabolites was analysed. Results Intra-acinar arteries are equipped with a discontinuous spiral of α-smooth muscle actin-immunoreactive cells. They exhibit a monophasic HPV (medium gassed with 1% O2 that started to fade after 40 min and was lost after 80 min. This HPV, but not vasoconstriction induced by the thromboxane analogue U46619, was effectively blocked by nitro blue tetrazolium and diphenyleniodonium, indicating the involvement of ROS and flavoproteins. Inhibition of mitochondrial complexes II (3-nitropropionic acid, thenoyltrifluoroacetone and III (antimycin A specifically interfered with HPV, whereas blockade of complex IV (sodium azide unspecifically inhibited both HPV and U46619-induced constriction. Succinate blocked HPV whereas fumarate had minor effects on vasoconstriction. Conclusion This study establishes the first model for investigation of basic characteristics of HPV

  12. Regulation of glutamine synthetase, aspartokinase, and total protein turnover in Klebsiella aerogenes. (United States)

    Fulks, R M; Stadtman, E R


    When suspensions of Klebsiella aerogenes are incubated in a nitrogen-free medium there is a gradual decrease in the levels of acid-precipitable protein and of aspartokinase III (lysine-sensitive) and aspartokinase I (threonine-sensitive) activities. In contrast, the level of glutamine synthetase increases slightly and then remains constant. Under these conditions, the glutamine synthetase and other proteins continue to be synthesized as judged by the incorporation of [14C]leucine into the acid-precipitable protein fraction and into protein precipitated by anti-glutamine synthetase antibodies, by the fact that growth-inhibiting concentrations of chloramphenicol also inhibit the incorporation of [14C]leucine into protein and into protein precipitated by anti-glutamine synthetase antibody, and by the fact that chloramphenicol leads to acceleration in the loss of aspartokinases I and III and promotes a net decrease in the level of glutamine synthetase and its cross-reactive protein. The loss of aspartokinases I and III in cell suspensions is stimulated by glucose and is inhibited by 2,4-dinitrophenol. Glucose also stimulates the loss of aspartokinases and glutamine synthetase in the presence of chloramphenicol. Cell-free extracts of K. aerogenes catalyze rapid inactivation of endogenous glutamine synthetase as well as exogenously added pure glutamine synthetase. This loss of glutamine synthetase is not associated with a loss of protein that cross-reacts with anti-glutamine synthetase antibodies. The inactivation of glutamine synthetase in extracts is not due to adenylylation. It is partially prevented by sulfhydryl reagents, Mn2+, antimycin A, 2,4-dinitrophenol, EDTA, anaerobiosis and by dialysis. Following 18 h dialysis, the capacity of extracts to catalyze inactivation of glutamine synthetase is lost but can be restored by the addition of Fe2+ (or Ni2+) together with ATP (or other nucleoside di- and triphosphates. After 40-60 h dialysis Fe3+ together with NADH (but

  13. Mitochondrial dysfunction leads to deconjugation of quercetin glucuronides in inflammatory macrophages.

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    Akari Ishisaka

    Full Text Available Dietary flavonoids, such as quercetin, have long been recognized to protect blood vessels from atherogenic inflammation by yet unknown mechanisms. We have previously discovered the specific localization of quercetin-3-O-glucuronide (Q3GA, a phase II metabolite of quercetin, in macrophage cells in the human atherosclerotic lesions, but the biological significance is poorly understood. We have now demonstrated the molecular basis of the interaction between quercetin glucuronides and macrophages, leading to deconjugation of the glucuronides into the active aglycone. In vitro experiments showed that Q3GA was bound to the cell surface proteins of macrophages through anion binding and was readily deconjugated into the aglycone. It is of interest that the macrophage-mediated deconjugation of Q3GA was significantly enhanced upon inflammatory activation by lipopolysaccharide (LPS. Zymography and immunoblotting analysis revealed that β-glucuronidase is the major enzyme responsible for the deglucuronidation, whereas the secretion rate was not affected after LPS treatment. We found that extracellular acidification, which is required for the activity of β-glucuronidase, was significantly induced upon LPS treatment and was due to the increased lactate secretion associated with mitochondrial dysfunction. In addition, the β-glucuronidase secretion, which is triggered by intracellular calcium ions, was also induced by mitochondria dysfunction characterized using antimycin-A (a mitochondrial inhibitor and siRNA-knockdown of Atg7 (an essential gene for autophagy. The deconjugated aglycone, quercetin, acts as an anti-inflammatory agent in the stimulated macrophages by inhibiting the c-Jun N-terminal kinase activation, whereas Q3GA acts only in the presence of extracellular β-glucuronidase activity. Finally, we demonstrated the deconjugation of quercetin glucuronides including the sulfoglucuronides in vivo in the spleen of mice challenged with LPS. These results

  14. Kalispel Non-Native Fish Suppression Project 2007 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Wingert, Michele; Andersen, Todd [Kalispel Natural Resource Department


    Non-native salmonids are impacting native salmonid populations throughout the Pend Oreille Subbasin. Competition, hybridization, and predation by non-native fish have been identified as primary factors in the decline of some native bull trout (Salvelinus confluentus) and westslope cutthroat trout (Oncorhynchus clarki lewisi) populations. In 2007, the Kalispel Natural Resource Department (KNRD) initiated the Kalispel Nonnative Fish Suppression Project. The goal of this project is to implement actions to suppress or eradicate non-native fish in areas where native populations are declining or have been extirpated. These projects have previously been identified as critical to recovering native bull trout and westslope cutthroat trout (WCT). Lower Graham Creek was invaded by non-native rainbow (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis) after a small dam failed in 1991. By 2003, no genetically pure WCT remained in the lower 700 m of Graham Creek. Further invasion upstream is currently precluded by a relatively short section of steep, cascade-pool stepped channel section that will likely be breached in the near future. In 2008, a fish management structure (barrier) was constructed at the mouth of Graham Creek to preclude further invasion of non-native fish into Graham Creek. The construction of the barrier was preceded by intensive electrofishing in the lower 700 m to remove and relocate all captured fish. Westslope cutthroat trout have recently been extirpated in Cee Cee Ah Creek due to displacement by brook trout. We propose treating Cee Cee Ah Creek with a piscicide to eradicate brook trout. Once eradication is complete, cutthroat trout will be translocated from nearby watersheds. In 2004, the Washington Department of Fish and Wildlife (WDFW) proposed an antimycin treatment within the subbasin; the project encountered significant public opposition and was eventually abandoned. However, over the course of planning this 2004 project, little public

  15. Evaluation of methylmercury biotransformation using rat liver slices

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, A. [Biochemistry Section, National Inst. for Minamata Disease, Minamata, Kumamoto (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji (Japan)


    To examine the demethylation reaction of methylmercury (MeHg) in rat liver, slices prepared from MeHg-treated rats were incubated in L-15 medium under 95% O{sub 2}/5% CO{sub 2} atmosphere. During the incubation, the amount of inorganic Hg in the slices markedly increased in a time-dependent manner, although the concentration of total Hg remained unchanged. Since the C-Hg bond in MeHg was demonstrated to be cleaved by the action of some reactive oxygen species, the effects on MeHg demethylation of several reagents that could modify reactive oxygen production were examined in the present system. Methylviologen was found to be an effective enhancer of the demethylation reaction with only a minor effect on lipid peroxidation. On the other hand, ferrous ion added to the medium showed no effect on demethylation in the presence or absence of methylviologen, although lipid peroxide levels were increased significantly by ferrous ion. Similarly, deferoxamine mesylate, which effectively suppressed the increase in lipid peroxide levels, also had no effect on demethylation. Furthermore, hydroxy radical scavengers, such as mannitol and dimethylsulfoxide, had no effect on inorganic Hg production. Rotenone, an inhibitor of complex I in the mitochondrial electron transport system, increased levels of both inorganic Hg and lipid peroxide. However, other inhibitors, such as antimycin A, myxothiazole and NaCN, significantly suppressed the demethylation reaction. Cell fractionation of the MeHg-treated rat liver revealed that the ratio of inorganic Hg to total Hg was highest in the mitochondrial fraction. Furthermore, superoxide anion could degrade MeHg in an organic solvent but not in water. These results suggested that the demethylation of MeHg by the liver slice would proceed with the aid of superoxide anion produced in the electron transfer system at the hydrophobic mitochondrial inner membrane. Furthermore, the involvement of hydroxy radicals, which have been demonstrated to be

  16. High Intensity Interval Training (HIIT Induces Specific Changes in Respiration and Electron Leakage in the Mitochondria of Different Rat Skeletal Muscles.

    Directory of Open Access Journals (Sweden)

    Dionizio Ramos-Filho

    Full Text Available High intensity interval training (HIIT is characterized by vigorous exercise with short rest intervals. Hydrogen peroxide (H2O2 plays a key role in muscle adaptation. This study aimed to evaluate whether HIIT promotes similar H2O2 formation via O2 consumption (electron leakage in three skeletal muscles with different twitch characteristics. Rats were assigned to two groups: sedentary (n=10 and HIIT (n=10, swimming training. We collected the tibialis anterior (TA-fast, gastrocnemius (GAST-fast/slow and soleus (SOL-slow muscles. The fibers were analyzed for mitochondrial respiration, H2O2 production and citrate synthase (CS activity. A multi-substrate (glycerol phosphate (G3P, pyruvate, malate, glutamate and succinate approach was used to analyze the mitochondria in permeabilized fibers. Compared to the control group, oxygen flow coupled to ATP synthesis, complex I and complex II was higher in the TA of the HIIT group by 1.5-, 3.0- and 2.7-fold, respectively. In contrast, oxygen consumed by mitochondrial glycerol phosphate dehydrogenase (mGPdH was 30% lower. Surprisingly, the oxygen flow coupled to ATP synthesis was 42% lower after HIIT in the SOL. Moreover, oxygen flow coupled to ATP synthesis and complex II was higher by 1.4- and 2.7-fold in the GAST of the HIIT group. After HIIT, CS activity increased 1.3-fold in the TA, and H2O2 production was 1.3-fold higher in the TA at sites containing mGPdH. No significant differences in H2O2 production were detected in the SOL. Surprisingly, HIIT increased H2O2 production in the GAST via complex II, phosphorylation, oligomycin and antimycin by 1.6-, 1.8-, 2.2-, and 2.2-fold, respectively. Electron leakage was 3.3-fold higher in the TA with G3P and 1.8-fold higher in the GAST with multiple substrates. Unexpectedly, the HIIT protocol induced different respiration and electron leakage responses in different types of muscle.

  17. High Intensity Interval Training (HIIT) Induces Specific Changes in Respiration and Electron Leakage in the Mitochondria of Different Rat Skeletal Muscles. (United States)

    Ramos-Filho, Dionizio; Chicaybam, Gustavo; de-Souza-Ferreira, Eduardo; Guerra Martinez, Camila; Kurtenbach, Eleonora; Casimiro-Lopes, Gustavo; Galina, Antonio


    High intensity interval training (HIIT) is characterized by vigorous exercise with short rest intervals. Hydrogen peroxide (H2O2) plays a key role in muscle adaptation. This study aimed to evaluate whether HIIT promotes similar H2O2 formation via O2 consumption (electron leakage) in three skeletal muscles with different twitch characteristics. Rats were assigned to two groups: sedentary (n=10) and HIIT (n=10, swimming training). We collected the tibialis anterior (TA-fast), gastrocnemius (GAST-fast/slow) and soleus (SOL-slow) muscles. The fibers were analyzed for mitochondrial respiration, H2O2 production and citrate synthase (CS) activity. A multi-substrate (glycerol phosphate (G3P), pyruvate, malate, glutamate and succinate) approach was used to analyze the mitochondria in permeabilized fibers. Compared to the control group, oxygen flow coupled to ATP synthesis, complex I and complex II was higher in the TA of the HIIT group by 1.5-, 3.0- and 2.7-fold, respectively. In contrast, oxygen consumed by mitochondrial glycerol phosphate dehydrogenase (mGPdH) was 30% lower. Surprisingly, the oxygen flow coupled to ATP synthesis was 42% lower after HIIT in the SOL. Moreover, oxygen flow coupled to ATP synthesis and complex II was higher by 1.4- and 2.7-fold in the GAST of the HIIT group. After HIIT, CS activity increased 1.3-fold in the TA, and H2O2 production was 1.3-fold higher in the TA at sites containing mGPdH. No significant differences in H2O2 production were detected in the SOL. Surprisingly, HIIT increased H2O2 production in the GAST via complex II, phosphorylation, oligomycin and antimycin by 1.6-, 1.8-, 2.2-, and 2.2-fold, respectively. Electron leakage was 3.3-fold higher in the TA with G3P and 1.8-fold higher in the GAST with multiple substrates. Unexpectedly, the HIIT protocol induced different respiration and electron leakage responses in different types of muscle.

  18. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    Directory of Open Access Journals (Sweden)

    Fröbert Ole


    glycol catalase (300 u/ml inhibited H2O2 vasodilation, but failed to affect vasodilation to O2 lowering. Neither did PEG-SOD (polyethylene glycol superoxide dismutase(70 u/ml affect vasodilation to O2 lowering. The mitochondrial inhibitors rotenone (1 μM and antimycin A (1 μM both inhibited hypoxic vasodilatation. Conclusion The present results in porcine coronary arteries suggest NO contributes to hypoxic vasodilation, probably through K channel opening, which is reversed by addition of ET-1 and enhanced by endothelin receptor antagonism. These latter findings suggest that endothelin receptor activation counteracts hypoxic vasodilation.

  19. A84a


    T. Zavarykina; A. Burdennyy; Loginov, V.; E. Ignatova; E. Glazkova; M. Frolova; M. Stenina


    There is increasing evidence that BRCA1-related DNA-repair defects determine sensitivity to certain agents, such as platinum-based chemotherapy. There is a lot of evidence about a link between TNBC and BRCA1 deficiency. Many clinical characteristics and molecular features are shared by sporadic triple-negative breast cancer and BRCA1-associated breast cancer. The majority of BRCA1-related breast cancers are of basal-like/triple-negative phenotype. Identification of specific markers of BRCA1-d...

  20. Modulation of the Pasteur effect in retinal cells: implications for understanding compensatory metabolic mechanisms. (United States)

    Winkler, Barry S; Sauer, Michael W; Starnes, Catherine A


    The purpose of the present experiments was to enhance understanding of the factors that are critical for the survival of retinal cells exposed to mitochondrial inhibition. Confluent cultures of Müller cells (rMC-1) and human retinal pigment epithelial cells (hRPE) were incubated in Dulbecco's minimal essential medium in the presence and absence of 1x10(-5)M Antimycin A, an inhibitor of mitochondrial electron transport. To modulate the rates of aerobic and anaerobic glycolysis, cells were incubated in media containing varying concentrations of glucose and 1-100 micro M of iodoacetic acid (IAA), an inhibitor of glyceraldehdye-3-phosphate dehydrogenase (G3PDH). Measurements were made of G3PDH, lactic acid production, and cellular ATP levels, along with an examination of cellular morphology, the latter providing an index of cellular viability. Control rMC-1 and hRPE produced lactate aerobically, respectively, at 0.48 and 1.50 micro molhr(-1)/10(6) cells. Anaerobically, lactate production increased 2-fold in rMC-1 and 3-fold in hRPE. Anaerobic ATP levels in both types of cells were maintained at control levels over 8hr. Experimental conditions were sought that would modulate only the capacity of rMC-1 and hRPE to increase glycolysis following mitochondrial inhibition, i.e. alter their Pasteur effect. We used low concentrations of IAA to partially inhibit G3PDH. Incubation of rMC-1 with IAA for 6hr caused a graded inhibition of G3PDH: 70% inhibition with 1 micro M, 90% with 5 micro M, 97% with 10 micro M, and 100% with 100 micro M. While the aerobic and anaerobic rates of lactic acid production were not altered by 1 micro M IAA, both were suppressed completely by 100 micro M IAA. However, incubation of rMC-1 with 5 micro M IAA caused a decrease of 30% in the rate of anaerobic lactic acid production but no change in the rate of aerobic glycolysis. Moreover, with 5 micro M IAA, rMC-1 incubated aerobically maintained ATP levels, but anaerobic ATP content decreased to a low


    Directory of Open Access Journals (Sweden)

    Subota I.Yu.


    Full Text Available We studied an impact of the widely spread intra-cellular signals Ca2+ and сAMP on activity of the protein phosphorylation in maize mitochondria. The use of the isolated mitochondria is a convenient model system for investigation of the different physiological processes, for example for simulation of the different stress conditions. The treatment of maize mitochondria with high concentration of calcium ions which mimics the initial stage of apoptosis led to an increase of the phosphorylation level of some proteins and to an additional phosphorylation of the 59 and 66 kDa proteins. The treatment of the mitoplasts, i.e., the mitochondria devoid of the outer membrane with calcium ions insignificantly induced the activity of protein phosphorylation. It is assumed that the outer membrane is essential for Ca2+ signal transduction to plant mitochondria. We also identified a 94 kDa protein involved in phosphorylation of the mitochondrial proteins. This protein might be a single-subunit protein kinase or one of the subunits of the protein kinase complex. Antimycin A and KCN which are the inhibitors of mitochondria respiration increased the phosphorylation activity of the mitochondrial polypeptides. The effect of this inhibitors was similar both in in organello system and at the level of the whole plant. It should be noticed that at the level of the whole plant the effect of KCN on activity of the mitochondrial protein phosphorylation was more essential. Some considerable differences were found both at the level of protein phosphorylation and in electrophoresis patterns representing the intact mitochondria, the mitoplasts and the outer membrane fraction. The activity of protein phosphorylation in mitoplasts and the outer membrane fraction was extremely high compared to the phosphorylation activity of the mitochondrial proteins. This could be explained by the higher level of “substrate phosphoprotein phosphatase” in the outer membrane of mitochondria

  2. Apparent Km of mitochondria for oxygen computed from Vmax measured in permeabilized muscle fibers is lower in water enriched in oxygen by electrolysis than injection

    Directory of Open Access Journals (Sweden)

    Zoll J


    Full Text Available Joffrey Zoll,1 Jamal Bouitbir,1 Pascal Sirvent,2 Alexis Klein,3 Antoine Charton,1,4 Liliana Jimenez,3 François R Péronnet,5 Bernard Geny,1 Ruddy Richard61Physiology Department, Faculty of Medicine and EA3072, Université de Strasbourg, Strasbourg, 2Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l’Exercice en Conditions Physiologiques et Pathologiques, Clermont-Ferrand, 3Danone Research, Centre Daniel Carasso, Palaiseau, 4Department of Anesthesia and Critical Care and EA3072, Hôpital de Hautepierre, Université de Strasbourg, France; 5Kinesiology Department, Université de Montréal, Montréal, QC, Canada; 6Department of Sport Medicine and Functional Explorations and INRA UMR 1019, Faculty of Medicine, Université d’Auvergne, Clermont-Ferrand, FranceBackground: It has been suggested that oxygen (O2 diffusion could be favored in water enriched in O2 by a new electrolytic process because of O2 trapping in water superstructures (clathrates, which could reduce the local pressure/content relationships for O2 and facilitate O2 diffusion along PO2 gradients.Materials and methods: Mitochondrial respiration was compared in situ in saponin-skinned fibers isolated from the soleus muscles of Wistar rats, in solution enriched in O2 by injection or the electrolytic process 1 at an O2 concentration decreasing from 240 µmol/L to 10 µmol/L (132 mmHg to 5 mmHg, with glutamate–malate or N, N, N', N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD–ascorbate (with antimycin A as substrates; and 2 at increasing adenosine diphosphate (ADP concentration with glutamate–malate as substrate.Results: As expected, maximal respiration decreased with O2 concentration and, when compared to glutamate–malate, the apparent Km O2 of mitochondria for O2 was significantly lower with TMPD–ascorbate with both waters. However, when compared to the water enriched in O2 by injection, the Km O2 was

  3. A Writer, a Translator and a Translator


    Katarina Marinčič


    The article deals with the French translation of the short story Amy by the Slovenian writer Mira Mihelič, made by Elza Jereb for the anthology Nouvelles slovènes (Paris, 1969). The original text, a classical narrative involving some modernist strategies, presents a syntactical feature rather unusual in Slovenian (although typical of the author Mira Mihelič): a very frequent use of participles and participial structures. Elza Jereb’s translation is accurate and precise, preserving not only th...

  4. A container

    DEFF Research Database (Denmark)


    A container assembly for the containment of fluids or solids under a pressure different from the ambient pressure comprising a container (2) comprising an opening and an annular sealing, a lid (3) comprising a central portion (5) and engagement means (7) for engaging the annular flange, and seali...

  5. Hepatitis A (United States)

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  6. Vitamin A (United States)

    Vitamins are substances that your body needs to grow and develop normally. Vitamin A plays a role in your Vision Bone growth Reproduction Cell functions Immune system Vitamin A is an antioxidant. It can come from ...

  7. A literatura e a teologia

    Directory of Open Access Journals (Sweden)

    Genilma Boehler


    Full Text Available Trata-se de uma reflexão sobre literatura e teologia, pontualmente sobre poesia e teologia. Como afirmou Edgar Morin “a literatura tem a vantagem de refletir sobre a complexidade do ser humano e sobre a quantidade incrível de seus sonhos” (MORIN, 2009:6. Já a teologia, como definida por Rubem Alves, é “um jeito de falar sobre tais coisas dando-lhes um nome e apenas distinguindo-se da poesia porque a teologia é sempre feita como prece...” (ALVES, 2005:21. O encontro das duas é a ocasião para que seja feita uma reflexão acerca de Deus, a partir do espaço da poesia, recorrendo a outra linguagem, outro conhecimento, outras bibliotecas, considerando o corpo, o desejo, a vida, o mundo na medida em que apresenta a pessoa, a sociedade e a cultura.

  8. Algebra? A Gate! A Barrier! A Mystery! (United States)

    Mathematics Educatio Dialogues, 2000


    This issue of Mathematics Education Dialogues focuses on the nature and the role of algebra in the K-14 curriculum. Articles on this theme include: (1) "Algebra For All? Why?" (Nel Noddings); (2) "Algebra For All: It's a Matter of Equity, Expectations, and Effectiveness" (Dorothy S. Strong and Nell B. Cobb); (3) "Don't Delay: Build and Talk about…

  9. Northrop A-17A Nomad (United States)


    Northrop A-17A Nomad: In the spring of 1939 the NACA tested an experimental cowling and cooling system on Northrop's A-17A. Various types and combinations were tried, but the NACA cowl first used seemed to work best, as no modifications made their way onto 'line' aircraft.

  10. A118

    Directory of Open Access Journals (Sweden)

    A. Kozlov


    It can be concluded that expression of protogenes, evolutionarily young and/or novel genes in tumors might be a new biological phenomenon, a phenomenon of carcino-evo-devo genes, predicted by the hypothesis of evolution by tumor neofunctionalization.

  11. Hemophilia A (United States)

    Factor VIII deficiency; Classic hemophilia; Bleeding disorder - hemophilia A ... When you bleed, a series of reactions take place in the body that helps blood clots form. This process is called the coagulation ...

  12. Vitamin A (United States)

    ... carotenoid is beta-carotene. Beta-carotene is an antioxidant. Antioxidants protect cells from damage caused by substances called ... A can lead to hyperkeratosis or dry, scaly skin. If you get too much vitamin A, you ...

  13. A Dream

    Institute of Scientific and Technical Information of China (English)

    Cecile; Fries


    <正>The rising sun flames clouds. Through the airplane window I am enjoying the clouds with golden edges. In a few hours I will set foot on the soil of China, a country that has always been in my dreams. Thoughts thronged my mind. Perhaps, in my life I will never have a chance to travel to China, a faraway, strange and mysterious country;

  14. A nudez

    Directory of Open Access Journals (Sweden)

    Viviana C. Velasco Martínez

    Full Text Available O objetivo deste artigo é apresentar um mito e o seu herói. É com esse material simbólico que pretendo enfocar temas freudianos clássicos, como a sexualidade infantil, o pudor, a crueldade, o fetichismo, o exibicionismo e a castração e, assim, esboçar o contorno de uma possível fantasia neurótica inconsciente, onde a perversão encontrase em negativo.

  15. A new

    NARCIS (Netherlands)

    Giusberti, L.; Bannikov, A.; Galazzo, F.B.; Fornaciari, E.; Frieling, J.; Luciani, V.; Papazzoni, C.A.; Roghi, G.; Schouten, S.; Sluijs, A.; Bosellini, F.R.; Zorzin, R.


    Hemipelagic dark limestones within calciturbiditic deposits at Monte Solane in the western Lessini Mountains of northern Italy yield a fish fauna dominated by stomiiforms. A minor component of the fossil assemblage is represented by a macroalgal non-calcareous flora associated with rarer terrestrial

  16. Hepatitis A (United States)

    ... inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There are at least 5 hepatitis viruses. Hepatitis A is contracted when a child eats food or drinks water that is contaminated with the virus or has ...

  17. Hepatitis A (United States)

    ... receiving the shot. About 1 out of 10 children may have a mild fever or poor appetite. If these problems occur, they usually last a day or two. However, vaccines like any medicine, could ver y rarely cause a severe allergic ... as children grow up. •Prevents hospitalizations among older children and ...

  18. A prog

    DEFF Research Database (Denmark)

    Meldgaard, Anette; Hansen, Torben Bæk; Dalsgaard, Jesper


    Background: Endoscopic carpal tunnel release with a single portal technique has been shown to reduce sick leave compared to open carpal tunnel release, claiming to be a less invasive procedure and reducing scar tenderness leading to a more rapid return to work, and the purpose of this study was t...

  19. A Keyboard

    DEFF Research Database (Denmark)


    The present invention relates to a keyboard with a plurality of keys with key switches that are covered by a flexible display for displaying individual labels of the keys whereby the label can be changed during operation of the keyboard by appropriate control of the keyboard. The flexible display...

  20. A laser

    Energy Technology Data Exchange (ETDEWEB)

    Togo, N.


    It is reported that an improved laser design employing pumping of the active gas medium has been developed. A diagram of the laser system is given and its principle of operation is described in detail. Gas pumping is achieved using a pump whose oil reservoir is sealed by a sealing element. When the sealing element fails, the oil from the reservoir pollutes the laser substance. It is proposed that an additional oil reservoir pumping loop be used to maintain a lower pressure. The reservoir pressure is recorded by a sensor. When the sealing element fails, the pressure in the reservoir increases. The sensor records the change in pressure and generates a signal which shuts down the laser system. Thus, the possibility for oil penetration into the gas system is totally eliminated.

  1. A "Network" and a "Dictum"

    DEFF Research Database (Denmark)

    Harder, Henrik


    The spatial problems encountered in urban areas, for instance "sprawl", "the fragmented town" etc. However, the critic should concentrate more on a small "network" of a few architects and planners, including an inspector (C. D. Buchanan, UK) and a single policeman (H. Alker Tripp, UK) who were he...

  2. A Joke

    Institute of Scientific and Technical Information of China (English)



    O ne hot sum m er day, a student in sweat, fanning him self w ith abook,asked his teacher,“Its rather too hotin the classroom .M ay I wearshorts while having classes, Sir?” “Itdoesn t m atter whether you wearshorts or not, but I m ust let you know , when you enter the classroom ,you m ust wear a pair oftrousers,”the teacher replied.A Joke!河北@王秀军

  3. A dor

    Directory of Open Access Journals (Sweden)

    Manoel Tosta Berlinck

    Full Text Available Este trabalho relata pesquisa sobre a natureza psicopatológica da dor partindo da noção de que o humano habita na dor. Esta passa, assim, a ser um conceito-limite do humano que não consegue ultrapassá-la, apesar dos recursos farmacológicos e psíquicos disponíveis para dela se proteger. Nesta perspectiva, o corpo humano solicita uma concepção que seja capaz de levar em consideração tanto a dor física como a psíquica.

  4. A Dog

    Institute of Scientific and Technical Information of China (English)



    A dog can't speak words, but it can "talk", It has feelings just as you do. At times it may feel angry or afraid. Watching a dog closely, you can find out what it feels. You can see what it is trying to tell you.

  5. A Proposal

    Institute of Scientific and Technical Information of China (English)


    正All the students in our school, A sudden 8.0 earthquake happened in Wenchuan, Sichuan Province at 2:28 on the afternoon of May 12, 2008. Many houses fell down and lots of people have become homeless. A large number of people were badly injured and so many people lost their lives. The people in

  6. A Joke

    Institute of Scientific and Technical Information of China (English)

    Simon; Lindley


    W orking at the post office,Im used to dealing with a m oody public.So w hen one irate custom er storm ed m y desk,I responded in m y calm estvoice,“W hats the trouble?”“I w ent out this m orning,”she began,“and when I cam e hom e Ifound a card saying the m ailm an tried to deliver a package but no onewas hom e.M y husband was in allm orning.H e never heard a thing!”A fter apologizing,I gother parcel.“O h,good,”she gushed.“W e ve been w aiting for this for ages.”“W hat is it?”I asked.“M y husband s new hear...

  7. A Rejoinder

    Directory of Open Access Journals (Sweden)

    Nelson Lichtenstein


    Full Text Available It is a pleasure and a challenge to engage these commentaries on my recent book, State of the Union: a Century of American Labor. The pleasure is there because this author, like almost every other, is deeply appreciative of the kind of critical attention, and sheer energy, to which his work is subject. The commentators assembled by Jean‑Christain Vinel understood with remarkable precision the main line of argument I was trying to advance, which has not always been the case on the American sid...

  8. A quackery with a difference

    DEFF Research Database (Denmark)

    Wahlberg, Ayo


    in which regulatory authorities in the UK have come to address what is invariably described as a ‘growing interest in CAM’, I will show how the problem of quackery today is increasingly located in an ethical field of practitioner competency, qualifications, conduct, responsibility and personal professional...... health. Yet, in this paper, I argue that this is only one form that the problem of ‘quackery’ has taken in the past two centuries or so in the United Kingdom. Just as Roy Porter showed how the mid-19th century professionalization of medicine gave rise to a ‘quackery with a difference’ as a whole range...

  9. Hall A (United States)

    Federal Laboratory Consortium — The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electroand photo-induced reactions at very high luminosity...

  10. A madruga

    Directory of Open Access Journals (Sweden)

    Porfirio Robau


    Full Text Available Yo soy de allá, de Madruga, un pueblo próspero y sano, adonde la piel del llano no envejece ni se arruga. De donde el guajiro enyuga los bueyes de madrugada, y la carreta cargada, del corte al basculador va repartiendo un olor a caña recién cortada.   Madruga, verde paisaje de valles, lomas y ríos, de pintorescos bohíos y cielo azul sin celaje. Desde mi último viaje no sé de tus cordilleras tus calles tus palmeras ni el hogar que yo tenía, adonde alegre vivía sin pesares ni quimeras.   Porfirio Robau (1914-1993 Poeta Cubano

  11. Q & A

    Directory of Open Access Journals (Sweden)

    Prof.. Adam Micolich


    Full Text Available Prof. Adam Micolich is a researcher based at the University of New South Wales, specializing in the study of semiconductor systems. Materials Today recently spoke to Adam for our podcast.

  12. Bisphenol A (United States)

    ... Radon Solvents Styrene Sulfur Dioxide Toluene Uranium Volatile Organic Compounds (VOCs) For Educators Introduction Tox Town-Based Curriculum Units / Science Club Careers in Environmental Health, Chemistry, and Toxicology More Resources Bisphenol A (BPA) en ...

  13. A Symposium. (United States)

    Rachal, John R.


    Uses the framework of a symposium to present an imagined discussion by historical figures about whether and how knowledge might be acquired. Discussants include Democritus, Protagoras, Heraclitus, Socrates, Jesus, Gorgias, Nietzsche, Buddha, and Kierkegaard. (Contains 40 endnotes.) (SK)

  14. A laser

    Energy Technology Data Exchange (ETDEWEB)

    Togo, N.


    The development of an improved gas laser system employing pumping of the active gaseous medium is reported. The layout of the design is given and its principle of operation is described in detail. The oil reservoir in the vacuum pump which pumps the gas through the laser system is separated by a sealing element; when this element fails, the oil may pollute the active medium. It is proposed that an additional oil reservoir pumping loop be used with the pump that operates continuously and maintains a lower pressure in the reservoir. The pressure in the reservoir is monitored by a special sensor. When the sealing element fails, the pressure sensor records the pressure drop in the oil reservoir. A signal is then generated and the laser system ceases operation, and eliminates the possibility for the oil penetrating into the pumping system.

  15. A laser

    Energy Technology Data Exchange (ETDEWEB)

    Togo, N.; Syundzo, Yo.


    It is reported that an improved gas laser design using pumping of the active medium has been developed. A diagram of the laser system is given in graph form and its principle of operation is briefly described. A special sealing element is used in such lasers to seal the reservoir containing the oil in the pump which pumps the gas active medium. When the sealing element fails, there is the danger of oil penetration into the active laser medium. It is proposed that an additional pump which continually evacuates the oil reservoir during laser system operation be used. Thus, a low pressure is maintained in the reservoir. If the sealing element fails, the secondary pump generates a gas flow from the pumping system to the reservoir and eliminates gas penetration into the laser medium.

  16. A110

    Directory of Open Access Journals (Sweden)

    T. Malivanova


    Conclusions: This study found out the opposite effect of polymorphisms at −238 and −308 positions in TNF promoter on the outcome of BC patients. Carriers of low expressed allele −238(A have poor outcome because of low response to standard hormone therapy which presumably connected with the activation of Her2 pathway. The obtained results allow supposing that a special approach to the treatment of this group of BC patients should be used.

  17. A JOKE

    Institute of Scientific and Technical Information of China (English)


    Grandpa and granddaughter were sitting talking when she asked,“Did God make you,Grandpa?”“Yes,God made me,”the grandfather answered.A few minutes later,the little girl asked him,“Did God make me too?”“Yes,He did,”the older man answered.For a few minutes,the little girl seemed to be studying

  18. A Queda

    Directory of Open Access Journals (Sweden)



    Full Text Available O mundo é outro, desde a queda do Muro
    de Berlim. Ela representa o fim do século XX, da
    geografia baseada na divisão entre Primeiro, Segundo
    e Terceiro Mundos e do modelo monolítico soviético.
    Após a queda, expandiu-se o processo de formação
    de blocos econômicos e o surgimento de um pólo
    dinâmico do capitalismo que muitos consideram
    como sinal de um novo ciclo hegemônico (asiático,
    capitaneado pela China. Mas os dilemas e riscos
    atuais não são menores do que os do passado. Que
    o digam a queda das torres gêmeas e o ataque ao
    Pentágono, no 11 de setembro de 2001, a proliferação
    de redes terroristas, a ameaça nuclear latente e as
    crises econômicas sistêmicas.

  19. A School without a Principal. (United States)

    Barnett, Demian; McKowen, Charlene; Bloom, Gary


    Teachers at a central California high school operate the school according to a strict, progressive set of principles. The Anzar communication guidelines specify teachers' commitment to communicating well, collective ownership of problems and problem solving, tolerance of differing ideas, individual accountability, dedication to helping and…

  20. A Wolf and a Dog

    Institute of Scientific and Technical Information of China (English)

    薛刘阳; 方言(注); 陈恩枫(指导老师)


    A wolf and a dog live near the farm.One day,the wolf was very hungry.So he wanted to eat something.The wolf saw some chickens on the farm.He thought,"Oh,I'd like to eat them!"At night,the wolf ran into the chickens' home slyly.

  1. A Marshmallow and a Song (United States)

    Kenney, Susan


    Music exists in time. One cannot get to the end of the song before going through the song. Is this significant for helping children wait? And can the way we present a singing game activity intensify the delay of what might be a gratifying moment at the end of the song? In this article, the author reflects on whether music can teach delayed…

  2. A Blizzard of a Value (United States)

    Bostic, Jonathan D.


    "Who has been to Dairy Queen® and purchased a Blizzard?®" Ms. Bosetti asked her students. During the summer, Bosetti had seen many of her former and future students at the local Dairy Queen enjoying Blizzard desserts and wondered, "Which Blizzard size is the best value?" She used this context for a ratios and proportions task…

  3. A Giant or a Dwarf?

    DEFF Research Database (Denmark)

    Schmid, Herman


    EU may appear to be a giant when it can act on behalf of a united Europe, but usually it is hampered by conflicting member state interests. The EU economic and administrative resources for foreign and trade policy are quite small (on level with one of its major member states) and the hopes in man...


    Energy Technology Data Exchange (ETDEWEB)



    Sudoku, also known as Number Place, is a logic-based placement puzzle. The aim of the puzzle is to enter a numerical digit from 1 through 9 in each cell of a 9 x 9 grid made up of 3 x 3 subgrids (called ''regions''), starting with various digits given in some cells (the ''givens''). Each row, column, and region must contain only one instance of each numeral. Completing the puzzle requires patience and logical ability. Although first published in a U.S. puzzle magazine in 1979, Sudoku initially caught on in Japan in 1986 and attained international popularity in 2005. Last fall, after noticing Sudoku puzzles in some newspapers and magazines, I attempted a few just to see how hard they were. Of course, the difficulties varied considerably. ''Obviously'' one could use Trial and Error but all the advice was to ''Use Logic''. Thinking to flex, and strengthen, those powers, I began to tackle the puzzles systematically. That is, when I discovered a new tactical rule, I would write it down, eventually generating a list of ten or so, with some having overlap. They served pretty well except for the more difficult puzzles, but even then I managed to develop an additional three rules that covered all of them until I hit the Oregonian puzzle shown. With all of my rules, I could not seem to solve that puzzle. Initially putting my failure down to rapid mental fatigue (being unable to hold a sufficient quantity of information in my mind at one time), I decided to write a program to implement my rules and see what I had failed to notice earlier. The solver, too, failed. That is, my rules were insufficient to solve that particular puzzle. I happened across a book written by a fellow who constructs such puzzles and who claimed that, sometimes, the only tactic left was trial and error. With a trial and error routine implemented, my solver successfully completed the Oregonian puzzle, and has successfully

  5. Thailandepsin A

    Directory of Open Access Journals (Sweden)

    Cheng Wang


    Full Text Available Thailandepsin A [systematic name: (E-(1S,5S,6R,9S,20R-6-[(2S-butan-2-yl]-5-hydroxy-20-[2-(methylsulfanylethyl]-2-oxa-11,12-dithia-7,19,22-triazabicyclo[7.7.6]docosa-15-ene-3,8,18,21-tetraone], C23H37N3O6S3, is a newly reported [Wang et al. (2011. J. Nat. Prod. doi:10.1021/np200324x] bicyclic depsipeptide that has potent histone deacetylase inhibitory activity and broad-spectrum antiproliferative activity. The absolute configuration of thailandepsin A has been determined from the anomalous dispersion and the stereochemistry of all chiral C atoms. Intramolecular N—H...O and N—H...S hydrogen bonds occur. Intermolecular N—H...O and O—H...O hydrogen bonds are observed in the crystal structure.

  6. A Model

    Institute of Scientific and Technical Information of China (English)

    Liu Zhiyang


    Similar to ISO Technical Committees,SAC Technical Committees undertake the management and coordination of standard's development and amendments in various sectors in industry,playing the role as a bridge among enterprises,research institutions and the governmental standardization administration.How to fully play the essential role is the vital issue SAC has been committing to resolve.Among hundreds of SAC TCs,one stands out in knitting together those isolated,scattered,but highly competitive enterprises in the same industry with the "Standards" thread,and achieving remarkable results in promoting industry development with standardization.It sets a role model for other TCs.

  7. A madruga


    Porfirio Robau


    Yo soy de allá, de Madruga, un pueblo próspero y sano, adonde la piel del llano no envejece ni se arruga. De donde el guajiro enyuga los bueyes de madrugada, y la carreta cargada, del corte al basculador va repartiendo un olor a caña recién cortada.   Madruga, verde paisaje de valles, lomas y ríos, de pintorescos bohíos y cielo azul sin celaje. Desde mi último viaje no sé de tus cordilleras tus calles tus palmeras ni el h...

  8. A Life for a Life

    Institute of Scientific and Technical Information of China (English)



    The English author, Richard Savage, was once living in London ingreat poverty. In order to earn a little money he had written the story" ofhis life. But not many copies of the book had been sold in the shops, and

  9. A75

    Directory of Open Access Journals (Sweden)

    D. Korobkov


    It may be concluded that the cellular and molecular mechanisms of breast cancer are complex. Therefore, carcinogenesis has a “multistep” nature and at least two or more mutations in the cells of the same clone – parent and child are required to generate malignant tumors. Thus, the development of oncogenic transformation does not necessarily mean the process of tumor formation.

  10. A Beginning. (United States)

    Healy, Mary K.; Root, Phyllis

    Selected for their focus on man, acting to know, preserve and improve his environment, the items noted in this booklet furnish a resource base for developing an environmental ethic. Introductory statements enumerate values, understandings, and realizations to be developed and sample activities that may be conducted or adapted for grades K-12.…

  11. A111

    Directory of Open Access Journals (Sweden)

    L. Buchynska


    Conclusion: Quantitative changes of some components of the tumor microenvironment such as CD4+-, CD8+-, FOXP3+-lymphocytes and content of FOXP3+-tumor cells correlate with the biological characteristics of EC and apparently have a significant role in the progression of this cancer.

  12. Appendix A

    DEFF Research Database (Denmark)

    Henriksen, M. S.; Brincker, Rune; Heshe, Gert


    In this appendix a brief summary of experiments on reinforced concrete beams in three-point bending performed at Aalborg University is given. The aim of the investigation is to determine the full load-deflection curves for different beam sizes, different types of concrete and different amounts an...

  13. A Pulsar and a Disk (United States)

    Kohler, Susanna


    Recent, unusual X-ray observations from our galactic neighbor, the Small Magellanic Cloud, have led to an interesting model for SXP 214, a pulsar in a binary star system.Artists illustration of the magnetic field lines of a pulsar, a highly magnetized, rotating neutron star. [NASA]An Intriguing BinaryAn X-ray pulsar is a magnetized, rotating neutron star in a binary system with a stellar companion. Material is fed from the companion onto the neutron star, channeled by the objects magnetic fields onto a hotspot thats millions of degrees. This hotspot rotating past our line of sight is what produces the pulsations that we observe from X-ray pulsars.Located in the Small Magellanic Cloud, SXP 214 is a transient X-ray pulsar in a binary with a Be-type star. This star is spinning so quickly that material is thrown off of it to form a circumstellar disk.Recently, a team of authors led by JaeSub Hong (Harvard-Smithsonian Center for Astrophysics) have presented new Chandra X-ray observations of SXP 214, tracking it for 50 ks (~14 hours) in January 2013. These observations reveal some very unexpected behavior for this pulsar.X-ray PuzzleThe energy distribution of the X-ray emission from SXP 214 over time. Dark shades or blue colors indicate high counts, and light shades or yellow colors indicate low counts. Lower-energy X-ray emission appeared only later, after about 20 ks. [Hong et al. 2016]Three interesting pieces of information came from the Chandra observations:SXP 214s rotation period was measured to be 211.5 s an increase in the spin rate since the discovery measurement of a 214-second period. Pulsars usually spin down as they lose angular momentum over time so what caused this one to spin up?Its overall X-ray luminosity steadily increased over the 50 ks of observations.Its spectrum became gradually softer (lower energy) over time; in the first 20 ks, the spectrum only consisted of hard X-ray photons above 3 keV, but after 20 ks, softer X-ray photons below 2 ke

  14. A, a Brominated Flame Retardant

    Directory of Open Access Journals (Sweden)

    Tomomi Takeshita


    Full Text Available Tetrabromobisphenol A (TBBPA, a brominated flame retardant, has been found to exacerbate pneumonia in respiratory syncytial virus- (RSV- infected mice. We examined the effect of Brazilian propolis (AF-08 on the exacerbation of RSV infection by TBBPA exposure in mice. Mice were fed a powdered diet mixed with 1% TBBPA alone, 0.02% AF-08 alone, or 1% TBBPA and 0.02% AF-08 for four weeks and then intranasally infected with RSV. TBBPA exposure increased the pulmonary virus titer and level of IFN-γ, a representative marker of pneumonia due to RSV infection, in the lungs of infected mice without toxicity. AF-08 was significantly effective in reducing the virus titers and IFN-γ level increased by TBBPA exposure. Also, AF-08 significantly reduced proinflammatory cytokine (TNF-α and IL-6 levels in the lungs of RSV-infected mice with TBBPA exposure, but Th2 cytokine (IL-4 and IL-10 levels were not evidently increased. Neither TBBPA exposure nor AF-08 treatment affected the anti-RSV antibody production in RSV-infected mice. In flow cytometry analysis, AF-08 seemed to be effective in reducing the ratio of pulmonary CD8a+ cells in RSV-infected mice with TBBPA exposure. TBBPA and AF-08 did not exhibit anti-RSV activity in vitro. Thus, AF-08 probably ameliorated pneumonia exacerbated by TBBPA exposure in RSV-infected mice by limiting excess cellular immune responses.

  15. A mascarada e a feminilidade

    Directory of Open Access Journals (Sweden)

    Grant Walkiria Helena


    Full Text Available Marcada por produções freudianas, a literatura analítica e, mais especificamente, aquela influenciada pelo ensino lacaniano, não pára de mostrar que as considerações anatômicas não são índices para falar da diferença de identidade sexual entre homens e mulheres. Diante do fato de que características masculinas continuavam presentes em mulheres adultas normais, Freud responde que ser mulher é ser mãe. A vacilação da verdade desta equação pode ser observada nas situações mais diversas nas quais podemos nos defrontar com mulheres, mães, desempenhando papéis de homens. Como pensar esta constatação? Este trabalho permitir-nos-á mostrar a imbricação do feminino e do masculino num caso de uma mulher com todas as características de uma feminilidade considerada normal, e também discutir a questão do gozo fálico e do Outro gozo - propostos por Lacan como índices de diferenciação da posição masculina e da feminina.

  16. A115

    Directory of Open Access Journals (Sweden)

    E. Dmitrieva


    Conclusion: Head and neck tumors are a rare group of clinically and biologically diverse neoplastic diseases. Among the residents of the Chelyabinsk region, men are 2–3 times more susceptible to cancer of the oral cavity and pharynx than women. High mortality rate is due to late referral of patients to specialized clinics; most head and neck cancer patients are diagnosed at advanced stages.

  17. A Valedictory (United States)

    Lagowski, J. J.


    "No man is an Iland, intire of it selfe.". These words were written by John Donne, the Dean of St. Paul's, and appear as his 17th Meditation in "Devotions upon emergent Occasions and several steps in my Sickness," published in 1624, a work in which he reflects upon his life in the midst of a serious illness (most likely typhus). Like many literary works, the words are timeless, and their meaning is not constrained to the occasion of their birth. Donne's meditation is easily transferred to the person who was, is, or will be, editor of this or any journal. No editor is an island. No editor can honestly claim to be "intire of it selfe." The Editor of the Journal rides on the tide generated by his staff, his reviewers, and his readers. I have been blessed with a marvelous staff, enormously energetic and dedicated. They have always been willing to go the last mile--and more if need be. Most--but not all--came to the Journal soon after it arrived in Austin. The bedrock on which the Journal has been built is its numerous reviewers, too many to thank individually on this page, but appreciated nonetheless for their individual contributions. Reviewers define the quality of a journal, and we have had a superb cohort working for us--voluntarily. I have to apologize publicly to some (you know who you are) who were abused by repeated requests on a short time base for their comments on manuscripts. This condition, which occurred more often than I would have liked, arose from the idiosyncratic confluence of manuscript flow, momentarily popular topics, and the need for certain kinds of expertise. I know that multiple requests for comments came too rapidly in some cases, but it was of paramount importance to get "good reviews" whom I could trust, and I knew where to turn. Thanks to all of you who stepped forward in such circumstances, with grace and good humor, to produce the quality reviews that were so valuable to me. No editor is an "Iland, intire of it selfe," especially when it

  18. A Stone and a Diamond

    Institute of Scientific and Technical Information of China (English)



    一、故事内容 After a storm, a dry river is filled with water again. Many stones fall down into the river from the hill. Most of the stones are very happy. They sing and dance together. There are two special (特别的) stones. One is black, and the other is white. The white stone is as white as snow. She is proud of herself and she looks down on all the other stones. So no one wants to play with her.

  19. A LDB e a psicologia

    Directory of Open Access Journals (Sweden)

    Oswaldo H. Yamamoto

    Full Text Available Este estudo discute as implicações para a formação acadêmica e para o exercício profissional do psicólogo, da aprovação da Lei de Diretrizes e Bases da Educação Nacional (LDB. São pontuados alguns dos pressupostos subjacentes à lei, os aspectos principais do texto legal e algumas de suas decorrências, como a regulamentação dos cursos seqüenciais e diretrizes curriculares.

  20. A Leader, Not a Hero (United States)

    Rutledge, Lynda


    The author writes her experience in leading. She points out that a good leader should know when and how to let go than trying to do all the work by herself. It changed her focus on looking at details, implementation, dealing with the contractors, to leading leading people.

  1. A Question about a Triangle (United States)

    Vinogradova, Natalya


    In fall 2013 the author taught a graduate course entitled Topics in Geometry for Middle and High School Teachers. The majority of the participants had extensive experience teaching mathematics in middle school or high school. The fact that participants were rather comfortable with the basic concepts of school geometry made it both possible and…

  2. A quackery with a difference

    DEFF Research Database (Denmark)

    Wahlberg, Ayo


    The figure of the ‘miracle cure’-peddling quack pretending spectacular properties for worthless tonics is iconic. From their 19th century traveling wagon shows to their 21st century Internet spam scams, hucksters and cranks have been consistently targeted by health authorities as a danger to publ...

  3. A112

    Directory of Open Access Journals (Sweden)

    E. Kisseleva


    Full Text Available Recruitment of mononuclear phagocytes from the blood into tissues is considered to be a crucial process during inflammatory reactions, wound healing and tumor growth. Macrophages are known to reveal high plasticity and may change under the influence of microenvironment. The aim of the study was to evaluate the changes of macrophage functional activity under the influence of Vascular endothelial growth factor (VEGF in vitro. This factor is known to be the main angiogenic factor but also possesses several immunomodulatory properties. Here we report that VEGF revealed a dose-dependent effects on cultured freshly isolated murine resident peritoneal macrophages: modulated iNOS mRNA expression, nitroxide and superoxide anion production, decreased 5′-nucleotidase (5′-N activity, but had no influence on fluid-phase pinocytosis. Moreover, VEGF increased expression of its own mRNA via autocrine pathway as well as of VEGF protein expression. VEGF also induced up-regulation of extracellular matrix protein thrombospondin-1 (TSP-1 mRNA, which is considered as a part of macrophage activation phenotype. Production of cytokines and chemokines by macrophages was screened with the help of Multi- analyte ELISArray kits. It was found that incubation of macrophages in the presence of VEGF increased the production of angiogenic cytokines – TNF-α and IL-6 as well as several monocyte and leukocyte chemoattractants such as MCP-1, RANTES and MIP-1β. Therefore, we suggest that locally established VEGF gradient may influence inflammatory phenotype of tissue macrophages as well as potentiate their pro-angiogenic properties. This work was supported by Russian Foundation for Basic Research – Russia, Grant No. 15-04-06150.

  4. A honra e a vida


    Hentz, Isabel Cristina


    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Programa de Pós-Graduação em História, Florianópolis, 2013. A primeira grande legislação aprovada no período republicano, antes ainda do primeiro aniversário da República brasileira, foi o Codigo Penal dos Estados Unidos do Brazil. Publicada em 1890, substituiu o Codigo Criminal do Império do Brazil, de 1830. A aprovação do Código Penal de 1890 introduziu pela primeira vez na legislação...

  5. A violencia contra a muller


    Rodríguez Calvo, María Sol


    Grao en Medicina Esta unidade didáctica denominada “Violencia contra a muller”, está incluída no bloque de “Clínica forense” da materia “Medicina legal”, que se imparte no segundo semestre do 5º curso do Grao en Medicina. Esta materia é froito da interrelación entre a Medicina e o Dereito nun dobre sentido: o primeiro refírese á aplicación dos coñecementos médicos para resolver cuestións xudiciais (Medicina legal propiamente dita). O segundo ocúpase da regulación xurídica da práctica médic...

  6. A Whale of A Controversy

    Institute of Scientific and Technical Information of China (English)


    Despite heavy international criticism,the Japanese refuse to end their national tradition of whale hunting When the Japanese whale-hunting fleet set sail for the Antarctic waters on November 18,the crew members must have known that their voyage would not be smooth sailing. Japan’s annual whaling program rou- tinely sets off a firestorm of protest from anti-whaling countries and organizations. In January 2006,Greenpeace’s icebreaker Arctic Sunrise collided with the Jaoanese


    Directory of Open Access Journals (Sweden)

    Mukesh Ratnaparkhi


    Full Text Available Recent advances in understanding the pathophysiology of underlying psychotic disorder and subsequent development of new antipsychotic drugs to treat these diseases have altered clinicians? pharmacological approach. It has also helped researcher to produce a new generation antipsychotic agents (NGA which could show better clinical results. However methodical approach as well as in-depth research in this area has provided several potent atypical antipsychotic agents. Now days all the atypical antipsychotics agents are FDA approved and being frequently used for pharmacotherapy of schizophrenia, acute mania, bipolar mania, psychotic agitation, bipolar maintenance, and other indications. Atypical antipsychotics are associated with the numbers of clinical benefits such as higher rate of responders, efficiency in patients with refractory disease, lower risk of suicides, better functional capacity and an improved quality of life and thus, have showed their efficacy against previous modes of treatment. The present review highlights the advantages, disadvantages as well as risk factors associated with novel antipsychotic agent with a view to outline their future scope.

  8. Blood Test: Immunoglobulin A (IgA) (United States)

    ... Your 1- to 2-Year-Old Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin A (IgA) Print A A A What's in ... An IgA test measures the blood level of immunoglobulin A, one of the most common antibodies in ...

  9. A midface swelling in a child - A possible diagnostic dilemma. (United States)

    Patel, Kuntal; Oudit, Deemesh; Ross, G; Nicolson, Caroline; Howcroft, Aj


    A lump on the midface of a child can pose as a diagnostic dilemma. There is a wide variety of possible differential diagnoses, ranging from simple benign conditions such as a sebaceous cyst, dermoid cyst, lipoma, neuroma and neurofibroma, to potentially devastating conditions such as odontogenic myxoma. A case of a child in which the formulation of a definite diagnosis was clinically and histologically challenging is presented.

  10. The Northrop A-17A Nomad (United States)


    The Northrop A-17A Nomad: Although another A-17 was used as a cowling testbed, this Northrop A-17A was only slightly modified during the course of its short NACA career at Langley. These modifications were done to determine the profile drag of a wing in flight.

  11. Relaparotomía a demanda. Factores asociados a mortalidad


    José Luis Martínez-Ordaz; Roberto Manuel Suárez-Moreno; Óscar Javier Felipez-Aguilar; Roberto Blanco-Benavides


    Objetivo: revisar los factores asociados con la mortalidad de los pacientes sometidos a relaparotomía a demanda. Introducción: algunos pacientes sometidos a laparotomía son reintervenidos debido a complicaciones agudas. Pueden ser manejados de manera programada o conforme su evolución. Todavía no está determinado cuál de los dos abordajes es mejor. Material y métodos: 33 pacientes fueron relaparotomizados a demanda en un servicio de cirugía general. Resultados: en total se realizaron 51 relap...

  12. A method for making a hydrogen electrode

    Energy Technology Data Exchange (ETDEWEB)

    Ikeyama, M.; Ivaki, T.; Yanagikhara, N.


    A metallic grid is pressed to the surface of a foam metallic plate which contains powders of a compound which adsorb H2. The electrode is processed at the powder caking temperature. The electrode has a long service life.

  13. A Stroke Mimic: A Case Report

    Directory of Open Access Journals (Sweden)

    Annia Martínez Rivas


    Full Text Available Diseases mimicking a stroke are a major health problem for a large number of hospitals. This paper aims at presenting a disease that has a stroke-like presentation. The case of a 46-year-old man admitted to the stroke unit with a clinical and radiological diagnosis of cerebral infarction is presented. The patient developed fever and a serious deterioration of consciousness. Changes on computed tomography consistent with a brain abscess were observed. Broad-spectrum antibiotics were administered and a follow-up tomography was performed. Once the treatment was completed, the clinical and radiological suspicion of a brain abscess was confirmed.

  14. A Bíblia e a cultura


    Gonçalves, Joaquim Cerqueira


    1. Pensar a Bíblia 2. A Bíblia e a cultura 3. Bíblia, cultura e linguagem 4. A revelação 5. O possível, o irrecusável e a Escritura 6. A Bíblia e as culturas no horizonte da ontologia 7. Jesus Cristo e a comunidade: manifestação ontológica 8. A religião cristã e as culturas


    Institute of Scientific and Technical Information of China (English)



    Under the framework of a real Hilbert space, we introduce a new iterative method for finding a common element of the set of solution of a general equilibrium problem and the set of fixed points of a nonexpansive semigroup. Moreover, a numerical example is presented. This example grantee the main result of the paper.

  16. Choosing a Breast Prosthesis: A Survivor's Perspective (United States)

    ... Choosing a Breast Prosthesis: A Survivor’s Perspective Choosing a Breast Prosthesis: A Survivor’s Perspective Andrea Zinn June 16, 2015 · Amber ... preferences. Q: Why did you decide to wear a breast form/prosthesis rather than have a reconstruction? ...

  17. A case of a horseshoe appendix


    Takabatake, Kazuya; Ikeda, Jun; Furuke, Hirotaka; Kato, Chikage; Kishimoto, Takuya; Kumano, Tatsuya; Imura, Kenichiro; Shimomura, Katsumi; Kubota, Takeshi; Taniguchi, Fumihiro; Shioaki, Yasuhiro


    Anomalies of the appendix are extremely rare, and a horseshoe appendix is even rarer. A literature search has revealed only five reported cases. In this report, we present a case of a horseshoe appendix. A 78-year-old man was referred for further examination following a positive fecal occult blood test. A mass in his ascending colon was detected on colonoscopy, while computed tomography showed that it was connected to the appendix. Tumor invasion derived from the ascending colon or appendix w...

  18. Respiratory Contribution of the Alternate Path during Various Stages of Ripening in Avocado and Banana Fruits. (United States)

    Theologis, A; Laties, G G


    The respiration of fresh slices of preclimacteric avocado (Persea americana Mill. var. Hass) and banana (Musa cavendishii var. Valery) fruits is stimulated by cyanide and antimycin. The respiration is sensitive to m-chlorobenzhydroxamic acid in the presence of cyanide but much less so in the presence of antimycin. In the absence of cyanide the contribution of the cyanide-resistant pathway to the coupled preclimacteric respiration is zero. In uncoupled slices, by contrast, the alternate path is engaged and utilized fully in avocado, and extensively in banana. Midclimacteric and peak climacteric slices are also cyanide-resistant and, in the presence of cyanide, sensitive to m-chlorobenzhydroxamic acid. In the absence of uncoupler there is no contribution by the alternate path in either tissue. In uncoupled midclimacteric avocado slices the alternate path is fully engaged. Midclimacteric banana slices, however, do not respond to uncouplers, and the alternate path is not engaged. Avocado and banana slices at the climacteric peak neither respond to uncouplers nor utilize the alternate path in the presence or absence of uncoupler.The maximal capacities of the cytochrome and alternate paths, V(cyt) and V(alt), respectively, have been estimated in slices from preclimacteric and climacteric avocado fruit and found to remain unchanged. The total respiratory capacity in preclimacteric and climacteric slices exceeds the respiratory rise which attends fruit ripening. In banana V(alt) decreases slightly with ripening.The aging of thin preclimacteric avocado slices in moist air results in ripening with an accompanying climacteric rise. In this case the alternate path is fully engaged at the climacteric peak, and the respiration represents the total potential respiratory capacity present in preclimacteric tissue. The respiratory climacteric in intact avocado and banana fruits is cytochrome path-mediated, whereas the respiratory climacteric of ripened thin avocado slices comprises

  19. A batuta da morte a orquestrar a vida

    Directory of Open Access Journals (Sweden)

    Altair Macedo Lahud Loureiro

    Full Text Available Com colocações de outros estudiosos da morte, teço e apresento apontamentos rápidos sobre a morte a organizar a vida. Esposo a idéia da necessidade da morte para que a vida tenha sentido nesta busca humana da completude. Endereço o olhar para uma situação especial de relação com a morte: a reação dos que ficam ao presenciar e sentir a morte de um dos seus idosos; daquele familiar, ou não, que assume o seu cuidado e acompanha o seu fim iminente; que presencia, humanamente impotente, a hora da solitária partida. Solitária morte, pois que exclusiva, própria daquele idoso do qual cuidava, do seu fim natural, por ser humano.

  20. A Little Area Challenge: A Sod Story (United States)

    Myers, Perla L.; Pelak, Colleen N.


    As partners in a professional development project, the authors jumped at the opportunity to use a real-life problem to engage elementary and middle school teachers in a one-day exploration of the concept of area. "Length times width"--a common response to the question, "What is area?"--is a rote formulaic expression that applies only to certain…

  1. A farmer becomes a social pedagogue

    DEFF Research Database (Denmark)

    Mellon, Karsten


    is a tremendously complex process that involves taking on a new professional identity and acquiring new skills. In order to ascertain the extent of this complexity, this article uses a psychosocietal approach derived from a Danish/German life history research approach. This article offers a brief presentation...

  2. A psychological profile of a serial killer: a case report. (United States)

    Dogra, T D; Leenaars, Antoon A; Chadha, R K; Manju, Mehta; Lalwani, Sanjeev; Sood, Mamta; Lester, David; Raina, Anupuma; Behera, C


    Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer.

  3. Having a Whale of a Time (United States)

    du Feu, Chris


    A classroom practical exercise exploring the reliability of a basic capture-mark-recapture method of population estimation is described using great whale conservation as a starting point. Various teaching resources are made available.

  4. Helping a Child Manage a Chronic Illness (United States)

    ... Helping a Child Manage a Chronic Illness Feeling they have control over their ... News) -- Children and teens who feel confident handling a chronic illness on their own appear better able ...

  5. Scarlet Fever: A Group A Streptococcal Infection (United States)

    ... this? Submit Button Past Emails CDC Features Scarlet Fever: A Group A Streptococcal Infection Language: English Español ( ... red rash that feels rough, like sandpaper. Scarlet Fever Podcast A pediatrician explains the cause, treatment, and ...


    Directory of Open Access Journals (Sweden)

    Mureşan Ioana


    Full Text Available This article is a theoretical article regarding Six Sigma. Six Sigma has been interpreted over time within quality theory as a metric, methodology or a management system. We explain Six Sigma using a logistics context: Delivery-On-Time (DOT rate problem. It is a theoretical context useful both for academic users and practitioners. At the beginning of the paper the DOT problem is generally described, while Sigma is presented according to statisticians view in the second part of the paper. Six Sigma is then presented as a metric for process’ capability. The fourth part of this article contains details regarding Six Sigma usage as a methodology for improvement, while the fifth part of this article refers to Six Sigma as a management system which can be used at firms’ level. The last chapter is dedicated to conclusions regarding the possible use of Six Sigma in Romania.

  7. Tiling a figure using a height in a tree

    Energy Technology Data Exchange (ETDEWEB)

    Remila, E. [Institut Universitaire de Technologie de Roanne, Paris (France)


    We first give a new presentation of an algorithm from Thurston of tiling with lozenges formed from two cells of the triangular lattice A. Secondly we extend the method to get a linear algorithm of tiling with leaning dominoes (parallelograms formed from four cells of {Lambda}) and triangles (formed from four cells of {Lambda}). Thirdly, we produce a quadratic algorithm of tiling with leaning dominoes.



    Elcio Alcione Cordeiro


    Apresento neste breve artigo uma noção de justiça segundo o pensamento de DavidHume. A justiça humeana se posiciona totalmente em prol da ordem social, isto é, o objetivo éque a segurança na sociedade seja instaurada. Para que isso aconteça de fato, é preciso quealgumas regras desta virtude artificial venham a ser respeitada por todos os homens. Ajustificação da propriedade é uma máxima que deve ser assegurada estavelmente. Os homensestão predispostos ao egoísmo que vence a benevolência natur...

  9. A method for making a nickel electrode

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, I.; Ikeyama, M.; Isikava, T.; Ivaki, T.; Yanashkhara, N.


    A powder of an active mass is applied to a foam metal plate and it is pressed into the pores of the base. The excess mass is removed from the surface, after which a grid structure is formed on this surface with heating of a powder of a thermally seating resin of the polyethylene type. Then, submerging the electrode plate into the resin suspension, the entire surface of the electrode is covered with a thin layer of powder of a fluorine bearing resin. The electrode has a long service life.

  10. A new peritrichous Ciliate as a symphoriont on a Tardigrade

    NARCIS (Netherlands)

    Land, van der J.


    INTRODUCTION On 24 September 1962 a number of Tardigrada was obtained from a sample of lichens from the French Alps. The lichens had been collected Figs. 1, 2. Pyxidium tardigradum n. sp. on Hypsibius oberhaeuseri (Doy.). on 27 June 1961 from a rock in the department Haute Savoie and had been preser

  11. A Study of Urban Education. A Report. (United States)

    Illinois State School Problems Commission, Springfield.

    To obtain a clearer understanding of the problems of urban education in Illinois, a committee of seven State legislators and 14 lay citizens engaged in a three-part study: (1) A series of statewide public hearings was held, resulting in 27 proposed solutions, and five universities submitted plans for their increased participation in the…

  12. [A woman with a rare vascular malformation

    NARCIS (Netherlands)

    Koning, G.G.; Vries, M. de


    A 30-year-old woman with trisomy 8 syndrome and coagulopathy was diagnosed with a malformation of the vena cava superior. This is a rare anatomical variation, which originates from a non-development of Marshall's ligament during the 8th week of gestation (prevalence: 0.3%).


    Directory of Open Access Journals (Sweden)

    Elcio Alcione Cordeiro


    Full Text Available Apresento neste breve artigo uma noção de justiça segundo o pensamento de DavidHume. A justiça humeana se posiciona totalmente em prol da ordem social, isto é, o objetivo éque a segurança na sociedade seja instaurada. Para que isso aconteça de fato, é preciso quealgumas regras desta virtude artificial venham a ser respeitada por todos os homens. Ajustificação da propriedade é uma máxima que deve ser assegurada estavelmente. Os homensestão predispostos ao egoísmo que vence a benevolência natural. A partir do momento em queos homens percebem que são egoístas e que viver em sociedade é vantajoso, acrescentam-seentão as convenções para que a ordem social seja instaurada.

  14. Remembering a Shape -- Assembling a Memory (United States)

    Zeravcic, Zorana; Murugan, Arvind; Brenner, Michael; Leibler, Stanislas


    Recently we have been developing a new connection between self-assembly and neural networks, where a multi-component particle system with specified interaction rules between its components is mapped onto a multi-state Hopfield neural network model. Within this framework, a fixed interaction pattern of neurons representing a ``memory'' maps to particle interactions encoding a certain structure. Properties of neural networks motivate new types of questions: Can the interaction energies of particles code for multiple structures at the same time? Can stored structures be retrieved by throwing in a nucleation seed (i.e., a small assembly of particles) and have it complete into the desired stored structure? Can we define a capacity, i.e., a maximal number of structures that can be retrieved with limited error? We investigate these questions using numerical simulations of different types of building blocks with short-range interactions.

  15. 43 CFR Appendix A to Subpart A of... - Appendix A to Subpart A of Part 17 (United States)


    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Appendix A to Subpart A of Part 17 A Appendix A to Subpart A of Part 17 Public Lands: Interior Office of the Secretary of the Interior... Race, Color, or National Origin Pt. 17, Subpt. A, App. A Appendix A to Subpart A of Part 17...

  16. A search for a new gauge boson A'

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Eric L. [College of William and Mary, Williamsburg, VA (United States)


    In the Standard Model, gauge bosons mediate the strong, weak, and electromagnetic forces. New forces could have escaped detection only if their mediators are either heavier than order(TeV) or weakly coupled to charged matter. New vector bosons with small coupling {alpha}' arise naturally from a small kinetic mixing with the photon and have received considerable attention as an explanation of various dark matter related anomalies. Such particles can be produced in electron-nucleus fixed-target scattering and then decay to e+e-+ pairs. New light vector bosons and their associated forces are a common feature of Standard Model extensions, but existing constraints are remarkably sparse. The APEX experiment will search for a new vector boson A' with coupling α'/αfs > 6 × 10-8 to electrons in the mass range 65MeV < mass A' < 550MeV. The experiment will study e+e- production off an electron beam incident on a high-Z target in Hall A at Jefferson Lab. The e- and e+ will be detected in the High Resolution Spectrometers (HRSs). The invariant mass spectrum of the e+e- pairs will be scanned for a narrow resonance corresponding to the mass of the A'. A test run for the APEX experiment was held in the summer of 2010. Using the test run data, an A' search was performed in the mass range 175-250 MeV. The search found no evidence for an A' → e+e-reaction, and set an upper limit of {alpha}'/{alpha}{sub fs} ~ 10-6.

  17. A Project Team: a Team or Just a Group?


    Kateřina; Daniela; Martina,


    This paper deals with issues related to work in either teams or groups. The theoretical part discusses a team and a group with regards to its definition, classification and basic distinction, brings in more on the typology of team roles, personality assessment and sociometric methods. The analytical part tests the project (work) team of a medical center represented in terms of personality and motivational types, team roles and interpersonal team relations concerning the willingness of coopera...

  18. A Project Team: A Team or Just a Group?


    Katerina Hrazdilova Bockova; Daniela Maťovcikova


    This paper deals with issues related to work in either teams or groups. The theoretical part which discusses a team and a group with regards to its definition, classification and basic distinction brings in more on the typology of team roles, personality assessment and sociometric methods. The analytical part tests the project (work) team of a medical center represented in terms of personality and motivational types, team roles and interpersonal team relations concerning t...

  19. [A fetus is a person with a right to exist]. (United States)

    Bischofberger, E


    This article is the contribution of a Jesuit priest, a teacher of medical ethics at Uppsala, to a debate inspired by a Swedish official report "The pregnant woman and fetus--2 individuals. On fetal diagnostics. On late abortions." In a society which depends upon a structured consensus as much as Sweden does, the report has been criticized for not making clearer recommendations. The author points out that the ethical dilemmas involved are so complex that they cannot be treated from a simple either/or point of view. Fetal diagnostics, for example, serve the cause of life when the aim is to avoid abortion of a healthy fetus and make it possible to cure, even at the fetal stage, or to strengthen prospective parents' readiness to accept a handicapped child. The use of fetal diagnostic for sorting out damaged and sick fetuses, however, is selective abortion and implies a violation of the principle that all human life is of equal value. The question is no longer if one will have a child or not, but which child will one have. This collision of values has inspired so many polemic statements that it is worthwhile recalling that there is always a tension between the ethically desirable and the politically possible, The report has succeeded in formulating the ethical principles in spite of the impossibility of seeing them presented as concrete recommendations. Even so, Thomas Aquinas wrote in 13th century that one cannot always apply ethical rules to laws of society. That can lead to more evil than good.

  20. A visit to Absurdistan: a nightmare of a sleep specialist. (United States)

    Rodenstein, Daniel; Duran Cantolla, Joaquin


    During a nocturnal dream, the authors discover a strange and unknown country, Absurdistan. Absurdistanis main concern appears to be sleep, whether nocturnal or diurnal, rather than wakefulness. They are fond of sleeping in any form, and devote much time to this activity. The authors follow a guide that shows them all kinds of strange sleep habits and keeps explaining the complex as well as the obvious. As the journey evolves, the explanations turn more and more confusing, becoming also amazingly surrealistic. The dream ends with a welcome wakefulness leaving the authors unsure of which is the waking state and which the dream.

  1. A toy model for a diatomic molecule (United States)

    Hecker Denschlag, Johannes


    We introduce a toy model for a diatomic molecule which is based on coupling electronic and nuclear spins to a rigid rotor. Despite its simplicity, the model can be used scientifically to analyze and understand complex molecular hyperfine spectra. In addition, the model has educational value as a number of fundamental symmetries and conservation laws of the molecule can be studied. Because of its simple structure, the model can be readily implemented as a computer program with comparatively short computing times on the order of a few seconds.

  2. Building a Database for a Quantitative Model (United States)

    Kahn, C. Joseph; Kleinhammer, Roger


    A database can greatly benefit a quantitative analysis. The defining characteristic of a quantitative risk, or reliability, model is the use of failure estimate data. Models can easily contain a thousand Basic Events, relying on hundreds of individual data sources. Obviously, entering so much data by hand will eventually lead to errors. Not so obviously entering data this way does not aid linking the Basic Events to the data sources. The best way to organize large amounts of data on a computer is with a database. But a model does not require a large, enterprise-level database with dedicated developers and administrators. A database built in Excel can be quite sufficient. A simple spreadsheet database can link every Basic Event to the individual data source selected for them. This database can also contain the manipulations appropriate for how the data is used in the model. These manipulations include stressing factors based on use and maintenance cycles, dormancy, unique failure modes, the modeling of multiple items as a single "Super component" Basic Event, and Bayesian Updating based on flight and testing experience. A simple, unique metadata field in both the model and database provides a link from any Basic Event in the model to its data source and all relevant calculations. The credibility for the entire model often rests on the credibility and traceability of the data.

  3. A Condition for a Translation Quiver to Be a Coil

    Institute of Scientific and Technical Information of China (English)

    Bin ZHU; Zong Yi HU


    We single out a class of translation quivers and prove combinatorially that the translationquivers in this class are coils. These coils form a class of special coils. They are easier to visualize, butstill show all the strange behaviour of general coils, and contain quasi-stable tubes as special examples.

  4. A Proposal for a Mindset of a Project Manager

    DEFF Research Database (Denmark)

    Eriksson, Joakim; Hansen, Claus Thorp


    A company’s product strategy and its management of the product development process have been found to be key factors for a product’s success on the market [1]. Project managers of development projects need support to make process decisions and defining goals that are consistent with the business’...

  5. Giuseppe Moscati: a man, a physician and a scientist. (United States)

    Ponti, Giovanni; D'Onofrio, Felice; Ruini, Cristel; Muscatello, Umberto; Tomasi, Aldo


    The life of Giuseppe Moscati (1880-1927) as a man, as a physician and as a scientist may be framed within the cultural climate of Positivism, which spread over the last years of the 19th century and the beginning of the 20th Century. His activity contributed to patients' care improvement; in addition to meticulous drug regimens, he also prescribed a methodology of spiritual care, involving meditation and self-control as part of an holistic approach to healthcare. Our review deals with his published researches, highlighting the innovative findings on the juvenile diabetes treatment and extensive clinical changes consequent upon nephritis. This extraordinary man put considerable emphasis on primary care and holistic health in Italy, pioneering a new patient-centred, and holistic approach to medicine.

  6. A Project Team: a Team or Just a Group?

    Directory of Open Access Journals (Sweden)



    Full Text Available This paper deals with issues related to work in either teams or groups. The theoretical part discusses a team and a group with regards to its definition, classification and basic distinction, brings in more on the typology of team roles, personality assessment and sociometric methods. The analytical part tests the project (work team of a medical center represented in terms of personality and motivational types, team roles and interpersonal team relations concerning the willingness of cooperation and communication. The main objective of this work is to verify the validity of the assumptions that the analyzed team represents a very disparate group as for its composition from the perspective of personality types, types of motivation, team roles and interpersonal relations in terms of the willingness of cooperation and communication. A separate output shall focus on sociometric investigation of those team members where willingness to work together and communicate is based on the authors’ assumption of tight interdependence.

  7. Generalizing a study of a rotating rod carrying a collar

    Energy Technology Data Exchange (ETDEWEB)

    Campos, I [Departamento de Fisica, Facultad de Ciencias, universidad Nacional Autonoma de Mexico, Apartado Postal 21-939, Mexico 04000 D.F. (Mexico); Del Valle, G; Hernandez, M G [Area de Fisica, Division de Ciencias Basicas e IngenierIa, Universidad Autonoma Metropolitana-Azcapotzalco, Apartado Postal 21-939, Mexico 04000 D.F. (Mexico); Jimenez, J L, E-mail: jlj@xanum.uam.m [Departamento de Fisica, Division de Ciencias Basicas e IngenierIa, Universidad Autonoma Metropolitana-Iztapalapa, Apartado Postal 21-939, Mexico 04000 D.F. (Mexico)


    The present work is a generalization of the work of Ribberfors and Reitz (2000 Eur. J. Phys. 21 151-7). These authors study a system consisting of a collar that is restricted to move in a path defined by a rod of some prescribed form which passes through the collar. We generalize the analysis of this system by means of canonical treatment. We show in this way that this excellent example can also be used in advanced courses on mechanics to show the power of the methods of analytical mechanics. We have that the present treatment of this example will be useful for advanced undergraduate and graduate students as well as for the teachers of these courses on classical mechanics. (letters and comments)

  8. Entomology: A Bee Farming a Fungus. (United States)

    Oldroyd, Benjamin P; Aanen, Duur K


    Farming is done not only by humans, but also by some ant, beetle and termite species. With the discovery of a stingless bee farming a fungus that provides benefits to its larvae, bees can be added to this list.

  9. A microcontroller system of a biotelemetric

    Directory of Open Access Journals (Sweden)

    O. B. Sharpan


    Full Text Available The system of a short-range biotelemetry is circumscribed which records and transmits biosignals to distance in tens meters. The system is intended for work in a composition of the pulse cardiologic analyzer.

  10. A. A. Laanessaare luule / Ruth Mirov

    Index Scriptorium Estoniae

    Mirov, Ruth, 1928-


    Ilmunud ka kogumikus: Mirov, Ruth. Sõnast sõnasse : valik artikleid ja retsensioone. Tallinn ; Tartu : Eesti Keele Sihtasutus, 2002, lk. 200-230. August Annisti luulest, avaldatud A. A. Laanessaare varjunime all

  11. A gas jet impacting a cavity (United States)

    Stiffler, A. Kent; Bakhsh, Hazoor


    A subsonic jet impinging upon a cavity is studied to explain the resultant heating phenomenon. Flow visualization within the cavity shows a large central vortex dominating the flow pattern. Velocity measurements inside the cavity are made using a hot-wire anemometer. Temperature is measured with a copper-constantan thermocouple. The velocity field within the cavity is described by a modified Rankine combined vortex. An uncommon form of the energy equation is used to account for turbulent heating in adverse pressure gradients. A theoretical solution is developed to model the temperature field in the cavity. There is a good agreement between the calculated and measured temperatures. The heating effect is related to Ranque-Hilsch tubes.

  12. Life of a Tooth: A Visual Timeline

    Medline Plus

    Full Text Available ... Decay? Headaches and Jaw Pain? Check Your Posture! Men: Looking for a Better Job? Start by Visiting the Dentist Why is Oral Health Important for Men? What is a Composite Resin (White Filling)? Learn ...

  13. Founding a Foundation: A Mini Case Study. (United States)

    Lake, Dale B.


    Lists factors contributing to the need for increased fund raising in community colleges. Discusses advantages of a foundation as a means of obtaining private funds. Delineates specifics of establishing, organizing, and implementing the Kalamazoo Valley Community College Foundation. (DMM)

  14. A Reinforced Blade for a Wind Turbine

    DEFF Research Database (Denmark)


    The present invention relates to a reinforced blade for a wind turbine having elongated reinforcing members in the blade extending substantially in the plane of the profile chord in order to strengthen the blade against edgewise and flapwise forces....

  15. A Novel Fortunate A from Cryptomerica fortunei

    Institute of Scientific and Technical Information of China (English)

    Zong Ping ZHENG; Li Hong HU; Jing Yu LIANG


    A novel compound, named fortunate A, was isolated from the ethanol extract of the stem bark of Cryptomerica fortunei. Its structure was established on the basis of the spectral evidences including 1D and 2D NMR spectrum.

  16. Broadcasting a message in a parallel computer (United States)

    Berg, Jeremy E.; Faraj, Ahmad A.


    Methods, systems, and products are disclosed for broadcasting a message in a parallel computer. The parallel computer includes a plurality of compute nodes connected together using a data communications network. The data communications network optimized for point to point data communications and is characterized by at least two dimensions. The compute nodes are organized into at least one operational group of compute nodes for collective parallel operations of the parallel computer. One compute node of the operational group assigned to be a logical root. Broadcasting a message in a parallel computer includes: establishing a Hamiltonian path along all of the compute nodes in at least one plane of the data communications network and in the operational group; and broadcasting, by the logical root to the remaining compute nodes, the logical root's message along the established Hamiltonian path.

  17. A method for making a storage cell

    Energy Technology Data Exchange (ETDEWEB)

    Tanakhasi, K.; Ivaki, T.


    The electrode unit is placed in a tank and water is poured into it until the electrodes are completely submerged. A liquid is poured in from above which is a solution of a synthetic resin of the polyvinylchloride type in a solvent insoluble in water of the tetrahydrofurane type. The solvent spreads along the surface of the water. The resin is removed, hardening and forming a porous layer on the wave shaped coagulated flakes. Then the liquid is poured off, passing through the pores of the resin layer. The water is replaced by an electrolyte. The layer of resin prevent splashing and excess evaporation of the electrolyte. A plug with a catalyst for recombining the gases formed in the storage device may be installed additionally in the storage device.

  18. A method for making a dry element

    Energy Technology Data Exchange (ETDEWEB)

    Abe, T.; Isikhara, K.; Kimura, T.; Momose, K.; Sakata, Y.


    The agglomerate is coated along the lateral surface by a separator and is enclosed in a zinc cylinder which serves as the anode. A separating plate is installed in the upper part of the agglomerate between the agglomerate and the anode. A current outlead is attached to the anode. The element is inserted into a body, pressing the plate into the agglomerate with a punch which has a recess. A guide cylinder is used for precise installation of the element. The space between the plate and the body in the upper part of the element is filled with wax or another substance. Short circuiting (KZ) between the current outlead and the agglomerate is prevented in the element.

  19. A Burger, a Beer, and a Side of Science (United States)

    Wiehe, B. R.; Landsberg, R. H.; Wyatt, R. J.; Turner, M. S.


    Science cafés (a.k.a. café scientifiques) engage unconventional adult audiences and help researchers hone their communication skills in a relaxed and fun setting. Typically held in restaurants and pubs, science cafés provide a comfortable place for the public to speak with a scientist. National and local evaluations of the café format indicate that café are an effective way to engage adult audiences (especially non-scientists). Continued media coverage also demonstrates that something about them captures the public's imagination. This paper is based on an interactive oral presentation about organizing, presenting, and partnering with science café to bring IYA themes (and other current research) directly to new audiences. Real world examples from experienced café organizers and presenters provide an overview of what a science café is, how to start one, and how to use the format to draw attention to astronomy topics. The discussion includes suggestions for tapping into the existing national and international community of cafés (there are more than 60 in the U.S. alone), and information about free outreach resources. Break-out exercises in the original oral presentation were designed to help prepare participants to: find a suitable venue, advertise, work with café speakers, and foster the inclusive conversation that is the hallmark of a science café. Participants also learned about the impacts that can be expected from a science café, including benefits to audiences, café presenters, and hosting organizations. The overall goal of the original oral presentation was to stimulate a discussion about strategies for facilitating face-to-face communication between scientists and lay audiences.

  20. Becoming a Vegetarian (United States)

    ... A Week of Healthy Breakfasts Shyness Becoming a Vegetarian KidsHealth > For Teens > Becoming a Vegetarian A A ... en español Hacerse vegetariano Why Do People Become Vegetarians? For much of the world, vegetarianism is largely ...

  1. A Pile of Legos. (United States)

    DePino, Andrew, Jr.


    Describes the relationships a high school built with neighborhood industry, a national laboratory, a national museum, and a large university while trying to build a scale model of the original atomic pile. Provides suggestions for teachers. (MVL)

  2. Aprendiendo a leer y a escuchar

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rodríguez


    Full Text Available Cuando Discépolo llegó al tango, el tango estaba ya hecho.Había pasado de su época legendaria a su época mítica. El tango se había convertido en mito. Y el mito tiene un problema básico. Pierde su contacto con la realidad para transmutarse a sí mismo en la expresión de esa realidad.

  3. Transforming a foundation into a cooperative

    Directory of Open Access Journals (Sweden)

    Juan Ramón Manzano Malaxechevarría


    Full Text Available The author charts a path between entities that meet needs in the general interest such as foundations and others which are neither entities of general interest nor have purely mercantile legal personality such as cooperatives. Transforming a foundation into a cooperative calls for a broad interpretation of the principle of free will that the legislation wishes to foster.Received: 12.02.2013Accepted: 20.04.2013

  4. Ankylosing Spondylitis: a Reflection and a Question

    Directory of Open Access Journals (Sweden)

    Annia Deysi Hernández Martín


    Full Text Available Ankylosing spondylitis is a chronic inflammatory disease that affects the synovial membrane, joint entheses and para-articular structures of the spine, including the sacroiliac joints and limbs. We present a case of ankylosing spondylitis that had evolved for 12 years despite the relatively early diagnosis and treatment, showing flexion deformity and limitation of spinal movements. On radiological examination an early evolution to ankylosis was observed, which motivated us to make a reflection and a question.

  5. A Spinning Particle in a Mobius Strip

    CERN Document Server

    Nieto, J A


    We develop the classical and quantum theory of a spinning particle moving in a Mobius strip. We first propose a Lagrangian for such a system and then we proceed to quantize the system via the constraint Hamiltonian system formalism. Our results may be of particular interest in several physical scenarios, including solid state physics and optics. In fact, the present work may shed some new light on the recent discoveries on condensed matter concerning topological insulators.

  6. Finding a Forest in a Tree

    DEFF Research Database (Denmark)

    Bacci, Giorgio; Miculan, Marino; Rizzi, Romeo


    computations, because they allow one to connect processes which can be at different places in the system, possibly crossing boundaries and firewalls. For instances, remote procedure calls can be modeled as a process in place i activating a reaction in a different place j; code mobility can be modeled...

  7. A Model Technology Educator: Thomas A. Edison (United States)

    Pretzer, William S.; Rogers, George E.; Bush, Jeffery


    Reflecting back over a century ago to the small village of Menlo Park, New Jersey provides insight into a remarkable visionary and an exceptional role model for today's problem-solving and design-focused technology educator: Thomas A. Edison, inventor, innovator, and model technology educator. Since Edison could not simply apply existing knowledge…

  8. A minimal model of a tidewater glacier

    NARCIS (Netherlands)

    Oerlemans, J.; Nick, Faezeh Maghami


    We propose a simple, highly parameterized model of a tidewater glacier. The mean ice thickness and the ice thickness at the glacier front are parameterized in terms of glacier length and, when the glacier is calving, water depth. We use a linear relation between calving rate and water depth. The cha

  9. SecA, a remarkable nanomachine

    NARCIS (Netherlands)

    Kusters, Ilja; Driessen, Arnold J. M.


    Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy

  10. A Method of Operating a Fuel Cell

    DEFF Research Database (Denmark)


    The present invention relates to a method of determining the net water drag coefficient (rd) in a fuel cell. By measuring the velocity of the fluid stream at the outlet of the anode, rd can be determined. Real time monitoring and adjustments of the water balance of a fuel cell may be therefore...

  11. Stabilizing a Bicycle: A Modeling Project (United States)

    Pennings, Timothy J.; Williams, Blair R.


    This article is a project that takes students through the process of forming a mathematical model of bicycle dynamics. Beginning with basic ideas from Newtonian mechanics (forces and torques), students use techniques from calculus and differential equations to develop the equations of rotational motion for a bicycle-rider system as it tips from…

  12. What a Time to Be a Bunny

    Institute of Scientific and Technical Information of China (English)



    It is the dead of the night and the city is sleeping. A stray car cruises the street until its lonesome passenger responds in a zombie-like manner to a traffic light that turns red, stopping an invisible flow of traffic.

  13. When a regulation becomes a learning process

    DEFF Research Database (Denmark)

    Nunez, Heilyn Camacho; Cespedes, Paula

    Adoption and effective use of information and communication technology (ICT) becomes a need for organizations of any size and type, however, ICT adoption is still a challenge for organizations, its implementation must be a strategic decision that involves design, delivery and use of software syst...

  14. A Lonely Heart Could Worsen a Cold (United States)

    ... page: A Lonely Heart Could Worsen a Cold People who feel isolated tend to have ... 30, 2017 THURSDAY, March 30, 2017 (HealthDay News) -- A cold is never fun, but it's even more ...

  15. A microfluidic device with a diffusion barrier

    DEFF Research Database (Denmark)


    The invention provides a microfiuidic device for macromoiecuie amplification by sequential addition of liquid reagents. The device of the invention comprises a chip forming a plurality of reaction chambers each extending between an inlet and an outlet, each inlet being in fluid communication with...

  16. Sustainable Competence: A Study of a Bank (United States)

    Hagstrom, Tom; Backstrom, Tomas; Goransson, Susanna


    Purpose: Decentralization and company cultures have emerged to master increasing external flexibility, as in a competitive bank in Sweden, raising issues of the sustainability in terms of competence and competence development. The purpose of this paper is to study how the staff members in a bank perceive a company culture and how this perception…

  17. A modified total synthesis of cystothiazole A

    Institute of Scientific and Technical Information of China (English)


    A modified total synthesis of cystothiazole A is described. In this synthetic strategy, a one-step transformation of acylated oxazolidinone to β-ketoester has been successfully applied, thus making the synthetic route more efficient. This method may also be potentially applied in synthesis of other related β-substituted-β-methoxyl acrylates (bb-MOAs).

  18. A modified total synthesis of cystothiazole A

    Institute of Scientific and Technical Information of China (English)

    BAI YueXia; BAO JiLai; REN Jun; WANG ZhongWen


    A modified total synthesis of cystothiazole A is described.In this synthetic strategy,a one-step transformation of acylated oxazolidinone to β-ketoester has been successfully applied,thus making the synthetic route more efficient.This method may also be potentially applied in synthesis of other related β-substituted-β-methoxyl acrylates (bb-MOAs).

  19. A device for reforming a hydrocarbon fuel

    Energy Technology Data Exchange (ETDEWEB)

    Kendzi, T.; Ikuo, M.


    In order to utilize the heat from the reaction of reforming of a hydrocarbon fuel and the heat scattered from a heater, a design is proposed for a fuel reforming reactor in which the gases entering the reactor first pass inside the reactor along the external wall and are heated by the heat dispersed inside the reactor. Then they go in the opposite direction along a clearance between the interior shell of the reactor and the internal body of the reactor itself with a catalyst (Kt) and a heated electrical cylindrical heater. Then the gases, already heated, go directly into the cavity of the reactor filled with the catalyst where the reforming reaction occurs and then the gases and the vapors of the reformed fuel are discharged, passing through a system of heat exchangers. The layout of such a reactor, which contains a cylindrical shell inside, a cylindrical sleeve coaxial with it and the body of the reactor itself with the heater, is given. A system for attaching the internal sleeve and the body of the reactor to the catalyst is cited. The course of the gases inside the reactor is also given.

  20. A lattice for a lead storage battery

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, S.; Fukunaga, K.; Kumano, Y.


    Lattices for a lead storage cell are made of a lead alloy which contains (in percent by mass): 0.05 to 0.3 strontium; 0.02 to 0.1 aluminum; 0.05 to 3.0 tin and 0.01 to 3.0 cadmium. The storage cell has low autodischarge and a long service life.

  1. Teratogenia da vitamina A Vitamin A teratogenicity

    Directory of Open Access Journals (Sweden)

    Maria Helena de Castro Chagas


    Full Text Available A vitamina A é essencial à preservação e ao funcionamento normal dos tecidos, assim como, ao crescimento e desenvolvimento. No humano há evidência indireta que a vitamina A em excesso, durante as primeiras semanas de gestação é teratogênica. Do contrário, não há dúvidas sobre os efeitos deletérios, de uma alimentação carente neste micronutriente e sobre a disponibilidade do conhecimento técnico para evitá-los. A preocupação com o fato de que a vitamina A conduziria a teratogenia em humanos, tem retardado a implementação de programas de combate a carência de vitamina A, atingindo principalmente os programas de enriquecimento de alimentos. A literatura é controvertida e dispõe de poucas informações sobre as doses para suplementação de gestantes. Como o retinol circulante materno é controlado homeostaticamente após o consumo de alimentos fonte de vitamina A, espera-se a mesma resposta metabólica após o consumo de alimentos fortificados, indicando que não há risco de teratogenia. Consequentemente, parece altamente improvável que o consumo de alimentos enriquecidos ou de suplementos de vitamina A pré-formada, nas doses unitárias habituais, tenha efeito teratogênico no homem.The vitamin A is essential to the preservation and the normal functioning of tissues, as well as, to the growth and development. In the human being it has indirect evidence that the vitamin A in excess, during the first weeks of gestation is teratogenic. Of the opposite, it does not have doubts on the deleterious effect, of a devoid feeding in this micronutrient and on the availability of the knowledge technician to prevent them. The concern with the fact of that the vitamin A would lead it the teratogenicity in human beings, has delayed the implementation of combat programs the vitamin A lack, mainly reaching the programs of food enrichment. Literature is controverted and makes use of few information on the doses for supplementation of

  2. A Psychological Factor Affecting a Cardiac Condition in a Psychotherapist

    Directory of Open Access Journals (Sweden)

    R Waxman


    Full Text Available It has been established that intense emotions can affect the development and course of cardiac arrhythmias. This study sought to convey that a lack of expression of emotion can also have an effect on arrhythmias. A psychotherapist with Idiopathic Ventricular Fibrillation and an Implantable Cardioverter Defibrillator measured his rate of Premature Ventricular Contractions using a Holter monitor during three separate six-week periods and in three domains: A work days vs. off days, B a 27 hour work week vs. 22 hour work week, and C in 5 different modalities including 1 Meeting with department head 2 Individual psychotherapy with patients 3 Group therapy with patients 4 Supervision of residents 5 Personal psychoanalysis. The results showed more than a 3-fold increase of arrhythmogenic activity during the 27-hour work week vs. 22 and a 5-fold increase in arrhythmogenic activity on work days compared to days off. Department Head meetings were found to be most arrhythmogenic and personal psychoanalysis was least. The data suggest that the psychiatrist’s lack of emotional expression in his clinical work has been demonstrated to markedly worsen his arrhythmia. The results also point to the potential ameliorating effects of the therapist’s own psychotherapy.


    Institute of Scientific and Technical Information of China (English)

    Ozden BAYAZIT; Birsen KARPAK; Ayhan YAGCI


    Supplier selection is one of the most crucial activities performed by organizations because of its strategic importance. Supplier selection is a multi-objective problem involving both quantitative and qualitative criteria. Over the years a number of quantitative approaches have been tried. Although the Analytic Hierarchy Process (AHP) has previously been used in supplier selection problems, one major weakness of the application-oriented AHP literature is that it tends to focus on the mechanics of AHP instead of on the theoretical and practical implications associated with finding a solution. Though it is one of the most extensively used Multiple Criteria Decision Analysis methodologies, our literature search indicated that most studies found the best solution and stopped there, ignoring sensitivity analysis. Performing sensitivity analysis is very important for practical decision making, sometimes even as important as finding the best solution. In this paper for the first time a comprehensive application of AHP for a real-world case is presented along with sensitivity analysis in choosing the best suppliers for a Turkish construction company. As a result of this study the company decided to allocate the order quantities between the two top suppliers.

  4. A diferença e a alteridade

    Directory of Open Access Journals (Sweden)

    Eurídice Figueiredo


    Full Text Available Este texto se propõe a discutir o pensamento diferencialista da crítica e da literatura norte-americanas presente no tratamento da alteridade em relação às representações dos mestiços e a mostrar que ele é diferente da lógica universalista brasileira. Muito se falou da ideologia do branqueamento no Brasil, que possibilita a passagem de uma cor/raça a outra, considerada superior. Este fenômeno, chamado de passing em inglês, em que os mulatos/mestiços claros podem ocultar sua origem, mudar de região e se fazer passar por brancos, também existe na América do Norte. Este tema – que aparece em vários romances – é altamente problemático nos dias de hoje, em que as minorias são instadas, pelo pensamento politicamente correto, a se assumir e lutar pelo direito à diferença. Esta visão nega ao personagem do mestiço-quase-branco o direito à singularidade e à construção de uma identidade individual(ista, já que ele deve se inserir sempre no âmbito de uma luta coletiva.

  5. Eurasian Union: A Utopia, a Dream or a Coming Reality?

    Directory of Open Access Journals (Sweden)

    Tuğçe Varol SEVIM


    Full Text Available Twenty years passed after the dissolution of the USSR and the re-birth of Russian Federation and Central Asian states in the world arena in such a unipolar world. Since the rise of Vladimir Putin to power Russia resists on unipolar system and sees that as a treat to its security. Hence, Kremlin perceives that the economic strength is the sine qua non for the future of Russia in order to sustain a Big Power status not only in its region but also in the world. In 2011, Russia, Belarus and Kazakhstan have achieved to form a Customs Union among them and invited all the states in the region to join the organization. There were thesis which mainly argued that Russia would no longer be a “power” in the Central Asia and could only be a regional power just in case of maintaining of its own unity. However, the circumstances have changed in the region accordingly Russian weight as a result of the new conjuncture. In 2012, Russia had a new presidential election and Putin returned to Kremlin as President himself. It has been understood from his words that Kremlin's new strategy to be focused on creating a Eurasian Union including Kyrgyzstan and Tajikistan at the first stage. It is aimed to analyze in this study that whether this project could be successful and if so, what could be the impacts on world order in terms of competition between Russia, the United States and China also. And finally, what could be the result of such an organization for the Russia.

  6. A study of a simple gyrotron equation

    Energy Technology Data Exchange (ETDEWEB)

    Goetz, Markus [Max-Planck-Institut fuer Plasmaphysik, EURATOM-Association, D-85748 Garching (Germany); Meyer-Spasche, Rita [Max-Planck-Institut fuer Plasmaphysik, EURATOM-Association, D-85748 Garching (Germany); Weitzner, Harold [New York University, Courant Institute of Mathematical Sciences, New York, NY 10012 (United States)


    A simple standard equation for the evolution of the electrons and electromagnetic fields in a gyrotron cavity is studied. A number of mathematical properties are shown: existence and uniqueness of solutions for a limited axial extent and existence and uniqueness for all axial lengths in one case of particular interest. A Poynting theorem is obtained directly from the model and the Hamiltonian character of the electron motion is demonstrated. The start-up and final state in the gyrotron cavity are also examined. The efficiency of energy flux transfer from the electron beam to the wave is estimated.

  7. Homenagem a Ecléa Bosi

    Directory of Open Access Journals (Sweden)

    Marilena Chauí


    Full Text Available Neste ensaio, buscamos a principal contribuição de Ecléa Bosi para a Psicologia Social, qual seja, a relação entre teoria, método e técnicas de pesquisa e militância social, política e cultural, a partir da definição da psicologia como fenomenologia dos atos expressivos e da relação de amizade entre o pesquisador e o pesquisado como pessoa.

  8. A child with a large bladder stone: A case report

    Directory of Open Access Journals (Sweden)

    Hulya Ozturk


    Full Text Available Bladder stones account for approximately 5% of all urinary system stones and are prevalent among children living in poor or rural regions. The symptoms and findings in children with bladder stones are usually urgency, frequency, incontinence, dysuria, pyuria, difficulty voiding, and fever, small caliber of urinary stream, lower abdominal pain and urinary intermittency. Most bladder stones are composed of calcium oxalate, followed by calcium phosphate, and they are usually larger than 2.5 cm in diameter. We present a case of a larger-than 2.5-cm bladder stone in a child.

  9. A Spectrum is Worth a Thousand Pictures (United States)

    Gelderman, Richard F.


    A wise astronomer once pointed out that if a picture is worth a thousand words, then a spectrum is worth a thousand pictures. Unfortunately, spectra are rarely emphasized in the introductory astronomy courses and few students exit such a course with any meaningful understanding or appreciation of spectroscopy. Part of the problem is lack of background knowledge; the typical introductory astronomy student has little experience with spectroscopy or atomic physics. Another issue is that spectra are not pretty pictures and are not intuitively understandable. We present and discuss a series of “minds-on” exercises and activities built into a college-level “stars, galaxies, and cosmology” intro astronomy course. The lessons are structured to help students improve their ability to recognize patterns and improve their ability to really see the details in front of them. Another goal is for students to realize there is “more than meets the eye” to learn how to discover “hidden” diagnostics, such as different sources of light their eyes see as white light. A curriculum that emphasizes spectroscopy also provides the opportunity to stress the story of the “Harvard Women,” a tale that bridges gender gaps and often humanizes scientists in the eyes of non-science majors. Finally, with a solid foundation in spectroscopy, students are better prepared to understand exciting topics such as Hubble’s Law and the importance of primordial nucleosynthesis.

  10. A case of a horseshoe appendix. (United States)

    Takabatake, Kazuya; Ikeda, Jun; Furuke, Hirotaka; Kato, Chikage; Kishimoto, Takuya; Kumano, Tatsuya; Imura, Kenichiro; Shimomura, Katsumi; Kubota, Takeshi; Taniguchi, Fumihiro; Shioaki, Yasuhiro


    Anomalies of the appendix are extremely rare, and a horseshoe appendix is even rarer. A literature search has revealed only five reported cases. In this report, we present a case of a horseshoe appendix.A 78-year-old man was referred for further examination following a positive fecal occult blood test. A mass in his ascending colon was detected on colonoscopy, while computed tomography showed that it was connected to the appendix. Tumor invasion derived from the ascending colon or appendix was suspected. We diagnosed ascending colon cancer prior to laparoscopic ileocecal resection. Macroscopic findings showed that the appendix connected to the back side of the mass, while microscopic findings showed that the mucosa and submucosa were continuous from the appendiceal orifice in the cecum to the other orifice in the ascending colon, where a type 1 tumor was observed on the orifice. We eventually diagnosed the patient with tubulovillous adenoma and a horseshoe appendix.A horseshoe appendix communicates with the colon at both ends and is supplied by a single fan-shaped mesentery. Cases are classified by the disposal of the mesentery and the location of the orifice. Anatomical anomalies should be considered despite the rarity of horseshoe appendices.

  11. A Random Laser as a Dynamical Network

    CERN Document Server

    Höfner, M; Henneberger, F


    The mode dynamics of a random laser is investigated in experiment and theory. The laser consists of a ZnCdO/ZnO multiple quantum well with air-holes that provide the necessary feedback. Time-resolved measurements reveal multimode spectra with individually developing features but no variation from shot to shot. These findings are qualitatively reproduced with a model that exploits the specifics of a dilute system of weak scatterers and can be interpreted in terms of a lasing network. Introducing the phase-sensitive node coherence reveals new aspects of the self-organization of the laser field. Lasing is carried by connected links between a subset of scatterers, the fields on which are oscillating coherently in phase. In addition, perturbing feedback with possibly unfitting phases from frustrated other scatterers is suppressed by destructive superposition. We believe that our findings are representative at least for weakly scattering random lasers. A generalization to random laser with dense and strong scattere...

  12. A marketing strategy for a nursing college

    Directory of Open Access Journals (Sweden)

    M. Pryde


    Full Text Available The objective of this study is to explore and describe a marketing strategy for a nursing college. An explorative and descriptive research design, within the context of a nursing college and affiliated hospitals, was followed. A literature study of marketing models was undertaken and the Delphi-method was utilised to determine the contribution of marketing staff and the possible content of a marketing strategy for a nursing college. The results were utilised to describe guidelines for such a strategy, consisting of marketers/marketing agents, target market, product, price, promotional activities, place and market research. Recommendations include the planning, implementation and evaluation of strategy, inservice training for potential marketing agents, inclusion of marketing as part of the formal education of tutors and nurse managers,as well as an impact study of the scholar as the main consumer.

  13. A marketing strategy for a nursing college. (United States)

    Pryde, M; Muller, M


    The objective of this study is to explore and describe a marketing strategy for a nursing college. An explorative and descriptive research design, within the context of a nursing college and affiliated hospitals, was followed. A literature study of marketing models was undertaken and the Delphi-method was utilised to determine the contribution of marketing staff and the possible content of a marketing strategy for a nursing college. The results were utilised to describe guidelines for such a strategy, consisting of marketers/marketing agents, target market, product, price, promotional activities, place and market research. Recommendations include the planning, implementation and evaluation of strategy, inservice training for potential marketing agents, inclusion of marketing as part of the formal education of tutors and nurse managers, as well as an impact study of the scholar as the main consumer.


    Directory of Open Access Journals (Sweden)

    Nino Panagia


    Full Text Available The story of the SN 1987A explosion is briefly reviewed. Although this supernova was somewhat peculiar, the study of SN 1987A has clarified quite a number of important aspects of the nature and the properties of supernovae, such as the confirmation of the core collapse of a massive star as the cause of the explosion, as well the confirmation that the decays 56Ni–56Co–56Fe at early times and 44Ti–44Sc at late times, are the main sources of the energy radiated by the ejecta. Still we have not been able to ascertain whether the progenitor was a single star or a binary system, nor have we been able to detect the stellar remnant, a neutron star that should be produced in the core collapse process.

  15. A reductive coupling strategy towards ripostatin A. (United States)

    Schleicher, Kristin D; Jamison, Timothy F


    Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim to construct the C9-C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1-C9 has been synthesized in high yield and demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10-C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted decarboxylation enables construction of the C15-C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment.

  16. A Project Team: A Team or Just a Group?

    Directory of Open Access Journals (Sweden)

    Katerina Hrazdilova Bockova


    Full Text Available This paper deals with issues related to work in either teams or groups. The theoretical part which discusses a team and a group with regards to its definition, classification and basic distinction brings in more on the typology of team roles, personality assessment and sociometric methods. The analytical part tests the project (work team of a medical center represented in terms of personality and motivational types, team roles and interpersonal team relations concerning the willingness of cooperation and communication. The main objective of this work was to determine whether the existing team is not by its nature rather a working group that contributes to the generally perceived stagnation of that field.

  17. A coinsidence, a chance or a misfortune? Hangman's fracture. (United States)

    Dalbayrak, Sedat; Yaman, Onur


    William R. Francis and Bassam El-Effendi shared a common ground: they were the first individuals to classify Hangman's Fractures. Interestingly, although they were unaware of each other, they classified and published their findings in the same year, published in the same edition of the same journal (but on different pages). This new classification system was a chance for notoriety for El-Effendi, yet it was a misfortune for Francis. Both physicians graduated in 1973 (from different universities). Also fellows at different universities in 1981, they were also both unaware they studied the same topic. Coincidentally, their paths crossed in the same edition of a journal where their studies were published in the same year, which was unprecedented in the literature. One classification scheme is well-known while the other is almost completely unheard of for no apparent reason other than chance for one and misfortune for the other.

  18. When is a theory a theory? A case example. (United States)

    Alkin, Marvin C


    This discussion comments on the approximately 20years history of writings on the prescriptive theory called Empowerment Evaluation. To do so, involves examining how "Empowerment Evaluation Theory" has been defined at various points of time (particularly 1996 and now in 2015). Defining a theory is different from judging the success of a theory. This latter topic has been addressed elsewhere by Michael Scriven, Michael Patton, and Brad Cousins. I am initially guided by the work of Robin Miller (2010) who has written on the issue of how to judge the success of a theory. In doing so, she provided potential standards for judging the adequacy of theories. My task is not judging the adequacy or success of the Empowerment Evaluation prescriptive theory in practice, but determining how well the theory is delineated. That is, to what extent do the writings qualify as a prescriptive theory.

  19. Haemorrhage in a scrotal lymphangioma in a child: A rarity

    Directory of Open Access Journals (Sweden)

    Rattan Kamal


    Full Text Available We report here a case of cystic lymphangioma of scrotum presenting as acute scrotum due to haemorrhage. The diagnosis was confirmed on ultrasonography and magnetic resonance imaging and managed successfully by surgical excision. There was past history of bilateral congenital cataract for which the patient had undergone surgery with complete visual recovery. Scrotal cystic lymphangioma complicated by haemorrhage is rare; hence, the case is being reported with a review of literature.

  20. IgA Nephropathy (United States)

    ... reliable ways to diagnose IgA nephropathy; therefore, the diagnosis of IgA nephropathy requires a kidney biopsy. A kidney biopsy is ... reliable ways to diagnose IgA nephropathy; therefore, the diagnosis of IgA nephropathy requires a kidney biopsy. Researchers have not yet ...

  1. Tricolorin A as a Natural Herbicide

    Directory of Open Access Journals (Sweden)

    Blas Lotina-Hennsen


    Full Text Available Tricolorin A acts as pre- and post-emergence plant growth inhibitor. In pre-emergence it displays broad-spectrum weed control, inhibiting germination of both monocotyledonous (Lolium mutliflorum and Triticum vulgare and dicotyledonous (Physalis ixocarpa and Trifolium alexandrinum seeds, being the dicotyledonous seeds the most inhibited. Tricolorin A also inhibited seedling growth, and seed respiration, and since the concentrations required for inhibiting both germination and respiration were similar, we suggest that respiration is one of its targets. Tricolorin A at 60 µM acts as a post- emergence plant growth inhibitor by reducing dry plant biomass by 62%, 37%, 33%, and 22% for L. multiflorum, T. alexandrinum, T. vulgare, and P. ixocarpa, respectively, 18 days after its application. In order to determine the potency of tricolorin A as a plant growth inhibitor, paraquat was used as control; the results indicate that tricolorin A acts as a non-selective post-emergence plant growth inhibitor similar to paraquat, since both reduced the biomass production in P. ixocarpa and T. alexandrinum. Therefore, we suggest that tricolorin A will be a good biodegradable herbicide for weeds.

  2. A system architecture for a planetary rover (United States)

    Smith, D. B.; Matijevic, J. R.


    Each planetary mission requires a complex space vehicle which integrates several functions to accomplish the mission and science objectives. A Mars Rover is one of these vehicles, and extends the normal spacecraft functionality with two additional functions: surface mobility and sample acquisition. All functions are assembled into a hierarchical and structured format to understand the complexities of interactions between functions during different mission times. It can graphically show data flow between functions, and most importantly, the necessary control flow to avoid unambiguous results. Diagrams are presented organizing the functions into a structured, block format where each block represents a major function at the system level. As such, there are six blocks representing telecomm, power, thermal, science, mobility and sampling under a supervisory block called Data Management/Executive. Each block is a simple collection of state machines arranged into a hierarchical order very close to the NASREM model for Telerobotics. Each layer within a block represents a level of control for a set of state machines that do the three primary interface functions: command, telemetry, and fault protection. This latter function is expanded to include automatic reactions to the environment as well as internal faults. Lastly, diagrams are presented that trace the system operations involved in moving from site to site after site selection. The diagrams clearly illustrate both the data and control flows. They also illustrate inter-block data transfers and a hierarchical approach to fault protection. This systems architecture can be used to determine functional requirements, interface specifications and be used as a mechanism for grouping subsystems (i.e., collecting groups of machines, or blocks consistent with good and testable implementations).

  3. When is a bottleneck a bottleneck?

    CERN Document Server

    Schadschneider, Andreas; Popkov, Vladislav


    Bottlenecks, i.e. local reductions of capacity, are one of the most relevant scenarios of traffic systems. The asymmetric simple exclusion process (ASEP) with a defect is a minimal model for such a bottleneck scenario. One crucial question is "What is the critical strength of the defect that is required to create global effects, i.e. traffic jams localized at the defect position". Intuitively one would expect that already an arbitrarily small bottleneck strength leads to global effects in the system, e.g. a reduction of the maximal current. Therefore it came as a surprise when, based on computer simulations, it was claimed that the reaction of the system depends in non-continuous way on the defect strength and weak defects do not have a global influence on the system. Here we reconcile intuition and simulations by showing that indeed the critical defect strength is zero. We discuss the implications for the analysis of empirical and numerical data.

  4. GRB 130427A: a Nearby Ordinary Monster

    CERN Document Server

    Maselli, A; Nava, L; Mundell, C G; Kawai, N; Campana, S; Covino, S; Cummings, J R; Cusumano, G; Evans, P A; Ghirlanda, G; Ghisellini, G; Guidorzi, C; Kobayashi, S; Kuin, P; La Parola, V; Mangano, V; Oates, S; Sakamoto, T; Serino, M; Virgili, F; Zhang, B -B; Barthelmy, S; Beardmore, A; Bernardini, M G; Bersier, D; Burrows, D; Calderone, G; Capalbi, M; Chiang, J; D'Avanzo, P; D'Elia, V; De Pasquale, M; Fugazza, D; Gehrels, N; Gomboc, A; Harrison, R; Hanayama, H; Japelj, J; Kennea, J; Kopac, D; Kouveliotou, C; Kuroda, D; Levan, A; Malesani, D; Marshall, F; Nousek, J; O'Brien, P; Osborne, J P; Pagani, C; Page, K L; Page, M; Perri, M; Pritchard, T; Romano, P; Saito, Y; Sbarufatti, B; Salvaterra, R; Steele, I; Tanvir, N; Vianello, G; Weigand, B; Wiersema, K; Yatsu, Y; Yoshii, T; Tagliaferri, G


    Long-duration Gamma-Ray Bursts (GRBs) are an extremely rare outcome of the collapse of massive stars, and are typically found in the distant Universe. Because of its intrinsic luminosity ($L\\sim 3 \\times 10^{53}$ erg s$^{-1}$) and its relative proximity ($z=0.34$), GRB 130427A was a unique event that reached the highest fluence observed in the gamma-ray band. Here we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-m Liverpool and Faulkes telescopes and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early Universe and over the full range of GRB isotropic energies.

  5. A Wonderful Adventure to a Rainforest

    Institute of Scientific and Technical Information of China (English)



    I’d like to go to a rainforest—the place I’ve alw ays dream t of going to. D uring m y long holiday in M ay, it m ay take a w eek to be on m y adventure. A nd I think it’ll be a really fantastic journey as there m ust be a va- riety of creatures along m y w ay. W henever I get tired and bored,they’ll cheer m e up.D if- ferent creatures m ake m e excited. A nd the m ore dangerous m y journey is, the m ore curi- ous I w ill be. I m ay get to m y destination by air, but in order to enjoy m y journey to the ful...

  6. Death ends a life not a relationship

    DEFF Research Database (Denmark)

    Christensen, Dorthe Refslund; Sandvik, Kjetil


    When parents are expecting, the child is usually awaited with hope and plans and reflections on how to share the life and future with this new child. As such the child opens the parents' perspective to a new future, a span of time or potentiality, a certain narrative—that is, being parents, raising...... a child. When a child is stillborn or dies at a very young age, this event not only turns off all hopes for this particular child, but also all good things envisioned for the child and his or her family, the world itself changes radically. At the Danish website, parents engage in ritualizations...... through which they resituate themselves in the world through performing their grief and loss, re-relating themselves to others and renewing their acquaintance with themselves and the world. These ritualizations are carried out through narratives and performances dealing with different aspects of the loss...

  7. A tunable DNA spring in a nanochannel (United States)

    Riehn, Robert; Staunton, Rory; Lim, Shuang Fang; Bruinsma, Robijn; Reisner, Walter; Austin, Robert


    dsDNA becomes linearized when it is confined to nanofluidic channels with a cross-section of (100 nm)^2 or less, which has made them interesting for genomic DNA analyses. DNA is typically manipulated by means of electric fields. We have found that DNA undergoes a phase transition to a condensed state if an a.c. electric field is applied along the channel direction. The molecule collapses to about 1/4 of it's initial contour length. We will discuss how the effect depends on parameters such as frequency, field strength, channel dimensions, and will discuss the origin of the effect. Interestingly, DNA behaves like an artifical muscle that can be triggered by an a.c. electric field. Since the interaction is expected to hold for any solubilized polyelectrolyte, we speculate that the mechanism may lead to a new class of polymer-based mechanical actuators. These would not suffer from depolarization like piezo transducers.

  8. A água e a vida

    Directory of Open Access Journals (Sweden)



    Full Text Available Trata-se de exercício de interpretação da frase “tudo é água”, atribuída a Tales de Mileto. Depois da exposição dos pontos de vista do senso comum, da ciência e da filosofia sobre a utilidade da água para a vida, tenta-se recuperar, na dimensão simbólica, suas significações mais profundas como fonte, purificação e regeneração da vida humana. O artigo sugere que a poluição das águas pela moderna sociedade industrial agride brutalmente não só a vida biológica como também a vida psíquica.

  9. Starting a business through a franchise

    Directory of Open Access Journals (Sweden)

    Dubravka Mahaček


    Full Text Available A business can be launched by establishing a new entity, purchasing an existing entity or through a franc - hise. There are certain prerequisites for starting a business, the most important ones being a quality idea and start-up capital. Potential start-up difficulties are inadequate financing, existing competition as well as the process of building your own market position. By purchasing an existing business some risks may be avoided and the opportunity for gaining profit may arise. Profitable operation is possible only if this business has up-to-date products and no outstanding liabilities. This paper discusses franchising business opportunities and the requisite investments and costs, which will bring success if they are accompanied by franchisee’s efforts. The paper aims to present the main characteristics of a franchise business, the necessary investment and the costs which arise in the process, as well as advantages, disadvantages and experiences with this kind of business

  10. Stretching a Semiflexible Polymer in a Tube

    Directory of Open Access Journals (Sweden)

    Runhua Li


    Full Text Available How the statistical behavior of semiflexible polymer chains may be affected by force stretching and tube confinement is a classical unsolved problem in polymer physics. Based on the Odijk deflection theory and normal mode decomposition in terms of Fourier expansion, we have derived a new compact formula for the extension of a wormlike chain of finite length strongly confined in a tube and simultaneously stretched by an external force. We have also suggested a new deflection length, which together with the force-extension relation is valid for a very extended range of the tube-diameter/persistence-length ratio comparing to the classic Odijk theory. The newly derived formula has no adjustable fitting parameters for the whole deflection regime; in contrast, the classic Odijk length needs different prefactors to fit the free energy and average extension, respectively. Brownian dynamics simulations based on the Generalized Bead-Rod (GBR model were extensively performed, which justified the theoretical predictions.

  11. A Small Deformation of a Simple Theory

    CERN Document Server

    Buican, Matthew


    We study an interesting relevant deformation of the simplest interacting N=2 SCFT---the original Argyres-Douglas (AD) theory. We argue that, although this deformation is not strictly speaking Banks-Zaks like (certain operator dimensions change macroscopically), there are senses in which it constitutes a mild deformation of the parent AD theory: the exact change in the "a" anomaly is small and is essentially saturated at one loop. Moreover, contributions from IR operators that have a simple description in the UV theory reproduce a particular limit of the IR index to a remarkably high order. These results lead us to conclude that the IR theory is an N=1 SCFT with the smallest-known "a" and "c" central charges for an interacting SCFT in four dimensions.

  12. Broadcasting a message in a parallel computer

    Energy Technology Data Exchange (ETDEWEB)

    Archer, Charles J; Faraj, Daniel A


    Methods, systems, and products are disclosed for broadcasting a message in a parallel computer that includes: transmitting, by the logical root to all of the nodes directly connected to the logical root, a message; and for each node except the logical root: receiving the message; if that node is the physical root, then transmitting the message to all of the child nodes except the child node from which the message was received; if that node received the message from a parent node and if that node is not a leaf node, then transmitting the message to all of the child nodes; and if that node received the message from a child node and if that node is not the physical root, then transmitting the message to all of the child nodes except the child node from which the message was received and transmitting the message to the parent node.

  13. Locating a circle on a sphere

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita


    We consider the problem of locating a spherical circle with respect to existing facilities on a sphere, such that the sum of weighted distances between the circle and the facilities is minimized, or such that the maximum weighted distance is minimized. The problem properties are analyzed, and we...... give solution procedures. When the circle to be located is restricted to be a great circle, some simplifications are possible....

  14. A numerical simulation of a contrail

    Energy Technology Data Exchange (ETDEWEB)

    Levkov, L.; Boin, M.; Meinert, D. [GKSS-Forschungszentrum Geesthacht GmbH, Geesthacht (Germany)


    The formation of a contrail from an aircraft flying near the tropopause is simulated using a three-dimensional mesoscale atmospheric model including a very complex scheme of parameterized cloud microphysical processes. The model predicted ice concentrations are in very good agreement with data measured during the International Cirrus Experiment (ICE), 1989. Sensitivity simulations were run to determine humidity forcing on the life time of contrails. (author) 4 refs.

  15. [Pneumomediastinum during a dermatomyositis: a rare entity]. (United States)

    Majdoub, Senda; Zemni, Houcem; Zaghouani, Houneida; Ben Salem, Halima Houda; Amara, Habib; Bakir, Dajla; Kraeim, Chakib


    Dermatomyositis is a connective characterized by inflammation of skeletal muscle with cutaneous manifestations. Their etiologies, still unknown, associate environmental and genetic factors. Among lung complications described, interstitial pneumopathies are common complications. Other complications are rarely reported as pneumomediastinum. We report a case of pneumomediastinum with aeric in massive skin dissection occurred in a patient with dermatomyositis. We will discuss the frequency, causes and pathophysiology of the disease according to the literature.

  16. Opportunity of a Lifetime: A Student's Perspective (United States)

    Gomez, Carlos


    In this article, the author shares his journey of obstacles he has endured in his life. The author's journey begins in Tequila, a small town of Mexico, with his cherished and young mother giving birth at the age of 16. He is the oldest and only son, in a family of two younger sisters and two hard-working parents. Poverty has been a reality for his…

  17. Transforming a small business: A learning intervention

    Directory of Open Access Journals (Sweden)

    Dirk J. Geldenhuys


    Full Text Available Orientation: This article reports on a learning intervention in a brokers company with fewer than 50 employees. A rich description of the participants’ experience is provided. Research purpose: The purpose of the study was to explore the use of an experiential learning process during an organisation development (OD intervention in a small business by means of a case study.Motivation for the study: This study explored the important role of small businesses; the role of management; and, more specifically, organisation development models that were developed for large corporations; as these emphasise the need to study the purpose of organisation development interventions in small businesses.Research design, approach and method: The study reported on in this article was a qualitative case study in a small brokers company with 21 staff members. The data were analysed manually by means of qualitative content analysis.Main findings: The main finding of the research concerned how experiential learning intervention provided a space for participants to start exploring, and gradually changing the dynamics of their small business, by transforming their business into a more formal company.Practical/managerial implications: The primary implication is that experiential learning interventions that are operationalised, from a psychodynamic perspective, can be valuable when consulted by small businesses during their transformation towards becoming more formal companies.Contribution/value-add: This article contributes to the OD literature on small businesses, with fewer than 50 employees, by providing data on how the learning process, that commenced during an experiential learning intervention, assisted a small company to develop its identity towards that of a more formal company.

  18. SN 1987A - a linear polarimetric study

    Energy Technology Data Exchange (ETDEWEB)

    Mendez, M.; Clocchiatti, A.; Benvenuto, O.G.; Feinstein, C.; Marraco, H.G.


    Multicolor linear polarimetric observations of SN 1987A have been obtained between February 28 and April 29, 1987. The intrinsic polarization was shown to decrease at a constant position angle of 27 deg during the first month after the explosion, and 30 days after the explosion the polarization began to grown in the V, R, and I filters at a different position angle. A model to interpret this behavior is proposed. Results are presented for the expansion of the outer layers of the SN and the evolution of the photospheric density. 28 references.

  19. Converting a Display Screen into a Touchscreen

    Institute of Scientific and Technical Information of China (English)

    Qun Wang; Jun Cheng; San-Ming Shen; Yi-Jiang Shen; Jian-Xin Pang


    A method is presented to convert any display screen into a touchscreen by using a pair of cameras. Most state of art touchscreens make use of special touch-sensitive hardware or depend on infrared sensors in various configurations. We describe a novel computer-vision-based method that can robustly identify fingertips and detect touch with a precision of a few millimeters above the screen. In our system, the two cameras capture the display screen image simultaneously. Users can interact with a computer by the fingertip on the display screen. We have two important contributions:first, we develop a simple and robust hand detection method based on predicted images. Second, we determine whether a physical touch takes places by the homography of the two cameras. In this system, the appearance of the display screen in camera images is inherently predictable from the computer output images. Therefore, we can compute the predicted images and extract human hand precisely by simply subtracting the predicted images from captured images.

  20. CASAS: A Smart Home in a Box. (United States)

    Cook, Diane J; Crandall, Aaron S; Thomas, Brian L; Krishnan, Narayanan C


    While the potential benefits of smart home technology are widely recognized, a lightweight design is needed for the benefits to be realized at a large scale. We introduce the CASAS "smart home in a box", a lightweight smart home design that is easy to install and provides smart home capabilities out of the box with no customization or training. We discuss types of data analysis that have been performed by the CASAS group and can be pursued in the future by using this approach to designing and implementing smart home technologies.

  1. CASAS: A Smart Home in a Box


    Cook, Diane J.; Crandall, Aaron S.; Thomas, Brian L.; Krishnan, Narayanan C.


    While the potential benefits of smart home technology are widely recognized, a lightweight design is needed for the benefits to be realized at a large scale. We introduce the CASAS “smart home in a box”, a lightweight smart home design that is easy to install and provides smart home capabilities out of the box with no customization or training. We discuss types of data analysis that have been performed by the CASAS group and can be pursued in the future by using this approach to designing and...

  2. A City Is a Complex Network

    CERN Document Server

    Jiang, Bin


    A city is not a tree but a semi-lattice. To use a more fashionable term, a city is a complex network. The complex network constitutes a unique topological perspective on cities and enables us to better understand the kind of problem a city is. The topological perspective differentiates it from the perspectives of Euclidean geometry and Gaussian statistics that deal with essentially regular shapes and more or less similar things. Many urban theories, such as the Central Place Theory, Zipf's Law, the Image of the City, and the Theory of Centers can be interpreted from the point of view of complex networks. A livable city consists of far more small things than large ones, and their shapes tend to be irregular and rough. This chapter illustrates the complex network view and argues that we must abandon the kind of thinking guided by Euclidean geometry and Gaussian statistics, and instead adopt fractal geometry, power-law statistics, and Alexander's living geometry to develop sustainable cities. Keywords: Scaling, ...

  3. Simulating a Guitar with a Conventional Sonometer (United States)

    Burstein, Zily; Gower, Christina M.; Varieschi, Gabriele U.

    Musical acoustics is an interesting sub-field of physics which is usually able to engage students in a dual perspective, by combining science and art together. The physics principles involved in most musical instruments can be easily demonstrated with standard laboratory equipment and can become part of lecture or lab activities. In particular, we will show in this paper how to simulate a guitar using a conventional sonometer, in relation to the problem of the instrument intonation, i.e., how to obtain correctly tuned notes on a guitar or similar string instruments.

  4. Simulating a guitar with a conventional sonometer

    CERN Document Server

    Burstein, Zily; Varieschi, Gabriele U


    Musical acoustics is an interesting sub-field of physics which is usually able to engage students in a dual perspective, by combining science and art together. The physics principles involved in most musical instruments can be easily demonstrated with standard laboratory equipment and can become part of lecture or lab activities. In particular, we will show in this paper how to simulate a guitar using a conventional sonometer, in relation to the problem of the instrument intonation, i.e., how to obtain correctly tuned notes on a guitar or similar string instruments.

  5. A água e a vida




    Trata-se de exercício de interpretação da frase “tudo é água”, atribuída a Tales de Mileto. Depois da exposição dos pontos de vista do senso comum, da ciência e da filosofia sobre a utilidade da água para a vida, tenta-se recuperar, na dimensão simbólica, suas significações mais profundas como fonte, purificação e regeneração da vida humana. O artigo sugere que a poluição das á...

  6. Registered access: a 'Triple-A' approach. (United States)

    Dyke, Stephanie O M; Kirby, Emily; Shabani, Mahsa; Thorogood, Adrian; Kato, Kazuto; Knoppers, Bartha M


    We propose a standard model for a novel data access tier - registered access - to facilitate access to data that cannot be published in open access archives owing to ethical and legal risk. Based on an analysis of applicable research ethics and other legal and administrative frameworks, we discuss the general characteristics of this Registered Access Model, which would comprise a three-stage approval process: Authentication, Attestation and Authorization. We are piloting registered access with the Demonstration Projects of the Global Alliance for Genomics and Health for which it may provide a suitable mechanism for access to certain data types and to different types of data users.

  7. A method for making a battery

    Energy Technology Data Exchange (ETDEWEB)

    Yamadzaki, K.; Kumano, Y.; Nakanisi, M.; Yamane, T.


    A layer of electrolyte which is melted with heating is made by pressing at a pressure of 0.1 to 0.8 tons of force per square centimeter a powder form compound. The inorganic adsorbent is first impregnated with an electrolyte, hardened by cooling and ground. The obtained disk with an interior opening is pressed at high pressure of 0.5 to 3 tons of force per square centimeter with a layer of an agglomerate mass. Elements made from the two layered disk, the anode and the body, have high mechanical strength. The internal resistance in the element is reduced. The battery has high discharge characteristics.

  8. Hepatitis A and HIV (United States)

    ... Problems : Hepatitis A Subscribe Translate Text Size Print Hepatitis A What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis B and Hepatitis C . Hepatitis A and HIV Hepatitis A is preventable with ...

  9. What's a Vegetarian? (United States)

    ... What Happens in the Operating Room? What's a Vegetarian? KidsHealth > For Kids > What's a Vegetarian? A A ... cows) and eggs (from chickens). Many Types of Vegetarians There are many kinds of vegetarians. Here are ...

  10. Making a Quit Plan (United States)

    ... Driving Finishing a meal Finishing a meal Drinking coffee Drinking coffee Taking a work break Taking a work break ... you smoke to relieve stress or improve your mood? Do you smoke to relieve stress or improve ...

  11. Towards a personalized Internet: a case for a full decentralization. (United States)

    Kermarrec, Anne-Marie


    The Web has become a user-centric platform where users post, share, annotate, comment and forward content be it text, videos, pictures, URLs, etc. This social dimension creates tremendous new opportunities for information exchange over the Internet, as exemplified by the surprising and exponential growth of social networks and collaborative platforms. Yet, niche content is sometimes difficult to retrieve using traditional search engines because they target the mass rather than the individual. Likewise, relieving users from useless notification is tricky in a world where there is so much information and so little of interest for each and every one of us. We argue that ultra-specific content could be retrieved and disseminated should search and notification be personalized to fit this new setting. We also argue that users' interests should be implicitly captured by the system rather than relying on explicit classifications simply because the world is by nature unstructured, dynamic and users do not want to be hampered in their actions by a tight and static framework. In this paper, we review some existing personalization approaches, most of which are centralized. We then advocate the need for fully decentralized systems because personalization raises two main issues. Firstly, personalization requires information to be stored and maintained at a user granularity which can significantly hurt the scalability of a centralized solution. Secondly, at a time when the 'big brother is watching you' attitude is prominent, users may be more and more reluctant to give away their personal data to the few large companies that can afford such personalization. We start by showing how to achieve personalization in decentralized systems and conclude with the research agenda ahead.

  12. A characterization of associativity (United States)

    Charlesworth, Arthur


    A necessary and sufficient condition for associativity of a function is given, in terms of a particular relation being a function. The concept of an associative function is generalized to the concept of a function being asssociative relative to a sequence and a characterization of such relative associativity is also given. These two characteristics are applied to the problem of proving the associativity, or relative associativity, of a function.

  13. Designing for a Dollar a Day

    DEFF Research Database (Denmark)

    Kyng, Morten


    for independent end user design activities. I go on by presenting a set of "cheap tools" and techniques, including the use mockup's. This set covers the issues of establishing the possibility of alternatives, of creating visions of new and different uses of technology, and of designing computer support. A central...

  14. Marketing Education on a Shoestring: A Model. (United States)

    Shreeve, William; And Others

    Few educators envision themselves as marketing or public relations experts, yet economic reality is forcing many academicians into these roles. Over the past four years, the Eastern Washington University Department of Education has developed a successful marketing model for educators. The model begins with a successful reform of department…

  15. Quest for a Sustainable University: A Review (United States)

    Amaral, Luís P.; Martins, Nelson; Gouveia, Joaquim B.


    Purpose: The paper aims to deliver a general review of the methods used to pursue the concept of a "sustainable university". Design/methodology/approach: The research was Internet based, and it included research papers, books, conference proceedings, technical reports and Internet Web sites. The review was divided in two main parts:…

  16. Decapitation: A Case for a Better Guillotine (United States)


    to success. 30 Robert S. Litwak, “Regime Change or Change in a Regime,” in Proliferation of WMD in the Middle East, editor James A. Russell (New...Bush, The National Security Strategy of the United States of America (Washington D.C.: The White House, March 2006). 35 John King, David Ensor , Jamie

  17. A linguistic integration of a biological database

    Energy Technology Data Exchange (ETDEWEB)

    Collado-Vides, J. [Univ. Nacional Autonoma de Mexico, Morelos (Mexico)


    One of the major theoretical concerns associated with the Human Genome Project is that of the methodology to decipher ``raw`` sequences of DNA. This work is concerned with a subsequent problem, the one of how huge amounts of already deciphered information that will emerge in the near future can be integrated in order to enhance their biological understanding. The formal foundations for a linguistic theory of the regulation of gene expression will be discussed. The linguistic analysis presented here is restricted to sequences with known biological function since: (1) there is no way to obtain, from DNA sequences alone, a regulatory representation of transcription units, and (2) the elements of substitution -- methodologically equivalent to phonemes -- are complete sequences of the binding sites of proteins. The authors have recently collected and analyzed the regulatory regions of a large number of E. coli promoters. The number of sigma 70 promoters studied may well represent the largest homogeneous body of knowledge of gene regulation at present. This collection is a data set for the construction of a grammar of the sigma 70 system of transcription and regulation. This grammatical model generates all the arrays of the collection, as well as novel combinations predicted to be consistent with the principles of the data set. This Grammar is testable, as well as expandable if the analysis of emerging data requires it. The elaboration of a linguistic methodology capable of integrating prokaryotic data constitutes a preliminary step towards the analysis and integration of the more complex eukaryotic systems of regulation.

  18. A Transmedia Topology of 'Making a Murderer'

    NARCIS (Netherlands)

    Hook, Alan; Barrios-O'Neill, Danielle; Mairs Dyer, Jolene


    textabstractThis article constructs a transmedia topology of the Making a Murderer text, demonstrating influences of various forms of documentary, interactive gaming culture, and post-digital writing on the series itself as well as on the paratextual cloud of works that grew up around it. Here we de

  19. Building a Digital Library on a Shoestring (United States)

    Boyd, Kate Foster; Creighton, Alma


    In this article, the authors discuss ways one can create a digital library on a shoestring despite the current high technology costs. Here, they describe the University of South Carolina's digital library development. The cost associated with building and maintaining the digital collections seems to have been worth it based on the feedback that…

  20. Glomus jugulare (Type A: A case review

    Directory of Open Access Journals (Sweden)

    Vinod T Kandakure


    Full Text Available We report a glomus jugulare tumor in a 60 yrs old female; non diabetic, non hypertensive who presented with continuous pulsatile hissing tinnitus in right ear with progressive hearing impairment and fullness in the ear. Detailed history and examination with aid of investigations it turned out to be glomus jugulare, treated by surgical excision by post auricular hypotympanotomy approach.


    Directory of Open Access Journals (Sweden)

    Valentin BUTOESCU


    Full Text Available A vortex model of a helicopter rotor is presented. Each blade of the rotor has three degrees of freedom: flapping, lagging and feathering. The motions after each degree of freedom are also known for all blades. The blade is modelled as a thin vortex surface. The wakes are free fluid surfaces. A system of five equations are obtained: the first one is the integral equation of the lifting surface (rotor, the next three describe the wakes motion, and the last one relates the vortex strength on the wakes and the variation of vorticity on the rotor. A numerical solution of this system is presented. To avoid the singularities that can occur due to the complexity of vortex system, a desingularized model of the vortex core was adopted. A Mathcad worksheet containing the method has been written.The original contribution of the work. The calculation method of the motion of the wakes free vortex system, the development of the vortex cores in time and a new method to approximate the aerodynamic influence of remoted wake regions.

  2. [A strong man with a weak shoulder]. (United States)

    Henket, Marjolijn; Lycklama á Nijeholt, Geert J; van der Zwaal, Peer


    A 47-year-old former olympic athlete had pain and weakness of his left shoulder. There was no prior trauma. He had full range-of-motion and a scapular dyskinesia. There was atrophy of the trapezius and sternocleidomastoideus muscles. He was diagnosed with 'idiopathic neuritis of the accessorius nerve'.

  3. Just a routine operation: a critical discussion. (United States)

    McClelland, G; Smith, M B


    This article has summarised a critical discussion of the human factors that contributed to the death of a patient from a failure to respond appropriately to a 'can't intubate, can't ventilate' scenario. The contributory factors included the clinical team's inability to communicate, prioritise tasks and demonstrate effective leadership and assertive followership. The film Just a routine operation has now been in circulation for several years. When a system is designed and introduced with the intention of making a change to clinical practice, it can quickly become just another component of an organisation's architecture and complacency around its use can develop. This article has been written specifically for perioperative practitioners to renew the debate around the human factors that contribute to patient harm. By critically discussing Just a routine operation and attempting to review why the incident occurred, this article has attempted to emphasise that some of the conditions and behaviours that contributed to the death of Elaine Bromiley may be latent within our organisations and teams, and may continue to contribute to failures that affect patient safety.

  4. How Could a Beaver Start a War? (United States)

    Millward, Robert


    Students gain a better understanding of war and economics when the variables come alive through stories, artifacts, and paintings. In this article, the author describes a short story about the fur trade which can generate lots of student questions about the fur economics, the Eastern Woodland Indians, trade artifacts, and war. The author also…

  5. Merging a Library and a Computing Center. (United States)

    Plane, Robert A.


    Details are provided of the development of a new library at Clarkson College. It was seen from the start that the new center needed to be viewed as the hub of a campus-wide system to provide integrated informational support for instructional, research, and administrative activities of the entire college. (MP)

  6. Matematicas: Nivel A (Mathematics: Level A). (United States)

    Duron, Dolores; And Others

    A teacher's manual was developed for an elementary level mathematics course in Spanish as part of an immersion program for English speaking children. The Level A manual is designed for kindergarten and grade 1 pupils. Teaching procedures, conceptual objectives, vocabulary, and structures are included. Activities are designed to teach either…

  7. A Reverse Shock in GRB 160509A

    CERN Document Server

    Laskar, Tanmoy; Berger, Edo; Fong, Wen-fai; Margutti, Raffaella; Shivvers, Isaac; Williams, Peter K G; Kopac, Drejc; Kobayashi, Shiho; Mundell, Carole; Gomboc, Andreja; Zheng, WeiKang; Menten, Karl M; Graham, Melissa L; Filippenko, Alexei V


    We present the second multi-frequency radio detection of a reverse shock in a $\\gamma$-ray burst. By combining our extensive radio observations of the Fermi-LAT GRB 160509A at $z = 1.17$ up to $20$ days after the burst with Swift X-ray observations and ground-based optical and near-infrared data, we show that the afterglow emission comprises distinct reverse shock and forward shock contributions: the reverse shock emission dominates in the radio band at $\\lesssim10~$days, while the forward shock emission dominates in the X-ray, optical, and near-infrared bands. Through multi-wavelength modeling, we determine a circumburst density of $n_0\\approx10^{-3}~$cm$^{-3}$, supporting our previous suggestion that a low-density circumburst environment is conducive to the production of long-lasting reverse shock radiation in the radio band. We infer the presence of a large excess X-ray absorption column, $N_{\\rm H} \\approx 1.5\\times10^{22}~$cm$^{-2}$, and a high rest-frame optical extinction, $A_{\\rm V}\\approx3.4~$mag. We...

  8. A Report on A Christmas Carol

    Institute of Scientific and Technical Information of China (English)



    @@ Charles Dickens is generally considered the greatest English novelist of the Victorian period,as well as a vigorous social campaigner.His works are characterized by attacks on social evils,injustice and hypocrisy,and among which there is one that Dickens called his "little Christmas Book",that is A Christmas Carol.

  9. Radioactivity a history of a mysterious science

    CERN Document Server

    Malley, Marjorie C


    Beginning with an obscure discovery in 1896, radioactivity led researchers on a quest for understanding that ultimately confronted the intersection of knowledge and mystery. This book tells the story of a new science that profoundly changed physics and chemistry, as well as areas such as medicine, geology, meteorology, archaeology, industry, politics, and popular culture.

  10. Marry a Man, Not a House

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiang


    I used to consider owning a house a must for my future husband.Men without good finances weren't appealing to me.After graduating university,I met my first boyfriend.I loved him,but I loved his money,too.Our romance only lasted several months and ended in my heartbreak.

  11. A phylogenetic blueprint for a modern whale. (United States)

    Gatesy, John; Geisler, Jonathan H; Chang, Joseph; Buell, Carl; Berta, Annalisa; Meredith, Robert W; Springer, Mark S; McGowen, Michael R


    The emergence of Cetacea in the Paleogene represents one of the most profound macroevolutionary transitions within Mammalia. The move from a terrestrial habitat to a committed aquatic lifestyle engendered wholesale changes in anatomy, physiology, and behavior. The results of this remarkable transformation are extant whales that include the largest, biggest brained, fastest swimming, loudest, deepest diving mammals, some of which can detect prey with a sophisticated echolocation system (Odontoceti - toothed whales), and others that batch feed using racks of baleen (Mysticeti - baleen whales). A broad-scale reconstruction of the evolutionary remodeling that culminated in extant cetaceans has not yet been based on integration of genomic and paleontological information. Here, we first place Cetacea relative to extant mammalian diversity, and assess the distribution of support among molecular datasets for relationships within Artiodactyla (even-toed ungulates, including Cetacea). We then merge trees derived from three large concatenations of molecular and fossil data to yield a composite hypothesis that encompasses many critical events in the evolutionary history of Cetacea. By combining diverse evidence, we infer a phylogenetic blueprint that outlines the stepwise evolutionary development of modern whales. This hypothesis represents a starting point for more detailed, comprehensive phylogenetic reconstructions in the future, and also highlights the synergistic interaction between modern (genomic) and traditional (morphological+paleontological) approaches that ultimately must be exploited to provide a rich understanding of evolutionary history across the entire tree of Life.

  12. Making a Computer Club, Making a Community. (United States)

    Gillingham, M.; Youniss, E.


    Describes the development of a computer club at an inner city elementary school in Chicago. Discusses the sense of community that grew; parent involvement; scaffold learning; self-control; community service; difficulties in creating a sustainable innovation; and possible future directions. (Contains 11 references.) (LRW)

  13. A Miracle over A Decadef Wuxi Sunmart

    Institute of Scientific and Technical Information of China (English)


    @@ Miracle started A decade ago, Wuxi Sunmart was just no name.At that time, few people noticed Jiangsu Snow Leopard Atomi-zation Pot Industry Limited Company, which was established in early 1998, as it was a small workshop with the registered capital of only RMB 1.6 million.And that is where Wuxi Sunmart's miracle began.

  14. A Note on a Result of Pesin

    Institute of Scientific and Technical Information of China (English)

    Qu Yan-hui


    Pesin gives an equivalent definition of the pressures defined respectively by open covering and Bowen covering of the dynamical system which plays an important role in the studies on dimension theory in dynamical systems.In this note,we show a gap of his proof and present a proof for this result.

  15. A strong start, a promising future

    Institute of Scientific and Technical Information of China (English)

    Zihe Rao


    @@ Protein & Cell has made a very strong start in its first full year of publication, covering 12 monthly issues with a consistently high standard of content and production. Thanks to the contributors, editors, editorial board, editodal staff and publishers, both the scientific quality and the production quality of the journal have been outstanding.

  16. A false explosion for a real intervention

    CERN Multimedia


    Together with their French and Swiss counterparts, the CERN Fire Brigade carried out a spectacular exercise in the LHCb cavern. It was designed to test the coordination of the fire and rescue services of the Organization's two Host States. Inside a temporary medical station set up above ground, the emergency teams deliver medical care to the injured before they are taken to hospital.An accident victim in the underground cavern about to be evacuated. 'I was taking a group of visitors on a tour of the LHCb cavern when there was a huge explosion and I suffered serious burns to the thorax. The rescue services arrived on the scene and I was taken to the medical station'. Fortunately, this is not an account of real events but a scenario given to one of 20 volunteer 'victims' who took part in a large-scale safety exercise in the LHCb cavern. On 26 September, the CERN Fire Brigade organised a spectacular exercise in collaboration with the CERN Medical Service, the Fire and Rescue Service (SDIS) of the Department of t...

  17. A Super Computer For a Super City

    Institute of Scientific and Technical Information of China (English)



    It’s a gigantic construction site that stretches beyond the horizon. Blue and red heavy-duty trucks in endless lines trundle about beneath a gaggle of cranes hoisting steel. And all the while enormous ultramodern buildings,bearing the names of the largest local and international companies,rise from the earth.

  18. A Reverse Shock in GRB 130427A

    CERN Document Server

    Laskar, T; Zauderer, B A; Margutti, R; Soderberg, A M; Chakraborti, S; Lunnan, R; Chornock, R; Chandra, P; Ray, A


    We present extensive radio and millimeter observations of the unusually bright GRB 130427A at z=0.340, spanning 0.67 to 12 days after the burst. Taken in conjunction with detailed multi-band UV, optical, NIR, and X-ray observations we find that the broad-band afterglow emission is composed of distinct reverse shock and forward shock contributions. The reverse shock emission dominates in the radio/millimeter and at 0.1 days in the UV/optical/NIR. We further find that the optical and X-ray data require a Wind circumburst environment, pointing to a massive star progenitor. Using the combined forward and reverse shock emission we find that the parameters of the burst are an isotropic kinetic energy of E_Kiso~2e53 erg, a mass loss rate of Mdot~3e-8 Msun/yr (for a wind velocity of 1,000 km/s), and a Lorentz factor at the deceleration time of Gamma(200s)~130. Due to the low density and large isotropic energy, the absence of a jet break to ~15 days places only a weak constraint on the opening angle of theta_j>2.5 deg...

  19. With a little help from a friend.

    NARCIS (Netherlands)

    Schildwacht, R.; Bolhuis, S.; Broeders, A.


    The artcle describes the outcomes of a pilot study on professional development of teachers. The project was initiated by the school management. Nine teachers volunteered to work on their professional development in a programme consisting of: • meetings discussing on relevant teacher topics • meetin

  20. A Small Essay About a Big Boulevard

    Directory of Open Access Journals (Sweden)

    Elena Grigoryeva


    Full Text Available The essay presents the analogies of turning city borders and walls into boulevards and gardens through the examples of Moscow and Irkutsk. The main street of Irkutsk is viewed in a new light, as a boulevard. It is proposed to take into consideration the peculiarities of the four sense-parts of the street when working on design codes.

  1. When a body meets a body

    DEFF Research Database (Denmark)

    Pelowski, Matthew John; Liu, Tao; Palacios, Victor


    We consider the phenomenon of social interactions within the art museum, arguing that even the bare possibility of meeting others or intruding into their gaze can have a profoundly detrimental effect on art experience. This is done by tracing a finding from our previous studies in which we consid...

  2. Death Ends a Life, not a Relationship

    DEFF Research Database (Denmark)

    Christensen, Dorthe Refslund; Sandvik, Kjetil


    In the final chapter, “Death Ends a Life, not a Relationship: objects as media on children’s graves”, Dorthe Refslund Christensen and Kjetil Sandvik investigate the relational affordances offered by objects as media in practices of death and commemoration on children’s graves. The authors argue t...

  3. "One Wears a Melon, Another a Cylinder"

    DEFF Research Database (Denmark)

    Shaw, Philip; Caudery, Tim; Petersen, Margrethe

    This paper analyses interviews with exchange students in four Scandinavian universities and conducts a longitudinal analysis of three picture descriptions spread over a twenty-week period. It briefly describes the opportunities available to exchange students for language learning, both English an...

  4. A sun holiday is a sunburn holiday

    DEFF Research Database (Denmark)

    Petersen, Bibi; Thieden, Elisabeth; Philipsen, Peter Alshede


    Many people take holidays in sunny locations with the express aim of sunbathing. This may result in sunburn, which is a risk factor for skin cancer. We investigated 25 Danish sun seekers during a week's holiday in the Canary Islands. The percentage of body surface area with sunburn was determined...

  5. Danish - a Language with a Future?

    DEFF Research Database (Denmark)

    Petersen, Margrethe; Shaw, Philip


    A project on the use of English for academic purposes in Denmark has revealed that the academic article written in Danish may be a dying genre. Based on this finding and on observations on the use of English in Danish texts (or contexts), the future of the Danish language and of translation and i...

  6. From a magnet to a heat pump

    DEFF Research Database (Denmark)

    Navickaité, Kristina; Neves Bez, Henrique; Engelbrecht, Kurt


    The magnetocaloric effect (MCE) is the thermal response of a magnetic material to an applied magnetic field. Magnetic cooling is a promising alternative to conventional vapor compression technology in near room temperature applications and has experienced significant developments over the last fi...

  7. Ciencia: Nivel A (Science: Level A). (United States)

    Duron, Dolores; And Others

    A teacher's manual was developed for an elementary level science course in Spanish as part of an immersion program for English speaking children. The Level A manual is designed for kindergarten and grade 1 pupils. The five units cover the basic concepts of the weather, colors, animals, plants, and the five senses. Each unit includes vocabulary,…

  8. A military home with a heart. (United States)

    Cowper, Andy


    A classically inspired and iconic building by the Thames in south west London, the Royal Hospital Chelsea is home to the equally iconic Chelsea pensioners--retired ex-military staff who have come to live in this unique retirement community. Now the nursing needs of this special group are being met in a new wing of the site, called the Margaret Thatcher Infirmary.

  9. A step up for a few postdocs

    CERN Multimedia


    Dutch postdocs at the Netherlands Cancer Institute complained recently of their lack of research independance and poor career progress. As a result they are now getting a proper career structure. Other institutions should also tackle this problem before serious recruitment problems develop (1/2 p).

  10. Could a zygote be a human being? (United States)

    Burgess, John


    This paper re-examines the question of whether quirks of early human foetal development tell against the view (conceptionism) that we are human beings at conception. A zygote is capable of splitting to give rise to identical twins. Since the zygote cannot be identical with either human being it will become, it cannot already be a human being. Parallel concerns can be raised about chimeras in which two embryos fuse. I argue first that there are just two ways of dealing with cases of fission and fusion and both seem to be available to the conceptionist. One is the Replacement View according to which objects cease to exist when they fission or fuse. The other is the Multiple Occupancy View - both twins may be present already in the zygote and both persist in a chimera. So, is the conceptionist position tenable after all? I argue that it is not. A zygote gives rise not only to a human being but also to a placenta - it cannot already be both a human being and a placenta. Neither approach to fission and fusion can help the conceptionist with this problem. But worse is in store. Both fission and fusion can occur before and after the development of the inner cell mass of the blastocyst - the entity which becomes the embryo proper. The idea that we become human beings with the arrival of the inner cell mass leads to bizarre results however we choose to accommodate fission and fusion.

  11. A child with pica. A case presentation.

    Directory of Open Access Journals (Sweden)

    Lidia Rosa Pérez González


    Full Text Available This is a case of a 4 year old child who was brought to the provincial Pediatric Hospital because of faecal stones. Iron deficit and intestinal parasites were found . The patient received treatment for 6 months till the ingestion of stones disappeared with the control of the etiologic factors that caused it.

  12. Mapping a Space for a Rhetorical-Cultural Analysis: A Case of a Scientific Proposal (United States)

    Dorpenyo, Isidore Kafui


    This article analyzes a proposal submitted to a funding unit in Michigan Technological University by a PhD Forestry student. A rhetorical-cultural approach of the text provides evidence to argue that scientific writing is rooted in a cultural practice that valorizes certain kinds of thought, practices, rituals, and symbols; that a scientist's work…

  13. Ever Fly a Tetrahedron? (United States)

    King, Kenneth


    Few things capture the spirit of spring like flying a kite. Watching a kite dance and sail across a cloud spotted sky is not only a visually appealing experience it also provides a foundation for studies in science and mathematics. Put simply, a kite is an airfoil surface that flies when the forces of lift and thrust are greater than the forces of…

  14. A Pleasing Birth

    NARCIS (Netherlands)

    Vries, De Raymond


    Women have long searched for a pleasing birth-a birth with a minimum of fear and pain, in the company of supportive family, friends, and caregivers, a birth that ends with a healthy mother and baby gazing into each other's eyes. For women in the Netherlands, such a birth is defined as one at home un

  15. A Reverse Shock in GRB 160509A (United States)

    Laskar, Tanmoy; Alexander, Kate D.; Berger, Edo; Fong, Wen-fai; Margutti, Raffaella; Shivvers, Isaac; Williams, Peter K. G.; Kopač, Drejc; Kobayashi, Shiho; Mundell, Carole; Gomboc, Andreja; Zheng, WeiKang; Menten, Karl M.; Graham, Melissa L.; Filippenko, Alexei V.


    We present the second multi-frequency radio detection of a reverse shock in a γ-ray burst. By combining our extensive radio observations of the Fermi-Large Area Telescope γ-ray burst 160509A at z = 1.17 up to 20 days after the burst with Swift X-ray observations and ground-based optical and near-infrared data, we show that the afterglow emission comprises distinct reverse shock and forward shock contributions: the reverse shock emission dominates in the radio band at ≲10 days, while the forward shock emission dominates in the X-ray, optical, and near-infrared bands. Through multi-wavelength modeling, we determine a circumburst density of {n}0≈ {10}-3 {{cm}}-3, supporting our previous suggestion that a low-density circumburst environment is conducive to the production of long-lasting reverse shock radiation in the radio band. We infer the presence of a large excess X-ray absorption column, N H ≈ 1.5 × 1022 {{cm}}-2, and a high rest-frame optical extinction, A V ≈ 3.4 mag. We identify a jet break in the X-ray light curve at {t}{jet}≈ 6 {days}, and thus derive a jet opening angle of {θ }{jet}≈ 4^\\circ , yielding a beaming-corrected kinetic energy and radiated γ-ray energy of {E}{{K}}≈ 4× {10}50 erg and {E}γ ≈ 1.3× {10}51 erg (1-104 keV, rest frame), respectively. Consistency arguments connecting the forward shocks and reverse shocks suggest a deceleration time of {t}{dec} ≈ 460 s ≈ T 90, a Lorentz factor of {{Γ }}({t}{dec})≈ 330, and a reverse-shock-to-forward-shock fractional magnetic energy density ratio of {R}{{B}}\\equiv {ɛ }{{B},{RS}}/{ɛ }{{B},{FS}}≈ 8. Our study highlights the power of rapid-response radio observations in the study of the properties and dynamics of γ-ray burst ejecta.

  16. A cabeça voraz

    Directory of Open Access Journals (Sweden)

    Betty Mindlin


    Full Text Available o artigo focaliza um mito indígena sobre a cabeça voadora e voraz, registrado pela autora em vários grupos indígenas da Amazônia, como os Tupari, os Macurap, os Jabuti, os Aruá, os Sateré-Mawé. Cada versão do mito tem um enredo diferente, mas o tema intrigante é sempre o mesmo: a mutilação do corpo, a cabeça que se transforma ou cola-se num outro ser. Procura-se mergulhar no significado desse mito, ao qual Claude Lévi-Strauss dedicou boa parte de dois livros magistrais, A origem das maneiras da mesa e A oleira ciumenta, e que foi usado por Mário de Andrade no livro clássico sobre o herói brasileiro, Macunaína, uma das poucas obras de fição brasileira a se inspirar em temas e personagens míticos indígenas. O registro de campo desse mito é uma pequena ponta de um amplo trabalho de documentação da tradição e dos mitos indígenas brasileiros, que a autora vem realizando há alguns anos. A intenção, nesse texto, é compreender a riqueza do imaginário indígena brasileiro, insistir na necessidade de documentar culturas que são nossas contemporâneas e ainda bastante desconhecidas. A fição e a arte brasileiras poderiam ampliar muito o seu universo ao explorar e tentar compreender as raízes brasileiras que nos são dadas por mais de 200 povos indígenas do país. Também para os índios, escrever, contar, divulgar e usar nas próprias escolas os seus mitos é importante para reafirmar a identidade étnica e valorizar sua participação na sociedade brasileira.The article focuses an indian myth about a flying and voracious head, that was told to the author by several indian tribes from the Amazon, such as the Tupari, the Macurap, the Jabuti, the Aruá, the Sateré-Mawé. Each version has a different plot, but the intriguing theme is always the same: the mutilation of the body, a head that is transformed or attaches itself to another being. The essay delves into the meaning of this myth, to which Claude L

  17. A Fat Higgs with a Magnetic Personality

    CERN Document Server

    Craig, Nathaniel; Thaler, Jesse


    We introduce a novel composite Higgs theory based on confining supersymmetric QCD. Supersymmetric duality plays a key role in this construction, with a "fat" Higgs boson emerging as a dual magnetic degree of freedom charged under the dual magnetic gauge group. Due to spontaneous color-flavor locking in the infrared, the electroweak gauge symmetry is aligned with the dual magnetic gauge group, allowing large Yukawa couplings between elementary matter fields and the composite Higgs. At the same time, this theory exhibits metastable supersymmetry breaking, leading to low-scale gauge mediation via composite messengers. The Higgs boson is heavier than in minimal supersymmetric theories, due to non-decoupling D-terms and a large F-term quartic coupling. This theory predicts quasi-stable TeV-scale pseudo-modulini, some of which are charged under standard model color, possibly giving rise to long-lived R-hadrons at the LHC.

  18. Education:a discipline or a field?

    Institute of Scientific and Technical Information of China (English)

    WANG Hongcai


    Historically,scholars have made unfailing efforts to position education as a standard science,but no solid success has been achieved regardless of the positivistic paradigm,quantitative approaches,or value-free neutral stances they adopted.In China,scholars have set up a so-called"three independency"standard for the scientific study of education,but it has been finally proved invalid in practice.As interdisciplines permeate the field of education,education experiences a crisis of being colonized.After serious rethinking,interdisciplines were widely believed to do more good than harm to education.Therefore,education is beginning to transform from a"colony"to an"empire".In this transformation,education finds it necessary to break the traditional disciplinary boundaries and make it a field in which interdisciplinary communication is contributory to the enrichment of scholarship.

  19. A Hop, Skip and a Jump Away

    DEFF Research Database (Denmark)

    Smith, Shelley


    This paper will address spatial experience and issues of ownership, exchange and indeterminateness in urban public space. The contemporary urban situation is characterised by media and mobility, where the potential for alienation - not only from each other, but also from the spaces we occupy......, is prevalent. Themed and ‘designed' spaces - many of the most common public spaces of the contemporary urban environment - often propagate a limitation in the diversity of their users, but they also propagate a kind of spatial inertia - an object-fixation prescribing use within a pre-determined schematic...... that focuses on clearly demarcated borders for containment. The discipline of parkour - the art of movement - will be used as a lens through which to view the potential that lies in activating the indeterminate city, and accessing a sense of ownership, belonging and interconnectivity in urban public space....

  20. Workplace spirituality: A tool or a trend?

    Directory of Open Access Journals (Sweden)

    Philip J.W. Schutte


    Full Text Available Workplace spirituality is a construct widely discussed over the past few decades and it is a much-disputed inquiry field which is gaining the interest of practitioners and scholars. Some clarifications regarding concepts and definitions are necessary in order to structure and direct the current debate. The aim of this conceptual article is to gain a better understanding regarding the direction in which this field of study is progressing and to put the question on the table namely, whether workplace spirituality is only a new tool to be used in leadership development or is it a trend to be taken seriously? The results showed that this field has potential to further development. This article can be used as foundation for future studies within the knowledge area of practical theology.

  1. Gingivectomía a bisel externo

    Directory of Open Access Journals (Sweden)

    Teresita Burgos Fuentes


    Full Text Available ResumenEl propósito de este reporte es describir el alargamiento coronario como tratamiento estético periodontal. La gingivectomía es un tratamiento quirúrgico antiguo. La indicación para la gingivectomía es la eliminación completa de la bolsa periodontal, hiperplasias. El diseño fisiológico del margen libre gingival por el medio quirúrgico debe ser tomado en consideración. Se reporta un caso clínico de un paciente masculino de 32 años de edad que exhibe gran cantidad de encía cuando sonríe. El logro de resultados estéticos excelentes en la terapia no es una cuestión de azar, es algo planificado antes de iniciar el tratamiento. (Duazary 2008; 125-128AbstractThe purpose of this report is to describe the external level gingivectomy as a periodontal esthetic treatment; the gingivectomy is the oldest surgical approach in periodontal therapy. Indication for performance of the gingivectomy is the complete elimination of the periodontal pocket and hyperplasia gingival. The physiologic design of the free gingival margin by surgical means, gingivoplasty, must be taken under consideration. A clinic case is been reported, a 32 years old with a big amount of gum tissue when she smiles. The achievement of excellent esthetics results on a therapy is not a matter of luck, must be into the treatment plan before starting this one.Key words: periodontal treatment; gingivectomy; gingival hyperplasia.

  2. Biodiesel: A fuel, a lubricant, and a solvent (United States)

    Biodiesel is well-known as a biogenic alternative to conventional diesel fuel derived from petroleum. It is produced from feedstocks such as plant oils consisting largely of triacylglycerols through transesterification with an alcohol such as methanol. The properties of biodiesel are largely compet...

  3. A Clubhouse Is a Clubhouse Is a Clubhouse. (United States)

    Zhao, Y.; Mishra, P.; Girod, M.


    Describes the design, development, and implementation of a technology-rich after-school program for middle schools called KLICK (Kids Learning in Computer Klubhouses). Topics include learning activities; learning environments; constructivism; social and organizational arrangements; collaboration; the culture of schooling; and issues of innovation,…

  4. Determining a rotation of a tetrahedron from a projection

    CERN Document Server

    Gardner, Richard J; Theobald, Thorsten


    The following problem, arising from medical imaging, is addressed: Suppose that $T$ is a known tetrahedron in $\\R^3$ with centroid at the origin. Also known is the orthogonal projection $U$ of the vertices of the image $\\phi T$ of $T$ under an unknown rotation $\\phi$ about the origin. Under what circumstances can $\\phi$ be determined from $T$ and $U$?

  5. A Year To Make a Difference (United States)

    Howell, J. Emory


    Secondary School Feature Articles * Animating Reactions: A Low-Cost Activity for Particle Conceptualization at the Secondary Level, by Robert W. Milne, p 50. * The Gravity of the Situation, by Damon Diemente, p 55. You must be the change you wish to see in the world. Mahatma Ghandi The beginning of a new year always brings with it a feeling of anticipation, a desire to achieve new goals, and a certain urgency to accomplish. Beginning the last year of the 1900s seems somehow to amplify these feelings. This week I was reminded twice of the challenge that lies in focusing on those things that we can change and not being fettered by those we cannot. The first example occurred in my office on a Monday afternoon. A young woman was considering the choice between entering graduate school or seeking a high school teaching position. After approximately 10 years in the workforce, she had entered college and was now within a semester of graduation. While pursuing her studies she had served as a substitute teacher in her home community, believing the experience would affirm her longstanding desire to teach. The behavioral characteristics of some students seemed to be at odds with her memories of high school only a dozen years earlier. Now she was questioning whether she could make a difference in young lives or if she should give up the idea of teaching in high school in favor of graduate degrees in her discipline, which would lead to a career in post-secondary education. Although I assured her that she could indeed have a great impact on high school students, I empathized with the concern she was feeling. The second example occurred the same day, in a class for chemistry majors who are preparing to teach high school chemistry. While considering the importance of performance assessment, with discussion centered on a JCE article ((a href="//1998/jan/abs64.html">Rasp, S. L. J. Chem. Educ. 1998, 75, 64-66), one class member asked why we only discussed and read about what teachers

  6. A geomechanical model of a sinkhole formation (United States)

    Danchiv, Alexandru; Zamfirescu, Florian; Mocuta, Marius; Popa, Iulian; Zlibut, Alexandru; Huggenberger, Peter; Zechner, Eric; Dresmann, Horst; Scheidler, Stefan; Wiesmeier, Stefan


    On December 2010 a sinkhole was suddenly formed close to the eastern flank of Ocna-Mures salt dome. Soon after the collapse the sinkhole was filled with brine forming a salt lake called Plus Lake. The total volume of sinkhole of about 100000 m3 remained constant since February 2011. The Ocna Mures salt dome is situated on the western border of the Transylvanian basin (Romania) and has been exploited for a long time. The ceilings of some shallow mine chambers are now collapsed and filled with brine. Along the eastern flank of the salt dome there is a disturbed zone due to diapirism. Its presence is suggested by the strong fragmentation of rock in the boreholes drilled along the salt-sterile contact, as it resulted from the low values of RQD index. The sinkhole is probably due to a pressure increase along the diapir flank. The causes of this sudden increase of pressure are not well known. Most probably it is due to the damage of the tubing of a flank borehole as mentioned in a technical report of the exploiting company. The injected fresh water expelled through the breaches of the damaged borehole and, due to the high pressure flushed up the crushed material of the disturbed zone. In order to better understand the setting up of the Plus Lake joint research efforts were performed by teams from Bucharest and Basel Universities since 2013. For the geomechanical approach a numerical model was performed using the Flac 7.0 code. In a first stage the creep behavior of salt was analyzed considering a Norton creep law. It resulted that after 100 years the salt reached equilibrium, the creep could be neglected and in a first approximation mechanical equilibrium could be analyzed considering only an elasto-plastic behavior of both the salt and the sterile. For both the salt and the surrounding sedimentary rocks the Mohr-Coulomb criterion was considered. The properties of sterile rocks were estimated following the GSI system. Due to poor rock quality the strength parameters have

  7. Birth of a theorem a mathematical adventure

    CERN Document Server

    Villani, Cédric


    This man could plainly do for mathematics what Brian Cox has done for physics" (Sunday Times). What goes on inside the mind of a rock-star mathematician? Where does inspiration come from? With a storyteller's gift, Cedric Villani takes us on a mesmerising journey as he wrestles with a new theorem that will win him the most coveted prize in mathematics. Along the way he encounters obstacles and setbacks, losses of faith and even brushes with madness. His story is one of courage and partnership, doubt and anxiety, elation and despair. We discover how it feels to be obsessed by a theorem during your child's cello practise and throughout your dreams, why appreciating maths is a bit like watching an episode of Columbo, and how sometimes inspiration only comes from locking yourself away in a dark room to think. Blending science with history, biography with myth, Villani conjures up an inimitable cast of characters including the omnipresent Einstein, mad genius Kurt Godel, and Villani's personal hero, John Nash. Bir...

  8. A Transmedia Topology of 'Making a Murderer'

    Directory of Open Access Journals (Sweden)

    Alan Hook


    Full Text Available This article constructs a transmedia topology of the Making a Murderer text, demonstrating influences of various forms of documentary, interactive gaming culture, and post-digital writing on the series itself as well as on the paratextual cloud of works that grew up around it. Here we define transmedia topology as a tracing of what we could call the geography of the text, as defined by its features and boundaries (or lack thereof. We will discuss the intentionality of the series creators, as well as the emergence of a transmedial textuality that is owed largely to audiences and the textual terrain. The Making a Murderer series thus becomes the basis for a larger transmedia narrative that sprawls across social-digital networks, a pastiche of multifarious public reaction and unsanctioned investigation.The article maps the ecologies of interaction, participation and creation with and of the text by the audience to map the thresholds of the transmedial text and investigate new approaches to analysing transmedial work in the context of non-fiction media forms.

  9. A reductive coupling strategy towards ripostatin A

    Directory of Open Access Journals (Sweden)

    Kristin D. Schleicher


    Full Text Available Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim to construct the C9−C10 bond by a nickel(0-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1−C9 has been synthesized in high yield and demonstrated to be a competent substrate for the nickel(0-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10−C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted decarboxylation enables construction of the C15−C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment.

  10. A microtube viscometer with a thermostat

    Energy Technology Data Exchange (ETDEWEB)

    Silber-Li, Z.H. [LNM, Institute of Mechanics, Chinese Academy of Sciences, 15, Bei Si Huan Xi Lu, 100080, Beijing (China); Tan, Y.P. [LNM, Institute of Mechanics, Chinese Academy of Sciences, 15, Bei Si Huan Xi Lu, 100080, Beijing (China); Shanghai Institute of Applied Mathematics and Mechanics, Shanghai University, 200072, Shanghai (China); Weng, P.F. [Shanghai Institute of Applied Mathematics and Mechanics, Shanghai University, 200072, Shanghai (China)


    The viscometer presented in this paper is suitable for measuring the viscosity of liquids in micro-litre quantities. It consists of a micro-flow experimental system with a thermostat. Using the measurements of the flow rates and pressure drops of a liquid passing through a microtube, the liquid's viscosity can be calculated from on Hagen-Poiseuille theory. After calibration, the viscometer was used to measure viscosities of deionized water and ethyl alcohol at temperatures ranging from 0 to 40 C. For both test liquids, the relative deviation of the measured values from those quoted in the literature (obtained using other viscometers) was less than 2.6%. The relative uncertainty of the experimental system was reduced to {+-}1.8% using the relative measuring method. Due to the micro-scale of the test section, only a micro-litre quantity of liquid is needed for a test; this is a potential advantage for measurement of bio-liquid viscosities. (orig.)

  11. [Utilities: a solution of a decision problem?]. (United States)

    Koller, Michael; Ohmann, Christian; Lorenz, Wilfried


    Utility is a concept that originates from utilitarianism, a highly influential philosophical school in the Anglo-American world. The cornerstone of utilitarianism is the principle of maximum happiness or utility. In the medical sciences, this utility approach has been adopted and developed within the field of medical decision making. On an operational level, utility is the evaluation of a health state or an outcome on a one-dimensional scale ranging from 0 (death) to 1 (perfect health). By adding the concept of expectancy, the graphic representation of both concepts in a decision tree results in the specification of expected utilities and helps to resolve complex medical decision problems. Criticism of the utility approach relates to the rational perspective on humans (which is rejected by a considerable fraction of research in psychology) and to the artificial methods used in the evaluation of utility, such as Standard Gamble or Time Trade Off. These may well be the reason why the utility approach has never been accepted in Germany. Nevertheless, innovative concepts for defining goals in health care are urgently required, as the current debate in Germany on "Nutzen" (interestingly translated as 'benefit' instead of as 'utility') and integrated outcome models indicates. It remains to be seen whether this discussion will lead to a re-evaluation of the utility approach.

  12. Tesla - A Flash of a Genius (United States)

    Teodorani, M.


    This book, which is entirely dedicated to the inventions of scientist Nikola Tesla, is divided into three parts: a) all the most important innovative technological creations from the alternate current to the death ray, Tesla research in fundamental physics with a particular attention to the concept of "ether", ball lightning physics; b) the life and the bright mind of Nikola Tesla and the reasons why some of his most recent findings were not accepted by the establishment; c) a critical discussion of the most important work by Tesla followers.

  13. A woman with a dangling digit. (United States)

    Roesch, Alexander; Kinner, Bernd; Schaechinger, Ulrich; Obermann, Ellen C; Landthaler, Michael; Hohenleutner, Ulrich


    Ainhum (dactylolysis spontanea) is a distinct clinical and radiological disorder of dark-skinned people characterized by a progressive development of a constricting band encircling the toe which usually results in spontaneous amputation. Ainhum mainly occurs in African natives, but in times of global migration and tourism, Ainhum is likely to be more often encountered outside Africa. Even though the clinical presentation can mimic more common entities such as arthritis and trauma, the correct diagnosis and treatment is easy if one knows this unusual entity.

  14. Dialog between a Lexicographer and a Translator

    Directory of Open Access Journals (Sweden)

    Mark Kit


    Full Text Available Dialog between a Lexicographer and a Translator The discussion between the authors of the paper concerns the most pressing issues encountered in natural language semantics, as well as in corpus linguistics and computational linguistics. A broad range of knowledge, allowing linguists and information scientists to work together, is required in these areas. The paper describes some primary problems of human and machine translation caused by gaps between different fields of knowledge. The authors suggest that interdisciplinary approach is required when it comes to contrastive studies in linguistics.

  15. Locating a circle on a sphere

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita


    We consider the problem of locating a spherical circle with respect to existing facilities on a sphere, such that the sum of distances between the circle and the facilities is minimized or such that the maximum distance is minimized. The problem properties are analyzed, and we give solution...... procedures. When the circle to be located is restricted to be a great circle, some simplifications are possible. The models may be used in preliminary studies on the location of large linear facilities on the earth's surface, such as superhighways, pipelines, and transmission lines, or in totally different...

  16. A certain ambiguity a mathematical novel

    CERN Document Server

    Suri, Gaurav


    While taking a class on infinity at Stanford in the late 1980s, Ravi Kapoor discovers that he is confronting the same mathematical and philosophical dilemmas that his mathematician grandfather had faced many decades earlier--and that had landed him in jail. Charged under an obscure blasphemy law in a small New Jersey town in 1919, Vijay Sahni is challenged by a skeptical judge to defend his belief that the certainty of mathematics can be extended to all human knowledge--including religion. Together, the two men discover the power--and the fallibility--of what has long been considered the pinn

  17. Aproximaciones a la Econometría


    Espasa, Antoni


    En la concepción de la Econometría pueden adoptarse básicamente dos tipos de enfoques, que corresponden a dos formas distintas de concebir esta disciplina. Esta nota se hace eco de los comentarios críticos que la orientación econométrica basada en el supuesto de que las relaciones económicas son exactas ha recibido en la literatura, y se alinea en la corriente econométrica que se ha venido desarrollando a partir del trabajo pionero de Haavelmo (1944). Sobre esta publicación se puede decir, ut...

  18. A case study, Bagnoli: a difficult transition

    Directory of Open Access Journals (Sweden)

    Maria Antonietta Selvaggio


    In this research work we intend to verify how a particular physical-spatial dimension has influenced the social relations and the same identities of the people and their “community”, how we can delineate the perception and the performance of a urban transformation largely failed, and which contribution the citizens of Bagnoli can give to the urban design through their own imaginary and meanings they ascribe to their environment (Lynch 1960. In this sense, the study aim at giving a contribution to the participative practice, that up to now is out of the transition dynamics.

  19. A mathematical model for a gaming community

    CERN Document Server

    Breban, Romulus


    We consider a large community of individuals who mix strongly and meet in pairs to bet on a coin toss. We investigate the asset distribution of the players involved in this zero-sum repeated game. Our main result is that the asset distribution converges to the exponential distribution, irrespective of the size of the bet, as long as players can never go bankrupt. Analytical results suggests that the exponential distribution is a stable fixed point for this zero-sum repreated game. This is confirmed in numerical experiments.

  20. A Planck Vacuum Cosmology

    Directory of Open Access Journals (Sweden)

    Daywitt W. C.


    Full Text Available Both the big-bang and the quasi-steady-state cosmologies originate in some type of Planck state. This paper presents a new cosmological theory based on the Planck- vacuum negative-energy state, a state consisting of a degenerate collection of negative- energy Planck particles. A heuristic look at the Einstein field equation provides a con- vincing argument that such a vacuum state could provide a theoretical explanation for the visible universe.

  1. Guide for a typewriter (United States)

    Dubois, R. D.; Pinson, G. T. (Inventor)


    The invention relates to accessories for typewriters, and more particularly to an improved guide for use in aligning a sheet of paper preparatory to an application of typed indicia to selected spaces. The device includes an aligning plate pivotally mounted on a line guide having formed therein a plurality of aligned apertures. The plate is so positioned that an aperture is positioned immediately above a target area for a type slug so that a slug will imprint a character in selected spaces.

  2. The information a history, a theory, a flood

    CERN Document Server

    Gleick, James


    Winner of the Royal Society Winton Prize for Science Books 2012, the world's leading prize for popular science writing. We live in the information age. But every era of history has had its own information revolution: the invention of writing, the composition of dictionaries, the creation of the charts that made navigation possible, the discovery of the electronic signal, the cracking of the genetic code. In 'The Information' James Gleick tells the story of how human beings use, transmit and keep what they know. From African talking drums to Wikipedia, from Morse code to the 'bit', it is a fascinating account of the modern age's defining idea and a brilliant exploration of how information has revolutionised our lives.

  3. Harry Minti- a project for a book (United States)

    Gaina, Alex


    A short biography and an account of scientific research of the Associated Professor of the Hebrew University in Jerusalem (Israel), Dr. Harry Minti (b. 1938, Bucharest) is given. His activity as translator was also mentioned.

  4. A Subdermal Osteochondroma in a Young Girl (United States)

    Correa, Hernan


    Osteochondromas are common benign tumors of cartilage and bone. They are usually found as contiguous bone with a cartilage cap at the end of the growth plate of long bones. Similar to structure are extraskeletal osteochondromas. However, unlike typical osteochondromas, extraskeletal osteochondromas are noncontinuous with bone. To our knowledge, all reported extraskeletal osteochondromas have been contained within fascial compartments. Here we present the case of a 5-year-old female who had a slow growing mass of the anterior distal right thigh. Imaging studies revealed an ossified mass extending from dermal layer of the subcutaneous tissue with no connection to the underlying deep fascia. An excisional biopsy was performed and proved to be a subdermal extraskeletal osteochondroma. PMID:28133559

  5. Schizandrol A: a lignan from Schisandra chinensis

    Directory of Open Access Journals (Sweden)

    Liang Zhao


    Full Text Available The title compound (systematic name: 1,2,3,10,11,12-hexamethoxy-6,7-dimethyl-5,6,7,8-tetrahydrodibenzo[a,c]cycloocten-6-ol, C24H32O7, has a dibenzocyclooctadiene skeleton. There are three molecules in the asymmetric unit, which are related by a pseudo-translation in the direction of the c axis. Nevertheless, the three molecules differ in the torsion angle of one of the methoxy groups. The dihedral angles between the two aromatic rings are 62.39 (10, 62.65 (10 and 61.84 (10° for the three molecules. The crystal packing is stabilized by a series of O—H...O and C—H...O hydrogen bonds, as well as C—H...π interactions.

  6. Regenerating a kidney in a lymph node. (United States)

    Francipane, Maria Giovanna; Lagasse, Eric


    The ultimate treatment for end-stage renal disease (ESRD) is orthotopic transplantation. However, the demand for kidney transplantation far exceeds the number of available donor organs. While more than 100,000 Americans need a kidney, only 17,000 people receive a kidney transplant each year (National Kidney Foundation's estimations). In recent years, several regenerative medicine/tissue engineering approaches have been exploited to alleviate the kidney shortage crisis. Although these approaches have yielded promising results in experimental animal models, the kidney is a complex organ and translation into the clinical realm has been challenging to date. In this review, we will discuss cell therapy-based approaches for kidney regeneration and whole-kidney tissue engineering strategies, including our innovative approach to regenerate a functional kidney using the lymph node as an in vivo bioreactor.

  7. Can a Humean be a Contractarian?

    Directory of Open Access Journals (Sweden)

    Robert Sugden


    Full Text Available In this paper I argue, contrary to Hartmut Kliemt, that it is possible to be both a Humean and, in James Buchanan's sense, a contractarian. Hume sees principles of justice and political allegiance not as actual or hypothetical products of explicit agreement, but as conventions that have emerged spontaneously. However, it is fundamental to Hume's analysis that conventions are mutually advantageous, and hence cognate with agreements. The core idea in Buchanan's contractarianism is that the proper role of government is to implement voluntary exchanges between individuals, not to define and maximise a unified conception of social welfare. Although real politics cannot be based entirely on unanimous agreement, the voluntary exchange approach provides a valuable structure for normative economics.

  8. Umbanda: entre a cruz e a encruzilhada

    Directory of Open Access Journals (Sweden)



    Full Text Available O artigo considera a umbanda, religião afro-brasileira de constituição recente, como estando dividida entre os apelos de suas raízes negras e os atrativos legitimadores da adoção dos princípios éticos cristãos. Embora pouco racionalizada e postulando uma visão de mundo predominantemente encantada, vem crescentemente moralizando-se a partir, sobretudo, das influências do ideal kardecista da caridade. Tal incorporação não é, contudo, linear, mas reinterpretada a partir da vivência concreta de seus agentes e moderada pela necessidade da cobrança por serviços religiosos prestados e pela "demanda", concepção mágica de conflito inter-individual.

  9. What Makes a Wetland a Wetland? (United States)

    Naturescope, 1986


    Provides descriptions of and activities about various kinds of wetlands. Contains seven learning activities ranging from creating wetland scenes with picture cutouts to actually exploring a wetland. Includes reproducible handouts and worksheets for several of the activities. (TW)

  10. Triple A Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Murat Atmaca


    Full Text Available Triple A syndrome is a rarely seen autosomal recessive disease characterized by achalasia, adrenal failure and alacrima. The syndrome is frequently seen in childhood. The appearance of its components are usually ordered as alacrima, achalasia and adrenal failure. The majority of the patients diagnosed in the later stages predominantly present with neurological symptoms. In this study, a 21-year-old male who was referred to our clinic with clinical findings of chronic adrenal failure and was diagnosed WİTH triple A syndrome is presented. This patient had been operated three years ago due to achalasia. The diagnosis and treatment of adrenal failure in this syndrome is the most important determinant and indicator in the prognosis of the disease. Turk Jem 2014; 18: 97-99

  11. Pseudomyrmex nigropilosa: A Parasite of a Mutualism. (United States)

    Janzen, D H


    Pseudomyrmex nigropilosa is a parasite ofthe ant-acacia mutualism in Central America in that it harvests the resources of swollen-thorn acacias but does not protect the acacias. In the process, it also lowers the rate of occupation by the obligate acacia-ants, species of ants that do protect swollen-thorn acacias. Tenancy ofan acacia by P. nigropilosa must be temporary, since the unoccupied plant is shortly killed by herbivores or competing plants, or is taken over by obligate acacia-ants. As expected of a species of short-lived ant, a P. nigropilosa colony produces reproductives earlier in the life of the colony and maintains fewer grams of workers per gram of brood than does a colony of the long-lived obligate acacia-ants.

  12. A thing finished is a thing dead

    DEFF Research Database (Denmark)

    Baumeister, Ruth


    The article gives a general overview of Asger Jorn´s position in architecture. Besides his theoretical stands, it exemplifies his position by showing the artist´s private house and garden in Albissola, Italy....

  13. A teahouse in a tea garden


    Macfarlane, Alan


    The Japanese place tea at the centre of their social and ceremonial life. In this beautiful tea garden in Kyoto, the tea mistress makes tea and offers it to Alan Macfarlane, who talks a little about its role in history.

  14. Packing a cake into a box

    CERN Document Server

    Skopenkov, Mikhail


    Given a cake in form of a triangle and a box that fits the mirror image of the cake, how to cut the cake into a minimal number of pieces so that it can be put into the box? The cake has an icing, so that we are not allowed to put it into the box upside down. V.G. Boltyansky asked this question in 1977 and showed that three pieces always suffice. In this paper we provide examples of cakes that cannot be cut into two pieces to put into the box. This shows that three is the answer to V.G. Boltyansky's question. Also we give examples of cakes which can be cut into two pieces.

  15. A blackbody is not a blackbox

    CERN Document Server

    Smerlak, Matteo


    We discuss carefully the blackbody approximation, stressing what it is (a limit case of radiative transfer), and what it is not (the assumption that the body is perfectly absorbing, i.e. black). Furthermore, we derive the Planck spectrum without enclosing the field in a box, as is done in most textbooks. Athough convenient, this trick conceals the nature of the idealization expressed in the concept of a blackbody: first, the most obvious examples of approximate blackbodies, stars, are definitely not enclosed in boxes; second, the Planck spectrum is continuous, while the stationary modes of radiation in a box are discrete. Our derivation, although technically less elementary, is conceptually more consistent, and brings the opportunity to introduce to students the important concept of local density of states, via the resolvent formalism.

  16. A blackbody is not a blackbox (United States)

    Smerlak, Matteo


    We discuss carefully the blackbody approximation, stressing what it is (a limit case of radiative transfer), and what it is not (the assumption that the body is perfectly absorbing, namely black). Furthermore, we derive the Planck spectrum without enclosing the field in a box, as is done in most textbooks. Although convenient, this trick conceals the nature of the idealization expressed in the concept of a blackbody: first, the most obvious examples of approximate blackbodies, stars, are definitely not enclosed in boxes; second, the Planck spectrum is continuous, while the stationary modes of radiation in a box are discrete. Our derivation, although technically less elementary, is conceptually more consistent, and brings the opportunity to introduce to advanced undergraduate and graduate students the important concept of the local density of states via the resolvent formalism.

  17. A wave lab inside a coaxial cable (United States)

    Serra, João M.; Brito, Miguel C.; Alves, J. Maia; Vallera, A. M.


    The study of electromagnetic wave propagation in a coaxial cable can be a powerful approach to the study of waves at an undergraduate level. This study can explore different experimental situations, going from those where the finite velocity of propagation must be considered (distributed or transmission line behaviour), to those where this velocity may be considered infinite (lumped behaviour). We believe that the student observation of the existence of these two regimes can be important for the understanding of wave phenomena in general. In this work we show that this can be achieved using low-cost equipment and a set of quite simple experiments, such as the measurement of wave propagation velocity or the study of standing waves and resonance. The results obtained in a coherent set of selected experiments are discussed.

  18. Life of a Tooth: A Visual Timeline

    Medline Plus

    Full Text Available ... About | Contact InfoBites Quick Reference Learn more Children's Oral Health Men: Looking for a Better Job? Start by Visiting the Dentist Why is Oral Health Important for Men? Headaches and Jaw Pain? Check ...

  19. Gingivectomía a bisel externo


    Teresita Burgos Fuentes; Diana Marcela Palomino Romero; Antonio Díaz Caballero


    ResumenEl propósito de este reporte es describir el alargamiento coronario como tratamiento estético periodontal. La gingivectomía es un tratamiento quirúrgico antiguo. La indicación para la gingivectomía es la eliminación completa de la bolsa periodontal, hiperplasias. El diseño fisiológico del margen libre gingival por el medio quirúrgico debe ser tomado en consideración. Se reporta un caso clínico de un paciente masculino de 32 años de edad que exhibe gran cantidad de encía cuando sonríe. ...

  20. Can a dike "feel" a free surface? (United States)

    Pansino, S.; Taisne, B.


    This study uses analogue experiments to examine the various factors that could influence the dynamic or arrest of a dike prior to an eruption. Dike propagation has been well-studied from the perspective of analogue experiments and it has been shown how various competing forces interact (buoyancy, viscosity, elastic properties, fracture toughness,…). It has been observed that dikes experience acceleration as they approach a free surface, which theoretically is due to increasing stress intensity as distance to the free surface decreases. Other unrelated studies analysed the constant-volume propagation of low-surface-energy liquids (e.g. hydrophilic liquids) in a semi-infinite medium and found the propagation rate to decelerate, as liquid gradually transferred from the head region to the tail and buoyancy abated. In contrast, high-surface-energy fluids transfer negligible quantities of their volume into the tail region, essentially maintain their volume, and experience no such deceleration. This study focuses on the aforementioned factors influencing dike propagation, acceleration due to a free surface and deceleration due to head volume loss, to determine what their combined effect is on magma eruptability. As previous studies used hydrophobic liquids to investigate free-surface effects, and as magma is expected to have a low surface energy with the crust (they are both silicate), hydrophilic liquids (e.g. glucose syrup) are used in this study. Each experiment is arranged to have a free surface condition occupying half of the apparatus, and a no-slip condition occupying the other half, which allows for side-by-side comparison. The results are analysed to determine the minimum volume needed for a dike to erupt; failure to erupt implies that the dike would instead come to arrest in the crust.

  1. Ventana a la farmacología


    Revista Facultad de, Medicina


    Aspirina para prevenir el ataque cardiaco o apoplético / Alteraciones fetales causados por los inhibidores de la enzima de conversión de la angiotensina (eca) / Efectos teratogénicos de los derivados de la vitamina a / Efectos teratogénicos de la warfarina / Algunos avances en farmacología en la última década / ¿Anticonceptivos que previenen el cáncer de seno?

  2. What makes a movement a gesture? ☆


    Novack, Miriam A.; Wakefield, Elizabeth M.; Goldin-Meadow, Susan


    Theories of how adults interpret the actions of others have focused on the goals and intentions of actors engaged in object-directed actions. Recent research has challenged this assumption, and shown that movements are often interpreted as being for their own sake (Schachner & Carey, 2013). Here we postulate a third interpretation of movement—movement that represents action, but does not literally act on objects in the world. These movements are gestures. In this paper, we describe a framewor...

  3. A Reality Check on a Cyber Force (United States)


    policy and global affairs at the Air Force Re- search Institute. His research interests include the intersection of cyberspace and global security. He...holds PhD and MS degrees in global affairs from Rutgers University and an ALB degree in philosophy from Harvard University. A Reality Check on a Cyber...mili- tary strategy and doctrine as an operational domain in which to orga- nize, train, and equip forces to ensure it has the necessary capabilities

  4. Malaria vaccine: A myth or a reality


    Sarita Mohapatra


    Malaria is a common parasitic disease caused by Plasmodium spp. and transmitted by anopheles mosquito. Every year several million people are affected and killed due to this infection in the endemic regions of the world. Recently, drug resistance to the common antimalarial drugs has pressurized upon the development of an effective vaccine for the elimination of malaria along with other control measures. A number of vaccine trials are in the pipeline. Indeed, some were proven to have potential ...

  5. A note on a walrus’ European odyssey

    Directory of Open Access Journals (Sweden)

    E W Born


    Full Text Available This study reports on the first successful identification of the site of origin of an extralimital walrus in Europe. On 24 February 2010 an adult male Atlantic walrus (Odobenus rosmarus rosmarus migrant was instrumented with a SPOT-5 satellite-linked transmitter (SLT while hauled out on a beach on the Faroe Islands at 62° 15' N/06° 32' W. This SLT transmitted until 5 March during which period the walrus made local movements, likely for feeding. Transmissions were not received during 6-25 March, however, visual observations during this time indicated that the walrus remained at the Faroe Islands. A second transmitter was deployed on the same animal on 25 March 2010 at another site on the islands (62° 16' N/07° 04' W. Activity data collected over 13 days indicated that the walrus hauled out in three different places in the Faroe Islands and used a total of 24% of its time resting on land.  On 29 March 2010 the walrus left the Faroe Islands and headed WNW towards NE Iceland. On 2 April it took a NNE course and swam towards Svalbard where the last location was received from a sea ice covered area on 25 April 2010 at 78° 27' N/09° 20' E (i.e. ca. 40 km west of the island of Prins Karls Forland in the western Svalbard archipelago. During 29 March-22 April the walrus swam a minimum distance of 2216 km between the last location at the Faroe Islands and the first location at Svalbard, with an average swimming speed of 4.5 km/h. A genetic analysis indicated that this walrus belonged to the Svalbard-Franz Josef Land subpopulation, thereby confirming that it returned to its site of origin.

  6. A Deep Chandra Observation of A2052 (United States)

    Blanton, E. L.; Douglass, E. M.; Sarazin, C. L.; Clarke, T. E.; McNamara, B. R.

    We present initial results from a long (125 ksec) Chandra observation of Abell 2052. A2052 is a bright, nearby, cooling core cluster at a redshift of z=0.0348. It was previously observed for 36 ksec with Chandra [3,4]. The longer observation reveals ripples in the surface brightness, similar to what has been seen in e.g., the Perseus cluster [5] and M87/Virgo [6]. The southern cavity now appears to be split into two cavities with the southernmost cavity likely representing a ghost bubble from earlier radio activity. There also appears to be a ghost bubble present to the NW of the cluster center. Bright emission in the X-ray corresponds very well with optical line emission, and the correlated X-ray emission is seen to continue from the N bubble edge closer to the AGN in this longer exposure, tracking the H-α emission. The energy deposited by the radio source, as determined by measuring the pressure in the bright, X-ray shells, averaged over the repetition rate of the radio source (determined from either the ripple separation or the ghost cavity distances) can easily offset the cooling in the core of the cluster.

  7. De Analogía a Digitalia

    Directory of Open Access Journals (Sweden)

    Dr. Xaime Fandiño Alonso


    Full Text Available La transformación hacia la tecnología numérica ha provocado en el último decenio cambios importantes en los entornos de creación, operación, transformación y distribución de productos audiovisuales.Los restos de la era analógica están dando sus últimos estertores de la mano de unos entornos digitales, desarrollados velozmente.Estos nuevos equipos son en la mayoría de los casos prototipos. La velocidad del mercado, la competencia, las joint-ventures..., no permiten ningún tipo de relajo a las empresas tecnológicas que participan en esta carrera desenfrenada de competitividad.Las maquinarias dedicadas a procesos puntuales, cada vez más, son historias para el recuerdo. Hoy todo es efímero y la tecnología de antaño basada en equipos mecánicos (magnetoscopios..., plataformas y soportes lineales (cintas... están abocados a la desaparición.Conceptos de solvencia empresarial tales como "los grandes y los pequeños", utilizados en otros ámbitos de la industria, son en el sector audiovisual cada vez más delicados. En los diarios económicos podemos leer cómo, con cierta asiduidad, empresas muy posicionadas en el sector se ven abocadas a establecer fusiones, compras y participaciones, con pequeñas células de creación y desarrollo que surgen de la creatividad de jóvenes emprendedores, hasta ayer desconocidos.La era digital está corriendo un enorme telón y deja atrás, por suerte, una etapa analógica en la que la posesión de los medios de producción, debido a sus costes, era motivo suficiente para negar la participación y el acceso, a equipos tecnológicos audiovisuales de carácter profesional, a los creadores.Hoy, lo digital proporciona nuevos sistemas con entornos productivos más amables a la vez que reduce considerablemente coste de los equipamientos. En este momento, despojados ya de los inconvenientes analógicos, el talento es el verdadero motor de la industria audiovisual, en un sector que aglutina tecnología

  8. A Design for a Quantum Time Machine

    CERN Document Server

    Gray, A


    In the new ``History Selection'' formulation of Quantum Mechanics an entire cosmic history is selected over all space and time, with a probability for selection assigned to each possible history. As this probability depends on the whole history, and is not merely composed of the product of probabilities for each step in the history, the theory is not a causal theory. It shall be shown that this violation of causality is usually completely unobservable and confined to the microscopic world, occurring inbetween ``observations''. However it shall also be shown that in certain special circumstances it is possible to exploit the intrinsic non-causal nature of the theory to violate causality at the macroscopic level. A practical design for a device which can exploit this effect is shown. Such a device would effectively enable one to see into the future, and is thus a kind of time machine. Finally it shall be shown that, according to this new formulation of Quantum Mechanics, this does not give rise to any unpleasan...

  9. Worldviews: A blessing or a curse?

    Directory of Open Access Journals (Sweden)

    Bert Olivier


    Full Text Available The concept of a worldview resonates with other concepts, such as those of ‘culture’, ‘civilisation’, and ‘way of life’. Arguably, it is a modern phenomenon, the possibility of which was actualised at the dawn of the modern epoch. Nevertheless, in principle, its ‘possibility’ goes back as far as Plato’s Republic. It is Heidegger, however, who is most informative for understanding what a worldview is, as well as why the modern epoch is its time of provenance. Consequently, an analysis of Heidegger’s essay, ‘The time of the world picture’ (or worldview provided the framework within which it was argued that worldviews are both blessings and curses in the current era: blessings, because, as Harries has argued, we have been disabused of the modern idea of one encompassing worldview or ideology, so that one can no longer believe in only a single ’correct’ view of the world; curses, because they bedevil any wellintended attempts at communicating with understanding on issues of common concern. It was the burden of this article to provide a way of addressing this state of affairs with some hope of transcending the causes of alienation and it is again Heidegger who is the source of such a way, through his notion of the ‘fourfold’.

  10. A proposal of a local modified QCD

    CERN Document Server

    de Oca, Alejandro Cabo Montes


    A local and renormalizable version of a modified PQCD introduced in previous works is presented. The construction indicates that it could be equivalent to massless QCD. The case in which only quark condensate effects are retained is discussed in more detail. Then, the appearing auxiliary fermion fields can be integrated leading to a theory with the action of massless QCD, to which one local and gauge invariant Lagrangian term for each quark flavour is added. These terms are defined by two gluon and two quark fields, in a form curiously not harming power counting renormalizability. The gluon self-energy is evaluated in second order in the gauge coupling and all orders in the new quark couplings, and the result became transversal as required by the gauge invariance. The vacuum energy was calculated in the two loop approximation and also became gauge parameter independent. The possibilities that higher loop contributions to the vacuum energy allow the generation of a quark mass hierarchy as a flavour symmetry br...

  11. A leitura: um passaporte para a vida

    Directory of Open Access Journals (Sweden)

    Armindo Teixeira Mesquita


    Full Text Available Nas sociedades actuais, a capacidade para usar material escrito é indispensável ao acesso a todo tipo de informação, tornando o uso da leitura cada vez mais necessário à participação real do cidadão em actividades produtivas e colectivas, porque ajuda a formar seres pensantes. O contacto com os livros deve ser iniciado o mais cedo possível, não só pelo manuseio, como também pela história contada ou pelos jogos rítmicos. Com efeito, na idade da infância, toda a energia do indivíduo é dirigida para a construção da sua identidade. Logo, as primeiras leituras entram no período da formação e da fundação, isto é, consignamos à leitura uma grande força de desenvolvimento pessoal. Os livros, para além de auxiliares na aprendizagem do mundo, formam o leitor no gosto. Formar o gosto e possibilitar escolhas são realidades fundamentais na vida adulta.

  12. A tribute to Peter A. Rona: A Russian Perspective (United States)

    Sagalevich, Anatoly; Lutz, Richard A.


    In July 1985 Peter Rona led a cruise of the National Oceanic and Atmospheric Administration (NOAA) ship Researcher as part of the NOAA Vents Program and discovered, for the first time, black smokers, massive sulfide deposits and vent biota in the Atlantic Ocean. The site of the venting phenomena was the Trans-Atlantic Geotraverse (TAG) Hydrothermal Field on the east wall of the rift valley of the Mid-Atlantic Ridge at 26°08‧N; 44°50‧W (Rona, 1985; Rona et al., 1986). In 1986, Peter and an international research team carried out multidisciplnary investigations of both active and inactive hydrothermal zones of the TAG field using the R/V Atlantis and DSV Alvin, discovering two new species of shrimp (Rimicaris exoculata and Chorocaris chacei) (Williams and Rona, 1986) and a hexagonal-shaped form (Paleodictyon nodosum) thought to be extinct (Rona et al., 2009). In 1991 a Russian crew aboard the R/V Akademik Mstislav Keldysh, with two deep-diving, human-occupied submersibles (Mir-1 and Mir-2) (Fig. 1), had the honor of having Peter Rona and a Canadian IMAX film crew from the Stephen Low Company on board to visit the TAG hydrothermal vent field. This was the first of many deep-sea interactions between Russian deep-sea scientists and their colleagues from both the U.S. and Canada. This expedition to the TAG site was part of a major Russian undersea program aimed at exploring extreme deep-sea environments; between 1988 and 2005, the Mir submersibles visited hydrothermal vents and cold seep areas in 20 deep-sea regions throughout the world's oceans (Sagalevich, 2002). Images of several of these areas (the TAG, Snake Pit, Lost City and 9°50‧N vent fields) were obtained using an IMAX camera system emplaced for the first time within the spheres of the Mir submersibles and DSV Alvin in conjunction with the filming of science documentaries (e.g., "Volcanoes of the Deep Sea") produced by the Stephen Low Company in conjunction with Emory Kristof of National Geographic and

  13. A sabedoria da democracia

    Directory of Open Access Journals (Sweden)

    Gilson Matilde Diana


    Full Text Available a maior parte da história, a democracia foi desprezada como uma forma política inferior – a regra do povo, ou “dos muitos”, era logo identificada como a regra da ralé, da escória. Herdando do povo a volubilidade e a instabilidade, a democracia estava sempre perigosamente próxima do arbítrio e da anarquia, com toda a violência que se costuma associar a isso.

  14. Dial-a-Ride



    The Dial-a-Ride problem is a Vehicle Routing problem in its most general form. The problem was formulated in the beginning of the 1970's and since then a large number of researchers have worked on developing efficient algorithms for use in automated planning of Dial-a-Ride transportation systems. In a Dial-a-Ride transportation system, passengers request a trip between two stops with either a desired time of departure from the pickup stop or a desired time of arrival at the destination. The t...

  15. A Fat strange Repeller

    Institute of Scientific and Technical Information of China (English)

    申影; 何阅; 姜玉梅; 何大韧


    This article reports an observation on a fat strange repeller, which appears after a characteristic crisis observed in a kicked rotor subjected to a piecewise continuous force field. The discontinuity border in the definition range of the two-dimensional mapping, which describes the system, oscillates as the discrete time develops. At a threshold of a control parameter a fat chaotic attractor suddenly transfers to a fat transient set. The strange repeller, which appears after the crisis, is also a fat fractal. This is the reason why super-transience happens

  16. Epilepsy is a disease!

    Directory of Open Access Journals (Sweden)

    Walter Oleschko Arruda


    Full Text Available According to the definition of disease, epilepsy shall not be considered neither a symptom nor a syndrome. Epilepsy is a generic term for a group of diseases characterized by seizures. It implies a state quite distinct from health. Therefore it seems worthy to keep epilepsy as such in the International Classification of Diseases (ICD.

  17. A Night's Sleep, Ultracheap

    Institute of Scientific and Technical Information of China (English)


    @@ You tote your own luggage, the bed's a bit stiff, and the decor in the spartan rooms and lobby is reminiscent of a college dorm. Oh-and you can't buy a beer. But for $22 a night,the indi One Hotel is one heck of a bargain.

  18. A Montessori Odyssey (United States)

    Hanson, Peter


    Forty years ago, Peter Hanson decided to attend the 38th Indian Montessori Training Course. In this article he describes himself as a college-educated generalist who liked kids but was working for little more than minimum wage as a delivery boy. Becoming a teacher in an alternative school seemed like a good move, and a step up without…

  19. [A peripheral osteoma].

    NARCIS (Netherlands)

    Mizbah, K.; Soehardi, A.; Maal, T.J.J.; Weijs, W.L.J.; Merkx, M.A.W.; Barkhuysen, R.


    A 43-year-old man appeared with a painless, asymptomatic swelling on the left side of his neck, which had existed for years and had slowly been progressing. After surgical removal, it became clear that it had to do with a peripheral osteoma. This is a benign lesion with a low incidence. Generally, c

  20. Designing a Weather Station (United States)

    Roman, Harry T.


    The collection and analysis of weather data is crucial to the location of alternate energy systems like solar and wind. This article presents a design challenge that gives students a chance to design a weather station to collect data in advance of a large wind turbine installation. Data analysis is a crucial part of any science or engineering…

  1. Smile: A review. (United States)

    Manjula, W S; Sukumar, M R; Kishorekumar, S; Gnanashanmugam, K; Mahalakshmi, K


    "Beauty is in the mind of the beholder, each mind perceives a different beauty" famously said by writer Margeret Wolfe Hungerford. A beautiful smile is a gateway to the world. The aim of this article was to identify the criteria for designing the perfect smile. It was determined, smile design is a multifactorial process and various steps are involved in designing a radiant smile.

  2. What's a Fart? (United States)

    ... dientes Video: Getting an X-ray What's a Fart? KidsHealth > For Kids > What's a Fart? Print A A A en español ¿Qué es ... How can your body make something so stinky? Farts — also called flatus (say: FLAY-tuss) or intestinal ( ...

  3. 40 CFR Appendix A to Subpart A of... - Appendix A to Subpart A of Part 750 (United States)


    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Appendix A to Subpart A of Part 750 A Appendix A to Subpart A of Part 750 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... ACT Procedures for Rulemaking Under Section 6 of the Toxic Substances Control Act Pt. 750, Subpt....

  4. A Hydrostatic Paradox Revisited (United States)

    Ganci, Salvatore


    This paper revisits a well-known hydrostatic paradox, observed when turning upside down a glass partially filled with water and covered with a sheet of light material. The phenomenon is studied in its most general form by including the mass of the cover. A historical survey of this experiment shows that a common misunderstanding of the phenomenon…

  5. Writing a Movie. (United States)

    Hoffner, Helen


    Explains a reading and writing assignment called "Writing a Movie" in which students view a short film segment and write a script in which they describe the scene. Notes that this assignment uses films to develop fluency and helps students understand the reading and writing connections. Concludes that students learn to summarize a scene from film,…

  6. Creating a Marketing Plan. (United States)

    Sevier, Robert A.


    A guide to developing a college marketing plan defines key marketing terms, outlines the development of a plan (including institutional analysis, market research, strategy formation and execution, and program evaluation), and provides a list of important principles with which to operate a program. (MSE)

  7. Traveling Along a Zipline (United States)


    and providing a one- dimensional (1D) analogy [5] to the 2D illustration of a heavy marble rolling around on a stretched rubber sheet [6]. A 1D...117–122 (1997). [3] Gruber, R.P., Gruber, A.D., Hamilton, R. and Matthews, S.M., Space curvature and the “heavy banana paradox”, Phys. Teach. 29

  8. A Causal Rhythm Grouping

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer


    This paper presents a method to identify segment boundaries in music. The method is based on a multi-step model; first a features is measured from the audio, then a measure of rhythm is calculated from the feature, the diagonal of a self-similarity matrix is calculated, and finally the segment bo...

  9. Defining a monophyletic Cardinalini: a molecular perspective. (United States)

    Klicka, John; Burns, Kevin; Spellman, Garth M


    Within the New World nine-primaried oscine assemblage, feeding morphology and behavior have long been used as a guideline for assigning membership to subgroups. For example, birds with stout, conical bills capable of crushing heavy seeds have generally been placed within the tribe Cardinalini (cardinal-grosbeaks). Many workers have tried to characterize this group more definitively, using a variety of morphological characters; however, the characters used often conflicted with one another. Previous molecular studies addressing the monophyly of Cardinalini have had only limited sampling within the group. In this study, we analyze mtDNA sequence data from all genera and 34 of the 42 Cardinalini species (sensu [Sibley, C.G., Monroe, B.L., 1990. Distribution and Taxonomy of the Birds of the World, Yale University Press, New Haven, CT]) to address the monophyly of the group and to reconstruct the most complete phylogeny of this tribe published to date. We found strong support for a redefined Cardinalini that now includes some members previously placed within Thraupini (tanagers; the genera Piranga, Habia, Chlorothraupis, and Amaurospiza) and some members previously placed within the Parulini (wood-warblers; the genus Granatellus). In addition, some genera traditionally considered members of the Cardinalini are shown to have affinities with other groups (the genera Porphyrospiza, Parkerthraustes, and Saltator). Our redefined Cardinalini contains 48 species, six more than are listed in Sibley and Monroe's (1990) taxonomy of the group. Within the nine-primaried oscine assemblage, the Cardinalini are more closely related to the Thraupini (tanagers) than they are to the Emberizini (sparrows), Parulini (wood-warblers), or Icterini (blackbirds), consistently forming a monophyletic group with Thraupini across all analyses. The reconfigured Cardinalini is comprised of five well-supported, major clades: (1) a "masked" clade (Piranga, Cardinalis, Caryothraustes, Periporphyrus, and

  10. A cidadania, o universalismo e a diferença

    Directory of Open Access Journals (Sweden)

    Paulo Manuel Costa


    Full Text Available The contemporary debate on citizenship has been dominated by three theoretical currents: liberalism, communitarianism and republicanism. It reveals different ways of conceptualising citizenship and thus a diversity of proposals for the design and organization of political institutions. In this article we intend to grasp how these theories deal with the specific issue of difference and cultural diversity. The systematization of the debate was made with reference to four thematic axes: first, the relationship to be established between the public sphere and the private sphere; as a function of this joint, which identity prevails in the political community; thirdly, what is the role assigned to political participation; and, finally, the reflexes that citizenship may have on social cohesion of the political community. The existence of a core of common values and principles is essential to the stability and cohesion of the community, but it must be able to incorporate the difference in order to develop an identity that can be shared by various cultural and ethnic groups and thus prevent exclusion, marginalization and oppression. The best way to ensure quantitative and qualitative expansion of citizenship seems to be one that promotes the participation and involvement of individuals and groups in the process of (redefinition of common values and principles that ensure life together. This process also seems to involve moving away from rigid and dogmatic readings of the liberal principles and the refusal of non-liberal claims and principles, particularly those that question the freedom of individuals against the political power and social groups.

  11. Making a Difference: a Global Geoscience Initiative (United States)

    Nickless, E.


    Since 2009, an informal group, comprising four former board members of the International Year of Planet Earth, has been promoting the concept of a so-called Global Geoscientific Initiative. The GGI should: i.Be inclusive, involve a geoscience community, which is broad both in terms of discipline and nationality, and involve the social sciences; ii.Have a clear socio-economic context and global societal relevance; iii.Focus on a globally significant science theme and preferably involve global processes; iv.Attract the support of geoscientific communities, funding agencies, governments and other institutions in many countries, under the umbrella of UNESCO, ICSU and its geoscientific unions. A series of five town hall meetings have been held at which usually three invited, well-respected figures from the geoscientific community gave presentations. Those presentations were followed by discussion about the importance or otherwise of particular areas of science, and the need to engage better with legislators, policy makers, the media and the lay public. No one challenged the desirability of a large-scale programme that would attract researchers from many geoscientific disciplines and potentially involve the geo-unions. The discussions can be summarised under three broad themes: i.Mineral and hydrocarbon resources and their waste products; ii.Living with natural hazards; iii.Strategic Earth science in Africa through the Africa Alive corridors. During the course of development of the GGI, ICSU has issued a number of papers, most recently a strategic plan, covering the period 2012-2017, working parties have been undertaking foresight analysis and there have also been discussions concerning regional environmental change: human action and adaptation with the question "what does it take to meet the Belmont challenge?". The Belmont Forum brings together a number of funding agencies and could provide the resource to enable some initiative to go forward. More recently a programme

  12. Having a Healthy Pregnancy (United States)

    ... Week of Healthy Breakfasts Shyness Having a Healthy Pregnancy KidsHealth > For Teens > Having a Healthy Pregnancy A ... or she can help you to get treatment. Pregnancy Discomforts Pregnancy can cause some uncomfortable side effects. ...


    Directory of Open Access Journals (Sweden)

    Valdivia I


    Full Text Available Bendamustine is a cytotoxic drug used in the treatment of Chronic Lymphocytic Leukemia can cause various adverse skin reactions. We report the case of a woman who received Bendamustine and developed a skin rash

  14. A Nonideal Flow Experiment. (United States)

    Gonzalez-Velasco, Juan Ramon; Elorriaga, Javier Bilbao


    Considers the deviation from the ideal flows of both a backmix tank and a backmix tank followed by a flow vessel. Background information, apparatus used, and experimental procedures are provided. Typical results are also provided and discussed. (JN)

  15. A major safety overhaul

    CERN Multimedia


    A redefined policy, a revamped safety course, an environmental project... the TIS (Technical Inspection and Safety) Division has begun a major safety overhaul. Its new head, Wolfgang Weingarten, explains to the Bulletin why and how this is happening.

  16. Checking a printed board

    CERN Multimedia


    An 'Interactive Printed Circuit Board Design System' has been developed by a company in a Member-State. Printed circuits are now produced at the SB's surface treatment workshop using a digitized photo-plotter.

  17. Preventing hepatitis A (United States)

    Hepatitis A is inflammation (irritation and swelling) of the liver caused by the hepatitis A virus. You can take several steps to ... reduce your risk of spreading or catching the hepatitis A virus: Always wash your hands thoroughly after ...

  18. Dyslexia: A Survivor's Story. (United States)

    Rogers, Trumbull


    A successful adult with dyslexia recounts his experiences as a child including poor school reports, emotional problems, clumsiness, as well as the help provided by a special school for boys with dyslexia. (DB)

  19. Vitamin A blood test (United States)

    ... this page: // Vitamin A blood test To use the sharing features on this page, please enable JavaScript. The vitamin A test measures the level of vitamin A ...

  20. Building a Better Planet

    Institute of Scientific and Technical Information of China (English)


    Transitioning into a broader role as senior civil servant of the United Nations after 37 years as a Chinese diplomat,UN Under Secretary General Sha Zukang certainly has had a tough task to quickly understand UN culture

  1. A mechanised microirrigation system. (United States)

    Gould, J S; Henson, P G; Gould, S H


    A mechanised microirrigation system for microvascular surgery, which is operated by a foot pedal, utilises a large sterile reservoir, and allows control of flow rate and volume, has been designed for use in the laboratory and operating room.

  2. A semiconductor laser

    Energy Technology Data Exchange (ETDEWEB)

    Naoko, O.; Masaru, K.


    A semiconductor laser with enhanced characteristics is patented in which bleaching coatings are generated on the outcoupling mirrors by sputtering alternating coating layers made from A1203 and A10, with high and low indices of refraction.

  3. A Colorful Equatorial Wonderland

    Institute of Scientific and Technical Information of China (English)


    @@ Papua New Guinea (PNG) is one of the least visited countries in the world... a last frontier for international travelers. PNG is a colorful equatorial wonderland as well as a living example of human's culture 1000 years ago.

  4. Decavanadate: a journey in a search of a role. (United States)

    Aureliano, Manuel


    Currently, efforts have been directed towards using decavanadate as a tool for the understanding of several biochemical processes such as muscle contraction, calcium homeostasis, in vivo changes of oxidative stress markers, mitochondrial oxygen consumption, mitochondrial membrane depolarization, actin polymerization and glucose uptake, among others. In addition, studies have been conducted in order to make vanadium available and safe for clinical use, for instance with decavanadate compounds that present interesting pharmacological properties, eventually useful for the treatment of diabetes. Here, recent contributions of decavanadate to the effects of vanadium in biological systems, not only in vitro, but also in vivo, are analysed.

  5. You are not a gadget a manifesto

    CERN Document Server

    Lanier, Jaron


    A programmer, musician, and father of virtual reality technology, Jaron Lanier was a pioneer in digital media, and among the first to predict the revolutionary changes it would bring to our commerce and culture. Now, with the Web influencing virtually every aspect of our lives, he offers this provocative critique of how digital design is shaping society, for better and for worse. Informed by Lanier’s experience and expertise as a computer scientist, You Are Not a Gadget discusses the technical and cultural problems that have unwittingly risen from programming choices—such as the nature of user identity—that were “locked-in” at the birth of digital media and considers what a future based on current design philosophies will bring. With the proliferation of social networks, cloud-based data storage systems, and Web 2.0 designs that elevate the “wisdom” of mobs and computer algorithms over the intelligence and wisdom of individuals, his message has never been more urgent.

  6. Use a defibrillator, save a life

    CERN Multimedia

    Joannah Caborn Wengler


    With the work for Long Shutdown 1 looming on the horizon, the CERN Fire Brigade is anticipating a heavy workload: more people working at CERN means more call-outs. So the more trained first-aiders around to help out before the paramedics arrive, the better. Would you know what to do in a medical emergency?   It could happen at any time: two colleagues are having a coffee at work, when one suddenly clutches his or her chest and falls to the floor unconscious. What would you do? Run to find a first-aider? Call the ambulance and wait, finishing your coffee? Neither response is entirely correct. On Monday 11 June in Building 40 the CMS safety group, in collaboration with the Fire Brigade and the Medical Service, demonstrated the recommended, potentially life-saving response to cardiac arrest (see the video), including the correct use of a defibrillator, ten of which were recently installed in key CERN locations (the Bulletin reported).     “In countries where...

  7. A Review on Noma: A Recent Update. (United States)

    Ashok, Nipun; Tarakji, Bassel; Darwish, Shourouk; Rodrigues, Jean C; Altamimi, Mohammad A


    Noma is a gangrenous infection primarily affecting under developed countries. The aim of this paper was to review all recent articles on noma from January 2003 to August 2014 and briefly update the latest information related to the topic. A literature search was done on PUBMED using the keywords "noma/cancrum oris". Noma is commonly seen in malnourished children. There has been an increased incidence of noma in HIV patients. Apart from these, noma has also been reported in association with cyclic neutropenia, herpetic stomatitis, leukemia, Down's syndrome and Burkett's disease. Treatment of acute noma includes transfusion of blood and intravenous fluids, administration of antibiotics, putting the patient on a high protein diet and debridement of necrotic areas. Surgical phase is usually initiated 6 to 18 months after a period of quiescence. Although, the mortality rate associated with noma has reduced significantly with the advent of modern generation antibiotics, the functional, cosmetic and psychological challenges associated with the destruction of soft or hard tissues still remains a huge challenge. Adequate steps must be implemented by the government or medical professionals to prevent the disease and provide an early intervention.

  8. Pop in a Popper (United States)

    Reading Teacher, 2011


    This article describes Pop in a Popper, an effective lesson for teaching students how to choose and use words to give their writing fluency and flair. Pop in a Popper introduces the appositive: a group of words inserted after a noun to modify that noun. In simplest terms, writers pop this group of words into a sentence to tell more about a noun.…

  9. 'A Place to Sit'

    DEFF Research Database (Denmark)

    Hvejsel, Marie Frier; Klok, Julie Skovgaard; Bøhnke, Mia Marker

    Published in 2014 on the occasion of the third 'A Place to Sit' exhibition as a reflection upon three years of teaching tectonic method in architecture using the furniture scale as a learning basis.......Published in 2014 on the occasion of the third 'A Place to Sit' exhibition as a reflection upon three years of teaching tectonic method in architecture using the furniture scale as a learning basis....

  10. A Workshop that Works

    CERN Document Server

    Yunes, Nicolas


    The main goal of a scientific workshop is to bring together experts in a specific field or related fields to collaborate, to discuss, and to creatively make progress in a particular area. The organizational aspects of such a meeting play a critical role in achieving these goals. We here present suggestions from scientists to scientists that hopefully help in organizing a successful scientific workshop that maximizes collaboration and creativity.

  11. Buying a New Car?

    Institute of Scientific and Technical Information of China (English)

    Paul; Maghielse


    You read it here first, folks: a car buying processthat first counsels its readers not to buy a car! Why?Because, no matter what mystical incantations a carsalesperson may whisper in your ear, cars are notinvestments. Certainly, there are a few exceptions to that rule,but in general. vehicles are what the accountantsamong us call depreciating assets. Think of a vehiclepurchase in comparison with the other big-ticketpurchases we make during our lifetimes. Buying a

  12. Mitochondrial swelling impairs the transport of organelles in cerebellar granule neurons. (United States)

    Kaasik, Allen; Safiulina, Dzhamilja; Choubey, Vinay; Kuum, Malle; Zharkovsky, Alexander; Veksler, Vladimir


    Organelle transport in neuronal processes is central to the organization, developmental fate, and functions of neurons. Organelles must be transported through the slender, highly branched neuronal processes, making the axonal transport vulnerable to any perturbation. However, some intracellular structures like mitochondria are able to considerably modify their volume. We therefore hypothesized that swollen mitochondria could impair the traffic of other organelles in neurite shafts. To test this hypothesis, we have investigated the effects of mitochondrial swellers on the organelle traffic. Our data demonstrate that treatment of neurons with potassium ionophore valinomycin led to the fast time-dependent inhibition of organelle movement in cerebellar granule neurons. Similar inhibition was observed in neurons treated with the inhibitors of the mitochondrial respiratory chain, sodium azide and antimycin, which also induced swelling. No decrease in the motility of organelles was observed in cultures treated with inhibitors of ATP production or transport, oligomycin or bongkrekic acid, suggesting that inhibition of the ATP-generating activity itself without swelling does not affect the motility of organelles. The effect of swellers on the traffic was more important in thin processes, thus indicating the role of steric hindrance of swollen mitochondria. We propose that the size and morphology of the transported cargo is also relevant for seamless axonal transport and speculate that mitochondrial swelling could be one of the reasons for impaired organelle transport in neuronal processes.

  13. A Brilliant Conductor with a Potential Enterprise

    Institute of Scientific and Technical Information of China (English)


    Huafang Co.,LTD is a large integrated textile printing and dyeing enterprise,which is in Binzhou,a beautiful city located in the Yellow River Delta.It has a wide variety of textile products, including 1200 million meters of fabric,70 million meters of printed fabrics,50,000,000 meters of textile fabrics,five million sets of bedding and two million pieces of dress.It has been awarded as "top 10 enterprises" in textile industry for nine consecutive years by China National Textile&Apparel Council.Wang Limin is the general manager,who successfully runs this textile enterprise in China and puts it into the stock market.

  14. A cutaneous mixed tumor in a dog (United States)

    WATANABE, Ken-ichi; CHAMBERS, James K.; UCHIDA, Kazuyuki; NIBE, Kazumi; USHIO, Nanako; HORIUCHI, Noriyuki; KOBAYASHI, Yoshiyasu; NAKAYAMA, Hiroyuki


    The atypical cutaneous tumor of a 9-year-old mixed breed female dog was examined. The tumor was well-demarcated and histologically composed of a trichoblastic area, tricholemmal area and apocrine glandular area. Neoplastic cells in trichoblastic area and tricholemmal area had PAS-positive granules in the cytoplasm and were positive for pan-cytokeratin, cytokeratin 5/6, 14 and 19 and p63. Neoplastic cells in trichoblastic area were also positive for cytokeratin 15 and CD34. Neoplastic cells in apocrine glandular area were positive for pan-cytokeratin and cytokeratin 7, 18 and 19. Myoepithelial cell proliferation with osteocartilaginous metaplasia was observed in this area. Since neoplastic cells showed multiphenotypic differentiation for hair follicles and apocrine glands, the present case was diagnosed as a cutaneous mixed tumor. PMID:28132963

  15. When is a word a word? (United States)

    Vihman, M M; McCune, L


    Although adult-based words co-occur in the period of transition to speech with a variety of non-word vocalizations, little attention has been given to the formidable problem of identifying these earliest words. This paper specifies explicit, maximally 'inclusive' identification procedures, with criteria based on both phonetic and contextual parameters. A formal system for evaluating phonetic match is suggested, as well as a set of child-derived functional categories reflecting use in context. Analysis of word use across two samples of 10 children each, followed from 0;9 to 1;4, provides evidence to suggest that context-bound words can be 'trained' by focusing on eliciting language, but that the timing of context-flexible word use remains independent of such training.

  16. Suicide after a stroke: a population study

    DEFF Research Database (Denmark)

    Teasdale, T W; Engberg, A W


    cases of suicide were identified. MAIN RESULTS: Annual incidence rates, both observed and expected, together with standardised mortality ratios (SMR) were computed based on annual population and suicide statistics, stratified by age and gender. The overall annual incidence rate of suicide in the cohort.......19) and highest for those hospitalised for less than two weeks (2.32; 1.92, 2.80). Survival analysis suggested that the risk for suicide is greatest up to about five years after a stroke. CONCLUSIONS: Stroke patients are at an approximately doubled risk for suicide. This risk is greater among younger patients...... and causes of death. SETTING: The population of Denmark, 1979-1993. PATIENTS: A study cohort was defined comprising all 114 098 stroke patients discharged alive from hospital during the period 1979-1993. These patients were then screened in a register of causes of death over the same time period, and 359...

  17. Hiding a neutron star inside a wormhole

    CERN Document Server

    Dzhunushaliev, Vladimir; Kleihaus, Burkhard; Kunz, Jutta


    We consider neutron-star-plus-wormhole configurations supported by a massless ghost scalar field. The neutron fluid is modeled by an anisotropic equation of state. When the central energy density of the fluid is of comparable magnitude to the one of the scalar field, configurations with an equator at the center and a double-throat arise. These double-throat wormholes can be either partially or completely filled by the neutron fluid. In the latter case, the passage of light - radiated by the neutron matter - through these wormholes is studied. A stability analysis indicates that all considered configurations are unstable with respect to linear perturbations, independent of whether the fluid is isotropic or anisotropic.

  18. Packing a cake into a box

    KAUST Repository

    Skopenkov, Mikhail


    Given a triangular cake and a box in the shape of its mirror image, how can the cake be cut into a minimal number of pieces so that it can be put into the box? The cake has icing, so we are not allowed to put it into the box upside down. V. G. Boltyansky asked this question in 1977 and showed that three pieces always suffice. In this paper we provide examples of cakes that cannot be cut into two pieces to be put into the box. This shows that three is the answer to Boltyansky\\'s question. We also give examples of cakes which can be cut into two pieces. © THE MATHEMATICAL ASSOCIATION OF AMERICA.

  19. A Blue Lagoon Function

    DEFF Research Database (Denmark)

    Markvorsen, Steen


    We consider a specific function of two variables whose graph surface resembles a blue lagoon. The function has a saddle point $p$, but when the function is restricted to any given straight line through $p$ it has a {\\em{strict local minimum}} along that line at $p$.......We consider a specific function of two variables whose graph surface resembles a blue lagoon. The function has a saddle point $p$, but when the function is restricted to any given straight line through $p$ it has a {\\em{strict local minimum}} along that line at $p$....

  20. A Study on a Software Quality Assurance of a Process and a Product

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Tae [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)


    Since nuclear plants and facilities have made increasing use of digital technology, the safety and reliability of software is a primary concern. Software errors are more difficult to detect and handle than hardware-related failures. It is crucial to consider the a process and a product of a software life cycle to increase the quality of a software. This paper discusses the quality assurance of a process and a product of a software life cycle based on two prominent standards, ISO 9001:2000 and CMMI.